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UNIVERSITY OF CALIFORNIA 

TECHNOLOGY LICENSING 

OPPORTUNITIES 

CANCER 

Fall 2005 

Prepared by: 

Office of Technology Transfer 

University of California 

Office of the President 

1111 Franklin Street, 5th Floor 

Oakland, California 94607-5200 

Phone: (510) 587-6000, Fax: (510) 587-6090 

Web: http://techtransfer.universityofcalifornia.edu 

The information on this CD is current as of October 2005. 

For the most up-to-date information on available UC 

technologies, please refer to the Web sites on the 

following page.

UC Technology Transfer on the Web 

The Technology listings on this CD were current at the time the CD was created. New 

technologies are added and available technologies are licensed frequently. To learn about the 

University’s technology transfer offices and find the latest available technologies, visit the 

following Web sites: 

(Prefix with http://) 

UC Office of the President: 

Office of Technology Transfer (OTT) www.ucop.edu/ott 

UC Berkeley: 

Office of Intellectual Property and Industry Research Alliances (IPIRA) ipira.berkeley.edu 

UC Davis: 

Technology and Industry Alliances (TIA) www.research.ucdavis.edu/tia 

UC Irvine: 

Office of Technology Alliances (OTA) www.ota.uci.edu 

UC Los Angeles: 

Office of Intellectual Property Administration (OIPA) www.research.ucla.edu/oipa 

UC Riverside: 

Office of Intellectual Property Services (OIPS) www.ora.ucr.edu/ip 

UC Santa Barbara: 

Technology and Industry Alliances (TIA) research.ucsb.edu 

UC Santa Cruz: 

Office of Sponsored Projects www.ucsc.edu/osp 

UC San Diego: 

Technology Transfer and Intellectual Property Services (TechTIPS) invent.ucsd.edu 

UC San Francisco: 

Office of Technology Management (OTM) www.otm.ucsf.edu 

Los Alamos National Laboratory: 

Technology Transfer Division (TTD) www.lanl.gov/opportunities 

Lawrence Berkeley National Laboratory: 

Technology Transfer Department (TTD) www.lbl.gov/Tech-Transfer 

Lawrence Livermore National Laboratory: 

Industrial Partnerships and Commercialization (IPAC) www.llnl.gov/IPandC

NCD Search Results 

NCD 

Search Result 

Your query cancer matched 181 out of 1342 documents, shown below. 

[Next] 

Title 

1. A BREAST CANCER METASTASES TRANSGENE MODEL 

2. A CELL PROLIFERATION INHIBITOR 

3. A METHOD FOR CREATING NUCLEAR RECEPTOR ACTIVITY MODULATING 

PHARMACEUTICALS 

4. A METHOD FOR CREATING SPECIFIC, HIGH AFFINITY NUCLEAR RECEPTOR 


5. A METHOD FOR IN VIVO VISUALIZATION OF MUTATED MOUSE CELLS 

6. A Method for Providing Unique Spatial Addresses for Molecules (With application to array 

diagnostics design for cancer therapy) 

7. A New EGF Receptor Associated With Inhibition Of Pancreatic Cancer Cell Growth 

8. A NEW ETS-RELATED GENE OVEREXPRESSED IN HUMAN BREAST AND 

EPITHELIAL CANCERS 

9. A New Strategy for Leukemia Therapy 

10. A NON-INVASIVE AND CLOSED LOOP SYSTEM FOR DETECTION AND 

TREATMENT OF PROSTATE CANCER 

11. A NOVEL THERAPEUTIC TARGET FOR BREAST CANCER 

http://patron.ucop.edu/search97cgi/s97_cgi.exe?QueryZi...rtOrder=Asc&ResultStart=1&ResultCount=100&ResultStyle= (1 of 7)10/21/2005 2:50:11 AM


12. A NOVEL TUMOR SUPPRESSOR GENE 

13. A SPECTROSCOPIC ASSAY FOR HELICASE ACTIVITY AND INHIBITORS 

14. A SYSTEM FOR TARGETING INVASIVE PATHOGENS AND CANCER CELLS FOR 

ATTACK BY THE HUMAN IMMUNE SYSTEM 

15. A TISSUE-SPECIFIC SELF-PROPAGATING RETROVIRAL VECTOR SYSTEM FOR 

GENE THERAPY 

16. AMPLIFIED AND OVEREXPRESSD GENE IN COLORECTAL CANCERS 

17. ANIMAL MODEL OF HPV-INDUCED DYSPLASIA 

18. ANTI-CD22 MONOCLONAL ANTIBODIES USED FOR THE TREATMENT OF 

LYMPHOMA AND LEUKEMIA 

19. ANTICANCER SEED EXTRACT 

20. AP1 ASSAY FOR ESTROGEN RECEPTORS ER-ALPHA AND ER-BETA 

21. ASSAY OF GTP/GDP BOUND TO RAS AND OTHER G PROTEINS 

22. ASSAYS AND ANTIBODIES FOR N-MYC PROTEINS 

23. ASSESSMENT OF ALLELE-SPECIFIC EXPRESSION IN CELLS AND TISSUE 

24. Asthenons: Novel Gene Expression Attenuator Elements 

25. BIFUNCTIONAL CHELATORS FOR RADIODIAGNOSIS/ THERAPY AND METHOD 

FOR THEIR EFFICIENT RADIOLABELING 

26. BLEOMYCIN BIOSYNTHETIC GENES 

27. BORON COMPOUNDS AND LIPOSOME DELIVERY SYSTEMS FOR BORON 

NEUTRON CAPTURE THERAPY 





29. BORON COMPOUNDS SUITABLE FOR LIPOSOMAL DELIVERY TO TUMORS FOR 

THE PURPOSE OF BORON NEUTRON CAPTURE THERAPY 

30. BRAIN GLYCOGEN PHOSPHORYLASE CANCER ANTIGEN 

31. Cancer Vaccine 

32. CLONED RECEPTOR FOUND IN BREAST CANCER CELLS 

33. CNL878, A Cytotoxic and Antifungal Terpene from a Marine Fungus 

34. COMBINED USES OF IMPDH INHIBITORS WITH TOLL-LIKE RECEPTOR 

AGONISTS 

35. CONSTRAINTS-BASED ANALYSIS OF GENE EXPRESSION DATA 

36. COUMARIN COMPOUNDS AS MICROTUBULE STABILIZING AGENTS AND 

THERAPEUTIC USES THEREOF 

37. CYTOTOXIC ANTIBODY FUSION PROTEIN 

38. DETECTION OF ATM MUTATIONS AND POLYMORPHISMS WITH MEGA-SSCP 

39. DETECTION/DEPOLYMERIZATION OF POLYSIALIC ACID CHAINS IN VARIOUS 

DEVELOPMENTAL AND DISEASE STATES 

40. DEVELOPMENT OF NEW SELECTIVE ESTROGEN RECEPTOR MODULATORS 

(SERMs) 

41. DIAGNOSIS AND TREATMENT OF CRYPTOSPORIDIOSIS, INCLUDING HUMAN 

VACCINE 

42. DIAGNOSTIC TEST FOR CANCER SUSCEPTIBILITY 

43. DIAGNOSTIC TEST FOR MUTATIONS IN THE AT GENE 



44. Dianestatin: A New Tumor-Specific Cytotoxin Conjugate 

45. DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HER-2/NEU 

OVEREXPRESSION 

46. DIHYDROXYVITAMIN D3 PHARMACEUTICAL SYSTEM 


48. DIRECT ASSAY FOR ANDROGEN RECEPTOR MODULATORS 

49. DNA BINDING COMPOUNDS FOR GENETIC REGULATION AND MEDICAL 

DIAGNOSIS AND THERAPY 

50. EARLY DETECTION OF COLON CANCER 

51. Early Detection Of Pancreatic & Other Cancers 

52. END-SPECIFIC ANTIBODY TO DETECT APOPTOSIS 

53. ENDOSCOPIC LASER INSTRUMENT 

54. ENDOVASCULAR DEVICE FOR HYPERTHERMIA 


56. EPLIN, A MARKER FOR HUMAN CANCER 

57. EXONS 4 AND 7 ENCODE SEPARATE TRANSACTIVATING AND CHROMATIN- 

LOCALIZING DOMAINS IN ESX 

58. EXPRESSION AND PURIFICATION OF ATM PROTEIN USING VACCINIA VIRUS 

59. EXPRESSION OF HUMAN NUCLEAR RECEPTORS IN MICE 



60. FAS-ASSOCIATED FACTOR 1 

61. FLUORESCENCE ASSAY FOR DNA-MODIFYING ENZYMES: APPLICATIONS TO 

HIGH THROUGHPUT LIBRARY SCREENING OF POTENTIAL REGULATORS 

62. FROZEN TISSUE MICROARRAY TECHNOLOGY FOR ANALYSIS OF RNA, DNA, 

AND PROTEINS 

63. GDOX, A NOVEL CANDIDATE PROTO-ONCOGENE 

64. GLUCOSE EMULATING RADIOPHARMACEUTICAL FOR CONVENTIONAL 

GAMMA CAMERA IMAGING 

65. HER-2/NEU OVEREXPRESSION ABROGATES GROWTH INHIBITORY PATHWAYS 

66. HER2 AND HER3 APTAMERS 

67. HUMAN CELLULAR RECEPTORS FOR LYSOPHOSPHOLIPIDS AND 

SPHINGOLIPIDS 


SPHINGOLIPIDS 


SPHINGOLIPIDS 


SPHINGOLIPIDS 

71. IDENTIFICATION, CLONING AND CHARACTERIZATION OF A NOVEL HUMAN 

HDAC HIGHLY EXPRESSED IN THE THYMUS 

72. IDENTIFICATION, DIAGNOSIS AND THERAPY FOR CELL DEATH-RELATED 

DISEASES 

73. Imaginal Cell Growth Factor 

74. IMPROVED LIPOSOMAL ENCAPSULATION OF DRUGS 

75. IMPROVED TAXANE PRODUCTION 





78. IN VITRO SCREEN TO IDENTIFY COMPOUNDS WITH ESTROGENIC OR ANTI- 

ESTROGENIC ACTIVITY 

79. INDUCTION OF PHAGOCYTIC HOST DEFENSE 

80. INEXPENSIVE RESOLUTION OF AMBIGUOUS PAP SMEARS 


82. INHIBITORS OF ANDROGEN ANTAGONISTS-REFRACTORY PROSTATE CANCER 

83. INHIBITORS OF THE IL-4/IL-13 SIGNALING PATHWAY 


85. IRRADIATED PROBIOTIC FOR IBD 

86. ISS RECEPTOR AS A DRUG DISCOVERY TOOL 

87. KNOWN HORMONE WITH POTENTIAL THERAPEUTIC ACTION IN BRAIN 

DISEASES 

88. LIPOSOMAL DELIVERY OF ISS-BASED VACCINES 

89. LIPOXYGENASE INHIBITORS AS DRUGS AGAINST CANCER, ASTHMA AND 

ATHEROSCLEROSIS 

90. LIQUID ASSOCIATION WITH APPLICATION IN GENE EXPRESSION 

91. LONG WAVELENGTH PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY 

AND DIAGNOSIS OF TUMORS 



92. MACROMOLECULE-LIPID COMPLEXES FOR SYNTHETIC GENE-DELIVERY 

SYSTEMS 

93. MACROPHAGE-COLONY STIMULATING FACTOR CRYSTALS 

94. MAGNETIC RESONANCE FOR EVALUATING TISSUE NECROSIS IN 

NEOPLASTIC, INFLAMMATORY AND INFECTIOUS DISORDERS 

95. MECHANOSENSORY TRANSDUCTION CHANNEL GENE 

96. METHOD FOR DEVELOPING ANTAGONISTS FOR NUCLEAR HORMONE 

RECEPTORS 

97. METHOD FOR DIAGNOSING BREAST CANCER 

98. METHOD FOR EARLY DIAGNOSIS OF, AND DETERMINATION OF PROGNOSIS 

IN, CANCER 

99. METHOD FOR ENHANCING AN IMMUNE RESPONSE 

100. METHOD FOR INHIBITING PROTEIN KINASES IN CANCER CELLS 

http://patron.ucop.edu/search97cgi/s97_cgi.exe?QueryZi...rtOrder=Asc&ResultStart=1&ResultCount=100&ResultStyle= (7 of 7)10/21/2005 2:50:11 AM 

1 2


NCD 

Search Result 


[Prev] 

Title 

101. METHOD FOR MAKING UNIVERSAL DONOR CELLS 

102. Method for Rational Induction of Drought Resistance in Plants Suppression of Stomatal 

Farnesyl Transferase Activity 

103. METHOD FOR SELECTIVE METHIONINE STARVATION OF MALIGNANT CELLS 

104. METHOD OF ANALYZING ATAXIA-TELANGIECTASIA PROTEIN 

105. METHOD OF INHIBITING ANGIOGENESIS 

106. METHOD TO IDENTIFY EDITED mRNA'S 

107. METHODS AND MATERIALS FOR CHARACTERIZING AND MODULATING 

INTERACTION BETWEEN HEREGULIN AND HER3 

108. METHODS FOR DETECTION AND TREATMENT OF NEURAL CANCERS 

109. METHODS FOR IDENTIFYING NOVEL THERAPEUTICS AND DIAGNOSTICS IN 

THE p53 PATHWAY 

110. METHODS FOR INCREASING A CYTOTOXIC T LYMPHOCYTE RESPONSE IN 

VIVO 

111. METHODS FOR INHIBITING NUCLEAR RECEPTORS 

http://patron.ucop.edu/search97cgi/s97_cgi.exe?QueryZi...Order=Asc&ResultStart=101&ResultCount=100&ResultStyle= (1 of 6)10/21/2005 2:50:12 AM


112. METHODS FOR SCREENING NUCLEAR TRANSCRIPTION FACTORS FOR THE 

ABILITY TO MODULATE AN ESTROGEN RESPONSE 

113. MICROMACHINED CANTILEVERS FOR BIOAGENT DETECTION 

114. MODIFIED PCR FOR QUANTITATIVE GENE ANALYSIS 

115. Modulation Of Cell Growth And Growth Factor Signaling Through Removal Of Glypicans 

116. Molecular Cytological Evaluation For Pancreatic Cancer By Screening Liquid Stool 

117. Molecular Cytological Evaluation For Pancreatic Cancer By Screening Pancreatic Juice 

118. Molecular Signature Test For Pancreatic Cancer 

119. Multimeric Forms of CD40L and Other TNF Family Members 

120. MURINE MODEL FOR EPITHELIAL NEOPLASTIC PROGRESSION 

121. New Laser Based Treatment Of Bacterial Infections 

122. NEW USES FOR INHIBITORS OF INOSINE MONOPHOSPHATE 

DEHYDROGENASE 

123. NOVEL AGONISTS OF TOLL-LIKE RECEPTORS 

124. Novel Anticancer Compound From Marine Ascidian 

125. Novel Antigen for Immunization in Cancer 

126. NOVEL MELANOCORTIN RECEPTOR ANTAGONISTS FOR THE TREATMENT 

OF MELANOMA 

127. NOVEL METHODS AND COMPOSITIONS FOR DELIVERING NUCLEIC ACID 

DRUGS TO SPECIFIC CELLS AND SUBCELLULAR ORGANELLES 



128. NOVEL MITOGEN ACTIVATED C-FOS REGULATING KINASE, FRK 

129. Novel Modified Marine Polypeptides with Antimicrobial and Anticorrosion Properties 

130. Novel Screening System for Microtubule-based Herbicides or Pesticides: New Generation 

Having Exceptional Species Selectivity and Safety 

131. NOVEL STRATEGIES FOR THE TREATMENT OF HIV INFECTION 

132. NOVEL TREATMENT FOR HYPERPLASTIC DISEASE 

133. Novel, Virus-Independent In Vivo Gene Therapy Approach 

134. P21-ACTIVATED KINASE (PAK I) AND RELATED PEPTIDES 


136. PEPTIDE NUCLEIC ACID MIMICS 

137. pH SENSITIVE LIPOSOMES FOR DRUG DELIVERY 

138. Phosphonate Esters of Nucleosides and Methods of Use for Same 

139. PHOSPHORYLATION OF HISTONE H2B AS A MARKER FOR CELL 

PROLIFERATION AND DIFFERENTIATION IN DEVELOPMENT AND DISEASE 

140. PHOSPHOTYROSINE BINDING DOMAIN 

141. PHOSPHOTYROSINE BINDING DOMAIN INVOLVED IN SIGNALING 

PATHWAYS THAT TRIGGER BREAST CANCER 

142. PII: S0301-472X(01)00681-6 

143. PORPHYRIN-BASED NEUTRON CAPTURE AGENTS FOR CANCER THERAPY 



144. Porphyrin-Based Neutron Capture Agents for Cancer Therapy 

145. Prodrugs of Pharmaceuticals with Improved Bioavailability 

146. PROTEIN MARKER OF CERTAIN CANCERS AND JOINT DISEASES, 

ALCOHOLIC CIRRHOSIS, AND STREPTOCOCCUS PNEUMONIA 



148. Protein That Down Regulates Oncogenic Growth Factor Receptor 

149. PROTEIN WITH SIGNAL TRANSDUCTION ACTIVITY 

150. PSEUDOPTEROSIN AND SYNTHETIC DERIVATIVES THEREOF 

151. QUANTITATIVE ALLELE ANALYSIS: AN IMPROVED METHOD FOR 

ENUMERATING DNA COPY NUMBER OF MULTIPLE ALLELES 

152. QUANTITATIVE MEASUREMENT OF TISSUE PROTEIN IDENTIFIED BY 

IMMUNOHISTOCHEMISTRY AND STANDARDIZED PROTEIN DETERMINATION 

153. RAPID ACTIVATIOIN OF FLOURIDE-18 FOR USE IN POSITRON EMISSION 

TOMOGRAHY 

154. Rapid Assay For GSH In Biological Samples 

155. RECEPTOR ACTIVATION IN TUMORS 

156. RECOMBINANT PROLACTIN ANTAGONIST 

157. REGULATION OF INTRACELLULAR SIGNALING WITH PHOSPHATIDYL 

INOSITOL KINASES 

158. REVERSIBLE INHIBITORS OF CYTOSINE-C5 DNA METHYLTRANSFERASE 

159. ROLD OF THE VDUP1 GENE IN LIPID DISORDERS AND CANCER 



160. ROLE OF THE VDUP1 GENE IN LIPID DISORDERS AND CANCER 

161. Schlafen, New Gene Family Regulating Cell Growth 

162. Screening Assays For Glycosylation Inhibitors 

163. SINGLE AND MULTIPLE TYROSINE KINASE KNOCKOUT MICE 

164. SMALL INTERFERING RNA TO INHIBIT TRANSCRIPTION FACTOR 

EXPRESSION IN MAMMALIAN CELLS 

165. STRUCTURE OF ESTROGEN RECEPTOR AND CO-ACTIVATOR 

166. SYNTHESIS OF PROTEIN CONJUGATES FOR THE DEVELOPMENT OF 

IMMUNOASSAYS FOR AAL MYCOTOXINS 

167. TARGET FOR THERAPEUTICS FOR MODULATION OF THE IMMUNE SYSTEM 

168. The Use of Detergents to Enhance Drug Uptake In Vivo: With Particular Emphasis on 

Cancer Chemotherapy Agents 

169. Therapeutics and Diagnostic for Septic Shock 

170. THERAPY AND DIAGNOSIS OF CONDITIONS RELATED TO TELOMERE 

LENGTH AND/OR TELOMERASE ACTIVITY 

171. TOOLS FOR GENE DELIVERY AND TRANSFECTION 

172. TRANSCRIPTION FACTOR FOR THE REGULATION OF SKIN AND HAIR 

DEVELOPMENT 

173. Treating Cancer And Atherosclerosis With Photodynamic Therapy 

174. TREATMENT OF PLATELET DERIVED GROWTH FACTOR RELATED 

DISORDERS SUCH AS CANCER 

175. TUMOR-RELATED ENDOTHELIAL MARKER GENE 



176. UNIVERSAL VECTORS FOR DRUG DELIVERY 

177. Unnatural Amino Acids That Mimic Peptide Beta-Strands 

178. Use Of Infectious And Pathogenic Clone Of A Lung Cancer-Inducing Retrovirus For 

Generation Of Therapeutic Reagents And Diagnostic Tests Or Reage 

179. VECTORS AND CELL LINES FOR CLASS SWITCH RECOMBINATION 

180. VESOSOMES: BILAYER-ENCAPSULATED VESICLE AGGREGATES 

181. WNT AND FRIZZLED RECEPTORS AS POTENTIAL TARGETS FOR CANCER 

IMMUNOTHERAPY 

http://patron.ucop.edu/search97cgi/s97_cgi.exe?QueryZi...Order=Asc&ResultStart=101&ResultCount=100&ResultStyle= (6 of 6)10/21/2005 2:50:12 AM 

1 2

A BREAST CANCER METASTASES TRANSGENE MODEL 

Non-Confidential Description 


BACKGROUND: Prevention of metastasis in primary breast cancer is essential for long-term patient 

survival. However, few animal models are available for studying the metastatic process in situ. This new 

model has the advantage over older models of tumor metastases because the responsible oncogenes are 

well characterized and the major signal transduction pathway is known. 

DESCRIPTION: Researchers at the University of California have developed high and low metastatic 

transplantable breast cancer cell lines in nude mice. Tissue culture lines were also developed from the 

same tumors. In addition, transplantable and tissue culture lines were generated from both high and low 

metastatic foci. 

APPLICATIONS: The UC breast cancer transgene model can be used to investigate the myriad aspects 

of cancer metastases. These in vivo and in vitro tumor cell lines provide an ideal experimental breast 

cancer model in which cells of similar genetic background with predictable high or low pulmonary 

metastases occur within a short period of time. The model can be used to address critical aspects of 

metastasis such as angiogenesis and invasion of the vasculature by tumor cells in situ, in addition to 

studying the complex interactions between tumor cells and the extracellular matrix, stromal cells, and 

the vasculature in their physiological microenvironment. 

ADVANTAGES: This metastatic breast cancer model represents a truly unique system whereby all 

facets of the metastatic process can be analyzed. It consists not only of high and low metastatic cancer 

lines but also multiple cell lines derived from metastatic foci obtained from the high and low lines. Also, 

each transplantable cell line has a corresponding tissue culture line. This paired in vivo and in vitro 

system will permit the initial assessment of pharmaceutical products prior to extensive and expensive 

whole animal pre-clinical pharmacological studies leading to Phase I and II clinical studies. The system 

is also useful to study the initial metastatic processes of intra- and extra-vasation, angiogenesis, and 

colonization. Biochemical, biological, and genetic pathways can be studied, and pharmacological 

compounds can be easily tested for interference at various points of the metatstatic cascade. 

INQUIRIES TO: Silka Weintraub silka.weintraub@ucop.edu 

http://patron.ucop.edu/ncd/docs/ott.1997-159-0.00.html (1 of 2)10/21/2005 2:50:13 AM


REFERENCE: 1997-159 

Technology Categories 

● Biotechnology 

● Go to Faculty Guidance 

● Go to UC Bridges to Industry 



1111 Franklin Street, Fifth Floor 

Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 

● Go to Resources for Administrators 

© Copyright 1996 The Regents of the University of California. All Rights Reserved. 


A CELL PROLIFERATION INHIBITOR 



BACKGROUND: Unchecked cell proliferation can cause a variety of dangerous diseases including 

cancer and atherosclerosis. One strategy for developing treatments for these diseases is to identify genes 

that are necessary for cell proliferation, and then to find agents that will specifically inhibit their 

expression or activity. 

DESCRIPTION: UC scientists have identified a protein that is required for platelet-derived growth 

hormone (PDGF) and serum stimulated cell proliferation. Transfection with an anti-sense 

oligodeoxynucleotide directed towards the gene that encodes this protein leads to inhibition of cell 

proliferation. The oligos cause no generalized toxic effects and are highly effective in vascular smooth 

muscle cells. Inhibition of the protein could also be accomplished by addition of antibodies or ligands. 

APPLICATIONS: Inhibition of the protein may be used for treatment or prevention of cell proliferative 

diseases in vascular smooth muscle cells or tumor cells. Conditions that could be treated include 

atherosclerosis, angioplasty restenosis, renal mesangial cell proliferation, the vascular smooth muscle 

proliferation seen after coronary angioplasty, and cancer. Since this gene is also important for matrix 

protein synthesis, use of these oligos may also decrease matrix production, and therefore scarring, seen 

in renal, atherosclerotic and other diseases. 

INQUIRIES TO: Neil Kilcoin neil.kilcoin@ucop.edu 



● Biotechnology > Other biotechnology 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




A METHOD FOR CREATING NUCLEAR RECEPTOR ACTIVITY MODULATING PHARMACEUTICALS 


A METHOD FOR CREATING NUCLEAR RECEPTOR ACTIVITY 

MODULATING PHARMACEUTICALS 

BACKGROUND: Nuclear receptors control cell differentiation, development, metabolism and organ 

physiology. These regulatory proteins activate or repress target gene transcription in response to 

molecules such as steroids, retinoids and thyroid hormone. Although structurally different, they are all 

single polypeptide chains composed of evolutionarily conserved functional domains: an N-terminal 

activation domain, a central DNA binding domain and a C-terminal ligand-binding domain (LBD). 

Nuclear receptors generally bind to DNA either as homodimers or heterodimers. Homodimer function is 

the norm for the steroid receptors (e.g. the estrogen receptor), while other receptors, such as thyroid 

hormone receptor, partner with the master control receptor, retinoid X receptor (RXR). Binding of RXR 

to these receptors is crucial for their function in inhibiting or stimulating transcription. As there are 

many diseases caused by an excess of nuclear receptor function, disruption of this interaction in a 

specific manner could have important clinical relevance. 

DESCRIPTION: Researchers at the University of California have discovered a thyroid hormone 

receptor antagonist, GC-24, that binds to a newly discovered surface cavity that is part of the receptor 

important for heterodimer formation. Structurally, GC-24 mimics RXR in its binding to the thyroid 

receptor. It is therefore likely that GC-24 would block the formation of heterodimers between RXR and 

thyroid hormone receptor. This could enable GC-24 to act as a powerful inhibitor of thyroid receptor 

function. 

ADVANTAGES: 

● There are currently no known inhibitors of nuclear hormone receptor activity or dimerization. 

Derivatives of GC-24 could provide very valuable antagonists of various nuclear hormones. 

● Classical antagonists are analogs of agonists and therefore cross-react with other nuclear 

receptors. Inhibitors of dimerization described in this invention (GC-24 and its derivatives) need 

not resemble natural ligands and therefore will not cross-react with other nuclear receptors. 

APPLICATIONS: 


A METHOD FOR CREATING NUCLEAR RECEPTOR ACTIVITY MODULATING PHARMACEUTICALS 

● Derivatives of GC-24 could be developed to inhibit dimerization of other nuclear hormone 

receptors. 

● Pharmaceuticals made from GC-24 and its derivatives could aid in the treatment of diseases that 

result from an excess of hormone function, such as hyperthyroidism and Cushing's syndrome. 

● These pharmaceuticals might also be useful in the treatment of hormone-dependent cancers such 

as breast cancer and prostate cancer. 

INQUIRIES TO: Yashwant Vaishnav yashwant.vaishnav@ucop.edu 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






A METHOD FOR CREATING SPECIFIC, HIGH AFFINITY NUCLEAR RECEPTOR PHARMACEUTICALS 


A METHOD FOR CREATING SPECIFIC, HIGH AFFINITY 

NUCLEAR RECEPTOR PHARMACEUTICALS 

BACKGROUND: Nuclear receptors control cell differentiation, development, metabolism and organ 

physiology. These regulatory proteins activate or repress target gene transcription in response to 

molecules such as steroids, retinoids, and thyroid hormone. Although structurally different, they are all 

single polypeptide chains composed of evolutionarily conserved functional domains: an N-terminal 

activation domain, a central DNA binding domain and a C-terminal ligand-binding domain. The nuclear 

receptors predominantly function as heterodimers. 

Recent research in nuclear receptor structure and function has illuminated the roles of these receptors in 

cardiovascular disease, obesity, diabetes, drug metabolism, bone disease, cancer and other diseases. In 

fact, 20% of prescribed drugs in the United States are ligands for nuclear receptors. Thus, an important 

goal is to identify novel small molecules that activate or inhibit the actions of nuclear receptors in 

specific ways. Efforts to produce new compounds are hampered by problems with low receptor affinity, 

cross-reactivity between similar receptors and difficulty in predicting the effects of the compounds upon 

receptor activity. 

DESCRIPTION: Researchers at the University of California have invented a new method for 

producing specific, high affinity agonists of nuclear receptors. Traditional agonists bind exclusively to 

the ligand binding domain. In this new method, researchers add extensions to the agonist that contact 

regions of the receptor that are outside the ligand binding domain. Importantly, this extra contact is 

designed to not disrupt the normal function of that receptor domain. As many nuclear receptors are 

structurally similar, this extra contact can provide much needed agonist specificity as well as enhanced 

affinity. 

ADVANTAGES: This methods allows for the invention of agonists that are highly specific for a given 

nuclear receptor. As different receptor isoforms (closely related receptors) are relevant to different 

diseases, the ability to selectively activate one isoform over another can provide for more diseasespecific 

treatment. 

APPLICATIONS: 


A METHOD FOR CREATING SPECIFIC, HIGH AFFINITY NUCLEAR RECEPTOR PHARMACEUTICALS 

● Produce, identify and design agonists for a variety of nuclear receptors. 

● Produce, identify and design agonists that distinguish between nuclear receptor isoforms, thereby 

allowing the generation of tissue specific or function specific agonists (or both). 

● Construct libraries of agonists, receptors, and receptor/agonist complexes. 

● Develop novel therapeutics for diseases treatable with appropriate nuclear receptor agonists, 

including obsesity, cardiac disease, bone disease, depression, and some forms of cancer. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






A METHOD FOR IN VIVO VISUALIZATION OF MUTATED MOUSE CELLS 


A METHOD FOR IN VIVO VISUALIZATION OF MUTATED 

MOUSE CELLS 

BACKGROUND: One method of studying tumors in mice is by using the CRE recombination system 

to delete or overexpress cancer-control genes in particular tissues at particular times. However, a hurdle 

in studying tumorogenesis is the difficulty in monitoring the progress of tumors in vivo. Current 

techniques require sacrifice of the animal followed by in situ work. These methods require the use of 

large numbers of animals and preclude the possibility of following the progress of a particular tumor 

over time. 

DESCRIPTION: UC scientists have developed a sensitive, non-invasive technique for in vivo 

visualization of cells mutated by the CRE recombination system. Using positron emission topography 

(PET), they are able to follow the development of the potentially tumorous cells over time. 

ADVANTAGES: Since no sacrifice is required to visualize the affected cells, fewer mice can be used to 

obtain statistically valid data. Tumor cells can be detected at the very earliest stages, and the effects of 

therapy, environment, and type and severity of mutation can all be assessed in vivo. 




● Biotechnology > Genetic engineering sys > Recombinant DNA (rDNA) 

● Pharmaceuticals > Diagnostic agents 




Oakland, CA 94607-5200 


A METHOD FOR IN VIVO VISUALIZATION OF MUTATED MOUSE CELLS 



Phone: (510) 587-6000 Fax: (510) 587-6090 




A Method for Providing Unique Spatial Addresses for Molecules (With application to array diagnostics design for cancer therapy) 

A Method for Providing Unique Spatial Addresses for Molecules 

(With application to array diagnostics design for cancer therapy) 

BACKGROUND: Using two-dimensional monolayer arrays of discrete DNA or RNA molecule 

"96spots", it is possible to test for nucleic acid hybridization in a test sample against several hundred 

different analytes relating to the disease in question, using an appropriate visualization and quantitation 

technique. In this way response patterns corresponding to the unique expression of genes in that cell 

sample can be obtained, and compared to the pattern of gene expression responses of reference samples 

known to be associated with a disease state. By using roboticization for scanning and reading, together 

with modem pattern recognition algorithms, it is possible to extend this to three-dimensional stacks of 

arrays as well. The result can be a definitive diagnosis for the condition in question. 

DESCRIPTION: A new technique has been developed for creation of solid state molecular arrays, with 

special application to diagnosis of cancer susceptibility to therapy selection, based on the sensitivity of 

the cell. Several dozen unique injury response genes have been characterized in cancer cells (there may 

be hundreds); the ability of cancer cells to express patterns of these genes determines their ability to 

withstand various therapeutic strategies. Thus, a detailed knowledge of the genomics of a cell type's 

injury response "strategy" can guide the selection of drugs which can circumvent those strategies. 

Similarly, the effectiveness of the 70+ currently utilized cancer treatment protocols is closely related to 

the pattern of injury response genes they induce in target cells and normal cells. Matching these in the 

patient has the potential to pair the sensitivities if the cell with the best possible first treatment protocol 

for that cancer. It is well known that the extent of favorable response to the first therapy approach 

correlates positively with the likelihood of full recovery of the cancer patient (reflecting the targeting of 

the cancer with effective drugs that do not endice resistance). 

ADVANTAGES: This technique allows a large number of genes and gene fragments associated with 

injury response to be assessed for expression potential simultaneously. Further, it is not necessary to 

understand the function of the wound response genes utilized. The pattern of genes on the array that 

"light up" in response a sample can simple be compared by computer to those of cancers susceptible to 

the drug in question, allowing a better selection of therapeutic approach . 

CASE NUMBER: SD98-036 

http://patron.ucop.edu/ncd/docs/ucsd.1998-036.html10/21/2005 2:50:15 AM

A New EGF Receptor Associated With Inhibition Of Pancreatic Cancer Cell Growth 

Technology/Business Opportunity 

Non-Confidential Executive Summary 

UC CASE 1996-230-1 

NUMBER: 

TITLE: A New EGF Receptor Associated With Inhibition Of Pancreatic 

Cancer Cell Growth 

DEPARTMENT: Department of Medicine - Endocrinology 

SUMMARY: BACKGROUND: Pancreatic cancer has an overall 5-year survival rate under 0.4%, 

and is characterized by early metastasis and resistance to chemotherapeutic agents. 

With such dismal prospects for pancreatic cancer patients, there is a pressing need 

for alternatives to conventional anti-cancer strategies. One possible approach 

involves genetic modification of tumor cells. Pancreatic and related cancers 

overexpress the epidermal growth factor receptor (EGF-R). EGF-R is a 170kilodalton 

transmembrane glycoprotein that, upon ligand binding, dimerizes and 

undergoes phosphorylation events within the intracellular domain. Various studies 

of the dimerization process suggest that it is possible to attenuate the EGF-R 

overexpression characteristic of metastatic cells using special vector constructs, 

offering a possible avenue for treating pancreatic cancer. DESCRIPTION: Scientists 

at the University of California have developed a vector that confers dominant 

negative expression of a modified EGF-R phenotype. This modified EGF-R inhibits 

the growth of human pancreatic cancer cells and increases their sensitivity to 

cisplatinum, an alkylating agent commonly used in chemotherapy. 

APPLICATIONS: The relative uniformity and ease of infection with the UC vector 

raises the possibility that the vector or its analogues may have a significant role in 

the treatment of pancreatic cancer and other malignancies where EGF-R is 

overexpressed. 

http://patron.ucop.edu/ncd/docs/uci.1996-230-1.html (1 of 2)10/21/2005 2:50:15 AM

A New EGF Receptor Associated With Inhibition Of Pancreatic Cancer Cell Growth 

CONTACT: Vithal Rajadhyaksha - UCI 

Email: vjrajadh@uci.edu 

Office of Technology Alliances 


380 University Tower 

Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


A NEW ETS-RELATED GENE OVEREXPRESSED IN HUMAN BREAST AND EPITHELIAL CANCERS 


A NEW ETS-RELATED GENE OVEREXPRESSED IN HUMAN 

BREAST AND EPITHELIAL CANCERS 

DESCRIPTION: Researchers at the University of California have isolated partial and full-length cDNA 

and genomic clones and synthesized recombinant protein (polyclonal and monoclonal antibodies to the 

recombinant protein are currently being developed) corresponding to a new human gene that belongs to 

the ETS family of transcription factors. This particular gene is overexpressed in a portion of human 

epithelial cancers, including breast cancer and colon cancer. In some cases, this overexpression appears 

to be due to increased gene copy in these malignancies. 

APPLICATIONS: This novel ETS factor represents a possible tumor etiologic factor and protooncogene, 

and has promise as a tumor prognostic factor and a potential target for antitumor therapies. 

Newly developed reagents pertaining to this ETS gene and its protein product could be used for: 

● Diagnostic purposes 

● Screening purposes 

● Prognostic purposes 

● Therapeutic purposes 

● Basic research 




● Biotechnology > Immunology systems > Anticancer systems 


● Medical Eqp & Svcs > Medical diagnostic eqp > Cancer test kits 


A NEW ETS-RELATED GENE OVEREXPRESSED IN HUMAN BREAST AND EPITHELIAL CANCERS 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




A New Strategy for Leukemia Therapy 


A new strategy has been developed to treat chronic Myelogenous Leukemia (CML) and Acute 

Lymphocytic Leukemia (ALL). Unlike current approaches, this new strategy is able to treat the acute 

phase of leukemia, thus potentially providing a more effective therapy. The strategy depends on 

transient exposure of cancerous cells to a combination of drugs that act synergistically. The combined 

action of the drugs produces no significant toxic effect on normal cells while leukemia cells are 

irreversibly killed. The mechanism of action of the drugs tested has been determined, thereby providing 

a screening strategy for new, potentially more effective drug combinations. The protocol has so far been 

developed using cultured cells and remains to be tested in animal models. 


INQUIRIES TO: invent@ucsd.edu 


A NON-INVASIVE AND CLOSED LOOP SYSTEM FOR DETECTION AND TREATMENT OF PROSTATE CANCER 


A NON-INVASIVE AND CLOSED LOOP SYSTEM FOR 

DETECTION AND TREATMENT OF PROSTATE CANCER 

BACKGROUND: Current methods for detection and treatment of prostate cancer present several 

drawbacks. For example, although the prostate specific antigen (PSA) blood test has proven to be a 

highly effective tool for diagnosis and treatment, it is not an absolute test for prostate cancer. In order to 

confirm the diagnosis, doctors must perform a biopsy of the prostate, which can be painful, 

uncomfortable, or even lead to bleeding complications for the patient. Available treatment methods, 

whether invasive or non-invasive, can result in several unwanted side effects and complications, such as 

acute cystitis, incontinence, and impotence. 

DESCRIPTION: Scientists at the University of California have developed an improved method for 

prostate cancer diagnosis and treatment. This new system uses an ultrasound probe that is equipped to 

collect cancer markers as well as deliver drugs directly to the prostate. 

APPLICATIONS: This new UC technology has applications in cancer diagnosis and treatment. 

ADVANTAGES: The new UC technology provides the following benefits: 

● Non-invasive, convenient, and painless diagnosis and treatment technique; 

● In diagnosis, it measures marker (PSA) concentration in the interstitial fluid of the prostate, as 

opposed to systemic levels, which may result in increased sensitivity; 

● In treatment, it delivers the drugs directly to the tumor, which limits side effects. 

INQUIRIES TO: Sherylle Mills Englander englander@research.ucsb.edu 


PATENT STATUS: US Patent # 6,589,173 issued July 8, 2003 



A NON-INVASIVE AND CLOSED LOOP SYSTEM FOR DETECTION AND TREATMENT OF PROSTATE CANCER 

● Medical Eqp & Svcs > Surgical/medical eqp > Med/surgical instruments 



University of California, Santa Barbara 

Office of Research 

3227 Cheadle Hall 

Santa Barbara, CA 93106-2050 

Phone: (805) 893-4036 




A NOVEL THERAPEUTIC TARGET FOR BREAST CANCER 



BACKGROUND: Immunohistochemical and mRNA expression profiling studies of large numbers of 

breast cancers have reproducibly identified a subset of tumors that express markers that are 

characteristic of the basal layer of the mammary gland. It has been suggested that these malignancies 

arise from basal or supra-basal progenitor cells with stem cell attributes. This is in contrast to many 

human breast cancers that uniformly express markers suggestive of their origins as transformed luminal 

epithelial cells. 

Human breast cancers with basal properties are aggressive malignancies that are not responsive to 

established targeted therapies such as anti-estrogens or Herceptin since they are invariably estrogen 

receptor (ER) negative and rarely contain amplified HER-2.Although high frequencies of p53 mutations 

have been associated with basal cancers and tumors arising in BRCA1 carriers fall into this basal class, 

the oncogenic molecules and key molecular pathways that drive the progression of these tumors are 

unknown. 

DESCRIPTION: Researchers at the University of California have used microarray profiling and 

Northern blot confirmation to identify a protein that is specifically upregulated in primary human breast 

cancers with an ER negative, basal phenotype. Additionally, the researchers found high expression of 

this protein in several human breast cancer cell lines that co-express basal markers, while expression of 

this protein was not detected in any luminal cell lines. Importantly, the level of expression of this protein 

detected in basal, malignant cell lines was significantly higher than in non-malignant cells. The 

researchers further found that tumors expressing this protein are associated with a poor prognosis, and 

the percentage of poor prognosis tumors in the group expressing this protein (70% of sporadic) is higher 

than for any other single prognostic gene analyzed including Her-2, EGFR, VEGF, FLT3 myc and UPA/ 

PAI. Thus, this protein may be a powerful prognostic tool for breast cancer and a possible therapeutic 

target for the highly malignant basal breast cancers. 

ADVANTAGES: 

● The identified protein has not previously been associated with any particular cancer and thus may 

provide a powerful new therapeutic, diagnostic, and prognostic target. 

● The identified protein is specifically overexpressed in basal breast cancers, a type of cancer that 



is not amenable to current therapies. 

APPLICATIONS: 

● Methods of interfering with the expression or function of this protein may be therapeutically 

useful in the treatment of breast cancer. 

● Transgenic animals that over-express this protein may be useful for the development and 

screening of therapeutically useful reagents. 

● Detection of expression of this protein may be useful as a diagnostic/prognostic marker for breast 

cancers. 

● Detection of expression of this protein may be useful in characterizing breast cancer subtypes. 

INQUIRIES TO: Bernadette McCafferty bernadette.mccafferty@ucop.edu 



● Biotechnology > Genetic engineering sys 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






A NOVEL TUMOR SUPPRESSOR GENE 



BACKGROUND: Tumor suppressor genes are genes that, when damaged, fail to suppress 

tumorigenesis. Typically, tumor suppressor genes are genes that, in their wild-type alleles, express 

proteins that suppress abnormal cellular proliferation. When the gene coding for a tumor suppressor 

protein is mutated or deleted, the resulting mutant protein or the complete lack of tumor suppressor 

protein expression may fail to correctly regulate cellular proliferation, and abnormal cellular 

proliferation may take place, particularly if there are coincidental perturbations of other cellular 

regulatory mechanisms. Because loss of function or inactivation of tumor suppressor genes may play a 

central role in the initiation and/or progression of a significant number of human cancers, there is a need 

for the identification of additional tumor suppressor genes in order to further improve diagnosis and 

therapy. 

DESCRIPTION: Researchers at the University of California have identified a novel tumor suppressor 

gene, called H37. The evaluation of the status of the H37 gene provides information useful in diagnostic 

and prognostic protocols to assess the status of cells that may have disregulated growth. In addition, 

methods involving the H37 gene may be utilized in a therapeutic context in a manner analogous to 

therapeutic methods used with other tumor suppressor genes, such as introduction of polypeptides or 

oligonucleotides containing the H37 gene. Methods for the use of H37 in the diagnosis, prognosis and 

treatment of cancer are available. Diagnostic kits based on H37 expression are also available. 

ADVANTAGES: The identification of H37 provides the basis for a variety of diagnostics, prognostics, 

and therapeutics for cancer. 

APPLICATIONS: 

● Diagnostics for cancers, including breast, ovarian, and lung cancer. 

● Prognostics to assess the status, severity, and likelihood of developing breast, ovarian, and lung 

cancer. 

● Therapeutics for the treatment of cancers, including breast, ovarian, and lung cancer. 

● Research tools to characterize the role of H37 in normal physiological processes as well as its 

associated pathological conditions including aberrant cell growth such as cancer. 



PATENT STATUS: U.S. Patent Application Publication No. 20030225008 



PATENT STATUS: US Patent # 6,929,910 issued August 16, 2005 


● Biotechnology > Genetic engineering sys > DNA/RNA probes 

● Biotechnology > Genetic engineering sys > Human therapeutic rDNA 

● Pharmaceuticals > Antineoplastic agents 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






A SPECTROSCOPIC ASSAY FOR HELICASE ACTIVITY AND INHIBITORS 


A SPECTROSCOPIC ASSAY FOR HELICASE ACTIVITY AND 

INHIBITORS 

Helicases play an important role in viral infection, cancer, and other disease states. Kinetic studies of the 

activity of these enzymes, particularly in regards to measuring the transition between single and doublestranded 

states of DNA or DNA-RNA hybrids, has been limited by the nature of the quantitative assays 

involved. Typically, these assays are non-continuous and require considerable manipulation of the 

experimental system before results are obtained. 

An improved approach for assaying the activity of such enzymes and inhibitors of enzyme activity has 

been developed by scientists at the University of California. The crucial advance over prior methods is 

the identification of certain fluorescent dyes that readily act as markers of the double-stranded state 

without interfering with enzyme activity. With these UC dyes, spectrophotometric techniques are 

instantaneously sensitive to changes in fluorescence brought about by the formation or dissassociation of 

double-strands. Thus, the UC assay is fast, continuous, sensitive, and yields real-time data. No 

complicated labeling or detection methods are required. Initial studies by the UC scientists on E. coli 

helicase activity confirm the utility of the assay in such kinetic studies. 



PATENT STATUS: US Patent # 5,747,247 issued May 5, 1998 


● Biotechnology > Genetic engineering sys > Ribonucleic acid (RNA) R&D 


● Pharmaceuticals > Anti-infective agents > Antiviral agents 



A SPECTROSCOPIC ASSAY FOR HELICASE ACTIVITY AND INHIBITORS 





Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




A SYSTEM FOR TARGETING INVASIVE PATHOGENS AND CANCER CELLS FOR ATTACK BY THE HUMAN IMMUNE SYSTEM 


A SYSTEM FOR TARGETING INVASIVE PATHOGENS AND 

CANCER CELLS FOR ATTACK BY THE HUMAN IMMUNE 

SYSTEM 

The most serious diseases owe their perniciousness to an ability to evade the effective response of the 

natural immune system. The microorganisms responsible for malaria, cholera, meningitis, and amebic 

dysentery, for example, all fail to elicit a full-scale immune response, because characteristic molecules 

on their cell surfaces, by which the immune system would normally identify them, are constantly 

changing. HIV and other viruses evade an individual's natural defenses in the same way, and cancer cells 

evade immune recognition because their surface molecules do not identify them as foreign. University of 

California (UC) researchers have developed a system promising a means to target evasive cells and 

viruses. Targeted with selected effector molecules, the pathogens and cancer cells will no longer be able 

to avoid an wholesale attack by the immune system. The approach could provide an extremely powerful 

means of treating a great many of the most serious diseases. 

The system relies on specialized synthetic hybrid molecules. The hybrid molecules possess three 

regions, or moieties: a binding region, an effector region, and a linkage connecting the two. The effector 

moiety exhibits a molecular structure capable of eliciting an immune response. The binding region can 

specifically attach to the pathogen by a similar mechanism by which invading viruses or microorganisms 

first attach themselves, and then gain entry into a host cell. (Alternatively, the binding moiety can be 

chosen to mimic cell surface structures through which cancer cells initiate metastasis). Chosen in this 

way, the binding moiety of the hybrid molecule is specific to a surface protein of the virus or pathogen 

which does not change. By choosing as an effector moiety a structure which mimics a ubiquitous 

antigen, a targeting molecule can be constructed which precipitates an immediate immune response. 

UC investigators have established the effectiveness of their targeting system with diverse tests. They 

have synthesized hybrid molecules which bind to systematically invasive E. coli strains and elicit both a 

humoral and cell mediated immune response towards the pathogen. 

In a second example, small molecules have been constructed that specifically bind to HIV: test to stop 

infectivity using neutralizing antibodies. 


A SYSTEM FOR TARGETING INVASIVE PATHOGENS AND CANCER CELLS FOR ATTACK BY THE HUMAN IMMUNE SYSTEM 

UC researchers have also developed a suitable pharmaceutical carrier for the targeting molecules. 

INQUIRIES TO: Marwan Harara marwan.harara@ucop.edu 




● Biotechnology > Immunology systems 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






A TISSUE-SPECIFIC SELF-PROPAGATING RETROVIRAL VECTOR SYSTEM FOR GENE THERAPY 


A TISSUE-SPECIFIC SELF-PROPAGATING RETROVIRAL 

VECTOR SYSTEM FOR GENE THERAPY 

BACKGROUND: Recombinant retroviruses are the most widely used vectors for gene therapy trials. 

Retroviral vectors are produced using packaging cell lines. The packaging cell lines express the essential 

viral genes that have been deleted from the vector. The vector contains all the cis elements for 

replication, packaging and integration, but the viral genes are replaced by the therapeutic gene or genes 

of interest. The vector, released from the packaging cells and collected from the culture medium, 

transfers the therapeutic gene by infecting target cells. However, lacking essential viral genes, the vector 

is not capable of reproducing itself in the infected target cells to infect other cells. 

This retroviral system as currently practiced has important limitations. First, the vectors are derived from 

murine virus, which is not tissue-specific in humans. Hence, the tissue or organs for which gene transfer 

are intended are usually removed from the patient, and the therapeutic gene is introduced into the cells 

which are then returned to the patient. This is know as ex vivo gene therapy. Secondly, for the 

transduction of cells by retrovirus, cell division is required. Thus, this type of treatment can be applied 

only to tissues that can be cultured ex vivo. Human pluripotent stem cells and many cancer cells are 

difficult to culture in vitro and therefore are not effectively transduced by retroviral vectors. The third 

problem is that retroviral titers are relatively low. This makes it nearly impossible to infect all the cells 

which is a requirement, for example, to treat cancer. 

DESCRIPTION: Researchers at the University of California have devised a retroviral-based gene 

transfer system, consisting of a pair of packageable vectors that complement each other in functions, and 

carry one or more therapeutic genes. One of the vectors also carries a gene for a chimeric envelope 

protein that permits infection of only the targeted cells. Co-transfection into the target cells, in addition 

to transferring the therapeutic gene(s), will also produce a mixture of virions. Some virions among the 

mixture that emerge will contain both vector genomes. These virions will infect adjacent cells in a tissuespecific 

manner, replicate, and spread the therapeutic gene in the targeted tissue. This will greatly 

increase the efficiency of gene transduction and potentially can be used directly in vivo. Specific cell 

types can be targeted by engineering specific envelope proteins. 

APPLICATIONS: This retroviral gene transfer system system is suitable for spreading therapeutic 

genes to treat genetic diseases, cancer and other conditions that would benefit from gene therapy. It is 



especially applicable in cancer therapy where cancerous cells can be targeted for killing, for example, by 

expression of a therapeutic gene. These vectors may also be used to express antigens for vaccines. 

ADVANTAGES: 

● Initial high titers of the transducing virions are not necessary because the vectors replicate in the 

target cells. 

● This method produces a highly efficient infection of the target cells because replication of the 

vector provides a continuous supply of vector at the site of infection. 

● Infection of the target cells is specific because the chimeric envelope protein is tissue-specific 

and retroviruses infect only dividing cells. 

● There is no need for packaging cells or producer cells for vector production because the vectors 

carry all the essential genes for replication, and the target tissue serves as the packaging cells. 

● Initial vector-producing cells may be made from primary cells, such as fibroblasts, from the 

recipient. 

● Potentially, the vector system would allow in vivo administration, circumventing the need for the 

laborious and expensive procedures of ex vivo cell culture and infection. 

● In vivo administration would also allow gene transfer into some primary cancer cells, such as 

most breast cancer cells, that are difficult to grow ex vivo. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 








AMPLIFIED AND OVEREXPRESSD GENE IN COLORECTAL CANCERS 


AMPLIFIED AND OVEREXPRESSD GENE IN COLORECTAL 

CANCERS 

BACKGROUND: Chromosome abnormalities are often associated with genetic disorders, degenerative 

diseases, and cancer. In fact, the deletion or multiplication of copies of whole chromosomes, 

chromosomal segments, or specific regions of chromosomes are common occurrences in cancer, and can 

be the cause of some cancers. One such amplified region found in studies of breast and colon cancer 

cells is on chromosome 20, specifically 20q13.2. Increased copy number of 20q13.2 is found in greater 

than 25% of cancers of the ovary, colon, head-and-neck, brain, and pancreas. However, it is unknown 

what gene target(s) is/are responsible for this increase in cancer. 

DESCRIPTION: Researchers at the University of California have identified a novel oncogene, 26#77, 

by virtue of its RNA expression profile in a breast cancer cell line. The 26#77 gene is located on 

chromosome 20q13.2, a region whose amplification is associated with poor cancer prognosis. They 

found that 26#77 is amplified and 26#77 RNA and protein are overexpressed in 60% of colorectal 

cancers. The researchers have used this discovery to develop methods for diagnosing and treating 

diseases and disorders, such as colorectal cancer, characterized by amplification of the 26#77 gene and/ 

or overexpression of 26#77 gene products. The diagnostics include use of Northern blots, in situ 

hybridization, and immunoassays to determine the levels of 26#77 RNA and protein in biological 

samples. Treatment methods include the use of antisense and siRNA to decrease levels of 26#77. 

Cultured cells expressing 26#77 are also available. 

ADVANTAGES: The identification of 26#77 provides a novel basis for the development of diagnostics 

and therapeutics for colorectal cancer. 

APPLICATIONS: 

● Diagnosis and treatment of colorectal cancer. 

● Determination of efficacy of a therapeutic regimen to treat colorectal cancer. 



AMPLIFIED AND OVEREXPRESSD GENE IN COLORECTAL CANCERS 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




ANIMAL MODEL OF HPV-INDUCED DYSPLASIA 



Human papillomaviruses (HPV's) are an important world-wide health problem, with over half of all 

women being carriers of HPV. Certain "high risk" HPV's are associated with anogenital cancer, which 

proceeds through several stages. The initial stage involves the development of hyperplastic lesions, most 

of which will spontaneously regress. About 10% of HPV16 lesions (and similar percentages of other 

"high risk" HPV's), however, will proceed to the next stage, where the individual lesions display 

immature cell types (dysplasia). Finally, the dysplasias "advance in grade" to become malignant 

precursors of cervical cancer. 

Currently, there are no animal models of this neoplastic progression. Attempts to infect laboratory mice 

seem to have failed because of an inability to target HPV expression to the critical cell layer or because 

of an unfavorable physiochemical milieu in mice as compared to humans. Given the ubiquity of HPV 

infection and its significant morbidity if untreated, such an animal model would be a valuable tool for 

discovering the mechanisms that control the disease progression and to screen compounds that are 

candidate pharmaceuticals for preventing carcinogenesis. 

University of California researchers have developed a transgenic mouse strain and protocols for their use 

in providing a model of progressive neoplasia induced by HPV16. Without special protocols, the UC 

mice express HPV16 oncogenes in the basal cells of a variety of squamous epithelia including skin, oral, 

cavity, and anus. With the UC protocol, the mice can also express HPV16 genes in equivalent cells of 

the vagina and cervix. Moreover, this cervico-vaginal expression faithfully matches the neoplastic 

progression found in human patients, a feature of the UC animal model that is of great clinical and 

therapeutic significance. With the UC mice and protocols, HPV16-induced squamous dysplasia can now 

be reproduced for research purposes. Current work with potential anti-HPV pharmaceutical agents such 

as retinoids, anti-estrogens, and synthetic progestins could immediately benefit from the UC animal 

model. Both the search for optimal compounds and the generation of data in phase I testing for FDA 

applications would be greatly facilitated using the UC animal model. 

INQUIRIES TO: Matthew Berman mat.berman@ucop.edu 





● Biotechnology > Animal biotech systems > Laboratory animals 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




ANTI-CD22 MONOCLONAL ANTIBODIES USED FOR THE TREATMENT OF LYMPHOMA AND LEUKEMIA 


ANTI-CD22 MONOCLONAL ANTIBODIES USED FOR THE 

TREATMENT OF LYMPHOMA AND LEUKEMIA 

BACKGROUND: Non-Hodgkins lymphoma and chronic lymphocytic leukemia are B-cell 

malignancies that remain important contributors to cancer mortality. The response of these malignancies 

to various forms of treatment is mixed. While some cases respond to treatment with chemotherapy and 

radiation therapy, about one-half of patients die from these diseases. In addition, current therapies have 

toxic side effects. Therefore, there is a need for new treatment options that are more effective and less 

toxic than current treatments. 

DESCRIPTION: Researchers at the University of California have developed several monoclonal 

antibodies directed against CD22, a membrane glycophosphoprotein found on nearly all healthy Blymphocytes 

and most B-cell lymphomas. These antibodies bind to the extracellular domain of CD22, 

induce signal transduction processes and apoptosis in lymphoma cell lines and cause lymphoma 

shrinkage in xenograft models. 

ADVANTAGES: 

● Unlike other antibodies, which serve solely to target treatments, such as radiation and chemicals, 

to cancer cells, these antibodies directly induce apoptosis in cancer cells. 

● Because the mechanism of action of these antibodies is known, they can be rationally combined 

with other agents. 

● In mouse lymphoma xenograft models, treatment with anti-CD22 antibodies shows increased 

tumor volume reduction and superior cure and survival rates compared to traditional treatments. 

● Treatment with anti-CD22 antibodies does not cause toxic side effects in mouse lymphoma 

xenograft models. 

APPLICATIONS: Anti-CD22 antibodies show great promise in the treatment of B-cell malignancies, 

such as non-Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, chronic lymphocytic 

leukemia, hairy cell leukemia and prolymphocytic leukemia. 



ANTI-CD22 MONOCLONAL ANTIBODIES USED FOR THE TREATMENT OF LYMPHOMA AND LEUKEMIA 



● Biotechnology > Genetic engineering sys > Human therapeutic 





Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






ANTICANCER SEED EXTRACT 



The ability of a tumor to initiate and sustain capillary formation (angiogenesis) is closely related to its 

growth and progression to metastasis. This is particularly important in the case of all solid cancers. Rates 

of mortality are high once the disease reaches an invasive or metastatic phase. 

Scientists at the University of California have found a plant seed extract that offers a non-toxic yet 

potent angiogenic inhibitor. Unlike current anti-angiogenic drugs, which are very expensive, the UC 

seed extract offers a relatively inexpensive alternative that shows low toxicity in tumor animal models. 

The extract significantly inhibits the growth and metastasis of tumor xenografts in these animals. 

Laboratory analysis of the extract showed that the active extract is heat-stable and resistant to many 

degradative enzymes, thus showing the feasibility of oral administration. 

These findings suggest that the UC extract could be useful in a variety of applications related to 

inhibition of angiogenesis and tumor growth. It is likely that this extract could give rise to a non-toxic, 

easily administrable therapy to help fight many types of solid cancer. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 








AP1 ASSAY FOR ESTROGEN RECEPTORS ER-ALPHA AND ER-BETA 


AP1 ASSAY FOR ESTROGEN RECEPTORS ER-ALPHA AND ER- 

BETA 

BACKGROUND: Estrogen is a steroid nuclear hormone and has an important role in uterine, breast 

and bone development. Estrogen first acts by binding to a specific nuclear receptor, the Estrogen 

Receptor (ER). The ligand-activated ER then modulates transcription of a variety of estrogen-responsive 

genes by binding to specific regulatory DNA sequences (response elements) within their promoter 

region. 

To date, multiple subtypes of ER (ER-alpha and ER-beta) and at least two different responsive elements 

(estrogen responsive element; ERE and AP1) have been discovered. In addition to this diversity, 

expression of estrogen-responsive genes has been observed to be tissue-dependent. Therefore, regulation 

of estrogen-responsive genes is now recognized to be a complex process. For instance, some ligands can 

function as agonists or antagonists depending on the physiological context. Tamoxifen, for example, 

functions as an antiestrogen in breast tissue, while it acts as an agonist in the uterus. Therefore, 

prolonged exposure to tamoxifen increases risk of endometrial cancer. On the other hand, a related 

compound, Raloxifene, while retaining its antiestrogenic activity in breast tissues, has minimal effect in 

the uterus. However, it has significant estrogen-like activity in the bone and cardiovascular tissues that 

may be useful in therapeutic treatment of osteoporosis and cardiac diseases respectively. 

The tissue-specific estrogen/antiestrogen activity of ligand-bound ER may, therefore, be due to different 

transactivation properties when bound to different types of DNA response elements as well as various 

tissue-specific co-activators or co-repressors. Since estrogens and antiestrogens have been in use for 

sometime as therapeutic agents and their use can often lead to contradictory and undesired adverse 

effects, there is a clear need for understanding and evaluating all modes and pathways of action. 

DESCRIPTION: Researchers at the University of California have discovered a distinct difference in 

the transactivation properties of the two estrogen receptors, ER-alpha and ER-beta, when bound to 

different ligands in the context of an estrogen response element and AP1 element. This discovery has 

been used to devise methods to screen for agonist/antagonist compounds that regulate differential ERalpha 

and ER-beta mediated transcription at an AP1 site. The method briefly consists of evaluating 

transcription of a reporter gene construct with an AP1 site in the presence of various combinations of the 

two ER subtypes, estrogen and/or test compounds. 


AP1 ASSAY FOR ESTROGEN RECEPTORS ER-ALPHA AND ER-BETA 

ADVANTAGES: 

● Provides rapid assay for evaluation of agonist/antagonist effects of test compounds rather than 

more time consuming biological assays. 

● Allows specific effects of ER-alpha or ER-beta mediated transcription to be distinguished in the 

context of ERE or AP1 response elements. 

APPLICATIONS: 

● Permits identification and evaluation of novel compounds that modulate activity of native 

estrogen or have independent estrogenic/antiestrogenic activity. 

● Allows for assaying drug compounds specifically designed to modulate ERE or AP1 pathway. 

● Facilitates search for other genes in estrogen target tissues regulated by ER-beta/AP1 complexes. 




● Pharmaceuticals 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






ASSAY OF GTP/GDP BOUND TO RAS AND OTHER G PROTEINS 


ASSAY OF GTP/GDP BOUND TO RAS AND OTHER G 

PROTEINS 

A University of California scientist has invented a method for measuring femtomolar amounts of GTP 

and GDP, and has used this method to determine absolute amounts of Ras-bound GTP and GDP in 

mammalian cells. Other researchers have previously associated tumors with Ras mutations that block the 

reaction converting bound GTP to GDP. Initial studies using the UC invention confirm that certain 

tumor cells have elevated levels of bound GTP (in the case of a leukemic cell line, 45 times as much as 

the non-leukemic counterpart) due to the blockage of phosphate cleavage. 

Given the importance of G-proteins in regulating cell proliferation and cell function, direct quantitative 

assays of bound GTP and GDP permit detection and detailed characterization of a variety of cancers and 

genetic disorders linked to G-protein dysfunction. Consequently, the UC quantitation method is 

potentially significant both as a research and a diagnostic tool. In clinical use, the invention might be 

adapted to a kit format for detecting tumor cells in tissue samples. It is expected that such diagnostic 

applications of the invention would provide more accurate and precise results than current antibodybased 

methods. 



PATENT STATUS: US Patent # 5,741,635 issued April 21, 1998 






Oakland, CA 94607-5200 


ASSAY OF GTP/GDP BOUND TO RAS AND OTHER G PROTEINS 



Phone: (510) 587-6000 Fax: (510) 587-6090 




ASSAYS AND ANTIBODIES FOR N-MYC PROTEINS 



BACKGROUND: N-myc is a human proto-oncogene that is amplified in about 25% of neuroblastomas 

and is an indicator of poor prognosis. N-myc is also amplified in several additional pediatric tumors of 

mostly, but not exclusively, neuroectodermal origin, including rhabdomyosarcoma, medulloblastoma, 

retinoblastoma, astrocytoma, glioblastoma, and small cell lung carcinoma. There is good evidence that 

N-myc plays a causal role in tumorigenesis, as mice overexpressing N-myc in neuroectodermal cells 

develop neuroblastoma. 

DESCRIPTION: Researchers at the University of California have developed methods to detect the 

presence of N-myc protein in lung lavage, blood, urine and sputum samples. With this method, 

fragments of the N-myc protein are used to raise antibodies that have high specificity and affinity for the 

N-myc protein. These antibodies are then used to detect the presence of N-myc protein in biological 

samples. This patented invention includes composition of matter claims directed to fragments of the 

oncogene that are useful for raising antibodies with high specificity and affinity for N-myc protein. 

ADVANTAGES: 

● The antibodies have a high affinity and specificity for the N-myc protein. 

● The antibodies allow for the early and accurate diagnosis of cancer. 

APPLICATIONS: 

● Useful for the detection, prognosis and treatment of various cancers, such as neuroblastomas, 

retinoblastomas and small cell lung cancers. 

● Distinguishes between morphologically similar tumor types, such as the various round cell 

tumors of childhood. 

● Allows early detection of certain cancers, such as small cell lung cancers. 

● Allows the identification of tumor origin for cancers that have metastasized. 

● As the level of N-myc expression is a strong prognostic factor for the clinical outcome of 

neuroblastoma, detection of the level of N-myc protein gives prognostic information that can be 

used in the design of treatment strategies. 

● The antibodies may be used for targeted therapies such as radioimmunotherapy (RIT). 











Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






ASSESSMENT OF ALLELE-SPECIFIC EXPRESSION IN CELLS AND TISSUE 


ASSESSMENT OF ALLELE-SPECIFIC EXPRESSION IN CELLS 

AND TISSUE 

BACKGROUND: Apart from monitoring the phenotypic expression of genes, there is currently no 

effective method available for accurately determining the cellular and tissue distribution of the 

expression of specific alleles. This is a significant problem in the case of patients undergoing gene 

therapy, as there is no direct way to know whether or not genes have been corrected nor is there a way to 

map the tissues where replacement cDNA or genomic DNA sequences are being expressed. Early 

diagnosis of genetic diseases is also impeded in cases where the phenotypic effects of mutant alleles are 

not detected until a comparatively late stage of an individual's development. 

DESCRIPTION: Researchers at the University of California have developed methods and compounds 

enabling facile measurement and allelic differentiation of mRNA expression in cell samples. It can be 

employed over a wide spectrum of mammalian cells, including fetal cells derived from amnioanalysis 

and samples of suspect tissue of precancerous or potentially cancerous cells. 

APPLICATIONS: The UC assay is sufficiently accurate for use in diagnosis of genetic diseases and 

monitoring of gene therapy. In gene therapy applications, it will very likely be useful for both 

measurement of transfection rates in vitro and gene correction rates in vivo. The invention might find 

immediate use for patients with genetic diseases where gene therapy methods are already available 

(notably adenosine deaminase deficiency and cystic fibrosis) as well as for early diagnosis of genetic 

defects in suspect fetal or precancerous tissue. 

ADVANTAGES: With a cell-specific assay of allele expression, it should be possible to sample tissues 

to diagnose genetic diseases and to carefully monitor the progress of gene therapy treatments, providing 

essential clinical data that is otherwise not available. In addition, it will be possible to employ this 

technique to evaluate the role that tissue-specific expression of alternatively spliced mRNA plays in the 

development of pathological states and/or organismal development. 

INQUIRIES TO: Gonzalo Barrera-Hernandez gonzalo.barrera-hernandez@ucop.edu 


ASSESSMENT OF ALLELE-SPECIFIC EXPRESSION IN CELLS AND TISSUE 


PATENT STATUS: US Patent # 5,804,383 issued September 8, 1998 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




Asthenons: Novel Gene Expression Attenuator Elements 

Asthenons: Novel Gene Expression Attenuator Elements 

BACKGROUND: Animal cell genomes contain repeating sequences that regulate gene expression. 

These sequences include poly-dispersed simple tandemly repeated microsatellites which have been 

reported to be polymorphic (with repeating units of about 2-5 nucleotides), abundant (≥2 x 10 5 copies 

per genome) and unstable. Certain microsatellites have been linked etiologically with human 

neurological disorders and gastrointestinal malignancies associated with familial colorectal cancer. In 

several cases, the disorders are thought to be caused by the unstable transmission of amplified stretches 

of tandem triplet repeats, resulting in the expression of aberrant repeats in the 5' untranslated region, 

coding region or 3' untranslated region of disease-associated mRNAs. 

DESCRIPTION: Researchers at the University of California, San Diego, have discovered a novel form 

of cis-regulatory genetic elements termed "Asthenons" (from Gk astheneia - to weaken the force). 

Asthenons are derived from DNA regions composed of specific microsatellite triplet repeats. Unlike 

silencers and repressors which completely shut off gene expression, Asthenons attenuate gene 

expression when situated in a specific sequence orientation with respect to a gene. 

ADVANTAGES: Asthenons allow for down-regulation of gene expression in a rheostat-like manner. 

They can be made cheaply and inserted easily into appropriate delivery systems which makes them ideal 

for use in gene therapy for physiological conditions in which a reduced level of gene expression is 

needed to prevent or cure an inherited or acquired disorder. They are also useful as molecular biology 

reagents for research relating to gene expression. 



BIFUNCTIONAL CHELATORS FOR RADIODIAGNOSIS/ THERAPY AND METHOD FOR THEIR EFFICIENT RADIOLABELING 


BIFUNCTIONAL CHELATORS FOR RADIODIAGNOSIS/ 

THERAPY AND METHOD FOR THEIR EFFICIENT 

RADIOLABELING 

BACKGROUND: Bifunctional chelating agents (BCAs) contain reactive groups capable of both 

attaching to monoclonal antibodies (mAbs) and chelating metallic radioisotopes. Such mAb-BCAradioisotope 

complexes are used to detect cancer cells and to target cancer cells for therapeutic purposes. 

Although the mAbs are specific to cancer cells, the mAb-BCA-radioisotope complexes can also bind to 

non-cancer cells, with particularly high accumulations in the liver. This causes damage to non-target 

cells and background problems for radiographic imaging of tumors. 

In addition, conventional labeling procedures consist of chelating the radiometal to the BCA after the 

BCA is attached to the antibody. This requires great excesses of BCA to radiometal (>1,000:1) to 

efficiently incorporate the radiometal. Conventional procedures also may result in conjugates with the 

metal bound unstably to sites on the antibody rather than to the BCA. 

DESCRIPTION: Researchers at the University of California synthesized a new BCA incorporating a 

short peptide sequence linking the BCA to the mAb, and that is cleaved by an enzyme present in the 

liver. When non-specific binding occurs, the linker is eventually cleaved and the remaining BCAradioisotope 

complex is expected to be rapidly cleared out of the body. The BCA binds tightly to 

commonly used metallic radioisotopes (e.g. 111 In, 90 Y, 67 Cu) and is stable over a long period of time. 

The researchers have also developed a prelabeling technique that provides a simple, practical method for 

chelating the radiometal and purifying the BCA-radiometal complex before it is conjugated to the 

antibody. The overall yield of pure 90 Y or 111 In immunoconjugates is approximately 50%, and the 

products are fully immunoreactive and free of unlabeled conjugates and non-specifically labeled 

antibodies. 

ADVANTAGES: The stability and cleavage properties of the new BCA significantly reduces nonspecific 

activity in radiodiagnostic and radiotherapeutic procedures using monoclonal antibodies. 

Additionally, the prelabeling technique for preparing radioimmunoconjugates should significantly 


BIFUNCTIONAL CHELATORS FOR RADIODIAGNOSIS/ THERAPY AND METHOD FOR THEIR EFFICIENT RADIOLABELING 

advance the radioimmunodiagnosis and radioimmunotherapy of cancer. 






● Biotechnology > Proteins/protein eng sys > Protein engineering sys 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






BLEOMYCIN BIOSYNTHETIC GENES 



Bleomycins (BLMs) are a family of glycopeptide-derived anti-tumor antibiotics originally isolated from 

the fermentation broth of Streptomyces verticillus. BLMs exhibit strong anti-tumor activity and are one 

member of the family of anti-cancer drugs that is widely used for the treatment of lymphoma 

(particularly Hodgkin's disease), testicular tumors, various squamous cell carcinomas, and malignant 

effusions in ovarian and breast cancer. In the late 1970s and early 1980s, there was a great emphasis on 

the development of high-yield strains and the isolation of BLM biosynthetic intermediates and 

metabolites. More recently, there has been interest in bleomycin biosynthesis as a means of facilitating 

the characterization of biosynthetic enzymes with a view towards the development of improved drugs 

derived from the manipulation of BLM biosynthetic genes. 

The chief obstacle to the realization of these research objectives has been the unavailability of the BLM 

genes themselves. However, a University of California researcher has isolated and characterized the 

BLM gene cluster. The UC BLM genes can be modified in numerous ways, offering numerous potential 

therapeutic applications such as improved yield in recombinant organisms, improved potency, alteration 

of effects on the cell cycle or cell morphology (e.g. cytoskeleton), and the production of novel BLM 

analogs with added functionality or greater anti-tumor specificity. The BLM gene cluster also provides a 

key component for further research on bleomycin biosynthesis. 

Related Publications: 

Du, L.; Shen, B. Identification and Characterization of a Type II Peptidyl Carrier Protein from the 

Bleomycin Producer Streptomyces verticillus ATCC15003. Chem. Biol. 1999, 6:507-517. 

Du, L.; Sanchez, C.; Chen, M.; Edwards, D.J.; Shen, B. The Biosynthetic Gene Cluster for the 

Antitumor Drug Bleomycin from Streptomyces verticillus ATCC15003 Supporting Functional 

Interactions between Nonribosomal Peptide Synthetases and a Polyketide Synthase Chem. Biol. 2000, 

7:623-642. (Featured in C&E News, August 14, 2000, p.32) 

Du, L.; Chen, M.; Sanchez, C.; Shen, B. An Oxidation Domain in the BlmIII Nonribosomal Peptide 

Synthetase Probably Catalyzing Thiazole Formation in the Biosynthesis of the Antitumor Drug 

Bleomycin in Streptomyces verticillus ATCC15003. FEMS Microbiol. Lett., 2000, 189:171-175. 



INQUIRIES TO: Barbara Boczar baboczar@ucdavis.edu 




● Pharmaceuticals > Anti-infective agents 





Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






BORON COMPOUNDS AND LIPOSOME DELIVERY SYSTEMS FOR BORON NEUTRON CAPTURE THERAPY 


BORON COMPOUNDS AND LIPOSOME DELIVERY SYSTEMS 

FOR BORON NEUTRON CAPTURE THERAPY 

BACKGROUND: Boron neutron capture therapy (BNCT) is an experimental therapy for treating 

certain types of cancer. In the ideal case, boron-containing compounds injected into the blood stream 

will accumulate in tumor cells. Next, the tumor is exposed to neutrons from a nuclear reactor. These 

neutrons pass harmlessly through normal, boron-free cells. The boron atoms in cancer cells capture the 

neutrons, become unstable, and fission into two fragments, destroying the cells. These fragments are 

unable to travel more than the width of one cell, thereby sparing nearby healthy cells. 

There have been many hindrances to this ideal situation. For example, it has proven difficult to find 

methods of synthesizing compounds with large amounts of boron. In addition, concentrating boron 

exclusively in tumor cells, such that normal cells are not damaged by the therapy, has proven 

challenging. 

DESCRIPTION: Researchers at the University of California have developed methods for the rapid and 

efficient production of a variety of boron-rich macromolecules suitable for BNCT. In addition, they have 

developed methods for making specially formulated liposomes that encapsulate boron-containing 

compounds. These liposomes retain high concentrations of boron compounds, are structurally stable, and 

accumulate specifically in tumor cells after intravenous injection. 

ADVANTAGES: 

● The improved liposomes incorporate high concentrations of boron compounds without breakage 

of the liposome or leakage of its contents. 

● The boron compounds and liposome delivery systems are highly selective for tumor cells, with 

low accumulation in non-cancerous cells or the bloodstream. 

APPLICATIONS: 

● The new boron compounds and liposome delivery systems will be extremely useful for BNCT. 

● This improved BNCT may be useful in the treatment of tumors in the head, neck, prostate and 



breast. 

● The new boron compounds and liposome delivery system may also be useful for boron neutron 

synovectomies (i.e. removal of the synovial membrane) in the treatment of arthritis. 

INQUIRIES TO: 




● Chemicals 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 








BORON COMPOUNDS AND LIPOSOME DELIVERY SYSTEMS 

FOR BORON NEUTRON CAPTURE THERAPY 










challenging. 






ADVANTAGES: 





APPLICATIONS: 





breast. 



INQUIRIES TO: 


US Patent # 5,856,551 issued January 5, 1999; US Patent # 6,248,916 issued June 

PATENT STATUS: 

19, 2001 


● Chemicals 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






BORON COMPOUNDS SUITABLE FOR LIPOSOMAL DELIVERY TO ...RS FOR THE PURPOSE OF BORON NEUTRON CAPTURE THERAPY 


BORON COMPOUNDS SUITABLE FOR LIPOSOMAL DELIVERY 

TO TUMORS FOR THE PURPOSE OF BORON NEUTRON 

CAPTURE THERAPY 










challenging. 






ADVANTAGES: 





APPLICATIONS: 



BORON COMPOUNDS SUITABLE FOR LIPOSOMAL DELIVERY TO ...RS FOR THE PURPOSE OF BORON NEUTRON CAPTURE THERAPY 


breast. 



INQUIRIES TO: 


US Patent # 5,648,532 issued July 15, 1997; US Patent # 5,888,473 issued March 

PATENT STATUS: 30, 1999; US Patent # 6,274,116 issued August 14, 2001; US Patent # 6,517,808 

issued February 11, 2003 


● Chemicals 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






BRAIN GLYCOGEN PHOSPHORYLASE CANCER ANTIGEN 



BACKGROUND: T cells recognize and interact with other cells via cell surface complexes consisting 

of various molecules, including peptides. They recognize and destroy other cells that have been altered, 

e.g. by infection with a virus or by transformation into cancer cells. While many cancer cells have 

devised ways to get around T cells, certain tumor cells express peptide antigens that are recognized by 

cytolytic T lymphocytes. These peptides, called "tumor rejection antigens" or "TRAs", are processed 

from proteins called "tumor rejection antigen precursors" or "TRAPs". Because tumor cells expressing 

TRAPs are vulnerable to attack by the immune system, it is important to identify proteins that act as 

TRAPs. 

DESCRIPTION: Researchers at the University of California have discovered that the brain glycogen 

phosphorylase gene encodes tumor rejection antigens and their precursors. The brain glycogen 

phosphorylase gene is normally expressed in the adult brain and retinal pigment epithelium and is 

overexpressed in certain renal, hepatoma and stomach cancers. 

ADVANTAGES: Identification of a novel TRAP provides the basis for development of novel 

therapeutics and diagnostics for certain cancers. 

APPLICATIONS: 

● Diagnosis of certain cancers based on the presence of brain glycogen phosphorylase TRAs, TRA/ 

HLA complexes, or brain glycogen phosphorylase itself. 

● Treatment of certain cancers by administering to a patient an agent that selectively enriches 

complexes of HLA and brain glycogen phosphorylase TRA 

● Production of a tumor vaccine based on brain glycogen phosphorylase TRAs. 













Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




Cancer Vaccine 



UC CASE 2000-250-1 

NUMBER: 

TITLE: Cancer Vaccine 

DEPARTMENT: Pathology 

SUMMARY: The immune system protects against disease by recognizing the agent causing the 

disease as foreign. However, in cancer, the disease causing agent is the organism's 

own cells. Because of this, the immune system fails to elicit an immune response 

against the cancer cells. Researchers at the University of California, Irvine, have 

discovered a compound and developed a process that yields antigenic cancer cells. 

These antigenic cancer cells are capable of inducing an immune response. In 

particular, Lewis Lung Cancer (3LL) cells were treated with a sub-lethal dose of the 

compound and then injected into mice. In addition to withstanding a challenge of 

untreated 3LL, the surviving mice contained antibodies against 3LL. This 

compound and process have substantial implications for the development of cancer 

vaccines. 

CONTACT: Trice Bryan - UCI 

Email: bfbryan@.uci.edu 




Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 

http://patron.ucop.edu/ncd/docs/uci.2000-250-1.html10/21/2005 2:50:23 AM

CLONED RECEPTOR FOUND IN BREAST CANCER CELLS 



University of California scientists have isolated a novel cDNA encoding a receptor of the tyrosine kinase 

type. The extracellular domain of this receptor is similar to the carbohydrate-binding protein discoidin I, 

and there are other indications that the ligand for this receptor may include carbohydrate determinants. 

The receptor is therefore termed the discoidin I domain receptor, or DDR. The DDR is specifically 

expressed in certain epithelia (breast, lung, and pancreas) and in tumors derived from these tissues. In 

these tumor cell lines, there is substantially greater expression of the DDR polypeptide than in normal 

cell lines derived from the same tissue. DDR is overexpressed in 7 out of 10 breast carcinoma cell lines. 

Thus, reagents derived from either the DDR DNA sequence or the DDR amino acid sequence have 

potential utility as diagnostic markers and therapeutic anti-cancer agents. 

Possible uses for DDR-derived reagents include the construction of DNA or antibody probes for 

diagnostic screening of tissue samples. Based on DDR sequence data, there is reason to suspect that 

DDR fragments can be found in the bloodstream. Consequently, tissue sampling need not be confined to 

suspected cancer sites, but might also be applied to blood serum samples in a general screening 

procedure. Therapeutic applications of DDR center on using the receptor binding site as a target for 

controlling cell proliferation, or on sequestering DDR's ligand to block the receptor-ligand interaction. 

DDR is an alternative to other receptor systems that are overexpressed in cancer cells, such as erbB-2. 

As erbB-2 is overexpressed in less than half of the tumor cells, and acts on a completely different ligand 

than DDR, it is expected that DDR has a different tissue distribution in the body (a potentially 

significant issue for in vivo applications) and may have complementary and/or superior binding 

properties as a tumor marker. 













Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




CNL878, A Cytotoxic and Antifungal Terpene from a Marine Fungus 

CNL878, A Cytotoxic and Antifungal Terpene from a Marine Fungus 

BACKGROUND: During routine screening of organisms from deep marine sediments, a novel 

compound was discovered which was found to possess potent anti-fungal activity and cytotoxicity to 

cultured cancer cells. 

DESCRIPTION: A novel terpenoid compound was discovered during the course of biodiversity 

screening of deep benthic sediments. Because these organisms have not been in contact with terrestrial 

microorganisms for millions of years, the potential exists for them to produce antifungal and 

antibacterial agents with low susceptibility to the resistance pathways of land-based pathogens. 

ADVANTAGES: Novel anti-fungal compound, potential for low susceptibility to resistance 

development 



COMBINED USES OF IMPDH INHIBITORS WITH TOLL-LIKE RECEPTOR AGONISTS 


COMBINED USES OF IMPDH INHIBITORS WITH TOLL-LIKE 

RECEPTOR AGONISTS 

BACKGROUND: Innate immunity is the first host defense response against pathogens such as bacteria 

and viruses. Cells of the innate immune system express a set of conserved receptors called Toll-like 

receptors (TLRs 1-10) that recognize unique molecular structures like cell wall components, bacterial 

DNA and viral RNA associated with invading pathogens. Members of the TLR family are distinguished 

by the different microbial ligands they bind to, which then initiate a signaling cascade that results in the 

production of cytokines in lymphocytes and macrophages. 

Among the cytokines produced, interferons (IFNs) mediate host defense against virus infections and 

cancer, and also mitigate the course of several inflammatory diseases. Guanosine nucleoside analogs, 

which are immunostimulatory ligands for TLR7, are efficient in inducing IFNs. However, since in many 

instances viruses produce antagonists that either block production of or inhibit action of interferon, 

treatments based on use of agonists of TLR7 signaling alone are insufficient in inducing an effective 

immune response. Therefore, compounds that enhance signaling mediated by TLR agonists would be 

attractive candidates in combination therapy. 

DESCRIPTION: Researchers at the University of California have discovered that targeting enzymes 

involved in the production of Guanosine Monophosphate (GMP) has synergistic effects on the 

therapeutic action of TLR agonists. UC researchers have developed several inhibitors of Inosine 

Monophosphate Dehydrogenase (IMPDH), a key enzyme in the GMP production pathway. These 

IMPDH inhibitors when used in combination with TLR agonists enhance their cytokine-inducing effects 

with no significant toxicity. 

ADVANTAGES: 

● Increased efficacy of treatment due to synergistic effects of the drugs in combination therapy. 

● Use of lower dosage of individual inhibitors reduces non-specific side effects. 

● Allows for different routes of drug delivery through inhalation, orally or by injection. 

APPLICATIONS: 


COMBINED USES OF IMPDH INHIBITORS WITH TOLL-LIKE RECEPTOR AGONISTS 

● Therapy directed to increasing host resistance to infectious pathogens. 

● Chemotherapy of a variety of cancers. 

● Treatment of diseases involving inflammation such as, multiple sclerosis and pulmonary fibrosis. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






CONSTRAINTS-BASED ANALYSIS OF GENE EXPRESSION DATA 


CONSTRAINTS-BASED ANALYSIS OF GENE EXPRESSION 

DATA 

BACKGROUND: Cancer is a heterogeneous disease in most respects, including its cellularity, different 

genetic alterations and diverse clinical behaviors. Many analytical methods have been used to study 

human tumors and to classify samples into homogeneous groups that can predict clinical behavior. DNA 

microarrays, for example, have made significant contributions to this field by detecting similarities and 

differences among tumors through the simultaneous analysis of the expression of thousands of genes. 

Current methods for analyzing the vast amount of microarray data look for trends and correlations in the 

expression of large numbers of genes in different cancers or tumors. While this approach is valuable, it 

is "blind" in that it does not focus on genes already implicated in cancer pathology and prognosis. 

DESCRIPTION: Researchers at the University of California have developed a new method for 

analyzing microarray gene expression data. This method is constrained in that it focuses on genes and 

related pathways that are likely to be important in disease progression. As such, this method is useful in 

providing likely candidates that will serve as targets for therapeutics, prognostics and diagnostics. 

ADVANTAGES: The new method focuses on genes and related pathways that are likely to be 

important in disease progression. 

APPLICATIONS: The new method allows for the analysis of large quantities of publicly available 

expression data to identify potential targets for therapeutics and diagnostic and prognostic expression 

profiles. 





CONSTRAINTS-BASED ANALYSIS OF GENE EXPRESSION DATA 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




COUMARIN COMPOUNDS AS MICROTUBULE STABILIZING AGENTS AND THERAPEUTIC USES THEREOF 


COUMARIN COMPOUNDS AS MICROTUBULE STABILIZING 

AGENTS AND THERAPEUTIC USES THEREOF 

BACKGROUND: Microtubules are dynamic protein tube-shaped polymers that are essential for normal 

cellular activities including cell division, various kinds of cell motility, and intracellular signal 

transduction. Microtubules are in dynamic equilibrium with their soluble protein subunits, alpha and 

beta tubulin heterodimers. The dynamics of microtubules are critical for their functions. Various 

diseases and disorders are associated with microtubule assembly, disassembly, and/or function, 

including diseases and disorders associated with cell proliferation such as cancer, neurodegenerative 

diseases such as Alzheimer's, atherosclerosis, and restenosis. Several powerful agents that affect 

microtubules are known, some of which destabilize or disassemble microtubules, and others such as 

taxol, which promote the formation of microtubules. Most of the agents affect the normal dynamic 

behaviors of the microtubules that are required for cell division and proliferation. Most of the drugs that 

affect microtubule polymerization and dynamics, such as paclitaxel, are highly toxic. Therefore, a need 

exists for microtubule stabilizing agents that are less toxic than taxol for treating, preventing or 

inhibiting diseases and disorders associated with microtubule formation. 

DESCRIPTION: Researchers at the University of California have discovered that naturally occurring 

organic compounds found in a wide variety of plants, called coumarin compounds, inhibit, prevent and/ 

or modulate microtubule disassembly. They further discovered that these compounds are useful in the 

treatment of diseases associated with microtubule formation or function. Methods for stabilizing and 

modulating microtubules with coumarin compounds, as well as pharmaceutical preparations containing 

coumarins and methods for treating diseases associated with microtubule formation or function are 

available. 

ADVANTAGES: 

Coumarin compounds: 

● have low toxicity and a simple chemical structure. 

● represent a new class of compounds that stabilize microtubule dynamics 

● may prove useful in formulating combination therapy approaches. 


COUMARIN COMPOUNDS AS MICROTUBULE STABILIZING AGENTS AND THERAPEUTIC USES THEREOF 

APPLICATIONS: Therapeutics made from coumarins may be useful in the treatment, prevention, or 

inhibition of diseases and disorders associated with microtubule formation or microtubule function, such 

as cancer, Alzheimer's disease, atherosclerosis, restenosis, or gout. 



PATENT STATUS: US Patent # 6,660,767 issued December 9, 2003 


● Pharmaceuticals > Other pharmaceuticals 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






CYTOTOXIC ANTIBODY FUSION PROTEIN 



University of California researchers have developed an antibody fusion protein that functions as a novel 

cytotoxic drug, though both, the antibody and the non-antibody partner by themselves are not cytotoxic. 

This fusion protein serves to decrease or eliminate cell proliferation by stopping cell division and 

causing cell death (apoptosis). In addition, it could be used as a universal delivery system to selectively 

deliver proteins, nucleic acids, and other chemicals into various kinds of cancer cells. Initial studies have 

demonstrated promising results using the antibody fusion protein specially against cancer cells of 

hematopoietic origin such as lymphomas, leukemias, and myelomas. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 








DETECTION OF ATM MUTATIONS AND POLYMORPHISMS WITH MEGA-SSCP 


DETECTION OF ATM MUTATIONS AND POLYMORPHISMS 

WITH MEGA-SSCP 

BACKGROUND: Ataxia telangiectasia is an autosomal recessive disorder characterized by progressive 

cerebellar degeneration, immunodeficiency, growth retardation, premature aging, chromosomal 

instability, acute sensitivity to ionizing radiation, and a predisposition to cancer, particularly breast 

cancer. It is caused by mutations in the ATM gene which lead to defects in the DNA repair process and 

cell cycle control. Given the severity of the disease, there is a need for efficient and accurate diagnosis. 

However, current methods of mutation screening are cumbersome when applied to large genes, such as 

the ATM gene. 

DESCRIPTION: Scientists at the University of California have used a new technique, mega-SSCP 

(single-strand conformation polymorphism), to identify previously unknown mutations and 

polymorphisms in the ATM gene. In the method, nucleic acid segments are amplified, and the products 

are analyzed by gel electrophoresis. In an improvement over the usual SSCP procedure, certain 

amplicons can be run concurrently on a smaller number of gels. 

APPLICATIONS: 

● The mutations and variants identified are essential for ataxia telangiectasia screening. 

● This information is needed to design DNA chips for automated screening, and to interpret the 

data obtained, as it eliminates false positives and differentiates disease-causing mutations from 

normal variations. 

● Mega-SSCP detects mutations and polymorphisms in any gene, for example, APC (colon 

cancer), BRCA1 and 2 (breast cancer), CFTR (cystic fibrosis), HBB (?-thalassemia), and APOE 

(atherosclerosis). 

● Mega-SSCP may be used for genetic counseling, prenatal testing, and carrier detection. 

ADVANTAGES: 

● Mega-SSCP is a novel, efficient, and accurate method for screening large genes for mutations 


DETECTION OF ATM MUTATIONS AND POLYMORPHISMS WITH MEGA-SSCP 

and polymorphisms. 

● The method can be carried out with typical laboratory equipment, without the need to purchase 

additional expensive equipment. 

● It detects mutations missed by other screening techniques. 



US Patent # 6,458,536 issued October 1, 2002; US Patent # 6,951,724 issued 


October 4, 2005 


● Biotechnology > Genetic engineering sys > DNA/RNA probes 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






DETECTION/DEPOLYMERIZATION OF POLYSIALIC ACID CHAINS IN VARIOUS DEVELOPMENTAL AND DISEASE STATES 


DETECTION/DEPOLYMERIZATION OF POLYSIALIC ACID 

CHAINS IN VARIOUS DEVELOPMENTAL AND DISEASE STATES 

A research team led by a University of California scientist has identified and characterized a unique 

endo-sialidase that is highly specific for polysialic acid polymer chains (polySia chains) found in a broad 

array of glycoproteins. The UC sialidase in its purified form can be used for facile and unambiguous 

identification and characterization of polySia chains on cells as divergent as neuropathogenic bacteria, 

neuronal cells, human brain tumors, fish eggs, and cells involved in fertilization and development in sea 

urchins. The research team also demonstrated that the UC sialidase could be used as a reagent to alter 

the structure of gangliosides and other cell surface glycoconjugates, and as a diagnostic probe in 

microinjection experiments. 

