IP Library › Patent Application 11927507
Patent Application
App. No. 11/927,507

Optimized Fc Variants and Methods for Their Generation

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Patent No.
US None
App. No.
11/927,507
Abstract

The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.

Claims (19)

1 . An antibody or immunoadhesin of a parent Fc polypeptide, said antibody or immunoadhesin comprising an amino acid substitution at a position selected from the group consisting of 228, 230, 231, 232 and 244, and wherein numbering is according to the EU index.

2 . An antibody or immunoadhesin of a parent Fc polypeptide, said antibody or immunoadhesin comprising an amino acid substitution selected from the group consisting of P228E, P228G, P228K, P228Y, P230A, P230A/E233D, P230A/E233D/I332E, P230E, P230G, P230Y, A231E, A231G, A231K, A231P, A231Y, P232E, P232G, P232K, P232Y, P244H and P244H/P245A/P247V, wherein numbering is according to the EU index.

3 . An antibody or immunoadhesin of a parent Fc polypeptide, said antibody or immunoadhesin comprising an amino acid substitution at position selected from the group consisting of 228, 230, 231, 232 and 244, wherein said antibody or immunoadhesin further comprises an amino acid substitution at a position selected from the group consisting of 221, 222, 224, 227, 228, 230, 231, 223, 233, 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 246, 247, 249, 250, 258, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 278, 280, 281, 283, 285, 286, 288, 290, 291, 293, 294, 295, 296, 297, 298, 299, 300, 302, 313, 317, 318, 320, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335 336 and 428, wherein numbering is according to the EU index.

4 . An antibody or immunoadhesin according to claim 3 comprising an amino acid substitution selected from the group consisting of P228E, P228G, P228K, P228Y, P230A, P230A/E233D, P230A/E233D/I332E, P230E, P230G, P230Y, A231E, A231G, A231K, A231P, A231Y, P232E, P232G, P232K, P232Y, P244H and P244H/P245A/P247V, said antibody or immunoadhesin further comprises an amino acid substitution at a position selected from the group consisting of 221, 222, 224, 227, 228, 230, 231, 223, 233, 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 246, 247, 249, 250, 258, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 278, 280, 281, 283, 285, 286, 288, 290, 291, 293, 294, 295, 296, 297, 298, 299, 300, 302, 313, 317, 318, 320, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335 336 and 428.

5 . An antibody or immunoadhesin according to claim 1 further comprising an amino substitution at a position selected from the group consisting of 239 and 332.

6 . An antibody or immunoadhesin according to claim 1 wherein said antibody or immunoadhesin increases binding affinity to an FcγR as compared to said parent polypeptide, wherein numbering is according to the EU index.

7 . An antibody or immunoadhesin according to claim 6 wherein said FcγR is FcγRIIIa.

8 . An antibody or immunoadhesin according to claim 7 wherein said FcγRIIIa is a V158 or F158 allotype of FcγRIIIa.

9 . An antibody or immunoadhesin according to claim 1 wherein said antibody or immunoadhesin is an antibody.

10 . An antibody according to claim 9 wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, a monoclonal antibody and an antibody fragment.

11 . An antibody or immunoadhesin according to claim 1 wherein said antibody or immunoadhesin further comprises an engineered glycoform.

12 . An antibody or immunoadhesin according to claim 1 wherein said antibody or immunoadhesin has specificity for a target antigen selected from the group consisting of CD19, CD20, CD22, CD30, CD33, CD40, CD40L, CD52, Her2/neu, EGFR, EpCAM, MUC1, GD3, CEA, CA 125, HLA-DR, TNFalpha, MUC18, prostate specific membrane antigen (PMSA) and VEGF.

13 . A composition comprising the antibody or immunoadhesin according to claim 1 further comprising a pharmaceutically acceptable carrier.

14 . A method of treating a mammal in need of said treatment, comprising administering an antibody or immunoadhesin of a parent Fc polypeptide, said antibody or immunoadhesin comprising an amino acid substitution at a position selected from the group consisting of 228, 230, 231, 232 and 244, and wherein numbering is according to the EU index.

15 . A method according to claim 14 wherein said antibody or immunoadhesin further comprises an amino acid substitution at a position selected from the group consisting of 221, 222, 224, 227, 228, 230, 231, 223, 233, 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 246, 247, 249, 250, 258, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 278, 280, 281, 283, 285, 286, 288, 290, 291, 293, 294, 295, 296, 297, 298, 299, 300, 302, 313, 317, 318, 320, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335 336 and 428, wherein numbering is according to the EU index.

16 . A method according to claim 14 , wherein said antibody or immunoadhesin is an antibody.

17 . A method according to claim 16 wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, a monoclonal antibody and an antibody fragment.

18 . A method of treating a mammal in need of said treatment, comprising administering an antibody or immunoadhesin according to claim 13 wherein said antibody or immunoadhesin further comprises an engineered glycoform.

19 . A method according to claim 13 wherein said antibody or immunoadhesin has specificity for a target antigen selected from the group consisting of CD19, CD20, CD22, CD30, CD33, CD40, CD40L, CD52, Her2/neu, EGFR, EpCAM, MUC1, GD3, CEA, CA 125, HLA-DR, TNFalpha, MUC18, prostate specific membrane antigen (PMSA) and VEGF.