Peptide compositions and methods of use
Inventors
BESIRLI, Cagri G. • Bridges, Alexander J. • FRESHLEY, John K. • Hunke, William A. • JOHNSON, Linda L. • Smith, Francis X. • SYLVAIN, Ethan • Zacks, David N.
Assignees
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Publication Number
US-12258425-B2
Publication Date
2025-03-25
Expiration Date
Abstract
Provided herein are compositions including peptides, pharmaceutical preparations thereof, and methods of preventing photoreceptor death therewith and protecting of retinal cells, including, but not limited to, photoreceptors and retinal pigment epithelium, from Fas- or TRAIL-mediated apoptosis.
Core Innovation
The invention concerns peptide-based, aqueous ocular formulations centered on a C-terminally amidated Met-12-derived peptide (Compound 1) provided as a free base and as tri-/polyacetate salts. The disclosed peptide composition is used in the eye to prevent Fas- and/or TRAIL-mediated extrinsic apoptosis of retinal cells, including photoreceptors, retinal pigment epithelium (RPE), and retinal ganglion cells.
The invention addresses photoreceptor cell death and retinal disease by administering a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt. The document links this approach to preventing FasL- and TRAIL-related signaling events, including Fas receptor and TRAIL-mediated apoptosis, with downstream caspase-8 inhibition described as a key mechanism-related effect.
The rationale for using a C-terminal amide focuses on improving solubility/formulability and improving dose potency compared with Met-12. The disclosure further describes ocular pharmacokinetics and sustained exposure after intravitreal dosing, with exposure in vitreous/retina being modulated by formulation type, including micellar surfactant formulations and a contrast between poloxamer and polysorbate.
Claims Coverage
The provided set includes one independent claim directed to a method for treating photoreceptor cell death in an eye by administering a specified compound. Dependent claims narrow the administration to particular ocular injection routes and add quantitative constraints on administered amount and formulation volume.
Treating photoreceptor cell death in an eye using a therapeutically effective amount of a compound defined by a specified chemical formula
A method of treating photoreceptor cell death in an eye comprising administering to the eye a therapeutically effective amount of a compound having the specified formula, or a pharmaceutically acceptable salt thereof.
Ocular injection route (intraocular, intravitreal, or periocular)
The method further comprises administering the compound by intraocular, intravitreal, or periocular injection.
Therapeutically effective administered amount range
The method further comprises administering the compound in an amount of 25 µg to 200 µg.
Therapeutic formulation volume range (10 µL to 500 µL)
The method further comprises administering the pharmaceutical formulation in a volume ranging from 10 µL to 500 µL.
Across the independent claim and its dependents, the core coverage is a treatment method for photoreceptor cell death using a compound defined by a specified chemical formula (or a pharmaceutically acceptable salt), further limited by ocular injection routes and by specified ranges for administered amount and formulation volume.
Stated Advantages
Improved solubility/formulability associated with C-terminal amidation.
Improved dose potency compared with Met-12, including effects on caspase-8 inhibition.
Prevention of Fas- and/or TRAIL-mediated extrinsic apoptosis of retinal cells.
Reduced TUNEL+ apoptotic cells in rat retinal detachment.
Sustained vitreous/retina exposure after intravitreal dosing modulated by formulation type.
Documented Applications
Treating photoreceptor cell death in an eye of an individual in need thereof.
Preventing Fas- and/or TRAIL-mediated extrinsic apoptosis of retinal cells, including photoreceptors, RPE, and retinal ganglion cells.
Treatment/prevention in retinal detachment, including an in vivo rat retinal detachment context with reduced TUNEL+ apoptotic cells.
Treatment of retinal diseases explicitly mentioned in the document summary, including AMD and glaucoma.
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