Claims for Patent: 9,278,995

Summary for Patent: 9,278,995

Title:	Therapeutic agents for reducing parathyroid hormone levels
Abstract:	Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X1-X2-X3-X4-X5-X6-X7, wherein the X1 subunit comprises a thiol-containing moiety and the distribution of charge on the X2-X7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.
Inventor(s):	Felix Karim, Amos Baruch, Derek MacLean, Kanad Das, Qun Yin
Assignee:	Kai Pharmaceuticals Inc
Application Number:	US13/769,744
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,278,995
Patent Claims:	1. A compound comprising a peptide and a conjugating group, wherein the peptide comprises an amino acid sequence having the formula X1-X2-X3-X4-X5-X6-X7 wherein X1 is D-cysteine; X2 is an amino acid selected from the group consisting of D-arginine and D-alanine; X3 is D-arginine; X4 is an amino acid selected from the group consisting of D-arginine and D-alanine; X5 is D-arginine; X6 is a non-cationic amino acid; X7 is D-arginine; wherein when X2 is D-arginine, X4 is D-alanine and when X2 is D-alanine, X4 is D-arqinine; and wherein the peptide X1 residue is linked to the conjugating group by a disulfide bond. 2. The compound of claim 1, wherein the N-terminus of the peptide is acetylated. 3. The compound of claim 2, wherein the C-terminus of the peptide is amidated. 4. The compound of claim 1, wherein the C-terminus of the peptide is amidated. 5. The compound of claim 1, wherein the conjugating group is acetylated. 6. The compound of claim 5, wherein the conjugating group is cysteine. 7. The compound of claim 1, wherein the compound is a homodimer. 8. The compound of claim 1, wherein the peptide is 8 to 15 amino acid residues in length. 9. The compound of claim 8, wherein the peptide is 8 to 11 amino acid residues in length. 10. The compound of claim 9, wherein the peptide is 8 to 9 amino acid residues in length. 11. The compound of claim 1, wherein the peptide consists of the amino acid sequence having the formula: X1-X2-X3-X4-X5-X6-X 7. 12. The compound of claim 1, wherein the conjugating group is cysteine. 13. The compound of claim 12, wherein the conjugating group is L-cysteine. 14. The compound of claim 13, wherein the L-cysteine is acetylated. 15. The compound of claim 12, wherein the conjugating group is D-cysteine. 16. The compound of claim 15, wherein the D-cysteine is acetylated. 17. The compound of claim 1, wherein the conjugating group is selected from the group consisting of cysteine, homocysteine, glutathione, pegylated cysteine and a thiol-containing polypeptide. 18. The compound of claim 17, wherein the compound is a homodimer. 19. The compound of claim 17, wherein X2 is D-arginine and X4 is D-alanine. 20. The compound of claim 19, wherein the compound is a homodimer. 21. The compound of claim 19, wherein the conjugating group is cysteine. 22. The compound of claim 21, wherein the conjugating group is acetylated. 23. The compound of claim 19, wherein the N-terminus of the peptide is acetylated. 24. The compound of claim 23, wherein the C-terminus of the peptide is amidated. 25. The compound of claim 19, wherein the conjugating group is L-cysteine. 26. The compound of claim 25, wherein the conjugating group is acetylated. 27. The compound of claim 19, wherein the conjugating group is D-cysteine. 28. The compound of claim 27, wherein the conjugating group is acetylated. 29. The compound of claim 17, wherein X4 is D-arginine and X2 is D-alanine. 30. The compound of claim 29, wherein the conjugating group is cysteine. 31. The compound of claim 30, wherein the conjugating group is acetylated. 32. The compound of claim 29, wherein the N-terminus of the peptide is acetylated. 33. The compound of claim 32, wherein the C-terminus of the peptide is amidated. 34. The compound of claim 29, wherein the compound is a homodimer. 35. The compound of claim 17, wherein the conjugating group is cysteine. 36. The compound of claim 35, wherein the conjugating group is acetylated. 37. A compound comprising Ac-c(C)rrarar-NH2 (SEQ ID NO:28). 38. A compound comprising Ac-c(C)rrarar-NH2 (SEQ ID NO:28), wherein the C is acetylated. 39. A compound comprising 40. A compound comprising Ac-c(C)arrrar-NH2 (SEQ ID NO:3), wherein the C is acetylated. 41. A compound comprising