Anti-c-Met antibody having HGF activity and use thereof
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.
1. A human antibody comprising: a human complementarity-determining region (CDR) that binds specifically to c-Met; and a framework region (FR), wherein said human antibody comprises 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.
2. 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.
3. The human antibody of claim 1 , wherein the human antibody induces HGF/c-Met signaling.
4. The human antibody of claim 1 , wherein the human antibody is a glycosylated and/or PEGylated antibody.
5. The human antibody of claim 4 , wherein the antibody has an altered glycosylation and/or PEGylation pattern.
6. A polynucleotide encoding the heavy-chain variable region and light-chain variable region of the human antibody of claim 1 .
7. The polynucleotide of claim 6 , 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.
8. An expression vector comprising the polynucleotide of claim 7 .
9. A transformant transformed with the expression vector of claim 8 .
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 9 ; 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.
11. A wound healing composition comprising the human antibody of claim 1 as an active ingredient together with a pharmaceutically acceptable carrier.
12. A composition for regenerating cells, the composition comprising the human antibody of claim 1 as an active ingredient together with a pharmaceutically acceptable carrier.
13. The composition of claim 12 , wherein the cells are liver cells, neural cells, muscle cells or skin cells.
14. The composition of claim 13 , wherein the neural cells are brain cells.
15. The composition of claim 13 , wherein the muscular cells are myocardial cells.
16. 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.
17. The composition of claim 16 , wherein the neurodegenerative disease is Parkinson's disease, ischemic disease leading to neuronal infraction, or Alzheimer's disease.
18. 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.
19. The composition of claim 18 , wherein the organ is heart, kidney, liver or lung.
20. A drug conjugate comprising a drug linked to the human antibody of claim 1 .