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US 2016/0243255 A1Published application
Compositions and methods for the manufacture of lipid nanoparticles
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsLubomir Nechev, Stuart Price
Life of this patent
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Abstract
The invention relates to methods, processes and apparatuses for the manufacture of lipid nanoparticles having a therapeutic payload.
Claims28
A method of preparing a formulation comprising lipid nanoparticles comprising an RNAi agent payload comprising;
- (a) mixing a first solution with a second solution in a mixing connector, wherein
- (i) said first solution comprises an ethanolic solution comprising one or more lipids and having a total lipid concentration of approximately 30 mg/mL, and
- (ii) said second solution comprises citrate buffered aqueous solution comprising one or more RNAi agents and having an RNAi agent concentration of approximately 1 mg/mL and a pH of between 3 and 6, and
- (b) diluting the mixture produced in (a) in a vessel containing a buffer solution thereby producing a formulation comprising lipid nanoparticles comprising an RNAi agent payload;
- wherein the linear flow rate of said first solution into the mixing connector is approximately 606,267 cm/h and the linear flow rate of said second solution into the mixing connector is approximately 1,818,801 cm/h and the volume ratio of said first solution to said second solution is approximately 1:3.
2 more elements
A system for the manufacture of a formulation comprising lipid nanoparticles comprising an RNAi agent payload comprising;
- (a) a first reservoir providing a first solution, wherein said first solution is an ethanolic solution comprising one or more lipids,
- (b) a second reservoir providing a second solution, wherein said second solution is a buffered aqueous solution comprising one or more RNAi agents,
- (c) a first pump, operably connected to said first reservoir and configured to regulate the flow of said first solution at a linear flow rate of between 303,133-909,400 cm/h,
- (d) a second pump, operably connected to said second reservoir and configured to regulate the flow of said second solution at a linear flow rate of between 1,515,667-2,121,934 cm/h,
- (e) a mixing connector comprising at least a first inlet, a second inlet and an outlet, wherein said first inlet receives flow from said first pump and said second inlet receives flow from said second pump,
- (f) at least one heat exchanger operably connecting each of said first and said second pumps to said inlets of the mixing connector, respectively, and
- (g) a vessel for receiving effluent from the outlet of said mixing connector.
4 more elements
The method of any of the preceeding claims, wherein the RNAi agent is selected from the group consisting of siRNA, dsRNA, miRNA, and nucleotide sequences encoding the same.
Dependencies are inferred from the claim text.