The UC sialidase has potentially significant diagnostic, prognostic, and therapeutic applications, as 

exemplified by the researchers using the UC sialidase to depolymerize the polysialic capsule of a 

neurovirulent form of E. coli K1. Another important example is their use of the UC sialidase to 

characterize the role of neural cell adhesion molecules (N-CAMs) in neuronal development and to 

depolymerize them. Since polysialated N-CAMs are oncodevelopmental antigens whose expression on 

cell surfaces has been correlated with metastasis in some human cancers, polysialylated N-CAMs 

represent an attractive target for diagnostic and therapeutic agents derived from the UC sialidase. 




● Biotechnology > Enzyme technology systems > Diagnostic enzymes 

● Biotechnology > Enzyme technology systems > Other enzyme technology 




DETECTION/DEPOLYMERIZATION OF POLYSIALIC ACID CHAINS IN VARIOUS DEVELOPMENTAL AND DISEASE STATES 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




DEVELOPMENT OF NEW SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMs) 


DEVELOPMENT OF NEW SELECTIVE ESTROGEN RECEPTOR 

MODULATORS (SERMs) 

BACKGROUND: Hormone replacement therapy, involving either estrogen alone or a combination of 

estrogen and progestin, is considered the first-line approach for prevention and treatment of multiple 

conditions affecting women's health. However, recent studies conducted by NIH and MRC have shown 

that long-term use of this type of therapy is not without significant risks. 

In an effort to broaden the treatment options available to postmenopausal women, research efforts have 

been directed at the development of compounds that maintain the vasomotor, skeletal and cardiovascular 

benefits of estrogen replacement therapy but have little to no significant adverse effect on reproductive 

organs and the clotting processes. The search for this "ideal" compound has led to the development of a 

class of drugs termed "selective estrogen receptor modulators" (SERMs). These agents may provide the 

beneficial effects of estrogen replacement therapy without some of its serious side effects. An example 

of these traditional SERMs is Raloxifene, which has the ability to bind to and activate the estrogen 

receptor while exhibiting tissue-specific effects distinct from 17beta-estradiol. 

DESCRIPTION: Further research has led to a new class of SERMs that potentiate rapid estrogen 

responses in hypothalamic neurons but do not bind to or activate the classical nuclear estrogen receptors 

ER-alpha or ER-beta. Researchers at the University of California have synthesized these new SERMs 

and, with their colleagues at Oregon Health and Science University, have characterized one of them. 

Interestingly, this compound did not have any peripheral estrogenic activity (neither agonist nor 

antagonist), and did not bind to nuclear estrogen receptors. Further work revealed that the compound 

activates the rapid, non-genomic, hypothalamic responses of estrogen, and that these responses are likely 

to be mediated by a novel G -protein-coupled membrane receptor. The rapid hypothalamic estrogen 

responses are thought to be involved in thermal regulation and mood state, which are directly related to 

the undesirable effects of menopause, such as hot flashes, night sweats and mood swings. 

ADVANTAGES: Current hormone replacement therapy involving either estrogen alone or a 

combination of estrogen and progestin is fraught with serious side effects including increased 

susceptibility to breast cancer, endometrial cancer, and stroke. The novel SERM studied here should be 

devoid of negative side effects arising from peripheral estrogen receptor activation since it does not bind 

to the classical nuclear estrogen receptors. 


DEVELOPMENT OF NEW SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMs) 

APPLICATIONS: Safe treatment of undesirable menopausal symptoms, such as hot flashes, night 

sweats and mood swings, without the side effects associated with current hormone replacement therapy. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






DIAGNOSIS AND TREATMENT OF CRYPTOSPORIDIOSIS, INCLUDING HUMAN VACCINE 


DIAGNOSIS AND TREATMENT OF CRYPTOSPORIDIOSIS, 

INCLUDING HUMAN VACCINE 

BACKGROUND: Cryptosporidium parvum is a water- and food-borne protozoan parasite responsible 

for gastrointestinal disease and, in the case of immunocompromised individuals (notably AIDS patients 

and cancer patients undergoing chemotherapy), a devastating persistent diarrhea that is potentially fatal. 

Cryptosporidium infections have become an increasingly serious public health problem in recent years, 

as was highlighted by an April 1993 incident where the water supply of Milwaukee was contaminated, 

resulting in 400,000 cases of cryptosporidiosis and over 100 deaths among AIDS and cancer patients. 

Unfortunately, little is known of the basic biology of this disease organism, and no effective therapy 

currently exists. 

DESCRIPTION: University of California researchers have developed a family of inventions related to 

the detection, prophylaxis, and therapy of Cryptosporidium infections. The original basis for this work 

was the identification of candidate protective antigens, which in turn facilitated the discovery and 

cloning of a Crpytosporidium-specific molecule (GP900) that is essential to the organism's infectivity. 

The purified molecule competitively inhibits functional forms of the molecule found in the organism, 

preventing invasion. In addition, the researchers developed a suite of polyclonal antibodies suitable for 

the detection of Cryptosporidium parvum. 

APPLICATIONS: The purified UC Cryptosporidium molecule, or its derivatives, have possible 

application to the creation of vaccines, antibodies, pharmaceutical targets, diagnostic DNA or RNA 

sequences, and other related compounds for clinical use in diagnosis and treatment of patients with 

cryptosporidiosis. The purified UC Cryptosporidium molecule (or its derivatives), in light of its ability 

to competitively inhibit the native form of the molecule, is itself a strong candidate for use as a novel 

therapeutic compound. 

ADVANTAGES: Prior methods for boosting immunogenic response against Cryptosporidium, 

involving the use of hyperimmune bovine colostrum (HBC) collected from animal sources, has proven 

to be inconsistent in immunogenicity and potency. The UC inventions may allow for more controllable 

immunogenicity and potency, thus providing more reliable protection to both ordinary cases of 

cryptosporidiosis and life-threatening cases involving immunocompromised patients than is possible 

with HBC. 


DIAGNOSIS AND TREATMENT OF CRYPTOSPORIDIOSIS, INCLUDING HUMAN VACCINE 

INQUIRIES TO: John Shih john.shih@ucop.edu 


US Patent # 6,254,869 issued July 3, 2001; US Patent # 6,759,044 issued July 6, 


2004 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






DIAGNOSTIC TEST FOR CANCER SUSCEPTIBILITY 



BACKGROUND: 

Researchers at the University of California have discovered a novel tumor suppressor gene, CDK4I, that 

inhibits the activity of the oncogene CDK4. The CDK4I gene is mutated in the majority of malignant 

melanomas, gliomas, non-small cell lung cancers, and leukemias. CDK4I is located immediately 

adjacent to the methylthioadenosine phosphorylase (MTAse) gene, on chromosome 9p21. Deficiencies 

in CDK4I and MTAse have previously been shown to be directly related to the onset of certain cancers. 

One of the U.S. patent applications that is available for licensing was involved in two interference 

proceedings with two parties before the U.S.P.T.O. The Regents of the University of California won the 

proceedings on the claims involved in both interferences. The Regents believes that these claims are not 

dominated by the U.S. patent claims of the other party to the interferences. However, any party must 

obtain its own opinion of counsel regarding the extent of issued claim coverage. 

DESCRIPTION: The technology comprises diagnostic methods to detect mutations of the CDK4I gene 

as well as detecting deficiencies in the expression products of the gene. In addition, the technology also 

provides for the detection of mutations and altered gene product of the CDK4I-linked gene MTAse. 

APPLICATIONS: The technique can be used to diagnose individuals who carry mutations in CDK4I 

or MTAse genes, and are therefore more susceptible to developing malignant melanoma and certain 

other familial and environmental cancers. Successful early detection of a pre-cancerous condition can 

enable effective measures to be taken to prevent subsequent cancer progression. 

The methods can also be applied to the screening and identification of anti-cancer molecules that will 

target aberrant CDK4I and MTAse gene products. 

In addition, these discoveries will be applied to research in the field of cell cycle regulation. 

ADVANTAGES: While there have been significant advances in cancer therapies of late, early detection 

and subsequent treatment greatly increases the survival rate. The prevalence of mutations in the CDK4I 



gene in malignant cells makes it an important diagnostic target for early detection of cancer 

susceptibility. The procedures allow for the rapid analysis of CDK4I and MTAse gene and gene 

products for detection of mutations that may lead to uncontrolled cell proliferation and subsequent 

cancer progression. 



US Patent # 6,689,561 issued February 10, 2004; US Patent # 6,689,864 issued 


February 10, 2004 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






DIAGNOSTIC TEST FOR MUTATIONS IN THE AT GENE 



BACKGROUND: Ataxia telangiectasia (AT) is a genetic recessive disorder involving a large range of 

symptoms including telangiectasia (dilation of blood vessels) on the eyes, face, and shoulders, ataxia 

(loss of balance), cerebellar degeneration, radiosensitivity, cancer predisposition, immunodeficiency and 

premature aging. At a cellular level, AT cells display cell cycle checkpoint defects, chromosomal 

instability and sensitivity to ionizing radiation. The protein mutated in AT is ATM (Ataxia 

Telangiectasia -Mutated), a large protein of 370 kDa that is involved in DNA repair. 

DESCRIPTION: Researchers at the University of California have identified a large number of 

mutations in the ATM gene. They have further developed PCR-based diagnostic methods to identify the 

presence of an ATM gene mutation in a patient. 

ADVANTAGES: 

● Provides an important diagnostic tool for AT. 

● Provides the basis for study of the role of heterozygosity of AT gene mutation in diseases such as 

breast cancer. 

APPLICATIONS: 

● Diagnosis of AT through identification of mutations in the ATM gene. 

● Development of a mouse model for AT using ATM gene mutations. 

● Treatment of AT using gene therapy. 

SEE ALSO: EXPRESSION AND PURIFICATION OF ATM PROTEIN USING VACCINIA VIRUS 

and METHOD FOR ANALYZING ATAXIA-TELANGIECTASIA PROTEIN 













Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




Dianestatin: A New Tumor-Specific Cytotoxin Conjugate 

Dianestatin: A New Tumor-Specific Cytotoxin Conjugate 

BACKGROUND: This is a continuation of the fundamental discovery of Ruoslahti, et at., who found 

that discrete small peptides (homing peptides), when injected into mice with cancerous tumors, had the 

specific property of binding to receptor sites within the vasculature of the tumors in question. In a recent 

publication, Ruoslahti and co-workers have shown that conjugation of the anticancer drug doxorubicin 

with these homing peptides provided for an efficient delivery system of the drug to the tumor. The 

benefit of this strategy of tumor targeting was that cures were obtained at much lower overall 

concentrations, concentrations in which negligible results would have been observed with the drug 

alone. The non-selective cytotoxin used here as starting material is a molecule discovered by Rinehart 

and co-workers at the University of Illinois. This is a patented molecule which the NCI has taken to 

phase 11 clinical trials only to discover that didemnin B did not illustrated sufficient clinical efficacy. In 

retrospect, although didemnin B is one of the most poterit cytotoxins acting by the inhibition of protein 

synthesis, the molecule shows almost zero selectivity in the NCI's 60 cancer cell line bioassay. Thus, 

although protected by University of Illinois patents, this molecule has been concluded as of no future 

interest for the treatment of cancer. 

DESCRIPTION: The experimental hypothesis tested here is the concept that an effective cancer 

treatment can be derived by conjugating potent, non-selective cytotoxins to the homing peptide. The 

second hypothesis tested by synthesis of Dianestatin is that conjugation of the homing peptide using an 

ester, rather than an amide bond, will create an in vivo-active reagent which can readily generate the 

parent cytotoxin at the active site by an expected lipase- mediated ester bond hydrolysis. It is thus 

conceived that Dianestatin will be rapidly directed to the tumor vasculature, accumulate there, and then 

undergo enzymatic hydrolysis to liberate the parent cytotoxin. We hope, but have no data to show, that 

the rate of liberation of the parent cytotoxin, didemnin B (3), will be consistent with diffusion of the 

drug through the tumor tissue. 

ADVANTAGES: The bioactivity of Dianestatin (1) itself was evaluated in a continuous exposure, 

clonogenic bioassay employing an HCT-1 16 human colon tumor cell line. In this assay, didemnin B 

shows IC50 = 0.4 ng/mi while Dianestatin shows IC50 = 16.5 ng/ml. Based upon the recorded potency 

and qualitatively different dose response curve, it is concluded that the molecule does not undergo 

hydrolysis to didemnin B during the time course of these in vitro experiments. 

STAGE OF DEVELOPMENT: Pre-Clinical 



DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HER-2/NEU OVEREXPRESSION 


DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH 

HER-2/NEU OVEREXPRESSION 

BACKGROUND: The human HER-2/neu proto-oncogene encodes a transmembrane receptor tyrosine 

kinase with extensive sequence homology to the epidermal growth factor receptor. Amplification and/or 

overexpression of HER-2/neu has been found in one-third of human breast and one-fifth of ovarian 

cancers. In addition, the HER-2/neu alteration is associated with a poor clinical outcome in that women 

whose tumors contain it experience earlier disease relapse and shorter overall survival. Considerable 

circumstantial evidence supports the possibility that overexpression of HER-2/neu plays a direct causal 

role in the pathogenesis of the malignancies in which it occurs. 

DESCRIPTION: Researchers at the University of California have identified a new set of proteins, 

called Her-2/neu overexpression modulated proteins (HOMPS), based on differential expression in 

breast cancer cell lines with or without overexpressed HER-2/neu. The HOMPS include proteins having 

both new and known amino acid sequences. Upregulation of one of the novel proteins, called H41, was 

confirmed in a human breast cancer specimen in association with HER-2/neu overexpression and in 

HER-2/neu overexpressing ovarian cancer cells. Polynucleotides that encode H41, polynucleotide 

probes for the H41 gene, PCR primers for amplifying the H41 gene, and cell lines expressing H41 are 

available. 

ADVANTAGES: The HOMPS genes represent novel targets for the development of diagnostics and 

therapeutics for breast and ovarian cancer. 

APPLICATIONS: 

● Research tools to analyze the role of HOMPS in the pathogenesis of breast and ovarian cancers. 

● May be useful in the development of diagnostics and therapeutics for breast and ovarian cancers. 




DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HER-2/NEU OVEREXPRESSION 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




DIHYDROXYVITAMIN D3 PHARMACEUTICAL SYSTEM 



Vitamin D 3 is capable of generating a host of biological responses in higher animals via its participation 

in the vitamin D endocrine system, where it is metabolized to yield daughter metabolites that function as 

steroid hormones. The principal metabolite is 1-alpha, 25 dihydroxyvitamin D 3 [1,25(OH) 2 D 3 , or 

hormone D], which is generally thought to be the hormonally-active form of vitamin D. Hormone D 

regulates the maintenance of calcium homeostasis, promoting bone calcium mobilization (BCM) and 

intestinal calcium absorption (ICA, also known as transcaltachia). In addition, hormone D is a potent 

immunosuppressant, stimulator of selective cell differentiation, and stimulator of apoptosis. 

Analogs of hormone D that mimic these metabolites have been employed in numerous pharmacological 

applications, as such compounds have the potential to treat a large variety of disorders, notably 

osteoporosis, renal osteodystrophy, Alzheimer's disease, hypoparathyroidism, and psoriasis. There are 

also potential benefits in using these compounds for immunosuppression during organ transplantation or 

for treating cancers such as leukemia, breast cancer, colon cancer, and prostate cancer. Unfortunately, 

commonly-used hormone D analogs also display undesirable side effects due to the numerous 

physiological responses that these compounds produce. 

Specifically, the metabolism of vitamin D 3 in the liver and kidney gives rise to the hormone D 

metabolite, which is then transported via the circulatory system to all parts of the body. Vitamin D 3 

metabolite circulation requires the binding of the metabolite to the vitamin D binding protein (DBP). 

Once the metabolite/DBP complex arrives at a target cell and delivers hormone D, this molecule then 

binds to either a well-characterized nuclear receptor (VDR nuc ) or to a newly discovered cell membrane 

receptor. Thus, hormone D can trigger two distinct signal transduction pathways to generate biological 

responses. 

In one pathway, the cell membrane receptor activity is either directly coupled to the opening of voltagegated 

calcium channels, effecting rapid changes in calcium distribution, or to the activation of a MAP 

kinase within the cell. The activated MAP kinase, in conjunction with hormone D, acts on the VDR nuc 

receptor to slowly change the rate of genomic mRNA synthesis. VDR nuc regulates gene transcription in 

over 30 different target organs. 



To prevent undesirable side effects, agonists and antagonists specific to each signal transduction 

pathway would be highly desirable as candidate drugs for achieving more specific pharmacological 

responses. For example, a compound that stimulated the slow genomic response without simultaneously 

inducing hypercalcemia via the rapid non-genomic response may be valuable for suppressing cell 

proliferation (e.g. for treating cancer). 

University of California researchers have developed a family of inventions that offers a comprehensive 

pharmaceutical system for the development of such pathway-specific drugs. The UC inventions include 

multiple classes of DBP-compatible hormone D analogs, including analogs that are agonists of the rapid 

non-genomic pathway, analogs that are antagonists of the rapid non-genomic pathway, and analogs that 

are agonists of both pathways. Some of these classes of analogs are characterized by syntheses that are 

far simpler than is the case for many of the non-specific and/or DBP-incompatible vitamin D 3 analogs 

that are currently available. Preliminary analyses have also shown that they are as potent as the naturallyoccurring 

metabolites. 

In addition, these UC researchers have also described the three-dimensional structure of the ligandbinding 

domain of the hormone D nuclear receptor. With this information, it should be possible to 

design, generate, and select nuclear receptor-specific agonists and antagonists for controlling the slow 

genomic pathway. Thus, there is a potential for further extending the range of available hormone D 

analogs with important therapeutic applications. 

The ability to produce potent, DBP-compatible hormone D analogs with receptor-specific effects 

represents a significant improvement over existing vitamin D 3 -based pharmaceuticals. Ultimately, these 

inventions will probably give rise to several new compounds for use in therapeutic formulations with 

application in a wide variety of clinical circumstances. 



PATENT STATUS: US Patent # 6,516,294 issued February 4, 2003 


● Biotechnology > Enzyme technology systems 

● Pharmaceuticals > Hormones/synthetic subs 

● Pharmaceuticals > Skin/mucous membrane drugs 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 







Vitamin D 3 is capable of generating a host of biological responses in higher animals via its participation 

in the vitamin D endocrine system, where it is metabolized to yield daughter metabolites that function as 

steroid hormones. The principal metabolite is 1-alpha, 25 dihydroxyvitamin D 3 [1,25(OH) 2 D 3 , or 

hormone D], which is generally thought to be the hormonally-active form of vitamin D. Hormone D 

regulates the maintenance of calcium homeostasis, promoting bone calcium mobilization (BCM) and 

intestinal calcium absorption (ICA, also known as transcaltachia). In addition, hormone D is a potent 

immunosuppressant, stimulator of selective cell differentiation, and stimulator of apoptosis. 

Analogs of hormone D that mimic these metabolites have been employed in numerous pharmacological 

applications, as such compounds have the potential to treat a large variety of disorders, notably 

osteoporosis, renal osteodystrophy, Alzheimer's disease, hypoparathyroidism, and psoriasis. There are 

also potential benefits in using these compounds for immunosuppression during organ transplantation or 

for treating cancers such as leukemia, breast cancer, colon cancer, and prostate cancer. Unfortunately, 

commonly-used hormone D analogs also display undesirable side effects due to the numerous 

physiological responses that these compounds produce. 

Specifically, the metabolism of vitamin D 3 in the liver and kidney gives rise to the hormone D 

metabolite, which is then transported via the circulatory system to all parts of the body. Vitamin D 3 

metabolite circulation requires the binding of the metabolite to the vitamin D binding protein (DBP). 

Once the metabolite/DBP complex arrives at a target cell and delivers hormone D, this molecule then 

binds to either a well-characterized nuclear receptor (VDR nuc ) or to a newly discovered cell membrane 

receptor. Thus, hormone D can trigger two distinct signal transduction pathways to generate biological 

responses. 

In one pathway, the cell membrane receptor activity is either directly coupled to the opening of voltagegated 

calcium channels, effecting rapid changes in calcium distribution, or to the activation of a MAP 

kinase within the cell. The activated MAP kinase, in conjunction with hormone D, acts on the VDR nuc 

receptor to slowly change the rate of genomic mRNA synthesis. VDR nuc regulates gene transcription in 

over 30 different target organs. 



To prevent undesirable side effects, agonists and antagonists specific to each signal transduction 

pathway would be highly desirable as candidate drugs for achieving more specific pharmacological 

responses. For example, a compound that stimulated the slow genomic response without simultaneously 

inducing hypercalcemia via the rapid non-genomic response may be valuable for suppressing cell 

proliferation (e.g. for treating cancer). 

University of California researchers have developed a family of inventions that offers a comprehensive 

pharmaceutical system for the development of such pathway-specific drugs. The UC inventions include 

multiple classes of DBP-compatible hormone D analogs, including analogs that are agonists of the rapid 

non-genomic pathway, analogs that are antagonists of the rapid non-genomic pathway, and analogs that 

are agonists of both pathways. Some of these classes of analogs are characterized by syntheses that are 

far simpler than is the case for many of the non-specific and/or DBP-incompatible vitamin D 3 analogs 

that are currently available. Preliminary analyses have also shown that they are as potent as the naturallyoccurring 

metabolites. 

In addition, these UC researchers have also described the three-dimensional structure of the ligandbinding 

domain of the hormone D nuclear receptor. With this information, it should be possible to 

design, generate, and select nuclear receptor-specific agonists and antagonists for controlling the slow 

genomic pathway. Thus, there is a potential for further extending the range of available hormone D 

analogs with important therapeutic applications. 

The ability to produce potent, DBP-compatible hormone D analogs with receptor-specific effects 

represents a significant improvement over existing vitamin D 3 -based pharmaceuticals. Ultimately, these 

inventions will probably give rise to several new compounds for use in therapeutic formulations with 

application in a wide variety of clinical circumstances. 



US Patent # 6,103,709 issued August 15, 2000; US Patent # 6,121,469 issued 

PATENT STATUS: September 19, 2000; US Patent # 6,307,075 issued October 23, 2001; US Patent 

# 6,329,357 issued December 11, 2001 


● Pharmaceuticals > Vitamins 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




DIRECT ASSAY FOR ANDROGEN RECEPTOR MODULATORS 



BACKGROUND: Prostate cancer is an important cause of morbidity and mortality today, and the 

incidence will increase as our population ages. The androgen receptor (AR) is the primary therapeutic 

target for this disease. Upon binding androgen, the receptor moves into the nucleus where it regulates 

gene expression. Inhibition of AR function is the mainstay of prostate cancer therapy, although this 

approach fails because the ARs eventually adapt to the AR inhibitors. In addition, mutations in AR lead 

to a variety of diseases, including androgen insensitivity syndrome (AIS), prostate cancer, and the 

progressive neurodegenerative disease spinobulbar muscular atrophy (SBMA). Thus, there is an unmet 

need for the development of therapeutics that modulate the function of the AR. 

DESCRIPTION: UC researchers have developed a screening method, based on Fluorescence 

Resonance Energy Transfer (FRET), for the identification of compounds that modulate the function of 

AR. This method allows for the direct reading of changes in the conformation of the AR that occur upon 

activation. 

ADVANTAGES: Current functional assays to identify modulators of the activity of AR are based on 

reporter genes whose activity is easily assayed, but that interpose many biological steps between binding 

of androgen to the AR and expression of the reporter gene. Thus, when identifying modulators of AR 

function, it is difficult to know for certain which of these many steps might be affected. 

This novel screening method offers the advantage of directly assaying the modulation of AR 

conformation, avoiding limitations associated with secondary readouts such as transcription activation. 

Thus, it will enable new approaches to identify inhibitors of AR function based exclusively on a 

biophysical phenomenon: conformation change. These new approaches could potentially overcome the 

adaptation of ARs to the therapeutic AR inhibitors currently in use. 

APPLICATIONS: This invention could be used for the identification of drug therapeutics for the 

treatment of: 

● prostate cancer, 

● androgen insensitivity syndrome (AIS), 

● spinobulbar muscular atrophy (SBMA), and 



● other diseases involving the AR. 

F:\LifeSci3\Ximena\NCDs\2004\NCD^2004-136.Diamond.GBH.2004-09-07.doc 09/10/04 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






DNA BINDING COMPOUNDS FOR GENETIC REGULATION AND MEDICAL DIAGNOSIS AND THERAPY 


DNA BINDING COMPOUNDS FOR GENETIC REGULATION AND 

MEDICAL DIAGNOSIS AND THERAPY 

Compounds that bind to DNA could be used to target drugs to DNA and to regulate expression of genes. 

Indeed, many compounds have been discovered (e.g. Distamycin) which bind to the minor groove of 

DNA, but the bond is too weak for reliable medical application. 

Scientists at the University of California have discovered a class of novel compounds that have a high 

binding affinity for DNA (K eq >=10 9 M -1 ). The compounds bind in the minor grooves of the double 

helix and extend into the major groove to a substituent which interacts strongly in the major groove, 

particularly at the phosphodiester linkages. The side groups of the compounds also may bind metal ions. 

These novel compounds have multiple therapeutic and diagnostic applications. The compounds inhibit 

mammalian topoisomerase, a molecule that unwinds and rewinds the DNA double helix during 

replication. They function by competing for binding sites, altering the conformation of the DNA, and 

changing the affinity of DNA manipulating enzymes for sites on the double helix. Further, these 

compounds could be effective to arrest cell growth and act as anti-cancer agents. Since these compounds 

detect nucleic acid with high sensitivity, they may be used for diagnostic purposes. For instance, they 

may be used to assay for the presence of DNA or RNA markers of a disease in a sample of infectious 

material. Protein, mass produced by recombinant DNA technology, may be checked for the presence of 

minute quantities of DNA or RNA. 

For therapeutic treatments, the compounds may be combined with pharmaceutical carriers and made into 

a liquid, tablet, powder, suppository, or ointment. Besides oral or topical application of the dose, the 

compounds may be introduced intravenously or by injection directly into the peritoneal cavity, 

lymphatic system, or malignant tumors. 

INQUIRIES TO: Oren Livne livne@research.ucsb.edu 



DNA BINDING COMPOUNDS FOR GENETIC REGULATION AND MEDICAL DIAGNOSIS AND THERAPY 










Phone: (805) 893-4036 




EARLY DETECTION OF COLON CANCER 



BACKGROUND: Colorectal cancer is the second leading cause of cancer-related deaths and the third 

most common cancer in the US and other Western countries. Adenomatous polyps are well-known, 

clear-cut histologic lesions that have been identified as precursors to colorectal cancer. Therefore, polyps 

are of critical importance in the early identification and potential prevention of colorectal cancer. These 

pre-cancerous lesions are very common in the normal population, with frequencies of 30-40% in people 

60 years and older. Fortunately, they can often be removed easily and in a time/cost effective way before 

they develop into actual cancers. 

Polyps recur in a statistically significant subset of people who undergo polypectomy. Currently, there 

are no predictive factors to determine who will have recurrent polyps and eventually colon cancer 

among polypectomy patients, although people with high-grade polyps are believed to have a worse 

prognosis. As a consequence, the only method presently available for the diagnosis of colon lesions and 

determination of their prognosis is direct examination by a pathologist. This is a very approximate and 

subjective approach, however, and there is a need for markers that could help clinicians decide which 

high-grade polyps are more likely to become colorectal cancer. 

DESCRIPTION: Amplification of a region of human chromosome 20 is a frequent event in colon 

adenocarcinomas, occurring in approximately 70% of cases (or ∼35%, when correction for chromosome 

20 polysomy is applied). Researchers at the University of California have now found that intermediary 

diagnostic states of the adenoma to adenocarcinoma sequence that are thought to be the immediate 

precursors of adenocarcinoma, such as high-grade dysplasia and intramucosal carcinoma, also display 

increased copy number of this chromosomal region. Specifically, the researchers found amplifications of 

this region in approximately 40% (or ∼30%, when correction for chromosome 20 polysomy is applied) 

of high-grade dysplasia lesions and intramucosal carcinomas. Methods of screening for colon carcinoma 

precursor cells by determining the presence of increased copy number of this region are covered by a U. 

S. patent assigned to the University of California (see below). 

ADVANTAGES: 

● Detection of increased copy number of the chromosome 20 region, either alone or in addition to 

pathology, could provide a more objective, reliable measure for adenocarcinoma and adenoma 



diagnosis and prognosis than pathology alone. 

● The new methods may be particularly useful in the diagnosis of precursor states, which are often 

difficult to diagnose using traditional pathological methods but, unlike carcinomas, are uniformly 

curable. 

APPLICATIONS: 

● Diagnosis in humans: Detection of increased copy number of the chromosome 20 region in colon 

tissue polyps could be used to diagnose/confirm the stage and therefore the gravity of the lesion. 

● Prognosis: The presence of increased copy number of the chromosome 20 region in high-grade 

dysplasia /intramucosal carcinoma lesions may be useful in predicting whether the lesions will 

have features similar to the invasive colon carcinomas. Thus, this assay could potentially become 

an important tool in decision-making for both surgery and therapy of those patients that have 

high-grade preadenomatous lesions. 

● Research in the area of tumorigenesis. 

● Drug discovery: Proteins coded by genes mapping to the chromosome 20 region that are 

differentially expressed in tumors having copy number alterations of this region may be 

candidate targets for tumor-specific drug development. 

INQUIRIES TO: Candace L. Voelker Candy.Voelker@ucop.edu 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 








Early Detection Of Pancreatic & Other Cancers 



UC CASE 1992-097-1 

NUMBER: 

TITLE: Early Detection Of Pancreatic & Other Cancers 


SUMMARY: Pancreatic cancer is known to be one of the most deadly carcinomas. One of the 

reasons for this is the fact that symptoms do not appear until the disease is well 

established and, possibly, metastasized. Early detection and diagnosis of such 

carcinomas, therefore, is vital to the patients survival. Other carcinomas such as 

colon cancer, etc. are also difficult to detect early enough for successful treatment. 

Researchers at the University of California have discovered that human pancreatic 

cancer cells exhibit a unique profile of molecular expression of growth factors and 

their receptors. This discovery forms the basis of a new test method for the 

determination of the site of origin of metastatic lesions. This will allow for rapid 

diagnostic screening for pancreatic cancer. One version of this test is based upon the 

fact that pancreatic cancer cells are shed into the intestines. The method then 

involves the induction of liquid stools which are then collected and the 






Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


END-SPECIFIC ANTIBODY TO DETECT APOPTOSIS 



BACKGROUND: Programmed cell death or apoptosis is a critical event in normal cellular 

differentiation and development as well as in degenerative diseases, cancer and aging. Currently, the 

most widely used assay for detecting apoptosis is DNA fragmentation. However, since DNA 

fragmentation can occur in a variety of situations without apoptosis, is a late stage nuclear event in 

apoptosis, and increases with postmortem time, it is not a reliable indicator of apoptosis. 

DESCRIPTION: Researchers at the University of California have developed an antibody that 

specifically labels apoptotic, but not necrotic cells. This antibody detects the most abundant protein 

fragments generated by caspases, enzymes that are activated during apoptosis. 

ADVANTAGES: The UC antibody is the first end-specific antibody for the detection of an apoptosisrelated 

event (caspase activation) and offers significant advantages over current DNA fragmentation 

assays which are widely regarded as non-specific. In addition, because the UC antibody detects the most 

abundant caspase cleavage product, it is more sensitive than recently available probes which recognize 

the activated caspase enzymes themselves. 

APPLICATIONS: The UC antibody can be used to accurately detect the activation of apoptotic 

machinery. Apoptosis has been shown to play a role in many pathological conditions including 

Alzheimer's disease, stroke, Huntington's disease, cancer and trauma. 












Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




ENDOSCOPIC LASER INSTRUMENT 



Scientists at the University of California have invented an improved endoscopic laser instrument for 

efficiently and effectively treating maladies by tissue evaporation and tissue thermal coagulation. The 

instrument comprises an outer tubular sheath which houses an optical fiber transmitting a CO 2 laser 

beam. An adjustable mirror is used to reflect the beam to selected tissue without changing the 

divergence of the beam. A standard endoscope viewing optic is also mounted in the sheath to permit 

visual tissue inspection. A gas is continuously circulated through the instrument for inflation and 

purging purposes. 

The invention has several advantages over other endoscopic techniques. With sheath rotation and 

tipping, a full 360° range is achieved for both viewing and laser treatment. This wide range enables 

treatment in wide areas such as bladder walls. Unlike conventional instruments using optical fiber 

bending to direct the laser beam, the invention uses a mirror configuration which does not alter the 

divergence of the laser beam. This divergence is critical in laser treatments. The use of a CO 2 laser 

results in cytodestructive effects without the problematic photosensitizer and reduced scarring from laser 

lesions. The invention is also modular. The sheath can be initially inserted to the desired position before 

the laser fiber and endoscope are introduced. 

Applications include many laser treatments requiring tissue evaporation or thermal coagulation of tissue, 

such as treatment of primary bladder cancer and urethral stricture disease. 





● Medical Eqp & Svcs > Surgical/medical eqp 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




ENDOVASCULAR DEVICE FOR HYPERTHERMIA 



BACKGROUND: The use of hyperthermia for preferential killing of malignant tumor cells is a wellestablished 

method. Heating solid tumors and other vascular lesions can be difficult to arrange because 

of the cooling action of blood flow. In those tumors where blood flow is highly nonuniform, avoidance 

of cold spots becomes a particularly difficult problem. If the heated tumor contains even small volumes 

of inadequately heated sections, its eradication by hyperthermia is unlikely. Some cancers are so virulent 

that survival of just a few cells can lead to regrowth. 

DESCRIPTION: Scientists at the University of California have developed a device for the 

hyperthermic treatment of tissue. This device can be used to directly heat flowing blood by placing it in 

direct contact with fluid or blood flowing to the tissue. The tissue can thus be subjected to a controlled 

amount of heat for a specified amount of time. 

APPLICATIONS: This device can be used for the hyperthermic treatment of tissue, such as cancerous 

tumors. 

ADVANTAGES: The new University of California device provides the following important benefits: 

● It allows controlled and direct heating of blood flowing to a desired region; 

● Blood flow can continue without significant interruption. 

INQUIRIES TO: Tim Wan tim.wan@ucop.edu 


RELATED CASES: 1999-306 

PATENT STATUS: US Patent # 6,011,995 issued January 4, 2000 




● Medical Eqp & Svcs > Medical therapeutic eqp 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 







BACKGROUND: The use of hyperthermia for preferential killing of malignant tumor cells is a wellestablished 

method. Heating solid tumors and other vascular lesions can be difficult to arrange because 

of the cooling action of blood flow. In those tumors where blood flow is highly nonuniform, avoidance 

of cold spots becomes a particularly difficult problem. If the heated tumor contains even small volumes 

of inadequately heated sections, its eradication by hyperthermia is unlikely. Some cancers are so virulent 

that survival of just a few cells can lead to regrowth. 

DESCRIPTION: Scientists at the University of California have developed a device for the 

hyperthermic treatment of tissue. This device can be used to directly heat flowing blood by placing it in 

direct contact with fluid or blood flowing to the tissue. The tissue can thus be subjected to a controlled 

amount of heat for a specified amount of time. 

APPLICATIONS: This device can be used for the hyperthermic treatment of tissue, such as cancerous 

tumors. 

ADVANTAGES: The new University of California device provides the following important benefits: 

● It allows controlled and direct heating of blood flowing to a desired region; 

● Blood flow can continue without significant interruption. 

INQUIRIES TO: Tim Wan tim.wan@ucop.edu 







● Medical Eqp & Svcs > Medical therapeutic eqp 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




EPLIN, A MARKER FOR HUMAN CANCER 



BACKGROUND: EPLIN, a novel gene not previously described encodes a protein expressed in human 

epithelial cells. EPLIN is of significant importance because its expression is diminished in many forms 

of human cancers including breast and prostate cancer. Restoring the expression of EPLIN in cancer 

cells antagonizes oncogenic transformation. 

DESCRIPTION: UC researchers have discovered a gene encoding EPLIN. EPLIN cDNA has been 

cloned, completely sequenced, and tested to detect its expression in human cells and tissues. The EPLIN 

gene has been cloned to determine the structure of the EPLIN gene including the regulatory sequences 

for the expression of EPLIN. In addition, EPLIN has been bacterially expressed to generate polyclonal 

antibodies to detect the expression of EPLIN by immunoblotting, immunohistochemistry, and in situ 

immunofluorescence. 

APPLICATIONS: EPLIN-based molecular reagents can be used in cancer detection, prognosis, and 

therapy. The EPLIN gene can be used to determine how the expression of EPLIN is down-regulated in 

cancer cells. 

ADVANTAGES: 

● EPLIN-based molecular reagents will prove useful because there are a limited number of 

biomarkers with proven utility for detection of breast and prostate cancer. 

● EPLIN-based biomarkers can be used in conjunction with or independently of existing 

biomarkers to facilitate the diagnosis and prognosis of these cancers. 



PATENT STATUS: US Patent # 6,864,066 issued March 8, 2005 











Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




EXONS 4 AND 7 ENCODE SEPARATE TRANSACTIVATING AND CHROMATIN-LOCALIZING DOMAINS IN ESX 


EXONS 4 AND 7 ENCODE SEPARATE TRANSACTIVATING AND 

CHROMATIN-LOCALIZING DOMAINS IN ESX 

BACKGROUND: The ets gene family of transcriptional regulators includes more than thirty known 

members that are involved in early embryonic development and late tissue maturation. ETS transcription 

factors are recognizable primarily by their 85 amino acid ETS DNA-binding domains. Ets genes can 

produce malignancies in humans and other vertebrates when overexpressed or rearranged into chimeras 

retaining the ETS domain. In fact, fusion proteins involving ETS family members are thought to account 

for a significant fraction of all human leukemias and lymphomas as well as virtually all Ewings 

Sarcomas and Primitive Neuro-Ectodermal Tumors (a type of childhood sarcoma). Epithelial-specific 

ETS family members like ESX (also known as ELF-3, ESE-1, JEN or ERT) have been shown to be 

essential for normal epithelial tissue (e.g. gastrointestinal) maturation and differentiation, and have been 

implicated in the development of such epithelial malignancies as breast cancer. 

DESCRIPTION: Researchers at the University of California were the first to clone, characterize and 

report on the novel Ets factor, ESX, which they found to be transcriptionally upregulated in breast and 

other human cancer cell lines as well as a subset of early breast cancers. They subsequently 

characterized the promoter and exon-intron structure of the ESX gene, and determined the function of its 

several modular protein domains. In particular, they characterized the acidic exon 4-encoded 

transactivation domain of ESX and showed it has unique dual capabilities in being able to not only 

recruit essential basal components of the cell's transcriptional machinery but also essential members of 

the DNA replication complex. They have also identified the basic exon 7-encoded domain of ESX as 

having unique nuclear and chromatin/matrix sublocalizing functions as well as the inducible ability to 

become post-translationally modified by acetylation. Critical epithelial cell behavior and function 

activated by ESX and dependent on these domains have now been identified. Others have now shown 

that ESX is transcriptionally upregulated during early human mammary stem cell differentiation, and 

markedly upregulated during human ovarian tumorigenesis. UCSF investigators were first to produce 

antibodies (useful for both immunoprecipition and immunoblotting) to full-length and domain-specific 

portions of ESX. 

ADVANTAGES: ESX represents a unique member of the ETS family of transcription factors. It is an 

early and key regulator of epithelial cell differentiation due to its unique domain-specific regulation of 

specific epithelial gene programs. Dysregulation of ESX is implicated in the early tumorigenic stages of 


EXONS 4 AND 7 ENCODE SEPARATE TRANSACTIVATING AND CHROMATIN-LOCALIZING DOMAINS IN ESX 

several epithelial malignancies including breast and ovarian cancer. As such, ESX-specific reagents are 

considered important for the study of, diagnosis and even treatment of these common epithelial cancers. 

APPLICATIONS: 

● Creation of methods of screening for potential modulators of ESX activity. 

● Use in determining risk and/or predisposition to human epithelial cancers. 

● Use in the diagnosis and/or prognosis of human epithelial cancers. 

● Use in designing novel treatments for ESX expressing cancers. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






EXPRESSION AND PURIFICATION OF ATM PROTEIN USING VACCINIA VIRUS 


EXPRESSION AND PURIFICATION OF ATM PROTEIN USING 

VACCINIA VIRUS 





instability and sensitivity to ionizing radiation. The protein mutated in AT, ATM (Ataxia Telangiectasia- 

Mutated), is a large protein of 370 kDa and is very difficult to purify. All previous efforts (using 

bacterial, yeast, and baculovirus systems) have failed to achieve a meaningful level of protein 

expression. Purified protein is important not only to further research regarding biochemical and 

functional characterization of this protein, but is also crucial for development of diagnostic assays. 

DESCRIPTION: Researchers at the University of California have developed a method for 

recombinantly producing a high yield of functional ATM protein. Specifically, they have generated a 

recombinant vaccinia virus containing ATM that can be used to infect mammalian cells. Once infected, 

the cells produce large amounts of ATM protein, which is then purified from the cells. 

ADVANTAGES: 

● The vaccinia virus expression system can be used to purify ATM protein at substantially higher 

levels than possible using previously reported methods. 

● The new method is further scalable, allowing production of large amounts of ATM protein. 

● The ATM protein generated using this method is fully functional. 

APPLICATIONS: 

● Purified ATM protein can be used for research purposes requiring biologically active protein, 

such as for biochemical and functional characterization of the protein. 

● Purified ATM protein can be used for the development of diagnostic assays. 

SEE ALSO: METHOD FOR ANALYZING ATAXIA-TELANGIECTASIA PROTEIN 


EXPRESSION AND PURIFICATION OF ATM PROTEIN USING VACCINIA VIRUS 

and DIAGNOSTIC TEST FOR MUTATIONS IN THE AT GENE 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






EXPRESSION OF HUMAN NUCLEAR RECEPTORS IN MICE 



Nuclear receptors regulate the proliferation and differentiation of adult cells in numerous tissues, 

including reproductive tract, mammary gland, bone, heart, blood vessel, and hair follicle cells. They are 

also implicated in the development of tumors, including breast, prostate, uterine, cervical, and ovarian 

cancers; in the prevention of disorders such as osteoporosis of the bones and atherosclerosis of coronary 

arteries; and in the mediation of male pattern baldness. There is a growing list of drugs that treat these 

disorders either by binding directly to these receptors (e.g. tamoxifen, raloxifene) or by modulating the 

metabolism of the steroid ligands that bind to these receptors (e.g. Propecia®). 

Given the pharmaceutical importance of these nuclear receptors, it would be highly advantageous to 

identify and test novel drugs for their activity as agonists or antagonists by using an in vivo model that 

phenotypically expresses a nuclear receptor. University of California researchers have developed, as a 

prototype, a mouse model that expresses a human nuclear receptor, namely the keratin-14 estrogen 

receptor, in the epithelial tissues of mice. Under such a model, drug/receptor interactions can be easily 

evaluated by visual and microscopic inspection, antibody screening, and DNA labeling. This invention 

offers a simple way to investigate the effects of drugs on nuclear receptors and their related metabolic 

enzymes by using such methods to visually inspect the epidermis of mice for changes in thickening, 

redness, or flaking. 

INQUIRIES TO: John Gill john.gill@ucop.edu 




● Biotechnology > Animal biotech systems > Disease detection systems 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




FAS-ASSOCIATED FACTOR 1 



BACKGROUND: The Fas receptor is a membrane-bound protein that in its activated state induces 

programmed cell death (apoptosis). Apoptosis has been implicated in the suppression of cancer, 

autoimmunity, and viral infections, so any ligands interacting with Fas are of great interest in 

development of potential therapeutic agents for induction or repression of the Fas receptor pathway. 

DESCRIPTION: University of California researchers have discovered and characterized a gene, called 

Fas-associated Factor-1 (FAF1), that potentiates Fas-mediated apoptosis via binding to the cytoplasmic 

domain of Fas. 

APPLICATIONS: It is anticipated that FAF1 can be used to develop pharmaceuticals or in gene 

therapy in therapeutic contexts requiring Fas-receptor activation, and specifically could be used for 

manipulating immune tolerance and/or privilege. If FAF1 or FAF1-derived pharmaceuticals are 

successful in sensitizing cells to Fas-mediated cell death, it could have direct therapeutic benefits in 

relieving autoimmune disorders, infectious diseases, an myocardial or neuronal infarctions. 



US Patent # 5,750,653 issued May 12, 1998; US Patent # 5,962,652 issued 




● Biotechnology > Proteins/protein eng sys > Proteins 




Oakland, CA 94607-5200 





Phone: (510) 587-6000 Fax: (510) 587-6090 




FLUORESCENCE ASSAY FOR DNA-MODIFYING ENZYMES: APPLI...HROUGHPUT LIBRARY SCREENING OF POTENTIAL REGULATORS 


FLUORESCENCE ASSAY FOR DNA-MODIFYING ENZYMES: 

APPLICATIONS TO HIGH THROUGHPUT LIBRARY SCREENING 

OF POTENTIAL REGULATORS 

DESCRIPTION: Scientists at the University of California have developed a fluorescence-based assay 

for DNA modifying enzymes. This assay technique has broad potential applications. It can be used to 

screen for modulators of enzymes such as: 

● Bacterial (e.g. DAM) and mammalian (e.g. cancer related) DNA methyltransferases; 

● DNA-repair enzymes; 

● DNA cytosine C5 demethylases. 

ADVANTAGES: The new University of California assay offers the following important advantages: 

● It is very rapid compared to conventional assays for enzyme activity. For example, monitoring 

the activity of DNA methyltransferases with a radiometric assay requires from one to several 

hours. The fluorescence assay requires only 1 to 5 minutes; 

● It is significantly less expensive than other methods and uses commercially available materials. 








FLUORESCENCE ASSAY FOR DNA-MODIFYING ENZYMES: APPLI...HROUGHPUT LIBRARY SCREENING OF POTENTIAL REGULATORS 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




FROZEN TISSUE MICROARRAY TECHNOLOGY FOR ANALYSIS OF RNA, DNA, AND PROTEINS 


FROZEN TISSUE MICROARRAY TECHNOLOGY FOR ANALYSIS 

OF RNA, DNA, AND PROTEINS 

BACKGROUND: Tissue microarray technology is a new method used to analyze several hundred 

tumor samples on a single slide allowing high throughput analysis of genes and proteins. This 

technology is useful in that it allows rapid analysis of a large number of samples, as well as 

simultaneous analysis of different genes and proteins through the use of serial sections. This new 

technology has already proven useful for rapidly characterizing the prevalence and prognostic 

significance of differentially expressed genes identified using cDNA array technology as well as genes 

involved in cancer development and progression. Tissue microarrays have also been useful in 

identifying genes that are targets of chromosomal amplification as well as to study the expression 

patterns of putative tumor suppressor genes. 

Current methods for making tissue microarrays involve coring tissues from paraffin-embedded tissue 

donor blocks and placing them into a single paraffin block. One difficulty with paraffin embedded tissue 

relates to antigenic changes in proteins and mRNA degradation induced by the fixation and embedding 

process. Consequently, there is a need to identify additional methods that allow for the optimal 

preservation of DNA, RNA, and proteins in tissue microarrays. 


preparing tissue microarrays using non-fixed, fresh frozen tissue. Sections prepared from these tissue 

microarrays provide excellent target material for the study of DNA, RNA and proteins as each section 

can be fixed in a manner specific to the corresponding technique used. Thus, this method circumvents 

the fixation problems associated with paraffin arrays. 

ADVANTAGES: 

● Allows fixation sensitive reagents to work effectively. 

● Procedures requiring fixation can be conducted in samples fixed in an identical manner, 

providing greater uniformity than with paraffin embedded tumor microarrays. 

● Each tissue array slide can be individually fixed in a manner specific to the corresponding 

technique used, allowing optimal fixation for DNA, RNA and protein targets. 


FROZEN TISSUE MICROARRAY TECHNOLOGY FOR ANALYSIS OF RNA, DNA, AND PROTEINS 

APPLICATIONS: 

● Frozen tissue microarray technology allows for analysis of RNA through RNA in situ 

hybridization, DNA through the use of FISH based experiments and proteins using 

immunohistochemistry. 

● By allowing simultaneous analysis of uniformly and optimally fixed DNA, RNA and proteins 

from 100s of tumor samples, this technology may lead to advances in the understanding of tumor 

pathobiology, and the identification and/or validation of new targets for therapy. 





May 17, 2005 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






GDOX, A NOVEL CANDIDATE PROTO-ONCOGENE 



BACKGROUND: Glioblastoma multiforme is the most common primary neoplasm of the central 

nervous system and remains among the most deadly of human cancers. It has previously been shown 

that accumulation of multiple genetic lesions underlies the malignant progression of this cancer. 

Although some of these genetic abnormalities have been well-documented, recent insight into the extent 

of gene expression differences underlying malignancy reveals that hundreds of gene transcripts may be 

expressed at significantly different levels between normal and neoplastic cells. Identification of these 

genes has direct clinical relevance if combined with the development of innovative rational therapies 

that specifically target these differentially expressed gene products. 

DESCRIPTION: Researchers at the University of California have identified a novel tumor-associated 

gene using representational difference analysis (RDA) and differential immuno-absorption (DIA), 

coupled with cDNA microarray analysis. The novel gene, which the researchers have called GDOX 

(glioma-derived oncogene on X), is overexpressed in a variety of gliomas. Transfection of a murine glial 

cell line and human glioblastoma cells with sense cDNA for GDOX results in a dramatic increase in cell 

proliferation, while transfection with antisense GDOX cDNA results in significant growth arrest and 

morphological changes. In addition, anti-GDOX antibody-treated tumor cells from various types of 

human cancers exhibit a dose-dependant decrease in cellular proliferation. Importantly, GDOX overexpression 

correlates with shorter survival times in human glioblastoma patients. These results suggest 

that the novel GDOX gene may be clinically useful for the development of cancer diagnostics, 

prognostics, and therapeutics. 

APPLICATIONS: The novel GDOX gene may be useful as the basis for novel therapeutics, 

diagnostics, and prognostics for cancer. 

INQUIRIES TO: Claire Wake cwake@resadmin.ucla.edu 











Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




GLUCOSE EMULATING RADIOPHARMACEUTICAL FOR CONVENTIONAL GAMMA CAMERA IMAGING 


GLUCOSE EMULATING RADIOPHARMACEUTICAL FOR 

CONVENTIONAL GAMMA CAMERA IMAGING 

Glucose transport protein is present on every living cell's membrane, and its concentration is up- and 

down-regulated with the cell's need for glucose. Thus a tracer of this transport protein is a tracer of 

glucose metabolism itself. Studies with radioactive fluordeoxyglucose, a glucose tracer in positron 

emission tomography (PET), show a unique utility for the diagnosis of most cancers, for indicating 

whether a patient with coronary artery disease will benefit from a revascularization procedure, and for 

providing information on patients with brain tumors, epilepsy and Alzheimer's disease. However, the 

PET technique is extremely expensive compared with conventional nuclear medicine scanning. 

Researchers at UC San Francisco have designed an alternative glucose analog which will bind strongly 

to the glucose transport protein, and its biodistribution also will correlate with glucose metabolism. 

Their version of this analog can be engineered to contain either an aromatic side chain labeled with 

common radioiodine, or a derivative synthesized with a chelating function for the incorporation of other 

radionuclides. These compounds will be detected with much less expensive conventional gamma camera 

imaging. 

Everything in the literature supports this new glucose analog and its use as a tracer. Tritiated versions, 

unsafe for clinical tests, have indicated an unprecedented 100% specificity. We are looking for a partner 

who can do the organic synthesis of this compound. The UC researchers can perform the biological 

testing necessary to confirm the analog's proper activity and distribution. 

INQUIRIES TO: Linda Stevenson linda.stevenson@ucop.edu 




April 18, 1995 



GLUCOSE EMULATING RADIOPHARMACEUTICAL FOR CONVENTIONAL GAMMA CAMERA IMAGING 

● Chemicals > Application-specific chems > Medical chemicals 

● Medical Eqp & Svcs > Medical diagnostic eqp > Medical imaging systems 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




HER-2/NEU OVEREXPRESSION ABROGATES GROWTH INHIBITORY PATHWAYS 


HER-2/NEU OVEREXPRESSION ABROGATES GROWTH 

INHIBITORY PATHWAYS 

BACKGROUND: The human HER-2/neu proto-oncogene encodes a transmembrane receptor tyrosine 

kinase with extensive sequence homology to the epidermal growth factor receptor. Amplification and/or 

overexpression of HER-2/neu has been found in one-third of human breast and one-fifth of ovarian 

cancers. In addition, the HER-2/neu alteration is associated with a poor clinical outcome in that women 

whose tumors contain it experience earlier disease relapse and shorter overall survival. 

Recently, this genetic alteration has been successfully targeted in humans using the monoclonal antibody 

HERCEPTIN. However, the molecular pathways leading from HER-2/neu overexpression to increased 

malignancy remain unclear and few targets downstream of HER-2/neu have been identified. Much 

remains to be learned about how HERCEPTIN functions as an anti-tumor agent and why certain HER-2/ 

neu overexpressing tumors respond to therapy while many others do not. 

DESCRIPTION: Researchers at the University of California have conducted a comprehensive gene 

analysis or "profile" of human breast cancer cells engineered to overexpress HER-2/neu. These profiling 

experiments have revealed that HER-2/neu overexpression results in characteristic patterns of gene 

expression that are associated with the malignant phenotype, including alterations in the Transforming 

Growth Factor-Beta (TGF-Beta) pathway. In addition, the researchers found that antibodies capable of 

inhibiting HER-2/neu receptor function and a TGF-Beta family member synergistically inhibit the 

growth of mammalian cells. 

Available technologies resulting from these discoveries include methods for obtaining genetic profiles of 

cancer cells in order to assess the status of a cancer in an individual, methods for inhibiting the growth 

of cancer cells that exhibit certain genetic profiles, and methods for the treatment of cancer using an 

antibody capable of inhibiting HER-2/neu and a TGF-Beta family member. 

ADVANTAGES: This invention provides: 

● New therapeutic options for the treatment of cancers that overexpress HER-2/neu. 

● New insight into the mechanism by which HER-2/neu overexpression leads to cancer. 


HER-2/NEU OVEREXPRESSION ABROGATES GROWTH INHIBITORY PATHWAYS 

● Methods to gain valuable information useful for the diagnosis and prognosis of cancer. 

APPLICATIONS: 

● Therapeutics, diagnostics, and prognostics for cancers that overexpress HER-2/neu. 

● Research tools to investigate the mechanisms by which HER-2/neu overexpression leads to 

cancer. 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






HER2 AND HER3 APTAMERS 



BACKGROUND: The human epidermal growth factor (EGF) receptor homologs, HER2 and HER3, 

are cell surface receptor kinases that are involved in the control of cell proliferation and differentiation. 

Overexpression of these kinases is found in several solid tumor malignancies, such as breast and ovarian 

cancers. Inhibiting signaling through these kinases is therefore an important clinical intervention, as is 

evidenced by the success of Herceptin, a humanized antibody against HER2. However, antibodies have 

some disadvantages as therapeutics, such as relatively large production costs and difficulty of selection. 

Furthermore, a significant portion of patients with HER2 overexpression does not respond to Herceptin. 

Thus, there is a need to develop novel small molecule therapeutics that inhibit HER2 and/or HER3. 

These new small molecule drugs could provide new diagnostics tools as well as treatment options for 

patients that fail to respond to Herceptin. 

DESCRIPTION: Researchers at the University of California have used the SELEX (systematic 

evolution of ligands by exponential enrichment) methodology to select RNA aptamers that bind the 

extracellular domains of HER2 and/or HER3. (Aptamers are single stranded RNA and DNA molecules 

that, like antibodies, bind target molecules with high specificity and affinity). They have identified one 

particular aptamer that is capable of inhibiting the activation of HER2 and HER3 in breast cancer cells 

in 10nM range. This aptamer may provide a clinically and medically relevant lead compound for the 

development of cancer therapeutics. 

ADVANTAGES: Aptamers provide many advantages over antibodies and other protein-based 

inhibitors, such as: 

● Ease of selection 

● Large quantities of chemically stable derivatives can be inexpensively synthesized by 

conventional phosphoramidite chemistry 

● Can easily attach various other compounds, such as fluorescent markers, cross-linkers or 

cytotoxic drugs 

APPLICATIONS: 

● Development of diagnostics using modified aptamers (such as with fluorescent labels). 



● Development of therapeutics using chemically stable aptamer derivatives. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






HUMAN CELLULAR RECEPTORS FOR LYSOPHOSPHOLIPIDS AND SPHINGOLIPIDS 


HUMAN CELLULAR RECEPTORS FOR LYSOPHOSPHOLIPIDS 

AND SPHINGOLIPIDS 

BACKGROUND: Sphingosine1-phosphate (S1P) mediates and modulates cellular proliferation as well 

as several other vital cellular functions specific to various organ systems. In the cardiovascular system, 

S1P protects against both hypoxia and hyperoxia; in the injured nervous system, S1P facilitates remyelination 

and other aspects of nerve repair; and in the immune system, S1P controls T lymphocyte 

homing and other responses in tissue. Cells of many mammalian organ systems express one or more of 

the five related G protein-coupled receptors for S1P (formerly known as Edg receptors). Exogenous S1P 

is not bioavailable. A variety of derivatives and modifications of S1P have shown a lack of potency as 

agonists and antagonists. Potent new reagents are needed in order to modify the activities of these 

receptors with organ system- and disease-specificity. 

DESCRIPTION: Researchers at the University of California have cloned the genes for two S1P 

receptors and expressed them in stable rat cell lines with null backgrounds. These cloned receptors and 

cell lines are available for the development of monoclonal antibodies and/or small molecules that will 

exibit receptor-specific agonist and antagonist actions. The antibodies will be useful for cytochemical 

and histochemical studies. The chemical compounds with functionality will have widespread utility for 

therapeutics, in a field with few potent pharmacological agents. It is hoped that humanized monoclonal 

antibodies and/or small molecule agonists and antagonists can be used to treat diseases and disorders as 

heterogeneous as autoimmune diseases, neural injury, transplant rejection, forms of gender-specific 

cancer, and neoangiogenesis. 

ADVANTAGES: Unlike the parent lysosphingolipid, these monoclonal antibodies and other agonists 

and antagonists would be bioavailable and specific for each S1P receptor-subtype. 

APPLICATIONS: 

S1P receptor-specific monoclonal antibodies and other small molecule agonists and antagonists could be 

useful for: 

● An initial platform for therapeutics 



● Proof-of-principle studies of S1P receptors in animal models 

● Cell, tissue or organ transplantation 

● Treatment of rheumatic/autoimmune diseases with S1P receptor components 

● Treatment of Ischemic heart disease 

● Treatment of some forms of cancer 



RELATED CASES: 1997-311, 2002-270, 2003-080 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






























APPLICATIONS: 


useful for: 











RELATED CASES: 1997-311, 2002-270, 2003-093 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 

















agonists and antagonists. Specific new reagents are needed in order to pursue the activities of these 

receptors. 

DESCRIPTION: Researchers at the University of California have been successful in developing anti- 

S1P receptor monoclonal antibodies with functional effects highly specific to each S1P receptor. Such 

antibodies are not only useful for cytochemical and histochemical studies, but also exert agonist or 

antagonist actions on the receptors. It is hoped that such monoclonal antibodies can be humanized and 

used as a therapeutic platform to treat diseases and disorders as heterogeneous as autoimmune diseases, 

transplant rejection, forms of gender-specific cancer, and neoangiogenesis. 

ADVANTAGES: Unlike the parent lysosphingolipid, these monoclonal antibodies are bioavailable and 

specific for each S1P receptor-subtype. They exhibit agonist or antagonist effects in many instances, can 

be used for proof-of-principle studies of S1P receptors in animal models, and may serve as the initial 

platform for therapeutic antibodies. 

APPLICATIONS: 

● Rheumatic/autoimmune diseases with S1P receptor components 


● Ischemic heart disease 

● Cancer 

● Research reagents 





RELATED CASES: 1997-311, 2003-080, 2003-093 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






























APPLICATIONS: 


useful for: 











RELATED CASES: 2002-270, 2003-080, 2003-093 

PATENT STATUS: US Patent # 6,812,335 issued November 2, 2004 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






IDENTIFICATION, CLONING AND CHARACTERIZATION OF A NOVEL HUMAN HDAC HIGHLY EXPRESSED IN THE THYMUS 


IDENTIFICATION, CLONING AND CHARACTERIZATION OF A 

NOVEL HUMAN HDAC HIGHLY EXPRESSED IN THE THYMUS 

BACKGROUND: Acetylation of core histones has been correlated with transcription, chromatin 

assembly, DNA repair, and recombinational events. Transfer of an acetyl group from acetyl-CoA onto 

the epsilon-amino group of different lysine residues in the NH 2 -terminal tail of core histones is a 

ubiquitous modification found in all euykaryotic species examined. Histone acetylation levels are 

controlled by the competing activities of histone acetyltransferases and histone deacetylases. Histone 

deacetylases are the catalytic subunits of multiprotein complexes that are targeted to specific promoters 

through their interaction with sequence-specific DNA-binding factors. 

DESCRIPTION: UC scientists have identified, cloned and characterized a novel human histone 

deacetylase (HDAC). This protein is highly expressed in specific populations of T lymphocytes in the 

thymus and at lower levels in other tissues. This newly discovered histone deacetylase is associated with 

histone deacetylase activity that is dependent on binding another identified histone deacetylase. 

APPLICATIONS: Since HDACs are involved in the control of gene regulation, HDAC genes are 

potential candidates as tumor suppressors. As such, their mutation could be associated with the 

development of cancers such as lymphomas, thymomas, or tumors of other organs. A probe of the newly 

discovered HDAC, or probes derived from its sequence, could become important tools for the diagnosis 

of specific cancers. Similarly, preparation and use of specific inhibitors of UC's newly discovered 

HDAC could play a significant role in the control of immunoproliferation, such as in 

immunosuppression for organ transplantation, as well as in the control of tumor development. 





IDENTIFICATION, CLONING AND CHARACTERIZATION OF A NOVEL HUMAN HDAC HIGHLY EXPRESSED IN THE THYMUS 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




IDENTIFICATION, DIAGNOSIS AND THERAPY FOR CELL DEATH-RELATED DISEASES 


IDENTIFICATION, DIAGNOSIS AND THERAPY FOR CELL 

DEATH-RELATED DISEASES 

BACKGROUND: Many diseases in humans are associated with excessive programmed cell death, also 

called apoptosis. HIV leads to AIDS by promoting apoptotic death of CD4+ T cells. Similarly, a number 

of neurodegenerative diseases, including ALS, spinal muscular atrophy, Alzheimer's and Parkinson's 

diseases, involve the inappropriate activation of the cell death pathway. Lastly, ischemia results in the 

apoptotic death of cardiomyocytes and neurons following myocardial infarction and stroke, respectively. 

Conversely, inappropriate repression of apoptosis has been implicated in a wide array of diseases. 

Productive viral infection often requires active repression of apoptosis by a virally encoded product. As 

self-reactive lymphocytes are normally eliminated by apoptosis, autoimmune diseases such as lupus 

erythematosus can arise should such cells survive. Morover, the failure of cells to undergo apoptosis is 

implicated in tumorigenesis in a variety of human malignancies. Apoptosis appears to function as a first 

line of defense against the proliferation of cells that might form a tumor (growth control dysregulation 

resulting in oncogenic transformation often triggers apoptosis.) The dysregulation of apoptosis may be a 

key causative event or therapeutic target in many, if not all, cancers. 

DESCRIPTION: UC researchers have identified a novel and previously unknown role for a 

Caenorhabditis elegans gene and its apparent human homologue in the regulation of apoptosis. 

Upregulation of this gene represses apoptosis in a number of cell types, including neurons; 

downregulation decreases survival of cells. Homologous proteins may perform the same functions in 

apoptosis in humans. One new class of pharmaceuticals has already been identified based on this 

homology between worm and human apoptosis, and is being tested in an effort to prevent the progress of 

neurodegenerative diseases. 





IDENTIFICATION, DIAGNOSIS AND THERAPY FOR CELL DEATH-RELATED DISEASES 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




Imaginal Cell Growth Factor 



UC CASE 1998-139-1 

NUMBER: 

TITLE: Imaginal Cell Growth Factor 

DEPARTMENT: Developmental & Cell Biology 

SUMMARY: Scientists at the University of California, Irvine have identified a new family of 

growth factors (Imaginal Disc Growth Factors or IDGFs) that are the first 

polypeptide growth factors to be reported from invertebrates. The proteins were 

identified by their ability to stimulate the growth of cultured cells of the fruit fly 

Drosophila. The family includes at least five members, three of which are encoded 

by three genes in a tight cluster. The proteins are structurally unrelated to known 

mammalian factors, but similar proteins are found in mammals and may constitute a 

novel class of growth factors. Growth factors are important components of cell 

culture media, which are commercially important in the production of many kinds 

of biological agents. Insect cells are being used increasingly for such processes such 

as cell lines for production of proteins. An insect expression system has the 

advantage that the cells grow rapidly at 27-degrees C without CO2 and with 

minimal maintenance. Imaginal Disc Growth Factors or homologous proteins from 

other species will be useful in culture media for insect cells, since they can be 

produced in unlimited quantities and in pure form by recombinant DNA technology. 

They can therefore replace the use of fly extracts and similar undefined components 

of insect cell culture medium. Furthermore, these proteins have mammalian 

counterparts that may have similar potential in mammalian cell culture. Some 

members of the family are overexposed in certain disease states (arthritis, Gaucher 

disease, and breast cancer), and may be useful for the design of diagnostics or 

therapeuti 


Imaginal Cell Growth Factor 

CONTACT: Trice Bryan - UCI 

Email: bfbryan@.uci.edu 




Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


IMPROVED LIPOSOMAL ENCAPSULATION OF DRUGS 



Many pharmacologically-active compounds have poor solubility in water due to the presence of 

hydrophobic regions, particularly organic compounds with long carbon chains or peptide regions that 

promote solubility in fat or in cell membranes. An example of such a compound is the Pacific Yew Treeextract 

taxol and synthetic taxol analogs, which have recently been found to be effective tumor 

suppressants in ovarian and breast cancer but require extremely prolonged delivery (~6 hours) due to 

poor solubility. To solubilize hydrophobic compounds in water, encapsulation in liposomes is a common 

technique. While this is effective for some hydrophobic compounds, existing encapsulation methods 

have serious problems such as excessively laborious procedures, low efficiencies and/or rates of 

encapsulation, and creation of vesicle structures that are not suitable for preferred routes of 

administration. 

To create an improved method for liposomal encapsulation of taxol and other hydrophobic compounds, 

University of California scientists have invented a method for modifying both the interior of liposomes 

and the compound of interest so that hydrophobic compounds can be incorporated into vesicles in a very 

efficient manner. Thus, involved encapsulation procedures and procedures for recovering 

unincorporated drugs are not needed with the UC method, and excessive distortion of vesicle structures 

is avoided. The modifications involved are physiologically benign, so the UC encapsulation method will 

likely be strongly preferred over existing methods in pharmaceutical delivery applications. 



PATENT STATUS: US Patent # 5,827,532 issued October 27, 1998 


● Biotechnology > Biomaterials 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




IMPROVED TAXANE PRODUCTION 



BACKGROUND: Taxanes, a family of naturally-occurring compounds found in conifers, have 

acquired great importance as a source of pharmaceuticals. The best known member of the family, 

paclitaxel (sold under the trademark "Taxol"), has been approved by the U.S. Food and Drug 

Administration as an anti-cancer compound, and is widely used in chemotherapy. Other taxanes are also 

being considered for use as anti-cancer compounds. 

Paclitaxel was originally isolated from the bark of the Pacific Yew, Taxus brevifolia. However, the 

Pacific Yew is scarce, grows very slowly, and yields paclitaxel in small quantities, making direct 

extraction from T. brevifolia impractical as a significant source of paclitaxel. Organic syntheses of 

paclitaxel are not commercially viable either, prompting the use of two other methods for obtaining 

paclitaxel. One method, called "semi-synthesis", involves the extraction of other taxanes from more 

abundant Taxus species (e.g. T. canadensis) and the conversion of these taxanes to paclitaxel. The 

second method uses plant cell cultures to provide a relatively enriched source of paclitaxel or other 

taxanes. 

DESCRIPTION: University of California researchers have made a number of inventions for improving 

taxane-producing cell culture systems and expanding the range of natural taxane sources. This invention 

portfolio includes: 

● Haploid cell cultures - Female gametophyte cells and their derivatives have been cultured to 

produce paclitaxel and related taxanes [US Patent # 5,547,866]. These cells are distinctive in 

having no hetereozygous genetic traits, which makes them more amenable to genetic 

modification for the development of higher-yielding cell strains. 

● Compounds to improve taxane yields from cell cultures - Taxane yields from cell cultures can be 

increased by using cyclodextrin in the nutrient formulation [US Patent # 6,087,176] and by using 

compounds that arrest the cell cycle such as the herbicide chlorsulfuron [US Patent # 5,981,777]. 

● Taxanes from non-Taxus conifers - Taxanes can be produced from non-Taxus conifers (including 

pines, spruces, cypresses, and South American conifers such as Brazilian pines and Fitzroy 

cypresses) in significant quantities using either the semi-synthesis method or the cell culture 

method [US Patent # 5,670,663]. 



● Antibodies - The University of California has developed taxane-specific antibodies. These can be 

used in various systems to isolate or purify taxanes from various sources. These antibodies can 

also be used to identify taxane-producing plant material [US patent # 5,981,777] and specifically 

to screen non-Taxus conifers for the presence of taxanes [US Patent # 5,955,621]. 

APPLICATIONS: These inventions may find application in two general areas. First, all of these 

inventions may find employment in the production of taxanes using cell culture systems, as taxane 

yields from cell cultures are likely to increase with the development of improved cell strains (including 

both gametophyte-derived cells and cells derived from novel non-Taxus sources) and with the use of 

yield-enhancing compounds in culture media. Second, the inventions relating to non-Taxus conifers may 

be of considerable interest to those who produce paclitaxel from natural sources using the semi-synthesis 

method. 

ADVANTAGES: 

● Haploid cell cultures do not harbor lethal alleles that can inhibit growth in heterozygous diploid 

cells, and can be more easily screened for improved genetic traits and subjected to genetic 

engineering; 

● Cyclodextrins can more than double taxane yields from cell culture systems; 

● Plant growth inhibitors like chlorsulfuron can halt the cell cycle (and the diversion of material 

and energy away from taxane production to cell division) without harming cells or causing 

leakage of metabolites into the culture medium, as is typcial of techniques that rely on 

withholding nutrients or changing subculturing routines; and 

● Non-Taxus conifers are potentially much cheaper as natural taxane sources than Taxus species, 

especially if waste byproducts of other wood-based industries can be used as novel taxane 

sources. 



RELATED CASES: 1992-082, 1998-093 

US Patent # 5,670,663 issued September 23, 1997; US Patent # 5,955,621 issued 


September 21, 1999 


● Biotechnology > Cell culture technologies > Plant cell cultures 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 



















taxanes. 



























method. 

ADVANTAGES: 



engineering; 








sources. 



RELATED CASES: 1992-082, 1996-047 




● Biotechnology > Plant biotech systems > Other plant biotechnology 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 



















taxanes. 



























method. 

ADVANTAGES: 



engineering; 








sources. 



RELATED CASES: 1996-047, 1998-093 



July 11, 2000 










Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




IN VITRO SCREEN TO IDENTIFY COMPOUNDS WITH ESTROGENIC OR ANTI-ESTROGENIC ACTIVITY 


IN VITRO SCREEN TO IDENTIFY COMPOUNDS WITH 

ESTROGENIC OR ANTI-ESTROGENIC ACTIVITY 

Pharmaceuticals, foods, and environmental substances with estrogenic activity are a public health 

concern. Recent evidence suggests that increased exposure to estrogens may increase the risk of breast 

cancer. Environmental estrogens may also be partially responsible for increases in the incidence of 

testicular cancer and male fertility problems in industrialized nations. Currently, however, chemicals and 

pharmaceuticals are not screened for estrogenic activity. 

Researchers at the University of California have developed and tested a sensitive and convenient screen 

that yields qualitative or quantitative information regarding a compound's estrogenic activity. This 

screen, which may eventually be marketed as a standard assay kit, measures estrogenic activity by 

tracking the biosynthesis of specific reporter molecules in genetically altered cells. By introducing the 

suspected estrogenic compound to the altered cells, which contain the estrogen receptor and a novel 

reporter plasmid, a researcher may easily determine the relative estrogenic potency of numerous 

compounds. (For further information regarding such a cell line, please refer to UC Case 92-062.) 

Apart from screening environmental compounds that are suspected of possessing estrogenic or antiestrogenic 

activity, the screen is also useful for developing novel pharmaceuticals. Researchers recently 

used the screen to identify five non-steroidal compounds with estrogenic activity from a library of 

twenty-five stilbene derivatives produced using a novel combinatorial synthesis technique. The 

identified lead compounds can now be further modified and screened to produce and identify more 

potent non-steroidal estrogens. 

APPLICATIONS: 

● Identification of environmental compounds, such as herbicides, pesticides, 

pharmaceuticals, plastic components, and dietary plant estrogens, that have 

unwanted or unsuspected estrogen-like or anti-estrogen-like action. 

● Development of pharmaceutical compounds with desired estrogenic or 

anti-estrogenic activity for therapeutic purposes. 


IN VITRO SCREEN TO IDENTIFY COMPOUNDS WITH ESTROGENIC OR ANTI-ESTROGENIC ACTIVITY 

ADVANTAGES: 

● The screen is extremely sensitive to natural human estrogen (17-beta- estradiol), approaching 

concentrations as low as 10^-12 Molar. 

● This screen directly measures estrogenic and anti-estrogenic activity, while other 

screens merely identify non-estrogen specific endpoints or receptor binding 

activity, which does not necessarily correlate with estrogenic and anti-estrogenic 

activity. 

● Rapid, straight-forward protocols are being developed for qualitative or quantitative results. 

● Compounds may be screened against 17-beta-estradiol, or against any chosen standard. 

● Screening of multiple combinations of compounds under various conditions is facile. 

● Prospective standard assay kits should be well-suited to testing conditions used by the FDA, the 

EPA, or any number of local health or regulatory agencies. 



US Patent # 5,723,291 issued March 3, 1998; US Patent # 6,156,723 issued 


December 5, 2000; US Patent # 6,884,577 issued April 26, 2005 


● Biotechnology > Animal biotech systems > Animal hormones 

● Biotechnology > Genetic engineering sys > Human diagnostic 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






INDUCTION OF PHAGOCYTIC HOST DEFENSE 



BACKGROUND: C1q, the recognition protein of the classical complement cascade in blood and body 

fluids, functions as an activation factor for stimulating the phagocytic activity of monocytes. C1q acts as 

a ligand for the surface receptors on these cells, triggering phagocytosis of infectious agents 

independently of the cytokines involved in inflammatory responses. 

DESCRIPTION: University of California researchers have sequenced and characterized a novel 

transmembrane receptor protein for C1q present in myeloid cells. Ligation of the UC protein results in 

enhanced phagocytic activity of myeloid cells without triggering proinflammatory cytokines. 

APPLICATIONS: The UC receptor protein can be used for designing a specific and efficacious ligand/ 

agonist that promotes phagocytic activity of myeloid cells. Such agents would potentially be of great 

value in preventing opportunistic infections in patients whose immune systems are compromised via 

inherited immunodeficiency, disease (particularly AIDS), and treatment regimens involving 

immunosuppression (as in various cancer therapies or transplantation procedures). Also, a soluble form 

of the receptor itself might serve as an inhibitor of C1q-mediated responses, providing a means for downregulation 

of these responses under selective conditions. 

ADVANTAGES: It is expected that agents specifically designed to interact with the UC protein will 

not, unlike C1q itself, affect the functioning of other receptors like the superoxide anion production 

mediated by the neutrophil C1q receptor. Thus, a ligand targeted to the UC protein could promote 

phagocytosis of infectious agents while avoiding increased production of toxic superoxides. 

INQUIRIES TO: Ronnie Hanecak rhanecak@uci.edu 


PATENT STATUS: US Patent # 5,965,439 issued October 12, 1999 










Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




INEXPENSIVE RESOLUTION OF AMBIGUOUS PAP SMEARS 



The Pap smear has been the diagnostic screening tool of choice for the early detection of cervical cancer 

for over half a century, with over 50% of U.S. women tested annually. However, the procedures for 

sample collection, preparation, and analysis cause sufficiently poor sensitivity and specificity to give rise 

to significant numbers of false negative and false positive results. 

Two areas of Pap smear diagnosis are particularly problematic. They are Atypical Squamous Cells of 

Undetermined Significance (ASCUS) and Atypical Glandular Cells of Undetermined Significance 

(AGCUS). There are approximately 250,000 AGCUS diagnoses per annum and 1.5 million ASCUS 

diagnoses. An indication of the problem with these diagnoses - where the oncologist is left not knowing 

if a dysplastic or malignant lesion is present or not - is that approximately 40% of patients who receive 

an AGCUS diagnosis harbor a high-grade dysplasic lesion or carcinoma. While biopsies can provide a 

more definitive result, they are much more expensive than Pap smears, costing $400 to $1200 to perform. 

To minimize the need for expensive biopsies to resolve ambiguous Pap smears, a University of 

California researcher has discovered that these ambiguous cell types express a certain antigen when they 

are derived from cancerous or pre-cancerous lesions. Using appropriate compounds for detecting the 

antigen, a cytologist could rapidly and economically discriminate between benign and cancerous/precancerous 

atypical cells. Thus, this invention has the potential to find clinical application in routine 

screening procedures, eliminating up to 150,000 biopsies annually. 




PATENT STATUS: US Patent # 6,403,327 issued June 11, 2002 










Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 







The Pap smear has been the diagnostic screening tool of choice for the early detection of cervical cancer 

for over half a century, with over 50% of U.S. women tested annually. However, the procedures for 

sample collection, preparation, and analysis cause sufficiently poor sensitivity and specificity to give rise 

to significant numbers of false negative and false positive results. 

Two areas of Pap smear diagnosis are particularly problematic. They are Atypical Squamous Cells of 

Undetermined Significance (ASCUS) and Atypical Glandular Cells of Undetermined Significance 

(AGCUS). There are approximately 250,000 AGCUS diagnoses per annum and 1.5 million ASCUS 

diagnoses. An indication of the problem with these diagnoses - where the oncologist is left not knowing 

if a dysplastic or malignant lesion is present or not - is that approximately 40% of patients who receive 

an AGCUS diagnosis harbor a high-grade dysplasic lesion or carcinoma. While biopsies can provide a 

more definitive result, they are much more expensive than Pap smears, costing $400 to $1200 to perform. 

To minimize the need for expensive biopsies to resolve ambiguous Pap smears, a University of 

California researcher has discovered that these ambiguous cell types express a certain antigen when they 

are derived from cancerous or pre-cancerous lesions. Using appropriate compounds for detecting the 

antigen, a cytologist could rapidly and economically discriminate between benign and cancerous/precancerous 

atypical cells. Thus, this invention has the potential to find clinical application in routine 

screening procedures, eliminating up to 150,000 biopsies annually. 














Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




INHIBITORS OF ANDROGEN ANTAGONISTS-REFRACTORY PROSTATE CANCER 


INHIBITORS OF ANDROGEN ANTAGONISTS-REFRACTORY 

PROSTATE CANCER 

SUMMARY: Researchers of the University of California have identified a crystal structure that may 

lead to the creation of small molecules for the treatment of prostate cancer, and hormone refractory 

prostate cancer in particular. 

BACKGROUND: Despite recent advances in early diagnosis and treatment, prostate cancer remains the 

most common and second most lethal tumor in American men, and no curative treatment currently exists 

for metastatic disease. Prostate cancer patients are currently treated with various testosterone 

antagonists, but most of the patients become refractory to these antagonists after 3-5 years of treatment. 

DESCRIPTION: UC investigators have developed a co-crystal structure of the human androgen 

receptor (AR) with peptide domains of receptor coactivators. Thus, UC researchers have identified a 

binding cleft in the human AR that could allow for the creation of small molecules that bind to the AR 

and block the activation of downstream genes. 

ADVANTAGES: This newly identified structure provides the basis for the creation of novel small 

organic molecules that bind tightly to the AR and prevent patients to become refractory to testosterone 

antagonists. 

APPLICATIONS: This invention has the potential to be used for the development of orally available 

human pharmaceuticals for the treatment of prostate cancer, particularly hormone refractory prostate 

cancer. 





INHIBITORS OF ANDROGEN ANTAGONISTS-REFRACTORY PROSTATE CANCER 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




INHIBITORS OF THE IL-4/IL-13 SIGNALING PATHWAY 



BACKGROUND: Interleukin-4 (IL-4) and interleukin-13 (IL-13) are cytokines produced by T helper 

type 2 (Th2) lymphocytes. IL-4 and IL-13 are involved in multiple aspects of immune function, such as 

humoral (B cell) responses and IgE production, mastocytosis and eosinophilia. Clinically, IL-4 and IL- 

13 have long been recognized for their important role in the pathogenesis of allergic diseases and 

asthma. More recently, signaling through the IL-4/IL-13 pathway has been shown to play a role in 

fibrosis and cancer. Thus, inhibition of the IL-4/IL-13 signaling pathway is of clinical importance. 

DESCRIPTION: Researchers at the University of California have developed small molecule 

antagonists of IL-4/IL-13 signal transduction. These molecules inhibit the survival of malignant B cells 

and sensitize them to other chemotherapeutic agents, but are nontoxic to normal lymphocytes. The 

compounds also enhance the efficacy of interferons, glycoproteins that are useful in the treatment of 

viral infections and cancer. Interestingly, the compounds also inhibit the p53 stress response, and thus 

could be useful in the treatment of diseases where DNA damage or oxidative stress is involved. 

ADVANTAGES: 

● While there are antibodies to IL-4 and IL-13 in clinical trials, these antibodies only block IL-4 or 

IL-13, not both. However, as IL-4 and IL-13 have redundant activities, blocking only one of them 

is insufficient in many instances. The novel compounds block both IL-4 and IL-13 signaling. 

● The compounds are small molecules. 

APPLICATIONS: May be useful for: 

● Treatment of leukemia, lymphoma, Hodgkin's, lung, head, neck, glioblastomas and other cancers 

expressing IL-4 and/or IL-13 receptors. 

● Sensitization of cancer cells to monoclonal antibodies and chemotherapeutic agents. 

● Use in vaccines against cancer and viral diseases to increase cytotoxic T cell responses. 

● Treatment of proliferative fibrotic diseases, such as rheumatoid arthritis, pulmonary fibrosis, liver 

cirrhosis, and chronic kidney diseases. 

● Use alone or in combination with therapeutic agents for treatment of viral diseases such as 

hepatitis, papilloma or RNA viruses such as Semliki Forest virus, San Angelo virus, Punta Toro 



virus, and Banzi virus. 

● Use alone or in combination with therapeutic agents for treatment of autoiummune diseases such 

as lupus erythematosus, multiple sclerosis, infertility from endometriosis, type I diabetes 

mellitus, Crohn's disease, ulcerative colitis, inflammatory bowel disease and rheumatoid arthritis. 

● Treatment of asthma and allergies. 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 









BACKGROUND: Interleukin-4 (IL-4) and interleukin-13 (IL-13) are cytokines produced by T helper 

type 2 (Th2) lymphocytes. IL-4 and IL-13 are involved in multiple aspects of immune function, such as 

humoral (B cell) responses and IgE production, mastocytosis and eosinophilia. Clinically, IL-4 and IL- 

13 have long been recognized for their important role in the pathogenesis of allergic diseases and 

asthma. More recently, signaling through the IL-4/IL-13 pathway has been shown to play a role in 

fibrosis and cancer. Thus, inhibition of the IL-4/IL-13 signaling pathway is of clinical importance. 

DESCRIPTION: Researchers at the University of California have developed small molecule 

antagonists of IL-4/IL-13 signal transduction. These molecules inhibit the survival of malignant B cells 

and sensitize them to other chemotherapeutic agents, but are nontoxic to normal lymphocytes. The 

compounds also enhance the efficacy of interferons, glycoproteins that are useful in the treatment of 

viral infections and cancer. Interestingly, the compounds also inhibit the p53 stress response, and thus 

could be useful in the treatment of diseases where DNA damage or oxidative stress is involved. 

ADVANTAGES: 

● While there are antibodies to IL-4 and IL-13 in clinical trials, these antibodies only block IL-4 or 

IL-13, not both. However, as IL-4 and IL-13 have redundant activities, blocking only one of them 

is insufficient in many instances. The novel compounds block both IL-4 and IL-13 signaling. 

● The compounds are small molecules. 

APPLICATIONS: May be useful for: 

● Treatment of leukemia, lymphoma, Hodgkin's, lung, head, neck, glioblastomas and other cancers 

expressing IL-4 and/or IL-13 receptors. 

● Sensitization of cancer cells to monoclonal antibodies and chemotherapeutic agents. 

● Use in vaccines against cancer and viral diseases to increase cytotoxic T cell responses. 

● Treatment of proliferative fibrotic diseases, such as rheumatoid arthritis, pulmonary fibrosis, liver 

cirrhosis, and chronic kidney diseases. 

● Use alone or in combination with therapeutic agents for treatment of viral diseases such as 

hepatitis, papilloma or RNA viruses such as Semliki Forest virus, San Angelo virus, Punta Toro 



virus, and Banzi virus. 

● Use alone or in combination with therapeutic agents for treatment of autoiummune diseases such 

as lupus erythematosus, multiple sclerosis, infertility from endometriosis, type I diabetes 

mellitus, Crohn's disease, ulcerative colitis, inflammatory bowel disease and rheumatoid arthritis. 

● Treatment of asthma and allergies. 










Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






IRRADIATED PROBIOTIC FOR IBD 



BACKGROUND: Inflammatory bowel disease (IBD) consists of a group of chronic inflammatory 

disorders involving the gastrointestinal tract. IBD can be divided into two major groups, ulcerative 

colitis (UC) and Crohn's disease (CD). Immunosuppressive and anti-inflammatory agents in high 

maintenance doses are the principal drugs used in the therapy of IBD. However, about 20-25% of 

patients with UC fail to respond to this intensive therapy and are therefore referred to surgery. In 

general, patients with CD are even less responsive to medical therapy and usually do not respond to 

surgical treatment. 

Probiotics are live microorganisms that confer health benefits by altering indigenous microflora. 

Probiotic therapy has been effective for attenuating experimental colitis, preventing flare up of CD and 

maintaining the remission of patients with UC. However, the molecules and molecular pathways by 

which probiotics ameliorate experimental colitis and IBD are largely unknown. 

DESCRIPTION: Researchers at the University of California have discovered that both gamma 

irradiated (non-viable) probiotics and isolated probiotic DNA have profound anti-inflammatory effects 

in mouse models of IBD. These results confront the current dogma that only viable probiotic bacteria 

have anti-inflammatory or immunomodulatory effects. The use of non-viable probiotics may prove to be 

an important new treatment for IBD. 

ADVANTAGES: 

● The use of irradiated probiotics provides a safer means of preparation and administration that 

does not require the use of live microorganisms. 

● The administration of gamma-irradiated probiotic provides a simple vehicle to deliver probiotic 

DNA (naturaceutical) that can bypass multiple clinical, medical and pharmaceutical regulations. 

APPLICATIONS: 

● Gamma irradiated probiotics may be useful in the treatment of IBD. 

● The use of gamma-irradiated probiotics may also be useful in other applications in which 

probiotic therapy has been found to be beneficial, such as allergy, asthma, hyperlipidemia and 



prevention of colon cancer. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






ISS RECEPTOR AS A DRUG DISCOVERY TOOL 



BACKGROUND: The ability of a multicellular organism to defend itself against invasion by pathogens 

(bacteria, fungi, viruses, etc.) depends on its ability to mount immune responses. The most basic type of 

immunity consists of inborn defense mechanisms, i.e. innate immunity. The innate immune response 

involves the effective and rapid recognition of highly conserved and repeated foreign structures such as 

those found in polysaccharides, lectins, complexed lipids and double stranded RNA. Recently, bacterial 

DNA and immunostimulatory DNA sequences (ISS) have also been shown to activate innate immunity. 

However, the molecular machinery that mediates innate immune responses initiated by ISS, i.e. a 

receptor or an ISS binding protein, is unknown. 

DESCRIPTION: Researchers at the University of California have discovered that Ku, an intercellular 

protein, interacts with ISS. Ku is the regulatory subunit of a DNA dependant protein kinase (DNA-PK) 

that plays a pivotal role in repair of DNA double-stranded breaks created by environmental insults or by 

intrinsic cellular processes such as programmed DNA rearrangements during lymphocyte differentiation. 

The researchers further discovered that ISS activates the catalytic subunit of DNA-PK, and that this 

activation is essential for the induction of innate cytokines by ISS. Thus, the researchers not only 

discovered the ISS binding protein, they elucidated an important signaling pathway for the generation of 

innate immune responses. 

ADVANTAGES: This invention provides a useful tool for discovering drugs that either mimic or 

inhibit the bioactivity of ISS. 

APPLICATIONS: 

● Identification of small molecules or therapeutics that either mimic or inhibit the 

immunomodulatory effects of ISS. 

● Identified compounds could be used in a variety of clinical fields for which ISS administration 

has already been proposed, such as allergy, infectious diseases, cancer and vaccine design. 

● Identification of agonists or antagonists of DNA-PK, which could be useful for the development 

of therapeutics for conditions relating to DNA damage and apoptosis. 











Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






KNOWN HORMONE WITH POTENTIAL THERAPEUTIC ACTION IN BRAIN DISEASES 


KNOWN HORMONE WITH POTENTIAL THERAPEUTIC ACTION 

IN BRAIN DISEASES 

BACKGROUND:Because there are currently no effective treatments for neurodegenerative diseases 

and some types of brain tumors, a great deal of research has been focused on proteins important in 

affecting neuronal development. These same proteins have also been found to be expressed in a 

developing brain. 

DESCRIPTION:UC researchers have discovered a previously unknown functional characteristic of 

these peptides found to be important in regulating the proliferation of neuronal cells. These peptides 

bind to various receptors and activate signalling pathways inducing cGMP, calcium, phospholipase C 

activity, inhibition of specific kinases, and regulation of the proliferation and survival of neuronal 

precursors. 

APPLICATIONS: 

● The activities of these peptides, although previously known for their importance in 

cardiovascular activity, can have utility in diseases in brain development, nerve injury, strokes, 

neurodegeneration, loss of brain function with age, and brain tumors. 

● Non-toxic ligands can be designed to block or enhance the ability of these peptides to regulate the 

proliferation of brain cells in cancer, or to enhance their survival in neurodegenerative diseases. 

● Development of drugs for the treatment of neurological diseases can ensue based upon the studies 

of this family of peptide receptors. 




● Pharmaceuticals > Central nervous sys drugs 


KNOWN HORMONE WITH POTENTIAL THERAPEUTIC ACTION IN BRAIN DISEASES 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




LIPOSOMAL DELIVERY OF ISS-BASED VACCINES 



BACKGROUND: Unlike mammalian DNA, which under normal conditions is immunologically inert, 

bacterial DNA exhibits powerful immunostimulatory activities. These activities result from short 

sequence motifs termed immunostimulatory sequences. Short synthetic oligonucleotides based on these 

sequences, called ISS-ODN, have also been shown to have potent immunostimulatory activities. In 

animal studies, synthetic ISS-ODN have shown powerful immuno-adjuvant activity, augmenting the 

potency of vaccines against various microorganisms and cancer. In addition, treatment with ISS-ODN 

alone can act both prophylactically and therapeutically in animals exposed to pathogenic 

microorganisms. ISS-ODN are also effective in controlling allergic reactions. 

ISS-ODN are currently used in soluble form either alone or combined with various vaccines. Because of 

the fast clearance/degradation of the molecules after in vivo administration, relatively large doses and 

repetitive administrations are required to obtain optimal responses. This not only complicates treatment 

logistics, but it can also lead to adverse reactions and toxic effects. Thus, there is a need for alternative 

methods of delivering ISS-ODN in vivo. 

DESCRIPTION: Researchers at the University of California have developed a novel liposome delivery 

system for ISS-ODN. The researchers found that ISS-ODN can be entrapped, with up to 90% efficiency, 

in large multilamellar liposomes using a simple and fast procedure. They further found that vaccine 

formulations containing liposomal ISS-ODN co-administered with either soluble antigen or liposomal 

antigen (from influenza or hepatitis B) are up to 30 times more effective than formulations containing 

unencapsulated ISS-ODN in inducing a variety of immune responses in mice. Importantly, no adverse 

reactions were found in these mice. Thus, liposomal ISS-ODN may prove highly effective as an 

adjuvant for vaccines. 

ADVANTAGES: 

● Liposomes could allow slow release of entrapped ISS-ODN over an extended period of time. 

● Since liposomes are taken up rapidly and efficiently by antigen-presenting cells (APCs), thereby 

initiating the immune response, co-delivery of the antigen and ISS-ODN to the same APC may 

optimally activate the immune system. 

