Claims for Patent: 8,440,193

Summary for Patent: 8,440,193

Title:	Method for inhibiting bone resorption
Abstract:	The invention is directed to a method of inhibiting bone resorption. The method comprises administering to a human an amount of sclerostin inhibitor that reduces a bone resorption marker level for at least 2 weeks. The invention also provides a method of monitoring anti-sclerostin therapy comprising measuring one or more bone resorption marker levels, administering a sclerostin binding agent, then measuring the bone resorption marker levels. Also provided is a method of increasing bone mineral density; a method of ameliorating the effects of an osteoclast-related disorder; a method of treating a bone-related disorder by maintaining bone density; and a method of treating a bone-related disorder in a human suffering from or at risk of hypocalcemia or hypercalcemia, a human in which treatment with a parathyroid hormone or analog thereof is contraindicated, or a human in which treatment with a bisphosphonate is contraindicated.
Inventor(s):	Padhi; Ian Desmond (Newbury Park, CA), Jang; Graham Richard (Santa Monica, CA)
Assignee:	Amgen Inc. (Thousand Oaks, CA)
Application Number:	13/090,075
Patent Claims:	1. A method for inhibiting bone resorption in a human, the method comprising administering to the human an amount from about 1 mg/kg to about 8 mg/kg of a monoclonal anti-sclerostin antibody or fragment thereof that demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-9 M, wherein the monoclonal anti-sclerostin antibody or fragment thereof cross-blocks the binding of an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80 to sclerostin and/or is cross-blocked from binding to sclerostin by an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80, wherein bone resorption is inhibited. 2. The method of claim 1, wherein the amount of anti-sclerostin antibody or fragment thereof does not result in hypocalcemia or hypercalcemia. 3. The method of claim 1, wherein an amount of anti-sclerostin antibody or fragment thereof is administered to the human once every two weeks. 4. The method of claim 1, wherein an amount of anti-sclerostin antibody or fragment thereof is administered to the human once a month. 5. The method of claim 1, wherein the anti-sclerostin antibody or fragment thereof comprises CDRH-1, CDR-H2, CDR-H3, CDR-L1 CDR-L2 and CDR-L3 wherein CDR-H1 is SEQ ID NO:245, CDR-H2 is SEQ ID NO:246, CDR-H3 is SEQ ID NO:247, CDR-L1 is SEQ ID NO:78, CDR-L2 is SEQ ID NO:79 and CDR-L3 is SEQ ID NO:80. 6. The method of claim 1, wherein the anti-sclerostin antibody is a human antibody, a humanized antibody, or a chimeric antibody. 7. A method for increasing bone mineral density in a human, the method comprising administering to the human an amount from about 1 mg/kg to about 8 mg/kg of a monoclonal anti-sclerostin antibody or fragment thereof that demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-9 M, wherein the monoclonal anti-sclerostin antibody or fragment thereof cross-blocks the binding of an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80 to sclerostin and/or is cross-blocked from binding to sclerostin by an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80, wherein bone mineral density is increased. 8. The method of claim 7, wherein hip, spine, wrist, finger, shin bone and/or heel bone mineral density is increased by at least about 1%. 9. The method of claim 8, wherein bone mineral density in the spine is increased by at least about 1%. 10. The method of claim 7, wherein bone mineral density is increased to the range of about 1 to 2.5 standard deviations below the normal bone mineral density of a healthy young adult. 11. The method of claim 7, wherein bone mineral density is increased to the range of about 0 to 1 standard deviations below the normal bone mineral density of a healthy young adult. 12. The method of claim 7, wherein an amount of anti-sclerostin antibody or fragment thereof is administered to the human once every two weeks. 13. The method of claim 7, wherein an amount of anti-sclerostin antibody or fragment thereof is administered to the human once a month. 14. The method of claim 7, wherein the anti-sclerostin antibody or fragment thereof comprises CDRH-1, CDR-H2, CDR-H3, CDR-L1 CDR-L2 and CDR-L3 wherein CDR-H1 is SEQ ID NO:245, CDR-H2 is SEQ ID NO:246, CDR-H3 is SEQ ID NO:247, CDR-L1 is SEQ ID NO:78, CDR-L2 is SEQ ID NO:79 and CDR-L3 is SEQ ID NO:80. 15. The method of claim 7, wherein the anti-sclerostin antibody is a human antibody, a humanized antibody, or a chimeric antibody. 