Extended release of neuregulin for treating heart failure

• US 10,098,834 B2
• Filed: 05/22/2014
• Issued: 10/16/2018
• Est. Priority Date: 05/22/2013
• Status: Active Grant

• Current Assignee: Zensun (Shanghai) Science & Technology, Co., Ltd.
• Original Assignee: Zensun (Shanghai) Science & Technology, Co., Ltd.
• Inventors: Zhou, Mingdong
• Primary Examiner(s): Saoud, Christine J
• Assistant Examiner(s): Lockard, Jon M
• Application Number:
  US14/892,183
• Publication Number:
  US 20160089329A1
• Time in Patent Office: 1,608 Days
• Field of Search: None
• CPC Class Codes: A61K 38/1883 Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

The present invention provides methods and kits for preventing, treating or delaying various cardiovascular diseases or disorders especially heart failure by extended release of neuregulin to a mammal. Moreover, the extended release of neuregulin is administered by subcutaneous infusion with a pump.

Claims

1. A method for treating heart failure in a mammal, the method comprising administering subcutaneous extended release of neuregulin into a mammal in an amount of 0.3 μ

g/kg/day to 3.0 μ

g/kg/day, wherein the subcutaneous extended release of neuregulin into a mammal is accomplished through the use of a pump.

2. The method of claim 1, wherein the mammal is human.

3. The method of claim 1, wherein the subcutaneous extended release of neuregulin into a mammal is accomplished through the use of a syringe pump.

4. The method of claim 3, wherein the syringe pump is a mini pump.

5. The method of claim 4, wherein the mini pump is an insulin pump.

6. The method of claim 1, wherein neuregulin is in an amount of 1.2 μ

g/kg/day to 2.0 μ

g/kg/day.

7. The method of claim 1, wherein neuregulin is in an amount of 1.2 μ

g/kg/day.

8. The method of claim 1, wherein neuregulin is in an amount of 2.0 μ

g/kg/day.

9. The method of claim 1, wherein neuregulin is in an amount of 6 EU/kg/day to 60 EU/kg/day.

10. The method of claim 1, wherein neuregulin is in an amount of 24 EU/kg/day to 40 EU/kg/day.

11. The method of claim 1, wherein neuregulin is in an amount of 24 EU/kg/day.

12. The method of claim 1, wherein neuregulin is in an amount of 40 EU/kg/day.

13. The method of claim 1, wherein the neuregulin is administered to the mammal for an introduction regimen.

14. The method of claim 13, wherein the introduction regimen includes an administration of neuregulin for at least 3, 5, 7, 10 or 15 consecutive days.

15. The method of claim 14, wherein the introduction regimen includes an administration of neuregulin for at least 3 consecutive days.

16. The method of claim 14, wherein the introduction regimen includes an administration of neuregulin for at least 5 consecutive days.

17. The method of claim 14, wherein the introduction regimen includes an administration of neuregulin for at least 7 consecutive days.

18. The method of claim 14, wherein the introduction regimen includes an administration of neuregulin for at least 10 consecutive days.

19. The method of claim 14, wherein the introduction regimen includes an administration of neuregulin for at least 15 consecutive days.

20. The method of claim 13, wherein the introduction regimen includes an administration of neuregulin for 10 consecutive days.

21. The method of claim 13, wherein the neuregulin is administered for at least 2, 4, 6, 8, 10, 12, 16, 20 or 24 consecutive hours every day.

22. The method of claim 21, wherein the neuregulin is administered for at least 2 consecutive hours every day.

23. The method of claim 21, wherein the neuregulin is administered for at least 4 consecutive hours every day.

24. The method of claim 21, wherein the neuregulin is administered for at least 6 consecutive hours every day.

25. The method of claim 21, wherein the neuregulin is administered for at least 10 consecutive hours every day.

26. The method of claim 21, wherein the neuregulin is administered for at least 12 consecutive hours every day.

27. The method of claim 21, wherein the neuregulin is administered for at least 16 consecutive hours every day.

28. The method of claim 21, wherein the neuregulin is administered for at least 20 consecutive hours every day.

29. The method of claim 21, wherein the neuregulin is administered for at least 24 consecutive hours every day.

30. The method of claim 13, wherein the neuregulin is administered for 8 consecutive hours every day.

31. The method of claim 13, wherein the neuregulin is administered to the patients for a maintenance regimen after the introduction regimen.