● Liposomes can be formed in various formulations and sizes, on a large scale, and can be safely 



administered by various routes (parenteral, oral, nasal). 

● Liposomes are biocompatible-namely, they are non-toxic, non-immunogenic, and biodegradable, 

and are approved for human use (delivery of antibiotics, anti-cancer drugs, vaccines). 

APPLICATIONS: 

● Vaccine adjuvant against pathogens and cancer 

● Therapeutic treatment of diseases caused by certain infectious microorganisms 

● Treatment of certain allergic diseases 

● Boost innate immunity 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






LIPOXYGENASE INHIBITORS AS DRUGS AGAINST CANCER, ASTHMA AND ATHEROSCLEROSIS 


LIPOXYGENASE INHIBITORS AS DRUGS AGAINST CANCER, 

ASTHMA AND ATHEROSCLEROSIS 

BACKGROUND: Lipoxygenases are enzymes that catalyze the oxidation of fatty acids. The bioactive 

products play critical roles in such areas as inflammation, cell-proliferation and asthma. Selective 

inhibition of these enzymes could have many therapeutic benefits. 

DESCRIPTION: UC researchers have synthesized a group of related compounds that act as potent and 

specific inhibitors of 15- and 12-lipoxygenases. The compounds bind to an allosteric site on the enzyme 

and are more soluble than currently available inhibitors. 

APPLICATIONS: The inhibitors could be used as drugs against cancer, atherosclerosis and asthma. 

Their relatively high solubility makes them more suitable for therapeutic use than other currently 

available inhibitors. In addition, the interaction between the inhibitor and lipoxygenase may be used as 

the basis of a screen to discover other therapeutically-useful inhibitors. 

INQUIRIES TO: Gerald Barnett gbarnett@ucsc.edu 




● Pharmaceuticals > Antihistamine drugs 

University of California, Santa Cruz 

Office for the Management of Intellectual Property 

477 Kerr Hall 

1156 High Street 

Santa Cruz, CA 95064 

Phone: (831) 459-5415 Fax: (831) 459-1658 


LIPOXYGENASE INHIBITORS AS DRUGS AGAINST CANCER, ASTHMA AND ATHEROSCLEROSIS 






LIQUID ASSOCIATION WITH APPLICATION IN GENE EXPRESSION 


LIQUID ASSOCIATION WITH APPLICATION IN GENE 

EXPRESSION 

BACKGROUND: Microarrays have generated an enormous amount of data about gene activities, but 

the distilled biological information is still very limited. Current gene activity elucidation methods hinge 

on the notion of profile similarity, meaning that two co-expressed genes are likely to participate in a 

common structural complex, metabolic pathway, or biological process. Yet the reality is that most genes 

have multiple cellular roles. Those engaged in a common process under certain conditions may later 

disengage and embark on activities of their own, which implies that both the strength and pattern of 

profile association should vary as the intrinsic cellular state changes. However, numerous intracellular 

and intercellular conditions that can alter the cellular state compounds the problem. At present, no 

general bioinformatics tools exist for exploring this issue. 

DESCRIPTION: Scientists at the University of California have developed a novel bioinformatics 

method that overcomes this difficulty. The method conducts a genome-wide search and identifies the 

most critical cellular players that may affect the co-expression pattern for genes that may participate in 

more than one pathway. 

APPLICATIONS: This new UC invention can be applied in any large microarray study. For N genes, 

the algorithm returns a huge amount of information, in the order of N to the cubic power, for a variety of 

uses. In pharmaceutical applications, the same method can be applied to predict the responsiveness of a 

drug based on the gene profile of the patient. 

ADVANTAGES: This is the first high-throughput bioinformatics tool to explore and exploit the 

dynamic, as oppose to the static, aspect of gene expression in cells. It eliminates the need to specify the 

cellular state before applying this method. Instead, the method provides results for portraying the 

intrinsic state that facilitates the change of co-expression pattern. The detected state change can then 

explain the differential cancer drug responsiveness among different cell- lines. 


LIQUID ASSOCIATION WITH APPLICATION IN GENE EXPRESSION 

INQUIRIES TO: 



● Computer Software > Program development sof > Code algorithms 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






LONG WAVELENGTH PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY AND DIAGNOSIS OF TUMORS 


LONG WAVELENGTH PHOTOSENSITIZERS FOR 

PHOTODYNAMIC THERAPY AND DIAGNOSIS OF TUMORS 

Photodynamic therapy (PDT) shows great promise as a method for cancer diagnosis and treatment. PDT 

involves the administration of a photosensitizer -- a therapeutically inactive, photosensitive compound 

which tumor cells selectively take up and retain -- followed by illumination of the tumor or lesion with 

visible light. Photoactivation causes the photosensitizer to generate cytotoxic singlet oxygen which 

destroys the tumor cell without effecting surrounding, nontumorous tissue. Since 1976, thousands of 

cancer patients worldwide have undergone experimental PDT treatments, with trials on new types of 

photosensitizers still ongoing. 

Although current photosensitizers have shown broad diagnostic and therapeutic potential for use in PDT, 

they have several drawbacks. Some have weak absorbance in the red (600-800 nm) where visible light 

has its greatest tissue penetration, limiting the tissue depth at which photoactivation can occur. In some 

cases, nontumorous tissues, including liver, kidney, spleen, and skin, tend to take up and retain the 

photosensitizer, leading to undesirable side effects. These compounds can lack rapid clearance from 

normal tissues, rendering patients photosensitive and in danger of cutaneous phototoxicity for a month 

or longer after treatment. Other drawbacks include chemical instability, potential human toxicity, and 

difficult syntheses. 

Researchers at the University of California have developed several new classes of long wavelength (600- 

800 nm) photosensitizers for use in PDT. These stable, highly water-soluble compounds have relatively 

easy and inexpensive syntheses which use naturally abundant plant and algae chlorophyll as the starting 

material. They have strong absorbance at longer wavelengths, allowing for increased tissue penetration, 

better photosensitizing efficacy, and improved tumor photodestruction. They also act on a much shorter 

time scale and do not cause severe cutaneous photosensitization or other side effects after 24 hours. 

ADVANTAGES: 

● Strong absorbance at longer wavelengths (600-800 nm) 

● Relatively easy and inexpensive to synthesize 

● Chemically stable 


LONG WAVELENGTH PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY AND DIAGNOSIS OF TUMORS 

● Water-soluble 

● Fast acting 





● Medical Eqp & Svcs > Surgical/medical eqp > Cancer therapy lasers 





Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






MACROMOLECULE-LIPID COMPLEXES FOR SYNTHETIC GENE-DELIVERY SYSTEMS 


MACROMOLECULE-LIPID COMPLEXES FOR SYNTHETIC 

GENE-DELIVERY SYSTEMS 

BACKGROUND: In the last few years a very large research effort has been devoted to developing new 

compounds that are carriers of DNA and other macromolecules into human cells. Compounds composed 

of DNA and cationic liposomes (CL-DNA complexes) are especially promising vectors for non-viral 

gene-therapy applications. These compounds have numerous advantages over viral methods, such as 

their lower toxicity, simpler preparation, lack of immune response from the body, and ability to carry 

large pieces of DNA. 

DESCRIPTION: Scientists at the University of California at Santa Barbara have developed 

macromolecule-lipid complexes with precisely defined structures for ex vivo and in vivo gene and drug 

delivery. This technology allows for the control of critical material parameters, such as the lipidmembrane 

thickness and the intermolecular spacing of encapsulated molecules. New cationic lipids have 

been synthesized which contain hydrophilic poly(ethylene glycol) spacers and multivalent cationic end 

groups. These novel spacer-containing lipids are designed for in vivo gene/drug delivery applications. 

New cationic lipid-cosurfactant synthetic gene-delivery systems have been designed to optimize 

transfection. 

APPLICATIONS: These macromolecule-lipid complexes can be used as non-viral delivery systems for 

macromolecules such as DNA, peptides, or polysaccharides. More specifically, this technology can be 

used in the areas of: 

● New synthetic gene/drug-delivery systems (gene replacement, gene addition, genes for toxin 

synthesis, genes in cancer therapy strategies); 

● Nucleic acid based vaccine development. 

ADVANTAGES: The quantitative control of the macromolecule-lipid complex's properties allows for 

improved reliability of delivery. For instance, the new technology offers: 

● New spacer-containing cationic lipids for in vivo gene/drug delivery; 


MACROMOLECULE-LIPID COMPLEXES FOR SYNTHETIC GENE-DELIVERY SYSTEMS 

● Cationic lipid/cosurfactant synthetic gene/drug delivery; 

● The ability to correlate structural parameters and delivery efficiencies; 

● The ability to control electrostatic interactions for optimal delivery; 

● Potential for increased compacting of DNA inside the complex, enhancing DNA transport into 

cells. 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






MACROPHAGE-COLONY STIMULATING FACTOR CRYSTALS 



Macrophage-colony stimulating factor (M-CSF) belongs to a group of biological agonists that promote 

the production of blood cells and acts as a specific growth and differentiation factor for bone marrow 

progenitor cells of mononuclear phagocytes. M-CSF also stimulates the proliferation and function of 

mature macrophages. M-CSF has shown promise in clinical trials in the amelioration of blood cell 

deficiencies arising as a side effect of chemotherapy or radiation therapy in cancer treatment. Also, M- 

CSF has potential application in treating fungal infections associated with bone-marrow transplants. 

University of California researchers have obtained high-quality crystals of dimeric M-CSF and have 

characterized its three-dimensional structure. Such detailed information concerning M-CSF structure is 

of great utility in design of M-CSF agonists or antagonists, thus permitting the accelerated development 

of agents for improved pharmaceutical control of M-CSF-mediated processes. Also, the crystallization 

process itself has great promise for significantly improved purification and stabilization of M-CSF over 

other preparative methods, making higher-quality M-CSF preparations available for clinical use. 





February 15, 2000 


● Biotechnology > Proteins/protein eng sys 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 








MAGNETIC RESONANCE FOR EVALUATING TISSUE NECROSIS IN NEOPLASTIC, INFLAMMATORY AND INFECTIOUS DISORDERS 


MAGNETIC RESONANCE FOR EVALUATING TISSUE 

NECROSIS IN NEOPLASTIC, INFLAMMATORY AND 

INFECTIOUS DISORDERS 

BACKGROUND: Many magnetic resonance imaging (MRI) techniques have been designed in recent 

years to differentiate viable from necrotic tissue in patients. All these attempts, however, have been 

characterized by a lack of specificity, with marked overlap between viable and necrotic tissue in the 

images. Although MR contrast agents hold the potential to provide improved discrimination between 

viable and necrotic tissue, they have several drawbacks. The use of MR contrast agents requires both the 

additional cost of the contrast agent (>$100/dose) and the need for additional MR sequences, resulting in 

increased imaging time and expense. 

DESCRIPTION: Scientists at the University of California have developed a new non-invasive, in vivo 

technique for using MRI to differentiate between viable and necrotic tissue. It has been tested 

extensively and is likely to have significant impact on the use of imaging to monitor and quantify the 

patient response to various treatments. 

APPLICATIONS: This MRI technique is effective for studying and assessing tissue necrosis and will 

provide a valuable tool for: 

● Monitoring the effects of antineoplastic therapy (e.g. chemotherapy, radiation therapy or 

hyperthermia) in cancer patients; 

● Monitoring the effects of anti-inflammatory therapy in inflammatory disorders; 

● Monitoring the effects of antibiotic therapy in infectious disorders. 

ADVANTAGES: Treatment-induced changes in tissue viability can be assessed non-invasively in a 

wide array of different neoplastic, inflammatory, and infectious disorders. This new technique eliminates 

the need for MR contrast agents, thereby helping decrease the total imaging cost. 



MAGNETIC RESONANCE FOR EVALUATING TISSUE NECROSIS IN NEOPLASTIC, INFLAMMATORY AND INFECTIOUS DISORDERS 




● Medical Eqp & Svcs > Medical diagnostic eqp > Magnetic resonance eqp 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






MECHANOSENSORY TRANSDUCTION CHANNEL GENE 



Mechanosensory transduction, found throughout the animal kingdom, comprises a wide variety of 

signaling systems as diverse as those for hearing and light touching of the skin. It is thought that 

mechanically-gated cation channels in receptor cell membranes mediate the various modalities of this 

type of transduction in vertebrates - light touch, heavy touch, proprioception, baroreception, balance, 

and hearing. However, the molecules that make up these channels have not been identified or isolated. 

Using electrophysiological screening, researchers at the University of California identified a severe 

mechanosensory mutant in Drosophila melanogaster that showed almost no mechanoelectrical 

transduction. This in turn led them to clone and characterize the first eukaryotic gene known to be 

involved in mechanosensory transduction. The researchers discovered that this gene encodes a novel ion 

channel that has homology to vertebrate sensory ion channels. Thus, manipulation of the UC gene might 

serve as a model for eukaryotic mechanosensory channels in general, allowing the development of novel 

treatments for mechanosensory transduction disorders in humans. In particular, a mechanosensory 

transduction model may have significant implications for the treatment of congenital, casual, and 

environmentally-induced hearing loss, as well as some forms of metastatic cancers. 









Oakland, CA 94607-5200 





Phone: (510) 587-6000 Fax: (510) 587-6090 




METHOD FOR DEVELOPING ANTAGONISTS FOR NUCLEAR HORMONE RECEPTORS 


METHOD FOR DEVELOPING ANTAGONISTS FOR NUCLEAR 

HORMONE RECEPTORS 

BACKGROUND: Nuclear receptor proteins represent a superfamily of transcription factors that 

activate or repress transcription in a ligand, promoter and cell-type specific manner. These proteins 

mediate action of hormones, vitamins, prostaglandins and other small molecule ligands such as thyroid 

hormone, vitamin D, progestin and retinoids. In addition to the nuclear receptors with known ligands, 

the superfamily also includes a group of structurally similar "orphan receptors" for which ligands have 

not been yet identified. 

Nuclear receptors have an extensive overlap in their overall architecture of their functional domains that 

can be organized into a transcriptional activation domain, a DNA-binding domain and a ligand-binding 

domain (LBD). In addition to the ligands that bind to the LBD, nuclear receptor action is also regulated 

by binding of chaperones co-repressors or co-activators. In this context, LBDs act as molecular switches 

that control transcriptional activity of nuclear receptors by influencing their interaction with such 

molecules. 

Current drugs for diseases with nuclear receptor signaling dysfunction are modeled on ligands that bind 

to the deep-seated LBD and alternative target sites including the co-activator binding site, have been 

unexplored because structural and functional basis for their use has been unavailable. Accordingly, there 

is a need to identify and characterize co-activator binding sites in nuclear receptors for the development 

of drugs directed to a new target site. 

DESCRIPTION: Researchers at the University of California have discovered a previously unknown 

structure that serves as the coupling surface for binding co-activators to the thyroid hormone receptor, 

using atomic models derived from co-crystals. This forms the basis of other inventions that the 

researchers describe to identify co-activator binding sites of other nuclear receptors and, includes 

computational methods for identifying small molecule or peptide antagonists that mimic the co-activator 

and for designing compounds that can distinguish nuclear receptor isoforms. 

ADVANTAGES: 


METHOD FOR DEVELOPING ANTAGONISTS FOR NUCLEAR HORMONE RECEPTORS 

● Novel target site different from the traditional hormone binding site. 

● Circumvents disadvantages of context-dependent agonist/antagonist activity of LBD-directed 

drugs like tamoxifen 

● Computational methods described offer shorter timeline towards specific drugs 

● Allows design of well-characterized drugs for variety of members of nuclear receptor family 

including orphan receptors. 

APPLICATIONS: 

● Structure-aided design of antagonists and agonists of nuclear receptors that can be used as drugs 

in a variety of medical conditions such as breast cancer, prostate cancer, cardiac arrhythmia, 

diabetes and hyperthyroidism that involve nuclear receptors. 




● Pharmaceuticals > Hormones/synthetic subs 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






METHOD FOR DIAGNOSING BREAST CANCER 



BACKGROUND: Breast cancer is reported to be the most frequently diagnosed cancer in American 

women. The key to increasing survival is early diagnosis. Current methods of diagnosis, however, are 

imperfect. Mammography, for example, misses as many as 20% of the cases of breast cancer, while 

breast biopsies following abnormal mammograms confirm the disease in only 5-10% of the cases. 

Methods for measuring serum tumor markers do exist, but are not useful for diagnosing breast cancer. 

DESCRIPTION: Researchers at the University of California, Los Angeles, have discovered a novel 

method for diagnosing breast cancer. The level of a nipple fluid tumor marker can be measured in 

patient samples, and the level of this marker in this type of sample is found to be significantly higher in 

cancer patients than in non-cancer patients. Levels are elevated as well in women at risk for breast 

cancer. 

APPLICATIONS: The level of this nipple fluid tumor marker found may be used to both screen and 

diagnose breast cancer. 

ADVANTAGES: 

● The measurement of this nipple fluid tumor marker is useful in the diagnosis of breast cancer 

because, unlike other methods of measuring serum tumor markers, its level is found to be 

significantly higher in patients with breast cancer. 

● Samples are obtained via a non-invasive procedure. 

● The diagnostic test may be performed using pre-packaged diagnostic kits. 













Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




METHOD FOR EARLY DIAGNOSIS OF, AND DETERMINATION OF PROGNOSIS IN, CANCER 


METHOD FOR EARLY DIAGNOSIS OF, AND DETERMINATION 

OF PROGNOSIS IN, CANCER 

BACKGROUND: Studies of tumor cell lines and gross primary tumors have identified a region of 

chromosome 21, 9p21, that is deleted in certain cancers. This chromosomal region harbors five different 

genes within about 120kb, including two tumor suppressor genes and the gene for the metabolic enzyme 

methylioadenosine phosphorylase (MTAP). As the deletion of this region is thought to be causally 

related to the development of cancer, markers from this region could be helpful in the diagnosis of 

cancers both at early and more advanced stages of tumor development. 

DESCRIPTION: Researchers at the University of California have used specific primers to sequence 

tagged sites (STS), as well as for the different exons of the 9p21 genes, to map deletion breakpoints in 

different stages and types of tumors. They discovered that in many cancers, derangements of 9p21 begin 

at the MTAP gene locus at the onset of tumor development and progress centromerically as tumor 

development advances. Thus, the stage of the tumor can be determined by analyzing whether just the 

MTAP locus is deleted, or whether more centromeric loci are also deleted; the former indicates an early 

stage cancer, while the latter indicates an advanced stage. Methods based on this discovery are covered 

by U.S. Patent No. 6,576,420. 

ADVANTAGES: This method provides a molecular basis for determining whether a cancer is at an 

early or advanced stage, thereby allowing a determination of a diagnosis or prognosis for cancer. 

APPLICATIONS: The reagents and methods described could be used to produce a kit for the diagnosis 

of or prognosis for cancer. 






METHOD FOR EARLY DIAGNOSIS OF, AND DETERMINATION OF PROGNOSIS IN, CANCER 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




METHOD FOR ENHANCING AN IMMUNE RESPONSE 



BACKGROUND: Adjuvants are substances that amplify or modulate the immune response to a codelivered 

antigen. One use of adjuvants is in vaccines; they are often administered in conjunction with 

antigen to increase the effectiveness of a vaccine. Currently, few adjuvants (e.g. alum and MF59) have 

been approved for use in human vaccination. 

DESCRIPTION: Researchers at the University of California have discovered a new method for 

amplifying an immune response to a substance, such as an antigen administered to a subject, or a 

pathogen to which the subject is exposed. The method can be used to activate innate immunity, to 

generate cytotoxic T cell activity, and to bias the subsequent immune response toward a Th1 immune 

response. (Th1 cells help in the induction of delayed-type hypersensitivity responses). The method 

comprises administering an immunostimulatory nucleotide sequence (ISS) to the subject prior to 

exposure of the subject to the antigen. This "pre-priming" of the subject with ISS prior to antigen 

administration or pathogen exposure results in amplification of the immune response to the substance as 

compared with co-administration of ISS and antigen. This method is useful for providing an enhanced 

immune response to infectious pathogens, allergens, or cancer antigens. In addition, the method can be 

used either prophylactically, e.g. for immunization, or therapeutically, e.g. for immunotherapy. 

ADVANTAGES: 

● Provides an effective strategy for protection against a broad range of substances. 

● Suppresses Th2 associated responses, thereby reducing the risk of prolonged allergic 

inflammation and antigen-induced anaphylaxis. 

APPLICATIONS: 

● Protection against infectious diseases, such as viral, bacterial , mycobacterial and parasitic 

diseases. 

● Prevention and treatment of allergies, such as to plant pollens, dust mite proteins, animal dander, 

saliva and fungal spores. 

● Preparation of tumor vaccines for cancer. 

● Use in contraception, where the antigen is a sperm protein. 











Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






METHOD FOR INHIBITING PROTEIN KINASES IN CANCER CELLS 


METHOD FOR INHIBITING PROTEIN KINASES IN CANCER 

CELLS 

BACKGROUND: Protein kinases are key signaling enzymes regulating a variety of cellular processes. 

They have also been shown to play a pivotal role in all aspects of cancer physiology including 

proliferation, invasion, metastasis and angiogenesis and, therefore, have been considered as attractive 

targets for the development of inhibitory drugs. 

The two major types of protein kinases - serine/threonine kinases and tyrosine kinases - use adenosine 

triphosphate (ATP) as the donor for the phosphate group that they transfer to the protein substrate. A 

majority of the kinase drugs act as a competitive inhibitor of enzyme activity by binding to the same site 

that ATP binds to. Although the high degree of structure conservation in the ATP binding site among the 

different kinases has hindered development of drugs specific for individual kinases in the past, recent 

progress in structure-aided design of drugs has to a great extent helped circumvent this problem. 

However, the inefficiency of these drugs to compete with the high concentration of ATP within cells has 

limited their use. Therefore, any method that will lower the intracellular concentration of ATP would 

serve to enhance the binding of the drug to the kinase and inhibit its activity more effectively. 

DESCRIPTION: Researchers at the University of California have identified several methods to lower 

the intracellular concentration of ATP that could be used in combination therapy with protein kinase 

inhibitors for cancer treatment. They have discovered that inhibitors of protein kinases, when used in 

combination with either inhibitors of ATP synthesis (inhibitors to Inosine MonoPhosphate 

Dehydrogenase, IMPDH), inhibitors of de novo purine biosynthesis, or inhibitors of the salvage pathway 

of ATP biosynthesis, are more effective than protein kinase inhibitors used alone. 

ADVANTAGES: 

● Increased efficacy over available therapies due to use of drugs in combination therapy. 

● Use of lower dosage of kinase inhibitors, leading to a reduction in non-specific interaction with 

other cellular kinases. 

● Ability to target different pathways defective in cancer cells. 


METHOD FOR INHIBITING PROTEIN KINASES IN CANCER CELLS 

APPLICATIONS: 

● Chemotherapy of a variety of cancers such as chronic myeloid leukemia (CML), non-Hodgkin's 

lymphoma (NHL), non-small cell lung cancer (NSCLC) and other malignancies where protein 

kinase inhibitor drugs are useful. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 







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138. Phosphonate Esters of Nucleosides and Methods of Use for Same 

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141. PHOSPHOTYROSINE BINDING DOMAIN INVOLVED IN SIGNALING 

PATHWAYS THAT TRIGGER BREAST CANCER 

142. PII: S0301-472X(01)00681-6 

143. PORPHYRIN-BASED NEUTRON CAPTURE AGENTS FOR CANCER THERAPY 



144. Porphyrin-Based Neutron Capture Agents for Cancer Therapy 

145. Prodrugs of Pharmaceuticals with Improved Bioavailability 





148. Protein That Down Regulates Oncogenic Growth Factor Receptor 

149. PROTEIN WITH SIGNAL TRANSDUCTION ACTIVITY 

150. PSEUDOPTEROSIN AND SYNTHETIC DERIVATIVES THEREOF 

151. QUANTITATIVE ALLELE ANALYSIS: AN IMPROVED METHOD FOR 

ENUMERATING DNA COPY NUMBER OF MULTIPLE ALLELES 

152. QUANTITATIVE MEASUREMENT OF TISSUE PROTEIN IDENTIFIED BY 

IMMUNOHISTOCHEMISTRY AND STANDARDIZED PROTEIN DETERMINATION 

153. RAPID ACTIVATIOIN OF FLOURIDE-18 FOR USE IN POSITRON EMISSION 

TOMOGRAHY 

154. Rapid Assay For GSH In Biological Samples 

155. RECEPTOR ACTIVATION IN TUMORS 

156. RECOMBINANT PROLACTIN ANTAGONIST 

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INOSITOL KINASES 

158. REVERSIBLE INHIBITORS OF CYTOSINE-C5 DNA METHYLTRANSFERASE 

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160. ROLE OF THE VDUP1 GENE IN LIPID DISORDERS AND CANCER 

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162. Screening Assays For Glycosylation Inhibitors 

163. SINGLE AND MULTIPLE TYROSINE KINASE KNOCKOUT MICE 

164. SMALL INTERFERING RNA TO INHIBIT TRANSCRIPTION FACTOR 

EXPRESSION IN MAMMALIAN CELLS 

165. STRUCTURE OF ESTROGEN RECEPTOR AND CO-ACTIVATOR 

166. SYNTHESIS OF PROTEIN CONJUGATES FOR THE DEVELOPMENT OF 

IMMUNOASSAYS FOR AAL MYCOTOXINS 

167. TARGET FOR THERAPEUTICS FOR MODULATION OF THE IMMUNE SYSTEM 

168. The Use of Detergents to Enhance Drug Uptake In Vivo: With Particular Emphasis on 

Cancer Chemotherapy Agents 

169. Therapeutics and Diagnostic for Septic Shock 

170. THERAPY AND DIAGNOSIS OF CONDITIONS RELATED TO TELOMERE 

LENGTH AND/OR TELOMERASE ACTIVITY 

171. TOOLS FOR GENE DELIVERY AND TRANSFECTION 

172. TRANSCRIPTION FACTOR FOR THE REGULATION OF SKIN AND HAIR 

DEVELOPMENT 

173. Treating Cancer And Atherosclerosis With Photodynamic Therapy 

174. TREATMENT OF PLATELET DERIVED GROWTH FACTOR RELATED 

DISORDERS SUCH AS CANCER 

175. TUMOR-RELATED ENDOTHELIAL MARKER GENE 



176. UNIVERSAL VECTORS FOR DRUG DELIVERY 

177. Unnatural Amino Acids That Mimic Peptide Beta-Strands 

178. Use Of Infectious And Pathogenic Clone Of A Lung Cancer-Inducing Retrovirus For 

Generation Of Therapeutic Reagents And Diagnostic Tests Or Reage 

179. VECTORS AND CELL LINES FOR CLASS SWITCH RECOMBINATION 

180. VESOSOMES: BILAYER-ENCAPSULATED VESICLE AGGREGATES 

181. WNT AND FRIZZLED RECEPTORS AS POTENTIAL TARGETS FOR CANCER 

IMMUNOTHERAPY 

http://patron.ucop.edu/search97cgi/s97_cgi.exe?QueryZi...Order=Asc&ResultStart=101&ResultCount=100&ResultStyle= (6 of 6)10/21/2005 2:48:10 AM 

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NCD 

Search Result 


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Title 

1. A BREAST CANCER METASTASES TRANSGENE MODEL 

2. A CELL PROLIFERATION INHIBITOR 

3. A METHOD FOR CREATING NUCLEAR RECEPTOR ACTIVITY MODULATING 


4. A METHOD FOR CREATING SPECIFIC, HIGH AFFINITY NUCLEAR RECEPTOR 


5. A METHOD FOR IN VIVO VISUALIZATION OF MUTATED MOUSE CELLS 

6. A Method for Providing Unique Spatial Addresses for Molecules (With application to array 

diagnostics design for cancer therapy) 

7. A New EGF Receptor Associated With Inhibition Of Pancreatic Cancer Cell Growth 

8. A NEW ETS-RELATED GENE OVEREXPRESSED IN HUMAN BREAST AND 

EPITHELIAL CANCERS 

9. A New Strategy for Leukemia Therapy 

10. A NON-INVASIVE AND CLOSED LOOP SYSTEM FOR DETECTION AND 

TREATMENT OF PROSTATE CANCER 

11. A NOVEL THERAPEUTIC TARGET FOR BREAST CANCER 



12. A NOVEL TUMOR SUPPRESSOR GENE 

13. A SPECTROSCOPIC ASSAY FOR HELICASE ACTIVITY AND INHIBITORS 

14. A SYSTEM FOR TARGETING INVASIVE PATHOGENS AND CANCER CELLS FOR 

ATTACK BY THE HUMAN IMMUNE SYSTEM 

15. A TISSUE-SPECIFIC SELF-PROPAGATING RETROVIRAL VECTOR SYSTEM FOR 

GENE THERAPY 

16. AMPLIFIED AND OVEREXPRESSD GENE IN COLORECTAL CANCERS 

17. ANIMAL MODEL OF HPV-INDUCED DYSPLASIA 

18. ANTI-CD22 MONOCLONAL ANTIBODIES USED FOR THE TREATMENT OF 

LYMPHOMA AND LEUKEMIA 

19. ANTICANCER SEED EXTRACT 

20. AP1 ASSAY FOR ESTROGEN RECEPTORS ER-ALPHA AND ER-BETA 

21. ASSAY OF GTP/GDP BOUND TO RAS AND OTHER G PROTEINS 

22. ASSAYS AND ANTIBODIES FOR N-MYC PROTEINS 

23. ASSESSMENT OF ALLELE-SPECIFIC EXPRESSION IN CELLS AND TISSUE 

24. Asthenons: Novel Gene Expression Attenuator Elements 

25. BIFUNCTIONAL CHELATORS FOR RADIODIAGNOSIS/ THERAPY AND METHOD 

FOR THEIR EFFICIENT RADIOLABELING 

26. BLEOMYCIN BIOSYNTHETIC GENES 







29. BORON COMPOUNDS SUITABLE FOR LIPOSOMAL DELIVERY TO TUMORS FOR 

THE PURPOSE OF BORON NEUTRON CAPTURE THERAPY 

30. BRAIN GLYCOGEN PHOSPHORYLASE CANCER ANTIGEN 

31. Cancer Vaccine 

32. CLONED RECEPTOR FOUND IN BREAST CANCER CELLS 

33. CNL878, A Cytotoxic and Antifungal Terpene from a Marine Fungus 

34. COMBINED USES OF IMPDH INHIBITORS WITH TOLL-LIKE RECEPTOR 

AGONISTS 

35. CONSTRAINTS-BASED ANALYSIS OF GENE EXPRESSION DATA 

36. COUMARIN COMPOUNDS AS MICROTUBULE STABILIZING AGENTS AND 

THERAPEUTIC USES THEREOF 

37. CYTOTOXIC ANTIBODY FUSION PROTEIN 

38. DETECTION OF ATM MUTATIONS AND POLYMORPHISMS WITH MEGA-SSCP 

39. DETECTION/DEPOLYMERIZATION OF POLYSIALIC ACID CHAINS IN VARIOUS 

DEVELOPMENTAL AND DISEASE STATES 

40. DEVELOPMENT OF NEW SELECTIVE ESTROGEN RECEPTOR MODULATORS 

(SERMs) 

41. DIAGNOSIS AND TREATMENT OF CRYPTOSPORIDIOSIS, INCLUDING HUMAN 

VACCINE 

42. DIAGNOSTIC TEST FOR CANCER SUSCEPTIBILITY 

43. DIAGNOSTIC TEST FOR MUTATIONS IN THE AT GENE 



44. Dianestatin: A New Tumor-Specific Cytotoxin Conjugate 

45. DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HER-2/NEU 

OVEREXPRESSION 



48. DIRECT ASSAY FOR ANDROGEN RECEPTOR MODULATORS 

49. DNA BINDING COMPOUNDS FOR GENETIC REGULATION AND MEDICAL 

DIAGNOSIS AND THERAPY 

50. EARLY DETECTION OF COLON CANCER 

51. Early Detection Of Pancreatic & Other Cancers 

52. END-SPECIFIC ANTIBODY TO DETECT APOPTOSIS 

53. ENDOSCOPIC LASER INSTRUMENT 



56. EPLIN, A MARKER FOR HUMAN CANCER 

57. EXONS 4 AND 7 ENCODE SEPARATE TRANSACTIVATING AND CHROMATIN- 

LOCALIZING DOMAINS IN ESX 

58. EXPRESSION AND PURIFICATION OF ATM PROTEIN USING VACCINIA VIRUS 

59. EXPRESSION OF HUMAN NUCLEAR RECEPTORS IN MICE 



60. FAS-ASSOCIATED FACTOR 1 

61. FLUORESCENCE ASSAY FOR DNA-MODIFYING ENZYMES: APPLICATIONS TO 

HIGH THROUGHPUT LIBRARY SCREENING OF POTENTIAL REGULATORS 

62. FROZEN TISSUE MICROARRAY TECHNOLOGY FOR ANALYSIS OF RNA, DNA, 

AND PROTEINS 

63. GDOX, A NOVEL CANDIDATE PROTO-ONCOGENE 

64. GLUCOSE EMULATING RADIOPHARMACEUTICAL FOR CONVENTIONAL 

GAMMA CAMERA IMAGING 

65. HER-2/NEU OVEREXPRESSION ABROGATES GROWTH INHIBITORY PATHWAYS 

66. HER2 AND HER3 APTAMERS 


SPHINGOLIPIDS 


SPHINGOLIPIDS 


SPHINGOLIPIDS 


SPHINGOLIPIDS 

71. IDENTIFICATION, CLONING AND CHARACTERIZATION OF A NOVEL HUMAN 

HDAC HIGHLY EXPRESSED IN THE THYMUS 

72. IDENTIFICATION, DIAGNOSIS AND THERAPY FOR CELL DEATH-RELATED 

DISEASES 

73. Imaginal Cell Growth Factor 

74. IMPROVED LIPOSOMAL ENCAPSULATION OF DRUGS 






78. IN VITRO SCREEN TO IDENTIFY COMPOUNDS WITH ESTROGENIC OR ANTI- 

ESTROGENIC ACTIVITY 

79. INDUCTION OF PHAGOCYTIC HOST DEFENSE 



82. INHIBITORS OF ANDROGEN ANTAGONISTS-REFRACTORY PROSTATE CANCER 



85. IRRADIATED PROBIOTIC FOR IBD 

86. ISS RECEPTOR AS A DRUG DISCOVERY TOOL 

87. KNOWN HORMONE WITH POTENTIAL THERAPEUTIC ACTION IN BRAIN 

DISEASES 

88. LIPOSOMAL DELIVERY OF ISS-BASED VACCINES 

89. LIPOXYGENASE INHIBITORS AS DRUGS AGAINST CANCER, ASTHMA AND 

ATHEROSCLEROSIS 

90. LIQUID ASSOCIATION WITH APPLICATION IN GENE EXPRESSION 

91. LONG WAVELENGTH PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY 

AND DIAGNOSIS OF TUMORS 



92. MACROMOLECULE-LIPID COMPLEXES FOR SYNTHETIC GENE-DELIVERY 

SYSTEMS 

93. MACROPHAGE-COLONY STIMULATING FACTOR CRYSTALS 

94. MAGNETIC RESONANCE FOR EVALUATING TISSUE NECROSIS IN 

NEOPLASTIC, INFLAMMATORY AND INFECTIOUS DISORDERS 

95. MECHANOSENSORY TRANSDUCTION CHANNEL GENE 

96. METHOD FOR DEVELOPING ANTAGONISTS FOR NUCLEAR HORMONE 

RECEPTORS 

97. METHOD FOR DIAGNOSING BREAST CANCER 

98. METHOD FOR EARLY DIAGNOSIS OF, AND DETERMINATION OF PROGNOSIS 

IN, CANCER 

99. METHOD FOR ENHANCING AN IMMUNE RESPONSE 

100. METHOD FOR INHIBITING PROTEIN KINASES IN CANCER CELLS 

http://patron.ucop.edu/search97cgi/s97_cgi.exe?QueryZi...rtOrder=Asc&ResultStart=1&ResultCount=100&ResultStyle= (7 of 7)10/21/2005 2:48:12 AM 

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METHOD FOR MAKING UNIVERSAL DONOR CELLS 



Although there is acceptable graft survival in the first year for nearly all types of transplants, by five and 

ten years after transplantation, only 40-50% of all grafts are still functioning. This low rate is due to the 

relentless attack of the graft recipient's immune system on the graft tissue. In addition, the 

immunosuppressant drugs used to treat transplant recipients cause a non-specific depression of the 

immune system, making the patient far more susceptible to life-threatening infections and a variety of 

neoplasia. The low rate of long term success, and the serious risks of infection and cancer are the two 

main challenges now facing the entire field of tissue and organ transplantation. 

Scientists at the University of California have developed a method for creating "universal donor" cells 

and organs that are invisible to the immune system. The problem of rejection is thus eliminated without 

resorting to nonspecific immunosuppression, leaving the immune system active to defend against 

infection and neoplasia. 

The U.C. method entails creating transplantation antigen-depleted cells. The reduced levels of 

transplantation antigens expressed on the surface of the donor cells, tissues or organs cause them not to 

be recognized as foreign and not to elicit a rejection response. This will lead to improved graft survival 

rates in the recipient and result in lower levels of immunosuppressant drug administration when 

necessary. This U.C. method also has applications in the treatment of individuals with autoimmune 

diseases characterized by dysfunctional expression of a transplantation antigen. 



US Patent # 5,859,226 issued January 12, 1999; US Patent # 6,410,721 issued 


June 25, 2002 










Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




Method for Rational Induction of Drought Resistance in Plants Suppression of Stomatal Farnesyl Transferase Activity 

Method for Rational Induction of Drought Resistance in Plants Suppression of 

Stomatal Farnesyl Transferase Activity (SD98-83 & SD99-020) 

BACKGROUND: A major influence on the successful harvest of nearly every type of crop is adequate 

rainfall or irrigation. Particularly at critical phases in crop life cycle, drought conditions can delay, 

diminish or destroy productivity. Naturally drought resistant and zone plants acutely control water 

metabolism through modification of stomatal opening. A simple and robust technology has now been 

developed which imparts exceptional drought resistance to any crop plant through manipulation of the 

enzyme famesyl transferase. This enzyme plays a key role in mediating the hormonal regulation by 

Abscisic Acid (ABA) of stomatal opening and moisture retention during light and dark cycles. Inhibition 

or suppression of famesyl transferase activity results in prolonged stomatal closing and water retention. 

DESCRIPTION: Non-toxic chemical inhibitors of the enzyme originally developed for pharmaceutical 

use have been demonstrated to effectively impart drought resistance when applied to plants (wheat, 

arabidopsis). Block of protein farnesylation has a protective anti-cancer activity in animals. The 

technology thus can be used to impart temporary drought resistance as needed by spray application to 

the crop. Alternatively, the invention can be delivered via anti-sense suppression of the enzyme by 

transgenic constructs under the control of stomatal-specific promoters which have been characterized. 

ADVANTAGES: For the first time, it should be possible to protect from transient drought conditions 

any crops, ranging from grains to high value ornamentals, to forestry species. The approach would 

involve an enzyme inhibitor spray or an activatible transgene incorporated into the plant. Both 

approaches have been tested successfully. 

CASE NUMBER: SD98-093 & SD99-020 


METHOD FOR SELECTIVE METHIONINE STARVATION OF MALIGNANT CELLS 


METHOD FOR SELECTIVE METHIONINE STARVATION OF 

MALIGNANT CELLS 

BACKGROUND: The amino acid methionine (MET) is necessary for the growth of normal and 

malignant cells. For some malignant cells, this requirement is absolute, i.e., without an adequate supply 

of MET, the cells die. In mammalian cells, MET is obtained from three sources, from the diet, from 

biochemical synthesis of MET from homocysteine, and from conversion of methylthioadenosine (MTA) 

to MET by the enzyme methylthioadenosine phosphorylase (MTAP). 

Researchers have identified many malignant cell lines and cancers that lack MTAP and cannot, 

therefore, convert MTA to MET. MTAP negative cells principally fulfill their requirement for MET 

through conversion of homocysteine; when homocysteine is not available, the cells generally die. 

Theoretically, therefore, one could starve malignant cells that lack MTAP by degrading plasma MET 

and homocysteine. Normal MTAP positive cells would escape starvation by their ability to convert 

MTA to MET. This strategy could potentially serve as a treatment for MTAP negative cancers. 

DESCRIPTION: Researchers at the University of California have patented a method for selectively 

starving MTAP negative cells in a mammal. First, cells that are suspected of being MTAP negative are 

tested to determine whether transcript for MTAP is present. Once lack of transcript is confirmed, a 

therapeutically effective amount of an enzyme, called METase, that degrades both MET and 

homocysteine is administered. This serves to eliminate potential sources of MET for MTAP negative 

cells, causing them to starve. At the same time that METase is administered, MTA or an analog (such as 

EFA) is also given to the mammal, thus ensuring that cells expressing MTAP are kept alive. 

APPLICATIONS: This patented method of selective methionine starvation of malignant cells in 

mammals could be an important tool in the treatment of MTAP-negative cancers, such as melanoma, 

lymphoma, leukemia, lung cancer, breast cancer and glioma. 




METHOD FOR SELECTIVE METHIONINE STARVATION OF MALIGNANT CELLS 



US Patent # 5,571,510 issued November 5, 1996; US Patent # 6,210,917 issued 

April 3, 2001 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




METHOD OF ANALYZING ATAXIA-TELANGIECTASIA PROTEIN 







instability and sensitivity to ionizing radiation. People who are carriers of AT (i.e. are heterozygous for 

AT mutations) often exhibit adverse health effects as well. In particular, carriers of AT have increased 

susceptibility to various cancers, particularly breast cancer, as well as heart disease, compared to their 

homozygous normal counterparts. It is therefore clinically important to have a test to determine the level 

of ATM protein in an individual. 

DESCRIPTION: Researchers at the University of California have developed a highly sensitive and 

specific ELISA to measure the level of ATM protein in an individual. This method is sensitive enough 

to distinguish the level of protein expressed in normal individuals, heterozygous carriers and 

homozygous mutants. 

ADVANTAGES: 

● The ELISA is rapid and can be used to test large numbers of samples. 

● Provides an important screening tool of a risk factor for breast cancer. 

APPLICATIONS: 

● Screening patients to determine whether they are carriers of AT, and therefore have increased 

susceptibility to breast cancer and heart disease. 

● Diagnosing AT through measurement of the levels of ATM protein. 

SEE ALSO: EXPRESSION AND PURIFICATION OF ATM PROTEIN USING VACCINIA VIRUS 

and DIAGNOSTIC TEST FOR MUTATIONS IN THE AT GENE 






● Biotechnology > Immunology systems > Immunodiagnostics 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






METHOD OF INHIBITING ANGIOGENESIS 



BACKGROUND: Angiogenesis, the growth of new blood vessels, is an important physiological 

process both for normal health and disease. In healthy people, angiogenesis is crucial for healing wounds 

and for restoring blood flow to tissues after injury or insult. In females, angiogenesis also occurs during 

the monthly reproductive cycle and during pregnancy. In many serious diseases states, however, 

including cancer, diabetic blindness, age-related macular degeneration, rheumatoid arthritis, psoriasis 

and more than 70 other conditions, angiogenesis is deregulated such that too much angiogenesis occurs. 

Therefore, methods of inhibiting angiogenesis may be of clinical importance. 

DESCRIPTION: Researchers at the University of California have identified a new role for a cell 

surface receptor expressed on multiple cell types, in in vivo angiogenesis. They have found that blocking 

this receptor inhibits in vivo angiogenesis on chick chorio-allontoic membranes in response to VEGFA. 

These results suggest that blocking this receptor may be an important strategy for inhibiting 

angiogenesis. 

APPLICATIONS: Human blocking antibodies, peptides, or small molecule inhibitors that block this 

receptor may be useful in treating diseases characterized by excessive angiogenesis, such as cancer, 

diabetic blindness, age-related macular degeneration, rheumatoid arthritis, and psoriasis. 








Oakland, CA 94607-5200 





Phone: (510) 587-6000 Fax: (510) 587-6090 




METHOD TO IDENTIFY EDITED mRNA'S 



BACKGROUND: Messenger RNA's can be modified post-transcriptionally, by a process known as 

RNA editing, to produce a protein product or products different from what would be predicted from the 

genomic DNA sequence. There are several enzymes involved in editing mRNA. Overexpression of one 

such RNA editing protein in the liver and intestine of transgenic mice leads to the development of liver 

cancer or obesity, implying that RNA editing normally plays a critical role in controlling these diseases. 

DESCRIPTION: UC scientists have developed a method to identify and clone edited genes from a 

library of cDNAs or in electronic databases of sequenced DNA. 

APPLICATIONS: The new method can be used to identify the edited genes involved in cancer and 

obesity. More generally, the methods can be used to identify and clone any novel edited gene. 










Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 








METHODS AND MATERIALS FOR CHARACTERIZING AND MODULATING INTERACTION BETWEEN HEREGULIN AND HER3 


METHODS AND MATERIALS FOR CHARACTERIZING AND 

MODULATING INTERACTION BETWEEN HEREGULIN AND 

HER3 

BACKGROUND: The HER2 receptor is overexpressed in ovarian and breast cancer cells and this 

overexpression has been correlated with increased morbidity and mortality. HER2 forms a heterodimer 

complex with the related receptor HER3, and this complex has a growth stimulatory response when 

activated by the ligand heregulin. Therefore, it has been suggested that binding of heregulin to the HER2/ 

HER3 heterodimer may be important in the pathogenesis of breast and ovarian cancer. However, the 

domains of HER3 involved in ligand binding and heterodimerization have not been identified. 

DESCRIPTION: Researchers at the University of California have identified and characterized the 

domains in the HER3 receptor that interact with the heregulin ligand and HER2. Using this information, 

they have developed HER3 variant polypeptides that bind heregulin but have impaired binding to HER2. 

These polypeptides inhibit the interaction between wild type HER3 and heregulin. Methods for making 

these peptides are available. In addition, methods for identifying compounds that specifically bind to the 

heregulin binding domain of the polypeptides or that inhibit the interaction between variant HER3 and 

wild-type HER3 are available. Additional methods are available for screening for compounds that either 

increase or decrease heregulin induced tyrosine kinase activity. 

ADVANTAGES: The discovery of the domains responsible for binding of HER3 to heregulin 

represents a novel basis for the development of therapeutics for breast and ovarian cancer. 

APPLICATIONS: 

● The screening methods may be used to identify compounds that inhibit heregulin binding and/or 

HER3 activity. 

● These compounds can be used to develop novel therapeutics for the treatment of breast and 

ovarian cancer. 

PATENT STATUS: U.S. Patent Application Publication No. 20030413568 


METHODS AND MATERIALS FOR CHARACTERIZING AND MODULATING INTERACTION BETWEEN HEREGULIN AND HER3 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






METHODS FOR DETECTION AND TREATMENT OF NEURAL CANCERS 


METHODS FOR DETECTION AND TREATMENT OF NEURAL 

CANCERS 

BACKGROUND: Cancer is the result of cumulative multiple genetic mutations, which result in the 

activation of oncogenes and/or the inactivation of tumor suppressor genes. It is the differential 

expression of these critical genes and their downstream effectors that enables cells to override growth 

controls and undergo carcinogenesis. While a variety of methods are currently employed to isolate genes 

associated with particular differential phenotypes, these techniques identify tissue-enriched mRNAs 

rather than tissue-specific proteins. Thus, there remains a need for a differential screening technique that 

provides actual confirmation of the presence of a protein product, not just the capacity to synthesize a 

protein. In addition, there is a need for proteins with antigenic determinants that may be recognized by 

the immune system. 


identifying differentially expressed gene products that are translated from mRNA species. This method, 

termed differential immuno-absorption (DIA), uses subtractive antibody-based screening of target versus 

control tissues followed by screening of a cDNA expression library to identify differentially expressed 

proteins. DIA can be coupled to cDNA microarray hybridization and used in the identification of genes 

that play a role in the malignant progression of cancer. 

Using this method, the researchers identified a putative growth factor gene, granulin D, which may play 

a role in the malignant progression of glioblastomas. The researchers determined that granulin D 

stimulates growth of glial cells in vitro. In addition, antibodies to granulin D inhibit growth of earlypassage 

human brain tumor cell cultures in vitro. Thus, inhibition of granulin D could be of clinical 

importance. 

ADVANTAGES: 

● The new method selects gene products that are actually translated from mRNA species. 

● Antibodies to clones of interest can be generated for antibody-based studies. 

APPLICATIONS: 


METHODS FOR DETECTION AND TREATMENT OF NEURAL CANCERS 

● Identification of gene products that are differentially expressed in tumors 

● Development of therapeutics for nervous system cancer based on inhibition of granulin D 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






METHODS FOR IDENTIFYING NOVEL THERAPEUTICS AND DIAGNOSTICS IN THE p53 PATHWAY 


METHODS FOR IDENTIFYING NOVEL THERAPEUTICS AND 

DIAGNOSTICS IN THE p53 PATHWAY 

BACKGROUND: Current non-surgical cancer therapies rely on the use of compounds or radiation 

doses that are non-specific for the tumor cells and are highly toxic to humans. Although these treatments 

are particularly effective against tumor cells, they are also destructive to the surrounding normal cells, 

which leads to severe side effects. In addition, the non-specificity of these therapies limits their efficacy. 

Efforts to develop more specific treatments have focused on targeting the defective processes in the 

tumor cells, such as those involving mutations in oncogenes and tumor suppressor genes. One of the 

most desirable molecular targets for clinical intervention in cancer is the p53 tumor suppressor gene, 

since it is the most frequently mutated gene in human cancers. However, scientists have encountered 

difficulty in studying the anti-tumor function of p53 due to limited simple situations in which to study 

the gene. In particular, it has not been possible to take advantage of classical genetic methods to identify 

genes that act with p53 to suppress tumor formation. 

DESCRIPTION: Scientists at the University of California have developed a method for discovering 

genes that regulate, are regulated by, or act in conjunction with the tumor suppressor gene p53. In 

addition, scientists can use this system to search for compounds that restore function to mutant forms of 

p53 commonly found in cancer or that are specifically toxic to cancer cells defective for p53 function. 

APPLICATIONS: This new invention has applications in discovering new therapeutics or 

prophylactics as well as diagnostic or prognostic tests for cancer. 


● Classical genetics can now be used to identify p53- relevant proteins; 

● Provides a means for identifying anti-cancer agents. 




METHODS FOR IDENTIFYING NOVEL THERAPEUTICS AND DIAGNOSTICS IN THE p53 PATHWAY 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




METHODS FOR INCREASING A CYTOTOXIC T LYMPHOCYTE RESPONSE IN VIVO 


METHODS FOR INCREASING A CYTOTOXIC T LYMPHOCYTE 

RESPONSE IN VIVO 

BACKGROUND: Immunostimulatory nucleic acid molecules are DNA sequences, originally found in 

bacteria, that enhance the immune system through activation of cells and proteins important for immune 

function. One way these molecules work is through activation of cytotoxic T cells. Cytotoxic T cells 

(CTLs) recognize and destroy cells in the body that have been altered, e.g. by infection with a virus or 

by transformation into cancer cells. It is unclear whether immunostimulatory nucleic acid molecules 

activate CTLs directly, or instead require helper T cells for this function. 

DESCRIPTION: Researchers at the University of California have discovered that immunostimulatory 

nucleic acid molecules linked to specific antigens can directly activate CTLs, without the need to use 

helper T cells as a go between. This property makes it possible to use immunostimulatory nucleic acid 

molecules to increase CTL function in helper T cell deficient individuals, such as those undergoing 

chemotherapy, with AIDS, or with hereditary immunodeficiencies. Methods of using 

immunostimulatory nucleic acid molecules to increase CTL activity in helper T cell deficient individuals 

have been patented by the researchers and are available for licensing. 

ADVANTAGES: This invention provides, for the first time, methods for activating CTLs in helper T 

cell deficient individuals, thereby helping these individuals to combat opportunistic infections. 

APPLICATIONS: May be useful in the treatment of infections in individuals with: 

● Temporary immunodeficiency due to radiation therapy, chemotherapy, bone marrow 

transplantation, or organ transplant. 

● Acquired immunodeficiency such as AIDS. 

● Primary immunodeficiency. 




METHODS FOR INCREASING A CYTOTOXIC T LYMPHOCYTE RESPONSE IN VIVO 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




METHODS FOR INHIBITING NUCLEAR RECEPTORS 



BACKGROUND: Nuclear receptors represent a superfamily of proteins that bind and mediate action of 

hormones, vitamins, prostaglandins and other small molecule ligands. They are ligand-dependent 

transcription factors that control many important physiological processes such as cellular differentiation, 

metabolism, development and cell death. It has been recognized that dysfunctional nuclear receptor 

mediated signaling results in diseases such as cancer, obesity, infertility and diabetes and consequently, 

therapeutic modulation of nuclear receptor ligand binding by agonists or antagonists has gained much 

attention. 

Traditional methods of screening compounds have yielded some drugs currently in use such as 

tamoxifen for oestrogen receptors (for breast cancer) or thiazolidinediones for PPAR-gamma (for type II 

diabetes). However, since the nuclear receptor family proteins have an extensive overlap in their overall 

architecture, a more rational approach to drug design that exploits divergences in the ligand binding 

domains of individual members will yield selective agonists or antagonist drugs. Knowledge of the three 

dimensional structure of nuclear receptor with the bound ligand would greatly aid not only in design of 

drugs targeted to specific nuclear receptors but also help in understanding of their mechanism of action. 

DESCRIPTION: : Researchers at the University of California have discovered the co-crystal structure 

of the human Thyroid Hormone (TR) beta-receptor with a hormone analog and with a novel synthetic 

ligand. Based on the structure of the ligand binding region, the researchers have designed a series of 

analogs that function as agonists or antagonists of TR. The invention also provides methods for 

computational design and methods for identifying compounds that selectively modulate the activity of 

TR including those for general use in drug design for nuclear receptors with known ligands or other 

orphan receptors. 

ADVANTAGES: 

● Avoids time-consuming and expensive trial and error methods of compound screening. 

● Permits design of novel antagonists and agonists to thyroid hormone receptor with increased 

selectivity and affinity. 

● Permits design of compounds that modulate specific subsets of functions of TR. 

● Allows design of compounds with degrees of full, partial or inverse activity. 



APPLICATIONS: 

The invention could be used to design drugs for diseases involving defective nuclear receptor signaling 

in general. More specifically, medical conditions that involve defective thyroid hormone receptor 

mediated function include: 

● Hypercholesterolemia, hypertriglyceridemia, obesity, tachycardia and atrial arrhythmias. 



US Patent # 6,236,946 issued May 22, 2001; US Patent # 6,266,622 issued July 


24, 2001 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






METHODS FOR SCREENING NUCLEAR TRANSCRIPTION FACTORS FOR THE ABILITY TO MODULATE AN ESTROGEN RESPONSE 


METHODS FOR SCREENING NUCLEAR TRANSCRIPTION 

FACTORS FOR THE ABILITY TO MODULATE AN ESTROGEN 

RESPONSE 

BACKGROUND: Estrogen is a steroid hormone that plays an important role in uterine, breast and bone 

development by modulating transcription of specific genes. Estrogen acts by first binding to a specific 

nuclear receptor, called the estrogen receptor. This interaction induces a conformational change in the 

receptor, allowing it to bind to specific recognition sequences in the DNA, called "response elements", 

located upstream of regulated genes. The estrogen receptor can bind to two different response elements, 

called AP-1 and the estrogen response element (ERE). This binding serves to modulate transcription of 

estrogen-regulated genes. 

The effect of estrogen on gene transcription can be modulated by many different compounds, including 

ligands for other nuclear transcription factors, their agonists, and their antagonists. This modulation of 

estrogenic activity has complex effects that may be beneficial or harmful. For example, agonistic 

activity may have beneficial effects, such as preventing osteoporosis and reducing serum cholesterol. 

Conversely, agonist activity can also be harmful. For example, tamoxifen, used as an estrogen antagonist 

in the treatment of breast cancer, can act as an estrogen agonist in the uterus and can increase 

endometrial tumor incidence. Because of the widespread use of nuclear transcription factor ligands as 

therapeutics, it is important to determine what role these ligands might have on the estrogen response. 

DESCRIPTION: Researchers at the University of California have invented a method for testing the 

effect of nuclear receptor ligands, and putative or known transcription factor ligand agonists or 

antagonists, on estrogen-activated transcription. In this method, a cell is first transfected with an 

estrogen receptor, a receptor for the nuclear transcription factor ligand, and a promoter comprising either 

an AP-1 site or an ERE site that regulates expression of a reporter gene. In some cases, both sites can be 

used, each regulating expression of a different reporter gene. The cell is then contacted with a compound 

having estrogenic activity, in the presence or absence of a nuclear transcription factor ligand, and 

expression of the reporter gene is analyzed. 

ADVANTAGES: 


METHODS FOR SCREENING NUCLEAR TRANSCRIPTION FACTORS FOR THE ABILITY TO MODULATE AN ESTROGEN RESPONSE 

● Provides rapid and inexpensive evaluation of transcriptional activity rather than time consuming 

and expensive monitoring of physiological changes induced by hormonal treatment in animals. 

● Allows effects on AP-1 and ERE response elements to be distinguished. 

APPLICATIONS: 

● Permits the identification of transcription factor agonists or antagonists that either act on or act 

independently of the estrogen response. 

● Facilitates the design and administration of therapeutics whose activity is well characterized 




● Biotechnology > Animal biotech systems > Animal hormones 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






MICROMACHINED CANTILEVERS FOR BIOAGENT DETECTION 



BACKGROUND: Biosensing devices with mechanical detection systems use microcantilever bi- 

material (e.g. Au-Si) beams as sensing elements. The metal side is generally coated with a particular 

receptor, which then binds with the analyte (e.g., biological molecules such as proteins or biological 

agents). This causes the microcantilever to deflect in a way proportional to the analyte concentration. 

Biochips having microcantilevers as sensing elements do not require external power, labeling, external 

electronics, or fluorescent molecules for operation or signal transduction. These advantages make these 

type of biochips promising for screening certain diseases, such as cancer, and detecting specific 

hazardous chemical and biological warfare agents, such as botulinum toxin, anthrax, and aflatoxin. Early 

detection of chemical and biological agents in the body or environments allow for early treatment of 

patients before symptoms appear. However, current mechanical detection systems present a few 

disadvantages. Turbulence in the liquid flow affects the accuracy of the measurements, while drift due to 

slow electromechanical reactions on cantilever surfaces decreases sensitivity, especially for low analyte 

concentrations. 

DESCRIPTION: Scientists at the University of California have developed novel microcantilever 

assemblies for detection systems that can be fabricated and integrated into biochips. These devices 

overcome the drawbacks of current detection systems by using new photomechanical, exterior mass 

loading, and piezoresistive effects, as well as dynamic and thermal control of the flow characteristics. 

APPLICATIONS: This new UC invention has applications in screening and early detection of 

biological and chemical agents in individual patients as well as in a given environments. 


● Increases the biosensitivity of the cantilevers through increased biosensing area; 

● Improved sensitivity for low analyte concentrations; 

● Can be integrated into biocompatible microfluid channel devices that could be deployed in the 



field or from aircraft for biowarfare detection. 




● Test & Measurement > Analyzers 

● Test & Measurement > Detection eqp 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






MODIFIED PCR FOR QUANTITATIVE GENE ANALYSIS 



Polymerase Chain Reaction (PCR) is a widely used laboratory method that permits rapid amplification 

of DNA or cDNA. It is limited with respect to gene quantification because of the exponential 

amplification of DNA, the tendency to occasionally amplify non-specific DNA, and the semiquantitative 

character of such common DNA measurement techniques as Southern blotting or 

densitometry. While there have been attempts to use internal amplification standards and hybridization 

with sequence-specific oligonucleotides to improve PCR quantification, the difficulty of precise 

quantification with sequence-specific probes (involving competition with DNA strands that complement 

the probe target, background problems with membranes, and nonavailability of sensitive measurements 

of bound probes) still remains. 

A modified form of PCR has been developed by scientists at the University of California for overcoming 

this limitation. The UC method combines certain features of PCR and enzyme-linked immunoassay 

(ELISA) techniques for accurate, high-precision measurements of hybridization with sequence-specific 

probes. Unlike Southern blotting, the combined PCR-ELISA allows for complete removal of competing 

DNA strands prior to hybridization and does not have the background problems associated with 

membranes. The quantification of the input DNA using this method is independent of the number of 

PCR amplification cycles, and can be calculated automatically with a standard laboratory ELISA plate 

reader. 

With these advances over current technology, the UC gene quantification method should find wide 

application in a variety of diagnostic and research applications in clinical chemistry, microbiology, and 

genetics. Possible applications include: 

● Diagnosis and typing of infectious diseases such as HIV, venereal diseases, hepatitis, 

mycobacterial infections, etc.; 

● HLA typing for organ transplantation and autoimmune disease diagnosis; 

● Cancer diagnosis through oncogene detection; 

● Diagnosis of genetic diseases; and 

● Monitoring of inflammatory diseases by assaying cytokine gene expression. 












Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






Modulation Of Cell Growth And Growth Factor Signaling Through Removal Of Glypicans 



UC CASE 1998-280-3 

NUMBER: 

TITLE: Modulation Of Cell Growth And Growth Factor Signaling Through 

Removal Of Glypicans 

DEPARTMENT: Developmental & Cell Biology 

SUMMARY: Growth of tumor cells is controlled by growth factors, several of which are of the 

classes that would be expected to be sensitive to the removal of 

glycosylphosphatidylinositol-anchored (GPI-anchored) proteins. In tissue culture, 

when pancreatic cancer cells were treated with an enzyme that removes GPIanchored 

proteins, these cells became insensitive to two growth factors that drive 

their growth. Furthermore, this enzyme was sufficient to remove all proteoglycan 

function from these cells and is expected to have therapeutic value. In pancreatic 

cancer cells, glypican-1, a GPI-anchored protein, is strongly and specifically 

overexpressed. Because many types of cells shed glypican-1 in soluble form, we 

would expect to find glypican-1 in the serum of patients with pancreatic cancer (and 

perhaps other cancers). Thus, the levels of serum glypican-1 can be used as a 

diagnostic marker in pancreatic (and perhaps other) cancer. 






Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


Molecular Cytological Evaluation For Pancreatic Cancer By Screening Liquid Stool 



UC CASE 1992-099-1 

NUMBER: 

TITLE: Molecular Cytological Evaluation For Pancreatic Cancer By 

Screening Liquid Stool 



















Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


Molecular Cytological Evaluation For Pancreatic Cancer By Screening Pancreatic Juice 



UC CASE 1992-100-1 

NUMBER: 

TITLE: Molecular Cytological Evaluation For Pancreatic Cancer By 

Screening Pancreatic Juice 



















Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


Molecular Signature Test For Pancreatic Cancer 



UC CASE 1992-098-1 

NUMBER: 

TITLE: Molecular Signature Test For Pancreatic Cancer 



















Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


Multimeric Forms of CD40L and Other TNF Family Members 

Multimeric Forms of CD40L and Other TNF Family Members 

UCSD researchers have developed an invention useful for: 

1. augmenting immunity (both cellular and antibodies) against cancer and infectious 

diseases 

2. expanding immune cells (B cells, dendritic cells, macrophages and T cells) in vitro 

for reinfusion of them or their products 

3. immunological testing of immune function. In one embodiment, the invention is a 

soluble recombinant fusion protein containing multiple CD40 ligands ("CD40L"). 

This protein affects macrophages and B cells in the same manner as membrane CD40L. The 

same technology can be applied to produce other members of the TNF family, such as TNFalpha, 

FasL, TRAIL, RANKL, 4-1BBL, and others. 

The advantages of this new form of CD40L are: 

● Versatile - treatment for cancer and infectious disease agents such as HIV and 

Mycobacterium tuberculosis; vaccines; expanding immune cells; and diagnostic tests of 

immune function; may have utility in neutralizing autoimmune response in diseases such 

as lupus or multiple sclerosis. 

● Potent - affects macrophages and B cells in the same manner as membrane CD40L. 


MURINE MODEL FOR EPITHELIAL NEOPLASTIC PROGRESSION 


MURINE MODEL FOR EPITHELIAL NEOPLASTIC 

PROGRESSION 

The malignancies most frequently encountered in clinical practice arise in epithelial tissues, including 

lung, colon, breast, liver, head and neck, and cervical cancers. These cancers typically develop through 

multiple stages in response to a diverse array of factors; consequently it is an important goal of cancer 

research programs to identify and characterize the molecules which regulate the progression through 

various stages of neoplastic development so that early detection and treatment becomes possible. 

University of California researchers have expressed the oncogenes of a human DNA tumor virus in basal 

cells of squamous epithelia in transgenic mice. The transgenic epidermis displays a multi-step neoplastic 

progression, ultimately leading to the development of invasive squamous cancers. Thus, these mice offer 

a general model for spontaneous neoplastic progression which, unlike previous murine models for 

carcinogenesis, is predictable and faithfully recapitulates the genesis of human cancers. Among the key 

parameters identified are the early activation of matrix metallo-proteinases and consequent remodeling 

of the dermis, inductive and progressive upregulation of angiogenesis, and immune surveillance. It is 

also anticipated that these mice will provide powerful research tools that the pharmaceutical industry can 

employ in assessing the specificity, potency, and efficacy of novel anti-cancer agents. 










MURINE MODEL FOR EPITHELIAL NEOPLASTIC PROGRESSION 



Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




New Laser Based Treatment Of Bacterial Infections 



UC CASE 1995-164-1 

NUMBER: 

TITLE: New Laser Based Treatment Of Bacterial Infections 

SUMMARY: Researchers at the University of California, Irvine have developed a photodynamic 

therapeutic technique for the elimination of bacterial infections. One example of an 

application of this technique is in the case of digestive system infections where there has 

been a close link established between gastric Helicobacter Pylori colonization and 

various forms of gastritis, gastric and duodenal ulcers as well as a possible link to gastric 

cancer. This technique would enjoy exceptional utility where side effects of traditional 

chemo-therapy are problematic due to poor tolerance, poor compliance, and multiple 

recurrence. This new technique would virtually eliminate all of the complications arising 

from conventional treatment. 

CONTACT: James Song - UCI 

Email: jimsong@uci.edu 




Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


NEW USES FOR INHIBITORS OF INOSINE MONOPHOSPHATE DEHYDROGENASE 


NEW USES FOR INHIBITORS OF INOSINE MONOPHOSPHATE 

DEHYDROGENASE 

BACKGROUND: : Guanosine Triphosphates (GTP) are necessary for a variety of cellular functions 

that include not only DNA, RNA and protein biosynthesis but are also components of signal 

transduction mechanisms controlling cellular proliferation, differentiation and apoptosis. A series of 

reactions are involved in the biosynthesis of GTP and the controlling step that determines new GTP 

production is catalyzed by the enzyme, Inosine Monophosphate Dehydrogenase (IMPDH). IMPDH has 

a crucial role in GTP synthesis and it is indispensable particularly in cells that actively divide and 

replicate. Processes that require new GTP synthesis such as proliferation of B-cells and T-cells in 

response to antigen, actively dividing cancer and tumor cells and viruses undergoing replication, show 

an increase in the activity of IMPDH. Inhibition of IMPDH activity, therefore, is an attractive target in 

conditions requiring immunosuppression, anti-cancer and anti-viral therapies. 

Currently available inhibitors of IMPDH are being mainly used in the clinic for immunosuppression 

(mizoribine, mycophenolate mofetil) and anti-viral (ribovarin) therapy. These inhibitors are of limited 

use in aggressive anti-cancer therapy since they inhibit normal cell proliferation in addition to that of 

cancer cells. Hence, there is a need for more effective therapy protocols for treating cancer cell 

proliferation. 

DESCRIPTION: Researchers at the University of California have discovered three biochemical 

abnormalities in cancer cells that sensitize them to therapy using IMPDH inhibitors. Combining 

inhibitors of these pathways along with IMPDH inhibitors enhances the specificity towards cancer cells 

and improves efficacy of treatment. UC researchers have also developed novel prodrugs of the inhibitors 

that circumvent problems associated with short half -life and gastrointestinal side effects. 

ADVANTAGES: 

● Increased efficacy due to synergistic effects of the drugs in combination. 

● Use of lower dosage of individual inhibitors reducing non-specific side effects. 

● Treatment regimen directed specifically to anti-cancer therapy. 

● Ability to target different pathways defective in cancer cells. 


NEW USES FOR INHIBITORS OF INOSINE MONOPHOSPHATE DEHYDROGENASE 

APPLICATIONS: 

● Chemotherapy of a variety of cancers such as chronic lymphocytic leukemia, lymphoma, 

multiple myeloma and other hematological malignancies. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






NOVEL AGONISTS OF TOLL-LIKE RECEPTORS 



BACKGROUND: Toll-like receptors (TLRs 1-10) are a set of conserved cellular receptors that play a 

important role in the recognition of microbial pathogens and in initiating the first line of host innate 

immune response. These receptors recognize distinct molecular components of invading pathogens such 

as cell wall structures and nucleic acids that are often referred to as pathogen associated molecular 

patterns (PAMPs). 

While most TLRs are expressed in the plasma membrane, TLRs 3, 7, 8 and 9 are located in the 

endosomes that suggests a role in intracellular events for these receptors. The discovery that endogenous 

ligands as well as synthetic small molecule compounds can activate TLRs has sparked tremendous 

interest in the development of new therapeutics for diseases related to immune response. For example, 

TLR7 and TLR8 have been identified as the receptors for the small molecule drugs, imiquimod and 

resiquimod. These compounds have potent anti-viral and anti-tumor activity that is due to induction of 

the synthesis of interferon-gamma and other cytokines. However, current approaches of treatment are of 

limited use due to inherent short half-life of these TLR agonists in addition to antagonism by other viral 

mechanisms that block interferon production. Therefore, there is a distinct need for other synthetic small 

molecule compounds that are long-lasting enhancers of TLR action and/or circumvent the problem of 

viral antagonism of interferon production. 

DESCRIPTION: Researchers at the University of California have synthesized a series of novel 

synthetic compounds that are agonists of the TLR pathway. These small molecule compounds are more 

potent and have a longer half-life than imiquimod. UC researchers have discovered that these 

compounds can be further adjusted to modulate their half-life and be targeted to specific tissues where 

treatment is desired. In addition, when conjugated to specific macromolecules or whole cells, these 

compounds have a enhanced ability to activate the innate immune system than when used alone. 

ADVANTAGES: 

● Longer half-life and enhanced potency than currently available TLR 7/8 agonists. 

● Use of lower dosage of agonist compound reduces non-specific side effects. 

● Suitable for oral, injection or infusion formulations for administration. 



APPLICATIONS: 

● Vaccines against infectious diseases caused by bacteria and viruses. 

● Antiviral therapy against Hepatitis B, Hepatitis C and RSV. 

● Immunotherapy of a variety of cancers including skin cancers. 

● Treatment of diseases involving inflammation such as viral exacerbated asthma. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






Novel Anticancer Compound From Marine Ascidian 

Novel Anticancer Compound From Marine Ascidian 

A novel brominated indolylpiperazine has been identified from the marine ascidian Didemnum cadidum. 

The compound has been determined by a battery of in vitro screens to possess potent cytotoxic, antiproliferative 

and anti-cancer potential. Unlike many marine natural products, the compound is readily 

synthesized and contains no chiral centers. The compound is available for evaluation by a partner under 

an exclusive option arrangement. 



Novel Antigen for Immunization in Cancer 

Novel Antigen for Immunization in Cancer (SD2000-051) 

Vaccination against an enzyme common to a variety of human tumors might effectively mobilize the 

body’s own immune system to attack and kill cancer cells. Telomerase, an enzyme involved in 

maintaining normal chromosome length during replication and key to the uncontrolled replication of 

cancerous cells, is considered to play a direct role in tumor transformation by allowing the 

immortalization of precancerous cells. A prototype vaccine made from peptides of telomerase reverse 

transcriptase (hTRT) has been devised that can activate cytotoxic T-lymphocytes (CTL) in vitro. 

Lymphocytes from prostate cancer patients were readily activated into CTL following immunization 

with the prototype vaccine, leading to destruction of the cancer cells. CTL produced in prostate cancer 

cells were also effective in targeting hTPT peptides in other human cancer cells such as breast, colon, 

lung and melanoma and in attacking and killing these cancer cells. 

Experiments have also been conducted using transgenic mice engineered to mimic the human immune 

system. The prototype telomerase vaccine induced a CTL response in these mice with no apparent 

negative side effects, demonstrating the potential of this vaccine in an animal model. Since telomerase is 

essential in the normal process of cell division, autoimmune reactions are a concern for this type of 

vaccine. In addition to the lack of side effects observed in the mouse model, tests of the vaccine on 

normal human stem cells, which have higher levels of telomerase than other normal cells, showed no 

adverse effects. 


NOVEL MELANOCORTIN RECEPTOR ANTAGONISTS FOR THE TREATMENT OF MELANOMA 


NOVEL MELANOCORTIN RECEPTOR ANTAGONISTS FOR THE 

TREATMENT OF MELANOMA 

BACKGROUND: Modulation of melanocortin receptor (MCR) activity on the surface of melanocytes, 

by the melanocyte stimulating hormone (MSH), is a key determinant of melanin formation. The MSH/ 

MCR interaction is also known to have trophic stimulant actions (growth and proliferation) on normal 

melanocytes and on melanoma cell lines. Targeting this hormone-receptor interaction with antagonists 

may have therapeutic utility in altering the course of disseminated melanoma, a fatal form of cancer 

which causes over 7000 deaths per year in the United States. 

DESCRIPTION: Researchers at the University of California have identified a group of low molecular 

weight peptides, within the dynorphin family and from other groups, which are potent antagonists of 

MSH on the melanocortin receptor (subtype 1). These antagonists are specific for MSH and have no 

effect on the melanin-dispersing properties of serotonin, isoproterenol or vasotocin. These prototypes 

may serve as the basis for the discovery of lead compounds. 

APPLICATIONS: Melanocortin receptor antagonists may provide new therapeutic strategies for the 

control or management of melanoma. Other conditions where modulation of MCR may have clinical 

significance are in the areas of inflammation and appetite control. 

ADVANTAGES: There is no effective treatment at the present time for disseminated melanoma. 

Hormone receptor antagonists could have a valuable role, since the use of such antagonists is wellestablished 

for treating hormone-dependent breast and prostate cancers. Marginally improved response 

rates have resulted from various experimental regimens in disseminated melanoma, including: antipigmentary 

agents, retinoids, high-dose chemotherapy, immunotherapy, and antibodies conjugated to 

isotopes, drugs, and toxins. More recently, immunotherapy with interleukin-2 and alpha-interferon has 

also been tried. The potent and selective UC melanocortin receptor antagonists may provide an 

alternative and more effective method of treatment for melanoma. 



NOVEL MELANOCORTIN RECEPTOR ANTAGONISTS FOR THE TREATMENT OF MELANOMA 










Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




NOVEL METHODS AND COMPOSITIONS FOR DELIVERING NUCLEI...D DRUGS TO SPECIFIC CELLS AND SUBCELLULAR ORGANELLES 


NOVEL METHODS AND COMPOSITIONS FOR DELIVERING 

NUCLEIC ACID DRUGS TO SPECIFIC CELLS AND 

SUBCELLULAR ORGANELLES 

BACKGROUND: Gene therapy, the introduction of functional genes into mammalian cells to correct 

the effect of defective genes, is now feasible, and holds great promise for the treatment of many serious 

human diseases. Antisense therapy, the use of antisense DNA, RNA OR siRNA to suppress or regulate 

gene expression, likewise holds great promise for treatment of cancer, autoimmune diseases, transplant 

rejection, and many other disorders. Both these promising new therapeutic modalities generally require 

agents that can direct the therapeutic gene or antisense oligonucleotide to the desired cell, transport the 

oligonucleotide across the cell membrane, and direct the oligonucleotide to the intended intracellular 

target or organelle. A number of vectors and agents have been developed that may perform one or more 

of these functions, but there is still a great need for an efficient and safe oligonucleotide delivery vehicle 

that is broadly applicable to different oligonucleotides and targets. 

DESCRIPTION: Researchers at the University of California have developed a novel, patented selfassembling 

polynucleotide delivery system that can be readily adapted to a wide range of 

oligonucleotides and cellular and intracellular targets. This system consists of an oligonucleotide 

attachment moiety, functional groups to which cellular and intracellular targeting moieties can be 

attached, and a membrane-permeabilizing component that facilitates efficient transport of 

polynucleotides across the cell membrane. The system can be used with either dendrimer or liposomebased 

transfection protocols. The compounds and methods of this invention can selectively target a 

selected gene to a specified cell type, and efficiently transfect the cell with resulting expression of the 

gene. The researchers have further developed patented methods to facilitate the process of transfection. 

First, they have developed novel methods to separate active transfection complexes from individual 

components in a mixture of polynucleotides and transfection reagent. Second, the researchers have 

developed a method of stabilizing the polynucleotide complexes by adding a cryoprotectant compound 

and lyophilizing the resulting formulation. Together with the polynucleotide delivery system, these tools 

provide powerful new methods and compositions for delivering polynucleotides into cells. 

ADVANTAGES: 

http://patron.ucop.edu/ncd/docs/ott.1991-268-0.GT.html (1 of 2)10/21/2005 2:48:21 AM

NOVEL METHODS AND COMPOSITIONS FOR DELIVERING NUCLEI...D DRUGS TO SPECIFIC CELLS AND SUBCELLULAR ORGANELLES 

● The system operates with either liposomal or dendrimer based transfection protocols. 

● The novel gene delivery system allows genes to be targeted to specific cells and subcellular 

compartments. 

● The novel separation and storage methods make transfection less time consuming and more efficient. 

APPLICATIONS: The novel methods and compositions will be useful in any context where 

polynucleotides must be efficiently transfected into specific cells, such as for research purposes, gene 

therapy, and antisense therapy. 

For related technologies, please go to (UC Case No. 1991-268). 




September 22, 1998; US Patent # 5,955,365 issued September 21, 1999; US 

PATENT STATUS: Patent # 5,972,600 issued October 26, 1999; US Patent # 5,977,084 issued 

November 2, 1999; US Patent # 5,990,089 issued November 23, 1999; US Patent 

# 6,113,946 issued May 5, 2000; US Patent # 6,300,317 issued October 9, 2001 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 





http://patron.ucop.edu/ncd/docs/ott.1991-268-0.GT.html (2 of 2)10/21/2005 2:48:21 AM

NOVEL MITOGEN ACTIVATED C-FOS REGULATING KINASE, FRK 


NOVEL MITOGEN ACTIVATED C-FOS REGULATING KINASE, 

FRK 

BACKGROUND: The transcription factor AP-1 is a heterodimer formed by two proteins, c-Jun and c- 

Fos. AP-1 binds to DNA sequences in the promoter region of many genes that are involved in regulating 

cell proliferation. In cells that have lost their growth regulatory mechanisms, it is believed that AP-1 

may "sit" on these DNA sequences, causing overexpression of a particular gene. This overexpression of 

otherwise normal genes can result in proliferative disorders such as cancer. Therefore, it would be 

desirable to identify compositions that interfere with the ability of AP-1 to induce overexpression of 

these genes. 

DESCRIPTION: Researchers at the University of California have identified a novel Fos regulating 

protein kinase (FRK) that phosphorylates c-Fos and potentiates its activity. FRK is characterized by 

having a molecular weight of about 88kD and having threonine and serine kinase activity. Specifically, 

FRK phosphorylates threonine residue 232 in c-Fos's activation domain. DNA encoding this gene, 

expression vectors containing FRK DNA, the isolated FRK protein, antibodies to FRK protein, and 

methods of identifying compounds that inhibit or stimulate FRK activity are available. 

ADVANTAGES: The identification of FRK represents a novel basis for diagnostics and therapeutics 

for cell proliferative disorders. 

APPLICATIONS: 

● Screening to identify compounds or compositions that effect the activity of FRK. 

● These compounds and compositions may be useful in the treatment of cell proliferative disorders 

associated with FRK, such as cancer. 

● Diagnosis of cell proliferative disorders through analysis of the level of FRK activity in a cell. 




NOVEL MITOGEN ACTIVATED C-FOS REGULATING KINASE, FRK 



US Patent # 5,747,318 issued May 5, 1998; US Patent # 5,837,451 issued 

November 17, 1998; US Patent # 5,925,557 issued July 20, 1999; US Patent # 

6,054,560 issued April 25, 2000 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




Novel Modified Marine Polypeptides with Antimicrobial and Anticorrosion Properties 

Novel Modified Marine Polypeptides with Antimicrobial and Anticorrosion 

Properties 

A Scripps Institute of Oceanography scientist has discovered a family of unusual, post-translationally 

modified marine polypeptides with novel properties. The polypeptides display potent antimicrobial 

activity that is preserved in conditions of high salinity (250 mM) and is enhanced at slightly acidic pH 

against antibiotic resistant microorganisms. The peptides are also cytotoxic against certain human cancer 

cell lines. 

These polypeptides are easily purified from readily available source material and have undergone 

extensive biochemical characterization. They are cationic polypeptides and have properties in common 

with other peptides in this category that are being considered for medical applications; they differ, 

however, in their unprecedented post-translational modifications. In addition to their applications in 

medicine, veterinary science and aquaculture, these peptides show a strong affinity for cellulose and 

could be used as finishing agents in the textile industry for protection of cellulosic fibers from microbial 

attack. 

Furthermore, the peptides show a strong affinity for metals and can act as passivating agents. They 

not only coat the titanium alloys used extensively in medical implants but also act as effective corrosion 

inhibitors. The bioactivity of these polypeptides combined with their other diverse properties suggests 

that they will find applications, not only as therapeutic agents, but also as molecular "blue prints" for 

new materials. 



Novel Screening System for Microtubule-based Herbicides or Pesticides: New Generation Having Exceptional Species Selectivity and Safety 

Novel Screening System for Microtubule-based Herbicides or Pesticides 

New Generation Having Exceptional Species Selectivity and Safety 

BACKGROUND: A number of commercially important herbicides (e.g., Trifluralin, Oryzalin, 

other dinitroanilines, sulfonamides and N-phenylcarbamates) as well as major pesticides (e.g., 

Benomyl, Captan, benzofurans) have in common the targeting of the microtubule system as a 

cidal mechanism. This approach, which disrupts cell division and many other critical cellular 

processes, is highly effective, and is also utilized by the anti-cancer drugs taxol and vincristine. 

However, a major shortcoming of all these agents is that the microtubule system and structural 

elements have been highly conserved through evolution, and consequently, agents such as 

these, which non-specifically aggregate or disaggregate the microtubule framework, do not 

possess good selectivity across species. This is a major shortcoming not only limiting efficacy 

in differentiating crop plants from weeds or in differentiating pests from livestock or pollinators, 

but also respecting human safety in occupational exposure. 

DESCRIPTION: The current invention defines a new approach to the design and selection of 

microtubule-active herbicides and pesticides. The targets of this approach are certain 

accessory and regulatory proteins associated with the microtubule system, which control their 

assembly and function. Unlike the microtubule tubulin monomers, these accessory proteins are 

not conserved structures, and appear to differ greatly across even closely related species, and 

even among different tissues in the same species. Heretofore, it has not been possible to use 

the accessory proteins in assays, however, recent technology has made high-throughput 

screens practical. 

ADVANTAGES: It should be possible to design powerful blockers of microtubule function 

which, for example, target grass-family weeds while sparing wheat, rice or corn crops 

regardless of timing of application. Similarly, lepidopteran pests can be effectively targeted 

without harming pollinators or livestock. By this approach, exceptionally powerful herbicides 

and pesticides having no characteristic microtubule toxicity to man should be possible. Pilot 

screening of some available chemical libraries has already uncovered potent new structures 

targeting species-specific microtubule accessory proteins, as predicted. 


NOVEL STRATEGIES FOR THE TREATMENT OF HIV INFECTION 



BACKGROUND: Acquired immunodeficiency syndrome (AIDS) was first reported in the United 

States in 1981 and has since become a major worldwide epidemic. AIDS is caused by a lentivirus called 

human immunodeficiency virus (HIV), which acts by progressively destroying cells of the body's 

immune system. People diagnosed with AIDS are plagued by opportunistic infections, as the immune 

system is no longer effective to combat bacteria, fungi, viruses, parasites, and other microbes. In 

addition, AIDS patients are susceptible to a variety of cancers and can exhibit neurological symptoms. 

Although several drugs have been approved for treatment of this devastating disease, none of the 

available drugs used to combat HIV is completely effective and treatment frequently gives rise to drugresistant 

virus. Thus, there is a great need for additional drugs that are suitable for treating HIV infection. 

A detailed understanding of HIV and how it establishes infection and causes AIDS is crucial to 

identifying and developing effective drugs and vaccines to fight HIV and AIDS. Researchers at the 

University of California have made significant progress towards this goal. In particular, they have 

studied the mechanisms by which HIV fuses with an immune cell, transcribes its viral genetic material, 

and manipulates the immune cell to allow formation of new virus particles. In addition, they have 

studied the mechanism by which HIV can remain latent in immune cells. Finally, they have devised 

ways to use HIV viral proteins for beneficial purposes. 

FUSION OF HIV WITH AN IMMUNE CELL 

Infection of mammalian cells by HIV begins with the interaction of glycoproteins on the surface of the 

virion with a receptor expressed on the surface of the target cell. This interaction triggers a fusion 

between the two membranes. Interference with this membrane fusion event represents an important 

therapeutic strategy. UC Researchers have devised two assays to detect fusion of HIV with a cell. 

1) Cell-based fusion assay for HIV 

UC Researchers have developed cell-cell fusion assays that are optimized for pharmaceutical screening 

purposes. The cell lines express enveloped virion glycoproteins and target cell receptors in a stable 

manner. Virion fusion yields a fluorescent signal that can be readily quantitated using available reagents 

and equipment in a microwell format, allowing high throughput screening for antiviral agents. (UC Case 

http://patron.ucop.edu/ncd/docs/ott.2001-136-0.OV.html (1 of 4)10/21/2005 2:48:22 AM


No. 2001-136) 

2) Virion-based fusion assay for HIV 

UC Researchers have developed a virion-based fusion assay that allows the detection of the fusion of 

HIV-1 to various target cells by microscopy, flow cytometry, or UV spectrometry. The assay 

incorporates an enzymatic amplification reaction that provides for high sensitivity, high specificity, and 

ease of use. This assay has the advantage of measuring fusion of actual virions to target cells and is 

suitable for high throughput screening for antiviral agents. (UC Case No. 2002-438) 

TRANSCRIPTION OF HIV GENETIC MATERIAL 

Tat is an HIV regulatory protein that critically regulates HIV transcription and allows the generation of 

full-length transcripts necessary for the formation of virus particles. Tat is also found in the circulation, 

where it can affect uninfected T cells. UC Researchers have discovered that Tat can exist in a modified, 

acetylated form. They further found that acetylated Tat plays a critical role in HIV transcription. Unlike 

unmodified Tat, acetylated Tat is highly immunogenic, and anti-acetylated Tat antibodies completely 

block Tat-mediated HIV transcription. Acetylated Tat polypeptides may therefore be useful as a vaccine 

for the prevention and treatment of AIDS. (UC Case No. 2003-171) 

HIV MANIPULATION OF HOST CELL TO INCREASE VIRAL PRODUCTION 

1) Methods for identifying inhibitors of Vpr 

Viral Protein R (Vpr), a protein found in all primate lentiviruses, is produced late in the viral life cycle 

and is incorporated into the virion. One of the more deleterious activities of Vpr is its arrest of HIVinfected 

cells in the G2 phase of the cell cycle, which results in increased viral production. UC 

Researchers have found that Cyclosporin A (CsA) induces a block in the de novo synthesis of Vpr in 

multiple cell types. While CsA itself is immunosuppressive, this finding indicates that nonimmunosuppressive 

CsA-related compounds could be screened for activity as drugs that inhibit 

lentivirus replication by blocking the synthesis of Vpr. (UC Case No. 2002-149) 

2) Methods for identifying inhibitors of Vif 

HIV-1 relies on the virally encoded Vif (virion infectivity factor) protein in order to establish a 

productive infection. Vif principally functions by suppressing the antiviral factor APOBEC3G/CEM15. 

Without Vif, APOBEC3G/CEM15UC would be able to suppress HIV infection. UC Researchers have 

discovered the method used by Vif to inhibit the activity of APOBEC3G/CEM15. They have used this 

information to develop methods for identifying agents that inhibit the activity of Vif protein. (UC Case 

No. 2003-521) 



MECHANISM BY WHICH THE LATENT STATE OF HIV IS ESTABLISHED 

Despite the complete suppression of detectable HIV infection in many patients during treatment, viremia 

reemerges rapidly after interruption of treatment, consistent with the existence of latent viral reservoirs. 

The presence of latent reservoirs has prevented the eradication of HIV from infected patients 

successfully treated with antiretroviral therapy. To learn more about these latent reservoirs, UC 

researchers have created model stable cell lines that harbor a latent, non-defective HIV provirus linked 

to a readily selectable, green fluorescent protein marker. This cell line can be used to screen compounds 

for the identification of agents that activate latent HIV infections in order to combat the problem of 

latent reservoirs in HIV-infected individuals. (UC Case No. 2002-174) 

USE OF HIV PROTEINS FOR BENEFICIAL PURPOSES 

UC researchers have identified synthetic Vpr (sVpr), derived from HIV, as a new class of proteins that 

are able to cross the plasma membrane in a receptor independent fashion. sVpr has all of the 

characteristics of the natural viral protein and can be synthesized at high yields in a water soluble form. 

The protein can be used for the delivery of heterologous proteins and other molecules into a variety of 

cell types. sVPr can also be efficiently imported into the nucleus of transduced cells and induce G2 cell 

cycle arrest, suggesting that it could be used as a cytotoxic agent for the desired cell. A transducible 

form of sVpr that does not induce G2 arrest and does not enter the nucleus can also be engineered. (UC 

Case No 2000-362) 

REFERENCE 

Stopak et. al. Molecular Cell 12 (3) 2003, 591-601 









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NOVEL TREATMENT FOR HYPERPLASTIC DISEASE 



BACKGROUND: Hyperplastic diseases, which are typically characterized by the uncontrolled growth 

of cells, are non-malignant conditions that represent an unmet medical need. Examples of hyperplastic 

diseases are benign prostatic hypertrophy, fibroplastic dysplasia of the breast, fibroplastic growths in the 

uterus or cervix, and gastric hyperplastic polyposis. In many patients, hyperplastic diseases do not lead 

to the development of cancer, and are not treated with the conventional chemotherapeutic agents used 

against malignant diseases. Therefore, a continuing need exists for new, potent, and selective agents 

useful to prevent detrimental effects or control the growth of hyperplastic cells. 

DESCRIPTION: Researchers at the University of California have identified a small molecule 

compound that may be useful in the treatment of hyperplastic diseases. Specifically, the researchers 

found that this compound could reduce prostate size and inhibit disease progression in a mouse model of 

prostate disease. 

APPLICATIONS: The small molecule compound may be useful, alone or in combination with other 

chemotherapeutic agents, in the treatment of hyperplastic diseases such as benign prostatic hypertrophy, 

fibroplastic dysplasia of the breast, fibroplastic growths in the uterus or cervix, and gastric hyperplastic 

polyposis. 








Oakland, CA 94607-5200 





Phone: (510) 587-6000 Fax: (510) 587-6090 




Novel, Virus-Independent In Vivo Gene Therapy Approach 

Novel, Virus-Independent In Vivo Gene Therapy Approach (98-035) 

A novel, highly efficient method has been developed that allows therapeutic gene delivery directly into 

tissues such as skin, tendons, ligaments or muscles. The approach is applicable to the treatment of a 

wide range of diseases and traumas such as cancer, rheumatoid- and osteo-arthritis, osteoporosis, 

muscular dystrophies and tendon or ligament damage. Gene delivery does not require the use of viral 

vectors, thereby eliminating the danger of anti-viral immune responses, and has been shown to be highly 

efficient both ex vivo and in vivo in rabbit and dog models of osteochondral defect repair and flexor 

tendon healing. 

Using this method, greater than 70% of primary rabbit perichondrium and cartilage cells transfected in 

vitro were positive for the introduced gene. After reintroduction into the rabbit knee, the cells continued 

to express the transgene for at least a week. The transfection method also allows for introduction of the 

therapeutic gene by direct injection into the appropriate site. With this type of delivery the gene becomes 

distributed approximately 100 cell layers deep in the tissue, in contrast to viral delivery, which generally 

distributes the gene only a few cell layers deep. In addition to being highly efficient, it is relatively quick 

to perform—adding only a few extra minutes to the total time of surgery. 

CASE NUMBER: SD 98-035 


P21-ACTIVATED KINASE (PAK I) AND RELATED PEPTIDES 



University of California scientists have purified p21-activated protein kinase (PAK I), a unique inhibitor 

of cell division, cleavage, and programmed death (apoptosis), physiological processes that are associated 

with several important diseases. PAK I is cleaved during the onset of apoptosis, playing a key role in the 

regulation of cell death and possibly in the maintenance of cells in their non-dividing state (cytostasis). 

