Therapeutic vitamin D conjugates
The invention provides non-hormonal vitamin D conjugated to apelin proteins that result in increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms. In some embodiments, the vitamin D targeting groups are coupled to the apelin proteins via the third carbon on the vitamin D backbone.
1. A method of treating osteoporosis or hypoparathyroidism in a patient in need thereof, comprising administering an effective amount of a pharmaceutical composition comprising a carrier-drug conjugate comprising a targeting group that is a vitamin D that is not hydroxylated at the carbon 1 position conjugated via a scaffold to a therapeutic peptide at the carbon 3 position of said vitamin D targeting group, wherein said targeting group interacts with the vitamin D binding protein (DBP) to increase the absorption, bioavailability, or half-life of said therapeutic peptide in circulation when compared to a form of said therapeutic peptide conjugated to said vitamin D targeting group at the carbon 25 position; wherein said therapeutic peptide has PTH activity and comprises an amino acid sequence with at least a 90% sequence identity to either SEQ ID NO:10 or SEO ID NO:17.
2. The method of claim 1 , wherein said pharmaceutical composition is administered to said patient by a transdermal, oral, parenteral, subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intralesional, intracranial injection, infusion, inhalation, ocular, topical, rectal, nasal, buccal, sublingual, vaginal, or implanted reservoir mode.
3. The method of claim 1 , wherein said scaffold is poly(ethylene glycol).
4. The method of claim 1 , wherein said peptide has the sequence of SEQ ID NO:10.
5. The method of claim 4 , wherein said scaffold is poly(ethylene glycol).
6. The method of claim 1 , wherein said therapeutic peptide has the sequence of SEQ ID NO:17.
7. The method of claim 6 , wherein said scaffold is poly(ethylene glycol).
8. The method of claim 1 , wherein said scaffold is poly(propyleneglycol).
9. The method of claim 4 , wherein said scaffold is poly(propyleneglycol).
10. The method of claim 6 , wherein said scaffold is poly(propyleneglycol).