Patent ID: 11883424
Assignee: HIGHLIGHT THERAPEUTICS, S.L.
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A  C

Claim 0:
1. A method for preparing an aqueous composition comprising one or more particles wherein:
(a) each particle comprises a complex of at least one double-stranded polyribonucleotide, or a salt or solvate thereof, and at least one water-soluble, linear polyethyleneimine, or a salt and/or solvate thereof, wherein
(i) the double-stranded polyribonucleotide is polyinosinic-polycytidylic acid [poly(I:C)], or a salt or solvate thereof, wherein
at least 40% of the poly(I:C) have at least 850 base pairs, and
at least 50% of poly(I:C) have between 400 and 5000 base pairs; and
between 5% and 60% of poly(I:C) have less than 400 base pairs;
between 15% and 30% of poly(I:C) have between 400 and 850 base pairs,
between 10% and 70% of poly(I:C) have between 850 and 5000 base pairs;
between 0% and 10% of poly(I:C) have more than 5000 base pairs, and

(ii) the average molecular weight of the water-soluble, linear polyethyleneimine is between 17 and 23 kDa and has a polydispersity index of <1.5;

(b) at least 90% of the particles have a mono-modal diameter distribution of below 300 nm;
(c) the one or more particles each have a z-average diameter of 80+/−20 nm measured according to ISO standard 22412:2017, and each particle diameter has a polydispersity index between 0.1 and 0.6;
(d) the poly(I:C) concentration is at least 0.5 mg/mL;
(e) the composition has a pH of between 3.0+/−0.2 and an osmolality of between 300 and 310 mOsm/kg; and
(f) the composition has a zeta potential between 35 mV and 50 mV measured according to ISO standard 13099-2:2012,
wherein the method comprises:
(i) preparing a first aqueous solution of poly(I:C) or a salt or solvate thereof, and a second aqueous solution of linear polyethyleneimine or a salt or solvate thereof;
(ii) independently filtering each respective first and second aqueous solution through a filter having a pore diameter of less than or equal to 500 nm thereby forming a corresponding first and second sterilized solution; and
(iii) mixing each resulting first and second sterilized solution in a mixing chamber thereby forming the aqueous composition.