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Structure-Based Optimization of Antibody-Based Biotherapeutics for Improved Developability: A Practical Guide for Molecular Modelers

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Computer-Aided Antibody Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2552))

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Abstract

A great effort to avoid known developability risks is now more often being made earlier during the lead candidate discovery and optimization phase of biotherapeutic drug development. Predictive computational strategies, used in the early stages of antibody discovery and development, to mitigate the risk of late-stage failure of antibody candidates, are highly valuable. Various structure-based methods exist for accurately predicting properties critical to developability, and, in this chapter, we discuss the history of their development and demonstrate how they can be used to filter large sets of candidates arising from target affinity screening and to optimize lead candidates for developability. Methods for modeling antibody structures from sequence and detecting post-translational modifications and chemical degradation liabilities are also discussed.

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Author information

Authors and Affiliations

  1. Scientific Services Manager, Biologics, Chemical Computing Group ULC, Montreal, QC, Canada

    Nels Thorsteinson

  2. Computational Biochemistry and Bioinformatics Group, Biotherapeutics Discovery, Boehringer Ingelheim Pharmaceutical Inc., Ridgefield, CT, USA

    Stephen R. Comeau Jr & Sandeep Kumar

Authors
  1. Nels Thorsteinson
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  2. Stephen R. Comeau Jr
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  3. Sandeep Kumar
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Corresponding author

Correspondence to Sandeep Kumar .

Editor information

Editors and Affiliations

  1. School of Engineering, The University of Tokyo, Tokyo, Japan

    Kouhei Tsumoto

  2. School of Engineering, The University of Tokyo, Tokyo, Japan

    Daisuke Kuroda

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Thorsteinson, N., Comeau, S.R., Kumar, S. (2023). Structure-Based Optimization of Antibody-Based Biotherapeutics for Improved Developability: A Practical Guide for Molecular Modelers. In: Tsumoto, K., Kuroda, D. (eds) Computer-Aided Antibody Design. Methods in Molecular Biology, vol 2552. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2609-2_11

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  • DOI: https://doi.org/10.1007/978-1-0716-2609-2_11

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2608-5

  • Online ISBN: 978-1-0716-2609-2

  • eBook Packages: Springer Protocols

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