Searching for siRNA and miRNA in STN® patent ... - STN International
Searching for siRNA and miRNA in STN® patent ... - STN International
Searching for siRNA and miRNA in STN® patent ... - STN International
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<strong>Search<strong>in</strong>g</strong> <strong>for</strong> <strong>siRNA</strong> <strong>and</strong> <strong>miRNA</strong><br />
<strong>in</strong> <strong>STN</strong> ® <strong>patent</strong> databases<br />
Robert Aust<strong>in</strong> – FIZ Karlsruhe
Agenda<br />
• Introduction to RNAi, <strong>miRNA</strong> <strong>and</strong> <strong>siRNA</strong><br />
• Underst<strong>and</strong><strong>in</strong>g <strong>siRNA</strong> <strong>and</strong> <strong>miRNA</strong> <strong>in</strong>dex<strong>in</strong>g <strong>in</strong><br />
DGENE, DWPISM , REGISTRY, <strong>and</strong> CAplusSM • Sequence search<strong>in</strong>g us<strong>in</strong>g DGENE, USGENE ® ,<br />
PCTGEN <strong>and</strong> REGISTRY<br />
– Sequence Code Match (SCM) <strong>and</strong> GETSIM<br />
– Multi-file BLAST search <strong>and</strong> post-process<strong>in</strong>g<br />
See also: Sequence Basics e-Sem<strong>in</strong>ar (July 2012):<br />
http://www.stn-<strong>in</strong>ternational.com/Sequence_Basics_Sem<strong>in</strong>ar.html<br />
2
Why use <strong>STN</strong> sequence databases?<br />
• Sequence <strong>in</strong><strong>for</strong>mation on <strong>STN</strong> is comprehensive<br />
– Four sequence databases allow users to achieve a<br />
comprehensive search of sequences from both <strong>patent</strong><br />
<strong>and</strong> non-<strong>patent</strong> documents<br />
• Sequence databases on <strong>STN</strong> are timely<br />
– Allows you to keep up-to-date with the most current<br />
<strong>in</strong><strong>for</strong>mation<br />
• Sequence <strong>in</strong>dex<strong>in</strong>g is unique<br />
– Allows you to retrieve sequences conta<strong>in</strong><strong>in</strong>g<br />
uncommon residues or chemical modifications that<br />
are difficult to f<strong>in</strong>d<br />
3
<strong>STN</strong> sequence searchable databases<br />
• DGENE<br />
– Thomson Reuters GENESEQ TM<br />
– Value-added <strong>patent</strong> sequence data from around the globe<br />
• USGENE<br />
– The USPTO Genetic Sequence Database<br />
– All available sequence data from the USPTO<br />
• PCTGEN<br />
– WIPO/PCT Patent Application Biosequences<br />
– All available e-published sequence data from WIPO<br />
• CAS REGISTRY SM<br />
– Chemical Abstracts Service (CAS) REGISTRY<br />
– Worldwide value-added <strong>patent</strong> <strong>and</strong> non-<strong>patent</strong> sequences<br />
4
RNA <strong>in</strong>terference (RNAi) is a mechanism<br />
that <strong>in</strong>hibits translation of targeted mRNA<br />
• 2006 Nobel Prize<br />
– Andrew Z. Fire<br />
• Stan<strong>for</strong>d University, Cali<strong>for</strong>nia<br />
– Craig C. Mello<br />
• University of Massachusetts Medical School <strong>in</strong><br />
Worcester<br />
– Double-str<strong>and</strong>ed RNA triggers suppression of gene<br />
activity <strong>in</strong> a homology-dependent manner, a process<br />
named RNA <strong>in</strong>terference (RNAi)<br />
5
RNAi pathway<br />
<strong>miRNA</strong><br />
RISC<br />
RISC<br />
<strong>siRNA</strong> complexes<br />
with RISC<br />
RISC<br />
Dicer<br />
dsRNA<br />
<strong>siRNA</strong><br />
The antisense <strong>siRNA</strong> (guide<br />
str<strong>and</strong>) with<strong>in</strong> RISC b<strong>in</strong>ds<br />
complementary to the mRNA<br />
Diagram Key:<br />
Dicer = an enzyme that cleaves double str<strong>and</strong>ed RNA<br />
dsRNA = double str<strong>and</strong>ed RNA<br />
mRNA = messenger RNA<br />
<strong>miRNA</strong> = micro RNA<br />
RISC = RNA‐<strong>in</strong>duced silenc<strong>in</strong>g complex<br />
<strong>siRNA</strong> = short <strong>in</strong>terfer<strong>in</strong>g RNA<br />
The cleaved mRNA<br />
undergoes degradation<br />
RISC<br />
Cleaved<br />
mRNA<br />
An enzyme with<strong>in</strong><br />
RISC cleaves the<br />
mRNA<br />
mRNA<br />
6
Two types of RNA seen <strong>in</strong> RNAi<br />
• Short <strong>in</strong>terfer<strong>in</strong>g RNA (<strong>siRNA</strong>)<br />
– Also known as small <strong>in</strong>terfer<strong>in</strong>g RNA or silenc<strong>in</strong>g RNA<br />
– <strong>siRNA</strong>s are double-str<strong>and</strong>ed (ds) <strong>and</strong> orig<strong>in</strong>ate from<br />
perfectly base-paired dsRNA precursors<br />
– Short 19-25 nucleotides (typically, 21)<br />
• Micro RNA (<strong>miRNA</strong>)<br />
– <strong>miRNA</strong>s are s<strong>in</strong>gle-str<strong>and</strong>ed (ss) <strong>and</strong> orig<strong>in</strong>ate from<br />
imperfectly base-paired hairp<strong>in</strong> structure transcripts<br />
– Short 19-23 nucleotides (typically, 22)<br />
• Both play a role <strong>in</strong> the RNAi pathway<br />
– Interfere with the expression of a specific gene<br />
7
http://en.wikipedia.org/wiki/Small_<strong>in</strong>terfer<strong>in</strong>g_RNA<br />
<strong>siRNA</strong> sequence structure<br />
8
<strong>miRNA</strong> sequence structure<br />
Example from miRBase:<br />
www.mirbase.org.<br />
9
Applications of RNAi <strong>and</strong> <strong>siRNA</strong><br />
• Functional studies of genes<br />
– Decrease gene expression (gene knockdown)<br />
– Design genome-wide RNAi libraries <strong>for</strong> RNAi screen<strong>in</strong>g<br />
• Human disease therapy<br />
– Possible reversal of <strong>in</strong>duced liver failure <strong>in</strong> mouse models<br />
– Treat <strong>in</strong>fection by herpes simplex virus type 2<br />
– Inhibition of viral gene expression <strong>in</strong> cancerous cells<br />
– Potential treatments <strong>for</strong> neurodegenerative diseases<br />
• Biotechnology uses<br />
– Eng<strong>in</strong>eer<strong>in</strong>g plants that produce lower levels of natural<br />
plant tox<strong>in</strong>s<br />
• Diagnosis us<strong>in</strong>g <strong>miRNA</strong>-profiles<br />
– Indicative of disease states, e.g. heart disease, cancers<br />
10
Effective RNAi <strong>and</strong> <strong>siRNA</strong> therapy<br />
• RNAi <strong>and</strong> <strong>siRNA</strong> target specificity<br />
– Depends on the position <strong>and</strong> the sequence<br />
• The sequence length of RNAi <strong>and</strong> <strong>siRNA</strong><br />
• The effectiveness of RNAi <strong>and</strong> <strong>siRNA</strong> with<strong>in</strong> a<br />
cell be<strong>for</strong>e degradation<br />
• Delivery method of RNAi <strong>and</strong> <strong>siRNA</strong><br />
11
Agenda<br />
• Introduction to RNAi, <strong>miRNA</strong> <strong>and</strong> <strong>siRNA</strong><br />
• Underst<strong>and</strong><strong>in</strong>g <strong>siRNA</strong> <strong>and</strong> <strong>miRNA</strong> <strong>in</strong>dex<strong>in</strong>g <strong>in</strong><br />
DGENE, DWPI, REGISTRY, <strong>and</strong> CAplus<br />
• Sequence search<strong>in</strong>g us<strong>in</strong>g DGENE, USGENE,<br />
PCTGEN <strong>and</strong> REGISTRY<br />
– Sequence Code Match (SCM) <strong>and</strong> GETSIM<br />
– Multi-file BLAST search <strong>and</strong> post-process<strong>in</strong>g<br />
12
<strong>siRNA</strong> <strong>and</strong> <strong>miRNA</strong> <strong>in</strong> sequence databases<br />
• DGENE<br />
– A clear description (/DESC) is provided, e.g. “Human<br />
APOC3 gene targeted <strong>siRNA</strong> antisense str<strong>and</strong>”<br />
– Keywords (/KW) are provided: “Micro RNA”, “<strong>miRNA</strong>”,<br />
“short <strong>in</strong>terfer<strong>in</strong>g RNA”, “<strong>siRNA</strong>”; others may <strong>in</strong>clude “RNA<br />
<strong>in</strong>terference”, “gene silenc<strong>in</strong>g”, <strong>and</strong>/or “DNA-RNA hybrid”<br />
