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1. WO2020181376 - TSG-6 ANTIBODIES AND USES THEREFOR

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Claims

What Is Claimed Is:

1. An antibody comprising:

a) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 1 and a light chain variable region comprising an amino acid sequence of SEQ ID NO:2;

b) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO:3 and a light chain variable region comprising an amino acid sequence of SEQ ID NO:4;

c) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 5 and a light chain variable region comprising an amino acid sequence of SEQ ID NO:6;

d) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO:7 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 8;

e) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 9 a light chain variable region comprising an amino acid sequence of SEQ ID NO: 10;

f) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 11 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 12;

g) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 13 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 14;

8) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 15 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 16;

h) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 17 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 18;

i) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 19 and a light chain variable region comprising an amino acid sequence of SEQ ID NO:20;

j) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO:21 and a light chain variable region comprising an amino acid sequence of SEQ ID NO:22;

k) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO:23 and a light chain variable region comprising an amino acid sequence of SEQ ID NO:24;

l) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 25 and a light chain variable region comprising an amino acid sequence of SEQ ID NO:26;

2. An antibody comprising:

a) a vhCDRl comprising SEQ ID NO:27, a vhCDR2 comprising SEQ ID NO:28, a vhCDR3 comprising SEQ ID NO:29, a vlCDRl comprising SEQ ID NO:30, a vlCDR2 comprising SEQ ID NO:31, and a vlCDR3 comprising SEQ ID NO:32;

b) a vhCDRl comprising SEQ ID NO:33, a vhCDR2 comprising SEQ ID NO:34, a vhCDR3 comprising SEQ ID NO:35, a vlCDRl comprising SEQ ID NO:36, a vlCDR2 comprising SEQ ID NO:37, and a vlCDR3 comprising SEQ ID NO:38;

c) a vhCDRl comprising SEQ ID NO:39, a vhCDR2 comprising SEQ ID NO:40, a vhCDR3 comprising SEQ ID NO:41, a vlCDRl comprising SEQ ID NO:42, a vlCDR2 comprising SEQ ID NO:43, and a vlCDR3 comprising SEQ ID NO:44;

d) a vhCDRl comprising SEQ ID NO:45, a vhCDR2 comprising SEQ ID NO:46, a vhCDR3 comprising SEQ ID NO:47, a vlCDRl comprising SEQ ID NO:48, a vlCDR2 comprising SEQ ID NO:49, and a vlCDR3 comprising SEQ ID NO:50;

e) a vhCDRl comprising SEQ ID NO:51, a vhCDR2 comprising SEQ ID NO:52, a vhCDR3 comprising SEQ ID NO:53, a vlCDRl comprising SEQ ID NO:54, a vlCDR2 comprising SEQ ID NO:55, and a vlCDR3 comprising SEQ ID NO:56;

f) a vhCDRl comprising SEQ ID NO:57, a vhCDR2 comprising SEQ ID NO:58, a vhCDR3 comprising SEQ ID NO:59, a vlCDRl comprising SEQ ID NO:60, a vlCDR2 comprising SEQ ID NO:61, and a vlCDR3 comprising SEQ ID NO:62;

g) a vhCDRl comprising SEQ ID NO:63, a vhCDR2 comprising SEQ ID NO:64, a vhCDR3 comprising SEQ ID NO:65, a vlCDRl comprising SEQ ID NO:66, a vlCDR2 comprising SEQ ID NO:67, and a vlCDR3 comprising SEQ ID NO:68;

h) a vhCDRl comprising SEQ ID NO:69, a vhCDR2 comprising SEQ ID NO:70, a vhCDR3 comprising SEQ ID NO:71, a vlCDRl comprising SEQ ID NO:72, a vlCDR2 comprising SEQ ID NO:73, and a vlCDR3 comprising SEQ ID NO:74;

i) a vhCDRl comprising SEQ ID NO:75, a vhCDR2 comprising SEQ ID NO:76, a vhCDR3 comprising SEQ ID NO:77, a vlCDRl comprising SEQ ID NO:78, a vlCDR2 comprising SEQ ID NO:79, and a vlCDR3 comprising SEQ ID NO:80;

j) a vhCDRl comprising SEQ ID NO:81, a vhCDR2 comprising SEQ ID NO:82, a vhCDR3 comprising SEQ ID NO: 83, a vlCDRl comprising SEQ ID NO: 84, a vlCDR2 comprising SEQ ID NO: 85, and a vlCDR3 comprising SEQ ID NO: 86;

k) a vhCDRl comprising SEQ ID NO: 87, a vhCDR2 comprising SEQ ID NO: 88, a vhCDR3 comprising SEQ ID NO:89, a vlCDRl comprising SEQ ID NO:90, a vlCDR2 comprising SEQ ID NO:91, and a vlCDR3 comprising SEQ ID NO:92;

l) a vhCDRl comprising SEQ ID NO:93, a vhCDR2 comprising SEQ ID NO:94, a vhCDR3 comprising SEQ ID NO:95, a vlCDRl comprising SEQ ID NO:96, a vlCDR2 comprising SEQ ID NO:97, and a vlCDR3 comprising SEQ ID NO:98;

m) a vhCDRl comprising SEQ ID NO:99, a vhCDR2 comprising SEQ ID NO: 100, a vhCDR3 comprising SEQ ID NO: 101, a vlCDRl comprising SEQ ID NO: 102, a vlCDR2 comprising SEQ ID NO: 103, and a vlCDR3 comprising SEQ ID NO: 104;

