Details for Patent: 7,271,238
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Title: | Amylin agonist peptides and uses therefor |
Abstract: | Agonist analogues of amylin and related pharmaceutical compositions, and methods of treatment of diabetes and other insulin-requiring states, as well as methods of treatment of hypoglycemia, are provided. |
Inventor(s): | Gaeta; Laura S. L. (La Jolla, CA), Jones; Howard (Poway, CA), Albrecht; Elisabeth (San Diego, CA) |
Assignee: | Amylin Pharmaceuticals, Inc. (San Diego, CA) |
Filing Date: | Aug 26, 2003 |
Application Number: | 10/649,138 |
Claims: | 1. An agonist analog of amylin having the sequence des-.sup.1Lys.sup.25Pro.sup.26Val.sup.28,29Pro-h-amylin (SEQ ID NO: 40). 2. The agonist analog of amylin of claim 1 as an acetate salt. 3. A method of treating diabetes mellitus in a mammal comprising administering the agonist analog of amylin of claim 2 to the mammal. 4. The agonist analog of amylin of claim 1 as a hydrochloride salt. 5. A method of treating diabetes mellitus in a mammal comprising administering the agonist analog of amylin of claim 1 to the mammal. 6. The method of claim 5 further comprising administration of insulin. 7. An agonist analog of amylin having the amino acid sequence of (SEQ ID NO: 44) .sup.1A.sub.J-X-Asn-Thr-.sup.5Ala-Thr-Y-Ala-Thr-.sup.10Gln-Arg-Le- u-B.sub.1-Asn-.sup.15Phe-Leu-C.sub.1-D.sub.1-E.sub.1-.sup.20F.sub.1-G.sub.- 1-Asn-H.sub.1-Gly-.sup.25I.sub.1-J.sub.1-Leu-K.sub.1-L.sub.1.sup.30Thr-M.s- ub.1-Val-Gly-Ser-.sup.35Asn-Thr-Tyr-Z, wherein A.sub.1 is Lys, Ala, Ser or hydrogen, B.sub.1 is Ala, Ser or Thr; C.sub.1 is Val, Leu or Ile; D.sub.1 is His or Arg; E.sub.1 is Ser or Thr; F.sub.1 is Ser, Thr, Gln or Asn; G.sub.1 is Asn, Gln or His; H.sub.1 Phe, Leu or Tyr; I.sub.1 is Ala or Pro; J.sub.1 is Ile, Val, Ala or Leu; K.sub.1 is Ser, Pro, Leu, Ile or Thr; L.sub.1 is Ser, Pro or Thr; M.sub.1 is Asn, Asp, or Gln; X and Y are independently selected residues having side chains which are chemically bonded to each other to form an intramolecular linkage; and Z is hydroxy, amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, alkyloxy, aryloxy or aralkyloxy; and provided that when (a) A.sub.1 is Lys, B.sub.1 is Ala, C.sub.1 is Val, D.sub.1 is His, E.sub.1 is Ser, F.sub.1 is Ser, G.sub.1 is Asn, H.sub.1 is Phe, I.sub.1 is Ala, J.sub.1 is Ile, K.sub.1 is Ser, L.sub.1 is Ser, and M.sub.1 is Asn (SEQ ID NO: 45); (b) A.sub.1 is Lys, B.sub.1 is Ala, C.sub.1 is Ile, D.sub.1 is Arg, E.sub.1 is Ser, F.sub.1 is Ser, G.sub.1 is Asn, H.sub.1 is Leu, I.sub.1 is Ala, J.sub.1 is Ile, K.sub.1is Ser, L.sub.1is Pro, and M.sub.1 is Asn (SEQ ID NO: 46); (c) A.sub.1 is Lys, B.sub.1 is Ala, C.sub.1 is Val, D.sub.1 is Arg, E.sub.1 is Thr, F.sub.1 is Ser, G.sub.1 is Asn, H.sub.1 is Leu, I.sub.1 is Ala, J.sub.1 is Ile, K.sub.1 is Ser, L.sub.1 is Pro, and M.sub.1 is Asn (SEQ ID NO: 47); (d) A.sub.1 is Lys, B.sub.1 is Ala, C.sub.1 is Val, D.sub.1 is Arg, E.sub.1 is Ser, F.sub.1 is Ser, G.sub.1 is Asn, H.sub.1 is Leu, I.sub.1 is Pro, J.sub.1 is Val, K.sub.1 is Pro, L.sub.1 is Pro and M.sub.1 is Asn (SEQ ID NO: 48); (e) A.sub.1 is Lys, B.sub.1 is Ala, C.sub.1 is Val, D.sub.1 is His, E.sub.1 is Ser, F.sub.1 is Asn, G.sub.1 Asn, H.sub.1 is Leu, I.sub.1 is Pro, J.sub.1 is Val, K.sub.1 is Ser, L.sub.1 is Pro, and M.sub.1 is Asn (SEQ ID NO: 49); or (f) A.sub.1 is Lys, B.sub.1 is Thr, C.sub.1 is Val, D.sub.1 is Arg, E.sub.1 is Ser, F.sub.1 is Ser, G.sub.1 His, H.sub.1 is Leu, I.sub.1 is Ala, J.sub.1 is Ala, K.sub.1 is Leu, L.sub.1 is Pro, and M.sub.1 is Asp (SEQ ID NO: 50); then one or more of any of A.sub.1 to M.sub.1 is a D-amino acid and Z is not amino; as a salt. 8. The agonist analog of amylin of claim 7 as an acetate salt. 9. A method of treating diabetes mellitus in a mammal comprising administering the agonist analog of amylin of claim 8 to the mammal. 10. The method of claim 9 wherein the diabetes mellitus is type I diabetes. 11. The method of claim 9 wherein the diabetes mellitus is insulin-requiring type II diabetes. 12. A method of treating diabetes mellitus in a mammal comprising administering the agonist analog of amylin of claim 7 to the mammal. 13. The method of claim 12 further comprising administration of insulin. 14. The method of claim 12 wherein the diabetes mellitus is type I diabetes. 15. The method of claim 12 wherein the diabetes mellitus is insulin-requiring type II diabetes. 16. The method of claim 12 wherein the agonist analog of amylin is given by intravenous, intramuscular, nasal, oral, or transdermal administration. 17. A composition comprising a therapeutically effective amount of the agonist analog of amylin of claim 7 and insulin. 18. A method of treating diabetes mellitus in a mammal comprising administering the composition of claim 17. 19. The method of claim 18 wherein the composition is given by intravenous, intramuscular, nasal, oral or transdermal administration. |