| US 7,452,858 B2 | ||
| Treatment of gestational diabetes | ||
| Richard A. Hiles, San Diego, Calif. (US); and Kathryn S. Prickett, San Diego, Calif. (US) | ||
| Assigned to Amylin Pharmaceuticals, Inc., San Diego, Calif. (US) | ||
| Filed on Nov. 17, 2005, as Appl. No. 11/282,085. | ||
| Application 11/282085 is a continuation of application No. 10/342014, filed on Jan. 13, 2003. | ||
| Application 10/342014 is a continuation of application No. 09/323867, filed on Jun. 01, 1999, granted, now 6,506,724. | ||
| Prior Publication US 2006/0074012 A1, Apr. 06, 2006 | ||
| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. A61K 38/28 (2006.01); A61K 38/00 (2006.01); C07K 2/00 (2006.01); C07K 17/00 (2006.01) | ||
| U.S. Cl. 514—2 [514/3; 514/4; 514/12; 530/300; 530/324; 530/325] | 19 Claims |
| 1. A method for treating gestational diabetes mellitus in a human in need thereof comprising subcutaneously injecting the
human with about 1 microgram to about 50 micrograms per day of a peptide having the amino acid sequence of SEQ ID NO. 3, SEQ
ID NO. 4, or SEQ ID NO. 5 to treat the gestational diabetes mellitus in the human in need thereof; wherein the peptide does
not have the amino acid sequence of SEQ ID NO. 2; and
wherein SEQ ID NO. 3 is:
Xaa1 Xaa2 Xaa3 Gly Thr Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Ser Lys Gln Xaa9 Glu Glu Glu Ala Val Arg Leu Xaa10 Xaa11 Xaa12 Xaa13 Leu Lys Asn Gly Gly Xaa14 Ser Ser Gly Ala Xaa15 Xaa16 Xaa17 Xaa18-Z;
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 Try; and
Z is —OH or —NH2;
wherein SEQ ID NO. 4 is:
Xaa1 Xaa2 Xaa3 Gly Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Xaa15 Xaa16 Xaa17 Ala Xaa19 Xaa20 Xaa21 Xaa22 Xaa23 Xaa24 Xaa25 Xaa26 Xaa27 Xaa28-Z1;
wherein:
Xaa1 is His, Arg, or Tyr;
Xaa2 is Ser, Gly, Ala, or Thr;
Xaa3 is Asp or Glu;
Xaa5 is Ala or Thr;
Xaa6 is Ala, Phe, Tyr, or naphthylalanine;
Xaa7 is Thr or Ser;
Xaa8 is Ala, Ser, or Thr;
Xaa9 is Asp or Glu;
Xaa10 is Ala, Leu, Ile, Val, pentylglycine, or Met;
Xaa11 is Ala or Ser;
Xaa12 is Ala or Lys;
Xaa13 is Ala or Gln;
Xaa14 is Ala. Leu, Ile, pentylglycine, Val, or Met;
Xaa15 is Ala or Glu;
Xaa16 is Ala or Glu;
Xaa17 is Ala or Glu;
Xaa19 is Ala or Val;
Xaa20 is Ala or Arg;
Xaa21 is Ala or Leu;
Xaa22 is Ala, Phe, Tyr, or naphthylalanine;
Xaa23 is Ile, Val, Leu, pentylglycine, tert-butylglycine, or Met;
Xaa24 is Ala, Glu, or Asp;
Xaa25 is Ala, Trp, Phe, Tyr, or naphthylalanine;
Xaa26 is Ala or Leu;
Xaa27 is Ala or Lys;
Xaa28 is Ala or Asn;
Z1 is —OH,
—NH2,
Gly-Z2,
Gly Gly-Z2,
