Claims for Patent: 9,464,133

Summary for Patent: 9,464,133

Title:	CDR-modified anti-Siglec-15 antibody
Abstract:	Provided is a pharmaceutical composition for the treatment and/or prophylaxis of abnormal bone metabolism targeting a protein encoded by a gene strongly expressed in osteoclasts. Specifically provided is a pharmaceutical composition containing an antibody which specifically recognizes human Siglec-15 and has an activity of inhibiting osteoclast formation, and the like.
Inventor(s):	Hiruma; Yoshiharu (Tokyo, JP), Kimura; Takako (Tokyo, JP), Shimizu; Hironari (Tokyo, JP)
Assignee:	Daiichi Sankyo Company, Limited (Tokyo, JP)
Application Number:	14/388,347
Patent Claims:	1. An antibody or an antigen binding fragment, comprising: a heavy chain sequence that comprises a variable region having CDRH1, CDRH2, and CDRH3, wherein CDRH1 comprises SEQ ID NO: 7, CDRH2 comprises SEQ ID NO: 9, and CDRH3 comprises SEQ ID NO: 11; and a light chain sequence that comprises a variable region having CDRL1, CDRL2, and CDRL3, wherein CDRL1 comprises SEQ ID NO: 12, CDRL2 comprises SEQ ID NO: 13, and CDRL3 comprises SEQ ID NO: 14, wherein the antibody or antigen binding fragment binds Siglec-15. 2. The antibody or an antigen binding fragment according to claim 1, comprising a heavy chain variable region sequence that comprises amino acid residues 20 to 140 of SEQ ID NO: 6 and a light chain variable region sequence that comprises amino acid residues 21 to 133 of SEQ ID NO: 4. 3. The antibody or an antigen binding fragment according to claim 1, comprising a heavy chain sequence that comprises amino acid residues 20 to 466 of SEQ ID NO: 6 and a light chain sequence that comprises amino acid residues 21 to 238 of SEQ ID NO: 4. 4. The antibody or an antigen binding fragment according to claim 1, comprising a heavy chain sequence that comprises amino acid residues 20 to 465 of SEQ ID NO: 6 and a light chain sequence that comprises amino acid residues 21 to 238 of SEQ ID NO: 4. 5. The antigen binding fragment according to claim 1, which is selected from the group consisting of Fab, F(ab')2, Fab' and Fv. 6. The antibody according to claim 1, wherein the antibody is an scFv. 7. A pharmaceutical composition, characterized by comprising at least one antibody or antigen binding fragment according to claim 1, wherein said antibody or antigen binding fragment inhibits osteoclast formation and/or osteoclastic bone resorption. 8. The pharmaceutical composition according to claim 7, wherein the composition is a therapeutic and/or prophylactic agent for abnormal bone metabolism, wherein said abnormal bone metabolism is characterized by insufficient bone mass or density. 9. A pharmaceutical composition for the treatment and/or prophylaxis of abnormal bone metabolism, comprising at least one antibody or antigen binding fragment according to claim 1, wherein said antibody or antigen binding fragment inhibits osteoclast formation and/or osteoclastic bone resorption, and wherein said abnormal bone metabolism is characterized by insufficient bone mass or density, and at least one therapeutic agent selected from the group consisting of bisphosphonates, active vitamin D.sub.3, calcitonin and derivatives thereof, hormones, estradiol, SERMs (selective estrogen receptor modulators), ipriflavone, vitamin K.sub.2 (menatetrenone), calcium preparations, PTH (parathyroid hormone), nonsteroidal anti-inflammatory agents, soluble TNF receptors, anti-TNF-.alpha. antibodies or antigen binding fragments of the antibodies, anti-PTHrP (parathyroid hormone-related protein) antibodies or antigen binding fragments of the antibodies, IL-1 receptor antagonists, anti-IL-6 receptor antibodies or antigen binding fragments of the antibodies, anti-RANKL antibodies or antigen binding fragments of the antibodies, and OCIF (osteoclastogenesis inhibitory factor). 10. The pharmaceutical composition according to claim 8, 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, osteopenia, tooth loss due to periodontitis, osteolysis around a prosthetic joint, bone destruction in chronic osteomyelitis, bone Paget's disease, renal osteodystrophy, and osteogenesis imperfecta. 