PAK I activation requires two autophosphorylation steps, the first one involving a regulatory domain 

and the second one involving a catalytic domain. Since the regulatory domain can interact with a number 

of different compounds, PAK I can be activated under several different conditions. 

The UC scientists have obtained PAK I's DNA coding sequences, and have also developed a synthetic 

peptide that mimics the recognition/phosphorylation site of PAK I. The synthetic peptide is 

preferentially phosphorylated by PAK I relative to other major protein kinases (e.g. cAMP-dependent 

protein kinase and protein kinase C), so its interaction with the PAK I regulatory domain is both 

sensitive and highly specific. This allows the assay of PAK I activity in cell extracts or with partially 

purified enzyme in the presence of other protein kinases. 

With apoptosis playing an important role in the suppression of cancer, autoimmunity, and viral 

infections, the detection of PAK I activity using the synthetic peptide may be of considerable 

importance. Such detection techniques might be useful for the elucidation of apoptosis induction, the 

characterization of disorders associated with such apoptosis-induction mechanisms, and the formulation 

and screening of agents for preventing or treating these major medical disorders. Likewise, the cytostatic 

properties of PAK I itself may make it useful as a drug-design target. PAK I can be produced using 

physiological and recombinant DNA techniques, which could potentially be combined with various drugdelivery 

procedures or gene therapy to help treat patients with PAK-related disorders. 








● Biotechnology > Biomass/biochemicals > Biochemicals 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 







University of California scientists have purified p21-activated protein kinase (PAK I), a unique inhibitor 

of cell division, cleavage, and programmed death (apoptosis), physiological processes that are associated 

with several important diseases. PAK I is cleaved during the onset of apoptosis, playing a key role in the 

regulation of cell death and possibly in the maintenance of cells in their non-dividing state (cytostasis). 

PAK I activation requires two autophosphorylation steps, the first one involving a regulatory domain 

and the second one involving a catalytic domain. Since the regulatory domain can interact with a number 

of different compounds, PAK I can be activated under several different conditions. 

The UC scientists have obtained PAK I's DNA coding sequences, and have also developed a synthetic 

peptide that mimics the recognition/phosphorylation site of PAK I. The synthetic peptide is 

preferentially phosphorylated by PAK I relative to other major protein kinases (e.g. cAMP-dependent 

protein kinase and protein kinase C), so its interaction with the PAK I regulatory domain is both 

sensitive and highly specific. This allows the assay of PAK I activity in cell extracts or with partially 

purified enzyme in the presence of other protein kinases. 

With apoptosis playing an important role in the suppression of cancer, autoimmunity, and viral 

infections, the detection of PAK I activity using the synthetic peptide may be of considerable 

importance. Such detection techniques might be useful for the elucidation of apoptosis induction, the 

characterization of disorders associated with such apoptosis-induction mechanisms, and the formulation 

and screening of agents for preventing or treating these major medical disorders. Likewise, the cytostatic 

properties of PAK I itself may make it useful as a drug-design target. PAK I can be produced using 

physiological and recombinant DNA techniques, which could potentially be combined with various drugdelivery 

procedures or gene therapy to help treat patients with PAK-related disorders. 









July 29, 2003 







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Phone: (510) 587-6000 Fax: (510) 587-6090 




PEPTIDE NUCLEIC ACID MIMICS 



University of California scientists have designed synthetic polypeptides that function as mimics of 

nucleic acid strands. These peptide nucleic acid mimics (PENAMs) can be readily made in a costeffective 

manner using standard automated peptide synthesizer technology. Unlike ordinary peptides, 

PENAMs closely match the geometry of nucleic acid structure. PENAMs bind tightly to sequencespecific 

nucleic acid strands, enabling the PENAMs to be used as antisense regulators or hybridization 

probes in a wide variety of applications. 

The primary advantage to employing PENAMs versus standard DNA or RNA complements in such 

applications is that PENAMs are not subject to degradation by cellular nucleases and can cross cell 

membranes more easily than nucleic acid strands. Thus, PENAMs are ideal in situations where crude 

cell preps or in vivo procedures are desired. Toleration of cellular components could greatly increase the 

utility of antisense regulation and hybridization techniques. 

It is anticipated that PENAMs would facilitate in vivo inhibition or modulation of gene expression; and 

PENAMs might make viable simpler and more rapid hybridization procedures for diagnostic 

identification of DNA sequences associated with disease organisms, cancers, and genetic disorders. 














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pH SENSITIVE LIPOSOMES FOR DRUG DELIVERY 



BACKGROUND: There are many challenges associated with safely delivering drugs to their intended 

targets in the body. Drugs in the blood stream are often vulnerable to attack from proteases, nucleases or 

scavenging agents in the blood, and may be toxic, insoluble, or too large to cross cell membranes. One 

way to solve these problems is to encapsulate the drugs in liposomes, which prevent direct contact of the 

drugs with the blood. Ideally, the liposomes are then taken up by target cells into endosomes where they 

release their contents. 

DESCRIPTION: UC researchers have developed a coating that confers pH sensitivity upon liposomes. 

In the blood stream, the coated liposomes are stable and release none of their contents. In more acidic 

environments however, the liposomes become unstable and allow the drug they are carrying to leak out. 

Since endosomes have a lower pH than the bloodstream, this method allows the specific release of drugs 

inside cells. 

APPLICATIONS: The coated liposomes can be used to deliver drugs to cells in vivo or in vitro. They 

may also be used to transfect cells with DNA for gene therapy. Since many tumors are more acidic than 

surrounding tissue, the liposomes are suitable for targeting anti-cancer drugs to tumors. 

ADVANTAGES: 

● The coated liposomes are stable and can be prepared to exhibit long half lives 

● The coating can be applied to rigid, fluid or sterically stabilized liposomes 

● The liposomes release 20-80% of their contents in acidic conditions resembling those inside 

endosomes 

● The coating is non-toxic and does not significantly interfere with the targeting of the liposomes to 

particular tissues 







● Biotechnology > Biomaterials 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




Phosphonate Esters of Nucleosides and Methods of Use for Same 

Phosphonate Esters of Nucleosides and Methods of Use for Same 

Key Words: AIDS, cancer, osteoporosis, antiviral, anticancer, prodrug. 

Invention: UCSD researchers have developed novel prodrugs of phosphonate-containing drugs that 

have increased activity (versus the native drug), the basis of which is the inclusion through an ester 

functionality of certain moieties onto the native drug. These compounds are useful for the treatment of 

viral infections (including HIV), cancer and osteoporosis. The advantages are: 

● Highly active against target. 

● Reduction or elimination of side effects by use of a lower dose to achieve similar efficacy. 

Background: Certain important drugs, which are administered orally, have undesirable side effects due 

to the high dose required in order to achieve efficacy. In some cases, the requirement for the high dose is 

due to the poor oral availability of the drug. In those instances, there is a clear need for new derivatives 

of these drugs with better oral availability. 




PHOSPHORYLATION OF HISTONE H2B AS A MARKER FOR CELL P...RATION AND DIFFERENTIATION IN DEVELOPMENT AND DISEASE 


PHOSPHORYLATION OF HISTONE H2B AS A MARKER FOR 

CELL PROLIFERATION AND DIFFERENTIATION IN 

DEVELOPMENT AND DISEASE 

BACKGROUND: Determining the cell cycle state of human cells can provide an important method for 

early detection of cancerous growth, especially the detection of cells at the G2/M phase of beginning cell 

division, or mitosis. However, current cell cycle detection methods cannot be correlated unambiguously 

with mitosis. Many cell cycle regulators are expressed during the entire cell cycle and are activated 

posttranslationally during cell division by modifications such as phosphorylation, so antibodies that 

recognize these proteins are not indicators. Furthermore, many cell cycle regulators carry several 

posttranslational modifications, and the primary sequence of these regulators is not phytogenetically 

conserved, so animal studies may not correlate with potential human indicators or targets. To date, 

antibodies that recognize modified or unmodified versions of the cell cycle regulators are not available. 

DESCRIPTION: Scientists at the University of California and Wisconsin have identified a novel 

histone modification, phosphorylation of serine 33 in histone H2B (H2B-S33), and have correlated this 

modification with transcriptional activation of the essential cell regulator string/Cdc25. String regulates 

cell cycle progression through G2/M phase. The presence of phosphorylated H2B (H2B-S33P) at the 

transcriptionally active string/cdc25 promoter provides a unique method and tool to determine the 

proliferative type and cell cycle status of cells. Such novel method is available for licensing as a 

diagnostic tool for identifying abnormal proliferating cells. 

In addition, these scientists have developed a proprietary antibody recognizing the phosphorylated H2B 

motif. This antibody was raised against a recombinant Drosophila H2B peptide phosphorylated at serine 

33, and named "anti-H2B-S33P." Anti-H2B-S33P recognizes the phosphorylated, evolutionarilyconserved 

motif in human cells, and can be used to determine the specific proliferation state of cells and 

tissues. Anti-H2B-S33P is available for licensing and represents a novel tool for cancer prognosis, 

diagnosis, and research. 

APPLICATIONS and ADVANTAGES: 

● Detection of H2B-S33P at the string/cdc25 promoter determines cell cycle progression, as string/ 


PHOSPHORYLATION OF HISTONE H2B AS A MARKER FOR CELL P...RATION AND DIFFERENTIATION IN DEVELOPMENT AND DISEASE 

cdc25 is exclusively expressed during G2/M phase. Furthermore, string/cdc25 is not transcribed 

in the absence of H2B-S33P despite the presence of other histone modifications at the string/ 

cdc25 promoter. Thus, H2B-S33P represents a specific cell cycle marker. 

● This H2B-S33P modification is phylogenetically conserved and can be used as a marker for cell 

cycle progression for both basic research with various animals and medical studies in humans. 

● Detection of H2B-S33P at the string/cdc25 promoter provides the opportunity to determine the 

cell cycle state of human cells. Consequently, this method can be used for early detection of 

cancerous growth. 

PUBLICATION: Maile T, Kwoczynski S, Katzenberger RJ, Wassarman DA, Sauer F. TAF1 activates 

transcription by phosphorylation of serine 33 in histone H2B. Science. 2004 May 14;304(5673):1010-4. 




● Biotechnology > Genetic engineering sys > Diagnostic polyclonal 

● Biotechnology > Genetic engineering sys > Therapeutic polyclonal 




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PHOSPHOTYROSINE BINDING DOMAIN 



BACKGROUND: One way that signals can be transmitted across cell membranes is by means of 

receptors that become phosphorylated upon binding to extracellular ligands. Intracellular signaling 

proteins that recognize the active phosphorylated form of the receptor become activated, beginning a 

signaling cascade that may have wide range of effects throughout the cell. Extracellular ligands that bind 

to these receptor tyrosine kinases include growth factors, cytokines and hormones; the results of their 

activation include such vital processes as cell proliferation, differentiation and cell cycle control. 

DESCRIPTION: UC researchers have identified a novel domain in signaling proteins that binds 

specifically to the tyrosine-phosphorylated form of its target protein. The phosphorylated target may be 

the receptor tyrosine kinase, a variety of known intermediate signaling proteins, or as yet unknown 

molecules that play a role in the down stream signaling pathway. 

APPLICATIONS: Polypeptides containing the new domain may be able to block the effects of the 

various classes of ligands that activate receptor tyrosine kinases. This property could be useful both as a 

research tool and therapeutically. As blockers of growth factors for example, they could treat a variety of 

proliferative cell disorders including atherosclerosis, inflammatory joint diseases, psoriasis, restenosis 

following angioplasty, and cancer. In addition, the polypeptides can be used to identify all the down 

stream tyrosine-phosphorylated cell signaling molecules to which they bind in the cell. A quantitative 

version of this technique could serve as the basis of a screen to analyze the effects on cell signaling of 

drugs including, but not limited to, putative agonists or antagonists to receptor tyrosine kinases. Finally, 

the three dimensional structure of the polypeptides may be determined and used to design drugs for the 

control of cell signaling. 



US Patent # 5,744,313 issued April 28, 1998; US Patent # 5,925,547 issued July 


20, 1999 










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Phone: (510) 587-6000 Fax: (510) 587-6090 




PHOSPHOTYROSINE BINDING DOMAIN INVOLVED IN SIGNALING PATHWAYS THAT TRIGGER BREAST CANCER 


PHOSPHOTYROSINE BINDING DOMAIN INVOLVED IN 

SIGNALING PATHWAYS THAT TRIGGER BREAST CANCER 

BACKGROUND: Growth factors, cytokines, and oncogenes activate proteins in signaling pathways via 

phosphorylation of regulatory proteins at their tyrosine residues, which in turn bind to the signaling 

proteins containing suitable binding domains. One such domain that has been studied in detail is the Src 

homology 2 (SH2) domain, which binds specifically to tyrosine-phosphorylated proteins that participate 

in signaling and so is of interest because of its role in enabling assembly of SH2-containing proteins and 

thus intiating the further activation of downstream effectors. 

DESCRIPTION: University of California scientists have discovered a phosphotyrosine binding domain 

(PTB) that has a functionality similar to SH2, even though SH2 and PTB binding are quite distinct. Of 

particular significance among the phosphorylated proteins that bind to PTB is the product of the protooncogene 

c-erbB2/c-neu, a tyrosine kinase receptor that has been implicated in breast cancer. 

APPLICATIONS: Proteins containing PTB domains can bind to tyrosine-phosphorylated targets to 

block interaction of the targets with signaling molecules, so PTB domains are attractive targets for 

developing agents to modulate signaling activity, as well as to identify novel signaling proteins 

containing the domain. This might, in the case of c-erbB2 for example, yield therapeutic agents for 

controlling breast carcinomas. Ras oncogene signaling via the SHC protein is yet another system that 

has been identified as involving the PTB binding mechanism molecules. 





● Biotechnology > Proteins/protein eng sys > Protein/peptide sequence 


PHOSPHOTYROSINE BINDING DOMAIN INVOLVED IN SIGNALING PATHWAYS THAT TRIGGER BREAST CANCER 






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Experimental Hematology 29 (2001) 1125–1134 

HOXB4 overexpression mediates very rapid stem 

cell regeneration and competitive hematopoietic repopulation 

a 

b 

a,c 

Jennifer Antonchuk , Guy Sauvageau , and R. Keith Humphries 

aTerry 

Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; 

c 

Clinical Research Institute of Montreal, Montreal, Quebec, Canada; The Department of Medicine, University of British Columbia, Vancouver, BC, Canada 

b 

(Received 5 April 2001; revised 7 May 2001; accepted 11 May 2001) 

Objective. Hox transcription factors have emerged as important regulators of hematopoiesis. 

In particular, we have shown that overexpression of HOXB4 in mouse bone marrow can 

greatly enhance the level of hematopoietic stem cell (HSC) regeneration achieved at late times 

(� 4 months) posttransplantation. The objective of this study was to resolve if HOXB4 increases 

the rate and/or duration of HSC regeneration, and also to see if this enhancement was 

associated with impaired production of end cells or would lead to competitive reconstitution of 

all compartments. 

Methods. Retroviral vectors were generated with the GFP reporter gene � HOXB4 to enable 

the isolation and direct tracking of transduced cells in culture or following transplantation. 

Stem cell recovery was measured by limit dilution assay for long-term competitive repopulating 

cells (CRU). 

Results. HOXB4-overexpressing cells have enhanced growth in vitro, as demonstrated by 

their rapid dominance in mixed cultures and their shortened population doubling time. Furthermore, 

HOXB4-transduced cells have a marked competitive repopulating advantage in 

vivo in both primitive and mature compartments. CRU recovery in HOXB4 recipients was extremely 

rapid, reaching 25% of normal by 14 days posttransplant or some 80-fold greater 

than control transplant recipients, and attaining normal numbers by 12 weeks. Mice transplanted 

with even higher numbers of HOXB4-transduced CRU regenerated up to but not beyond 

the normal CRU levels. 

Conclusion. HOXB4 is a potent enhancer of primitive hematopoietic cell growth, likely by increasing 

self-renewal probability but without impairing homeostatic control of HSC population 

size or the rate of production and maintenance of mature end cells. © 2001 International 

Society for Experimental Hematology. Published by Elsevier Science Inc. 

Hematopoietic stem cells (HSCs) play a pivotal role in the 

establishment and subsequent lifelong maintenance of hemopoiesis. 

A critical property of HSCs is their ability to undergo 

self-renewal—a feature that is the cornerstone of 

stem cell transplantation–based therapies, in which HSCs 

are required not only to differentiate to repopulate mature 

hematopoietic tissues but also to regenerate a functional 

totipotent stem cell compartment. Studies in the murine 

model using rigorous and quantitative assays for HSCs have 

Corresponding Author: R. Keith Humphries, M.D., Ph.D., Terry Fox 

th 

Laboratory, BC Cancer Agency, 601 West 10 Avenue, Vancouver, British 

Columbia V5Z 1L3, Canada; E-mail: khumphri@bccancer.bc.ca 

Presented in part during the Presidential Symposium at the 28th annual 

meeting of the International Society for Experimental Hematology, Monte 

Carlo, Monaco, July 12, 1999. 

interestingly revealed that the level of HSC recovery following 

bone marrow transplantation is incomplete. Even at 

relatively high transplant doses with adult bone marrow 

cells, recovery reaches only approximately 10% of the normal 

level [1]. Somewhat higher levels of recovery are apparent 

following transplantation of stem cells from fetal 

liver [2–4], but again regeneration of the stem cell compartment 

is incomplete, in contrast to apparently normal reconstitution 

of later progenitor and end cell compartments. 

A number of studies suggest that both intrinsic and extrinsic 

regulatory mechanisms underlie HSC behavior. 

Thus, for example, the increased proliferative capacity of 

fetal compared to adult-derived HSCs is suggestive of some 

intrinsic genetic determinants of self-renewal potential. The 

observed incomplete regeneration of the HSC compartment 

in primary transplant recipients, and a limited ability to serially 

transplant bone marrow cells [5], have also suggested 

0301-472X/01 $–see front matter. Copyright © 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. 

PII S0301-472X(01)00681-6

1126 

an inherent exhaustibility of HSC self-renewal, possibly indicative 

of an intrinsic mitotic clock [6]. Limitations in stem 

cell expansion, however, may also reflect the presence of 

negative extrinsic regulatory mechanisms, since the regenerated 

HSCs can be shown to retain significant self-renewal 

potential [7]. A greater understanding of the genes and processes 

controlling HSC self-renewal could provide important 

new strategies for achieving enhanced or even selective 

HSC expansion. 

Recent attempts to identify stem cell control genes have 

included linkage analysis on mouse strains with differing 

HSC functional abilities [8], and expression profiling on hematopoietic 

populations with differing HSC contents [9]. 

While these studies have identified an expanding list of potential 

HSC regulators, the involvement of these genes in 

control of HSC self-renewal remains unclear. Candidate 

HSC regulators have also been identified based on phenotypic 

effects in loss- or gain-of-function mouse models. For 

example, overexpression of the anti-apoptotic gene bcl-2 

led to increased numbers of Thy-1.1 

J. Antonchuk et al./Experimental Hematology 29 (2001) 1125–1134 

lo 

, Sca-1 

hi 

, c-kit 

hi 

, lin 

cells, which have long-term multilineage repopulation potential 

[10], while absence of the cell cycle regulator p21 led 

to reduced radioprotection upon serial transplantation [11]. 

A number of recent studies have brought attention to the 

Hox family of transcription factors as potential hematopoietic 

regulators. Multiple gene members of the Hox A, B, and 

C clusters are expressed in hematopoietic cells, and this expression 

appears to be restricted to the most primitive cell 

types, such as human CD34 

� 

CD38 

� 

neg 

bone marrow cells, and 

down-regulated in more mature compartments[12]. These 

patterns of expression are suggestive of Hox gene functional 

roles in early hematopoietic cells. Consistent with 

this, lack of a functional Hoxa-9 gene led to impaired myeloid 

and lymphoid differentiation [13,14]. In contrast, numerous 

studies have revealed myeloproliferative effects of 

overexpression of several different Hox genes [15–17]. Interestingly, 

these studies have demonstrated Hox gene–specific 

effects at multiple levels of hemopoiesis. For example, 

HOXB3 overexpression impaired lymphoid but enhanced 

myeloid development [17], while HOXA10 overexpression 

altered megakaryocyte, macrophage, and B-cell differentiation, 

and was associated with a myeloproliferative syndrome 

[15]. 

Of particular interest in the context of HSC regulation 

are our previous findings from overexpression of HOXB4 

[16]. Observed in vitro effects of HOXB4 overexpression 

include increased clonogenic progenitor replating and increased 

recovery of colony-forming units in the spleen 

(CFU-S) in vitro, indicating enhanced growth of primitive 

cells [16]. In vivo assays also reflected enhanced growth at 

the primitive cell level. While there was no change in the 

proportion or number of end cells in mice transplanted with 

HOXB4-overexpressing cells, and only a modest increase in 

clonogenic progenitors, there was a marked increase in the 

level of HSC regeneration [16]. Polyclonal competitive re- 

populating unit (CRU) levels in HOXB4 recipients reached 

the normal (i.e., pretransplant) level by 4 months posttransplant, 

and were sustained at this level for at least one year, 

in sharp contrast to the limited regeneration in control-transplanted 

mice [16,18]. 

In earlier studies, our goal was to determine the maximal 

level of HSC regeneration, and whether the enhancement 

would be associated with stem cell exhaustion; we therefore 

analyzed mice at late times posttransplant (up to one year). In 

the current study we have focused on very early times posttransplant, 

so as to assess the effect of HOXB4 on the rate of 

HSC regeneration. We found significant regeneration in the 

first 2 weeks posttransplant, arguing that the enhanced recovery 

of HSCs results mainly from an increased rate and/or 

probability of self-renewal, rather than a prolonged period of 

recovery. Further to this, we also assessed regulation of HSC 

growth with HOXB4 overexpression, by examination of 

CRU regeneration following transplantation of very large cell 

doses. The HSC population size remains strictly controlled, 

as CRU contents do not rise above the normal level even over 

a 30-fold range of transplant cell doses. Finally, we questioned 

whether the HOXB4-mediated HSC self-renewal enhancement 

was accompanied by a compensatory inhibition of 

differentiation. Although recipients of nonselected HOXB4transduced 

bone marrow cells developed mature blood cells 

in all lineages, we were unable with previous constructs to directly 

assess the contribution by transduced cell progeny to 

the various hematopoietic lineages. In the current study we 

have exploited the green fluorescent protein (GFP) marker 

gene to facilitate the isolation and tracking of transduced 

cells, allowing us to directly test the competitive growth potential 

of HOXB4-transduced cells, and to directly assess 

whether HOXB4 HSC retain full differentiative potential. 

These studies reveal that HOXB4 overexpression confers a 

marked competitive growth advantage on hematopoietic cells 

in vitro, and a competitive repopulation advantage in vivo. 

Differentiation was not compromised, as all lineages of mature 

blood cells contained normal distributions of HOXB4- 

GFP 

� 

cells. These studies highlight HOXB4 as a candidate 

HSC regulator that can be exploited to enhance the growth of 

primitive hematopoietic cells without deleterious effects on 

HSC regulation or differentiation, and to further our understanding 

of the processes controlling HSC growth. 

Materials and methods 

Retroviral vectors 

The MSCV 2.1 [19] vector (kindly provided by Dr. R. Hawley, 

American Red Cross, Rockville, MD, USA), was first modified by 

replacing the pgk-neo cassette with a sequence containing the internal 

ribosomal entry site (IRES) sequence derived from the encephalomyocarditis 

virus and the gene for enhanced green fluorescent 

protein (GFP) (this cassette was kindly provided by Dr. P. LeBoulch, 

Massachusetts Institute of Technology, Cambridge, MA, 

USA). This MSCV IRES GFP vector (GFP vector) served as a con-

trol and backbone for cloning of a HOXB4 cDNA upstream of the 

IRES, to create MSCV HOXB4 IRES GFP (HOXB4-GFP vector). 

Production of high-titer helper-free retrovirus was carried out by 

standard procedures [20], using virus-containing supernatants from 

transfected amphotropic Phoenix packaging cells [21] to infect the 

� 

ecotropic packaging cell line GP E86 [22]. The retroviral titers of 

5 

the GFP and HOXB4-GFP producer cells were 3 � 10 /mL and 2 � 

5 10 /mL respectively, as assessed by transfer of GFP expression to 

NIH-3T3 cells. Absence of helper-virus generation in the GFP and 

HOXB4-GFP producer cells was verified by failure to serially 

transfer virus-conferring GFP expression to NIH-3T3 cells. 

Mice 

Parental strain mouse breeders were originally purchased from The 

Jackson Laboratory (Bar Harbor, ME, USA) and subsequently bred 

and maintained at the British Columbia Cancer Research Centre animal 

facility. They were housed in microisolator units and provided 

with sterilized food, water, and bedding. Irradiated animals were additionally 

provided with acidified water (pH 3.0). Strains used as bone 

marrow transplant donors were either C57Bl6/Ly-Pep3b (Pep3b) or 

the F1 hybrid of (C57Bl/6Ly-Pep3b � C3H/HeJ) ([PepC3] F1), 

and 

41 41 41 41 

those used as recipients were either C57Bl/6-W /W (W /W ) or 

the F1 hybrid of (C57Bl/6J � C3H/HeJ) ([B6C3] F1). 

Donor and recipient 

strains are phenotypically distinguishable on the basis of allelic 

differences at the Ly5 locus: donor Pep3b are Ly5.1 homozygous and 

41 

donor [PepC3] F1 are Ly5.1/5.2 heterozygous, whereas recipient W / 

41 W and [B6C3] F1 are Ly5.2 homozygous. 

Infection of primary murine bone marrow cells 

Primary mouse bone marrow cells were transduced as previously 

described [16,23]. Briefly, bone marrow cells were extracted from 

mice treated 4 days previously with 150 mg/kg 5-fluorouracil 

(Faulding) and cultured for 48 hours in Dulbecco’s modified eagle’s 

medium (DMEM) supplemented with 15% fetal bovine serum 

(FBS), 10 ng/mL hIL-6, 6 ng/mL mIL-3, and 100 ng/mL mSF. Media 

and serum were purchased from StemCell Technologies (Vancouver, 

BC, Canada), and growth factors were expressed in COS 

cells and purified in the Terry Fox Laboratory. The cells were then 

harvested and cocultured with irradiated (1500 cGy x-ray) GP 


� 

E86 

viral producer cells for 48 hours in the same medium with the addition 

of 5 �g/mL protamine sulfate (Sigma, Oakville, ON, Canada). 

Loosely adherent and nonadherent cells were recovered from the 

cocultures and incubated a further 48 hours in the same medium 

without protamine sulfate. Retrovirally transduced bone marrow 

cells were selected based on GFP expression using a FACStar 

(Becton-Dickinson, Mississauga, ON, Canada). 

In vitro culture of hematopoietic cells 

� Ly5.1 bone marrow cells transduced with HOXB4-GFP and 

� Ly5.2 cells transduced with GFP vectors were cultured after GFP 

selection in DMEM supplemented with 15% FBS, 10 ng/mL hIL-6, 

6 ng/mL mIL-3, and 100 ng/mL mSF. We tracked the proportion of 

� 

� 

Ly5.1 and GFP cells over time in cultures initiated with mixtures 

of GFP-transduced and HOXB4-GFP–transduced cells using a 

FACScan (Becton-Dickinson). Total cell numbers were evaluated 

4 

from cultures initiated with 5 � 10 cells/well, by harvesting cells 

from 3 wells every 4 days and counting on a hematocytometer. 

In vivo repopulation 

41 41 

Recipient [PepC3] F1 or W /W mice were irradiated with 900 cGy 

137 

� 

or 450 cGy of Cs �-radiation, 

respectively. FACS-selected GFP 

1127 

bone marrow cells were then injected into the tail vein of irradiated 

recipient mice. Peripheral blood cell progeny of transduced cells 

were tracked at various intervals posttransplant by expression of 

GFP and Ly5.1. One hundred �L of blood was extracted from the 

tail vein, and the erythrocytes were lysed with ammonium chloride 

(StemCell Technologies). Leukocyte samples suspended in Hank’s 

balanced salt solution (StemCell Technologies) with 2% FBS (HF) 

were incubated sequentially on ice with 6 �g/mL of 2.4.G2 (anti-Fc 

receptor antibody produced in Terry Fox Lab), then biotinylated 

anti-Ly5.1 (Pharmingen, Mississauga, ON, Canada), and finally 

phycoerythrin (PE)-labeled streptavidin (SA) (Pharmingen). All 

samples were washed with HF and 1 �g/mL propidium iodide (PI; 

Sigma) prior to analysis on FACScan, FACSort, or FACScalibur 

(Becton-Dickinson) flow cytometry machines. Expression of Ly5.1 

identified donor-derived cells, and expression of GFP identified retrovirally 

transduced cells. At the time of animal sacrifice, bone 

marrow samples were analyzed by FACS in the same manner. 

CFC assay 

Hematopoietic clonogenic progenitor frequencies were determined 

by plating suitable aliquots of bone marrow or spleen cells in methylcellulose 

medium (HCC-3334, StemCell Technologies) containing 

3 U/mL erythropoietin, and supplemented with 50 ng/mL 

mSF, 10 ng/mL hIL-6, and 10 ng/mL mIL-3, and then scoring the 

resultant colonies after 10 days of incubation. 

CRU assay 

HSCs were detected and evaluated using a limit-dilution transplantation-based 

assay for cells with competitive, long-term, lymphomyeloid 

repopulation function. The basic procedure [24], and a modi- 

41 41 

fication employing sublethally irradiated W /W recipients (450 cGy 

137Cs 

�-radiation) 

as a source of endogenous competitor cells [25], 

41 41 

have been described in detail previously. Briefly, irradiated W /W 

2 

5 

recipients were injected with 10 to 2 � 10 cells, and the blood obtained 

by tail vein bleeding of these mice was analyzed by FACS 

more than 12 weeks posttransplant for evidence of lympho-myeloid 

� 

repopulation. Mice that had greater than 1% donor-derived (GFP ) 

low low 

hi hi 

cells in both lymphoid (SSC , FSC ) and myeloid (SSC , FSC ) 

subpopulations were considered to be repopulated with transduced 

cells. Discrimination by flow cytometry of myeloid and lymphoid 

cells was confirmed using cell-surface staining to detect lineage-specific 

markers (Gr-1, Mac-1 vs B220). CRU frequencies in the test 

bone marrow sample were calculated by applying Poisson statistics to 

the proportion of negative recipients at different dilutions using Limit 

Dilution Analysis (StemCell Technologies) software. 

Proviral integration analysis 

Genomic DNA was extracted from producer cell lines or primary hematopoietic 

tissues using DNAzol (GibcoBRL, Burlington, ON, Canada). 

Proviral size was examined by digestion of DNA with XbaI, 

which cleaves within the MSCV LTRs. Unique integrations were identified 

by digestion of DNA with HindIII, which cleaves once within the 

provirus. Digested DNA was then separated in 1% agarose gel by electrophoresis 

and transferred to zeta-probe (Bio-Rad, Mississauga, ON, 

Canada) membranes by standard Southern blotting techniques [26]. 

32 

Membranes were probed with � P-dCTP-labeled GFP sequence. 

Results 

To gain further insight into the nature and magnitude of 

HOXB4-induced alterations on hematopoietic cell growth,

1128 

we examined the effects of HOXB4 overexpression in murine 

adult bone marrow cells following retroviral transduction. 

To facilitate isolation and tracking of transduced cells 

and their progeny, we incorporated the HOXB4 gene into a 

vector also carrying the GFP reporter gene. As shown in 

Figure 1A, the MSCV retroviral vector backbone was modified 

to support viral LTR-driven expression of GFP alone 

(GFP vector) or of a bicistronic cassette encoding HOXB4 

and GFP (HOXB4-GFP vector). Retrovirus-mediated gene 

transfer was then used to generate hematopoietic cells that 

overexpressed HOXB4 (Fig. 1B), and the growth of these 

cells was assessed both in vitro and in vivo. We confirmed 

the biological activity of this new vector through its ability 

to confer enhancement of CFU-S growth in vitro (not 

shown), as previously reported by our group [16]. 

Growth-enhancing effects of HOXB4 in vitro 

Incorporation of the GFP reporter gene allowed us to perform 

a simple yet quantitative assessment of the relative 

growth of transduced cells in a series of mixed cultures. 

Liquid cultures were initiated with equivalent total cell 

numbers but varying proportions of HOXB4-GFP–trans- 

duced (Ly5.1 

� 

) and GFP-transduced (Ly5.1 


� 

) cells (Fig. 

2A), and the proportion of HOXB4-overexpressing cells 

was monitored by Ly5.1 expression. Cultures in which the 

HOXB4-GFP–transduced cells initially contributed only 

10% or 50% rapidly became dominated by HOXB4-overexpressing 

cells. For example, the proportion of HOXB4- 

GFP–derived cells in a culture initiated with just 10% of 

these cells increased to a majority within 20 days and 

reached 75% by the end of the culture period. The predominance 

of HOXB4-GFP–transduced cells was confirmed by 

Southern blot analysis of DNA taken from 3-week cultures 

(Fig. 2B). These findings additionally indicate that the 

growth advantage conferred by HOXB4 overexpression is 

cell autonomous, as only the HOXB4-transduced cells were 

enhanced in these mixed cultures. 

Analysis of population doubling times were determined 

to be 26.4 hours for GFP-transduced cells vs 22.4 hours for 

HOXB4-GFP–transduced cells (Fig. 2C). Neither culture 

had a significant number of apoptotic cells, as measured by 

propidium iodide staining (data not shown). These data suggest 

that HOXB4 overexpression did not lead to a block in 

apoptosis, and that the growth rate of the culture is enhanced, 

possibly reflecting an increased division rate or an 

increased proportion of dividing cells. 

The data presented here suggest a cell-autonomous 

growth-enhancing effect of HOXB4 on late hematopoietic 

progenitor cells as found in short-term liquid-culture expansions. 

Furthermore, the data provide a straightforward assay 

for some aspects of HOXB4 proliferative effects. 

Competitive reconstitution of hematopoietic cells in vivo 

To directly assess the growth-enhancing effects of HOXB4 

on earlier stages of hematopoiesis, we next examined its abil- 

Figure 1. Construction and testing of the GFP and HOXB4-GFP retroviral 

vectors. (A) Structure and expected sizes of integrated provirus for the two 

vectors used in this study, including XbaI restriction sites (X). (B) Representative 

histogram showing 80% gene transfer to murine bone marrow 

cells after transduction with the HOXB4-GFP vector. Transduced, GFP � 

cells (indicated by M8 gating) can be selected by FACS. 

ity to enhance reconstitution. In initial experiments to address 

this, mice were transplanted with various mixtures of GFP- 

� 

� 

transduced (Ly5.1 ) and HOXB4-GFP–transduced (Ly5.1 ) 

cells, and the relative hematopoietic contributions of the two 

populations were monitored over time. Keeping the total 

transplant dose constant, competitions of either equal numbers 

of GFP-transduced and HOXB4-GFP–transduced cells 

or a 20-fold greater number of GFP-transduced cells were inoculated. 

Representative peripheral blood FACS profiles 

from recipients representative of both input transplant ratios 

are shown for early and late times posttransplant (Fig. 3), and 

data compiled from all mice in the 5:95 transplant group are 

summarized in Figure 4. As early as 6 weeks posttransplant, 

the vast majority of the peripheral blood cells ( �75%) 

were 

� � 

HOXB4-GFP derived (Ly5.1 , GFP ), even for recipients in 

which HOXB4 cells were in competition with a 20-fold 

greater number of control cells. Furthermore, this repopulation 

advantage demonstrated by peripheral blood analysis 

was sustained to at least 35 weeks posttransplant, the last time 

point analyzed. The data in Figure 4 are derived from the ra- 

� � 

tio of HOXB4-transduced (Ly5.1 GFP ) to GFP-transduced 

� � 

(Ly5.1 GFP ) cells in the peripheral blood, to exclude residual 

host cells from the calculations. At 6 weeks there was a 

� � 

large host (Ly5.1 GFP ) cell contribution, which diminished 

by the week-35 analysis. However, there were also a number 

of HOXB4-GFP–transduced cells in which GFP expression 

� � 

from the viral LTR was reduced or absent (Ly5.1 GFP ). 

These cells were also not included in the calculations for Figure 

4, which may therefore slightly underestimate the magnitude 

of the HOXB4 competitive advantage.

Figure 2. Expansion of transduced bone marrow cells in liquid culture. 

(A) Cultures were initiated with 0% (�), 10% (�), 50% (�), or 100% (�) 

HOXB4-GFP–transduced Ly5.1 � cells, and the reciprocal percentage control-transduced 

Ly5.1 � cells. The graph depicts the rise in the proportion of 

HOXB4-transduced (Ly5.1 � ) cells over time. (B) Southern blot analysis of 

DNA taken from mixed cultures at 30 days, digested with XbaI and probed 

with GFP, showing disappearance of the 2.8 kb control GFP proviral band. 

(C) Growth of sorted, transduced cells in culture. The HOXB4-GFP culture 

has a shorter doubling time than the control GFP-transduced culture. 

HOXB4 HSC retained normal differentiation to end 

cells. In a separate experiment, detailed analysis of mice 

transplanted exclusively with HOXB4-GFP–transduced or 

control-transduced cells confirmed normal proportions of 


1129 

cells in lymphoid and myeloid lineages. As shown in Figure 

4B, there was no significant difference in the proportions of 

cells expressing B220, Gr-1, Mac-1, or Ter119 between 

HOXB4-GFP–transduced and GFP-transduced peripheral 

blood compartments. 

Analysis of the bone marrow cells at 8 months posttransplant 

demonstrated that the dominant contribution by 

HOXB4-GFP–transduced cells also extended to more primitive 

compartments. As shown in Figure 3, virtually all bone 

marrow cells from both transplant groups were Ly5.1 

� 

GFP 

and thus derived from HOXB4-GFP–transduced repopulating 

cells. These data together provide the first direct evidence 

that HOXB4 overexpression confers complete dominance in 

reconstitution of both mature end cells in the peripheral blood 

and primitive precursors in the bone marrow. Importantly, 

this competitive advantage appears to extend to the most 

primitive HSC compartment, since secondary mice transplanted 

with bone marrow cells from this primary transplant 

also showed nearly exclusive HOXB4-GFP–derived peripheral 

blood repopulation (Fig. 3). 

Rapid regeneration of competitive repopulating units (CRU) 

The above results are consistent with HOXB4 conferring a 

marked growth advantage at the repopulating cell level, 

with no impairment of later differentiation steps. To examine 

more closely the effects of HOXB4 on CRU regeneration, 

we assessed the magnitude and kinetics of regeneration 

in the bone marrow using the limit dilution assay for competitive, 

long-term, lympho-myeloid repopulating cells. 

In previous studies, the earliest time CRU had been examined 

was 16 weeks posttransplant. To examine early 

stages of reconstitution we began to assess CRU regeneration 

beginning 2 weeks after transplantation, and at 2- to 4-week 

intervals up to 16 weeks posttransplant. Primary recipients 

received 225,000 GFP-transduced or HOXB4-GFP–transduced 

and FACS-selected cells, a dose estimated to contain 50 

CRU per recipient. Sublethally irradiated W 

41 

/W 

41 

� 

, 

mice were 

used as recipients in this study, as they provide compromised, 

endogenous competitor cells for the CRU assay [25]. Both primary 

and secondary transplants were done in this competitive 

setting, to minimize “contaminating” CRU from primary hosts 

while allowing transplant engraftment. At intervals spanning 2 

to16 weeks posttransplant, four cohorts from each group were 

sacrificed and analyzed for transplant engraftment, progenitor 

content, and CRU content. 

Engraftment was measured by analysis of Ly5.1 and 

GFP expression in peripheral blood and bone marrow by 

FACS. As shown in Figure 5, transduced cell progeny were 

detected in the circulation of both HOXB4-GFP and GFP 

transplant recipients as early as 2 weeks, and rose to plateau 

values at approximately 8 weeks. HOXB4-GFP recipients 

showed a modest acceleration of peripheral blood reconstitution, 

most notable at 4–8 weeks posttransplant. Accelerated 

repopulation of the bone marrow by HOXB4-GFP–transduced 

cells was more pronounced. At 2 weeks posttrans-

1130 

Figure 3. Competitive reconstitution by HOXB4-GFP–transduced 

(Ly5.1 � GFP � ) and GFP-transduced (Ly5.1 � GFP � ) cells. Representative 

peripheral blood FACS profiles from n � 4 mice transplanted with 50:50 

(left) or 5:95 (right) HOXB4-GFP to control GFP transplant cell ratios. At 

6 weeks posttransplant, the vast majority of the GFP � peripheral blood 

cells were derived from the HOXB4-GFP–transduced cells (Ly5.1 � , upper 

right quadrant). By 35 weeks posttransplant, the host contribution (Ly5.1 � 

GFP � , lower right quadrant) was diminished, and there was a clear dominance 

of HOXB4-GFP–derived cells in the white blood cell compartment, 

in mice from both the 50:50 and 5:95 transplant ratios. Bone marrow at 35 

weeks was made up almost exclusively of HOXB4-overexpressing cells. 

Secondary transplant recipients (n � 4 per group) also showed a predominance 

of HOXB4-GFP–derived cells in the peripheral blood. Representative 

FACS profiles are shown. 

plant, 74% of the bone marrow cells in HOXB4-GFP recip- 

� 

ients were GFP , compared to only 42% of the cells in 

control recipients. Furthermore, HOXB4-GFP–transduced 

cells had a complete competitive advantage over the endog- 

41 41 

enous W /W bone marrow cells, as these cells reached 

nearly 100% GFP positivity, compared to only 60% in the 

control mice. The HOXB4-mediated repopulation advantage 

was further reflected in the magnitude and rate of bone 

marrow clonogenic progenitor recovery. Recipients of 

HOXB4-GFP cells had between twofold and 10-fold more 

bone marrow progenitors than control recipients, and pro- 


genitor content approached a plateau earlier in the HOXB4- 

GFP recipients compared to the GFP recipients. 

The rapid hematopoietic recovery in HOXB4-GFP recipients 

was most dramatic at the CRU level. This assay quantitates 

stem cell numbers by transplantation of a test sample 

at limiting dilutions, and assaying for long-term, lymphomyeloid 

repopulation. However, our a priori estimation of 

CRU recovery in the control mice overestimated the recovery 

rate, and as a result the bone marrow dilutions transplanted 

at 4 and 12 weeks were too low. None of the CRU 

test mice were repopulated by the test samples, and we were 

unable to get an accurate quantitation of the CRU frequencies 

at these two times. At two weeks posttransplant, the 

bone marrow CRU content in control mice was only 0.2% 

of normal, and gradually increased to a maximum of 24% at 

16 weeks (Fig. 6). In contrast, the CRU levels in HOXB4- 

GFP recipients had already reached 25% of normal by two 

weeks posttransplant and were within the normal range by 

12 weeks. The rapid CRU expansion in HOXB4-GFP transplant 

recipients was confirmed in a second trial, where CRU 

expansion was 10-fold greater in HOXB4-GFP recipients at 

2 weeks posttransplant (Table 1). HOXB4 overexpression is 

thus associated with increases in both the rate of CRU recovery 

and the magnitude of maximum recovery. 

CRU regeneration at high transplant cell doses 

In the above experiments, HOXB4-GFP recipient mice 

were transplanted with approximately 50 CRU, resulting in 

regeneration of CRU to within the normal range of unmanipulated 

mice. To assess whether similar CRU levels 

would be achieved with higher transplant doses, thus suggesting 

a ceiling on CRU population size, or whether “super” 

plateau levels might be achieved, we tested the effect 

of transplant dose on CRU recovery. Mice were trans- 

5 

7 

planted over a 30-fold cell range, from 3 � 10 cells to 10 

cells. At all three doses, CRU recovery at 8 months posttransplant 

was within the normal range (Fig. 7). Thus, transplant 

inoculums spanning an estimated range of 60 to 2400 

CRU all resulted in CRU levels within, but not beyond, the 

level found in unmanipulated mice. We confirmed that the 

regenerated CRUs were derived from the HOXB4-GFP– 

transduced cells, as there was complete concordance be- 

� 

tween mice reconstituted by donor (Ly5.1 ) cells and those 

expressing GFP (data not shown). A high degree of polyclonality 

was found in the bone marrow from mice at all cell 

doses (data not shown), confirming that multiple CRU 

clones had expanded in vivo. 

Discussion 

In this study we undertook a detailed analysis of the ability 

of HOXB4 to effect the growth of hematopoietic cells in 

vitro and in vivo. Previous studies demonstrated that 

HOXB4 overexpression enhanced plateau levels of CRU recovery, 

as assessed at relatively late times posttransplant

[18]. In this study we have focused instead on very early 

times posttransplant and found a striking enhancement on 

the rate of CRU regeneration. Furthermore, this enhancement 

of HSC self-renewal does not appear to come at the 

expense of either responsiveness to HSC regulation or terminal 

differentiation. 

By incorporating GFP as a selectable marker in retroviral 

vectors, we were able to isolate control- or HOXB4-transduced 

cells and rigorously track their growth. We provide 

clear evidence of a competitive growth advantage of 

HOXB4-transduced cells in vivo, manifest in both mature 

and primitive hematopoietic cell populations. Transplant inoculums 

containing just 5% HOXB4-transduced cells resulted 

in complete repopulation of both primitive and mature 

hematopoietic compartments by HOXB4-overexpressing 

cells. This competitive repopulation argues strongly that the 

effects of HOXB4 are cell autonomous, as the growth advantage 

was not conferred to accompanying cells present in 

the same transplant inoculum. This was further supported 

by in vitro data, where only the HOXB4-transduced cells 

showed increased growth in mixed cultures. Furthermore, 

we provide direct evidence that HOXB4 overexpression 

J. Antonchuk et al./Experimental Hematology 29 (2001) 1125–1134 1131 

Figure 4. Competitive repopulation and normal differentiation. (A) Relative proportions of HOXB4-GFP– (�) or GFP- (�) transduced cells in circulating 

white blood cells from recipients of 5 � 10 3 HOXB4-GFP–transduced cells and 9.5 � 10 4 GFP-transduced cells (5:95 cell ratio), calculated as the proportion 

HOXB4-GFP–transduced (Ly5.1 � ) or GFP-transduced (Ly5.1 � ) cells within the GFP � gate. n � 4 mice were analyzed every 6–12 weeks and sacrificed after 

35 weeks for transplantation into secondary recipients. (B) Mean proportion of GFP � cells that expressed each marker, �SEM in n � 12 GFP-transduced 

(light bars) or n � 15 HOXB4-GFP–transduced (dark bars) bone marrow recipient mice. There was no significant difference (p � 0.1) in expression of Gr-1, 

Mac-1, B220, or Ter119 within the GFP � compartments of these two groups. 

does not inhibit hematopoietic differentiation, as evident by 

normal recovery and maintenance of circulating blood cells 

of all lineages, cells proven to be derived from HOXB4- 

GFP–transduced cells by the presence of GFP. 

HSC recovery was accelerated in recipients of HOXB4- 

GFP–transduced cells. HSC regeneration in recipients of 

GFP control–transduced marrow was barely detectable at 2 

weeks posttransplant, reaching only 0.2% of the normal 

level, and even by 16 weeks had reached plateau levels of 

only 24%. In contrast, CRU number in recipients of 

HOXB4-GFP–transduced bone marrow had already recovered 

to 80-fold higher levels (or 25% of normal) by 2 weeks 

and reached plateau levels within the normal range as early 

as 12 weeks posttransplant. 

The HOXB4-induced acceleration in HSC regeneration 

could reflect a number of possible mechanisms. One possibility 

is that HOXB4 overexpression may shorten the stem 

cell cycle time and/or increase the proportion of stem cells 

actively dividing. The later explanation seems unlikely, 

given observations that virtually all HSCs are actively proliferating 

shortly after bone marrow transplantation [7]. 

Studies on RAT-1 fibroblasts engineered to overexpress

1132 J. Antonchuk et al./Experimental Hematology 29 (2001) 1125–1134 

Figure 5. Repopulation by GFP- or HOXB4-GFP–transduced cells in sublethally 

irradiated W 41 /W 41 recipients. Shown is the mean (� SEM) donorderived 

repopulation of peripheral blood (top graph) or bone marrow (middle 

graph) by HOXB4-GFP–transduced (dark bars) or GFP-transduced 

(light bars) cells in n � 4 recipient cohorts at each time point. The 

HOXB4-overexpressing cells repopulate more rapidly and to a greater 

extent in this competitive setting. Mean (� SEM) bone marrow CFC 

recovery is elevated at all time points in the HOXB4-GFP transplant group 

(bottom graph). 

HOXB4 revealed increased proliferation associated with 

upregulation of cell-cycle regulators of the AP1 complex as 

well as cyclin D [27]. A shortening of cell cycle is further 

supported by the significantly shorter population doubling 

time in bulk bone marrow cultures. While the degree of 

CRU growth in the first few weeks in vivo is beyond that 

accountable solely by the enhanced growth kinetics demonstrated 

in vitro, these cultures contained a vast majority of 

more mature cells, which might not be affected by HOXB4 

overexpression. 

A second possibility is that HOXB4 levels directly alter 

the probability of HSC self-renewal. The acceleration of 

CRU expansion is consistent with this, particularly if we 

suppose that both control and HOXB4 HSC are maximally 

cycling. Additionally, HOXB4 may alter the responsiveness 

of HSCs to extrinsic regulators. Increased responsiveness to 

Figure 6. Kinetics of CRU expansion in vivo. The number of CRU in 

femurs of 4 cohorts of HOXB4-GFP (�) or GFP (�) recipients were evaluated 

at 2, 4, 8, 12, and 16 weeks posttransplantation using the CRU assay. 

At 4 and 12 weeks, the CRU values in control GFP mice were below the 

level of detection, as no GFP tertiary recipients were repopulated by transduced 

cells. The CRU values at these times are below the points indicated 

(↓) on the graph. For all other time points, the results are expressed as the 

average � SEM of the CRU numbers in one femur of HOXB4-GFP or 

GFP control mice. The dashed lines represent the normal number of CRU 

in 1 femur of an unmanipulated mouse, based on previous data [3]. CRU 

regeneration by HOXB4-GFP–transduced cells was significantly greater 

than by GFP-transduced cells at 2 weeks (p � 0.001), 8 weeks (p � 0.05), 

12 weeks (p � 0.001), and 16 weeks (p � 0.05). 

self-renewal stimulation is suggested by the accelerated 

growth demonstrated in the early period posttransplant, and 

a decreased responsiveness to negative regulation is suggested 

by the ability to reach much higher plateau levels. Intriguingly 

however, even with large transplant cell doses, 

Figure 7. CRU regeneration following transplantation of high HOXB4- 

GFP transplant cell doses. CRU frequency in the transplant innoculum was 

determined to be approximately 1/4000, giving the input CRU numbers 

shown on the x-axis. CRU content in the bone marrow of n � 4 recipient 

mice was determined at 8 months posttransplant, and is represented as the 

mean (�95% confidence interval [CI]) CRU content per mouse. At each 

dose tested, CRU recovery is within the 95% CI of the CRU content determined 

from an unmanipulated control mouse.

Table 1. CRU regeneration at two weeks posttransplant 

HSC regeneration did not exceed normal levels, indicating 

that HOXB4 does not override extrinsic mechanisms that 

appear to control HSC population size. This is in contrast to 

the findings seen with bone marrow cells engineered to 

overexpress MDR1, which had continued HSC growth in 

vivo, leading to a myeloproliferative syndrome [28,29]. 

Another intriguing, although purely speculative, possibility 

is that HOXB4 might allow for recruitment of other cell 

types into a stem cell fate, by forcing somewhat more mature 

hematopoietic cells to “de-differentiate” to hematopoietic 

totipotency. A number of recent studies have demonstrated 

that lineage commitments can be reversible given sufficient 

alternate stimulus. Examples include “trans-differentiation” 

of muscle [30], neural [31], or hematopoietic [32–37] stem 

cells when transplanted to alternate body environments, as 

well as a recent report of oligodendrocyte precursor cell “dedifferentiation” 

into neural stem cells [38]. 

If we speculate that the effects demonstrated here represent 

an exaggeration of the normal role of HOXB4, then this 

transcription factor could play a critical role in HSC regulation. 

While we cannot rule out the possibility that the very 

high levels of HOXB4 in this setting are mimicking the effects 

of another, closely related gene, it appears as though 

HOXB4 levels could regulate stem cell self-renewal under 

steady-state conditions and be a limiting factor in HSC regeneration. 

This is in agreement with Hox expression data, 

which showed Hox genes—particularly those at the 3� end 

of the clusters, such as HOXB4—to be preferentially expressed 

in primitive cells and downregulated with hematopoietic 

differentiation [12]. 

The growth-enhancing effects demonstrated here in vitro 

and in vivo raise the possibility of exploiting HOXB4 as a 

stem cell amplifying factor, for example to provide a selective 

growth advantage to transduced cells in gene therapy 

models. These data raise interesting speculation on possible 

growth enhancing effects of HOXB4 on HSC in vitro, a 

property that has yet to be tested. Additionally, downstream 

genes whose expression is affected by HOXB4 are also potentially 

important HSC effectors, and identification of such 

genes will be of interest to further our understanding of 

HSC regulation. 

Acknowledgments 

We thank Patty Rosten and Gayle Thornbury for technical assistance 

and cell sorting. 

J. Antonchuk et al./Experimental Hematology 29 (2001) 1125–1134 1133 

Expt No. Transplant type CRU frequency (95% CI) No. CRU/femur (95% CI) % of normal 

1 HOXB4-GFP 1/28,000 (1/12,000–1/67,000) 620 (260–1,500) 25 

GFP 1/1,490,000 (1/200,000–1/11,000,000) 6 (1–46) 0.2 

2 HOXB4-GFP 1/57,000 (1/23,000–1/141,000) 400 (160–1,000) 16 

GFP �1/470,000 �30 �1.2 

CI, confidence interval. 

References 

1. Harrison DE, Stone M, Astle CM (1990) Effects of transplantation on 

the primitive immunohematopoietic stem cell. J Exp Med 172:431 

2. Rebel VI, Miller CL, Eaves CJ, Lansdorp PM (1996) The repopulation 

potential of fetal liver hematopoietic stem cells in mice exceeds that of 

their liver adult bone marrow counterparts. Blood 87:3500 

3. Pawliuk R, Eaves C, Humphries RK (1996) Evidence of both ontogeny 

and transplant dose-regulated expansion of hematopoietic stem 

cells in vivo. Blood 88:2852 

4. Chen J, Astle CM, Harrison DE (1999) Development and aging of 

primitive hematopoietic stem cells in BALB/cBy mice. Exp Hematol 

27:928 

5. Harrison DE (1979) Proliferative capacity of erythropoietic stem cells 

lines and aging: an overview. Mech Aging Dev 9:409 

6. Vaziri HDW, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM 

(1994) Evidence for a mitotic clock in human hematopoietic stem cells: 

loss of telomeric DNA with age. Proc Natl Acad Sci U S A 91: 9857 

7. Iscove N, Nawa K (1997) Hematopoietic stem cells expand during serial 

transplantation in vivo without apparent exhaustion. Curr Biol 7: 805 

8. Chen J, Astle CM, Harrison DE (2000) Genetic regulation of primitive 

hematopoietic stem cell senescence. Exp Hematol 28:442 

9. Phillips RL, Ernst RE, Brunk B, et al. (2000) The genetic program of 

hematopoietic stem cells. Science 28:1635 

10. Domen J, Cheshier SH, Weissman IL (2000) The role of apoptosis in the 

regulation of hematopoietic stem cells: Overexpression of bcl-2 increases 

both their number and repopulation potential. J Exp Med 191: 253 

11. Cheng T, Rodrigues N, Shan H, et al. (2000) Hematopoietic stem cell 

quiescence maintained by p21cip1/waf1. Science 287:1804 

12. Sauvageau G, Lansdorp PM, Eaves CJ, et al. (1994) Differential expression 

of homeobox genes in functionally distinct CD34 � subpopulations 

of human bone marrow cells. Proc Natl Acad Sci U S A 91: 12223 

13. Izon DJ, Rozenfeld S, Fong ST, Komuves L, Largman C, Lawrence HJ 

(1998) Loss of function of the homeobox gene Hoxa-9 perturbs early 

T-cell development and induces apoptosis in primitive thymocytes. 

Blood 92:383 

14. Lawrence HJ, Helgason CD, Sauvageau G, Fong S, Izon DJ, 

Humphries RK, et al. (1997) Mice bearing a targeted interruption of 

the homeobox gene HOXA9 have defects in myeloid, erythroid, and 

lymphoid hematopoiesis. Blood 89:1922 

15. Thorsteinsdottir U, Sauvageau G, Hough MR, et al. (1997) Overexpression 

of HOXA10 in murine hematopoietic cells perturbs both myeloid 

and lymphoid differentiation and leads to acute myeloid leukemia. 

Mol Cell Biol 17:495 

16. Sauvageau G, Thorsteinsdottir U, Eaves CJ, et al. (1995) Overexpression 

of HOXB4 in hematopoietic cells causes the selective expansion 

of more primitive populations in vitro and in vivo. Genes Dev 9:1753 

17. Sauvageau G, Thorsteinsdottir U, Hough MR, et al. (1997) Overexpression 

of HOXB3 in hematopoietic cells causes defective lymphoid 

development and progressive myeloproliferation. Immunity 6:13 

18. Thorsteinsdottir U, Sauvageau G, Humphries RK (1999) Enhanced in 

vivo regenerative potential of HOXB4-transduced hematopoietic stem 

cells with regulation of their pool size. Blood 94:2605 

19. Hawley RG, Lieu FH, Fong A, Hawley TS (1994) Versatile retroviral 

vectors for potential use in gene therapy. Gene Ther 1:136 

20. Pawliuk R, Kay R, Lansdorp P, Humphries RK (1994) Selection of ret-

1134 J. Antonchuk et al./Experimental Hematology 29 (2001) 1125–1134 

rovirally transduced hematopoietic cells using CD24 as a marker of 

gene transfer. Blood 84:2868 

21. Kinsella TM, Nolan GP (1996) Episomal vectors rapidly and stably 

produce high-titer recombinant retrovirus. Hum Gen Ther 7:1405 

22. Markowitz D, Goff S, Bank A (1988) A safe packaging line for gene 

transfer: separating viral genes on two different plasmids. J Virol 62: 1120 

23. Kalberer CP, Pawliuk R, Imren S, et al. (2000) Preselection of retrovirally 

transduced bone marrow avoids subsequent stem cell gene silencing 

and age-dependent extinction of expression of human �-globin in 

engrafted mice. Proc Natl Acad Sci U S A 97:5411 

24. Szilvassy SJ, Humphries RK, Lansdorp PM, Eaves AC, Eaves CJ (1990) 

Quantitative assay for totipotent reconstituting hematopoietic stem cells 

by a competitive repopulation strategy. Proc Natl Acad Sci U S A 87:8736 

25. Miller CL, Eaves CJ (1997) Expansion in vitro of adult murine hematopoietic 

stem cells with transplantable lympho-myeloid reconstituting 

ability. Proc Natl Acad Sci U S A 94:13648 

26. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory 

manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory 

Press 

27. Krosl J, Sauvageau G (2000) AP-1 complex is effector of hox-induced 

cellular proliferation and transformation. Oncogene 19:5134 

28. Bunting KD, Galipeau J, Topham D, Benaim E, Sorrentino BP (1998) 

Transduction of murine bone marrow cells with an MDR1 vector enables 

ex vivo stem cell expansion, but these expanded grafts cause a 

myeloproliferative syndrome in transplanted mice. Blood 92:2269 

29. Bunting KD, Zhou S, Lu T, Sorrentino BP (2000) Enforced P-glycoprotein 

pump function in murine bone marrow cells results in expansion 

of side population stem cells in vitro and repopulating cells in 

vivo. Blood 96:902 

30. Jackson KA, Mi T, Goodell MA (1999) Hematopoietic potential of 

stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci 

U S A 96:14482 

31. Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL 

(1999) Turning brain into blood: a hematopoietic fate adopted by adult 

neural stem cells in vivo. Science 283:534 

32. Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate 

throughout forebrain and cerebellum, and they differentiate into 

astrocytes after injection into neonatal mouse brains. Proc Natl Acad 

Sci U S A 96:10711 

33. Lagasse E, Connors H, Al-Dhalimy M, et al. (2000) Purified hematopoieitic 

stem cells can differentiate into hepatocytes in vivo. Nat Med 

6:1229 

34. Pereira RF, O’Hara MD, Laptev AV, et al. (1998) Marrrow stromal 

cells as a source of progenitor cells for nonhematopoietic tissues in 

transgenic mice with a phenotype of osteogenesis imperfecta. Proc 

Natl Acad Sci U S A 95:1142 

35. Periera RF, Halford KW, O’Hara MD, et al. (1995) Cultured adherent 

cells from marrow can serve as long-lasting precursor cells for 

bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A 

92: 4857 

36. Gussoni E, Soneoka Y, Strickland CD, et al. (1999) Dystrophin expression 

in the mdx mouse restored by stem cell transplantation. Nature 

401:390 

37. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo 

AG, Mavilio F (1998) Muscle regeneration by bone marrow–derived 

myogenic progenitors. Science 279:1528 

38. Kondo T, Raff M (2000) Oligodendrycyte precursor cells reprogrammed 

to become multipotential CNS stem cells. Science 289:1754

PORPHYRIN-BASED NEUTRON CAPTURE AGENTS FOR CANCER THERAPY 


PORPHYRIN-BASED NEUTRON CAPTURE AGENTS FOR 

CANCER THERAPY 

BACKGROUND: Boron neutron capture therapy (BNCT) is an emerging therapeutic modality for the 

treatment of cancer. In BNCT, cytotoxic high linear energy transfer (high-LET) particles, created by the 

10 B(n, α) 7 nuclear reaction, destroy localized boron-containing tissue. This therapy has been particularly 

effective in the treatment of malignant brain tumors due to its ability to target and destroy malignant 

cells in the presence of normal cells without the problematic side effects common in other types of 

treatments. Porphyrins and their diamagnetic metal complexes are highly fluorescent, which provides a 

means for detection of tumor cells and investigation of the 10 B localization in tumors and surrounding 

tissue. Currently, there are two BNCT agents undergoing Phase I and Phase II clinical studies. However, 

although these agents have been shown to be safe and efficacious in animal models, they do possess 

limitations, such as moderate selectivity for tumor cells and low retention times in tissues. Porphyrins 

are good photosensitizers and one porphyrin derivative is currently the only drug with FDA approval for 

the photodynamic therapy (PDT) of tumors, which is another cancer treatment modality that involves the 

activation of the tumor-localized sensitizer with light. 

DESCRIPTION: Scientists at the University of California have developed improved porohyrin-based 

drugs using a new synthetic method. A unique linkage involving the porphyrin ring results in increased 

in vitro and in vivo stability over existing drugs. 

APPLICATIONS: This new invention has application in cancer detection and treatment modalities, 

such as BNCT and PDT. 


● Expeditious, high-yielding routes to very promising new drugs; 

● Improved stability; 

● Higher solubility allows for easy administration into the bloodstream without a co-solvent. 

INQUIRIES TO: 


PORPHYRIN-BASED NEUTRON CAPTURE AGENTS FOR CANCER THERAPY 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






Porphyrin-Based Neutron Capture Agents for Cancer Therapy 

TTC Homepage | Invention Categories | All Inventions 



A new synthetic method producing porphyrin-based neutron capture agents for use in cancer therapy has been 

developed by University of California, Davis researchers. Through a unique linkage involving the porphyrin 

ring, these new compounds afford increased selectivity for tumor cells and improved in vitro and in vivo 

stability over existing drugs. Boron neutron capture therapy (BNCT) is an emerging therapeutic modality for the 

treatment of cancer. By targeting localized boron-containing tissue, high linear energy transfer (high-LET) 

particles are able to destroy malignant cells in the presence of normal cells without causing damage to healthy 

tissue. This therapy has been particularly effective in the treatment of malignant brain tumors. Porphyrins are 

highly fluorescent and presently the best-known carriers of elements such as boron for selective uptake by 

cancerous cells. 

The new UC Davis compounds are superior to existing neutron capture agents in that: 

● Retention times for boron in malignant tissue are greatly increased 

● Greater solubility allows for simple administration into the bloodstream without a co-solvent 

● Increased stability improves overall performance and selectivity 

● Efficient synthesis involves readily available reagents 

Related categories: 

Human Medicine 

INQUIRIES TO: Nancy E Rashid 

E-MAIL: nerashid@ucdavis.edu 

REFERENCE: UC Case No.2000-299 

University of California, Davis 

http://patron.ucop.edu/ncd/docs/ucd2000-299.html (1 of 2)10/21/2005 2:48:28 AM


Technology Transfer Center 

1850 Research Park Drive, Suite 100 

Davis, CA 95616-4664 

Phone: (530) 757-3432 Fax: (530) 758-3276 

http://patron.ucop.edu/ncd/docs/ucd2000-299.html (2 of 2)10/21/2005 2:48:28 AM

Prodrugs of Pharmaceuticals with Improved Bioavailability 

Prodrugs of Pharmaceuticals with Improved Bioavailability 

BACKGROUND: Bioavailability refers to the extent to which a drug reaches its site of action or a 

biological fluid from which the drug has access to its site of action. Bioavailability of orally 

administered drugs minimally requires their absorption through the mucosal cells of the small intestine. 

This absorption depends primarily on their ability to pass through the lipid barrier of enterocyte 

membranes. Drugs having poor oral bioavailability may nevertheless be usable if administered by 

injection. Bioavailability of injected drugs requires their uptake by the target tissue, and this uptake 

depends in part on their ability to penetrate the lipid barrier of the cell membranes of such tissue. Many 

drug candidates having poor oral bioavailability fail because the parenteral route of administration is not 

widely acceptable to patients. 

DESCRIPTION: The UCSD researchers have discovered second-generation lipid prodrug derivatives 

which enhance oral bioavailability and/or cellular uptake and retention regardless of the route of 

administration. The new prodrugs would be metabolized in target tissues to release the parent drug. 

These prodrugs are expected to have substantially enhanced activity over the parent compounds against 

various cancers, viral diseases, autoimmune diseases, and other inflammatory and proliferative diseases. 

Types of parent drugs which may be utilized include HIV protease inhibitors, anti-viral and anti-cancer 

nucleoside analogs, antibiotics, short peptides, peptidomimetics or other compounds having a suitable 

chemical group for attachment of the lipid moiety. 

ADVANTAGES: The enhanced activity of the new prodrug derivatives is expected to permit oral 

therapy at lower doses than the parent drug, thereby lessening toxicity without sacrificing therapeutic 

efficacy. Compounds of this class are predicted to have increased oral absorption and increased central 

nervous system uptake. 

CASE NUMBERS: SD95-161 


PROTEIN MARKER OF CERTAIN CANCERS AND JOINT DISEASES, ALCOHOLIC CIRRHOSIS, AND STREPTOCOCCUS PNEUMONIA 


PROTEIN MARKER OF CERTAIN CANCERS AND JOINT 

DISEASES, ALCOHOLIC CIRRHOSIS, AND STREPTOCOCCUS 

PNEUMONIA 

DESCRIPTION: University of California researches have developed a sensitive and precise 

immunoassay for detecting the presence and degree of certain diseases related to breast and colorectal 

cancers, inflammatory and degenerative joint diseases, hepatic fibrosis, and bacterial pneumonia. This 

immunoassay involves measuring free-circulating, human glycoprotein (UC glycoprotein) that is 

secreted in the blood serum and synovial fluid upon release of UC glycoprotein by certain cells, such as 

chondrocytes, synovial cells, macrophages and neutrophils. 

APPLICATIONS: 

Breast Cancer and Colorectal Cancer: In certain types of metastatic cancers, the break down of 

connective tissue in vessel walls and possibly, body organs, causes cells to migrate from the primary 

cancer tissue and trigger the secretion of UC glycoprotein into the serum. An immunoassay that 

measures the UC glycoprotein levels in the blood serum has been shown to detect the presence and 

degree of metastatic cancers. 

A study involving a clinical group of 60 patients with recurrent, metastatic breast cancer showed 

elevated serum levels of the UC glycoprotein as compared to a control group of 137 patients. In 

addition, when comparing the serum levels of the 60 patients who had cancer, the level of UC 

glycoprotein directly corresponded with the expected period of survival. Patients who had a higher level 

of UC glycoprotein in their serum had a shorter period of survival. 

Similar results were shown in a more recent clinical study involving patients with colorectal cancer. 

Immunoassays were performed on 863 patients, comprising of 603 patients with pre-operative cancer 

and 260 control patients. In this study, among the 603 patients who had pre-operative cancer, researchers 

found a strong correlation between higher serum levels of UC glycoprotein levels and shorter periods of 

survival. This relationship was also found when other variables were held constant, such as other 

preoperative indicators of morbidity. 



Inflammatory and Degenerative Joint Diseases: An important step in detecting joint disease and 

measuring the effects of treatment is to develop an assay that measures a biochemical marker of 

inflammation and cartilage remodeling. At the present, the most widely used assay is one that measures 

the serological markers associated with rheumatoid arthritis, called C-reactive protein (CRP) and 

erythrocyte sedimentation rate (ESR). Because joint destruction in patients with rheumatoid arthritis is 

irreversible, a major goal in treating this disease is to identify those patients that have active, ongoing 

joint destruction. This is particularly difficult when joint destruction can occur independently of any 

clinical symptom, such as swollen and tender joints, morning stiffness, and detection of the serological 

markers, CRP and ESR. 

The UC researchers have discovered that serum levels of the UC glycoprotein may not only measure 

disease activity associated with clinical symptoms of rheumatoid arthritis (i.e. swollen tender joints, and 

morning stiffness), but may also measure disease activity associated with joint destruction that is 

independent of clinical symptoms or acute phase reactants as measured by CRP and ESR. Recent studies 

have shown that patients who have few or no clinical symptoms still have elevated serum levels of the 

UC glycoprotein. 

In another study, immunoassays were performed on a clinical group of 99 patients - a group comprising 

of 42 patients with inflammatory joint disease (i.e., rheumatoid, crystal, psoriatic, and reactive arthritis), 

7 patients with osteoarthritis of the knee and 50 control patients. The results showed that among the 49 

patients who had inflammatory joint disease or osteoarthritis, levels of the UC glycoprotein in both the 

serum and synovial fluid were significantly higher than the levels of the 50 control patients. In 

particularly, the level of UC glycoprotein found in the synovial fluid was 15 fold higher than that of 

serum, with a significant correlation of r=0.55, p


cirrhosis. 

Bacterial Pneumonia: Pneumonia is a condition caused by infectious agents that result in inflammation 

and consolidation of the lung tissue. The desired course of treatment is dependent upon early detection 

of pneumonia, assessment of its severity, and identification of the causative agent. 

In a study involving 90 patients who were hospitalized with pneumonia of supposed bacterial origin, 

immunoassays showed an increase in serum levels of the UC glycoprotein that was due to both the type 

of infectious agent and the presence or absence of antibiotic treatment. For example, patients infected 

with S. pneumoniae showed a nine-fold increase in serum concentrations of UC glycoprotein as 

compared to healthy patients. On the other hand, patients who had been observed as having atypical 

pneumonia or Haemophilus influenzae pneumoniae showed little or no elevation of UC glycoprotein 

levels. When patients infected with S. pneumoniae were treated with antibiotics, their serum 

concentrations of the UC glycoprotein rapidly declined to normal base line levels indicative of healthy 

patients, usually within one week. It was noted that patients infected with S. pneumoniae had displayed 

greater infiltration of the lung when compared to other patients. This may suggest that levels of the UC 

glycoprotein is determined by the extent of lung infiltration or by the specific etiology attributed to S. 

pneumoniae. 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 










PROTEIN MARKER OF CERTAIN CANCERS AND JOINT 

DISEASES, ALCOHOLIC CIRRHOSIS, AND STREPTOCOCCUS 

PNEUMONIA 

DESCRIPTION: University of California researches have developed a sensitive and precise 

immunoassay for detecting the presence and degree of certain diseases related to breast and colorectal 

cancers, inflammatory and degenerative joint diseases, hepatic fibrosis, and bacterial pneumonia. This 

immunoassay involves measuring free-circulating, human glycoprotein (UC glycoprotein) that is 

secreted in the blood serum and synovial fluid upon release of UC glycoprotein by certain cells, such as 

chondrocytes, synovial cells, macrophages and neutrophils. 

APPLICATIONS: 

Breast Cancer and Colorectal Cancer: In certain types of metastatic cancers, the break down of 

connective tissue in vessel walls and possibly, body organs, causes cells to migrate from the primary 

cancer tissue and trigger the secretion of UC glycoprotein into the serum. An immunoassay that 

measures the UC glycoprotein levels in the blood serum has been shown to detect the presence and 

degree of metastatic cancers. 

A study involving a clinical group of 60 patients with recurrent, metastatic breast cancer showed 

elevated serum levels of the UC glycoprotein as compared to a control group of 137 patients. In 

addition, when comparing the serum levels of the 60 patients who had cancer, the level of UC 

glycoprotein directly corresponded with the expected period of survival. Patients who had a higher level 

of UC glycoprotein in their serum had a shorter period of survival. 

Similar results were shown in a more recent clinical study involving patients with colorectal cancer. 

Immunoassays were performed on 863 patients, comprising of 603 patients with pre-operative cancer 

and 260 control patients. In this study, among the 603 patients who had pre-operative cancer, researchers 

found a strong correlation between higher serum levels of UC glycoprotein levels and shorter periods of 

survival. This relationship was also found when other variables were held constant, such as other 

preoperative indicators of morbidity. 



Inflammatory and Degenerative Joint Diseases: An important step in detecting joint disease and 

measuring the effects of treatment is to develop an assay that measures a biochemical marker of 

inflammation and cartilage remodeling. At the present, the most widely used assay is one that measures 

the serological markers associated with rheumatoid arthritis, called C-reactive protein (CRP) and 

erythrocyte sedimentation rate (ESR). Because joint destruction in patients with rheumatoid arthritis is 

irreversible, a major goal in treating this disease is to identify those patients that have active, ongoing 

joint destruction. This is particularly difficult when joint destruction can occur independently of any 

clinical symptom, such as swollen and tender joints, morning stiffness, and detection of the serological 

markers, CRP and ESR. 

The UC researchers have discovered that serum levels of the UC glycoprotein may not only measure 

disease activity associated with clinical symptoms of rheumatoid arthritis (i.e. swollen tender joints, and 

morning stiffness), but may also measure disease activity associated with joint destruction that is 

independent of clinical symptoms or acute phase reactants as measured by CRP and ESR. Recent studies 

have shown that patients who have few or no clinical symptoms still have elevated serum levels of the 

UC glycoprotein. 

In another study, immunoassays were performed on a clinical group of 99 patients - a group comprising 

of 42 patients with inflammatory joint disease (i.e., rheumatoid, crystal, psoriatic, and reactive arthritis), 

7 patients with osteoarthritis of the knee and 50 control patients. The results showed that among the 49 

patients who had inflammatory joint disease or osteoarthritis, levels of the UC glycoprotein in both the 

serum and synovial fluid were significantly higher than the levels of the 50 control patients. In 

particularly, the level of UC glycoprotein found in the synovial fluid was 15 fold higher than that of 

serum, with a significant correlation of r=0.55, p


cirrhosis. 

Bacterial Pneumonia: Pneumonia is a condition caused by infectious agents that result in inflammation 

and consolidation of the lung tissue. The desired course of treatment is dependent upon early detection 

of pneumonia, assessment of its severity, and identification of the causative agent. 

In a study involving 90 patients who were hospitalized with pneumonia of supposed bacterial origin, 

immunoassays showed an increase in serum levels of the UC glycoprotein that was due to both the type 

of infectious agent and the presence or absence of antibiotic treatment. For example, patients infected 

with S. pneumoniae showed a nine-fold increase in serum concentrations of UC glycoprotein as 

compared to healthy patients. On the other hand, patients who had been observed as having atypical 

pneumonia or Haemophilus influenzae pneumoniae showed little or no elevation of UC glycoprotein 

levels. When patients infected with S. pneumoniae were treated with antibiotics, their serum 

concentrations of the UC glycoprotein rapidly declined to normal base line levels indicative of healthy 

patients, usually within one week. It was noted that patients infected with S. pneumoniae had displayed 

greater infiltration of the lung when compared to other patients. This may suggest that levels of the UC 

glycoprotein is determined by the extent of lung infiltration or by the specific etiology attributed to S. 

pneumoniae. 






June 17, 2003; US Patent # 6,794,150 issued September 21, 2004 


● Biotechnology > Genetic engineering sys > Immunoassay polyclonal 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 








Protein That Down Regulates Oncogenic Growth Factor Receptor 

Protein That Down Regulates Oncogenic Growth Factor Receptor 

BACKGROUND: The regulation of cell proliferation is controlled by various intracellular and 

extracellular factors. In epithelial cells, it is regulated, in part, by epidermal growth factor (EGF), which 

binds to a specific epithelial cell surface receptor, the EGF receptor (EGFR). The expression of EGFR 

on the cell surface is regulated such that, upon binding of EGF, a signal is transduced into the cell 

resulting in stimulation of cell growth and division. In due course, however, the EGF-EGFR complex is 

transported from the cell surface into lysosomes. The removal of these receptors from the cell surface 

(down regulation) is an important adaptive response used by cells to control proliferation. Though 

certain motifs within growth factor receptors have been identified as required for down regulation, the 

proteins that bind to them to have not been identified. 

DESCRIPTION: The UCSD researchers have discovered a family of human proteins, referred to as 

Sorting Nexins (SNX) and cDNAs encoding them. SNXs act by down regulating the expression of cell 

surface receptors (related to cell proliferation) by binding to them and directing their translocation to 

lysosomes within the cell. 

ADVANTAGES: The cDNAs discovered would be useful for identifying other members of the SNX 

family of proteins likely to have specificity for other growth factor receptors that may be important in 

malignancy and other abnormal cell growth states. They would also be useful as specific therapeutic 

approach to certain forms of cancer. 



PROTEIN WITH SIGNAL TRANSDUCTION ACTIVITY 



BACKGROUND: Receptor signaling pathways are the subject of widespread research efforts, with 

particular attention being paid to growth factors and their role in cell growth and differentiation. 

Ultimately, such research may make it possible to design novel pharmaceuticals for improved treatment 

of many diseases, including developmental disorders, cancer, atherosclerosis, and inflammation of 

injured tissues. 

DESCRIPTION: University of California researchers have cloned a cDNA expressing a protein with 

unique inositol polyphosphate 5-phosphatase/phosphatidylinositol 5-phosphatase activity. This 

phosphatase is an important cytosolic molecule that acts on phospholipid signaling molecules generated 

by PI3 kinase (a well-known growth regulatory signaling molecule) and inositol phosphates known to 

regulate Ras signaling. 

APPLICATIONS: This protein is a likely target for drugs designed to modulate the Ras pathway and 

other growth regulatory pathways dependent on phospholipid signaling. The UC protein encoded by this 

cDNA should prove to be valuable for screening candidate agonists and antagonists to Ras phospholipidregulated 

signaling pathways. The protein itself may be useful for treating proliferative disorders. 



US Patent # 6,001,354 issued December 14, 1999; US Patent # 6,296,848 issued 


October 2, 2001; US Patent # 6,472,197 issued October 29, 2002 


● Biotechnology > Proteins/protein eng sys > Protein/peptide sequence 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




PSEUDOPTEROSIN AND SYNTHETIC DERIVATIVES THEREOF 



BACKGROUND: Caribbean gorgonians (O. Gorgonacea, Ph. Cnidaria) are a diverse group of marine 

animals that are commonly known as sea whisps and sea fans. A few of the Caribbean gorgonians have 

been analyzed for their chemical content and found to be a source of many diverse biologically active 

substances, such as steroids, prostaglandins, and lactones. Since only a small percentage of the total 

number of Caribbean gorgonian species have been examined for natural chemical products, there has 

been a continuing effort by a number of researchers to examine additional gorgonian species in order to 

isolate possible novel natural chemical compounds. 

DESCRIPTION Researchers at the University of California have isolated and identified a novel 

compound from Caribbean gorgonians called Pseudopterosin A. They have found that Pseudopterosin A 

and certain natural and synthetic derivatives of Pseudopterosin A are effective as anti-inflammatory 

agents, anti-proliferative agents and analgesic agents. These compounds, as well as pharmaceutical 

compositions of the compounds, are available. 

ADVANTAGES: The pseudopterosin compounds represent a basis for the development of novel 

therapeutics. 

APPLICATIONS: The pseudopterosin compounds may be useful in the treatment of: 

● Rheumatoid arthritis, osteoarthritis, rheumatic carditis, auto-immune diseases such as myasthenia 

gravis, allergic diseases, bronchial asthma. 

● Ocular and skin inflammatory diseases such as poison ivy, richen planus and pemphigus. 

● Proliferative diseases such as psoriasis. 

● Leukemia type cancers, such as acute lymphoblastic leukemia, acute myeoblastic leukemia, 

chronic lymphocytic leukemia and chronic granulocytic leukemia.. 

● Neurological diseases involving metabolism of nervous tissue phospholipid, such as multiple 

sclerosis. 

● Insect bites, bee or wasp stings or any venom in which a major constituent is the enzyme 

phospholipase A2. 

● Pain resulting from traumatic injury or acute progressive disease, such as post operative pain, 

burns, or other conditions involving a coincident inflammation. 





US Patent # 4,745,104 issued May 17, 1988; US Patent # 4,849,410 issued July 


18, 1989 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






QUANTITATIVE ALLELE ANALYSIS: AN IMPROVED METHOD FOR ENUMERATING DNA COPY NUMBER OF MULTIPLE ALLELES 


QUANTITATIVE ALLELE ANALYSIS: AN IMPROVED METHOD 

FOR ENUMERATING DNA COPY NUMBER OF MULTIPLE 

ALLELES 

In the search for many disease genes, particularly those for cancer, a genome-wide search for regions 

containing such genes is often used to implicate a particular chromosome or chromosome fragment in 

the disease process. Further localization of the region is often done using loss of heterozygosity (LOH) 

studies. Unfortunately, LOH is often hampered by insufficient heterozygosity, such that in humans an 

LOH marker is homozygous (and therefore not interpretable) about 50% of the time. In pure bled 

laboratory animals polymorphic content is very close to 0%. 

To overcome LOH's shortcomings, researchers at the University of California have developed a novel 

method for determining relative DNA copy numbers at many polymorphic marker loci throughout the 

genome. Using a PCR-based analysis, the UC method (called "Quantitative Allele Analysis" or 

"Quantitative Microsatellite Analysis" or QuMA) is able to measure copy number at many microsatellite 

loci. Initial applications of QuMA included tests on radiation-induced leukemia in mice (associated with 

an aberration on mouse chromosome 2), sexual differentiation of human cells (using copy numbers of X 

chromosome markers), and confirming the allelic loss of human chromosome 8p in a primary prostate 

adenocarcinoma sample. In these tests, QuMA proved to be very reproducible and sensitive enough to 

readily detect regional single copy differences between test and reference DNA samples. 

The relative simplicity, non-invasiveness, and low cost of QuMA also suggest likely applications of 

genomic copy number analysis that extend well beyond the usual range of LOH applications, especially 

in areas currently dominated by traditional karyotyping methods and FISH. For example, QuMA might 

be widely used in prenatal diagnostics of allele imbalances. QuMA also offers many advantages in the 

field of cancer diagnosis, prognosis and therapy, its high resolution enabling superior discrimination 

among different kinds of tumors (a crucial factor in optimizing the course of treatment). 

INQUIRIES TO: Candace L. Voelker Candy.Voelker@ucop.edu 


QUANTITATIVE ALLELE ANALYSIS: AN IMPROVED METHOD FOR ENUMERATING DNA COPY NUMBER OF MULTIPLE ALLELES 










Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




QUANTITATIVE MEASUREMENT OF TISSUE PROTEIN IDENTIFIE...ISTOCHEMISTRY AND STANDARDIZED PROTEIN DETERMINATION 


QUANTITATIVE MEASUREMENT OF TISSUE PROTEIN 

IDENTIFIED BY IMMUNOHISTOCHEMISTRY AND 

STANDARDIZED PROTEIN DETERMINATION 

BACKGROUND: The ability to manipulate cells, relate the characteristics of the cells to status and 

function, and associate various markers with physiological state and disease has improved substantially 

in recent years. For example, it has been found that cancer prognosis can be related to the level of 

particular cellular components, such as oncogenes and receptors. There is therefore substantial interest in 

being able to provide methods which can reproducibly provide reliable quantitative or semi-quantitative 

data on the amount of specific components in a cell. This data can be used in the understanding of 

physiological processes, particularly cellular processes, for predictive capabilities of disease progress, 

disease responsiveness to therapy, cancer aggressiveness, and the like. 

DESCRIPTION: Researchers at the University of California have developed methods and 

compositions for quantitating a molecular cellular component on a cellular basis by employing 

immunohistochemical staining and cellular standards to define quantitatively the amount of the cellular 

component per cell. In this method, cells are fixed to a support, the cellular sample is contacted with a 

label under conditions which provide for an amplified signal per component molecule, the signal level is 

detected by means of computerized image analysis and the signal level is related to an amount of 

component per cell by use of standards. Kits are available comprising a plurality of cells having different 

levels of expression of the component for serving as controls and defining the relationship of the 

observed signal to the amount of component present. 

The researchers successfully used this method to quantitate the oncogene HER-2/neu from breast cancer 

tissue as a prognostic of relapse. Kits are available for this purpose. 

ADVANTAGES: Other immunohistochemistry methods provide information on the relative, not 

absolute, amounts of proteins in cells. The current method allows quantitation of the actual amount of a 

protein identified in a cell. 

APPLICATIONS: 


QUANTITATIVE MEASUREMENT OF TISSUE PROTEIN IDENTIFIE...ISTOCHEMISTRY AND STANDARDIZED PROTEIN DETERMINATION 

● Determination of the risk of relapse of breast cancer. 

● Research tool to establish a better understanding of physiological processes and the interactions 

of individual cellular components in providing for proliferation, differentiation, and function. 









Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






RAPID ACTIVATIOIN OF FLOURIDE-18 FOR USE IN POSITRON EMISSION TOMOGRAHY 


RAPID ACTIVATIOIN OF FLOURIDE-18 FOR USE IN POSITRON 

EMISSION TOMOGRAHY 

BACKGROUND: Positron Emission Tomography (PET) is a molecular imaging technique that uses 

radiolabeled molecules to image molecular interactions of biological processes in vivo. PET can be used 

to image and measure physiological processes such as transcription and translation of DNA, signal 

transduction, cell communication, and synthesis and metabolism of substrates that perform cellular 

functions. In addition, PET has been shown to be useful for the diagnosis of certain diseases, such as 

Alzheimer's Disease and cancer. PET is currently limited by the availability of useful radiolabeled 

molecules. 

DESCRIPTION: Researchers at the University of California have invented a new method for activating 

fluoride-18 ions. During this process, mercuracycles are used to rapidly sequester fluoride-18 ion and 

separate it from 18 O-labeled water. The anhydrous fluoride-18 salt is then released into organic solvent 

for subsequent reactions with organic substrates. Because this process provides neutral, anhydrous 

conditions for fluorination reactions with organic substrates, a wide variety of substrates may be used, 

including amino acids, oligonucleotides, sugars, enzymes, etc. 

ADVANTAGES: 

● Allows fluoride-18 to be attached to a wide range of biological molecules. 

● The time for activation is short, allowing longer organic synthesis times. 

● Allows expensive 18 O water to be recovered for recycling. 

● Does not require use of toxic and expensive Krpytofix reagent. 

APPLICATIONS: 

● This process can be used to create fluorinated versions of a wide variety of biological molecules. 

● The fluorinated compounds can be used in PET for research, diagnostic, and therapeutic 

purposes. 

INQUIRIES TO: 


RAPID ACTIVATIOIN OF FLOURIDE-18 FOR USE IN POSITRON EMISSION TOMOGRAHY 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






Rapid Assay For GSH In Biological Samples 



UC CASE 1996-126-1 

NUMBER: 

TITLE: Rapid Assay For GSH In Biological Samples 

DEPARTMENT: Community & Environmental Medicine 

SUMMARY: Glutathione (GSH) is the major non-protein thiol in mammalian cells, and serves to 

protect the cells against damage caused by carcinogens, reactive oxygen species, 

free radicals, and radiation. Low levels of GSH are found in erythrocytes of patients 

with diabetes mellitus, in irreversible cataracts, and in plasma and lymphocytes of 

AIDS patients, making GSH levels an important diagnostic indicator. There are also 

projects underway to develop therapeutic agents that raise GSH levels. GSHstimulating 

agents might delay the onset of age-related and diabetic cataracts and 

enhance the specificity of anti-cancer drugs for cancer cells by shielding normal 

cells from treatment-related toxicity. The measurement of physiological GSH levels, 

if sufficiently fast, accurate, and inexpensive, would have extensive applications in 

clinical analysis and in monitoring drug efficacy and toxicity in model animal 

systems. University of California researchers have developed such a practical 

quantitative assay that is specific for GSH in biological samples (including plasma, 

cells, and tissues of humans and animals). The UC GSH assay employs a rapid 

chemical modification of GSH to render it much more sensitive to detection in 

capillary electrophoresis. The UC assay requires smaller quantities of buffers and 

reactants and considerably less time to perform than existing HPLC techniques, and 

produces no hazardous waste. The assay can be automated, or the components 

marketed as a diagnostic kit, enabling several possible ways to commercialize this 

technology. 


Rapid Assay For GSH In Biological Samples 






Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


RECEPTOR ACTIVATION IN TUMORS 



University of California researchers have discovered a novel form of regulation of receptor activity in a 

transgenic mouse model of tumor development. The UC researchers found that the two major classes of 

solid tumor, sarcoma and carcinoma, show differential activity in the activity of certain intracellular 

hormone receptors. When dermal fibroblasts are transformed into end-stage fibrosarcoma tumors, the 

transcriptional regulatory activity of the receptors is upregulated relative to the activity of the receptors 

in normal fibroblasts or pre-malignant stages. In all these cells, the receptors themselves are expressed 

normally. Moreover, overexpression of the receptors did not increase activity in the normal and earlierstage 

pre-tumor cells nor further upregulation in the end-stage tumor cells. Thus, the upregulation of the 

receptor activity must involve another regulatory factor whose expression is significantly altered at the 

solid tumor stage. 

Similar findings were obtained in studies of squamous cell carcinomas induced by human 

papillomavirus type 16 oncogenes, and of foreskin keratinocytes and transformed derivatives of these 

keratinocytes. The existence of such a general regulatory factor opens up new possibilities for designing 

drugs that modulate receptor activity in tumors. The UC mouse model and assays of receptor activity 

should prove to be useful for (1) investigating other types of cancer that might also involve receptor 

upregulation, and (2) identifying the putative regulator of receptor activity to aid in the design of 

diagnostic and antitumorigenic therapeutic agents. 













Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




RECOMBINANT PROLACTIN ANTAGONIST 



The hormone prolactin (PRL) exerts various effects in a wide range of physiological processes. Research 

suggests that PRL may promote cellular proliferation in both breast cancer and prostate cancer cells. 

University of California researchers have developed a modified PRL analog (S179D) that acts as a 

strong antagonist to PRL in cell proliferation assays. S179D consists of a wild-type PRL with a single 

amino acid substitution. This substitution alters the activity of the molecule such that it antagonizes the 

growth-promoting effects of unmodified PRL in experimental breast cancer and prostate cancer cell 

lines. 

Research results indicate that the modified S179D retains some functions of normal PRL. In other 

words, S179D may be a selective inhibitor of cell proliferation in certain systems, which suggests that it 

could potentially be used as a cancer therapeutic that did not wholly disrupt PRL metabolism throughout 

the body. 

The University of California holds a soon-to-issue United States Patent claiming S179D and related PRL 

mutants. 

The University is searching for commercial partners that are interested in investigating the potential of 

S179D as a therapeutic. 

Examples 

Figure 1. Effects of S179D on the proliferation of MCF-7 breast cancer cells 



Normal MCF-7 cells produce PRL, making it difficult to study the effects of exogenous PRL. In 

this study, MCF-7 breast cancer cells were developed that are deficient in PRL production so that 

the effects of exogenously applied hormone could be elucidated. 

Cells were cultured in media containing wild-type human PRL at 100 ng/ml. Cell numbers were 

measured at 48 hours, and the percent increase over the number of cells in the vehicle only control 

was calculated. In the absence of S179D, wild type PRL induced a near doubling in the number of 

MCF-7 cells. When treated with either of two forms of S179D (A or B), the growth-promoting 

effects of PRL were significantly reduced in a dose-dependent manner. 

