Claims for Patent: 12,403,182

Summary for Patent: 12,403,182

Title:	Liquid pharmaceutical formulations of PTH conjugates
Abstract:	A liquid pharmaceutical formulation, wherein the pharmaceutical formulation comprises a PTH conjugate, a buffering agent, an isotonicity agent, a preservative and optionally an antioxidant and wherein the PTH conjugate comprises a PTH moiety that is covalently and reversibly conjugated to a water-soluble carrier moiety.
Inventor(s):	Anja R. H. Skands, Felix Cleemann, Michael Duelund Sørensen, Julia Baron, Eric Hoffmann, Kennett Sprogøe
Assignee:	Ascendis Pharma Bone Diseases AS
Application Number:	US17/428,608
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,403,182
Patent Claims:	1. A liquid pharmaceutical formulation, wherein the pharmaceutical formulation comprises a PTH conjugate of formula or a pharmaceutically acceptable salt thereof, wherein the unmarked dashed line indicates attachment by an amide bond to an N-terminal amine of a PTH moiety, which is PTH1-34 (SEQ ID NO:51); and the dashed line marked with the asterisk indicates attachment to a moiety wherein m and p are independently an integer from 400-500, succinic acid, D-mannitol and m-cresol, wherein the PTH moiety is at about 0.3 mg/ml mg/ml, the succinic acid is at about 1.18 mg/ml, the D-mannitol is at about 41.7 mg/ml, and the m-cresol is at about 2.5 mg/ml and wherein the pH is about 4.0, wherein about indicates variation of +/−10% of a stated value. 2. A method of manufacturing the liquid pharmaceutical formulation of claim 1, wherein the method comprises the steps of (i) admixing the PTH conjugate with the succinic acid, D-mannitol and m-cresol; (ii) adjusting the pH of the admixture of step (i); (iii) optionally, filtering the admixture from step (ii); (iv) transferring amounts of the admixture from step (ii) or (iii) equivalent to the desired number of dosages into a container; (v) sealing the container; and wherein the order of steps (ii) and (iii) may optionally be reversed. 3. The method of manufacturing of claim 2, wherein steps (ii) and (iii) are not reversed. 4. A method of treating, controlling, delaying or preventing in a patient one or more diseases which can be treated by PTH, the method comprising administering to the patient a therapeutically pharmaceutical formulation of claim 1. 5. The method of claim 4, wherein the disease is selected from the group consisting of hypoparathyroidism, hyperphosphatemia, osteoporosis, fracture repair, osteomalacia, osteomalacia and osteoporosis in patients with hypophosphatasia, steroid-induced osteoporosis, male osteoporosis, arthritis, osteoarthritis, osteogenesis imperfecta, fibrous dysplasia, rheumatoid arthritis, Paget's disease, humoral hypercalcemia associated with malignancy, osteopenia, periodontal disease, bone fracture, alopecia, chemotherapy-induced alopecia and thrombocytopenia, chronic periodontitis, osteonecrosis of jaw and poorly healing fractures due to ALPL gene mutations. 6. The method of claim 4, wherein the disease is hypoparathyroidism. 7. The liquid pharmaceutical formulation of claim 1, wherein the PTH conjugate is of the formula wherein the unmarked dashed line indicates attachment by an amide bond to an N-terminal amine of a PTH moiety, which is PTH1-34 (SEQ ID NO:51); and the dashed line marked with the asterisk indicates attachment to a moiety wherein m and p are independently an integer from 400-500. 8. The liquid pharmaceutical formulation of claim 1, which is free of an antioxidant.