– <strong>siRNA</strong> are <strong>in</strong>dexed as s<strong>in</strong>gle sequences; ds or ss is<br />
<strong>in</strong>dexed <strong>in</strong> the keyword (/KW) field as appropriate<br />
• REGISTRY<br />
– The <strong>in</strong>dex name (/CN) may <strong>in</strong>clude “<strong>miRNA</strong>”, “<strong>siRNA</strong>”, etc<br />
– A description is provided as CAplus l<strong>in</strong>ked term text<br />
– <strong>siRNA</strong> may be registered either <strong>in</strong> s<strong>in</strong>gle str<strong>and</strong>ed or<br />
double (multi-) str<strong>and</strong>ed RNA records<br />
13
Example: <strong>siRNA</strong> <strong>patent</strong> sequence<br />
5’-UGCUUAAAAGGGACAGUAUUC-3’<br />
3’-CAACGAAUUUUCCCUGUCAUA-5’<br />
WO2010083615.<br />
14
Example: <strong>siRNA</strong> <strong>in</strong> DGENE<br />
L1 ANSWER 1 OF 1 DGENE COPYRIGHT 2012 THOMSON REUTERS on <strong>STN</strong><br />
AN AYE62425 RNA DGENE<br />
TI Composition useful <strong>for</strong> treat<strong>in</strong>g atherosclerosis, hypertriglyceridemia<br />
<strong>and</strong> hypercholesterolemia, comprises small <strong>in</strong>terfer<strong>in</strong>g RNA that<br />
silences apolipoprote<strong>in</strong> C-III gene expression.<br />
IN Lee A C H; Macdonald M; Maclachlan I<br />
PA (PROT-N) PROTIVA BIOTHERAPEUTICS INC.<br />
PI WO 2010083615 A1 20100729 159<br />
AI WO 2010-CA120 20100126<br />
PRAI US 2009-147235P 20090126<br />
US 2010-293452P 20100108<br />
PSL Claim 9; Page 130<br />
DED 16 SEP 2010 (first entry)<br />
DT Patent<br />
LA English<br />
OS 2010-J73486 [50]<br />
DESC Human APOC3 gene targeted <strong>siRNA</strong> antisense str<strong>and</strong> #532.<br />
ALL <strong>for</strong>mat.<br />
This record is <strong>for</strong> the <strong>siRNA</strong> antisense<br />
str<strong>and</strong>. There is a separate record <strong>in</strong><br />
DGENE <strong>for</strong> the sense str<strong>and</strong>.<br />
KW APOC3 gene; Apolipoprote<strong>in</strong> C3; anorectic; antiarteriosclerotic;<br />
antidiabetic; anti<strong>in</strong>flammatory; antilipemic; atherosclerosis;<br />
cardiant; cardiovascular disease; cardiovascular-gen.; coronary<br />
artery disease; diabetes mellitus; drug delivery; gastro<strong>in</strong>test<strong>in</strong>algen.;<br />
gene silenc<strong>in</strong>g; hypercholesterolemia; hypertriglyceridemia;<br />
lipid metabolism disorder; metabolic-gen.; nutrition-disorder-gen.;<br />
obesity; pancreatitis; prophylactic to disease; rna <strong>in</strong>terference;<br />
short <strong>in</strong>terfer<strong>in</strong>g RNA; <strong>siRNA</strong>; ss; steatosis; therapeutic; vasotropic.<br />
15
Example: <strong>siRNA</strong> <strong>in</strong> DGENE (cont.)<br />
ORGN Homo sapiens.<br />
AB The present <strong>in</strong>vention provides a novel composition compris<strong>in</strong>g ALL <strong>for</strong>mat a (cont.)<br />
small<br />
<strong>in</strong>terfer<strong>in</strong>g RNA (<strong>siRNA</strong>) that silences apolipoprote<strong>in</strong> C-III (APOC3)<br />
gene expression useful <strong>for</strong> treat<strong>in</strong>g atherosclerosis,<br />
hypertriglyceridemia <strong>and</strong> hypercholesterolemia. The present <strong>in</strong>vention<br />
also provides methods of deliver<strong>in</strong>g <strong>and</strong>/or adm<strong>in</strong>ister<strong>in</strong>g the lipid<br />
particles <strong>for</strong> the treatment of lipid diseases or disorders. The<br />
present <strong>in</strong>vention <strong>in</strong>dependently claims: a nucleic acid-lipid particle<br />
compris<strong>in</strong>g <strong>siRNA</strong>, cationic lipid <strong>and</strong> non-cationic lipid; <strong>and</strong> a method<br />
<strong>for</strong> <strong>in</strong>troduc<strong>in</strong>g <strong>siRNA</strong> that silences APOC3 gene expression <strong>in</strong>to cell.<br />
The composition <strong>and</strong> nucleic acid-lipid particle of the present<br />
<strong>in</strong>vention are useful <strong>for</strong> prevent<strong>in</strong>g, treat<strong>in</strong>g, ameliorat<strong>in</strong>g <strong>and</strong>/or<br />
delay<strong>in</strong>g the onset of atherosclerosis or dyslipidemia (such as<br />
hypertriglyceridemia <strong>and</strong> hypercholesterolemia), The DGENE abstract coronary concludes heart with a<br />
disease, coronary artery disease, fatty liver disease, pancreatitis,<br />
sentence plac<strong>in</strong>g the <strong>siRNA</strong> sequence<br />
diabetes, obesity <strong>and</strong> cardiovascular disease <strong>in</strong> humans. The<br />
composition <strong>and</strong> nucleic acid-lipid <strong>in</strong> the particle context of the overall present <strong>in</strong>vention. <strong>in</strong>vention<br />
are so beneficial as they have high solubility, bioavailability,<br />
biological half-life, <strong>and</strong> shelf life. The present sequence is a human<br />
APOC3 gene targeted <strong>siRNA</strong> antisense str<strong>and</strong>, which silences the<br />
apolipoprote<strong>in</strong> C-III (APOC3) gene expression <strong>and</strong> is useful <strong>in</strong> a<br />
method <strong>for</strong> treat<strong>in</strong>g atherosclerosis, hypertriglyceridemia <strong>and</strong><br />
hypercholesterolemia as described <strong>in</strong> the present <strong>in</strong>vention.<br />
NA 6 A; 6 C; 2 G; 0 T; 7 U; 0 Other<br />
SQL 21<br />
SEQ<br />
1 auacuguccc uuuuaagcaa c<br />
16
Example: <strong>siRNA</strong> <strong>in</strong> REGISTRY<br />
L1 ANSWER 1 OF 1 REGISTRY COPYRIGHT 2012 ACS on <strong>STN</strong><br />
RN 1237573-07-7 REGISTRY<br />
CN RNA, (A-U-A-C-U-G-U-C-C-C-U-U-U-U-A-A-G-C-A-A-C), complex with RNA<br />
(U-G-C-U-U-A-A-A-A-G-G-G-A-C-A-G-U-A-U-U-C) (1:1) (CA INDEX NAME)<br />
OTHER NAMES:<br />
CN 843: PN: WO2010083615 TABLE: 10 claimed RNA<br />
FS NUCLEIC ACID SEQUENCE<br />
SQL 42,21,21<br />
NA 13 a 9 c 7 g 13 u<br />
NTE multistr<strong>and</strong>ed (2)<br />
PATENT ANNOTATIONS (PNTE):<br />
Sequence |Patent<br />
Source |Reference<br />
=========+=============<br />
Not Given|WO2010083615<br />
|claimed TABLE<br />
|10<br />
SEQ 1 auacuguccc uuuuaagcaa c<br />
SEQ 1 ugcuuaaaag ggacaguauu c<br />
MF Unspecified<br />
CI MAN<br />
SR CA<br />
LC <strong>STN</strong> Files: CA, CAPLUS, TOXCENTER<br />
. . . .<br />
SQIDE <strong>for</strong>mat.<br />
In REGISTRY, <strong>siRNA</strong> may be<br />
<strong>in</strong>dexed as either s<strong>in</strong>gle or double<br />
str<strong>and</strong>ed records, depend<strong>in</strong>g on<br />
the applicant/author’s description.<br />
So, <strong>in</strong> this example, the<br />
antisense <strong>and</strong> sense<br />
str<strong>and</strong>s are comb<strong>in</strong>ed <strong>in</strong>to<br />
a multi-str<strong>and</strong>ed record.<br />
17
Example: <strong>siRNA</strong> <strong>in</strong> CAplus<br />
L2 ANSWER 1 OF 1 HCAPLUS COPYRIGHT 2012 ACS on <strong>STN</strong><br />
AN 2010:941189 HCAPLUS<br />
BIB HITIND <strong>for</strong>mat.<br />
DN 153:278052<br />
TI Small <strong>in</strong>terfer<strong>in</strong>g RNA-lipid compositions <strong>and</strong> methods <strong>for</strong> silenc<strong>in</strong>g<br />
apolipoprote<strong>in</strong> C-III expression <strong>and</strong> treatment of associated disorders<br />
IN MacDonald, Marcia; Lee, Amy C. H.; MacLachlan, Ian<br />
PA Protiva Biotherapeutics, Inc., Can.<br />
. . . .<br />
FAN.CNT 1<br />
PATENT NO. KIND DATE APPLICATION NO. DATE<br />
--------------- ---- -------- -------------------- --------<br />
PI WO 2010083615 A1 20100729 WO 2010-CA120 20100126<br />
. . . .<br />
IPCI A61K0031-713 [I,A]; A61K0009-14 [I,A]; A61K0009-48 [I,A]; A61P0003-06<br />
[I,A]; A61P0003-00 [I,C*]; A61P0009-10 The [I,A]; <strong>siRNA</strong> A61P0009-00 sequence is [I,C*]; l<strong>in</strong>ked to<br />
C12N0015-113 [I,A]; C12N0015-88 [I,A]; C12N0015-87 [I,C*]; C07H0021-02<br />
