A novel approach to investigate the effect of methionine oxidation on pharmacokinetic properties of therapeutic antibodies.

ABSTRACT: Preserving the chemical and structural integrity of therapeutic antibodies during manufacturing and storage is a major challenge during pharmaceutical development. Oxidation of Fc methionines Met252 and Met428 is frequently observed, which leads to reduced affinity to FcRn and faster plasma clearance if present at high levels. Because oxidation occurs in both positions simultaneously, their individual contribution to the concomitant changes in pharmacokinetic properties has not been clearly established. A novel pH-gradient FcRn affinity chromatography method was applied to isolate three antibody oxidation variants from an oxidized IgG1 preparation based on their FcRn binding properties. Physico-chemical characterization revealed that the three oxidation variants differed predominantly in t

SUBMITTER: Stracke J 

PROVIDER: S-EPMC4622569 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature