Anti-tirc7 antibodies in therapy of inflammatiory diseases

• US 20060251646A1
• Filed: 12/23/2002
• Published: 11/09/2006
• Est. Priority Date: 12/21/2001
• Status: Active Grant

• Current Assignee: Genpatt77 Pharmacognetics AG
• Original Assignee: Genpatt77 Pharmacognetics AG
• Inventors: Utku, Nalan
• Granted Patent: US 7,794,715 B2
• Time in Patent Office: Days
• US Class Current: 424/143.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/39541 against normal tissues, cells
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues

Abstract

A method for the treatment of inflammatory disorders is disclosed, particularly the treatment of arthritis. The method comprises particular therapeutic and preventive treatment regimens for the administration of a T-cell immune response cDNA 7 (TIRC7) antagonist, preferably an anti-TIRC7 antibody. Particularly useful monoclonal, in particular chimeric anti-TIRC7 antibodies are described. Furthermore, a combination therapy for the treatment of an inflammatory disease, particularly rheumatoid arthritis, is provided involving the use of TIRC7 antagonist, such as anti-TIRC7 antibody in conjunction with an anti-inflammatory drug such as TNF-α antagonist

Claims

1. Use of T-cell immune response cDNA 7 (TIRC7) antagonist for the preparation of a pharmaceutical composition for preventing or treatment of mammal subject afflicted with an inflammatory disease, wherein said pharmaceutical composition is in a form adapted for administration wherein

(a) said administration of TIRC7 antagonist to the patient is in a dosage which is in the range of from 0.5 mg/kg/day to 50 mg/kg/day and wherein said administration is at intervals of one to three times a week during a period of at least two weeks for a therapeutic treatment regimen and at daily intervals over a week for a preventive treatment regimen;

(b) said therapeutic treatment regimen and preventive treatment regimen may be combined and/or repeated at one or several intervals.

2. The use of claim 1, wherein said therapeutic treatment regimen is preceded by a preventive treatment regimen.

3. The use of claim 1, wherein the dosage is in the range of 5 mg/kg/day to 30 mg/kg/day.

4. The use of any claim 1, wherein the administration is intravenously or subcutaneous.

5. The use of claim 1, wherein said inflammatory disease is arthritis.

6. The use of claim 1, wherein said TIRC7 antagonist is anti-TIRC7 antibody or fragment thereof.

7. The use of claim 1, wherein said antibody is a chimeric or humanized antibody.

8. The use of claim 1, wherein said antibody is an antibody.

9. An article of manufacture comprising a container;

a pharmaceutically acceptable anti-inflammatory composition comprising an TIRC7 antagonist disposed within said container; and

accompanying said container, instructions for administration of said an TIRC7 antagonist composition to a patient suffering from an inflammatory disease, said instructions directing the administration of TIRC7 antagonist to the patient in a dosage and regimen as defined in claim 1.

10. The article of manufacture of claim 9, wherein said inflammatory disease is arthritis and said TIRC7 antagonist is a TIRC7 antagonist.

11. An anti-TIRC7 antibody or binding fragment thereof comprising in its variable region at least one complementarity determining region (CDR) of the V_H and/or V_L of the variable region comprising the amino acid sequence depicted in FIG. 1 (V_H) (SEQ ID NO:

2) and FIG. 2 (V_L) (SEQ ID NO;

     4) or depicted in FIG. 9 (V_H) (SEQ ID NO;

     9) and FIG. 10 (V_L) (SEQ ID NO;

     11).

12. The antibody of claim 11, wherein said antibody is a chimeric or humanized antibody.

13. The antibody of claim 11 comprising the amino acid sequence of the V_H and/or V_L region depicted in FIG. 1 (V_H) (SEQ ID NO:

2) and FIG. 2 (V_L) (SEQ ID NO;

     4) or depicted in FIG. 9 (V_H) (SEQ ID NO;

     9) and FIG. 10 (V_L) (SEQ ID NO;

     11).

14. A polynucleotide encoding at least a variable region of an immunoglobulin chain of the antibody of claim 11.

15. A vector comprising the polynucleotide of claim 14, optionally in combination with a polynucleotide that encodes the variable region of the other immunoglobulin chain of said antibody.

