US 2026/0250883 A1 · LIPID NANOPARTICLE PRODUCTION SYSTEM AND METHOD OF MONITORING AND CONTROLLING THE SAME

Abstract

The present invention relates to automated nanoparticle synthesis systems and computer-implemented methods of monitoring and controlling a process of manufacturing lipid nanoparticles (LNPs) containing nucleic acid cargo. The present invention furthermore relates to a computer program product comprising computer-readable instructions, which, when loaded and executed on a computer system, causes the computer system to perform operations according to said methods.

Claims28

Dependent claims

A computer-implemented method for the high throughput preparation of lipid nanoparticles (LNPs) containing a nucleic acid cargo, comprising the steps of

(a) providing one or more solution(s) comprising a nucleic acid cargo;
(b) providing one or more solution(s) comprising a lipid;
(c) mixing the one or more solution(s) comprising a nucleic acid cargo with the one or more solution(s) comprising a lipid at an acidic pH;
(d) neutralizing the pH of the mixed solution obtained in step (c) via dilution to stabilize the LNPs obtained in step (c);
(e) performing a buffer exchange on the neutralized solution obtained in step (d) via ultrafiltration and/or diafiltration (UF/DF) to concentrate the LNPs obtained in step (d) and reformulate the same into a cryogenic buffer, thereby generating one or more LNP preparation(s);
wherein
during each of steps (c) to (e), as well as after step (e), one or more of the particle size, polydispersity, and nucleic acid encapsulation of the one or more LNPs are monitored in real-time, thereby generating a data set for each LNP preparation;
and the generated data set is associated with the respective LNP preparation.

5 more elements

A computer-implemented method of monitoring and controlling a process of manufacturing lipid nanoparticles containing nucleic acid cargo,

wherein said process of manufacturing lipid nanoparticles containing nucleic acid cargo comprises the steps of
(i) mixing a solution containing the nucleic acid cargo with a lipid-containing solution at an acidic pH;
(ii) stabilizing the nanoparticles obtained in step (i) for a particular residence time;
(iii) neutralizing the pH of the mixed solution obtained in step (i) via dilution to further stabilize the nanoparticles obtained in step (ii);
(iv) performing a buffer exchange on the neutralized solution obtained in step (iii) via ultrafiltration and/or diafiltration (UF/DF) to concentrate the nanoparticles obtained in step (iii) and reformulate the same into a cryogenic buffer;
said computer-implemented method of monitoring and controlling said process of manufacturing lipid nanoparticles containing nucleic acid cargo comprising the steps of:
(a) monitoring, during each of steps (i) to (iv), as well as after step (iv), one or more quality parameters, such as particle size, polydispersity, and nucleic acid encapsulation of lipid nanoparticles in real-time;
(b) determining whether the quality parameters obtained in step (a) during each of steps (i) to (iv), as well as after step (iv), are within predetermined target ranges;
(c) in case any of the quality parameters obtained in step (a) during each of steps (i) to (iv), as well as after step (iv), are not within said predetermined target ranges, providing feedback control to adjust operating parameters of the respective step in real-time, in order to bring the respective quality parameters into the predetermined target ranges.

6 more elements

An automated nanoparticle synthesis system, comprising:

(a) a first dispenser assembly having a first pump integrated with a first valve;
(b) a second dispenser assembly having a second pump integrated with a second valve;
(c) a third valve;
(d) a microfluidic mixer;
(e) a lipid reservoir for holding a lipid stock solution;
(f) a nucleic acid reservoir for holding a nucleic acid stock solution;
and
(g) a waste reservoir, a buffer reservoir, and an ethanol reservoir;
wherein
(i) the lipid reservoir is fluidly connected to the first valve and the nucleic acid reservoir is fluidly connected to the second valve, or vice versa;
(ii) the first valve is fluidly connected to the first pump and the second valve is fluidly connected to the second pump;
(iii) each of the first valve and the second valve is fluidly connected to the waste reservoir, the buffer reservoir, and the ethanol reservoir, wherein the ports of the first valve and the second valve that are fluidly connected to the waste reservoir, the buffer reservoir, and the ethanol reservoir are different ports from those that are fluidly connected to the lipid reservoir and the nucleic acid reservoir;
(iv) each of the first valve and the second valve is fluidly connected to the microfluidic mixer;
and
(v) the third valve is fluidly connected to the microfluidic mixer, to the waste reservoir, and to one or more collection reservoir(s) for collecting produced lipid nanoparticles (LNPs).

12 more elements

Dependencies are inferred from the claim text.

