# US 2019/0233541 A1 · Human antibody against aggrecanase-type adamts species for therapeutics of aggrecanase-related diseases

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- Number: US 2019/0233541 A1
- Document ID: US20190233541A1
- Status: Published application
- Kind: A1
- Application number: 16/153,413
- Filed: 2018-10-05
- Published: 2019-08-01
- Earliest claimed: 2013-10-15
- Assignees: GeneFrontier Corporation; Keio University
- Applicants: GeneFrontier Corporation; Keio University
- Inventors: Akira MIYAKOSHI; Mikiko NAKAMURA; Kanehisa KOJOH; Satsuki MOCHIZUKI; Yasunori OKADA
- Web page: https://patentgrep.com/patent/US20190233541A1

## CPC

- C07K 16/40: against enzymes
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 2317/21: from primates, e.g. man
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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

### Claim at position 1

1-23. (canceled)

### Claim 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.

### Claim 25 (depends on 24)

The method according to claim 24, wherein the epitope is a continuous partial sequence of the amino acid sequence of SEQ ID NO: 15.

### Claim 26 (depends on 24)

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.

### Claim 27 (depends on 24)

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

### Claim 28 (depends on 24)

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

### Claim 29 (depends on 24)

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

### Claim 30 (depends on 24)

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.

### Claim 31 (depends on 24)

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.

### Claim 32 (depends on 24)

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.

### Claim 33 (depends on 32)

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.

### Claim 34 (depends on 32)

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 consisting of SEQ ID NOs: 1 to 6.
