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Details for Patent: 8,318,669

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Details for Patent: 8,318,669

Title:Method of regulating glucose metabolism, and reagents related thereto
Abstract: The present invention provides methods for modification and regulation of glucagon-like peptide 1 (GLP-1) metabolism by administering therapeutically effective amounts of an inhibitor of dipeptidylpeptidase IV (DPIV) or a pharmaceutically acceptable salt thereof, where the inhibitor has a Ki for inhibition of DPIV of 10 nM or less; and the inhibitor is administered in an amount sufficient to inhibit DPIV proteolysis of GLP-1 but not sufficient to suppress the immune system of the animal.
Inventor(s): Bachovchin; William W. (Cambridge, MA), Plaut; Andrew G. (Lexington, MA), Drucker; Daniel J. (Toronto, CA)
Assignee: Trustees of Tufts College (Boston, MA) New England Medical Center Hospitals, Inc. (Boston, MA) 1149336 Ontario, Inc. (Toronto, Ontario, CA)
Filing Date:Nov 09, 2010
Application Number:12/942,313
Claims:1. A method for modifying metabolism of glucagon-like peptide 1 (GLP-1), comprising administering orally to an animal in need thereof a therapeutically effective amount of an inhibitor of dipeptidylpeptidase IV (DPIV) or a pharmaceutically acceptable salt thereof once daily, wherein the inhibitor has a Ki for inhibition of DPIV of 10 nM or less; the duration of the therapeutic effect is at least about 24 hours; and the inhibitor is administered in an amount sufficient to inhibit DPIV proteolysis of GLP-1 but not sufficient to suppress the immune system of the animal.

2. The method of claim 1, wherein the inhibitor has a Ki for inhibition of DPIV of 1.0 nM or less.

3. The method of claim 2, wherein the inhibitor has a Ki for inhibition of DPIV of 0.1 nM or less.

4. The method of claim 3, wherein the inhibitor has a Ki for inhibition of DPIV of 0.01 nM or less.

5. The method of claim 1, wherein the inhibitor has an EC.sub.50 for modification of GLP-1 metabolism at least one order of magnitude less than its EC.sub.50 for immunosuppression.

6. The method of claim 5, wherein the inhibitor has an EC.sub.50 for modification of GLP-1 metabolism at least two orders of magnitude less than its EC.sub.50 for immunosuppression.

7. The method of claim 1, wherein the inhibitor has a molecular weight less than 5000 amu.

8. The method of claim 7, wherein the inhibitor has a molecular weight less than 2000 amu.

9. The method of claim 8, wherein the inhibitor has a molecular weight less than 1000 amu.

10. The method of claim 1, wherein said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.

11. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours.

12. The method of claim 1, wherein the animal is a human.

13. The method of claim 1, wherein the inhibitor is administered in the form of a tablet.

14. The method of claim 1, wherein the inhibitor is administered in the form of a coated tablet.

15. The method of claim 1, wherein the animal is a human; and the duration of the therapeutic effect is about 24 hours.

16. The method of claim 1, wherein the animal is a human; and the inhibitor has a molecular weight less than 1000 amu.

17. The method of claim 1, wherein the animal is a human; and the inhibitor is administered in the form of a tablet.

18. The method of claim 1, wherein the animal is a human; and the inhibitor is administered in the form of a coated tablet.

19. The method of claim 1, wherein the inhibitor has a molecular weight less than 1000 amu; and the duration of the therapeutic effect is about 24 hours.

20. The method of claim 1, wherein the inhibitor has a molecular weight less than 1000 amu; and the inhibitor is administered in the form of a tablet.

21. The method of claim 1, wherein the inhibitor has a molecular weight less than 1000 amu; and the inhibitor is administered in the form of a coated tablet.

22. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; and the inhibitor is administered in the form of a tablet.

23. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; and the inhibitor is administered in the form of a coated tablet.

24. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; the inhibitor is administered in the form of a tablet; and the inhibitor has a molecular weight less than 1000 amu.

25. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; the inhibitor is administered in the form of a coated tablet; and the inhibitor has a molecular weight less than 1000 amu.

26. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; the inhibitor is administered in the form of a tablet; the inhibitor has a molecular weight less than 1000 amu; and said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.

27. The method of claim 1, wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; the inhibitor is administered in the form of a coated tablet; the inhibitor has a molecular weight less than 1000 amu; and said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.
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