Chapter 1: Monoclonal Antibodies: Structure, Physicochemical Stability, and Protein Engineering

Abstract

Monoclonal antibodies (mAbs) are the largest class of therapeutic proteins. Owing to their versatile structure and function, mAbs are used for a wide range of therapeutic indications including oncology, immunology, neurology, metabolic, and cardiovascular diseases. Over the past three decades, more than 50 mAbs have been approved in the United States and Europe, and by 2020, about 70 mAb-based products are expected to be in the market (Ecker DM, Jones SD, Levine HL, MAbs 7:9–14, 2015). In 2017, 5 of the top 10 best-selling drugs in the global market are mAbs (Urquhart L, Nat Rev Drug Discov 17:232, 2018). In addition, several new therapeutic modalities based on mAbs including antibody-drug conjugates (ADCs), bispecific antibodies, and Fc fusion proteins have been approved or are in clinical trials. mAbs are complex glycoproteins that pose several challenges for development into viable commercial drug products. In this chapter, the general structure of mAbs, the common routes of degradation, and advances in protein engineering to improve stability, pharmacokinetics, and efficacy of mAbs are discussed as it relates to drug product development. Other mAb-based modalities are discussed in detail in separate chapters of the book.