Low molecular weight cyclic amine containing cationic lipids for oligonucleotide delivery

Patent metadata

Field	Value
Publication number	US-10337014-B2
Application number	US-201715706041-A
Country	US
Kind code	B2
Filing date	Sep 15, 2017
Priority date	Nov 5, 2010
Publication date	Jul 2, 2019
Grant date	Jul 2, 2019

Abstract

The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids comprising at least one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

First claim

What is claimed:

1. A cationic lipid of Formula A:

wherein:
R 1 is selected from H, (C 1 -C 6 )alkyl, wherein said alkyl, is optionally substituted with one to three substituents selected from R′;
n and m are 1;
X is O;
L 1 is

and
L 2 is selected from C 3 -C 9 alkyl and C 3 -C 9 alkenyl, said alkyl and alkenyl are optionally substituted with one or more substituents selected from R′;
R′ is independently selected from halogen, R″, OR″, SR″, CN, CO 2 R″ and CON(R″) 2 ;
R″ is independently selected from H and (C 1 -C 6 )alkyl;

or any pharmaceutically acceptable salt or stereoisomer thereof.

2. A lipid nanoparticle comprising a cationic lipid according to claim 1 .

3. The lipid nanoparticle according to claim 2 further comprises an oligonucleotide.

4. The lipid nanoparticle according to claim 3 wherein the oligonucleotide is siRNA or miRNA.

5. The lipid nanoparticle according to claim 4 wherein the oligonucleotide is siRNA.

Assignees

• Sirna Therapeutics Inc

Inventors

• Stanton Matthew G
• Beutner Gregory L

Classifications

• C12N15/1137 Primary

  against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138) · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C07D211/40

  Oxygen atoms · CPC title