Roles <strong>and</strong> Index Terms <strong>in</strong> CAplus.<br />
[I,A]; C07H0021-00 [I,C*]; C07K0014-775 [I,A]; C07K0014-435 [I,C*]<br />
CC 1-8 (Pharmacology)<br />
IT 1237559-26-0 1237559-27-1 . . . . 1237573-07-7 1237861-74-3<br />
1237861-75-4 1237861-76-5 1237861-77-6 1237861-78-7 1237861-79-8<br />
RL: PRP (Properties); THU (Therapeutic use); BIOL (Biological study);<br />
USES (Uses)<br />
(<strong>siRNA</strong> 2'-OMe modified duplex; <strong>siRNA</strong>-lipid compns. <strong>and</strong> methods <strong>for</strong><br />
silenc<strong>in</strong>g apolipoprote<strong>in</strong> C-III expression <strong>and</strong> treatment of<br />
associated disorders)<br />
RE.CNT 4 THERE ARE 4 CITED REFERENCES AVAILABLE FOR THIS RECORD<br />
ALL CITATIONS AVAILABLE IN THE RE FORMAT<br />
18
Example: <strong>miRNA</strong> <strong>patent</strong> sequence<br />
WO2009070653.<br />
Note: this is the miRBase<br />
example shown on slide 9.<br />
19
Example: <strong>miRNA</strong> <strong>in</strong> DGENE<br />
L1 ANSWER 1 OF 2 DGENE COPYRIGHT 2012 THOMSON REUTERS on <strong>STN</strong><br />
AN AWW08667 RNA DGENE<br />
TRIAL <strong>for</strong>mat.<br />
TI Determ<strong>in</strong><strong>in</strong>g whether a subject has, or is at risk <strong>for</strong> develop<strong>in</strong>g, lung<br />
cancer associated diseases, comprises measur<strong>in</strong>g the level of microRNA<br />
(miR) gene product <strong>in</strong> a peripheral blood sample from the subject.<br />
DESC Human stem-loop microRNA miR-101-2 used as tumor marker SEQ ID:173.<br />
KW drug screen<strong>in</strong>g; tumor marker; rna detection; rna quantitation;<br />
prognosis; diagnostic test; prophylactic to disease; therapeutic;<br />
lung tumor; carc<strong>in</strong>oma; cytostatic; respiratory tract tumor;<br />
respiratory-gen.; non-small-cell lung cancer; adenocarc<strong>in</strong>oma;<br />
squamous cell carc<strong>in</strong>oma; dermatological; ss; micro RNA; <strong>miRNA</strong>;<br />
microRNA 101-2; MIR101-2.<br />
SQL 79<br />
The pre-<strong>miRNA</strong> gene transcript <strong>and</strong>/or the<br />
mature <strong>miRNA</strong> sequence may be separately<br />
L1 ANSWER 2 OF 2 DGENE COPYRIGHT 2012 THOMSON REUTERS on <strong>STN</strong><br />
AN AWW08666 RNA DGENE disclosed <strong>and</strong> <strong>in</strong>dexed <strong>in</strong> DGENE.<br />
TI Determ<strong>in</strong><strong>in</strong>g whether a subject has, or is at risk <strong>for</strong> develop<strong>in</strong>g, lung<br />
cancer associated diseases, comprises measur<strong>in</strong>g the level of microRNA<br />
(miR) gene product <strong>in</strong> a peripheral blood sample from the subject.<br />
DESC Human mature microRNA miR-101-2 used as tumor marker SEQ ID:172.<br />
KW drug screen<strong>in</strong>g; tumor marker; rna detection; rna quantitation;<br />
prognosis; diagnostic test; prophylactic to disease; therapeutic;<br />
lung tumor; carc<strong>in</strong>oma; cytostatic; respiratory tract tumor;<br />
respiratory-gen.; non-small-cell lung cancer; adenocarc<strong>in</strong>oma;<br />
squamous cell carc<strong>in</strong>oma; dermatological; ss; micro RNA; <strong>miRNA</strong>;<br />
microRNA 101-2; MIR101-2.<br />
SQL 21<br />
20
Example: <strong>miRNA</strong> <strong>in</strong> REGISTRY<br />
L1 ANSWER 1 OF 2 REGISTRY COPYRIGHT 2012 ACS on <strong>STN</strong><br />
SQIDE <strong>for</strong>mat.<br />
RN 1159623-40-1 REGISTRY<br />
CN RNA (human microRNA hsa-mir101-2No1 stem-loop sequence)(CA INDEX NAME)<br />
OTHER NAMES:<br />
CN 173: PN: WO2009070653 SEQID: 173 claimed RNA<br />
FS NUCLEIC ACID SEQUENCE<br />
SQL 79<br />
NA 20 a 12 c 20 g 27 u<br />
. . . .<br />
L1 ANSWER 2 OF 2 REGISTRY COPYRIGHT 2012 ACS on <strong>STN</strong><br />
RN 1159623-39-8 REGISTRY<br />
CN RNA, (U-A-C-A-G-U-A-C-U-G-U-G-A-U-A-A-C-U-G-A-A) (CA INDEX NAME)<br />
OTHER NAMES:<br />
CN 172: PN: WO2009070653 SEQID: 172 claimed RNA<br />
FS NUCLEIC ACID SEQUENCE<br />
SQL 21<br />
NA 8 a 3 c 4 g 6 u<br />
. . . .<br />
The pre-<strong>miRNA</strong> gene transcript <strong>and</strong>/or the<br />
mature <strong>miRNA</strong> sequence may be separately<br />
disclosed <strong>and</strong> <strong>in</strong>dexed <strong>in</strong> REGISTRY.<br />
Note: These SQIDE displays are edited<br />
to fit on the slide (shown with “….”).<br />
21
Example: <strong>miRNA</strong> <strong>in</strong> CAplus<br />
L2 ANSWER 1 OF 1 HCAPLUS COPYRIGHT 2012 ACS on <strong>STN</strong><br />
AN 2009:676652 HCAPLUS<br />
BIB HITIND <strong>for</strong>mat.<br />
DN 151:30960<br />
TI MicroRNA profil<strong>in</strong>g <strong>in</strong> peripheral blood <strong>in</strong> the diagnosis <strong>and</strong> prognosis<br />
of lung cancer <strong>and</strong> <strong>in</strong> the selection of therapies<br />
IN Nana-S<strong>in</strong>kham, Serge P.; Marsh, Clay B.; Hunter, Melissa G.; . . . .<br />
PA The Ohio State University Research Foundation, USA<br />
SO PCT Int. Appl., 102pp.<br />
CODEN: PIXXD2<br />
DT Patent<br />
LA English<br />
FAN.CNT 1<br />
PATENT NO. KIND DATE Further APPLICATION descriptive text NO. <strong>for</strong> the <strong>miRNA</strong> DATE<br />
--------------- ---- -------- -------------------- --------<br />
sequences is provided as L<strong>in</strong>ked<br />
Terms <strong>in</strong> the CAplus Index Terms field.<br />
PI WO 2009070653 A1 20090604 WO 2008-US84821 20081126<br />
. . . .<br />
IT 1159623-39-8<br />
RL: ANT (Analyte); DGN (Diagnostic use); PRP (Properties); ANST<br />
(Analytical study); BIOL (Biological study); USES (Uses)<br />
(nucleotide sequence, microRNA hsa-mir101-2No1; microRNA profil<strong>in</strong>g<br />
<strong>in</strong> peripheral blood <strong>in</strong> diagnosis <strong>and</strong> prognosis of lung cancer <strong>and</strong><br />
<strong>in</strong> selection of therapies)<br />
IT . . . . 1159623-38-7 1159623-40-1 1159623-42-3 1159623-45-6 . . . .<br />
RL: ANT (Analyte); DGN (Diagnostic use); PRP (Properties); ANST<br />
(Analytical study); BIOL (Biological study); USES (Uses)<br />
(nucleotide sequence; microRNA profil<strong>in</strong>g <strong>in</strong> peripheral blood <strong>in</strong><br />
diagnosis <strong>and</strong> prognosis of lung cancer <strong>and</strong> <strong>in</strong> selection of<br />
therapies)<br />
. . . .<br />
22
Example: <strong>miRNA</strong> <strong>in</strong> USGENE<br />
L2 ANSWER 1 OF 2 USGENE COPYRIGHT 2012 SEQUENCEBASE CORP on <strong>STN</strong><br />
AN 20100323357.173 USGENE<br />
TI MicroRNA Expression Profil<strong>in</strong>g <strong>and</strong> Target<strong>in</strong>g <strong>in</strong> Peripheral Blood <strong>in</strong><br />
Lung Cancer (PublishedApplication)<br />
DESC Artificial RNA; Synthetic oligonucleotide; sequence 173 of 206<br />
MTY RNA<br />
SQL 79<br />
Patent applicants often do not<br />
L2 ANSWER 2 OF 2 USGENE COPYRIGHT provide 2012 SEQUENCEBASE an <strong>in</strong><strong>for</strong>mative CORP description.<br />
on <strong>STN</strong><br />
AN 20100323357.172 USGENE<br />
TI MicroRNA Expression Profil<strong>in</strong>g <strong>and</strong> Target<strong>in</strong>g <strong>in</strong> Peripheral Blood <strong>in</strong><br />
Lung Cancer (PublishedApplication)<br />
DESC Artificial RNA; Synthetic oligonucleotide; sequence 172 of 206<br />
MTY RNA<br />
SQL 21<br />
Note: These sequences come from US20100323357, which<br />
is equivalent to WO2009070653 (previous slides).<br />
TRIAL <strong>for</strong>mat.<br />
23
Search example <strong>for</strong> CAplus <strong>and</strong> DWPI<br />
Search Question:<br />
F<strong>in</strong>d recent <strong>patent</strong>s that describe us<strong>in</strong>g <strong>siRNA</strong><br />
therapeutically.<br />
24
Tips <strong>for</strong> search<strong>in</strong>g <strong>in</strong> CAplus<br />
• Use both completely spelled out terms <strong>in</strong><br />
addition to the acronym, e.g. <strong>for</strong> <strong>siRNA</strong><br />
