IP Library › Patent Application 11766609
Patent Application
App. No. 11/766,609

Fc Variants with Increased Affinity for FcyRlla

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Patent No.
US None
App. No.
11/766,609
Abstract

The present invention relates to Fc variants having increased affinity for FcγRIIa, methods for their generation, Fc polypeptides comprising optimized Fc variants, and methods for using optimized Fc variants.

Claims (13)

1 . A polypeptide comprising an Fc variant comprising at least one amino acid substitution in the Fc region of a parent polypeptide, wherein said Fc variant comprises at least one substitution at a position selected from the group consisting of: 227, 228, 230, 233, 234, 235, 236, 239, 243, 263, 264, 265, 271, 274, 281, 291, 292, 295, 296, 299, 303, 327, 328, 329, and 332, wherein numbering is according to the EU Index, and wherein said Fc variant increases binding affinity to FcγRIIa as compared to said parent polypeptide.

2 . A polypeptide according to claim 1 , wherein said Fc variant comprises at least one substitution at a position selected from the group consisting of: 227, 228, 291, 292, 303, and 329, wherein numbering is according to the EU Index, and wherein said Fc variant increases binding affinity to FcγRIIa as compared to said parent polypeptide.

3 . A polypeptide according to claim 1 , wherein said Fc variant comprises at least one substitution selected from the group consisting of: 227E, 228K, 228Y, 230E, 233A, 233G, 2331, 233T, 234G, 234S, 235P, 236D, 236E, 2361, 236S, 236V, 236W, 239D, 239E, 239L, 243W, 263T, 264N, 264R, 264T, 265G, 265I, 265K, 265P, 271G, 271I, 274F, 274G, 274I, 274M, 281D, 281K, 291D, 291H, 291I, 291Q, 292D, 292T, 295E, 295H, 2951, 295M, 295T, 295V, 296E, 296G, 296Q, 296V, 299F, 303E, 303Y, 327K, 327R, 328A, 328S, 328W, 329R, 332D, 332E, 332H, 332N, 332Q, 332S, 332T, and 332Y.

4 . A polypeptide according to claim 1 , wherein said Fc variant comprises multiple substitutions selected from the group consisting of: 234I/235D, 235D/239D/330Y/332E, 239E/332E, 239Q/332E, 239D/332D, 239D/332E, 239D/332N, 239D/332Q, 239E/332D, 239E/332N, 239N/332D, 239N/332E, 239Q/332D, 239E/264I/332E, 239D/272I/332E, 239D/272S/332E, 239D/272Y/332E, 239D/274E/332E, 239D/326E/332E, 239D/326T/332E, 239D/330L/332E, 239D/240I/330Y/332 E, 239E/264I/330Y/332E, 239D/264T/330Y/332E, 239D/272I/330L/332E, 239D/274E/330L/332E, 239D/326E/330Y/332E, 239D/326T/330Y/332E, 264I/330Y/332E, 265Y/297D/299L/332E, 328D/332E, 328I/332E, 328Q/332E, 328T/332E, 330L/332E, and 330Y/332E.

5 . A polypeptide according to claim 1 , wherein said parent polypeptide is an antibody.

6 . A polypeptide according to claim 1 , wherein said parent polypeptide is an Fc fusion protein.

7 . A polypeptide according to claim 1 , wherein said polypeptide further comprises an engineered glycoform.

8 . A polypeptide according to claim 7 wherein said engineered glycoform comprises an altered level of fucosylation or bisecting oligosaccharides as compared to the parent polypeptide.

9 . A pharmaceutical composition comprising a polypeptide according to claim 1 and a pharmaceutically acceptable carrier.

10 . A method of treating a mammal in need of said treatment, comprising administering a polypeptide of claim 1 .

11 . A polypeptide according to claim 1 wherein said polypeptide is a full length antibody.

12 . A polypeptide according to claim 1 wherein said polypeptide is a human antibody.

13 . A polypeptide according to claim 1 wherein said polypeptide is an antibody fragment.