Methods of using (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid
Inventors
Silverman, Richard B. • Dewey, Stephen L. • Miller, Steven
Assignees
Brookhaven Science Associates LLC • Northwestern University • Catalyst Pharmaceuticals Inc
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Publication Number
US-8969413-B2
Publication Date
2015-03-03
Expiration Date
Abstract
(1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid also known as CPP-115 or its pharmaceutically acceptable salts can be used to treat addiction and neurological disorders such as epilepsy without side effects such as visual field defects caused by vigabatrin (Sabril).
Core Innovation
The invention relates to using (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid, also referred to as CPP-115, or a salt thereof, in methods associated with reducing collateral damage selected from visual field defects and intramyelinic edema that are associated with the administration of the GABA aminotransferase inhibitor vigabatrin to a patient in need thereof. The methods include administering CPP-115 or its salt at specified amounts.
A mechanistic refinement is provided in which CPP-115 inactivates GABA aminotransferase through a di-fluoromethylene intermediate instead of 4-oxohex-5-enoic acid. A further formulation feature is that GABA aminotransferase is inhibited without preventing reuptake of GABA.
The documented discussion further contrasts the approach against vigabatrin by describing selectivity considerations and preclinical findings. The document associates CPP-115 with reduced collateral damage outcomes, including visual function endpoints, and with activity in addiction and neurological disorder contexts, including epilepsy models and cocaine-related measures.
Claims Coverage
The relevant independent claims are 1, 14, and 19. Across these claims, CPP-115 or salts are administered in specified amounts to reduce collateral damage selected from visual field defects and intramyelinic edema associated with vigabatrin, with mechanistic and functional limitations that distinguish the inhibition of GABA aminotransferase.
Reducing collateral damage with CPP-115 alongside vigabatrin
A method of reducing collateral damage selected from the group consisting of visual field defects and intramyelinic edema associated with the administration of the GABA aminotransferase inhibitor vigabatrin to a patient in need thereof, comprising the administration of (1 S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid or a salt thereof.
Di-fluoromethylene intermediate inactivating GABA aminotransferase
A method of reducing collateral damage selected from the group consisting of visual field defects and intramyelinic edema associated with the administration of the GABA aminotransferase inhibitor vigabatrin to a patient in need thereof, comprising the administration of (1 S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid or a salt thereof; wherein the (1 S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid inactivates GABA aminotransferase through a di-fluoromethylene intermediate instead of 4-oxohex-5-enoic acid.
Inhibiting GABA aminotransferase without preventing reuptake of GABA
A method of reducing collateral damage selected from the group consisting of visual field defects and intramyelinic edema associated with the administration of the GABA aminotransferase inhibitor vigabatrin to a patient in need thereof, comprising the administration of (1 S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid or a salt thereof; wherein GABA aminotransferase is inhibited without preventing reuptake of GABA.
The claim coverage centers on administering (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid, also referred to as CPP-115, or a salt thereof, in methods that reduce vigabatrin-associated collateral damage. The coverage further includes mechanistic and functional limitations tied to inactivation via a di-fluoromethylene intermediate and inhibition of GABA aminotransferase without preventing GABA reuptake.
Stated Advantages
Reduction of collateral damage selected from visual field defects and intramyelinic edema associated with administration of the GABA aminotransferase inhibitor vigabatrin.
CPP-115 inactivates GABA aminotransferase through a di-fluoromethylene intermediate instead of 4-oxohex-5-enoic acid.
GABA aminotransferase is inhibited without preventing reuptake of GABA.
Documented Applications
Treating addiction and neurological disorders, notably epilepsy.
Reducing collateral damage, including visual field defects and intramyelinic edema, associated with administration of vigabatrin to a patient in need thereof.
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