Claims for Patent: 7,776,826

Summary for Patent: 7,776,826

Title:	Method for fostering bone formation and preservation
Abstract:	A method of inducing bone formation in a subject in need of such inducement comprises the steps of mechanically inducing an increase in osteoblast activity in the subject and elevating blood concentration of at least one bone anabolic agent in the subject. The method steps may be performed in any order, but in sufficient time proximity that the elevated concentration of the anabolic agent and the mechanically induced increase in osteoblast activity overlaps. The method may additionally comprise providing the subject with an elevated blood concentration of at least one antiresorptive agent, wherein the elevated concentration is sufficient to prevent resorption of new bone growth produced due to the osteoblast activity. Use of the method permits targeting of specific bones of the subject for bone production and preservation, faster bone production and earlier discontinuation of bone anabolic pharmaceuticals. Kits adapted for performing the method are provided.
Inventor(s):	Vignery; Agnes (Branford, CT), Mehta; Nozer M. (Randolph, NJ), Gilligan; James P. (Union, NJ)
Assignee:	Unigene Laboratories, Inc. (Boonton, NJ) Yale University (New Haven, CT)
Application Number:	12/059,662
Patent Claims:	1. A method of inducing bone formation in a subject suffering from diminished bone mass or bone trauma, said method comprising a medical treatment including the steps of: (a) targeting for treatment at least one bone of said subject, each said targeted bone defining a bone marrow cavity therein, said bone marrow cavity containing a quantity of bone marrow and a plurality of osteoblasts; (b) mechanically altering the contents of said cavity by a surgical treatment thereof to thus induce an increase in osteoblast activity therein; and (c) administering to said subject at least one bone anabolic agent for a duration and at a concentration sufficient to raise blood levels of said anabolic agent within said subject above natural levels thereof to thereby prolong said increased osteoblast activity, such that the mechanical alteration of the bone marrow cavity permits specific bones of said subject to be targeted by said method to permit enhanced bone formation therein, wherein step (b) is performed no later than step (c) and in sufficient time proximity that the elevated concentration of said bone anabolic agent and said increased osteoblast activity at least partially overlaps. 2. The method of claim 1, wherein said bone formation is induced at a location of a long bone fracture in a bone of said subject to increase rapidity of healing of said fracture. 3. The method of claim 1, which further comprises reshaping or modeling at least one targeted bone of said subject by inducing additional bone formation in a controlled manner thereon. 4. The method of claim 1, wherein the bone anabolic agent is administered orally, intravenously, intramuscularly, subcutaneously, via implant, transmucosally, rectally, nasally, by depot injection, by inhalation and pulmonary absorption or transdermally. 5. The method of claim 1, wherein said bone anabolic agent also substantially prevents resorption of new bone produced due to said osteoblast activity. 6. The method of claim 5, wherein the bone anabolic agent is estrogen, strontium ranalate or a selective estrogen receptor modulator (SERM). 7. The method of claim 1, which further comprises administering to said subject an amount of Factor VII or Factor VIIA calculated to further increase said osteoblast activity. 8. A method of inducing bone formation in a subject suffering from diminished bone mass or bone trauma, said method comprising a medical treatment including the steps of: (a) targeting for treatment at least one bone of said subject, each said targeted bone defining a bone marrow cavity therein, said bone marrow cavity containing a quantity of bone marrow and a plurality of osteoblasts; (b) mechanically altering the contents of said cavity by a surgical treatment thereof to induce an increase in osteoblast activity therein, whereby bone mass is correspondingly increased within said cavity; (c) administering to said subject at least one bone anabolic agent for a duration and at a concentration sufficient to raise blood levels of said anabolic agent within said subject above natural levels thereof and thereby prolong said increased osteoblast activity; and (d) additionally administering, either contemporaneous with or subsequent to the administration of said bone anabolic agent, an antiresorptive agent for a duration and at a concentration sufficient to substantially prevent resorption of new bone produced due to said osteoblast activity, such that the mechanical alteration of the bone marrow cavity permits specific bones of said subject to be targeted by said method to permit enhanced bone formation therein, wherein step (b) is performed no later than step (c) and in sufficient time proximity that the elevated concentration of the bone anabolic agent and said increased osteoblast activity at least partially overlaps. 9. The method of claim 8, wherein the bone anabolic agent is calcitonin gene related peptide (CGRP). 10. The method of claim 8, wherein the bone anabolic agent is parathyroid hormone related peptide (PTHrP). 11. The method of claim 8, wherein the bone anabolic agent is a parathyroid hormone (PTH) selected from the group consisting of PTH[1-84] in the free acid form, PTH[1-84]NH.sub.2, PTH[1-34] in the free acid form, PTH[1-30]NH.sub.2, PTH[1-31]NH.sub.2, PTH[1-32]NH.sub.2, PTH[1-33]NH.sub.2, PTH[1-34]NH.sub.2 and combinations thereof. 