Methods for treating lysosomal acid lipase deficiency in patients
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Publication Number
US-12076376-B2
Publication Date
2024-09-03
Expiration Date
Abstract
The present invention provides methods of treating LAL deficiency comprising administering to a mammal a therapeutically effective amount of lysosomal acid lipase with an effective dosage frequency. Methods of improving growth and liver function, increasing LAL tissue concentration, and increasing LAL activity in a human patient suffering from LAL deficiency are also provided.
Core Innovation
The invention relates to recombinant human lysosomal acid lipase (rhLAL), including SBC-102, for treating human lysosomal acid lipase (LAL) deficiency, including Wolman disease (WD) and cholesteryl ester storage disease (CESD). The approach emphasizes administering rhLAL with low-frequency dosing schedules to a human infant, or to a human subject that is a child or an adult, by intravenous administration, including intravenous infusion and intravenous injection.
The patent describes administration of rhLAL at specified dose amounts per kilogram body weight, with dosing frequency constrained to one time every 5 days to once every 30 days, including options such as once every 7 days or once every 14 days depending on the subject group. Intravenous infusion duration is described as 1 to 8 hours.
The document also describes mechanistic data supporting lysosomal delivery of LAL activity, including internalization to lysosomal compartments via GlcNAc/mannose receptor and mannose-6-phosphate (M6P) targeting, together with in vitro and in vivo activity and localization. Clinical evaluation includes safety and tolerability, pharmacokinetics, biomarker changes, immunogenicity/ADA, and first-in-human dosing outcomes in infant and adult cases.
Claims Coverage
The partial content provides four independent claims directed to methods of treating a human subject with lysosomal acid lipase (LAL) deficiency using recombinant human LAL at specified doses and administration patterns. Across the independent claims, the inventive features are the specified dosing amounts by patient group, the low-frequency or interval-constrained dosing schedule, the intravenous infusion parameters, and an antihistamine followed by rhLAL sequential administration pattern.
Infant dosing with 1 mg, 3 mg, or 5 mg recombinant human LAL per kg
A method of treating a human infant suffering from a lysosomal acid lipase (LAL) deficiency comprising administering to the infant 1 milligram (mg), 3 mg, or 5 mg of recombinant human LAL per kilogram (kg) body weight.
Child or adult dosing with 1 mg/kg or 3 mg/kg recombinant human LAL
A method of treating a human subject suffering from a lysosomal acid lipase (LAL) deficiency, wherein the subject is a child or an adult, comprising administering to the subject 1 mg/kg or 3 mg/kg of recombinant human LAL.
Intravenous infusion of 1 mg/kg, 3 mg/kg, or 5 mg/kg over 1 to 8 hours
A method of treating a human subject suffering from a lysosomal acid lipase (LAL) deficiency, comprising administering to the subject 1 mg/kg, 3 mg/kg, or 5 mg/kg of recombinant human LAL over a period of 1 to 8 hours by intravenous infusion.
Antihistamine followed by 1 mg/kg or 5 mg/kg recombinant human LAL
A method of treating a human subject suffering from a lysosomal acid lipase (LAL) deficiency, comprising administering an antihistamine to the subject; and after administration of the antihistamine, administering 1 mg/kg or 5 mg/kg of recombinant human LAL to the subject.
The independent claims collectively cover treating LAL deficiency in an infant with defined per-kg rhLAL doses, treating a child or adult with defined per-kg rhLAL doses, administering rhLAL by intravenous infusion over 1 to 8 hours, and a sequential protocol in which an antihistamine is given prior to rhLAL dosing.
Stated Advantages
Not explicitly described in patent.
Documented Applications
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