Prediction and Reduction of the Aggregation of Monoclonal Antibodies.

ABSTRACT: Protein aggregation remains a major area of focus in the production of monoclonal antibodies. Improving the intrinsic properties of antibodies can improve manufacturability, attrition rates, safety, formulation, titers, immunogenicity, and solubility. Here, we explore the potential of predicting and reducing the aggregation propensity of monoclonal antibodies, based on the identification of aggregation-prone regions and their contribution to the thermodynamic stability of the protein. Although aggregation-prone regions are thought to occur in the antigen binding region to drive hydrophobic binding with antigen, we were able to rationally design variants that display a marked decrease in aggregation propensity while retaining antigen binding through the introduction of artificial aggregatio

SUBMITTER: van der Kant R 

PROVIDER: S-EPMC5397608 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature