Therapeutic derivatives of interleukin-22

1. A derivative of IL-22 comprising a fatty acid covalently attached to an IL-22 protein by a linker, wherein:

(i) the fatty add comprises C18 diacid;

(ii) the IL-22 protein is a variant of human IL-22 (hIL-22), wherein hIL-22 comprises the amino acid sequence of SEQ ID NO: 1, wherein the variant comprises:

(a) a Cys substitution at position 1 of hIL-22;

(b) an N-terminal G-P-G, and

wherein the fatty acid is covalently attached to the Cys substitution at position 1 of hIL-22 by the linker.

2. A pharmaceutical composition comprising a derivative as claimed in claim 1 and a pharmaceutically acceptable vehicle.

3. The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or occularly.

4. The pharmaceutical composition of claim 3 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

5. The derivative as claimed in claim 1 , wherein the variant comprises one or two more variations within SEQ ID NO: 1, wherein said variations are amino acid substitutions.

6. The derivative as claimed in claim 5 , wherein the variant comprises amino acid substitutions at positions 35 and 64 of hIL-22.

7. The derivative as claimed in claim 6 , wherein the linker comprises yGlu-OEG-OEG-C2DA-Ac.

8. A pharmaceutical composition comprising a derivative as claimed in claim 7 and a pharmaceutically acceptable vehicle.

9. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

10. The pharmaceutical composition of claim 9 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

11. The derivative as claimed in claim 7 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

12. A pharmaceutical composition comprising a derivative as claimed in claim 11 and a pharmaceutically acceptable vehicle.

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

14. The pharmaceutical composition of claim 13 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

15. The derivative as claimed in claim 6 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

16. A pharmaceutical composition comprising a derivative as claimed in claim 15 and a pharmaceutically acceptable vehicle.

17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

18. The pharmaceutical composition of claim 17 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

19. A pharmaceutical composition comprising a derivative as claimed in claim 6 and a pharmaceutically acceptable vehicle.

20. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

21. The pharmaceutical composition of claim 20 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

22. The derivative as claimed in claim 5 , wherein the linker comprises yGlu-OEG-OEG-C2DA-Ac.

23. The derivative as claimed in claim 22 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

24. A pharmaceutical composition comprising a derivative as claimed in claim 23 and a pharmaceutically acceptable vehicle.

25. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

26. The pharmaceutical composition of claim 25 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

27. A pharmaceutical composition comprising a derivative as claimed in claim 22 and a pharmaceutically acceptable vehicle.

28. The pharmaceutical composition of claim 27 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

29. The pharmaceutical composition of claim 28 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

30. The derivative as claimed in claim 5 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

31. A pharmaceutical composition comprising a derivative as claimed in claim 30 and a pharmaceutically acceptable vehicle.

32. The pharmaceutical composition of claim 31 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

33. The pharmaceutical composition of claim 32 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

34. A pharmaceutical composition comprising a derivative as claimed in claim 5 and a pharmaceutically acceptable vehicle.

35. The pharmaceutical composition of claim 34 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

36. The pharmaceutical composition of claim 35 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

37. The derivative as claimed in claim 1 , wherein the variant comprises amino acid substitutions N35Q and N64Q of hIL-22.

38. The derivative as claimed in claim 37 , wherein the linker comprises γGlu-OEG-OEG-C2DA-Ac.

39. The derivative as claimed in claim 38 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

40. A pharmaceutical composition comprising a derivative as claimed in claim 39 and a pharmaceutically acceptable vehicle.

41. The pharmaceutical composition of claim 40 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

42. The pharmaceutical composition of claim 41 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

43. A pharmaceutical composition comprising a derivative as claimed in claim 38 and a pharmaceutically acceptable vehicle.

44. The pharmaceutical composition of claim 43 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

45. The pharmaceutical composition of claim 44 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

46. The derivative as claimed in claim 37 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

47. A pharmaceutical composition comprising a derivative as claimed in claim 46 and a pharmaceutically acceptable vehicle.

48. The pharmaceutical composition of claim 47 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

49. The pharmaceutical composition of claim 48 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

50. A pharmaceutical composition comprising a derivative as claimed in claim 37 and a pharmaceutically acceptable vehicle.

51. The pharmaceutical composition of claim 50 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

52. The pharmaceutical composition of claim 51 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

53. The derivative as claimed in claim 1 , wherein the variant comprises the amino acid sequence of SEQ ID NO: 16 or SEQ ID NO: 18.

