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Assignees
Member
Oklahoma Medical Research FoundationFounded in 1946, this independent nonprofit biomedical research institute conducts basic, translational, and clinical research in critical areas such as heart disease, cancer, autoimmune, and neurodegenerative diseases. Its mission focuses on understanding biological mechanisms and advancing diagnostics and therapeutics. Activities include conducting clinical trials, managing a patent portfolio, commercializing biotechnologies, and supporting the biotech community. Research efforts are funded by grants and philanthropy, and the institute hosts advanced facilities, interdisciplinary research teams, and collaborations with academia and industry.
Founded in 1946, this independent nonprofit biomedical research institute conducts basic, translational, and clinical research in critical areas such as heart disease, cancer, autoimmune, and neurodegenerative diseases. Its mission focuses on understanding biological mechanisms and advancing diagnostics and therapeutics. Activities include conducting clinical trials, managing a patent portfolio, commercializing biotechnologies, and supporting the biotech community. Research efforts are funded by grants and philanthropy, and the institute hosts advanced facilities, interdisciplinary research teams, and collaborations with academia and industry.
Publication Number
US-10555915-B2
Publication Date
2020-02-11
Expiration Date
Abstract
The current invention provides methods and compositions for treating sensorineural hearing loss including but not limited to acute acoustic trauma (AAT). The composition 2,4-disulfonyl α-phenyl tertiary butyl nitrone and N-acetylcysteine (NAC). Preferably, the compositions for treating AAT will be administered orally. However, other methods which deliver the compositions for treating AAT systemically to the body should work equally well.
Core Innovation
The invention provides methods and compositions to treat sensorineural hearing loss using 2,4-disulfonyl α-phenyl tertiary butyl nitrone (referred to as 2,4-disulfonyl PBN or HPN-07), administered alone or in combination with N-acetylcysteine (NAC). The specification describes acid and salt forms, pharmaceutically acceptable cations, and multiple delivery and formulation options including oral delivery, salts, nanoparticles or dendrimers, and local or systemic administration. The disclosure also identifies additional antioxidants and mitochondria-targeting peptides as possible adjuncts.
The document frames the problem as treating sensorineural hearing loss, particularly following acute acoustic trauma, by addressing free-radical-mediated injury and related pathways. The specification describes a proposed mechanism of free-radical trapping and possible inhibition of inducible nitric oxide synthase and reports in vivo efficacy in chinchilla and rat acute acoustic trauma models where HPN-07 reduces auditory threshold shifts and HPN-07 combined with NAC provides synergistic, more robust protection. [procedural detail omitted for safety]
Claims Coverage
The claims include one independent claim directed to a method of treating sensorineural hearing loss by orally delivering a composition comprising 2,4-disulfonyl α-phenyl tertiary butyl nitrone. The coverage focuses on oral administration of the active compound for treatment of sensorineural hearing loss.
Oral delivery of 2,4-disulfonyl α-phenyl tertiary butyl nitrone
Orally delivering to a patient in need a composition comprising a pharmaceutically effective amount of 2,4-disulfonyl α-phenyl tertiary butyl nitrone for treating sensorineural hearing loss.
The independent claim centers on oral administration of a composition comprising a pharmaceutically effective amount of 2,4-disulfonyl α-phenyl tertiary butyl nitrone to treat sensorineural hearing loss; dependent claims further narrow the invention by adding co-agents (e.g., N-acetylcysteine) and timing or frequency constraints.
Stated Advantages
HPN-07 reduces auditory threshold shifts in animal acute acoustic trauma models.
Combination of HPN-07 with N-acetylcysteine provides synergistic, more robust protection compared to HPN-07 or NAC alone.
Oral delivery is described as a preferred route of administration.
The compositions allow formulation flexibility, including acid and salt forms, pharmaceutically acceptable cations, and delivery via nanoparticles/dendrimers or local/systemic routes.
Documented Applications
Treating sensorineural hearing loss.
Treating sensorineural hearing loss resulting from acute acoustic trauma.
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