abstract |
The present invention relates to a therapeutic agent that modulates the activity of PTH and PTHrP. According to the present invention, regulators of PTH and PTHrP may comprise (a) a PTH / PTHrP regulatory domain; And (b) excipients such as polymers (eg PEG or dextran) or Fc domains (preferably), wherein the excipients are covalently linked to the C-terminus of the PTH / PTHrP regulatory domain. The excipient and the PTH / PTHrP regulatory domain will be bound through the N-terminus or C-terminus of the PTH / PTHrP regulatory domain, as described further below. Preferred excipients are Fc domains and preferred Fc domains are IgG Fc domains. Preferred PTH / PTHrP regulatory domains include the PTH and PTHrP-derived amino acid sequences described below. Other PTH / PTHrP regulatory domains can be generated by phage display, RNA-peptide screening and other techniques mentioned herein. Although such techniques can be used to generate peptide sequences that act as selective regulators (eg, agonists of PTH activity rather than PTHrP activity), these peptides typically are regulators of both PTH and PTHrP activity. Will be. |