IP Library › Granted Patent US 8,476,405
Granted Patent B2
US 8,476,405 · App. 12/095,904 · Granted Jul 2, 2013

Neuregulin variants and methods of screening and using thereof

Inventor: Mingdong Zhou (Shanghai, CN)
Assignee: Zensun (Shanghai) Science & Technology Ltd.
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Quick Facts
Patent No.
US 8,476,405
App. No.
12/095,904
Granted
Jul 2, 2013
Kind
B2
Abstract

The present invention provides polypeptide variants of neuregulin-1β (NRG-1β) that have enhanced or decreased binding affinity to ErbB3 and/or ErbB4. The invention also provides methods of screening and producing polypeptide variants of NRG-1β and methods of using polypeptide variants of NRG-1β for treating diseases.

Claims (86)

1. An isolated polypeptide variant of neuregulin-1β comprising amino acid sequence shown in SEQ ID NO:1, wherein the polypeptide variant comprises two different amino acids than that in SEQ ID NO:1, wherein the polypeptide variant has an enhanced binding affinity to ErbB4 compared to polypeptide of SEQ ID NO:1, and wherein

at residue 47 the first of said two different amino acids is A, C, D, E, F, G, H, I, K, L, M, P, Q, R, S, T, V, W, or Y, and

at residue 8 the second of said two different amino acids is A.

2. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is A.

3. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is C.

4. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is D.

5. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is E.

6. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is F.

7. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is G.

8. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is H.

9. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is I.

10. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is K.

11. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is L.

12. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is M.

13. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is P.

14. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is Q.

15. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is R.

16. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is S.

17. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is T.

18. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is V.

19. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is W.

20. The polypeptide variant of claim 1 , wherein the amino acid at residue 47 is Y.

21. A composition comprising the polypeptide variant of claim 1 .

22. The composition of claim 21 , wherein the composition further comprises a pharmaceutically acceptable excipient.

23. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid A.

24. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid C.

25. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid D.

26. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid E.

27. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid F.

28. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid G.

29. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid H.

30. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid I.

31. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid K.

32. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid L.

33. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid M.

34. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid P.

35. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid Q.

36. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid R.

37. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid S.

38. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid T.

39. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid V.

40. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid W.

41. The composition of claim 21 , wherein the polypeptide variant comprises at residue 47 the amino acid Y.

42. A kit comprising the polypeptide variant of 1 .

43. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid A.

44. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid C.

45. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid D.

46. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid E.

47. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid F.

48. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid G.

49. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid H.

50. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid I.

51. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid K.

52. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid L.

53. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid M.

54. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid P.

55. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid Q.

56. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid R.

57. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid S.

58. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid T.

59. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid V.

60. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid W.

61. The kit of claim 42 , wherein the polypeptide variant comprises at residue 47 the amino acid Y.

62. The polypeptide variant of claim 1 , wherein the polypeptide variant consists of the amino acid sequence shown in SEQ ID NO:1 and wherein the amino acid at residue 47 is A, C, D, E, F, G, H, I, K, L, M, P, Q, R, S, T, V, W, or Y, and the amino acid at residue 8 is A.

63. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is A.

64. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is C.

65. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is D.

66. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is E.

67. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is F.

68. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is G.

69. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is H.

70. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is I.

71. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is K.

72. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is L.

73. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is M.

74. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is P.

75. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is Q.

76. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is R.

77. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is S.

78. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is T.

79. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is V.

80. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is W.

81. The polypeptide variant of claim 62 , wherein the amino acid at residue 47 is Y.

82. A composition comprising the polypeptide variant of claim 62 .

83. The composition of claim 82 , wherein the composition further comprises a pharmaceutically acceptable excipient.

84. A kit comprising the polypeptide variant of 62 .

Assignments (2)
CHANGE OF NAME Recorded Jun 8, 2016
From: ZENSUN (SHANGHAI) SCIENCE & TECHNOLOGY, LTD.
To: ZENSUN (SHANGHAI) SCIENCE & TECHNOLOGY, CO., LTD.
Reel/Frame 038925/0398 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 31, 2008
From: ZHOU, MINGDONG
To: ZENSUN (SHANGHAI) SCIENCE AND TECHNOLOGY LTD.
Reel/Frame 022044/0905 →
Continuity (2)
Continuation In Part 11293879 · Dec 2, 2005
Related Publication 20090203595A1 · Aug 13, 2009