CHEMOKINE-BINDING PROTEIN AND METHODS OF USE

• US 20100317592A1
• Filed: 06/25/2010
• Published: 12/16/2010
• Est. Priority Date: 12/18/2001
• Status: Abandoned Application

• Current Assignee: Francois Amalric, Jean-Philippe Girard, Myriam Roussigne
• Original Assignee: Francois Amalric, Jean-Philippe Girard, Myriam Roussigne
• Inventors: Roussigne, Myriam, Amalric, Francois, Girard, Jean-Philippe
• Application Number:
  US12/823,876
• Publication Number:
  US 20100317592A1
• Time in Patent Office: Days
• US Class Current: 514/18.9
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Abstract

Described herein are chemokine-binding domains of THAP-family polypeptides and pharmaceutical compositions which include a polypeptide comprising a chemokine-binding domain of a THAP-family polypeptide. Also disclosed are methods of binding chemokines, inhibiting the activity of chemokines, detecting chemokines, and reducing the symptoms associated with a chemokine mediated or influenced condition by contacting the chemokine with an agent that includes a polypeptide comprising a chemokine binding domain of a THAP-family polypeptide.

Claims

1. A method of inhibiting the activity of a chemokine, said method comprising contacting a chemokine with an agent comprising a polypeptide selected from the group consisting of SEQ ID NO:

3, a polypeptide having at least 95% sequence identity to SEQ ID NO;

3, a chemokine-binding domain of SEQ ID NO;

3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO;

3, wherein the activity of said chemokine is inhibited.

2. The method of claim 1, wherein said polypeptide is selected from the group consisting of SEQ ID NO:

3 and a chemokine-binding domain of SEQ ID NO;

3.

3. The method of claim 1, wherein polypeptide is selected from the group consisting of a polypeptide having at least 95% sequence identity to SEQ ID NO:

3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO;

3.

4. The method of claim 1, wherein said polypeptide is SEQ ID NO:

3.

5. The method of claim 1, wherein said polypeptide has at least 95% sequence identity to SEQ ID NO:

3.

6. The method of claim 1, wherein said polypeptide is a chemokine-binding domain of SEQ ID NO:

3.

7. The method of claim 6, wherein said chemokine-binding domain of SEQ ID NO:

3 comprises the amino acid sequence 143-213 of SEQ ID NO;

3.

8. The method of claim 1, wherein said polypeptide has at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO:

3.

9. The method of claim 1 further comprising administering a nucleic acid encoding said polypeptide to a subject.

10. The method of claim 1 further comprising administering said polypeptide to a subject.

11. A method of inhibiting the activity of a chemokine, said method comprising contacting a chemokine selected from the group consisting of Secondary Lymphoid-tissue Chemokine (SLC), CCL19, CCL5, CXCL9 and CXCL10 with an agent comprising a polypeptide selected from the group consisting of SEQ ID NO:

3, a polypeptide having at least 95% sequence identity to SEQ ID NO;

3, a chemokine-binding domain of SEQ ID NO;

3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO;

3, wherein the activity of said chemokine is inhibited.

12. The method of claim 11, wherein said chemokine is selected from the group consisting of SLC, CCL19 and CCL5.

13. The method of claim 11, wherein said chemokine is selected from the group consisting of CXCL9 and CXCL10.

14. The method of claim 11, wherein said chemokine is SLC.

15. The method of claim 11, wherein said chemokine is CC19.

16. The method of claim 11, wherein said chemokine is CCS.

17. The method of claim 11, wherein said chemokine is CXCL9.

18. The method of claim 11, wherein said chemokine is CXCL10.

19. The method of claim 11, wherein said polypeptide selected from the group consisting of a polypeptide having at least 95% sequence identity to SEQ ID NO:

3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO;

3, wherein the activity of said chemokine is inhibited.

20. The method of claim 11, wherein said polypeptide has at least 95% sequence identity to SEQ ID NO:

3.

21. The method of claim 11, wherein said polypeptide has at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO:

3.

22. The method of claim 21, wherein said chemokine-binding domain of SEQ ID NO:

3 comprises the amino acid sequence 143-213 of SEQ ID NO;

3.

23. The method of claim 11 further comprising administering a nucleic acid encoding said polypeptide to a subject.

24. The method of claim 11 further comprising administering said polypeptide to a subject.

25. A method of binding a chemokine, said method comprising contacting a chemokine with an agent comprising a polypeptide selected from the group consisting of SEQ ID NO:

3, a polypeptide having at least 95% sequence identity to SEQ ID NO;

3, a chemokine-binding domain of SEQ ID NO;

3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO;

3, wherein said chemokine is bound.

26. The method of claim 25, wherein said polypeptide is selected from the group consisting of SEQ ID NO:

3 and a chemokine-binding domain of SEQ ID NO;

3.

27. The method of claim 25, wherein polypeptide is selected from the group consisting of a polypeptide having at least 95% sequence identity to SEQ ID NO:

3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO;

3.

28. The method of claim 25, wherein said polypeptide is SEQ ID NO:

3.

29. The method of claim 25, wherein said polypeptide has at least 95% sequence identity to SEQ ID NO:

3.

30. The method of claim 25, wherein said polypeptide is a chemokine-binding domain of SEQ ID NO:

3.

31. The method of claim 30, wherein said chemokine-binding domain of SEQ ID NO:

3 comprises the amino acid sequence 143-213 of SEQ ID NO;

3.

32. The method of claim 25, wherein said polypeptide has at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO:

3.

33. The method of claim 25 further comprising administering a nucleic acid encoding said polypeptide to a subject.

34. The method of claim 25 further comprising administering said polypeptide to a subject.

35. A method of binding a chemokine, said method comprising contacting a chemokine selected from the group consisting of Secondary Lymphoid-tissue Chemokine (SLC), CCL19, CCL5, CXCL9 and CXCL10 with an agent comprising a polypeptide selected from the group consisting of SEQ ID NO:

3, a polypeptide having at least 95% sequence identity to SEQ ID NO;

3, a chemokine-binding domain of SEQ ID NO;

3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO;

3, wherein said chemokine is bound.

36. The method of claim 35, wherein said chemokine is selected from the group consisting of SLC, CCL19 and CCL5.

37. The method of claim 35, wherein said chemokine is selected from the group consisting of CXCL9 and CXCL10.

38. The method of claim 35, wherein said chemokine is SLC.

39. The method of claim 35, wherein said chemokine is CC19.

40. The method of claim 35, wherein said chemokine is CCS.

41. The method of claim 35, wherein said chemokine is CXCL9.

42. The method of claim 35, wherein said chemokine is CXCL10.

43. The method of claim 35, wherein said polypeptide selected from the group consisting of a polypeptide having at least 95% sequence identity to SEQ ID NO:

3 and a polypeptide having at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO;

3, wherein the activity of said chemokine is inhibited.

44. The method of claim 35, wherein said polypeptide has at least 95% sequence identity to SEQ ID NO:

3.

45. The method of claim 35, wherein said polypeptide has at least 95% sequence identity to a chemokine-binding domain of SEQ ID NO:

3.

46. The method of claim 45, wherein said chemokine-binding domain of SEQ ID NO:

3 comprises the amino acid sequence 143-213 of SEQ ID NO;

3.

47. The method of claim 35 further comprising administering a nucleic acid encoding said polypeptide to a subject.

48. The method of claim 35 further comprising administering said polypeptide to a subject.