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-11597749-B2
Publication Date
2023-03-07
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 disclosed subject matter relates to a peptide compound having the structure His-His-Ile-Tyr-Leu-Gly-Ala-Val-Asn-Tyr-Ile-Tyr-amide (SEQ ID NO:1), including pharmaceutically acceptable salts. The peptide is described together with ocular aqueous formulations that include pharmaceutically acceptable excipients and components such as salts/buffers, optional non-ionic surfactants, and cosolvents, with specified pH ranges and salt forms including polyacetate/triacetate salts.
The peptide compound is positioned as an apoptosis inhibitor that blocks Fas- or TRAIL-mediated apoptosis. The described intended protective effect is on retinal cells, including photoreceptors, retinal pigment epithelium (RPE), and retinal ganglion cells. The described scope of use includes retinal detachment and related retinal degenerative diseases, with explicit mention of Fas-mediated RPE apoptosis and TRAIL-mediated apoptosis as mechanistic targets.
The partial content reports comparative potency and in vivo protective performance relative to a comparator peptide identified as Met-12. Compound 1 shows approximately 10-fold greater potency than Met-12 in vitro based on caspase 8 activation, and it also reports superior in vivo photoreceptor protection versus Met-12 in a rat retinal detachment model.
Claims Coverage
The independent claim covers a pharmaceutically acceptable salt of a compound having the stated formula, with dependent claims refining salt identity and ocular formulation context. The provided claim family information reflects at least five inventive features: acetate salt, triacetate salt, ocular injection route, surfactant excipient concentration range, and buffered pH range.
Pharmaceutically-acceptable acetate salt
A pharmaceutically acceptable salt where the salt is specifically an acetate salt.
Triacetate polyacetate salt
A pharmaceutically acceptable salt where a polyacetate salt is specifically a triacetate salt.
Ocular injection route formulation
A pharmaceutically acceptable salt in an aqueous composition formulated for intraocular, intravitreal, or periocular injection.
Surfactant excipient concentration range
A composition including a surfactant excipient present at 0.01% to 20% w/w.
Buffered formulation with pH 2.5 to 6.0
A composition including a buffering agent, where the formulation is buffered at a pH between 2.5 and 6.0.
Across the provided claim-family information, the coverage centers on pharmaceutically acceptable salts of the disclosed compound, with dependent refinements specifying acetate and triacetate salts and ocular injection formulations with surfactant and buffered pH constraints.
Stated Advantages
Greater in vitro potency for caspase 8 activation compared to Met-12.
Superior in vivo photoreceptor protection versus Met-12 in a rat retinal detachment model.
Extended vitreous/retina exposure after intravitreal injection supported by formulation-dependent pharmacokinetics/retention.
Documented Applications
Protecting retinal cells, including photoreceptors, RPE, and retinal ganglion cells, in retinal detachment and related retinal degenerative diseases.
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