54. The derivative as claimed in claim 53 , wherein the linker comprises γGlu-OEG-OEG-C2DA-Ac.

55. The derivative as claimed in claim 54 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

56. A pharmaceutical composition comprising a derivative as claimed in claim 55 and a pharmaceutically acceptable vehicle.

57. The pharmaceutical composition of claim 56 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

58. The pharmaceutical composition of claim 57 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

59. A pharmaceutical composition comprising a derivative as claimed in claim 54 and a pharmaceutically acceptable vehicle.

60. The pharmaceutical composition of claim 59 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

61. The pharmaceutical composition of claim 60 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

62. The derivative as claimed in claim 53 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

63. A pharmaceutical composition comprising a derivative as claimed in claim 62 and a pharmaceutically acceptable vehicle.

64. The pharmaceutical composition of claim 63 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

65. The pharmaceutical composition of claim 64 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

66. A pharmaceutical composition comprising a derivative as claimed in claim 53 and a pharmaceutically acceptable vehicle.

67. The pharmaceutical composition of claim 66 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

68. The pharmaceutical composition of claim 67 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

69. The derivative as claimed in claim 1 , wherein the linker comprises γGlu-OEG-OEG-C2DA-Ac.

70. The derivative as claimed in claim 69 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

71. A pharmaceutical composition comprising a derivative as claimed in claim 70 and a pharmaceutically acceptable vehicle.

72. The pharmaceutical composition of claim 71 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

73. The pharmaceutical composition of claim 72 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

74. A pharmaceutical composition comprising a derivative as claimed in claim 69 and a pharmaceutically acceptable vehicle.

75. The pharmaceutical composition of claim 74 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

76. The pharmaceutical composition of claim 75 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

77. The derivative as claimed in claim 1 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

78. A pharmaceutical composition comprising a derivative as claimed in claim 77 and a pharmaceutically acceptable vehicle.

79. The pharmaceutical composition of claim 78 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

80. The pharmaceutical composition of claim 79 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

81. A derivative IL-22 comprising a fatty acid covalently attached by a linker to a variant of hIL-22, wherein hIL-22 comprises the amino acid sequence of SEQ ID NO: 1, wherein:

(a) the fatty acid comprises a C18 diacid;

(b) the variant comprises the amino acid sequence of SEQ ID NO: 16; and

(b) the linker comprises γGlu-OEG-OEG-C 2 DA-Ac; and

wherein the linker is covalently attached to the Cys residue at position 4 of SEQ ID NO: 16.

82. The derivative as claimed in claim 81 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

83. A pharmaceutical composition comprising a derivative as claimed in claim 82 and a pharmaceutically acceptable vehicle.

84. The pharmaceutical composition of claim 83 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

85. The pharmaceutical composition of claim 84 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

86. A pharmaceutical composition comprising a derivative as claimed in claim 81 and a pharmaceutically acceptable vehicle.

87. The pharmaceutical composition of claim 86 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

88. The pharmaceutical composition of claim 87 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

89. A derivative of IL-22 comprising a fatty acid covalently attached by a linker to a variant of hIL-22, wherein hIL-22 comprises the amino acid sequence of SEQ ID NO: 1, wherein:

(a) the fatty acid comprises a C18 diacid;

(b) the variant comprises the amino acid sequence of SEQ ID NO: 18; and

(c) the linker comprises γGlu-OEG-OEG-C 2 DA-Ac; and

wherein the linker is covalently attached to the Cys residue at position 4 of SEQ ID NO: 18.

90. The derivative as claimed in claim 89 , wherein the derivative of IL-22 has prolonged circulatory half-life as compared to hIL-22 without the fatty acid.

91. A pharmaceutical composition comprising a derivative as claimed in claim 90 and a pharmaceutically acceptable vehicle.

92. The pharmaceutical composition of claim 91 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

93. The pharmaceutical composition of claim 92 , wherein the injection is intraperitoneal, subcutaneous or intravenous.

94. A pharmaceutical composition comprising a derivative as claimed in claim 89 and a pharmaceutically acceptable vehicle.

95. The pharmaceutical composition of claim 94 , wherein the pharmaceutical composition is suitable for administration by inhalation, by injection, topically, orally, or ocularly.

96. The pharmaceutical composition of claim 95 , wherein the injection is intraperitoneal, subcutaneous or intravenous.