Antibody targeting osteoclast-related protein siglec-15

• US 10,723,800 B2
• Filed: 05/25/2012
• Issued: 07/28/2020
• Est. Priority Date: 10/11/2007
• Status: Active Grant

• Current Assignee: Daiichi Sankyo Company Limited
• Original Assignee: Daiichi Sankyo Company Limited
• Inventors: Hiruma, Yoshiharu, Tsuda, Eisuke
• Primary Examiner(s): Kemmerer, Elizabeth C.
• Application Number:
  US13/481,016
• Publication Number:
  US 20120230988A1
• Time in Patent Office: 2,986 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2851 : against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 2317/14 : Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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.

Claims

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.

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.

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.

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 D₃, ipriflavone, vitamin K₂ (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.

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

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 D₃, ipriflavone, vitamin K₂ (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.

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 claim 31, wherein the antigen binding fragment is a Fv, a Fab, a Fab′

or a (Fab′

)₂.

34. The method of claim 31, wherein the antibody or antigen binding fragment thereof is characterized by its ability to inhibit osteoclast differentiation in an in vitro assay.

35. The method of claim 34, wherein the ability to inhibit osteoclast differentiation in the in vitro assay is characterized by a decrease in the number of differentiated osteoclast cells, a decrease in the rate of differentiation of osteoclast cells or by the presence of markers of osteoclast differentiation.

36. The method of claim 31, further comprising administering a drug or hormone to the mammal.

37. The method of claim 31, wherein the mammal has a condition characterized by a deficiency in bone growth or need for bone growth or replacement.

38. The method of claim 31, wherein the mammal has a condition characterized by an undesirably high level of bone resorption.

39. The method of claim 31, wherein the mammal is a human.

40. The method of claim 31, wherein the mammal suffers from osteoporosis.

41. The method of claim 31, wherein the mammal suffers from multiple myeloma.

42. The method of claim 31, wherein the mammal suffers from osteogenesis imperfecta.