Polypeptide variants with altered effector function
AssigneeGenentech, Inc.
InventorLeonard Presta
Life of this patent
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Abstract
The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.
Claims79
A variant of a parent polypeptide comprising an Fc region, which variant mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of human effector cells more effectively, or binds an Fc gamma receptor (FcγR) with better affinity, than the parent polypeptide and comprises at least one amino acid modification in the Fc region.
A polypeptide comprising a variant Fc region with altered Fc gamma receptor (FcγR) binding affinity, which polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296, 298, 301, 303, 305, 307, 309, 312, 315, 320, 322, 324, 326, 327, 329, 330, 331, 333, 334, 335, 337, 338, 340, 360, 373, 376, 378, 382, 388, 389, 398, 414, 416, 419, 430, 434, 435, 437, 438 or 439 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
A polypeptide comprising a variant Fc region with altered neonatal Fc receptor (FcRn) binding affinity, which polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 252, 253, 254, 255, 256, 265, 272, 286, 288, 303, 305, 307, 309, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 386, 388, 400, 413, 415, 424, 433, 434, 435, 436, 439 or 447 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
A polypeptide comprising a variant Fc region which comprises amino acid modifications at amino acid positions 298, 333 and 334 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
A polypeptide comprising a variant Fc region which comprises amino acid modifications at amino acid positions 298 and 334 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
A polypeptide comprising a variant Fc region which comprises an amino acid modification at amino acid position 298 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
A polypeptide comprising a variant Fc region with altered affinity for an FcγR allotype, which polypeptide comprises an amino acid modification at any one or more of amino acid positions 265, 267, 268, 270, 290, 298, 305, 307, 315, 317, 320, 331, 333 or 334 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
A polypeptide comprising a variant Fc region which comprises amino acid modifications at two or all of amino acid positions 307, 380 and 434 of the Fc region, wherein the numbering of the residues is that of the EU index as in Kabat.
A method for making a variant Fc region with altered Fc receptor (FcR) binding affinity, or altered antibody-dependent cell-mediated cytotoxicity (ADCC) activity, comprising:
- (a) introducing one or more amino acid modifications into an Fc region of a parent polypeptide in order to generate a variant Fc region;
- (b) determining binding of the variant Fc region to an FcR, or determining ADCC activity of the variant Fc region.
The method of claim 79 wherein the Fc receptors include human Fc gamma receptor II (FcγRII) and human Fc gamma receptor III (FcγRIII).
Dependencies are inferred from the claim text.