Low molecular weight cationic lipids for oligonucleotide delivery

Patent metadata

Field	Value
Publication number	US-9669097-B2
Application number	US-201113823830-A
Country	US
Kind code	B2
Filing date	Sep 20, 2011
Priority date	Sep 20, 2010
Publication date	Jun 6, 2017
Grant date	Jun 6, 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 with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

First claim

The invention claimed is:

1. A cationic lipid of Formula A:

wherein:
R 1 and R 2 are each methyl;
R 3 is H;
n is 2;
L 1 is C 12 -C 24 alkenyl; and
L 2 is selected from C 3 -C 9 alkyl and C 3 -C 9 alkenyl;
or any pharmaceutically acceptable salt or stereoisomer thereof.

2. The cationic lipid according to claim 1 which is:
(13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine (Compound 32);
or any pharmaceutically acceptable salt or stereoisomer thereof.

3. A lipid nanoparticle comprising a cationic lipid of claim 1 .

4. The lipid nanoparticle of claim 3 , wherein the lipid nanoparticle further comprises an oligonucleotide.

5. The lipid nanoparticle of claim 4 , wherein the oligonucleotide is siRNA.

6. The lipid nanoparticle of claim 3 , wherein the lipid nanoparticle further comprises cholesterol, DSPC and PEG-DMG.

7. The lipid nanoparticle of claim 3 , wherein the lipid nanoparticle comprises, the cationic lipid (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine (Compound 32), cholesterol, DSPC and PEG-DMG.

Assignees

• Stanton Matthew G
• Budzik Brian W
• Beutner Gregory L
• Liao Hongbiao
• Sirna Therapeutics Inc

Inventors

• Stanton Matthew G
• Budzik Brian W
• Beutner Gregory L
• Liao Hongbiao

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07D207/06

  with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• C07C211/04

  Mono-, di- or tri-methylamine · CPC title

• C07C211/08

  containing alkyl groups having a different number of carbon atoms · CPC title