US 11,814,417 B2
GIP agonist compounds and methods
Anne Pernille Tofteng Shelton, Søborg (DK); Pia Nørregaard, Søborg (DK); Maria Alexandrovna Deryabina, Søborg (DK); Bjarne Due Larsen, Søborg (DK); and Jacob Ulrik Fog, Søborg (DK)
Assigned to Zealand Pharma A/S, Søborg (DK)
Filed by Zealand Pharma A/S, Søborg (DK)
Filed on Apr. 2, 2021, as Appl. No. 17/221,287.
Application 17/221,287 is a continuation of application No. 16/281,347, filed on Feb. 21, 2019, granted, now 11,001,619.
Application 16/281,347 is a continuation of application No. 15/521,631, granted, now 10,253,078, issued on Apr. 9, 2019, previously published as PCT/EP2015/075120, filed on Oct. 29, 2015.
Claims priority of application No. 2014 00629 (DK), filed on Oct. 29, 2014; and application No. 2015 00381 (DK), filed on Jul. 20, 2015.
Prior Publication US 2022/0041676 A1, Feb. 10, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/00 (2006.01); C07K 14/575 (2006.01); A61K 38/22 (2006.01); A61K 45/06 (2006.01)
CPC C07K 14/575 (2013.01) [A61K 38/22 (2013.01); A61K 45/06 (2013.01); A61K 38/00 (2013.01)] 21 Claims
 
1. A method of treating a metabolic disorder in an individual in need thereof, comprising administering to said individual (i) a GIP analogue in combination with (ii) a GLP-1 agonist;
whrerein the GIP analog is represented by the general Formula I:
 
 (SEQ ID NO: 42)
 
 R1-Tyr-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-X10-
 
 
 
 X11-X12-Glu-Leu-X15-X16-X17-X18-X19-X20-X21-
 
 
 
 Phe-X23-X24-X25-Leu-X27-X28-X29-Y1-Y2-R2
 
 (I)
wherein
R1 is H-, Ac or pGlu;
X2 is Aib, Ala, D-Ala, Gly, Ser, N-Me-Ser, Ac3c, Ac4c or Ac5c;
X10 is Tyr, Leu or Ser;
X11 is Ser or Leu;
X12 is Lys, ψ or Ile;
X15 is Asp or Glu;
X16 is Ser, Glu, Lys or ψ:
X17 is Ile, Lys, Gln, Arg or ψ:
X18 is His, Arg or Ala;
X19 is Gln, Lys, Ala or Glu;
X20 is Gln, Lys, Ala, His or Arg;
X21 is Ala, Leu, Asp or Glu;
X23 is Val or Ile;
X24 is Asn or Glu;
X25 is Tyr or Trp;
X27 is Leu, Glu, Ser, Lys or Val;
X28 is Ala, Ser or Arg;
X29 is Aib, Gly, Ala, Gln, Thr, Ser or Lys or is absent;
Y1 is Lys-Gly, Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO: 43), Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser (SEQ ID NO: 44), Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO: 45), Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser (SEQ ID NO: 46), Gly-Lys-Lys-Asn-Asp-Trp-Lys-His-Asn-Ile-Thr-Gln (SEQ ID NO: 47) or absent;
Y2 is ψ or is absent;
R2 is —NH2 or —OH;
wherein ψ is a residue independently selected from Lys, Arg, Orn and Cys and wherein the side chain of said residue is conjugated to a lipophilic substituent;
and wherein the GIP analogue contains one and only one residue ψ;
or a pharmaceutically acceptable salt thereof.