Optimized Fc variants and methods for their generation
The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.
1 - 67 . (canceled)
68 . An antibody or immunoadhesin of a parent Fc polypeptide, said antibody or immunoadhesin comprising an amino acid substitution selected from the group consisting of 330L, 330Y, 330V, 330I, 330F, 330R and 330H, wherein numbering is according to the EU index.
69 . An antibody or immunoadhesin of a parent Fc polypeptide, said antibody or immunoadhesin comprising an amino acid substitution selected from the group consisting of 330L, 330Y, 330V, 330I, 330F, 330R and 330H, wherein said antibody or immunoadhesin further comprises an amino acid substitution at a position selected from the group consisting of 234, 235, 240, 241, 243, 244, 245, 247, 256, 262, 263, 264, 265, 266, 267, 269, 270, 290, 296, 297, 298, 299, 312, 313, 322, 325, 326, 327, 328, 329, 331, 332, 333, 334 and 339, wherein numbering is according to the EU index.
70 . An antibody or immunoadhesin of a parent Fc polypeptide, said antibody or immunoadhesin comprising an amino acid substitution selected from the group consisting of 330L, 330Y, 330V, 330I, 330F, 330R and 330H, wherein said antibody or immunoadhesin further comprises at least one an amino acid substitution at a position selected from the group consisting of 239 and 332, wherein numbering is according to the EU index.
71 . An antibody or immunoadhesin according to claim 68 wherein said antibody or immunoadhesin increases binding affinity to an FcγR as compared to said parent polypeptide.
72 . An antibody or immunoadhesin according to claim 68 wherein said antibody or immunoadhesin increases binding affinity to an FcγR as compared to said parent polypeptide.
73 . An antibody or immunoadhesin according to claim 74 wherein said FcγR is FcγRIIIa.
74 . An antibody or immunoadhesin according to claim 73 wherein said FcγRIIIa is a V158 or F158 allotype of FcγRIIIa.
75 . An antibody or immunoadhesin according to claim 68 wherein said antibody or immunoadhesin decreases binding affinity to an FcγR as compared to said parent polypeptide.
76 . An antibody or immunoadhesin according to claim 68 wherein said antibody or immunoadhesin is an antibody.
77 . An antibody according to claim 76 wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, a monoclonal antibody and an antibody fragment.
78 . An antibody or immunoadhesin according to claim 68 wherein said antibody or immunoadhesin further comprises an engineered glycoform.
79 . An antibody or immunoadhesin according to claim 68 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.
80 . A composition comprising the antibody or immunoadhesin according to claim 68 further comprising a pharmaceutically acceptable carrier.
81 . 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 selected from the group consisting of 330L, 330Y, 330V, 330I, 330F, 330R and 330H, and wherein numbering is according to the EU index.
82 . A method according to claim 81 wherein said antibody or immunoadhesin further comprises an amino acid substitution at a position selected from the group consisting of 234, 235, 240, 241, 243, 244, 245, 247, 256, 262, 263, 264, 265, 266, 267, 269, 270, 290, 296, 297, 298, 299, 312, 313, 322, 325, 326, 327, 328, 329, 331, 332, 333, 334 and 339 .
83 . A method according to claim 81 wherein said antibody or immunoadhesin increases binding affinity to an FcγR as compared to said parent polypeptide.
84 . A method according to claim 83 wherein said FcγR is FcγRIIIa.
85 . A method according to claim 84 wherein said FcγRIIIa is a V158 or F158 allotype of FcγRIIIa.
86 . A method according to claim 81 wherein said antibody or immunoadhesin decreases binding affinity to an FcγR as compared to said parent polypeptide.
87 . A method according to claim 81 wherein said antibody or immunoadhesin is an antibody.
88 . A method according to claim 81 wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, a monoclonal antibody and an antibody fragment.
89 . A method according to claim 88 wherein said antibody or immunoadhesin further comprises an engineered glycoform.
90 . A method according to claim 81 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.