Patent ID: 9579338
Date: 2017-02-28
CPC Classifications: A61K,C12N

Claim:
1. A method for preparing a lipid nanoparticle encapsulating a RNA molecule, comprising the steps of (a) transferring to a mixing container a first aqueous buffer, pH 3.5-6.5, comprising the RNA molecule at 0.08 to 0.8 mg/ml; (b) injecting a lipid solution comprising a cationic lipid, a helper lipid, a sterol, and a PEG lipid dissolved in a water-miscible organic solvent into the aqueous solution in the mixing container at a constant rate for 1-100 minutes while stirring the aqueous solution until a mixture comprising 25-45% (v:v) organic solvent is reached; (c) diluting the organic solvent in the mixture to less than 10% (v:v); and (d) removing the organic solvent from the diluted mixture by diafiltration against a second aqueous buffer, pH 6.5-8; wherein step (b) is performed batchwise, and wherein the mixture comprises lipid nanoparticles having a RNA:lipid ratio 0.06 to 0.16 (w:w), and a RNA:lipid charge ratio of 1:2.5 to 1:1.