# US 2014/0193431 A1 · Anti-c-met antibody having hgf activity and use thereof

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- Number: US 2014/0193431 A1
- Document ID: US20140193431A1
- Status: Published application
- Kind: A1
- Application number: 14/123,533
- Filed: 2012-06-04
- Published: 2014-07-10
- Earliest claimed: 2011-06-03
- Assignees: Korea Research Institute of Bioscience and Biotechnology
- Inventors: Young Woo Park; KiWon Jo; Chan Woong Park; Seok Ho Yoo; Myeoung Hee Jang; Hye Nan Kim; Seon Ha Yun; Kyu Won Cho; Mi Ra Park
- Web page: https://patentgrep.com/patent/US20140193431A1

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- 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
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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
- 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)

## Abstract

Disclosed are a human antibody comprising a human complementarity-determining region (CDR), which binds specifically to c-Met, and a framework region (FR), a polynucleotide encoding the human antibody, an expression vector comprising the polynucleotide, a transformant transformed with the expression vector, a method of producing the human antibody B7 by culturing the transformant, a wound healing composition comprising the human antibody as an active ingredient, a cell regeneration composition comprising the antibody as an active ingredient, and a drug conjugate comprising a drug linked to the human antibody. The c-Met-specific human antibody can function as an HGF mimic that can be used as a wound healing composition. The antibody can be widely used to determine the treatment and prognosis of various diseases, including neuronal infarction, progressive nephropathy, liver cirrhosis, lung fibrosis, kidney injury, liver injury, lung injury, and ulcerative wounds, which are treated by activation of HGF or c-Met.

## Claims

### Claim 1

A human antibody comprising: a human complementarity-determining region (CDR) that binds specifically to c-Met; and a framework region (FR).

### Claim 2 (depends on 1)

The human antibody of claim 1, comprising: a heavy-chain variable region comprising a heavy-chain CDR1 set forth in SEQ ID NO: 1, a heavy-chain CDR2 set forth in SEQ ID NO: 2, and a heavy-chain CDR3 set forth in SEQ ID NO: 3; and a light-chain variable region comprising a light-chain CDR1 set forth in SEQ ID NO: 4, a light-chain CDR2 set forth in SEQ ID NO: 5, and a light-chain CDR3 set forth in SEQ ID NO: 6.

### Claim 3 (depends on 1)

The human antibody of claim 1, comprising a heavy-chain variable region amino acid sequence set forth in SEQ ID NO: 7 and a light-chain variable region amino acid sequence set forth in SEQ ID NO: 8.

### Claim 4 (depends on 1)

The human antibody of claim 1, wherein the human antibody induces HGF/c-Met signaling.

### Claim 5 (depends on 1)

The human antibody of claim 1, wherein the human antibody is a glycosylated and/or PEGylated antibody.

### Claim 6 (depends on 5)

The human antibody of claim 5, wherein the antibody has an altered glycosylation and/or PEGylation pattern.

### Claim 7 (depends on 1)

A polynucleotide encoding the heavy-chain variable region and light-chain variable region of the human antibody of claim 1.

### Claim 8 (depends on 7)

The polynucleotide of claim 7, wherein the polynucleotide encoding the heavy-chain variable region is composed of a nucleotide sequence set forth in SEQ ID NO: 9, and the polynucleotide encoding the light-chain variable region is composed of a nucleotide sequence set forth in SEQ ID NO: 10.

### Claim 9 (depends on 8)

An expression vector comprising the polynucleotide of claim 8.

### Claim 10 (depends on 9)

A transformant transformed with the expression vector of claim 9.

### Claim 11 (depends on 10)

A method for producing a human antibody that binds specifically to c-Met, the method comprising the steps of:
(i) culturing the transformant of claim 10; and
(ii) purifying the human antibody comprising: a human complementarity-determining region (CDR) that binds specifically to c-Met; and a framework region (FR) from the culture.

### Claim 12 (depends on 1)

A wound healing composition comprising the human antibody of claim 1 as an active ingredient together with a pharmaceutically acceptable carrier.

### Claim 13 (depends on 1)

A composition for regenerating cells, the composition comprising the human antibody of claim 1 as an active ingredient together with a pharmaceutically acceptable carrier.

### Claim 14 (depends on 13)

The composition of claim 13, wherein the cells are liver cells, neural cells, muscle cells or skin cells.

### Claim 15 (depends on 14)

The composition of claim 14, wherein the neural cells are brain cells.

### Claim 16 (depends on 14)

The composition of claim 14, wherein the muscular cells are myocardial cells.

### Claim 17 (depends on 1)

A composition for treating neurodegenerative disease, the composition comprising the human antibody of claim 1 as an active ingredient together with a pharmaceutically acceptable carrier.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the neurodegenerative disease is Parkinson's disease, ischemic disease leading to neuronal infraction, or Alzheimer's disease.

### Claim 19 (depends on 1)

A composition for treating ulcerative damage to an organ, the composition comprising the human antibody of claim 1 as an active ingredient together with a pharmaceutically acceptable carrier.

### Claim 20 (depends on 19)

The composition of claim 19, wherein the organ is heart, kidney, liver or lung.

### Claim 21 (depends on 1)

A drug conjugate comprising a drug linked to the human antibody of claim 1.

### Claim 22 (depends on 1)

A wound healing method comprising administering to a subject the human antibody of claim 1 or a wound healing composition comprising the human antibody as an active ingredient or the drug conjugate comprising a drug linked to the human antibody.

### Claim 23 (depends on 1)

A method for treating neurodegenerative disease, the method comprising administering to a subject the human antibody of claim 1 or the composition for treating neurodegenerative disease comprising the human antibody as an active ingredient or the drug conjugate comprising a drug linked to the human antibody.

### Claim 24 (depends on 1)

A method for treating damage to ulcerative damage to an organ, the method administering to a subject the human antibody of claim 1 or the composition for treating ulcerative damage to an organ comprising the human antibody as an active ingredient or the drug conjugate comprising a drug linked to the human antibody.