Oral dosing of GLP-1 compounds

Patent metadata

Field	Value
Publication number	US-10278923-B2
Application number	US-201715651043-A
Country	US
Kind code	B2
Filing date	Jul 17, 2017
Priority date	May 2, 2013
Publication date	May 7, 2019
Grant date	May 7, 2019

Abstract

The present invention relates to improved uses of GLP-1 peptides in oral therapy.

First claim

The invention claimed is:

1. A method for treating diabetes and/or obesity in a subject in need of such treatment, said method comprising:
orally administering to said subject a therapeutically effective amount of a solid oral dosage form composition comprising a glucagon-like peptide-1 (GLP-1) peptide and an enhancer,
wherein:
(a) the GLP-1 peptide is an acylated GLP-1 analogue having 3 amino acid substitutions or less relative to native GLP-1 (7-37) peptide, and has a plasma half-life in humans of at least 60 hours;
(b) the enhancer is a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; and
(c) said composition is administered such that the ratio between the plasma half-life in days in humans of said peptide and the dosing interval in days of said composition is more than 2:1.

2. The method of claim 1 , wherein said GLP-1 peptide is selected from the group consisting of N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37) (semaglutide), and
N ε37 {2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl}-[Aib 8 ,Arg 34 ,Lys 37 ]GLP-1(7-37)-OH.

3. The method of claim 2 , wherein said composition is administered every second day or more frequently.

4. The method of claim 3 , wherein said composition is administered once daily.

5. The method of claim 3 , wherein said composition is in the form of a tablet, capsule, sachet, or granules.

6. The method of claim 5 , wherein said composition is in the form of a tablet.

7. The method of claim 3 , wherein said GLP-1 peptide is semaglutide.

8. The method of claim 6 , wherein the enhancer is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC).

9. The method of claim 8 , wherein said composition comprises 2-40 mg semaglutide and 200-400 mg SNAC.

10. The method of claim 9 , wherein said composition is administered every second day or more frequently.

11. The method of claim 10 , wherein said composition is administered once daily.

12. The method of claim 9 , wherein said composition is in the form of a tablet, capsule, sachet, or granules.

13. The method of claim 12 , wherein said composition is in the form of a tablet.

14. A method for treating diabetes and/or obesity in a subject in need of such treatment, said method comprising:
orally administering to said subject a therapeutically effective amount of a solid oral dosage form composition comprising a glucagon-like peptide-1 (GLP-1) peptide and an enhancer,
wherein the GLP-1 peptide is:
(a) selected from the group consisting of N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37) (semaglutide) and N ε37 {2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl}-[Aib 8 ,Arg 34 ,Lys 37 ]GLP-1(7-37)-OH; and
(b) has a plasma half-life in humans of at least 60 hours;

wherein the enhancer is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and
wherein said composition is administered every second day or more frequently.

15. The method of claim 14 , wherein said composition comprises 2-40 mg semaglutide and 200-400 mg SNAC.

16. The method of claim 15 , wherein said composition is administered once daily.

17. The method of claim 15 , wherein said composition is in the form of a tablet, capsule, sachet, or granules.

18. The method of claim 17 , wherein said composition is in the form of a tablet.

19. The method of claim 8 , wherein said composition comprises 300 mg of SNAC.

20. The method of claim 15 , wherein said composition comprises 300 mg of SNAC.

21. A method for treating diabetes and/or obesity in a subject in need of such treatment, said method comprising:
orally administering to said subject a therapeutically effective amount of a solid oral dosage form composition comprising a glucagon-like peptide-1 (GLP-1) peptide and an enhancer,
wherein:
(a) the GLP-1 peptide is N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37) (semaglutide) and has a plasma half-life in humans of at least 60 hours;
(b) the enhancer is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and
(c) the composition is administered once daily.

22. The method of claim 21 , wherein said composition comprises 2-40 mg semaglutide and 200-400 mg SNAC.

23. The method of claim 22 , wherein said composition comprises 300 mg of SNAC.

Assignees

• Novo Nordisk As

Inventors

• Nielsen Flemming S
• Sauerberg Per

Classifications

• A61K9/2013 Primary

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K31/166

  having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title