32. The method of claim 31, wherein the maintenance regimen includes an administration of neuregulin for at least 3 months, 6 months, 12 months, 1 year, 5 years or even longer after the introduction regimen.

33. The method of claim 32, wherein the maintenance regimen includes administration of neuregulin for at least 3 months.

34. The method of claim 32, wherein the maintenance regimen includes administration of neuregulin for at least 6 months.

35. The method of claim 32, wherein the maintenance regimen includes administration of neuregulin for at least 12 months.

36. The method of claim 32, wherein the maintenance regimen includes administration of neuregulin for at least 1 year.

37. The method of claim 32, wherein the maintenance regimen includes administration of neuregulin for at least 5 years.

38. The method of claim 32, wherein the maintenance regimen includes administration of neuregulin for longer than 5 years.

39. The method of claim 31, wherein the maintenance regimen includes a repeat of the induction regimen every 3 months, 6 months or 12 months.

40. The method of claim 39, wherein the maintenance regimen includes a repeat of the induction regimen every 3 months.

41. The method of claim 39, wherein the maintenance regimen includes a repeat of the induction regimen every 6 months.

42. The method of claim 39, wherein the maintenance regimen includes a repeat of the induction regimen every 12 months.

43. The method of claim 1, wherein the extended release of neuregulin into the mammal enhances the ejection fraction (EF) value of the mammal.

44. The method of claim 1, wherein the extended release of neuregulin into the mammal reduces the Left Ventricular End-Diastolic Volume (LVEDV) of the mammal.

45. The method of claim 1, wherein the extended release of neuregulin into the mammal reduces the Left Ventricular End-Systolic Volume (LVESV) of the mammal.

46. The method of claim 1, wherein the extended release of neuregulin into the mammal improves 6 Minute Walk Distance (6 MWD) of the mammal.

47. The method of claim 1, wherein the extended release of neuregulin into the mammal improves quality of life of the mammal.

48. The method of claim 1, wherein the neuregulin comprises the EGF-like domain of NRG-1, NRG-2, NRG-3 or NRG-4.

49. The method of claim 48, wherein the neuregulin comprises the EGF-like domain of NRG-1.

50. The method of claim 48, wherein the neuregulin comprises the EGF-like domain of NRG-2.

51. The method of claim 48, wherein the neuregulin comprises the EGF-like domain of NRG-3.

52. The method of claim 48, wherein the neuregulin comprises the EGF-like domain of NRG-4.

53. The method of claim 1, wherein the neuregulin comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO;

3 and SEQ ID NO;

4.

54. The method of claim 53, wherein the neuregulin comprises the amino acid sequence SEQ ID NO:

1.

55. The method of claim 53, wherein the neuregulin comprises the amino acid sequence SEQ ID NO:

2.

56. The method of claim 53, wherein the neuregulin comprises the amino acid sequence SEQ ID NO:

3.

57. The method of claim 53, wherein the neuregulin comprises the amino acid sequence SEQ ID NO:

4.

58. The method of claim 1, wherein the neuregulin is selected from the group consisting of NRG-1, NRG-2, NRG-3 and NRG-4.

59. The method of claim 58, wherein the neuregulin is NRG-1.

60. The method of claim 58, wherein the neuregulin is NRG-2.

61. The method of claim 58, wherein the neuregulin is NRG-3.

62. The method of claim 58, wherein the neuregulin is NRG-4.

63. The method of claim 1, wherein the neuregulin is NRG-1 β

2.