Ligands of B7H receptor in the treatment of osteopenia and osteoporosis
A novel use of ligands of B7h receptor in the treatment of osteoporosis or osteopenia is disclosed as well as the use of B7h receptor as target for the screening of pharmaceutical active agents useful in the treatment of osteopenia or osteoporosis.
1. A method of treating osteoporosis or osteopenia, comprising the steps of: administering to a patient a medicament comprising an isolated ligand of receptor B7h, and thereby reducing osteoporosis or osteopenia in the patient, wherein the ligand comprises:
a) a human ICOS polypeptide having the amino acid sequence set forth in SEQ ID NO: 29;
b) a polypeptide having at least 90% sequence homology to the amino acid sequence set forth in SEQ ID NO: 29, wherein the polypeptide is capable of binding to receptor B7h;
c) a fragment of a human ICOS polypeptide having the amino acid sequence set forth in SEQ ID NO: 29, wherein the fragment is capable of binding to receptor B7h;
d) a human ICOS extracellular domain having the amino acid sequence set forth in SEQ ID NO: 2;
e) a fragment of a human ICOS extracellular domain having the amino acid sequence set forth in SEQ ID NO: 2, wherein the fragment is capable of binding to receptor B7h; or
f) a polypeptide having at least 90% sequence homology to the amino acid sequence set forth in SEQ ID NO: 2, wherein the polypeptide is capable of binding to receptor B7h, and
wherein the patient
has been diagnosed with osteopenia but has not been diagnosed with rheumatoid arthritis.
2. The method according to claim 1 wherein the ligand is to be administered by injection, or infusion.
3. The method according to claim 1 wherein the ligand is fused or conjugated to a stabilizing molecule.
4. The method according to claim 3 wherein the stabilizing molecule is selected from: polyethylene glycols or derivatives thereof, poly-L-lysine citramide, styrenemaleic acid anhydride, poly-hydroxypropylmetacrylamide, and human Fc antibody domain.
5. The method according to claim 4 wherein the polyethylene glycols derivatives are selected from: epoxide PEG, aldehyde PEG, nitrophenyl carbonate PEG, succinimidyl ester PEG, orthopyridyl disulfide PEGs, PEG-COOH activated with N-hydroxysuccinimide or hydroxybenzotriazole, PEG-polyacetal with pH-dependent hydrolysis, and PEG-dextrin.
6. The method according to claim 1 wherein the ligand is hyperglycosylated or conjugated to mannose residues.
7. The method according to claim 1 wherein the ligand of the receptor B7h has the ability of triggering the receptor B7h activity in osteoclasts thus inhibiting differentiation, maturation and/or function of osteoclasts.
8. The method according to claim 7 wherein the ligand is to be administered by injection, or infusion.
9. The method according to claim 7 wherein the ligand is fused or conjugated to a stabilizing molecule.
10. The method according to claim 7 wherein the ligand is hyperglycosylated or conjugated to mannose residues.
11. The method according to claim 10 wherein the stabilizing molecule is selected from: polyethylene glycols or derivatives thereof, poly-L-lysine citramide, styrenemaleic acid anhydride, poly-hydroxypropylmetacrylamide, and human Fc antibody domain.
12. The method according to claim 11 wherein the polyethylene glycols derivatives are selected from: epoxide PEG, aldehyde PEG, nitrophenyl carbonate PEG, succinimidyl ester PEG, orthopyridyl disulfide PEGs, PEG-COOH activated with N-hydroxysuccinimide or hydroxybenzotriazole, PEG-polyacetal with pH-dependent hydrolysis, and PEG-dextrin.
13. The method of claim 1 , wherein the patient has cancer.
14. A method of treating osteoporosis or osteopenia, comprising the steps of: administering to a patient having osteoporosis or osteopenia a medicament comprising a ligand of receptor B7h, and thereby reducing osteoporosis or osteopenia in the patient, wherein the ligand comprises ICOS-Fc (SEQ ID NO: 1).