Figure 2. In one experiment, the administration of S179D prior to cancer cell injection was 

effective in decreasing both the incidence and size of tumors in mice injected with prostate cancer 

cells (A and B). In a second experiment, mice previously injected with prostate cancer cells were 

treated with S179D, which was effective in reducing tumor size (C). 



http://patron.ucop.edu/ncd/docs/ott.1996-166-0.00.html (3 of 5)10/21/2005 2:48:32 AM 

2A. At day 1, nude mice were implanted with 

minipumps administering control vehicle, wild 

type PRL, or S179D. On day 4, mice were 

injected with DU145 human prostate cancer 

cells. On day 22, mice were assayed for tumor 

incidence and size. S179D significantly reduced 

the incidence of tumors. 

2B. PRL slightly increased tumor size while 

S179D significantly reduced tumor size.


2C. In a separate experiment, mice were 

injected on day 1 with DU145 human prostate 

cancer cells. At day 18, mice were implanted 

with minipumps administering control vehicle, 

wild type PRL, or S179D. On day 42, tumor 

size was measured. PRL promoted increased 

tumor size while S179D significantly reduced 

the size of well-established tumors. 

References 

X. Xu, E. Kreye, C.B. Kuo, and A.M. Walker. A molecular mimic of phosphorylated prolactin markedly 

reduced tumor incidence and size when DU145 human prostate cancer cells were gown in nude mice. 

Cancer Research 61:6098 (2001) 

M.D. Schroeder, J.L. Brockman, A.M. Walker, and L.A. Schuler. Inhibition of Prolactin (PRL)-Induced 

Proliferative Signals in Breast Cancer Cells by a Molecular Mimic of Phosphorylated PRL, S179D-PRL. 

Endocrinology 144: 5300 – 5307 (2003) 

T.J. Chen, C.B. Kuo, F.F. Tsai, J.W. Liu, D.Y. Chen, and A.M. Walker. Development of Recombinant 

Human Prolactin Receptor Antagonists by Molecular Mimicry of the Phosphorylated Hormone. 

Endocrinology 139: 609-616 (1998). 







● Biotechnology > Genetic engineering sys > Protein rDNA 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




REGULATION OF INTRACELLULAR SIGNALING WITH PHOSPHATIDYL INOSITOL KINASES 


REGULATION OF INTRACELLULAR SIGNALING WITH 

PHOSPHATIDYL INOSITOL KINASES 

BACKGROUND: Phosphatidyl inositol kinases (PI-kinases) are enzymes that modify the lipid 

constituents of cell membranes, producing second messengers that are involved in such diverse and 

important cellular processes as cell cycle progression and intracellular protein sorting. In order to 

understand these processes, and to treat diseases stemming from their inappropriate regulation, it is 

necessary to analyze the signaling pathways in detail. 

DESCRIPTION: UC researchers have identified a family of polypeptides related to and/or derived 

from the family of proteins known as PI-3 kinases. These signaling proteins interact with receptor 

tyrosine kinases and are characterized by a highly specific enzymatic reaction with phosphatidyl inositol 

in which the inositol ring is phosphorylated and thus converted to an active second messenger. Because 

of this enzymatic activity, PI-3 kinases play a critical role in the early stages of many signaling cascades. 

APPLICATIONS: The polypeptides could be used to create screens to identify factors that regulate cell 

signaling. Specifically, their activity as PI kinases may be quantified under baseline conditions, and then 

monitored in the presence of putative regulators. Deviation from the baseline would indicate that the test 

factors could play an important role in the regulation of phosphorylated inositol and thus in the 

regulation of cell signaling. In addition, the polypeptides or antibodies against them may be used 

therapeutically to treat conditions in which there is a defect in cell signaling. Such conditions include 

proliferative disorders such as atherosclerosis, inflammatory joint diseases, psoriasis, restenosis 

following angioplasty, and cancer. 



US Patent # 5,948,664 issued September 7, 1999; US Patent # 6,291,220 issued 


September 18, 2001 


REGULATION OF INTRACELLULAR SIGNALING WITH PHOSPHATIDYL INOSITOL KINASES 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




REVERSIBLE INHIBITORS OF CYTOSINE-C5 DNA METHYLTRANSFERASE 


REVERSIBLE INHIBITORS OF CYTOSINE-C5 DNA 

METHYLTRANSFERASE 

BACKGROUND: In eukaryotes, the methylation state of a gene specifically affects its transcription. 

Proper function of the methylation enzyme is crucial for viable development and normal cellular 

activity. Increased activity of the enzyme cytosine-C5 DNA methyltransferase (DCMTase) has been 

directly associated with neoplastic development and excess methylation by DCMTase may constitute a 

key step in carcinogenesis. Currently, the drugs available for inhibiting DCMTase bind irreversibly to 

the enzyme and have toxic side effects. 

DESCRIPTION: Scientists at the University of California have discovered synthetic ligands that inhibit 

DCMTase activity by binding to an allosteric site. These modulators bind reversibly, permitting greater 

therapeutic versatility. In one embodiment, the inhibition constant, 20 nanomolar, is suitably tight for 

drug design. 

APPLICATIONS: Recent reports indicate that degenerative conditions such as cancer and aging may 

be halted by inhibition of DCMTase. It is also perceivable that regeneration of healthy tissues may be 

stimulated. The modulators are likely to be useful tools for basic research as well. 

ADVANTAGES: By binding to an allosteric site, the UC modulators have the potential to either up- or 

down-regulate DCMTase activity. As inhibitors, the UC compounds offer superior characteristics over 

the currently used inhibitors, including: 

● Noncovalent, reversible inhibition; 

● Strong inhibition constant of 20 nanomolar; 

● Likely to have fewer side effects due to their high specificity for DCMTase. 

US PATENT APPLICATION: US 2003-0114402-A1 



REVERSIBLE INHIBITORS OF CYTOSINE-C5 DNA METHYLTRANSFERASE 



● Biotechnology > Cell culture technologies > Human tissue cell cultures 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






ROLD OF THE VDUP1 GENE IN LIPID DISORDERS AND CANCER 


ROLD OF THE VDUP1 GENE IN LIPID DISORDERS AND 


BACKGROUND: The HcB-19/Dem mutant mouse strain, also known as the Hyplip1 strain, arose by 

spontaneous mutation during the development of a recombinant congenic strain between two parent 

strains. The HcB-19/Dem mouse has been useful as a mouse model for Familial combined 

Hyperlipidemia (FCHL), a common genetic lipid disorder that accounts for 10-20% of premature 

coronary heart disease. In addition, this mouse has an increased incidence of hepatic tumors in 

comparison to its parental control strains. Thus, the HcB-19/Dem mouse may also be useful as a model 

for hepatic cancer. 

DESCRIPTION: Researchers at the University of California have identified Vdup1 as the gene 

responsible for both combined hyperlipidemia and hepatic cancer in HcB-19/Dem mice. Vitamin D3 upregulated 

protein 1 (VDUP1) was first identified based on its ability to mediate dihydroxyvitamin D3induced 

macrophage differentiation. In addition, it has been shown to bind to and inhibit the activity of 

thioredoxin (TRX), a thiol oxido-reductase that plays an important role in many cellular processes, 

including cell proliferation, apoptosis, signal transduction and gene regulation. The researchers have 

cloned both the human and mouse Vdup1 genes. 

ADVANTAGES: 

● Provides an animal model to study hepatic cancer and hyperlipidemia. 

● Provides insight into the etiology of liver cancer and hyperlipidemia. 

● Provides evidence for the involvement of VDUP1 in lipid metabolism. 

● Sequence variation of the Vdup1 gene may indicate a predisposition to lipid disorder or cancer. 

APPLICATIONS: 

● Study of metabolic pathways and cellular mechanisms to identify genes, receptors, and 

relationships that are associated with lipid disorder and cancer. 

● The cloning of the Vdup1 gene allows for the development of vectors and expression systems for 

the production of recombinant Vdup1 DNA and protein, respectively. 


ROLD OF THE VDUP1 GENE IN LIPID DISORDERS AND CANCER 

● Diagnostics and prognostics based on sequence variations in the Vdup1 gene. 

● Screening of drugs for lipid disorders and cancer. 

● Gene therapy for disorders caused by mutation in the Vdup1 gene. 






● Pharmaceuticals > Cardiovascular drugs > Antilipemic agents 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






ROLE OF THE VDUP1 GENE IN LIPID DISORDERS AND CANCER 


ROLE OF THE VDUP1 GENE IN LIPID DISORDERS AND 


BACKGROUND: The HcB-19/Dem mutant mouse strain, also known as the Hyplip1 strain, arose by 

spontaneous mutation during the development of a recombinant congenic strain between two parent 

strains. The HcB-19/Dem mouse has been useful as a mouse model for Familial combined 

Hyperlipidemia (FCHL), a common genetic lipid disorder that accounts for 10-20% of premature 

coronary heart disease. In addition, this mouse has an increased incidence of hepatic tumors in 

comparison to its parental control strains. Thus, the HcB-19/Dem mouse may also be useful as a model 

for hepatic cancer. 

DESCRIPTION: Researchers at the University of California have identified Vdup1 as the gene 

responsible for both combined hyperlipidemia and hepatic cancer in HcB-19/Dem mice. Vitamin D3 upregulated 

protein 1 (VDUP1) was first identified based on its ability to mediate dihydroxyvitamin D3induced 

macrophage differentiation. In addition, it has been shown to bind to and inhibit the activity of 

thioredoxin (TRX), a thiol oxido-reductase that plays an important role in many cellular processes, 

including cell proliferation, apoptosis, signal transduction and gene regulation. The researchers have 

cloned both the human and mouse Vdup1 genes. 

ADVANTAGES: 

● Provides an animal model to study hepatic cancer and hyperlipidemia. 

● Provides insight into the etiology of liver cancer and hyperlipidemia. 

● Provides evidence for the involvement of VDUP1 in lipid metabolism. 

● Sequence variation of the Vdup1 gene may indicate a predisposition to lipid disorder or cancer. 

APPLICATIONS: 

● Study of metabolic pathways and cellular mechanisms to identify genes, receptors, and 

relationships that are associated with lipid disorder and cancer. 

● The cloning of the Vdup1 gene allows for the development of vectors and expression systems for 

the production of recombinant Vdup1 DNA and protein, respectively. 


ROLE OF THE VDUP1 GENE IN LIPID DISORDERS AND CANCER 

● Diagnostics and prognostics based on sequence variations in the Vdup1 gene. 

● Screening of drugs for lipid disorders and cancer. 

● Gene therapy for disorders caused by mutation in the Vdup1 gene. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






Schlafen, New Gene Family Regulating Cell Growth 

New Gene Family Regulating Cell Growth (SD98-059) 

UCSD researchers have discovered there is a novel gene family, Schlafen, comprising three genes for 

different isoforms and implications that there are additional genes in the family. This gene family is 

involved in the initiation of apoptosis and disruption of cell growth. Certain family members function as 

agonists to cell growth while others function as antagonists. Not previously described, the expression 

profile of this gene family can be used as a diagnostic marker for cancer identification providing a new 

approach to early stage malignancies. It may also suggest a therapeutic strategy to treat tumors via gene 

therapy, or induction of expression. 

Advantages are: 

● Early indentification of cancerous cells 

● Treatment of malignancies 

● Potent cell growth agonist/antagonist 

● Role in initiation of apoptosis 

Background 

At this point there are only a select panel of tumor suppressor and oncogenes which serve as markers for 

premalignant cells. These genes can be identified using in vitro diagnostic assays. Once identified 

malignant cells are treated by gene therapy. 


Screening Assays For Glycosylation Inhibitors 

Screening Assays For Glycosylation Inhibitors 

BACKGROUND: The involvement of carbohydrate moieties, both within the cell or on its surface, 

plays a major role in various pathological states, as cancer, inflammation, and bacterial or viral infection. 

One aspect of the study of such pathologies is the synthesis of complex carbohydrates by cells and the 

modulation of such synthesis. The search for inhibitors of the synthesis of complex carbohydrates is 

time consuming in that currently available methods usually involve two steps - screening for inhibition 

in a cell-free system, followed by screening in a cell-based system. 

DESCRIPTION: UCSD researchers have discovered simple, rapid, and high throughput methods for 

screening synthetic mixtures (as libraries) and natural products (as plant extracts) for membranepermeable 

compounds that modulate the synthesis of complex carbohydrates in living animal cells. 

ADVANTAGES: The novel methods are in vitro assays involving the use of living cells, with the 

advantage that the need for separate enzyme/receptor inhibitor studies and cell growth inhibition studies 

is obviated. In addition, the assay methods are rapid, specific, and therefore, cost effective. 



SINGLE AND MULTIPLE TYROSINE KINASE KNOCKOUT MICE 



BACKGROUND: Cytoplasmic tyrosine kinases play critical roles in regulating the intracellular 

signaling pathways by which blood cells respond to growth factors, cytokines, antigens or pathogens. 

The kinases encoded by the hck, fgr, and lyn genes have been implicated in signaling pathways elicited 

by cytokines, lipopolysaccharide, and crosslinking of IgM and Fc receptors. Hematopoietic cells often 

express multiple members of the Src-family kinases, and these proteins are all highly related. It is 

therefore likely that the kinases encoded by these three genes may serve overlapping or redundant 

functions in different signal transduction pathways. Previously, there have been no animal models 

available to study specifically the effects of the loss of hck, fgr, or lyn gene function. 

DESCRIPTION: Researchers at the University of California have generated mice with mutations in the 

hck, fgr, and lyn genes that encode the corresponding protein members of the Src-family of tyrosine 

kinases and have intercrossed the single gene mutant mice to generate double and triple gene knockout 

mice. These mice represent the only models that can be used to specifically study the effects of Srcfamily 

kinases on the development and function of myeloid blood cells. In particular, the triple gene 

mutant mice is the only available animal model in which the neutrophils and macrophages lack all 

members of the Src-family kinases typically present in normal cells. 

APPLICATIONS: The UC single and multiple gene knockout mice are essential for studying the role 

of tyrosine kinases in the regulation of signal transduction pathways in myeloid cells and Blymphocytes. 

These mice can be used in a variety of disease models, for example human infectious or 

inflammatory disease, to determine if the hck, fgr, or lyn genes, either alone or in combination, are valid 

targets for the design of specific therapeutics. The knockout mice can also be interbred with other 

mutant mice to evaluate the effects of loss of the respective gene on pre-established murine genetic 

diseases which mimic human diseases. Such models can be used to study cancer malignancy, 

cardivascular and neurodegenerative diseases. 

ADVANTAGES: The major advantage of using knockout mice to screen for new therapeutic targets is 

that the effect on disease pathogenesis due to loss of biological function associated with a specific 

protein can be analyzed in an appropriate physiological context using the whole animal rather than in 

isolated cells or in subcellular extracts. 






● Biotechnology > Genetic engineering sys > Animal genetic systems 




Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






SMALL INTERFERING RNA TO INHIBIT TRANSCRIPTION FACTOR EXPRESSION IN MAMMALIAN CELLS 


SMALL INTERFERING RNA TO INHIBIT TRANSCRIPTION 

FACTOR EXPRESSION IN MAMMALIAN CELLS 

BACKGROUND: Small interfering RNAs (siRNAs) are double stranded RNAs that, when introduced 

into cells, specifically reduce the expression of homologous RNAs. This method has been used 

successfully, in organisms such as Drosophila and C. elegans, to reduce the level of expression of 

specific genes. Recently, some investigators have used this approach to target genes in mammalian cells. 

DESCRIPTION: Researchers at the University of California have developed a double stranded RNA 

that inhibits the expression of a ubiquitously expressed transcription factor known to be critical for cell 

growth and survival in a number of different systems, e.g. neural, hematopoietic, and cancer cells. 

ADVANTAGES: This technology represents the first siRNA approach to specifically downregulate this 

key transcription factor. 

APPLICATIONS: 

● Study the signaling pathways responsible for growth and survival of cells, including cancer cells. 

● May be useful as a gene therapy, to treat cancer patients. 









SMALL INTERFERING RNA TO INHIBIT TRANSCRIPTION FACTOR EXPRESSION IN MAMMALIAN CELLS 



Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




STRUCTURE OF ESTROGEN RECEPTOR AND CO-ACTIVATOR 



BACKGROUND: Estrogen receptor (ER) alpha is a prototype member of the nuclear receptor proteins 

superfamily of transcription factors that activate or repress transcription in a ligand, promoter and celltype 

specific manner. ER-alpha binds estrogen hormone and mediates the differentiation and 

maintenance of neural, skeletal, cardiovascular and reproductive tissues. It binds a variety of ligands 

including synthetic molecules differing in their structure, size and action, through the ligand-binding 

domain (LBD) located at its C-terminus. Ligand binding not only regulates the transcriptional activity of 

ER-alpha directly, but also modulates binding of other coactivator proteins such as GRIP1 and SRC-1. 

These proteins further enhance transcriptional activity of ligand-bound ER-alpha complexes. 

In general, ligands are either strict agonists or antagonists. However, it is now recognized that some 

ligands can function as agonists or antagonists depending on the tissue and promoter contexts. In the 

case of estrogen receptor, these ligands are known as selective estrogen receptor modulators (SERMs) 

and are represented by synthetic molecules such as tamoxifen and raloxifene. The tissue-specific 

modulation of transcriptional activity by the SERMs, therefore, can have complex effects that may be 

beneficial or harmful. For example, although tamoxifen as an antagonist is a effective drug for breast 

cancer, its agonist function in the uterus is associated with higher incidence of endometrial cancer upon 

prolonged use. On the other hand, raloxifene acts as an antagonist of ER in the breast and uterus, but as 

an agonist in bone and heart. This differential effect seems to depend on tissue-specific coactivators/ 

corepressors. 

Although a number of molecules that interact with ER-alpha have been identified, the precise structural 

mechanism by which ligand binding can influence coactivator association is still unclear. Hence, there is 

a need for further characterization and identification of structural features of the LBD of ER-alpha and 

associating molecules. 

DESCRIPTION: Researchers at the University of California have discovered the structural basis for 

agonist and antagonistic action of different ligands. They have solved the co-crystal structure of ERalpha 

LBD with an agonist bound and, LBD with an antagonist bound to elucidate the structural 

differences between these complexes that explain their functional effects. The atomic models developed 

by the UC researchers provide methods for identifying and designing compounds that modulate ER 

alpha activity. 



ADVANTAGES: 

● Rational design of specific agonists or antagonists possible. 

● Computational methods described reduce development time of specific drugs. 

● Allows design of well-characterized drugs for variety of members of nuclear receptor family. 

APPLICATIONS: 

● Development of improved SERMs and other compounds with well characterized properties for 

use as drugs in diseases such as breast cancer, osteoporosis and cardiovascular disease that 

involve estrogen receptors. 








Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 






SYNTHESIS OF PROTEIN CONJUGATES FOR THE DEVELOPMENT OF IMMUNOASSAYS FOR AAL MYCOTOXINS 


SYNTHESIS OF PROTEIN CONJUGATES FOR THE 

DEVELOPMENT OF IMMUNOASSAYS FOR AAL MYCOTOXINS 

Mycotoxins from Alternaria alternata (AAL toxins) and Fusarium moniliforme (fumonisins) are 

widespread in corn-based and other food products, where they pose a significant contamination problem. 

Fumonisins induce effects ranging from cancer (especially esophageal cancer in humans) to renal, 

neural, and hepatic necrosis. The closely related structures, the common mode of biochemical action of 

AAL compounds and fumonisins, and the diverse toxicological effects of these mycotoxins raises 

concern about the presence of both classes of toxins in the food chain. There is a pressing need to protect 

food supplies with highly specific and sensitive rapid assays to detect these mycotoxins in plant 

materials. 

Inexpensive enzyme-linked immunosorbent assays (ELISAs) offer the most promising way to satisfy 

these requirements; sensitive ELISAs have already been developed for fumonisins. University of 

California scientists have made significant progress in developing similar immunoassay systems for 

AAL-toxins. They used novel syntheses to obtain protein conjugates of an AAL-toxin and then used 

these conjugates to develop AAL toxin-immunoassays. Polyclonal mouse antisera were raised against 

the UC conjugates. The resulting antibodies selectively recognized all AAL toxins with no significant 

cross-reactivities for sphinganine, fumonisin FB1, and other related natural products. 

The best ELISAs derived from this multiconjugate-multiantibody approach had detection limits for 

AAL-toxins in the low- to mid-parts per billion range. The specificity and sensitivity of these 

immunoassays for AAL toxins indicates that the UC conjugates are very attractive candidate 

immunogens for producing monoclonal antibodies and further polyclonal antisera. Such antibody 

production in turn will enable the creation of rapid and inexpensive assays for the detection of AAL 

toxins in large numbers of food samples. A further advantage of the anti-AAL antibodies would be the 

potential to develop an immunoaffinity sample-cleanup method, which could also remarkably enhance 

other analyses for AAL compounds than immunoassays (e.g., instrumental methods). 



SYNTHESIS OF PROTEIN CONJUGATES FOR THE DEVELOPMENT OF IMMUNOASSAYS FOR AAL MYCOTOXINS 



● Biotechnology > Biotechnology eqp > Accessories/supplies 

● Biotechnology > Genetic engineering sys > Industrial monoclonal 

● Biotechnology > Genetic engineering sys > Industrial polyclonal 

● Biotechnology > Immunology systems > Immunodiagnostics 

● Chemicals > Application-specific chems > Food additives 

● Chemicals > Chemical services > Chemical testing services 

● Test & Measurement > Analyzers > Chemical/physics analyzers 






Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




TARGET FOR THERAPEUTICS FOR MODULATION OF THE IMMUNE SYSTEM 


TARGET FOR THERAPEUTICS FOR MODULATION OF THE 

IMMUNE SYSTEM 

BACKGROUND: The nervous system extends its influence to a variety of bodily functions that include 

control of immunity. Immune responses are modulated by diverse neuropeptides, that signal changes in 

target cells by interacting with specific receptors, predominantly of the G-protein-coupled receptor 

(GPCR) class. One type of neuropeptide, the Vasoactive Intestinal Peptide (VIP) and its GPCRs 

(VPACs) have been recognized as systems that mediate and regulate immunity and inflammation 

predominantly through their effects on T-cells. These receptors differentially modulate the responses of 

specialized T-cells (Th1 and Th2) that are critical in maintaining a balance between host defense and 

inflammation-allergy. The VPACs could therefore provide a basis for the development of drugs that will 

be used for the treatment of disorders with inflammatory and/or autoimmune components. 

DESCRIPTION: UC researchers have identified a natural mutant form of a mouse VIP receptor, the 

VPAC2 GPCR (Type II VIP G protein-coupled receptor) found on activated T cells, that is a splice 

variant without a portion of the last transmembrane domain and tail. This mutant VPAC2 binds VIP with 

the same affinity as the non-mutant VPAC2, but is impaired in passing on the VIP signal to the interior 

of the cell to mediate a response. Thus, this mutant form of VPAC2 could be used to study VIP 

neuroimmune signaling pathways and as a decoy receptor to develop therapeutics that inhibit VIPmediated 

signaling. 

ADVANTAGES: The present invention represents the first VIP receptor mutant ever identified with the 

potential to be used as a modulator of the VIP signaling pathway. Until now, no mutants of VPAC2 have 

been described for use in dominant negative approaches or as decoys. Ligands that bind selectively to 

the mutant form or agents that upregulate its expression could provide insights for the design of better 

drugs directed to the wild type VIP GPCR. 

APPLICATIONS: This invention could be used to screen modulators of the expression of the mutant 

VPAC2 that can be used to increase or decrease VIP-mediated signaling for the treatment of the 

following diseases: 

● acute and chronic inflammatory diseases like allergy and asthma 


TARGET FOR THERAPEUTICS FOR MODULATION OF THE IMMUNE SYSTEM 

● autoimmune diseases like systemic lupus erythematosus and multiple sclerosis, 

● neurodegenrative diseases like Alzheimers disease, 

● other diseases like cancer and erectile dysfunction. 








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Phone: (510) 587-6000 Fax: (510) 587-6090 






The Use of Detergents to Enhance Drug Uptake In Vivo: With Particular Emphasis on Cancer Chemotherapy Agents 

The Use of Detergents to Enhance Drug Uptake In Vivo 

With Particular Emphasis on Cancer Chemotherapy Agents 

BACKGROUND: The primary physical barrier to the uptake of drugs into target cells is the lipid 

bilayer membrane of the cell. A number of drug design and delivery strategies have been developed to 

overcome this resistance to uptake, which is particularly severe in the case of charged, highly polar or 

higher molecular weight (MW>300 daltons) compounds. Amphipathic agents, including both ionic and 

nonionic surfactants, have been used in vitro to permeablize cell membranes, and on the skin to deliver 

drugs transdermally, however, this strategy has heretofore not proven practical to use in vivo, due to the 

injurious effect of prolonged exposure to detergents on cell membranes. 

DESCRIPTION: The current invention describes a novel composition and method of use that permits 

the safe and effective use of select detergent compounds in vivo to enhance drug efficacy. Coadministration 

of a select group of surfactant molecules with the chemotherapy agents, Cisplatin and 

Carboplatin, two high-value drugs having marginal cell-permeating capability that partially limits the 

exceptional effectiveness that they display in vitro. 

Potentially, the strategy found effective in the invention could be applied to a wide variety of drugs, 

combined with an equally wide variety of surfactants. It should be possible to tailor the properties and 

pharmacokinetics of individual surfactants to the drug with which it is combined to assure optimum 

efficacy of the trans-membranal delivery system. 

ADVANTAGES: More effective uptake of drug actives by target cells means that a lower dose to the 

patient is possible, which in turn reduces non-selective side effects and in the case of costly therapeutic 

products, reduces costs as well. Because individual cells types may be permeabilized selectively by 

different classes of surfactants, there is an opportunity to improve selectivity by this route as well. Most 

key, it may well be possible through this formulation approach to shorten the development cycle and 

time-to-market for many classes of new drugs -- since molecular re-design of attractive new therapeutics 

is often required when the in vivo efficacy of the prototype or best screening candidate proves to be far 

less than the in vitro enzyme inhibition of ligand binding studies had indicated, due to poor tissue 

uptake. 

In the case of the example used in the invention, Cisplatin and Carboplatin were both shown to be 

effective at lower doses (4-6 fold potentiation) when used with the surfactant-formulated dosing system. 

The lowered cisplatin permeability of a drug-resistant human ovarian carcinoma cell line was effectively 

reversed by surfactant dosing. 

http://patron.ucop.edu/ncd/docs/ucsd.1996-041.html (1 of 2)10/21/2005 2:48:36 AM

The Use of Detergents to Enhance Drug Uptake In Vivo: With Particular Emphasis on Cancer Chemotherapy Agents 


http://patron.ucop.edu/ncd/docs/ucsd.1996-041.html (2 of 2)10/21/2005 2:48:36 AM

Therapeutics and Diagnostic for Septic Shock 

Therapeutics and Diagnostic for Septic Shock 

Bacterial sepsis remains a major challenge for modern medicine. Septic shock is the most severe form of 

sepsis, in which perfusion of the liver, kidney and other vital organs is compromised. This syndrome, 

which can be caused by both gram-negative and gram-positive bacteria, has a mortality rate of 30-60%. 

Systemic infection is a complication of many types of medical therapy, such as surgery, 

immunosuppression for transplant or cancer chemotherapy. The number of patients with sepsis in North 

America and Europe is large and will probably increase as intensive medical therapy becomes more 

widespread. 

In the past, non-antibiotic approaches to sepsis therapy, such as the use of antibodies to bacterial 

products have not been accepted, even when successful, because of the expense and difficulty compared 

to antibiotic treatments. This position is being reconsidered with the increasing appearance of antibioticresistant 

bacteria. 

Researchers at UCSD have expressed soluble human MD-2 protein that binds to lippopolysaccharide 

(LPS), the most well established trigger of septic shock. The data generated using the recombinant MD- 

2 indicate that MD-2, or mutant derivatives of MD-2, are promising candidate therapeutics for septic 

shock. 

Additionally, several monoclonal antibodies to MD-2 that inhibit LPS binding have been isolated and 

characterized. These antibodies have potential use as an alternative therapeutic approach and could also 

be exploited to develop a rapid diagnostic test for sepsis. Since no other diagnostic tests are currently in 

use, this would be a valuable addition to the physicians’ arsenal. 




THERAPY AND DIAGNOSIS OF CONDITIONS RELATED TO TELOMERE LENGTH AND/OR TELOMERASE ACTIVITY 


THERAPY AND DIAGNOSIS OF CONDITIONS RELATED TO 

TELOMERE LENGTH AND/OR TELOMERASE ACTIVITY 

BACKGROUND: Telomeres are highly conserved structures that cap and protect the ends of linear 

chromosomes. In normal somatic cells, telomeres are subject to progressive shortening leading 

ultimately to irreversible growth arrest. In contrast, in germline cells as well as in many rapidly dividing 

tissues, the telomerase enzyme is present and serves to maintain chromosome length and integrity during 

cell division. 

The amount of telomerase in a cell is thought to be important for both normal development and disease. 

For example, the lack of telomerase in normal somatic cells has been implicated in the aging process. In 

contrast, telomeres in cancer cells are stabilized in length and are effectively immortalized by abnormal 

telomerase expression. Therefore, the regulation of telomerase activity and telomere length is of clinical 

importance. 

DESCRIPTION: Researchers at the University of California have developed a battery of methods for 

screening for compounds that regulate telomerase activity and for diagnosing conditions characterized 

by elevated levels of telomerase activity. These methods are protected by four U.S. patents assigned to 

the University of California. These patents cover methods for screening for an agent which inhibits 

telomerase activity (U.S. Patent No, 5,645,986), methods of screening to determine whether a test 

compound can inhibit telomerase activity in a cell (U.S. Patent No. 6,368,789), methods for screening 

for a telomerase derepression agent (U.S. Patent No. 6,007.989), and methods for diagnosing a condition 

in a patient associated with an elevated level of telomerase activity within a mammalian cell (U.S. Patent 

No. 6,551,774). These methods represent an impressive portfolio useful for the development of 

diagnostics and therapeutics for telomerase-related diseases. 

APPLICATIONS: 

● Cancer treatment and diagnosis 

● Treatment of fungal diseases 

● Development of anti-aging therapeutics 


THERAPY AND DIAGNOSIS OF CONDITIONS RELATED TO TELOMERE LENGTH AND/OR TELOMERASE ACTIVITY 



US Patent # 5,645,986 issued July 8, 1997; US Patent # 6,007,989 issued 


December 28, 1999 






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Phone: (510) 587-6000 Fax: (510) 587-6090 






TOOLS FOR GENE DELIVERY AND TRANSFECTION 



BACKGROUND: Gene therapy, the introduction of functional genes into mammalian cells to correct 

the effect of defective genes, is now feasible, and holds great promise for the treatment of many serious 

human diseases. Antisense therapy, the use of antisense DNA, RNA or siRNA to suppress or regulate 

gene expression, likewise holds great promise for treatment of cancer, autoimmune diseases, transplant 

rejection, and many other disorders. Both these promising new therapeutic modalities require agents that 

can direct the therapeutic gene or antisense oligonucleotide to the desired cell, transport the 

oligonucleotide across the cell membrane, and direct the oligonucleotide to the intended intracellular 

target or organelle. 

Researchers at the University of California have invented a battery of tools for delivering 

polynucleotides into cells. The tools include methods and compositions for targeting gene delivery 

vehicles to specific cells and for transfecting DNA or RNA into those cells. These methods and 

compositions utilize liposomes and dendrimers. 

AVAILABLE TECHNOLOGIES: 

LIPOSOMES: Liposomes are widely used as models of membrane bilayers and as carriers for the 

delivery of drugs and other biologically active compounds. Liposomes have been particularly useful in 

the delivery and transfection of genetic material into cells. The researchers have invented improved 

rapid methods for liposome preparation (UC Case No. 1988-090), methods to attach effectors to the 

surface of liposomes that increase the efficiency of effector delivery (UC Case No. 2000-159), and 

liposomes that specifically bind to a cell surface receptor found on many tumors (UC Case No. 2000- 

162). 

DENDRIMERS: Dendrimers are highly branched spherical molecules with branches terminating at 

charged amino groups. Due to controlled chemical synthesis, dendrimers have a very precise size and 

defined shape. This ensures consistent transfection-complex formation and reproducibility of 

transfection. The researchers have invented methods of using dendrimers for transfection of cells in vitro 

and in vivo as well as compositions comprising polynucleotides and dendrimers (UC Case No. 1991- 

268). 



GENE DELIVERY SYSTEM : The researchers have invented a gene delivery system comprising 

polynucleotides coupled to a DNA-associating component (such as a dendrimer), and optionally other 

agents such as DNA masking agents, cell recognition agents, charge-neutralization agents, membranepermeabilization 

agents, and subcellular-localization agents. The compounds and methods of this 

invention can selectively target a selected gene to a specified cell type, and efficiently transfect the cell 

with resulting expression of the gene (UC Case No. 1991-268). 

APPLICATIONS: 

● Gene therapy 

● Antisense therapy 

● Generation of transgenic animals or cells 

● Research tools 

PATENT STATUS: All of the above technologies have either patent applications or issued patents. 




September 22, 1998; US Patent # 5,955,365 issued September 21, 1999; US 

PATENT STATUS: Patent # 5,972,600 issued October 26, 1999; US Patent # 5,977,084 issued 

November 2, 1999; US Patent # 5,990,089 issued November 23, 1999; US Patent 

# 6,113,946 issued May 5, 2000; US Patent # 6,300,317 issued October 9, 2001 






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Phone: (510) 587-6000 Fax: (510) 587-6090 








TRANSCRIPTION FACTOR FOR THE REGULATION OF SKIN AND HAIR DEVELOPMENT 


TRANSCRIPTION FACTOR FOR THE REGULATION OF SKIN 

AND HAIR DEVELOPMENT 

In higher organisms, DNA binding proteins known as transcription factors play a key role in facilitating 

or inhibiting the transcription of specific sets of genes. Since expression of these genes at certain times 

specifies the state of the cell, the characterization of these transcription factors is an important step in 

developing new methods for manipulating cell proliferation. 

One such potentially valuable transcription factor has been discovered and characterized by University 

of California researchers. The UC research team has also investigated the factor's effect on tissue 

development in a model animal system, and has confirmed that a protein homologous to the factor exists 

in humans. The factor is alternatively and selectively expressed in at least two different forms in 

terminally differentiating epidermal and hair follicle cells. In one form, the factor has a region that 

inhibits its own DNA binding ability and contains a region that transfers inhibition of DNA binding to 

other transcription factors. The second form of the factor does bind to DNA and serves as a 

transcriptional activator of genes involved in skin development. It is believed that controlled expression 

of the factor could assist in the clinical control of skin cell proliferation, which might be of value in 

regenerating skin that has suffered injury at the basal cell level (as in severe burns, for example). 

Stimulation of this transcription factor would be useful in treating skin cancer. Also, controlled factor 

expression might lead to further insights into the regulation of skin development and the nature of 

certain skin and hair loss disorders. 








TRANSCRIPTION FACTOR FOR THE REGULATION OF SKIN AND HAIR DEVELOPMENT 







Oakland, CA 94607-5200 

Phone: (510) 587-6000 Fax: (510) 587-6090 




Treating Cancer And Atherosclerosis With Photodynamic Therapy 



UC CASE 1986-041-1 

NUMBER: 

TITLE: Treating Cancer And Atherosclerosis With Photodynamic Therapy 

DEPARTMENT: Department of Medicine - Cardiology 

SUMMARY: University of California researchers have discovered a light sensitive agent that 

allows for the selective destruction of cancer cells and atherosclerotic plaques (U.S. 

Pat. 4,886,831), while leaving normal tissues intact. The agent, phycocyanin, is a 

chromophore derived from a blue-green algae. Photosensitive agents have been used 

in the past to treat aberrant growths. However, the specificity of targeting 

pathological tissues was not always high, and patients often became sensitized to 

sunlight. Phycocyanin overcomes both these problems. When it is injected into the 

patient intravenously, it is selectively absorbed by any atherosclerotic plaques or 

tumor cell membranes present. Light is then delivered to the site of pathology 

through a fiber-optic catheter or through the use of light emitting liquids. For 

atherosclerotic plaques, photoactivation causes the release of singlet oxygen free 

radicals that are destructive to the plaque cells. In the case of tumors, 

photoactivation of the sequestered compound results in membranous damage and 

subsequent death of the diseased tissue. This new agent has great potential for 

treating two of the most prevalent and life-threatening diseases in America. Unlike 

existing cancer treatments like chemotherapy or radiation, the cell killing properties 

of photoactivated phycocyanin are highly specific to the diseased tissue, and thus 

avoid problems of severe toxicity or secondary carcinogenesis. Current 

artherosclerotic procedures also have their drawbacks that can be overcome with 

effective phototherapy. Grafts or drugs tend to be expensive and have long-term 

risks to the patient. Phototherapy with phycocyanin is relatively cheap, effective, 

and free of the complications of established techniques. 


Treating Cancer And Atherosclerosis With Photodynamic Therapy 






Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


TREATMENT OF PLATELET DERIVED GROWTH FACTOR RELATED DISORDERS SUCH AS CANCER 


TREATMENT OF PLATELET DERIVED GROWTH FACTOR 

RELATED DISORDERS SUCH AS CANCER 

BACKGROUND: Platelet derived growth factor receptor (PDGF-R) is a transmembrane receptor 

tyrosine kinase involved in the growth of mesenchymal, neuroectodermal, and endothelial cells. 

Inappropriate PDGF-R activity can contribute to cell proliferative disorders, such as cancer, blood 

proliferative disorders, and fibrotic disorders, by increasing the production of growth factors, causing 

aberrant growth of a cell, and increasing formation and spreading of blood vessels in solid tumors 

thereby supporting tumor growth. Therefore, inhibition of PDGF-R activity has therapeutic potential for 

the treatment of these disorders. 

DESCRIPTION: Researchers at the University of California have developed compounds that inhibit 

PDGF-R activity. In addition, they have developed methods to screen for additional compounds that 

inhibit other members of the PDGF-R super family. The compounds are active on cell cultures to reduce 

the activity of PDGF-R and related kinases. They can also inhibit growth of tumor cells in vivo. Specific 

compounds, as well as methods for using these compounds, alone or in combination with cytotoxic 

agents, to treat solid tumors due to inter-axial brain cancer, ovarian cancer, colon cancer, prostate 

cancer, lung cancer, Kaposi's sarcoma, and melanoma are patented and available for licensing. 

ADVANTAGES: 

● The discovery of compounds that inhibit PDGF-R activity provides the basis for novel 

therapeutics in the treatment of cell-proliferative diseases. 

● The screening methods can be used to identify compounds that alter the activity not only of 

PDGF-R, but of related receptor tyrosine kinases such as Flt and KDR. 

APPLICATIONS: 

● Treatment of cancers with solid tumors characterized by inappropriate PDGF-receptor activity, 

such as intra-axial brain cancer, ovarian cancer, colon cancer, prostate cancer, lung cancer, 

Kaposi's sarcoma, and melanoma. 

● Treatment of blood vessel proliferation disorders such as restenosis, retinopathies, and 


TREATMENT OF PLATELET DERIVED GROWTH FACTOR RELATED DISORDERS SUCH AS CANCER 

atherosclerosis. 

● Treatment of fibrotic disorders, i.e. disorders characterized by abnormal formation of 

extracellular matrix, such as hepatic cirrhosis and mesangial cell proliferative disorders. 




PATENT STATUS: December 23, 1997; US Patent # 5,932,602 issued August 3, 1999; US Patent # 

6,331,555 issued December 18, 2001 






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TUMOR-RELATED ENDOTHELIAL MARKER GENE 



A University of California scientist has identified a novel cDNA of an endothelial-derived gene from 

humans, designated endothelial-derived gene 1 (EG-1). Endothelial genes are important for the study 

and possibly for the control of tumor angiogenesis, since the growth and metastasis of solid tumors 

depends on their ability to initiate and sustain new capillary growth. Such rapid capillary growth 

requires the proliferation, migration, and differentiation of endothelial cells. 

The UC scientist focused on trying to find endothelial gene products that are expressed in response to a 

mixture of tumor-derived growth factors found in tumor-conditioned growth media. EG-1 is noteworthy 

in that it is expressed in endothelial cells in several tissues and has upregulated expression when 

endothelial cell growth is stimulated by tumor-conditioned media or by specific angiogenic factors. EG- 

1 transcripts are found in highly vascularized tissues such as placenta, testis, and liver (both endothelial 

and epithelial cell types), and are found at elevated levels in breast, prostate, and colon cancer cells. 

These data suggest that EG-1 is associated with a stimulated state in endothelial and epithelial cells, and 

may play a significant role in tumor angiogenesis. 








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UNIVERSAL VECTORS FOR DRUG DELIVERY 



Researchers at the University of California have developed a broad-spectrum universal drug delivery 

vector with several proven applications. Employing state of the art genetic engineering techniques, they 

have constructed a transferrin receptor-specific antibody fused to an avidin subunit that effectively 

delivers a wide range of chemically biotynlated compounds to target areas. Moreover, this vector is far 

superior to its earlier counterparts in that it has the capacity to deliver a much wider range of compounds 

and nucleic acids. In addition, because it can be produced by genetic engineering, large yields of a 

homogenous product can be made with it, which has proven pharmokinetic advantages. 

Of the many advantages of the vector, its ability to cross the blood-brain barrier (BBB) gives rise to 

many potential applications in the diagnosis and/or therapy of various central nervous system (CNS) 

disorders. For example, the efficacy of current treatments of many CNS disorders, including various 

infectious diseases, brain tumors, and degenerative diseases like Parkinson's and Huntington's, are 

limited to intravenous drug delivery mechanisms. Utilizing this novel mode of delivery, such limitations 

can be overcome, allowing for direct drug delivery to the brain. In addition to targeting the cerebral 

hemisphere, the UC vector can be used to target other CNS components where the BBB poses an 

obstacle to drug delivery, such as the cerebellum and the spinal cord. 

Another type of application for this multi-purpose vector is anti-cancer therapeutics and diagnostics. For 

example, the antigenic specificity of the vector allows it to directly target cancer cells that overexpress 

the transferrin receptor. Such specificity not only increases the delivery of anti-cancer agents, it also 

decreases the toxicity of such drugs relative to non-cancerous cells. Furthermore, the vector's ability to 

deliver nucleic acids could make it useful for gene therapy. Yet another possible type of therapeutic 

application of the vector is for treating bacterial infections. 

Lastly, the UC vector may serve as a powerful research tool for a variety of in vitro and in vivo 

experiments, particularly to take advantage of the vector's ability to target the transferrin receptor, 

transfer compounds across the BBB, etc. Thus, the potential applications of this broad-spectrum delivery 

vector are of great significance for the pharmaceutical industry and for many areas of research. 







● Pharmaceuticals > Autonomic drugs > Anticholinergic agents 

● Pharmaceuticals > Autonomic drugs > Sympatholytic agents 




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Phone: (510) 587-6000 Fax: (510) 587-6090 






Unnatural Amino Acids That Mimic Peptide Beta-Strands 



UC CASE 2000-037-4 

NUMBER: 

TITLE: Unnatural Amino Acids That Mimic Peptide Beta-Strands 

DEPARTMENT: Chemistry 

SUMMARY: After a protein is translated, sections of the polypeptide can fold into a number of 

structures including alpha helices and beta-pleated sheets. Beta-sheet interactions 

between proteins are involved in protein dimerization, protein-protein interactions 

and protein aggregations, which are important in a variety of biological processes 

including those involved in cancer, AIDS and Alzheimer's disease. A number of 

researchers have begun to achieve the goal of developing new drugs based on 

compounds that can block, modulate, or mediate beta-sheet interactions between 

proteins. Researchers at the University of California, Irvine, have synthesized a nonnatural 

amino acid. This amino acid and its derivatives mimic tripeptide betastrands. 

When incorporated into peptides, peptidomimetics or proteins all three 

types of structures will dimerize by means of beta-sheet interactions. A logical 

extension of this work is to use this amino acid in agents designed to block the bet 






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Telephone: (949) 824-7295 

Fax: (949) 824-2899 


Use Of Infectious And Pathogenic Clone Of A Lung Cancer-Inducing Retrovirus For Generation Of Therapeutic Reagents And Diagnostic Tests Or Reage 



UC CASE 2000-008-2 

NUMBER: 

TITLE: Use Of Infectious And Pathogenic Clone Of A Lung Cancer-Inducing 

Retrovirus For Generation Of Therapeutic Reagents And Diagnostic 

Tests Or Reage 

DEPARTMENT: Molecular Biology & Biochemistry 

SUMMARY: Jaagsiekte sheep retrovirus (JSRV) causes broncheolo-alveolar carcinoma in sheep 

and is a significant veterinary problem world-wide. Clinically and 

histopathologically, this disease has strong resemblance to broncheolo-alveolar 

carcinoma (BAC) in humans which accounts for approximately 25% of human lung 

cancers. Researchers at the University of California, Irvine have isolated the first 

infectious molecular clone of JSRV and have developed techniques for production 

of infectious JSRV that allowed the researchers to prove that JSRV alone was 

sufficient to induce BAC in sheep. The molecular clone of JSRV has potential for 

the generation of diagnostic reagents for infection in sheep, the generation of 

vaccines against JSRV, and the generation of novel retroviral vectors for targeting 

lung tissue. Finally, this line of research can serve as a starting point for searching 

for analogous viruses in human. 






Irvine, CA 92697-7700 

Telephone: (949) 824-7295 

Fax: (949) 824-2899 


VECTORS AND CELL LINES FOR CLASS SWITCH RECOMBINATION 


VECTORS AND CELL LINES FOR CLASS SWITCH 

RECOMBINATION 

The induction of a specific immune response by production of immunoglobulins to a specific pathogen 

is known as an acquired immune response. The primary functions of immunoglobulins are binding of a 

complement to initiate the complement cascade and mediating cell responses to enable macrophages and 

phagocytes to engulf microorganisms. 

There are five main isotypes of immunoglobulins, IgM, IgD, IgG, IgE and IgA. The immune system can 

alter its response to particular antigens by regulating the isotypes of the immunoglobulins produced. 

Such regulation is controlled by a process known as Class Switch Recombination (CSR), which enables 

the expression of many different immunoglobulin isotypes while retaining antigen specificity. The role 

of immunoglobulin CSR in the diversification of effector functions of the immune response has attracted 

the attention of researchers for more than twenty years. However, the underlying molecular mechanisms 

of CSR have resisted characterization, frustrating progress in this field. 

Researchers at the University of California have developed a novel switch recombination system, based 

on Green Fluorescent Protein (GFP) expression, which closely mimics CSR. The UC switch 

recombination system is a cell-integrated system. Its recombinational activity is dependent on inducible 

promoters that regulate recombinase activity by controlling access to switch region DNA. 

The vectors and cell lines associated with this system represent a powerful tool for identifying both the 

general recombinase and isotype specific components and specifying conformational requirements of the 

switch region DNA. Thus, this system provides an enabling technology for identifying targets involved 

in the human humoral response, targets which will have important commercial applications in 

controlling immune responses involved in allergic (e.g. asthma, hay fever), autoimmune (lupus 

erythematosis), immunodeficiency (IgA deficiency), and infectious diseases. This technology may also 

be used to identify targets to prevent the class of cancers (lymphomas) where chromosome translocation 

mechanisms related to CSR are involved. 



VECTORS AND CELL LINES FOR CLASS SWITCH RECOMBINATION 







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VESOSOMES: BILAYER-ENCAPSULATED VESICLE AGGREGATES 


VESOSOMES: BILAYER-ENCAPSULATED VESICLE 

AGGREGATES 

BACKGROUND: Vesicles of lipid bilayers are useful structures for drug delivery. The permeation rate, 

membrane charge, specific recognition particles, steric stabilizers, membrane rigidity, and phase 

transition temperatures all play a role in optimization of vesicles for particular delivery applications. 

Currently, vesicle design is restricted by conflicts among these properties, forcing trade-offs in the 

design of vesicle delivery systems. 

DESCRIPTION: Researchers at the University of California have constructed vesosomes by 

aggregating lipid-bilayer vesicles using biotin-streptavidin complexation and then encapsulating these 

aggregates in a larger lipid bilayer using the same molecular-recognition technique. These multicompartment 

vesosomes offer a versatile means for designing delivery systems because they can 

distribute often incompatible attributes among the various membranes. Interior vesicle sizes range from 

20-500 nm and vesosome sizes range from about 0.1 micron to greater than 1.0 micron. Details of 

preparation and sample images of the resulting vesosomes are presented in Nature (1997), vol. 387, p. 

61. 

APPLICATIONS: By optimizing both interior and exterior bilayer compositions, the size and size 

distribution of the interior vesicles, the overall size of the vesosome, the nature of the attachments of the 

vesicles, and the type of additives to the outer bilayer (such as polymers or specific recognition sites), an 

extremely versatile drug delivery system can be developed for a variety of applications. For example, 

one possibility is to deliver toxic drugs directly to cancer cells using cancer-specific recognition 

molecules on the vesosome surface. 

ADVANTAGES: The vesosome's multi-vesicle and self-assembly properties permit: 

● Division of incompatible membrane properties among the various membranes, allowing the 

possibility for sophisticated drug-delivery schemes; 

● Optimization of bilayer composition and aggregate size at each step of the self-assembly process. 


VESOSOMES: BILAYER-ENCAPSULATED VESICLE AGGREGATES 

INQUIRIES TO: Sherylle Mills Englander englander@research.ucsb.edu 


US Patent # 6,221,401 issued April 24, 2001; US Patent # 6,565,889 issued May 


20, 2003 







Phone: (805) 893-4036 






WNT AND FRIZZLED RECEPTORS AS POTENTIAL TARGETS FOR CANCER IMMUNOTHERAPY 


WNT AND FRIZZLED RECEPTORS AS POTENTIAL TARGETS 

FOR CANCER IMMUNOTHERAPY 

BACKGROUND: In the past decade there has been tremendous progress in identifying genetic and 

molecular changes that occur during the transformation of malignant cells. These studies have shown 

that many malignant cells have a less differentiated phenotype, and a higher growth fraction, than 

normal adult tissues. As these basic characteristics are similar to immature and embryonic cells, it is 

possible that ligands and receptors that are normally expressed exclusively in immature and embryonic 

cells are abnormally expressed in malignant cells. For example, the diverse receptor-ligand pairs of the 

Wnt and frizzled (Fz) families play important roles during embryonic development, and thus may be 

overexpressed in cancers that arise from immature cells. Because these ligands and receptors are 

expressed on the cell surface, they could be important targets for the immunotherapy of tumors that have 

arisen from residual immature cells, or that have undergone de-differentiation. 

DESCRIPTION: Researchers at the University of California have discovered that members of the Wnt 

and Fz families are upregulated in a variety of cancers. Using a combination of real time PCR and 

antibody studies, the researchers found that certain members of the Wnt and Fz families are expressed in 

human squamous cell carcinomas, breast cancers, and lymphomas, but not in their normal tissue 

counterparts. The specific family members upregulated depends on the cancer type. In addition, the 

researchers found that blocking Wnt signaling through the use of antibodies can in some cases lead to 

apoptosis of the cancer cells. Thus, specific antibodies to Wnt and Fz family members may be useful in 

the treatment of these cancers. 

ADVANTAGES: The methods used in these studies can be applied to the study of any cancer type, thus 

providing potential diagnostic and therapeutic targets for these cancers. 

APPLICATIONS: 

● Cancer immunotherapy using antibodies that inhibit signaling through the specific Wnt/Fz 

receptors overexpressed in that cancer. 

● Cancer immunotherapy using antibodies against specific Wnt/Fz receptors that are coupled to 

cytotoxic agents. 


WNT AND FRIZZLED RECEPTORS AS POTENTIAL TARGETS FOR CANCER IMMUNOTHERAPY 

● Diagnostics based on the elevated expression of specific Wnt/Fz receptors in different cancers. 








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Cancer Technologies Available for License 

Case No. Title 

B94-041 Genetic Markers for Breast and Ovarian Cancer 

B95-040 p19, A Novel Cell Cycle Inhibitor 

B96-055 Human Telomerase Protein Component 

B99-039 GLYCOSYLATED POLYAMINES AS ANTICANCER, AND CANCER CHEMOTHERAPEUTIC 

COMPOUNDS 

B01-014 SPAS-1 CANCER ANTIGEN 

B02-105 BTLA: COMPOSITIONS AND METHODS FOR MODULATING LYMPHOCYTE ACTIVITY 

B05-068 Pentabromopseudilin and its Derivatives are Lipoxygenase Inhibitors and Potential Anticancer 

Agents 

B05-075 A new approach to flow cytometry, "NanoCytometry" 

B05-077 Optical Probes for Biological Hydrogen Peroxide 

B05-099 Synthetic Design of a Therapeutic Bacterium: Density-Dependent Invasion of Cancer Cells 

B05-134 High Throughput Cellular Communication Chip

Technology Detail - IPIRA 

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Technology Detail 

Abstract: 

TECHNOLOGY/BUSINESS OPPORTUNITY 

Non-Confidential Disclosure 

Genetic Markers for Breast and Ovarian Cancer 

UCB Case No.: B94-041 

Patents: 

Patent No.: 5,622,829 

Date Issued: 1997-04-22 

Patent No.: 5,821,328 


Patent No.: 6,512,091 


Specific BRCA1 mutations, PCR primers and hybridization probes are used in 

nucleic acid-based methods for diagnosis of inheritable breast cancer 

susceptibility. Additionally, binding agents, such as antibodies, specific for 

peptides encoded by the subject BRCA1 mutants are used to identify 

expression products of diagnostic mutations/rare alleles in patient derived fluid 

or tissue samples. Compositions with high binding affinity for transcription or 

translation products of the disclosed BRCA1 mutations and alleles are of 

potential use in therapeutic intervention. Such products include anti-sense 

nucleic acids, peptides encoded by the subject nucleic acids, and binding 

agents such as antibodies, specific for such peptides. 

http://otl.berkeley.edu/inventiondetail.php?inventionId=1000210 (1 of 2)10/21/2005 7:49:23 AM 

PDF Version


Applications: 

● DNA sequence identification of BRCA1 mutants and methods for identifying 

patients with such mutations. 

● Methods for the identification of polypeptides produced from BRCA1 mutant 

genes. 

Features/Benefits: 

● Breast cancer screening based on genetic propensity 

Contact: 

Irvin J Mettler, Ph.D. (IJM) 

Sr. Licensing Officer, Life Sciences 

510.643.7201 (phone) 

510.642.4566 (fax) 

imettler@berkeley.edu 

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Abstract: 



p19, A Novel Cell Cycle Inhibitor 


Scientists at the University of California at Berkeley have cloned a novel human 

and mouse cyclin-dependent kinase (CDK) inhibitor. p19, a novel CDK inhibitor, 

is part of family of known kinase inhibitors that play a role in cell cycle regulation 

and tumorigenesis of T cells. p16 and p15 are well documented in the scientific 

literature, and may function as tumor suppressor genes. 

The cyclins and cyclin-dependent kinases control the cell cycle and are subject 

to several levels of regulation. The G1/S checkpoint is mainly controlled by the 

kinase activity of G1 kinases, which are in turn regulated by cell cycle inhibitors 

that cause cellular arrest at the G1 phase. p19 was discovered while searching 

for activation induction of apoptosis in T cell hybridomas. Apoptosis is 

programmed cellular death and apoptosis modulation is currently of great 

interest to companies seeking to develop new therapeutic approaches to the 

treatment of a wide range of human diseases, especially cancer. T cell 

apoptosis occurs simultaneously with G1 arrest when induced by anti-T-cell 

receptor antibody. 


p19 associates with CDK4 and CDK6 in vivo, two cyclin-dependent kinases 

which control the G1 to S cell cycle transition. The possibility of a tumor 

suppressor therapeutic could be enabled through the elucidation of the 

mechanism of action by which tumor suppressor genes affect the cell cycle and 

PDF Version


Contact: 

apoptosis. p19 is but the most recently discovered member of a family of genes 

believed to act as tumor suppressors in T cells. 



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Abstract: 



Human Telomerase Protein Component 


Patents: 

Patent No.: 5,917,025 


Patent No.: 5,770,422 


Related To: 

B01-004 

DNA at the end of chromosomes is maintained in a dynamic balance of loss and 

addition of simple sequence repeats (telomeres). Telomeric repeat addition is 

regulated and is catalyzed by the enzyme telomerase. Because normal somatic 

cells do not appear to highly express or require telomerase but cancer cells do 

highly express and require telomerase, molecules that can inhibit or effect 

telomerase activity are potential anti-cancer agents. 


The invention provides methods and compositions relating to a human 

telomerase and related nucleic acids, including four distinct human telomerase 

subunit proteins called p140, p105, p48, and p43 having human telomerase- 

specific activity. The proteins may be produced recombinantly from transformed 

host cells from the disclosed telomerase encoding nucleic acids or purified from 

human cells. Also included are human telomerase RNA components, as well as 

specific, functional derivatives thereof. The invention provides isolated 

telomerase hybridization probes and primers capable of specifically hybridizing 

with the disclosed telomerase gene, telomerase-specific binding agents such as 

specific antibodies, and methods of making and using the subject compositions 

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Contact: 

in diagnosis, therapy and in the biopharmaceutical industry. 



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GLYCOSYLATED POLYAMINES AS ANTICANCER, AND 

CANCER CHEMOTHERAPEUTIC COMPOUNDS 

Abstract: 


Patents: 

Patent No.: 6,420,344 


Patent No.: 6,531,454 


Glycosylated polyamines comprising of mono- or oligo-saccharides that are 

glycosidically linked to an aliphatic polyamine, their pharmaceutically acceptable 

salts, prodrugs and derivatives are useful, for example, as anticancer 

compounds, and for the treatment of a variety of cancers. Methods for synthesis 

of glycosylated polyamines are disclosed. In addition, metal complexes of 

glycosylated polyamines, the preparation of such metal complexes and 

analytical methods using the metal complexes are provided. Methods for 

detecting equitorial and axial conformation of a group other than hydrogen at 

the C2 position of a saccharide molecule are also provided. 

Also see: 

S.P. Gaucher, S.P. Peterson, and J.A. Leary, Stereospecific Synthesis and 

Characterization of Amino Glycoside Ligands from Diethylenetriamine, J.Org. 

Chem., 1999 May 28: 64(11): 4012-15. 

http://otl.berkeley.edu/inventiondetail.php?inventionId=1000511 (1 of 2)10/21/2005 7:49:27 AM


Applications: 

● These compounds can be used as anticancer, and chemotherapeutic agents 

against breast, ovarian, and a variety of other cancers. 

● Based on the crystallographic studies of the structure of one of the compounds, 

these compounds are predicted to interact with the estrogen receptor, and thus 

can be used to modulate estrogen receptor activity in a variety of conditions or 

diseases involving estrogen-mediated activities including: (1) prevention or 

delay of the onset of breast cancer, (2) treatment or prevention of osteoporosis, 

(3) treatment, prevention or delaying of the onset of uterine disorders, (4) as a 

modulator of ovulation for purposes of fertility treatment and/or contaception, 

and (5) for reducing cardiovascular disease in postmenupausal women. 

● Can be used as ligands in preparing metal complexes for developing analytical 

methodology. 


● In screening assays conducted by the Natinal Cancer Institute, one of the 

compounds has been shown to be more potent than tamoxifen in inhibiting 

growth of certain cancer cell lines. 

● A detailed drug development plan is available for this technology. 

● Stereochemically pure product is easily isolated and crystallized as a 

Contact: 

hydrochloride salt. 

Javed Afzal, Ph.D. (JXA) 


510.643.7201 (phone) 

510.642.4566 (fax) 

jafzal@berkeley.edu 

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Abstract: 



SPAS-1 CANCER ANTIGEN 


United States Patent Application # 20020150588 

Abstract: 

United States Patent Application # 20020150588 

The compounds include polypeptides that contain at least one immunogenic 

portion of one or more SPAS-1 proteins and DNA molecules encoding such 

polypeptides. Such compounds may be formulated into vaccines and 

pharmaceutical compositions for immunization against cancer, or can be used 

for the diagnosis of cancer and the monitoring of cancer progression. The SPAS- 

1 antigen was the first to be found as a marker for prostate cancer and target 

validation is currently underway. 


• The invention may be useful in the therapy and diagnosis of prostate cancer 

including use as a target for human monoclonal antibody. 

• The SPAS-1 polypeptides and polynucleotides can be used in vaccines and 

pharmaceutical compositions for prevention and treatment of prostate cancer, 

and for the diagnosis and monitoring of such cancers including but not limited to 

prostate cancer and other tumors that express this gene. The present invention 

also relates to methods of identifying and cloning T cell-defined tumor antigens 

PDF Version


Applications: 

● The present invention relates generally to therapy and diagnosis of cancer, 

such as prostate cancer. The invention is more specifically related to 

polypeptides comprising at least a portion of a SPAS-1 protein, and to 

polynucleotides encoding such polypeptides. Such polypeptides and 

polynucleotides can be used in vaccines and pharmaceutical compositions for 

prevention and treatment of prostate cancer, and for the diagnosis and 

monitoring of such cancers including but not limited to prostate cancer and 

other tumors that express this gene. The present invention also relates to 

methods of identifying and cloning T cell-defined tumor antigens 


● Such polypeptides and polynucleotides can be used in vaccines and 

pharmaceutical compositions for prevention and treatment of prostate cancer, 

and for the diagnosis and monitoring of such cancers including but not limited 

to prostate cancer and other tumors that express this gene. 

● The present invention also relates to methods of identifying and cloning T cell- 

Contact: 

defined tumor antigens 

Joshua J Shinoff, Ph.D. (JJS) 

Licensing Officer, Life Sciences 

510.643.4219 (phone) 

510.642.4566 (fax) 

jshinoff@berkeley.edu 

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BTLA: COMPOSITIONS AND METHODS FOR MODULATING 

LYMPHOCYTE ACTIVITY 

Abstract: 

Contact: 


A novel pair of co-stimulatory molecules, B and T lymphocyte attenuator 

(BTLA), have been identified. BTLA delivers a negative signal that inhibits CD4+ 

lymphocyte activation and IL-2 production, as well as suppressing B cell 

proliferation after B-cell receptor-mediated activation. BTLA is not expressed by 

naïve T cells, but is induced during activation and remains expressed only on T 

helper type 1 (TH1) cells. BTLA may provide a mechanism to down-regulate 

TH1-mediated inflammatory and autoimmune responses. 

• The identification of BTLA may offer new approaches to selectively modulate 

the function of activated TH1 cells in the context of both cancer as well as auto- 

immune diseases. 

• BTLA activation may serve as a means to dampen inappropriate auto-reactive 

T-cells and provide a subset-specific means for treating transplant rejection as 

well as rheumatoid arthritis and multiple sclerosis. 





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Pentabromopseudilin and its Derivatives are Lipoxygenase 

Inhibitors and Potential Anticancer Agents 

Abstract: 


Lipoxygenases have been implicated as contributing factors in numerous 

human diseases including cancer, heart disease, psoriasis, and asthma. There 

are three major human lipoxygenases (HLO): 5-, 12-, and 15-HLO. These 

lipoxygenase products are the precursors of hormones, such as leukotrienes 

and lipoxins, which have been implicated as critical signaling molecules in a 

variety of inflammatory diseases and cancers. 5-HLO products cause bronchial 

constriction, while 12-HLO plays a major role in psoriasis, and 15-HLO oxidizes 

low-density lipoproteins that are thought to initiate the primary stage of 

atherosclerosis. Lipoxygenase isozymes are also involved in uncontrolled cell 

growth and/or regulation. 15-HLO has been shown to be a key biological agent 

in colorectal cancers, while 12-HLO is involved in pancreatic, breast and 

prostate cancers. 5-HLO is up-regulated in prostate cancer and its inhibition 

abolishes all cell proliferation, inducing apoptosis. 

• The inventors have found that pentabromopseudilin acts as an inhibitor to two 

of the three types of human lipoxygenase. 


• The invention includes six unique analogs of pentabromopseudilin which have 

varying levels of inhibitory effect on lipoxygenase activity.


Contact: 



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Abstract: 




A new approach to flow cytometry, "NanoCytometry" 


Patents: 

Patent No.: US Application #10/056,103 


Conventional flow cytometry has made valuable contributions to cancer 

diagnosis and management as well as to the understanding of fundamental 

cancer cell biology. Flow cytometry is used routinely in the clinical diagnosis of 

the hematologic malignancies; in tumor immunology to define lymphocyte 

subsets; and in basic research to facilitate cell separations based on the 

expression of particular proteins or phospholipids at the cell-surface. However, it 

does require a large sample of cells and usually requires labeling. 

Researchers at the University of California, Berkeley have developed a new 

approach to flow cytometry; the researchers call it "NanoCytomerty." The novel 

technology uses an integrated microfluidic chip which can adapt to sort cancer 

and other types of cells based on their cell-surface protein expression. The 

technology allows for significant improvements over conventional flow 

cytometry, because the system permits label free signal detection, extreme 

reproducibility and sensitivity, and cell separations using very few cells. 

By developing a more sensitive technique to perform cell separations, in 

addition to one that relies on fewer cells, we anticipate that NanoCytometry 

could provide an important new technology applicable to cancer. For instance, 

NanoCytometry could be used to improve upon physicians' ability to detect 

PDF Version


minimal residual disease states and upon a scientist's ability to study cell 

populations that occur in very small numbers such as stem cells. 

Nanocytometry builds upon previous work which includes an all-electronic 

technique for detecting the binding of unlabeled antibody-antigen pairs (US 

Patent Appl. # 10/056,103). 

Applications: 

● Cancer diagnostics, cancer and stem cell research, clinical diagnostics. 


● Reproducibility, sensitivity, extremely small sample size. 

Contact: 

Curt A Theisen (CAT) 

Sr. Licensing Officer 

510.643.7201 (phone) 

510.642.4566 (fax) 

curt@berkeley.edu 

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Abstract: 

Contact: 



Optical Probes for Biological Hydrogen Peroxide 


UC Berkeley researchers have invented a novel probe designed for the optical 

imaging of intracellular H2O2. 

H2O2 is a source of oxidative stress, and oxidative damage resulting from 

cellular imbalance of H2O2 and other reactive oxygen species oxidants is 

connected to aging and severe human diseases such as cancer, cardiovascular 

disorders, and Alzheimer’s and related neurodegenerative diseases. 

This fluorescein-based reagent features excellent selectivity for H2O2 over 

competing cellular ROS, a large dynamic response range owing to its dual 

colorimetric/ fluorometric detection mechanism, and long-wavelength visible 

excitation and emission profiles to minimize cell and tissue damage while 

avoiding interfering autofluorescence from native cellular species. 

Furthermore, we have demonstrated the value of this probe by measuring 

changes in intracellular H2O2 within living mammalian cells. 

Current efforts are directed toward applying PF1 and related tools for studying 

the oxidation biology of living systems. 


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Synthetic Design of a Therapeutic Bacterium: Density- 

Dependent Invasion of Cancer Cells 

Abstract: 

Contact: 


Bacteria are known to localize to tumors after intravenous injection. Based on 

this phenomenon, therapeutic strains have been developed that attack tumor 

cells, elicit an immune response, or deliver a therapeutic agent. These strains 

are often based on attenuated pathogens and display toxicity in humans. 

Starting with non-pathogenic E. coli as a chassis, we have engineered a strain 

that can attack malignant cells by linking genetic modules from heterologous 

species. To induce cellular invasion at high densities of bacteria, a gene from 

Yersinia pseudotuberculosis is placed under the control of the quorum sensing 

system from Vibrio fischeri. This bacterium is able to invade cultured human 

cancer cells under conditions of high bacterial cell density, conditions known to 

occur selectively in the tumor microenvironment. This strain represents a 

platform onto which modules can be added that confer specific adhesion to host 

cells and program the release of a therapeutic agent. 

Advantages of the technology: 

• Non-toxic, specific targeting of malignant tumors 

• Virulent only in the tumor environment 





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Abstract: 



High Throughput Cellular Communication Chip 


Direct cell-cell communication between adjacent cells is vital for the 

development and regulation of functional tissues. It has been noted for over 40 

years that membrane contact with neighboring cells can cause changes in 

morphology, gene expression, and growth. Impaired cellular communication has 

been implicated in numerous diseases, and is correlated with most forms of 

cancer. 

Currently, the most widely used method for screening and research of cellular 

communication involves the transfer of fluorescent dye between a labeled cell 

and an unlabeled cell in contact with a membrane. This is generally 

accomplished by labeling one population of cells with a diffusible dye and 

culturing them in the presence of an unlabeled population of cells. While this 

experimental approach has proven successful, information about single cell 

transfer kinetics is lost due to the difficulty of manipulating the time and location 

of cell to cell contact. The development of an improved in-vitro method to 

monitor cellular communication could greatly increase the throughput of 

discovery in the field. 


Researchers at UC Berkeley have developed and demonstrated a microfluidic 

device for selective trapping of cell-pairs and simultaneously providing optical 

characterizations. The device provides an effective biophysical tool for the 

analysis of molecular mechanisms that underlie intercellular communication. 

PDF Version


Integration with lab-on-a-chip technologies offers promising applications for cell 

based analytical tools such as drug screening, clinical diagnostics, and soft- 

state biophysical devices. 

Applications: 

● Drug screening, clinical diagnostics, cellular research, soft-state biophysical 

devices 


● High throughput, single cell transfer kinetics, integration with lab-on-a-chip 

Contact: 

technologies 

Curt A Theisen (CAT) 

Sr. Licensing Officer 

510.643.7201 (phone) 

510.642.4566 (fax) 

curt@berkeley.edu 

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CANCER PREVENTION, DETECTION, DIAGNOSTIC, AND TREATMENT TECHNOLOGIES 

This page allows you to view Non-Confidential Descriptions (NCDs) of Cancer related technologies available for licensing from the 

University of California, Davis (UC Davis) through the campus Technology Transfer Services (TTS) or the systemwide Office of Technolo 

Transfer (OTT). Please select one of the inventions listed below. 

� 2005-584 - An MRI compatible PET scanner for simultaneous MRI/PET Imaging 

� 2005-543 - Breast CT for early cancer detection and diagnosis 

� 2005-529 - Multiplexed point-of-care breast cancer marker detection system 

� 2005-112 - Nanoparticle Enhanced X-ray Therapy (NEXT) 

� 2004-650 - Glucosinolate Accumulation in Plants 

� 2004-500 - Non-destructive, Non-invasive Single-Cell Raman Spectroscopy 

� 2004-325 - Ligands for Alpha-4-Beta-1 Integrin 

� 2004-315 - Novel Receptor-Binding Cyclic Peptides 

� 2004-314 - Fibrinogen Domain as a Target for Apoptosis 

� 2004-266 - Magnetic Quantum Dots for Use in Imaging 

� 2004-265 - Amino Acid and Peptide Conjugates of Amiloride 

� 2004-118 - Spectroscopic Enhancement of Endoscopy 

� 2004-056 - Selective High Affinity Ligands (SHALS) for Malignant Diseases 

� 2004-018 - On-Demand Cleavable Linker System for Use in Cancer Imaging and Therapy 

� 2003-528 - Treatment and Diagnosis of Primary Biliary Cirrhosis 

� 2002-276 - Use of Novel Indolocarbazoles in Radiosensitization of Cancer Cells 

� 2002-233 - Inhibitor of Tumor Progression 

� 2001-463 - Dietary Cancer Prevention 

� 2001147b - Novel Cytokine Receptor for Treatment and Diagnosis of Prostate Cancer 

� 2001-337 - Novel Human Anti-MUC-1 scFv Antibodies for Cancer Diagnosis and Treatment 

� 2000-299 - Porphyrin-Based Neutron Capture Agents for Cancer Therapy 

� 2000-123 - Technology for Engineering Antibodies with Infinite Affinity for their Antigen 

� 1999-177 - Biosynthetic Genes for a Potent Antitumor Agent 

www.research.ucdavis.edu/technologies 

1850 Research Park Drive, Suite 100 

tel: (530) 757-3432 fax: (530) 758-3276 

Copyright © 2004, The Regents of the University of California

| TECHNOLOGY TRANSFER SERVICES | AVAILABLE TECHNOLOGIES 

NON-CONFIDENTIAL DESCRIPTION 

© 2005 , Regents of the University of California 

Nanoparticle Enhanced X-ray Therapy (NEXT) 

Researchers at the University of California, Davis have invented, and demonstrated the working 

principle of, a new radiation therapeutic method, which uses gold nanoparticles as x-ray 

radiation sensitizers. For instance, when tested with an x-ray tube operated at 100keV on a 

5,000 base-pair supercoiled DNA decorated with 100 gold nanoparticles, the equivalent 

radiation dosage delivered to the nanoparticle-DNA was found to be tripled compared with that 

found from pure DNA. The theoretical upper limit of such radiation enhancement can be 1000% 

or higher. 

Used together with monochromatic or collimated high energy x-ray sources, the nanoparticlebased 

radiation sensitizers of this invention provide a means for a new type of treatment for 

cancer and other diseases including HIV. Because it is possible to functionalize those gold 

nanoparticles with various peptides, proteins, antibodies, polymers, and other ligands, the DNA 

or membranes of different tumor or viral sites can be targeted. The method is termed 

nanoparticle enhanced x-ray therapy (NEXT). 

The method of this invention may be used as a diagnostic tool to detect cancer and HIV at an 

early stage. The method may also be used as a generic diagnostic or visualizing device, in 

which x-ray fluorescence from gold nanoparticles in the target area is produced as a result of 

excitation with a collimated scanning x-ray beam, and the fluorescence is detected with an x-ray 

detector. 

This invention is covered by pending patent rights. 

UC Case No. 2005-112 

For more information contact: 

Clinton H Neagley 

chneagley@ucdavis.edu 

530-757-3471 


Technology & Industry Alliances 

Technology Transfer Services 

1850 Research Park Drive 

Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 

www.research.ucdavis.edu/tia




Glucosinolate Accumulation in Plants 

Glucosinolates are natural compounds synthesized by plants of the crucifer family, including 

nutritionally important Brassica crops such as broccoli and cauliflower. Products derived from 

glucosinolate breakdown exert a variety of biological activities in plants, animals, and humans, 

which range from the participation in plant defense against pathogens and herbivores to the 

prevention of cancers. The prospect of modifying glucosinolate content and composition to 

improve nutritional qualities of food crops has renewed interest in glucosinolate biosynthesis 

and metabolic engineering. 

To uncover regulatory mechanisms of glucosinolate production, researchers at the University of 

California, Davis have screened a collection of Arabidopsis mutants for plants with a highglucosinolate 

phenotype. They have identified and functionally characterized a gene, AtGCC7, 

involved in the regulation of glucosinolate accumulation and have demonstrated a positive role 

of AtGCC7 in glucosinolate synthesis and plant protection. This research indicates that the 

encoded protein, GCC7, regulates the glucosinolate pathway and other defense-related genes 

in Arabidopsis. GCC7 is a member of a large protein family in Arabidopsis, whose 

approximately 30 members share a plant-specific and novel conserved domain of 70 amino 

acids that likely regulates their interaction with calcium-sensing proteins. AtGCC7-like gene 

families are present in the genomes of rice, sunflower and other plant species that do not 

synthesize glucosinolates. AtGCC7-related genes may thus play an important and ubiquitous 

role in plant protection, including modulating glucosinolate accumulation in cruciferous crops. 

AtGCC7 and related genes in other plant genomes may enable marker-assisted molecular 

breeding or rational metabolic engineering of (i) Brassica crops for altered glucosinolate profiles, 

with the prospect to reduce antinutritional glucosinolates in Brassica seeds for animal feed, to 

modify glucosinolate composition for crop protection, or to design functional foods with optimal 

content of health-beneficial glucosinolates in cancer prevention strategies, and (ii) noncruciferous 

crops for increased resistance against fungal and herbivorous pathogens. 


UC Case No. 2004-650 




530-757-3471 





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© 2004 - 2005, Regents of the University of California 

Non-destructive, Non-invasive Single-Cell Raman 

Spectroscopy 

A novel method of single-cell and laser-tweezers Raman spectroscopy for the non-destructive, 

non-invasive analysis of cells, particles (e.g., lipoproteins), and subcellular components has 

been developed by researchers at the University of California, Davis and Lawrence Livermore 

National Laboratory. Raman spectroscopy of a single, non-affixed cell is a novel technology that 

yields a defining bio-molecular fingerprint of the cell, or subcellular component under study 

without altering its biology. 

Advantages 

� High reproducibility; 

� Significantly reduced damage to cells under study; and, 

� Rapid identification and sorting of single cells on the basis of distinct subcellular biology. 

Current radiological, pharmacological, histological, and molecular techniques of single cell or 

subcellular analysis are invasive, destructive, perturbing or a combination, thereof. The current 

methods of analyzing lipoprotein distributions and lipoprotein chemistry are also destructive and 

usually work only in bulk samples. 

Potential uses include: 

� Detection of diseases (cancer, etc.); 

� Screening of patients (e.g., to determine risk of recurrence of a disease); 

� Identification of bacteria types; 

� Cell sorting on live, untagged cells; and 

� Prognostic applications (e.g., to quantitative evaluation of a disease as treatment 

progresses). 

Raman spectroscopy is the laser-based spectroscopic analysis of molecular vibrations and 

allows for non-destructive composition analysis. The result is a molecular fingerprint of the 

material under investigation. When combined with confocal microscopy, micro-Raman 

spectroscopy is possible and the technique can be applied to individual cells or subcellular 

components. Furthermore, combined with a special method of isolating cells (laser tweezers), 

the individual cells can be analyzed simultaneously. 

Combining laser tweezers with confocal micro-Raman spectroscopy also allows for noninvasive, 

non-destructive analysis of individual lipoproteins in their native environment without 

the need for particle adhesion to a surface. This technique allows one to determine lipoprotein 

composition, distributions, and monitor dynamic changes in these parameters with time. 

UC Case No. 2004-500 


Nancy E Rashid 

nerashid@ucdavis.edu 

530-757-3429 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Ligands for Alpha-4-Beta-1 Integrin 

Highly potent ligands for activated alpha-4 beta-1 integrin have been identified by University of 

California, Davis researchers. These ligands can potentially be used as targeting agents for 

cancer as well as anti-inflammatory agents for autoimmune diseases. 

Notable applications of these alpha-4 beta-1 ligands include: 

� Targeting therapy for imaging of cancers including lymphoid malignancies, which have 

high level of activated alpha-4 beta-1 integrin on the cell surface; 

� Therapeutic uses as anti-inflammatory agents for autoimmune diseases such as multiple 

sclerosis, rheumatoid arthritis and lupus; and, 

� Treatment of both human and dog diseases listed above. 

The compounds for activated alpha-4 beta-1 integrin of the present invention have high affinity 

to human malignant lymphoid cells (both T- and B-cells, and including fresh malignant cells from 

patients with acute lymphocytic leukemia). Importantly, the binding affinities of these ligands are 

much higher than products currently developed. 

REFERENCES: 

� Patent pending 

UC Case No. 2004-325 


Luanna K Putney 

lkputney@ucdavis.edu 

530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Novel Receptor-Binding Cyclic Peptides 

The present invention provides novel receptor-binding cyclic peptides (e.g., antagonists) that 

advantageously display high receptor binding affinity and selectively. More particularly, the 

present invention provides integrin-binding cyclic peptides, methods for identifying receptorbinding 

cyclic peptides and for using the cyclic peptides of the present invention for imaging a 

tumor, organ, or tissue and for treating cancer, inflammatory diseases, and autoimmune 

diseases. 

Novel peptides and methods to restrain ring structures in preferred, rigid conformations have 

been invented by University of California, Davis researchers. By manipulating peptide ring 

conformation, the efficiency and selectivity of the peptide towards a panel of integrins can be 

greatly improved. Although structural chemistry approaches to binding efficiency and selectivity 

have been utilized in the past, manipulation of individual peptide residues has been shown to 

result in a number of distinct and unpredictable conformations. 

A novel approach is needed to identify these preferred conformations and to fix peptide rings 

appropriately for receptor site binding efficiency and selectivity. 

This UC Davis invention provides a method for locking peptide rings into a preferred, rigid 

conformation through organic synthesis. In addition, it describes NOESY and TOCSY NMR 

results prior to and after the addition of the fixing agent, exhibiting the correlation between 

structure and binding efficiency and selectivity. Novel advantages of the UC Davis method 

include: 

� Production of a highly specific potent peptide (in the IC 50 nMolar range), suggesting an 

application in therapeutics; and, 

� Potential to be used for locking other motifs in a more restrained structure for binding. 

REFERENCES: 


UC Case No. 2004-315 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Fibrinogen Domain as a Target for Apoptosis 

Researchers at the University of California, Davis have isolated a domain on fibrinogen that 

induces apoptosis of endothelial cells. This fibrinogen domain effectively blocks proliferation of 

cultured bovine artery endothelial cells. 

Features and uses of this fibrinogen domain include: 

� Possible new anti-angiogenic cancer therapeutic; 

� Excellent stability due to its human origin, with no expectation of immunoreactivity; 

� Easily tested in an animal model such as mice; and, 

� Easily synthesized by eukaryotic and bacterial expression systems. 

This domain of fibrinogen contains major binding sites for integrins. In contrast to native 

fibrinogen, which generates proliferative signals upon binding to integrins, this fibrinogen 

domain effectively blocks proliferation of cultured bovine artery endothelial cells and calf 

pulmonary artery endothelial cells. 

In addition, the domain induces apoptosis of bovine artery endothelial cells and calf pulmonary 

artery endothelial cells analyzed using annexin V binding assays and caspase assays. The 

domain also induces massive MAP kinase activation in CHO cells that is resistant to apoptosis, 

but does not induce massive MAP kinase activation in endothelial cells, suggesting that the 

domain may transduce intracellular signals that lead to apoptosis rather than block binding of 

cells to other integrin ligands. 

REFERENCES: 

� Patent Pending 

UC Case No. 2004-314 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Magnetic Quantum Dots for Use in Imaging 

Researchers at the University of California, Davis have invented nanoparticle quantum-dot 

compositions, and associated methods, for use in clinical and therapeutic imaging. The 

nanoparticles are dual-mode agents, being visible via both optical methods and magnetic 

resonance imaging (MRI). This advance permits the combination of positive features associated 

with optical imaging and magnetic resonance imaging. The invention embraces a variety of 

nanoparticle compositions including, e.g., silicon-based nanoparticles and cadmium-based 

nanoparticles. 

The nanoparticle compositions provide optical read-out based on their ability to produce bright 

luminescence of a form that does not fade over time or with repeated irradiations. This nonbleaching 

luminescence makes the compositions useful for imaging applications requiring 

repeated interrogation of regions of interest. The optical imaging permits collection and 

assessment of tissue in histological investigation. 

The nanoparticle compositions also provide magnetic resonance imaging based on the 

presence of metals which alter the signal and provide contrast enhancement. The nanoparticle 

compositions can be constructed in much smaller size diameters than is typical for MRI agents. 

The compositions can thus be used to obtain in vivo magnetic resonance images as a 

complement to the optical imaging at the histological stage. For instance, the compositions can 

be used to confirm, via optical imaging, that biopsied tissue comes from the same area of 

interest as identified by magnetic resonance imaging. 

The nanoparticle compositions of the invention are water soluble, and may be coated with nontoxic 

groups. The compositions may also be attached to specific molecules of interest to allow 

targeting to specific cell or tissue types, or to allow binding of other molecules. 


UC Case No. 2004-266 




530-757-3471 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Amino Acid and Peptide Conjugates of Amiloride 

Novel amiloride conjugates have been developed by researchers at the University of California, 

Davis. This invention includes compounds generated by conjugating amino acids and peptides 

to amiloride at the C(5)-amino goup or C(2)-guanidine moiety, furnishing inactive prodrugs that 

can be selectively activated by tissue endopeptidases. 

The C5-conjugates of the invention are highly selective and potent inhibitors of sodium-proton 

exchange (i.e., NHE1). The C5-conjugates are particularly useful for reducing tissue swelling 

(e.g., acute brain swelling from stroke or head trauma). 

The C2-conjugates of the invention are potent inhibitors of sodium-calcium exchange (i.e., 

NCX). C2-conjugates have been shown to kill specific cancers residing in poorly vascularized 

tumor regions. Furthermore, by design, these compounds can be regionally activated to protect 

against ischemic-reperfusion injury. 

The conjugates are considerably more polar than existing amiloride derivatives. This property 

assists with aqueous solubility and with reducing toxicity by restricting cellular permeation. The 

peptide linkages are designed to be cleaved by enzymes that are tissue-specific, tumor-specific 

or are generated by injured tissue (e.g., brain tissue following head trauma or stroke). 

This invention has the following advantageous features: 

� Amiloride-peptide conjugates with peptidase cleavage sites are not only capable of 

traversing the blood brain barrier but, upon cleavage by brain- or tumor-specific 

peptidases in the central nervous system, release hydrophilic proteolytic products that 

act at the tumor cell surface, thus minimizing toxic side-effects. 

� The conjugates kill hypoxic-ischemic tumor cells (i.e., tumor cells with little or no blood 

supply) that are not normally killed by conventional therapy. 

� These compounds are subject to conventional approaches involving peptido-mimeticism 

for their additional stabilization. 

The invention is covered by pending patent rights. 

Literature Citation: 

� Palandoken H, By K, Hegde M, Harley WR, Gorin FA, and Nantz MH. Amiloride Peptide 

Conjugates: Prodrugs for Sodium-Proton Exchange Inhibition. J Pharmacol Exp Ther. 

2005 Mar;312(3):961-7. Epub 2004 Oct 27. 

UC Case No. 2004-265 




530-757-3471 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Spectroscopic Enhancement of Endoscopy 

Researchers at the Lawrence Livermore National Laboratory and the University of California, 

Davis have developed novel optical imaging instrumentation that can accurately determine 

tumor margins. This invention incorporates the new instrumentation into existing cystoscope 

designs for in-vivo and real-time imaging of bladder cancer. 

The technology involves multimodal imaging using Near Infra-Red (NIR) light coupled with 

image processing algorithms to differentiate human tissue components. 

This new design can be used in a clinical environment to diagnose and image bladder cancer. 

Advantages over the current standard cystoscopy include that this device can: 

� Reduce false positives by accurately detecting whether cancer is present in the bladder 

through a simple "yes" or "no" readout on the screen; 

� Eliminate the need for unnecessary surgical resections in the bladder, resulting in 

tremendous costs savings; and, 

� Accurately determine the margins of the tumor for precise resection, without removing 

healthy tissue and causing more damage than necessary. 

REFERENCES: 

� U.S. Patent Continuation-In-Part Application No. 20040006276 published January 8, 

2004. 

� Parent U.S. Patent Application No. 20040006275 published January 8, 2004. 

UC Case No. 2004-118 




530-757-3429 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Selective High Affinity Ligands (SHALS) for Malignant 

Diseases 

Selective High Affinity Ligands (SHALs) for diagnosis and treatment of malignant diseases have 

been discovered by researchers at the University of California, Davis. The invention 

encompasses selection of chemical or protein ligands based upon intended target docking sites, 

sometimes found through insights into antibody binding epitopes, modeling or determination of 

crystal or NMR structures. The linkage of two or more ligands generates a SHAL having high 

selectivity and avidity for the intended target. The target may be malignant cell unique, or 

associated, but present in greater density or having greater accessibility on the malignant cell 

when compared to normal cells. 

The SHALs advantage: 

� Direct malignant cell killing or imaging when a radioisotope is attached; 

� Robust treatment when cytotoxic agents are attached; 

� Incorporation of SHALs for malignant diseases into larger molecules when it is 

advantageous to do so; 

� Production of a high therapeutic index in the patient readily and economically; 

� Long shelf life compared to other similar agents; and, 

� Generation of different SHALs for different malignant cells/diseases. 

REFERENCES: 


UC Case No. 2004-056 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





On-Demand Cleavable Linker System for Use in Cancer 

Imaging and Therapy 

Novel compositions and methods for improving site-specific delivery of biological agents to the 

site of a tumor and enhancing removal of those agents from normal tissues and organs have 

been developed by researchers at the University of California, Davis. 

The dose limiting toxicities of radioimmunotherapy (RIT) are often due to excessive radiation to 

normal tissues and organs such as liver, kidney, and bone marrow. As a result, new strategies 

are required to enhance the therapeutic index of cancer-targeting agents by not only improving 

the delivery of the radiopharmaceutical to the tumor, but also by enhancing the rapid removal of 

the radioactive agent from normal tissues and organs. 

This new technology provides for tumor-targeting agents that can image and treat cancer. 

Advantages over the current standard technology include that this linking system provides for 

existing and future tumor targeting agents that: 

� Have an enhanced therapuetic index; 

� Are resistant to cleavage or degradation from proteases found in plasma or tumor cells; 

� Are selectively cleaved by the administration of an exogenous protease; and, 

� Are rapidly removed from normal tissues and organs following protease cleavage. 

REFERENCES: 

� International Application Publication No. WO2005051315 published June 9, 2005. 


UC Case No. 2004-018 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Treatment and Diagnosis of Primary Biliary Cirrhosis 

The likely cause of primary biliary cirrhosis (PBC) has been identified as a microorganism by 

University of California, Davis researchers. There are several lines of evidence that suggest this 

microorganism is the causative agent of PBC, including: 

� Two proteins expressed by the microorganism have significant homology with the 

immunodominant epitope of the major autoantigen in PBC, the E2 component of the 

pyruvate dehydrogenase complex (PDC-E2); 

� There is strong reactivity in nearly both antimitochondrial antibody (AMA) positive and 

AMA negative PBC patients, with antibody titer up to 10 -6 regardless of the disease 

stage; and, 

� This microorganism is present in sewage treatment plants and is involved in the 

degradation of 17-b estradiol, perhaps explaining the pathogenesis of PBC given the 

predominance of PBC in females. 

The present invention provides methods of using anti-microbial agents for the treatment of 

autoimmune conditions. This invention also provides methods and kits useful for diagnosis or 

prognosis of PBC by using agents capable of detecting the presence of the causative agent of 

the disease. 

REFERENCES: 

� U.S. Patent Application Publication No. US 2005/0042214 published February 24, 2005 

� Selmi C., et al., Patients with Primary Biliary Cirrhosis React Against a Ubiquitous 

Xenobiotic-Metabolizing Bacterium. Hepatology. 2003 Nov;38(5):1250-7. 

UC Case No. 2003-528 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Use of Novel Indolocarbazoles in Radiosensitization of 

Cancer Cells 

The use of a new class of indolocarbazole compounds for selectively enhancing radiation 

cytotoxicity to cancer cells has been developed by University of California, Davis researchers. 

This class of compounds is targeting at DNA topoisomerase I (TOP1). TOP1 is important for 

many aspects of nucleic acid metabolism including DNA replication, RNA transcription and 

regulation of DNA supercoiling. TOP1 is elevated in cancer cells, thereby providing a molecular 

basis for tumor-selective targeting by TOP1-targeted compounds. 

These indolocarbazole compounds are: 

� Potent radiosensitizers; 

� Able to radiosensitize mammalian cells at relatively non-cytotoxic concentrations; and, 

� Easily combined with well-established methods for monitoring effective dosing and 

timing of drug delivery. 

REFERENCES: 

� Patent pending; 

� Chen AY, Shih SJ, Hsiao M, Rothenberg ML, and Prudhomme M. Induction of 

Radiosensitization by Indolocarbazole Derivatives: The Role of DNA topoisomerase I. 

Mol Pharmacol. 2004 Sep;66(3):553-60. 

UC Case No. 2002-276 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Inhibitor of Tumor Progression 

A protein that suppresses the cellular levels of ErbB3, a protein involved in the progression of 

some solid tumors, has been identified and characterized by researchers at the University of 

California, Davis. Animal studies to validate ErbB3 suppression are currently underway. 

The University of California, Davis invention: 

� May be employed to suppress tumor progression in cancer patients. 

� May be used to promote neural tissue regeneration in stroke, head trauma or spinal cord 

injury patients. 

� May be effective in treating patient tumors without cardiotoxic side effects. 

REFERENCES: 

� International application WO03072712, published on September 04, 2003. 

UC Case No. 2002-233 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Dietary Cancer Prevention 

A key gene related to dietary cancer prevention has been isolated by University of California, 

Davis researchers. Cancer prevention linked to the consumption of cruciferous vegetables has 

long been established. The high levels of compounds known as glucosinolates in cruciferous 

plants are the basis of their anticarcinogenic action, which works by inducing enzymes that 

detoxify carcinogens in the body. Glucosinolate compounds are found in cruciferous plants such 

as broccoli, cauliflower, and oilseeds. 

The gene isolated by University researchers is a key to the biosynthesis of anticarcinogenic 

glucosinolate compounds. Using this gene pathway, a number of glucosinolate compositions 

can be manipulated in the same plant, which can: 

� Maximize levels of anticarcinogenic compounds in cruciferous plants 

� Improve the taste and nutritional value of cruciferous plants 

� Block formation of other glucosinolates that are known anti-nutrients, solving a 

significant problem with animal feed and oilseed crops 

With 10.3 million new cancer cases yearly, there is significant market potential for varieties of 

high-glucosinolate cruciferous vegetables. This gene could be rapidly implemented to engineer 

or select varieties of anticarcinogenic broccoli and other crops. 

