Pre-mixes of glp-1 and basal insulin

• US 20040235710A1
• Filed: 02/09/2004
• Published: 11/25/2004
• Est. Priority Date: 08/28/2001
• Status: Active Grant

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Ng, Kingman, DiMarchi, Richard Dennis, DeFelippis, Michael Rosario
• Granted Patent: US 7,238,663 B2
• Time in Patent Office: Days
• US Class Current: 514/3
• 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 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention encompasses pre-mixed formulations comprising a GLP-1 polypeptide and a basal insulin.

Claims

1. A pre-mixed formulation comprising a GLP-1 compound and an acylated basal insulin or a pI shifted basal insulin.

2. The pre-mixed formulation of claim 1 wherein the GLP-1 compound is selected from the group consisting of GLP-1 compounds of SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, and SEQ ID NO;

6.

3. The pre-mixed formulation of claim 2 wherein the GLP-1 compound has an amino acid sequence of SEQ ID NO:

2.

4. The pre-mixed formulation of claim 1 wherein the GLP-1 compound is selected from the group consisting of GLP-1 compounds of Table 8 or Table 9.

7. The pre-mixed formulation of any one of claims 1 to 4 wherein the basal insulin is selected from the group consisting of basal insulins of Table 1, Table 2, or Table 3.

8. The pre-mixed formulation of claim 7 wherein the basal insulin is GlyA21-Human insulin-ArgB31-ArgB32-OH.

9. The pre-mixed formulation of any one of claims 1 to 4 wherein the GLP-1 compound is selected from the group consisting of GLP-1 compounds of SEQ ID NO:

2 and SEQ ID NO;

3 and the basal insulin is selected from the group consisting of basal insulins of Table 2 or Table 3.

10. The pre-mixed formulation of claim 9 wherein the GLP-1 compound has an amino acid sequence of SEQ ID NO:

2 and the basal insulin is GlyA21-Human insulin-ArgB31-ArgB32-OH.

13. The pre-mixed formulation of claim 1 wherein the GLP-1 compound is Val⁸-Glu²²-GLP-1 (7-37)OH and the basal insulin is GlyA21-Human insulin-ArgB31-ArgB32-OH.

14. The pre-mixed formulation of claim 1 wherein the GLP-1 compound is Val⁸-Glu²²-GLP-1(7-37)OH and the basal insulin is A0^Arg-B0^Arg-B29^Lys-N-Arg.

15. The pre-mixed formulation of claim 1 wherein the GLP-1 compound has an amino acid sequence of SEQ ID NO:

2 and the basal insulin is A0^Arg-B0^Arg-B29^Lys-N-Arg.

18. A process of preparing the pre-mixed formulation of any one of claims 1 to 15, wherein the process comprises the steps of;

mixing a GLP-1 compound with basal insulin in an aqueous medium.

19. A method of administering a pre-mixed formulation of any one of claims 1 to 15, wherein the method comprises the step of administering an effective amount of the formulation to a patient in need thereof.

20. A method of treating a condition selected from the group consisting of non-insulin dependent diabetes, insulin dependent diabetes, hyperglycemia, obesity, functional dyspepsia, irritable bowel syndrome, catabolic changes after surgery, myocardial infarction, and stroke comprising administering an effective amount of a pre-mixed formulation of any one of claims 1 to 15 to a patient in need thereof.

21. The method of claim 20, wherein the condition is non-insulin dependent diabetes.

22. The method of claim 20, wherein the condition is insulin dependent diabetes.

23. The method of claim 20, wherein the condition is obesity.

5. (cancelled)

6. (cancelled)

11. (cancelled)

12. (cancelled)

16. (cancelled)

17. (cancelled)

24-28. -28. (cancelled)

29. A pre-mixed formulation comprising a GLP-1 compound and NPL basal insulin.

30. The pre-mixed formulation of claim 29 wherein the GLP-1 compound is selected from the group consisting of GLP-1 compounds of SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, and SEQ ID NO;

6.

31. The pre-mixed formulation of claim 29 wherein the GLP-1 compound is selected from the group consisting of GLP-1 compounds of Table 8 or Table 9.

32. A method of treating a condition selected from the group consisting of non-insulin dependent diabetes, insulin dependent diabetes, hyperglycemia, obesity, functional dyspepsia, irritable bowel syndrome, catabolic changes after surgery, myocardial infarction, and stroke comprising administering an effective amount of a pre-mixed formulation of any one of claims 29 to 31 to a patient in need thereof.

33. The method of claim 32, wherein the condition is non-insulin dependent diabetes.

34. The method of claim 32, wherein the condition is insulin dependent diabetes.

35. The method of claim 32, wherein the condition is obesity.

37. A method of treating a condition selected from the group consisting of non-/insulin dependent diabetes, insulin dependent diabetes, hyperglycemia, obesity, functional dyspepsia, irritable bowel syndrome, catabolic changes after surgery, myocardial infarction, and stroke comprising administering an effective amount of a pre-mixed formulation of claim 33 to a patient in need thereof.

38. The method of claim 37, wherein the condition is non-insulin dependent diabetes.

39. The method of claim 37, wherein the condition is insulin dependent diabetes.

40. The method of claim 37, wherein the condition is obesity.

36. A pre-mixed formulation comprising a GLP-1 compound and a basal insulin selected from the group consisting of NPH, NPL, PZI, Ultralente, and Semilente, wherein the GLP-1 compound has an amino acid sequence of SEQ ID NO:

2.