SPETZLER, Jane,SCHÄFFER, Lauge,LAU, Jesper,KRUSE, Thomas,GARIBAY, Patrick William,RUNGE, Steffen,THØGERSEN, Henning,PETTERSSON, Ingrid
申请号：
ES08803724
公开号：
ES2672770T3
申请日:
2008.09.05
申请国别(地区):
ES
年份:
2018
代理人:
摘要：
A derivative of GLP-1 comprising a modified GLP-1 (7-37) sequence having: a total of 2-12 amino acid modifications compared to GLP-1 (7-37) (sec. With No. of Ident .: 1), which has the sequence of the formula (I): Xaa7-Xaa8-Xaa9-Gly-Thr-Phe-Thr-Ser-Asp-Xaa16-Ser-Xaa18-Tyr- Xaa20- Glu-Glu-Xaa23 - Xaa24-Xaa25-Arg- Xaa27-Xaa28-Ile-Xaa30 -Xaa31-Leu-Xaa33-Xaa34-Xaa35- Xaa36 -Xaa37 -Xaa38- Xaa39-Xaa40- Xaa41-R formula (I) (sec. With identification number .: 2) where (Xaa7-Xaa8) is (L-histidine-Aib), (deamino-histidine-alanine), or (deamino-histidine-Aib)； Xaa9 is Glu； Xaa16 is Val, or Leu； Xaa18 is Ser, Lys, Cys, or Arg； Xaa20 is Leu, or Lys； Xaa23 is Gln, Glu, Lys, Cys, or Arg； Xaa24 is Ala, or Asn； Xaa25 is Ala, or Val； Xaa27 is Glu, Ala, or Leu； Xaa28 is Phe； Xaa30 is Ala, Glu, Lys, or Arg； Xaa31 is Trp, Cys, or Lys； Xaa33 is Val, Cys, or Lys； Xaa34 is Lys, Cys, Glu, Asn, Dap, or Arg； Xaa35 is Gly, Arg, Lys, Aib, or is absent； Xaa36 is Arg, Lys, or is absent； Xaa37 is Gly, Aib, Cys, Lys, epsilon-amino-Lys, Pro, Arg, or is absent； Xaa38 is Lys, Glu, Arg, or is absent； Xaa39 is Lys, Arg, or is absent； Xaa40 is Arg, or is absent； Xaa41 is Arg, or is absent； and R is amide, or is absent； as long as if Xaa37, Xaa38, Xaa39, or Xaa40 is absent, then each amino acid residue downstream is also absent； and wherein the amino acid at the position equivalent to position 31 of GLP-1 (7-37) is derived with ABCD where A- is selected from the group consisting of ** Formula ** and ** Formula ** where the tetrazole ring is optionally N-substituted, and where n is selected from the group consisting of 14, 15, 16, 17, 18 and 19, p is selected from the group consisting of 10, 11, 12, 13 and 14, and d is selected from the group consisting of 0, 1, 2, 3, 4 and 5, -B- is selected from the group consisting of ** Formula ** where bye each is independently selected from the group consisting of 0, 1 and 2, ycyf are each independently selected from the group consisting of 0, 1 and 2 as long as b is
