Polypeptide variants with altered effector function

• US 20060194290A1
• Filed: 05/08/2006
• Published: 08/31/2006
• Est. Priority Date: 01/15/1999
• Status: Abandoned Application

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Presta, Leonard
• Application Number:
  US11/429,792
• Publication Number:
  US 20060194290A1
• Time in Patent Office: Days
• US Class Current: 435/69.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/4291 against IgE
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• 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 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus

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.

Claims

1. A polypeptide comprising a variant Fc region which displays reduced binding to an Fcγ

R and comprises an amino acid substitution at any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 292, 293, 294, 295, 296, 298, 301, 303, 322, 324, 327, 329, 333, 335, 338, 340, 373, 376, 382, 388, 389, 414, 416, 419, 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.

2. The polypeptide of claim 1 wherein the variant Fc region comprises a variant human IgG Fc region.

3. The polypeptide of claim 1 which displays reduced binding to an Fcγ

RI.

4. The polypeptide of claim 3 which displays reduced binding to the Fcγ

RI and comprises an amino acid substitution at any one or more of amino acid 238, 265, 269, 270, 327 or 329 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.

5. The polypeptide of claim 1 which displays reduced binding to an Fcγ

RII.

6. The polypeptide of claim 5 which displays reduced binding to the Fcγ

RII and comprises an amino acid substitution at any one or more of amino acid positions 238, 265, 269, 270, 292, 294, 295, 298, 303, 324, 327, 329, 333, 335, 338, 373, 376, 414, 416, 419, 435, 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.

7. The polypeptide of claim 1 which displays reduced binding to an Fcγ

RIII.

8. The polypeptide of claim 7 which displays reduced binding to the Fcγ

RIII and comprises an amino acid substitution at any one or more of amino acid 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289,293, 294, 295, 296, 301, 303, 322, 327, 329, 338, 340, 373, 376, 382, 388, 389, 416, 434, 435 or 437 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.

9. The polypeptide of claim 1 which comprises an antibody.

10. The polypeptide of claim 1 which comprises an immunoadhesin.

11. The polypeptide of claim 1 which comprises two or more amino acid substitutions at the amino acid positions listed therein.

12. The polypeptide of claim 1 which comprises three or more amino acid substitutions at the amino acid positions listed therein.

13. The polypeptide of claim 1 with reduced binding to all Fcγ

Rs.

14. An antibody or immunoadhesin polypeptide comprising a variant human IgG1 Fc region which displays reduced binding to an Fcγ

R, which polypeptide comprises an amino acid substitution at any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 292, 293, 294, 295, 296, 298, 301, 303, 322, 324, 327, 329, 333, 335, 338, 340, 373, 376, 382, 388, 389, 414, 416, 419, 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.

15. The polypeptide of claim 14 which comprises an antibody.

16. The polypeptide of claim 14 which comprises an immunoadhesin.

17. An antibody or immunoadhesin polypeptide comprising a variant human IgG1 Fc region, wherein the amino acid residue at any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 292, 293, 294, 295, 296, 298, 301, 303, 322, 324, 327, 329, 333, 335, 338, 340, 373, 376, 382, 388, 389, 414, 416, 419, 434, 435, 437, 438 or 439 of the Fc region is substituted with Ala, and wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.

18. An antibody or immunoadhesin polypeptide comprising a variant human IgG1 Fc region, which polypeptide comprises an amino acid substitution at any two or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 292, 293, 294, 295, 296, 298, 301, 303, 322, 324, 327, 329, 333, 335, 338, 340, 373, 376, 382, 388, 389, 414, 416, 419, 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.

19. The polypeptide of claim 18 which comprises three or more amino acid substitutions at the amino acid positions listed therein.