Fc variants having increased affinity for fcyrllc

• US 8,735,545 B2
• Filed: 06/19/2007
• Issued: 05/27/2014
• Est. Priority Date: 03/03/2003
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Lazar, Gregory Alan, Dang, Wei, Desjarlais, John, Karki, Sher Bahadur, Vafa, Omid, Hayes, Robert, Vielmetter, Jost
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US11/765,353
• Publication Number:
  US 20070248602A1
• Time in Patent Office: 2,534 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 16/2893 against CD52
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/71 Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/72 Increased 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 2317/77 Internalization into the cell

Abstract

The present invention relates to Fc variants having increased affinity for FcγRIIc, methods for their generation, Fc polypeptides comprising optimized Fc variants, and methods for using optimized Fc variants.

Claims

1. A protein comprising an Fc variant region comprising amino acid substitutions at residues 236 and 239, wherein said amino acid substitutions are an alanine or a serine that is not the wild-type amino acid at position 236 and an aspartic acid that is not the wild-type amino acid at position 239, wherein said Fc variant is not a human IgG2 and wherein numbering is according to the EU index.

2. A protein according to claim 1, wherein said Fc variant comprises 236A/239D/332E.

3. A protein according to claim 1 wherein said protein is an antibody.

4. An antibody according to claim 3 wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a monoclonal antibody.

5. An antibody according to claim 4 wherein said antibody comprises a IgG1 region.

6. A protein according to claim 3, wherein said antibody has specificity for a target antigen selected from the group consisting of CD19, CD20, CD22, CD30, CD33, CD40, CD40L, CD52, Her2/neu, EGFR, EpCAM, MUC1, G03, CEA, CA 125, HLA-DR, TNFalpha, MUC18, prostate specific membrane antigen (PMSA) and VEGF.

7. A protein according to claim 1, wherein said protein is an antibody or immunoadhesin.

8. A protein comprising an Fc variant region comprising amino acid substitutions at residues 236 and 239, wherein said amino acid substitutions are an alanine that is not the wild-type amino acid at position 236 and an aspartic acid that is not the wild-type amino acid at position 239, wherein said Fc variant is not a human IgG2 and wherein numbering is according to the EU index.

9. A protein comprising an Fc variant region comprising amino acid substitutions at residues 236 and 239, wherein said amino acid substitutions are a serine that is not the wild-type amino acid at position 236 and an aspartic acid that is not the wild-type amino acid at position 239, wherein said Fc variant is not a human IgG2 and wherein numbering is according to the EU index.