Claims for Patent: 9,114,131

Summary for Patent: 9,114,131

Title:	Antibody targeting osteoclast-related protein Siglec-15
Abstract:	An isolated antibody capable of binding Siglec-15 which inhibits osteoclast formation and/or osteoclastic bone resorption, or a functional fragment thereof. The heavy chain of the antibody comprises a CDRH1 comprising a sequence having at least 80% sequence identity to SEQ ID NO: 106, a CDRH2 comprising a sequence having at least 80% sequence identity to SEQ ID NO: 107, and a CDRH3 comprising a sequence having at least 80% sequence identity to one of SEQ ID NOS: 35, 45, 55, 65 or 80. The light chain of the antibody comprises a CDRL1 comprising a sequence having at least 80% sequence identity to SEQ ID NO: 73 or 83, a CDRL2 comprising a sequence having at least 80% sequence identity to SEQ ID NO: 108, and a CDRL3 comprising a sequence having at least 80% sequence identity to one of SEQ ID NOS: 40, 50, 60, 70, 90, 100 or 109.
Inventor(s):	Watanabe; Ichiro (Tokyo, JP), Hiruma; Yoshiharu (Tokyo, JP), Tsuda; Eisuke (Tokyo, JP), Matsuoka; Tatsuji (Tokyo, JP), Ohtsuka; Toshiaki (Tokyo, JP), Takahashi; Tohru (Tokyo, JP), Agatsuma; Toshinori (Tokyo, JP), Miller; Sandra (Munich, DE), Muhlbacher; Robert (Martinsried/Planegg, DE), Baehs; Kathrin-Ladetzki (Martinsried/Planegg, DE), Runz; Steffen (Martinsried/Planegg, DE), Schubert; Ulrike (Munich, DE), Schuster; Ingrid (Munich, DE), Ponsel; Dirk (Germering, DE)
Assignee:	Daiichi Sankyo Company, Limited (Tokyo, JP)
Application Number:	13/877,779
Patent Claims:	1. An isolated antibody capable of binding Siglec-15 which inhibits osteoclast formation and/or osteoclastic bone resorption, or an antigen-binding fragment thereof comprising (a) a heavy chain comprising a CDRH1 comprising a sequence of SEQ ID NO: 106, a CDRH2 comprising a sequence of SEQ ID NO: 107, and a CDRH3 comprising a sequence of any one of SEQ ID NOS: 80, 55, 65, 35 or 45; and (b) a light chain comprising a CDRL1 comprising a sequence of SEQ ID NO: 83 or 73, a CDRL2 comprising a sequence of SEQ ID NO: 108, and a CDRL3 comprising a sequence of any one of SEQ ID NOS: 90, 60, 100, 70, 40, 50 or 109, wherein the antibody or antigen-binding fragment binds to and inhibits Siglec-15, thereby inhibiting osteoclast formation and/or osteoclastic bone resorption. 2. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the CDRH1 comprises a sequence of any one of SEQ ID NOS: 78, 53, 63, 33 or 43. 3. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the CDRH2 comprises a sequence of any one of SEQ ID NOS: 104, 54, 94, 64, 34, 44 or 79. 4. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the CDRL1 comprises a sequence of any one of SEQ ID NOS: 88, 58, 68, 38 or 48. 5. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the CDRL2 comprises a sequence of any one of SEQ ID NOS: 89, 59, 69, 39 or 49. 6. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the sequences of CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 in the antibody comprise: a) SEQ ID NOS: 103, 104, 105, 88, 89 and 90, respectively; b) SEQ ID NOS: 53, 54, 55, 58, 59 and 60, respectively; c) SEQ ID NOS: 93, 94, 95, 98, 99 and 100, respectively; d) SEQ ID NOS: 63, 64, 65, 68, 69 and 70, respectively; e) SEQ ID NOS: 33, 34, 35, 38, 39 and 40, respectively; f) SEQ ID NOS: 43, 44, 45, 48, 49 and 50, respectively; or g) SEQ ID NOS: 78, 79, 80, 88, 89 and 90, respectively. 7. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises: a heavy chain variable region selected from the group consisting of a1) an amino acid sequence comprising: amino acid residues 20 to 140 of SEQ ID NO: 102, amino acid residues 20 to 137 of SEQ ID NO: 52, amino acid residues 20 to 138 of SEQ ID NO: 92, amino acid residues 20 to 136 of SEQ ID NO: 62, amino acid residues 20 to 136 of SEQ ID NO: 32, amino acid residues 20 to 135 of SEQ ID NO: 42, or amino acid residues 20 to 138 of SEQ ID NO: 77; and a light chain variable region selected from the group consisting of b1) an amino acid sequence comprising: amino acid residues 20 to 134 of SEQ ID NO: 87, amino acid residues 20 to 129 of SEQ ID NO: 57, amino acid residues 20 to 133 of SEQ ID NO: 97, amino acid residues 20 to 129 of SEQ ID NO: 67, amino acid residues 20 to 129 of SEQ ID NO: 37, or amino acid residues 20 to 129 of SEQ ID NO: 47. 8. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises: a heavy chain selected from the group consisting of a1) an amino acid sequence comprising the sequence of any one of SEQ ID NOS: 102, 52, 92, 62, 32, 42 or 77; and a light chain selected from the group consisting of b1) an amino acid sequence comprising the sequence of any one of SEQ ID NOS: 87, 57, 97, 67, 37 or 47. 9. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody comprises a heavy chain consisting of an amino acid sequence comprising SEQ ID NO: 102, and a light chain consisting of an amino acid sequence comprising SEQ ID NO: 87. 10. The isolated antibody or functional fragment thereof according to claim 1, wherein the antibody comprises a heavy chain consisting of an amino acid sequence comprising SEQ ID NO: 52, and a light chain consisting of an amino acid sequence comprising SEQ ID NO: 57. 11. The isolated antibody or functional fragment thereof according to claim 1, wherein the antibody comprises a heavy chain consisting of an amino acid sequence comprising SEQ ID NO: 92, and a light chain consisting of an amino acid sequence comprising SEQ ID NO: 97. 12. The isolated antibody or functional fragment thereof according to claim 1, wherein the antibody comprises a heavy chain consisting of an amino acid sequence comprising SEQ ID NO: 62, and a light chain consisting of an amino acid sequence comprising SEQ ID NO: 67. 13. The isolated antibody or functional fragment thereof according to claim 1, wherein the antibody comprises a heavy chain consisting of an amino acid sequence comprising SEQ ID NO: 32, and a light chain consisting of an amino acid sequence comprising SEQ ID NO: 37. 14. The isolated antibody or functional fragment thereof according to claim 1, wherein the antibody comprises a heavy chain consisting of an amino acid sequence comprising SEQ ID NO: 42, and a light chain consisting of an amino acid sequence comprising SEQ ID NO: 47. 15. The isolated antibody or functional fragment thereof according to claim 1, wherein the antibody comprises a heavy chain consisting of an amino acid sequence comprising SEQ ID NO: 77, and a light chain consisting of an amino acid sequence comprising SEQ ID NO: 87. 16. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the antigen-binding fragment is selected from the group consisting of Fab, F(ab')2, Fab' and Fv. 17. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the antigen-binding fragment is a scFv. 18. A method for treating a patient suffering from abnormal bone metabolism comprising administering a therapeutically effective amount of the isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the abnormal bone metabolism is characterized by insufficient bone mass or density. 19. A pharmaceutical composition comprising at least one antibody or antigen-binding fragment thereof according to claim 1. 20. The pharmaceutical composition according to claim 19, wherein the composition is a therapeutic agent for abnormal bone metabolism, wherein the abnormal bone metabolism is characterized by insufficient bone mass or density. 21. A pharmaceutical composition for treating abnormal bone metabolism comprising at least one antibody or antigen-binding fragment thereof according to claim 1, and at least one member selected from the group consisting of bisphosphonates, active vitamin D.sub.3, calcitonin, hormones, ipriflavone, vitamin K.sub.2 (menatetrenone), calcium, PTH (parathyroid hormone), nonsteroidal anti-inflammatory agents, soluble TNF receptor, anti-TNF-.alpha. antibodies or antigen-binding fragments thereof, anti-PTHrP (parathyroid hormone-related protein) antibodies or antigen-binding fragments thereof, anti-IL-6 receptor antibodies or antigen-binding fragments thereof, anti-RANKL antibodies or antigen-binding fragments thereof, and OCIF (osteoclastogenesis inhibitory factor). 