Compositions and methods for treating oculopharyngeal muscular dystrophy
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Publication Number
US-9084720-B2
Publication Date
2015-07-21
Expiration Date
Abstract
The present invention provides intravenous compositions of trehalose for the treatment of signs and symptoms of oculopharyngeal muscular dystrophy (OPMD).
Core Innovation
The disclosed invention relates to intravenously administering a trehalose aqueous formulation for intravenous injection to alleviate a sign or symptom of oculopharyngeal muscular dystrophy (OPMD). The formulation is a single active ingredient formulation consisting of trehalose, provided with defined formulation parameters for pH and endotoxin level and with an administration schedule that is completed within less than 120 minutes.
The invention targets protein aggregation by providing a trehalose intravenous formulation intended to achieve cellular uptake and retention over about 48 to 72 hours. The disclosed effects include reduced protein aggregation, including abnormal PABPN1, as described in the supporting discussion.
The disclosed intravenous formulation is characterized by a pH about 4.5 to 7.0, a low endotoxin level of less than 0.75 endotoxin units per mL, and a defined per-administration trehalose dose between 5 to 50 grams, with administration completed within less than 120 minutes. The formulation parameters described in the content include 10% (w/v) trehalose and osmolality about 280 to 330 mOsm/kg, along with endotoxin control constraints during administration.
Claims Coverage
The independent claim covers a method for alleviating a sign or symptom of OPMD using an intravenous trehalose single-active-ingredient aqueous formulation with specific formulation quality parameters and timing constraints. One independent claim is provided, with dependent refinements that further constrain dosage, frequency, endotoxin-rate limits, concentration, and osmolality.
Intravenous trehalose aqueous formulation with specified pH, endotoxin, dose, and completion time
Alleviating a sign or symptom of oculopharyngeal muscular dystrophy (OPMD) by intravenously administering to a subject in need thereof an aqueous formulation for intravenous injection comprising a single active ingredient consisting of trehalose, wherein the formulation has a pH about 4.5 to 7.0, contains less than 0.75 endotoxin units per mL, and 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 intravenous administration schedule
The method is carried out with the formulation administered once weekly.
Weight-based trehalose per administration dose
The method is practiced by administering the formulation at a dose of about 0.5 gram trehalose per kilogram body weight per administration.
Administration-rate tied endotoxin maximum
The method further specifies that the administration rate is set so the maximum endotoxin level is less than 5 EU per kilogram of body weight per hour.
10% (w/v) trehalose formulation
The method is performed with trehalose present at 10% (w/v).
280 to 330 mOsm/kg osmolality formulation
The method is performed using a formulation with an osmolality of about 280 to 330 mOsm/kg.
Overall, the claim coverage is directed to alleviating OPMD signs or symptoms using an intravenous single-active-ingredient trehalose aqueous formulation with defined pH and endotoxin limits and with administration completed in less than 120 minutes. The dependent refinements further specify administration frequency, weight-based dosing, an administration-rate-linked endotoxin maximum, and specific formulation concentration and osmolality.
Stated Advantages
Alleviating a sign or symptom of oculopharyngeal muscular dystrophy (OPMD).
Reduced protein aggregation, including abnormal PABPN1.
Cellular uptake and retention over about 48 to 72 hours.
Documented Applications
A planned multi-center randomized clinical trial in genetically diagnosed OPMD patients using weekly intravenous Cabaletta® (10% trehalose) with dose escalation and efficacy and safety assessments.
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