METHODS FOR INCREASING EFFICACY OF LIPID FORMULATED siRNA
AssigneeArbutus Biopharma Corporation
InventorsKevin Fitzgerald, Maria Frank-Kamenetsky, Akin Akinc, Martin A. Maier
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Abstract
This invention relates to methods for increasing the efficiency of siRNA administrations via pre-administration of an agent that lowers LDL receptor levels.
Claims44
A method for administering a neutral liposomal formulated, siRNA targeting a gene to a subject comprising administering to the subject an agent that increases LDLR levels, and subsequently administering a first effective dose of the neutral liposomal formulated, siRNA targeting a gene, wherein said first effective dose is lower than a dose of the neutral liposomal formulated siRNA administered to the subject without the agent.
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A method for administering a neutral liposomal formulated, PCSK9 targeted dsRNA to a human comprising administering to the human an initial dose of neutral liposomal formulated, PCSK9 targeted dsRNA resulting in an initial lowering of total serum cholesterol levels in the human by at least 15%, and subsequently administering a first effective dose of the neutral liposomal formulated, PCSK9 targeted dsRNA resulting in maintenance of lowering of total serum cholesterol levels in the human by at least 15%, wherein said first effective dose is at least two fold lower than a dose of the neutral liposomal formulated, PCSK9 targeted dsRNA administered to the subject without the initial dose of the PCSK9 targeted dsRNA.
A method for increasing the uptake efficiency of a neutral liposomal formulated AD-9680 dsRNA in a subject comprising administering an initial bolus dose of 3 mg/kg of the neutral liposomal formulated AD-9680 to the subject resulting in a first result of a lowering in total serum cholesterol levels by about 60% 3 days after the initial dose, wherein after administering the initial dose, subsequent administrations of the neutral liposomal formulated AD-9680 at lower dosages of 1.0 or 0.3 mg/kg achieve a second result similar to the first result.
A kit comprising an agent for lowering LDLR levels in a human and a lipid formulated gene siRNA targeting a gene.
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Dependencies are inferred from the claim text.