Correspondence: Karl Ziegelbauer,, Protein Therapeutics, Bayer HealthCare AG, Wuppertal 42096, Germany. Tel: +49 202 36 5293; Fax: +49 202 36 4585; E-mail: karl.ziegelbauer@bayerhealthcare.com

¹is a Vice President for Protein Therapeutics at Bayer HealthCare AG. He received his PhD from the University of Tübingen. For the past 14 years, he has been involved in drug discovery in various positions with increasing responsibilities in Germany, Japan, and the United States. His experience covers all aspects of drug discovery in various indications up to proof of concept in humans as well as lifecycle management and research alliance management.

²received his PhD from the University of Wisconsin and completed a fellowship at the Massachusetts Institute of Technology before joining the newly formed Biocatalysis Department (later Genencor) in Genentech. He joined Berlex, a wholly owned subsidiary of Schering AG, as a protein chemist to develop biologic therapeutics including soluble thrombomodulin in Cardiovascular Research and later was project team leader of the factor Xa inhibitor project. Most recently, he headed the Antibody Technology Group focussing on antibody targets in cancer before joining the Protein Therapeutics group in Bayer.

Received 26 October 2007; Revised 26 October 2007; Published online 27 November 2007.

Abstract

A close look at the biology and pharmacology of monoclonal antibodies reveals both their continuing promise as therapeutic agents to address unmet medical needs, as well as a number of challenges to the future discovery and development of this unique class of biologics. A remarkably consistent experience of reliable clinical efficacy and safety ensures that Biotech and Pharma have strong incentives to accelerate the antibody drug discovery process. Their attractive commercial potential invites consideration of potential challenges to the future expansion of the monoclonal antibody drug market. Four challenges arise from scientific and technical aspects of the antibody drug format: drug target limitations, biodistribution limitations, species specificity issues, and limitations to the route of administration and four challenges are based in the commercial and clinical use of antibody drugs: cost of goods, product differentiation within the antibody market, competition from small molecule drugs, and price sensitivity of clinical acceptance. Despite these challenges and recent setbacks, such as the withdrawal and subsequent relaunch of Tysabri and the TGN1412 Phase I disaster, the prevailing opinion is that monoclonal antibodies will continue to be safe and effective medicines that are worthy of commercialisation.