– Short <strong>in</strong>terfer<strong>in</strong>g RNA, Small <strong>in</strong>terfer<strong>in</strong>g RNA,<br />
Silenc<strong>in</strong>g RNA, <strong>siRNA</strong>, si RNA, <strong>siRNA</strong>i or siNA<br />
• Controlled terms (/CT) are available from 2007<br />
– <strong>siRNA</strong>, MicroRNA, RNA <strong>in</strong>terference<br />
• Consider older related l<strong>in</strong>ked-terms to get<br />
enhanced retrieval prior to 2007<br />
– Double str<strong>and</strong>ed RNA (L) small <strong>in</strong>terfer<strong>in</strong>g/CT<br />
– RNA (L) microRNA/CT<br />
– Post-transcriptional process<strong>in</strong>g (L) <strong>in</strong>terference/CT<br />
25
=> FILE HCAPLUS<br />
Runn<strong>in</strong>g the search <strong>in</strong> CAplus…<br />
=> S SHORT INTERFERING RNA OR SMALL INTERFERING RNA OR SIRNA OR<br />
SI RNA OR SINA OR SILENCING RNA OR (DOUBLE STRANDED RNA (L)<br />
SMALL INTERFERING)<br />
L1 51201 SHORT INTERFERING RNA OR SMALL INTERFERING RNA OR SIRNA OR<br />
SI RNA OR SINA OR SILENCING RNA OR (DOUBLE STRANDED RNA (L)<br />
SMALL INTERFERING)<br />
=> S L1 (L) (THU/RL OR ?THERAP?)<br />
L2 20385 L1 (L) (THU/RL OR ?THERAP?)<br />
=> S L2 AND PATENT/DT AND PY.B>2010<br />
L3 1517 L2 AND PATENT/DT AND PY.B>2010<br />
Use the (L) operator so that the<br />
search terms <strong>and</strong> therapeutic<br />
role are <strong>in</strong> the same /IT field.<br />
Use left <strong>and</strong> right truncation with the<br />
term Therap to pick up words, such as<br />
therapy, therapeutic, chemotherapy.<br />
Limit by <strong>patent</strong> document type<br />
(P/DT) <strong>and</strong> to recent basic<br />
<strong>patent</strong> publication years (PY.B).<br />
26
Example: CAplus record retrieved<br />
L3 ANSWER … OF 1517 HCAPLUS COPYRIGHT 2012 ACS on <strong>STN</strong><br />
AN 2011:848465 HCAPLUS<br />
DN 155:144431<br />
TI Receptor tyros<strong>in</strong>e k<strong>in</strong>ase-like orphan receptor 1 (ROR-1) <strong>in</strong>hibitors <strong>for</strong><br />
treatment of cancer<br />
IN Mellstedt, Haakan; Rabbani, Hodjattallah; Teige, Ingrid<br />
PA Biolnvent <strong>International</strong> AB, Swed.<br />
SO PCT Int. Appl., 82pp.<br />
CODEN: PIXXD2<br />
DT Patent<br />
LA English<br />
FAN.CNT 2<br />
PATENT NO. KIND DATE APPLICATION NO. DATE<br />
--------------- ---- -------- -------------------- --------<br />
PI WO 2011079902 A2 20110707 WO 2010-EP7524 20101210<br />
. . . .<br />
AB The <strong>in</strong>vention relates to antibodies <strong>and</strong> <strong>siRNA</strong> mols. <strong>for</strong> <strong>in</strong>duc<strong>in</strong>g cell<br />
death by the specific b<strong>in</strong>d<strong>in</strong>g of ROR1, doma<strong>in</strong>s thereof or nucleotide<br />
mols. encod<strong>in</strong>g ROR1. The therapeutic <strong>in</strong>hibition of ROR-1 . . . .<br />
IT Antisense RNA<br />
Double str<strong>and</strong>ed RNA<br />
<strong>siRNA</strong><br />
BIB ABS HITIND display.<br />
The terms <strong>siRNA</strong> <strong>and</strong> therapeutic are <strong>in</strong><br />
the abstract, <strong>and</strong> the Index Term fields.<br />
The terms <strong>siRNA</strong> <strong>and</strong> THU<br />
are l<strong>in</strong>ked <strong>in</strong> the IT field.<br />
RL: DMA (Drug mechanism of action); PAC (Pharmacological activity);<br />
PRP (Properties); THU (Therapeutic use); BIOL (Biological study);<br />
USES (Uses)<br />
(receptor tyros<strong>in</strong>e k<strong>in</strong>ase-like orphan receptor 1 (ROR-1) <strong>in</strong>hibitors<br />
<strong>for</strong> treatment of cancer)<br />
27
Tips <strong>for</strong> search<strong>in</strong>g <strong>in</strong> DWPI<br />
• As <strong>for</strong> CAplus, use both completely spelled out<br />
terms <strong>in</strong> addition to the acronym, e.g. <strong>for</strong> <strong>miRNA</strong><br />
– MicroRNA, micro RNA, <strong>miRNA</strong>, mi RNA<br />
• Manual Codes (/MC) are available from 2005<br />
– <strong>siRNA</strong>: B04-E07C <strong>and</strong> D05-H12D8A<br />
– <strong>miRNA</strong>: B04-E07D <strong>and</strong> D05-H12D8B<br />
• Extend the search to f<strong>in</strong>d additional relevant results<br />
us<strong>in</strong>g the DWPI claims (/CLM) field, e.g.<br />
=> SET SFIELDS BI CLM (or: SET SFIELDS BI BIEX)<br />
• Option: focus a DWPI search us<strong>in</strong>g the mechanismof-action<br />
(/ACTN) abstract field, e.g.<br />
=> S ((RNA OR SIRNA OR MIRNA)(W)INTERFER? OR RNAI )/ACTN<br />
28
=> FILE WPIX<br />
Runn<strong>in</strong>g the search <strong>in</strong> DWPI…<br />
=> SET SFIELDS BI CLM<br />
SET COMMAND COMPLETED<br />
=> S SHORT INTERFERING RNA OR SMALL INTERFERING RNA OR SIRNA OR<br />
SI RNA OR SINA OR SILENCING RNA OR B04-E07C/MC OR D05-H12D8A/MC<br />
B04-E07C SIRNA (SHORT INTERFERING RNA)<br />
D05-H12D8A SIRNA<br />
L4 8448 SHORT INTERFERING RNA/BI,CLM OR SMALL INTERFERING RNA/BI,CLM<br />
OR SIRNA/BI,CLM OR SI RNA/BI,CLM OR SINA/BI,CLM OR . . . .<br />
=> S L4 AND (?THERAP? OR ?TREAT? OR CURE? OR B14/MC)<br />
B14 PHARMACEUTICAL ACTIVITIES<br />
L5 7518 L4 AND (?THERAP?/BI,CLM OR ?TREAT?/BI,CLM OR CURE?/BI,CLM OR<br />
B14/MC)<br />
=> S L5 AND PY.B>2010<br />
L6 1437 L5 AND PY.B>2010<br />
Extend the search to f<strong>in</strong>d<br />
additional relevant results us<strong>in</strong>g<br />
the DWPI claims (/CLM) field.<br />
Limit to recent basic <strong>patent</strong><br />
publication years (PY.B).<br />
29
Example: DWPI record retrieved<br />
L6 ANSWER … OF 1437 WPIX COPYRIGHT 2012 THOMSON REUTERS on <strong>STN</strong><br />
AN 2011-F64480 [201135] WPIX<br />
CR 2006-252595<br />
BIB AB MC display.<br />
TI New purified small <strong>in</strong>terfer<strong>in</strong>g RNA (<strong>siRNA</strong>) sequence, useful <strong>for</strong><br />
modulat<strong>in</strong>g nuclear factor (NF)-kappa-B dependent gene transcription <strong>in</strong><br />
a cell, <strong>and</strong> <strong>for</strong> treat<strong>in</strong>g <strong>in</strong>flammatory diseases <strong>and</strong> autoimmune<br />
diseases, e.g. osteoarthritis <strong>and</strong> asthma<br />
DC B04; D16<br />
IN CATRON K M; LI J; LI X<br />
PA (BOEH-C) BOEHRINGER INGELHEIM PHARM INC<br />
PIA US 20110124099 A1 20110526 (201135)* EN 27[10]<br />
<strong>siRNA</strong> <strong>and</strong> therapeutic are <strong>in</strong> the title,<br />
abstract, <strong>and</strong> Manual Code fields.<br />
. . . .<br />
AB US 20110124099 A1 UPAB: 20110605<br />
NOVELTY - A purified small <strong>in</strong>terfer<strong>in</strong>g RNA (<strong>siRNA</strong>) sequence<br />
compris<strong>in</strong>g fully def<strong>in</strong>ed 64 bp (SEQ ID NO. 1) given <strong>in</strong> the<br />
specification, is new.<br />
DETAILED DESCRIPTION - INDEPENDENT CLAIMS are:<br />
(1) an expression vector that expresses the <strong>siRNA</strong>; <strong>and</strong> . . . .<br />
ACTIVITY - Antiarthritic; Osteopathic; Vasotropic; . . . .<br />
MECHANISM OF ACTION - NF-Kappa-B-Modulator; Gene Therapy;<br />
RNA Interference; I-kappa-B-k<strong>in</strong>ase-Alpha-Modulator; RNAi is <strong>in</strong>dicated as a<br />
I-kappa-B-k<strong>in</strong>ase-Beta-Modulator.<br />
therapeutic mechanism-<br />
USE - The <strong>siRNA</strong> is useful <strong>for</strong> modulat<strong>in</strong>g nuclear factor<br />
of-action (/ACTN).<br />
(NF)-kappa-B dependent gene transcription <strong>in</strong> a cell; <strong>and</strong> <strong>for</strong> treat<strong>in</strong>g<br />
<strong>in</strong>flammatory diseases <strong>and</strong> autoimmune diseases, . . . . .<br />
MC CPI: B04-E07C; B04-E08; B04-E99; B04-F11B1E; B14-C03; B14-C09;<br />
B14-C09A; B14-E08; B14-E10C1; B14-F05; B14-G02C; B14-G02D;<br />
B14-J01; B14-K01A; B14-N17C; B14-S01; B14-S03A; B14-S03C;<br />
D05-H12D8A; D05-H12E<br />
30
Agenda<br />
• Introduction to RNAi, <strong>miRNA</strong> <strong>and</strong> <strong>siRNA</strong><br />
