AIntibody: an experimentally validated in silico antibody discovery design challenge

M Frank Erasmus¹, Laura Spector², Fortunato Ferrara², Roberto DiNiro², Thomas J Pohl², Katheryn Perea-Schmittle², Wei Wang³, Peter M Tessier⁴, Crystal Richardson⁵, Laure Turner⁵, Sumit Kumar⁵, Daniel Bedinger⁶, Pietro Sormanni⁷, Monica L Fernández-Quintero⁸, Andrew B Ward⁸, Johannes R Loeffler⁸, Olivia M Swanson⁸, Charlotte M Deane⁹, Matthew I J Raybould⁹, Andreas Evers¹⁰, Carolin Sellmann¹⁰, Sharrol Bachas¹¹, Jeff Ruffolo¹², Horacio G Nastri¹³, Karthik Ramesh¹³, Jesper Sørensen¹⁴, Rebecca Croasdale-Wood¹⁵, Oliver Hijano¹⁶, Camila Leal-Lopes¹⁶, Melody Shahsavarian¹⁷, Yu Qiu¹⁶, Paolo Marcatili¹⁸, Erik Vernet¹⁸, Rahmad Akbar¹⁸, Simon Friedensohn¹⁹, Rick Wagner²⁰, Vinodh Babu Kurella²¹, Shipra Malhotra²¹, Satyendra Kumar²¹, Patrick Kidger²², Juan C Almagro²³, Eric Furfine²⁴, Marty Stanton²⁴, Christilyn P Graff²⁴, Santiago David Villalba²⁵, Florian Tomszak²⁵, Andre A R Teixeira²⁶, Elizabeth Hopkins²⁷, Molly Dovner²⁷, Sara D'Angelo², Andrew R M Bradbury²⁸

Affiliations

¹ Specifica LLC, an IQVIA business, Santa Fe, USA. mfrank.erasmus@iqvia.com.
² Specifica LLC, an IQVIA business, Santa Fe, USA.
³ University of California, San Diego, USA.
⁴ University of Michigan, Ann Arbor, USA.
⁵ GENEWIZ from Azenta Life Sciences, South Plainfield, USA.
⁶ Carterra, Salt Lake City, USA.
⁷ University of Cambridge, Cambridge, UK.
⁸ Scripps Research Institute, San Diego, CA, USA.
⁹ University of Oxford, Oxford, UK.
¹⁰ Merck KGaA, Darmstadt, Germany.
¹¹ Evolutionary Scale, San Francisco, USA.
¹² Profluent Bio, Berkeley, USA.
¹³ Incyte, Inc, Wilmington, USA.
¹⁴ OpenEye, Cadence Molecular Sciences, Santa Fe, USA.
¹⁵ Astrazeneca, Cambridge, UK.
¹⁶ Sanofi, Inc, Cambridge, USA.
¹⁷ Eli Lilly, San Diego, USA.
¹⁸ Novo Nordisk, A/S, Bagsværd, Denmark.
¹⁹ Alloy Therapeutics, Basel, Switzerland.
²⁰ Bonito Biosciences, Waltham, USA.
²¹ Takeda, Inc, Cambridge, USA.
²² Cradle Bio, Zürich, Switzerland.
²³ GlobalBio, Inc., Cambridge, MA, USA.
²⁴ Mosaic Biosciences, Boulder, USA.
²⁵ Bayer AG, Leverkusen, Germany.
²⁶ Institute for Protein Innovation, Boston, USA.
²⁷ Sapidyne Instruments, Inc. & GmbH, Boise, USA.
²⁸ Specifica LLC, an IQVIA business, Santa Fe, USA. andrew.bradbury@iqvia.com.

PMID: 39496931
PMCID: PMC12688036
DOI: 10.1038/s41587-024-02469-9

AIntibody: an experimentally validated in silico antibody discovery design challenge

M Frank Erasmus et al. Nat Biotechnol. 2024 Nov.

. 2024 Nov;42(11):1637-1642.

doi: 10.1038/s41587-024-02469-9.

