Opko Ireland Global Holdings, Limited

Opko Renal, LLC

Eirgen Pharma Ltd.

Cytochroma Inc.

Proventiv Therapeutics, LLC

Opko IP Holdings Ii, Inc.

Opko Ireland Global Hodlings, Ltd.

Cytochrama Inc.

Wisconsin Alumni Research Foundation

Aovatechnologies, Inc.

Christian F Helvig

P Martin Petkovich

Charles W Bishop

Eric J Messner

Keith H Crawford

Joel Z Melnick

Mark Eric Cook

Samir P Tabash

Martin Petkovich

Uttam Saha

Erica Hellestad

Martin P Petkovich

The invention relates to methods and compositions for reducing toxicity associated with administration of vitamin D3, its 25-hydroxylated and 1-hydroxylated forms, and analogs thereof.

Method of treating vitamin D insufficiency and deficiency

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, and/or wherein the method includes administering predominantly or solely 25-hydroxyvitamin Dfor 25-hydroxyvitamin D repletion and/or maintenance.

Method of treating and preventing secondary hyperparathyroidism

Methods for diagnosing, treating, and preventing catabolism-related vitamin D deficiency and related disorders, related compositions, apparatus and kits, are disclosed. A method involves measuring CYP24 expression and/or activity, or a proxy thereof such as FGF23 level, in a patient and correlating abnormally elevated CYP24 expression and/or activity with catabolism-related vitamin D deficiency or with susceptibility for catabolism-related vitamin D deficiency. In response to abnormally elevated CYP24 expression and/or activity, the method further includes administering a CYP24 inhibitor to the vitamin D deficient or at-risk patient, and preferably avoiding activation of the vitamin D binding receptor, such as by avoiding administration of active vitamin D compounds to such patients. Optionally, a vitamin D prohormone or prohormone can be administered.

Methods useful for vitamin D deficiency and related disorders

Methods and compositions for measuring the amount of vitamin D derivatives are disclosed. Fluorescence Resonance Energy Transfer (FRET) in combination with a modified ligand-binding domain of the vitamin D receptor (LBD-VDR) to measure vitamin D derivatives are also disclosed.

Methods and composition for measuring the amount of vitamin D derivatives

This invention relates to methods and small molecules having a phosphate group that can be used to inhibit phosphate transport and to treat or prevent diseases that are related to disorders in the maintenance of normal serum phosphate levels.

Phosphate management with small molecules

Methods and composition for measuring the amount of Vitamin D derivatives

The a 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, and/or wherein the method includes administering predominantly or solely 25-hydroxyvitamin Dfor 25-hydroxyvitamin D repletion and/or maintenance.

Growing community of inventors

Markham, Canada

Christian F Helvig