3. The antibody according to any of the previous claims, wherein the antibody binds human and/or mouse TSG-6.

4. The antibody according to any one of the previous claims, wherein the antibody comprises a constant region with an amino acid sequence at least 90% identical to a human IgG.

5. The antibody according to claim 4, wherein the human IgG is selected from a group consisting of IgGl, IgG2, IgG3 and IgG4.

6. The antibody according to claim 5, wherein the IgG is an IgGl.

7. The antibody according to claim 5, wherein the IgG is an IgG2b.

8. A nucleic acid composition encoding the antibody according to any one of the previous claims.

9. An expression vector composition comprising the nucleic acid composition according to claim 8, wherein the first nucleic acid is contained in a first expression vector and the second nucleic acid is contained in a second expression vector.

10. An expression vector composition comprising the nucleic acid composition according to claim 8, wherein the first nucleic acid and the second nucleic acid are contained in a single expression vector.

11. A host cell comprising the expression vector composition of claim 9 or 10.

12. A method of making an antibody comprising culturing said host cell of claim 11 under conditions wherein the antibody is expressed, and recovering the antibody.

13. A composition comprising the antibody according to any one of claims 1-8, and a pharmaceutical acceptable carrier or diluent.

14. A method of modulating an immune response in a subject, the method comprising administering to the subject an effective amount of the antibody according to any one of the claims 1-8 or the composition according to claim 13.

15. The method of claim 14, wherein the method stimulates an immune response in a subject, the method comprising administering to the subject an effective amount of the antibody according to any one of the claims 1-8 or the composition according to claim 13, wherein the antibody serves as a TSG-6 antagonist.

16. The method of claim 14, wherein the method suppresses an immune response in a subject, the method comprising administering to the subject an effective amount of the antibody according to any one of the claims 1-8 or the composition according to claim 13, wherein the antibody serves as a TSG-6 agonist.

17. A method of treating cancer in a subject comprising administering to the subject an effective amount of the antibody according to any one of the claims 1-8 or the composition according to claim 13, wherein the antibody serves as a TSG-6 antagonist.

18. The method of claim 17, wherein the cancer has high expression of TSG-6 and/or HC-HA.

19. The method of claims 15, 17, or 18, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA.

20. The method according to any one of claims 17-19, wherein the cancer is a solid tumor.

21. The method according to any one of claims 17-20, wherein the cancer is melanoma.

22. The method according to any one of the claims 17-21, wherein the antibody is combined with one or more additional therapeutic agents to treat cancer.

23. The method of claim 22, wherein the additional therapeutic agents are other immune checkpoint inhibitors.

24. The method of claim 23, wherein the other immune checkpoint inhibitors are selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a TIM-3 inhibitor, and a LAG-3 inhibitor.

25. A method of treating fibrosis in a subject comprising administering to the subject an effective amount of the antibody according to any one of the claims 1-8 or the composition according to claim 13, wherein the antibody serves as a TSG-6 antagonist.

26. The method of claim 25, wherein the fibrotic tissue has high expression of TSG-6 and/or HC-HA.

27. The method of claims 25 or 26, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA.

28. The method of any one of claims 25-27, wherein the antibody is combined with one or more additional therapeutic agents to treat fibrosis.

29. A method of treating an autoimmune or inflammatory disorder in a subject comprising administering to the subject an effective amount of the antibody according to any one of the claims 1-8 or the composition according to claim 13, wherein the antibody serves as a TSG-6 antagonist.

30. The method of claim 29, wherein the autoimmune or inflammatory disorder is idiopathic pulmonary artery hypertension.

31. The method of claims 29 or 30, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA.

32. The method of claims 30 or 31, wherein the subject to be treated also has lung fibrosis.

33. The method of any one of claims 29-32, wherein the antibody is combined with one or more additional therapeutic agents to treat pulmonary artery hypertension and/or lung fibrosis.

34. The method of claim 29, wherein the autoimmune or inflammatory disorder is asthma.

35. The method of claim 34, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA.

36. The method of claims 34 or 35, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA in the lung.

37. The method of any one of claims 34-36, wherein the subject to be treated has increased airway eosinophilia.

38. A method of treating an autoimmune or inflammatory disorder in a subject comprising administering to the subject an effective amount of the antibody according to any one of the claims 1-8 or the composition according to claim 13, wherein the antibody serves as a TSG-6 agonist.