• Underst<strong>and</strong><strong>in</strong>g <strong>siRNA</strong> <strong>and</strong> <strong>miRNA</strong> <strong>in</strong>dex<strong>in</strong>g <strong>in</strong><br />
DGENE, DWPI, REGISTRY, <strong>and</strong> CAplus<br />
• Sequence search<strong>in</strong>g us<strong>in</strong>g DGENE, USGENE,<br />
PCTGEN <strong>and</strong> REGISTRY<br />
– Sequence Code Match (SCM) <strong>and</strong> GETSIM<br />
– Multi-file BLAST search <strong>and</strong> post-process<strong>in</strong>g<br />
31
<strong>siRNA</strong> sequence search example<br />
Search Question:<br />
Apart from WO2010083615, are there any other<br />
<strong>patent</strong> publications which have disclosed<br />
this <strong>siRNA</strong>, or other closely related sequences?<br />
5’-UGCUUAAAAGGGACAGUAUUC-3’<br />
3’-CAACGAAUUUUCCCUGUCAUA-5’<br />
32
Search Strategy <strong>for</strong> DGENE<br />
1) Run a GETSEQ sequence code match search<br />
<strong>for</strong> the <strong>siRNA</strong> sense <strong>and</strong> antisense str<strong>and</strong>s<br />
2) Extend the search to the correspond<strong>in</strong>g, closely<br />
related, DNA sequences (i.e. U -> T)<br />
3) Option: repeat the search <strong>in</strong> USGENE to f<strong>in</strong>d<br />
additional USPTO results<br />
4) Option: run a GETSIM similarity search to f<strong>in</strong>d<br />
other closely-related RNA or DNA sequences<br />
Note: <strong>in</strong> USGENE (<strong>and</strong> PCTGEN) it is also relatively common <strong>for</strong> RNA<br />
sequences to have Ts <strong>in</strong>stead of Us (follow<strong>in</strong>g the NCBI st<strong>and</strong>ard).<br />
33
Sequence code match search <strong>in</strong> DGENE<br />
=> FILE DGENE<br />
=> RUN GETSEQ AUACUGUCCCUUUUAAGCA|UGCUUAAAAGGGACAGUAU/SQSN<br />
. . . .<br />
Search simultaneously <strong>for</strong> the<br />
L1 RUN STATEMENT CREATED<br />
antisense <strong>and</strong> sense str<strong>and</strong>s<br />
L1 5 AUACUGUCCCUUUUAAGCA|UGCUUAAAAGGGACAGUAU/SQSN<br />
us<strong>in</strong>g the pipe “|” symbol (L1).<br />
=> S L1 NOT WO2010083615/PN<br />
L2 0 L1 NOT WO2010083615/PN<br />
=> RUN GETSEQ ATACTGTCCCTTTTAAGCA|TGCTTAAAAGGGACAGTAT/SQSN<br />
. . . .<br />
L3 RUN STATEMENT CREATED<br />
L3 54 ATACTGTCCCTTTTAAGCA|TGCTTAAAAGGGACAGTAT/SQSN<br />
=> S L3 NOT WO2010083615/PN<br />
L4 52 L3 NOT WO2010083615/PN<br />
=> SOR L4 SQL A<br />
PROCESSING COMPLETED FOR L4<br />
L5 52 SOR L4 SQL A<br />
No additional answers are retrieved via<br />
the RNA search (L2), but some are<br />
retrieved via the DNA search, <strong>and</strong> sorted<br />
by sequence length (shortest first) (L5).<br />
34
=> D TRIAL ALIGN 1-2<br />
L5 ANSWER 1 OF 52 DGENE COPYRIGHT 2012 THOMSON REUTERS on <strong>STN</strong><br />
AN AUO55141 DNA DGENE<br />
TI New different expression construct library, useful <strong>for</strong> determ<strong>in</strong><strong>in</strong>g<br />
functional effect of DNA polymorphism or DNA mutation <strong>in</strong> posttranscriptional<br />
activity, <strong>and</strong> <strong>for</strong> determ<strong>in</strong><strong>in</strong>g impact of regulatory<br />
sequences <strong>in</strong> untranslated regions (UTRs).<br />
DESC Human UTR sequence, SEQ ID 2920.<br />
KW DNA library; untranslated region; UTR; translation; ds.<br />
SQL 187<br />
SEQ<br />
tgcttaaaag ggacagtat<br />
========== =========<br />
HITS AT: 83-101<br />
L5 ANSWER 2 OF 52 DGENE COPYRIGHT 2012 THOMSON REUTERS on <strong>STN</strong><br />
AN AJT18724 cDNA DGENE<br />
TI New array compris<strong>in</strong>g a transcriptome from a diseased tissue, useful<br />
<strong>for</strong> diagnos<strong>in</strong>g a pathological condition or <strong>for</strong> determ<strong>in</strong><strong>in</strong>g<br />
responsiveness of a patient afflicted with a pathological condition<br />
to a therapeutic agent.<br />
DESC Human diseased liver tissue cDNA transcript SEQ ID NO:310368.<br />
KW Diagnosis; prognosis; screen<strong>in</strong>g; neoplasm; <strong>in</strong>flammation; . . . .<br />
SQL 451<br />
SEQ<br />
Review the additional records<br />
atactgtccc ttttaagca<br />
========== =========<br />
HITS AT: 91-109<br />
Good DNA-based hits <strong>for</strong> the sense <strong>and</strong><br />
antisense <strong>siRNA</strong> str<strong>and</strong>s are retrieved.<br />
However, the additional hits are<br />
much longer than the query.<br />
35
Option: repeat the search <strong>in</strong> USGENE<br />
=> FILE USGENE<br />
=> RUN GETSEQ AUACUGUCCCUUUUAAGCA|UGCUUAAAAGGGACAGUAU|ATACTGTCCCT<br />
TTTAAGCA|TGCTTAAAAGGGACAGTAT/SQSN<br />
. . . .<br />
L6 RUN STATEMENT CREATED<br />
L6 76 AUACUGUCCCUUUUAAGCA|UGCUUAAAAGGGACAGUAU|ATACTGTCCC<br />
TTTTAAGCA|TGCTTAAAAGGGACAGTAT/SQSN<br />
=> SOR L6 SQL A<br />
PROCESSING COMPLETED FOR L6<br />
L7 76 SOR L6 SQL A<br />
=> D TRI ALIGN 1-76<br />
L7 ANSWER … OF 76 USGENE COPYRIGHT 2012 SEQUENCEBASE CORP on <strong>STN</strong><br />
TI Viral <strong>and</strong> viral associated MiRNAs <strong>and</strong> uses thereof<br />
(PublishedApplication)<br />
DESC Homo sapiens RNA; sequence 531403<br />
MTY RNA<br />
SQL 64<br />
SEQ<br />
ugcuuaaaag ggacaguau<br />
========== =========<br />
HITS AT: 25-43<br />
=> D BRIEF<br />
Search simultaneously <strong>for</strong> the<br />
antisense str<strong>and</strong>, sense str<strong>and</strong>, <strong>and</strong><br />
correspond<strong>in</strong>g DNA sequences,<br />
us<strong>in</strong>g the pipe “|” symbol (L6).<br />
The results are sorted by<br />
sequence length (shortest<br />
first) be<strong>for</strong>e review (L7).<br />
36
Example: additional USGENE record<br />
L7 ANSWER … OF 76 USGENE COPYRIGHT 2012 SEQUENCEBASE CORP on <strong>STN</strong><br />
AN 20070003575.531403 RNA USGENE<br />
TI Viral <strong>and</strong> viral associated MiRNAs <strong>and</strong> uses thereof . . . .<br />
IN Bentwich Itzhak (Rosh Haay<strong>in</strong>, IL); Avniel Amir . . . .<br />
PA NO ASSIGNEE AT PUBLICATION<br />
PI US 20070003575 A1 20070104<br />
AI US 2006-511035 20060828<br />
PRAI US 2006-511035 20060828<br />
WO 2005-IB2352 20050526<br />
US 2004-709739 20040526<br />
PSL SEQ ID NO 531403<br />
DESC Homo sapiens RNA; sequence 531403<br />
DT Patent<br />
AB Described here<strong>in</strong> are novel polynucleotides associated with viral<br />
<strong>in</strong>fections. The polynucleotides are <strong>miRNA</strong>s . . . .<br />
ECLM US20070003575 A1: 1. An isolated nucleic acid compris<strong>in</strong>g . . . .<br />
SSO NUCLEIC; PSIPS; APPLICATION<br />
ORGN Homo sapiens<br />
SQL 64<br />
SEQ<br />
1 aucuccaggg cugccccugu agguugcuua aaagggacag uauucucagu<br />
====== ========== ===<br />
51 gcucuccuac ccca<br />
HITS AT: 25-43<br />
FEATURE TABLE:<br />
Key |Location|<br />
The sense str<strong>and</strong> of the <strong>siRNA</strong><br />
query is a perfect match on this<br />
<strong>miRNA</strong> sequence <strong>in</strong> USGENE.<br />
Click this l<strong>in</strong>k to access the orig<strong>in</strong>al sequence<br />
data as published via PSIPS (next slide).<br />
=======+========+==========================================================<br />
PSIPS | |http://www.sequencebase.com/psips.php?d=20070003575.531403<br />
37
Example: additional USGENE record (cont.)<br />
This is the source sequence data <strong>for</strong> the<br />
USGENE record on the previous slide.<br />
Note: “Human” is converted to “Homo<br />
sapiens” <strong>for</strong> USGENE records.<br />
38
=> FILE DGENE<br />
Option: run a similarity search<br />
=> RUN GETSIM AUACUGUCCCUUUUAAGCA/SQN BOTH BATCH<br />
PLEASE ENTER BATCH IDENTIFIER (MAX. 8 CHARS):SIRNA<br />
TO BE NOTIFIED WHEN THIS BATCH SEARCH IS COMPLETE,<br />
PLEASE ENTER YOUR EMAIL ADDRESS (MAX. 50 CHARS) OR "NONE"<br />
INPUT: OR (END):ROBERT.AUSTIN@FIZ-KARLSRUHE.DE<br />
RUN GETSIM AT 17:18:35 ON 09 AUG 2012<br />
COPYRIGHT (C) 2012 FIZ KARLSRUHE GMBH<br />
BATCH PROCESSING STARTED FOR SIRNA<br />
