# US 8,147,836 B2 · Compositions and methods for treating osteolytic disorders comprising MMP-14 binding proteins

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- Number: US 8,147,836 B2
- Document ID: US8147836B2
- Status: Granted
- Kind: B2
- Application number: 12/337,140
- Filed: 2008-12-17
- Published: 2009-07-23
- Granted: 2012-04-03
- Earliest claimed: 2007-12-17
- Assignees: Dyax Corp.
- Inventors: Clive R. Wood; Daniel T. Dransfield; Laetitia Devy
- Web page: https://patentgrep.com/patent/US8147836B2

## CPC

- C07K 16/40: against enzymes
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 19/10: for osteoporosis
- A61P 35/00: Antineoplastic agents
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- Y10T 428/13: Hollow or container type article [e.g., tube, vase, etc.]
- 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
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

Provided are methods and compositions for using MMP-14 or MMP-9 binding proteins alone or in combination with other therapeutic agents to treat osteolytic disorders such as osteotropic cancer and osteoporosis.

## Claims

### Claim 1

A method for treating osteotropic cancer arising from metastatic prostate cancer in a subject, the method comprising administering to said subject an effective amount of an antibody that specifically binds to a MMP-14 polypeptide comprising SEQ ID NO: 1, wherein the antibody inhibits the activity of MMP-14 and comprises a heavy chain immunoglobulin variable domain sequence and a light chain immunoglobulin variable domain, wherein the heavy chain immunoglobulin variable domain sequence comprises the heavy chain CDR1, CDR2 and CDR3 of SEQ ID NO:22 and the light chain immunoglobulin variable domain sequence comprises the CDR1, CDR2 and CDR3 of SEQ ID NO: 23, thereby treating the osteotropic cancer in the subject.

### Claim 2 (depends on 1)

The method of claim 1, further comprising administering an additional therapeutic to said subject.

### Claim 3 (depends on 2)

The method of claim 2, wherein the additional therapeutic is selected from the group consisting of: a bisphosphonate a hormone-related compound, a RANKL antagonist, a αγβ3 antagonist, a Src inhibitor, a cathepsin K inhibitor and calcitonin.

### Claim 4

A method for reducing the development of osteolytic lesions arising from metastatic prostate cancer in a subject, the method comprising administering to said subject an effective amount of an antibody that specifically binds to a MMP-14 polypeptide comprising SEQ ID NO: 1, wherein the antibody inhibits the activity of MMP-14 and comprises a heavy chain immunoglobulin variable domain sequence and a light chain immunoglobulin variable domain sequence, wherein the heavy chain immunoglobulin variable domain sequence comprises the heavy chain CDR1, CDR2 and CDR3 of SEQ ID NO:22 and the light chain immunoglobulin variable domain sequence comprises the CDR1, CDR2 and CDR3 of SEQ ID NO:23, thereby reducing the development of said osteolytic lesions in the subject.

### Claim 5 (depends on 4)

The method of claim 4, further comprising administering an additional therapeutic to said subject.

### Claim 6 (depends on 5)

The method of claim 5, wherein the additional therapeutic is selected from the group consisting of: a bisphosphonate a hormone-related compound, a RANKL antagonist, a αγβ3 antagonist, a Src inhibitor, a cathepsin K inhibitor and calcitonin.

### Claim 7 (depends on 1, 4)

The method of claim 1 or claim 4, wherein the antibody is an antibody fragment selected from the group consisting of a Fab fragment, an soluble Fab (sFab) fragment, an F(ab′)2 fragment, an Fd fragment, and an Fv fragment.

### Claim 8 (depends on 1, 4)

The method of claim 1 or 4, wherein the prostate cancer is androgen-independent prostate cancer.

### Claim 9 (depends on 1, 4)

The method of claim 1 or claim 4, wherein the antibody comprises the heavy chain variable region comprising SEQ ID NO:22.

### Claim 10 (depends on 1, 4)

The method of claim 1 or claim 4, wherein the antibody comprises the light chain variable region comprising SEQ ID NO:23.

### Claim 11 (depends on 1, 4)

The method of claim 1 or claim 4, wherein the antibody comprises the heavy chain variable region comprising SEQ ID NO:22 and the light chain variable region comprising SEQ ID NO:23.

### Claim 12 (depends on 1, 4)

The method of claim 1 or claim 4, wherein the antibody is an IgG-1 antibody.

### Claim 13 (depends on 1, 4)

The method of claim 1 or claim 4, wherein the antibody is a humanized antibody or a deimmunized antibody.

### Claim 14 (depends on 1, 4)

The method of claim 1 or 4, wherein the antibody is PEGylated.

### Claim 15 (depends on 1, 4)

The method of claim 1 or claim 4, wherein the antibody is a primate antibody or a chimeric antibody comprising a primate Fc domain.

### Claim 16 (depends on 1, 4)

The method of claim 1 or 4, wherein the antibody is a scFv.