Lipids and lipid nanoparticle formulations for delivery of nucleic acids

Patent metadata

Field	Value
Publication number	US-10106490-B2
Application number	US-201715624548-A
Country	US
Kind code	B2
Filing date	Jun 15, 2017
Priority date	Jun 25, 2014
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

Compounds are provided having the following structure:

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R 1a , R 1b , R 2a , R 2b , R 3a , R 3b , R 4a , R 4b , R 5 , R 6 , R 7 , R 8 , R 9 , L 1 , L 2 , a, b, c, d and e are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

First claim

The invention claimed is:

1. A compound having the following structure:

or a pharmaceutically acceptable salt thereof, wherein:
X is OH or Cl;
each R is independently a saturated or unsaturated C 1 -C 24 alkyl or saturated or unsaturated cycloalkyl;
m is 0 or 1; and
each n is independently an integer from 5 to 24.

2. The compound of claim 1 , wherein X is OH.

3. The compound of claim 1 , wherein X is Cl.

4. The compound of claim 1 , wherein each n is the same.

5. The compound of claim 1 , wherein each n is 5.

6. The compound of claim 1 , wherein each R is the same.

7. The compound of claim 1 , wherein each R is independently a saturated or unsaturated C 1 -C 24 alkyl.

8. The compound of claim 7 , wherein each R is the same.

9. The compound of claim 1 , wherein each R is independently a saturated C 1 -C 24 alkyl.

10. The compound of claim 9 , wherein each R is the same.

11. The compound of claim 1 , wherein each R is independently a saturated C 16 -C 24 alkyl.

12. The compound of claim 1 , wherein each R is independently a saturated C 16 alkyl, saturated C 17 alkyl or saturated C 20 alkyl.

13. The compound of claim 1 , wherein each R independently has one of the following structures:

14. The compound of claim 1 , wherein m is 1.

15. The compound of claim 1 , having one of the following structures:

16. The compound of claim 1 , having one of the following structures:

17. A method for preparing the compound of claim 1 , the method comprising the following transformation:

wherein:
each R is independently a saturated or unsaturated C 1 -C 24 alkyl or saturated or unsaturated cycloalkyl;
m is 0 or 1; and
each n is independently an integer from 5 to 24.

18. The method of claim 17 , further comprising the following transformation:

19. The method of claim 17 , further comprising the following transformation:

Assignees

• Acuitas Therapeutics Inc
• Acuitas Therapeutics Inc

Inventors

• Du Xinyao

Classifications

• A61P43/00

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

• A61K47/18

  Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids · CPC title

• C07C229/24 Primary

  having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid · CPC title

• A61K48/0041

  the non-active part being polymeric · CPC title

• C12Y304/21022

  Coagulation factor IXa (3.4.21.22) · CPC title