The Fc domain of IgG has been the target of multiple mutational studies aimed at altering the
pH-dependent IgG/FcRn interaction to modulate IgG pharmacokinetics. These studies have
yielded antibody variants with disparate pharmacokinetic characteristics, ranging from
extended in vivo half-life to those exhibiting extremely rapid clearance. To better understand
pH-dependent binding parameters that govern these outcomes and limit FcRn-mediated half-
life extension, we generated a panel of novel Fc variants with high affinity binding at acidic …