Antibody variants and uses thereof
Described herein are polypeptides and related antibodies comprising a variant Fc domain. The variant Fc domain provide for stabilized Fc:Fc interactions when the polypeptide(s), antibody or antibodies are bound to its target, antigen or antigens on the surface of a cell, thus providing for improved effector functions, such as CDC-response.
1. A variant of a parent antibody comprising an Fc domain of an IgG immunoglobulin and an antigen-binding region, wherein the variant comprises (i) an E345R mutation and (ii) a K439E mutation or an S440K mutation, wherein the numbering of positions is according to the EU Index.
2. A kit-of-parts comprising the variant of claim 1 and instructions for use.
3. The variant of claim 1 , wherein the variant comprises an E345R mutation and a K439E mutation.
4. The variant of claim 1 , wherein the variant comprises an E345R mutation and an S440K mutation.
5. The variant of claim 1 , wherein the antigen-binding region binds to an antigen expressed on a cell membrane.
6. The variant of claim 1 , wherein the antigen-binding region binds to a tumor cell antigen.
7. The variant of claim 1 , wherein the variant is an IgG1 antibody.
8. The variant of claim 3 , wherein the variant is an IgG1 antibody.
9. The variant of claim 4 , wherein the variant is an IgG1 antibody.
10. A kit-of-parts comprising the variant of claim 3 and instructions for use.
11. A kit-of-parts comprising the variant of claim 4 and instructions for use.
12. A mixture of variant antibodies, wherein the mixture comprises (i) a first IgG antibody comprising an E345R mutation and a K439E mutation and (ii) a second IgG antibody comprising an E345R mutation and a S440K mutation, wherein the numbering of positions is according to the EU Index.
13. The mixture of variant antibodies of claim 12 , wherein the first and second IgG antibodies bind to an antigen on a cell membrane.
14. The mixture of variant antibodies of claim 12 , wherein the first and second IgG antibodies bind to a tumor cell antigen.
15. The mixture of variant antibodies of claim 12 , wherein the first IgG antibody or second IgG antibody is an IgG1 antibody.
16. The mixture of variant antibodies of claim 12 , wherein the first and second IgG antibodies are IgG1 antibodies.
17. A kit-of-parts comprising the mixture of variant antibodies of claim 12 and instructions for use.