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):	Lau; Jesper (Farum, DK), Doerwald; Florencio Zaragoza (Smorum, DK), Bloch; Paw (Taastrup, DK), Hansen; Thomas Kruse (Herlev, DK)
Assignee:	Novo Nordisk A/S (Bagsvaerd, DK)
Application Number:	13/412,283
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): ##STR00064## wherein Xaa.sub.7 is L-histidine, D-histidine, desamino-histidine, 2-amino-histidine, .beta.-hydroxy-histidine, homohistidine, N.sup..alpha.-acetyl-histidine, a-fluoromethyl-histidine, a-methyl-histidine, 3-pyridylalanine, 2-pyridylalanine, or 4-pyridylalanine; Xaa.sub.8 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; Xaa.sub.16 is Val or Leu; Xaa.sub.18 is Ser, Lys, or Arg; Xaa.sub.19 is Tyr or Gln; Xaa.sub.20 is Leu or Met; Xaa.sub.22 is Gly, Glu, or Aib; Xaa.sub.23 is Gln, Glu, Lys, or Arg; Xaa.sub.25 is Ala or Val; Xaa.sub.27 is Glu or Leu; Xaa.sub.33 is Ala, Glu, or Arg; Xaa.sub.33 is Val or Lys; Xaa.sub.34 is Lys, Glu, Asn, or Arg; Xaa.sub.35 is Gly or Aib; Xaa.sub.36 is Arg, Gly, Lys, or is absent; Xaa.sub.37 is Gly, Ala, Glu, Pro, Lys, or is absent; Xaa.sub.38 is Lys, Ser, amide, or is absent; and where U is a spacer selected from ##STR00065## 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 ##STR00066## 2. A GLP-1 analog according to claim 1, wherein Xaa.sub.7 is His or desamino-histidine; Xaa.sub.8 is Gly, Val, Leu, Ile, Lys or Aib; Xaa.sub.16 is Val; Xaa.sub.18 is Ser; Xaa.sub.19 is Tyr; Xaa.sub.20 is Leu; Xaa.sub.22 is Gly, Glu or Aib; Xaa.sub.23 is Gln or Glu; Xaa.sub.25 is Ala; Xaa.sub.27 is Glu; Xaa.sub.30 is Ala or Glu; Xaa.sub.33 is Val; Xaa.sub.34 is Lys or Arg; Xaa.sub.35 is Gly or Aib; Xaa.sub.36 is Arg or Lys Xaa.sub.37 is Gly, amide or is absent; and Xaa.sub.38 is absent. 3. A GLP-1 analog according to claim 2, wherein Xaa.sub.7 is His Xaa.sub.8 is Gly, or Aib; Xaa.sub.16 is Val; Xaa.sub.18 is Ser; Xaa.sub.19 is Tyr; Xaa.sub.20 is Leu; Xaa.sub.22 is Glu or Aib; Xaa.sub.23 is Gln; Xaa.sub.25 is Ala; Xaa.sub.27 is Glu; Xaa.sub.30 is Ala; Xaa.sub.33 is Val; Xaa.sub.34 is Lys or Arg; Xaa.sub.35 is Gly or Aib; Xaa.sub.36 is Arg Xaa.sub.37 is Gly and Xaa.sub.38 is absent. 4. A GLP-1 analog according to claim 1, wherein said GLP-1 analog comprises Aib.sup.8 or Gly.sup.8 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 Aib.sup.8. 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 Aib.sup.8, Arg.sup.34-GLP-1(7-37) or Aib.sup.8,22, Arg.sup.34-GLP-1(7-37). 10. A compound according to claim 1, wherein U is a spacer selected from ##STR00067## 11. A compound according to claim 10, wherein B is ##STR00068## 12. A compound according to claim 1 selected from the following: ##STR00069## ##STR00070## ##STR00071## 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.