Method for control of post-prandial glucose

• US 9,034,323 B2
• Filed: 09/24/2013
• Issued: 05/19/2015
• Est. Priority Date: 04/28/2008
• Status: Expired due to Fees

• Current Assignee: Halozyme, Inc. (Halozyme Therapeutics, Inc.)
• Original Assignee: Halozyme, Inc. (Halozyme Therapeutics, Inc.)
• Inventors: Frost, Gregory I., Bilinsky, Igor, Vaughn, Daniel, Sugarman, Barry
• Primary Examiner(s): Cordero Garcia, Marcela M
• Application Number:
  US13/998,040
• Publication Number:
  US 20140135682A1
• Time in Patent Office: 602 Days
• US Class Current: 424/94.62
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

Provided are methods for control of post-prandial glucose in diabetic subjects by administering a fast-acting insulin analog and a hyaluronidase degrading enzyme. The fast-acting insulin analog and a hyaluronidase are administered between 15 minutes before the meal and 30 minutes after commencing the meal.

Claims

1. A method for controlling post-prandial glucose levels in a subject, comprising administering to the subject a regular insulin and a hyaluronan-degrading enzyme between 5 and 15 minutes before a meal, whereby the action of the regular insulin has an onset and a duration of action of a fast-acting insulin analog, wherein:

the amount of hyaluronan degrading enzyme administered is sufficient so that the regular insulin can be administered between 5 and 15 minutes before a meal;

the sufficient amount of a hyaluronan degrading enzyme is 1 Unit or more hyaluronidase activity/mL; and

administration of the regular insulin and the hyaluronan degrading enzyme is effected via subcutaneous, intradermal, intramuscular or intraperitoneal administration.

2. The method of claim 1, wherein the post-prandial duration of the regular insulin is about 3 to 4 hours.

3. The method of claim 1, wherein the subject has type II diabetes.

4. The method of claim 1, wherein the subject has type I diabetes.

5. The method of claim 1, wherein regular insulin and hyaluronan degrading enzyme are administered within 10 minutes before a meal.

6. The method of claim 1, wherein the regular insulin and hyaluronan degrading enzyme are administered within 5 minutes before a meal.

7. The method of claim 1, wherein the regular insulin and hyaluronan degrading enzyme are co-formulated.

8. The method of claim 1, wherein the regular insulin and hyaluronan degrading enzyme are administered separately.

9. The method of claim 8, wherein the regular insulin and hyaluronan degrading enzyme are administered sequentially or simultaneously.

10. The method of claim 1, wherein the regular insulin and hyaluronan degrading enzyme are administered to the subject via syringe, insulin pen, insulin pump or a closed loop system.

11. The method of claim 10, wherein the regular insulin and hyaluronan degrading enzyme are co-formulated.

12. The method of claim 10, wherein the regular insulin and hyaluronan degrading enzyme are administered separately.

13. The method of claim 10, wherein the regular insulin and hyaluronan degrading enzyme are in separate reservoirs in a closed loop system.

14. The method of claim 1, wherein the dosage of the regular insulin is less than the dosage of regular insulin administered by the same route in the absence of the hyaluronan degrading enzyme.

15. The method of claim 1, wherein

the amount of regular insulin is from or from about 10 U/mL to at or about 500 U/ml insulin;

and

the amount of a hyaluronan degrading enzyme is at least or about 1 U hyaluronidase activity/mL, 2 U/mL, 3 U/mL, 4 U/mL, 5 U/mL, 6 U/mL, 7 U/mL, 8 U/mL, 9 U/mL, 10 U/mL, 15 U/mL, 20 U/mL, 25 U/mL, 30 U/mL, 35 U/mL, 37.5 U/mL, 40 U/mL, 50 U/mL, 60 U/mL, 70 U/mL, 80 U/mL, 90 U/mL, 100 U/mL, 200 U/mL, 300 U/mL, 400 U/mL, 500 U/mL, 600 U/mL, 700 U/mL, 800 U/mL, 900 U/mL, 1000 U/mL, 2000 U/mL, 3000 U/mL or 5000 U/mL hyaluronidase activity/mL.

16. The method of claim 1, wherein the amount of a hyaluronan degrading enzyme is at least or about 30 Units hyaluronidase activity/mL.

17. The method of claim 1, wherein the amount of regular insulin for a single dosage is or is about 0.05 Units, 0.06 Units, 0.07 Units, 0.08 Units, 0.09 Units, 0.1 Units, 0.2 Units, 0.3 Units, 0.4 Units, 0.5 Units, 0.6 Units, 0.7 Units, 0.8 Units, 0.9 Units, 1 Unit, 2 Units, 5 Units, 10 Units, 15 Units, 20 Units, 25 Units, 30 Units, 35 Units, 40 Units, 50 Units or 100 units;

and/or

the amount of hyaluronan degrading enzyme for a single dosage is at least or to about 0.3 Units, 0.5 Units, 1 Unit, 2 Units, 5 Units, 10 Units, 20 Units, 30 Units, 40 Units, 50 Units, 100 Units, 150 Units, 200 Units, 250 Units, 300 Units, 350 Units, 400 Units, 450 Units, 500 Units, 600 Units, 700 Units, 800 Units, 900 Units, 1000 Units, 2,000 Units, 3,000 Units, 4,000 Units or more of hyaluronidase activity.

