Methods of treating neurodegenerative disorders in a particular population
Inventors
Abushakra, Susan • Power, Aidan • TOLAR, Martin • Hey, John • Yu, Jeremy • Kocis, Petr
Assignees
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Publication Number
US-11191742-B2
Publication Date
2021-12-07
Expiration Date
Abstract
Disclosed herein are methods for treating, ameliorating, and/or preventing Alzheimer's Disease in a specific patient population using tramiprosate, valyl-3-amino-1-propanesulfonic acid, or a pharmaceutically acceptable salt thereof based upon a combination of APOE4 status and disease severity.
Core Innovation
The disclosed invention is a method of treating Alzheimer’s Disease in a subject by administering a pharmaceutical composition comprising valyl-3-amino-1-propanesulfonic acid, or a pharmaceutically acceptable salt thereof, in an amount effective to reduce cognitive decline. The administering is restricted to subjects determined to be APOE4/4 homozygous and to have a baseline Mini-mental State Examination (MMSE) score of ≥22, where the MMSE is performed within sixty days prior to the first administration of the composition.
The disclosure further characterizes the treatment by tying suitability and selection to both APOE4 status and Alzheimer’s disease severity measured by baseline MMSE. The document describes determining a subject’s suitability for treatment and selecting a patient for treatment only when the subject is APOE4/4 homozygous and meets the MMSE threshold and timing condition.
The invention also includes composition and dosing constraints directed to the same genotype-and-severity eligibility. The disclosed treatment includes compositions comprising valyl-3-amino-1-propanesulfonic acid in quantified amounts, including delivering about 150 mg tramiprosate per dose and/or comprising between 260 and 270 mg valyl-3-amino-1-propanesulfonic acid, including 265 mg, and, in some embodiments, an instant release oral tablet or capsule, with administration frequency limited to twice daily.
Claims Coverage
The independent claims provide coverage for treating Alzheimer’s Disease with valyl-3-amino-1-propanesulfonic acid only for APOE4/4 homozygous subjects meeting a baseline MMSE threshold measured within sixty days, determining suitability based on APOE4 status and baseline MMSE timing, and selecting and then treating a patient using the same eligibility criteria. Across the independent claims, the inventive features are centered on APOE4/4 homozygosity, baseline MMSE eligibility (≥22, with timing within sixty days), and, in some claim sets, quantified tramiprosate/valyl-3-amino-1-propanesulfonic acid delivery plus instant release oral tablet/capsule and twice-daily administration.
APOE4/4 homozygous eligibility for treatment
Administering a pharmaceutical composition comprising valyl-3-amino-1-propanesulfonic acid, or a pharmaceutically acceptable salt thereof, in an amount effective to reduce cognitive decline only if the subject is determined to be APOE4/4 homozygous.
Baseline MMSE threshold and timing condition
Administering the pharmaceutical composition only if the subject is determined to have a baseline Mini-mental State Examination (MMSE) score of ≥22, wherein the MMSE is performed within sixty days prior to the first administration of the composition.
Delivering about 150 mg tramiprosate per dose for eligible subjects
Administering to the subject a pharmaceutical composition that delivers about 150 mg of tramiprosate/dose, only if the subject is determined to be APOE4/4 homozygous and to have a baseline MMSE score of ≥22, wherein the MMSE is performed within sixty days prior to the first administration of the composition.
Quantified valyl-3-amino-1-propanesulfonic acid amount for eligible subjects
Administering to the subject a pharmaceutical composition comprising between 260 and 270 mg valyl-3-amino-1-propanesulfonic acid, or a pharmaceutically acceptable salt thereof, only if the subject is determined to be APOE4/4 homozygous and to have a baseline MMSE score of ≥22, wherein the MMSE is performed within sixty days prior to the first administration of the composition.
Instant release oral tablet or capsule formulation
Using a pharmaceutical composition that includes 265 mg of valyl-3-amino-1-propanesulfonic acid and is formulated as an instant release oral tablet or capsule.
Twice daily administration for eligible subjects
Administering the pharmaceutical composition twice daily.
Suitability determination based on APOE4 status and baseline MMSE
Determining the APOE4 status of the subject and the severity of the subject’s Alzheimer’s disease, wherein only if the subject is APOE4/4 homozygous and has a baseline Mini-mental State Examination (MMSE) score of ≥22, wherein the MMSE is performed within sixty days prior to the first administration of the composition, the subject is determined to be suitable for treatment.
Selecting and treating a patient based on eligibility criteria
Selecting the patient if the patient is both APOE4/4 homozygous and has a baseline Mini-mental State Examination (MMSE) score of ≥22, wherein the MMSE is performed within sixty days prior to the first administration of the composition, and administering to the selected patient a pharmaceutical composition comprising valyl-3-amino-1-propanesulfonic acid, or a pharmaceutically acceptable salt thereof, in an amount effective to reduce cognitive decline.
Across the independent claims, the claim coverage is directed to methods that restrict valyl-3-amino-1-propanesulfonic acid treatment for Alzheimer’s Disease to subjects who are APOE4/4 homozygous and meet a baseline MMSE eligibility condition (MMSE score ≥22 performed within sixty days prior to first administration). Additional independent coverage includes suitability determination and patient selection using the same criteria, and, in some independent claim sets, compositions that deliver about 150 mg tramiprosate per dose or contain quantified 260–270 mg valyl-3-amino-1-propanesulfonic acid, together with dependent-claim constraints on instant release oral tablet/capsule and twice-daily administration.
Stated Advantages
Reduce cognitive decline.
Documented Applications
Methods for treating Alzheimer’s Disease using valyl-3-amino-1-propanesulfonic acid in eligible subjects based on APOE4/4 homozygosity and baseline MMSE score (≥22) performed within sixty days prior to first administration.
Methods for determining a subject’s suitability for treatment with valyl-3-amino-1-propanesulfonic acid based on APOE4 status and severity measured by baseline MMSE.
Methods of selecting and treating an Alzheimer’s disease patient by selecting only patients meeting APOE4/4 homozygous and baseline MMSE (≥22) eligibility with MMSE performed within sixty days prior to first administration.
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