Lipids and compositions for the delivery of therapeutics

Patent metadata

Field	Value
Publication number	US-10117941-B2
Application number	US-201715603069-A
Country	US
Kind code	B2
Filing date	May 23, 2017
Priority date	Nov 10, 2008
Publication date	Nov 6, 2018
Grant date	Nov 6, 2018

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

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; E is O, S, N(Q), C(O), N(Q)C(O), C(O)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O) 2 N(Q), S(O) 2 , N(Q)S(O) 2 , SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ω-aminoalkyl, ω-(substituted)aminoalky, ω-phosphoalkyl or ω-thiophosphoalkyl.

First claim

We claim:

1. A lipid having the structure

or a salt or isomer thereof.

2. A lipid particle comprising a lipid of claim 1 .

3. The lipid particle of claim 2 , wherein the particle further comprises a neutral lipid and a lipid capable of reducing aggregation.

4. A lipid particle consisting essentially of
a. a lipid having the structure

or a salt or isomer thereof;
b. a neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM;
c. a sterol; and
d. PEG-DMG or PEG-DMA,
in a molar ratio of about 20-60% lipid: 5-25% neutral lipid: 25-55% sterol: 0.5-15% PEG-DMG or PEG-DMA.

5. The lipid particle of claim 2 , further comprising a therapeutic agent.

6. The lipid particle of claim 5 , wherein the therapeutic agent is a nucleic acid.

7. The lipid particle of claim 6 , wherein the nucleic acid is a plasmid.

8. The lipid particle of claim 6 , wherein the nucleic acid is an immunostimulatory oligonucleotide.

9. The lipid particle of claim 6 , wherein the nucleic acid is selected from the group consisting of an siRNA, an antisense oligonucleotide, a microRNA, an antagomir, an aptamer, and a ribozyme.

10. The lipid particle of claim 5 , wherein the therapeutic agent is siRNA.

11. The lipid particle of claim 5 , wherein the therapeutic agent is mRNA.

12. The lipid particle of claim 4 , wherein the sterol is cholesterol.

13. A pharmaceutical composition comprising a lipid particle of claim 2 and a pharmaceutically acceptable excipient, carrier, or diluent.

14. A pharmaceutical composition comprising a lipid particle of claim 5 and a pharmaceutically acceptable excipient, carrier, or diluent.

Assignees

• Arbutus Biopharma Corp

Inventors

• Manoharan Muthiah
• Rajeev Kallanthottathil G
• Jayaraman Muthusamy
• Butler David
• Nair Jayaprakash K
• Maier Martin
• Eltepu Laxman

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61K9/5123

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

• C12N2310/14

  interfering nucleic acids [NA] · CPC title