Claims for Patent: 7,531,518

Summary for Patent: 7,531,518

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:	11/128,095
Patent Claims:	1. A method of medical treatment producing a targeted increase in bone strength, form or volume in a subject in need thereof, which method comprises the steps of: (a) mechanically inducing an increase in osteoblast activity in said subject by a surgical treatment of at least one bone of said subject; and (b) elevating blood concentration of at least one bone anabolic agent in said subject, wherein steps (a) and (b) are performed in any order, but in sufficient time proximity that said elevated concentration of said anabolic agent and said mechanically induced increase in osteoblast activity at least partially overlaps. 2. The method of claim 1, wherein the blood concentration of the bone anabolic agent is elevated by direct administration of a bone anabolic agent to said subject. 3. The method of claim 1, which further comprises targeting one or more specific bones of said subject for said induced bone growth by mechanically altering the contents of a bone marrow cavity within each said targeted bone so as to induce said increased osteoblast activity therein. 4. The method of claim 1, which further comprises providing said subject with an elevated blood concentration of at least one antiresorptive agent, wherein said elevated concentration is sufficient to substantially reduce resorption of new bone growth produced due to said increased osteoblast activity. 5. The method of claim 1 additionally comprising forming a sufficient amount of additional bone in a jaw region of said subject to provide an anchor for a dental implant implanted into said jaw region. 6. The method of claim 1 additionally comprising forming a sufficient amount of additional bone in one or more targeted bones of said subject to permit a prosthetic device implanted into at least one said targeted bone to be securely anchored thereto. 7. The method of claim 1, additionally comprising forming a sufficient amount of additional bone in said subject to serve as a secure anchor for a hollow, adjustable insert anchored to said additional bone. 8. The method of claim 1, which further comprises targeting at least one vertebra of said subject for additional bone formation and wherein a sufficient amount of bone is added to said at least one vertebra such that the subject is substantially freed from chronic pain caused due to vertebral crush. 9. The method of claim 1, wherein additional bone is formed on at least one vertebra of said subject in an amount sufficient to stabilize said at least one vertebra due to strengthening thereof. 10. The method of claim 1 wherein the mechanical induction of osteoblast activity is accomplished by inserting, into the bone marrow cavity of a bone targeted for enhanced bone formation, an object configured or adapted to physically alter the contents of said cavity and thereby to stimulate said osteoblast activity within said cavity. 11. The method of claim 10, wherein said physical alteration further comprises removal of at least a portion of said altered cavity contents to provide additional room in the cavity for increased bone mass. 12. The method of claim 1, wherein said at least one bone anabolic agent is selected from the group consisting of parathyroid hormone (PTH), anabolic Vitamin D analogs, a low-density lipoprotein receptor-related protein 5 (LRP5), an activator of non-genomic estrogen-like signaling (ANGELS), a bone morphogenic protein (BMP), an insulin-like growth factor (IGF), a fibroblast growth factor (FGF), sclerostin, leptin, a prostaglandin, a statin, strontium, a growth hormone, a growth hormone releasing factor (GHRF), hepatocyte growth factor (HGF), calcitonin gene related peptide (CGRP), parathyroid hormone related peptide (PTHrP), transforming growth factor (TGF)-.beta.1 and combinations thereof. 13. The method of claim 12, wherein the bone anabolic agent is at least one parathyroid hormone selected from the group consisting of natural parathyroid hormone, a truncate of natural parathyroid hormone, an amidated truncate of natural parathyroid hormone, an amidated natural parathyroid hormone, and combinations thereof. 14. The method of claim 13, wherein the bone anabolic agent is 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. 15. The method of claim 13, wherein a sufficient amount of said parathyroid hormone is administered to said subject to achieve a pulsatile blood concentration thereof in said subject of between about 50-350 pg/ml. 16. The method of claim 15, wherein said sufficient amount of parathyroid hormone is from about 10 .mu.g-10 mg pure weight of PTH hormone per dose. 17. The method of claim 15, wherein said parathyroid hormone is administered via injection and the sufficient amount of parathyroid hormone is from about 10-200 .mu.g per dose. 18. The method of claim 15, wherein the blood concentration of said parathyroid hormone in said subject is raised to a level of between about 50-350 pg/ml by no later than 7 days following mechanical alteration of the contents of the bone marrow cavity. 19. The method of claim 1 which further comprises a step of: (c) administering to said subject an antiresorptive agent for a time and at a concentration sufficient to substantially reduce resorption of the new bone produced due to said osteoblast activity, wherein steps (b) and (c) are performed in any order, but in sufficient time proximity that said elevated concentration of said anabolic agent and said mechanically induced increase in osteoblast activity by a surgical treatment of at least one bone of said subject, at least partially overlaps. 20. The method of claim 19, wherein administration of said antiresorptive agent is commenced during administration of the bone anabolic agent and continues beyond termination of said bone anabolic agent administration. 21. The method of claim 19, wherein the antiresorptive agent is administered orally, intravenously, intramuscularly, subcutaneously, via implant, transmucosally, rectally, nasally, by depot injection, by inhalation and pulmonary absorption or transdermally. 22. The method of claim 19, wherein the antiresorptive agent is a calcitonin selected from the group consisting of human calcitonin, salmon calcitonin, eel calcitonin, elkatonin, porcine calcitonin, chicken calcitonin, calcitonin gene related peptide (CGRP) and combinations thereof. 23. The method of claim 22, wherein the antiresorptive agent is salmon calcitonin and wherein the salmon calcitonin is administered to said subject in an amount calculated to achieve a substantially continuous blood concentration thereof of between about 5-500 pg/ml. 24. The method of claim 23, wherein the amount of said salmon calcitonin is from about 5 .mu.g to 5 mg pure weight of the calcitonin per dose. 25. The method of claim 23, wherein the salmon calcitonin is administered via injection and the amount of said salmon calcitonin is from about 5 .mu.g -200 .mu.g per dose. 26. A medical treatment for inducing bone formation in a subject in need of such inducement, comprising the steps of: (a) mechanically inducing an increase in osteoblast activity in said subject by a surgical treatment of at least one bone of said subject; and (b) administering to said subject at least one agent that causes elevated blood levels of an endogenous bone anabolic agent within said subject, wherein steps (a) and (b) are performed in any order, but in sufficient time proximity that said elevated concentration of said anabolic agent and said mechanically induced increase in osteoblast activity at least partially overlaps. 27. The method of claim 26, wherein the agent causing an increased expression of said endogenous bone anabolic agent within said subject is a calcilytic agent.

Details for Patent 7,531,518

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