Fc variants with increased affinity for FcyRIIc

• US 10,113,001 B2
• Filed: 12/19/2014
• Issued: 10/30/2018
• Est. Priority Date: 03/03/2003
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Lazar, Gregory, Dang, Wei, Desjarlais, John, Karki, Sher Bahadur, Vafa, Omid, Hayes, Robert
• Primary Examiner(s): Dahle, Chun W
• Application Number:
  US14/578,305
• Publication Number:
  US 20150232567A1
• Time in Patent Office: 1,411 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 increased affinity for FcγRIIc, methods for their generation, Fc polypeptides comprising optimized Fc variants, and methods for using optimized Fc variants.

Claims

1. A nucleic acid encoding a protein, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an amino acid substitution at position 243 in the Fc region of said parent IgG Fc polypeptide, wherein numbering is according to the EU index.

2. The nucleic acid according to claim 1, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an amino acid substitution selected from the group consisting of 243L and 243W amino acid substitutions in the Fc region.

3. An expression vector comprising the nucleic acid of claim 2.

4. The nucleic acid according to claim 2, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an 243L amino acid substitution in the Fc region.

5. An expression vector comprising the nucleic acid of claim 4.

6. The nucleic acid according to claim 4, wherein said parent IgG Fc polypeptide is a human IgG1.

7. A host cell comprising a nucleic acid encoding a protein, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an amino acid substitution at position 243 in the Fc region of said parent IgG Fc polypeptide, and wherein numbering is according to the EU index.

8. The host cell according to claim 7, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an amino acid substitution selected from the group consisting of 243L and 243W amino acid substitutions in the Fc region.

9. The host cell according to claim 7, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an 243L amino acid substitution in the Fc region.

10. The host cell according to claim 7, comprising a nucleic acid encoding a protein, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an amino acid substitution selected from the group consisting of 243L and 243W amino acid substitutions in the Fc region.

11. The host cell according to claim 7, comprising an expression vector comprising a nucleic acid encoding a protein, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an amino acid substitution selected from the group consisting of 243L and 243W amino acid substitutions in the Fc region.

12. The host cell according to claim 7, comprising a nucleic acid encoding a protein, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an 243L amino acid substitution in the Fc region.

13. The host cell according to claim 7, comprising an expression vector comprising a nucleic acid encoding a protein, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an 243L amino acid substitution in the Fc region.

14. The host cell according to claim 12 or 13, wherein said protein is an antibody or Fc fusion.

15. The host cell according to claim 14, wherein said protein is an antibody.

16. The host cell according to claim 14, wherein said protein is an Fc fusion.

17. The host cell according to claim 15, wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a chimeric antibody.

18. The host cell according to claim 17, wherein said antibody is a humanized antibody.

19. The host cell according to claim 17, wherein said antibody is a chimeric antibody.

20. The host cell according to claim 7, wherein said parent IgG Fc polypeptide is a human IgG1.

21. A method of making a protein comprising:

a) culturing a host cell comprising a nucleic acid encoding a protein, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an amino acid substitution at position 243 in the Fc region, wherein numbering is according to the EU index, under conditions wherein said protein is produced; and

b) purifying said protein.

22. The method of making according to claim 21, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an amino acid substitution selected from the group consisting of 243L and 243W amino acid substitutions in the Fc region.

23. The method of making according to claim 21, wherein said protein comprises an Fc variant of a parent IgG Fc polypeptide, said Fc variant comprising an 243L amino acid substitution in the Fc region.

24. The method of making according to claim 21, wherein said protein is an antibody or Fc fusion.

25. The method of making according to claim 24, wherein said protein is an antibody.

26. The method of making according to claim 24, wherein said protein is an Fc fusion.

27. The method of making a protein according to claim 25, wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a chimeric antibody.

28. The method of making according to claim 27, wherein said antibody is a humanized antibody.

29. The method of making according to claim 27, wherein said antibody is a chimeric antibody.

30. The method of making according to claim 21, wherein said parent IgG Fc polypeptide is a human IgG1.