Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids

Patent metadata

Field	Value
Publication number	US-2017283367-A1
Application number	US-201715624548-A
Country	US
Kind code	A1
Filing date	Jun 15, 2017
Priority date	Jun 25, 2014
Publication date	Oct 5, 2017
Grant date	—

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

1 - 53 . (canceled)

54 . 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.

55 . The compound of claim 54 , wherein X is OH.

56 . The compound of claim 54 , wherein X is Cl.

57 . The compound of claim 54 , wherein n is an integer from 5 to 24.

58 . The compound of claim 54 , wherein n is 5.

59 . The compound of claim 54 , wherein R is a saturated or unsaturated C 1 -C 24 alkyl or saturated or unsaturated cycloalkyl.

60 . The compound of claim 54 , wherein each R is independently a saturated or unsaturated C 1 -C 24 alkyl.

61 . The compound of claim 54 , wherein R is a saturated or unsaturated C 1 -C 24 alkyl.

62 . The compound of claim 54 , wherein each R is independently a saturated C 1 -C 24 alkyl.

63 . The compound of claim 54 , wherein R is a saturated C 1 -C 24 alkyl.

64 . The compound of claim 54 , wherein R is a saturated C 16 -C 24 alkyl.

65 . The compound of claim 54 , wherein R is a saturated C 16 alkyl, saturated C 17 alkyl or saturated C 20 alkyl.

66 . The compound of claim 54 , wherein R has one of the following structures:

67 . The compound of claim 54 , wherein m is 1.

68 . The compound of claim 54 , having one of the following structures:

69 . The compound of claim 54 having one of the following structures:

70 . A method for preparing the compound of claim 54 , 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.

71 . The method of claim 70 , further comprising the following transformation:

72 . The method of claim 70 , further comprising the following transformation:

Assignees

• Acuitas Therapeutics Inc

Inventors

• Ansell Steven M
• Du Xinyao

Classifications

• A61P43/00

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

• C07D295/13

  to an acyclic saturated chain · CPC title

• C07C219/06

  having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton · CPC title

• C07C235/06

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• A61K47/28

  Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid · CPC title