이 애플리케이션의 일부 콘텐츠는 현재 사용할 수 없습니다.
이 상황이 계속되면 다음 주소로 문의하십시오피드백 및 연락
1. (WO2018163185) ANTI CCL24 (EOTAXIN2) ANTIBODIES FOR USE IN THE TREATMENT OF HEPATIC DISEASES
유의사항: 이 문서는 자동 광학문자판독장치(OCR)로 처리된 텍스트입니다. 법률상의 용도로 사용하고자 하는 경우 PDF 버전을 사용하십시오

CLAIMS:

1. An isolated anti CCL24 (eotaxin 2) antibody, or any antigen-binding fragment thereof, for use in the treatment of hepatic pathologies.

2. The isolated anti CCL24 antibody for use of claim 1 wherein said hepatic pathologies are selected from the group consisting of non-alcoholic fatty liver diseases (NAFLD), cholestasis, intrahepatic cholestatic liver diseases, alcoholic hepatitis, and liver cirrhosis.

3. The isolated anti CCL24 antibody for use of claim 2 wherein said NAFLD is nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH).

4. The isolated anti CCL24 antibody for use of claim 2 wherein said hepatic pathology is Hepatocellular carcinoma resulting from NASH.

5. The isolated anti CCL24 antibody for use of claim 2 wherein said intrahepatic cholestatic liver disease is primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC).

6. The isolated anti CCL24 antibody for use of claim 2 wherein said hepatic pathology is cholangiocarcinoma resulting from PSC.

7. An isolated anti CCL24 antibody, or any antigen-binding fragment thereof, for use in:

a. reducing elevated serum levels of liver enzymes upon liver damage;

b. reducing liver damage or necrosis; and/or

c. attenuating the transition of hepatic stellate cells (HSC) to myofibroblasts.

8. The isolated anti CCL24 antibody for use of any one of the preceding claims, wherein said antibody is a monoclonal antibody.

9. The isolated anti CCL24 antibody for use of claim 8 wherein said monoclonal antibody is a chimeric antibody, a human antibody, a humanized antibody or a fully humanized antibody.

10. The isolated anti CCL24 antibody for use of any one of the preceding claims wherein said antigen-binding fragment thereof is selected from the group consisting of Fv, single chain Fv (scFv), heavy chain variable region capable of binding the antigen, light chain variable region capable of binding the antigen, Fab, F(ab)2' and any combination thereof.

11. The isolated anti CCL24 antibody for use of any one of the preceding claims, wherein said antibody is a fully humanized antibody comprising a heavy chain variable region comprising:

a) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 1 or a variant thereof;

b) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 2 or a variant thereof; and

c) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 3 or a variant thereof; and

a light chain variable region comprising

d) the complementary determining region VK CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 4 or a variant thereof;

e) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 5 or a variant thereof; and

f) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 6 or a variant thereof.

12. The isolated anti CCL24 antibody for use of any one of the preceding claims, wherein said antibody is a fully humanized antibody comprising the heavy chain variable region denoted by SEQ ID NO: 7 or a variant thereof and the light chain variable region denoted by SEQ ID NO: 8 or a variant thereof.

13. The isolated anti CCL24 antibody for use of any one of claims 1 to 10, wherein said antibody is a fully humanized antibody comprising six CDR sequences as denoted by SEQ ID Nos 1-6, and a heavy chain variable region having at least 90% sequence homology to SEQ ID NO:7 and a light chain variable region having at least 90% sequence homology to SEQ ID NO: 8.

14. The isolated anti CCL24 antibody for use of any one of claims 1 to 10, wherein said antibody binds the same epitope as an antibody comprising:

(a) a heavy chain CDR1 comprising NSGMN (SEQ ID NO: 1), a heavy chain CDR2 comprising WINTYNGEPTYTDDFKG (SEQ ID NO: 2), and a heavy chain CDR3 comprising HSYGSSYAMDN (SEQ ID NO: 3); and

(b) a light chain CDR1 comprising KASQSVDYDGDSYMN (SEQ ID NO: 4), a light chain CDR2 comprising VASNLKS (SEQ ID NO: 5), and a light chain CDR3 comprising QQSNEEPWT (SEQ ID NO: 6).

15. The isolated anti CCL24 antibody for use of any one of the preceding claims, wherein said antibody is administered in combination with at least one additional therapeutic agent.

