Modulation of the high concentration viscosity of IgG₁ antibodies using clinically validated Fc mutations.

ABSTRACT: The self-association of therapeutic antibodies can result in elevated viscosity and create problems in manufacturing and formulation, as well as limit delivery by subcutaneous injection. The high concentration viscosity of some antibodies has been reduced by variable domain mutations or by the addition of formulation excipients. In contrast, the impact of Fc mutations on antibody viscosity has been minimally explored. Here, we studied the effect of a panel of common and clinically validated Fc mutations on the viscosity of two closely related humanized IgG_1, κ antibodies, omalizumab (anti-IgE) and trastuzumab (anti-HER2). Data presented here suggest that both Fab-Fab and Fab-Fc interactions contribute to the high viscosity of omalizumab, in a four-contact model of self-associati

SUBMITTER: Heisler J 

PROVIDER: S-EPMC11262234 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature