COMPOSITIONS AND METHODS FOR TREATING BONE CONDITIONS

• US 20130202612A1
• Filed: 08/10/2012
• Published: 08/08/2013
• Est. Priority Date: 08/10/2011
• Status: Active Grant

• Current Assignee: Case Western Reserve University
• Original Assignee: Case Western Reserve University
• Inventors: Lin, Feng, Dennis, James E., Tu, Zhidan
• Granted Patent: US 9,289,467 B2
• Time in Patent Office: Days
• US Class Current: 424/158.1
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/1725 Complement proteins, e.g. anaphylatoxin, C3a or C5a
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 47/6843 the antibody targeting a material from animals or humans
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6871 the antibody targeting an enzyme
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/351 Conjugate

Abstract

A method of treating a degenerative bone condition of a subject includes administering to hematopoietic progenitor cells or osteoclast progenitor cells of the subject at least one agent that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and/or C5a receptor (C5aR), a STAT3/IL-6 signaling pathway antagonist, and a combination thereof, the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells at an amount effective to inhibit osteoclast differentiation of hematopoietic progenitor cells or osteoclast progenitor cells.

Claims

1. A method of treating a degenerative bone condition, the method comprising:

administering to hematopoietic progenitor cells or osteoclast progenitor cells of the subject at least one agent that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and/or C5a receptor (C5aR), a STAT3/IL-6 signaling pathway antagonist, and a combination thereof, the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells at an amount effective to inhibit osteoclast differentiation of hematopoietic progenitor cells or osteoclast progenitor cells.

2. The method of claim 1, the agent comprising at least one complement antagonist selected from the group consisting of a small molecule, a polypeptide, and a polynucleotide.

3. The method of claim 2, the at least one complement antagonist selected from the group consisting of DAF or an antibody directed against at least one of C3, C5, C3 convertase, C5 convertase, C3a, C5a, C3aR, or C5aR.

4. The method of claim 2, the polynucleotide comprising a small interfering RNA directed against a polynucleotide encoding at least one of C3, C5, C3aR, or C5aR.

5. The method of claim 3, the at least one complement antagonist including an antibody directed against C5aR and an antibody directed against C3aR.

6. The method of claim 3, the at least one complement antagonist including an antibody directed against C5a and an antibody directed against C3a.

7. The method of claim 3, the at least one complement antagonist including an antibody directed against C5 and an antibody directed against C3.

8. The method of claim 1, the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells in vitro.

9. The method of claim 1, the agent being administered locally to the hematopoietic progenitor cells or osteoclast progenitor cells at the site of the bone condition.

10. The method of claim 1, the agent being conjugated to a targeting moiety that targets hematopoietic progenitor cells or osteoclast progenitor cells.

11. The method of claim 1 wherein the bone condition comprises osteopenia or osteoporosis.

12. A method of treating post-menopausal osteoporosis, the method comprising:

administering to hematopoietic progenitor cells or osteoclast progenitor cells of the subject at least one complement antagonist that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and/or C5a receptor (C5aR), the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells at an amount effective to inhibit osteoclast differentiation of hematopoietic progenitor cells.

13. The method of claim 12, the at least one complement antagonist selected from the group consisting of DAF or an antibody directed against at least one of C3, C5, C3 convertase, C5 convertase, C3a, C5a, C3aR, or C5aR.

14. The method of claim 12, the at least one complement antagonist including an antibody directed against C5aR and an antibody directed against C3aR or an antibody directed against C5a and an antibody directed against C3a.

15. The method of claim 12, the agent being administered to the hematopoietic progenitor cells or osteoclast progenitor cells in vitro.

16. The method of claim 12, the agent being administered locally to the hematopoietic progenitor cells or osteoclast progenitor cells of the bone marrow.

17. The method of claim 12, the agent being conjugated to a targeting moiety that targets hematopoietic progenitor cells or osteoclast progenitor cells of the bone marrow.

18. A method of treating post-menopausal osteoporosis of a subject, the method comprising:

administering locally to bone marrow of the subject at least one complement antagonist that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and C5a receptor (C5aR), the agent being administered locally to the bone marrow cells of the subject at an amount effective to inhibit osteoclast differentiation of hematopoietic progenitor cells or osteoclast progenitor cells.

19. The method of claim 18, the at least one complement antagonist selected from the group consisting of DAF or an antibody directed against at least one of C3, C5, C3 convertase, C5 convertase, C3a, C5a, C3aR, or C5aR.

20. The method of claim 19, the at least one complement antagonist including an antibody directed against C5aR and an antibody directed against C3aR or an antibody directed against C5a and an antibody directed against C3a.