Fusogenic compounds for delivery of biologically active molecules

Patent metadata

Field	Value
Publication number	US-12440445-B2
Application number	US-202217658078-A
Country	US
Kind code	B2
Filing date	Apr 5, 2022
Priority date	Nov 6, 2017
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

Abstract

Fusogenic compounds, and compositions and methods of use thereof. The fusogenic compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, compounds, compositions and methods are to provide nanoparticles to incorporate or encapsulate active agents, to deliver and distribute the active agents to cells, tissues, organs, and subjects.

First claim

What is claimed is:

1. A fusogenic compound having Formula VII:

wherein each amphiphile has a structure represented by Formula VIII:

wherein R 1 and R 2 are:
R 1 is CH 2 (CH 2 ) n O(C═O)R 4 , CH 2 (CH 2 ) n NH(C═O)R 4 , CH 2 (CH 2 ) n (C═O)OR 4 , or CH 2 (CH 2 ) n (C═O)NHR 4 ;

R 2 or CH 2 (CH 2 ) m O(C═O)R 5 , CH 2 (CH 2 ) m NH(C═O)R 5 , CH 2 (CH 2 ) m (C═O)OR 5 , or CH 2 (CH 2 ) m (C═O)NHR 5 ;
wherein:
n and m are each independently from 1 to 2;
R 4 and R 5 are independently for each occurrence a C(12-20) alkyl group or a C(12-20) alkenyl group;
wherein each AA a is independently an amino acid of the following structure, and any stereoisomer thereof:

wherein the linker has a structure:

wherein Q 1 is selected from the group consisting of branched or unbranched C(2-8)alkandiyl, branched or unbranched C(2-8)alkenediyl, branched or unbranched C(2-8)alkynediyl,

wherein Q 2 is

wherein Q 3 is

wherein X is selected from the group consisting of —O—, —S—, and —NH—;
n and p are independently for each occurrence 1 to 3;
m is independently 1 to 10; and
r and s are independently for each occurrence 1 to 5.

2. The fusogenic compound of claim 1 , wherein the compound is compound T9:

3. A composition comprising the fusogenic compound of claim 1 , and a pharmaceutically acceptable carrier.

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

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

6. The composition of claim 5 , wherein the fusogenic compound is from 0.01 mol % to 20 mol % of the lipids of the composition.

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

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

9. The composition of claim 5 , wherein the active agent is one or more DNAs, RNAs, mRNAs, siRNAs, or microRNAs.

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

11. The composition of claim 5 , wherein the active agent is selected from one or more RNAi molecules, one or more mRNA molecules, and modified forms thereof.

Assignees

• Nitto Denko Corp

Inventors

• Tsang Kwok Yin
• Majeti Bharat
• Gaudette John
• Adami Roger
• Bai Hao
• Ying Wenbin

Classifications

• C07C201/00

  Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title

• A61K31/7105 Primary

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61K47/6911

  the form being a liposome · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title