Antibody which specifically binds to human CRTH2

Patent metadata

Field	Value
Publication number	US-10100120-B2
Application number	US-201815932185-A
Country	US
Kind code	B2
Filing date	Feb 16, 2018
Priority date	Jul 15, 2015
Publication date	Oct 16, 2018
Grant date	Oct 16, 2018

Abstract

There is provided an anti-human CRTH2 antibody which has desired activity by recognizing and binding to a specific human CRTH2; the antibody fragment; DNA which encodes the amino acid sequence of the antibody; a vector which comprises the DNA; hybridomas and antibody producing cells which produce the antibody; a method of producing the antibody; a composition which comprises the antibody or the antibody fragment; a treatment method and a diagnostic method of an allergic disease, an autoimmune disease, a disease accompanied by at least one of increase and hyperergasia of eosinophils; a disease accompanied by at least one of increase and hyperergasia of Th2 cells using the antibody or the antibody fragment; and a medicine and a diagnostic agent which comprise the antibody or the antibody fragment.

First claim

The invention claimed is:

1. A nucleic acid molecule encoding an antibody or an antibody fragment thereof, said antibody or said antibody fragment recognizing at least one of 192th glycine and 194th aspartic acid in the amino acid sequence of human CRTH2 of SEQ ID NO: 2 and binding thereto, wherein the antibody comprises complementarity determining regions (CDR) 1 to 3 of an antibody heavy chain variable region (VH) which comprise amino acid sequences represented by SEQ ID NOS: 20 to 22, respectively, and CDRs 1 to 3 of an antibody light chain variable regions (VL) which comprise amino acid sequences represented by SEQ ID NOS: 23 to 25, respectively.

2. The nucleic acid molecule according to claim 1 , wherein the antibody comprises VH comprising the amino acid sequence represented by SEQ ID NO: 49 or the amino acid sequence obtained by introducing at least one modification selected from modifications of substituting 18th leucine with methionine, 77th asparagine with serine, 93th valine with threonine, and 117th threonine with valine in the amino acid sequence represented by SEQ ID NO: 49 and VL comprising the amino acid sequence represented by SEQ ID NO: 33 or the amino acid sequence obtained by at least one modification selected from modifications of substituting 2nd isoleucine with valine, 4th methionine with leucine, 15th proline with leucine, and 85th alanine with proline in the amino acid sequence represented by SEQ ID NO: 33.

3. The nucleic acid molecule according to claim 1 , wherein the antibody comprises VH comprising any one of the amino acid sequences represented by SEQ ID NOS: 49, 51, 53, 55, 57, and 59 and VL comprising any one of the amino acid sequences represented by SEQ ID NOS: 33, 35, 37, 39, 41, 43, 45, and 47.

4. The nucleic acid molecule according to claim 1 , wherein the antibody comprises a human Fc region.

5. The nucleic acid molecule according to claim 1 , wherein the antibody is an antibody which binds to monkey CRTH2.

6. The nucleic acid molecule according to claim 1 , wherein the antibody fragment is any one selected from Fab, Fab′, F(ab′) 2 , scFv, diabody, and dsFv.

7. A recombinant vector which comprises the nucleic acid molecule according to claim 1 .

8. A recombinant vector which comprises the nucleic acid molecule according to claim 2 .

9. A recombinant vector which comprises the nucleic acid molecule according to claim 3 .

10. A recombinant vector which comprises the nucleic acid molecule according to claim 4 .

11. A recombinant vector which comprises the nucleic acid molecule according to claim 5 .

12. A recombinant vector which comprises the nucleic acid molecule according to claim 6 .

13. A transformant host which comprises the recombinant vector according to claim 7 .

14. A transformant host which comprises the recombinant vector according to claim 8 .

15. A transformant host which comprises the recombinant vector according to claim 9 .

16. A transformant host which comprises the recombinant vector according to claim 10 .

17. A transformant host which comprises the recombinant vector according to claim 11 .

18. A transformant host which comprises the recombinant vector according to claim 12 .

19. A method of producing an antibody or the antibody fragment thereof, comprising:
culturing the transformant host according to claim 13 to produce the antibody or the antibody fragment thereof; and
recovering the antibody or the antibody fragment.

20. A hybridoma which produces an antibody or an antibody fragment thereof, said antibody or said antibody fragment recognizing at least one of 192th glycine and 194th aspartic acid in the amino acid sequence of human CRTH2 of SEQ ID NO: 2 and binds thereto, wherein the antibody comprises complementarity determining regions (CDR) 1 to 3 of an antibody heavy chain variable region (VH) which comprise amino acid sequences represented by SEQ ID NOS: 20 to 22, respectively, and CDRs 1 to 3 of an antibody light chain variable regions (VL) which comprise amino acid sequences represented by SEQ ID NOS: 23 to 25, respectively.

21. A method of producing an antibody or the antibody fragment thereof, comprising:
culturing the hybridoma according to claim 20 to produce the antibody or the antibody fragment thereof; and
recovering the antibody or the antibody fragment.

Assignees

• Kyowa Hakko Kirin Co Ltd

Inventors

• Kameyama Naoya
• Ando Munetoshi
• Ogawa Shinya
• Okada Kazuki

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/02

  Immunomodulators · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• G01N33/88

  involving prostaglandins {or their receptors} · CPC title