Polymer compounds and composition for nucleic acid delivery comprising the same

Patent metadata

Field	Value
Publication number	US-2025115715-A1
Application number	US-202418906527-A
Country	US
Kind code	A1
Filing date	Oct 4, 2024
Priority date	Oct 6, 2023
Publication date	Apr 10, 2025
Grant date	—

Abstract

Provided are a polymer compound and a composition for nucleic acid delivery comprising the same, wherein the polymer compound has a high binding affinity to nucleic acids and effectively protects nucleic acids from nucleases, thereby improving the nucleic acid delivery effect and stability.

First claim

1 . A compound represented by Formula 1:

wherein:
R 1 is an C 1 -C 10 alkyl group; —(CH 2 ) 3 —O—CH 3 ; or —(CH 2 ) x —[(CH 2 ) 2 —O] y —CH 3 ;
x is 0 or 1, y is an integer from 1 to 45, provided that where y is 1, x is 1, and where y is 2 or more, x is 0,
m and n are each independently an integer from 1 to 100, provided that m+n≥10,
a is an integer from 0 to 2, and
R 2 and R 3 are each independently represented by Formula 2,

wherein:
R 4 is selected from the group consisting of hydrogen; an amino group; a hydroxyl group; a C 1 -C 20 alkoxy group; a C 3 -C 20 aliphatic ring group; a C 6 -C 20 aryl group; a C 1 -C 20 heteroaryl group; a C 1 -C 20 heterocyclic group; —NH—C 1 ˜C 20 alkenyl group-NH 2 ; —NH—C 1 -C 20 hydroxyalkyl group; —N(C 1 -C 20 alkyl group)(C 1 -C 20 alkyl group); —N(C 1 -C 20 alkyl group)(C 1 -C 20 alkenyl group-NH 2 ); —(OH)(C 1 -C 20 alkyl group); and —(C 1 -C 20 hydroxyalkyl group)(C 1 -C 20 hydroxyalkyl group);
z is an integer from 0 to 45.

2 . The compound according to claim 1 , wherein R 1 is represented by any one of Formulas 1-1 to 1-3:

wherein:
y′ is an integer from 2 to 45, and
indicates the position to be bonded.

3 . The compound according to claim 1 , wherein R 2 or R 3 is represented by any one of Formulas 2-1 to 2-20:

wherein:
c is an integer from 0 to 12.

4 . A composition for nucleic acids delivery comprising a compound of claim 1 and a nucleic acid.

5 . The composition for nucleic acids delivery according to claim 4 , wherein the nucleic acid is selected from the group consisting of DNA, RNA, PNA, interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), dicer-substrate RNA (dsRNA), small hairpin RNA (shRNA), messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), antisense oligonucleotides (ASOs) and mixtures thereof.

6 . The composition for nucleic acids delivery according to claim 4 , further comprising a pharmaceutically acceptable carrier or a pharmaceutically acceptable salt.

7 . A nanoparticle formed by combination of the compound of claim 1 with a nucleic acid.

8 . The nanoparticle according to claim 7 , wherein a molar ratio of protonable amino groups in the compound to phosphate groups in the nucleic acid (N/P ratio) is 1 to 30.

9 . A vaccine composition comprising the nanoparticle according to claim 7 .

10 . A method for producing the compound represented by Formula 1 of claim 1 , comprising
1) a step of synthesizing a beta-amino acid N-thiocarboxyanhydrides (beta-NTAs) monomer; 2) a step of synthesizing a polymer precursor by ring-opening polymerization of the beta-NTAs monomer using butylamine as an initiator; 3) a step of modifying a side chain of the polymer precursor through an aminolysis reaction.

11 . A method of delivering a nucleic acid into a cell using the compound of claim 1 .

12 . The method of claim 11 , wherein the intracellular location is the cytoplasm or the nucleus.

Assignees

• Univ Inha Res & Business Found

Inventors

• Kim Hyun Jin
• Lim Sungbeen
• Kang Dong Hyun

Classifications

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/5146

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title

• C08G69/22

  Beta-lactams · CPC title

• B82Y30/00

  Nanotechnology for materials or surface science, e.g. nanocomposites · CPC title

• A61K31/787 Primary

  containing heterocyclic rings having nitrogen as a ring hetero atom · CPC title