# US 7,745,587 B2 · Antibodies that bind MMP-14

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- Number: US 7,745,587 B2
- Document ID: US7745587B2
- Status: Granted
- Kind: B2
- Application number: 11/648,423
- Filed: 2006-12-29
- Published: 2007-09-20
- Granted: 2010-06-29
- Earliest claimed: 2005-12-30
- Assignees: Dyax Corp.
- Inventors: Laetitia Devy; Henk Pieters; Robert C. Ladner; Rene Hoet; Daniel T. Dransfield; Clive R. Wood; Maria Henderikx
- Web page: https://patentgrep.com/patent/US7745587B2

## CPC

- C07K 16/40: against enzymes
- A61K 51/1075: {the antibody being against an enzyme}
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/30: from tumour cells
- G01N 33/573: for enzymes or isoenzymes
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2333/96486: Metalloendopeptidases (3.4.24)
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Proteins that bind to matrix metalloproteinase 14 and methods of using such proteins are described.

## Claims

### Claim 1

An isolated protein comprising a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein the HC and the LC immunoglobulin variable domain sequences form an antigen binding site that binds to a human membrane-type-matrix metalloproteinase 14 (MMP-14) and wherein the HC immunoglobulin variable domain comprises HC complementarity determining region (CDR) 1, CDR2, and CDR3, wherein the HC CDR1 sequence comprises residues 31-35 of SEQ ID NO:156, the HC CDR2 sequence comprises residues 50-66 of SEQ ID NO:156, and the HC CDR3 sequence comprises residues 99-104 of SEQ ID NO:156; and the LC immunoglobulin variable domain comprises LC CDR1, CDR2, and CDR3, wherein the LC CDR1 sequence comprises residues 25-35 of SEQ ID NO:157, the LC CDR2 sequence comprises residues 51-57 of SEQ ID NO:157, and the LC CDR3 sequence comprises residues 90-99 of SEQ ID NO:157.

### Claim 2 (depends on 1)

The protein of claim 1, wherein the protein inhibits human MMP-14 enzymatic activity.

### Claim 3 (depends on 1)

The protein of claim 1, wherein the HC and LC variable domain sequences are components of the same polypeptide chain.

### Claim 4 (depends on 1)

The protein of claim 1, wherein the protein comprises a human antibody framework region.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising the protein of claim 1 and a pharmaceutically acceptable carrier.

### Claim 6 (depends on 1)

The protein of claim 1, wherein the protein is a primate antibody.

### Claim 7 (depends on 1)

The protein of claim 1, wherein the protein comprises a primate antibody framework region.

### Claim 8 (depends on 1)

The protein of claim 1, wherein the protein is a humanized antibody.

### Claim 9 (depends on 1)

The protein of claim 1, wherein the HC immunoglobulin variable domain sequence comprises a sequence that has less than 10 conservative mutations in the framework regions relative to SEQ ID NO:156.

### Claim 10 (depends on 1)

The protein of claim 1, wherein the HC immunoglobulin variable domain sequence comprises SEQ ID NO:156.

### Claim 11 (depends on 1)

The protein of claim 1, wherein the LC immunoglobulin variable domain sequence comprises a sequence that has less than 10 conservative mutations in the framework regions relative to SEQ ID NO:157.

### Claim 12 (depends on 1)

The protein of claim 1, wherein the LC immunoglobulin variable domain sequence comprises SEQ ID NO:157.

### Claim 13 (depends on 1)

The protein of claim 1, wherein the HC immunoglobulin variable domain sequence comprises a sequence that has less than 10 conservative mutations in the framework regions relative to SEQ ID NO:156 and the LC immunoglobulin variable domain sequence comprises a sequence that is has less than 10 conservative mutations in the framework regions relative to SEQ ID NO:157.

### Claim 14 (depends on 1)

The protein of claim 1, wherein the HC immunoglobulin variable domain sequence comprises SEQ ID NO:156 and the LC immunoglobulin variable domain sequence comprises SEQ ID NO:157.

### Claim 15 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that is at least 90% identical to residues 20 to 464 of SEQ ID NO:182 in the framework regions.

### Claim 16 (depends on 1)

The protein of claim 1, wherein the protein comprises residues 20 to 464 of SEQ ID NO:182.

### Claim 17 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that is at least 90% identical to residues 20 to 234 of SEQ ID NO:181 in the framework regions.

### Claim 18 (depends on 1)

The protein of claim 1, wherein the protein comprises residues 20 to 234 of SEQ ID NO:181.

### Claim 19 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that is at least 90% identical to residues 20 to 464 of SEQ ID NO:182 in the framework regions and a sequence that is at least 90% identical to residues 20 to 234 of SEQ ID NO:181 in the framework regions.

### Claim 20 (depends on 1)

The protein of claim 1, wherein the protein comprises residues 20 to 464 of SEQ ID NO:182 and residues 20 to 234 of SEQ ID NO:181.

### Claim 21 (depends on 14)

A pharmaceutical composition comprising the protein of claim 14 and a pharmaceutically acceptable carrier.

### Claim 22 (depends on 20)

A pharmaceutical composition comprising the protein of claim 20 and a pharmaceutically acceptable carrier.

### Claim 23 (depends on 1)

The protein of claim 1, wherein the protein binds to human MMP-14.

### Claim 24 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that has less than 10 conservative mutations in the framework regions relative to residues 20 to 464 of SEQ ID NO:182.

### Claim 25 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that has less than 10 conservative mutations in the framework regions relative to residues 20 to 234 of SEQ ID NO:181.

### Claim 26 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that has less than 10 conservative mutations in the framework regions relative to residues 20 to 464 of SEQ ID NO:182 and a sequence that that has less than 10 conservative mutations in the framework regions relative to residues 20 to 234 of SEQ ID NO:181.

### Claim 27 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that has less than 5 conservative mutations in the framework regions relative to residues 20 to 464 of SEQ ID NO:182.

### Claim 28 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that has less than 5 conservative mutations in the framework regions relative to residues 20 to 234 of SEQ ID NO:181.

### Claim 29 (depends on 1)

The protein of claim 1, wherein the protein comprises a sequence that has less than 5 conservative mutations in the framework regions relative to residues 20 to 464 of SEQ ID NO:182 and a sequence that that has less than 5 conservative mutations in the framework regions relative to residues 20 to 234 of SEQ ID NO:181.

### Claim 30 (depends on 1)

The protein of claim 1, wherein the HC immunoglobulin variable domain sequence comprises a sequence that has less than 5 conservative mutations in the framework regions relative to SEQ ID NO:156.

### Claim 31 (depends on 1)

The protein of claim 1, wherein the LC immunoglobulin variable domain sequence comprises a sequence that has less than 5 conservative mutations in the framework regions relative to SEQ ID NO:157.

### Claim 32 (depends on 1)

The protein of claim 1, wherein the HC immunoglobulin variable domain sequence comprises a sequence that has less than 5 conservative mutations in the framework regions relative to SEQ ID NO:156 and the LC immunoglobulin variable domain sequence comprises a sequence that is has less than 5 conservative mutations in the framework regions relative to SEQ ID NO:157.