Optimized Fc variants

• US 9,657,106 B2
• Filed: 10/06/2014
• Issued: 05/23/2017
• Est. Priority Date: 03/03/2003
• Status: Expired due to Term

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Dang, Wei, Vafa, Omid, Vielmetter, Jost, Desjarlais, John, Karki, Sher, Lazar, Gregory, Hayes, Robert
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US14/507,783
• Publication Number:
  US 20150031862A1
• Time in Patent Office: 960 Days
• Field of Search: None
• 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 parent human IgG Fc polypeptide, said Fc variant comprising an amino acid substitution S267E in the Fc region, wherein said Fc variant exhibits increased binding to Fcγ

RIIb as compared to the parent Fc polypeptide and wherein numbering is according to the EU index.

2. The protein according to claim 1, where said protein is an antibody or immunoadhesion.

3. The protein according to claim 2, where said protein is an antibody.

4. The protein according to claim 2, wherein said protein is an antibody and wherein said antibody is selected from the group consisting of a humanized antibody and a monoclonal antibody.

5. The protein according to claim 4, wherein said antibody is a monoclonal antibody.

6. The protein according to claim 4, wherein said antibody is a humanized antibody.

7. The protein according to claim 1, wherein said parent Fc polypeptide is a human IgG1.

8. The protein according to claim 2, wherein said protein is an immunoadhesin.

9. A protein comprising an Fc variant of a parent human IgG Fc polypeptide, said Fc variant comprising an amino acid substitution S267D in the Fc region, wherein said Fc variant exhibits increased binding to Fcγ

RIIb as compared to the parent Fc polypeptide and wherein numbering is according to the EU index.

10. The protein according to claim 9, wherein said protein is an antibody or immunoadhesion.

11. The protein according to claim 10 where said protein is an antibody.

12. The protein according to claim 11, wherein said protein is an antibody, and wherein said antibody is selected from the group consisting of a humanized antibody and a monoclonal antibody.

13. The protein according to claim 12, wherein said antibody is a monoclonal antibody.

14. The protein according to claim 13, wherein said antibody is a humanized antibody.

15. The protein according to claim 9 wherein said parent Fc polypeptide is a human IgG1.

16. The protein according to claim 10, wherein said protein is an immunoadhesin.