Fc variants with optimized properties
AssigneeXencor, Inc.
InventorsGregory Lazar, Wei Dang, John Desjarlais, Sher Karki
Life of this patent
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Abstract
The present invention relates to Fc variants with optimized properties, methods for their generation, Fc polypeptides comprising Fc variants with optimized properties, and methods for using Fc variants with optimized properties.
Claims19
An Fc variant of a parent Fc polypeptide, wherein said Fc variant exhibits altered binding to at least on FcγR or altered antibody dependent cell-mediated cytotoxicity as compared to said parent Fc polypeptide, wherein said Fc variant comprises at least one amino acid modification in the Fc region of said parent Fc polypeptide, wherein said modification is selected from the group consisting of:
- 227G, 234D, 234E, 234G, 234I, 234Y, 235D, 235I, 235S, 236S, 239D, 246H, 255Y, 258H, 260H, 2641, 267D, 267E, 268D, 268E, 272H, 272I, 272R, 281D, 282G, 283H, 284E, 293R, 295E, 304T, 324G, 324I, 327D, 327A, 328A, 328D, 328E, 328F, 328I, 328M, 328N, 328Q, 328T, 328V, 328Y, 330I, 330L, 330Y, 332D, 332E, 335D, an insertion of G between positions 235 and 236, an insertion of A between positions 235 and 236, an insertion of S between positions 235 and 236, an insertion of T between positions 235 and 236, an insertion of N between positions 235 and 236, an insertion of D between positions 235 and 236, an insertion of V between positions 235 and 236, an insertion of L between positions 235 and 236, an insertion of G between positions 235 and 236, an insertion of A between positions 235 and 236, an insertion of S between positions 235 and 236, an insertion of T between positions 235 and 236, an insertion of N between positions 235 and 236, an insertion of D between positions 235 and 236, an insertion of V between positions 235 and 236, an insertion of L between positions 235 and 236, an insertion of G between positions 297 and 298, an insertion of A between positions 297 and 298, an insertion of S between positions 297 and 298, an insertion of D between positions 297 and 298, an insertion of G between positions 326 and 327, an insertion of A between positions 326 and 327, an insertion of T between positions 326 and 327, an insertion of D between positions 326 and 327, and an insertion of E between positions 326 and 327, wherein numbering is according to the EU index.
An IgG1 variant of a parent IgG1 polypeptide, wherein said IgG1 variant exhibits improved binding to at least on FcγR, wherein said Fc variant comprises at least one amino acid insertion in the Fc region of said parent IgG1 polypeptide.
An Fc variant of a parent Fc polypeptide, wherein said Fc variant exhibits altered complement dependent cytotoxicity as compared to said parent Fc polypeptide, wherein said Fc variant comprises at least one amino acid modification in the Fc region of said parent Fc polypeptide, wherein said modification is selected from the group consisting of:
- 233I, 234Y, 235D, 235Y, 239D, 267D, 267E, 267Q, 268D, 268E, 268F, 268G, 271A, 271D, 271I, 272H, 272I, 272R, 274E, 274R, 274Y, 276D, 276L, 276S, 278E, 278H, 278Q, 278R, 281D, 282G, 284D, 284E, 284T, 285Y, 293R, 300D, 300T, 320I, 320T, 320Y, 322H, 322T, 322Y, 324D, 324H, 324I, 324L, 324T, 324V, 326L, 326T, 327A, 327D, 327H, 327R, 328Q, 330E, 330G, 330H, 330I, 330L, 330N, 330V, 330Y, 331D, 331L, 332E, 333F, 334T, 335D, and 335Y, wherein numbering is according to the EU index.
An Fc variant of a parent Fc polypeptide, wherein said Fc variant exhibits improved complement dependent cytotoxicity as compared to said parent Fc polypeptide, wherein said Fc variant comprises at least one amino acid modification in the Fc region of said parent Fc polypeptide, wherein said modification is at a position selected from the group consisting of:
- 235, 239, 267, 268, 272, 276, 278, 282, 284, 285, 293, 300, 322, 324, 327, 330, 331, 332, and 335, wherein numbering is according to the EU index.
An Fc variant of a parent Fc polypeptide, wherein said Fc variant exhibits reduced binding to one or more FcγRs, reduced antibody dependent cell-mediated cytotoxicity, or reduced complement dependent cytotoxicity as compared to said parent Fc polypeptide, wherein said Fc variant comprises at least one amino acid modification in the Fc region of said parent Fc polypeptide, wherein said modification is selected from the group consisting of:
- 232G, 234G, 234H, 235D, 235G, 235H, 236I, 236N, 236P, 236R, 237K, 237L, 237N, 237P, 238K, 239R, 265G, 267R, 269R, 270H, 297S, 299A, 299I, 299V, 325A, 325L, 327R, 328R, 329K, 330I, 330L, 330N, 330P, 330R, and 331L, wherein numbering is according to the EU index.
An Fc variant of a parent Fc polypeptide, wherein said Fc variant reduces by at least 10 fold relative to said parent Fc polypeptide:
- affinity to human FcγRIIIa, affinity to human FcγRI, and complement dependent cytotoxicity.
An IgG antibody that targets CTLA-4, TNFα, VEGF, α4-integrin, or CD32b, wherein said antibody has reduced FcγR affinity, reduced antibody dependent cell-mediated cytotoxicity, or reduced complement dependent cytotoxicity relative to a WT antibody.
An IgG antibody variant of a parent IgG antibody, wherein said IgG variant exhibits improved antibody dependent cell-mediated cytotoxicity in the presence of competing IgG.
Dependencies are inferred from the claim text.