The invention is covered by pending patent rights. 

See United States Patent Application Publication No. US 2005/0055744 published March 10, 

2005 

UC Case No. 2001-463 




530-757-3471 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Novel Human Anti-MUC-1 scFv Antibodies for Cancer 

Diagnosis and Treatment 

Novel single chain variable fragment (scFV) antibodies against human Mucin-1 (MUC-1) have 

been developed by researchers at University of California, Davis to diagnose and treat 

adenocarcinoma cells, such as human breast, prostate and ovarian cancer cells. 

This method is superior to current methods for optimal diagnosis and treatment of these 

cancers. For example, while radioimmunotherapy using intact monoclonal antibodies (MoAbs) 

has been utilized in the treatment of breast cancer and other solid tumors, therapeutic success 

has been limited by the large size of the MoAb (150 kD) inhibiting blood clearance and retarding 

accumulation of the radiopharmaceutical at the tumor site(s). 

This powerful method utilizes small peptide antibodies that are specifically targeted to MUC-1, 

one of the epithelial mucin family of molecules that has received considerable interest as an 

antigen target because it is widely expressed on a large number of epithelial cancers and is 

aberrantly glycosylated, making it structurally and antigenically distinct from that expressed by 

non-malignant cells. These targeted antibodies make it possible to both image and treat primary 

and metastatic tumors associated with breast, prostate and ovarian cancer by killing only 

cancerous cells. New methods using these antibody peptides can be superior to current 

methods in that: 

� Identification of cancer cells is achieved through anti-MUC-1 peptide antibody binding 

profiles to select the scFv to the type of cancer by large tissue arrays (eg prostate and 

breast cancers); and, 

� Targeted therapy to MUC-1 positive cells is possible resulting in the death of only 

cancerous cells. 

Targeted imaging (eg PET or SPECT) for sensitive detection and treatment of cancerous cells 

can be made ideal using these innovative reagents. Efficient cost-effective production of the 

small cancer-specific peptide antibodies is possible using standard techniques. 

REFERENCES: 

� U.S. Patent Application Publication No. US 2004/0005647 published January 8, 2004 

� Natarajan A, Xiong CY, Albrecht H, DeNardo GL, and DeNardo SJ. Characterization of 

Site-Specific ScFv PEGylation for Tumor-Targeting Pharmaceuticals. Bioconjug Chem. 

2005 Jan-Feb;16(1):113-21. 

UC Case No. 2001-337 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 


Anti-MUC-1 MAb compared to anti-MUC1 scFv E1 and G1 binding to human prostate cancer (grade 3) 

(A-C) and not to normal human colon (D). A) BrE-3 MAb B) E1 scFv C) G1 scFv and D) G1 scFv on 

human colon. 

© 2001 - 2005, Regents of the University of California




Novel Cytokine Receptor for Treatment and Diagnosis of 

Prostate Cancer 

A novel cytokine receptor, IL-17RL, has been discovered by UC Davis Investigators. IL-17RL 

function is known to be a critical factor in androgen sensitivity and its loss has been correlated 

with the androgen insensitivity associated with more invasive, metastatic, high Gleason scoring 

carcinomas. Normal to low Gleason grade tissues express IL-17RL, therefore antibodies 

directed to IL-17RL make an effective yet objective assay for androgen sensitivity and thereby 

aggressiveness. 

The use of immunohistochemistry as an effective evaluational assay is well evidenced by the 

success of PSA assays. The present invention provides a validated novel target for prostate 

cancer assessment and treatment. 

This invention offers a: 

� Therapeutic agent for the restoration of androgen-responsiveness to a prostate cancer 

cell; 

� Diagnostic marker for prostate cancer growth; and, 

� Marker to determine the aggressiveness of a prostate cancer cell. 

REFERENCES: 

� United States Patent Application Publication No. US 2004/0171109 published 

September 2, 2004. 

� Haudenschild D, Moseley T, Rose L, and Reddi AH. Soluble and Transmembrane 

Isoforms of Novel Interleukin-17 Receptor-Like Protein by RNA Splicing and Expression 

in Prostate Cancer. J Biol Chem. 2002 Feb 8;277(6):4309-16. Epub 2001 Nov 12. 

� Moseley TA, Haudenschild DR, Rose L, and Reddi AH. Interleukin-17 Family and IL-17 

Receptors. Cytokine Growth Factor Rev. 2003 Apr;14(2):155-74. 

� Reddi AH. Cartilage Morphogenetic Proteins: Role in Joint Development, Homoeostasis, 

and Regeneration. Ann Rheum Dis. 2003 Nov;62 Suppl 2:ii73-8. 

UC Case No. 2001147b 




530-757-3166 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 





Porphyrin-Based Neutron Capture Agents for Cancer 

Therapy 

A new synthetic method producing porphyrin-based neutron capture agents for use in cancer 

therapy has been developed by University of California, Davis researchers. Through a unique 

linkage involving the porphyrin ring, these new compounds afford increased selectivity for tumor 

cells and improved in vitro and in vivo stability over existing drugs. Boron neutron capture 

therapy (BNCT) is an emerging therapeutic modality for the treatment of cancer. By targeting 

localized boron-containing tissue, high linear energy transfer (high-LET) particles are able to 

destroy malignant cells in the presence of normal cells without causing damage to healthy 

tissue. This therapy has been particularly effective in the treatment of malignant brain tumors. 

Porphyrins are highly fluorescent and presently the best-known carriers of elements such as 

boron for selective uptake by cancerous cells. 

The new UC Davis compounds are superior to existing neutron capture agents in that: 

� Retention times for boron in malignant tissue are greatly increased; 

� Greater solubility allows for simple administration into the bloodstream without a cosolvent; 

� Increased stability improves overall performance and selectivity; and, 

� Efficient synthesis involves readily available reagents. 

REFERENCES: 

� U.S. Patent Application Publication No. US 2004/0014737 published January 22, 2004 

� Vicente MG, Edwards BF, Shetty SJ, Hou Y, & Boggan JE. Syntheses and Preliminary 

Biological Studies of Four meso-Tetra[(nido-carboranylmethyl)phenyl]porphyrins. Bioorg 

Med Chem. 2002 Mar;10(3):481-92. 

� Vicente MGH, Nurco DJ, Shetty SJ, Osterloh J, Ventre E, Hegde V, & Deutsch WA. 

Synthesis, Dark Toxicity and Induction of in vitro DNA Photodamage by a tetra(4-nidocarboranylphenyl)porphyrin. 

J Photochem Photobiol B. 2002 Nov;68(2-3):123-32. 

� Vicente MGH, Wickramasinghe A, Nurco DJ, Wang HJ, Nawrocky MM, Makar MS, & 

Miura M. Synthesis, Toxicity and Biodistribution of Two 5,15-Di[3,5-(nidocarboranylmethyl)phenyl]porphyrins 

in EMT-6 Tumor Bearing Mice. Bioorg Med Chem. 

2003 Jul 17;11(14):3101-8. 

� Vicente MGH, Gottumukkala V, Wickramasinghe A, Anikovsky M, & Rodgers MAJ. 

Singlet Oxygen Generation and Dark Toxicity of a nido- and a closocarboranylporphyrin. 

Proceedings of SPIE -- Volume 5315; Optical Methods for Tumor 

Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIII. 

2004 June;5(4):33-40. 

� Bobadova-Parvanovaa P, Okua Y, Wickramasingheb A, Hall RW, & Vicente MGH. Ab 

initio and 1 H NMR Study of the Zn(II) Complexes of a nido- and a closocarboranylporphyrin. 

J. Porphyrins Phthalocyanines 2004;8(7):996-1006. 

� Gottumukkala V, Luguya R, Fronczek FR, & Vicente MG. Synthesis and Cellular Studies 

of an Octa-Anionic 5,10,15,20-tetra[3,5-(nido-carboranylmethyl)phenyl]porphyrin 

(H 2 OCP) for Application in BNCT. Bioorg Med Chem. 2005 Mar 1;13(5):1633-40. 

UC Case No. 2000-299 




530-757-3429 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 




Technology for Engineering Antibodies with Infinite 

Affinity for their Antigen 

Technology for engineering antibodies to bind irreversibly to their receptor has been developed 

by UC Davis researchers. This technology, enabling the formation of permanent antibodyantigen 

complexes has a number of potential applications in chemistry and biology, including: 

� targeted medical imaging 

� targeted medical therapies (e.g. cancer therapeutics) 

� synthetic tag to replace avidin-biotin 

� no competition from endogenous ligands 

� no dissociation after capture 

� humanized format 

This technology is an alternative to using combinatorial selection, directed evolution, or other 

methods for improving the affinity of antibodies to ligands. 

REFERENCES: 

� Corneillie TM, Whetstone PA, Lee KC, Wong JP & Meares CF. Converting Weak 

Binders Into Infinite Binders. Bioconjug Chem. 2004 Nov-Dec;15(6):1389-91. 

� Meares CF, Chmura AJ, Orton MS, Corneillie TM & Whetstone PA. Molecular Tools for 

Targeted Imaging and Therapy of Cancer. J Mol Recognit. 2003 Sep-Oct;16(5):255-9. 

� Chmura AJ, Orton MS & Meares CF. Antibodies with Infinite Affinity. Proc Natl Acad Sci 

U S A. 2001 Jul 17;98(15):8480-4. Epub 2001 Jul 10. 

� UC Case Numbers 2004-501, 2001-433, and 2000-123. 

Requirements for an antibody with infinite affinity: (a) When the antibody and ligand are apart, their 

complementary reactive groups do not react significantly with other molecules in the medium. (b) When 

the ligand binds to the antibody, the effective concentrations of their complementary reactive groups are 


UC Case No. 2000-123 


Barbara A Boczar 

baboczar@ucdavis.edu 

530-757-3428 





Suite 100 

Davis, CA 95616-6134 

Phone: 530-757-3432 

Fax: 530-758-3276 


sharply elevated, and a covalent link is formed. (c) The covalently linked antibody/ligand complex 

cannot dissociate. 

© 2000 - 2005, Regents of the University of California

BIOSYNTHETIC GENES FOR A POTENT ANTITUMOR AGENT 

The enediyne family of antitumor antibiotics comprises the most potent, most highly active antitumor agents 

ever discovered, with some members of this family being 1000 times more potent than adriamycin, one of the 

most effective antitumor antibiotics in current clinical use. However, the natural enediynes that have undergone 

testing so far have shown either a limited spectrum of activity or unpredictable toxicity, making them unsuitable 

for therapeutic applications. 

Superior attenuation of these undesirable side effects has been observed in polymer-based delivery systems and 

in enediyne-antibody conjugates, suggesting that enediynes can be developed into powerful drugs when their 

extremely potent cytotoxicity is harnessed and delivered into tumor cells with greater specificity. The needed 

modifications of enediynes can be most efficiently implemented via alterations of the genes responsible for 

enediyne biosynthesis. This in turn requires the cloning and sequencing of genes responsible for the synthesis of 

an appropriate enediyne and the development of in vivo systems for controlling the expression of these genes. 

A University of California scientist has cloned a cluster of genes from Streptomyces globisporus that synthesize 

C-1027 and developed a suitable expression system for them. Not only is this the first successful cloning of an 

enediyne biosynthetic gene cluster, C-1027 also happens to be the most potent member of the enediyne family. 

Thus, this invention represents a significant breakthrough in understanding the synthesis and assembly of the C- 

1027 apoprotein and chromophore and in making possible the creation of novel candidate antitumor drugs. As 

compared to natural enediynes, genetically-altered C-1027 compounds might display extremely high potency 

while having higher tumor specificity and lower systemic toxicity, making them potentially much more 

valuable as candidate anticancer agents. 

Related Publication: 

Liu, W.; Shen, B. Genes for Production of the Enediyne Antitumor Antibiotic C-1027 in Streptomyces 

globisporus are Clustered with the cagA Gene that Encodes the C-1027 Apoprotein. Antimicrob. Agents 

Chermother. 2000, 44:382-392. 


� Pharmaceuticals > Anti-infective agents 

� Pharmaceuticals > Antineoplastic agents 


INQUIRIES TO: Barbara Boczar baboczar@ucdavis.edu 





Oakland, CA 94607-5200

UC Irvine Cases matching the search term “cancer” 

UC Case No. Title 

2004-181-1 Second Harmonic Optical Coherence Tomography 

2003-408-2 

2002-208-3 

2002-020-2 

2001-352-2 

Method for Quantitative Digital Color Imaging of 

Objects 

High Resolution Optical Coherence Tomography Over 

a Greater Depth Range Using an Axicon Lens 

Novel Retinoblastoma Binding Protein-Related Gene 

And Potential Use As Cancer Vaccine 

2000-474-2 Treatment For Prostate Cancer 

2000-037-4 

1998-280-4 

A Soluble Type II TGF-ß Receptor To Suppress 

Pancreatic Cancer Growth 

2001-421-2 Novel Cytodiagnostic Markers For Cancer 

2001-270-3 

2000-008-2 

1996-046-1 

Wnt, Fz, and BMP-6 Receptors for the Treatment and 

Detection of Colon Cancer 

Unnatural Amino Acids That Mimic Peptide Beta- 

Strands 

Use Of Infectious And Pathogenic Clone Of A Lung 

Cancer-Inducing Retrovirus For Generation Of 

Therapeutic Reagents And Diagnostic Tests 

Modulation Of Cell Growth And Growth Factor 

Signaling Through Removal Of Glypicans 

Enhancement Of Host Defense Via Receptor(s) For 

C1q 

1989-069-2 Methods Of Diagnosis Of Amyloidoses

Title: Methods Of Diagnosis Of Amyloidoses 

UC Case No: 1989-069-2-ott 

Categories: Pharmaceuticals: Central Nervous System Disorders 

Biotechnology: Antibodies 

Licensing Opportunity 


Technology: A method of diagnosing a disease with cerebrovascular deposition of amyloid, including 

Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis-Dutch type and other 

amyloidoses, in a mammal is disclosed in which a sample of cerebrospinal fluid is obtained, the 

level of immunoreactivity toward a monoclonal antibody raised against native PN-2/.beta.APP 

or other amyloid precursor protein in the sample is measured, and this measured level is 

compared to the level of immunoreactivity toward this antibody in a sample from a normal 

subject. A lower level in the sample from the mammal indicates a likelihood of the disease. 

NOTICE OF GOVERNMENT SUPPORT This invention was made with Government support 

under Grant No. GM-31609 awarded by the National Institutes of Health. The Government has 

certain rights in this invention. American Cancer Society Grants CD 390 and BC 602/BE 22A 

provided further support for the development of this invention. 

Contact: David Schetter, Assistant Vice Chancellor 


University of California, Irvine 


Irvine, CA 92697-7700 

Phone: (949) 824-7297, FAX: (949) 824-2899 

Email: schetter@uci.edu 

Patent Status: U.S. Patent No. 5,270,165 

UCI School: College of Medicine 

Department: Microbiology & Molecular Genetics 

Keywords: Research Tool: antibody



Title: Enhancement Of Host Defense Via Receptor(s) For C1q 


Categories: Biotechnology: Drug Targets and Screening Tools 

Background: As the development of protein products and peptide mimetics becomes more prevalent in the 

biotechnology and pharmaceutical industries, the ability to mimic the protective and modulate 

the inflammatory effects of the recognition protein of the classical complement cascade in blood 

and body fluids will increase. 

Technology: Researchers of the University of California, Irvine, have discovered and sequenced a novel 

receptor molecule which can be used to develop agonists that will promote the initial host 

response of limiting or abrogating infection or trauma by pathogens or other detrimental 

material without the generation of extracellular toxic O2. This structural information will be used 

to design a specific and effective ligand that activates these cells to phagocytose infectious 

targets recognized by opsonic receptors on myeloid cells. 

Application: This activity will be highly advantageous in preventing opportunistic infections in individuals 

whose immune system is compromised by genetics (inherited immunodeficiency), disease 

(AIDS) or treatment regimens (immunosuppression for cancer therapy and transplantation). 

Contact: Ronnie Hanecak, Ph.D., Senior Licensing Officer 




Irvine, CA 92697-7700 

Phone: (949) 824-7186, FAX: (949) 824-2899 

Email: rhanecak@uci.edu 

Patent Status: U.S. Patent No. 5,965,439 

UCI School: School of Biological Sciences 

Department: Molecular Biology & Biochemistry



Title: Modulation Of Cell Growth And Growth Factor Signaling Through Removal Of Glypicans 


Categories: Biotechnology: Drug Targets and Screening Tools, Diagnostics 

Background: Membrane associated heparin sulfate proteoglycans (HSPGs) have been shown to play 

important roles in many aspects of cell behavior, including cell-cell and cell-extracellular matrix 

adhesion and growth factor signaling. Glypicans, members of the HSPGs, are a family of 

polypeptides that appear to carry the majority of the heparin sulfate on mammalian cells. These 

glypicans are attached to the plasma membrane via glycosylphophatidylinositol (GPI) anchors. 

Technology: Glycosylphosphatidylinositol-(GPI-) anchored HSPG glypican-1 (glypican-1) is strongly 

expressed in human breast and pancreatic cancer - both by the cancer cells and in the case of 

pancreatic cancer the adjacent fibroblasts. Expression of glypican-1 is low in normal pancreas 

and breast tissue. Pancreatic cancer cell lines that express glypican-1 were treated with the 

enzyme phosphinositide-specific phospholipase-C (PI-PLC) which enzymatically removes 

glypicans from the cell surface by cleaving the GPI anchors. This treatment resulted in the 

abrogation of the cells' mitogenic response to two heparin-binding growth factors. Treatment of 

breast cancer cell lines also abrogated their response to two different heparin-binding growth 

factors. 

Application: Glypican-1 can be used for the diagnosis and screening for the occurrence of breast and 

pancreatic cancer. Glypican-1 can also be targeted with small molecules and biologics to retard 

the growth of glypican-responsive cancers. 





Irvine, CA 92697-7700 

Phone: (949) 824-7186, FAX: (949) 824-2899 


Patent Status: Pending 


Department: Department of Medicine - Endocrinology 

Keywords: Diagnostic: assay, Diagnostic: antibody, Diagnostic: detection, Diagnostic: elisa, Diagnostic: 

immunoassay, Diagnostic: marker, Disease: cancer



Title: Use Of Infectious And Pathogenic Clone Of A Lung Cancer-Inducing Retrovirus For Generation 

Of Therapeutic Reagents And Diagnostic Tests 


Categories: Biotechnology: Drug Targets and Screening Tools 

Veterinary: Animal Health 

Background: Jaagsiekte sheep retrovirus (JSRV) causes broncheolo-alveolar carcinoma in sheep and is a 

significant veterinary problem world-wide. Clinically and histopathologically, this disease has 

strong resemblance to broncheolo-alveolar carcinoma (BAC) in humans which accounts for 

approximately 25% of human lung cancers. 

Technology: Researchers at the University of California, Irvine have isolated the first infectious molecular 

clone of JSRV and have developed techniques for production of infectious JSRV that allowed 

the researchers to prove that JSRV alone was sufficient to induce BAC in sheep. 

Application: The molecular clone of JSRV has potential for the generation of diagnostic reagents for 

infection in sheep, the generation of vaccines against JSRV, and the generation of novel 

retroviral vectors for targeting lung tissue. Finally, this line of research can serve as a starting 

point for searching for analogous viruses in human. 





Irvine, CA 92697-7700 

Phone: (949) 824-7186, FAX: (949) 824-2899 


Patent Status: U.S. Patent No. ABANDONED 

UCI School: School of Biological Sciences 

Department: Molecular Biology & Biochemistry



Title: Unnatural Amino Acids That Mimic Peptide Beta-Strands 


Categories: Biotechnology: Protein Folding and Interactions, Genomics and Proteomics 

Background: After a protein is translated, sections of the polypeptide can fold into a number of structures 

including alpha helices and beta-pleated sheets. Beta-sheet interactions between proteins are 

involved in protein dimerization, protein-protein interactions and protein aggregations, which are 

important in a variety of biological processes including those involved in cancer, AIDS and 

Alzheimer's disease. A number of researchers have begun to achieve the goal of developing 

new drugs based on compounds that can block, modulate, or mediate beta-sheet interactions 

between proteins. 

Technology: Researchers at the University of California, Irvine, have synthesized a non-natural amino acid. 

This amino acid and its derivatives mimic tripeptide beta-strands. When incorporated into 

peptides, peptidomimetics or proteins all three types of structures will dimerize by means of 

beta-sheet interactions. A logical extension of this work is to use this amino acid in agents 

designed to block the beta-sheet dimerization of proteins. Another line of development using 

this amino acid is to incorporate it in agents that interact with proteins through beta-sheet 

formations. 

Contact: V.J. "Raj" Rajadhyaksha, Ph.D., Associate Director, Strategic Technology Development 




Irvine, CA 92697-7700 

Phone: (949) 824-2920, FAX: (949) 824-2899 



UCI School: School of Physical Sciences 

Department: Chemistry 

Keywords: Chemical: amino acid, Genomics: proteomics, Research Tool: protein synthesis, Therapeutic: 

peptides, Therapeutic: proteins, Disease: AIDS, Disease: cancer, Disease: neurological

Title: Treatment For Prostate Cancer 


Categories: Pharmaceuticals: Cancer 



Contact: V.J. "Raj" Rajadhyaksha, Ph.D., Associate Director, Strategic Technology Development 




Irvine, CA 92697-7700 

Phone: (949) 824-2920, FAX: (949) 824-2899 




Department: Cancer Center



Title: Wnt, Fz, and BMP-6 Receptors for the Treatment and Detection of Colon Cancer 


Categories: Biotechnology: Drug Targets and Screening Tools, Gene Expression, Diagnostics 

Background: Ectopic activation of the Wnt signaling pathway leads to increased cellular growth and division 

in experimental organisms and mutations in the Wnt pathway. Wnt pathway genes are tightly 

linked to the genesis of certain cancers in humans, such as colon cancer. 

Technology: University of California, Irvine, researchers have found that factors of the Wnt signaling pathway 

are associated with colon carcinogenesis and may therefore be useful for prognosis, diagnosis 

or treatment of colon cancer. These factors include isolated polynucleotides and polypeptides of 

full-length lymphoid enhancer factor-1 (LEF-1). Researchers have also found that full-length 

LEF-1 and other factors such as Wnt2, Wnt5, BMP6, and FZ receptors may be used in the 

detection and treatment of colon cancer. 

Application: This finding provides the starting point to find an antagonist or agonist to target the full length 

LEF-1 protein or promoter that produces full length LEF-1 or proteins in the Wnt signalling 

pathway. In addition, a test may be developed to detect levels of full length LEF-1 or Wnt 

signalling proteins which would indicate the presence of colon cancer. 





Irvine, CA 92697-7700 

Phone: (949) 824-7186, FAX: (949) 824-2899 





Keywords: Diagnostic: detection, Diagnostic: marker, Genomics: gene, Genomics: receptor, Screening: 

target, Disease: cancer



Title: Novel Retinoblastoma Binding Protein-Related Gene And Potential Use As Cancer Vaccine 


Categories: Pharmaceuticals: Vaccines 

Biotechnology: Diagnostics 

Background: The central objective in the development of an effective immunotherapy is the identification of 

tumor antigens that can elicit antibody and cellular immune responses in humans. Human 

autologous or allogeneic antibodies from cancer patients are an alternative to the use of 

monoclonal antibodies. Though not as specific as monoclonal antibodies, serum antibodies are 

useful probes to identify tumor-associated antigen epitopes relevant to immune responses in 

cancer patients. 

Technology: Researchers at the University of California, Irvine, used human IgG antibodies to identify a 

novel retinoblastoma binding protein-related gene (RBP1L1) that encodes a nonameric antigen 

epitope. The epitope was recognized by IgG antibodies that were isolated from breast cancer 

patients. RBP-CT mRNA is expressed at high levels in various human carcinomas and in 

normal testis and expression is limited or absent in other normal tissues. 

Application: The properties of RBP-CT as a molecular marker may be used for the development of novel 

diagnostic tools for the detection of human malignancies. The identified antigenic peptide 

epitope may also serve as a potential target for a tumor vaccine. 





Irvine, CA 92697-7700 

Phone: (949) 824-7186, FAX: (949) 824-2899 





Keywords: Diagnostic: antibody, Diagnostic: marker, Research Tool: antibody, Therapeutic: antibody, 

Therapeutic: vaccine, Disease: cancer

Title: Novel Cytodiagnostic Markers For Cancer 


Categories: Biotechnology: Diagnostics 



Background: Cervical cancer is one of the leading causes of cancer-related death in women worldwide. 

Approximately 500,000 new cases are diagnosed each year and pre-cancerous abnormalities 

of the cervix occur in far greater numbers of women each year. Cervical carcinomas develop 

progressively from hyperplastic tissue changes over the course of years or even decades. The 

molecular mechanisms that regulate the induction and progression of neoplasias to cancer are 

poorly understood and supports the need to develop cytodiagnostic markers for cervical cancer 

progression. The promyelocyte protein (PML) has been shown to be overexpressed in 

tumerous situations associated with increased transcription and cell hyperactivity. It has also 

been shown that PML is modified by a small polypeptide which triggers targeting of PML to its 

corresponding nuclear bodies. 

Technology: Researchers at the University of California, Irvine, have used tissues from cervical biopsies to 

show that PML and its associated nuclear bodies exhibit changes in both size and number 

throughout the continuum of cervical neoplasia. Differences in the pattern of PML reflect the 

aggressiveness of the tumor. In addition, PML and loss of the partnership with the specific 

polypeptide parallels the progression from neoplasias to cervical carcinoma. 

Application: These findings have potential for the development of new prognostic markers for the prediction 

of disease progression as well as early detection of cervical cancer. 

Contact: Alvin K. Viray, Patent & Licensing Officer 




Irvine, CA 92697-7700 

Phone: (949) 824-3104, FAX: (949) 824-2899 

Email: aviray@uci.edu 


UCI School: Beckman Laser Institute 

Department: -- No Dept Listed -- 

Keywords: Diagnostic: detection, Diagnostic: marker, Medical Devices: diagnosis, Medical Devices: 

measurement, Medical Devices: treatment, Screening: assay, Screening: detection, Screening: 

screen, Screening: target, Therapeutic: cell signalling, Therapeutic: disease model, Disease: 

cancer, Disease: ObGyn



Title: A Soluble Type II TGF-ß Receptor To Suppress Pancreatic Cancer Growth 


Categories: Pharmaceuticals: Cancer 

Biotechnology: Gene and Cell Therapy, Gene Expression 

Background: Mammalian cells express three transforming growth factor ß (TGFß) isoforms that regulate 

many cellular processes. They inhibit the growth of cells of epithelial origin and modulate 

differentiation, migration, deposition of the extracellular matrix, immunosuppression, motility and 

cell death. Human pancreatic cancer is the fifth leading cause of cancer related mortality in 

Western industrialized countries. The mortality rate virtually equals its incidence rate. It has 

been established that 50% of these cancers have mutations that may cause these tumors to be 

resistant to TGFß-mediated growth inhibition. However, human pancreatic cancers overexpress 

TGFßs and this over-expression has been correlated with decreased patient survival. 

Technology: To determine whether blocking TGFß actions would suppress pancreatic cancer cell growth in 

vivo, researchers at the University of California, Irvine expressed a soluble TßRII in COLO-357 

human pancreatic cancer cells. COLO-357 cells express all three mammalian TGFß isoforms 

and are growth inhibited by TGFß in vitro. The results showed that COLO 357 clones 

expressing soluble TßRII were no longer growth inhibited by exogenous TGFß1 and exhibited a 

marked decrease in their invasive capacity in vitro. When injected into mice, these clones 

exhibited attenuated growth rates and angiogenesis as compared to tumors formed by sham 

transfected cells. This indicates that endogenous TGFßs can confer a growth advantage in vivo 

to a pancreatic cancer cell line that is growth inhibited in vitro and suggest that this approach 

can be used to block the tumorigenic effects of TGFß. These results may also be the basis for 

developing effective therapies for pancreatic cancer patients. 





Irvine, CA 92697-7700 

Phone: (949) 824-7186, FAX: (949) 824-2899 




Department: Department of Medicine - Endocrinology 

Keywords: Genomics: receptor, Therapeutic: gene therapy, Therapeutic: proteins, Disease: cancer, 

Disease: metabolic



Title: High Resolution Optical Coherence Tomography Over a Greater Depth Range Using an Axicon 

Lens 


Categories: Medical Imaging/Radiation: Other Imaging 

Background: Optical coherence tomography uses coherence gating to select minimum backscattered 

photons for image reconstruction. Axial and lateral resolutions are determined by the source 

coherence length and numerical aperture of the sampling lens, respectively. While axial 

resolution can be improved using a broadband light source, there is a trade-off between lateral 

resolution and focusing depth because a beam with a long focal depth and narrow lateral width 

cannot be produced simultaneously - high lateral resolution requires a large numerical aperture 

while a long focal depth requires a small aperture. In high speed OCT imaging, where an axial 

scanning mode is used, a tightly-focused lens produces a micrometer sized spot at only one 

particular depth. The coherence gate quickly moves out of the shallow depth of focus during the 

scan. Although dynamic focusing compensation can be used to overcome this limitation, current 

lenses can only be used at low speeds, which limit their use to low frame rate OCT systems. In 

addition, dynamic focusing lenses are bulky and cannot be implemented in circumstances 

where physical space is restricted such as endoscopic OCT. 

Technology: Researchers at the University of CA have developed a scanning OCT system to overcome 

these limitations. The invention incorporates an axicon lens into the sample arm of the 

interferometer. Using this axicon lens, 10um or better lateral resolution is maintained over a 

focusing depth of at least 6 mm. Thus high lateral resolution is simultaneously achieved with a 

greater depth of focus. The technology can simultaneously image fluid flow and morphology in 

a sample with fast scanning speed and high velocity sensitivity. 

Application: In addition to the conventional probe, the axicon lens can also be used in high resolution 

endoscopic (and/or catheter) OCT system. This is especially important because dynamic 

focusing is not possible in endoscopic (and/or catheter) OCT. High resolution is especially 

important for cancer diagnosis in the gastrointestinal (GI), respiratory, and urogenital tracts. It is 

also important in diagnosis of the cardiovascular disease. 





Irvine, CA 92697-7700 

Phone: (949) 824-3104, FAX: (949) 824-2899 





Keywords: Diagnostic: detection, Diagnostic: imaging, Diagnostic: measurement, Diagnostic: ultrasound, 

Medical Devices: imaging, Medical Devices: measurement, Medical Devices: diagnosis, 

Medical Devices: optical, Research Tool: equipment, Screening: detection, Disease: blood, 

Disease: cancer, Disease: ophthamological, Disease: dermatologic



Title: Method for Quantitative Digital Color Imaging of Objects 


Categories: Biotechnology: Diagnostics 

Background: In many disciplines, quantitative measurements of color are required to evaluate 

nondestructively the state of an object (e.g., quality of produce). This characterization is 

typically performed using contact point measurement devices. A limitation of these devices is 

that multiple measurements are required to characterize an entire object; if multiple objects 

must be characterized, then this process may be time consuming. Furthermore, these devices 

interrogate both superficial and deeper structures in the object, and do not possess the ability to 

discriminate between these structures. 

Technology: University of California researchers have developed a method for acquiring and analyzing 

polarization sensitive digital color images of objects. Polarization optics provide the user with 

the ability to discriminate between superficial and deeper structures in an object. Various linear 

transformations can be applied to the images to obtain information in alternate color spaces; 

this can be tailored to the specific colors of interest. For studies in which multiple color 

measurements are required over a relatively long period of time, the researchers have 

developed a device to position the object in a repeatable fashion, allowing for absolute color 

comparisons to be drawn among measurement sessions. 

Application: One successful application of this method has been for quantitative characterization of melanin 

and erythema content in skin. Other potential applications include (but are not limited to) the 

following. In the food industry, this method can be used to evaluate the effect of freeze-thaw 

cycles on food, quantify food quality during preparation, characterize the quality of meats for 

grading, measure the color of grain to assess quality, and study environmental effects on 

produce. In dermatology, the method can be used to quantify effects of ultraviolet radiation on 

skin, characterize skin irritation due to topical drug application, evaluate the color and/or 

potential irritation induced by cosmetics, quantify the efficacy of sunscreens, determine the 

efficacy of therapies of various skin conditions (e.g., psoriasis, nonmelanoma skin cancer), 

evaluate the irritation caused by baby wipes, and quantify the effects of anesthesia on skin 

perfusion. Other fields in which such a method can be used include soil chemistry, biomaterials 

testing, horticulture, and textiles. 





Irvine, CA 92697-7700 

Phone: (949) 824-3104, FAX: (949) 824-2899 




Department: -- No Dept Listed --

Keywords: Disease: dermatologic, Diagnostic: detection, Diagnostic: imaging, Diagnostic: measurement, 

Diagnostic: point of use, Medical Devices: diagnosis, Medical Devices: imaging, Medical 

Devices: measurement, Medical Devices: optical, Medical Devices: treatment

Title: Second Harmonic Optical Coherence Tomography 




Categories: Biomedical Engineering: Devices 

Medical Imaging/Radiation: Other Imaging 

Biotechnology: Diagnostics, Medical Devices, Research Tools 

Background: Optical coherence tomography (OCT) is a noninvasive, noncontact imaging modality for crosssectional 

imaging of biological tissue with micrometer scale resolution. Conventional OCT uses 

variations in tissue scattering (due to heterogeneities in the optical refractive index) as imaging 

contrast. However, in many instances and especially in the early stages of disease, the change 

in tissue scattering properties between normal and diseased tissue is tiny and difficult to 

measure. One of the great challenges for extending the clinical applications of OCT is to find 

more contrast mechanisms that are sensitive to molecular and tissue structural changes at 

early stage of diseases. 

Technology: Researchers at the University of California have developed a technology that combines the 

molecular contrast of second harmonic generation (SHG) with coherence gating of OCT. 

Compared with conventional OCT performed at fundamental wavelength, SH-OCT offers 

enhanced molecular contrast and spatial resolution. It is also an improvement over existing 

second harmonic scanning microscopy technology, as the coherence mechanism enables the 

detection and discrimination of SH signal generated at deeper locations. The enhanced 

molecular contrast of SH-OCT extends conventional OCT's capability for detecting small 

changes in molecular structure. 

Application: SH-OCT is promising for the diagnosis of cancers and other diseases at an earlier stage when 

changes in tissue and molecular structure are small. 





Irvine, CA 92697-7700 

Phone: (949) 824-3104, FAX: (949) 824-2899 





Keywords: Diagnostic: measurement, Diagnostic: imaging, Medical Devices: device, Medical Devices: 

imaging, Medical Devices: diagnosis, Medical Devices: measurement, Medical Devices: optical, 

Research Tool: Imaging, Research Tool: equipment, Screening: detection, Therapeutic: 

imaging, Optics/Imaging: Other

1: MURINE PTEN NULL PROSTATE CANCER MODEL 

2: MATERIALS FOR IDENTIFYING AND ASSESSING PROSTATE CANCER 

THERAPIES 

3: YY1: NOVEL PROGNOSTIC FACTOR IN HUMAN PROSTATE CANCER 

4: A SERUM TUMOR ASSOCIATED ANTIGEN FOR METASTATIC PROSTATE 


5: POTENT COMPOUNDS OVERCOME HORMONE REFRACTORY DRUG 

RESISTANCE IN PROSTATE CANCER 

6: POLYPHENOLIC COMPOUNDS INHIBIT PANCREATIC CANCER 

7: POST-TRANSLATIONAL MODIFIED HISTONES AS BIOMARKERS, 

SUCCESSFULLY DEMONSTRATED IN A STUDY OF PROSTATE CANCER 

TISSUES 

8: NOVEL PROSTATE SPECIFIC MEMBRANE ANTIGEN-BASED PROSTATE 


9: EFFICIENCY OF ANTI-PSMA ANTIBODIES 

10: SIMPLIFIED METHOD FOR PRODUCING A PANEL ARRAY OF BIOMARKERS 

FOR DETECTION, PROGNOSIS AND PREDICTION OF MULTIPLE CANCERS 

11: TRANSGENIC MOUSE WITH PROSTATE-SPECIFIC EXPRESSION OF A 

REPORTER GENE 

12: C-MYC TRANSGENIC MOUSE 

13: NOVEL PROGNOSTIC FACTOR AND THERAPEUTIC TARGET IN HUMAN 

RENAL CELL CARCINOMA 

14: NEURO-ENDOVASCULAR ULTRASOUND THROMBOLYSIS 

15: METHOD AND DEVICE FOR TREATING INTRACRANIAL VASCULAR 

ANEURYSMS 

16: DIAGNOSTIC TEST FOR PROLIFERATIVE SENESCENCE IN IMMUNE CELLS

17: A KNOWLEDGE-BASED METHOD FOR INDEXING CLINICAL TRIALS 

18: VECTOR CONTAINING TISSUE-SPECIFIC RNAP II PROMOTER FOR siRNA 

DELIVERY 

19: METHODS FOR INDUCING INTERLEUKIN-12 AND A TYPE1/TH1 T-CELL 

RESPONSE IN DERMATOLOGIC DISEASE 

20: HIV Protein Moderates Telomerase 

21: TARGETING LENTIVIRAL VECTORS TO SPECIFIC CELLS AND TISSUES 

22: USE OF SECONDARY LYMPHOID ORGAN CHEMOKINE TO INDUCE ANTI- 

TUMOR RESPONSE BY STIMULATING CELL-MEDIATED IMMUNE RESPONSE 

AND INHIBITING ANGIOGENESIS 

23: GENOMIC SCREENING WITH A CHEMICAL NUCLEASE 

24: GM-CSF AND IL-4 THERAPY FOR THE IN-SITU EXPANSION OF DENDRITIC 

CELLS AND ENHANCEMENT OF VACCINE-BASED IMMUNITY 

25: A MXXXL MOTIF CONFERING ENDOCYTOSIS OF BIOMOLECULES 

26: A NOVEL SYSTEM FOR MEASURING PROTEASE ACTIVITY 

27: A Transcriptionally-Regulated G Protein-Coupled Receptor Blocks Cells in G2/ 

M 

28: A FELINE BRONCHIOLOALVEOLAR LUNG CARCINOMA (BAC) XENOGRAFT 

AND CELL LINE FOR THE STUDY OF COMMON ANIMAL AND HUMAN 

PATHOGENS 

29: DETERMINING THE COMPONENTS OF BOTANICAL MIXTURES BY SINGLE- 

STRAND CONFORMATION POLYMORPHISM ANALYSIS (SCCP) 

30: RNA BINDING FLUOROCHROME: FLUORO NISSL GREEN 

31: REACTION OF PURINES WITH ELEMENTAL FLUORINE TO GENERATE 8- 

FLUOROPURINES 

32: CELL-TYPE SPECIFIC INTRACELLULAR DELIVERY USING 3E10 MUTANT 

33: GENETICALLY ENGINEERED MOUSE LACKING TUMOR SUPPRESSOR 

GENE IN THE BRAIN 

34: CERBERUS AND FRZB-1, SECRETORY MOLECULES WITH A 

REGENERATIVE FUNCTION AND AN INHIBITORY ACTIVITY ON WNTS, 

RESPECTIVELY

35: MUTATIONS IN ATAXIA-TELANGIECTASIA GENE 

36: A HUMAN INFLAMMATORY BREAST CARCINOMA XENOGRAFT MODEL OF 

THE INTRAVASATION STEP OF METASTASIS 

37: POLYNUCLEOTIDE DETECTION SYSTEM FOR LOW COPY NUMBERS FOR 

RESEARCH AND CLINICAL USES 

38: ARTIFICIAL HUMAN MUTATION CONTROLS FOR CLINICAL DIAGNOSTIC 

GENETIC AND PROFICIENCY TESTING

MURINE PTEN NULL PROSTATE CANCER MODEL 


UCLA Technology Available For Licensing 

BACKGROUND: In the western world, prostate cancer remains the most common malignancy and 

the second-leading cause of cancer-related deaths in men. The Pten gene (phosphotase and tensin 

homologue deleted on chromosome 10) has been well characterized as a tumor suppressor gene, and its 

malfunction/deletion has been linked to numerous cancer types, including prostate. Mutations or 

deletions of Pten have been found in 30% of primary prostate cancers and 63% of malignant cases, 

ranking it as one of the most common determinants of prostate tumor progression. Pten-controlled 

signaling pathways are therefore promising targets for therapeutic strategies, though significant 

problems in producing animal models have prevented serious gains toward this end. Lack of Pten leads 

to embryonic lethality and heterozygote Pten animals do not undergo normal prostate cancer 

development. A significant need remains for a workable Pten-null prostate cancer animal model system. 

INNOVATION: UCLA researchers have developed a prostate cancer model in mice by deleting the 

Pten tumor suppressor gene. The deletion is tissue-specific and leads to Pten loss specifically in the 

prostate. This model recaptures the disease progression seen in human prostate cancer and is nonresponsive 

to androgen-ablation therapy. Studying the consequences of Pten loss in prostate cancer in 

vivo was not possible before this innovation. Additionally, this is the first and only animal model where 

the initiating oncogenic event is not androgen-dependant. This Pten-null model has been utilized by 

UCLA researchers to successfully identify several down-stream targets of Pten, including known 

"signature" genes associated with human cancer metastasis. 

UCLA researchers have also established a Pten-null prostate cancer cell line from this animal model 

(UC case number 2005-007), as well as an isogenic Pten- fibroblast cell line (UC case 2005-059), and 

embryonic fibroblast and stem cell lines that lack Pten (UC case 2005-060). 

APPLICATIONS: This model is suitable for examination of prostate tumor development from 

initiation to metastasis, as well as androgen-independent growth. This innovation can be utilized in gene 

expression profiling related to prostate cancer progression and metastasis, which may lead to 

identification of novel targets and biomarkers for cancer diagnostics and therapeutics. The mechanism of 

resistance to angrogen-ablation therapy could also be studied using this model. 

The embryonic cell lines derived from the Pten-null model can be used in multiple ways from Pten 

characterization to diagnosis and therapeutic development, as well as generation of animal models. The 

isogenic cell line has potential for use in elucidating the specific role of Pten in cell proliferation, 

migration, and differentiation. 

Related Papers (Selected) 

http://www.research.ucla.edu/tech/ucla04-073.htm (1 of 2)10/21/2005 8:23:30 AM


● Wang, S. et al. Prostate specific deletion of the murine Pten tumor suppressor gene leads 

to metastaic prostate cancer. Cancer Cell. 2003 Sep;4(3):209-211. more... 

Reference: UCLA Case No. 2004-073 

For information on licensing this 

invention, 

please contact the office below. 

Office of Intellectual Property 

Administration 

University of California, Los 

Angeles 

10920 Wilshire Blvd., Suite 

1200 

Los Angeles, CA 90024-1406 

Tel: 310-794-0558 Fax: 310- 

794-0638 

email: ncd@resadmin.ucla. 

edu 

NCD URL: http://www.research.ucla.edu/tech/ucla04-073.htm 

Lead Inventor: Hong Wu 

UCLA Technologies Available for Licensing 

http://www.research.ucla.edu/tech 

Copyright © 2004 The Regents of the University of California 

keywords: uclancd ucla technologies intellectual property patents technology transfer invention business card 


MATERIALS FOR IDENTIFYING AND ASSESSING PROSTATE CANCER THERAPIES 

MATERIALS FOR IDENTIFYING AND ASSESSING PROSTATE CANCER 

THERAPIES 


BACKGROUND: Prostate cancer is the second leading cause of cancer deaths among men in the 

United States. Treatment of the disease typically involves the use of testosterone-lowering drugs and 

competitive androgen receptor (AR) antagonists. While these approaches are effective at blocking tumor 

growth for a brief period of time they eventually give rise to hormone refractory (HR) drug resistance, a 

fatal stage of the disease. 

Several mechanisms to explain HR drug resistance have been hypothesized, including mutation of the 

androgen receptor, ligand independent activation of the receptor and activation of alternative signaling 

pathways. However, none of these hypotheses are supported by compelling evidence. This lack of a 

clear dogma not only complicates our understanding of HR prostate cancer, but it hinders the search for 

therapies that can overcome HR resistance. Thus an accurate model of HR, late stage prostate cancer 

would be a valuable tool in the identification of lead therapeutic compounds. 

INNOVATION: UCLA scientists have established a hormone refractory, late stage prostate cancer cell 

line after having identified the underlying cause of HR drug resistance. Specifically, it was discovered 

that a modest 2-fold increase in androgen receptor mRNA levels confers drug resistance in late stage 

prostate cancer. Thus this cell line accurately reflects the clinical aspects of the HR drug resistant disease 

and can serve as a powerful tool in prostate cancer research. It can be valuable in all aspects of the drug 

development process, from the identification of a lead compound to the characterization of a lead 

compound's physiological effects on a mammalian prostate cancer cell. In addition, it allows for 

comparisons to normal, non-diseased prostate cells and hormone sensitive prostate cancer cells. 

ADVANTAGES 

● The augmented AR mRNA-expressing prostate cancer cell line is a biologically accurate 

representation of the clinical aspects of late stage prostate cancer. 

● The cell line can be used to test combinations of multiple compounds for their effects on an HR 

drug resistant prostate cancer cell. 

POTENTIAL APPLICATIONS 

● The cell line can be used in high-throughput drug screening to identify lead compounds that 

overcome HR drug resistance. 

● The cell line can also be used to examine the physiological effect of a lead compound on a 


MATERIALS FOR IDENTIFYING AND ASSESSING PROSTATE CANCER THERAPIES 

mammalian prostate cancer cell. 

● The cell line can be injected into SCID mice to produce a biologically relevant animal model of 

HR drug resistant prostate cancer. 

Related Paper 

● Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, 

Sawyers CL. Molecular determinants of resistance to antiandrogen therapy. Nat 

Med. 10, 33-9 (2004). more... 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Charles Sawyers 



Copyright © 2005 The Regents of the University of California. 

keywords: biological research tool uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


YY1: NOVEL PROGNOSTIC FACTOR IN HUMAN PROSTATE CANCER 



BACKGROUND: The initial development and progression of prostate cancer involve multiple 

molecular alterations. In tumor cells, genetic alterations and changes in the tissue microenvironment lead 

to altered levels of expression of many individual genes. Identification of those particular genes 

represents a critical step toward a more thorough understanding of prostate carcinogenesis, which in turn 

is critical to the improvement of diagnostic and therapeutic methods, prognostic capabilities, and more 

effective clinical management of prostate cancer patients. 

Genes that are consistently over-expressed in the vast majority of prostate cancers are of particular 

interest biologically and clinically. In addition to providing insight into the etiology of prostate cancer, 

those genes and their products are potentially useful as diagnostic markers, although few such genes 

have yet been identified. 

INNOVATION: Research at UCLA has resulted in the identification and characterization of a 

particular transcription factor that offers promise as a new marker for prostate cancer. Yin Yang 1 (YY1) 

(also known as NF-E1, CP-1 and UCRBP) is a multifunctional DNA binding protein that can activate or 

repress transcription, depending on the context in which it binds. As previously demonstrated, YY1, 

which plays an important role in the regulation of many cellular and viral genes, is over-expressed in the 

human prostate cancer cell line PC3. Its expression has also been shown to be associated with resistance 

to Fas apoptosis. 

Using tissue microarrays to investigate YY1 expression and cellular location in a large sample of 

patients who had undergone radical prostatectomy, researchers have now determined that YY1 

represents a gene product of both prognostic significance in the treatment of prostate cancer and 

diagnostic potential as a reliable biomarker. The consistency and robust nature of the YY1 transcription 

factor render it well suited as a diagnostic marker for use in the evaluation of prostate needle biopsy 

samples. 

To date the UCLA researchers have: (a) optimized the use of the YY1 antibody for 

immunohistochemistry; (b) analyzed tissue biopsies of hundreds of patients following radical 

prostatectomy; (c) performed statistical analyses of cytoplasm and nuclear staining; (d) established a 

correlation with several clinical and pathological variables; (e) determined a prognostic significance for 

patients with weaker nuclear YY1 expression, correlating with more rapid tumor recurrence; and (f) 

designed YY1 sequence-specific oligonucleotides for semi-quantitative RT-PCR. 

ADVANTAGES: The potential value of this technology lies in its superior diagnostic and prognostic 

capabilities and in its promising potential with regard to the development of improved therapeutic for 



prostate cancer (and potentially for other forms of cancer as well). 


Potential applications for this technology include: 

(a) Immunohistochemistry analysis of YY1 expression in cell nuclei or cytosol, either independently or 

in combination with other known markers, following needle biopsy. For example, analysis of YY1 

expression in conjunction with tests for the presence of the prostate basal cell marker p63 potentially 

will enhance diagnostic performance by providing a positive YY1 stain result in addition to a negative 

p63 stain indicative of cancerous cells. 

(b) Detection of YY1 expression in isolated cells using RT-PCR, following microlaser microdissection. 

(c) Determination of YY1 levels in fresh tumor biopsy tissue by analyzing cell lysates using either 

ELISA or the Western blot analysis, or by evaluating YY1 DNA-binding activity using EMSA. 

(d) Determination of critical needle biopsy sites and assessment of cancer progression within the 

prostate, based upon molecular imaging identification of individual cells or cell groups exhibiting YY1 

expression characteristic of prostate cancer. 

(e) Detection of metastatic prostate cancer in organs other than the liver and kidney, based upon 

systematic molecular imaging of YY1 expression. 

(f) Development of predictive methods or tools supportive of prostate cancer patient treatment decisions. 

(g) Development of new therapeutic methods based, for example, upon interference with YY1 

expression or activity. Such new methods could prove particularly beneficial in the treatment of prostate 

cancer determined to be resistant to chemotherapy or immunotherapy. 

INVENTOR: Dr. Benjamin Bonavida is a Professor in the Department of Microbiology, Immunology 

and Molecular Genetics at UCLA's David Geffen School of Medicine, and is a Member of the Tumor 

Immunology Research Group at UCLA's Jonsson Comprehensive Cancer Center. 





invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Benjamin Bonavida 




keywords: diagnostics uclancd ucla technologies intellectual property patents technology transfer invention business card 


A SERUM TUMOR ASSOCIATED ANTIGEN FOR METASTATIC PROSTATE CANCER 


A SERUM TUMOR ASSOCIATED ANTIGEN FOR METASTATIC PROSTATE 


BACKGROUND: Prostate cancer is the most common malignancy and the second leading cause of 

cancer-related death in American men. Since prostate cancer is a biologically and clinically 

heterogeneous disease, a majority of men with this malignancy harbor slow-growing tumors that may 

not impact an individual's natural lifespan, while others are struck by rapidly progressive, metastatic 

tumors. Screening for prostate cancer with prostate specific antigen (PSA) is limited by the test's lack of 

specificity and its inability to predict which patients are at risk to develop hormone refractory metatstatic 

disease. This leads to a number of patients being subjected unnecessarily to invasive diagnostic 

procedures or surgical procedures, which have economical and quality of life consequences. New 

markers that correlate with clinical outcome or identify patients with potentially aggressive disease can 

dramatically improve the diagnosis and management of prostate cancer. 

INNOVATION: In a comparative microarray analysis of expression data between an androgen 

dependent and a hormone refractory prostate cancer mouse model, Researchers at UCLA had identified 

a candidate gene differentially expressed in the hormone refractory mouse model. Such candidate gene 

had been confirmed to encode a secreted protein that may potentially function as a tumor-associated 

antigen (TAA) for identifying patients with hormone refractory metastasis and for monitoring cancer 

progression to metastasis in patients diagnosed with the disease. It may have other applications as a 

biomarker. 

The TAA's expression has been observed in a cancer progression tissue microarray (TMA) composing 

of benign prostate tissue, localized prostate cancer, and hormone refractory metastatic prostate cancer. 

Results of the analysis indicate benign or normal prostate tissue does not express the TAA and that 

expression of the TAA is highest in hormone refractory metastatic tumors. More importantly, the 

prevalence of TAA expression and the level of its expression correlate with prostate cancer progression 

to metastasis. 

APPLICATIONS 

1. TAA may be used as a prognostic marker for hormone refractory metastatic 

prostate cancer and metastatic prostate cancer; 

2. TAA may be used as a marker for monitoring prostate cancer progression; and, 

3. TAA and its receptor may be a target for drug or antibody therapy. 

ADVANTAGES 



1. Measured non-invasively in the serum using a standard immunoassay; 

2. Not expressed in normal prostate tissue; 

3. Expression level and prevalence of TAA is correlated with prostate cancer 

progression: 

a. Level of TAA expression increases as prostate cancers progress, particularly in 

metastatic cancer; and, 

b. Level of TAA expression is correlated with high tumor grade in localized 

tumors; 

c. Prevalence of TAA expression increases as prostate cancer progress from 

clinically benign to clinically localized to metastatic cases. 

4. TAA may have diagnostic applications in other forms of cancers such as 

colorectal and gastric cancer. 

DEVELOPMENT-TO-DATE: The researchers are developing antibodies to the TAA for research and 

diagnostic applications. Upon the identification of such antibodies, the researchers will develop a serum 

ELISA involving these antibodies and subsequently 1) assess its expression in tissue samples and 2) 

measure its circulating levels in normal and cancer patients. Further, they will determine if expression of 

the TAA in another organ interferes with the detection of the TAA from tumor tissue. 

The researchers' additional research plan involves characterizing the TAA's normal biochemical function 

and how its expression is regulated, in normal and in progression to prostate cancer metastasis. Further, 

the researchers hope to clone the TAA's cell surface receptor and study signal transduction downstream 

of the TAA's interaction with its receptor. 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 

http://www.research.ucla.edu/tech/ucla05-097.htm (2 of 3)10/21/2005 8:23:32 AM 


Lead Inventor: Robert Reiter





keywords: research tool uclancd ucla technologies intellectual property patents technology transfer invention business card 


POLYPHENOLIC COMPOUNDS INHIBIT PANCREATIC CANCER 



BACKGROUND: While considerable progress has been made towards the diagnosis and treatment of 

a plethora of cancers, very few inroads have been made with respect to pancreatic cancer. As the 5th 

leading cause of cancer-related deaths in the U.S. it is among the most devastating. Indeed, pancreatic 

cancer is difficult to diagnose, is largely untreatable and is highly metastatic. Thus the need for sufficient 

technology with which to combat the disease is self-evident. Unfortunately current clinical protocols for 

the diagnosis and treatment of pancreatic cancer have been met with little, if any, success. 

INNOVATION: Researchers at UCLA have identified a novel approach for the treatment of 

pancreatic cancer by down-regulating cellular survival factors while concomitantly inducing apoptosis 

(cell death). The simultaneous administration of plant-derived polyphenolic compounds with inhibitors 

of reactive oxygen species (ROS) was found to act synergistically to inhibit pancreatic cancer growth 

and tumor metastasis. Interestingly, one particular polyphenol, rottlerin, exhibited increased potency 

without the need for ROS-inhibitors. In vivo studies in mice using polyphenols revealed that pancreatic 

cancer cells selectively underwent apoptosis while non-diseased tissue was unaffected. Experimental 

evidence has revealed NF-kB, PI 3-kinase and ROS-generators as cell survival targets that are attenuated 

in this approach. In contrast, the mitochondrial permeability transition pore and caspases have been 

identified as molecular targets that are responsible for triggering apoptosis. This discovery can 

potentially be used for the treatment of other cancers, as well as for sensitizing refractory tumors to 

chemotherapeutic and/or radiation therapies. 

ADVANTAGES 

● A combination of polyphenols and ROS inhibitors dramatically reduces tumor size and inhibits 

tumor metastasis in a pancreatic cancer mouse model. 

● The polyphenol rottlerin is effective without added ROS inhibitors. 

● Non-diseased tissue is unaffected in in vivo studies in mice. 

● There is no immunological response since cells die via apoptosis. 

● There is no apparent toxicity. 

APPLICATIONS 

● Potential treatment for pancreatic cancer. 

● Potential to sensitize refractory cancer cells to other treatments. 

● May be applicable to other cancers. 

● Possible utility as a preventative for pancreatic cancer. 




● Mouria M, Gukovskaya AS, Jung Y, Buechler P, Hines OJ, Reber HA, Pandol SJ. Foodderived 

polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome 

C release and apoptosis. Int J Cancer. 2002 Apr 10;98(5):761-9 [more...] 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Stephen Pandol 




keywords: therapuetics antioxidant uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


POST-TRANSLATIONAL MODIFIED HISTONES AS BIOMARKERS, S...LY DEMONSTRATED IN A STUDY OF PROSTATE CANCER TISSUES 

POST-TRANSLATIONAL MODIFIED HISTONES AS BIOMARKERS, 

SUCCESSFULLY DEMONSTRATED IN A STUDY OF PROSTATE CANCER TISSUES 


BACKGROUND: Prostate cancer is the most common malignancy and the second leading cause of 

cancer-related death in American men. Since prostate cancer is a biologically and clinically 

heterogeneous disease, a majority of men with this malignancy harbor slow-growing tumors that may 

not impact an individual's natural lifespan, while others are struck by rapidly progressive, metastatic 

tumors. Screening for prostate cancer with prostate specific antigen (PSA) is limited by the test's lack of 

specificity and its inability to predict which patients are at risk to develop advance disease. This leads to 

a number of patients being subjected unnecessarily to invasive diagnostic procedures or surgical 

procedures, which have economical and quality of life consequences. New markers that correlate with 

clinical outcome or identify patients with potentially aggressive disease can dramatically improve the 

diagnosis and management of prostate cancer. 

INNOVATION: Kurdistani et al at UCLA are studying the use of specific forms of post-translational 

modifications of histones as tumor associated antigens for prognostic and diagnostic applications. This 

novel methodology, which is distinctive from looking at individual promoters, looks at specific modified 

histones across the entire chromatin structure, including promoter, non-promoter, and coding regions. 

This "global histone modification" method is successfully demonstrated in a proof-of-principle study in 

prostate cancer tissues. In a study performed on 183 primary prostate cancer tissue samples, Kurdistani 

et al correlated histone modification patterns with clinical outcome. They identified two disease 

subtypes with distinct and statistically significant risks of tumour recurrence in patients with low-grade 

(Gleason score less than 7) prostate cancer. These histone modification patterns were predictors of 

outcome independently of tumour stage, preoperative prostate-specific antigen levels, and capsule 

invasion. In the study, the researcher used highly specific antibodies to detect acetylated and 

dimethylation of five residues in histones H3 and H4. Specifically, they used antibodies against 

acetylated lysine 9 of histone H3, acetylated lysine 18 of histone H3, acetylated lysine 12 of histone H4, 

dimethylated lysine 4 of histone H3, and symmetric dimethylation of arginine 3 of histone H4. Of note, 

the above finding by Kurdistani et al has been validated on an independent set of samples that were 

obtained from patients at a different institution. 

POTENTIAL APPLICATIONS: 

1. Patterns of histone modifications of histones H3 and H4 may be used as prognostic markers for 

prostate cancer (with potential application to other cancer types). 

ADVANTAGES: 



1. The specific antibodies used for the detection of histone H3 and H4 in the prostate cancer 

study are readily available via commercial vendors and an extensive set of antibodies to other 

probe histone modifications are also available; 

2. The test looks at global histone modifications so histones over large regions of the chromatin 

structure are detected, thereby amplifying their signals; 

3. The test uses immunohistochemistry as the detection platform; immunohistochemical analysis 

has become a standard procedure available in most clinical laboratories and is a widely-accepted 

procedure to practicing oncologists; 

4. Patterns of histone modifications may be expanded to other types of cancers where 

immunohistochemistry is a standard practice for diagnosis. 

DEVELOPMENT-TO-DATE: The prognostic power of histone modifications H3 and H4 in prostate 

cancer had been validated in an additional independent set of 39 patient samples with low - grade 

prostate cancer. The researchers are planning to perform the necessary studies to develop this invention 

for commercial clinical use. They will also be applying this approach to other cancer types. 

RELATED PAPERS (Selected): 

● Global Histone Modification Patterns Predict Risk of Prostate Cancer Recurrence (in 

press) 



invention, 





Angeles 


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Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Siavash K. Kurdistani 








NOVEL PROSTATE SPECIFIC MEMBRANE ANTIGEN-BASED PROSTATE CANCER THERAPY 

NOVEL PROSTATE SPECIFIC MEMBRANE ANTIGEN-BASED PROSTATE 



BACKGROUND: Prostate cancer accounted for over 30,000 deaths in 2004, and 230,000 new cases 

are detected a year in the United States alone. Prostate specific membrane antigen (PSMA), which is 

highly expressed in prostate cancer cells versus normal prostate tissue, has been an attractive marker for 

the development of PSMA-targeted prostate cancer therapeutics and diagnostics. Monoclonal antibodies 

against PSMA have shown high affinity and specificity for prostate cancer cells in vitro and in mouse 

models. However, results have indicated that there are delivery problems with immunotherapy and that 

new approaches will be necessary to optimize the selective recognition of prostate cancer cells. 

INNOVATION: UCLA investigators generated a novel, non-antibody method of detecting PSMA and 

PSMA-expressing cells. This molecule is considerably smaller than currently available anti-PSMA 

antibodies and may not be subject to delivery problems associated with conventional antibodies. 

Additionally, this molecule could overcome the toxic side effects associated with antibody-based 

immunotherapy. The success of the PSMA-specific molecule in binding to PSMA suggests that related, 

even smaller, molecules could be developed that would retain their specificity for PSMA. 

APPLICATIONS: The PSMA-specific molecule could be utilized as a targeting domain to deliver 

reporter nanoparticles, such as luciferase, for use in prostate cancer diagnosis. Additionally, toxins and 

radioisotopes could be conjugated the PSMA-specific molecule to generate highly-specific anti-prostate 

cancer therapeutics. 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 



Lead Inventor: Ayyappan Rajasekaran

NOVEL PROSTATE SPECIFIC MEMBRANE ANTIGEN-BASED PROSTATE CANCER THERAPY 

edu 





keywords: therapeutics uclancd ucla technologies intellectual property patents technology transfer invention business card 


EFFICIENCY OF ANTI-PSMA ANTIBODIES 



BACKGROUND: Over 200,000 new cases of prostate cancer are reported a year in the US alone. 

Prostate specific membrane antigen (PSMA) has been identified as a valuable biomarker for prostate 

cancer cells and is associated with cells from high-grade tumors and metastases and not normal prostate 

tissue. Antibodies against PSMA have shown high specificity for prostate cancer cells in vitro and have 

reduced prostate tumor size in mouse models. Human versions of anti-PSMA antibodies have also been 

developed and are currently undergoing clinical trials. 

Due to problems with delivery of anti-PSMA antibodies to PSMA-expressing tissue, however, the 

therapeutic value of such antibodies will be limited. An approach that alleviates this problem of 

availability will be necessary to realize the full potential of anti-PSMA antibodies in treating prostate 

cancer. 

INNOVATION: UCLA researchers have developed a novel method for altering the sub-cellular 

trafficking of PSMA in prostate cancer cells. The implementation of these methods results in increased 

levels of PSMA antigen available to be bound by anti-PSMA antibodies. 

APPLICATIONS: The effectiveness of antibody therapy against PSMA could be dramatically 

improved utilizing this technology. Additionally, with human trials underway, the addition of this new 

technology should greatly improve prostate cancer patient outcome. 

UCLA researchers are also currently exploring the use of this method to improve the efficacy of certain 

other immunological-based cancer therapies. 

REFERENCE: UCLA Case No. 2004-435 




invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Ayyappan Rajasekaran 




keywords: uclancd ucla technologies intellectual property patents technology transfer invention business card 


SIMPLIFIED METHOD FOR PRODUCING A PANEL ARRAY OF BIOM...TECTION, PROGNOSIS AND PREDICTION OF MULTIPLE CANCERS 

SIMPLIFIED METHOD FOR PRODUCING A PANEL ARRAY OF BIOMARKERS 

FOR DETECTION, PROGNOSIS AND PREDICTION OF MULTIPLE CANCERS 


BACKGROUND: Detection of serum-derived antibodies against microbial antigens is routinely used 

for the diagnosis and prognosis of some infectious diseases. In the past 10 years, strong evidence has 

emerged to support the theory that the human immune system also mounts spontaneous humoral 

responses against autologous tumor-associated antigens (TAA). Up to now, there are at least 1800 TAA 

identified based on recognition by antibodies present in patients' sera. These TAA include targets from 

many cancer types, such as melanoma, renal cancer, Hodgkin's disease, esophageal cancer, lung cancer, 

colon cancer, gastric cancer, breast cancer, prostate cancer and so on. 

The discovery of these TAA awakens the old hope of finding serological markers for cancer detection, 

diagnosis and prognosis. However, the development of a sensitive, cost effective and comprehensive 

cancer diagnostic based on serological profiles to TAA has been limited by practical problems. For 

example, most of the antigens react with few - or no -- allogeneic sera. This indicates that an effective 

diagnostic for a given cancer must test for the presence of antibodies to a large number of TAA 

associated with that cancer. Such a test would require the recombinant production and purification of 

multiple TAA proteins, which is expensive and difficult to achieve. Multiplying these problems by each 

cancer for which a screen is desired makes developing a comprehensive test unfeasible. 

What is needed is a platform solution that enables the sensitive detection of serum antibodies to multiple 

TAA for multiple cancers. 

INNOVATION: The present invention enables the creation of a new product for the detection, 

prognosis and prediction of multiple cancers based on the simultaneous detection of serum antibodies to 

multiple TAA. The method bypasses the expensive and difficult requirement for purification of 

individual recombinant TAA proteins by using chemically synthesized peptides of the TAA. Utilizing 

prediction software, researchers at UCLA have demonstrated that one can systematically and efficiently 

predict peptide regions on a TAA that can (1) react to antibodies in a subset of patients with a specific 

cancer, and (2) effectively distinguish a cancer patient from a negative control as accurately as the 

recombinant TAA. This approach of using peptide fragments of TAA to detect their corresponding 

antibodies in a patient's serum can be repeated with any number of TAA to create a panel array of 

synthetic peptide fragments to provide a sensitive and comprehensive test for multiple cancers. 

The researchers have proven the feasibility of the approach by using their prediction software to identify 

a peptide fragment of NY-ESO-1, a tumor associated antigen highly expressed in different types of 

cancers. NY-ESO-1-specific antibodies present in the sera of patients with melanoma, prostate cancer, 

non-small cell lung cancer, esophageal cancer, gastric cancer, and hepatocellular carcinoma reacted with 



the synthetic peptide at a frequency similar to their reaction with the recombinant protein. This proof-ofprinciple 

demonstrates the feasibility of applying the same methodology to multiple TAA to create an 

entirely new product line of synthetic TAA fragments for the routine detection, prognosis and prediction 

of multiple cancers. 

The UCLA investigators would welcome the opportunity to collaborate with an industrial partner for the 

continued identification and validation of reactive fragments to other TAA. The UCLA researchers can 

bring to this collaboration two valuable assets: Know-how in identifying peptide fragments for use in 

serological detection of cancer; and access to clinical samples and clinical data in different cancer 

indications. 

APPLICATIONS: The approach described above may be used to create an entirely new product line 

of a library of synthetic TAA fragments. The fragments may be combined and sold as appropriate in 

panels for the routine screening of multiple types of cancer by a simple serum test (requiring no more 

than half ml of serum). Further, specialized arrays may be sold for the periodic testing post-diagnosis to 

assist in the evaluation of prognosis and treatment efficacy. 

ADVANTAGES 

1. The invention provides a practical, cost-effective method for developing an entirely 

new product line that fills an unmet market need for a simple test for cancer screening, 

monitoring prognosis, and predicting progression. 

2. The test provides a platform technology to which additional TAA peptides may be 

added as they become publicly available or newly identified and validated. The sensitivity 

and specificity for a specific cancer may be increased with the addition of more TAA for 

that cancer, and the array may be diversified with the addition of markers for multiple 

cancers. 

3. The test uses synthetic peptides in lieu of purified recombinant TAA, thereby reducing 

cost and labor while increasing quality and stability of the reagents. 

4. Peptide probes in the test give increased sensitivity since the decreased number of 

binding sites on the target antigens results in lower backgrounds. In addition, the peptides 

are flexible to be coated on most solid surfaces, e.g. gold, plastic for the development of 

new detection devices. 

5. The prediction software greatly expedites the identification of the optimal fragment for 

the assay since large numbers of fragments that span the entire TAA do not need to be 

generated and tested. 

6. By assaying for the presence of serum antibodies to TAA, the patient's humoral 

response serves as a natural signal amplifier and therefore increases the sensitivity of the 



test. Further, this approach permits the non-invasive screening for TAA that are expressed 

only in tissues. 

7. The principle of looking at a serological profile to an antigen has been adopted in 

routine serological tests for infectious agents such as Hepatitis B Virus (HBV), Hepatitis 

C Virus (HCV), and HIV. Thus, it may be readily adopted for cancer screening as well. 

DEVELOPMENT-TO-DATE: The result achieved on the common antigen NY-ESO-1 serves as a 

proof-of-principle for detection of antigen fragment from a TAA and further supports antigen based 

serological detection of cancer. Because only a certain portion of the disease population mounts a 

response to a specific antigen, other TAA fragments with serological profiles related to the same cancer 

will need to be identified for the test to be sensitive. For each cancer, it is envisioned that a panel of 

TAA will be required to accurately identify all individuals that have that cancer. Furthermore, it is 

believed that several cancers can be detected simultaneously by having antigenic peptide fragments that 

correspond to the different cancers on the same array. 

At this stage, the researchers are focusing on targets clinically relevant for prostate cancer, renal cancer, 

and non-small cell lung cancer. However, the study may be expanded to other forms of cancers as access 

to appropriate clinical samples is arranged. 



invention, 





Angeles 


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Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Gang Zeng 






keywords: diagnostic research tool uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


TRANSGENIC MOUSE WITH PROSTATE-SPECIFIC EXPRESSION OF A REPORTER GENE 

TRANSGENIC MOUSE WITH PROSTATE-SPECIFIC EXPRESSION OF A 

REPORTER GENE 


BACKGROUND: Prostate cancer is the second leading cause of cancer deaths among men in the 

United States. Current treatments include surgery, radiation and anti-androgen therapy, although each 

option carries with it undesirable side-effects. Development of new pharmaceuticals with which to treat 

the disease relies on animal models that allow investigators to see easily the effects of a drug on the 

prostate. Current prostate cancer animal models require sacrificing the animal before the 

pharmacological effects of a drug can be observed. This makes following a drug at multiple time points 

tedious and expensive. While the use of cell lines simplifies assaying a drug's potency, it does not 

provide in situ information. Thus the development of an animal model that would allow one to assay 

with ease the effectiveness of lead compounds could greatly accelerate development. 

INNOVATION: Scientists at UCLA have developed a transgenic mouse that allows for the direct 

imaging of the mouse prostate without invasive surgery. By placing a reporter gene under the control of 

an androgen-specific promoter the transgenic mouse over-expresses the reporter gene specifically in the 

prostate of the mouse. Thus reporter levels serve as an in situ indicator of androgen-mediated activation 

of the AR. Detection of the reporter is achieved through the use of commercially available devices. 

These mice can also be crossed with the c-Myc mouse model of prostate cancer (UC case No. 2002- 

135), allowing scientists to follow the progression of prostate cancer. This powerful tool can be used to 

test for pharmacological inhibitors of the androgen receptor as well as the progression of prostate cancer. 

ADVANTAGES 

● The activity of the androgen receptor can be easily quantified. 

● Changes in the reporter signal can be easily measured in situ. 

● The reporter signal can be measured multiple times over a 24-48 hour period without sacrificing 

the animal. 

● The transgenic mouse can be crossed with other transgenic mouse models. 

● The reporter signal can be measured in real-time. 

● The prostate-specific transgenic mice are more functional than reporter-expressing cell lines. 


● Pharmacological inhibitors of AR can be screened using the transgenic mouse and the effects of 

the drugs can be efficiently quantified. 

● The prostate-specific transgenic mice can be crossed with c-Myc transgenic mice to follow 

prostate cancer progression in real-time and in situ. 


TRANSGENIC MOUSE WITH PROSTATE-SPECIFIC EXPRESSION OF A REPORTER GENE 



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Angeles 


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Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 






keywords: research tools uclancd ucla technologies intellectual property patents technology transfer invention business 

card 


C-MYC TRANSGENIC MOUSE 

C-MYC TRANSGENIC MOUSE 


UCLA Researchers have developed a novel mouse model for prostate cancer which will be useful for 

preclinical trials and biochemical assays. The mouse model is unique in that it incorporates a naturally 

occuring oncogene implicated in a significant fraction of human prostate cancer and accurately reflects 

the gradual progression of human prostate cancer from prostatic intraepithelial neoplasia (PIN) to 

localized adenocarcinoma, to locally invasive disease and metastatis, with essentially 100% penetrance. 

The time course of disease progression allows therapeutic testing against all stages of disease, including 

prevention strategies. The model offers significant advantages over current transgenic prostate cancer 

models such as TRAMP, which require expression of the SV40 T antigen and generate mice with a large 

percentage of neuroendocrine, rather than adenocarcinomas of the prostate. 



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card 

http://www.research.ucla.edu/tech/ucla02-135.htm10/21/2005 8:23:34 AM

NOVEL PROGNOSTIC FACTOR AND THERAPEUTIC TARGET IN HUMAN RENAL CELL CARCINOMA 

NOVEL PROGNOSTIC FACTOR AND THERAPEUTIC TARGET IN HUMAN 

RENAL CELL CARCINOMA 


BACKGROUND: Renal cell carcinoma (RCC) is a form of kidney cancer that involves malignant 

transformation of cells of the renal tube. It is the most common type of kidney cancer in adults. In the 

United States more than 32,000 new cases of RCC are diagnosed every year, and approximately 12,000 

people die from the disease annually. 

RCC metastasizes easily, often spreading to the lungs and other organs. In cases where metastatic 

disease is not yet present at time of diagnosis, the five-year survival rate for RCC patients is 

approximately sixty to seventy-five percent (60-75%). However, metastasis is already present at 

diagnosis in approximately one-third of RCC cases. In cases where the tumor has metastasized to the 

lymph nodes, the five-year survival rate is reduced to five to fifteen percent (5-15%). In cases where the 

cancer has spread to other organs, the five-year survival rate is less than five percent (5%). 

RCC responds poorly to chemotherapy and radiation therapy. Cytotoxic chemotherapy, an integral 

therapeutic component for solid and non-solid tumors, shows little or no anti-tumor activity against 

RCC. Complete eradication of RCC by chemotherapy is therefore unlikely, unless all of the cancer can 

be removed by surgery. Radiation therapy is usually unsuccessful in treating RCC and is therefore not 

commonly used. In light of the fact that chemotherapy and radiation therapy mediate their anti-tumor 

effects by inducing apoptosis, poor response of RCC to these conventional therapies has been 

hypothesized to associate with the signal transduction pathway that mediates apoptosis in RCC. 

INNOVATION: Researchers at UCLA have identified the proapoptotic protein Smac/DIABLO as a 

gene product with significant prognostic and therapeutic value for RCC. 

It has been shown that expression level, transcription regulation, and biological activity of Smac/ 

DIABLO determine in large part the pathogenesis of RCC and the response of RCC to anti-tumor 

therapies and agents, including chemotherapy, irradiation, immunotherapy, gene therapy, toxins and 

antibodies. Smac/DIABLO offers promising utility as a prognostic biomarker for RCC. 

It has been shown also that the resistance of tumor cells to apoptotic stimuli is due in part to low 

expression of Smac/DIABLO. Furthermore, upregulation of Smac/DIABLO by certain drugs is known 

to sensitize cells to apoptosis. Aside from the role of Smac/DIABLO in the regulation of apoptotic 

activity, it is posited that activation of Smac/DIABLO expression is important in reversing RCC 

resistance to chemotherapy, irradiation, and immunotherapy. 




PROGNOSTIC APPLICATIONS: Use of Smac/DIABLO as a prognostic biomarker will focus on the 

relative expression levels of Smac/DIABLO in cancerous tissue cells of the RCC patient, as compared to 

measured expression levels in autologous normal kidney tissue, or to normal expression levels of control 

tissue. Detection and quantification of Smac/DIABLO activity (i.e., protein transcription and expression) 

in cancerous tissue following biopsy or surgery may be accomplished through immunohistochemistry, 

RT-PCR, Western blot analysis, flow cytometry, and/or HPLC. Low or negative expression of Smac/ 

DIABLO will generally indicate a poor prognosis. On the other hand, poor expression will also suggest 

a choice of therapy, which either may be independent of, or may involve the use of agents to upregulate, 

Smac/DIABLO expression. 

THERAPEUTIC APPLICATIONS: Analysis of Smac/DIABLO expression will be of significant clinical 

importance in the design of therapeutic strategies. Smac/DIABLO expression can be induced by use of 

agents that sensitize cells to apoptosis (e.g., chemicals, inhibitors, biologicals, antisense RNA, gene 

transfection reagents). An alternative strategy would be to use protease inhibitors to prevent degradation 

of Smac/DIABLO. Enhanced expression or reduced degradation resulting therefrom may then cause the 

spontaneous induction of apoptosis, or may be used synergistically in combination with low-dose 

chemotherapy, radiation, or immunotherapy. 

INVENTOR: Dr. Benjamin Bonavida is a Professor in the Department of Microbiology, Immunology 

and Molecular Genetics at UCLA's David Geffen School of Medicine, and is a Member of the Tumor 

Immunology Research Group at UCLA's Jonsson Comprehensive Cancer Center. 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Benjamin Bonavida 








NEURO-ENDOVASCULAR ULTRASOUND THROMBOLYSIS 



Stroke is the most common life-threatening neurologic disease and is the leading cause of death in the 

United States, after heart disease and cancer. Among the current U.S. population, some 11 million 

people have or will have brain aneurysms, which constitute the main cause of non-traumatic 

subarachnoid hemorrhage. 

Stroke is defined as the acute brain injury resulting from compromised cerebral blood flow or rupture of 

cerebral blood vessel. Cerebral thromboembolic event occurs when blood clots occlude a branch of the 

cerebral arteries. When it is not treated in a timely fashion, stroke can cause permanent neurological 

impairments and death. 

The current method of reestablishing blood flow in the blocked arteries involves the use of either 

systemic or local intra-arterial fibrinolytic therapy. Although there are many reports of successful 

recanalizations, these methods are not ideal. 

Researchers at UCLA have developed a new method of treating stroke using ultrasonic energy. There 

are several advantages of this method over conventional fibrinolytic therapy: (1) ultrasound can 

recanalize arteries much quicker that fibrinolytic therapy, (2) ultrasound does not cause bleeding 

complications, and (3) ultrasound can be more economical that fibrinolytic therapy in itself and in 

overall hospital costs. 

Reference: UCLA Case No. 1995-593 US Patent Number: 6,024,718 


invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 



Lead Inventor: Hank Chen


edu 




keywords: therapeutics medical devices uclancd ucla technologies intellectual property patents technology transfer 

invention business card 


METHOD AND DEVICE FOR TREATING INTRACRANIAL VASCULAR ANEURYSMS 

METHOD AND DEVICE FOR TREATING INTRACRANIAL VASCULAR 

ANEURYSMS 


Strokes are the most common life-threatening neurological disease, and are the third leading cause of 

death in developed countries after heart disease and cancer. Approximately 6-8 percent of all strokes 

results from non-traumatic subarachnoid hemorrhage, a condition where blood leaks from the cerebral 

vasculature into the subarachnoid space. About 8 percent of subarachnoid hemorrhages result from 

rupture of an intracranial aneurysm. 

Ruptured intracranial aneurysms are associated with a high rate of mortality. Approximately 15% of the 

patients die soon after the initial rupture. An additional 20 to 30% of the patients die during the first 2 

weeks following the initial rupture. Rebleeding is one of the major causes of death in the patients who 

survive the initial hemorrhage. In addition to the high mortality rate associated with ruptured intracranial 

aneurysms, there is also a high morbidity rate among patients who survive the rupture long term. Almost 

two-thirds of patients well enough to be discharged home after surgical obliteration of the aneurysm 

have a residual neurological deficit. 

Inventors at UCLA have developed a device, and a method, for the therapeutic management of 

intracranial vascular aneurysms. This technology involves the use of intravascular catheters that can 

directly image the aneurysm, and can occlude the entire lumen of the aneurysm sac using liquid sealing 

agents. The intracranial catheters are designed in various configurations so that they can be used to treat 

aneurysms regardless of their neck size, and their location within the intracranial vascular system. 



invention, 





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1200 


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Lead Inventor: Tarik Massoud

METHOD AND DEVICE FOR TREATING INTRACRANIAL VASCULAR ANEURYSMS 

edu 





keywords: medical devices uspatent uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


DIAGNOSTIC TEST FOR PROLIFERATIVE SENESCENCE IN IMMUNE CELLS 



Aging is accompanied by a dramatic decline in immune functions involving both B and T cells. Clinical 

findings of increased morbidity and mortality following infections, higher incidences of cancer, and 

diminished antibody responses to specific vaccines are examples of immunologically-based medical 

problems of the elderly. However, despite a large body of research on the nature of these immunological 

deficits, there is no known mechanism that explains the progressive decline of immune competence with 

age. Nor is there a reliable biomarker to identify which subset of chronologically old individuals are at 

risk immunologically. 

Investigators at UCLA's School of Medicine have previously shown that normal human T cells, like 

fibroblasts, have a limited proliferative potential. The senescent T cells nevertheless function normally 

in antigen recognition and cytotoxicity. These investigators have now identified a biological marker that 

identifies T cells that appear normal by standard surface staining analyses, but that are incapable of 

proliferating. The marker is a known molecule detectable with a commercially available monoclonal 

antibody using flow cytometric analysis of peripheral blood mononuclear cells. The assay, which has 

been tested in the elderly, may be clinically important to identify those individuals in a seemingly 

homogeneous group that are most likely to be at risk immunologically. This subset may be targeted for 

prophylaxis, immunomodulation, or more intensive study. The assay also may be a novel diagnostic tool 

in other clinical situations of T cell immunodeficiency involving proliferative hyporesponsiveness, such 

as AIDS. 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 



Lead Inventor: Rita Effros


edu 






A KNOWLEDGE-BASED METHOD FOR INDEXING CLINICAL TRIALS 



Researchers in the UCLA Department of Computer Science have developed and reduced to practice 

algorithms for generating conceptual phrase candidates in clinical texts and identifying phrases for 

indexing. The algorithms offer more flexible and faster retrieval of medical information using free form 

queries. The algorithms extend the capabilities of the Unified Medical Language System (UMLS). The 

methods use a set of data structures to reduce the problem of searching UMLS concepts to a simple 

counting process. 

BACKGROUND: Several methods are proposed in the literature for mapping free text into terms 

controlled by the Unified Medical Language System (UMLS). However, methods such as natural 

language processing (NLP) are not appropriate for Web-based applications. Some important concepts 

cannot be discovered through the static identification using noun phrases. Also, NLP tools work offline. 

It would be preferable for a Web-based tool to have the performance to operate in real time and have the 

capability of returning more text phrases in response to queries without generating irrelevant or 

improper responses. 

INNOVATION: The algorithms proposed, collectively referred to as IndexFinder, offer a suite of 

techniques to enhance the link between free form text queries and UMLS. First, there is query expansion 

wherein the user free form query cascades into further, more general or more detailed concepts using 

word associations derived from UMLS. For example, one can query on "cancer cure" and automatically 

generate responses for "chemotherapy" or "radiation therapy". This provides substantially stronger 

queries than simple "Google" type inverted files. The researchers are able to uncover more phrases or 

concepts not obtainable from simple noun phrases without creating irrelevant or improper combinations. 

The algorithms use novel indexing structure for matching text to UMLS concept as well as novel storage 

and searching techniques. 

IndexFinder includes algorithms for data mapping (generation of concepts from in the input text), 

removal of word inflection, the substitution of synonyms and filters to remove irrelevant concepts. For 

example, there is a subset filter that removes phrases if they are subsets of other phrases. For example, if 

results are {lung cancer} and {cancer}, the {cancer} will be removed since it is a subset of the former. 

Standard semantic filters defined in UMLS that are used by IndexFinder. 

DEVELOPMENT TO DATE: Algorithms have been implemented as a web-based service in C++. 

Experiments show that IndexFinder can process 43K bytes of text per second, which makes it usable for 

real time retrieval with results superior to current techniques. 





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edu 


Lead Inventor: Wesley Chu 




keywords: bioinformatics uclancd ucla technologies intellectual property patents technology transfer invention business 

card 


VECTOR CONTAINING TISSUE-SPECIFIC RNAP II PROMOTER FOR siRNA DELIVERY 

DELIVERY 

VECTOR CONTAINING TISSUE-SPECIFIC RNAP II PROMOTER FOR siRNA 


BACKGROUND: RNA interference has become a prevalent research tool for studying gene function 

and validating putative targets. It is also being explored as an alternative gene-silencing approach for 

therapeutic applications, replacing previous gene therapy strategies. Because tissue selectivity is an 

important property for expressing a transgene in vivo, achieving this property for RNA interference is an 

important development for improving this approach. Yet until now, there is no report on siRNAmediated 

gene silencing directly from a tissue-specific RNA polymerase II promoter rather than from 

ubiquitous RNA polymerase III. 

INNOVATION: Researchers at UCLA had demonstrated that siRNA-mediated gene silencing from a 

tissue-specific promoter is feasible. The proposed delivery system or vector comprises the following 

components: a) a tissue specific promoter with modifications b) a siRNA to a candidate gene and c) a 

polyadenylation site. The researchers have demonstrated proof-of-principle using the prostate-specific 

antigen (PSA) promoter. This promoter drives the expression of siRNA to the green fluorescent protein 

(GFP) gene. 

POTENTIAL APPLICATIONS: This delivery system can be used to silence genes for therapeutic 

purposes (such as knocking out genes implicated in carcinogenesis and metastasis). The researcher's 

goal is to use the PSA-vector they created to incorporate a siRNA to a knock-down candidate such as 

PI3K for tissue-specific prostate cancer therapy. 

ADVANTAGES: 

1. The modification is a technically feasible and systematic modification to what is currently 

available; and, 

2. The approach is flexible to accommodate any silencing gene candidates. 

DEVELOPMENT-TO-DATE: The researchers demonstrated in an androgen-dependent cell that 

siRNA expressed from either vector-based or lentiviral-based systems using PSA promoter not only 

specifically reduced expression of ectopic and endogenous genes in cells, but also acted in a tissuespecific 

and hormone-dependent manner. The researchers are currently studying the effectiveness of 

siRNA-mediated gene silencing from PSA promoter in an animal system. Results from this project may 

lay the groundwork for creating a potential gene therapy approach for the treatment of prostate cancer. 


VECTOR CONTAINING TISSUE-SPECIFIC RNAP II PROMOTER FOR siRNA DELIVERY 

Related Paper 

● Cancer Res. 2004 Nov 1;64(21):7661-3. Gene silencing in androgen-responsive 

prostate cancer cells from the tissue-specific prostate-specific antigen promoter. 

Song J, Pang S, Lu Y, Yokoyama KK, Zheng JY, Chiu R. more... 



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1200 


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edu 


Lead Inventor: Robert Chiu 




keywords: research tool uclancd ucla technologies intellectual property patents technology transfer invention business card 


METHODS FOR INDUCING INTERLEUKIN-12 AND A TYPE1/TH1 T-CELL RESPONSE IN DERMATOLOGIC DISEASE 

METHODS FOR INDUCING INTERLEUKIN-12 AND A TYPE1/TH1 T-CELL 

RESPONSE IN DERMATOLOGIC DISEASE 


UCLA investigators have identified a use for bacterial lipopeptides as a potent inducer of IL-12 

production and resulting type 1/Th-1 T-cell response. The technology encompasses a broad range of 

lipoproteins of defined structure that can be administered to a subject to trigger type 1/Th1 T cell 

response required for cell-mediated immunity in the context of infection, autoimmune disease or cancer. 

For example, and of current interest, the lipoprotein may be used as a topical agent for the treatment of 

skin infections and cancer, in which Th1 responses are required for host defense. Since this lipoprotein 

activates Toll-like receptor 2, it has a novel mechanism of action. 



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Lead Inventor: Robert Modlin 






HIV Protein Moderates Telomerase 

HIV PROTEIN MODERATES TELOMERASE 


Normal somatic cells are not immortal but rather reach a state of replicative senescence whereby they no 

longer divide. As they age, the terminal DNA repeats of their chromosomes become shorter with every 

cellular division, a phenomenon known as telomere shortening. Research has suggested that this 

reduction in DNA could result from a loss of telomerase activity, which catalyzes telomere elongation in 

normal aging cells. Conversely, immortal cells do not experience telomere shortening and retain high 

telomerase activity. Such cancer and germline cells therefore have the potential to proliferate 

indefinitely. Hence, the ability to modulate telomerase activity would have enormous applications in cell 

proliferation. 

Recent telomere length studies at UCLA have shown that CD4+ and CD8+ T lymphocytes extracted 

from HIV-1 infected individuals exhibited diverging patterns of telomere shortening. CD4+ T cells did 

not exhibit telomere shortening and retained high telomerase activity whereas CD8+ T cells showed 

telomere lengths as short as those found in T cells that reach replicative senescence. These results are 

difficult to reconcile with reports of high T cell turnover in HIV-1 infected individuals but suggest that 

the virus may have evolved a mechanism to influence telomerase dynamics. 

Given that specific proteins of HIV-1 have transcriptional influence, UCLA scientists began to study 

their effects on telomerase dynamics. What they found was that the addition of a highly purified HIV-1 

protein to uninfected lymphocytes resulted in the same diverging patterns of telomere shortening as they 

had observed in the lymphocytes from HIV-1 infected patients. The results indicate that a specific HIV- 

1 protein and not another component, independently modulates telomerase activity. To determine 

whether this protein had any effect on transformed cells, various tumor cells were exposed to the 

purified protein. Again, they obtained the same diverging patterns, for which the up-regulation of 

telomerase may account for the increased incidence of neoplasia associated with HIV-1 disease and the 

down-regulated effects may be of therapeutic significance. Moreover, the acceleration of tumor 

development from exposure to the protein suggests that HIV-1 may potentially be an oncogenic virus. 

Elucidation of the mechanistic basis of the relationship between this protein and telomerase may yield 

information on the poorly understood genetic control of telomerase induction, an area that is of 

significant relevance to cancer, immunotherapy, and stem cell expansion. 



HIV Protein Moderates Telomerase 


invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 

Lead Inventor: Rita Effros 






TARGETING LENTIVIRAL VECTORS TO SPECIFIC CELLS AND TISSUES 



BACKGROUND: Current gene therapy strategies are hindered by the inability to target genes to 

specific cell types. 

INNOVATION: Noted UCLA AIDS Professor and Director of UCLA's AIDS Institute Irvin Chen has 

developed a strategy to target lentiviral vectors and infect specific human cell types efficiently. Previous 

reports of cell targeting exist which use murine retroviruses, but titers have been low and specificity of 

targeting has been inefficient. This novel strategy can be used to target any cell for which there is a 

specific cell surface molecule. 

DEVELOPMENT TO DATE: We have validated this approach to target specific human immune cells 

as well as certain types of cancer cells. The approach has also been validated using a mouse model for 

prostate cancer. Ongoing modifications made to the vector further enhance the specificity of targeting 

and increase the titer of the vectors. These vectors should be useful in any human disease where 

targeting of specific cell types by gene therapy vectors would have therapeutic value. 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Irvin Chen 








USE OF SECONDARY LYMPHOID ORGAN CHEMOKINE TO INDUCE...EDIATED IMMUNE RESPONSE AND INHIBITING ANGIOGENESIS 

USE OF SECONDARY LYMPHOID ORGAN CHEMOKINE TO INDUCE ANTI- 

TUMOR RESPONSE BY STIMULATING CELL-MEDIATED IMMUNE RESPONSE AND 

INHIBITING ANGIOGENESIS 


BACKGROUND: Chemokines are a group of homologous yet functionally divergent proteins that 

mediate leukocyte migration and activation and play a role in regulating angiogenesis. Secondary 

lymphoid organ chemokine (SLC, also referred to as Exodus-2 or 6Ckine) is a chemokine expressed by 

high endothelial venules in T-cell zones of spleen and lymph nodes. It strongly attracts naïve T-cells and 

mature dendritic cells to the initial site of immune activation. 

INNOVATION: The present invention exploits the chemoattracting activity of SLC in co-localizing T 

lymphocytes and dendritic cells to potently enhance cell-mediated immunity against tumor cells and also 

takes advantage of SLC's anti-angiogenic activities. Using recombinant SLC, UCLA Researchers have 

demonstrated, in in vitro and in vivo models, that SLC mediates T cell-dependent anti-tumor responses. 

ADVANTAGES 

1. SLC has demonstrated both anti-angiogenic activities in addition to its ability to reduce tumor 

burden; and, 

2. SLC has many applications and therefore can be implemented into different immunotherapy 

strategies. 

