Compositions and methods for improving bone mass through...

Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Method of regulating cell metabolism or physiology

Reexamination Certificate

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C514S008800, C514S008900, C514S011800, C514S016700, C435S007100, C530S350000

Reexamination Certificate

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08008074

ABSTRACT:
The present invention relates to the discovery of novel receptors for the signaling of PTH and/or fragments of PTH, and the role of cPTH in bone development. The novel PTH receptors identified are selected from the group consisting of LRP5/6, TGFβRII, BMPRII (long form and short form), ActRIIA, and ActRIIB. Specifically, the present invention provides a novel screening tool for identifying compounds that improve bone mass by affecting certain pathways that promote or downregulate bone-forming activity. This promotion of bone-forming activity could provide for treatments for bone-loss or bone density disorders and/or kidney disease. The invention further encompasses the compounds, PTH ligands, and fragments of PTH ligands described herein; pharmaceutical compositions comprising the compounds, PTH ligands, or fragments of PTH ligand; and methods of increasing bone density using the compounds, PTH ligands, or fragments of PTH ligands.

REFERENCES:
Martin et al., 2006, “Mechanisms Involved in Skeletal Anabolic Therapies,” Ann. N.Y. Acad. Sci. vol. 1068, pp. 458-470.
PCT International Search Report for PCT/US07/64408 dated Aug. 21, 2008 (2 pages).
Atfi et al., 2010, “PTH Battles TGF-beta in Bone,” Nature Cell Biology, vol. 12(3):205-207.
Iqbal et al., 2009, “Coupling Bone Degradation to Formation,” Nature Medicine, vol. 15(7):729-731.
Qiu et al., 2010, “TGF-beta Type II Receptor Phosphorylates PTH Receptor to Integrate Bone Remodelling Signalling,” Nature Cell Biology, vol. 12(3):224-234 with Supplementary Information.
Tang et al., 2009, “TGF-beta1-Induced Migration of Bone Mesenchymal Stem Cells Couples Bone Resorption with Formation,” Nature Medicine, vol. 15(7):757-765.

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