Conjugated hepcidin mimetics
Inventors
Bourne, Gregory Thomas • Bhandari, Ashok • Frederick, Brian Troy • Zhang, Jie • STEPHENSON, Adam • Smythe, Mark Leslie • TARANATH, Roopa • Liu, David Y.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12234300-B2
Publication Date
2025-02-25
Expiration Date
Abstract
The present invention provides hepcidin analogues with improved in vivo half lives, and related pharmaceutical compositions and methods of use thereof.
Core Innovation
The disclosure describes a peptide or a peptide dimer thereof comprising or consisting of specified sequence variants, including hepcidin analogue and hepcidin-mimetic sequence elements with defined substitutions such as Dpa, PCI, Lys, b-hPhe, and aryl residues. The peptide is cyclized via a disulfide bond between two cysteines, and the described embodiments include variant amino-acid positions, illustrative sequence tables, and dimer forms linked by linker options.
The structures incorporate covalently attached half-life extension moieties selected from lipophilic substituents and polymeric PEG/PEO/POE-type options, including palmityl and PEG-containing constructs such as PEG11 and related PEGn/OEG variants. The disclosure also includes linker moieties such as isoglu, dapa, ahx, PEG-based linker options, and L1 linker variants including single bond, iso-Glu, Ahx, PEG, and PEG-Ahx, together with related dimer and half-life extension moiety embodiments.
The disclosure further describes pharmaceutical compositions, salts/solvates, and hepcidin/ferroportin activity in terms of ferroportin binding, internalization, and degradation. It also provides embodiments using disulfide bond connections between residues such as B3 residues and half-life extension moiety Z in dimer contexts, including Palm together with iminodiacetic acid arrangements.
Claims Coverage
The provided claim set centers on cyclized hepcidin analogue peptides or peptide dimers defined by specified sequence variants and disulfide cyclization, with covalently attached half-life extension moieties. Six inventive features are directly reflected across the independent-claim content and associated dependent claims.
Cyclized hepcidin analogue peptide or peptide dimer with specified sequence variants
A peptide or a peptide dimer thereof comprising or consisting of specified sequence variants, including hepcidin analogue and hepcidin-mimetic embodiments.
Disulfide cyclization via two cysteines
The peptide is cyclized via a disulfide bond between two cysteines.
Specified aryl residue and linker variants
The peptide includes specified aryl residue embodiments and linker options, including B1/B6 aryl residues and L1 linker variants such as single bond, iso-Glu, Ahx, PEG, and PEG-Ahx.
Half-life extension via lipophilic or PEG-containing moieties
The specified peptide sequences include half-life extension moieties, including palmityl-containing constructs and PEG-containing linker moieties such as Peg11-containing variants.
Pharmaceutical composition with pharmaceutically acceptable carrier, excipient, or vehicle
A pharmaceutical composition that includes the peptide or its peptide dimer together with a pharmaceutically acceptable carrier, excipient, or vehicle.
Ferroportin binding and inducing internalization and degradation
A method for binding ferroportin or inducing its internalization and degradation by contacting ferroportin with at least one pharmaceutical composition that includes the peptide or peptide dimer.
The inventive core is a cyclized hepcidin analogue peptide or peptide dimer defined by specified sequence variants, with disulfide cyclization and linked half-life extension moieties. The claim coverage further includes variant aryl residues, linker moieties, pharmaceutical composition formulations, and ferroportin-related use claims oriented to binding, internalization, and degradation.
Stated Advantages
Improved half-life/clearance/permeability.
Albumin binding.
Shielding from degradation.
Improved half-life by albumin binding and reduced clearance associated with the use of lipophilic substituents and polymeric PEG/PEO/POE-type moieties.
Potential improved solubility.
Potential improved stability.
Potential reduced aggregation.
Stated hepcidin/ferroportin activity including iron reduction, ferroportin degradation, and stability/half-life characteristics.
Documented Applications
Treating an iron metabolism disease, including through compositions and methods that bind ferroportin and induce its internalization and degradation.
Administering pharmaceutical compositions orally (as explicitly stated in dependent claim refinements).
Treatment of an iron metabolism disease.
Treatment of iron metabolism disorders, including iron overload diseases such as hereditary hemochromatosis, iron-loading anemias, transfusional iron overload, and thalassemia.
Interested in licensing this patent?