Claims for Patent: 7,879,322

Summary for Patent: 7,879,322

Title:	Compositions and methods for use for antibodies against sclerostin
Abstract:	The present invention relates to antibodies against sclerostin and compositions and methods of use for said antibodies to treat disease related to bone abnormalities such as osteoporosis. An embodiment of the invention herein provides an antibody or a functional protein comprising an antigen-binding portion of said antibody for a target in sclerostin polypeptide, characterized in that the antibody or functional protein specifically binds to sclerostin polypeptide and can increase at least one of bone formation, bone mineral density, bone mineral content, bone mass, bone quality and bone strength in a mammal.
Inventor(s):	Kneissel; Michaela (Basel, CH), Halleux; Christine (Dornach, CH), Hu; Shou-Ih (New Providence, NJ), Diefenbach-Streiber; Beate (Windach, DE), Prassler; Josef (Germering, DE)
Assignee:	Novartis AG (Basel, CH)
Application Number:	12/249,050
Patent Claims:	1. An isolated antibody that binds to a sclerostin polypeptide, comprising: (a) a heavy chain variable region CDR1 comprising an amino acid sequence consisting of SEQ ID NO: 4; (b) a heavy chain variable region CDR2 comprising an amino acid sequence consisting of SEQ ID NO: 15; (c) a heavy chain variable region CDR3 comprising an amino acid sequence consisting of SEQ ID NO: 26; (d) a light chain variable region CDR1 comprising an amino acid sequence consisting of SEQ ID NO: 37; (e) a light chain variable region CDR2 comprising an amino acid sequence consisting of SEQ ID NO: 48; and (f) a light chain variable region CDR3 comprising an amino acid sequence consisting of SEQ ID NO: 59. 2. The antibody according to claim 1, wherein said antibody binds to said sclerostin polypeptide with a K.sub.D less than 1 nM. 3. The antibody according to claim 1, wherein said antibody blocks the inhibitory effect of sclerostin in a cell based Wnt signalling assay. 4. The antibody according to claim 3, wherein said antibody has an IC.sub.50 less than 100 nM as measured in a cell-based Wnt signalling assay in HEK293 cell lines in the presence of sclerostin. 5. The antibody according to claim 1, wherein said antibody blocks the inhibitory effect of sclerostin in a cell based mineralization assay. 6. The antibody according to claim 5, wherein said antibody has an IC.sub.50 less than 500 nM as measured in BMP2-induced mineralization assay in MC3T3 cells in the presence of sclerostin. 7. The antibody according to claim 1, wherein said antibody inhibits LRP6/sclerostin interaction in a solution inhibition assay. 8. The antibody according to claim 7, wherein said antibody has an IC.sub.50 less than 10 nM as measured in LRP6/sclerostin ELISA. 9. The antibody according to claim 1, wherein said antibody blocks the inhibitory effect of sclerostin on BMP6 induced Smad1 phosphorylation in a cell-based functional assay. 10. The antibody according to claim 9, wherein said antibody has an IC.sub.50 less than 500 nM as measured in BMP6 Smad1 phosphorylation assay in a MC3T3-E1 cell line in the presence of sclerostin. 11. The antibody according to claim 1, comprising a VH polypeptide amino acid sequence haying at least 95 percent identity to the amino acid sequence set forth as SEQ ID NO: 70. 12. The antibody according to claim 1, comprising a VL polypeptide amino acid sequence haying at least 95 percent identity to the amino acid sequence set forth as SEQ ID NO: 81. 13. The antibody according to claim 1, comprising a VL polypeptide sequence comprising the amino acid sequence set forth as SEQ ID NO:81 and a VH polypeptide sequence comprising the amino acid sequence set forth as SEQ ID NO: 70. 14. The antibody according to claim 1, comprising a full length heavy chain amino acid sequence having at least 95 percent sequence identity to the amino acid sequence set forth as SEQ ID NO: 114. 15. The antibody according to claim 1, comprising a full length light chain amino acid sequence having at least 95 percent sequence identity to the amino acid sequence set forth as SEQ ID NO: 125. 16. The antibody according to claim 1, comprising the heavy chain amino sequence set forth as SEQ ID NO: 114 and the light chain amino acid sequence set forth as SEQ ID NO: 125. 