Impact of degradations on bioactivity: A reflection from a monoclonal antibody

BIOT 136

Bryan L Yu, leiy@amgen.com, Alona Vizel, Meagan Young, Ashley Morando, and Bing He. Pharmaceutics, Amgen Inc, One amgen center dr, Thousand oaks, CA 91320
Recombinant therapeutic monoclonal antibodies are subject to a variety of physical and chemical modifications that may affect their bioactivities. Protein degradation reactions include but not limited to aggregation, clipping, oxidation, deamidation, proteolysis cleavage, disulfide-bond scrambling, glycosylation and cyclization. These degradation reactions create size, charge, or preferred conformation heterogeneity, which may further influence their binding or neutralizing capability against their targets. The potential impact of these modifications depends on not only their nature but also the site. Our characterization works on various degradation products revealed the locations and the extent of the degradations. Together with corresponding bioassay results, the findings allowed us to attain a better appreciation of their relationships. These data were collected throughout the commercial formulation development process of an IgG2.