16. A host cell comprising a vector of claim 15.

17. An antibody which competes with an antibody of claim 11 for the binding of a peptide comprising the amino acid sequence of SEQ ID NO:

6.

18. A composition comprising the antibody of claim 11, optionally in combination with a pharmaceutically acceptable carrier.

19. Use of T-cell immune response cDNA 7 (TIRC7) antagonist and an anti-inflammatory drug for the preparation of pharmaceutical composition for the prevention or treatment of an inflammatory disease.

20. The use of claim 19, wherein a concurrent therapy of an inflammatory disease with said pharmaceutical composition promotes a positive therapeutic response in a treated subject, which response is greater than a therapeutic response that would be observed with therapy using said anti-inflammatory drug alone.

21. The use of claim 19, wherein said anti-inflammatory drug is selected from TNF-alpha antagonists, methotrexate, cyclosporin, IL-1 inhibitors, blocker of IL-1 receptor, COX inhibitors, T-cell activation inhibitors, blocker of ICAM-1, LFA-1 or other antibodies against membrane or non-membrane proteins, or non-steroidal anti-inflammatory drug (NSAID).

22. The use of claim 21, wherein said TNF antagonist is selected from the group consisting of etanercept, infliximab, pegylated soluble TNF receptor Type I (PEGsTNF-R1), CDP571 (a humanized monoclonal anti-TNF-alpha antibody), and D2E7 (a human anti-TNF mAb).

23. The use of claim 19, wherein said inflammatory disease is arthritis and said TIRC7 antagonist is a TIRC7 antagonist.

24. The use of claim 19, wherein said pharmaceutical composition is in a form adapted for administration to the patient in a dosage and regimen 4.

25. A pharmaceutical composition comprising an TIRC7 antagonist and TNF-antagonist.

26. The pharmaceutical composition of claim 25, wherein said anti-TIRC7 antagonist is an anti-TIRC7 antibody or fragment thereof and said TNF-antagonist is a compound selected from the group consisting of etanercept, infliximab, pegylated soluble TNF receptor Type I (PEGsTNF-R1), CDP571 (a humanized monoclonal anti-TNF-alpha antibody), and D2E7 (a human anti-TNF mAb).

28. The pharmaceutical composition of claim 26, wherein said anti-TIRC7 antibody is an antibody comprising in its variable region at least one complementarity determining region (CDR) of the V_H and/or V_L of the variable region comprising the amino acid sequence depicted in FIG. 1 (V_H) (SEQ ID NO:

2) and FIG. 2 (V_L) (SEQ ID NO;

     4) or depicted in FIG. 9 (V_H) (SEQ ID NO;

     9) and FIG. 10 (V_L) (SEQ ID NO;

     11) and said TNF-antagonist is etanercept or infliximab.

27. (canceled)

29. Use of TIRC7 antagonist for the preparation of a pharmaceutical composition for the treatment or prevention of an inflammatory disease for patients receiving previously, concomitantly or subsequently a medicament comprising an anti-inflammatory drug.

30. Use of an anti-inflammatory drug for the preparation of a pharmaceutical composition for the treatment or prevention of an inflammatory disease for patients receiving previously, concomitantly or subsequently a medicament comprising TIRC7 antagonist.

31. (canceled)

32. (canceled)

33. A method for preventing or treating a mammal subject afflicted with an inflammatory disease, comprising the step of administering to a mammal having or suspected to get an inflammatory disease an amount of TIRC7 antagonist in the range of from 0.5 mg/kg/day to 50 mg/kg/day and wherein said administration is at intervals of one to three times a week during a period of at least two weeks for a therapeutic treatment regimen and at daily intervals over a week for a preventive treatment regimen;

said therapeutic treatment regimen and preventive treatment regimen may be combined and/or repeated at one or several intervals.

34. A method for preventing or treatment of a mammal subject afflicted with an inflammatory disease, comprising the step of administering to a mammal having or suspected to get an inflammatory disease a therapeutic effective amount of TIRC7 antagonist in combination with an anti-inflammatory drug.

35. An oligonucleotide consisting essentially of the nucleotide sequence of any one of SEQ ID NOS:

12 to 40.

36. Use of an oligonucleotide comprising a nucleotide sequence of any one of SEQ ID NOS:

12 to 40 for the cloning of an anti-TIRC7 antibody or TIRC7 binding molecule.