Fc Engineering: Serum Half-Life Modulation Through FcRn Binding

Controlling the half-life of pharmaceuticals through Fc engineering is a desirable approach to achieve optimal exposure and targeting. The long serum residence time of gamma immunoglobulins is attributed to the Fc binding to the neonatal Fc receptor (FcRn). The residues in the Fc region that interact with FcRn have been mapped and individual mutations of these residues have demonstrated reduced affinity to FcRn and faster blood clearance. Here, we describe site-specific mutagenesis of Fc residues in a scFv-Fc fusion protein, as well as the mammalian production, purification, characterization, and the in vivo pharmacokinetics of these antibody fragments.