Gly Gly Xaa31 -Z2,
Gly Gly Xaa31 Ser-Z2,
Gly Gly Xaa31 Ser Ser-Z2,
Gly Gly Xaa31 Ser Ser Gly-Z2,
Gly Gly Xaa31 Ser Ser Gly Ala-Z2,
Gly Gly Xaa31 Ser Ser Gly Ala Xaa36-Z2,
Gly Gly Xaa31 Ser Ser Gly Ala Xaa36 Xaa37-Z2, or
Gly Gly Xaa31 Ser Ser Gly Ala Xaa36 Xaa37Xaa38-Z2;
Xaa31, Xaa36, Xaa37 and Xaa38 are independently Pro. homoproline, 3Hyp, 4Hyp. thioproline, N-alkylglycine, N-alkylpentylglycine, or N-alkylalanine; and
Z2 is —OH or —NH2;
provided that no more than three of Xaa3, Xaa5, Xaa6, Xaa8, Xaa10, Xaa11, Xaa12, Xaa13, Xaa14, Xaa15, Xaa16, Xaa17, Xaa19, Xaa20, Xaa21, Xaa24, Xaa25, Xaa26, Xaa27 and Xaa28 are Ala; and wherein SEQ ID NO. 5 is:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Xaa15 Xaa16 Xaa17 Ala Xaa19 Xaa20 Xaa21 Xaa22 Xaa23 Xaa24 Xaa25 Xaa26, Xaa27Xaa28-Z1;
wherein:
Xaa1 is His. Arg, Tyr, Ala, Norval, Val, or Norleu;
Xaa2 is Ser, Gly, Ala, or Thr;
Xaa3 is Ala, Asp, or Glu;
Xaa4 is Ala, Norval, Val, Norleu, or Gly;
Xaa5 is Ala or Thr;
Xaa6 is Phe, Tyr, or naphthylalanine;
Xaa7 is Thr or Ser;
Xaa8 is Ala, Ser or Thr;
Xaa9 is Ala, Norval, Val. Norleu, Asp, or Glu;
Xaa10 is Ala, Leu, Ile, Val, pentylglycine, or Met;
Xaa11 is Ala or Ser;
Xaa12 is Ala or Lys;
Xaa13 is Ala or Gln;
Xaa14 is Ala, Leu. Ile, pentylglycine, Val, or Met;
Xaa15 is Ala or Glu;
Xaa16 is Ala or Glu;
Xaa17 is Ala or Glu;
Xaa19 is Ala or Val;
Xaa20 is Ala or Arg;
Xaa21 is Ala or Leu;
Xaa22 is Phe, Tyr, or naphthylalanine;
Xaa23 is Ile, Val, Leu, pentylglycine, tert-butylglycine, or Met;
Xaa24 is Ala, Glu, or Asp;
Xaa25 is Ala, Trp, Phe, Tyr, or naphthylalanine;
Xaa26 is Ala or Leu;
Xaa27 is Ala or Lys;
Xaa28 is Ala or Asn;
Z1 is —OH,
—NH2 ,
Gly-Z2,
Gly Gly-Z2,
Gly Gly Xaa31 -Z2,
Gly Gly Xaa31 Ser-Z2,
Gly Gly Xaa31 Ser Ser-Z2,
Gly Gly Xaa31 Ser Ser Gly-Z2,
Gly Gly Xaa31 Ser Ser Gly Ala-Z2,
Gly Gly Xaa31 Ser Ser Gly Ala Xaa36-Z2,
Gly Gly Xaa31 Ser Ser Gly Ala Xaa36 Xaa37-Z2,
Gly Gly Xaa31 Ser Ser Gly Ala Xaa36 Xaa37 Xaa38-Z2, or
Gly Gly Xaa31 Ser Ser Gly Ala Xaa36 Xaa37 Xaa38 Xaa39-Z2;
wherein Xaa31, Xaa36, Xaa37 and Xaa38 are independently Pro, homoproline, 3Hyp, 4Hyp, thioproline, N-alkylglycine, N-alkylpentylglycine, or N-alkylalanine; and
Z2 is —OH or —NH2;
provided that no more than three of Xaa3, Xaa4, Xaa5, Xaa6, Xaa8, Xaa9, Xaa10, Xaa11, Xaa12, Xaa13, Xaa14, Xaa15, Xaa16, Xaa17, Xaa19, Xaa20, Xaa21, Xaa24, Xaa25, Xaa26, Xaa27 and Xaa28 are Ala; and provided also that, if Xaa1 is His, Arg, or Tyr, then at least one of Xaa3, Xaa4 and Xaa9 is Ala.
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