22. The method of claim 18, wherein the abnormal bone metabolism is selected from the group consisting of: osteoporosis, bone destruction accompanying rheumatoid arthritis, cancerous hypercalcemia, bone destruction accompanying multiple myeloma or cancer metastasis to bone, giant cell tumor, tooth loss due to periodontitis, osteolysis around a prosthetic joint, bone destruction in chronic osteomyelitis, Paget's disease of bone, renal osteodystrophy and osteogenesis imperfecta. 23. The method according to claim 22, characterized in that the abnormal bone metabolism is osteoporosis, bone destruction accompanying rheumatoid arthritis or bone destruction accompanying cancer metastasis to bone. 24. The method according to claim 23, characterized in that the osteoporosis is postmenopausal osteoporosis, senile osteoporosis, secondary osteoporosis due to the use of a therapeutic agent, or osteoporosis accompanying rheumatoid arthritis. 25. A polynucleotide which comprises a nucleotide sequence that encodes the antibody or functional antigen-binding fragment thereof according to claim 1. 26. The polynucleotide according to claim 25, wherein the nucleotide sequences encoding CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 comprise: a) nucleotides 148 to 162 of SEQ ID NO: 101, nucleotides 205 to 261 of SEQ ID NO: 101, nucleotides 358 to 387 of SEQ ID NO: 101, nucleotides 124 to 165 of SEQ ID NO: 86, nucleotides 211 to 231 of SEQ ID NO: 86 and nucleotides 328 to 363 of SEQ ID NO: 86, respectively; b) nucleotides 148 to 162 of SEQ ID NO: 51, nucleotides 205 to 255 of SEQ ID NO: 51, nucleotides 352 to 378 of SEQ ID NO: 51, nucleotides 124 to 156 of SEQ ID NO: 56, nucleotides 202 to 222 of SEQ ID NO: 56 and nucleotides 319 to 348 of SEQ ID NO: 56, respectively; c) nucleotides 148 to 162 of SEQ ID NO: 91, nucleotides 205 to 255 of SEQ ID NO: 91, nucleotides 352 to 381 of SEQ ID NO: 91, nucleotides 124 to 165 of SEQ ID NO: 96, nucleotides 211 to 231 of SEQ ID NO: 96 and nucleotides 328 to 360 of SEQ ID NO: 96, respectively; d) nucleotides 148 to 162 of SEQ ID NO: 61, nucleotides 205 to 255 of SEQ ID NO: 61, nucleotides 352 to 375 of SEQ ID NO: 61, nucleotides 124 to 156 of SEQ ID NO: 66, nucleotides 202 to 222 of SEQ ID NO: 66 and nucleotides 319 to 348 of SEQ ID NO: 66, respectively; e) nucleotides 148 to 162 of SEQ ID NO: 31, nucleotides 205 to 255 of SEQ ID NO: 31, nucleotides 352 to 375 of SEQ ID NO: 31, nucleotides 124 to 156 of SEQ ID NO: 36, nucleotides 202 to 222 of SEQ ID NO: 36 and nucleotides 319 to 348 of SEQ ID NO: 36, respectively; f) nucleotides 148 to 162 of SEQ ID NO: 41, nucleotides 205 to 255 of SEQ ID NO: 41, nucleotides 352 to 372 of SEQ ID NO: 41, nucleotides 124 to 156 of SEQ ID NO: 46, nucleotides 202 to 222 of SEQ ID NO: 46 and nucleotides 319 to 348 of SEQ ID NO: 46, respectively; or g) nucleotides 148 to 162 of SEQ ID NO: 76, nucleotides 205 to 255 of SEQ ID NO: 76, nucleotides 352 to 381 of SEQ ID NO: 76, nucleotides 124 to 165 of SEQ ID NO: 86, nucleotides 211 to 231 of SEQ ID NO: 86 and nucleotides 328 to 363 of SEQ ID NO: 86, respectively. 27. The polynucleotide according to claim 25, wherein the polynucleotide comprises: a nucleotide sequence encoding a heavy chain variable region comprising: nucleotides 58 to 420 of SEQ ID NO: 101, nucleotides 58 to 411 of SEQ ID NO: 51, nucleotides 58 to 414 of SEQ ID NO: 91, nucleotides 58 to 408 of SEQ ID NO: 61, nucleotides 58 to 408 of SEQ ID NO: 31, nucleotides 58 to 405 of SEQ ID NO: 41 or nucleotides 58 to 414 of SEQ ID NO: 76; and a nucleotide sequence encoding a light chain variable region comprising: nucleotides 58 to 402 of SEQ ID NO: 86, nucleotides 58 to 387 of SEQ ID NO: 56, nucleotides 58 to 399 of SEQ ID NO: 96, nucleotides 58 to 387 of SEQ ID NO: 66, nucleotides 58 to 387 of SEQ ID NO: 36 or nucleotides 58 to 387 of SEQ ID NO: 46. 