Therapeutic Monoclonal Antibodies: Past, Present, and Future

Abstract

In this chapter, an overview of the therapeutic antibody industry today, including the many commercial antibodies and Fc fusions and the rich clinical pipeline, is presented and analyzed. The long history of antibodies is given to bring context to the therapeutic antibody industry. This history includes serum therapy, the use of IVIG, and the evolution of those therapies into the development of the monoclonal Therapeutic Monoclonal Antibodies: From Bench to Clinic. Edited by Zhiqiang An Copyright # 2009 John Wiley & Sons, Inc.antibody business as we know it today. The history of technologies that fostered the revolution of therapeutic antibody development in the 1990s is also described. Finally, the future of the therapeutic monoclonal antibody and Fc fusion business is presented along with opportunities and challenges facing the business and those who work in it.Ã Based on published 2005 and 2006 sales, and 2010 projected sales of the top 70 biologics currently on the market, excluding vaccines (multiple sources). ÃÃ Projections were made prior to published safety concerns in mid-2007, which have depressed overall sales of epoetins. INTRODUCTIONÃ Data obtained from prescribing information released by the manufacturers, company websites, Prous Science Integrity. ÃÃConjugate is ozogamicin, a calecheamycin (natural product cytotoxin). ÃÃÃSuspended 2/28/05; reinstated under specified conditions.

Antibody and Antigen Contact Residues Define Epitope and Paratope Size and Structure

“…High-value commercial diagnostic, functional, and therapeutic mAbs must recognize full-length native proteins folded in native conformations as they exist in patients or patient samples. Given their potential value, strategies for developing mAbs to native protein Ags is of intense interest; however, the underlying biology dictating performance makes the task of developing such Abs both complicated and costly (1). For an Ab to exert a desired biological effect, it is usually the case that it must bind to a specific, predefined site.…”

Development of therapeutic proteins: advances and challenges

“…From the discovery of new molecules to their entrance into the pharmaceutical market, approximately 10 years are required, but the probability of success (POS) is not a guarantee (Shih, 2012;Strohl and Knight, 2009). For small molecules, the POS is 6%-7%, whereas for monoclonal antibodies and fusion proteins the POS is about 17% (Strohl, 2009). Therefore, it is important that molecules that have a maximum POS be selected.…”

“…All these agents are administered SC with the help of an autoinjector on a monthly schedule (Strohl and Knight, 2009). The most important feature of these therapeutic proteins is their safety and clinical efficacy, which can be achieved by a combination of several factors, including disease state, target biology, potency, safety margin, dosing, and selection of patient population (Carter, 2006;Presta, 2008;Strohl, 2009). The safety and clinical efficacy of the administered therapeutic substance can differentiate the best therapeutic agent from the others.…”

“…The following are some factors that should be considered (Carter, 2006;Presta, 2008;Shire, 2009;Stebbings et al, 2009;Strohl, 2009) in terms of safety and immunogenicity: 1) molecules that provide maximum margin of safety; 2) the delivery route; 3) prolonged half-life; 4) tissue distribution; 5) stability and enzymatic degradation; and 6) solubility of molecule underdevelopment.…”

Systematic review of chimpanzee use in monoclonal antibody research and drug development: 1981-2010

“…More than 30 mAb drugs have been approved to date by the U.S. Food and Drug Administration (FDA), and hundreds of mAbs have been tested in clinical trials, particularly in the fields of immunotherapy and oncology (Strohl, 2009).…”