VCAM-1 SPECIFIC MONOCLONAL ANTIBODY

• US 20070280941A1
• Filed: 05/31/2007
• Published: 12/06/2007
• Est. Priority Date: 05/31/2006
• Status: Active Grant

• Current Assignee: Hanwha Chemical Corporation
• Original Assignee: Hanwha Chemical Corporation
• Inventors: Ryu, Eun Kyung, Lee, Sukmook, Chung, Junho, Lee, Ji Eun
• Granted Patent: US 7,655,417 B2
• Time in Patent Office: Days
• US Class Current: 424/143.100
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/2836 against CD106
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The present invention relates to a monoclonal antibody that specifically binds to vascular cell adhesion molecule-1 (VCAM-1 or CD106). Specifically, the present invention relates to an antibody that specifically binds to both human and mouse vascular cell adhesion molecule-1 (VCAM-1), a method for producing the same, a composition for diagnosis or treatment comprising them and a method for diagnosis or treatment using them. The monoclonal antibody of the present invention is the first recombinant monoclonal antibodies that is specific to human and mouse VCAM-1. In addition, the monoclonal antibody of the present invention shows a strong affinity to VCAM-1 expressed in rat skeletal muscle and porcine endothelial cells as well as human and mouse endothelial cells and is found to strongly inhibit the interaction between leukocytes and activated endothelial cells. Accordingly, the monoclonal antibody of the present invention can inhibit a VCAM-1 mediated adhesion of leukocytes to endothelial cells and potently treat VCAM-1 mediated disease, especially inflammatory disease or cancer.

Claims

1. A monoclonal antibody that specifically binds to both human and mouse vascular cell adhesion molecule-1 (VCAM-1).

2. The monoclonal antibody according to claim 1 further specifically binding to human, mouse, rat, and porcine VCAM-1.

3. The monoclonal antibody according to claim 2, wherein the VCAM-1 is expressed in endothelial cells, or skeletal muscle cells.

4. The monoclonal antibody according to claim 1, which inhibits the interaction between leukocytes and activated endothelial cells.

5. The monoclonal antibody according to claim 1, wherein the monoclonal antibody is a recombinant monoclonal antibody.

6. The monoclonal antibody according to claim 1, comprising light chain variable regions CDR1, CDR2 and CDR3, and heavy chain variable regions CDR1, CDR2 CDR3.

7. The monoclonal antibody according to claim 6, wherein the light chain CDR1 region is defined by SEQ ID No. 5.

8. The monoclonal antibody according to claim 6, wherein the light chain CDR2 region is defined by SEQ ID No. 6.

9. The monoclonal antibody according to claim 6, wherein the light chain CDR3 region is defined by SEQ ID No. 7.

10. The monoclonal antibody according to claim 6, wherein the light chain CDR1 region is defined by SEQ ID No. 5, and wherein the light chain CDR2 region is defined by SEQ ID No. 6.

11. The monoclonal antibody according to claim 6, wherein the light chain CDR1 region is defined by SEQ ID No. 5, and wherein the light chain CDR3 region is defined by SEQ ID No. 7.

12. The monoclonal antibody according to claim 6, wherein the light chain CDR2 region is defined by SEQ ID No. 6, and wherein the light chain CDR3 region is defined by SEQ ID No. 7.

13. The monoclonal antibody according to claim 6, wherein the light chain CDR1 region is defined by SEQ ID No. 5, wherein the light chain CDR2 region is defined by SEQ ID No. 6, and wherein the light chain CDR3 region is defined by SEQ ID No. 7.

14. The monoclonal antibody according to claim 6, wherein the heavy chain CDR1 is defined by SEQ ID No. 8.

15. The monoclonal antibody according to claim 6, wherein the heavy chain CDR2 is defined by SEQ ID Nos. 9 or 11.

16. The monoclonal antibody according to claim 6, wherein the heavy chain CDR3 is defined by SEQ ID Nos. 10 or 12.

17. The monoclonal antibody according to claim 6, wherein the heavy chain CDR1 is defined by SEQ ID No. 8, and the heavy chain CDR2 is defined by SEQ ID Nos. 9 or 11.

18. The monoclonal antibody according to claim 6, wherein the heavy chain CDR1 is defined by SEQ ID No. 8, and the heavy chain CDR3 is defined by SEQ ID Nos. 10 or 12.

19. The monoclonal antibody according to claim 6, wherein the heavy chain CDR2 is defined by SEQ ID Nos. 9 or 11, and the heavy chain CDR3 is defined by SEQ ID Nos. 10 or 12.

20. The monoclonal antibody according to claim 6, wherein the heavy chain CDR1 is defined by SEQ ID No. 8, wherein the heavy chain CDR2 is defined by SEQ ID Nos. 9 or 11, and the heavy chain CDR3 is defined by SEQ ID Nos. 10 or 12.

21. The monoclonal antibody according to claim 5, wherein the monoclonal antibody is humanized.

22. A method of preparing the antibody according to claim 1 comprising:

(i) immunizing recombinant human VCAM-1/Fc chimera into mammalian animals;

(ii) determining antibody titer of the immunized mammalian animals;

(iii) purifying polyclonal sera from the immunized mammalian animals;

(iv) constructing non-human mammalian animal/human chimeric antibody library; and

(v) selecting anti-VCAM-1 specific antibody from antibody libraries.

23. A method for diagnosing a VCAM-1 mediated disease comprising contacting a bodily sample with the monoclonal antibody according to claim 1, wherein detection of binding of the monoclonal antibody to a substance in the sample indicates presence of VCAM-1 mediated disease.

24. The method according to claim 23, wherein the VCAM-1 mediated disease is an inflammatory disease or cancer.

25. The method according to claim 24, wherein the inflammatory disease is selected from a group consisted of arthritis, multiple sclerosis, bowl disease, asthma, atherosclerosis, myocardial infarction, transplantation rejection and stroke.

26. A method for treating a VCAM-1 mediated disease comprising administering a therapeutically effective amount of the monoclonal antibody according to claim 1 to a patient in need thereof.

27. The method according to claim 26, wherein the VCAM-1 mediated disease is an inflammatory disease or a cancer.

28. The method according to claim 27, wherein the inflammatory disease is selected from a group consisted of arthritis, multiple sclerosis, bowl disease, asthma, atherosclerosis, myocardial infarction, transplantation rejection and stroke.

29. A method for inhibiting a VCAM-1 mediated adhesion of a leukocyte to endothelial cell comprising contacting the monoclonal antibody according to claim 1 to the site thereof.

30. A composition comprising the monoclonal antibody according to claim 1 and an effective carrier thereof.

31. A pharmaceutical composition comprising the monoclonal antibody according to claim 1 and a pharmaceutically effective carrier thereof.

32. The monoclonal antibody according to claim 6, comprising a light chain of which the amino acid sequence in defined by SEQ ID No. 1 and/or a heavy chain of which the amino acid sequence is selected from the group consisting of the amino acid sequences that are defined by SEQ ID NOS. 2, 3 and 4.

33. The monoclonal antibody according to claim 21, comprising a light chain of which the amino acid sequence is defined by SEQ ID No. 13 and/or a heavy chain of which the amino sequence is defined by SEQ ID NOS 14 or 15.