Antibody targeting osteoclast-related protein siglec-15

Patent metadata

Field	Value
Publication number	US-10723800-B2
Application number	US-201213481016-A
Country	US
Kind code	B2
Filing date	May 25, 2012
Priority date	Oct 11, 2007
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

To provide a method of detecting abnormal bone metabolism by using a gene strongly expressed in an osteoclast; a method of screening a compound having a therapeutic and/or preventive effect on abnormal bone metabolism; and a pharmaceutical composition for treating and/or preventing abnormal bone metabolism. Provision of a method of detecting abnormal bone metabolism by using the expression of human Siglec-15 gene as an index; a pharmaceutical composition containing an antibody which specifically recognizes human Siglec-15 and has an activity of inhibiting osteoclast formation; and the like.

First claim

The invention claimed is:

1. A method of treating abnormal bone metabolism in a mammal comprising administering an antibody or antigen binding fragment thereof comprising the complementarity determining regions (CDRs) of an antibody produced by hybridoma #32A1, wherein the antibody binds one or more polypeptides comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 4, wherein said antibody or antigen binding fragment thereof inhibits osteoclast formation and/or osteoclastic bone resorption, and wherein abnormal bone metabolism is characterized by an imbalance of bone resorption and bone formation in which bone resorption is increased.

2. The method of claim 1 , wherein said antibody or antigen binding fragment thereof inhibits osteoclastic bone resorption.

3. A method for inhibiting osteoclast formation and/or osteoclastic bone resorption in a mammal comprising administering an antibody or antigen binding fragment thereof comprising the complementarity determining regions (CDRs) of an antibody produced by hybridoma #32A1, wherein the antibody binds one or more polypeptides selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 4.

4. The method of claim 3 , wherein the antibody or antigen binding fragment thereof inhibits osteoclast bone resorption.

5. The method of claim 3 , wherein the antibody or antigen binding fragment thereof inhibits osteoclast formation.

6. The method according claim 5 , wherein the antibody is a monoclonal antibody.

7. The method according to claim 5 , wherein the antibody is a chimeric antibody.

8. The method according to claim 5 , wherein the antibody is humanized.

9. The method according to claim 5 , wherein the antibody is a human antibody.

10. The method according to claim 5 , wherein the antigen binding fragment thereof is selected from the group consisting of Fab, F(ab′)2, Fab′ and Fv.

11. The method according to claim 1 , 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.

12. The method of claim 3 , further comprising administering a pharmaceutically acceptable carrier.

13. The method of claim 12 , further comprising administering at least one agent selected from the group consisting of bisphosphonate, active vitamin D 3 , ipriflavone, vitamin K 2 (menatetrenone), nonsteroidal anti-inflammatory agent, anti-TNF-α antibody or antigen binding fragment thereof, anti-PTHrP (parathyroid hormone-related protein) antibody or antigen binding fragment thereof, anti-IL-6 receptor antibody or antigen binding fragment thereof, anti-RANKL antibody or antigen binding fragment thereof and OCIF (osteoclastogenesis inhibitory factor).

14. A method for inhibiting osteoclast differentiation in a mammal, the method comprising administering an antibody or antigen binding fragment thereof comprising the complementarity determining regions (CDRs) of an antibody produced by hybridoma #32A1, which specifically binds to an amino acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 4.

15. The method of claim 14 , wherein the antibody or antigen binding fragment thereof inhibits an osteoclast differentiation activity of human Siglec-15 or murine Siglec-15.

16. The method of claim 15 , wherein the osteoclast differentiation activity is characterized by differentiation of osteoclast precursor cells into differentiated osteoclasts.

17. The method of claim 15 , wherein the antibody is a polyclonal antibody.

18. The method of claim 15 , wherein the antibody or antigen binding fragment thereof is a monoclonal antibody or antigen binding fragment thereof.

19. The method of claim 18 , wherein the monoclonal antibody or antigen binding fragment thereof is produced from an isolated mammalian cell.

20. The method of claim 19 , wherein the antibody or antigen binding fragment thereof comprises a constant region of a human antibody or a fragment thereof.

21. The method of claim 20 , wherein the antibody or antigen binding fragment thereof comprises a framework region of a human antibody.

22. The method of claim 15 , wherein the antibody or antigen binding fragment thereof is a Fv, a Fab, a Fab′ or a (Fab′) 2 .

23. The method of claim 16 , wherein the osteoclast precursor cells are human osteoclast precursor cells.

24. A method for inhibiting bone resorption in a mammal, thereby treating or preventing abnormal bone metabolism, comprising administering an antibody or an antigen binding fragment thereof comprising the complementarity determining regions (CDRs) of an antibody produced by hybridoma #32A1, which specifically binds to one or more polypeptides selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 4.

25. The method of claim 24 , wherein the antibody or antigen binding fragment thereof inhibits osteoclast differentiation.

26. The method of claim 24 , wherein the antibody or antigen binding fragment thereof is administered along with at least one therapeutic agent.

27. The method of claim 26 , wherein the therapeutic agent is selected from the group consisting of bisphosphonate, active vitamin D 3 , ipriflavone, vitamin K 2 (menatetrenone), nonsteroidal anti-inflammatory agents, anti-TNF-α antibody or antigen binding fragment thereof, anti-PTHrP (parathyroid hormone-related protein) antibody or antigen binding fragment thereof, anti-IL-6 receptor antibody or antigen binding fragment thereof, anti-RANKL antibody or antigen binding fragment thereof and OCIF (osteoclastogenesis inhibitory factor).

28. The method of claim 24 , 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.

29. The method of claim 19 , wherein the isolated mammalian cell is a human cell.

30. The method of claim 28 , wherein the osteoporosis is selected from the group consisting of postmenopausal osteoporosis, senile osteoporosis, secondary osteoporosis due to the use of a therapeutic agent and osteoporosis accompanying rheumatoid arthritis.

31. A method for inhibiting osteoclast differentiation in a mammal in need thereof, the method comprising administering a compound that inhibits osteoclast differentiation activity of SEQ ID NO.: 2, wherein the compound is an antibody or an antigen binding fragment thereof that binds to SEQ ID NO.: 2 and comprises the complementarity determining regions (CDRs) of an antibody produced by hybridoma #32A1.

32. The method of claim 31 , wherein the antibody or antigen binding fragment thereof is a monoclonal antibody, a chimeric antibody, a human antibody, or a humanized antibody.

33. The method of c

Assignees

• Hiruma Yoshiharu
• Tsuda Eisuke
• Daiichi Sankyo Co Ltd

Inventors

• Hiruma Yoshiharu
• Tsuda Eisuke

Classifications

• A61K31/593 Primary

  9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3 · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title