Therapeutic vitamin D conjugates
First Claim
1. 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.
4 Assignments
0 Petitions
Accused Products
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.
197 Citations
40 Claims
- 1. 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.
- 3. 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.
-
27. A pharmaceutical carrier comprising a formula I:
-
B-(L)a-S-(M)b-C
IWherein; 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. - View Dependent Claims (28, 29, 30)
-
-
31. 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. - View Dependent Claims (32, 33, 34, 35)
-
- 36. 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.
Specification