Claims for Patent: 9,474,780

Summary for Patent: 9,474,780

Title:	GIP and GLP-1 co-agonist compounds
Abstract:	The present invention relates to dual incretin peptide mimetic compounds that agonize receptors for both human glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and may be useful for treating type 2 diabetes mellitus (T2D).
Inventor(s):	Bokvist; Bengt Krister (Carmel, IN), Coskun; Tamer (Indianapolis, IN), Cummins; Robert Chadwick (Carmel, IN), Alsina-Fernandez; Jorge (Indianapolis, IN)
Assignee:	Eli Lilly and Company (Indianapolis, IN)
Application Number:	14/987,791
Patent Claims:	1. A compound of Formula: TABLE-US-00042 YX.sub.1EGTFTSDYSIX.sub.2LDKIAQKAX.sub.3VQWLIAGGPSSGAPPPS; wherein X.sub.1 is Aib; X.sub.2 is Aib; K at position 20 is chemically modified through conjugation to the epsilon-amino group of the K side-chain with ([2-(2-Amino-ethoxy)-ethoxy]-acetyl).sub.2-(.gamma.Glu).sub.a-CO--(CH.sub- .2).sub.b--CO.sub.2H wherein a is 1 to 2 and b is 10 to 20; X.sub.3 is Phe or 1-Nal; and the C-terminal amino acid is optionally amidated as a C-terminal primary amide (SEQ ID NO: 11), or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein X.sub.3 is Phe. 3. The compound of claim 1, wherein X.sub.3 is 1-Nal. 4. The compound of claim 2, wherein b is 14 to 18. 5. The compound of claim 4, wherein b is 16 to 18. 6. The compound of claim 5, wherein b is 18. 7. The compound of claim 4, wherein a is 1. 8. The compound of claim 4, wherein a is 2. 9. The compound of claim 4, wherein the C-terminal amino acid is amidated as a C-terminal primary amide. 10. The compound of claim 1, wherein X.sub.1 is Aib X.sub.2 is Aib; K at position 20 is chemically modified through conjugation to the epsilon-amino group of the K side-chain with ([2-(2-Amino-ethoxy)-ethoxy]-acetyl).sub.2-(.gamma.Glu).sub.1-CO--(CH.sub- .2).sub.18--CO.sub.2H; X.sub.3 is Phe; and the C-terminal amino acid is amidated as a C-terminal primary amide (SEQ ID NO: 3), or a pharmaceutically acceptable salt thereof. 11. The compound of claim 1, wherein X.sub.1 is Aib X.sub.2 is Aib; K at position 20 is chemically modified through conjugation to the epsilon-amino group of the K side-chain with ([2-(2-Amino-ethoxy)-ethoxy]-acetyl).sub.2-(.gamma.Glu).sub.2-CO--(CH.sub- .2).sub.18--CO.sub.2H; X.sub.3 is 1-Nal; and the C-terminal amino acid is amidated as a C-terminal primary amide (SEQ ID NO: 4), or a pharmaceutically acceptable salt thereof. 12. A pharmaceutical composition comprising the compound of claim 10 with a pharmaceutically acceptable carrier, diluent, or excipient. 13. A method of treating type 2 diabetes mellitus, comprising administering to a patient in need thereof, an effective amount of the compound of claim 10. 14. The method of claim 13, further comprising administering simultaneously, separately, or sequentially in combination with an effective amount of one or more agents selected from metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase 4 inhibitors, and sodium glucose co-transporters. 15. The compound of claim 1, wherein the Formula is ##STR00003## 16. A pharmaceutical composition comprising the compound of claim 15 with a pharmaceutically acceptable carrier, diluent, or excipient. 17. A method of treating type 2 diabetes mellitus, comprising administering to a patient in need thereof, an effective amount of the compound of claim 15. 18. The method of claim 17, further comprising administering simultaneously, separately, or sequentially in combination with an effective amount of one or more agents selected from metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase 4 inhibitors, and sodium glucose co-transporters.