Ionizable compounds and compositions and uses thereof

Patent metadata

Field	Value
Publication number	US-12319643-B2
Application number	US-202217658075-A
Country	US
Kind code	B2
Filing date	Apr 5, 2022
Priority date	Jun 24, 2015
Publication date	Jun 3, 2025
Grant date	Jun 3, 2025

Abstract

Ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, the compounds, compositions and methods are to provide nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.

First claim

What is claimed is:

1. A compound comprising the structure shown in Formula IV

wherein R 1 and R 2 are
R 1 ═C(═O)OR 4
R 2 ═C(═O)OR 5
wherein R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group:
wherein R 3 is selected from

wherein
each R 6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, and aminoalkyl;
each R 7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
each R 8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R 8 may form a ring;
q is from zero to four;
Q is O or NR 7 ;
p is from 1 to 4.

2. The compound of claim 1 , having a structure selected from

3. A composition comprising an ionizable compound of claim 1 and a pharmaceutically acceptable carrier.

4. The composition of claim 3 , wherein the composition comprises nanoparticles.

5. A pharmaceutical composition comprising an ionizable compound of claim 1 , an active agent, and a pharmaceutically acceptable carrier.

6. The composition of claim 5 , wherein the ionizable compound is from 15 mol % to 40 mol % of the lipids of the composition.

7. The composition of claim 5 , wherein the composition comprises nanoparticles.

8. The composition of claim 5 , wherein the active agent is one or more RNAi molecules.

9. The composition of claim 5 , wherein the active agent is one or more RNAi molecules selected from small interfering RNAs (siRNA), double stranded RNAs (dsRNA) that are Dicer substrates, microRNAs (miRNA), short hairpin RNAs (shRNA), DNA-directed RNAs (ddRNA), Piwi-interacting RNAs (piRNA), repeat associated siRNAs (rasiRNA), and modified forms thereof.

10. A composition for use in distributing an active agent for treating a condition or disease in a subject, the composition comprising an ionizable compound of claim 1 , a structural lipid, a stabilizer lipid, and a lipid for reducing immunogenicity of the composition.

11. The composition of claim 10 , wherein the active agent is one or more RNAi molecules and the composition comprises nanoparticles that encapsulate the RNAi molecules.

12. The composition of claim 11 , wherein the active agent is one or more RNAi molecules selected from small interfering RNAs (siRNA), double stranded RNAs (dsRNA) that are Dicer substrates, microRNAs (miRNA), short hairpin RNAs (shRNA), DNA-directed RNAs (ddRNA), Piwi-interacting RNAs (piRNA), repeat associated siRNAs (rasiRNA), and any modified forms thereof.

Assignees

• Nitto Denko Corp

Inventors

• Adami Roger
• Bai Hao
• Gaudette John
• Majeti Bharat
• Nukui Seiji
• Tsang Kwok Yin
• Wang Hai
• Yin Haiqing
• Ying Wenbin

Classifications

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• A61K47/16

  containing nitrogen, {e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates} · CPC title

• C07C237/50

  having the nitrogen atom of at least one of the carboxamide groups quaternised · CPC title

• C07C237/08

  having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms · CPC title