Optimized Fc variants

• US 20090042291A1
• Filed: 05/30/2008
• Published: 02/12/2009
• Est. Priority Date: 03/01/2002
• Status: Abandoned Application

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Vostiar, Igor, Lazar, Gregory Alan, Karki, Sher Bahadur, Desjarlais, John R., Chu, Seung Yup, Moore, Gregory L.
• Application Number:
  US12/156,184
• Publication Number:
  US 20090042291A1
• Time in Patent Office: Days
• US Class Current: 435/375
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

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

Claims

1. A method of inhibiting proliferative effects of at least one cell comprising

contacting the cell with an Fc variant, and

wherein said Fc variant coengages a target antigen on the cell'"'"'s surface and an Fcγ

R on the cell'"'"'s surface.

2. The method of claim 1, wherein said Fcγ

R is Fcγ

RIIb.

3. The method of claim 2, wherein said Fc variant has enhanced binding affinity to Fcγ

RIIb relative to a parent polypeptide.

4. The method of claim 3, wherein said Fc variant comprises at least one amino acid modification in the Fc region compared to a parent polypeptide, wherein said modification is at a position selected from 234, 235, 236, 237, 239, 266, 267, 268, 298, 327, 328, 329, 330, and 332, wherein numbering is according to the EU index.

5. The method of claim 4, wherein said modification is at least one amino acid substitution or combination of amino acid substitutions selected from the group consisting of 234F, 234G, 234I, 234K, 234N, 234P, 234Q, 234S, 234V, 234W, 234Y, 235H, 235I, 235N, 235P, 235Q, 235R, 235S, 235W, 235Y, 236D, 236F, 236H, 236I, 236K, 236L, 236M, 236P, 236Q, 236R, 236S, 236T, 236V, 236W, 236Y, 237E, 237H, 237K, 237L, 237P, 237Q, 237S, 237V, 237Y, 239D, 239E, 239N, 239Q, 266I, 266M, 267D, 267E, 268D, 268E, 268Q, 298D, 298E, 298M, 298Q, 327D, 327L, 327N, 328E, 328F, 329E, 330H, 330S, 267E/327D, 239D/267E, 239D/268D, 239D/332E, and 239D/267E/332E.