CA2650399A1 - Gpr119 receptor agonists in methods of increasing bone mass and of treating osteoporosis and other conditions characterized by low bone mass, and combination therapy relating thereto - Google Patents

Gpr119 receptor agonists in methods of increasing bone mass and of treating osteoporosis and other conditions characterized by low bone mass, and combination therapy relating thereto Download PDF

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CA2650399A1
CA2650399A1 CA002650399A CA2650399A CA2650399A1 CA 2650399 A1 CA2650399 A1 CA 2650399A1 CA 002650399 A CA002650399 A CA 002650399A CA 2650399 A CA2650399 A CA 2650399A CA 2650399 A1 CA2650399 A1 CA 2650399A1
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bone
individual
gpr119 agonist
loss
disease
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CA2650399C (en
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Zhi-Liang Chu
James N. Leonard
Juerg Lehmann
Robert M. Jones
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Arena Pharmaceuticals Inc
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Arena Pharmaceuticals, Inc.
Zhi-Liang Chu
James N. Leonard
Juerg Lehmann
Robert M. Jones
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Publication of CA2650399A1 publication Critical patent/CA2650399A1/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to the use of GPR119 receptor agonists for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. The present invention further relates to the use of a GPR119 receptor agonist in combination with a dipeptidyl peptidase IV (DPP-IV) inhibitor for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. A GPR119 receptor agonist and the combination of a GPR119 receptor agonist and a DPP-IV inhibitor promote bone formation in an individual.

Claims (74)