16. A method for treating a bone-related disorder in a human, the method comprising (a) administering to the human a monoclonal anti-sclerostin antibody or fragment thereof that demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-9 M in an amount from about 1 mg/kg to about 8 mg/kg for a first period of time, wherein the amount is effective to increase bone mineral density at the hip, spine, wrist, finger, shin bone and/or heel by at least about 3%, and (b) administering to the human the monoclonal anti-sclerostin antibody or fragment thereof in an amount of from about 1 mg/kg to about 8 mg/kg for a second period of time effective to maintain bone mineral density, wherein the monoclonal anti-sclerostin antibody or fragment thereof cross-blocks the binding of an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80 to sclerostin and/or is cross-blocked from binding to sclerostin by an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80. 17. The method of claim 16, wherein the first period of time is 3 months or less. 18. The method of claim 16, wherein the second period of time is at least 6 months. 19. The method of claim 16, wherein bone mineral density in the spine is increased by at least about 3%. 20. The method of claim 16, wherein an amount of anti-sclerostin antibody or fragment thereof is administered to the human once every two weeks. 21. The method of claim 16, wherein an amount of anti-sclerostin antibody or fragment thereof is administered to the human once a month. 22. The method of claim 16 in which the bone-related disorder is selected from the group consisting of achondroplasia, cleidocranial dysostosis, enchondromatosis, fibrous dysplasia, Gaucher's Disease, hypophosphatemic rickets, Marfan's syndrome, multiple hereditary exotoses, neurofibromatosis, osteogenesis imperfecta, osteopetrosis, osteopoikilosis, sclerotic lesions, pseudoarthrosis, pyogenic osteomyelitis, periodontal disease, anti-epileptic drug induced bone loss, primary and secondary hyperparathyroidism, familial hyperparathyroidism syndromes, weightlessness induced bone loss, osteoporosis in men, postmenopausal bone loss, osteoarthritis, renal osteodystrophy, infiltrative disorders of bone, oral bone loss, osteonecrosis of the jaw, juvenile Paget's disease, melorheostosis, metabolic bone diseases, mastocytosis, sickle cell anemia/disease, organ transplant related bone loss, kidney transplant related bone loss, systemic lupus erythematosus, ankylosing spondylitis, epilepsy, juvenile arthritides, thalassemia, mucopolysaccharidoses, Fabry Disease, Turner Syndrome, Down Syndrome, Klinefelter Syndrome, leprosy, Perthes' Disease, adolescent idiopathic scoliosis, infantile onset multi-system inflammatory disease, Winchester Syndrome, Menkes Disease, Wilson's Disease, ischemic bone disease, Legg-Calve-Perthes disease, regional migratory osteoporosis, anemic states, conditions caused by steroids, glucocorticoid-induced bone loss, heparin-induced bone loss, bone marrow disorders, scurvy, malnutrition, calcium deficiency, osteoporosis, osteopenia, alcoholism, chronic liver disease, postmenopausal state, chronic inflammatory conditions, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, inflammatory colitis, Crohn's disease, oligomenorrhea, amenorrhea, pregnancy, diabetes mellitus, hyperthyroidism, thyroid disorders, parathyroid disorders, Cushing's disease, acromegaly, hypogonadism, immobilization or disuse, reflex sympathetic dystrophy syndrome, regional osteoporosis, osteomalacia, bone loss associated with joint replacement, HIV associated bone loss, bone loss associated with loss of growth hormone, bone loss associated with cystic fibrosis, chemotherapy associated bone loss, tumor induced bone loss, cancer-related bone loss, hormone ablative bone loss, multiple myeloma, drug-induced bone loss, anorexia nervosa, disease associated facial bone loss, disease associated cranial bone loss, disease associated bone loss of the jaw, disease associated bone loss of the skull, bone loss associated with aging, facial bone loss associated with aging, cranial bone loss associated with aging, jaw bone loss associated with aging, skull bone loss associated with aging, and bone loss associated with space travel. 23. The method of claim 16, wherein the anti-sclerostin antibody or fragment thereof comprises CDRH-1, CDR-H2, CDR-H3, CDR-L1 CDR-L2 and CDR-L3 wherein CDR-H1 is SEQ ID NO:245, CDR-H2 is SEQ ID NO:246, CDR-H3 is SEQ ID NO:247, CDR-L1 is SEQ ID NO:78, CDR-L2 is SEQ ID NO:79 and CDR-L3 is SEQ ID NO:80. 24. The method of claim 16, wherein the anti-sclerostin antibody is a human antibody, a humanized antibody, or a chimeric antibody. 