Antibody Fc mutants with ablated effector functions
Antibody and other Fc-containing molecules with variations in the Fc region reduce binding to Fc gamma receptors and resulting activity and can be used in the treatment of various diseases and disorders.
1. A method of altering binding of an IgG2 based Fc-containing molecule to Fcγ receptors as compared to a wildtype IgG2 based Fc, comprising altering the sequence of an Fc domain based on an IgG2 constant region at residues 233, 234, 235, 237, and 238 defined by the EU numbering system, to comprise a sequence selected from PAAAS (SEQ ID NO:5) and SAAAS (SEQ ID NO:6), and altering the IgG2 based Fc-containing molecule to further comprise mutations H268A or H268Q, V309L, A330S and P331S, wherein the binding of the IgG2 based Fc-containing molecule to Fcγ receptors is reduced as compared to a wildtype IgG2 based Fc.