39. The method of claim 38, wherein the autoimmune or inflammatory disorder is rheumatoid arthritis.

40. The method of any one of claims 16, 38, or 39, wherein the subject to be treated has low expression of TSG-6 and/or HC-HA.

41. The method of any one of claims 29-40, wherein the antibody is combined with one or more additional therapeutic agents to treat an autoimmune or inflammatory disorder.

42. An antibody comprising:

a) a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 17 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 18;

43. An antibody comprising:

a) a vhCDRl comprising SEQ ID NO:75, a vhCDR2 comprising SEQ ID NO:76, a vhCDR3 comprising SEQ ID NO:77, a vlCDRl comprising SEQ ID NO:78, a vlCDR2 comprising SEQ ID NO:79, and a vlCDR3 comprising SEQ ID NO:80;

44. The antibody according to claim 42 or 43, wherein the antibody binds human and/or mouse TSG-6.

45. The antibody according to any one claims 42-44, wherein the antibody comprises a constant region with an amino acid sequence at least 90% identical to a human IgG.

46. The antibody according to claim 45, wherein the human IgG is selected from a group consisting of IgGl, IgG2, IgG3 and IgG4.

47. The antibody according to claim 46, wherein the IgG is an IgGl.

48. A nucleic acid composition encoding the antibody according to any one of claims 42-47.

49. An expression vector composition comprising the nucleic acid composition according to claim 48, wherein the first nucleic acid is contained in a first expression vector and the second nucleic acid is contained in a second expression vector.

50. An expression vector composition comprising the nucleic acid composition according to claim 48, wherein the first nucleic acid and the second nucleic acid are contained in a single expression vector.

51. A host cell comprising the expression vector composition of claim 49 or 50.

52. A method of making an antibody comprising culturing said host cell of claim 51 under conditions wherein the antibody is expressed, and recovering the antibody.

53. A composition comprising the antibody according to any one of claims 42-48, and a pharmaceutical acceptable carrier or diluent.

54. A method of modulating an immune response in a subject, the method comprising administering to the subject an effective amount of the antibody according to any one of the claims 42-48 or the composition according to claim 53.

55. The method of claim 54, wherein the method stimulates an immune response in a subject, the method comprising administering to the subject an effective amount of the antibody according to any one of the claims 42-48 or the composition according to claim 53, wherein the antibody serves as a TSG-6 antagonist.

56. A method of treating cancer in a subject comprising administering to the subject an effective amount of the antibody according to any one of the claims 42-48 or the composition according to claim 53, wherein the antibody serves as a TSG-6 antagonist.

57. The method of claim 56, wherein the cancer has high expression of TSG-6 and/or HC-HA.

58. The method of any one of claims 55-57, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA.

59. The method according to any one of claims 56-58, wherein the cancer is a solid tumor.

60. The method according to any one of claims 56-59, wherein the cancer is melanoma.

61. The method according to any one of claims 56-60, wherein the antibody is combined with one or more additional therapeutic agents to treat cancer.

62. The method of claim 61, wherein the additional therapeutic agents are other immune checkpoint inhibitors.

63. The method of claim 62, wherein the other immune checkpoint inhibitors are selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a TIM-3 inhibitor, and a LAG-3 inhibitor.

64. A method of treating fibrosis in a subject comprising administering to the subject an effective amount of the antibody according to any one of the claims 42-48 or the composition according to claim 53, wherein the antibody serves as a TSG-6 antagonist.

65. The method of claim 64, wherein the fibrotic tissue has high expression of TSG-6 and/or HC-HA.

66. The method of claims 64 or 65, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA.

67. The method of any one of claims 64-66, wherein the antibody is combined with one or more additional therapeutic agents to treat fibrosis.

68. A method of treating an autoimmune or inflammatory disorder in a subject comprising administering to the subject an effective amount of the antibody according to any one of the claims 42-48 or the composition according to claim 53, wherein the antibody serves as a TSG-6 antagonist.

69. The method of claim 68, wherein the autoimmune or inflammatory disorder is idiopathic pulmonary artery hypertension.

70. The method of claims 68 or 69, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA.

71. The method of claims 69 or 70, wherein the subject to be treated also has lung fibrosis.

72. The method of any one of claims 69-71, wherein the antibody is combined with one or more additional therapeutic agents to treat pulmonary artery hypertension and/or lung fibrosis.

73. The method of claim 68, wherein the autoimmune or inflammatory disorder is asthma.

74. The method of claim 73, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA.

75. The method of claim 73 or 74, wherein the subject to be treated has high expression of TSG-6 and/or HC-HA in the lung.

76. The method of any one of claims 73-75, wherein the subject to be treated has increased airway eosinophilia.

77. The method of any one of claims 68-76, wherein the antibody is combined with one or more additional therapeutic agents to treat an autoimmune or inflammatory disorder.