Mitigation of liquid-liquid phase separation of a monoclonal antibody by mutations of negative charges on the Fab surface.

ABSTRACT: Some monoclonal antibodies undergo liquid-liquid phase separation owing to self-attractive associations involving electrostatic and other soft interactions, thereby rendering monoclonal antibodies unsuitable as therapeutics. To mitigate the phase separation, formulation optimization is often performed. However, this is sometimes unsuccessful because of the limited time for the development of therapeutic antibodies. Thus, protein mutations with appropriate design are required. In this report, we describe a case study involving the design of mutants of negatively charged surface residues to reduce liquid-liquid phase separation propensity. Physicochemical analysis of the resulting mutants demonstrated the mutual correlation between the sign of second virial coefficient B2, the Fab dipole mom

SUBMITTER: Matsuoka T 

PROVIDER: S-EPMC7598502 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature