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omation mbers - Society for Laboratory Automation and Screening

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5:00 pm Wednesday, February 4 Emerging Technologies – Aut<strong>omation</strong> Systems Room A3<br />

Jaymie Sawyer<br />

Dyax Corporation<br />

109754 Torreyana Road, W-1<br />

San Diego, Cali<strong>for</strong>nia 92121<br />

jsawyer@dyax.com<br />

Managing Automated RFLP Analysis in Phage Display Antibody <strong>Screening</strong><br />

135<br />

Co-Author(s)<br />

I-wei Feng, Lee A. Morganelli,<br />

Rosanto Paramban, Roger Dettloff,<br />

Irina Mineyev, Paul Kotturi<br />

Caliper Technologies Corporation<br />

Automated screening of Dyax’s proprietary human Fab library is currently in use to discover new antibodies<br />

<strong>and</strong> develop research reagents in collaboration with BD Biosciences. PCR fingerprinting is a useful tool in the<br />

analysis of clones derived from large libraries containing similar sized inserts. The fingerprints allow us to assess<br />

the diversity in pools of selected phage be<strong>for</strong>e moving into high throughput screening, or to avoid repeated<br />

expression <strong>and</strong> purification of the same clone. Vector-specific primers amplify the insert which is then digested<br />

with a frequently cutting restriction enzyme. Typically, gel electrophoresis is then used to visualize RFLPs. The<br />

Caliper AMS 90 SE system allows 96-384 digested DNA samples to be analyzed without running or photographing<br />

gels. The series of DNA fragments within a given sample are identified by LabChip HT software. To fully exploit<br />

fingerprinting, the data output must allow comparison of digests run at different times <strong>and</strong> facilitate correlation of<br />

clone identity with functional assays. These final data h<strong>and</strong>ling procedures are tedious <strong>and</strong> not automated. We<br />

developed a software tool to analyze the results from an AMS 90 SE <strong>and</strong> automate the final clone identification.<br />

DNA fragments between 50 <strong>and</strong> 500 base pairs are binned into groups between 15 <strong>and</strong> 20 bps. The peaks within<br />

a group are assigned a letter of the alphabet, resulting in a clone ‘name’. The resulting clone names can then be<br />

exported <strong>and</strong> correlated with functional assays such as expression levels <strong>and</strong> ELISA per<strong>for</strong>mance to identify new<br />

antibodies generated by phage display.<br />

5:15 pm Wednesday, February 4 Emerging Technologies – Aut<strong>omation</strong> Systems Room A3<br />

David Semin<br />

Amgen, Inc.<br />

One Amgen Center Drive, Mailstop 29-M-B<br />

Thous<strong>and</strong> Oaks, Cali<strong>for</strong>nia 91320<br />

dsemin@amgen.com<br />

The Next Generation of a Compound Management System in Drug Discovery<br />

Co-Author(s)<br />

Janet Cheetham, Stewart Chipman,<br />

Peter Gr<strong>and</strong>sard, Colin McRavey,<br />

Sabrina Park, Jim Petersen<br />

As the competition in drug discovery intensifies companies need to become more operationally efficient <strong>and</strong> to<br />

maximize return on investment. Since the emergence of automated compound storage <strong>and</strong> retrieval systems in the<br />

1990s there has been considerable progress on overall compound management strategies to facilitate compound<br />

flow throughout research operations. Some of these recent strategies have evolved around the new market of<br />

small to medium sized storage <strong>and</strong> retrieval systems. In an ef<strong>for</strong>t to fully enable Amgen’s global lead discovery<br />

ef<strong>for</strong>ts we are developing a compound management system based on a modular <strong>and</strong> multi-tier approach with<br />

the concept of archival <strong>and</strong> operational compound stores. The modularity enables flexibility <strong>and</strong> incorporation<br />

of new technology plat<strong>for</strong>ms, while the multi-tier approach enables redundant <strong>and</strong> priority storage <strong>for</strong>mats. A<br />

system of operational stores will fuel the chemistry <strong>and</strong> high throughput screening activities, while an archival<br />

store will be used ensure long-term compound quantity <strong>and</strong> quality. A global software infrastructure solution<br />

with generic interfaces to the modular components will be presented. The infrastructure is designed to enable<br />

excellence at compound collection stewardship while maintaining flexibility <strong>for</strong> change in business processes<br />

<strong>and</strong> the incorporation of new technology plat<strong>for</strong>ms. This drive towards the next generation system built upon<br />

these hardware <strong>and</strong> software concepts should enable a compound management system in drug discovery to be<br />

operationally efficient <strong>and</strong> effectively stay off the critical path <strong>and</strong> timeline <strong>for</strong> research programs.<br />

PODIUM ABSTRACTS

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