Abstract: The present invention discloses a novel secreted polypeptide, termed osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind OPG, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis. Methods of treatment are described using the polypeptides in conjunction with various agents, including IL-1 inhibitors, TNF-? inhibitors, and serine protease inhibitors.

Abstract: The present invention concerns therapeutic agents that modulate the activity of PTH and PTHrP.

Abstract: The present invention concerns therapeutic agents that modulate the activity of PTH and PTHrP. In accordance with the present invention, modulators of PTH and PTHrP comprise: (a) a PTH/PTHrP modulating domain; and (b) a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the C-terminus of the PTH/PTHrP modulating domain. The vehicle and the PTH/PTHrP modulating domain may be linked through the N- or C-terminus of the PTH/PTHrP modulating domain, as described further below. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain. Preferred PTH/PTHrP modulating domains comprise the PTH and PTHrP-derived amino acid sequences described hereinafter. Other PTH/PTHrP modulating domains can be generated by phage display, RNA-peptide screening and the other techniques mentioned herein.

Abstract: The present invention concerns therapeutic agents that modulate the activity of PTH and PTHrP.

Abstract: The present invention concerns fusion of half-life extending vehicles, preferably Fc domains, with peptide sequences that act as antagonists of integrins, selectins, cell adhesion molecules, or their respective receptors. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The peptide may be an existing peptide or a peptide selected by phage display, E. coli display, ribosome display, RNA-peptide screening, chemical-peptide screening, or other methods.