IL-16 antagonists

• US 20030017990A1
• Filed: 08/15/2001
• Published: 01/23/2003
• Est. Priority Date: 08/05/1999
• Status: Active Grant

• Current Assignee: Trustees of Boston University
• Original Assignee: Center David, Hardy Kornfeld, William Cruikshank
• Inventors: Kornfeld, Hardy, Cruikshank, William, Center, David
• Granted Patent: US 6,723,697 B2
• Time in Patent Office: Days
• US Class Current: 514/15
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 14/70514 CD4
• CPC Class Codes: C07K 5/1013 the side chain containing O or S as heteroatoms, e.g. Cys, Ser
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids

Abstract

In accordance with the present invention, novel IL-16 antagonists, preferably peptides derived from CD4, have been isolated and synthesized. These peptides possess IL-16 antagonistic properties including the ability to selectively bind to IL-16 and inhibit IL-16-mediated biological activity. The peptides comprise specific portions of the native human CD4 receptor and variations thereof and therefore are non-immunogenic when administered to humans. The present invention also provides compositions containing at least one IL-16 antagonist peptide which can inhibit, suppress or cause the cessation of at least one IL-16-mediated biological activity in mammals, including humans.

The present invention provides a method and composition for treating inflammation associated with disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease (IBD) and systemic lupus (SLE) in mammals such as, for example, humans.

Claims

1. An isolated IL-16 antagonist peptide consisting of CLLS.

18. An isolated nucleic acid molecule coding for any one of the peptide of claims 1-6, 8 or 12.

19. An antibody directed against the peptide of any one of claims 1-6, 8 or 12.

20. A pharmaceutical composition comprising the peptide of any of claims 1-6, 8 or 12, and a pharmaceutically acceptable carrier.

22. A method of treating an IL-16 mediated disorder in a subject, comprising administering to the subject a therapeutically effective amount of the peptide of any of claims 1-6, 8 or 12 and a pharmaceutically acceptable carrier.

23. The method of claim 22, wherein said IL-16 mediated disorder is an inflammatory disease selected from asthma, arthritis, inflammatory bowel disease (IBD), Systemic Lupus (SLE), multiple sclerosis (MS), Graves opthalmopathy, atopic rhinitis, atopic dermatitis and bullous pemphigoid.

24. The method of claim 23, further comprising simultaneously administering an anti-inflammatory agent selected from NSAIDS, steroids, anti-TNFα

antibody, anti-CD4 antibodies, cyclosporin-A.

25. A method of inhibiting the binding of IL-16 to a CD4 receptor comprising the administration of at least one peptide of any one of claims 1-6, 8 or 12.

2. An isolated IL-16 antagonist peptide of any one of WQCLLS, WQALLS, VVQVVA or VKQVVA.

3. An isolated IL-16 antagonist peptide consisting of GMWQCLLS (SEQ ID NO:

13).

4. An isolated peptide consisting of GMWQCLLSDSGQVLLE (SEQ ID NO:

12)

5. An isolated peptide consisting of any one of TGLWQCLLSEGD (SEQ ID NO:

14) or VSEEQKVVQVVA (SEQ ID NO;

15).

6. An IL-16 antagonist peptide comprising Xaa₁-LL-Xaa₂ wherein Xaa₁ and Xaa₂ is any amino acid (SEQ ID NO:

1).

7. The IL-16 antagonist peptide of claim 6 wherein Xaa₁-LL-Xaa₂ is identical to the corresponding native sequence of a mammalian IL-16.

8. An IL-16 antagonist peptide comprising CLLS (SEQ ID NO:

2).

9. An IL-16 antagonist peptide comprising Xaa₁-Xaa₂-Xaa₃-L-L-Xaa₄ wherein Xaa₁-Xaa₄ is any amino acid (SEQ ID NO:

3).

10. The IL-16 antagonist peptide of claim 9, wherein Xaa₁ is Trp;

Xaa₂ is selected from Gln or Ala, Xaa₃ is selected from Cys or Ala and Xaa₄ is Ser.

11. The IL-16 antagonist peptide of claim 9, wherein Xaa₁-Xaa₂-Xaa₃-L-L-Xaa₄ identical to the corresponding native sequence of a mammalian IL-16.

14. The IL-16 antagonist peptide of claim 13, wherein Xaa₁-Val-Xaa₂-Val-Xaa₃-Xaa₄ is identical to the corresponding native sequence of a mammalian IL-16.

21. A pharmaceutical composition comprising the antibody of claim 19.

12. An IL-16 antagonist peptide comprising WQCLLS (SEQ ID NO:

4) or WQALLS (SEQ ID NO;

5).

13. An IL-16 antagonist peptide comprising Xaa₁-Val-Xaa₂-Val-Xaa₃-Xaa₄ wherein Xaa₁-Xaa₄ is an amino acid (SEQ ID NO:

8).

15. An IL-16 antagonist peptide comprising VVQVVA (SEQ ID NO:

9) or VVQKVA (SEQ ID NO;

11).

16. An IL-16 antagonist peptide comprising GMWQCLLS (SEQ ID NO:

13).

17. An IL-16 antagonist peptide comprising GMWQCLLSDSGQVLLE (SEQ ID NO:

12).

26. An IL-16 antagonist.

27. A pharmaceutical composition comprising an IL-16 antagonist and a pharmaceutically acceptable carrier.

28. A method of treating an IL-16 mediated disorder comprising blocking the interaction of IL-16 with an IL-16 receptor by the administration of an IL-16 antagonist.