Antibody Fc mutants with ablated effector functions
Antibody and other Fc-containing molecules with variations in the Fc region with reduced binding to Fc gamma receptors and resulting activity and can be used in the treatment of various diseases and disorders.
1. An isolated Fc-containing molecule, comprising a mutated IgG1 or IgG4 Fc domain and having binding reduced by at least 800 fold or undetectable binding to a Fcγ receptor (FcγR), selected from the group consisting of FcγRI, FcγRIIa-H131 variant, FcγRlIa-R131 variant, FcγRIIb, and FcγRIII-V158 variant, as compared to an Fc-containing molecule with a wild type Fc domain, wherein the mutated IgG1 Fc comprises the mutations L234A, L235A, G237A P238S, H268A, A330S, and P331S, and wherein the mutated IgG4 Fc comprises the mutations S228P, F234A, L235A, G237A, and P238S.
2. The molecule of claim 1 comprising an antibody Fc domain with a mutated IgG1 region comprising mutations L234A, L235A, G237A, P238S, H268A, A330S and P331S.
3. The molecule of claim 1 , wherein the molecule is an antibody, an antibody fragment or an Fc region.
4. The molecule of claim 1 comprising an antibody Fc domain with a mutated IgG4 region comprising mutations S228P, F234A, L235A, G237A, and P238S.
5. A pharmaceutical composition comprising the Fc containing molecule of claim 1 and a pharmaceutically acceptable excipient.