APPLICATIONS 

1. Recombinant human SLC may be administered alone via intra-tumor or intra-lymph node 

injection; 

2. SLC may be used as an adjuvant protein in enhancing anti-tumor activities in other therapeutic 

vaccines; 

3. SLC may expressed by dendritic cells in addition to tumor antigens in dendritic cell therapy; 

and, 

4. SLC gene may be delivered into tumor cells alone or together with other immuno-stimulator 

genes (GM-CSF, IL-2). 

DEVELOPMENT TO DATE: Intratumoral injection of recombinant SLC in mice leads to colocalization 

of both DC and T lymphocytes within tumor nodules and T cell dependent tumor rejection. 

Studies of SLC injected in the axillary lymph node region in the spontaneous lung cancer model leads to 

generation of systemic antitumor responses. Subsequent studies indicated that the antitumor properties 

of SLC are due to both its chemotatctic capacity in co-localizating DCs and T cells and its induction of 

key cytokines involved in cell-mediated responses. 


USE OF SECONDARY LYMPHOID ORGAN CHEMOKINE TO INDUCE...EDIATED IMMUNE RESPONSE AND INHIBITING ANGIOGENESIS 


● Secondary lymphoid tissue chemokine mediates T cell dependent anti-tumor responses 

in-vivo. J. Immunol 2000, 164: 4558-4563 more... 

● SLC/CCL21-mediated anti-tumor responses require IFNgamma, MIG/CXCL9 and IP- 

10/CXCL10. Mol Cancer. 2003 Apr 15;2(1):22. more... 

● Secondary lymphoid organ chemokine reduces pulmonary tumor burden in 

spontaneous murine bronchoalveolar cell carcinoma. Cancer Res. 2001 Sep 1;61 

(17):6406-12. more... 

Reference: UCLA Case No. 2001-381 US Published Pat. Application: 

20030175801 A1 


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Angeles 


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794-0638 


edu 


Lead Inventor: Steve M. Dubinett 




keywords: therapeutics cancer vaccine immunotherapy immunotherapeutic immunomodulation uclancd ucla technologies 

intellectual property patents technology transfer invention business card 


GENOMIC SCREENING WITH A CHEMICAL NUCLEASE 



Scientists at UCLA have developed a method that allows for screening of genetic variability within a 

PCR amplified locus. 

By following a proprietary protocol, scientists will now be able to locate mutations within genes for a 

variety of scenarios: for detecting sequence changes of HIV mutants which generate drug resistance and 

for detecting sequence changes of genes in relation to cancer development. 

Methods presently in use include cleavage of RNA-DNA hybrids at mutation sites using RNase A, 

reaction at mismatched sites using hydroxylamine or osmium tetroxide, and various electrophoretic 

techniques which can separate different DNA's based on intrastrand base pairing or mismatched 

duplexes. UCLA's procedure is superior to methods currently on the market because it does not require 

great skill, is applicable to all nucleic acid bases, does not require toxic reagents, and unlike its 

competitors, not only identifies the existance of a mutation, but its location as well. 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 

Lead Inventor: David Sigman 






keywords: research technologies uclancd ucla technologies intellectual property patents technology transfer invention 

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GM-CSF AND IL-4 THERAPY FOR THE IN-SITU EXPANSION OF ...RITIC CELLS AND ENHANCEMENT OF VACCINE-BASED IMMUNITY 

GM-CSF AND IL-4 THERAPY FOR THE IN-SITU EXPANSION OF DENDRITIC 

CELLS AND ENHANCEMENT OF VACCINE-BASED IMMUNITY 


Dendritic cells (DC) are a group of professional antigen presenting cells (APC) that provide a central 

stimulus for the generation of cell-mediated responses against foreign antigens. Dendritic cells are 

ubiquitously distributed throughout the body, where they pick up antigens, process them, and migrate to 

T-cell enriched areas of lymphoid tissue to activate corresponding antigen-specific T-cell clones.1 A 

major limitation in the human response to foreign challenges, including infections and tumors, is the 

limited number of DC and their suppression in individuals suffering from these conditions. As a result, 

patients often fail to respond to vaccines that might otherwise be effective. 

Previous in vitro data indicated that granulocyte-macrophage-colony stimulating factor (GM-CSF) and 

interleukin-4 (IL-4), when used in combination, induce precursor cells, such as CD34+ stem cells and 

monocytes, to mature into "dendritic cells." These cells were classified as DC by their expression of cell 

surface markers characteristic of DC cells (CD83, CD40, CD86, CD11c, etc.), by their ability to take-up 

and process antigens, and by their ability to stimulate the proliferation of T cells in an antigen-specific 

manner. The strategy of using GM-CSF AND IL-4 to enhance the number and/or function of antigen 

presenting cells (including dendritic cells) in the blood, tissues and lymphoid organs of patients may be 

employed as a mechanism to improve the immune responses of individuals with a suppressed immunity. 

Therefore, this method has implications in treating conditions such as cancer, infections, AIDS, 

malnutrition and shock. Cytokine therapy using GM-CSF and IL-4 may further be implemented into 

immunization and vaccination strategies for infections that respond poorly to conventional vaccine 

approaches. Examples of these indications include AIDS, pneumonia, and tuberculosis. 

This cytokine combination therapy produced promising tumor responses in Phase I testing and is 

currently being tested in Phase II studies in patients with prostate cancer. Additional preclinical testing is 

ongoing to optimize combination therapy with vaccines, to better evaluate the form and function of the 

dendritic cells generated, and to evaluate the use of combination cytokine therapy as a mechanism for 

harvesting DC for use in the production of cell-based vaccines. 


GM-CSF AND IL-4 THERAPY FOR THE IN-SITU EXPANSION OF ...RITIC CELLS AND ENHANCEMENT OF VACCINE-BASED IMMUNITY 


● Granulocyte Macrophage Colony-stimulating Factor and Interleukin 4 Enhance the 

number and Antigen-presenting Activity of Circulating CD14+ and CD83+ Cells in 

Cancer Patients. . Cancer Research, 60: 1934-1941, 2000. more... 

● Increased Dendritic Cell Number and Function Following Continuous in vivo Infusion 

of GM-CSF and IL-4. Blood, 99(8):2869-2879. 2002 more... 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Michael Roth 






A MXXXL MOTIF CONFERING ENDOCYTOSIS OF BIOMOLECULES 



BACKGROUND: Endocytosis is an essential process in living cells that ensures proper regulation of 

the surface expression of membrane receptors and enzymes. This process is generally regulated by 

specific sequence motif in the cytoplasmic tail of internalizing proteins. The two major internalization 

motifs reported are tyrosine-based and di-leucine-based signals. 

Prostate specific membrane antigen (PSMA), a potential therapeutic target and diagnostic marker, has 

been the subject of immense investigation due to its selective expression in human prostate cancer cells. 

Furthermore, PSMA over-expression is implicated in high-trade cancers and solid tumor formation. 

INNOVATION: Like other membrane spanning proteins, PSMA expression is regulated by 

endocytosis. In studying the mechanism of internalization of PSMA, Rajasekaran et al reported that 

PSMA is internalized via a clathrin-dependent endocytic mechanism. This internalization is mediated by 

a cytoplasmic motif on PSMA having the sequence MXXXL. This motif can further be transferred to a 

non-internalizing protein TAC, which is the alpha-chain of interleukin 2-receptor. This signal peptide 

can therefore be used for conferring endocytosis of biomolecules. 

APPLICATIONS: 

1. Research use for: 

a. Understanding internalization of protein of interest; 

b. Deciphering the presence of autonomous internalization motif 

2. Targeting of therapeutic molecules (proteins, pharmaceuticals, antibodies) into the cell. 

DEVELOPMENT: UCLA researchers observed that the signal motif is required for PSMA 

internalization. Mutagenesis of N-terminal amino acid residues showed that position 1and 5 of the signal 

are required. The Tac-MXXXL fusion protein was shown to internalize like wild-type PSMA and is 

targeted to the recycling endosomal compartment. 




● A novel cytoplasmic tail MXXXL motif mediates the internalization of prostatespecific 

membrane antigen. Mol Biol Cell. 2003 Dec;14(12):4835-45. Epub 2003 Oct 

03. more... 



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794-0638 


edu 


Lead Inventor: Ayyappan K. Rajasekaran 




keywords: therapeutics diagnostics uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


A NOVEL SYSTEM FOR MEASURING PROTEASE ACTIVITY 



BACKGROUND: Proteases or enzymes with proteolytic activity are fundamental to many key 

biological processes such as cell growth, cell death, blood clotting, matrix remodeling and immune 

defense. A large number of pathogens, including viruses, bacteria and multi-cellular parasites also use 

proteases to infect host cells, complete their life cycle and degrade the host immune system. Proteases 

have also been found to play a role in the pathogenesis of hypertension, liver cirrhosis, Alzheimer's 

disease, autoimmune diseases, rheumatoid- or osteoarthritis and cancer. 

There is considerable effort to understand the role of proteases in disease and to identify therapeutic 

agents targeting specific protease activities. A bottleneck for high throughput drug screening, however, 

is now at the level of bioassays. Many compounds initially identified using in vitro assays fail in later 

phases of drug development because they cannot be used in a biologically relevant environment. 

Therefore, drug discovery researchers are now aggressively looking for high-throughput in vivo assays 

using cells, or, ideally, whole organisms, to screen potential drugs. 

What are needed are efficient bioassays to (1) determine the role of proteases in normal and diseased 

cellular processes and (2) screen in biologically meaningful systems for pharmacologic modulators of 

proteases of interest. 

INNOVATION: The present invention provides a novel way to detect virtually any protease activity 

in cell cultures and in whole organisms. It can be used to screen for drugs or genes modulating a specific 

proteolytic activity. The system is based on DNA constructs, such as plasmids. It uses modular 

components, which makes it highly flexible. The system can be designed to detect any protease of 

interest. The DNA expression system can be delivered to cultured cells or used to generate transgenic 

organisms such as mice or zebrafish. Protease activity is directly related to a built-in reporter molecule. 

APPLICATIONS 

The invention may be used: 

● as an efficient bioassay to determine the role of proteases in both normal and diseased cellular 

processes in biologically relevant environments; 

● to screen for pharmacologic modulators of proteases. 

ADVANTAGES 



1. The system is highly flexible. It can: 

● be designed to detect virtually any protease activity of interest; 

● be designed to target proteases located in membranes or vesicles; and 

● accommodate any measurable reporter protein. 

2. The system can be used to observe proteolytic activity in vitro and in vivo in both healthy cells and 

diseased cells. 

3. The system appears to work in a wide range of cell-types. 

4. The system can be used to generate transgenic animals to permit study of proteases of interest in 

whole organisms. 

5. The system works in transgenic organisms such as zebrafish, a vertebrate model that allows genetic 

screening and in vivo studies. With its rapid development and transparent embryo, zebrafish are 

amenable to large-scale genetic screens in 96-well plates. Thus, high throughput drug screening for 

proteases modulators is possible in an intact vertebrate animal model using this invention. 

DEVELOPMENT-TO-DATE: The protease bioassay was tested by making a construct that detects 

caspase-3 activity. Caspace-3 is activated when a cell starts executing the cell death (apoptosis) 

program. The DNA construct was microinjected in one-cell-stage zebrafish embryos to generate 

transgenic fish in which apoptotic cells expressed a reporter protein (red fluorescent protein DsRed 

Express, in this case). Caspase-3 activity was detected in a wide variety of cells. Further, the proteolytic 

activity was inhibited by the addition of a caspase-3 inhibitor to the liquid medium containing the fish. 

These results confirmed the ability of the new protease bioassay system to function in a wide range of 

cell types in a vertebrate animal model, and to allow rapid, simple detection of pharmacologic 

modulation of the protease of interest. 





invention, 





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Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Arnaud Lacoste 




keywords: diagnostic uclancd ucla technologies intellectual property patents technology transfer invention business card 


A Transcriptionally-Regulated G Protein-Coupled Receptor Blocks Cells in G2/M 

A TRANSCRIPTIONALLY-REGULATED G PROTEIN-COUPLED RECEPTOR 

BLOCKS CELLS IN G2/M 


DNA checkpoints are integral components in regulating the growth of eukaryotic cells and are 

dependant on a variety of post-transcriptional and transcriptional modifications. Oncogenic 

transformation upstream in the cell cycle signaling pathway often leads to loss of cellular growth control 

and the induction of malignant potentials. Scientists at UCLA have isolated and sequenced a cell-cycle 

regulator, found to show homology with the G-Protein Coupled Receptor Superfamily. Activation of this 

regulator resulted in an arrest in the fundamental G2/Mitosis transistion, thus the protein is called G2A 

Receptor. The receptor is specifically expressed in T and B lymphocytes. Expression of G2A has been 

shown to inhibit the oncogenic potential of other genes by blocking the G2/M transition in a manner 

independent of known oncogenes, p53 and c-Abl suggesting utility in the realm of cancer therapy as 

well as for autoimmune diseases. 

Utilizing receptor activity assays, these scientists have further identified compounds that can activate or 

inhibit the cell signaling pathways of the G2A Receptor. A broad class of compounds activate or induce 

the gene providing the ability to potentiate conventional anti-mitotic therapy. The gene sequence, 

antibody and knock-out mouse model currently exist enabling the screening of potential drug candidates 

and known anti-mitotic compounds. This invention could allow known compounds used for autoimmune 

diseases, graft rejection or for various types of cancer to be used in the future at lower doses and with 

improved efficacy. 


● Immunity 2001 May;14(5):561-71. Mice lacking the orphan G protein-coupled 

receptor G2A develop a late-onset autoimmune syndrome. more... 

Reference: UCLA Case No. 1997-538 US Patent Numbers: 

6,709,830 

6,514,696 | 6,383,760 

6,214,562 | 6,207,412 


A Transcriptionally-Regulated G Protein-Coupled Receptor Blocks Cells in G2/M 


invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Owen Witte 






A FELINE BRONCHIOLOALVEOLAR LUNG CARCINOMA (BAC) X...FOR THE STUDY OF COMMON ANIMAL AND HUMAN PATHOGENS 

A FELINE BRONCHIOLOALVEOLAR LUNG CARCINOMA (BAC) 

XENOGRAFT AND CELL LINE FOR THE STUDY OF COMMON ANIMAL AND HUMAN 

PATHOGENS 


The clinicalpathology of tumor formation in animals share common properties with that of their human 

counterparts. As a result of this relationship, the disease associated molecular alterations in one species 

may provide insight into the tumorigenesis of that in another. Bronchioloalveolar carcinoma (BAC) is a 

form of lung cancer that is found in humans and animals and whose etiology and pathogenesis is 

controversial. Unlike many human lung cancers, BAC is most likely not associated with mainstream 

tobacco smoking or second hand smoke, as is evident by its animal presence. Additionally, given that 

humans and animals are presumably not exposed to the same exogenous carcinogenic factors, BAC is 

one such disease for which its molecular alterations could be of increased significance in the etiology of 

the disease. 

To better study the molecular alterations of feline BAC, UCLA scientists established the first 

transplantable nude mice xenograft (Sparky-X) and a feline BAC cell line (Sparky). Sparky-X exhibited 

the typical alveolar carcinoma growth pattern and induced angiogenesis. RT-PCR analysis of Sparky, 

showed expression of a retroviral gag transcript that was 90% identical to those expressed by JSRV, the 

retroviral cause of sheep BAC. Additionally, RT-PCR analysis of human BAC also showed gag 

expression with 95-100% similarity to its sheep counterpart. Further genetic analysis of the p53 

oncogene in Sparky showed a G to T transversion at codon 167, a mutation most commonly associated 

with smokers. These experimental findings strongly suggest that there is an overlapping pathway of 

tumorigenesis in felines, sheep and humans that in turn may give rise to a common treatment. 

In addition to the study of BAC, Sparky and Sparky-X can also be used to study other shared diseases. 

For example, toxoplasmosis is a parasitic pathogen commonly found in cats and transmittable to 

humans. In immuno-comprimised individuals and developing fetus the disease proposes a serious 

medical threat. To date, the inability to grow the organism in culture has limited the development of a 

toxoplasmosis vaccine. However, preliminary studies have shown that Sparky allows for the 

intracellular growth of toxoplasmosis paving the way for the production of a new vaccine. 

Reference: UCLA Case No. 1999-549 PCT Publication: WO 02/096364 


A FELINE BRONCHIOLOALVEOLAR LUNG CARCINOMA (BAC) X...FOR THE STUDY OF COMMON ANIMAL AND HUMAN PATHOGENS 

For information on licensing 

this invention, 

please contact the office 

below. 

Office of Intellectual 

Property Administration 

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email: ncd@resadmin. 

ucla.edu 

Lead Inventor: Sanford Barsky 

UCLA Technology Transfer Program 




business card 


DETERMINING THE COMPONENTS OF BOTANICAL MIXTURES BY...E-STRAND CONFORMATION POLYMORPHISM ANALYSIS (SCCP) 

DETERMINING THE COMPONENTS OF BOTANICAL MIXTURES BY SINGLE- 

STRAND CONFORMATION POLYMORPHISM ANALYSIS (SCCP) 


UCLA researchers have developed a molecular method for discrimination and identification of multiple 

plant species within a botanical mixture. Laboratory results of plant mixture analyses show that Single- 

Strand Conformation Polymorphism Analysis (SCCP) (developed originally for the detection of human 

DNA mutations), when combined with plant DNA sequencing, is a simple and effective technique for 

identifying individual botanical species within mixed populations. 

BACKGROUND: Many botanicals have a long history of use and are touted as offering a variety of 

health benefits, including prevention and treatment of heart disease, cancer, stroke, and other disease 

conditions. It is estimated that more than 80 million people in the U.S. use some type of botanical 

nutritional supplement. The global market for botanical supplements exceeded $15 billion in 1999 and 

continues to grow rapidly. 

Some herbal supplements, however, are known to have caused serious health complications. Variation 

of techniques used in cultivation, harvesting, and processing of botanical materials used to prepare or 

manufacture supplements can easily impact the efficacy of the preparation, either by causing significant 

variability in the relative quantities of pharmacologically relevant substances, or by introducing 

undesirable botanical or microbial species as contaminants. 

INNOVATION: Researchers at UCLA have adapted a PCR-based technique previously used in 

identifying species for animal and microbial communities for use in identifying botanical species and 

testing for the presence of contaminants in botanical samples. The invention has been fully developed 

and tested for the detection of botanical contaminants. 

APPLICATIONS: Potential end-users of this invention include herbal manufacturers, regulatory and 

quality assurance laboratories, and validation testing services. Potential applications include: 

● Confirmation of the identity of botanical species in herbal and other plant samples; and 

● Determination of the presence of contaminating organisms in dietary supplements and other 

products comprising processed plant materials. 

ADVANTAGES: The methodology presented provides a relatively simple and inexpensive way to 

identify components and potential contaminants in botanical samples and mixtures. 

Whereas prior techniques used for authenticating botanical products (including sequencing of PCR 

products, Restriction Fragment Length Polymorphism (RFLP), Random Amplified Polymorphic DNA 


DETERMINING THE COMPONENTS OF BOTANICAL MIXTURES BY...E-STRAND CONFORMATION POLYMORPHISM ANALYSIS (SCCP) 

(RAPD), and Amplified Fragment Length Polymorphism (APLF)) focus simply on confirming the 

anticipated identity of a botanical species, application of SSCP to botanical samples enables 

differentiation of multiple plant species and the detection and identification of contaminants. 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Ann Hirsch 




keywords: plants research tools uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


RNA BINDING FLUOROCHROME: FLUORO NISSL GREEN 

RNA BINDING FLUOROCHROME: FLUORO NISSL GREEN 


An efficient chemical synthesis has been developed for a new low molecular weight compound, Fluoro 

Nissl Green, which selectively binds RNA in vitro and in vivo in the presence of DNA. The compound 

is highly fluorescent with an emission at 510 nm and it has been purified and well characterized. Unlike 

other known RNA-binding compounds, it does not significantly bind to DNA. Unlike antibodies or 

oligonucleotide sequences targeted for detection of nucleic acids, it is inexpensive to prepare, stable to 

hydrolysis and is not limited by sequence specificity. 

Potential uses for Fluoro Nissl Green and related derivatives are in the areas of cancer diagnosis 

(specifically astrocytic neoplasia), fluorescent activated cell sorting as well as RNA labeling, targeting, 

separation and quantization. 



invention, 





Angeles 


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Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 

Lead Inventor: Craig Merlic 





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REACTION OF PURINES WITH ELEMENTAL FLUORINE TO GENERATE 8-FLUOROPURINES 

REACTION OF PURINES WITH ELEMENTAL FLUORINE TO GENERATE 8- 

FLUOROPURINES 


For the first time a simple synthetic method to produce 8-fluoropurines has been developed at UCLA. 

Although there has been successful halogenation of the 8-position of purines with bromine, chlorine and 

iodine, electrophilic flourination of purines with elemental flourine are not known. As a result, access to 

8- fluoropurines have been limited and very little is known about their biochemical and pharmacological 

properties. 

The advantages of UCLA's method are its simplicity and wider applicability. In general, fluorinated 

purines may find use in anti-cancer and anti-viral therapies. For example, we have evaluated the 

biological activity of 8-fluoroacycloguanines and have observed them to be functional substrates for 

HSV-tk. Extension of this electrophilic fluorination methodology to radiolabeling of purines with F-18 

(a radioisotope of fluorine) has resulted in 8-[F-18] fluoropurines for use in Positron Emission 

Tomography (PET) in monitoring gene expression in-vivo. 

The commercial and scientific importance of this discovery is enormous. By following this general and 

broadly applicable methodology, it is now possible, for the first time, to synthesize otherwise 

inaccessible 8-fluoropurine derivatives. If you are interested in commercializing this patented 

technology, please contact the University for additional information. 

Reference: UCLA Case No. 1997-543 US Patent Numbers: 5,861,503 | 

6,262,254 


invention, 





Angeles 


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Tel: 310-794-0558 Fax: 310- 

794-0638 



Lead Inventor: Jorge Barrio

REACTION OF PURINES WITH ELEMENTAL FLUORINE TO GENERATE 8-FLUOROPURINES 

edu 




keywords: synthetic chemistry uspatent uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


CELL-TYPE SPECIFIC INTRACELLULAR DELIVERY USING 3E10 MUTANT 



In vivo methods for cell type specific intracellular delivery of therapeutic molecules, (such as proteins 

and nucleic acids) to targeted tissue sites have remained limited. Investigators at UCLA have developed 

a murine monoclonal anti-dsDNA autoantibody mAB 3E10 and its single chain Fv (scFv) fragment. 

Both the whole antibody and the scFv are transported selectively into the nucleus of skeletal muscle 

cells in vivo. The cell type specificity of mAb 3E10 and 3E10 scFv is mediated by their interaction with 

a skeletal muscle antigen identified in the study. This antigen may further be investigated as a useful 

target for cellular and nuclear delivery of therapeutic agents into muscle cells in vivo. 

In vitro studies show no evidence of cellular toxicity in the cells that mAb 3E10 and scFv 3E10 

penetrate. These studies also indicate that both forms of 3E10 can transport relatively large proteins into 

the nucleus of cells. As a result, the tissue specificity and transport function of both mAb 3E10 and scFv 

3E10 suggest their potential therapeutic usefulness. Preliminary studies demonstrate the delivery of 

correctable p53 peptides into cancer cells for the treatment of cancer. Penetration of antibody into 

muscular dystrophy cells indicates the feasibility of delivering correctable muscle proteins into muscular 

dystrophy cells for the treatment of patients with muscular dystrophy. 



invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 

Lead Inventor: Richard Weisbart 








GENETICALLY ENGINEERED MOUSE LACKING TUMOR SUPPRESSOR GENE IN THE BRAIN 

GENETICALLY ENGINEERED MOUSE LACKING TUMOR SUPPRESSOR 

GENE IN THE BRAIN 


Mutation in the Pten tumor suppressor gene is associated with several human cancers and neurological 

abnormalities, such as enlarged brain (megacephaly), mental retardation, and malignant brain tumors. 

Inactivation of Pten in mouse models confirmed PTEN to be a bona fide tumor suppressor. However, 

since a null mutation of the gene leads to death during embryogenesis, there hasn't been a defined in vivo 

model for studying the exact functions of PTEN in brain development and tumor formation. 

To overcome the early embryonic lethal phenotype in Pten-/- mice and to study the roles of PTEN in 

embryonic development, adult tissue function, and tumorigenesis, researchers at UCLA have generated a 

knockout mouse model with the Pten gene functionally deleted in neural stem cells. The mouse model 

can be used in the following applications: 1) preclinical screening for compounds with activities that 

target the PTEN controlled signaling pathways in treating cancer and other neurological abnormalities 2) 

stem cell research for understanding how PTEN is involved in neural stem cell development, neural 

regeneration, and neuronal differentiation. 


● Wu H. Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor 

gene in vivo. Science 2001 Dec 7; 294 (5549): 2186-9. more... 

● Wu H. Cre/loxP-Mediated Inactivation for the Murine Pten Tumor Suppressor Gene. Genesis 32: 148- 

149 (2002) more... 

● Penninger and Woodgett PTEN-Coupling Tumor Suppressor to Stem Cells? Science 2001 Dec 7; 294 

(5549): 2116-2117. more... 

● Morrison Pten-uating neural growth. Nature Medicine 2002 8: 16-18. more... 



GENETICALLY ENGINEERED MOUSE LACKING TUMOR SUPPRESSOR GENE IN THE BRAIN 


invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Hong Wu 





card 


CERBERUS AND FRZB-1, SECRETORY MOLECULES WITH A REGEN...ION AND AN INHIBITORY ACTIVITY ON WNTS, RESPECTIVELY 

CERBERUS AND FRZB-1, SECRETORY MOLECULES WITH A 

REGENERATIVE FUNCTION AND AN INHIBITORY ACTIVITY ON WNTS, RESPECTIVELY 


Soluble growth and neurotrophic factors are valuable for their physiological activities and their utilities 

in therapeutic, clinical, research, diagnostic, and drug design applications. UCLA researchers have 

identified the functions of two novel proteins, designated "cerberus" and "frzb-1." 

Cerberus is expressed as a secreted peptide during embryogenesis of the Xenopus embryo, and is 

expressed specifically in the head organizer region. This new molecule has endodermal, cardiac, and 

neural tissue inducing activity, that should prove useful in therapeutic, diagnostic, and clinical 

applications requiring regeneration, differentiation, or repair of these and other tissues. 

Frzb-1 is a soluble antagonist of growth factors of the Wnt family that acts by binding to Wnt growth 

factors in the extracellular space. The gene for frzb-1 is expressed in adult tissues from different species, 

including Xenopus, mouse, and human. Based on its antagonistic activity on Wnts in vivo, frzb-1 is 

believed to have utility as a tumor suppressor since, since over-expressed Wnt proteins cause cancer. 

Frzb-1 may also be a useful vehicle for solubilization and therapeutic delivery of Wnt proteins 

complexed with it. 

Related Paper (Selected) 

● "The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals." Nature 

397, 707-710 more... 

Reference: UCLA Case No. 1996-592 US Patent No.: 

6,133,232 

US Patent Application No.: 

US 2002-128441-A1 


CERBERUS AND FRZB-1, SECRETORY MOLECULES WITH A REGEN...ION AND AN INHIBITORY ACTIVITY ON WNTS, RESPECTIVELY 


invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Edward De Robertis 




keywords: therapeutics diagnostics uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


MUTATIONS IN ATAXIA-TELANGIECTASIA GENE 



Ataxia-telangiestasia (A-T) is a rare genetic disease that presents in early childhood and progresses to 

various neurodegenerative disorders. The clinical symptomatology of A-T is primarily characterized by 

a degenerative state of the brain known as cerebellar ataxia and the subsequent formation of spider-like 

veins in the corners of the eye referred to telangiectases. Further manifestations of the disease often 

result in immunodeficiency, increased susceptibility to malignancies and hypersensitivity to radiation. 

As the phenotypes of the A-T gene are well defined, the disease is often diagnosed from the 

characteristic symptoms. However, this process is not completely accurate nor does it provide insight 

into the etiology of the disease. Moreover, early detection is also limited as parents of A-T afflicted 

individuals are asymptomatic for the gene is inherited in an autosommal recessive manner. 

The identification of the A-T gene and the isolation of a mutated A-T gene (ATM) in recent years have 

made genetic screening possible. UCLA researchers have identified several genetic mutations in ATM 

that may lead to the onset of A-T, thus allowing for presymptomatic and more accurate diagnosis. 

Genetic analysis of 41unrelated, A-T afflicted individuals showed twenty-one truncation mutations for 

which the relationship of such mutants can provide more insights into A-T etiology. In addition, UCLA 

researchers have developed new diagnostic tools and probes for A-T detection. 

Currently, there is no cure for A-T and most afflicted individuals die at early adolescence. Therefore, 

achieving a better understanding of the etiology of the disease, and the ability to diagnose the disease 

earlier, may give rise to the development of better treatments and perhaps a cure. Moreover, the 

identification of ATM mutations can be advantageous in other applications. For example, heterozygous 

A-T females may be five times more likely to develop breast cancer than non-carriers. Therefore, 

mutation analysis of ATM may also play a significant role in the etiology of breast cancer as well as that 

of A-T. 





invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 

Lead Inventor: Richard Gatti 






A HUMAN INFLAMMATORY BREAST CARCINOMA XENOGRAFT MODEL OF THE INTRAVASATION STEP OF METASTASIS 

A HUMAN INFLAMMATORY BREAST CARCINOMA XENOGRAFT MODEL OF 

THE INTRAVASATION STEP OF METASTASIS 


Most women that die from breast cancers do not succumb to the original disease but from the metastatic 

spread of the disease to other organs of the body. In order for tumors to metastasize, the cancerous cells 

must enter the body's vasculature and travel by way of the blood system, a process known as 

intravasation. Though the mechanism is poorly understood, recent experimental evidence has suggested 

that intravasation may be the rate-limiting step in the metastatic process. Further elucidation of the 

mechanics involved in intravasation may provide greater insight into the metastatic activity of cancers. 

UCLA researchers have developed the first transplantable human inflammatory carcinoma xenograft, 

designated MARY-X. Inflammatory breast carcinomas are one of the most aggressive human cancers, 

exhibiting an exaggerated degree of intravasation in situ and manifesting into florid lymphatic and 

vascular invasions. Therefore, MARY-X provides a good experimental model to dissect the molecular 

processes of intravasation. Additionally, comparison studies of inflammatory breast carcinoma 

xenografts in nude mice to the pathogenesis of the disease in humans, showed striking similarities. One 

of the most prominent was the fact that growth of MARY-X was exclusively limited to the murine 

lymphovascular spaces as exhibited in humans. 

These experimental models for inflammatory carcinoma provide the necessary research tools to dissect 

the process of intravasations on a molecular level as well as the manifestation of this specific cancer. 

Additionally, the model can be used to identify potential molecular targets for therapeutic intervention 

and to assess the efficacy of a broad spectrum of diagnostic and therapeutic agents. 

Reference: UCLA Case No. 1999-548 PCT Publication Number: WO 

01/19967 A1 


A HUMAN INFLAMMATORY BREAST CARCINOMA XENOGRAFT MODEL OF THE INTRAVASATION STEP OF METASTASIS 


invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 

Lead Inventor: Sanford Barsky 




keywords: therapeutic research technologies uclancd ucla technologies intellectual property patents technology transfer 

invention business card 


POLYNUCLEOTIDE DETECTION SYSTEM FOR LOW COPY NUMBERS FOR RESEARCH AND CLINICAL USES 

POLYNUCLEOTIDE DETECTION SYSTEM FOR LOW COPY NUMBERS FOR 

RESEARCH AND CLINICAL USES 


BACKGROUND: Detection of a polynucleotide species via hybridization involves separate steps that 

may compromise the scalability and accuracy of the assay. A detection system developed by researchers 

at UCLA is highly sensitive and specific while it reduces the steps needed to process a hybridization 

experiment. 

INNOVATION: Unlike conventional detection systems that rely on labeling of target DNA, the 

proposed method detects hybridization by detecting a conformational change in the probe sequence upon 

its hybridization to a complementary target. In this system, the probe may be labeled instead of the 

target. 

ADVANTAGES: 

1. Since the probes are the only species that is labeled, it enables the direct measurement of the 

amount of probe that is being used for the assay. 

2. Since the detection of hybridization is due to monitoring of the conformational changes in the 

probe DNA, this detection scheme is not concentration dependent. Concentrations of target DNA as low 

as 1 pM have been detected. It is hoped moving to low-volume microfluidic environments would lower 

this limit dramatically. 

3. The probe DNA (~ 6-7 fg) involved in each experiment is several orders of magnitudes lower 

than that involved in a single spot of a standard fluorescent-based array (~ 10 ng). Since this quantity 

provides a lower limit to the amount of target DNA to be detected, it is hoped one may work directly 

with mRNA as the target nucleotide. 

4. This technology makes possible a high-throughput DNA detection scheme which is unique in 

being inexpensive as well as fast. The duration of the assay is anywhere between a few minutes to at 

most a couple of hours depending on target concentration. 

5. The technology is such that it can be easily integrated in a microfluidic environment, for 

instance as one component of a microfluidic lab-on-a-chip device. 

APPLICATIONS: 

1. Expression profiling of genes, especially for small sub-populations of cells which cannot be 

analyzed with current methods because the quantities are too small; this is the case for stem cell 

research, a field of current intense interest. 

2. Detection of SNPs, mutations, and pathogens. 

3. Diagnostics related to certain types of cancer, such as minimal residual disease in leukemia. 


POLYNUCLEOTIDE DETECTION SYSTEM FOR LOW COPY NUMBERS FOR RESEARCH AND CLINICAL USES 

DEVELOPMENTTo DATE: The researchers are testing the system using patient samples from 

leukemia patients. The researchers are hopeful that due to the sensitivity of the system, mRNA may be 

directly detected from the sample without the need for sample processing steps (reverse transcription of 

RNA to DNA, DNA isolation and amplification, etc.). 

Reference: UCLA Case No. 2001-432 PCT Publication: WO 03/029435 A2 

US Publication Number: US-2004- 

0241699-A1 


invention, 





Angeles 


1200 


Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Giovanni Zocchi 




keywords: n-biotool hybridization biomolecules DNA RNA polynucleotide detection pathogen evanescent wave biosensor 

bioterrorism sample single molecule uclancd ucla technologies intellectual property patents technology transfer invention 

business card 


ARTIFICIAL HUMAN MUTATION CONTROLS FOR CLINICAL DIAGNOSTIC GENETIC AND PROFICIENCY TESTING 

ARTIFICIAL HUMAN MUTATION CONTROLS FOR CLINICAL DIAGNOSTIC 

GENETIC AND PROFICIENCY TESTING 


BACKGROUND: The rapid pace of disease gene discovery, fueled by the Human Genome Project, 

has caused an explosion in the number of analytes tested by molecular diagnostic laboratories, especially 

those involved in heritable disease testing. The lack of well-characterized control materials containing 

mutations of interest to serve as positive controls in the assays creates a major problem for genetic 

testing facilities. The lack is also an impediment for nationwide proficiency testing programs, such as 

that offered jointly by the college of American Pathologists (CAP) and the American College of Medical 

Genetics (ACMG). Procurement of suitable human mutation control materials from natural sources is 

hampered by the rarity of many disease mutations, the limited quantity in clinical specimens, the 

dependence on clinicians to recognize the need and take the trouble to deposit patient samples in 

existing repositories, and onerous informed consent, sample ownership and genetic privacy constraints. 

There is a recognized need for a comprehensive set of positive controls for clinical testing of human 

genetic mutations that is reliable, reproducible, widely available and readily utilized in standard testing 

platforms. 

INNOVATION: UCLA investigators and their colleagues have developed a generalized method for 

constructing artificial DNA samples containing any gene mutation of interest. The artificial DNA 

samples perform like conventional human-derived material on most of the commonly used technical 

platforms in molecular genetic testing. The method is far less expensive than clinical or laboratory 

approaches involving patient sample collection and/or human cell culture. It is anticipated that the 

artificial human mutation controls may be most easily commercialized as analyte-specific reagents 

(ASRs) sold to clinical diagnostic testing laboratories for use in "home brew" assays. 

ADVANTAGES: 

1. The protocol for constructing the artificial DNA samples is relatively simple, robust and 

reproducible. 

2. Scale-up to provide enough control material to last for years is easy and inexpensive. 

3. The procedure may be readily applied to a wide variety of mutation samples for many genes 

and diseases. 

4. It is amenable to a wide range of testing platforms. 

5. Artificial human mutation controls have the practical advantage of eliminating the burdensome 

requirements associated with collecting samples from patients. 

APPLICATIONS: 

1. The primary market for the artificial human mutation controls will be as positive controls in 



genetic tests performed by clinical diagnostic laboratories. 

2. The artificial DNA samples will also be useful in the nationwide proficiency testing of more 

than 200 genetic testing facilities that is conducted by CAP/ACMG. 

3. The method may be applied to non-genetic diseases as well, including cancer markers and 

even pathogen and host markers of infectious diseases. 

DEVELOPMENT TO DATE: The method of producing artificial human mutation samples was 

initially developed and tested using two known mutations of the cystic fibrosis gene (CFTR): G85E in 

exon 3 and 1078delT in exon 7. The artificial DNA samples of the CF gene were formulated for each of 

the following five genotypes: wild type (homozygous normal), homozygous G85E, homozygous 

1078delT, heterozygous G85E, and heterozygous 1078delT. The samples were constructed to 

approximate the relative molar concentration of a heterozygous mutation or a homozygous mutation that 

would be expected in a typical patent genomic DNA specimen used in a standard CAP/ACMG 

proficiency sample (50 mg DNA in 20 mL buffer). Each sample behaved indistinguishably from 

"natural" samples when assayed with PCR/restriction digest assay and standard reverse line blot 

technology. In a blinded pilot test, the five artificial DNA samples were sent to 9 genetic testing 

facilities that together employ a wide range of technical platforms for CFTR mutation screening. The 

results indicate that the five DNA mutation control samples were remarkably reproducible in mimicking 

the desired human genotypes across multiple testing platforms. 


● Quality in molecular genetic testing. Nature Rev. Genet. Sept 2001; 2(9), 717-723. 

more... 





invention, 





Angeles 


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Tel: 310-794-0558 Fax: 310- 

794-0638 


edu 


Lead Inventor: Wayne Grody 






UCSD TechTIPS Available Cancer Technologies 

● Variable Selectin Inhibition by Heparin - Disease Therapy Implications (SD2006-004) 

● Method for Generating Unlimited Numbers of Macrophage/Dendritic Cells and Neutrophils.(SD2005-114) 

● Treatment for Type II Diabetes and Cancer by Regulating Glucose Transporter Levels (SD2004-243) 

● Osmotic Stress and Human Disease (SD2004-155) 

● Adenovirus Vector Encoding Human GD40 (SD2004-163) 

● Superactive p53 (SD2004-160) 

● Mice Lacking IKK Beta in Intestinal Epithelial Cells (SD2004-133) 

● Novel Matrix Metalloproteinase Inhibitors. (SD2004-102) 

● New Anticancer Target (SD2004-088) 

● In vivo Propagated Murine A20 Lymphoma Cells (SD2004-085) 

● Novel Method to Inhibit Tumor Growth & Other Neovascular Diseases. (SD2004-076) 

● Oligonucleotides for the Treatment of Cancer and Autoimmune Diseases (SD2004-013) 

● Synthetic Fusion-Peptide Vaccine for Cancer and Viral Infection (SD2003-262) 

● Regulating genes in the COX-2 pathway for colon cancer (SD2003-261) 

● Mechanism of Protein Transduction and Enhancement by Transducible Fusogenic Peptides (SD2003-260) 

● Chemical Tools for Analysis and Manipulation of Enzymes in Biosynthetic Proteomes (SD2003-226) 

● Chronic Lymphocytic Leukemia B Cells (SD2003-185) 

● Markers for Resistance to Chemotherapeutic Agents (SD2003-120) 

● New Therapy for Solid Tumors and other Neovascular Diseases. (SD2002-241) 

● Novel therapeutic approach for cancer, fibrosis and auto-immune disorders. (SD2002-149) 

● Targeted Cancer Therapy (SD2002-020) 

● Novel Markers and Gene Targets useful for the Diagnosis and Suppression of Metastasis (SD2002-005) 

● A Novel Method to Detect and Inhibit Angiogenesis (SD2001-135) 

● Target for Development of Inhibitors of Cancer (SD2001-134) 

● Disaccharide inhibitors of Tumor Metastasis (SD2001-105) 

● Treatment of Cancer by Inducing Cell Apoptosis (SD2001-030) 

● A New Strategy for Leukemia Therapy (SD2000-159) 

● Disease Treatments Using Multimeric TNFSF Ligands (SD1999-003) 

● Diagnosis of Cancers with Metastatic Potential (SD1998-D00) 

● Diatom Nitrate Transporter Transgene Promoting Plant Growth on Low Nitrate Soils (SD1998-083)

● Selectin Inhibition: Novel Uses For An Already Approved Drug (SD1998-049) 

● Identification and Use of Vascular Surface Molecules for Disease Diagnosis and Treatment (SD1992-A32)

UCSD Technology Transfer Department 

TechTips Technology Case 

Variable Selectin Inhibition by Heparin - Disease Therapy Implications 

UCSD researchers have previously found that heparin preparations could be used to inhibit P- and Lselectin 

mediated pathologies, including such diseases as ischemia, reperfusion injury, acute 

inflammation, chronic inflammation and cancer metastasis. Further to these findings, the researchers 

have found that various heparin preparations vary widely for P- and L-selectin inhibition. The present 

invention details in vitro and in vivo approaches to comparing different types and lots of heparin for P- 

and L-selectin binding and screening for non-anticoagulation uses such as metastasis inhibition. Also, 

described here is a method in which a subset of fragments from a clinically-approved heparin can be 

isolated which has potential inhibitory activity relative to anticoagulant activity. 

The ability of various heparins to inhibit the P- and L-selectins has been shown to correlate with their 

ability to inhibit metastasis in two different types of syngeneic murine tumors. By inhibiting the 

interaction between leukocytes, platelets and endothelial cells with tumor cells and endogenous ligands, 

heparin minimizes metastasis. The reduction in metastasis was found to be independent of the 

heparins' anticoagulant activity. 

Case No: SD2006-004 

Inquiries To: invent@ucsd.edu 

Copyright © 2002. University of California, San Diego. Terms and Conditions 

http://invent.ucsd.edu/technology/cases/2006/SD2006-004.htm10/21/2005 7:37:02 AM



Method for Generating Unlimited Numbers of Macrophage/Dendritic 

Cells and Neutrophils. 

FEATURES: 

Macrophage/dendritic cells and neutrophils orchestrate the inflammatory response, communicating with 

each other and with T and B cells to induce cell activation and cell proliferation, to recruit more 

inflammatory cells, to kill the invader, to protect the surrounding tissue, to induce longer-term protective 

immunity, and to down regulate the response once the microorganism has been eliminated. These 

same processes can become chronically activated, leading to a variety of human diseases, such as 

autoimmune disease, multiple sclerosis, liver cirrhosis, arthritis, atherosclerosis, vascular disease, and 

even cancer. However it is expensive and time-consuming to harvest these differentiated and nonmitotic 

innate immune cells for academic and industrial research, drug screening, and therapy 

applications. This invention provides a unique method to generate unlimited numbers of 

immature progenitors that can differentiate into mature, normal macrophage/dendritic cells or 

neutrophils when directed to do so. By selecting specific oncoproteins to block differentiation and 

immortalize progenitor cells of macrophage/dendritic cells and neutrophils. These progenitors proliferate 

indefinitely, having been expanded in the laboratory continuously. Following oncoprotein inactivation, 

they stop dividing and mature into cells having the typical morphology of macrophage/dendritic cells and 

neutrophils. When activated by pro-inflammatory stimuli, these mature cells secrete the normal broad 

array of pro-inflammatory cytokines. 

BENEFITS: 

• Enables the creation of cultures of unlimited numbers of immature progenitors in a 

reproducible and cost-effective manner. 

• The culture progenitors are controllably differentiated into mature immune cells and 

exhibit their characteristic morphology, markers and inflammatory response upon 

activation. 

• Provides a nearly inexhaustible supply of macrophage/dendritic cells and neutrophils. 

• Useful for investigating the molecular events underlying macrophage/dendritic cell and 

neutrophil differentiation. 

• Useful for studying the role of innate immune cells in inflammatory human diseases. 

• Useful for pharmaceutical investigation. 

• May aid development of therapeutics for treatment of inflammatory diseases. 

DEVELOPMENT STATUS: This technology is offered exclusively or non-exclusively for US and/or 

worldwide territories. A commercial sponsor for potential future research application is sought 

ADDITIONAL INFORMATION and LINKS 

http://invent.ucsd.edu/technology/cases/2005/SD2005-114.htm (1 of 2)10/21/2005 7:37:02 AM


SD1999-053 

IP STATUS: A provisional patent application has been filed on this invention. 


Keywords :Inflammatory disease, autoimmune disease, multiple sclerosis, liver cirrhosis, arthritis, 

atherosclerosis, vascular disease, macrophage, dendritic cell, neutrophils, progenitor, differentiation, 

immune system 






Treatment for Type II Diabetes and Cancer by Regulating Glucose 

Transporter Levels 

Background: 

UCSD researchers have discovered that a certain gene encoding a glycosyltransferase is able to 

regulate levels of glucose transporters on pancreatic beta cells. Over-expression of this gene in mice 

promoted glucose transporter activity on the plasma membrane, increasing glucose uptake and insulin 

secretion. When the expression of this gene was impaired, the mice developed type II diabetes. 

Invention: 

This invention provides methods to treat diabetes by controlling the expression of a gene encoding a 

glycosyltransferase. This glycosyltransferase might also be a promising target for cancer, since the 

increase in glucose transport resulting from this enzyme's activity contributes to the high metabolic rates 

found in cancer cells. 







Osmotic Stress and Human Disease 

Novel and truly useful molecular targets for drug discovery are all too uncommon. Nevertheless, the 

identification of such biologically validated targets represents the critical first step in the drug discovery 

effort upon which all subsequent investment of resources is predicated. Environmental stress response 

pathways have been recognized as valid targets for a variety of diseases, including cancer and 

inflammatory conditions, because they are activated predominantly within the context of the disease 

state. At UCSD fundamental new insights have been made into the cell biology of the mammalian 

osmotic stress response that have clear and profound implications to human diseases. The relevance of 

osmotic stress to the normal function of the kidney has long been recognized, but there was previously 

little or no appreciation of the role of osmotic stress in either extrarenal or diseased tissues. 

Recent results from studies of an essential, ubiquitously expressed intermediate in the mammalian 

osmotic stress response pathway definitively demonstrate that the osmotic stress response is critical for 

normal cell growth and viability specifically under conditions of osmotic stress. In addition, conditions of 

osmotic stress in vivo are clearly not limited to the kidney, and are of particular relevance to the 

microenvironments found in association with disease. In addition to providing a completely novel, 

biologically validated target for drug development, these discoveries on the mammalian osmotic stress 

response pathway and the essential molecular components of the pathway may also provide the basis 

for diagnostics or unique methods for identifying therapeutic agents for a wide variety of diseases such 

as cancer, stroke, myocardial infarction, rheumatoid arthritis, etc. 





Research Reagents and Cell Lines 


Please call (858) 534-5815 or use the e-mail address invent@ucsd.edu if you are interested in licensing 

any of the following items. 

Antibodies Cell Lines Mice Nucleic Acid Tools Other Research Tools 

Antibodies 

http://invent.ucsd.edu/technology/research.htm (1 of 18)10/21/2005 7:37:07 AM 

Case No. Title Description 

SD2004-209 Monoclonal antibodies to rat giantin and 

Drosphila Golgi integral membrane protein 

SD2003-277 Polyclonal antibodies to Drosophila 

chromatin assembly factors Asf1 and p55 

subunit of CAF-1 

These two antibodies are generated to Golgi 

associated proteins. These are useful tools for 

monitoring Golgi-specific functions: structure 

and protein transport in cells (mammalian and 

Drosophila, respectively). 

for anti-giantin: Lesa GM, Seemann J, Shorter 

J, Vandekerckhove J, Warren G. The aminoterminal 

domain of the golgi protein giantin 

interacts directly with the vesicle-tethering 

protein p115. 

J Biol Chem. 2000 Jan 28;275(4):2831-6. 

for anti-Golgi integral membrane protein: 

Stanley H, Botas J, Malhotra V. The 

mechanism of Golgi segregation during 

mitosis is cell type-specific. 

Proc Natl Acad Sci U S A. 1997 Dec 23;94 

(26):14467-70. 

These are rabbit polyclonal antibodies against 

proteins that are involved in the assembly of 

chromatin. The antibodies recognize 

Drosophila Asf1 and Drosophila p55 subunit 

of CAF-1 (chromatin assembly factor-1). 

Reference: Tyler JK, Collins KA, Prasad- 

Sinha J, Amiott E, Bulger M, Harte PJ, 

Kobayashi R, Kadonaga JT. Interaction 

between the Drosophila CAF-1 and ASF1 

chromatin assembly factors. 

Mol Cell Biol. 2001 Oct;21(19):6574-84. 

SD2002-219 Reagents to block cell division An antibody to the C terminal fragment of 

the Golgi protein GRASP65, acting 

intracellularly, prevents entry of cells into 

mitosis. Targeting GRASP65 in the Golgi 

could be a novel way to screen 

compounds for anti-cancer activity by 

preventing the fragmentation of the Golgi 

and thereby preventing entry of cells into 

mitosis. (reference)


SD2001- 

224 

and 

SD2001-225 

Monoclonal and Polyclonal Antibodies 

Directed Against Myosin Motors, Useful 

for Study of Deafness 

SD2001-093 LJ-26, a recombinant chicken monoclonal 

antibody with defined molecular specificity 

for antibody VH regions. 

SD2000-066 KINESIN ANTIBODIES – KIF21A & 

KIF21B 

SD1999-128 


STAT1 POLYCLONAL ANTIBODIES 

Both monoclonal and polyclonal antibodies 

have been prepared which bind to the 

unconventional myosin, myosin VIIa, an actinbindin 

protein, which has been shown to be 

involved in auditory signal transmission and 

may be useful for the biochemical and 

immunohistochemical research on deafness, 

blindness, and phagocytic events. 

SD2001-224 (Monoclonal) and SD2001-225 

(Polyclonal) 

Recombinant avian antibody obtained by 

phage display technology. (reference) 

Kinesin proteins are used by neurons for 

transport along microtubules. The A protein is 

found throughout neurons while the B protein 

is enriched in dendrites. Antibodies were 

raised against these two newly discovered 

kinesins with amino acid similarity, but 

different localizations. The antibodies are 

affinity purified and were raised again fusion 

proteins containing amino acids 1124-1355 

(A) and 1135-1419 (B). (reference) 

Polyclonal antibodies to STAT1 have been 

prepared in rabbits and are suitable for use in 

immunoassays. 

SD1999-129 Polyclonal antibodies to IRF3 Polyclonal antibodies to IRF3 have been 

prepared by immunizing rabbits with fulllength 

human IRF3 fused to glutathione Stransferase. 

These antibodies are suitable for 

use in immunoprecipitations, western blotting, 

immunofluorescence and supershift assays. 

Reactive with human and bovine IRF3, weakly 

cross-reactive with murine IRF3. 

SD1997-107 MONOCLONAL ANTIBODIES TO PP2A 

SD1997-106 POLYCLONAL SERA TO DEFORMED 

HOMEOBOX PROTEINS 

Navarro, L. and David, M. Journal of 

Biological Chemistry Vol. 274, No. 50 (1999), 

35535-38 

Inquiries to: invent@ucsd.edu 


SD1996-079 Polyclonal Antibodies to Kinesin. Highly specific polyclonal antibody 

preparations are available that target kinesin 

molecular motors from a number of sources. 

These can be used for immunostaining, or 

functional inactivation of molecular motor 

function. The preparations are available as 

non-patented tangible research materials 

under an appropriate Material Transfer 

Agreement for non-commercial purposes, or 

for resale as laboratory reagents under a nonexclusive 

bailment license. 

SD1996-027 MONOCLONAL ANTIBODIES TO 

HUMAN CHROMAGRANIN A 

SD1995-179 MONOCLONAL ANTIBODIES TO ANTI- 

RAT ALCOHOL DEHYDROGENASE 


Inquiries to: invent@ucsd.edu


SD1982-297 MONOCLONAL ANTIBODIES TO RAT NA 

+/K+ PUMP (ATPase) 

Return to Top 

Cell Lines 




SD2005-106 Immune- 

Privileged 

Embryonic 

Mouse 

Progenitor Cell 

Lines 

SD2003-215 IMPROVED 

YEAST TWO- 

HYBRID 

SCREEN TO 

IDENTIFY 

SMALL 

MOLECULES 

THAT INHIBIT 

PROTEIN- 

PROTEIN 

INTERACTIONS 

SD2003-058 MONOCLONAL 

ANTIBODIES 

TO SOLUBLE 

HUMAN MD-2 

SD2000-027 SIGLEC 

PROTEINS AND 

PRODUCING 

CELL LINES 

UCSD researchers have discovered 

that cells derived from a mouse 

embryonic cell line have the properties 

of progenitor cells and can be used for 

xenogeneic and allogeneic 

transplantation into nonimmunosuppressed 

animals. The 

mouse cells have been transplanted 

into non-immunosuppressed adult rats 

and allogeneic mice and have been 

shown to survive for several months at 

least. The transplanted cells show 

progenitor cell-like properties but 

without the formation of tumors, and 

without the production of known 

infectious organisms. 

UCSD investigators have improved a 

version of the reverse two hybrid screen 

designed for the purpose of screening 

large chemical libraries of inhibitors of a 

given protein-protein interaction. They 

have created a small molecule 

permeable reporter yeast strain, a 

positive control activator and a panel of 

selective inhibitors which serve as 

positive controls. These improvements 

may significantly increase the 

probability of identifying a small 

molecule inhibitor of any protein-protein 

interaction that can be detected by twohybrid 

analysis. 

MD-2 is an adapter protein of an innate 

immunity receptor, toll-like receptor 4. 

Thirteen hybridoma cell lines have been 

generated that produce mAbs specific 

to soluble human MD-2. These Abs 

have been characterized and have 

applications in immunological assays 

and functional studies. Some of the 

mAbs cross-react with mouse MD-2. 

ref: Viriyakosol, S., Tobias, P.S., 

Kitchens, R.L. and Kirkland., T.N. 

(2001) J.Biol.Chem. 276: 38044-38051 

Siglecs represent a new group of sialic 

acid binding lectims that are selectively 

expressed in certain cell types and are 

targets for tyrosine phosphrylation. A 

role for certain siglec proteins has been 

proposed for leptin physiology. 

(reference)



SD2000-023 CELLS 

WITHOUT 

HYPOXIC 

RESPONSE 

SD2000-014 PITUITARY 

PROGENITOR 

CELL LINE 

(alpha T1-1) 

SD2000-005 pNEU 

PLASMIDS AND 

Tg1-1 CELL 

LINE 

SD1999-150 IMMORTALIZED 

PRESENILIN 

(PS-1) 

FIBROBLASTS 

SD1999-079 NOVEL 

THYROTROPE 

CELL LINE: Talpha-T1 

A unique embryonic stem cell line with a 

reduced transcriptional response to 

hypoxia. The cell line was created by 

targeting the murine HIF-1-alpha gene. 

It is useful for studies involving the 

regulation of target genes involved in 

the regulation of tissue oxygenation, 

including tumor vascularization and 

angiogenesis. Teratocarcinomas 

formed from these HIF-1a null ES cells 

displayed a 75% reduction in size 

compared to those from wild type ES 

cells. (reference) 

A mammalian cell line immortalized at a 

specific stage of development. Targeted 

oncogenesis using a fragment of the 

LH- alpha promoter linked to T-antigen 

resulted in this progenitor cell which 

expresses only the α-subunit of the 

human gene. This cell line represents a 

more primitive or less differentiated 

state of pituitary development. 

(reference) 

Overexpression of the neu oncogene is 

a factor in a significant percentage of all 

human breast cancers and is correlated 

with reduced survival and higher 

recurrence. This plasmid was 

developed to study the protective 

effects of the neu gene when used as a 

naked DNA vaccine. The expression 

vector encode either a 1) full length neu 

gene, 2) a truncated gene lacking the 

cytoplasmic kinase doman or 3) a 

truncated gene lacking both the 

cytoplasmic and transmembrane 

domains. The Tg1-1 cell line was 

established from a neu-expressing 

mammary tumor which arose 

spontaneously in a FVB/N neutransgenic 

mouse. (reference) 

Presenilin-1 is required for the 

production of beta-amyloid. The 

homozygous deficient and the 

hemizygous knock-out companion cell 

lines comprise a family of cell lines to 

study the biology of the presenilin 

protein and the production pathways of 

amyloid precursor protein and betaamyloid 

protein. Four immortalized cell 

lines are available: 

- / - (PS1 Deficient) 

+ / - (PS1) 

+ / - (PS2) 

+ / - (APP) 

(reference) 

A unique fully differentiated, clonal 

mouse thyrotrope cell line. This line is 

useful for studies of thyrotrope specific 

and thyroid hormone regulated TSH 

gene expression. (reference)


SD1998-005 LEUTENIZING 

HORMONE 

SECRETING 

CELL LINE 

SD1997-016 Cell Line to 

Monitor HIV 

Infection Using 

Green 

Fluorescent 

Protein 

Return to Top 

Mice 



SD2005-246 Elimination of N-glucolylneuraminic Acid 

from Animal Products for Human Use 

This cell line expresses the alpha and 

beta subunits of LH as well as GnRH 

receptor mRNAs, but not the beta 

subunit of FSH. Administration of 

gonadotropin releasing hormone results 

in the secretion of LH. It provides a 

unique tool to study the cellular 

mechanisms involved in gonadotrope 

function, as well as a model to study the 

relationship between the control of the 

cell cycle and the regulation of 

differentiation. (reference) 

UCSD inventors have developed a T 

cell line (CEM) containing the green 

fluorescent protein (GFP) to easily 

monitor HIV infection. Unlike the P24 

antigen assay, which is expensive and 

time consuming, and plaque assays, 

which are also expensive to use, this 

cell line allows accurate and cost 

effective monitoring of HIV infection. 

The cell line contains a plasmid, pEGFP- 

1, with the humanized S65T GFP driven 

by the HIV-1 long terminal repeat. HIV 

infection induces fluorescence up to a 

1000-fold higher than background. This 

cell line has a very low constitutive 

fluorescence and has extremely high 

sensitivity to HIV infection. Expression 

of the GF protein correlates to both p24 

and gp 120 expression. It can be used 

to monitor viral loads, measure 

efficiency of therapeutic agents, assess 

emergence of drug resistance isolates 

from patients, or determine the 

infectivity of viral isolates. The 

fluorescent assays can be performed 

using standard clinical laboratory 

equipment such as a fluorescent 

activated flow cytometer, a 

cytofluorimeter or a fluorescence 

microscope. (reference) 

The inventors have developed a mouse strain 

that is deficient in Neu5Gc, such that Neu5Gc 

is eliminated from all tissues and secretions, 

including muscle, serum and milk. They 

suggest that the same methodology could also 

be applied to animals that are used for food, 

medicines (stem cell technologies) and/or 

cosmetic products.


SD2005- 

033 


UGT1A Locus Transgenic Mice The UCP-glucuronosyltransferase 1A (UGT1A) 

gene locus has been shown to code for several 

different gene products that function as the 

means to eliminate a variety of drug 

substances, environmental toxins, steroids and 

heme metabolites. This classic detoxification 

process in vertebrates has been exploited to 

understand the contribution of glucuronidation 

toward epithelial first-pass metabolism. In 

rodents, where the gene locus is somewhat 

conserved, the regulation is slightly different. 

What this means is that when rodents are used 

for metabolic studies in classic drug 

development experiments, the results may not 

accurately predict the metabolic pattern which 

will later be observed in man. 

Researchers at UCSD have developed a 

transgenic mouse that carries the entire 

UGT1A locus, over 250 kb of DNA, and found 

that it is regulated, like in man, in a tissuespecific 

and inducible fashion. These 

humanized mice are viable and the expression 

patterns have been characterized. By placing 

the gene locus into an in vivo environment that 

can be targeted by tissue-specific regulatory 

elements, it will be possible to examine the 

events involved in the control of the locus. 

For the first time, rodents will be able to 

examine how the gene is controlled and 

ultimately to accurately demonstrate how drugs 

or toxins are cleared, imitating human drug 

metabolism. 

A patent application has been filed. 

SD2005-007 IKKBETA LOX/EE MICE Laura Wolszon - UCSD Technology Transfer 

and Intellectual Property Services, (858)534- 

5815 

SD2005-006 LYSM-CRE/IKKB LOXLOX/IL-1R+/- 

MICE 

SD2005-005 LYSM-CRE/IKKB LOX/LOX/TNFR1 +/- 

MICE 

Laura Wolszon - UCSD Technology Transfer 


5815 



5815 

SD2004-256 IKK BETA +/- MICE Laura Wolszon - UCSD Technology Transfer 


5815 

SD2004-162 Expression of Human CYP1A1 in Mice Invention: This invention is a transgenic 

mouse which carries the entire full-length 

human CYP1A1 gene plus the regulatory or 

flanking DNA. When the animals are exposed 

to certain environmental toxicants, the gene is 

induced through activation of the Aryl 

hydrocarbon (Ah) or dioxin receptor. Detection 

of gene expression can then be demonstrated 

by usual laboratory techniques such as 

enzymatic expression or Western blot. These 

mice are unique in that an entire human 

CYP1A1 gene is in a mouse. 

Commercial Applications: 

1. These mice can be used to identify agents


SD2004-154 MOUSE MODEL OF CROHN'S 

DISEASE AND A METHOD TO 

DEVELOP SPECIFIC THERAPEUTICS 

SD2004- 

144 


Animal Model to detect the Presence of 

Environmental Toxicants 

that induce the gene or activate the 

transcriptional regulator of the gene, i.e. 

toxicants. 

2. To identify drugs that are potential targets for 

the Ah receptor. 

3. An excellent model system to identify 

environmental toxicants. 

4. Can be used to "humanize" mice for the 

CYP1A1 gene. 

5. Can be used to explore the developmental 

impact of agents that might induce the CYP1A1 

gene during development. 

6. Can be used to understand signal 

transduction and events controlling the Ah 

receptor. 

Also see SD2004-144, for transgenic mice 

containing the CYP1A1 gene linked to a 

luciferase reporter gene. 



5815 

UCSD researchers have developed a 

transgenic mouse that carries a reporter gene, 

CYP1A1, constructed from the human gene 

P450 which is linked through its promoter and 

regulatory regions to a luciferase reporter 

gene. Previously, only mouse or rat CYP1A1 

genes were used, this is the first example of a 

human CYP1A1 gene integrated into the 

mouse genome. Activation of the gene is 

conducted through the dioxin or Ah receptor. 

Environmental toxicants, such as polycyclic 

aromatic hydrocarbons or heterocyclic aromatic 

hydrocarbons will induce the gene; this is then 

followed by the increase of luciferase activity in 

the mice.The luciferase activity can be 

measured in the usual way by either extracting 

liver tissue or using a CDD camera. 

The commercial applications of this invention 

are numerous: 

1. Can be used to identify agents that induce 

CYP1A1 or activate the controlling 

transcriptional regulator of this gene, the dioxin 

or Ah receptor. 

2. To identify drugs that are potential targets for 

the Ah receptor. 

3. Can be used to explore the developmental 

impact of agents that might induce the CYP1A1 

gene during development. 

4. The animals can be cross-bred with other 

mice that might be deficient in specific 

pathways that directly impact Ah receptor 

control. 

5. May be an excellent model system for the 

identification of environmental toxicants. 

SD2004-141 LYSM-CRE/IKKBETA LOXLOX MICE Laura Wolszon - UCSD Technology Transfer 


5815 

SD2004-140 VILLIN-CRE/IKKBETA LOXLOX MICE Laura Wolszon - UCSD Technology Transfer 


5815



SD2004-125 CaMKII Heart Failure and Arrythmic Mice Changes in intracellular calcium have been 

shown to be involved in multiple cardiomyocyte 

responses and are critical in the function of the 

heart. Calmodulin-dependent protein kinase II 

(CaMKII) is a transducer of calcium signals and 

is a significant component of cardiac function; 

changes in CaMKII have been shown to be 

associated with the development of heart 

failure. The enzyme acts by phosphorylating 

the ryanodine receptor, increasing the leakage 

of calcium from storage sites which are 

required for normal excitation-contraction 

coupling. 

SD2004-133 Mice Lacking IKK Beta in Intestinal 

Epithelial Cells 

SD2004-132 MICE LACKING IKKß IN 

MACROPHAGES 

SD2004-131 Mice with a Conditional IKK Beta Loss of 

Function 

SD2004-130 Mice Lacking IKK Beta in Liver Cells - 

Models for Acute Hepatic Failure, 

Hepatocellular Carcinoma and Increased 

Sensitivity to Insulin 

SD2004-129 ENHANCEMENT OF TH2-DEPENDENT 

ANTI-INFLAMMATORY RESPONSE 

SD2004-120 IKK BETA LIVER KNOCKOUT CRE 

MICE 

SD2004-085 IN-VIVO PROPAGATED MURINE A20 

LYMPHOMA CELLS 

SD2004-077 CROSSBRED MICE: 

CK19CREXIKKBETA(LOX P) 

SD2004-067 IN-VIVO PROPAGATED MURINE A20 

LYMPHOMA CELLS 

Summary of the invention: Scientists at UCSD 

have developed transgenic mice which 

overexpress one of the isoforms of CaMKII. 

The mice develop dilated cardiomyopathy, 

diminished contractile function, premature 

lethality and heart failure. This model of 

arrythmia and death from heart failure is 

reproducible and is the result of known factors. 

The molecular basis of the model has been 

elucidated and it reproduces the situation seen 

in human heart failure. Further, in vitro studies 

have demonstrated that the pharmacological 

treatment of the transgene reverses the effect. 

Since the model so closely mimics the human 

arrythmias and heart failure, these mice could 

be useful in the discovery of new 

pharmacological agents for treating human 

cardiac disease and may provide a unique 

method for prevention and treatment of cardiac 

disease. 

Mice Lacking IKK Beta in Intestinal Epithelial 

Cells - Models for Acute Organ Failure, 

Radiation Sensitivity, Colitis-Associated Cancer 

MICE LACKING IKKß IN MACROPHAGES 

Mice with a Conditional IKK Beta Loss of 

Function 

Mice Lacking IKK Beta in Liver Cells - Models 

for Acute Hepatic Failure, Hepatocellular 

Carcinoma and Increased Sensitivity to Insulin 

Licensing Contact: Laura Wolszon - UCSD 

Technology Transfer and Intellectual Property 

Services, (858) 534-5815 



Services, (858) 534-5815 



Services, (858) 534-5815 



Services, (858) 534-5815 



Services, (858) 534-5815



SD2004-015 IKKalpha +/- MICE Licensing Contact: Laura Wolszon - UCSD 


Services, (858) 534-5815 

SD2003-211 IKK ALPHA(AA) MICE Licensing Contact: Laura Wolszon - UCSD 


Services, (858) 534-5815 

SD2003-204 Mouse model for polycystic kidney 

disease and osteoporosis. 

A transgenic mouse line has been produced 

that exhibits polycystic kidneys and bone 

deformity. These phenotypes are likely the 

result of insertional inactivation by the 

transgene in the region of an expressed 

pseudogene, Makorin1-p1. The histological 

and macroscopic features of the mice bones 

are similar to those found in osteogenesis 

imperfecta and, additionally, the mice show 

progressive renal polycystic dilation with 

macroscopic liver cysts. The distinct 

phenotypic traits demonstrated by these mice 

make then valuable as screening tools to 

identify drugs for the treatment of polycystic 

kidney disease and osteoporosis. 

Additional Information: Novel Method and 

Novel Treatments 

SD2003-195 FLOXED IKKB MICE Licensing Contact: Laura Wolszon - UCSD 


Services, (858) 534-5815 

SD2003-189 MEKK1 -/- MICE Licensing Contact: Laura Wolszon - UCSD 


Services, (858) 534-5815 

SD2003-147 NEW MICE: CROSS-BRED JNK1 KO/ 

JNK2 KO MICE 



Services, (858) 534-5815 

SD2003-004 Knock-out Mice Deleting Kinesin 3a A knock-out mouse line has been developed 

that has deleted the kinesin 3a ATPase. This 

knock-out mouse is useful in the study of 

ATPase molecular motors, including their use 

as drug targets. 

SD2002-230 Knockout Mice Deleting 2a Subunit of 

Sodium Channel 

A line of knock-out mouse hase been 

developed that deletes the 2a subunit of the 

brain Na Channel. This mouse model makes 

possible the modellingof a variety of neurologic 

disorders, drug target validation, and the 

screening of neuroactive drug candidates for 

efficacy, side effects and mechanism of action. 

2002-154 IKKB+/-/TNFR-/- Licensing Contact: Laura Wolszon - UCSD 


Services, (858) 534-5815 

SD2002-153 IKKB LOX/LOX Licensing Contact: Laura Wolszon - UCSD 


Services, (858) 534-5815



SD2002-132 P53 KNOCKOUT/DBA1 MICE AS AN 

IMPROVED MODEL FOR 

RHEUMATOID ARTHRITIS 

Collagen-induced arthritis has been used for 

many years as a model to evaluate potential 

therapeutic agents in arthritis. We have 

developed a strain of mice with more severe 

arthritis than standard collagen-induced 

arthritis. This strain has defective apoptosis in 

the joints and increased production of 

proteases and cytokines. 

POTENTIAL COMMERCIAL APPLICATIONS: 

This mouse model will be useful for identifying 

and developing therapeutic agents that induce 

apoptosis in arthritis, thereby overcoming the 

defect. In addition, it provides a more stringent 

test of anti-inflammatory agents and protease 

inhibitors because the disease is more severe 

and destructive than in presently available 

strains. 

SD2002-121 JUNAA, JUNWT MICE Licensing Contact: Laura Wolszon - UCSD 


Services, (858) 534-5815 

SD2001-222 ANTI-LIGHT HYBRIDOMA CELL LINE Licensing Contact: Melissa Fitzgerald- UCSD 


Services, (858) 534-5815 

SD2001-110 IKK alpha -/-, IKK beta -/-, IKK gamma 

-/-, IKK wild type cell lines 



Services, (858) 534-5815 

SD2001-094 Transgenic Mice with Deletion of mMGL. UCSD researchers have constructed 

transgenic mice with a germline deletion of 

the mouse macrophage galactose/Nacetylgalactosamine-specific 

C-type lectiin 

(mMGL). This lectin is normally expressed in 

monocytes, macrophages, and dendritic 

cells. The deletion is maintained in C57BL/6 

mice. These transgenic animals are useful 

for research on tumoricidal activity and innate 

immunity to certain pathogens. (reference) 

SD2001-073 Transgenic Mice Expressing FADDdd in 

T Cells. 

UCSD researchers and collaborators have 

constructed transgenic mice expressing the 

Fas-associating protein with a novel death 

domain, but without the death effector domain 

(e.g., FADDdd). This gene is under the control 

of p56lck. Experiments with these transgenic 

animals have shown that FADD plays a 

previously uncharacterized role in T cell 

development and activation. (reference) 

SD2000-070 Zp3-CRE MICE* Cre expression controlled by regulatory 

sequences of the Zp3 gene allowing for oocyte 

specificity. (reference) 

SD2000-034 SYNAPSIN CRE MICE* These mice provice neuronal-specific Cre 

expression as controlled by the rat synapsin-1 

promotor/enhancer. (reference) 

SD2000-033 MHC-floxed-MKK6 MICE* Animal model for ventricular hypertrophy and 

other characteristics of heart failure useful for 

screening drug candidates of the MKK6 and 

p38 inhibitor type as well as an aid for the 

study of the mechanisms of heart disease. 

(reference)


SD2000-032 MHC-floxed-MKK3 MICE* Animal model for ventricular hypertrophy and 

other characteristics of heart failure useful for 

screening drug candidates of the MKK3 and 

p38 inhibitor type as well as an aid for the 

study of the mechanisms of heart disease. 

(reference) 

SD1999-071 MLC2A-CRE MICE Inquiries to: invent@ucsd.edu 

SD1999-091 JNK1 AND JNK2 DEFICIENT MICE Licensing Contact: Laura Wolszon - UCSD 


Services, (858) 534-5815 

*Use of these mice requires the recipient to have a license with DuPont. 

Return to Top 

Nucleic Acid Tools 



SD2005-186 Optimizing Expression of Recombinant 

Protein in Mammalian Cells 

SD2005-116 FLUORESCENT NUCLEOSIDE ANALOGS 

THAT MIMIC NATURALLY OCURRING 

NUCLEOSIDES 

Instead of modifying upstream promoter and 

enhancer elements, UCSD researchers 

have developed an innovative technology 

based on new insights on elements of a 

eukaryotic core promoter to achieve 

significantly higher expression of 

recombinant protein in mammalian cells. 

The inventors have designed, constructed, 

and optimized an extremely strong synthetic 

core promoter. They have demonstrated 

that an optimized synthetic core promoter 

can be at least four to five times stronger 

than currently widely used and known 

strongest promoters such as the adenovirus 

major late core promoter and the 

cytomegalovirus immediate early core 

promoter. This technology could greatly 

enhance the expression of a wide variety of 

recombinant proteins in mammalian cells, in 

vitro and in vivo. 

Methods and compounds validated by 

incorporating into macromolecules and 

authenticating molecular behavior while 

monitoring fluorescence. Patent is pending. 

SD2004-143 DNA:GST-AtNOS1 Plasmid UCSD inventors have identified and cloned 

a nitric oxide (NO) synthase gene from 

plants, AtNOS1, which has been shown to 

play a role in plant growth, stomatal 

movement, hormonal signaling and fertility. 

The protein was expressed in bacteria as a 

fusion protein with glutathione-S-transferase 

(GST-AtNOS1), purified and assayed. The 

inventors were able to show that extracts 

from bacteria expressing the fusion protein 

had higher levels of NOS activity. It is 

particularly interesting that this gene in 

plants has been known, but never isolated. 

Commercial Potential: 

Agriculture companies may be interested in 

obtaining the plasmid for genetic 

manipulation of their plants to enhance leaf 

greening and growth, and regulation of



SD2003-207 GENOMIC DNA FROM BUGULA NERITINA 

AND ITS 

SYMBIONT "CANDIADTUS ENDOBUGULA 

SERTULA) 

stomatal opening and closure. In addition, 

basic researchers might want antibodies 

made against the specific plant nitric oxide 

synthase. 

SD2003-256 Plant Regulatory Gene, SIR1 UCSD investigators have identified a key 

plant regulatory gene, SIR1, that works 

through the auxin signal transduction 

mechanism. The sir1 mutant is resistant to 

sirtinol, a small molecule that activates 

many auxin-inducible genes and promotes 

auxin-related developmental phenotypes. 

Auxins are plant hormones, universal in 

plants, that affect root and vascular 

development as well as many other aspects 

of plant growth. The cloned genes are 

available under Material Transfer 

Agreement. 

SD2003-146 Modulation of Gene Transcription in 

Transgenic Organisms 

Reference: Zhao Y, Dai X, Blackwell HE, 

Schreiber SL, Chory J. SIR1, an upstream 

component in auxin signaling identified by 

chemical genetics. Science. 2003 Aug 

22;301(5636):1107-10. 

UCSD investigators have discovered a new 

way to modulate gene expression using 

genetics and a virus sequence. This 

sequence, when incorporated into a target 

gene, can be shown to have modulating 

effects upon transcription in the presence of 

suppressing alleles placed in the same 

genome. This modification of transcript 

levels has been shown to work for mice, but 

could be applied to cell lines as well as 

other transgenic organisms. Current 

methods to modulate gene expression allow 

simple on or off in a temporal fashion, or 

else rely on maintenance of a drug regimen 

such as tetracycline. 

COMMERCIAL POTENTIAL: As a research 

tool in organisms from yeast to mice, or in 

cell lines, this method may have a 

modulating effect upon gene expression 

rather than a complete “on or off” switch. 

The present approach allows multiple 

discrete allele strengths to be obtained from 

a single transgene conditional upon a 

second unlinked transgene, a chromosomal 

locus or an expressed protein. 

SD2003-115 cDNA cDNA encoding mammalian molecular 

motor proteins KIF21A and KIF21B. 

SD2003-023 RNA Library from Drosophila Useful for 

Identification of Mammalian Signal 

Transduction Pathways 

A library of RNA constructs has been 

developed by combining Drosophila and 

mammalian signaling pathway components, 

which is intended for use in identifying new 

signal transduction pathway components.



SD2002-115 A RAPID AND AUTOMATABLE METHOD 

TO SILENCE GENE EXPRESSION 

SD2001-080 Plasmid for Testing Immune Receptors as 

Adjuvants 

SD2000-147 SCAVENGER RECEPTOR PROMOTER 

SEQUENCES 


method whereby one can very rapidly make 

double-stranded RNA from specific 

sequences of DNA, without the need for 

subcloning. This dsRNA can then be 

transfected into cultured cells for RNAi 

inhibition of any gene of interest. 

Because the subcloning step is eliminated, 

the generation of specific dsRNA can be 

accomplished within a single tube, and can 

be fully automated, thereby generating 

dsRNA from any gene or subsets of genes 

within a very short time. 

COMMERCIAL APPLICATIONS: RNAi 

transfected into cells results in the downregulation 

of its corresponding gene, thus 

enabling one to assay the gene’s function. 

When fully automated, as in a robotic 

system, this research tool can be used as a 

high-throughput screen to identify gene 

targets for drug development. This rapid 

analysis would have been impossible 

previously if one had to rely on the 

subcloning of specific DNA sequences into 

a specialized vector. 


plasmid, pNDK-OVA, which can be used to 

test soluble forms of different immune 

receptors as adjuvants in immunization 

protocols. The vector pNDK-OVA contains a 

1161 bp fragment of the ovalbumin gene 

(OVA) obtained from pACB-OVA (reference: 

1996.PNAS 93:5141) which has been 

inserted into pNDK. The vector pNDK vector 

is a pUC19-based plasmid which contains a 

kanamycin resistance gene, a 

cytomegalovirus (CMV) promoter enhancer 

sequence, a CMV immediate early intron 

and the bovine growth hormone (BGH) poly 

(A) signal. 

Suppressor (S), enhancer (E), and promoter 

(P) regions of the human scavenger 

receptor for class A gene regulatory 

elements were used along with a Human 

Growth Hormone reporter gene to generate 

SEP-H and EP-H transgenes. 

These transgenes can be used in the 

generation of transgenic mice to direct 

macrophage specific expression of foreign 

genes. (reference)



SD2000-078 RNA protection-Riboprobes for studying 

neurodegenerative diseases. 

UCSD researchers have developed over 25 

different human, mouse and rat Riboprobes 

for use in RNase Protection Assays for the 

study of neurodegeneration associated with 

Altzheimer’s and Parkinson’s disease. 

These products are cloned into pCRII and 

can be removed by EcoRI digestion. 

Riboprobes have been developed for 

protection of these genes: excitatory amino 

acid transporters (EAAT), amyloid precursor 

protein (APP), synuclein (alpha, beta and 

gamma), synaptophysin, microtubuleassociated 

protein 2 (MAP2), nuclear 

transport (RAN, Importin) and neural 

specific calmodulin-binding protein 

(mGAP43). Control Riboprobes, for 

monitoring actin and dehydrogenase 

transcripts, have also been developed. 

These nucleic acid tools could be developed 

as part of a kit or as stand-alone reagents. 

SD2000-076 Pcre-HYGRO PLASMID This plasmid can be used for stable or 

transient expression of the cre 

recombinase. (reference) 

*Use of this plasmid to generate transgenic 

mice requires the recipient to have a license 

with DuPont. 

SD2000-039 pF/LOX PLASMID For use in generating gene targeting 

constructs via homologous recombination in 

embryonic stem cells. It can be used to 

generate conditional or systemic events. 

(reference) 



with DuPont. 

SD2000-016 OVINE VEGF cDNA VEGF DNA was isolated from sheep 

placenta and various fetal tissues. A 164 

amino acid peptide was the dominant form, 

with lower level of expression found of the 

120 and 188 amino acid peptides. The 

VEGF 164 signal peptide sequence is highly 

conserved. This cDNA is useful as a probe 

in Northern/Southern hybridization studies 

and for localization of VEGF mRNA in ovine 

tissues or cells. It can also be used in 

transfection experiments. (reference) 

SD1999-153 PV-1, AN ENDOTHELIAL SPECIFIC 

PROTEIN AND ITS cDNA CLONE 

SD1999-110 BAG1 AND ITS HOMOLOG FROM 

BRASSICAEAE; USEFUL FOR 

MANUPULATION OF FLOWER 

STRUCTURE 

A UCSD researcher, along with researchers 

from sister academic institutions, have 

isolated from a caveolae-specific 

glycoprotein, named PV-1 and a cDNA 

encoding it from mouse and rat endothelial 

cells. PV-1 is an integral membrane protein 

of caveolae and appears to be expressed 

mostly in the lung, with little or no 

expression observed in the kidney, spleen, 

liver, heart, muscle and brain. PV-1 would 

be useful as a target for lung-specific drug 

delivery. 




SD1999-099 PHAGE DISPLAY EXPRESSION CLONING 

VECTOR pJF3H 

SD1999-077 HUMAN SODIUM BRAIN CHANNELS 

(cDNA) 

SD1998-051 HUMAN UGT PROTEINS (UDP- 

Glucuronosyltransferase) 

SD1998-045 NOVEL RECOMBINANT ADENOVIRUS 

VECTORS FOR TISSUE SPECIFIC GENE 

EXPRESSION IN HEART 

Selected Territories Available 

This vector offers increased frequency of 

functional inserts while minimizing the 

frequency of defective inserts because stop 

codons in the cDNA do not interfere with 

phage display. Cloning into this vector 

results in a c-terminal fusion product with 

the Fos protein and helper phage infection 

induces expression of the fusion product 

and the Jun-gpIII product. Selection is 

based on ampicillin resistance and 

expression is inducibile by the lac promotor. 

(reference) 

Although sodium channels often provide 

targets for various classes of drugs, studies 

of their molecular structure and specific 

pharmacology have been limited by the 

availability of tissue. Two full length cDNA 

(HBA AND HBB) clones specific for the 

sodium channel alpha subunit were isolated 

from cerebral cortex. The HBA clone has 

been expressed in CHO cells. These cDNA 

clones provide a new tool for the 

development of additional therapeutic 

compounds. (reference) 

Novel cDNAs taken from gastric tissue have 

been cloned and various products of the 

UDP-Glucuronosyltransferase gene 

expressed in a baculovirus system. These 

proteins are useful in the investigation of 

drug metabolism. They also have potential 

application in gene therapy studies for the 

treatment of the lethal negative mutation of 

the enzyme characteristic of Crigler-Najjar 

syndrome. (reference) 

UCSD researchers have developed a novel 

adenovirus vector which is useful for in vivo 

tissue-specific (e.g., cardiac muscle) 

expression of a transgene. Advantages are: 

Efficient - high gene delivery. 

Specific - tissue-specific expression of a 

transgene. 

Broad Application - applicable to other 

tissue types. 

SD1997-106 DEFORMED HOMEOBOX PROTEINS Homeobox proteins are homeodomaincontaining 

transcription factors which 

differentially regulate downstream gene 

expression important in morphological 

diversification. This antibody was raised 

against a full length recombinant Drosophila 

Dfd protein. The gene that encodes this 

protein is necessary for the development of 

the maxillary and mandibular segments of 

the fly head. (reference) 

SD1993-414 TYROSINE KINASE PRODUCED FROM 

EGF 


SD2000-076 Pcre-HYGRO PLASMID This plasmid can be used for stable or 

transient expression of the cre 

recombinase. (reference) 



with DuPont.


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Other Research Tools 



SD2005-246 Elimination of N-glucolylneuraminic 

Acid from Animal Products for Human 

Use 

SD2005-155 Optimizing Expression of 

Recombinant Protein in Mammalian 

Cells New Method for Promoting 

Nerve Regeneration 

SD2003-103 Blood sample library of rare leukemia 

forms. 

SD2003-077 Method for monitoring and detection of 

translational inhibition 

SD2001-192 C5 Epimerase for Use in 

Polysaccharide Production 

The inventors have developed a mouse strain that 

is deficient in Neu5Gc, such that Neu5Gc is 

eliminated from all tissues and secretions, 

including muscle, serum and milk. They suggest 

that the same methodology could also be applied 

to animals that are used for food, medicines (stem 

cell technologies) and/or cosmetic products. 

Technology: By studying pathways that play a 

crucial role in cell survival, plasticity and 

regeneration of neurons, UCSD researchers have 

identified a new use for a composition of matter 

that can promote nerve regeneration and protect 

neurons from apoptosis. The effectiveness of this 

compound is much better than neurotrophic 

factors, including BDNF or bFGF. In addition, the 

inventors have developed a novel delivery method 

to control the concentration of compound to 

achieve the maximal effect. The proof of concept 

has been demonstrated in animal model studies. 

This technology could be equally useful for the 

treatment of CNS or peripheral nerve injuries. 

Blood sample library of rare leukemia forms. 

Description: UCSD investigators have designed in 

vitro system which measures changing 

fluorescence intensity during the translocation 

step of protein biosynthesis with exquisite 

sensitivity. The system is an excellent research 

tool for the study of microbial translocation and 

translation mechanisms. The sensitivity, 

adaptability and ease of the assay is superior to 

other standard assays for monitoring translocation 

of tRNA-mRNA on ribosomes, such as puromycin 

or toeprinting assays. 

BACKGROUND: Chemical-enzymatic synthesis 

of commercially useful polysaccharides is 

hindered by the lack of suitable enzyme 

preparations. 

DESCRIPTION: A glucuronic C5 epimerase 

suitable for use in production chemistry of 

complex polysaccharides has been sequenced 

and made available through its recombinant form. 

Cells transformed with the cDNA for this C5 

epimerase are able to convert D-glucuronic acid 

to L-iduronic acid. Heparin and similar molecules 

in the cell are modified to iduronioc acid analogs, 

yielding modified glycans with differing properties. 

ADVANTAGES: The C-5 transformation of 

heparin and related molecules has not previously 

been practical to conduct in practical scale. 

STAGE OF DEVELOPMENT: Preclinical.



SD2000-092 A NOVEL PROTEIN THAT 

REGULATES RETROVIRUS 

EXPRESSION 

SD1999-153 PV-1, AN ENDOTHELIAL SPECIFIC 

PROTEIN AND ITS cDNA CLONE 

SD1999-111 ONE SELECTION -STEP, ZERO 

BACKGROUND SITE-DIRECTED 

MUTAGENESIS BY TOXIC PROTEIN 

SD1999-090 YEAST STRAINS WITH ZINC 

STORAGE MUTATIONS 

SD1999-061 KINESIN FUSION PROTEIN 

ANTIGENS 

SD1998-051 UGT PROTEINS IN BACULOVIRUS 

EXPRESSION SYSTEM 

SD1998-024 FLINCH TEST MONITOR / 

AUTOMATED NOCICEPTION 

ANALYZER 

SD1997-010 REGULATORY ELEMENTS USED IN 

THE EXPRESSION OF CARDIAC 

SERC A2 

SD1997-068 NOVEL GROWTH FACTORS FOUND 

IN LEUKEMIA 

PATENT STATUS:Pending 

REFERENCES: On request 

A novel human protein that regulates retrovirus 

expression of type D retroviruses. This protein 

specifically binds to RNA Helicase A and through 

the over-expression of this novel protein, viral 

gene expression is enhanced. This protein may 

be useful as a tool for the study of retroviral 

expression. 

A UCSD researcher, along with researchers from 

sister academic institutions, have isolated from a 

caveolae-specific glycoprotein, named PV-1 and a 

cDNA encoding it from mouse and rat endothelial 

cells. PV-1 is an integral membrane protein of 

caveolae and appears to be expressed mostly in 

the lung, with little or no expression observed in 

the kidney, spleen, liver, heart, muscle and brain. 

PV-1 would be useful as a target for lung-specific 

drug delivery. 

A novel method for site-directed mutagenesis 

through toxic protein selection. The advantages 

are: 

● Time Saving: Requires only 14 hours 

(including incubation) and employs only 

one round of transformation. 

● High Efficiency: 100% efficiency 

demonstrated with low to zero background. 

● Cost-Effective: Eliminates the need for 

complicated series of enzymatic steps 

used in other methods to select against 

parental strand. 

● Simple: Only requires T4 DNA polymerase 

and ligase. No need for PCR or other 

enzymes. 

● Versatile: Suitable for long target 

fragments. Only one subcloning of target 

and one selection primer needed to 

generate different point mutations. 

Saccharomyces cerevisiae strains that carry a 

mutation in their vacuolar protein sorting 

demonstrate a temperature conditional defect. 

These mutant strains can be used as model 

systems for similar vacuole and Golgi functions in 

plants. (reference) 



Click here for further details 




SD1996-001 PROTEIN RECRUITMENT SYSTEM Patent No. 5,776,689 

For product information please refer to the 

Stratagene website. 

Click here to view a copy of the License 

Agreement 

SD1995-048 PAW THERMAL STIMULATOR Click here for further details 

SD1993-414 TYROSINE KINASE PRODUCED 

FROM EGF 

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Copyright © 2002. Regents of the University of California. All rights reserved. 

Terms and Conditions of Use 





Superactive p53 

Aberrant forms of the tumor suppressor protein p53 correlate with a significant percentage of human 

cancer cell lines. In many cancers, aberrant p53 correlates with highly aggressive tumor behavior, as 

well as being an independent clinical prognostic marker of early relapse and death. Delivery of active, 

functional p53 to cancer cells shows promise as a potential cancer therapeutic strategy. 

UCSD investigators have discovered a method of making the tumor suppressor protein p53 

constitutively active in vivo. In cellular responses to various stresses, wild type p53 is activated through 

post-translational modifications that change its conformation, leading to cell cycle arrest and cellular 

apoptosis. While p53 is critical for suppression of human cancers, delivery of a wt p53 into 

cancer cells usually requires its activation in order to suppress tumors. Many cancer cells do not have 

the required post-translational mechanisms to activate p53, and therefore a constitutively active p53 

could be more useful as a therapeutic agent. Its utility has been demonstrated in vivo in a transgenic 

mouse model. 

COMMERCIAL APPLICATIONS: A constitutively active p53 protein could be utilized in a delivery 

system targeting therapeutic proteins (or the corresponding DNA or RNA) to tumors. It could also be 

useful as a drug screening target to overcome inhibitors or enhance activators of the p53 activation 

pathway. 







Novel Matrix Metalloproteinase Inhibitors 

Matrix Metalloproteinases (MMPs) are zinc containing hydrolytic enzymes that are able to degrade 

extracellular matrix components such as collagen. MMP’s have been implicated in a variety of diseases, 

including cancer, arthritis, inflammatory disease, and heart disease. Despite intensive research and 

clinical testing of MMP inhibitors, the only approved MMP inhibitor is a tetracycline for the treatment of 

periodontitis. 

UCSD researchers have developed a novel series of organic compounds that are potent inhibitors of 

MMPs. While most MMP inhibitors in development are based on small peptide mimetics that chelate the 

zinc ion using a hydroxamic acid moiety, the UCSD researchers designed a novel class of zinc-binding 

groups (ZBGs) by rational drug design. The binding mode of the ZBGs was optimized using structural, 

spectroscopic, and computational studies of the compounds bound to an inorganic zinc model complex 

for MMP’s. These new inhibitors are up to 700-fold more potent than acetohydroxamic acid in MMP 

binding assays and are expected to have better oral availability and pharmacokinetics when compared 

with hydroxamate-based compounds. These ZBG inhibitors have commercial applications in drug 

design against MMP’s and other metalloproteins related to human disease, such as histone 

deacetylases. 

Case Number: SD2004-102 






New Anticancer Target 

Background: Signal transduction pathways interact in order to regulate the cell growth cycle as well as 

to control apoptosis. It is anticipated that identification of the key regulators in these pathways will 

facilitate development of novel, specific agents for cancer therapy. One such key regulator, Akt (protein 

kinase B), has previiously been identified. Akt has been shown to be involved in malignant 

transformation and the inacivation of Akt has been shown to result in tumor suppression. To date, no 

compounds have been identified which directly inactivate Akt. UCSD researchers, however, have 

identified a protein whose mechanism of action is to deactivate Akt. 

Summary: Akt can be inactivated by dephosphorylation, and others have shown that PTEN 

dephosphorylates the lipids that cause signaling by Akt, but not Akt directly. No protein/kinase has yet 

been identified that directly targets Akt. UCSD researchers have found such a protein, naturally 

occurring, which acts by directly dephosphorylating Akt, thus inactivating it. The protein has been 

designated PHLPP (pronounced "flip"). The researchers have cloned the cDNA of human PHLPP, 

characterized it and studied its function. Evidence indicates that the dephosphorylation occurs at a 

specific site on Akt, which they have also identified. In addition, they found the activity of PHLPP was 

not regulated by PI3 kinase, and was effective even when PI3 kinase was inhibited. The researchers 

have shown that PHLPP is primarily located in the cytosol, but mitogen stimulation results in partial 

redistribution to the membrane. 

