GIP derivatives and uses thereof
AssigneeNovo Nordisk A/S
InventorsWouter Frederik Johan Hogendorf, Henning Thoegersen, Nicholas Raymond Cox, Patrick J. Knerr, Richard Dimarchi, Brian Finan, Jesper F. Lau, Steffen Reedtz-Runge, Fa Liu
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel peptides that are derivatives of glucose-dependent insulinotropic polypeptide (GIP) analogues having improved physical stability in solution and a protracted profile of action. More particular the invention relates to such peptides that are agonists at the GIP receptor and to their use in weight management or for treatment of diseases such as obesity, diabetes or non-alcoholic steatohepatitis (NASH).
Claims19
A GIP analogue derivative comprising a GIP analogue and a modifying group,
- wherein the GIP analogue is (SEQ ID NO:
- 48):
- X1-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Ala-
- X14-Asp-X16-Ile-X18-Gln-X20-Asp-Phe-Val-Lys-Trp-Leu-
- Leu-Ala-Gln-Lys-X31;
- wherein
- X1 is Tyr or D-Tyr;
- X2 is Aib, Ala, or D-Ala;
- X14 is Leu, Nle, Asp or Met;
- X16 is Lys or Ala;
- X18 is Arg or His;
- X20 is Gln, Glu or Aib;
- X31 is Gly or Pro;
- wherein the modifying group is A-B-C;
- wherein A is
- wherein p is an integer in the range of 14-20, and
- wherein * denotes the position of an amide bond connecting A- and B-;
- wherein B is
- wherein q is an integer in the range of 0-1,
- wherein r is an integer in the range of 1-3,
- wherein * denotes the position of the amide bond connecting A- and B-,
- wherein ** denotes the position of an amide bond connecting B- and C-;
- and
- wherein C is
- wherein s is an integer in the range of 1-3,
- wherein t is an integer in the range of 1-4,
- wherein u is an integer in the range of 1-3,
- wherein ** denotes the position of the amide bond connecting B- and C-, and
- wherein *** denotes the position of an amide bond connecting C- and the epsilon amino group of the lysine at position 24.
A method of treating type II diabetes by administering an effective amount of a pharmaceutical composition to a subject in need thereof,
- wherein the pharmaceutical composition comprises a GIP analogue derivative and a GLP-1 receptor agonist;
- wherein the GIP analogue derivative comprises a GIP analogue and a modifying group;
- wherein the GIP analogue is (SEQ ID NO:
- 48):
- X1-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Ala-
- X14-Asp-X16-Ile-X18-Gln-X20-Asp-Phe-Val-Lys-Trp-Leu-
- Leu-Ala-Gln-Lys-X31;
- wherein
- X1 is Tyr or D-Tyr;
- X2 is Aib, Ala, or D-Ala;
- X14 is Leu, Nle, Asp or Met;
- X16 is Lys or Ala;
- X18 is Arg or His;
- X20 is Gln, Glu or Aib;
- X31 is Gly or Pro;
- wherein the modifying group is A-B-C;
- wherein A is
- wherein p is an integer in the range of 14-20, and
- wherein * denotes the position of an amide bond connecting A- and B-;
- wherein B is
- wherein q is an integer in the range of 0-1,
- wherein r is an integer in the range of 1-3,
- wherein * denotes the position of the amide bond connecting A- and B-,
- wherein ** denotes the position of an amide bond connecting B- and C-;
- and
- wherein C is
- wherein s is an integer in the range of 1-3,
- wherein t is an integer in the range of 1-4,
- wherein u is an integer in the range of 1-3,
- wherein ** denotes the position of the amide bond connecting B- and C-, and
- wherein *** denotes the position of an amide bond connecting C- and the epsilon amino group of the lysine at position 24.
Dependencies are inferred from the claim text.