Fc variants with increased affinity for FcyRIIc

Patent metadata

Field	Value
Publication number	US-10113001-B2
Application number	US-201414578305-A
Country	US
Kind code	B2
Filing date	Dec 19, 2014
Priority date	Mar 3, 2003
Publication date	Oct 30, 2018
Grant date	Oct 30, 2018

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.

First claim

We claim:

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.

Assignees

• Xencor Inc

Inventors

• Lazar Gregory
• Dang Wei
• Desjarlais John
• Karki Sher Bahadur
• Vafa Omid
• Hayes Robert

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K16/2887

  against CD20 · CPC title

• C07K2317/734

  Complement-dependent cytotoxicity [CDC] · CPC title

• C07K2317/77

  Internalization into the cell · CPC title