ENGINEERED FC
Antigen-binding molecules comprising an Fc region comprising a polypeptide having: (i) C at the position corresponding to position 242, and C at the position corresponding to position 334, and (ii) one or more of: A at the position corresponding to position 236, D at the position corresponding to position 239, E at the position corresponding to position 332, L at the position corresponding to position 330, K at the position corresponding to position 345, and G at the position corresponding to position 430 are disclosed. Also discloses are constituent polypeptides of such Fc regions, nucleic acids encoding such antigen- binding molecules and polypeptides, compositions comprising such antigen-binding molecules, polypeptides and nucleic acids, and methods using the same.
1 . An antigen-binding molecule, optionally isolated, comprising an Fc region, the Fc region comprising a polypeptide having: (i) C at the position corresponding to position 242, and C at the position corresponding to position 334, and (ii) one or more of: A at the position corresponding to position 236, D at the position corresponding to position 239, E at the position corresponding to position 332, L at the position corresponding to position 330, K at the position corresponding to position 345, and G at the position corresponding to position 430.
2 . The antigen binding molecule according to claim 1 , wherein the Fc region comprises a polypeptide having: (i) C at the position corresponding to position 242, and C at the position corresponding to position 334, and (ii) A at the position corresponding to position 236, D at the position corresponding to position 239, E at the position corresponding to position 332, and L at the position corresponding to position 330;
or A at the position corresponding to position 236, D at the position corresponding to position 239, and E at the position corresponding to position 332; or A at the position corresponding to position 236, and D at the position corresponding to position 239; or K at the position corresponding to position 345, and G at the position corresponding to position 430.
3 . The antigen binding molecule according to claim 1 or claim 2 , wherein the Fc region comprises a polypeptide having: (i) C at the position corresponding to position 242, and C at the position corresponding to position 334, and (ii) A at the position corresponding to position 236, D at the position corresponding to position 239, E at the position corresponding to position 332, and L at the position corresponding to position 330.
4 . The antigen binding molecule according to claim 1 or claim 2 , wherein the Fc region comprises a polypeptide having: (i) C at the position corresponding to position 242, and C at the position corresponding to position 334, and (ii) A at the position corresponding to position 236, D at the position corresponding to position 239, and E at the position corresponding to position 332.
5 . The antigen binding molecule according to claim 1 or claim 2 , wherein the Fc region comprises a polypeptide having: (i) C at the position corresponding to position 242, and C at the position corresponding to position 334, and (ii) A at the position corresponding to position 236, and D at the position corresponding to position 239.
6 . The antigen binding molecule according to claim 1 or claim 2 , wherein the Fc region comprises a polypeptide having: (i) C at the position corresponding to position 242, and C at the position corresponding to position 334, and (ii) K at the position corresponding to position 345, and G at the position corresponding to position 430.
7 . The antigen binding molecule according to any one of claims 1 to 6 , wherein the Fc region comprises a polypeptide comprising an amino acid sequence having at least 60% sequence identity to SEQ ID NO:39, 38, 37, 41, 22, 21, 20 or 24.
8 . A polypeptide, optionally isolated, comprising: an amino acid sequence having at least 60% sequence identity to SEQ ID NO:31 or 6, wherein the polypeptide comprises the following amino acid residues at the specified positions numbered relative to SEQ ID NO:31 or 6: (i) C at position 15, and C at position 107, and (ii) one or more of: A at position 9, D at position 12, L at position 103, E at position 105, K at position 118, and G at position 203.
9 . The polypeptide according to claim 8 , wherein the polypeptide comprises the following amino acid residues at the specified positions numbered relative to SEQ ID NO:31 or 6: (i) C at position 15, and C at position 107, and (ii) A at position 9, D at position 12, L at position 103, and E at position 105; or A at position 9, D at position 12, and E at position 105; or A at position 9, and D at position 12; or K at position 118, and G at position 203.