1. A method of treating or preventing a condition characterized by low bone mass comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist, wherein said treatment or prevention comprises increasing a GIP level in the individual.
2. A method of treating or preventing a condition characterized by low bone mass comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a pharmaceutically acceptable carrier, wherein said treatment or prevention comprises increasing a GIP level in the individual.
3. The method of claim 1 or claim 2, wherein the condition characterized by low bone mass is selected from the group consisting of osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine, and loss of height.
4. The method of claim 1 or claim 2, wherein the condition characterized by low bone mass is osteoporosis.
5. A method of increasing bone mass comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist, wherein said method comprises increasing a GIP level in the individual.
6. A method of increasing bone mass comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a pharmaceutically acceptable carrier, wherein said method comprises increasing a GIP level in the individual.
7. The method of claim 5 or claim 6, wherein the individual has a bone mineral density (BMD) greater than 1 standard deviations (T-score < -1) below the young adult reference mean.
8. A method of treating bone fracture comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist.
9. A method of treating bone fracture comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a pharmaceutically acceptable carrier.
10. The method of claim 8 or claim 9, wherein the individual has a traumatic bone fracture, a long-term bone fracture, or an osteoporotic bone fracture.
11. A method of treating a bone disease comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist, wherein said treatment comprises increasing a GIP
level in the individual.
12. A method of treating a bone disease comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a pharmaceutically acceptable carrier, wherein said treatment comprises increasing a GIP level in the individual.
13. The method of claim 11 or claim 12, wherein the bone disease is selected from the group consisting of osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine, and loss of height.
14. The method of claim 11 or claim 12 wherein the bone disease is osteoporosis.
15. A method of enhancing bone healing following facial reconstruction, maxillary reconstruction, mandibular reconstruction, periodontal disease or tooth extraction, enhanced long bone extension, enhanced prosthetic ingrowth or increased bone synostosis comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist.
16. A method of enhancing bone healing following facial reconstruction, maxillary reconstruction, mandibular reconstruction, periodontal disease or tooth extraction, enhanced long bone extension, enhanced prosthetic ingrowth or increased bone synostosis comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a pharmaceutically acceptable carrier.
17. A method of treating or preventing a condition characterized by low bone mass, wherein said condition is selected from the group consisting of Primary osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine and loss of height comprising administering to an individual in need thereof a therapeutic amount of a GPR119 agonist.
18. The method of any one of claims 1 to 17, wherein the individual is human.
19. The method of any one of claims 1 to 18, wherein the GPR119 agonist is an agonist of human GPR119.
20 The method of any one of claims 1 to 19, wherein the GPR119 agonist is a small molecule.
21. The method of any one of claims 1 to 20, wherein the GPR119 agonist has an EC50 of less than about 10 µM.
22. Use of a GPR119 agonist for the manufacture of a medicament for the treatment or prevention of a condition characterized by low bone mass in an individual, wherein said treatment or prevention comprises increasing a GIP level in the individual.
23. The use of claim 22, wherein the condition characterized by low bone mass is selected from the group consisting of osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine, and loss of height.
24. The use of claim 22 or claim 23, wherein the condition characterized by low bone mass is osteoporosis.
25. Use of a GRP119 agonist for the manufacture of a medicament for increasing bone mass in an individual, wherein said increase in bone mass comprises increasing a GIP level in the individual.
26. The use of claim 25, wherein the individual has a bone mineral density (BMD) greater than 1 standard deviations (T-score < -1) below the young adult reference mean.
27. Use of a GPR119 agonist for the manufacture of a medicament for treating bone fracture in an individual.
28 The use of claim 27, wherein the bone fracture is traumatic bone fracture, long-term bone fracture, or osteoporotic bone fracture.
29. Use of a GPR119 agonist for the manufacture of a medicament for treating a bone disease in an individual, wherein said treatment comprises increasing a GIP level in the individual.
30. The use of claim 29, wherein the bone disease is selected from the group consisting of osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine, and loss of height.
31. The use of claim 29 or claim 30 wherein the bone disease is osteoporosis.
32. Use of a GPR119 agonist for the manufacture of a medicament for enhancing bone healing following facial reconstruction, maxillary reconstruction, mandibular reconstruction, periodontal disease or tooth extraction, enhanced long bone extension, enhanced prosthetic ingrowth or increased bone synostosis in an individual.
33. Use of a GPR119 agonist for the manufacture of a medicament for treating or preventing a condition characterized by low bone mass, wherein said condition is selected from the group consisting of Primary osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine and loss of height.
34. The use of any one of claims 22 to 33, wherein the individual is a human.
35. The use of any one of claims 22 to 34, wherein the GPR119 agonist is an agonist of human GPR119.
36. The use of any one of claims 22 to 35, wherein the GPR119 agonist is a small molecule.
37. The use of any one of claims 22 to 36, wherein the GPR119 agonist has an EC50 of less than about 10 µM.
38. A method of treating or preventing a condition by low bone mass comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist and a DPP-IV
inhibitor, wherein said treatment or prevention comprises increasing a GIP level in the individual.
39. A method of treating or preventing a condition by low bone mass comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a DPP-IV inhibitor and a pharmaceutically acceptable carrier, wherein said treatment or prevention comprising increases a GIP level in the individual.
40. The method of claim 38 or claim 39, wherein the condition characterized by low bone mass is selected from the group consisting of osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine, and loss of height.
41. The method or use of claim 38 or claim 39, wherein the condition characterized by low bone mass is osteoporosis.
