Claims for Patent: 9,913,852

Summary for Patent: 9,913,852

Title:	Method of treating and preventing secondary hyperparathyroidism
Abstract:	The method of treating elevated blood levels of iPTH by increasing or maintaining blood concentrations of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in a patient by administering, as necessary, both Vitamin D repletion and Vitamin D hormone replacement therapies, is disclosed. The blood concentrations of 25-hydroxyvitamin D are increased to and maintained at or above 30 ng/mL, and blood concentrations of 1,25-dihydroxyvitamin D are increased to or maintained within a patient\'s normal historical physiological range for 1,25-dihydroxyvitamin D without causing substantially increased risk of hypercalcemia, hyperphosphatemia or over suppression of plasma iPTH in the patient. The blood levels of 25-hydroxyvitamin D are maintained at or above 30 ng/mL between doses of Vitamin D repletion therapies, and the blood levels of 1,25-dihydroxyvitamin D are maintained in the patient\'s normal historical physiological range between doses of Vitamin D hormone replacement therapies. In one aspect, the disclosure includes methods wherein the blood concentration of 25-hydroxyvitamin D during treatment comprises predominantly 25-hydroxyvitamin D.sub.3, and/or wherein the method includes administering predominantly or solely 25-hydroxyvitamin D.sub.3 for 25-hydroxyvitamin D repletion and/or maintenance.
Inventor(s):	Bishop; Charles W. (Miami Beach, FL), Crawford; Keith H. (Lone Tree, CO), Messner; Eric J. (Lake Forest, IL), Petkovich; P. Martin (Kingston, CA), Helvig; Christian F. (Markham, CA)
Assignee:	OPKO IRELAND GLOBAL HODLINGS, LTD. (Grand Cayman, KY) OPKO RENAL, LLC (Miami, FL)
Application Number:	15/220,963
Patent Claims:	1. A method of treating or preventing secondary hyperparathyroidism in a human patient comprising administering to the patient both a 25-hydroxyvitamin D compound and an active Vitamin D hormone or active Vitamin D hormone analog, wherein the 25-hydroxyvitamin D compound is administered in an extended release composition comprising 1 .mu.g to 100 .mu.g 25-hydroxyvitamin D.sub.3 in a unit dose. 2. The method of claim 1, comprising administering the 25-hydroxyvitamin D compound and the active Vitamin D hormone or active Vitamin D hormone analog in an amount effective to lower plasma iPTH levels while avoiding supraphysiologic blood concentrations of 25-hydroxyvitamin D. 3. The method of claim 1, comprising administering the 25-hydroxyvitamin D compound and the active Vitamin D hormone or active Vitamin D hormone analog in an amount effective to decrease elevated plasma iPTH levels while avoiding substantially increased risk of hypercalcemia, hyperphosphatermia, or over suppression of plasma iPTH. 4. The method of claim 1, wherein the extended release composition reduces the maximum serum concentration of 25-hydroxyvitamin D.sub.3 in a dose interval (Cmax) compared to an equivalent amount of 25-hydroxyvitamin D.sub.3 administered by bolus IV injection and/or an equivalent immediate-release, oral dosage form. 5. The method of claim 1, wherein the extended release composition increases the time for the plasma concentration of 25-hydroxyvitamin D.sub.3 to reach its maximum in a dose interval following administration (Tmax) compared to an equivalent amount of 25-hydroxyvitamin D.sub.3 administered by bolus IV injection and/or an equivalent immediate-release, oral dosage form. 6. The method of claim 1, wherein the extended release composition reduces the ratio of the maximum serum concentration within 24 hours after administration of 25-hydroxyvitamin D.sub.3 to the concentration 24 hours after administration (Cmax.sub.24hr/C.sub.24hr) compared to an equivalent amount of 25-hydroxyvitamin D.sub.3 administered by bolus IV injection and/or an equivalent immediate-release, oral dosage form. 7. The method of claim 1, comprising administering the 25-hydroxyvitamin D compound and the active Vitamin D hormone or active Vitamin D hormone analog in an amount effective to lower the patient's plasma parathyroid hormone level by at least 30%. 8. The method of claim 1, comprising administering the 25-hydroxyvitamin D compound and the active Vitamin D hormone or active Vitamin D hormone analog in an amount effective to increase to or maintain the patient's blood level of 25-hydroxyvitamin D at or above 30 ng/mL. 9. The method of claim 1, comprising administering the 25-hydroxyvitamin D compound and the active Vitamin D hormone or active Vitamin D hormone in an amount effective to increase to or maintain the patient's blood level of 1,25-dihydroxyvitamin D at or above 30 .mu.g/mL. 10. The method of claim 1, wherein the active Vitamin D hormone or active Vitamin D hormone analog is selected from 1,25-dihydroxyvitamin D.sub.2, 1,25-dihydroxyvitamin D.sub.3, 1,25-dihydroxyvitamin D.sub.4, 1.alpha.-hydroxyvitamin D.sub.2, 1.alpha.-hydroxyvitamin D.sub.3, and combinations thereof. 11. The method of claim 1, wherein the active Vitamin D hormone or active Vitamin D hormone analog is selected from 1,25-dihydroxyvitamin D.sub.3, 1.alpha.-hydroxyvitamin D.sub.2, and an analog of 1,25-dihydroxyvitamin D.sub.2. 12. The method of claim 1, wherein the active Vitamin D hormone or active Vitamin D hormone analog is administered in an amount from 0.1 .mu.g to 10 .mu.g per unit dose. 13. The method of claim 1, wherein the 25-hydroxyvitamin D compound and active vitamin D hormone are administered daily. 14. The method of claim 1, wherein the 25-hydroxyvitamin D compound and active vitamin D hormone are administered one to three times a week. 15. The method of claim 1, wherein the 25-hydroxyvitamin D compound and active vitamin D hormone are administered daily or one to three times per week for at least four weeks. 16. The method of claim 1, wherein the 25-hydroxyvitamin D compound and active vitamin D hormone are administered orally. 17. The method of claim 1, wherein the patient has Chronic Kidney Disease Stage 3, Stage 4, or Stage 5. 18. The method of claim 17, comprising administering the 25-hydroxyvitamin D compound and the active Vitamin D hormone or active Vitamin D hormone analog in an amount effective to lower the patient's plasma PTH level to the target range for the CKD stage. 19. The method of claim 1, wherein the patient has is receiving hemodialysis. 20. A method of increasing or maintaining blood concentrations of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D comprising administering to the patient both a 25-hydroxyvitamin D compound and an active Vitamin D hormone or active Vitamin D hormone analog, wherein the 25-hydroxyvitamin D compound is administered in an extended release composition comprising 1 .mu.g to 100 .mu.g 25-hydroxyvitamin D.sub.3 in a unit dose, and wherein blood concentrations of 25-hydroxyvitamin D are increased to or maintained at or above 30 ng/mL while avoiding supraphysiologic levels and blood concentrations of 1,25-dihydroxyvitamin D are increased to or maintained at or above 25 .mu.g/mL, without causing substantially increased risk of hypercalcemia.

Details for Patent 9,913,852

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2026-06-21