Exendins and exendin agonist analogs to regulate gastrointestinal motility
AssigneeAmylin Pharmaceuticals, Inc.
InventorsAndrew A. Young, Bronislava Gedulin
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Abstract
Methods for reducing gastric motility and delaying gastric emptying for therapeutic and diagnostic purposes are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist. Methods for treating conditions associated with elevated, inappropriate, or undesired post-prandial blood glucose levels are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist alone or in conjunction with other anti-gastric emptying agents.
Claims21
A method for treating post-prandial dumping syndrome, ingestion of a toxin, or a gastrointestinal spasm in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an exendin-4 peptide comprising the amino acid sequence of SEQ ID NO:2 to treat the patient for post-prandial dumping syndrome, ingestion of a toxin, or the gastrointestinal spasm.
A method for treating post prandial hyperglycemia, post-prandial dumping syndrome, ingestion of a toxin, or a gastrointestinal spasm in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a peptide comprising the amino acid sequence of SEQ ID NO:
- 36 to treat the patient for post-prandial dumping syndrome, ingestion of a toxin, or the gastrointestinal spasm;
- wherein SEQ ID NO:
- 36 is:
- Xaa1 Xaa2 Xaa3 Gly Thr Xaa4 Xaa5 Xaa6 Xaa7 Xaa8
- 1 5 10
- Ser Lys Gln Xaa9 Glu Glu Glu Ala Val Arg Leu
- 15 20
- Xaa10 Xaa11 Xaa12 Xaa13 Leu Lys Asn Gly Gly Xaa14
- 25 30
- Ser Ser Gly Ala Xaa15 Xaa16 Xaa17 Xaa18-Z
- 35
- wherein
- Xaa1 is His, Arg or Tyr;
- Xaa2 is Ser, Gly, Ala or Thr;
- Xaa3 is Asp or Glu;
- Xaa4 is Phe, Tyr or naphthylalanine;
- Xaa5 is Thr or Ser;
- Xaa6 is Ser or Thr;
- Xaa7 is Asp or Glu;
- Xaa8 is Leu, Ile, Val, pentylglycine or Met;
- Xaa9 is Leu, Ile, pentylglycine, Val or Met;
- Xaa10 is Phe, Tyr or naphthylalanine;
- Xaa11 is Ile, Val, Leu, pentylglycine, tert-butylglycine or Met;
- Xaa12 is Glu or Asp;
- Xaa13 is Trp, Phe, Tyr, or naphthylalanine;
- Xaa14, Xaa15, Xaa16 and Xaa17 are independently Pro, homoproline, 3Hyp, 4Hyp, thioproline, N-alkylglycine, N-alkylpentylglycine or N-alkylalanine;
- Xaa18 is Ser, Thr or Tyr;
- and
- Z is —OH or —NH2;
- with the proviso that the peptide does not comprise the amino acid sequence of SEQ ID NO:
- 1 or SEQ ID NO:
- 2.
A method for treating post-prandial dumping syndrome, ingestion of a toxin, or a gastrointestinal spasm in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an exendin comprising the amino acid sequence of SEQ ID NO:2 or an exendin agonist analog having at least 90% sequence similarity to the amino acid sequence of SEQ ID NO:
- 2 to treat the patient for post-prandial dumping syndrome, ingestion of a toxin, or the gastrointestinal spasm.
Dependencies are inferred from the claim text.