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Molecular Assessment of Monoclonal Antibody-Based Therapeutics Enabling Lead Selection for Clinical Development

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Biobetters

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 19))

Abstract

Monoclonal antibodies (mAbs) and mAb-based therapeutics (e.g. antibody drug conjugates, bispecifics, Fab fragments, Fc-fusion proteins, etc.) have become an important class of drugs for the treatment of unmet medical needs. Efforts continue to develop mAb-based therapies for novel targets and indications as well as to develop “biobetters” to overcome limitations of existing approved products related to efficacy, safety, pharmacokinetics, and manufacturability/delivery. “Molecular-Assessment” (MA) or “Developability Assessment” initiatives have become an inherent part of early/pre-formulation work at several biopharmaceutical companies to ensure the success and de-risk technical hurdles associated with process development of mAb-based therapeutics. MA studies enable selection of an optimal “lead” mAb-based molecule in terms of a product “profile” encompassing manufacturability, stability, and delivery and inform regarding potential liabilities that may be associated with the lead molecule. For biobetters, MA studies also ensure that the lead molecule is indeed “better” with respect to the selected attribute. This chapter outlines the MA strategy, the results of which dictate decisions regarding lead candidates and the antibody engineering technologies that can be used to surmount the typical stability/delivery concerns for mAbs, the experimental tools used to assess these concerns, and provides some case studies exemplifying implementation of MA in lead molecule selection.

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Acknowledgements

The authors would like to acknowledge Boyan Zhang, Michael Kim, Li Yi, Benson Gikanga, Sabrina Lo, Rita Wong, Jessica Yang, Ankit Patel, and Bill Galush for contributing data presented in the case studies. The authors acknowledge Jamie Moore, William Galush, Barthélemy Demeule, Karen Rutherford, Samir Sane and Laura Simmons for their careful review of the chapter.

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  1. Pharmaceutical Development, Genentech, Inc., South San Francisco, CA, 94030, USA

    Vikas K. Sharma & Robert F. Kelley

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  1. Vikas K. Sharma
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Correspondence to Vikas K. Sharma .

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  1. Centre for Drug Evaluation and Research, Food and Drug Administration, Division of Biotechnology Review and Research III, Office of Biotechnology Products, Silver Spring, Maryland, USA

    Amy Rosenberg

  2. Genentech, Inc., South San Francisco, California, USA

    Barthélemy Demeule

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Sharma, V.K., Kelley, R.F. (2015). Molecular Assessment of Monoclonal Antibody-Based Therapeutics Enabling Lead Selection for Clinical Development. In: Rosenberg, A., Demeule, B. (eds) Biobetters. AAPS Advances in the Pharmaceutical Sciences Series, vol 19. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2543-8_10

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