Optimized Fc Variants

• US 8,735,547 B2
• Filed: 04/25/2013
• Issued: 05/27/2014
• Est. Priority Date: 09/27/2002
• Status: Expired due to Term

• 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:
  US13/870,781
• Publication Number:
  US 20130261289A1
• Time in Patent Office: 397 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 16/18 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 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/30 from tumour cells
• 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 2317/31 multispecific
• 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 2317/40 characterized by post-translational modification
• 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 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• 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
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The present invention relates to Fc variants having decreased affinity for FcγRIIb, 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 of a human IgG1 Fc polypeptide, wherein said Fc variant comprises an amino acid modification in the Fc region of said parent Fc polypeptide at position 243, wherein said protein exhibits altered binding affinity to an Fcγ

receptor (Fcγ

R) as compared to a parent polypeptide, wherein numbering is according to the EU index.

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

3. A protein according to claim 1 wherein said protein comprises an engineered glycoform.

4. A protein according to claim 1, 2 or 3 wherein said amino acid modification is selected from the group consisting of 243E, 243H, 243L, 243Q, 243R, 243W and 243Y.

5. A protein according to claim 4 wherein said amino acid modification is 243L.

6. A protein according to claim 2 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, GD3, CEA, CA 125, IgE, HLA-DR, TNFalpha, MUC18, prostate specific membrane antigen (PMSA) and VEGF.

7. A protein according to claim 6 wherein said antibody has specificity for her2/neu.

8. A protein comprising an Fc variant of a human IgG Fc polypeptide, wherein said Fc variant comprises an amino acid modification in the Fc region of said parent Fc polypeptide at position 243, wherein said amino acid modification is 243L, wherein said protein exhibits altered binding affinity to an Fcγ

receptor (Fcγ

R) as compared to a parent polypeptide, wherein numbering is according to the EU index.