Therapeutic vitamin D conjugates
AssigneeExtend Biosciences, Inc.
InventorsTarik Soliman, Laura M. Hales, Daniel B. Hall, Christopher So, Howard P. Sard, Vishnumurthy Hegde
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Abstract
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.
Claims40
A carrier-drug conjugate comprising a targeting group that is a vitamin D that is not hydroxylated at the carbon 1, conjugated to a therapeutic peptide at the carbon 3 position of said vitamin D targeting group position via a scaffold, wherein said carrier increases the absorption, bioavailability, or half-life of said therapeutic peptide in circulation when compared to a non-conjugated form of said therapeutic peptide.
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 to a therapeutic peptide at the carbon 3 position of said vitamin D targeting group via a scaffold.
A pharmaceutical carrier comprising a formula I:
- B-(L)a-S-(M)b-C I
- Wherein:
- B is a targeting group that is a vitamin D that is not hydroxylated at the carbon 1 position, conjugated at the carbon 3 position to (L)a;
- S is a scaffold moiety, comprising poly(ethylene glycol), polylysine, polyethyleneimine, poly(propyleneglycol), a peptide, an amino acid, a nucleic acid, a glycan, a modifying group that contains a reactive linker, polylactic acid, a water-soluble polymer, a small carbon chain linker, or an additional therapeutic moiety;
- C is an amine-reactive group, a thiol-reactive group, a maleimide group, a thiol group, a disulfide group, an aldehyde group, an NETS-ester group, a 4-nitrophenyl ester, an acylimidazole, a haloacetyl group, an iodoacetyl group, a bromoacetyl groups, a SMCC group, a sulfo SMCC group, a carbodiimide group and bifunctional cross-linkers such as NHS-Maleimido or combinations thereof;
- (L)a and (M)b are linkers independently selected from (CH2)n—, —C(O)NH—, —HNC(O)—, —C(O)O—, —OC(O)—, —O—, —S—S—, —S—, —S(O)—, —S(O)2— and —NH—;
- a is an integer from 0-4;
- b is an integer from 0-4;
- and
- n is an integer from 0-3.
A pharmaceutical composition, comprising:
- a) a therapeutic peptide,
- b) a stably attached scaffold,
- c) a targeting group that is a vitamin D that is not hydroxylated at the carbon 1 position, conjugated at the carbon 3 position,
- wherein after administration to a first test subject, said therapeutic peptide has a half life measured by Enzyme Linked Immunosorbant Assay (ELISA) analysis of blood samples taken at a plurality of time points that is greater than a half life of said therapeutic peptide administered to a second test subject without said stably attached scaffold moiety and targeting group as measured by said ELISA analysis of blood samples taken at said plurality of time points.
A carrier-drug conjugate comprising a targeting group that is vitamin D, not hydroxylated at the carbon 1, non-releasably conjugated at the carbon 3 position via a scaffold to a therapeutic peptide, wherein said carrier increases the absorption, bioavailability, or half-life of said therapeutic peptide in circulation when compared to a non-conjugated form of said therapeutic peptide.
Dependencies are inferred from the claim text.