Details for Patent: 6,610,824

Title:	Amylin agonist peptides and uses therefor
Abstract:	Agonist analogs 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:	Dec 06, 1999
Application Number:	09/454,533
Claims:	1. An agonist analogue of amylin having the amino acid sequence of .sup.1 A.sub.1 -X-Asn-Thr-.sup.5 Ala-Thr-Y-Ala-Thr-.sup.10 Gln-Arg-Leu-B.sub.1 -Asn-.sup.15 Phe-Leu-C.sub.1 -D.sub.1 -E.sub.1 -.sup.20 F.sub.1 -G.sub.1 -Asn-H.sub.1 -Gly-.sup.25 I.sub.1 -J.sub.1 -Leu-K.sub.1 -L.sub.1.sup.30 Thr-M.sub.1 -Val-Gly-Ser-.sup.35 Asn-Thr-Tyr-Z, wherein A.sub.1 is Lys, Ala, Ser or hydrogen, B.sub.1 is Ala, Set 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 is 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 amino acid residues having side chains which are chemically bonded to each other to form an intramolecular linkage; and Z is 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; (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.1 is Ser, L.sub.1 is Pro, and M.sub.1 is Asn; (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; (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; (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 is 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; 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 is His, H.sub.1 is Leu, I.sub.1 is Ala, J.sub.1 is Ala, K.sub.1 is Len, L.sub.1 is Pro, and M.sub.1 is Asp; then one or more of any of A.sub.1 to M.sub.1 is a D-amino acid and Z is not amino. 2. The agonist analogue of amylin according to claim 1, wherein the agonist analogue of amylin is not .sup.29 Pro-h-amylin. 3. The agonist analogue of amylin according to claims 2, wherein the agonist analogue of amylin is not 2-37-amylin. 4. The agonist analogue of amylin according to claim 3, wherein the agonist analogue of amylin is not .sup.23 Leu-h-amylin.