Commercial potential: Testing the hypothesis that PHLPP would be a potential target for cancer 

therapy, the researchers looked at PHLPP expression in a cancer cell line. They found that over 

expression of PHLPP caused the selective dephosphorylation of Akt and resulted in an increase in 

apoptotic cells. They also conducted the reverse experiment: knockdown of PHLPP in the same cancer 

cell line prevented the induction of apoptosis. Thus, the cell's inability to dephosphorylate Akt when 

PHLPP was down regulated resulted in cell survival; PHLPP's mechanism of action on Akt makes it a 

unique and significant target for the discovery and development of agents with tumor suppressor 

activity. In preliminary experiments with glioma cells, they found that the glioma tested had a large 

deletion in PHLPP which was confirmed by Western Blot. Further studies are planned. In addition, 

agonists of PHLPP can be designed to target the tumors with increased Akt expression. Increased Akt 

gene amplification in some cervical, ovarian, pancreatic and non-Hodgkin’s lymphomas has been 

reported by other investigators. 









Novel Method to Inhibit Tumor Growth & Other Neovascular Diseases 

Bone marrow-derived stem cells are known to contribute to the repopulation of tissues undergoing 

repair. A mechanism by which the emigration of endothelial precursor cells from the circulation to sites 

of angiogenesis has recently been elucidated by researchers at UCSD. Increased understanding of this 

mechanism has identified a target for the modulation of stem cell trafficking. 

Peptide, antibody or small molecule antagonists of the target may inhibit bone marrow-derived stem 

cells from entering tissues and from participating in tumor growth, atherosclerosis, restenosis and other 

neovascular diseases such as arthritis and psoriasis. Conversely, homing of stem cells to endothelium 

can be stimulated allowing enhancement of angiogenesis in ischemic disease, muscle repair and nerve 

repair. Additionally, the target provides a method to isolate stem cells from tissues such as bone 

marrow or peripheral blood so that they can be expanded and used for therapeutic applications such as 

the treatment of damaged heart tissue or repair of congenital muscle defects. 







Oligonucleotides for the Treatment of Cancer and Autoimmune Diseases 

SUMMARY: UCSD researchers have discovered new synthetic oligodeoxynucleotides (15-mers) useful 

in treating cancer and certain autoimmune diseases. These compounds induce apoptosis in chronic 

lymphocytic leukemia cells but actually stimulate normal human B cells. Their mechanism of action 

does not depend on CpG dinucleotides, and they do not require the addition of cationic lipids or any 

other adjuvant to exert their effects. 

POTENTIAL COMMERCIAL APPLICATIONS: These compounds can be used: (1) as therapeutic 

adjuvants with chemotherapeutic or biologic agents in the treatment of cancer; (2) to study mechanisms 

of cell death in cancer cells; (3) to design better vaccines to treat cancer and autoimmune diseases; and 

(4) to improve the design of antisense oligonucleotides. 

This technology is available for licensing, sponsored research or both. Further information can be 

obtained under a Confidentiality Agreement. 







Synthetic Fusion-Peptide Vaccine for Cancer and Viral Infection 

Problem : Cytotoxic T lymphocytes (CTL) are among the most direct and effective elements of the 

immune system against cancer cells and virus-infected cells. The malignant cells expressing the 

appropriate associated antigens can be effectively recognized and destroyed by CTL, which may result 

in dramatic clinical responses in a limited number of patients. A variety of peptides specific for human 

cancer cells and virus-infected cells have been discovered. Unfortunately all attempts to treat patients 

with these peptides have not yet been successful. One major reason is that the peptides have not been 

able to efficiently enter the antigen-presenting cells and subsequently translocate through the 

endoplasmic reticulum (ER) membrane in order to associate with the MHC molecules. Thus, the 

anticancer and antiviral CTL cannot be stimulated because there is inefficient presentation of antigen on 

the cell surface. 

Technology Description: This invention provides a new approach in peptide vaccine design to 

improve the translocation of antigens through the ER-membrane, thus to enhance the efficiency of the 

antigen presentation. By attaching specific signal sequences to the peptide antigens, UCSD researcher 

demonstrated that the fusion peptides could greatly improve the antigen presentation in human cells 

and induce CTL responses. Furthermore, the effective presentation of the loaded peptide constructs is 

a result of their efficient loading into the cytosol and not simple binding to the surface MHC molecules. 

Benefits: 

● Enhancing CTL responses against tumor and viral diseases 

● Immunizing with minimal determinant constructs may avoid the possible oncogenic effect of fulllength 

proteins. 

● May eliminate cross-reactivity with self-antigens or other highly homologous proteins. 

Features: 

● Fusion of signal sequences to peptide antigens 

● Bypassing the limiting step of ER translocation in the processing of MHC Class I-restricted 

antigens. 

Applications: 

● Development of effective and safe vaccines for both prevention and treatment of human cancer 

and viral diseases. 

● Synthetic fusion-peptide vaccines may be used directly to treat patients. 

● Dendritic cells loaded with these vaccines can be used to elicit powerful anti-tumor immune 

responses in patients with cancer. 

● Fusion-peptide induced CTL may be highly useful for cellular immunotherapy 



● Using combinations of different tumor-associated or viral peptide antigens to generate broader 

immune response against the tumor, and most importantly against the distant micro-metastases. 

Development Status: This technology is available for licensing, sponsored research, or both. 

Lead Inventor(s): Boris Minev 

License(s) available in selected markets. 


Keywords: Antigen presentation, signal sequence, cytotoxic T lymphocyte, immune response, MHC 






Regulating genes in the COX-2 pathway for colon cancer 

Colon cancer is the second leading cause of cancer deaths in the US and is the third most common 

cancer worldwide. The National Cancer Institute estimates 147,500 new cases and over 57,000 deaths 

in the United States in 2003, with a greater incidence in men than women. 

UCSD investigators have shown that decreased expression of 2 anti-apoptotic proteins in colon 

epithelial cells can inhibit colon cancer progression. Raising the expression of these 2 anti-apoptotic 

proteins in colon epithelial cells contributes to colon cancer development or progression. These 2 

proteins work through the cyclooxygenase (COX)-2 pathway. COX-2 is overexpressed in colorectal 

cancers and its inhibition has a cancer-protective effect. 

COMMERCIAL POTENTIAL: These gene targets would be useful for screening drugs for colon cancer 

specific for decreasing their gene expression. They could also become targets for regulated reduction 

of expression via gene therapy. The role of these genes in colon cancer has not been elucidated 

before. 







Chemical Tools for Analysis and Manipulation of Enzymes in 

Biosynthetic Proteomes 

The biosynthesis of natural products derived from polyketide (PK) and non-ribosomal peptide (NRP) 

origins is important for drug discovery and production. Examples of PK/NRP derived pharmaceuticals 

include the antibiotics erythromycin and vancomycin and the immunosuppressant cyclosporin. UCSD 

researchers have developed a novel assay for the high throughput identification of biosynthetic 

enzymes involved in PK and NRP secondary metabolite biosynthesis. Amenable to microarray 

platforms, this functional proteomic screen of modular synthase activity provides a systematic approach 

for identifying genomic and proteomic events associated with natural product synthesis in vivo and in 

engineered systems. A primary application of the technology lies in the discovery of novel natural 

products as therapeutics for cancer and infectious diseases. An additional application includes 

systematic monitoring and control of natural and engineered biosynthetic pathways. 







MARKERS FOR RESISTANCE TO A CHEMOTHERAPEUTIC AGENT- 

OXALIPLATIN 

Oxaliplatin is a cisplatin analog used in cancer chemotherapy because of its broader spectrum of 

activity and different mechanism of action compared to cisplatin and carboplatin. These platinumcontaining 

compounds are commonly used as cancer chemotherapeutic agents, yet 

many tumors develop resistance to these drugs and patient therapy is compromised. No molecular 

markers are currently known that reliably identify a tumor as being resistant to oxaliplatin. Identification 

of patients most likely to respond to chemotherapy or those who have 

tumors resistant to conventional chemotherapy would be of significant value in the management of 

cancer patients. 

UCSD investigators have identified molecular genetic markers in ovarian and squamous cancer cell 

lines that correlate to oxaliplatin resistance with a high degree of statistical significance. These markers 

could be used to identify tumors or cells that are resistant to oxaliplatin. Conversely, they can also 

identify tumors that are likely to be responsive to oxaliplatin therapy. 

COMMERCIAL POTENTIAL: These markers could be used to diagnose patients whose tumors will not 

respond to oxaliplatin in chemotherapy. Development could include an assay of mRNA levels for the 

identified genes, antibodies to gene products, or an assay for changes in gene copy number. 






TechTIPS Technology Case 

New Therapy for Solid Tumors and other Neovascular Diseases. 

Angiogenesis, the growth of new blood vessels from existing vessels, plays a major role in a number of 

human diseases that threaten the lives of millions of Americans. More than 800,000 Americans are 

diagnosed yearly with solid tumors, while several million are afflicted by the chronic diseases 

rheumatoid arthritis, diabetic retinopathy and macular degeneration. It is also now known that the 

growth and spread of most solid tumors, including lung, oral, laryngeal, bladder, renal, pancreatic, 

prostate, breast, colon and rectal cancers, depends on the development of a tumor-associated 

vasculature. Thus, new treatments designed to stop the development of these new blood vessels are 

sought as potential nontoxic therapies for cancer, arthritis and neovascular eye diseases. 

UCSD investigators have designed a vascular targeting bioconjugate for selective delivery of genes or 

chemotherapeutics to angiogenic endothelium in tumors. A receptor that is expressed on angiogenic 

endothelium is a prime candidate for targeted delivery of chemotherapeutic drugs or gene therapies. A 

targeted bioconjugate for the inhibition of angiogenesis and tumor growth in solid tumors is under 

development. This agent may be useful to deliver genes or drugs to proliferating vascular endothelium 

and may therefore allow therapeutic intervention for solid tumors. This approach is expected to inhibit 

angiogenesis and tumor growth without significant side effects. 

The creation of a new angiogenesis-specific drug and gene delivery macromolecule enables selective 

delivery of anti-angiogenic agents to tumors and the potential inhibition of tumor growth. Creation of a 

targeted gene delivery agent could rapidly lead to the development of a new mode of therapeutic 

intervention for cancer and other neovascular diseases. 







Novel therapeutic approach for cancer, fibrosis and auto-immune 

disorders. 

UCSD researchers have discovered a widely applicable method for inhibiting cell migration and invasion 

using pharmacological or genetic approaches. Activation of a specific cellular protein by 

pharmacological agents or by gene expression inhibits cell migration in all cell types in vitro and inhibits 

angiogenesis in vivo. 

This broad-based method provides a valuable, widely applicable strategy to suppress cell migration 

during many pathological conditions. Angiogenesis, tumor cell metastasis and fibrosis can all be 

inhibited by this novel method, thereby suggesting therapeutic approaches to a significant number of 

human diseases that afflict millions of people including cancer, fibrosis and auto-immune disorders such 

as psoriasis and arthritis. 







Targeted Cancer Therapy 

Current methods for the treatment of cancer, such as chemotherapy and radiation often damage normal 

cells, leading to mutations that can cause new types of cancer to develop many years after therapy for 

the original cancer was stopped. Another difficulty with effectively treating cancer is the upregulation of 

transporters to pump a drug back out of the cell before it can have the desired effect. 

UCSD researchers have invented a cancer therapy designed to target cancer cells directly, without 

affecting normal cells. This therapy does not require entry into the cell, circumventing the mechanisms 

used by cells to become resistant to chemotherapeutic agents. Cancer cells can be specifically targeted 

using tumor cell markers such as carcinoembryonic antigen, which have been well characterized for a 

wide range of cancers. Since the target can be varied based on the specific markers the tumor is 

presenting, the targeted therapy is applicable across a range of cancer cell types. 







Novel Markers and Gene Targets useful for the Diagnosis and 

Suppression of Metastasis 

Researchers at UCSD have identified differentially expressed genes in a unique breast metastasis 

model utilizing paired metastatic phenotyped human cell lines. Significantly higher gene expression 

levels were observed for a distinct set of genes in the non-metastatic cell-line, suggesting a role for 

these genes and their products in the inhibition of metastasis. Applications for these markers include the 

diagnosis, prognosis, and therapeutics of cancer and metastasis. 







A Novel Method to Detect and Inhibit Angiogenesis 

Researchers at the University of California, San Diego have discovered a novel method of detecting 

and inhibiting angiogenesis. In vivo experiments have shown that angiogenesis induced by a wide 

range of pro-angiogenic factors can be completely or significantly inhibited with antibody, peptide or 

organic molecule inhibitors of the newly identified target. Because angiogenesis plays a key role in the 

growth and spread of tumors, in neovascular eye diseases and in inflammatory diseases such as 

rheumatoid arthritis, this method has great potential as a highly specific therapeutic approach to the 

management of these diseases. 







Target for Development of Inhibitors of Cancer 

Researchers at UCSD have identified a key enzyme target in the development of mammary epithelial 

cells. Work with "knockin" mice has shown that this target is very specific and absolute for the 

proliferation of these cells. Inactivation of this enzyme does not affect other physiological processes. 

This enzyme is an ideal target for development of specific inhibitors of breast cancer. 







Disaccharide Inhibitors of Tumor Metastasis 

Novel chemistry has made possible the design and development of a series of new compounds that 

inhibit enzymatic glycosylation of macromolecules and large oligosaccharides. Glycosylation is an 

essential biosynthetic process in the specification of uniqueness of structure and function across a 

variety of biomolecules. Glycosylation is brought about by a related family of glycosyltransferases 

having specificity for both individual and classes of substrates involved in cellular regulation, signaling 

pathways, immune responses, toxin formation and molecular docking in macromolecule interactions. 

Selective inhibition of these processes is made possible by the novel compounds of the invention, 

providing new approaches for the design of novel therapies for a variety of disease processes, as well 

as the validation of targets involving glycosylated proteins and oligosaccharides. 

Development status: Pre-clinical 

Patent status: Pending 







Treatment of Cancer by Inducing Cell Apoptosis 

Cancer of different organs is a major unsolved health problem. Recent advances in understanding this 

disease process have revealed a prominent role for a deficient cell apoptosis in facilitating excessive 

tumor cell growth. 

UCSD inventors have developed an approach to the treatment of cancer based on an endogenous 

peptide selectively inhibiting the proliferation of the cancer cells. Using standard delivery techniques, the 

peptide triggers apoptosis selectively in the cancer cells but spares the normal cells. 








A new strategy has been developed to treat chronic Myelogenous Leukemia (CML) and Acute 

Lymphocytic Leukemia (ALL). Unlike current approaches, this new strategy is able to treat the acute 

phase of leukemia, thus potentially providing a more effective therapy. The strategy depends on 

transient exposure of cancerous cells to a combination of drugs that act synergistically. The combined 

action of the drugs produces no significant toxic effect on normal cells while leukemia cells are 

irreversibly killed. The mechanism of action of the drugs tested has been determined, thereby providing 

a screening strategy for new, potentially more effective drug combinations. The protocol has so far been 

developed using cultured cells and remains to be tested in animal models. 







Disease Treatments Using Multimeric TNFSF Ligands 

UCSD researchers have developed an invention useful for: 

1. augmenting immunity (both cellular and antibodies) against cancer and infectious 

diseases 

2. Expanding immune cells (B cells, dendritic cells, macrophages and T cells) in vitro for 

reinfusion of them or their products 

3. Immunological testing of immune function. In one embodiment, the invention is a soluble 

recombinant fusion protein containing multiple CD40 ligands ("CD40L"). 

This protein affects macrophages and B cells in the same manner as membrane CD40L. The same 

technology can be applied to produce other members of the TNF family, such as TNF-alpha, FasL, 

TRAIL, RANKL, 4-1BBL, and others. 

The advantages of this new form of CD40L are: 

● Versatile - treatment for cancer and infectious disease agents such as HIV and Mycobacterium 

tuberculosis; vaccines; expanding immune cells; and diagnostic tests of immune function; may 

have utility in neutralizing autoimmune response in diseases such as lupus or multiple sclerosis. 

● Potent - affects macrophages and B cells in the same manner as membrane CD40L. 






Diagnosis of Cancers with Metastatic Potential 

Background: PINCH (Particularly Interesting New Cys-His) protein and its associated Integin-linked 

Kinase (ILK), appear critical to signal transduction at a key convergence point among integrin, receptor 

tyrosine kinase, and Rac pathways. Their relevance for metastatic disease is highlighted by the 

consistent over-expression of PINCH in the stroma of cancers with metastatic potential and of ILK in the 

cancer itself; PINCH up-regulation is particularly intense in stroma at the cancer invasive edge and in 

stroma of metastatic lesions. 

In colorectal cancer, stromal PINCH immunostaining at the cancer invasive edge has been 

demonstrated to be a significant independent predictor of reduced survival Studies with other cancers 

such as breast, prostate, and lung cancer have shown similar results, with a pattern of PINCH upregulation 

in the tumor stroma. The common findings for a number of different cancers suggest that 

PINCH may be a broadly useful indicator of cancer invasive and metastatic potential, measured alone 

or in combination with ILK. 

Technology: The invention also provides a method for identifying a cell proliferative disorder in a 

subject comprising: 

● quantifying the expression of PINCH, ILK, or a combination thereof and 

● correlating the level of expression with the presence of a cell proliferative disorder, wherein an 

elevated level of PINCH and/or ILK is indicative of metastatic potential. 

The test is currently performed by immunohistochemistry of formalin-fixed, paraffin-embedded or frozen 

tissue sections. Quantitative polymerase chain reaction (qPCR) assays are under development for 

single target and multiplexed analysis. 

Advantages: There is a major need for the development of clinical tests that assess a cancer's 

metastatic potential. This invention may provide an objective means to: 

● identify low grade and in situ lesions that should be treated surgically vs. watchful waiting (e.g. 

breast and prostate biopsies) 

● assess surgical resection specimens to guide the selection of therapy in a large number of 

common cancers (e.g., among cancers with a generally favorable prognosis, identify more 

aggressive tumors, such as node-negative breast cancer and Dukes' B colon cancer, which 

would benefit from adjuvant chemotherapy) 

● monitor the progress of interventions and therapies 

In sum, this technology may provide a significant benefit in the ability to use one test to determine 

metastatic potential for a number of cancers. 

http://invent.ucsd.edu/technology/cases/1998/SD1998-D00.htm (1 of 2)10/21/2005 7:37:18 AM


Publications: 

● Stromal Staining for PINCH is an Independent Prognostic Indicator in Colorectal Cancer 

● New LIM Protein Containing an Autoepitope Homologous to “Senescent Cell Antigen” 

● The Signaling Adapter Protein PINCH is Up-Regulated in the Stroma of Common Cancers, 

Notably at Invasive Edges 

Additional publications substantiating ILK as a cancer marker: 

1. Takanami I: Increased expression of integrin-linked kinase is associated with shorter survival in 

non-small cell lung cancer BMC Cancer 2005, 5 :1 

2. Ahmed N et. al.: Cell-free 59 kDa immunoreactive integrin-linked kinase: a novel marker for 

ovarian carcinoma Clin Cancer Res 2004, 10 :2415-2420 

3. Dai DL et. al.: Increased expression of integrin-linked kinase is correlated with melanoma 

progression and poor patient survival Clin Cancer Res 2003, 9 :4409-4414 

4. Ito R et. al.: Expression of integrin-linked kinase is closely correlated with invasion and 

metastasis of gastric carcinoma Virchows Arch 2003, 442:118-123 

5. Graff JR et. al.: Integrin-linked kinase expression increases with prostate tumor grade Clin 

Cancer Res 2001, 7 :1987-1991 

6. Chung DH et. al.: ILK (beta1-integrin-linked protein kinase): a novel immunohistochemical 

marker for Ewing's sarcoma and primitive neuroectodermal tumour Virchows Arch 1998, 

433:113-117 

Patent: US 6,245,522 

Case Number: SD1998-D00 

Keywords: PINCH, ILK, prognosis, metastasis, breast, prostate, colorectal, lung 



http://invent.ucsd.edu/technology/cases/1998/SD1998-D00.htm (2 of 2)10/21/2005 7:37:18 AM



Diatom Nitrate Transporter Transgene Promoting Plant Growth on Low 

Nitrate Soils 

BACKGROUND: Currently many plants require high amounts of added nitrate fertilizers for optimal 

growth. Plant growth is often limited by the availability of soil nitrate, which is compensated for by the 

use of nitrate-containing fertilizers. Such fertilizers have numerous and serious environmental side 

effects, not to mention their occasional diversion by terrorists as a bomb component. Diatom nitrate 

transporters have an unusually high affinity for nitrate, which they concentrate from seawater (Dugdale, 

R.C. 1967. Limnol. Oceanog. 12:685; Eppley, et al., 1969. Limnol. Oceanog. 14:912). By transgenic 

expression, plants that contain them have the potential for growing on soil with lower nitrate levels. 

DESCRIPTION: A cDNA clone encoding a nitrate transporter homolog has been isolated from the 

diatom Cylindrotheca fusiformis. The gene contains no introns, and so is well suited to expression in 

other organisms. Constructs are made placing the cDNA clone under the control of plant root-specific 

promoters. Plant growth can then be optimized for low nitrate soils. 

ADVANTAGES: The advantages of this invention are that it could reduce or eliminate the need for 

nitrate fertilizers in crop plants, resulting in similar yield, but without the environmental contamination 

resulting from high amounts of nitrate. 







Selectin Inhibition: Novel Uses For An Already Approved Drug 

UCSD researchers have discovered a method of using currently approved clinical formulations of a 

known drug (heparin) to block in vivo L-selectin and/or P-selectin binding to its natural ligands. The 

method is thought to be useful for preventing and/or treating many diseases and pathological states 

involving inflammation, immune reactions and reperfusion injury, as well as the metastatic process of 

tumor cells. The advantages of this method are: 

● Versatile - has the potential to prevent and/or treat diseases and pathological states involving 

inflammation, immune reactions and reperfusion injury, as well as the metastatic process of 

tumor cells. 

● Potent and Safe - uses very low doses of a currently approved drug. 

SD1998-049 Reference: Lubor Borsig, Richard Wong, James Feramisco, David R. Nadeau, Nissi M. 

Varki, and Ajit Varki Heparin and cancer revisited: Mechanistic connections involving platelets, Pselectin, 

carcinoma mucins, and tumor metastasis PNAS 98: 3352-3357 







Identification and Use of Vascular Surface Molecules for Disease 

Diagnosis and Treatment 

Background: Molecules lining blood vessels are of great importance to researchers trying to find new 

ways to fight cancer. Tumor growth is characterized by complex interactions of neoplastic cells with the 

vascular system. It is known that various secreted molecules and surface proteins (especially aberrant 

adhesion receptors) play a role in tumor growth. With current methods, tissue preparation destroys the 

integrity of epithelial membranes, which limits the ability to understand underlying mechanisms and 

develop compounds effective against proteins as they present in situ . 

Technology: The invention describes a process for the isolation of luminal endothelial cell membrane 

from associated tissue and a method for the identification of characteristic molecules (primarily proteins 

and lipids) associated with the in situ luminal surface of any endothelial membrane. It is particularly 

applicable to vasculature, but broadly is applicable to all tissue cavities, which are accessible from 

adjacent perfusable lumens. The method requires perfusion with colloidal silica to form a pellicle; the 

coated area of tissue is then excised, homogenized, and centrifuged to isolate coated plasmalemma 

fragments. Normal vs. diseased and/or dysfunctional tissue can then be examined comparatively to 

identify proteins highly enriched and/or unique for normal and abnormal endothelia. 

Advantages: This invention has diagnostic and therapeutic applications. Specifically, one can: 

● fully characterize protein differences between normal and diseased tissues 

● identify tumor-specific variants for immunolocalization of tumor-specific proteins 

● create antibodies which specifically binding to membrane sites of interest 

Issued US Patents: 5,281,700, 5,587,297 & 5,610,008 

Issued International Patent : Australia 

Research interests can be found at: http://www.skcc.org/schnitzer.html 

Case Number: 1990-A32 

Keywords: endothelial membrane, blood vessel, separation 


http://invent.ucsd.edu/technology/cases/1995-prior/SD1992-A32.htm (1 of 2)10/21/2005 7:37:20 AM



http://invent.ucsd.edu/technology/cases/1995-prior/SD1992-A32.htm (2 of 2)10/21/2005 7:37:20 AM

UNIVERSITY OF CALIFORNIA, SAN FRANCISCO 

Office of Technology Management 

Cancer Technologies Available for Licensing 

University of California, San Francisco 


185 Berry Street, Suite 4603 

San Francisco, CA 94107 

Office: (415) 353-4469 

FAX: (415) 348-1579 

• Carcinogenesis Model Encompassing the Range of Prostate Cancer 

Progression and Metastasis (SF2005-005) 

• Method for Treating Leukemia by Inhibition of Wnt16 (SF2004-032) 

• Small Molecule Modulators of PKB and Wnt Pathways (SF2002-032 and 

SF2004-069) 

• Small Molecule Potentiator of Hormonal Therapy for Breast Cancer 

(SF2005-110) 

• Small Molecule Inhibitors of MDM2 Oncoprotein (SF2002-024) 

• Targeted Cytotoxic Gene Therapy for Human Papillomavirus Infections 

(SF2000-047) 

• saRNA-directed Transcriptional Activation (SF2005-066) 

• A diagnostic test to personalize patient therapy using platinum-based 

anticancer drugs (SF2005-121) 

• Cre-activatable BRAF Cancer Mouse Model (SF2005-124) 

• A Therapeutic Target and Diagnostic Mutations Associated with Distinct 

Melanoma Subgroups (SF2006-030) 

University of California, San Francisco top 


http://www.otm.ucsf.edu/

Carcinogenesis Model Encompassing the Range of Prostate Cancer Progression and 

Metastasis (SF2005-005) 

Currently there is a lack of information and models for understanding human prostate 

cancer progression. Most models currently available only allow for comparison of 

tumorigenic versus non-tumorigenic states. UCSF investigators have developed a series 

of human prostatic epithelial cell lines that encompass the range of prostate cancer 

progression. These cells are derived from the parental BPH-1 non-tumorigenic 

immortalized human prostatic epithelial cell line (see References below) using tissue 

recombination methods. Upon hormonal treatment, the cells exhibited either nontumorigenicity, 

tumorigenicity, epithelial to mesenchymal transition (EMT), and 

metastasis. Progression uniquely occurs in initiated but non-tumorgenic epithelial cells 

and has been characterized by histopathological criteria, tumor mass size, and associated 

changes in expression of gene products. 

ADVANTAGES: 

• First prostate cancer progression model that metastasizes. 

• Display full range of clinical stages of prostate cancer relevant to human disease. 

• Allows comparison between each cell line/condition to evaluate genetic and 

epigenetic changes associated with tumor progression. 

• Genetically altered prostatic inducers can be incorporated into this model. 

• Potential Uses: 

• Testing novel therapeutic regimens specific to cancer state and progression. 

• Development of biomarkers for cancer. 

REFERENCES: 

Wang, et al. Cancer Research (2001) 61:6064-6072 

Hayward, et al. Cancer Research (2001) 61:8135-8142 

If you would like to receive further information about this technology and potential 

licensing opportunities, please contact: 

Sunita Rajdev, Ph.D. 

Licensing Officer 

Tel: (415) 353-4470 

sunita.rajdev@ucsf.edu 




Method for Treating Leukemia by Inhibition of Wnt16 

(SF2004-032) 

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) accounts for 20% of all adult 

cancers and almost 25% of all childhood cancers, making it the most common pediatric 

cancer. ALL is a malignant disease characterized by large populations of immature white 

blood cells in the blood and bone marrow. Chromosomal translocations are often 

associated with ALL, with the t(1:19) translocation occurring most often. Cells 

possessing the t(1:19) translocation overexpress Wnt16, which is a member of a secreted 

glycoprotein family widely involved in proliferation, differentiation, and oncogenesis. 

B cell chronic lymphocytic leukemia (CLL) is the most common human leukemia and is 

characterized by the accumulation of mature, but functionally incompetent, B cells. 

These cancerous cells are believed to result from abnormal regulation of apoptosis and 

also overexpress Wnt16. 

DESCRIPTION: Researchers at the University of California, San Francisco have 

validated Wnt16 as a therapeutic target for leukemia using both siRNA and an anti- 

Wnt16 antibody. Inhibition of Wnt16 in ALL cell lines resulted in apoptosis and cell 

death. Additionally, the Wnt16b isoform, but not Wnt16a, was shown to be involved in 

ALL-associated disruption of apoptosis. Inhibition of Wnt16 expression led to a decrease 

in b-catenin, Dvl-2, and survivin expression, showing that Wnt16 dependent apoptosis 

occurs through the canonical Wnt pathway. These methods will assist in the 

development of treatments and diagnostics for ALL and CLL, two important human 

leukemias. 

POTENTIAL APPLICATIONS FOR THIS TECHNOLOGY: 

• Inhibition of Wnt16 through siRNA and an anti-Wnt16 antibody 

• Wnt16 inhibition induces apoptosis of ALL cells 

• Methods of using anti-Wnt16 treatments for ALL and CLL 

PUBLICATION 

http://www.nature.com/onc/journal/v24/n34/abs/1208568a.html;jsessionid=E957EF2975 

2CB0A00DE947E51CE95765 



Anson Nomura, Ph.D. 

Licensing Associate(415) 353-4626 phone 

(415) 348-1579 fax 

Anson.Nomura@ucsf.edu 




Small Molecule Modulators of PKB and Wnt Pathways 

(SF2002-032 and SF2004-069) 

BACKGROUND: 

The protein kinase B (PKB) pathway and Wnt protein pathway transmit cellular signals 

important in the regulation of cell growth, proliferation, and metabolism. Therefore, a 

good therapeutic strategy for the treatment of cancer may involve the modulation of 

either of these two different signaling pathways. More recently, Wnt proteins have also 

been associated with osteoporosis, rheumatoid arthritis, and osteoarthritis. 

DESCRIPTION: 

Scientists at UCSF have discovered several small molecule modulators of the PKB and 

Wnt pathways. Each of these small molecules is a beta-sheet mimic that targets PDZ 

domains. In particular, these molecules have been shown to bind to MAGI3 and 

Dishevelled, PDZ domain containing proteins in the PKB and Wnt pathways, 

respectively. Data shows one of the compounds causes apoptosis in cancer cells 

overexpressing Dishevelled and suppresses tumor growth in xenograft mouse models. 

These inhibitors were designed to functionally mimic beta sheets, a recurring structure in 

protein-protein interfaces. As a result, they may be employed to produce a wide array of 

pharmaceutical compositions that inhibit protein-protein interactions known to play a role 

in a variety of disease states. 

APPLICATIONS: 

• Cancer therapeutics 

• Treatments for rheumatoid arthritis and osteoarthritis 

• Functional probes of the activity of PDZ domain containing proteins 

• Proteomics reagents for isolation of active PDZ domains in cells 

• Inhibitors of protein-protein interactions relevant to other diseases 

ADVANTAGES: 

• Selective potent reversible and irreversible inhibitors 

• Inhibitors show cellular and mammalian activity 


licensing opportunities, please contact Ngoc-Ha Nguyen at ngoc-ha.nguyen@ucsf.edu or 

Karin Immergluck at Karin.Immergluck@ucsf.edu. 




Small Molecule Potentiator of Hormonal Therapy for Breast Cancer 

(SF2005-110) 

BACKGROUND: Breast cancer is the second leading cause of cancer deaths in women 

with every woman having a one in eight chance of developing the disease over her 

lifetime. Since their U.S. introduction in 1977, antiestrogens such as tamoxifen have 

been used to treat pre- and post-menopausal women with Estrogen Receptor positive 

(ER+) breast cancer. More recently aromatase inhibitors, which prevent estrogen 

synthesis, have been used to treat post-menopausal women with ER+ breast cancer. Both 

of these types of hormonal therapy are now used in combination with chemotherapy or 

alone for adjuvant therapy and can be used as a first-line agent. Hormonal therapy 

provides improved over-all survival and time to recurrence for patients with ER-rich 

tumors. 

Although hormonal therapy can be an effective cytostatic and cytotoxic agent, only 40% 

of the 50-70% of invasive breast cancers that are ER+ respond to such treatment, while 

only 5-10% of ER- tumors regress with endocrine treatment. Even responsive tumors 

eventually develop resistance to hormonal therapy, sometimes within 8-12 months, 

thereby limiting the effectiveness of treatment. Developing compounds capable of 

overcoming resistance to antiestrogen or aromatase inhibitor therapy, or increasing the 

potency of antiestrogen treatment will extend the utility of these widely used agents and 

offer better treatment options for breast cancer patients. 

DESCRIPTION: Researchers at the University of California, San Francisco (UCSF) have 

identified an FDA-approved small molecule that increases the cytotoxicity of 

antiestrogens or estrogen ablation and which could prove useful with multiple 

antiestrogen and aromatase inhibitor breast cancer treatments. The identified drug is 

approved for uses outside of oncology and is generically available. Experiments in which 

antiestrogens or estrogen ablation was used in combination with the compound in the 

therapeutically approved concentration range showed enhanced cytotoxicity. Additional 

cell culture and animal model experiments are ongoing. 

POTENTIAL BENEFITS AND APPLICATIONS FOR THIS TECHNOLOGY: 

• Combination therapy to increase cytotoxicity of antiestrogens or aromatase 

inhibitors for breast cancer 

• Potentiator drug is prescribed outside of oncology and generically available 



Karin Immergluck, Ph.D. 


(415) 353-4469 phone 

(415) 348-1579 fax 

Karin.Immergluck@ucsf.edu 




Small Molecule Inhibitors of MDM2 Oncoprotein 

(SF2002-024) 

BACKGROUND: 

The MDM2 protein antagonizes and blocks p53, an important tumor suppressor protein. 

MDM2 has been validated as a potential target for cancer drug development and MDM2 

overexpression has been determined as the cause of 7% of all cancers. Activation of p53 

in tumor cells by inhibiting the interaction of MDM2 with p53 has therefore been the 

focus of a large effort in drug discovery. 

DESCRIPTION: 

Scientists at UCSF have designed four diverse small molecule inhibitors of the p53- 

MDM2 interaction. One inhibitor was synthesized and was found to inhibit MDM2 in 

vitro. These inhibitors were designed to functionally mimic alpha helices, a recurring 

structure in protein-protein interfaces. As a result, they may be employed to produce a 

wide array of pharmaceutical compositions that inhibit protein-protein interactions 

known to play a role in a variety of disease states. 

APPLICATIONS: 

• Cancer therapeutics 

• Chemical probes of the p53 pathway 

• Inhibitors of protein-protein interactions relevant to other diseases 


licensing opportunities, please contact Ngoc-Ha Nguyen at ngoc-ha.nguyen@ucsf.edu or 

Karin Immergluck at Karin.Immergluck@ucsf.edu. 




Targeted Cytotoxic Gene Therapy for Human Papillomavirus Infections 

(UC Case No. SF2000-047) 

BACKGROUND: 

Human papillomavirus (HPV) is the most common sexually transmitted infection in the 

world, particularly among young adults. As many as 24 to 40 million men and women are 

infected with HPV in the U.S. alone and 0.5 to 1 million new HPV infections occur each 

year. HPV infects the epithelial surfaces of skin or mucosa leading to genital warts and 

squamous epithelial lesions. A persistent HPV infection can lead to cervical cancer, the 

leading cause of cancer-related deaths in women worldwide. At least 80% of squamous 

cell carcinomas of the cervix and vagina harbor HPV, with type 16 being the most 

common. Current treatments for HPV-associated lesions rely on painful removal of the 

HPV-infected tissue and do not treat the infection per se. Thus, there is an urgent need for 

developing treatment strategies for HPV infections that would prevent its progression to 

cancer. 

DESCRIPTION: 

The researchers at UCSF have designed a novel HPV-specific cytotoxic gene therapy 

vector for the treatment of HPV16 infections. Using a specific promoter that responds to 

a HPV-specific transcription factor, our investigators demonstrated that in cell culture 

this method specifically eliminates cells expressing the HPV16 gene with minimal toxic 

effects on HPV-negative cells. Cell killing was also observed in HPV18-positive HeLa 

cells. This method is amenable to developing a HPV-type specific approach to treat 

lesions caused by other strains of HPV. 

This approach represents an important therapeutic advance for the treatment of cervical 

and anal intraepithelial lesions, and is especially useful for eliminating the reservoir of 

HPV from cells with low-grade infection. The optimization of gene delivery methods to 

the anogenital epithelium as well as testing for the safety and efficacy in animal models is 

underway and can be accomplished in routine experimentation. 



Sunita Rajdev, Ph.D. 


Tel: (415) 353-4470 

sunita.rajdev@ucsf.edu 




saRNA-directed Transcriptional Activation 

(SF2005-066) 

BACKGROUND: 

Currently, there is no dependable and generalizable method for the targeted activation of 

endogenous genes. Efforts in gene therapy have been forestalled by problems of gene 

mutagenesis and oncogene activation, resulting in cancer. Yet the pursuit of a method for 

gene activation remains an important goal because the ability to selectively upregulate 

genes acting against a diseased state would have far reaching impact in almost every 

therapeutic realm. 

One of the most promising current approaches to combating disease at the genetic level 

employs small dsRNA molecules as therapeutic compounds to achieve gene silencing by 

RNA interference ("RNAi"). With the ever-increasing amount of research and 

development dollars being spent on RNAi therapeutics, solutions to potential specificity 

and toxicity issues have been addressed, and a large number of delivery methods have 

been developed. These advances have given gene silencing a distinct advantage over 

gene therapy but does not satisfy the need for gene activation methods. UCSF scientists 

have addressed this void by developing a gene activation approach which overcomes 

obstacles in gene therapy by utilizing the advances of RNAi. 

DESCRIPTION: 

Researchers at UCSF have discovered a method using small activating RNA ("saRNA") 

for inducing sequence-specific transcriptional activation. Human cell studies conducted 

at UCSF have shown that this method induced an 8-fold increase in transcriptional 

activation of tumor suppressor gene E-cadherin. Transcriptional activation lasted up to 

10 days and resulted in the anticipated phenotypic readout. 

ADVANTAGES: 

• Long lasting and possibly permanent effect across multiple cell divisions. 

• Overcomes insertional mutagenesis problem associated with gene therapy. 

• This gene activation method can be used in combination with other therapies, 

such as gene silencing. 

• Creates an avenue of therapy for those diseases in which gene silencing has failed 

or is inapplicable. 

• Approach incorporates high specificity and potency. 

APPLICATIONS: 

• Treatment of a wide variety of diseases such as cancer by targeted activation of 

gene expression such as tumor suppressor genes. 

• A fast and convenient research tool for the investigation of gene overexpression. 


licensing opportunities, please contact Karin Immergluck at karin.immergluck@ucsf.edu. 




A diagnostic test to personalize patient therapy using platinum-based anticancer 

drugs (UCSF Case No. 2005-121) 

BACKGROUND: 

Platinum-based anticancer drugs, such as the US approved drugs cisplatin, carboplatin, 

and oxaliplatin, are among the most active anticancer agents. These platinum compounds 

are known to bind to DNA and trigger cell cycle arrest and apoptosis of cancer cells. 

These drugs appear to have similar anticancer mechanism(s), but vary in their anticancer 

spectrum and toxicity. For example, oxaliplatin generally has comparable or superior 

anticancer activity but significantly lower nephrotoxicity compared to cisplatin. The drug 

is active against colorectal cancers, for which cisplatin and carboplatin are essentially 

clinically inactive. The clinical application of these platinum compounds, however, is still 

limited by their toxicity and chemoresistance. Thus, there remains a need for improved 

platinum-based anticancer therapies. 

DESCRIPTION: 

UCSF investigators have identified a class of proteins that play a critical role in the 

anticancer mechanism of oxaliplatin. Presence of these proteins increases the 

pharmacological effect of oxaliplatin, which can potentially lower the effective 

concentration to achieve equal or greater therapeutic effects with reduced systemic 

toxicity. Furthermore, this identified protein class would be good therapeutic targets to 

understand and prevent chemoresistance of oxaliplatin and other platinum-based drugs. 

Diagnostic tests could be developed based on the identified protein class to personalize 

platinum-based therapy and predict prognosis. Diagnostic tests would allow doctors to 

determine: 

(1) What types of cancer will better respond to which class of platinum-based 

therapy, which is dependent on the expression or activity level of the protein in the tumor 

tissue. 

(2) Which patients, based on their genotype for the identified protein, will better 

respond to certain therapies, where patients with genetic mutations of the protein 

(resulting in reduced protein expression or activity) might display chemoresistance. 

If you would like to receive more information about this technology and potential 

licensing opportunities, please contact Ha Nguyen at ngoc-ha.nguyen@ucsf.edu or Karin 

Immergluck at karin.immergluck@ucsf.edu. 




Cre-activatable BRAF Cancer Mouse Model 

(SF2005-124) 

BACKGROUND: BRAF is a member of the Raf family of protein kinases, which also 

includes ARAF and CRAF. Raf function is necessary for proper development, with 

BRAF having significant expression in neuronal tissue. Extra-cellular signals (e.g. 

mitogens, hormones, etc.) increase the concentration of cellular Ras-GTP, which binds 

and localizes BRAF to the plasma membrane. At the plasma membrane, phosphorylation 

and activation of BRAF leads to phosphorylation of MEK and ERK, causing 

phosphorylation of cytoskeletal proteins, kinases, and transcription factors. These 

downstream proteins are responsible for changes in cell proliferation, differentiation, and 

survival, among other effects. Activating mutations in BRAF have been detected in 

multiple human malignancies. 60-70% of melanomas, 35-70% of papillary thyroid 

cancers, and 10% of colon cancers contain BRAF mutations. Additionally, certain 

ovarian and lung cancers also possess BRAF mutations. Over 80% of the oncogenic 

BRAF mutants identified to date are a single valine to glutamic acid substitution at 

position 600. This mutant allele displays constitutive kinase activity leading to 

dysregulation of downstream effectors. 

DESCRIPTION: Researchers at the University of California, San Francisco have created 

a Cre-activatable V600E BRAF mouse that will be useful for generating multiple cancer 

models based on activated BRAF. This mouse strain expresses wild-type BRAF under 

the control of normal promoter/enhancer sequences except in cells expressing the Cre 

recombinase. Tissue specific expression of Cre results in substitution of wild-type BRAF 

expression with the activated V600E BRAF mutant still under control of the normal 

BRAF promoter/enhance and subject to wild-type splicing mechanisms. Many useful 

mouse models of human disease can be generated through crossbreeding with tissue 

specific Cre expressing lines. These cancer models will more closely mimic the initiation 

and progression of BRAF-induced cancers, originating from somatic mutations, over the 

less optimal over-expression strains that are widely used as tumor models. 

POTENTIAL BENEFITS AND APPLICATIONS: 

• V600E substitution identified in over 80% of oncogenic BRAF alleles 

• Generation of mouse models with tissue specific V600E BRAF under wild-type 

promoter/enhancer control instead of simple oncogene over-expression 

• Cross-breeding with Cre expressing lines will generate activated BRAF cancer 

models 



Anson Nomura, Ph.D. 

Licensing Associate 

(415) 353-4626 phone 

(415) 348-1579 fax 

Anson.Nomura@ucsf.edu 




A Therapeutic Target and Diagnostic Mutations Associated with Distinct Melanoma 

Subgroups 

(SF2006-030) 

BACKGROUND: 

The American Cancer Society estimates that there are currently 480,000 cases of 

melanoma in the U.S. today. In the U.S., Europe and Australia, 90,000 new cases are 

diagnosed per year, with the incidence increasing at a rate of 4.3% per year, one of the 

fastest increases in occurrence rates of all cancers. Melanoma remains difficult to treat. 

Current treatment regimens include surgical removal of the melanoma, general 

chemotherapy, radiation therapy, and immunotherapies such as with interferon and 

interleukin-2. It is known that melanomas from intermittently sun-exposed skin harbor 

frequent mutations in BRAF. However, the primary genetic contributions to melanomas 

from other anatomic sites are currently unknown. 

DESCRIPTION: 

Within distinct subgroups of melanoma, which do not harbor mutations in those 

oncogenes normally associated with melanoma, UCSF researchers have discovered 

recurrent genetic mutations affecting the activity and/or expression level of a gene not 

previously associated with the disease. 

APPLICATIONS: 

• New therapeutic target for distinct melanoma subgroups. 

• Diagnostic marker for determining those melanoma subgroups that might benefit 

from a targeted therapeutic. 


licensing opportunities, please contact Karin Immergluck at 

karin.immergluck@ucsf.edu. 




The following technologies related to cancer are available for licensing from Los Alamos 

National Laboratory. For more information, please contact LANL Technology Transfer at 

(505) 665-9090, or by e-mail: techtransfer@lanl.gov 

Wavelength-Based Sensors for the Early Detection of Cancer 

UV Absorbent Nanomaterials 

Acoustic Particle Focusing for Flow Cytometry 

Gold Coated Nanoparticles for Biotechnology Applications 

Polymeric Chelators for Radioisotope Delivery Systems 

Non-Invasive Diagnostics 

LANL Home: http://www.lanl.gov/orgs/tt/index.shtml

Wavelength-Based Sensors for the Early Detection of Cancer, a licensable technology at Los Alamos National Laboratory 

skip to: lanlbar | menubar | toolbar | links | content 

Licensing, TT 

● Technology Transfer 

(505) 665-9090 

e-mail: 

techtransfer@lanl. 

gov 

Wavelength-Based Sensors for the Early Detection of Cancer 

Abstract 

The inventors have developed methods for detecting cancers using tumor antigens with the optical waveguide technologies. 

The invention describes a rapid, sensitive and inexpensive method for detecting carcinoembryonic antigen (CEA), a 

clinically relevant marker for breast cancer and other tumors. 

Application(s) 

● Cancer diagnostics 

● Veterinary 

Advantages 

● Accuracy 

● Low cost 

● Ease of use 

● Creation of a reagent market 

IP Status: Available both Exclusively and Non Exclusively 

Reference Number: 306 

S Number: DOE reference no.(s): 102,367 

Patents & Applications: 

Application(s) Filed 

Posted: 11-03-2004 

Contact 

Allen Morris 

Technology Transfer Division 

Los Alamos National Laboratory 

P.O. Box 1663, MailStop C334 

(505) 665-9597 

tamorris@lanl.gov 

http://www.lanl.gov/orgs/tt/license/technologies/index.php?fuseaction=home.viewTechnology&id=306 (1 of 2)10/25/2005 7:45:28 AM

Wavelength-Based Sensors for the Early Detection of Cancer, a licensable technology at Los Alamos National Laboratory 

Operated by the University of California for the U.S. Department of Energy 

Inside | Privacy Policy | Copyright © 1993-2005 UC | Web Contact 


UV Absorbent Nanomaterials, a licensable technology at Los Alamos National Laboratory 


Licensing, TT 


(505) 665-9090 

e-mail: 


gov 

UV Absorbent Nanomaterials 

Abstract 

The American Academy of Dermatologists estimates that more than 1 million Americans will be diagnosed with skin cancer 

this year. The primary cause of skin cancer is overexposure to the dangerous ultraviolet (UV) radiation in sunlight. Existing 

organic sunscreen agents readily photo-degrade and are not broadband absorbers (unless used as mixtures). Further, existing 

inorganic sunscreens, based on wide-gap semiconductors, do not protect against the entire UV spectrum. Thus, there remain 

significant unmet needs for safe, long-lasting sun protection across the entire spectrum of dangerous UV light.LANL 

scientists have invented a new class of sun protective materials. These new sunscreen materials blend semiconductor or 

metal nanocrystals into a suitable carrier matrix. Nanocrystals provide substantial broadband absorption of ultraviolet light 

at wavelengths across the range of both UV-A (320-400 nm) and UV-B (280-320 nm).Related Links: 

http://www.aad.org/ 

http://www.skincancer.org/melanoma/sunscreens.php 

http://www.sciencenews.org/pages/sn_arc98/6_6_98/bob2.htm 


● Sunscreen 

● Cosmetics (e.g. makeup, lotions) 

● UV-protective materials such as coatings that block UV-A 

Advantages 

● A potentially superior inorganic medium designed to absorb UVB & UVA rays maximally across the 

spectrum and to confer skin bronzing. 

● Protect across the entire UVA spectrum 

● Longer lasting than organic sunscreens (organic sunscreens break down in sunlight) 

IP Status: Contact Licensing Executive for Details 





Posted: 02-16-2005 


UV Absorbent Nanomaterials, a licensable technology at Los Alamos National Laboratory 

Contact 

Laura Barber 




(505) 667-9266 

ljbb@lanl.gov 




ACOUSTIC PARTICLE FOCUSING FOR FLOW CYTOMETRY, a licensable technology at Los Alamos National Laboratory 


Licensing, TT 


(505) 665-9090 

e-mail: 


gov 

ACOUSTIC PARTICLE FOCUSING FOR FLOW CYTOMETRY 

Abstract 

Flow cytometry is a powerful biomedical assay technology used for many clinical applications including HIV and cancer 

diagnostics. Flow cytometry has also become an important analytical platform to perform biological point detection, biosurveillance, 

and forensic analysis in support of homeland defense. Several restrictions have limited flow cytometer 

applications to formal laboratory settings. These restrictions include the instrument size, large volume of consumables, and 

operating expense. A portable, low-cost flow cytometer would have a great impact on global health and research.LANL 

scientists have developed a novel method that addresses the most important limitation to low-cost portable flow cytometry: 

the focusing of particles in a flowing microfluidic stream.This has traditionally been performed using hydrodynamic sheath, 

which requires large volumes of filtered pH controlled sheath buffer. LANL's new method overcomes this limitation by 

using acoustic focusing. Results demonstrate tight focusing of 10 micron particles under realistic flow conditions. 





Application(s) Pending 

Posted: 08-08-2005 

Contact 

Laura Barber 




(505) 667-9266 

ljbb@lanl.gov 



http://www.lanl.gov/orgs/tt/license/technologies/index.php?fuseaction=home.viewTechnology&id=63810/25/2005 7:45:30 AM

Gold Coated Nanoparticles for Biotechnology Applications, a licensable technology at Los Alamos National Laboratory 


Licensing, TT 


(505) 665-9090 

e-mail: 


gov 

Gold Coated Nanoparticles for Biotechnology Applications 

Abstract 

A method for coating magnetic nanoparticles with a very thin layer of gold. Because many biological markers and linkers 

have been adapted to attach to gold surfaces, a functional coating of gold allows nanoparticles of other materials to be used 

with the established markers and linkers. Magnetic nanoparticles are of particular interest for in vivo imaging and treatment 

operations. 


● Image enhancement in magnetic based diagnostics (such as MRI or other proprietary techniques) 

● Cancer imaging and treatment 

Advantages 

● Avoids direct contact between biological tissue and the core nanoparticle material 

● Permits a wide range of magnetic materials to be used in biological tissue 

● Simple, rapid, and relatively inexpensive chemical process 






Posted: 09-01-2005 

Contact 

Allen Morris 




(505) 665-9597 



Gold Coated Nanoparticles for Biotechnology Applications, a licensable technology at Los Alamos National Laboratory 




Polymeric Chelators for Radioisotope Delivery Systems, a licensable technology at Los Alamos National Laboratory 


Licensing, TT 


(505) 665-9090 

e-mail: 


gov 

Polymeric Chelators for Radioisotope Delivery Systems 

Abstract 

Los Alamos National Laboratory (LANL) researchers have developed polymeric chelators that can bind hundreds of atoms 

of radioisotope per complex. With this high binding capacity, the system can be adjusted in real time to acquire activity 

loading levels that are appropriate for individual treatments. The chelator system currently in use for isotope delivery binds 

only one atom of the radioisotope being used. This low capacity requires the use of very pure isotopes, which release 

daughter nuclei when the radioisotope begins to decay, causing damage to surrounding tissue. LANL’s multi-atom binding, 

polymeric chelators retain and/or rebind daughter nuclei, increasing the cytotoxicity of the treatment at the target area and 

decreasing ancillary toxicity in surrounding tissue. In the event that high activity levels are not needed, the high binding 

capacity of polymeric chelators can be used with isotopically dilute media, which reduces the need for chemical or isotopic 

separations from reactor targets. Direct use of reactor-produced isotopes will facilitate bringing new isotopes to the market. 

In addition to the therapeutic uses for the polymeric chelators, the research shows that this radioisotope delivery system 

vastly improves diagnostic and imaging capabilities. For in vivo utilization, the polymeric chelators can be attached to cellspecific 

targeting molecules such as proteins and monoclonal antibodies, or injected directly at the localized tumors as 

colloids, or otherwise immobilized. This invention has not yet been tested in vivo. 


● Medical imaging 

● In vivo cancer therapy 

● In vivo diagnostics 

Advantages 

● Enables dose-tunable delivery system, increasing therapeutic efficacy Improves cytotoxic activity in 

specific area, with less damage to surrounding tissue 

● Can be used directly with reactor-produced isotopes, decreasing the cost and time to market for many 

isotopes 

● Highly specific for imaging, diagnostic and therapeutic applications 





Application(s) Pending 


Polymeric Chelators for Radioisotope Delivery Systems, a licensable technology at Los Alamos National Laboratory 

Posted: 05-23-2005 

Contact 

Allen Morris 




(505) 665-9597 





04/04 

Applications: 

■ Measuring absorption changes 

in tissue that result from 

changes in tissue morphology— 

cancer diagnosis and screening, 

probe localization in tissue 

■ Drug metabolism studies 

■ Comprehensive assessment of 

the optical characteristics of the 

human lens to identify early 

indicators of cataract or other 

disease processes 

Benefi ts: 

■ Real-time cancer screening, 

may replace more expensive, 

time-consuming lab tests 

■ Non- or minimally-invasive 

biopsy of suspicious lesions in 

patients 

Contact: 

Licensable 

Technologies 

Allen Morris, 505-665-9597, 


Non-Invasive Diagnostics 

Summary: 

A portfolio of patented technologies has been created by the Laboratory’s 

Biosciences and Chemistry Divisions. All of these technologies are related to 

the application of light and lasers for noninvasive diagnosis of human and 

animal conditions, including cancer. These methods can also be applied as 

in vivo clinical research tools to assess drug concentrations. The Laboratory is 

continuing to make innovative discoveries in this research area. A listing of 

issued and pending patents is provided below. 

Development Stage: 

Many of the technologies have been tested on various materials and tissues 

and may be ready for animal and clinical testing. 

Patent Status: 

�� 

�� 

U.S. Patent 6,381,018 Method for Measuring in Light Absorption of Highly 

Scattering Media 

U.S. Patent 6,011,626 Characterization of Highly Scattering Media by 

Measurement of Diffusely Backscattered Polarized Light 

U.S Patent 5,894,340 Method for Quantifying Optical Properties of the 

Human Lens 

U.S Patent 5,738,101 Optical Imaging Through Turbid Media with a 

Degenerate Four-Wave Mixing Correlation Time Gate 

Licensing Status: 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

UC/LANL is seeking to execute research and commercial license agreements. 

www.lanl.gov/partnerships/license/technologies/ 

Los Alamos National Laboratory, an affi rmative action/equal opportunity employer 

is operated by the University of California 

for the Department of Energy under contract W-7405-ENG-36.

LANL |Technology Transfer | Home Page 


Technology Transfer, TT 

● Division Leader 

Duncan McBranch 

● Office Administrator 

Arlene Lopez 

● Chief of Staff 

David Holmes 

● Program Managers 

Ken Freese 

Jerome Garcia 

John Mott 

Belinda Padilla 

Tech Transfer Division 

The Laboratory’s Technology Transfer Division helps move technologies 

from the Lab to the marketplace to benefit society and the U.S. economy. 

We do this by licensing a wide range of cutting-edge technologies to 

companies that have the financial, R & D, manufacturing, marketing, and 

managerial capabilities to successfully commercialize Lab inventions. 

In addition, we manage Lab-industry research partnerships, ensure that 

inventions receive proper intellectual protection, license technology to startup 

companies, and serve as the Lab resource on industry relations. 

Search licensable technologies: 

Technology Maturation Fund 

http://www.lanl.gov/orgs/tt/index.shtml (1 of 2)10/25/2005 7:45:33 AM 

A new one-page flyer about our Tech Mat 

Program 

Technology Transfer 2004 Progress 

Report 

Los Alamos technologies in the 

marketplace, partnerships with 

industry, awards for tech transfer, and 

much more... 

RELATED LINKS 

● TT News | Awards 

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● Training and Networking 

● Publications 

TECH TRANSFER NEWS 

Laboratory captures four R&D 

100 Awards 

See Lab Newsletter about all 

entries 

our technology to you 

Licensable Technologies 

Newest Available Technology: 

Nanophosphor Composite 

Scintillator Radiation Detection

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Inside | Privacy Policy | Copyright © 1993-2005 UC | techtransfer@lanl.gov 

http://www.lanl.gov/orgs/tt/index.shtml (2 of 2)10/25/2005 7:45:33 AM 

Materials 

● Bioscience/Biotechnology 

● Engineering 

● Information Technology 

● Materials 

● Physics & Chemistry 

● Security & Defense

Lawrence Berkley 

National Laboratory 

Profiles of Current Technologies 

Available for Licensing and Collaboration 

Please refer to the list of technologies below for licensing and research collaboration availability. 

For a full list of available technologies, see www.lbl.gov/tt. If you can't find the technology you're 

interested in, please contact us at TTD@lbl.gov. 

Last Updated: 9/20/2005 

Cancer Biotechnology and Medicine 

● Biomarker for Cell Senescence 

● Genes Encoding Telomere-Associated Proteins 

● Gene Therapy Target for Invasive Breast Cancer 

● Marker for Human Breast Cancer 

● Predictive Markers and Therapeutic Targets for Drug 

Resistant Ovarian Cancer 

● Quantum Dot Based Cell Motility, Invasion, and Metastasis 

Assays 

● Antibodies for Monitoring and Phosphorylation Sites for 

Inhibiting DNA Double-Strand Break Repair 

● Transgenic Mice: Breast Cancer and Leukemia 

● Breast Cancer Therapy and Potential Method for Enhancing 

Radiation Sensitivity via Inhibition of ß1 Integrin 

● Polymerized Nanoparticle Therapeutics

Technology Transfer at Berkeley Lab 

Available 

Technologies 

For Industry 

For LBNL 

Researchers 

About the Tech 

Transfer 

Department 

Technology 

Transfer Success 

Stories 

Contacts 

Get More Info 

Join Mailing 

SEARCH 

Privacy & Security 

http://www.lbl.gov/tt/10/24/2005 3:55:39 AM 

Berkeley Lab Technology Transfer 

in the News 

Fairchild Imaging licenses Berkeley Lab's CCD 

technology for near infrared imaging in the 

space and biotech industries. Read more here. 

Scientists at Lawrence Berkeley National 

Laboratory have garnered three R&D 100 

Awards, R&D Magazine's picks for the 100 

most technologically significant new products 

of 2005. This is the first time since 1992 that 

Berkeley Lab has captured three of the 

prestigious awards in a single year, bringing 

the Lab's total of these "Oscars of Invention" 

to 37. Read more here.

Biomarker for Cell Senescence 

Available 

Technologies 

For Industry 

For LBNL 

Researchers 


Transfer 

Department 

Technology 

Transfer 


Contacts 

Get More Info 

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SEARCH 

AVAILABLE TECHNOLOGIES 


E.O. Lawrence Berkeley National Laboratory 

APPLICATIONS OF 

TECHNOLOGY: 

● Screen compounds for 

effects on cell senescence, 

including high throughput 

applications 

● Pre and post surgical tissue 

assay 

● Cancer and aging research 

ADVANTAGES: 

This method provides a rapid, 

convenient and inexpensive basis 

to: 

● Screen biological or 

pharmaceutical compounds 

that have anti-tumor, antiaging, 

or proliferationmodulating 

properties. 

http://www.lbl.gov/Tech-Transfer/techs/lbnl1036.html (1 of 3)10/24/2005 3:55:40 AM 

A test developed by Berkeley 

National Laboratory researchers 

uses blue stain to detect the 

presence of senescent cells. The 

assay top left shows young tissue 

with no presence of blue; top right is 

young sunburned tissue, also 

negative. Older tissue cells, pictured 

in the bottom four assays, contain 

blue areas revealing evidence of the 

existence of senescent cells. 

● Identify senescent cells in culture without the use of 

radioactivity or costly and time-consuming immunodetection 

methods. 

● Identify senescent cells in situ in tissues or in freshly isolated 

cells, to distinguish them from quiescent, terminally 

differentiated, or physiologically compromised cells. This will 

provide a means to evaluate, in vivo, the physiological, as 

opposed to chronological, age of the tissue. 

● Separate, quantitate, and culture senescent cells from 

heterogeneous cell populations. 

● Rapidly provides information useful for pre- and post-surgical 

diagnoses and prognoses such as: 

❍ Degree to which benign or malignant tumors have 

escaped senescence,


ABSTRACT: 

❍ Regenerative capacity of tissues prior to surgical 

procedures, 

❍ Extent of proliferative capacity of a tissue or cell type 

Eukaryotic cells, after proceeding through a finite number of cell 

divisions, enter a state characterized by irreversible growth arrest 

and altered function. Researchers believe that entry into this 

senescent state is a dominant, genetically controlled process that 

constitutes a tumor suppressive mechanism. Berkeley Lab and New 

England Medical Center researchers have now developed a 

convenient, single cell-based technique that readily identifies 

senescent cells in heterogeneous populations. This is the first 

biomarker of cell senescence that does not rely on measurements of 

DNA synthesis for detection. Berkeley Lab's method clearly 

distinguishes senescent cells from quiescent, terminally 

differentiated or physiologically compromised cells grown in vitro. 

This method also identifies the senescent state in cells of certain 

tissues grown in vivo, including skin cells. Berkeley Lab's technique 

will provide a valuable tool to develop rational interventions in the 

areas of aging and cancer. A convenient kit incorporating Berkeley 

Lab's procedure, useful to medical staff in offices and hospitals, 

would simply, immediately, and inexpensively aid in the diagnosis 

and prognosis of a variety of surgical procedures and pharmaceutical 

regimens. 

STATUS: US Patents 5,491,069 and 5,795,728; available for 

licensing 

FOR ADDITIONAL INFORMATION, PLEASE SEE: 

Dimri, G.P. et al., "A biomarker that identifies senescent human cells 

in culture and in aging skin in vivo," Proc. Natl. Acad. Sci., 1995, 92, 

9363-9367. 

REFERENCE NUMBER: IB-1036 

Technology Licensing Interest Form Join Mailing List See More Biotech 

& Medicine Technologies 

http://www.lbl.gov/Tech-Transfer/techs/lbnl1036.html (2 of 3)10/24/2005 3:55:40 AM


CONTACT: 

Technology Transfer Department 


MS 90-1070 

Berkeley, CA 94720 

(510) 486-6467 FAX: (510) 486-6457 

TTD@lbl.gov 

Top · Home · Available Technologies · For Industry · For LBNL Researchers 

About Tech-Transfer · Success Stories · Contacts · Get More Info · Search 


Genes Encoding Telomere-Associated Proteins 

Available 

Technologies 

For Industry 

For LBNL 

Researchers 


Transfer 

Department 

Technology 

Transfer 


Contacts 

Get More Info 

Join Mailing 

SEARCH 



Ernest Orlando Lawrence Berkeley National Laboratory 

APPLICATIONS OF 

TECHNOLOGY: 

● Molecular 

biology research 

● Medical 

research 

ABSTRACT: 

Telomeres are 

believed to be critical 

regulators of the 

genome, and telomere 

stability important for 

preventing cancer and 

ageing. Regulation of 

telomere length is 

believed to be 

controlled by multiple 

telomere-associated 

proteins. Using a 

previously cloned 

human telomere 

binding protein, 

Berkeley Lab 

researchers Sahn-ho 

Kim and Judith 

Campisi cloned two 

novel human telomereassociated 

proteins, 

TANK-2 and TIN-2. 

The full length 

sequence of one, and 

a partial sequence of 

the other is known. 


a, Metaphase chromosomes from uninfected cell 

stained with anti-TIN2 (endogenous TIN2) 

antibody. b, Metaphase chromosomes from 

Myc–TIN2-expressing cell stained with anti-Myc 

(retroviral TIN2) antibody. c, Interphase nucleus 

of an HA–TRF-1/Myc–TIN2-expressing cell 

stained with anti-Myc (retroviral TIN2) antibody. 

d, Interphase nucleus of the same HA–TRF-1/ 

Myc–TIN2-expressing cell stained with anti-HA 

(retroviral TRF1) antibody. e, Co-localization of 

HA–TRF1 and Myc–TIN2 in nucleus shown in (c) 

and (d) (merged image). f, DAPI staining of 

nucleus shown in (c–e). g, Interphase nucleus of 

another HA–TRF-1/Myc–TIN2-expressing cell 

stained with anti-Myc (retroviral TIN2) antibody. 

h, Interphase nucleus of the same HA–TRF-1/ 

Myc–TIN2-expressing cells stained with anti-HA 

(retroviral TRF1) antibody. i, Co-localization of 

HA–TRF1/Myc–TIN2 in nucleus shown in (g) and 

(h) (merged image). j, DAPI staining of nucleus 

shown in (g–i). k, Metaphase chromosomes from 

HA–TRF1/Myc–TIN2-13–expressing cell stained 

with anti-HA antibody (telomeric localization of 

TRF1 in the presence of TIN2-13). l, Metaphase 

chromosomes from HA–TRF1/Myc–TIN2- 

13–expressing cells stained with anti-Myc 

antibody (telomeric localization of TIN2-13).


TANK-2 and TIN-2 may be important telomere regulators, and 

therefore of interest in the health care arena for the diagnosis or 

treatment of cancer or age-related diseases. 

STATUS: U.S. Patent # 6,409,648 /Available for licensing 

PUBLICATIONS: 

"TIN2, a new regulator of telomere length in human cells," Sahn-ho 

Kim, Patrick Kaminker & Judith Campisi, Nature volume 23 no. 4 

pp 405 - 412 (1999) 




CONTACT: 



MS 90-1070 


(510) 486-6467 FAX: (510) 486-6457 

TTD@lbl.gov 




Available Technologies: Gene Therapy Target for Invasive Breast Cancer 

Available 

Technologies 

For Industry 

For LBNL 

Researchers 


Transfer 

Department 

Technology 

Transfer 


Contacts 

Get More Info 

Join Mailing 

SEARCH 


Gene Therapy Target for Invasive Breast Cancer 

APPLICATIONS OF TECHNOLOGY: 

● Gene therapy 

target for 

suppressing 

breast cancer 

metastasis 

● Diagnostic and/or 

prognostic 

marker for 

invasive and 

metastatic breast 

cancer 

ADVANTAGES: 

● Identifies a gene 

target, Id-1, for 

developing 

breast cancer 

treatment that 

could be highly 

effective and 

more 


The mean number of lung metastases of tumorbearing 

mice treated with a control gene 

compared to those treated with Id-1 antisense. 

Systemically targeting Id-1 expression 

significantly reduced the spread of 4T1 breast 

cancer cells. 

discriminate than those currently available 

● Provides a highly accurate marker (ratio Id-1/Id-2) for invasive 

and metastatic breast cancer 

● Using Id-1 protein as a target would beneficially affect multiple 

aspects of breast cancer progression 

● Since Id-1 is scarce in most mature adult tissues, a majority of 

normal cells would not be affected by systemic therapy 

targeting this gene 

● Even a partial reduction in Id-1 levels can profoundly affect


ABSTRACT: 

tumor behavior 

Researchers at Berkeley Lab and the California Pacific Medical 

Center Research Institute (CPMCRI) have discovered a promising 

gene therapy target for suppressing aggressive and metastatic 

breast cancer cells. The same gene product can also serve as a 

reliable marker for breast cancer progression, invasion, and 

metastasis, allowing for accurate diagnoses and prognoses and 

therefore more appropriate therapies. 

Based on previous collaborative research with Judith Campisi of 

Berkeley Lab, Pierre-Yves Desprez and colleagues at CPMCRI have 

shown in pre-clinical studies that human metastatic breast cancer 

cells become significantly less invasive in culture and less metastatic 

in vivo when the Id-1 protein is down-regulated by antisense RNA 

directed against the Id-1 gene. In a highly successful proof-ofconcept 

experiment, these investigators targeted Id-1 expression 

systemically in tumor-bearing mice with a non-viral approach using 

liposomes, significantly reducing Id-1 levels and simultaneously the 

spread of breast cancer cells. These results point to the Id-1 gene as 

an extremely promising target for developing therapies to reduce 

breast cancer metastasis. 


Campisi and 

Desprez earlier 

determined that 

ectopic 

expression of Id- 

1 in murine 

mammary 

epithelial cells 

results in loss of 

differentiation 

and gain of 

invasive and 

proliferative 

abilities. Using


Immunochemistry analysis of Id-1 levels in 4T1 breast 

tumor cells harvested from the lungs of a control mouse 

(A) and an Id-1 antisense-treated mouse (B), Minimal 

staining in the breast tumor cells of the antisense-treated 

mice shows that Id-1 antisense was successful in 

reducing Id-1 levels. 

immunohistochemistry 

they found high 

levels of 

expression of 

the Id-1 protein 

in breast tumor 

biopsies from 

patients with 

aggressive 

cancer and low levels in ductal carcinomas, which are known to be 

noninvasive. In addition, ectopic expression of Id-1 in a noninvasive 

human breast cancer cell line rendered it invasive. 

CPMCRI Studies of Id-2, a gene closely related to Id-1, conclude that 

its expression follows a pattern opposite to that of Id-1. Id-2 is an 

important protein for the maintenance of a differentiated and 

noninvasive phenotype in normal and transformed breast cells. A 

highly accurate method or kit for predicting the likelihood of invasion 

and metastasis could be developed based on determining the ratio 

between Id-1 and Id-2 in breast cancer cells. 

STATUS: 

● Patent pending (application #952,534); available for licensing 

or collaborative research 

FOR MORE INFORMATION: 

Fong, S., Itahana, Y., Sumida, T., Singh, J., Coppe, J.P., Liu, Y., 

Richards, P.C., Bennington, J.L., Lee, N.M., Debs, R.J., Desprez, P. 

Y.," Id-1 as a Molecular Target in Therapy for Breast Cancer Cell 

Invasions and Metastasis," Proc. Natl. Acad. Sci., 2003, 100, 13543- 

48. 

Itahana, Y., Singh, J., Sumida, T., Coppe, J.P., Parrinello, S., 

Bennington, J.L., Desprez, P.Y., "Role of Id-2 in the Maintenance of 

a Differentiated and Noninvasive Phenotype in Breast Cancer 

Cells,"Cancer Res., 2003, 63, 7098-105. 



Lin, C.Q., Singh, J., Murata, K., Itahana, Y., Parrinello, S., Liang, S. 

H., Gillett, C.E., Campisi, J., Desprez, P.Y., "A Role for Id-1 in the 

Aggressive Phenotype and Steroid Hormone Response of Human 

Breast Cancer Cells," Cancer Res., 2000, 60, 1332-40. 




CONTACT: 



MS 90-1070 


(510) 486-6467 FAX: (510) 486-6457 

TTD@lbl.gov 




Marker for Human Breast Cancer 

Available 

Technologies 

For Industry 

For LBNL 

Researchers 


Transfer 

Department 

Technology 

Transfer 


Contacts 

Get More Info 

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SEARCH 




● Human healthcare 

ADVANTAGES: 

● Detects human breast 

cancer in early stage 

ABSTRACT: 

Mina Bissell 

Mina Bissell and colleagues have identified a molecular marker that 

could detect the early stages of human breast cancer. A comparison 

of gene expression among cells of a human breast cancer 

progression series, nonmalignant (S1), premalignant (S2) and 

malignant (T4-2) human breast cells, shows that the expression of a 

new gene, named "AZ-1," abruptly declines as cells become 

tumorigenic. Transcripts of AZ-1, obtained using differential display- 

PCR, were also not detected in ten other malignant human breast 

epithelial cell lines, whereas they were present in normal human 

myoepithelial and luminal epithelial cells. Chromosomal localization 

of the AZ-1 gene has been mapped by fluorescence in situ 

hybridization (FISH). AZ-1 was low or absent in 4 primary breast 

tumors and expressed in normal breast tissue. Based on the inverse 

relationship of its expression level and tumor phenotype in all of the 

tumor cell lines and tissues analyzed, AZ-1 is a potential candidate 

as a tumor marker for human breast cancer. 

STATUS: 

● U.S. Patent #6,753,154 

● Available for licensing 




SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD: 

● Gene Therapy Target and Marker for Invasive Human Breast 

Cancer (IB-1637) 

FOR FURTHER INFORMATION SEE: 

● Chen M, Schmeichel K, Mian IS, Lelièvre SA, Petersen OW 

and Bissell MJ. (2000) AZU-1: A candidate breast tumor 

suppressor and biomarker for tumorigenic reversion. Mol Biol 

Cell 11(4):1357-1367. 



CONTACT: 



MS 90-1070 


(510) 486-6467 FAX: (510) 486-6457 

TTD@lbl.gov 




Available Technologies: Predictive Markers and Therapeutic Targets for Drug Resistant Ovarian Cancer 

Available 

Technologies 

For Industry 

For LBNL 

Researchers 


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Department 

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Predictive Markers and Therapeutic Targets for 

Drug Resistant Ovarian Cancer 

JIB-2105, IB-2103, IB-2111 

APPLICATIONS OF TECHNOLOGIES: 

● Identifying ovarian cancers that are not likely to respond to 

current combination chemotherapies, e.g. platinum plus 

paclitaxel 

● Screening for clinical trials to identify patients with chemoresistant 

tumors 

● Developing new treatment strategies for chemo-resistant 

ovarian cancers 

● Researching cancer progression and chemo-resistance 

ADVANTAGES: 


● Eliminates debilitating chemotherapy treatments in cases 

where they won't be effective 

● Enables physicians to identify patients who may benefit from 

alternative treatments or alternative treatments coupled with 

conventional chemotherapy 

● Attacks mechanisms leading to drug resistance 

● Model based on BAC clones identifies patients with short 

survival time 

● Provides information on the relative importance of identified 

marker


Scientists at Berkeley Lab and the University of California at San 

Francisco (UCSF) have identified and developed several markers for 

ovarian cancers least likely to respond to modern platinum/paclitaxel 

or other chemotherapies currently in use. These markers can be 

used in a variety of assays to provide critical information for 

physicians and their patients facing treatment decisions. This is the 

first set of tools to provide this predictive ability for ovarian cancers. 

Small molecules, siRNAs, or other compounds that inhibit expression 

of the new markers are promising therapies for platinum/paclitaxel 

resistant ovarian tumors. While some other targeted agents for 

treating ovarian cancer have entered clinical trials, most of these do 

not specifically attack mechanisms leading to resistance, as do the 

Berkeley Lab/UCSF inhibitors. 

The following technologies are available for licensing or collaborative 

research: 

Tri-locus Test to Predict Drug Resistance in Ovarian Cancer 

Joe Gray, Wen-Lin Kuo, and Jane Fridlyand conducted genome wide 

analyses to identify aberrations that are most strongly associated 

with poor response to treatment with platinum/paclitaxel therapies in 

ovarian cancer. Comparative Genomic Hybridization (CGH) studies 

of genome copy number show recurrent amplification in regions at 

chromosome locations 8q24, 11q13, 20q13. Berkeley Lab and 

UCSF have developed markers that can be used in a variety of 

assaying techniques to detect these amplifications. Reference 

number JIB-2105 

PVT1 as a Prognostic and Therapeutic Marker for Ovarian 

Cancer 

Joe Gray and colleagues from Berkeley Lab and UCSF have 

identified amplification of the PVT1 gene as a potential predictor of 

drug resistant ovarian cancer tumors and a promising therapeutic 

target. The PVT1 gene maps to the region of amplification at the 

8q24 chromosome location that is most strongly associated with 

reduced survival duration in platinum/paclitaxel treated patients. The 

transcription levels of PVT1 are highly correlated with DNA copy 



number alterations in ovarian cell lines and high level amplification 

and/or over expression of the PVT1 gene are significantly associated 

with reduced survival time. 

Studies employing PVT1 inhibitors reinforce the value of PVT1 as 

both a predictive marker and therapeutic target for tumors that are 

not responsive to platinum/paclitaxel based therapies. After treating 

four cell lines that over express PVT1 with siRNAs that reduce PVT1 

transcription, Berkeley Lab/UCSF scientists found that cell 

proliferation was inhibited. siRNA treatment of cell lines that do not 

amplify or over express PVT1 did not inhibit growth or induce cell 

death. These studies indicate that siRNAs or small molecule 

inhibitors targeting the gene are promising therapies for 

chemoresistent tumors. Such therapies might be enhanced when 

combined with platinum plus paclitaxel treatments. Reference 

number IB-2103 

STATUS: Patent pending 

BAC Clones as Prognostic Markers for Ovarian Cancer 

Joe Gray, Anna Lapuk, and Wen-Lin Kuo have developed an array 

of 48 prognostic BAC clones as markers for predicting poor survival 

of late stage serous ovarian cancer patients. The regions that the 

clones span contain sequences located on 13 chromosomes and 

were found to be grade specific markers of poor and good 

prognosis. The prediction- method algorithm is based on the 

correlation of copy number changes within these 48 regions with 

patients’ outcome. 

This technique has been developed using tumor samples from a 

cohort of 40 patients and was tested on an independent cohort of 30 

patients with late stage serous ovarian cancer, where it predicted 

survival outcome with a 77% success rate. Reference number IB- 

2111 

CONTACT: 

Technology Transfer Department, Berkeley Lab 

(510) 486-6467 



TTD@lbl.gov 


● Gene Therapy Target for Invasive Breast Cancer, IB-1637 



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Rapid Detection of Cell Motility using Semiconductor Nanocrystals 

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Quantum Dot Based Cell Motility, Invasion, and 

Metastasis Assays 


● Rapid method for assaying 

metastatic potential in biopsies 

● Cancer drug development 

● Research on cell motility 

ADVANTAGES: 


● More photochemically robust than 

organic dyes 

● Less labor intensive than the 

Boyden Chamber invasion assay 

● Can be used with live cells – no 

fixation/processing required 

● Allows for real time variation of 

external conditions 

● Nanocrystals don’t perturb cell 

viability 

● Good film homogeneity, cellular resolution 

Engulfment of 

Nanocrystals Reveals 

Migratory Paths of 

Breast Tumor Cells.A 

wide variety of 

mammalian cells engulf 

quantum dots when 

migrating. This 

migration is correlated 

to the cell’s metastatic 

potential. After 24 hours, 

dark clearings in the 

nanocrystal layer are 

observed around motile 

tumor cells.


ABSTRACT: 

Carolyn Larabell, Paul Alivisatos, and colleagues have discovered a 

powerful tool for studying cell motility and migration - behaviors that 

are responsible for metastases of primary cancers. The Berkeley Lab 

researchers compared the motions of cancerous and healthy human 

breast cells, as well as several other cell types, as they migrated 

across a layer of colloidal semiconductor nanocrystals. As they 

move, they engulf the quantum dots and leave behind a phagokinetic 

track which yields information about the health of the cells. Migration 

of cells and their metastatic potential are well known to be correlated. 

Colloidal quantum dots are robust and efficient light emitters that 

have been used for static biological labeling. They are superior to 

organic dyes, which fade quickly and perturb the assayed cells. 

Larabell’s lab has shown that these nanocrystals are spontaneously 

ingested by a wide variety of cells while remaining fully luminescent, 

enabling researchers to examine live cells over extended time 

periods and to quantify changes in response to various molecular 

manipulations. 

The Berkeley Lab technique is less labor intensive than the Boyden 

Chamber invasion assay method, it does not require killing the cells, 

and it enables real-time variation of external conditions and analyses 

of cellular responses. It also overcomes the marker problems 

encountered in the original phagokinetic tracking methods. The 

method can be coupled to information about chemical signals and 

allows a wide variety of tissue culture substrates to be used, 

including growth on all extracellular matrix substances. 

The improved cell motility studies and rapid assaying of metastatic 

potential enabled by this quantum dot method will provide improved 

diagnostics and enhanced information for cancer drug development. 

STATUS: 


● Patent Pending (patent application #285,187); available for 

licensing



PUBLICATIONS: 

"Cell motility and metastatic potential studies based on quantum dot 

imaging of phagokinetic tracks," W. J. Parak, R. Boudreau, M. Le 

Gros, D. Gerion, D. Zanchet, C. M. Micheel, S.C.Williams, A. P. 

Alivisatos, C. Larabell, Advanced Materials 14 (12): 882-885 (June 

18 2002) 



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Available Technologies: Antibodies for Monitoring and Phosphorylation Sites for Inhibiting DNA Double-Strand Break Repair- 

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Antibodies for Monitoring and Phosphorylation Sites for Inhibiting DNA 

Double-Strand Break Repair 


● Developing therapeutics for the radiosensitization of cancer cells 

● Assessing the efficacy of cancer treatments 

● Cancer drug screening and development 

● Research on the in vivo activity of DNA-PK 

ADVANTAGES: 

● Identifies two major DNA-PKcs autophosphorylation sites which are involved in DNA double strand break 

repair 

● First technology to enable the in vivo monitoring of DNA-PK response to DNA damage 

● Offers an antibody for drug screening and development 

ABSTRACT: 


David Chen, Ping-Chi Benjamin Chen, and Doug Chan have demonstrated that autophosphorylation of DNA- 

PKcs is an important event in the repair of DNA double strand breaks (DSBs) by nonhomologous end-joining. 

The Berkeley Lab researchers have identified two autophosphorylation sites on the extremely large DNAdependent 

protein kinase catalytic subunit (DNA-PKcs) and have generated antibodies that will enable the in 

vivo monitoring of DNA-PK response to DNA damage. 

The newly discovered autophosphorylation sites are located at Threonine 2609 and Serine 2056. A mammalian 

cell line that expresses a mutation at Threonine 2609, preventing DNA-PKcs autophosphorylation at the site, 

showed an increase in cell radiosensitivity. 

Ionizing radiation and cancer drugs inflict DSBs in order to kill cancer cells. The ability to intervene in 

autophosphorylation of T2609 or S2056 and hinder DBS repair, either through application of a drug or an 

antibody, would increase the radiation-induced killing of cancer cells. Therefore, identification of these critical


autophosphorylation sites is a first and necessary step in advancing this line of cancer treatment. 

"A cell lacking this kinase will become extremely radiation sensitive," says David Chen. A drug that renders the 

two identified sites inert would "reduce a patient's radiation dose and reduce their side effects." 

Dr. Chen and colleagues have generated antibodies that recognize Threonine 2609 and Serine 2056 but do not 

bind to the unphosphorylated DNA-PKcs protein or peptide. These antibodies identify areas where DSBs are 

being repaired and therefore can be used to monitor the effectiveness of treatments that target the DNA repair 

pathway of cancer cells. Before the Berkeley Lab phosphorylation-specific antibodies were identified, DNA-PK 

activity could not be monitored in vivo. Because there is an abundance of DNA-PK in a cell’s nucleus, it has 

been impossible to distinguish between the large DNA-PK background signal and DNA repair protein foci using 

immunofluorescence and currently available antibodies. 

Left: gH2AX staining shows damaged DNA. Middle: pT2609 antibody staining shows phosphorylated DNA-PKcs. 

Right: Merging of the images on the left shows colocalization. Images of irradiated human primary fibroblasts 

provide the first evidence that DNA-PKcs is localized to sites of DSBs in the cell and is thus at the right location to 

play a direct role in DSB repair. The bright yellow spots show where the green and red foci are aligned. 

STATUS: 


● Patent application # 511,561; available for licensing



Chan, D.W., Chen, B.P., Prithivirajsingh, S., Kurimasa, A., Story, M.D., Qin, J., Chen, D.J., 

“Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA 

double-strand breaks,” Genes and Development 2002, 16, 2333-38. 


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Transgenic Mice: Breast Cancer and Leukemia 

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● Breast cancer research 

● In vivo testing of potential drug therapies for breast cancer and 

leukemia 

ADVANTAGES: 

● Novel in vivo model to study initiation and promotion of breast 

cancer and leukemia 

ABSTRACT: The extracellular matrix (ECM) is an important 

regulator of mammary epithelial cell function and morphology during 

normal development and appears to play an important role in the 

progression of breast cancer. ECM-degrading metalloproteinases 

(MMPs) have been implicated in remodeling the ECM and tissue 

morphogenesis. To facilitate study of the role of MMPs in ECM 

remodeling and their importance in mammary gland morphogenesis, 

Berkeley National Laboratory scientists have generated transgenic 

mice that overexpress autoactivated forms of rat stromelysin in the 

mammary gland, under the control of the mammary gland-specific 

whey acidic protein (WAP) promoter. These transgenic mice express 

autoactivated isoforms of the matrix metalloproteinase stromelysin-L 

gene, which disrupts the balance between proteinases and inhibitors 

and affects basement membrane integrity in the mammary gland. 

Increased tumor incidence in these mice permits research into the 

suggestion that disruption of the basement membrane can lead to 

breast cancer. Many of these transgenic mice also develop 

leukemia, which makes them useful as a model for that disease as 

well. 

STATUS: Available for licensing/bailment 




PUBLICATIONS: 

"Suppression of ICE and apoptosis in mammary epithelial cells by 

extracellular matrix." Boudreau N, Sympson C.J, Werb Z and Bissell 

M.J. Science 267:891-893 (1995). 

"Targeted expression of stromelysin-1 in mammary gland provides 

evidence for a role of proteinases in branching morphogenesis and 

the requirement for an intact basement membrane for tissue-specific 

gene expression" [published erratum appears in J Cell Biol 1996 

Feb;132(4):following 752] C.J. Sympson, R.S. Talhouk, C.M. 

Alexander, J.R. Chin, S.M. Clift, M.J. Bissell, and Z. Werb, J. Cell 

Biol. 1994 125: 681-693 

"Overexpression of Stromelysin-1 in the Mouse Mammary Gland 

Leads to Epithelial Hyperplasia and Tumor Formation." C.J. 

Sympson, N. Thomasset, C.M. Alexander, M.J. Bissell, and Z. Werb. 

Journal of Cell Biology 1994. 

"Overexpression of Stromelysin-1 Modifies Mammary Gland Stroma 

in Transgenic Mice." N. Thomasset, C.J. Sympson, L. Lund, Z. 

Werb, M.J. Bissell. Molecular Biology of the Cell 1994. 

"Expression of WAP-Stromelysin Transgene in CD-1 Mice Alters 

Mammary Specific Gene Expression and Morphology." C.J. 

Simpson, R.S. Talhouk, C.M. Alexander, J.R. Chin, Z Werb, and M.J. 

Bissell. Molecular Biology of the Cell. 1992. 

"A Critical balance between ECM-degrading proteinases and their 

inhibitors regulates tissue specific function." R.S. Talkhouk, C.M. 

Alexander, S.M. Clift, C.J Sympson, M.J. Bissell and Z. Werb. 

Journal of Cell Biology 1991. 



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Available Technologies: Breast Cancer Therapy and Potential Method for Enhancing Radiation Sensitivity via Inhibition of ß1 Integrin 

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Breast Cancer Therapy and Potential Method for 

Enhancing Radiation Sensitivity via Inhibition of ß1 

Integrin 

APPLICATIONS: 

● Antitumor 

therapy 

● Shows 

promise 

for 

increasing 

the 

radiation 

sensitivity 

of 

breast 

cancer 

cells 

ADVANTAGES: 


T4 xenographs with and without AIIB2 in vivo show the antibody's effectiveness against 

tumors 

● In vivo studies have demonstrated the effectiveness of ß1 integrin 

antibody for anti-tumor therapy 

● In vitro studies show enhancement of radiation sensitivity 

● The tissue environment responds to cancer in a consistent manner, 

providing a reliable mechanism for treatment (compared to the variable 

routes taken by cells to become cancerous) 

● ß1 integrin inhibitory antibody had little negative effect on a nonmalignant 

cell line 

● 3-D cell cultures can be used to distinguish tumors that are susceptible 

to the Berkeley Lab treatment


ABSTRACT: 

Most current research on cancer initiation and progression focuses on the 

genetics and the clonal expansion and acquisition of abnormal signaling 

pathways that characterize the tumor. What has been relatively overlooked is 

the microenvironment – specifically cell-extracellular matrix (ECM) 

interactions – and the role that these interactions play in tumor progression 

and development of resistance to treatment. 

Integrins are an important class of molecules that mediate crucial signals 

between cells and the ECM. There is a growing body of evidence, including 

clinical trials against specific integrins, showing that interfering with these 

signals by inhibiting integrin activity can profoundly affect tumor development. 

Research has shown that ß1 integrin specifically modifies response to 

chemotherapy in lung, leukemia, and colon cancers. It has also been shown 

to play a critical role in expression of the breast cancer phenotype (Weaver et 

al., 1997). 

Berkeley Lab Scientist Mina Bissell and University of California at San 

Francisco Radiation Oncologist Catherine Park, M.D. have now demonstrated 

that disrupting abnormal cell-ECM interactions by inhibiting ß1 integrin is an 

effective mechanism for advancing breast cancer therapy and shows promise 

as a means of enhancing the therapeutic efficacy of ionizing radiation (IR). 

AIIB2 increases radiation sensitivity in 

undifferentiated tumor cells 


Studies with mice implanted with 

invasive human breast cancer 

cell lines show that ß1 integrin 

inhibitory monoclonal antibody 

(AIIB2) inhibits formation of 

tumors and significantly 

enhances apoptosis and 

decreases proliferation, and it 

does so in a dose-dependent 

manner with minimal toxicity to 

animals. In addition, when 3-D 

cultured malignant cell lines are 

treated with IR combined with 

AIIB2, the effects are enhanced 

by up to 50% compared to the 

use of IR alone. Treatment with 

AIIB2 resulted in only minimal 

apoptosis in non-malignant cell 

lines that have undergone 

differentiation in a 3 –D model,


indicating that treatments focused on inhibiting ß1 activity might have little 

negative effect on healthy cells. 

REFERENCE: 

Weaver, V.M., Petersen, O.W., Wang, F., Larabell, C.A., Briand, P., Damsky, 

C. and Bissell, M.J., (1997) Reversion of the malignant phenotype of human 

breast cells in three-dimensional culture and in vivo using integrin blocking 

antibodies. J. Cell Biol. 1997, 137, 231-246. 

STATUS: 

● Patent pendng; available for licensing or collaborative research 


Bissell, M.J., Radisky, D.C., Rizki, A., Weaver, V.M., Petersen, O.W., "The 

organizing principle: microenvironmental influences in the normal and 

malignant breast," Differentiation 2002, 70, 537-546. 



● Gene Therapy Target and Marker for Invasive Human Breast Cancer, 

IB-1637 

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Available Technologies: Polymerized Nanoparticle Therapeutics 

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Polymerized Nanoparticle Therapeutics 



● Drug delivery 

● Therapeutic potential for inflammatory diseases such as: 

❍ Reperfusion injury 

❍ Rheumatoid arthritis 

❍ Adult respiratory distress syndrome 

❍ Spetic shock 

ADVANTAGES: 

● Easily polymerized 

● High-purity, stable 

● Carry specific biological ligands 

ABSTRACT: Researchers have developed a method for creating 

high-purity, nano-sized polymer particles that display specific 

biological ligands on their surfaces. The material starts out as a 

synthetic membrane in the spherical form of a liposome that has selfassembled 

from monomers. A quick and efficient polymerization by 

light gives a solid shell. Monomers which bind to pathogens (such as 

influenza virus) or bind to disease sites in-vivo (inflammed tissue) are 

incorporated into the self-assembling mixture. The result is a hollow, 

spherical, polymerized liposome that binds to a biological target and 

can, in itself, be used as an inhibitor or be used for delivering a drug 

loaded in its interior. This technology forms the basis for a new class 

of materials that have great therapeutic potential. 

STATUS: US Patents 5,985,852 , 5,962,422, 6,235,309, 6,299,897 , 

6,663,886 and other U.S. and Foreign patents pending 

FOR MORE INFORMATION PLEASE SEE: 


● Spevak W., Foxall C., Charych D., Dasgupta F., Nagy J., 

"Carbohydrates in an Acidic Multivalent Assembly: Nanomolar

Available Technologies: Polymerized Nanoparticle Therapeutics 

P-Selectin Inhibitors," Journal of Medical Chemistry, 1996, 39, 

1018-1020. 

● Charych D., Nagy J., "Artificial Cell Membranes for Diagnostics 

and Therapeutics", Chemtech, September 1996, 24. 

● Spevak W., Foxall C., Charych D., Dasgupta F., Nagy J., 

"Inhibition of Selectin Binding by Polymerized Liposomes 

Expressing Carbohydrates," Science, 1995. 




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