16. The isolated anti CCL24 antibody for use of claim 15, wherein said at least one additional therapeutic agent is selected from the group consisting of farnesoid X receptor (FXR) agonists, peroxisome proliferator-activated receptor (PPAR) agonists, anti-chemokine or anti-cytokine monoclonal antibodies, small molecules, anti-inflammatory agents, anti-fibrotic agents, and steroids.

17. A pharmaceutical composition comprising a fully humanized antibody comprising a heavy chain variable region comprising:

a) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 1 or a variant thereof;

b) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 2 or a variant thereof; and

c) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 3 or a variant thereof; and

a light chain variable region comprising

d) the complementary determining region VK CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 4 or a variant thereof;

e) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 5 or a variant thereof; and

f) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 6 or a variant thereof;

and a pharmaceutically acceptable carrier; wherein said pharmaceutical composition is for use in the treatment of hepatic pathologies.

18. The pharmaceutical composition of claim 17, wherein said fully humanized antibody further comprises a heavy chain variable region having at least 90% sequence homology to SEQ ID NO:7 and a light chain variable region having at least 90% sequence homology to SEQ ID NO: 8.

19. The pharmaceutical composition of claim 17 or claim 18, wherein said pharmaceutical composition is administered in combination with at least one additional therapeutic agent.

20. The pharmaceutical composition of claim 19, wherein said pharmaceutical composition is administered prior to, concomitantly or subsequently to the administration of said at least one additional therapeutic agent.

21. The pharmaceutical composition of claim 17 or claim 18, wherein said pharmaceutical composition further comprises at least one additional therapeutic agent.

22. The pharmaceutical composition of any one of claims 17-21, wherein said at least one additional therapeutic agent is selected from the group consisting of farnesoid X receptor (FXR) agonists, peroxisome proliferator-activated receptor (PPAR) agonists, anti-chemokine or anti-cytokine monoclonal antibodies, small molecules, antiinflammatory agents, anti-fibrotic agents, and steroids.

23. A method of treating hepatic pathologies comprising administering to a patient in need thereof a therapeutically acceptable amount of a fully humanized antibody comprising a heavy chain variable region comprising:

a) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 1 or a variant thereof;

b) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 2 or a variant thereof; and

c) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 3 or a variant thereof; and

a light chain variable region comprising

d) the complementary determining region VK CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 4 or a variant thereof;

e) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 5 or a variant thereof; and

f) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 6 or a variant thereof,

or the pharmaceutical composition of claim 17.

24. A method of reducing serum levels of liver enzymes upon liver damage and/or reducing liver damage or necrosis, and/or attenuating the transition of hepatic stellate cells (HSC) to myofibroblasts, comprising administering to a patient in need thereof a therapeutically acceptable amount of a fully humanized antibody comprising a heavy chain variable region comprising:

g) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 1 or a variant thereof;

h) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 2 or a variant thereof; and

i) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 3 or a variant thereof; and

a light chain variable region comprising

j) the complementary determining region VK CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 4 or a variant thereof;

k) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 5 or a variant thereof; and

1) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 6 or a variant thereof,

or the pharmaceutical composition of claim 17.

25. The method of claim 23 or 24, wherein said fully humanized antibody comprises a heavy chain variable region having at least 90% sequence homology to SEQ ID NO: 7 and a light chain variable region having at least 90% sequence homology to SEQ ID NO: 8.

26. The method of any one of claims 23 to 25, wherein the method further comprises administration of at least one additional therapeutic agent.

27. The method of claim 26 wherein said at least one additional therapeutic agent is selected from the group consisting of farnesoid X receptor (FXR) agonists, peroxisome proliferator-activated receptor (PPAR) agonists, anti-chemokine or anti-cytokine monoclonal antibodies, small molecules, anti-inflammatory agents, anti-fibrotic agents, and steroids.

28. A method of reducing or inhibiting CCR5 activation in a cell comprising administering a fully humanized antibody comprising a heavy chain variable region comprising:

a) the complementary determining region VH CDR1 comprising the amino acid sequence denoted by SEQ ID NO. 1 or a variant thereof;

b) the complementary determining region VH CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 2 or a variant thereof; and

c) the complementary determining region VH CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 3 or a variant thereof; and

a light chain variable region comprising

d) the complementary determining region VK CDRl comprising the amino acid sequence denoted by SEQ ID NO. 4 or a variant thereof;

e) the complementary determining region VK CDR2 comprising the amino acid sequence denoted by SEQ ID NO. 5 or a variant thereof; and

f) the complementary determining region VK CDR3 comprising the amino acid sequence denoted by SEQ ID NO. 6 or a variant thereof.