Low molecular weight cyclic amine containing cationic lipids for oligonucleotide delivery

Patent metadata

Field	Value
Publication number	US-9796977-B2
Application number	US-201514719513-A
Country	US
Kind code	B2
Filing date	May 22, 2015
Priority date	Nov 5, 2010
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

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 is:

1. A cationic lipid of Formula A:

wherein:
R 1 is selected from H and (C 1 -C 6 )alkyl, wherein said alkyl is optionally substituted with one to three substituents selected from R″;
n is 1 and m is 2 or 3; or m is 1 and n is 2 or 3;
X is O;
L 1 is C 12 -C 24 alkenyl, said alkenyl optionally substituted with one or more substituents selected from R″; and
L 2 is unsubstituted C 3 -C 9 alkyl;
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

• C07D211/40

  Oxygen atoms · CPC title

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• A61K9/5123

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

• C07D207/12 Primary

  Oxygen or sulfur atoms · CPC title

• C12N15/1137 Primary

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