Lipids and compositions for the delivery of therapeutics

Patent metadata

Field	Value
Publication number	US-11077197-B2
Application number	US-201715617520-A
Country	US
Kind code	B2
Filing date	Jun 8, 2017
Priority date	Nov 10, 2008
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention

provides lipids having the following structure XXXIII, wherein:

R 1 and R 2 are each independently for each occurrence optionally substituted C 10 -C 30 alkyl, optionally substituted C 10 -C 30 alkenyl, optionally substituted C 10 -C 30 alkynyl, optionally substituted C 10 -C 30 acyl, or -linker-ligand; R 3 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 2 -C 10 alkenyl, optionally substituted C 2 -C 10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

First claim

We claim:

1. A lipid particle comprising a lipid having the structure

or a salt or isomer thereof, wherein:
R 1 and R 2 are each independently C 10 -C 30 alkenyl;
R 3 is ω-aminoalkyl, ω-(substituted)aminoalkyl, or ω-thiophosphoalkyl; and
E is C(O)O;
provided that when R 3 is 2-(dimethylamino)ethyl, R 1 and R 2 are not each linoleyl.

2. The lipid particle of claim 1 , wherein R 3 is ω-(substituted)aminoalkyl.

3. The lipid particle of claim 1 , wherein R 3 is 2-(dimethylamino)ethyl, 3-(diisopropylamino)propyl, or 3-(N-ethyl-n-isopropylamino)-1-methylpropyl.

4. The lipid particle of claim 1 , wherein R 3 is alkylaminoalkyl, dialkylaminoalkyl, or alkylheterocycle.

5. The lipid particle of claim 1 , wherein R 1 and R 2 are each linoleyl.

6. The lipid particle of claim 1 , wherein the particle further comprises a neutral lipid and a lipid capable of reducing aggregation.

7. The lipid particle of claim 6 , wherein the lipid capable of reducing aggregation is a PEG-lipid.

8. The lipid particle of claim 1 , further comprising a therapeutic agent.

9. The lipid particle of claim 8 , wherein the therapeutic agent is a nucleic acid.

10. The lipid particle of claim 9 , wherein the nucleic acid is selected from the group consisting of an siRNA and an antisense oligonucleotide.

11. The lipid particle of claim 8 , wherein the nucleic acid is siRNA.

12. The lipid particle of claim 8 , wherein the nucleic acid is mRNA.

13. A pharmaceutical composition comprising a lipid particle of claim 1 and a pharmaceutically acceptable excipient, carrier, or diluent.

14. A pharmaceutical composition comprising a lipid particle of claim 8 and a pharmaceutically acceptable excipient, carrier, or diluent.

15. A method of modulating the expression of a target gene in a cell, comprising providing to the cell the lipid particle of claim 8 .

16. A method of modulating the expression of a target gene in a cell, comprising providing to the cell the lipid particle of claim 11 .

17. A method of modulating the expression of a target gene in a cell, comprising providing to the cell the lipid particle of claim 12 .

Assignees

• Arbutus Biopharma Corp

Inventors

• Manoharan Muthiah
• Jayaraman Muthusamy
• Rajeev Kallanthottathil G
• Eltepu Laxman
• Ansell Steven
• Chen Jianxin

Classifications

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• A61K47/24

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

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title