Optimized Fc variants

• US 8,802,823 B2
• Filed: 11/12/2013
• Issued: 08/12/2014
• 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:
  US14/078,501
• Publication Number:
  US 20140073768A1
• Time in Patent Office: 273 Days
• Field of Search: None
• US Class Current: 530/350
• 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 polypeptide comprising a variant Fc region comprising an amino acid substitution at position 271 of the Fc region as compared to a parent Fc region, wherein numbering is according to the EU index.

2. The polypeptide of claim 1, wherein said polypeptide is an antibody.

3. The polypeptide of claim 2, wherein said antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, a monoclonal antibody, and a human antibody.

4. The polypeptide of claim 1, wherein said polypeptide is an immunoadhesin.

5. The polypeptide of claim 1, wherein said amino acid substitution is selected from the group consisting of aspartic acid, glutamic acid, asparagine, glutamine, lysine, arginine, serine, threonine, histidine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, tyrosine, tryptophan, and glycine.

6. The polypeptide of claim 1, wherein said polypeptide comprises an engineered glycoform.

7. A polypeptide comprising a variant Fc region comprising an amino acid substitution at position 271 of the Fc region as compared to a parent Fc region, wherein the variant Fc region exhibits enhanced binding affinity to Fcγ

RIIb as compared with the parent Fc region, wherein numbering is according to the EU index.

8. The polypeptide of claim 7, wherein said polypeptide is an antibody.

9. The polypeptide of claim 8, wherein said antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, a monoclonal antibody, and a human antibody.

10. The polypeptide of claim 7, wherein said polypeptide is an immunoadhesin.

11. The polypeptide of claim 7, wherein said amino acid substitution is selected from the group consisting of aspartic acid, arginine, serine, threonine, valine, isoleucine, phenylalanine, methionine, tyrosine, and glycine.

12. The polypeptide of claim 7, wherein said amino acid substitution is selected from the group consisting of threonine, methionine, tyrosine, and glycine.

13. The polypeptide of claim 7, wherein said polypeptide comprises an engineered glycoform.

14. A polypeptide comprising a variant Fc region comprising an amino acid substitution at position 271 of the Fc region as compared to a parent Fc region, wherein the amino acid substitution is glycine, wherein said variant Fc region exhibits enhanced binding affinity to Fcγ

RIIb as compared with the parent Fc region, wherein numbering is according to the EU index.

15. The polypeptide of claim 14, wherein said polypeptide is an antibody.

16. The polypeptide of claim 15, wherein said antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, a monoclonal antibody, and a human antibody.

17. The polypeptide of claim 14, wherein said polypeptide is an immunoadhesin.

18. The polypeptide of claim 14, wherein said polypeptide comprises an engineered glycoform.