Polypeptide variants with altered effector function

• US 20060194291A1
• Filed: 05/08/2006
• Published: 08/31/2006
• Est. Priority Date: 01/15/1999
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Presta, Leonard
• Granted Patent: US 7,371,826 B2
• 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 human IgG Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434 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 which comprises an amino acid substitution at position 307.

3. The polypeptide of claim 1 which comprises an amino acid substitution at position 380.

4. The polypeptide of claim 1 which comprises an amino acid substitution at position 434.

5. The polypeptide of claim 1 which comprises amino acid substitutions at positions 380, and 434.

6. The polypeptide of claim 1 which comprises amino acid substitutions at positions 307, 380 and 434.

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

8. The antibody of claim 7 which binds to vascular endothelial growth factor (VEGF), HER2 receptor, CD20, IgE, or LFA-1.

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

17. A composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.

18. The composition of claim 17 which is sterile.

10. A polypeptide comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, or 424 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.

11. A polypeptide comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises amino acid substitutions at any two or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.

12. The polypeptide of claim 11 comprising substitutions at positions 380 and 434.

13. The polypeptide of claim 11 comprising substitutions at positions 307, 380 and 434.

14. A polypeptide comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises substitutions at positions 307, 380 and 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.

15. An antibody that binds CD20 comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises amino acid substitutions at any two or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.

16. An antibody that binds vascular endothelial growth factor (VEGF) comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises amino acid substitutions at any two or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.