HUMAN ANTIBODY AGAINST AGGRECANASE-TYPE ADAMTS SPECIES FOR THERAPEUTICS OF AGGRECANASE-RELATED DISEASES

• US 20190233541A1
• Filed: 10/05/2018
• Published: 08/01/2019
• Est. Priority Date: 10/15/2013
• Status: Active Grant

• Current Assignee: GeneFrontier Corporation (Kaneka Corporation)
• Original Assignee: GeneFrontier Corporation (Kaneka Corporation)
• Inventors: MIYAKOSHI, Akira, NAKAMURA, Mikiko, KOJOH, Kanehisa, MOCHIZUKI, Satsuki, OKADA, Yasunori
• Granted Patent: US 10,640,573 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• 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
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention provides an antibody that specifically binds to human aggrecanase, and inhibits enzymatic activity of the human aggrecanase. In one embodiment, aggrecanase is ADAMTS4. In one embodiment, the antibody recognizes a particular epitope in human ADAMTS4, and inhibits not only aggrecanase activity of human ADAMTS4 but also aggrecanase activity of human ADAMTS5. In addition, the present invention also provides use of said antibody in the prophylaxis or treatment of the progression of arthritis.

Claims

1-23. -23. (canceled)

24. A method of preventing or treating arthritis, the method comprising administering an antibody comprising a light chain variable region and a heavy chain variable region to a subject expressing a human aggrecanase,

wherein the antibody binds to an epitope of the human aggrecanase, and

wherein the epitope consists of 20 or less amino acid residues and comprises the amino acid sequence of SEQ ID NO:

9.

25. The method according to claim 24, wherein the epitope is a continuous partial sequence of the amino acid sequence of SEQ ID NO:

15.

26. The method according to claim 24, wherein the epitope consists of the amino acid sequence selected from the group consisting of SEQ ID NOs:

9-13.

27. The method according to claim 24, wherein the antibody inhibits aggrecanase activity of the human aggrecanase.

28. The method according to claim 24, wherein the human aggrecanase is human ADAMTS4.

29. The method according to claim 24, wherein the subject has arthritis.

30. The method according to claim 24,

wherein the light chain variable region comprises:

CDR1 comprising the amino acid sequence of SEQ ID NO;

1;

CDR2 comprising the amino acid sequence of SEQ ID NO;

2; and

CDR3 comprising the amino acid sequence of SEQ ID NO;

3, and

wherein the heavy chain variable region comprises;

CDR1 comprising the amino acid sequence of SEQ ID NO;

4;

CDR2 comprising the amino acid sequence of SEQ ID NO;

5; and

CDR3 comprising the amino acid sequence of SEQ ID NO;

6.

31. The method according to claim 24,

wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:

7, and

wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO;

8.

32. The method according to claim 24,

wherein the light chain variable region comprises:

CDR1 comprising the amino acid sequence of SEQ ID NO;

1;

CDR2 comprising the amino acid sequence of SEQ ID NO;

2; and

CDR3 comprising the amino acid sequence of SEQ ID NO;

3,

wherein the heavy chain variable region comprises;

CDR1 comprising the amino acid sequence of SEQ ID NO;

4;

CDR2 comprising the amino acid sequence of SEQ ID NO;

5; and

CDR3 comprising the amino acid sequence of SEQ ID NO;

6, and

wherein 1 to 3 amino acid residues are substituted, deleted, inserted, and/or added in at least one amino acid sequence selected from the group consisting of SEQ ID NOs;

1 to 6.

33. The method according to claim 32, wherein 1 or 2 amino acid residues are substituted, deleted, inserted, and/or added in at least one amino acid sequence selected from the group consisting of SEQ ID NOs:

1 to 6.

34. The method according to claim 32, wherein 1 amino acid residue is substituted, deleted, inserted, or added in at least one amino acid sequence selected from the group consis_ting of SEQ ID NOs:

1 to 6.