42. A method of increasing bone mass comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist and a DPP-IV inhibitor.
43. A method of increasing bone mass comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a DPP-IV
inhibitor and a pharmaceutically acceptable carrier, wherein said method comprises increasing a GIP level in the individual.
44. The method of claim 42 to 43, wherein the individual has a bone mineral density (BMD) greater than 1 standard deviations (T-score < -1) below the young adult reference mean.
45. A method of treating bone fracture comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist and a DPP-IV inhibitor.
46. A method of treating bone fracture comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a DPP-IV
inhibitor and a pharmaceutically acceptable carrier.
47. The method of claim 45 or claim 46, wherein the individual has a traumatic bone fracture, a long-term bone fracture, or an osteoporotic bone fracture.
48. A method of treating bone disease comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist and a DPP-IV inhibitor, wherein said treatment comprises increasing a GIP level in the individual.
49. A method of treating bone disease comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a DPP-IV
inhibitor and a pharmaceutically acceptable carrier, wherein the treatment comprises increasing a GIP level in the individual.
50. The method of claim 48 or claim 49, wherein the bone disease is selected from the group consisting of osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine, and loss of height.
51. The method of claim 48 or claim 49 wherein the bone disease is osteoporosis.
52. A method of enhancing bone healing following facial reconstruction, maxillary reconstruction, mandibular reconstruction, periodontal disease or tooth extraction, enhanced long bone extension, enhanced prosthetic ingrowth or increased bone synostosis comprising administering to an individual in need thereof a therapeutically effective amount of a GPR119 agonist and a DPP-IV inhibitor.
53. A method of enhancing bone healing following facial reconstruction, maxillary reconstruction, mandibular reconstruction, periodontal disease or tooth extraction, enhanced long bone extension, enhanced prosthetic ingrowth or increased bone synostosis comprising administering to an individual in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a GPR119 agonist and a DPP-IV inhibitor and a pharmaceutically acceptable carrier.
54. A method of treating or preventing a condition characterized by low bone mass, wherein said condition is selected from the group consisting of Primary osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine and loss of height comprising administering to an individual in need thereof a therapeutically amount of a GPR119 agonist and a DPP-IV
inhibitor.
55. The method of any one of claims 38 to 54, wherein the individual is a human.
56. The method of any one of claims 38 to 55, wherein the GPR119 agonist is an agonist of human GPR119 and/or the DPP-IV inhibitor is an inhibitor of human DPP-IV.
57. The method of any one of claims 38 to 56, wherein the GPR119 agonist is a small molecule and/or the DPP-IV inhibitor is a small molecule.
58. The method of any one of claims 38 to 57, wherein the GPR119 agonist has an EC50 of less than about 10 µM and/or the DPP-IV
inhibitor has an IC50 of less than about 10 µM.
59. Use of a GPR119 agonist and a DPP-IV inhibitor for the manufacture of a medicament for the treatment or prevention of a condition characterized by low bone mass in an individual, wherein said treatment or prevention comprises increasing a GIP level in the individual.
60. The use of claim 59, wherein the condition characterized by low bone mass is selected from the group consisting of osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine, and loss of height.
61. The use of claim 59 or claim 60, wherein the condition characterized by low bone mass is osteoporosis.
62. Use of a GPR119 agonist and a DPP-IV inhibitor for the manufacture of a medicament for the increasing bone mass in an individual, wherein said increasing bone mass comprises increasing a GIP level in the individual.
63. The use of claim 62, wherein the individual has a bone mineral density (BMD) greater than 1 standard deviations (T-score < -1) below the young adult reference mean.
64. Use of a GPR119 agonist and a DPP-IV inhibitor for the manufacture of a medicament for treating bone fracture in an individual.
65. The use of claim 64, wherein the bone fracture is traumatic bone fracture, long-term bone fracture, or osteoporotic bone fracture.
66. Use of a GPR119 agonist and a DPP-IV inhibitor for the manufacture of a medicament for treating a bone disease in an individual, wherein said treatment comprises increasing a GIP level in the individual.
67. The use of claim 66, wherein the bone disease is selected from the group consisting of osteopenia, osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions, curvature of the spine, and loss of height.
68. The use of claim 66 or claim 67 wherein the bone disease is osteoporosis.
69. Use of a GPR119 agonist and a DPP-IV inhibitor for the manufacture of a medicament for enhancing bone healing following facial reconstruction, maxillary reconstruction, mandibular reconstruction, periodontal disease or tooth extraction, enhanced long bone extension, enhanced prosthetic ingrowth or increased bone synostosis in an individual.
70. Use of a GPR119 agonist and a DPP-IV inhibitor for the manufacture of a medicament for treating or preventing a condition characterized by low bone mass, wherein said condition is selected from the group consisting of Primary osteoporosis, rheumatoid arthritis, osteoarthritis, periodontal disease, alveolar bone loss, osteotomy bone loss, childhood idiopathic bone loss, Paget's disease, bone loss due to metastatic cancer, osteolytic lesions curvature of the spine and loss of height.
71. The use of any one of claims 59 to 70, wherein the individual is a human.
72. The use of any one of claims 59 to 71, wherein GPR119 agonist is an agonist of human GPR119 and/or the DPP-IV inhibitor is an inhibitor of human DPP-IV.
73. The use of any one of claims 59 to 72, wherein GPR119 agonist is a small molecule and/or the DPP-IV inhibitor is a small molecule.
74. The use of any one of claims 59 to 73, wherein the GPR119 agonist has an EC50 of less than about 10 µM and/or the DPP-IV
inhibitor has an IC50 of less than about 10 µM.
CA2650399A 2006-04-11 2007-04-10 Gpr119 receptor agonists in methods of increasing bone mass and of treating osteoporosis and other conditions characterized by low bone mass, and combination therapy relating thereto Expired - Fee Related CA2650399C (en)

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Application Number Priority Date Filing Date Title
US79161306P 2006-04-11 2006-04-11
US60/791,613 2006-04-11
US83473706P 2006-07-31 2006-07-31
US60/834,737 2006-07-31
US85124406P 2006-10-12 2006-10-12
US60/851,244 2006-10-12
PCT/US2007/008926 WO2007120702A2 (en) 2006-04-11 2007-04-10 Use of gpr119 receptor agonists for increasing bone mass and for treating osteoporosis, and combination therapy relating thereto

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