Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids

Patent metadata

Field	Value
Publication number	US-2019270697-A1
Application number	US-201816132287-A
Country	US
Kind code	A1
Filing date	Sep 14, 2018
Priority date	Jun 25, 2014
Publication date	Sep 5, 2019
Grant date	—

Abstract

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8, R9, L1, L2, 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 (II):

wherein:
R 10 and R 11 are each independently a straight or branched, saturated or unsaturated alkyl chain containing from 12 to 16 carbon atoms; and
z is selected such that the polyethyleneglycol (PEG) portion,

of (II) has an average molecular weight of 400 to 6000 g/mol.

55 . The compound of claim 54 , wherein R 10 and R 11 are each independently straight, saturated alkyl chains containing from 12 to 16 carbon atoms.

56 . The compound of claim 54 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 12 carbon atoms.

57 . The compound of claim 54 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 14 carbon atoms.

58 . The compound of claim 54 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 16 carbon atoms.

59 . The compound of claim 54 , wherein z ranges from 30 to 60.

60 . The compound of claim 54 , wherein z is 45.

61 . The compound of claim 54 , wherein z is selected such that an average molecular weight of (II) is about 2500 g/mol.

62 . The compound of claim 54 , having the following structure:

wherein n ranges from 40 to 50.

63 . The compound of claim 62 , wherein n is 45.

64 . The compound of claim 54 , having the following structure:

wherein n is selected such that an average molecular weight of the compound is about 2500 g/mol.

65 . The compound of claim 54 , having the following structure:

wherein n ranges from 40 to 50.

66 . The compound of claim 65 , wherein n is 45.

67 . The compound of claim 54 , having the following structure:

wherein n is selected such that an average molecular weight of the compound is about 2500 g/mol.

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

wherein n ranges from 40 to 50.

69 . The compound of claim 68 , wherein n is 45.

70 . The compound of claim 54 , having the following structure:

wherein n is selected such that an average molecular weight of the compound is about 2500 g/mol.

71 . A lipid nanoparticle comprising the compound of claim 54 .

72 . The lipid nanoparticle of claim 71 , wherein R 10 and R 11 are each independently straight, saturated alkyl chains containing from 12 to 16 carbon atoms.

73 . The lipid nanoparticle of claim 71 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 12 carbon atoms.

74 . The lipid nanoparticle of claim 71 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 14 carbon atoms.

75 . The lipid nanoparticle of claim 71 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 16 carbon atoms.

76 . The lipid nanoparticle of claim 71 , wherein z ranges from 30 to 60.

77 . The lipid nanoparticle of claim 71 , wherein z is 45.

78 . The lipid nanoparticle of claim 71 , wherein z is selected such that an average molecular weight of (II) is about 2500 g/mol.

79 . The lipid nanoparticle of claim 71 , wherein the compound has the following structure:

wherein n ranges from 40 to 50.

80 . The lipid nanoparticle of claim 79 , wherein n is 45.

81 . The lipid nanoparticle of claim 71 , wherein the compound has the following structure:

wherein n is selected such that an average molecular weight of the compound is about 2500 g/mol.

82 . The lipid nanoparticle of claim 71 , wherein the compound has the following structure:

wherein n ranges from 40 to 50.

83 . The lipid nanoparticle of claim 82 , wherein n is 45.

84 . The lipid nanoparticle of claim 71 , wherein the compound has the following structure:

wherein n is selected such that an average molecular weight of the compound is about 2500 g/mol.

85 . The lipid nanoparticle of claim 71 , wherein the compound has the following structure:

wherein n ranges from 40 to 50.

86 . The lipid nanoparticle of claim 85 , wherein n is 45.

87 . The lipid nanoparticle of claim 71 , wherein the compound has the following structure:

wherein n is selected such that an average molecular weight of the compound is about 2500 g/mol.

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

• C07C229/16

  to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids · CPC title

• C07C219/10

  having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to an acyclic carbon atom of a carbon skeleton containing rings · CPC title

• A61K47/18

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

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title