Dosage forms and therapeutic uses L-4-chlorokynurenine
Inventors
Snodgrass, H. Ralph • CATO, Allen E. • HICKLIN, Jack S.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9993453-B2
Publication Date
2018-06-12
Expiration Date
Abstract
Compositions of L-4-chlorokynurenine are provided, as are methods for the treatment of neurological dysfunction.
Core Innovation
The invention provides unit-dose oral pharmaceutical compositions of L-4-chlorokynurenine (AV-101) for therapeutic use in neurological dysfunction. The compositions are described for treating depression and pain associated with overactive glutamatergic/NMDA-R signaling. L-4-chlorokynurenine is characterized as a prodrug that is converted in activated astrocytes to 7-chlorokynurenic acid, which enhances CNS access.
The background and summary rationale link the mechanism to excitotoxic neuronal damage through NMDA receptor signaling at the glycine B (GlyB) coagonist site. The document further summarizes therapeutic observations including tolerability and antihyperalgesic and anti-depressive effects. It describes reductions in pain measures such as allodynia, mechanical hyperalgesia, and heat hyperalgesia, and discusses increased “well-being” reports in an anti-depressive context.
The document also defines safety and tolerability criteria using “mild” adverse events, and reports that clinical study outcomes include pharmacokinetic profiles and dose-dependent reductions in pain measures. It presents randomized, double-blind placebo-controlled clinical study context and additional characterization of adverse events and tolerability. The summary emphasizes oral administration of therapeutically effective amounts and presents relevant dosing levels used in the described human studies.
Claims Coverage
The document provides two independent claims directed to treating depression in humans using orally administered L-4-chlorokynurenine with specified daily/unit dosing amounts. Across the independent claims, three main inventive aspects appear: oral administration, specified daily dose levels (360, 1080, 1440 mg), and the formulation as a pharmaceutical composition with a pharmaceutically acceptable carrier or excipient.
Oral administration of L-4-chlorokynurenine for treating depression
Orally administering to a human patient in need thereof a therapeutically effective amount of L-4-chlorokynurenine to treat depression.
Specified daily dose for depression treatment
Administering L-4-chlorokynurenine in a daily dose of 360, 1080 or 1440 mg to a human patient in need thereof for treating depression.
Pharmaceutical composition with unit dose and pharmaceutically acceptable carrier or excipient
Orally administering to a human patient in need thereof a pharmaceutical composition comprising a unit dose of 360, 1080 or 1440 mg of L-4-chlorokynurenine and a pharmaceutically acceptable carrier or excipient.
Overall, the claim coverage is directed to treating depression by oral administration of L-4-chlorokynurenine at specified dose levels (360, 1080, 1440 mg), either described as a therapeutically effective daily dose or as a pharmaceutical composition containing a unit dose with a pharmaceutically acceptable carrier or excipient. Dependent claims further emphasize tolerability constraints using “easily tolerated” adverse events with minimal discomfort that does not interfere with everyday activities, and also specify duration ranges in the depression-treatment regimen.
Stated Advantages
Treating depression with orally administered L-4-chlorokynurenine.
Reducing pain measures including allodynia, mechanical hyperalgesia, and heat hyperalgesia in the described context of neurological dysfunction.
Enhanced CNS access via conversion of L-4-chlorokynurenine to 7-chlorokynurenic acid in activated astrocytes.
Improved tolerability characterized by “mild” adverse events and “easily tolerated” adverse events with minimal discomfort not interfering with everyday activities.
Increasing “well-being” reports in an anti-depressive context.
Documented Applications
Treating depression in a human patient by orally administering L-4-chlorokynurenine at daily/unit doses of 360, 1080 or 1440 mg.
Treating pain associated with overactive glutamatergic/NMDA-R signaling, including reductions in allodynia and mechanical/heat hyperalgesia.
Interested in licensing this patent?