IONIZABLE CATIONIC LIPIDS

• US 20150166462A1
• Filed: 03/29/2013
• Published: 06/18/2015
• Est. Priority Date: 03/29/2012
• Status: Active Grant

• Current Assignee: Translate Bio, Inc. (Sanofi )
• Original Assignee: Shire Human Genetic Therapies, Inc. (Shire plc)
• Inventors: DeRosa, Frank, Guild, Braydon Charles, Heartlein, Michael
• Granted Patent: US 9,546,128 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 211/21 Monoamines
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12Y 302/01023 Beta-galactosidase (3.2.1.23), i.e. exo-(1-->4)-beta-D-galactanase

Abstract

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent transfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids.

Claims

1. A compound having the structure:

16. A pharmaceutical composition comprising the compound of claim 1.

2-15. -15. (canceled)

17-24. -24. (canceled)

25. A compound of having the structure:

26. The compound of claim 25 having the structure:

27. The compound of claim 25 having the structure:

28. A pharmaceutical composition comprising the compound of claim 25.

29. The pharmaceutical composition of claim 28, wherein the composition is a lipid nanoparticle.

30. The pharmaceutical composition of claim 29, wherein the lipid nanoparticle is substantially non-toxic when administered to a subject.

33. The pharmaceutical composition of claim 30, further comprising one or more therapeutic agents.

87. A method of treating disease in a subject, wherein the method comprises administering an effective amount of the pharmaceutical composition of claim 33 to the subject.

89. A method of transfecting one or more target cells with a polynucleotide, wherein the method comprises contacting the one or more target cells with the pharmaceutical composition of claim 33 such that the one or more target cells are transfected with the polynucleotide.

90. The compound of claim 25 having the structure:

31-32. -32. (canceled)

34. (canceled)

35. A compound having the structure:

46. A pharmaceutical composition comprising the compound of claim 35.

36-45. -45. (canceled)

47-54. -54. (canceled)

55. A compound having the structure:

56. A pharmaceutical composition comprising the compound of claim 55.

57. The pharmaceutical composition of claim 56, wherein the composition is a lipid nanoparticle.

61. The pharmaceutical composition of claim 57, further comprising one or more therapeutic agents.

91. A method of treating disease in a subject, wherein the method comprises administering an effective amount of the pharmaceutical composition of claim 61 to the subject.

93. A method of transfecting one or more target cells with a polynucleotide, wherein the method comprises contacting the one or more target cells with the pharmaceutical composition of claim 61 such that the one or more target cells are transfected with the polynucleotide.

58-60. -60. (canceled)

62. (canceled)

63. A compound having the structure:

76. A pharmaceutical composition comprising the compound of claim 63.

78. The pharmaceutical composition of claim 76, wherein the composition is a lipid nanoparticle.

79. The pharmaceutical composition of claim 78, further comprising one or more polynucleotides.

92. A method of treating disease in a subject, wherein the method comprises administering an effective amount of the pharmaceutical composition of claim 79 to the subject.

94. A method of transfecting one or more target cells with a polynucleotide, wherein the method comprises contacting the one or more target cells with the pharmaceutical composition of claim 79 such that the one or more target cells are transfected with the polynucleotide.

64-75. -75. (canceled)

77. (canceled)

80-85. -85. (canceled)

86. A compound having the structure:

88. (canceled)