Engineering FcRn binding kinetics dramatically extends antibody serum half-life and enhances therapeutic potential

This study presents a rational Fc engineering framework to optimize FcRn binding kinetics, addressing a previously unconsidered challenge-endogenous IgG competition during intracellular trafficking of therapeutic antibodies. The distinct kinetic behaviors of YML and EML highlight the critical necessity of precise control over pH-dependent association and dissociation rates in FcRn binding. YML represents a next-generation Fc platform, offering enhanced pharmacokinetics and improved effector functions, thus providing a powerful strategy for developing biologics with superior serum persistence and therapeutic efficacy.