Fc-region variants with modified fcrn-binding and methods of use

Abstract

Herein is reported an IgG class Fc-region comprising a first variant Fc-region polypeptide and a second variant Fc-region polypeptide, wherein a) the first variant Fc-region polypeptide is derived from a first parent IgG class Fc-region polypeptide and the second variant Fc-region polypeptide is derived from a second parent IgG class Fc-region polypeptide, whereby the first parent IgG class Fc-region polypeptide is identical to or different from the second parent IgG class Fc-region polypeptide, and b) the first variant Fc-region polypeptide differs from the second variant Fc-region polypeptide in one or more amino acid residues other than those amino acid residues in which the first parent IgG class Fc-region polypeptide differs from the second parent IgG class Fc-region polypeptide, and c) the IgG class Fc-region comprising the first variant Fc-region polypeptide and the second variant Fc-region polypeptide has an affinity to a human Fc-receptor that is different than that of an IgG class Fc-region comprising the first parent IgG class Fc-region polypeptide of a) and the second parent IgG class Fc-region polypeptide of a), wherein either the first Fc-region polypeptide or the second Fc-region polypeptide or both Fc-region polypeptides comprise independently of each other mutations or combination of mutations as specified in the application.

Description

field of invention [0001] The present invention relates to antibodies and Fc-region fusion polypeptides that are asymmetrically modified with respect to interaction with Fc-receptors, especially FcRn, and methods of their use. Background of the invention [0002] The neonatal Fc-receptor (FcRn) is important for the metabolic fate of IgG class antibodies in vivo. FcRn functions to rescue IgG from the lysosomal degradation pathway, resulting in reduced clearance and increased half-life. It is a heterodimeric protein consisting of 2 polypeptides: 50 kDa class I major histocompatibility complex-like protein (α-FcRn) and 15 kDa β2-microglobulin (β2m). FcRn binds with high affinity to the CH2-CH3 portion of the Fc region of IgG class antibodies. The interaction between IgG class antibodies and FcRn is pH-dependent and occurs in a 1:2 stoichiometry, i.e. one IgG antibody molecule can interact with two FcRn molecules via its two heavy chain Fc region polypeptides (see , eg Huber,...

AI Technical Summary

Problems solved by technology

FcRn functions to rescue IgG from the lysosomal degradation pathway, resulting in reduced clearance and increased half-life

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