Polypeptide variants with altered effector function

• US 20050233382A1
• Filed: 06/22/2005
• Published: 10/20/2005
• 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 7,332,581 B2
• Time in Patent Office: Days
• US Class Current: 435/7.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2839 against the integrin superfamily
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 16/4291 against IgE
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/524 CH2 domain
• CPC Class Codes: C07K 2317/71 Decreased effector function due to an Fc-modification
• 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 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• 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 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, 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.

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

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

4. The polypeptide of claim 1 which comprises at least one amino acid substitution in the Fc region.

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

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

7. The polypeptide of claim 1 comprising an amino acid substitution at position 265.

8. The polypeptide of claim 1 consisting of an amino acid substitution at position 265.

9. The polypeptide of claim 7 wherein the amino acid at position 265 is substituted with Ala.

10. The polypeptide of claim 7 wherein the amino acid at position 265 is substituted with Asn or Glu.

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

Rs.

12. A polypeptide comprising a variant human IgG1 Fc region which displays reduced binding to an Fcγ

R, which polypeptide comprises an amino acid substitution at two or more of amino acid positions 238, 265, 269, 270, 297, 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.

13. The polypeptide of claim 12 which comprises an antibody.

14. The polypeptide of claim 12 which comprises an immunoadhesin.

15. The polypeptide of claim 12 comprising amino acid substitutions at positions 265 and 297.