CTLA4 proteins and their uses

Patent metadata

Field	Value
Publication number	US-9587007-B2
Application number	US-201414524946-A
Country	US
Kind code	B2
Filing date	Oct 27, 2014
Priority date	Mar 12, 2010
Publication date	Mar 7, 2017
Grant date	Mar 7, 2017

Abstract

The present disclosure relates to CTLA4 proteins and uses of such proteins, for example to treat diseases associated with the dysregulation of immune responses.

First claim

What is claimed is:

1. A variant CTLA4 polypeptide comprising an amino acid sequence having at least 90% sequence identity to amino acids 21 to 112 of SEQ ID NO:1, wherein the variant polypeptide comprises the amino acid substitution T51Y, as compared to SEQ ID NO: 1.

2. The variant CTLA4 polypeptide of claim 1 , which further comprises the amino acid substitution L58G, K93Q, K93M or L96K as compared to a polypeptide of sequence SEQ ID NO: 1.

3. The variant CTLA4 polypeptide of claim 1 , which further comprises the amino acid substitution K28T as compared to a polypeptide of sequence SEQ ID NO:1.

4. The variant CTLA4 polypeptide of claim 1 , which further comprises the amino acid substitution L61H as compared to a polypeptide of sequence SEQ ID NO:1.

5. The variant CTLA4 polypeptide of claim 4 , which further comprises the amino acid substitution K93Q as compared to a polypeptide of sequence SEQ ID NO:1.

6. The variant CTLA4 polypeptide of claim 1 , which further comprises the amino acid substitution L104E as compared to a polypeptide of sequence SEQ ID NO:1.

7. The variant CTLA4 polypeptide of claim 1 which is a fusion protein.

8. The variant CTLA4 polypeptide of claim 7 , wherein the fusion protein comprises a CTLA4 extracellular domain linked to an immunoglobulin constant region and optionally a signal sequence.

9. The variant CTLA4 polypeptide of claim 8 , wherein the immunoglobulin constant region is selected from an IgG1, an IgG2, an IgG3 and an IgG4.

10. The variant CTLA4 polypeptide of claim 9 , wherein the immunoglobulin constant region is an IgG1.

11. The variant CTLA4 polypeptide of claim 10 , wherein at least one cysteine residue in the immunoglobulin constant region has been substituted with a serine or a proline.

12. The variant CTLA4 polypeptide of claim 1 , which comprises an amino acid sequence having at least 95% sequence identity to amino acids 21 to 112 of SEQ ID NO:1.

13. The variant CTLA4 polypeptide of claim 1 , which comprises an amino acid sequence having at least 97% sequence identity to amino acids 21 to 112 of SEQ ID NO:1.

14. The variant CTLA4 polypeptide of claim 1 , which comprises an amino acid sequence having at least 99% sequence identity to amino acids 21 to 112 of SEQ ID NO:1.

15. A variant CTLA4 polypeptide-drug conjugate comprising a variant CTLA4 polypeptide according to claim 1 .

16. A pharmaceutical composition comprising a variant CTLA4 polypeptide according to claim 1 or a variant CTLA4 polypeptide-drug conjugate according to claim 15 , and a pharmaceutically acceptable carrier.

17. A method of treating an autoimmune disease comprising administering to a human in need thereof a therapeutically effective amount of a pharmaceutical composition according to claim 16 .

18. The method of claim 17 , wherein the autoimmune disease is rheumatoid arthritis.

19. The method of claim 17 , wherein the autoimmune disease is idiopathic arthritis.

Assignees

• Abbvie Biotherapeutics Inc

Inventors

• Akamatsu Yoshiko
• Juan Veronica
• Dubridge Robert B

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title