Claims for Patent: 8,536,122

Summary for Patent: 8,536,122

Title:	Acylated GLP-1 compounds
Abstract:	Protracted GLP-1 compounds and therapeutic uses thereof.
Inventor(s):	Jesper Lau, Florencio Zaragoza Doerwald, Paw Bloch, Thomas Kruse Hansen
Assignee:	Novo Nordisk AS
Application Number:	US13/412,283
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,536,122
Patent Claims:	1. A compound of formula II (SEQ ID No. 3): wherein Xaa7 is L-histidine, D-histidine, desamino-histidine, 2-amino-histidine, β-hydroxy-histidine, homohistidine, Nα-acetyl-histidine, a-fluoromethyl-histidine, a-methyl-histidine, 3-pyridylalanine, 2-pyridylalanine, or 4-pyridylalanine; Xaa8 is Gly, Val, Leu, Ile, Lys, Aib, (1-aminocyclopropyl) carboxylic acid, (1-aminocyclobutyl) carboxylic acid, (1-aminocyclopentyl) carboxylic acid, (1-aminocyclohexyl) carboxylic acid, (1-aminocycloheptyl) carboxylic acid, or (1-aminocyclooctyl) carboxylic acid; Xaa16 is Val or Leu; Xaa18 is Ser, Lys, or Arg; Xaa19 is Tyr or Gln; Xaa20 is Leu or Met; Xaa22 is Gly, Glu, or Aib; Xaa23 is Gln, Glu, Lys, or Arg; Xaa25 is Ala or Val; Xaa27 is Glu or Leu; Xaa33 is Ala, Glu, or Arg; Xaa33 is Val or Lys; Xaa34 is Lys, Glu, Asn, or Arg; Xaa35 is Gly or Aib; Xaa36 is Arg, Gly, Lys, or is absent; Xaa37 is Gly, Ala, Glu, Pro, Lys, or is absent; Xaa38 is Lys, Ser, amide, or is absent; and where U is a spacer selected from where n is 12, 13, 14, 15, 16, 17, or 18, l is 12, 13, 14, 15, 16, 17, or 18, m is 0, 1, 2, 3, 4, 5, or 6, s is 0, 1, 2, or 3, p is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23; and where B is an acidic group selected from 2. A GLP-1 analog according to claim 1, wherein Xaa7 is His or desamino-histidine; Xaa8 is Gly, Val, Leu, Ile, Lys or Aib; Xaa16 is Val; Xaa18 is Ser; Xaa19 is Tyr; Xaa20 is Leu; Xaa22 is Gly, Glu or Aib; Xaa23 is Gln or Glu; Xaa25 is Ala; Xaa27 is Glu; Xaa30 is Ala or Glu; Xaa33 is Val; Xaa34 is Lys or Arg; Xaa35 is Gly or Aib; Xaa36 is Arg or Lys Xaa37 is Gly, amide or is absent; and Xaa38 is absent. 3. A GLP-1 analog according to claim 2, wherein Xaa7 is His Xaa8 is Gly, or Aib; Xaa16 is Val; Xaa18 is Ser; Xaa19 is Tyr; Xaa20 is Leu; Xaa22 is Glu or Aib; Xaa23 is Gln; Xaa25 is Ala; Xaa27 is Glu; Xaa30 is Ala; Xaa33 is Val; Xaa34 is Lys or Arg; Xaa35 is Gly or Aib; Xaa36 is Arg Xaa37 is Gly and Xaa38 is absent. 4. A GLP-1 analog according to claim 1, wherein said GLP-1 analog comprises Aib8 or Gly8 in position 8 of the GLP-1(7-37) sequence. 5. A GLP-1 analog according to claim 4, wherein said GLP-1 analog comprises Aib8. 6. A GLP-1 analog according to claim 1, wherein said GLP-1 analog comprises no more than six amino acid residues which have been exchanged, added or deleted as compared to GLP-1(7-37) (SEQ ID No. 1). 7. A GLP-1 analog according to claim 1, wherein said GLP-1 analog comprises no more than 3 amino acid residues which have been exchanged, added or deleted as compared to GLP-1(7-37) (SEQ ID No. 1). 8. A GLP-1 analog according to claim 1, wherein said GLP-1 analog comprises only one lysine residue. 9. A GLP-1 analog according to claim 1, which is Aib8, Arg34-GLP-1(7-37) or Aib8,22, Arg34-GLP-1(7-37). 10. A compound according to claim 1, wherein U is a spacer selected from 11. A compound according to claim 10, wherein B is 12. A compound according to claim 1 selected from the following: 13. A pharmaceutical composition comprising a compound according to claim 1, and a pharmaceutically acceptable excipient. 14. A pharmaceutical composition comprising a compound according to claim 12, and a pharmaceutically acceptable excipient. 15. A method for treating hyperglycemia and/or type 2 diabetes in a subject, said method comprising administering to a subject in need of such treatment an effective amount of a GLP-1 analog according to claim 1. 16. A method for treating hyperglycemia and/or type 2 diabetes in a subject, said method comprising administering to a subject in need of such treatment an effective amount of a GLP-1 analog according to claim 12.