Authors

Affiliations

¹ Specifica LLC, an IQVIA business, Santa Fe, USA. mfrank.erasmus@iqvia.com.
² Specifica LLC, an IQVIA business, Santa Fe, USA.
³ University of California, San Diego, USA.
⁴ University of Michigan, Ann Arbor, USA.
⁵ GENEWIZ from Azenta Life Sciences, South Plainfield, USA.
⁶ Carterra, Salt Lake City, USA.
⁷ University of Cambridge, Cambridge, UK.
⁸ Scripps Research Institute, San Diego, CA, USA.
⁹ University of Oxford, Oxford, UK.
¹⁰ Merck KGaA, Darmstadt, Germany.
¹¹ Evolutionary Scale, San Francisco, USA.
¹² Profluent Bio, Berkeley, USA.
¹³ Incyte, Inc, Wilmington, USA.
¹⁴ OpenEye, Cadence Molecular Sciences, Santa Fe, USA.
¹⁵ Astrazeneca, Cambridge, UK.
¹⁶ Sanofi, Inc, Cambridge, USA.
¹⁷ Eli Lilly, San Diego, USA.
¹⁸ Novo Nordisk, A/S, Bagsværd, Denmark.
¹⁹ Alloy Therapeutics, Basel, Switzerland.
²⁰ Bonito Biosciences, Waltham, USA.
²¹ Takeda, Inc, Cambridge, USA.
²² Cradle Bio, Zürich, Switzerland.
²³ GlobalBio, Inc., Cambridge, MA, USA.
²⁴ Mosaic Biosciences, Boulder, USA.
²⁵ Bayer AG, Leverkusen, Germany.
²⁶ Institute for Protein Innovation, Boston, USA.
²⁷ Sapidyne Instruments, Inc. & GmbH, Boise, USA.
²⁸ Specifica LLC, an IQVIA business, Santa Fe, USA. andrew.bradbury@iqvia.com.

PMID: 39496931
PMCID: PMC12688036
DOI: 10.1038/s41587-024-02469-9

No abstract available

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Conflict of interest statement

Competing interests L.S., F.F., R.D., T.J.P., K.P.-S., S.D., M.F.E. and A.R.M.B. are employees of Specifica, an IQVIA business. O.H., C.L.-L. and Y.Q. are employees of Sanofi. H.G.N. and K.R. are employees of Incyte and stockholders. M. Shahsavarian is an employee of Eli Lilly. D.B. is an employee of Carterra. R.W. is an employee of Bonito Biosciences. C.M.D. discloses membership of the Scientific Advisory Board of Fusion Antibodies and AI proteins. P.M.T. is a member of the scientific advisory board for Nabla Bio, Aureka Biotechnologies, and Dualitas Therapeutics. P.M., E.V. and R.A. are employees of Novo Nordisk A/S. J.S. is an employee of OpenEye, Cadence Molecular Sciences. R.C.W. is an employee of AstraZeneca. A.E. and C.S. are employees of Merck Healthcare KGaA. S.B. is an employee of Evolutionary Scale. J.R. is an employee of Profluent Bio. S.F. is an employee of Alloy Therapeutics. V.B.K., S.M. and S.K. are employees of Takeda. P.K. is an employee of Cradle Bio. J.C.A. is an employee of GlobalBio. E.F., M. Stanton and C.P.G. are employees of Mosaic Biosciences. S.D.V. and F.T. are employees of Bayer A.G. All other authors declare no competing interests.

Figures

**Figure 1 –. Study design of competition #1.**
a) Phase 1: DNA library diversity is introduced into L1+L2, L3, or H1+H2 of an ant-RBD scFv. b) Selective pressure is applied by FACS using RBD to select for improved binders. c) Phase 2: RBD binding diversity from each of the three arms (L1+L2, L3, H1+H2) is recovered, PCR-amplified and recombined into a yeast display vector. d) The combined diversity is transformed back into yeast and sorted for improved affinity and expression. Sequencing identifies final improved variants, which are reformatted into e) IgG for expression, f) binding affinity and g) developability measurements.

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References

1. Linden A & Fenn J Understanding Gartner’s hype cycles. Strategic Analysis Report N° R-20–1971. Gartner, Inc 88, 1423 (2003).
1. Lewis Chinery AMH, Mehta Brij Bhushan, Akbar Rahmad, Rawat Puneet, Slabodkin Andrei, Le Quy Khang, Lund-Johansen Fridtjof, Greiff Victor, Jeliazkov Jeliazko R., Deane Charlotte M.. Baselining the Buzz Trastuzumab-HER2 Affinity, and Beyond. bioRxiv (2024). 10.1101/2024.03.26.586756 - DOI
1. Wossnig L, Furtmann N, Buchanan A, Kumar S & Greiff V Best practices for machine learning in antibody discovery and development. Drug Discov Today 29, 104025 (2024). 10.1016/j.drudis.2024.104025 - DOI - PubMed
1. Bender A et al. Evaluation guidelines for machine learning tools in the chemical sciences. Nat Rev Chem 6, 428–442 (2022). 10.1038/s41570-022-00391-9 - DOI - PubMed
1. Moult J The current state of the art in protein structure prediction. Curr Opin Biotechnol 7, 422–427 (1996). 10.1016/s0958-1669(96)80118-2 - DOI - PubMed

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AIntibody: an experimentally validated in silico antibody discovery design challenge

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AIntibody: an experimentally validated in silico antibody discovery design challenge

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