=> FIL <strong>STN</strong>G<br />
. . . .<br />
Run a FASTA-based similarity<br />
search with RUN GETSIM.<br />
Add BOTH to search the<br />
query <strong>and</strong> its complement<br />
simultaneously.<br />
Add BATCH to run the<br />
GETSIM search <strong>in</strong> offl<strong>in</strong>e<br />
BATCH mode.<br />
39
Example: BATCH notification email<br />
40
Retrieve the additional results<br />
=> FILE DGENE; RUN GETBATCH SIRNA<br />
. . . .<br />
8124 ANSWERS FOUND ABOVE A THRESHOLD OF 52<br />
QUERY SELF SCORE VALUE IS 95<br />
BEST ANSWER SCORE VALUE IS 95<br />
. . . .<br />
ENTER EITHER THE NUMBER OF ANSWERS YOU WISH TO KEEP<br />
OR ENTER MINIMUM PERCENT OF SELF SCORE FOLLOWED BY %<br />
(BEST ANSWER PERCENTAGE OF SELF SCORE IS 100%)<br />
ENTER (ALL) OR ? :80%<br />
L8 RUN STATEMENT CREATED<br />
L8 139 AUACUGUCCCUUUUAAGCA/SQN.BOTH<br />
Answer set arranged by accession number; to sort by descend<strong>in</strong>g<br />
similarity score, enter at an arrow prompt (=>) "sor score d".<br />
=> S L8 NOT WO2010083615/PN<br />
L9 121 L8 NOT WO2010083615/PN<br />
=> S L9 NOT (L1 OR L3)<br />
L10 70 L9 NOT (L1 OR L3)<br />
=> SOR SCORE D<br />
PROCESSING COMPLETED FOR L10<br />
L11 70 SOR L10 SCORE D<br />
=> D TRIAL ALIGN 1-70<br />
Retrieve the results with<br />
RUN GETBATCH.<br />
Note: just the top<br />
scor<strong>in</strong>g (≥ 80%)<br />
answers are chosen.<br />
The similarity search has retrieved<br />
additional results, which are sorted by<br />
sequence score (best first) (L11).<br />
41
Review the additional records<br />
L11 ANSWER 1 OF 70 DGENE COPYRIGHT 2012 THOMSON REUTERS on <strong>STN</strong><br />
AN AXC99315 cDNA DGENE<br />
TI New substantially purified nucleic acid molecule <strong>and</strong> its encoded<br />
polypeptides isolated from Sorghum, useful <strong>for</strong> produc<strong>in</strong>g a<br />
genetically trans<strong>for</strong>med plant with improved properties, e.g. improved<br />
plant growth <strong>and</strong> development.<br />
DESC Sorghum bicolor cDNA sequence SEQ ID NO:23862.<br />
KW crop improvement; transgenic plant; plant growth regulant; . . . .<br />
SQL 604<br />
ALIGN Smith-Waterman score: 86<br />
19 na overlap start<strong>in</strong>g at 97 (490 <strong>in</strong> complement)<br />
auacugucccuuuuaagca<br />
: ::.:.:::....:::::<br />
“In complement” <strong>in</strong>dicates that<br />
aaactgtcccttttaagca<br />
L11 ANSWER 5 OF 70 DGENE COPYRIGHT 2012 THOMSON REUTERS on <strong>STN</strong><br />
AN AZF74667 DNA DGENE<br />
TI New compound targeted to a nucleic acid molecule encod<strong>in</strong>g<br />
apolipoprote<strong>in</strong> C-III (Apo CIII), useful <strong>for</strong> treat<strong>in</strong>g a disease<br />
associated with Apo CIII, e.g. atherosclerosis, hyperlipidemia,<br />
diabetes, obesity <strong>and</strong>/or cardiovascular disease.<br />
DESC Human APOC3 mRNA <strong>in</strong>hibit<strong>in</strong>g phosphorothioate oligonucleotide SEQID:78<br />
KW 2'-MOE w<strong>in</strong>g; APOC3 gene; Apolipoprote<strong>in</strong> C3; anorectic; . . . .<br />
SQL 20<br />
ALIGN Smith-Waterman score: 85<br />
17 na overlap start<strong>in</strong>g at 4<br />
auacugucccuuuuaag<br />
:.::.:.:::....:::<br />
atactgtcccttttaag<br />
this is a hit via the GETSIM<br />
complementary query.<br />
Note: unlike BLAST (later)<br />
GETSIM dist<strong>in</strong>guishes<br />
between Ts <strong>and</strong> Us.<br />
42
<strong>miRNA</strong> sequence search example<br />
Search Question:<br />
Are there any <strong>patent</strong> publications which disclose<br />
this <strong>miRNA</strong>, or similar RNA sequences (≥ 80%)?<br />
UACAGUACUGUGAUAACUGAA<br />
43
Search Strategy <strong>for</strong> DGENE, USGENE,<br />
PCTGEN <strong>and</strong> REGISTRY/CAplus<br />
1) RUN BLAST <strong>in</strong> DGENE, USGENE <strong>and</strong> PCTGEN<br />
us<strong>in</strong>g offl<strong>in</strong>e BATCH mode<br />
2) Repeat the search us<strong>in</strong>g CAS REGISTRY BLAST<br />
3) Retrieve, merge, organize by <strong>patent</strong> family, <strong>and</strong><br />
display DGENE, USGENE <strong>and</strong> PCTGEN results<br />
4) Retrieve, identify <strong>and</strong> display unique CAplus<br />
references from the REGISTRY BLAST search<br />
5) Post-process DGENE, USGENE <strong>and</strong> PCTGEN<br />
results us<strong>in</strong>g the <strong>STN</strong> Express Table Tool<br />
6) Post-process unique REGISTRY BLAST results<br />
us<strong>in</strong>g the BLAST Report Tool<br />
44
NCBI recommended sett<strong>in</strong>gs* <strong>for</strong> search<strong>in</strong>g<br />
small sequence queries<br />
Peptide sequences<br />
• E-value: 20,000 • Matrix: PAM-30<br />
• Word size: 2 • Gap cost: 9 <strong>and</strong> 1<br />
Nucleotide sequences<br />
• E-value: 1,000<br />
• Word size: 7<br />
* http://www.ncbi.nlm.nih.gov/blast/Why.shtml<br />
• Matrix: Leave as is<br />
• Gap cost: n/a<br />
45
RUN BLAST searches <strong>in</strong> DGENE, USGENE <strong>and</strong><br />
PCTGEN <strong>in</strong> offl<strong>in</strong>e BATCH mode<br />
=> FILE DGENE; RUN BLAST UACAGUACUGUGAUAACUGAA /SQN -F F -E 1000<br />
-W 7 BATCH<br />
Add BATCH to<br />
the end of the<br />
comm<strong>and</strong>.<br />
PLEASE ENTER BATCH IDENTIFIER (MAX. 8 CHARS):MIRNA<br />
. . . .<br />
BATCH PROCESSING STARTED FOR MIRNA<br />
=> FILE USGENE; RUN BLAST UACAGUACUGUGAUAACUGAA /SQN -F F -E 1000<br />
-W 7 BATCH<br />
Use the NCBI’s<br />
recommended<br />
BLAST sett<strong>in</strong>gs.<br />
PLEASE ENTER BATCH IDENTIFIER (MAX. 8 CHARS):MIRNA<br />
. . . .<br />
BATCH PROCESSING STARTED FOR MIRNA<br />
=> FILE PCTGEN; RUN BLAST UACAGUACUGUGAUAACUGAA /SQN -F F -E 1000<br />
-W 7 BATCH<br />
PLEASE ENTER BATCH IDENTIFIER (MAX. 8 CHARS):MIRNA<br />
. . . .<br />
BATCH PROCESSING STARTED FOR MIRNA Tip: BATCH mode BLAST searches can<br />
be run concurrently <strong>in</strong> each database.<br />
46
Repeat us<strong>in</strong>g CAS REGISTRY BLAST<br />
a) Launch BLAST<br />
b) Search the sequence<br />
c) Exam<strong>in</strong>e <strong>and</strong> evaluate alignment/relevance of<br />
sequence answers<br />
d) Retrieve REGISTRY records on <strong>STN</strong><br />
See also: Sequence Basics e-Sem<strong>in</strong>ar (May 2011):<br />
http://www.stn-<strong>in</strong>ternational.com/Sequence_Basics_Sem<strong>in</strong>ar.html<br />
47
Adjust the REGISTRY BLAST sett<strong>in</strong>gs <strong>for</strong><br />
optimal search retrieval<br />
Increase the maximum<br />
number of answers to 1,000.<br />
Use the NCBI’s<br />
recommended<br />
BLAST sett<strong>in</strong>gs.<br />
48
Retrieve references <strong>for</strong> sequences<br />
Note: <strong>in</strong> this<br />
example, BLAST<br />
sequences with<br />
scores of 34 or<br />
more (80%<br />
match or more)<br />
are selected.<br />
49
Retrieve REGISTRY results<br />
Get <strong>STN</strong> Data <strong>for</strong> records with BLAST scores of 34 or more (≥80%).<br />
=> FIL REGISTRY<br />
=> QUE (1319235-70-5 OR 1319788-38-9 OR 1322161-88-5 . . . . )/RN<br />
L1 QUE (1319235-70-5 OR 1319788-38-9 OR 1322161-88-5 . . . . )/RN<br />
=> QUE (1301790-19-1 OR 1309516-09-3 OR 1310781-96-4 . . . . )/RN<br />
L2 QUE (1301790-19-1 OR 1309516-09-3 OR 1310781-96-4 . . . . )/RN<br />
. . . .<br />
=> QUE (874419-11-1 OR 845594-31-2 OR 845700-64-3 . . . . )/RN<br />
L22 QUE (874419-11-1 OR 845594-31-2 OR 845700-64-3 . . . . )/RN<br />
=> S L1 OR L2 OR L3 OR L4 OR L5 OR L6 OR L7 OR L8 OR L9 OR L10 OR<br />
L11 OR L12 OR L13 OR L14 OR L15 OR L16 OR L17 OR L18 OR L19<br />
L23 250 L1 OR L2 OR L3 OR L4 OR L5 OR L6 OR L7 OR L8 OR L9 OR L10 OR<br />
L11 OR L12 OR L13 OR L14 OR L15 OR L16 OR L17 OR L18 OR L19<br />
=> S L20 OR L21 OR L22<br />
L24 35 L20 OR L21 OR L22<br />
=> S L23 OR L24<br />
L25 285 L23 OR L24<br />
285 similar sequences (L25) with<br />
BLAST scores of 34 or more.<br />
Comm<strong>and</strong>s with<strong>in</strong> the dotted box<br />
