Discloses a polypeptide comprising an Fc variant of a wild-type human IgG Fc region, said Fc variant comprising an amino acid substitution at position Pro329, wherein Pro329 of a wild-type human Fc region is substituted with glycine or arginine, and wherein the Fc variant comprises at least two further amino acid substitutions, wherein said further amino acid substitutions are L234A and L235A of the human IgG1 Fc region or S228P and L235E of the human IgG4 Fc region, wherein the residues are numbered according to the EU index of Kabat, and wherein said polypeptide exhibits an at least 10-fold reduced affinity to the human FcγRIIIA and a reduced affinity to the human, FcγRIIA, FcγRI and the human C1q receptor, compared to a polypeptide comprising the wildtype IgG Fc region, and wherein the ADCC induced by said polypeptide is reduced to 0-20% of the ADCC induced by the polypeptide comprising a wild-type human IgG Fc region. Also discloses use of the Fc region for down-modulation of ADCC or ADCP.
Antibody fc variants