Prolonged delivery of peptides

• US 6,284,727 B1
• Filed: 06/07/1995
• Issued: 09/04/2001
• Est. Priority Date: 04/07/1993
• Status: Expired due to Term

• Current Assignee: Scios, Inc. (Johnson & Johnson)
• Original Assignee: Scios, Inc. (Johnson & Johnson)
• Inventors: Qi, Hong, Lambert, William J., Kim, Yesook, Geoghegan, Kieran F., Danley, Dennis E., Gelfand, Robert A
• Primary Examiner(s): Huff, Sheela
• Application Number:
  US08/472,349
• Time in Patent Office: 2,281 Days
• Field of Search: 514/12, 530/324
• US Class Current: 514/6.9
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

There are disclosed methods for the treatment of non-insulin dependent diabetes mellitus in a mammal comprising the prolonged administration of GLP-1 (7-37), and related peptides. Also disclosed are compositions to prolong the administration of the peptides.

Claims

1. A composition of matter comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(E) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

2. A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising the administration of a composition according to claim 1.

3. A composition of matter comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

4. A composition according to claim 3 wherein said oil is selected from the group consisting of peanut oil, sesame oil, almond oil, castor oil, camellia oil, cotton seed oil, olive oil, corn oil, soy oil, safflower oil, coconut oil, and esters of fatty acids, esters of fatty alcohols.

5. A composition according to claim 3 further comprising a wetting agent.

6. A composition according to claim 5 wherein said wetting agent is a nonionic surfactant.

7. A composition according to claim 3 further comprising a suspending agent.

8. A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 3.

9. A composition of matter in an injectable formulation comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

10. A composition according to claim 9 capable of achieving sustained glycemic control.

11. A composition according to claim 9 which is an aqueous suspension.

12. A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 9.

36. The method of any one of claims 2, 8, 12, 15 or 18, 20, 24 or wherein said administration is subcutaneous.

37. The method of any one of claims 2, 8, 12, 15 or 18, 20, 24 or 28 wherein said administration is intramuscular.

13. A composition of matter in an injectable formulation comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

14. A composition according to claim 13 capable of achieving sustained glycemic control.

15. A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 13.

16. A composition of matter in an injectable formulation comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

17. A composition according to claim 16 wherein said phenolic compound is selected from the group consisting of phenol, cresol, resorcinol, and methyl paraben.

18. A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 16.

19. A composition of matter in an injectable formulation comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a Moypeptide comprising the primary structure

20. A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 19.

21. A composition of matter in an injectable formulation comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

22. A composition according to claim 21 wherein said basic polypeptide is protamine.

23. A composition according to claim 21 wherein said metal ion is zinc.

24. A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 21.

25. A composition of matter in an injectable formulation comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

26. A composition according to claim 25 wherein said conditions are high shear, exposure to salts;

or combinations thereof.

27. A composition according to claim 26 wherein said salt is selected from the group consisting of ammonium sulfate, sodium sulfate, lithium sulfate, lithium chloride, sodium citrate, ammonium citrate, sodium phosphate, potassium phosphate, sodium chloride, potassium chloride, ammonium chloride, sodium acetate, ammonium acetate, magnesium sulfate, calcium chloride, ammonium nitrate, and sodium formate;

and combinations thereof.

28. A method for the treatment of non-insulin dependent diabetes mellitus in a mammal in need of such treatment comprising of the administration of a composition according to claim 25.

29. A composition of matter in an injectable formulation comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) lays,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

30. A composition according to claim 29 capable of achieving sustained glycemic control.

31. A composition according to claim 29 which is an aqueous suspension.

32. A composition of matter in an injectable formulation comprising:

(i) a compound selected from the group consisting of;

(a) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly;

(SEQUENCE ID NO;

     2)

(b) a peptide having the amino acid sequence;

His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X (SEQUENCE ID NO;

     7)

wherein X is selected from the group consisting of;

(A) Lys,

(B) Lys-Gly, and

(C) Lys-Gly-Arg;

(c) a polypeptide comprising the primary structure

33. A composition according to claim 32 capable of achieving sustained glycemic control.

34. A composition according to claim 32 which is an aqueous suspension.

35. A composition according to claim 32 wherein the basic polypeptide is protamine.