are automatic comm<strong>and</strong>s.<br />
50
Retrieve REGISTRY results (cont.)<br />
=> S L25 AND SQL D SQIDE<br />
L27 ANSWER 1 OF 120 REGISTRY COPYRIGHT 2011 ACS on <strong>STN</strong><br />
RN 1322161-88-5 REGISTRY<br />
CN RNA, (U-A-C-A-G-U-A-C-U-G-U-G-A-U-A-A-C-U-G-A-A) (CA INDEX NAME)<br />
FS NUCLEIC ACID SEQUENCE<br />
SQL 21<br />
NA 8 a 3 c 4 g 6 u<br />
SEQ 1 uacaguacug ugauaacuga a<br />
Here the search is<br />
ref<strong>in</strong>ed further to<br />
short RNA (non-DNA)<br />
sequences (L27).<br />
An example of the<br />
type of a REGISTRY<br />
record retrieved.<br />
MF Unspecified<br />
CI MAN<br />
SR CA<br />
LC <strong>STN</strong> Files: CAPLUS<br />
DT.CA CAplus document type: Patent<br />
RL.P Roles from <strong>patent</strong>s: ANST (Analytical study); BIOL (Biological<br />
study); PRP (Properties); USES (Uses)<br />
1 REFERENCES IN FILE CAPLUS (1907 TO DATE)<br />
51
Retrieve the DGENE results<br />
=> FILE DGENE; RUN GETBATCH MIRNA<br />
. . . .<br />
ENTER (ALL) OR ? :80%<br />
L28 RUN STATEMENT CREATED<br />
L28 424 UACAGUACUGUGAUAACUGAA/SQN.-F F -E 1000 -W 7<br />
=> S L28 AND SQL
Retrieve the USGENE <strong>and</strong> PCTGEN results<br />
=> FILE USGENE; RUN GETBATCH MIRNA<br />
. . . .<br />
ENTER (ALL) OR ? :80%<br />
L30 RUN STATEMENT CREATED<br />
L30 586 UACAGUACUGUGAUAACUGAA/SQN.-F F -E 1000 -W 7<br />
=> S L30 AND SQL S L32 AND SQL
Merge <strong>and</strong> review the DGENE, USGENE <strong>and</strong><br />
PCTGEN BLAST search results<br />
=> SET DUPORDER FILE<br />
SET COMMAND COMPLETED<br />
=> DUP IDE L29 L31 L33<br />
. . . .<br />
FILE 'DGENE' ENTERED AT 22:24:23 ON 29 AUG 2011<br />
COPYRIGHT (C) 2011 THOMSON REUTERS<br />
FILE 'USGENE' ENTERED AT 22:24:23 ON 29 AUG 2011<br />
COPYRIGHT (C) 2011 SEQUENCEBASE CORP<br />
FILE 'PCTGEN' ENTERED AT 22:24:23 ON 29 AUG 2011<br />
COPYRIGHT (C) 2011 WIPO<br />
L34 435 DUP IDE L29 L31 L33 (INCLUDES 0 SETS OF DUPLICATES)<br />
ANSWERS '1-173' FROM FILE DGENE<br />
ANSWERS '174-372' FROM FILE USGENE<br />
ANSWERS '373-435' FROM FILE PCTGEN<br />
=> SOR SCORE D AN D<br />
PROCESSING COMPLETED FOR L34<br />
L35 435 SOR L34 SCORE D AN D<br />
SET DUPORDER FILE ensures that<br />
multifile records merged us<strong>in</strong>g DUP<br />
IDE are organized by database (file).<br />
DUPLICATE IDENTIFY<br />
(DUP IDE) is used here<br />
to create a s<strong>in</strong>gle<br />
multifile L-number (L34).<br />
The multifile L-number<br />
(L34) can be sorted by<br />
BLAST SCORE, or<br />
Percent Identity (IDENT).<br />
54
Use the <strong>STN</strong> Express 8.5 Patent Family<br />
Manager wizard to display the results<br />
Access the <strong>patent</strong> family<br />
manager wizard from the<br />
Discover! Menu.<br />
Choose a bibliographic display <strong>for</strong>mat with<br />
alignment <strong>for</strong> the first (best) hit.<br />
Option: choose a free-of-charge <strong>for</strong>mat with<br />
alignment <strong>for</strong> the rest of the family group.<br />
55
The <strong>patent</strong> family manager beg<strong>in</strong>s by organis<strong>in</strong>g<br />
the results us<strong>in</strong>g FSORT...<br />
=> FSORT L34<br />
. . . .<br />
L35 435 FSO L34<br />
Comm<strong>and</strong>s <strong>in</strong> RED are those<br />
issued automatically by the <strong>STN</strong><br />
Express Patent Family Manager.<br />
62 Multi-record Families Answers 1-419<br />
Family 1 Answers 1-2<br />
FSORT organizes Family 2 Answers 3-4<br />
the <strong>patent</strong><br />
Family 3 Answers 5-6<br />
sequence records Family 4 Answers 7-8<br />
Family 5 Answers 9-16<br />
by Publication,<br />
. . . .<br />
Application,<br />
Family 59 Answers 358-391<br />
Related, <strong>and</strong> Family 60 Answers 392-415<br />
Priority numbers.<br />
Family 61 Answers 416-417<br />
Family 62 Answers 418-419<br />
16 Individual Records Answers 420-435<br />
0 Non-<strong>patent</strong> Records In this example, 78 <strong>patent</strong> family<br />
. . . .<br />
groups (i.e. 62 + 16) are retrieved.<br />
56
...<strong>and</strong> then cont<strong>in</strong>ues by display<strong>in</strong>g the family<br />
groups <strong>in</strong> the specified <strong>for</strong>mats<br />
=> DIS L35 PFAM=1 1 BIB,SQL,SCORE,IDENT,ALIGN<br />
L35 ANSWER 1 OF 435 DGENE COPYRIGHT 2011 THOMSON REUTERS on <strong>STN</strong> FAMILY 1<br />
AN AZK14567 RNA DGENE<br />
TI Treat<strong>in</strong>g or prevent<strong>in</strong>g myocardial ischemia comprises modulat<strong>in</strong>g the<br />
expression or activity of microRNAs <strong>in</strong> the heart cells of the<br />
subject.<br />
IN Olson E N; Rooij E V; Quiat D<br />
PA (TEXA) UNIV TEXAS SYSTEM.<br />
PI WO 2011084460 A1 20110714 46<br />
AI WO 2010-US60460 20101215<br />
PRAI US 2009-286622P 20091215<br />
PSL Disclosure; SEQ ID NO 19<br />
DT Patent<br />
LA English<br />
OS 2011-J11773 [48]<br />
DESC Human ischemia regulated hsa-miR-101 <strong>miRNA</strong>, SEQ ID 19.<br />
SQL 21<br />
SCORE 42 100% of query self score 42<br />
IDENT 100%<br />
BLASTALIGN<br />
Query = 21 letters<br />
Length = 21<br />
Score = 42.1 bits (21), Expect = 6e-11<br />
Identities = 21/21 (100%)<br />
Str<strong>and</strong> = Plus / Plus<br />
Query: 1 tacagtactgtgataactgaa 21<br />
|||||||||||||||||||||<br />
Sbjct: 1 tacagtactgtgataactgaa 21<br />
Comm<strong>and</strong>s <strong>in</strong> RED are those<br />
issued automatically by the <strong>STN</strong><br />
Express Patent Family Manager.<br />
Note: BLAST does not<br />
dist<strong>in</strong>guish between Ts <strong>and</strong><br />
Us. All Us <strong>in</strong> the query <strong>and</strong><br />
answers are treated as Ts.<br />
57
...<strong>and</strong> then cont<strong>in</strong>ues by display<strong>in</strong>g selected<br />
results <strong>in</strong> the specified <strong>for</strong>mats (cont.)<br />
=> DIS L35 PFAM=60 1 BIB,SQL,SCORE,IDENT,ALIGN<br />
L35 ANSWER 392 OF 435 USGENE COPYRIGHT 2011 SEQUENCEBASE CORP on <strong>STN</strong><br />
FAMILY60<br />
AN 20100047784.3920 RNA USGENE<br />
TI Method <strong>for</strong> detect<strong>in</strong>g nucleic acids (PublishedApplication)<br />
IN Shlomit Gilad (Ganei Hadar, IL); Meiri Esther (Shoham, IL);<br />
Yerushalmi Noga (Nes Tziona, IL)<br />
PA ROSETTA GENOMICS LTD<br />
PI US 20100047784 A1 20100225<br />
AI US 2007-308954 20070629<br />
RLI WO 2007-IB3732 20070629<br />
PRAI US 2006-871095P 20061220<br />
. . . .<br />
PSL SEQ ID NO 3920<br />
DESC Xenopus tropicalis RNA; sequence 3920 of 21063<br />
DT Patent<br />
SQL 22<br />
SCORE 42 100% of query self score 42<br />
IDENT 100%<br />
BLASTALIGN<br />
Query = 21 letters<br />
Length = 22<br />
Score = 42.1 bits (21), Expect = 6e-11<br />
Identities = 21/21 (100%)<br />
Str<strong>and</strong> = Plus / Plus<br />
Query: 1 tacagtactgtgataactgaa 21<br />
|||||||||||||||||||||<br />
Sbjct: 1 tacagtactgtgataactgaa 21<br />
This USGENE hit<br />
family was not found <strong>in</strong><br />
the DGENE search.<br />
58
...<strong>and</strong> then cont<strong>in</strong>ues by display<strong>in</strong>g selected<br />
results <strong>in</strong> the specified <strong>for</strong>mats (cont.)<br />
=> DIS L35 PFAM=62 1 BIB,SQL,SCORE,IDENT,ALIGN<br />
L35 ANSWER 418 OF 435 PCTGEN COPYRIGHT 2011 WIPO on <strong>STN</strong> FAMILY 62<br />
AN 2011094335.649 RNA PCTGEN<br />
TI MicroRNA Signatures Predict<strong>in</strong>g Responsiveness to Anti-HER2 Therapy<br />
PA Yale University<br />
Weidhaas, Joanne B.<br />
PI WO 2011094335 20110804<br />
RLI US 2010-298454P 20100126<br />
ED 20110804<br />
DT Patent<br />
SQL 21<br />
SCORE 42 100% of query self score 42<br />
IDENT 100%<br />
BLASTALIGN<br />
Query = 21 letters<br />
Length = 21<br />
Score = 42.1 bits (21), Expect = 6e-11<br />
Identities = 21/21 (100%)<br />
Str<strong>and</strong> = Plus / Plus<br />
Query: 1 tacagtactgtgataactgaa 21<br />
|||||||||||||||||||||<br />
Sbjct: 1 tacagtactgtgataactgaa 21<br />
