LS-01
日 時 ：10 月 26 日 （ 火 ） 12:00-13:00

Cloud-Based Discovery Platform Identifies Hundreds ofDiverse SARS-CoV-2 Antibodies
M. Frank Erasmus1

ferasmus@specficia.bio
1Specifica, Inc. 1607 Alcaldesa St., Santa Fe, New Mexico 87501, USA.

Keywords: Antibody engineering, Antibody discovery, Next generation sequencing, Therapeuticantibodies, Drug discovery, In-vitro (phage and yeast) display, Bioinformatics, Immunoinformatics
Therapeutic antibodies, used to treat a variety of diseases, are the fastest growing class ofpharmaceuticals projected to grow to ~$240 billion by 2025 1 . Isolation of individual antibodies forbiophysical screening can been performed by a variety of technologies ranging from animal
immunization 2 , advanced methods harnessing the immune response 3-5 and in vitro display
technologies 6-8 . In most, if not all, of these cases, antibody engineers must sequence the outputs,
using low- (e.g., Sanger) and/or high-throughput (e.g., next generation sequencing (NGS)) to gaina deeper understanding of critical features including scaffold distribution, complementarity
determining region (CDR) composition, physicochemical similarity, sequence and/orstructure-based biophysical properties, and population-based NGS metrics. At Specifica, weroutinely combine Sanger and NGS to broaden the scope of selected antibody diversity forcharacterization. The goal is to minimize redundancy and maximize epitope coverage by selecting
antibody representatives from distinct CDR classes. To achieve this, Specifica built acomprehensive bioinformatics software package readily suited for the identification of therapeutic
leads from next generation sequencing (NGS), which even allows for the efficient ranking of
low-throughput clones identified by random picking. After teaming up with OpenEye Scientific,
we have integrated this antibody discovery pipeline into Orion™ to empower the antibody
engineering community with a cloud-based solution for the efficient identification of therapeuticcandidates for screening. This talk describes how we used this discovery software to identify apanel of leads with broad specificity, including many highly potent neutralizers against
SARS-CoV-2 Spike protein.
[1] https://apnews.com/press-release/pr-businesswire/af15cf4cf54e4698a93689afb4a906e8[2] Prabakaran, P., Rao, S., & Wendt, M. Animal immunization merges with innovativetechnologies: A new paradigm shift in antibody discovery. mAbs. 2021. 13. 1.
[3] Love, J.C., et al. A microengraving method for rapid selection of single cells producing
antigen-specific antibodies. Nat. Biotech. 2006. 24. 703-707.
[4] Jin, A. et al. A rapid and efficient single-cell manipulation method for screening
antigen-specific antibody-secreting cells from human peripheral blood. Nat. Med. 2009. 15.
1088-1092.
[5] Reddy, S.T. et al. Monoclonal antibodies isolated without screening by analyzing thevariable-gene repertoires of plasma cells. Nat. Biotechnol. 2010. 28. 965-969.
[6] Larrick, J.W. et al. Rapid cloning of rearranged immunoglobulin genes fromo humanhybridoma cells using mixed primers and the polymerase chain reaction. Biochem. Bioophys Rs.
Commun. 1989. 160. 1250-1256.
[7] Marks, J.D. et al. by-passing immunization. Human antibodies from V-gene libraries displayedon phage. J. Mol. Biol. 1991. 222. 581-597.
[8] Boder, E.T. & Wittrup, K.D. Yeast surface display for screening combinatorial polypeptide
libraries. Nat. Biotechnology. 1997. 15. 553-557.

About Specifica
Specifica is headquartered in Santa Fe, New Mexico, and provides antibody discovery
services to the pharmaceutical and biotech industries. Specifica’s flagship technology, theGeneration 3 Antibody Discovery Platform, is centered around a suite of novel patented invitro phage and yeast display library technologies which consistently yield antibodies withbroad diversities, extremely high affinities, and the relative absence of biophysicalliabilities. The Generation 3 platform may be accessed by engaging Specifica to carry out
antibody discovery or optimization campaigns, or by full transfer of the platform within anend-to end matrix that includes the critical tools required to generate a broad set ofdrug-like antibody leads that require minimal optimization. Libraries can be based onSpecifica’s in-house design or customized to suit customer preferences. As part of its
in-house antibody discovery services, Specifica developed AbXtract, a modular
bioinformatic platform designed to easily analyze next generation sequencing antibody
datasets to facilitate lead selection. This platform is now being co-marketed with OpenEyefor broader access to the biotech and pharma community.

About OpenEye
OpenEye Scientific is an industry leader in computational molecular design through rapid,
robust, and scalable software, consulting services, and Orion®, the only cloud-native fully
integrated software-as-a-service molecular modeling platform. Combining unlimited
computation and storage with powerful tools for data sharing, visualization and analysis in a
flexible development platform, Orion offers unprecedented capabilities for the advancement ofpharmaceuticals, biologics, agrochemicals, and flavors and fragrances. Founded in 1997,
OpenEye is a privately held company headquartered in Santa Fe, N.M., with offices in Boston,Mass.; Cologne, Germany; and Tokyo, Japan. For more information, go to www.openeye.inc.

About Orion
Orion® delivers the OpenEye computational tools scientists have trusted for more than twentyyears in an integrated web platform.
Run ligand-based or structure-based virtual screenings, molecular dynamics (MD)simulations, free energy predictions, quantum mechanics calculations, and more from justa web browser.
Integrate third-party or in-house tools.
Collaborate with colleagues without file transfers and formatting.
Leverage pre-built workflows or customize your own.