Compositions and methods for nanoparticle lyophile forms

Patent metadata

Field	Value
Publication number	US-11737982-B2
Application number	US-201916377032-A
Country	US
Kind code	B2
Filing date	Apr 5, 2019
Priority date	Jul 22, 2015
Publication date	Aug 29, 2023
Grant date	Aug 29, 2023

Abstract

This invention provides compositions for making a solid lyophile of one or more nucleic acid active agents, which can be reconstituted as a drug product. The composition can include an aqueous suspension of lipid nanoparticles in a pharmaceutically acceptable solution, wherein the lipid nanoparticles encapsulate one or more nucleic acid active agents, a dextrin compound, and a saccharide compound. The nucleic acid active agents can be RNAi molecules capable of mediating RNA interference, as well as other RNAs and oligonucleotides.

First claim

What is claimed is:

1. A process for making a solid lyophile, the process comprising:
synthesizing lipid nanoparticles, wherein the lipid nanoparticles encapsulate one or more nucleic acid active agents;
providing an aqueous suspension of the lipid nanoparticles in a pharmaceutically acceptable solution;
adding a dextrin compound to the solution containing the lipid nanoparticles;
adding a saccharide sugar compound to the solution containing the lipid nanoparticles; and
lyophilizing the solution containing the lipid nanoparticles, thereby forming the solid lyophile;
wherein the total amount of the dextrin and saccharide sugar compounds is 10% (w/v) of the solution containing the lipid nanoparticles;
wherein the dextrin compound is 40% (w/v) of the total amount of the dextrin and saccharide sugar compounds;

wherein the lipid nanoparticles comprise a compound selected from compound A6, compound A9, compound AA, compound AB, compound C2, compound F5, compound F7, compound C24, and HEDC;
wherein compound A6 is

compound A9 is

compound AA is

compound AB is

compound C2 is

compound F5 is

compound F7 is

compound C24 is

wherein upon reconstitution of the solid lyophile without filtering, the average size of the nanoparticles is within 5% of their size in the solution containing the lipid nanoparticles prior to lyophilization, with PDI less than or equal to 0.15;
wherein the dextrin compound is (2-hydroxypropyl)-β-cyclodextrin; and
wherein the saccharide sugar compound is sucrose.

2. The process of claim 1 , wherein the nanoparticles have an average diameter of from 45 nm to 110 nm.

3. The process of claim 1 , wherein the concentration of the nucleic acid active agents is from 1 mg/mL to 10 mg/mL.

4. The process of claim 1 , wherein the one or more nucleic acid active agents are RNAi molecules capable of mediating RNA interference.

Assignees

• Nitto Denko Corp

Inventors

• Adami Roger
• Wang Yuwei
• Yin Haiqing
• Wang Liping
• Liu Dong
• Ying Wenbin

Classifications

• A61K47/40

  Cyclodextrins; Derivatives thereof · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title