Facts

Application

18/993,397Filed 11 Jul 2023

Priority

12 Jul 2022

Published

27 Aug 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

B01J 19/0046
Chemical, physical or physico-chemical processes in general; Their relevant apparatus: sequential or parallel reactions, e.g. for the synthesis of…
C40B 50/08
Methods of creating libraries, e.g. combinatorial synthesis: liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase…
G05D 21/02
Control of chemical or physico-chemical variables, e.g. pH value: characterised by the use of electric means
G16C 20/62
In silico combinatorial chemistry: design of libraries

Abstract

Claims28

Dependent claims

A computer-implemented method for the high throughput preparation of lipid nanoparticles (LNPs) containing a nucleic acid cargo, comprising the steps of

(a) providing one or more solution(s) comprising a nucleic acid cargo;
(b) providing one or more solution(s) comprising a lipid;
(c) mixing the one or more solution(s) comprising a nucleic acid cargo with the one or more solution(s) comprising a lipid at an acidic pH;
(d) neutralizing the pH of the mixed solution obtained in step (c) via dilution to stabilize the LNPs obtained in step (c);
(e) performing a buffer exchange on the neutralized solution obtained in step (d) via ultrafiltration and/or diafiltration (UF/DF) to concentrate the LNPs obtained in step (d) and reformulate the same into a cryogenic buffer, thereby generating one or more LNP preparation(s);
wherein
during each of steps (c) to (e), as well as after step (e), one or more of the particle size, polydispersity, and nucleic acid encapsulation of the one or more LNPs are monitored in real-time, thereby generating a data set for each LNP preparation;
and the generated data set is associated with the respective LNP preparation.

5 more elements

A computer-implemented method of monitoring and controlling a process of manufacturing lipid nanoparticles containing nucleic acid cargo,

wherein said process of manufacturing lipid nanoparticles containing nucleic acid cargo comprises the steps of
(i) mixing a solution containing the nucleic acid cargo with a lipid-containing solution at an acidic pH;
(ii) stabilizing the nanoparticles obtained in step (i) for a particular residence time;
(iii) neutralizing the pH of the mixed solution obtained in step (i) via dilution to further stabilize the nanoparticles obtained in step (ii);
(iv) performing a buffer exchange on the neutralized solution obtained in step (iii) via ultrafiltration and/or diafiltration (UF/DF) to concentrate the nanoparticles obtained in step (iii) and reformulate the same into a cryogenic buffer;
said computer-implemented method of monitoring and controlling said process of manufacturing lipid nanoparticles containing nucleic acid cargo comprising the steps of:
(a) monitoring, during each of steps (i) to (iv), as well as after step (iv), one or more quality parameters, such as particle size, polydispersity, and nucleic acid encapsulation of lipid nanoparticles in real-time;
(b) determining whether the quality parameters obtained in step (a) during each of steps (i) to (iv), as well as after step (iv), are within predetermined target ranges;
(c) in case any of the quality parameters obtained in step (a) during each of steps (i) to (iv), as well as after step (iv), are not within said predetermined target ranges, providing feedback control to adjust operating parameters of the respective step in real-time, in order to bring the respective quality parameters into the predetermined target ranges.

6 more elements

An automated nanoparticle synthesis system, comprising:

(a) a first dispenser assembly having a first pump integrated with a first valve;
(b) a second dispenser assembly having a second pump integrated with a second valve;
(c) a third valve;
(d) a microfluidic mixer;
(e) a lipid reservoir for holding a lipid stock solution;
(f) a nucleic acid reservoir for holding a nucleic acid stock solution;
and
(g) a waste reservoir, a buffer reservoir, and an ethanol reservoir;
wherein
(i) the lipid reservoir is fluidly connected to the first valve and the nucleic acid reservoir is fluidly connected to the second valve, or vice versa;
(ii) the first valve is fluidly connected to the first pump and the second valve is fluidly connected to the second pump;
(iii) each of the first valve and the second valve is fluidly connected to the waste reservoir, the buffer reservoir, and the ethanol reservoir, wherein the ports of the first valve and the second valve that are fluidly connected to the waste reservoir, the buffer reservoir, and the ethanol reservoir are different ports from those that are fluidly connected to the lipid reservoir and the nucleic acid reservoir;
(iv) each of the first valve and the second valve is fluidly connected to the microfluidic mixer;
and
(v) the third valve is fluidly connected to the microfluidic mixer, to the waste reservoir, and to one or more collection reservoir(s) for collecting produced lipid nanoparticles (LNPs).

12 more elements

Dependencies are inferred from the claim text.

Lipid nanoparticle production system and method of monitoring and controlling the same

Life of this patent

Abstract

Claims28

Lipid nanoparticle production system and method of monitoring and controlling the same

Life of this patent

Abstract

Claims28