Polypeptide variants with altered effector function

• US 7,371,826 B2
• Filed: 05/08/2006
• Issued: 05/13/2008
• Est. Priority Date: 01/15/1999
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Presta, Leonard
• Primary Examiner(s): Haddad; Maher M.
• Assistant Examiner(s): DAHLE, CHUN WU
• Application Number:
  US11/429,793
• Publication Number:
  US 20060194291A1
• Time in Patent Office: 736 Days
• Field of Search: None
• US Class Current: 530/387.1
• 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. An antibody comprising a variant human IgG1 Fc region which is not a native sequence Fc region, wherein the antibody comprises an amino acid substitution at amino acid position 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat, and wherein the variant Fc region binds human neonatal Fc receptor (FcRn) with increased binding affinity compared to a native sequence human IgG1 Fc region.

2. The antibody of claim 1 which consists of an amino acid substitution at position 434 of the Fc region.

3. The antibody of claim 1 comprising a N434A substitution.

4. An antibody that binds vascular endothelial growth factor (VEGF) comprising a variant human IgG1 Fc region which is not a native sequence Fc region, wherein the antibody comprises an amino acid substitution at amino acid position 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat, and wherein the variant Fc region binds human neonatal Fc receptor (FcRn) with increased binding affinity compared to a native sequence human IgG1 Fc region.

5. An immunoadhesin comprising a variant human IgG1 Fc region which is not a native sequence Fc region, wherein the immunoadhesin comprises an amino acid substitution at amino acid position 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat, and wherein the variant Fc region binds human neonatal Fc receptor (FcRn) with increased binding affinity compared to a native sequence human IgG1 Fc region.

6. The immunoadhesin of claim 5 which consists of an amino acid substitution at position 434 of the Fc region.

7. The immunoadhesin of claim 5 comprising a N434A substitution.