Polypeptide variants and uses thereof
As described herein are polypeptides and antibodies having an Fc region and an antigen binding region where the Fc region has an Fc-Fc-enhancing mutation and a C1q binding-enhancing mutation providing for polypeptides or antibodies with increased CDC activity and/or agonistic activity.
1. A polypeptide comprising an Fc region of a human IgG1 and an antigen binding region, wherein the Fc region comprises the following substitutions: E430G, K326W, and E333S,
wherein the numbering position is according to EU numbering.
2. The polypeptide according to claim 1 , wherein the Fc region further comprises an F405L or a K409R substitution.
3. The polypeptide according to claim 1 , wherein the polypeptide is an antibody, monospecific antibody, bispecific antibody or multispecific antibody.
4. The polypeptide according to claim 3 , wherein the polypeptide is a bispecific antibody comprising a first heavy chain and a first antigen binding region, and a second heavy chain and a second antigen binding region, wherein
a. said first heavy chain comprises an F405L substitution, and
b. said second heavy chain comprises a K409R substitution.
5. The polypeptide according to claim 1 , wherein the polypeptide is a human antibody, humanized antibody or chimeric antibody.
6. A composition comprising at least one polypeptide according to claim 1 .
7. A kit of parts comprising the polypeptide of claim 1 , wherein said polypeptide is in one or more containers.
8. A composition comprising at least one polypeptide according to claim 2 .
9. A composition comprising at least one polypeptide according to claim 3 .
10. A composition comprising at least one polypeptide according to claim 4 .
11. A composition comprising at least one polypeptide according to claim 5 .
12. A kit of parts comprising the polypeptide of claim 2 , wherein said polypeptide is in one or more containers.
13. A kit of parts comprising the polypeptide of claim 3 , wherein said polypeptide is in one or more containers.
14. A kit of parts comprising the polypeptide of claim 4 , wherein said polypeptide is in one or more containers.
15. A kit of parts comprising the polypeptide of claim 5 , wherein said polypeptide is in one or more containers.