17. The antibody according to claim 1, comprising a VH polypeptide amino acid sequence having at least 95 percent sequence identity to the amino acid sequence set forth as SEQ ID NO: 70 and a VL polypeptide amino acid sequence having at least 95 percent identity to the amino acid sequence set forth as SEQ ID NO:81. 18. A pharmaceutical composition comprising the antibody according to claim 1. 19. The pharmaceutical composition of claim 18, in combination with one or more of a pharmaceutically acceptable excipient, diluent or carrier. 20. The pharmaceutical composition of claim 18, comprising at least one additional active ingredient. 21. An isolated polynucleotide sequence encoding the antibody of claim 1. 22. A cloning or expression vector comprising one or more polynucleotide sequences of claim 21. 23. The vector according to claim 22, wherein the vector comprises a nucleic acid sequence that encodes a VH polypeptide amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth as SEQ ID NO:70 and a VL polypeptide amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth as SEQ ID NO:81. 24. A host cell comprising the vector according to claim 22. 25. A process for the production of an antibody, comprising: (a) culturing a host cell comprising a cloning or expression vector comprising a polynucleotide encoding the antibody of claim 1, under conditions (i) wherein said vector expresses said polynucleotide; and (ii) wherein said polynucleotide is translated to said antibody; and (b) isolating said antibody. 26. A diagnostic kit comprising the antibody according to claim 1. 27. A method for identifying a cell or tissue expressing sclerostin, the method comprising contacting said cell or tissue with the antibody of claim 1, wherein said antibody further comprises a detectable label. 28. The method according to claim 27, wherein said label is radioactive, fluorescent, magnetic, paramagnetic, or chemiluminescent. 29. A method for increasing bone formation, comprising administering to a patient in need thereof a therapeutically effective amount of an antibody as set forth in claim 1. 30. A method for increasing bone mass, bone mineralization or bone density, comprising administering to a patient in need thereof a therapeutically effective amount of an antibody as set forth in claim 1. 31. The method according to claim 29, wherein said patient is suffering from a disease or disorder selected from the group consisting of primary and secondary osteoporosis, osteopenia, osteomalacia, osteogenesis imperfecta, avascular necrosis, fracture healing, implant healing, and bone loss. 32. The method according to claim 30, wherein said patient is suffering from a disease or disorder selected from the group consisting of primary and secondary osteoporosis, osteopenia, osteomalacia, osteogenesis imperfecta, avascular necrosis, fracture healing, implant healing, and bone loss. 33. The method according to claim 31, wherein said bone loss is due to HIV infection, cancers, or arthritis. 34. The method according to claim 30, wherein said antibody comprises a VH polypeptide amino acid sequence having at least 95 percent identity to the amino acid sequence set forth as SEQ ID NO: 70. 35. The method according to claim 30, wherein said antibody comprises a VL polypeptide amino acid sequence having at least 95 percent identity to the amino acid sequence set forth as SEQ ID NO: 81. 36. The method according to claim 30, wherein said antibody comprises a VH polypeptide amino acid sequence having at least 95 percent identity to the amino acid sequence set forth as SEQ ID NO: 70 and a VL polypeptide amino acid sequence having at least 95 percent identity to the amino acid sequence set forth as SEQ ID NO: 81. 37. The method according to claim 36, wherein said antibody comprises the VH polypeptide amino acid sequence set forth as SEQ ID NO: 70 and the VL polypeptide amino acid sequence set forth as SEQ ID NO: 81. 38. The method according to claim 30, further comprising administering an additional agent selected from the group consisting of a bisphosphonate, a parathyroid hormone, a parathyroid hormone releasing agent, alendronate, an LRP4 neutralizing antibody and a DKK-1 neutralizing antibody. 39. The method according to claim 38, wherein said additional agent is a bisphosphonate, and wherein said bisphosphonate is zoledronic acid. 40. The method according to claim 38, wherein said additional agent is a parathyroid hormone, and wherein said a parathyroid hormone is hPTH(1-34).

Details for Patent 7,879,322

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2027-10-12