10 . The polypeptide according to claim 8 or claim 9 , wherein the polypeptide comprises the following amino acid residues at the specified positions numbered relative to SEQ ID NO:31 or 6: (i) C at position 15, and C at position 107, and (ii) A at position 9, D at position 12, L at position 103, and E at position 105.
11 . The polypeptide according to claim 8 or claim 9 , wherein the polypeptide comprises the following amino acid residues at the specified positions numbered relative to SEQ ID NO:31 or 6: (i) C at position 15, and C at position 107, and (ii) A at position 9, D at position 12, and E at position 105.
12 . The polypeptide according to claim 8 or claim 9 , wherein the polypeptide comprises the following amino acid residues at the specified positions numbered relative to SEQ ID NO:31 or 6: (i) C at position 15, and C at position 107, and (ii) A at position 9, and D at position 12.
13 . The polypeptide according to claim 8 or claim 9 , wherein the polypeptide comprises the following amino acid residues at the specified positions numbered relative to SEQ ID NO:31 or 6: (i) C at position 15, and C at position 107, and (ii) K at position 118, and G at position 203.
14 . A polypeptide, optionally isolated, comprising the amino acid sequence of SEQ ID NO:39, 38, 37, 41, 22, 21, 20 or 24.
15 . An Fc region, optionally isolated, comprising a polypeptide according to any one of claims 8 to 14 .
16 . An antigen-binding molecule, optionally isolated, comprising a polypeptide according to any one of claims 7 to 13 , or an Fc region according to claim 14 .
17 . A nucleic acid, or a plurality of nucleic acids, optionally isolated, encoding an antigen-binding molecule according to any one of claim 1 to 7 or 16 , a polypeptide according to any one of claims 8 to 14 , or an Fc region according to claim 15 .
18 . An expression vector, or a plurality of expression vectors, comprising a nucleic acid or a plurality of nucleic acids according to claim 17 .
19 . A cell comprising an antigen-binding molecule according to any one of claim 1 to 7 or 16 , a polypeptide according to any one of claims 8 to 14 , an Fc region according to claim 15 , a nucleic acid or a plurality of nucleic acids according to claim 17 , or an expression vector or a plurality of expression vectors according to claim 18 .
20 . A method comprising culturing a cell comprising a nucleic acid or a plurality of nucleic acids according to claim 17 , or an expression vector or a plurality of expression vectors according to claim 18 , under conditions suitable for expression of the antigen-binding molecule, polypeptide or Fc region from the nucleic acid(s) or expression vector(s).
21 . A composition comprising an antigen-binding molecule according to any one of claim 1 to 7 or 16 , a polypeptide according to any one of claims 8 to 14 , an Fc region according to claim 15 , a nucleic acid or a plurality of nucleic acids according to claim 17 , an expression vector or a plurality of expression vectors according to claim 18 , or a cell according to claim 19 .
22 . An antigen-binding molecule according to any one of claim 1 to 7 or 16 , a polypeptide according to any one of claims 8 to 14 , an Fc region according to claim 15 , a nucleic acid or a plurality of nucleic acids according to claim 17 , an expression vector or a plurality of expression vectors according to claim 18 , a cell according to claim 19 , or a composition according to claim 21 for use in a method of medical treatment or prophylaxis.
23 . An antigen-binding molecule according to any one of claim 1 to 7 or 16 , a polypeptide according to any one of claims 8 to 14 , an Fc region according to claim 15 , a nucleic acid or a plurality of nucleic acids according to claim 17 , an expression vector or a plurality of expression vectors according to claim 18 , a cell according to claim 19 , or a composition according to claim 21 , for use in a method of treatment or prevention of a cancer, an infectious disease or an autoimmune disease.
24 . A method, optionally an in vitro method, of killing cells expressing a target antigen, comprising contacting cells expressing the target antigen with an antigen-binding molecule according to any one of claim 1 to 7 or 16 , a polypeptide according to any one of claims 8 to 14 , an Fc region according to claim 15 , a cell according to claim 19 , or a composition according to claim 21 .