《Antibody Structure》.pdf

MINIREVIEW Antibody Structure, Instability, and Formulation WEI WANG, SATISH SINGH, DAVID L. ZENG, KEVIN KING, SANDEEP NEMA Pfizer, Inc., Global Biologics, 700 Chesterfield Parkway West, Chesterfield, Missouri 63017 Received 14 March 2006; revised 17 May 2006; accepted 4 June 2006 Published online in Wiley InterScience (). DOI 10.1002/jps.20727 ABSTRACT: The number of therapeutic monoclonal antibody in development has increased tremendously over the last several years and this trend continues. At present there are more than 23 approved antibodies on the US market and an estimated 200 or more are in development. Although antibodies share certain structural similarities, development of commercially viable antibody pharmaceuticals has not been straightfor- ward because of their unique and somewhat unpredictable solution behavior. This article reviews the structure and function of antibodies and the mechanisms of physical and chemical instabilities. Various aspects of formulation development have been examined to identify the critical attributes for the stabilization of antibodies. 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1–26, 2007 Keywords: biotechnology; stabilization; protein formulation; protein aggregation; freeze drying/lyophilization INTRODUCTION currently in development (about 200).2 The global therapeutic antibody market was predicted to Protein therapies are entering a new era with reach $16.7 billion in 2008.3 the influx of a significant number of antibody There are several reasons for the incr