12. The method of claim 11, wherein a sufficient amount of amidated truncate of natural parathyroid hormone is administered to said subject to achieve a pulsatile blood concentration thereof in said subject of between about 50-500 pg/ml. 13. The method of claim 8, wherein said antiresorptive agent is a calcitonin selected from the group consisting of human calcitonin, salmon calcitonin, eel calcitonin, elcatonin, porcine calcitonin, chicken calcitonin, and combinations thereof. 14. The method of claim 13, wherein the antiresorptive agent is salmon calcitonin and wherein the salmon calcitonin is administered to said subject in an amount calculated to achieve a blood concentration thereof in said subject of between about 50-350 pg/ml. 15. A method of inducing bone formation in a subject suffering from diminished bone mass or bone trauma, said method comprising a medical treatment including the steps of: (a) targeting for treatment at least one bone of said subject, each said targeted bone defining a bone marrow cavity therein, said bone marrow cavity containing a quantity of bone marrow and a plurality of osteoblasts; (b) mechanically altering the contents of said cavity by a surgical treatment thereof to thus induce an increase in osteoblast activity therein; and (c) administering to said subject at least one bone anabolic agent for a duration and at a concentration sufficient to raise blood levels of said anabolic agent within said subject above natural levels to thereby prolong said increased osteoblast activity, such that the mechanical alteration of the bone marrow cavity permits specific bones of said subject to be targeted by said method to permit enhanced bone formation therein, wherein step (c) is performed no later than step (b) and in sufficient time proximity that the elevated concentration of said bone anabolic agent and said increased osteoblast activity at least partially overlaps. 16. The method of claim 15, wherein said bone formation is induced at a location of long bone fracture in a bone of said subject to increase rapidity of healing of said fracture. 17. The method of claim 15, which further comprises reshaping or modeling at least one targeted bone of said subject by inducing additional bone formation in a controlled manner thereon. 18. The method of claim 15, wherein the bone anabolic agent is administered orally, intravenously, intramuscularly, subcutaneously, via implant, transmucosally, rectally, nasally, by depot injection, by inhalation and pulmonary absorption or transdermally. 19. The method of claim 15, wherein said bone anabolic agent also substantially reduces resorption of new bone produced due to said osteoblast activity. 20. The method of claim 19, wherein the bone anabolic agent is estrogen, strontium ranalate or a selective estrogen receptor modulator (SERM). 21. The method of claim 15, which further comprises administering to said subject an amount of Factor VII or Factor VIIA calculated to further increase said osteoblast activity. 22. A method of inducing bone formation in a subject suffering from diminished bone mass or bone trauma, said method comprising a medical treatment including the steps of: (a) targeting for treatment at least one bone of said subject, each said targeted bone defining a bone marrow cavity therein, said bone marrow cavity containing a quantity of bone marrow and a plurality of osteoblasts; (b) mechanically altering the contents of said cavity by a surgical treatment thereof to induce an increase in osteoblast activity therein, whereby bone mass is correspondingly increased within said cavity; (c) administering to said subject at least one bone anabolic agent for a duration and at a concentration sufficient to raise blood levels of said anabolic agent within said subject above natural levels and thereby prolong said increased osteoblast activity; and (d) additionally administering, either contemporaneous with or subsequent to the administration of said bone anabolic agent, an antiresorptive agent for a duration and at a concentration sufficient to substantially prevent resorption of new bone produced due to said osteoblast activity, such that the mechanical alteration of the bone marrow cavity permits specific bones of said subject to be targeted by said method to permit enhanced bone formation therein, and wherein step (c) is performed no later than step (b) and in sufficient time proximity that the elevated concentration of the bone anabolic agent and said increased osteoblast activity at least partially overlaps. 23. The method of claim 22, wherein the bone anabolic agent is calcitonin gene related peptide (CGRP). 24. The method of claim 22, wherein the bone anabolic agent is parathyroid hormone related peptide (PTHrP). 25. The method of claim 22, wherein the bone anabolic agent is a parathyroid hormone selected from the group consisting of PTH[1-84] in the free acid form, PTH[1-84]NH.sub.2, PTH[1-34] in the free acid form, PTH[1-30]NH.sub.2, PTH[1-31]NH.sub.2, PTH[1-32]NH.sub.2, PTH[1-33]NH.sub.2, PTH[1-34]NH.sub.2 and combinations thereof. 26. The method of claim 22, wherein a sufficient amount of amidated truncate of natural parathyroid hormone is administered to said subject to achieve a pulsatile blood concentration thereof in said subject of between about 50-500 pg/ml. 27. The method of claim 22, wherein said antiresorptive agent is a calcitonin selected from the group consisting of human calcitonin, salmon calcitonin, eel calcitonin, eel calcitonin, pig calcitonin, chicken calcitonin, and combinations thereof. 28. The method of claim 27, wherein the antiresorptive agent is salmon calcitonin and wherein the salmon calcitonin is administered to said subject in an amount calculated to achieve a blood concentration thereof in said subject of between about 50-350 pg/ml.

Details for Patent 7,776,826

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2024-05-14