Claims for Patent: 6,583,114

Summary for Patent: 6,583,114

Title:	Fracture healing using pthrp analogs
Abstract:	This invention provides methods of bone healing and fracture repair comprising administering to a patient in need thereof an effective amount of a polypeptide analog of parathyroid hormone related peptide (PTHrP) and salts thereof, wherein amino acid residues 22-31 form an amphipathic .alpha.-helix. Systemic administration is a preferred mode of delivery.
Inventor(s):	Vickery; Brian Henry (Los Altos Hills, CA)
Assignee:	Roche Palo Alto LLC (Palo Alto, CA)
Application Number:	09/146,802
Patent Claims:	1. A method of bone fracture repair comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide analog of parathyroid hormone related peptide (PTHrP) and salts thereof, in which amino acid residues 22-31 of said PTHrP analog form an amphipathic I-helix, for a time and under conditions to achieve said fracture repair. 2. The method of claim 1, wherein the amphipathic I-helix is Glu Leu Leu Glu Xaa Leu Leu Glu Lys Leu (5Xaa-SEQ ID NO:2) wherein Xaa is a positively charged amino acid residue. 3. The method of claim 2, wherein Xaa is lysine or histidine. 4. The method of claim 3, wherein the PTHrP analog is: 5. The method of claim 2, wherein the PTHrP analog has at least two amino acid residues linked via their side chains to each other. 6. The method of claim 5, wherein the linked amino acid residues are at positions 13 and 17 or at positions 26 and 30. 7. The method of claim 6, wherein the amino acid residue at position 17 is an aspartic acid. 8. The method of claim 7, wherein the PTHrP analogs are: ##STR2## 9. The method of claim 1, wherein the PTHrP analog comprises an N-terminal truncation of 30 to 50 amino acid residues with at least one residue optionally substituted at any one of positions 5, 13, 17, 19, 26, 30, 32 and/or 34. 10. The method of claim 9, wherein the PTHrP analog is: 11. The method of claim 1, wherein the PTHrP analog is administered systemically. 12. The method of claim 11, wherein the PTHrP analog is administered by nasal delivery. 13. The method of claim 1, further comprising locally administering a second bone healing agent to the fracture. 14. The method of claim 1 wherein the fracture is in intramembraneous bone. 15. A method of treatment for non-union bone fracture repair comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide analog of PTHrP and salts thereof, in which amino acid residues 22-31 of said PTHrP analog form an amphipathic I-helix, for a time and under conditions to achieve said fracture repair. 16. The method of claim 15, wherein the amphipathic .alpha.-helix is Glu Leu Leu Glu Xaa Leu Leu Glu Lys Leu (.sup.5 Xaa-SEO ID NO:2) wherein Xaa is a positively charged amino acid residue. 17. The method of claim 16, wherein Xaa is lysine or histidine. 18. The method of claim 17, wherein the PTHrP analog is: 19. The method of claim 16, wherein the PTHrP analog has at least two amino acid residues linked via their side chains to each other. 20. The method of claim 19, wherein the linked amino acid residues are at positions 13 and 17 or at positions 26 and 30. 21. The method of claim 20, wherein the amino acid residue at position 17 is an aspartic acid. 22. The method of claim 21, wherein the PTHrP analogs are: ##STR3## 23. The method of claim 15, wherein the PTHrP analog comprises an N-terminal truncation of 30 to 50 amino acid residues with at least one residue optionally substituted at any one of positions 5, 13, 17, 19, 26, 30, 32 and/or 34. 24. The method of claim 23, wherein the PTHrP analog is: 25. The method of claim 15, wherein the PTHrP analog is administered systemically. 26. The method of claim 25, wherein the PTHrP analog is administered by nasal delivery. 27. The method of claim 15, further comprising locally administering a second bone healing agent to the fracture. 28. The method of claim 15, wherein the fracture is in intramembraneous bone.

Details for Patent 6,583,114

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2017-09-09