Polypeptide variants

• US 6,194,551 B1
• Filed: 03/31/1999
• Issued: 02/27/2001
• Est. Priority Date: 04/02/1998
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Presta, Leonard G., Mulkerrin, Michael George, Idusogie, Esohe Ekinaduese
• Primary Examiner(s): Chan, Christina Y.
• Assistant Examiner(s): DiBrino, Marianne
• Application Number:
  US09/282,505
• Time in Patent Office: 699 Days
• Field of Search: 424/142.1, 424/143.1, 424/144.1, 424/145.1, 424/152.1, 424/177.1, 424/178.1, 424/801, 435/69.1, 435/69.6, 514/12, 514/8, 514/885, 530/387.1, 530/389.1, 530/350, 530/388.15, 530/388.22, 530/388.25, 530/388.23, 530/388.7
• US Class Current: 530/387.1
• CPC Class Codes: A61K 47/6873 the antibody targeting an immunoglobulin; the antibody being an anti-idiotypic antibody
• 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 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]

Abstract

A variant of a polypeptide comprising a human IgG Fc region is described, which variant comprises an amino acid substitution at amino acid position 329, or at two or all of amino acid positions 329, 331 and 322 of the human IgG Fc region. Such variants display altered effector function. For example, C1q binding and/or complement dependent cytotoxicity (CDC) activity may be reduced or abolished in the variant polypeptide. The application also describes an immune complex and an assay for determining binding of an analyte, such as an Fc region-containing polypeptide, to a receptor.

Claims

1. A variant of an antibody comprising a human IgG Fc region, which variant comprises an amino acid substitution at amino acid position 329, or at two or all of amino acid positions 329, 331 and 322 of the human IgG Fc region, where the numbering of the residues in the IgG Fc region is that of the EU index as in Kabat, and wherein the variant retains the ability to bind antigen.

2. The variant of claim 1 having Pro329 of the human IgG Fc region substituted with another amino acid.

3. The variant of claim 1 wherein the antibody comprises a human IgG1 Fc region.

4. The variant of claim 1 which does not activate complement.

5. The variant of claim 4 which binds an FcR.

6. The variant of claim 5 which binds Ecγ

RI, Fcγ

RII, Fcγ

RIII or FcRn.

8. A composition comprising the variant of claim 1 and a physiologically acceptable carrier.

7. A variant of an antibody comprising a human IgG Fc region, which variant does not activate complement and comprises an amino acid substitution at amino acid position 322 or amino acid position 329, or both amino acid positions of the human IgG Fc region, where the numbering of the residues in the IgG Fc region is that of the EU index as in Kabat, and wherein the variant retains the ability to bind antigen.

9. A method for modifying an antibody comprising a human IgG Fc region comprising substituting an amino acid residue at amino acid position 329, or at two or all of amino acid positions 329, 331 and 322 of the human IgG Fc region, where the numbering of the residues in the IgG Fc region is that of the EU index as in Kabat, and wherein the variant retains the ability to bind antigen.