METHODS OF TREATING BONE-LOSS DISORDERS USING A GM-CSF ANTAGONIST
The invention is based on the discovery that GM-CSF antagonists can be used for the treatment of bone loss disorders, such as osteopenia. Accordingly, the invention provides methods of administering a GM-CSF antagonist, e.g., a GM-CSF antibody, to a patient that has a bone loss disorder and pharmaceutical compositions comprising such antagonists.
1 . A method for treating a patient that has osteopenia, the method comprising administering a therapeutically effective amount of an anti-GM-CSF antibody antagonist to the patient in an amount sufficient to reduce the symptoms of bone loss, wherein the antibody that binds to GM-CSF with a dissociation constant (K D ) less than 100 pM and is administered at a frequency of between once per week and once every three months.
2 . The method of claim 1 , wherein the antibody is administered approximately once per month.
3 . The method of claim 2 , wherein the osteopenia results from estrogen deficiency.
4 . The method of claim 1 , wherein the patient has not been diagnosed with rheumatoid arthritis.
5 . The method of claim 1 , wherein the antibody is a polyclonal antibody.
6 . The method of claim 1 , wherein the antibody is a monoclonal antibody.
7 . The method of claim 1 , wherein the antibody is an antibody fragment that is a Fab, a Fab′, a F(ab′) 2 , a scFv, or a dAB.
8 . The method of claim 7 , wherein the antibody fragment is conjugated to polyethylene glycol.
9 . The method of claim 1 , wherein the antibody has a dissociation constant of about 5 pM to about 50 pM.
10 . The method of claim 1 , wherein the antibody is a neutralizing antibody.
11 . The method of claim 1 , wherein the antibody is a recombinant or chimeric antibody.
12 . The method of claim 1 , wherein the antibody is a human antibody.
13 . The method of claim 1 , wherein the antibody comprises a human variable region.
14 . The method of claim 1 , wherein the antibody comprises a human light chain constant region.
15 . The method of claim 1 , wherein the antibody comprises a human heavy chain constant region.
16 . The method of claim 1 , wherein the human heavy chain constant region is a gamma chain.
17 . The method of claim 1 , wherein the antibody binds to the same epitope as chimeric 19/2.
18 . The method of claim 1 , wherein the antibody comprises the V H and V L regions of chimeric 19/2.
19 . The method of claim 18 , wherein the antibody comprises a human heavy chain constant region.
20 . The method of claim 19 , wherein the human heavy chain constant region is a gamma region.
21 . The method of claim 1 , wherein the antibody comprises the VH region and VL region CDR1, CDR2, and CDR3 of chimeric 19/2.
22 . The method of claim 1 , wherein the antibody comprises the VH region CDR3 and VL region CDR3 of chimeric 19/2.
23 . The method of claim 1 , further comprising administering a therapeutic agent selected from the group consisting of a bisphosphonate, raloxifene, teriparatide, and strontium ranelate, a RANKL antagonist, and an osteoprotegerin (OPG)-Fc fusion protein.
24 . The method of claim 23 , wherein the bisphosphonate is selected from the group consisting of alendronate, etidronate, risedronate and ibandronic acid.
25 . A method for treating a patient having osteopenia, the method comprising administering a therapeutically effective amount of a an anti-GM-CSF antibody, wherein the anti-GM-CSF antibody comprises a humaneered Fab′ with the binding specificity of chimeric 19/2 and has a dissociation constant (K D ) less than 100 pM and is administered at a frequency of between once per week and once every three months.
26 . The method of claim 26 , wherein the osteopenia results from estrogen deficiency.