This PCTGEN hit<br />
family was not found <strong>in</strong><br />
the DGENE search.<br />
59
Display unique CAplus answers <strong>in</strong>clud<strong>in</strong>g<br />
the HITRN <strong>for</strong> alignment post-process<strong>in</strong>g<br />
=> FILE HCAPLUS<br />
Transfer Publication Numbers (PN)<br />
=> TRA L35 PN<br />
from DGENE, USGENE <strong>and</strong> PCTGEN<br />
L36 TRANSFER L35 1- PN : (L35) 143 to f<strong>in</strong>d TERMS correspond<strong>in</strong>g HCAplus<br />
L37 92 L36<br />
records (L37).<br />
ALL TERMS IN L36 RETRIEVED.<br />
=> S L27 AND P/DT<br />
L38 79 L27 AND P/DT<br />
=> S L38 NOT L37<br />
L39 5 L38 NOT L37<br />
=> D BIB ABS HITRN 1-5<br />
The 285 REGISTRY records (L27)<br />
correspond to 79 HCAplus <strong>patent</strong><br />
records (L38).<br />
In this example, five additional relevant<br />
references have been found by <strong>in</strong>clud<strong>in</strong>g<br />
a REGISTRY/CAplus search (L39).<br />
60
Example: CAplus record retrieved<br />
L39 ANSWER ... OF 5 HCAPLUS COPYRIGHT 2011 ACS on <strong>STN</strong><br />
AN 2008:1508387 HCAPLUS<br />
DN 150:71776<br />
TI Reagents <strong>and</strong> methods <strong>for</strong> microRNA expression analysis <strong>and</strong><br />
identification of cancer biomarkers<br />
IN Ahlquist, Paul Gerald; Sengupta, Srikumar; Den Boon, Johan Arie;<br />
Sugden, Bill; Newton, Michael Abbott<br />
PA Wiscons<strong>in</strong> Alumni Research Foundation, USA<br />
SO PCT Int. Appl., 64pp.<br />
CODEN: PIXXD2<br />
DT Patent<br />
LA English<br />
FAN.CNT 1<br />
This unique HCAplus<br />
hit was not found <strong>in</strong> the<br />
DGENE,USGENE or<br />
PCTGEN searches.<br />
PATENT NO. KIND DATE APPLICATION NO. DATE<br />
--------------- ---- -------- -------------------- --------<br />
PI WO 2008154098 A2 20081218 WO 2008-US62938 20080507<br />
. . . .<br />
AB This <strong>in</strong>vention provides methods <strong>for</strong> amplify<strong>in</strong>g, Note: HITRN detect<strong>in</strong>g, must be measur<strong>in</strong>g, <strong>in</strong>cluded,<br />
<strong>and</strong> identify<strong>in</strong>g microRNAs from biol. samples, particularly . . . .<br />
so that the CAS REGISTRY<br />
IT 1093520-93-4<br />
RL: ADV (Adverse effect, <strong>in</strong>clud<strong>in</strong>g toxicity); BLAST ANT alignments (Analyte); can DGN be<br />
(Diagnostic use); PRP (Properties); ANST merged (Analytical <strong>in</strong>to the study); BLAST BIOL Report.<br />
(Biological study); USES (Uses)<br />
(nucleotide sequence; reagents <strong>and</strong> methods <strong>for</strong> microRNA expression<br />
anal. <strong>and</strong> identification of cancer biomarkers)<br />
OSC.G 3 THERE ARE 3 CAPLUS RECORDS THAT CITE THIS RECORD (3 CITINGS)<br />
61
<strong>STN</strong> Express post-process<strong>in</strong>g tools provide the<br />
f<strong>in</strong>ish<strong>in</strong>g touches to the multi-file search<br />
2)<br />
1) DGENE, USGENE <strong>and</strong> PCTGEN results (L35) can be<br />
conveniently tabulated us<strong>in</strong>g the <strong>STN</strong> Express Table<br />
Tool <strong>and</strong> exported to a Microsoft Excel worksheet<br />
2) The REGISTRY “BLAST Report with Alignment data”<br />
tool merges BLAST alignments with correspond<strong>in</strong>g<br />
unique CAplus records (L39) to <strong>for</strong>m a s<strong>in</strong>gle RTF file<br />
1)<br />
62
1) DGENE, USGENE <strong>and</strong> PCTGEN results<br />
can be tabulated <strong>and</strong> exported to Excel<br />
Preferred fields, fonts,<br />
labels, etc, can be<br />
saved as a Template<br />
<strong>for</strong> repeated re-use.<br />
63
Once <strong>in</strong> Excel there are various options to sort,<br />
filter <strong>and</strong> review the multi-file results<br />
Some tips <strong>for</strong> Microsoft Excel:<br />
• Resize columns <strong>and</strong> rows as desired –<br />
especially the BLAST alignment<br />
column width to approximately 77<br />
• View, Freeze panes – holds the top<br />
row fixed when scroll<strong>in</strong>g down<br />
• Add Filters – provides a great way to<br />
navigate results – <strong>for</strong> example by<br />
BLAST percent identity (above)<br />
64
2) REGISTRY BLAST Alignments can be<br />
merged with correspond<strong>in</strong>g CAplus records<br />
Preferred fields, fonts,<br />
labels, etc, can be<br />
saved as a Template<br />
<strong>for</strong> repeated re-use.<br />
REGISTRY BLAST alignments<br />
are merged with the CAplus<br />
records <strong>in</strong> the transcript.<br />
65
The REGISTRY “BLAST Report with Alignment<br />
data” tool provides an RTF file<br />
Download the post-process<strong>in</strong>g template (.PRF) files used <strong>in</strong> this sem<strong>in</strong>ar:<br />
http://www.stn-<strong>in</strong>ternational.com/stn_biosequence_search<strong>in</strong>g_mfs.html<br />
66
Patent classifications <strong>for</strong> RNAi topics<br />
• IPC: C12N0015-113 /IPC<br />
– Non-cod<strong>in</strong>g nucleic acids modulat<strong>in</strong>g the expression of<br />
genes, e.g. antisense oligonucleotides<br />
• ECLA: C12N0015-113+NT /EPC<br />
– Non-cod<strong>in</strong>g nucleic acids modulat<strong>in</strong>g the expression of<br />
genes, e.g. antisense oligonucleotides; comment:<br />
Antisense DNA or RNA; Triplex- <strong>for</strong>m<strong>in</strong>g oligonucleotides;<br />
Catalytic nucleic acids, e.g. . . .<br />
• USPC: 536024500 /NCL<br />
– DNA/RNA fragments – nucleic acid expression <strong>in</strong>hibitors<br />
• USPC: 51404400A/NCL<br />
– Polynucleotides – antisense or RNA <strong>in</strong>terference<br />
67
Summary<br />
• Introduction to RNAi, <strong>miRNA</strong> <strong>and</strong> <strong>siRNA</strong><br />
• Underst<strong>and</strong><strong>in</strong>g <strong>siRNA</strong> <strong>and</strong> <strong>miRNA</strong> <strong>in</strong>dex<strong>in</strong>g <strong>in</strong><br />
DGENE, DWPI, REGISTRY, <strong>and</strong> CAplus<br />
• Sequence search<strong>in</strong>g us<strong>in</strong>g DGENE, USGENE,<br />
PCTGEN <strong>and</strong> REGISTRY<br />
– Sequence Code Match (SCM) <strong>and</strong> GETSIM<br />
– Multi-file BLAST search <strong>and</strong> post-process<strong>in</strong>g<br />
68
Resources <strong>for</strong> sequence search<strong>in</strong>g on <strong>STN</strong><br />
• DGENE Workshop Manual<br />
http://www.stn-<strong>in</strong>ternational.com/dgene_wm.html<br />
• USGENE Workshop Manual<br />
http://www.stn-<strong>in</strong>ternational.com/usgene_wm.html<br />
• CAS REGISTRY sequence search<strong>in</strong>g resources<br />
http://www.cas.org/support/stngen/stndoc/sequences.html<br />
• Multifile BLAST search<strong>in</strong>g (step-by-step guide)<br />
http://www.stn-<strong>in</strong>ternational.com/usgene_wm_mfs.html<br />
69
Recorded <strong>STN</strong> e-Sem<strong>in</strong>ars are available to<br />
watch at your own pace….<br />
• FIZ Karlsruhe recorded e-Sem<strong>in</strong>ars:<br />
http://www.stn-<strong>in</strong>ternational.com/recorded_events.html<br />
– Sequence Basics (all databases)<br />
– Multifile <strong>patent</strong> sequence search<strong>in</strong>g (all databases)<br />
• CAS recorded e-Sem<strong>in</strong>ars:<br />
http://www.cas.org/support/stngen/stntra<strong>in</strong><strong>in</strong>g/recorded.html<br />
– Sequence motif search<strong>in</strong>g (all databases)<br />
– Process<strong>in</strong>g sequence data (REGISTRY)<br />
– Unmask<strong>in</strong>g the World of Antibodies (REGISTRY)<br />
70
CAS<br />
E-mail: help@cas.org<br />
Support <strong>and</strong> Tra<strong>in</strong><strong>in</strong>g:<br />
www.cas.org<br />
For more <strong>in</strong><strong>for</strong>mation …<br />
FIZ Karlsruhe<br />
helpdesk@fiz-karlsruhe.de<br />
Support <strong>and</strong> Tra<strong>in</strong><strong>in</strong>g:<br />
www.stn-<strong>in</strong>ternational.de