Humanized M-CSF specific monoclonal antibodies, kits, and uses thereof
M-CSF-specific RX1-based or RX-1 derived antibodies are provided, along with pharmaceutical compositions containing such antibody, kits containing a pharmaceutical composition, and methods of preventing and treating bone loss in a subject afflicted with an osteolytic disease.
1. A humanized antibody that binds to human M-CSF, wherein said antibody comprises all three CDRs of SEQ ID NO: 53 and all three CDRs of SEQ ID NO: 43.
2. The antibody of claim 1 comprising a variable light chain amino acid sequence which has at least 65% identity to the amino acid sequence set forth in SEQ ID NO: 4.
3. The antibody of claim 1 comprising a variable heavy chain amino acid sequence which has at least 65% identity to the amino acid sequence set forth in SEQ ID NO: 2.
4. The antibody of claim 1 comprising a constant region of a human antibody sequence and one or more heavy and light chain variable framework regions of a human antibody sequence.
5. The antibody of claim 4 wherein the human antibody sequence is an individual human sequence, a human consensus sequence, an individual human germline sequence, or a human consensus germline sequence.
6. The antibody of claim 5 that comprises a fragment of an IgG1 constant region.
7. The antibody of claim 6 that comprises a mutation in the IgG1 constant region that reduces antibody-dependent cellular cytotoxicity or complement dependent cytotoxicity activity.
8. The antibody of claim 5 that comprises a fragment of an IgG4 constant region.
9. The antibody of claim 8 that comprises a mutation in the IgG4 constant region that reduces formation of half-antibodies.
10. The antibody of claim 1 that comprises the heavy chain amino acid sequence set forth in SEQ ID NO: 43 and the light chain amino acid sequence set forth in SEQ ID NO: 53.
11. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically suitable carrier, excipient or diluent.
12. The pharmaceutical composition of claim 11 further comprising a second therapeutic agent.
13. The pharmaceutical composition of claim 12 wherein the second therapeutic agent is a cancer chemotherapeutic agent.
14. The pharmaceutical composition of claim 12 wherein the second therapeutic agent is a bisphosphonate.
15. The pharmaceutical composition of claim 14 wherein the bisphonate is zeledronate, pamidronate, clodronate, etidronate, tilundronate, alendronate, or ibandronate.
16. The pharmaceutical composition of claim 12 wherein the second therapeutic agent is another antibody.
17. A kit comprising a therapeutically effective amount of the antibody of claim 1 , packaged in a container, a vial or bottle, and further comprising a label attached to or packaged with the container, the label describing the contents of the container and providing indications and/or instructions regarding use of the contents of the container.
18. The kit of claim 17 further comprising a second therapeutic agent.
19. The kit of claim 18 wherein the second therapeutic agent is a cancer chemotherapeutic agent.
20. The kit of claim 18 wherein the second therapeutic agent is a non-M-CSF colony stimulating factor, or anti-RANKL antibody, or soluble RANKL receptor.
21. The kit of claim 18 wherein the second therapeutic agent is a bisphosphonate.
22. The kit of claim 21 wherein the bisphonate is zeledronate, pamidronate, clodronate, etidronate, tilundronate, alendronate, or ibandronate.
23. The kit of claim 22 comprising a dose of antibody effective to reduce the dosage of second therapeutic agent required to achieve a therapeutic effect.
24. The kit of claim 22 comprising a dose of antibody effective to inhibit osteoclast proliferation and/or differentiation induced by tumor cells.
25. The kit of claim 22 comprising a dose of antibody between about 2 pg/kg to 30 mg/kg body weight.
26. The kit of claim 25 comprising a dose of antibody between about 0.1 mg/kg to 30 mg/kg body weight.
27. The kit of claim 26 comprising a dose of antibody between about 0.1 mg/kg to 10 mg/kg body weight.