Compositions and methods for treating spinocerebellar ataxia
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Publication Number
US-9125924-B2
Publication Date
2015-09-08
Expiration Date
Abstract
The present invention provides intravenous compositions of trehalose for the treatment of signs and symptoms of spinocerebellar ataxia (SCA).
Core Innovation
The invention relates to an intravenous (IV) treatment for alleviating a sign or symptom of spinocerebellar ataxia (SCA) in a subject in need thereof. The treatment comprises intravenously administering an aqueous formulation for intravenous injection, wherein the aqueous formulation includes a single active ingredient consisting of trehalose.
The aqueous trehalose formulation is characterized by formulation parameters that include a pH about 4.5 to 7.0 and less than 0.75 endotoxin units per mL. The formulation is further characterized by an administration timing constraint in which the administration is completed within less than 120 minutes, and by a per administration dose of between 5 to 50 grams trehalose.
The disclosed therapeutic concept is that trehalose prevents pathological intracellular protein aggregation, including PABPN1 aggregates. The disclosure also includes sustained cellular uptake and retention for about 48 to 72 hours following administration, supporting the therapeutic effect for aggregation diseases related to intracellular protein aggregation.
The disclosure further ties the IV trehalose approach to therapeutic methods and dosing regimens for administering trehalose, including once weekly dosing in some embodiments, and addresses product quality and safety attributes such as sterility and trehalose formulation characteristics including pH and osmolality. The document also includes preclinical pharmacokinetics and clinical study planning for IV trehalose (Cabaletta®) in OPMD.
Claims Coverage
The claims are centered on an independent method claim that specifies alleviating SCA by intravenously administering a single-ingredient aqueous trehalose formulation with specific formulation quality parameters and an administration timing limit. Dependent claims further refine dosing frequency, dose amount expression, and additional formulation/safety constraints, including concentration and osmolality.
Intravenous trehalose aqueous formulation for alleviating SCA
A method of alleviating a sign or symptom of spinocerebellar ataxia (SCA) by intravenously administering to a subject an aqueous formulation for intravenous injection comprising a single active ingredient consisting of trehalose.
Quality-controlled trehalose pH and endotoxin for IV injection
The formulation has a pH about 4.5 to 7.0 and contains less than 0.75 endotoxin units per mL.
Dose and rapid administration completion time
The formulation is administered at a per administration dose of between 5 to 50 grams trehalose, wherein the administration is completed within less than 120 minutes.
Once weekly administration schedule
The formulation is administered once per week.
Per kilogram trehalose dose amount
The formulation is administered at a per-dose amount of about 0.5 gram trehalose per kilogram body weight.
Discrete per-day trehalose dose values
The method is performed using a per-day dose of 8, 15, or 30 grams.
10% (w/v) trehalose concentration
Trehalose is present at a concentration of 10% (w/v).
Osmolality-limited formulation
The formulation has an osmolality of about 280 to 330 mOsm/kg.
Across the independent and dependent claims, the invention coverage is directed to IV alleviation of SCA using a single-ingredient trehalose aqueous formulation with specified pH and endotoxin limits and a requirement that administration completes within less than 120 minutes, together with claim refinements covering specific dosing schedules and dose amount expressions and additional formulation constraints such as trehalose concentration and osmolality.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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