18. The method of claim 1, wherein the regular insulin is a human or porcine insulin.

19. The method of claim 18, wherein the regular insulin is selected from a regular insulin that:

has an A chain containing the sequence of amino acids set forth in SEQ ID NO;

103,

and a B chain containing a sequence of amino acids set forth in SEQ ID NO;

104;

or

has an A chain containing a sequence of amino acids set forth as amino acid residue positions 88-108 of SEQ ID NO;

123, and a B chain containing or having a sequence of amino acids set forth as amino acid residue positions 25-54 of SEQ ID NO;

123.

20. The method of claim 1, wherein the hyaluronan degrading enzyme is a hyaluronidase.

21. The method of claim 20, wherein the hyaluronidase is a soluble hyaluronidase.

22. The method of claim 21, wherein the soluble hyaluronidase is a PH20, or a truncated form thereof.

23. The method of claim 22, wherein the PH20 is an ovine, bovine or truncated human PH20.

24. The method of claim 23, wherein the hyaluronidase is a truncated human PH20 that is selected from among polypeptides having a sequence of amino acids set forth in any of SEQ ID NOS:

4-9, or allelic variants or other variants thereof that have at least 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to a polypeptide set forth in any of SEQ ID NOS;

4-9 and retain hyaluronidase activity.

25. The method of claim 24, wherein the hyaluronidase is a soluble hyaluronidase provided as a composition designated rHuPH20.

26. The method of claim 7, wherein the hyaluronan degrading enzyme is a hyaluronidase.

27. The method of claim 26, wherein the hyaluronidase is a soluble hyaluronidase.

28. The method of claim 27, wherein the soluble hyaluronidase is a PH20, or a truncated form thereof.

29. The method of claim 28, wherein the PH20 is an ovine, bovine or truncated human PH20.

30. The method of claim 29, wherein the hyaluronidase is a truncated human PH20 that is selected from among polypeptides having a sequence of amino acids set forth in any of SEQ ID NOS:

4-9, or allelic variants or other variants thereof that have at least 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to a polypeptide set forth in any of SEQ ID NOS;

4-9 and retain hyaluronidase activity.

31. The method of claim 30, wherein the hyaluronidase is a soluble hyaluronidase provided as a composition designated rHuPH20.

32. The method of claim 10, wherein the hyaluronan degrading enzyme is a hyaluronidase.

33. The method of claim 18, wherein the hyaluronan degrading enzyme is a hyaluronidase.

34. The method of claim 1, wherein post-prandial blood glucose concentrations are maintained between 70-130 mg/dL.

35. The method of claim 1, wherein post-prandial blood glucose concentrations are maintained between 90-110 mg/dL.

36. The method of claim 1, wherein the insulin and hyaluronan degrading enzyme are provided in a closed loop system.

37. The method of claim 1, wherein the insulin and hyaluronan degrading enzyme are provided in an insulin pump.

38. The method of claim 1, wherein the insulin and hyaluronan degrading enzyme are provided in an insulin pen.

39. The method of claim 36, wherein the closed loop system comprises:

a regular insulin; and

a hyaluronan degrading enzyme;

wherein

the regular insulin and the hyaluronan degrading enzyme are in the same or different reservoirs.

40. The method of claim 39, wherein the closed loop system further comprises one or more of a glucose sensor, a delivery system to deliver the hyaluronan degrading enzyme and regular insulin, and software programmed to integrate the pumping and monitoring functions, whereby the hyaluronan degrading enzyme and insulin are delivered so that the regular insulin can be administered 5 to 15 minutes before a meal.

41. The method of claim 39, wherein the regular insulin is a human insulin or pig insulin.

42. The method of claim 39, wherein the regular insulin is a recombinant insulin.

43. The method of claim 39, wherein the regular insulin is selected from an insulin with an A chain with a sequence of amino acids set forth in SEQ ID NO:

103, and a B chain with a sequence of amino acids set forth in SEQ ID NO;

104;

or an insulin with an A chain with a sequence of amino acids set forth as amino acid residue positions 88-108 of SEQ ID NO;

123, and a B chain with a sequence of amino acids set forth as amino acid residue positions 25-54 of SEQ ID NO;

123.

44. The method of claim 39, wherein the hyaluronan degrading enzyme is a hyaluronidase.

45. The method of claim 44, wherein the hyaluronidase is a soluble hyaluronidase.

46. The method of claim 39, wherein the hyaluronidase is a PH20, or a truncated form thereof.

47. The method of claim 39, wherein the hyaluronidase is a PH20 hyaluronidase and is selected from an ovine, bovine or truncated human PH20.

48. The method of claim 39, wherein the hyaluronidase is a truncated human PH20 that is selected from among polypeptides having a sequence of amino acids set forth in any of SEQ ID NOS:

4-9, or allelic variants or other variants thereof that have 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to a polypeptide set forth in any of SEQ ID NOS;

4-9, and that exhibit hyaluronidase activity.

49. The method of claim 39, wherein the hyaluronidase is a soluble hyaluronidase provided as a composition designated rHuPH20.

50. The method of claim 1, comprising:

instructing a patient to administer a regular insulin less than or about 15, 10, or 5 minutes prior to a meal, wherein the regular insulin is administered with a hyaluronidase.

51. The method of claim 50, wherein the regular insulin and the hyaluronidase are co-formulated.

52. The method of claim 50, wherein the regular insulin and the hyaluronidase are administered sequentially.