11. The pharmaceutical composition according to claim 10, wherein the abnormal bone metabolism is osteoporosis, bone destruction accompanying rheumatoid arthritis, or bone destruction accompanying cancer metastasis to bone. 12. The pharmaceutical composition according to claim 11, characterized in that the abnormal bone metabolism is osteoporosis. 13. The pharmaceutical composition according to claim 12, wherein the osteoporosis is postmenopausal osteoporosis, senile osteoporosis, secondary osteoporosis due to the use of a therapeutic agent, or osteoporosis accompanying rheumatoid arthritis. 14. A method for the treatment and/or prophylaxis of abnormal bone metabolism, wherein said abnormal bone metabolism is characterized by insufficient bone mass or density, comprising administering to a human at least one antibody or antigen binding fragment according to claim 1, wherein said antibody or antigen binding fragment inhibits osteoclast formation and/or osteoclastic bone resorption. 15. A method for the treatment and/or prophylaxis of abnormal bone metabolism, comprising simultaneously or successively administering to a human at least one antibody or antigen binding fragment according claim 1, wherein said antibody or antigen binding fragment inhibits osteoclast formation and/or osteoclastic bone resorption, and wherein said abnormal bone metabolism is characterized by insufficient bone mass or density, and at least one therapeutic agent selected from the group consisting of bisphosphonates, active vitamin D.sub.3, calcitonin and derivatives thereof, hormones, estradiol, SERMs (selective estrogen receptor modulators), ipriflavone, vitamin K.sub.2 (menatetrenone), calcium preparations, PTH (parathyroid hormone), nonsteroidal anti-inflammatory agents, soluble TNF receptors, anti-TNF-.alpha. antibodies or antigen binding fragments of the antibodies, anti-PTHrP (parathyroid hormone-related protein) antibodies or antigen binding fragments of the antibodies, IL-1 receptor antagonists, anti-IL-6 receptor antibodies or antigen binding fragments of the antibodies, anti-RANKL antibodies or antigen binding fragments of the antibodies, and OCIF (osteoclastogenesis inhibitory factor). 16. The method for the treatment and/or prophylaxis according to claim 14, wherein the abnormal bone metabolism is osteoporosis, bone destruction accompanying rheumatoid arthritis, or bone destruction accompanying cancer metastasis to bone. 17. The method for the treatment and/or prophylaxis according to claim 16, wherein the abnormal bone metabolism is osteoporosis. 18. The method for the treatment and/or prophylaxis according to claim 17, wherein the osteoporosis is postmenopausal osteoporosis, senile osteoporosis, secondary osteoporosis due to the use of a therapeutic agent, or osteoporosis accompanying rheumatoid arthritis. 19. A polynucleotide encoding the antibody according to claim 1. 20. The polynucleotide according to claim 19, comprising a nucleotide sequence that comprises nucleotides 58 to 420 of SEQ ID NO: 5 and a nucleotide sequence that comprises nucleotides 61 to 399 of SEQ ID NO: 3. 21. The polynucleotide according to claim 19, comprising a nucleotide sequence that comprises nucleotides 58 to 1398 of SEQ ID NO: 5 and a nucleotide sequence that comprises nucleotides 61 to 714 of SEQ ID NO: 3. 22. A vector, comprising a polynucleotide according to claim 19. 23. A transformed host cell, comprising a polynucleotide according to claim 19. 24. A transformed host cell, comprising the vector according to claim 22. 25. A method of producing an antibody, comprising culturing the host cell according to claim 23, and purifying an antibody from the resulting culture product. 26. The antibody or antigen binding fragment according to claim 1, wherein the heavy chain includes a deletion of one or two amino acids from the carboxyl terminus. 27. The antibody or antigen binding fragment according to claim 1, wherein glycosylation is controlled to enhance an antibody-dependent cytotoxic activity. 28. An immunoconjugate comprising the antibody according to claim 1 and a compound having a pharmacological effect.

Details for Patent 9,464,133

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2032-03-30