TREATMENT OF IDIOPATHIC INFLAMMATORY MYOPATHIES

Abstract

The invention provides a method of treating an idiopathic inflammatory myopathy in a human patient by administering an anti-CD26 antibody.

Description

Claims

1. A method of inhibiting inflammation in a human patient having an idiopathic inflammatory myopathy (IIM), the method comprising administering to the patient an effective amount of an antibody that specifically binds CD26; wherein the anti-CD26 antibody comprises (a) a heavy chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:7; (b) a heavy chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:8; (c) a heavy chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:9; (d) a light chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:10; (e) a light chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:11; and (f) a light chain variable region CDR3 comprising the sequence set forth in SEQ ID NO: 12.

2. A method of treating an idiopathic inflammatory myopathy (IIM), the method comprising administering to the patient an effective amount of an antibody that specifically binds CD26; wherein the anti-CD26 antibody comprises (a) a heavy chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:7; (b) a heavy chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:8; (c) a heavy chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:9; (d) a light chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:10; (e) a light chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:11; and (f) a light chain variable region CDR3 comprising the sequence set forth in SEQ ID NO: 12.

3. The method of claim 1, wherein the IIM is dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM), sporadic inclusion body myositis (IBM), or overlap myositis (OM).

4. The method of claim 1, wherein the anti-CD26 antibody is a full-length antibody.

5. The method of claim 1, wherein the antibody is a monoclonal, human, humanized, chimeric, multivalent antibody, or an antigen-binding fragment thereof.

6. (canceled)

7. The method of claim 1, wherein the antibody has an IgG2b isotype.

8. The method of claim 1, wherein the anti-CD26 antibody is begelomab, 1F7, or CM03.

9. The method of claim 8, wherein the anti-CD26 antibody is produced in Chinese hamster ovary (CHO) cells.

10. The method of any claim 1, wherein the anti-CD26 antibody is produced from a hybridoma cell line deposited at CBA-ICLC of Genoa (Italy) as deposit number PD 12002.

11. (canceled)

12. The method of claim 1, wherein the anti-CD26 antibody comprises heavy and light chain variable regions comprising the sequences set forth in SEQ ID NOs:3 and 5, respectively.

13. The method of claim 1, wherein the anti-CD26 antibody comprises heavy and light chains constant regions comprising the sequences set forth in SEQ ID NOs: 1 and 2, respectively.

14. The method of claim 1, further comprising administration of an immunosuppressive agent.

15. The method of claim 14, wherein the immunosuppressive agent is a corticosteroid, methotrexate, azathioprine, mycophenolate mofetil, methylprednisone, cyclophosphamide, cyclosporineA, tacrolimus, or a combination thereof.

16. The method of claim 14, wherein the immunosuppressive agent is given prior to, concomitantly with, or after the anti-CD26 antibody.

17. The method of claim 1, wherein the cycle is a period of 4 or 5 weeks, and wherein for each of the at least one cycle, 16 doses of the anti-CD26 antibody are administered at a dose of between 4.0 mg/m2 to 25 mg/m2.

18. The method of claim 1, wherein the anti-CD26 antibody is administered at a dose of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg/m2.

19. The method of claim 1, wherein a fixed dose of the anti-CD26 antibody is administered.

20. The method of claim 19, wherein the fixed dose is determined based on the immunosuppressive agent administered to the subject.

21. A method of inhibiting inflammation in a human patient having an idiopathic inflammatory myopathy (IIM), the method comprising administering to the patient an effective amount of an anti-CD26 antibody comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO:3, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:5, wherein the patient’s CD3+ T cells and/or CD31+ endothelial cells express CD26.

22. A method of treating an idiopathic inflammatory myopathy (IIM) in a human patient, the method comprising administering to the patient an effective amount of an anti-CD26 antibody comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO:3, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:5, wherein the patient’s CD3+ T cells and/or CD31+ endothelial cells express CD26.

23. The method of claim 21, wherein the method is administered to a patient that has not received prior therapy (e.g., first line therapy).

24. (canceled)

25. The method of claim 21, wherein expression of CD26 is assayed by RT-PCR, in situ hybridization, RNase protection, RT-PCR-based assay, immunohistochemistry, enzyme linked immuosorbent assay, in vivo imaging, or flow cytometry.

26. (canceled)

27. An antibody that specifically binds CD26 comprising the heavy chain and light chain nucleotide sequences comprising SEQ ID NO: 15 and SEQ ID NO: 16, respectively.

28-29. (canceled)