Development of therapeutic antibodies for the treatment of diseases

Abstract

It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.

Development of an intensified fed-batch production platform with doubled titers using N-1 perfusion seed for cell culture manufacturing

“…Monoclonal antibody (mAb) product development has had great success with over 80 mAbs granted marketing approvals, while the commercial pipeline is robust with over 570 mAbs in different clinical development stages (Ecker et al 2015;Kaplon and Reichert 2019;Walsh 2018). Global annual sales of mAbs were above $115 billion in 2018 and are predicted to rise above $300 billion in 2025 (Lu et al 2020). These great achievements are partially due to the higher approval success rates for mAbs than small molecule drug products (Hay et al 2014;Kaplon and Reichert 2019).…”

Developing therapeutic monoclonal antibodies at pandemic pace

“…There are several other mAb discovery approaches (reviewed in ref. 4 ) that may also be capable of rapid lead identification that would subsequently benefit from this development strategy.…”

Designing Feature-Controlled Humanoid Antibody Discovery Libraries Using Generative Adversarial Networks

“…Antibodies are an important class of biologics-based therapeutics with clear advantages of specificity and efficacy. 1,2,3 The high cost and long development times, however, present key challenges in the accessibility of monoclonal antibody therapeutics. 4,5 To quickly respond to known and new pathogens and disease, and to provide affordable, high quality treatment to patients around the globe, a molecule must be designed for activity; but it must also be made developable and safe for patients.…”