28. The polynucleotide according to claim 27, wherein the polynucleotide comprises: a nucleotide sequence encoding a heavy chain comprising the nucleotide sequence of any one of SEQ ID NOS: 101, 51, 91, 61, 31, 41 or 76; and a nucleotide sequence encoding a light chain comprising the nucleotide sequence of any one of SEQ ID NOS: 86, 56, 96, 66, 36 or 46. 29. A vector comprising at least one polynucleotide according to claim 25. 30. A transformed cell comprising at least one polynucleotide according to claim 25. 31. A transformed cell comprising at least one vector according to claim 29. 32. A method of producing the isolated antibody or antigen-binding fragment of claim 1, comprising (i)-culturing a transformed cell that comprises at least one polynucleotide encoding (a) a heavy chain comprising a CDRH1 comprising a sequence of SEQ ID NO: 106, a CDRH2 comprising a sequence of SEQ ID NO: 107, and a CDRH3 comprising a sequence of any one of SEQ ID NOS: 80, 55, 65, 35 or 45; and (b) a light chain comprising a CDRL1 comprising a sequence of SEQ ID NO: 83 or 73, a CDRL2 comprising a sequence of SEQ ID NO: 108, and a CDRL3 comprising a sequence of any one of SEQ ID NOS: 90, 60, 100, 70, 40, 50 or 109, (ii) collecting culturing materials, and (iii) purifying said antibody from said culturing materials. 33. The pharmaceutical composition according to claim 20, wherein the abnormal bone metabolism is selected from the group consisting of: osteoporosis, bone destruction accompanying rheumatoid arthritis, cancerous hypercalcemia, bone destruction accompanying multiple myeloma or cancer metastasis to bone, giant cell tumor, tooth loss due to periodontitis, osteolysis around a prosthetic joint, bone destruction in chronic osteomyelitis, Paget's disease of bone, renal osteodystrophy and osteogenesis imperfecta. 34. The pharmaceutical composition according to claim 21, wherein the abnormal bone metabolism is selected from the group consisting of: osteoporosis, bone destruction accompanying rheumatoid arthritis, cancerous hypercalcemia, bone destruction accompanying multiple myeloma or cancer metastasis to bone, giant cell tumor, tooth loss due to periodontitis, osteolysis around a prosthetic joint, bone destruction in chronic osteomyelitis, Paget's disease of bone, renal osteodystrophy and osteogenesis imperfecta. 35. The pharmaceutical composition according to claim 33, wherein the abnormal bone metabolism is osteoporosis, bone destruction accompanying rheumatoid arthritis or bone destruction accompanying cancer metastasis to bone. 36. The pharmaceutical composition according to claim 34, wherein the abnormal bone metabolism is osteoporosis, bone destruction accompanying rheumatoid arthritis or bone destruction accompanying cancer metastasis to bone. 37. The pharmaceutical composition according to claim 35, wherein the osteoporosis is postmenopausal osteoporosis, senile osteoporosis, secondary osteoporosis due to the use of a therapeutic agent, or osteoporosis accompanying rheumatoid arthritis. 38. The pharmaceutical composition according to claim 36, wherein the osteoporosis is postmenopausal osteoporosis, senile osteoporosis, secondary osteoporosis due to the use of a therapeutic agent, or osteoporosis accompanying rheumatoid arthritis. 39. The pharmaceutical composition according to claim 21, wherein the hormone is estradiol. 40. The pharmaceutical composition according to claim 24, wherein the secondary osteoporosis is due to the use of a steroid or an immunosuppressant. 41. The pharmaceutical composition according to claim 37, wherein the secondary osteoporosis is due to the use of a steroid or an immunosuppressant. 42. The pharmaceutical composition according to claim 38, wherein the secondary osteoporosis is due to the use of a steroid or an immunosuppressant.

Details for Patent 9,114,131

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2030-10-05