Lipid formulations

Patent metadata

Field	Value
Publication number	US-9394234-B2
Application number	US-201414319996-A
Country	US
Kind code	B2
Filing date	Jun 30, 2014
Priority date	Jun 10, 2009
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

The invention features a cationic lipid of formula I,

an improved lipid formulation comprising a cationic lipid of formula I and corresponding methods of use.

Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.

First claim

What is claimed is:

1. A method of making a cationic lipid of formula I, or a pharmaceutically acceptable salt thereof,

comprising reacting dilinoleyl methanol with dimethylaminobutyric acid, or a salt thereof, under conditions to provide the cationic lipid of formula I, or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the dilinoleyl methanol is reacted with a hydrochloride salt of dimethylaminobutyric acid under conditions to provide a compound of formula I, or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein dilinoleyl methanol is reacted with a salt of dimethylaminobutyric acid under conditions that include EDCI, DMAP and DIPEA.

4. The method of claim 1 , further comprising purifying the compound of formula I, or a pharmaceutically acceptable salt thereof.

5. The method of claim 4 , wherein the compound of formula I, or a pharmaceutically acceptable salt thereof, is purified using Flash column chromatography.

6. The method of claim 1 , further comprising providing the dilinoleyl methanol by converting linoleyl bromide to dilinoleyl methanol.

7. The method of claim 6 , wherein the converting is carried out by reacting linoleyl bromide with magnesium followed by water to provide a resulting mixture that comprises dilinoleyl methanol.

8. The method of claim 7 , further comprising treating the resulting mixture with a base to provide dilinoleyl methanol.

9. The method of claim 8 , further comprising purifying the dilinoleyl methanol.

10. The method of claim 9 , wherein the dilinoleyl methanol is purified using column chromatography.

Assignees

• Tekmira Pharmaceuticals Corp
• Arbutus Biopharma Corp

Inventors

• Chen Jianxin
• Ansell Steven
• Akinc Akin
• Dorkin Joseph Robert
• Qin Xiaojun
• Cantley William
• Manoharan Muthiah
• Rajeev Kallanthottathil G
• Narayanannair Jayaprakash K
• Jayaraman Muthusamy

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C07C29/58

  by elimination of halogen, e.g. by hydrogenolysis, splitting-off (C07C29/124 takes precedence) · CPC title

• C07C227/40

  Separation; Purification · CPC title

• A61K38/1709

  from mammals · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title