25. A method of treating a bone-related disorder in a human suffering from or at risk of hypocalcemia or hypercalcemia, the method comprising administering to the human a monoclonal anti-sclerostin antibody or fragment thereof that demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-9 M in a therapeutically effective amount from about 1 mg/kg to about 8 mg/kg, wherein the monoclonal anti-sclerostin antibody or fragment thereof cross-blocks the binding of an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80 to sclerostin and/or is cross-blocked from binding to sclerostin by an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80. 26. The method of claim 25, wherein the hypocalcemia or hypercalcemia results from chronic kidney disease, renal failure, primary or secondary hyperparathyroidism, pseudohyperparathyroidism, hypoparathyroidism, pseudohypoparathyroidism, magnesium depletion, severe hypermagnesemia, vitamin D deficiency, hyperphosphatemia, acute pancreatitis, hungry bone syndrome, chelation, osteoblastic metastases, sepsis, surgery, chemotherapy, neoplasia syndrome, hypoparathyroidism, familial hypocalciuric hypercalcemia, sarcoidosis, tuberculosis, berylliosis, histoplasmosis, Candidiasis, Coccidioidomycosis, histiocytosis X, Hodgkin's or Non-Hodgkin's lymphoma, Crohn's disease, Wegener's granulomatosis, pneumonia, silicone-induced granulomas, administration of thiazide diuretics or lithium, or immobilization. 27. A method of treating a bone-related disorder in (a) a human in which treatment with a parathyroid hormone or analog thereof is contraindicated or (b) a human in which treatment with bisphosphonate is contraindicated, the method comprising administering to the human a monoclonal anti-sclerostin antibody or fragment thereof that demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1.times.10.sup.-9 M in a therapeutically effective amount from about 1 mg/kg to about 8 mg/kg, wherein the monoclonal anti-sclerostin antibody or fragment thereof cross-blocks the binding of an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80 to sclerostin and/or is cross-blocked from binding to sclerostin by an antibody comprising heavy chains comprising SEQ ID NOs: 245-247 and light chains comprising SEQ ID NOs: 78-80. 28. The method of claim 7, wherein the anti-sclerostin antibody or fragment thereof is administered at about 2 mg/kg. 29. The method of claim 28, wherein the anti-sclerostin antibody or fragment thereof is administered once every two weeks. 30. The method of claim 28, wherein the anti-sclerostin antibody or fragment thereof is administered once per month. 31. The method of claim 14, wherein the anti-sclerostin antibody or fragment thereof is administered at about 2 mg/kg. 32. The method of claim 14, wherein the anti-sclerostin antibody or fragment thereof is administered once every two weeks. 33. The method of claim 14, wherein the anti-sclerostin antibody or fragment thereof is administered once per month. 34. The method of claim 7, wherein the human is a post-menopausal woman. 35. The method of claim 7, wherein the human is suffering from osteoporosis. 36. The method of claim 7, comprising administering to said human from about 1 mg/kg to about 3 mg/kg of the anti-sclerostin antibody or fragment thereof. 37. The method of claim 7, wherein the anti-sclerostin antibody or fragment thereof is administered to said human in an amount from about 70 mg to about 450 mg. 38. The method of claim 37, wherein the amount of anti-sclerostin antibody or fragment thereof administered to said human is about 70 mg. 39. The method of claim 37, wherein the amount of anti-sclerostin antibody or fragment thereof administered to said human is about 140 mg. 40. The method of claim 37, wherein the amount of anti-sclerostin antibody or fragment thereof administered to said human is about 210 mg. 41. The method of claim 1, wherein the anti-sclerostin antibody or fragment thereof is administered to said human in an amount from about 70 mg to about 450 mg. 42. The method of claim 16, wherein the human is a post-menopausal woman. 43. The method of claim 16, wherein the human is suffering from osteoporosis. 44. The method of claim 34, wherein the anti-sclerostin antibody or fragment thereof is administered to said human in an amount from about 70 mg to about 450 mg. 45. The method of claim 35, wherein the anti-sclerostin antibody or fragment thereof is administered to said human in an amount from about 70 mg to about 450 mg. 46. The method of claim 42, wherein the anti-sclerostin antibody or fragment thereof is administered to said human in an amount from about 70 mg to about 450 mg. 47. The method of claim 43, wherein the anti-sclerostin antibody or fragment thereof is administered to said human in an amount from about 70 mg to about 450 mg.

Details for Patent 8,440,193

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2025-05-03