VCAM-1 specific monoclonal antibody

• US 7,655,417 B2
• Filed: 05/31/2007
• Issued: 02/02/2010
• Est. Priority Date: 05/31/2006
• Status: Expired due to Fees

• Current Assignee: Hanwha Chemical Corporation
• Original Assignee: Hanwha Chemical Corporation
• Inventors: Lee, Ji Eun, Chung, Junho, Lee, Sukmook, Ryu, Eun Kyung
• Primary Examiner(s): Haddad; Maher M
• Application Number:
  US11/756,437
• Publication Number:
  US 20070280941A1
• Time in Patent Office: 978 Days
• Field of Search: None
• US Class Current: 435/7.1
• 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), comprising:

(a) a light chain CDR 1 region defined by SEQ ID NO;

5, a light chain CDR 2 region defined by SEQ ID NO;

6, and a light chain CDR 3 region defined by SEQ ID NO;

7; and

(b) a heavy chain CDR 1 region defined by SEQ ID NO;

8, a heavy chain CDR 2 region defined by SEQ ID NO;

9 or 11, and a heavy chain CDR 3 region defined by SEQ ID NO;

10 or 12.

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, wherein

(1) The heavy chain CDR 2 region is defined by SEQ ID NO:

9, and the heavy chain CDR 3 region is defined by SEQ ID NO;

10;

or

(2) The heavy chain CDR 2 region is defined by SEQ ID NO;

11, and the heavy chain CDR 3 region is defined by SEQ ID NO;

12.

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

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

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

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

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

9. A method for detecting VCAM-1 expressing cells comprising contacting a sample with the monoclonal antibody according to claim 1.

10. A method for inhibiting VCAM-1 mediated adhesion of a leukocyte to endothelial cell comprising contacting the endothelial cell with the monoclonal antibody according to claim 1 in vitro.

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

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

13. The monoclonal antibody according to claim 1, wherein the light chain amino acid sequence is defined by SEQ ID NO:

1.

14. The monoclonal antibody according to claim 7, wherein the light chain of which the amino acid sequence is defined by SEQ ID NO:

13.

15. The monoclonal antibody according to claim 1, wherein the heavy chain amino acid sequence is defined by SEQ ID NOs:

2, 3, or 4.

16. The monoclonal antibody according to claim 7, comprising wherein the heavy chain amino acid sequence is defined by SEQ ID NOs:

14 or 15.