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Details for Patent: 7,781,401

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Details for Patent: 7,781,401

Title:Glucagon-like peptide-2 analogs
Abstract: Analogs of glucagon-like peptide 2, a product of glucagon gene expression, have been identified as intestinal tissue growth factors. Their formulation as pharmaceutical, and therapeutic use in treating disorders of the small bowel, are described.
Inventor(s): Drucker; Daniel J. (Toronto, CA), Crivici; Anna E. (San Diego, CA), Sumner-Smith; Martin (Bolton, CA)
Assignee: NPS Pharmaceuticals, Inc. (Bedminster, NJ)
Filing Date:Nov 14, 2002
Application Number:10/293,941
Claims:1. A GLP-2 analog of SEQ ID NO:2, or pharmaceutically acceptable salt thereof, having intestinotrophic activity, wherein said analog comprises at least one amino acid substitution at sites selected from the group consisting of 5, 7, 25, 30, and 33, wherein site 5 may be substituted with Thr or Ala, site 7 may be substituted with Ala, site 25 may be substituted with Phe or Tyr, site 30 may be substituted with Arg, and site 33 may be substituted with Asn or Glu.

2. A pharmaceutical composition comprising a mammalian GLP-2 analog, or pharmaceutically acceptable salt thereof, according to claim 1 and a pharmaceutically acceptable carrier.

3. A method for promoting the growth of small bowel tissue in a patient in need thereof, comprising administering to the patient an effective amount of a pharmaceutical composition according to claim 2 to promote the growth of small bowel tissue.

4. The method for the treatment of a gastrointestinal disease, comprising administering to a patient having the gastrointestinal disease an effective amount of a pharmaceutical composition according to claim 2.

5. The method of claim 4 wherein the gastrointestinal disease is selected from the group consisting of ulcers, digestion disorders, malabsorption syndromes, short-gut syndrome, cul-de-sac syndrome, inflammatory bowel disease, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, radiation enteritis, infectious or post-infectious enteritis, regional enteritis (Crohn's disease), small intestinal damage due to toxic or other chemotherapeutic agents, and short bowel syndrome.

6. The method of claim 5 wherein the gastrointestinal disease is short bowel syndrome.

7. The method of claim 5 wherein the gastrointestinal disease is small intestinal damage due to toxic or other chemotherapeutic agents.

8. The method of claim 5 wherein the gastrointestinal disease is radiation enteritis.

9. A method for enhancing the nutritional absorption of the small intestine in a patient in need thereof, comprising administering to the patient an effective amount of the pharmaceutical composition according to claim 2.

10. The mammalian GLP-2 analog of claim 1 wherein the amino acid at position 5 of SEQ ID NO: 2 is substituted with Thr.

11. The mammalian GLP-2 analog of claim 1 wherein the amino acid at position 5 of SEQ ID NO: 2 and the amino acid at position 7 of SEQ ID NO: 2 are substituted with Ala.

12. The mammalian GLP-2 analog of claim 1 wherein the amino acid at position 25 of SEQ ID NO: 2 is substituted with Phe.

13. The mammalian GLP-2 analog of claim 1 wherein the amino acid at position 25 of SEQ ID NO: 2 is substituted with Tyr.

14. The mammalian GLP-2 analog of claim 1 wherein the amino acid at position 30 of SEQ ID NO: 2 is substituted with Arg.

15. The mammalian GLP-2 analog of claim 1 wherein the amino acid at position 33 of SEQ ID NO: 2 is substituted with Glu.

16. The mammalian GLP-2 analog of claim 1 wherein the amino acid at position 33 of SEQ ID NO: 2 is substituted with Asn.
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