Lipids and lipid nanoparticle formulations for delivery of nucleic acids

Patent metadata

Field	Value
Publication number	US-11634379-B2
Application number	US-202016906985-A
Country	US
Kind code	B2
Filing date	Jun 19, 2020
Priority date	Jun 25, 2014
Publication date	Apr 25, 2023
Grant date	Apr 25, 2023

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

The invention claimed is:

1. A method for inducing expression of a protein in a subject, comprising administering to the subject a lipid nanoparticle comprising:
i) a compound having the following structure (II):

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

of structure (II) has an average molecular weight of about 2000 to 6000 g/mol; and
ii) an mRNA encoding the protein.

2. The method of claim 1 , wherein expression of the protein induces a pharmacological effect in the subject.

3. The method of claim 2 , wherein the pharmacological effect is increased production of red blood cells.

4. The method of claim 2 , wherein the pharmacological effect is protection against infection by an infectious agent.

5. The method of claim 4 , wherein the infectious agent is a virus.

6. The method of claim 1 , wherein the mRNA encodes an antibody.

7. The method of claim 1 , wherein the protein is expressed in the subject's liver.

8. The method of claim 1 , wherein the subject is a mammal.

9. The method of claim 1 , wherein the subject is a non-human primate.

10. The method of claim 1 , wherein the subject is a human.

11. The method of claim 1 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 12 carbon atoms.

12. The method of claim 1 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 14 carbon atoms.

13. The method of claim 1 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 16 carbon atoms.

14. The method of claim 1 , wherein z ranges from 30 to 60.

15. The method of claim 1 , wherein z is 45.

16. The method of claim 1 , wherein z is selected such that an average molecular weight of structure (II) is about 2500 g/mol.

17. The method of claim 1 , having the following structure:

wherein n ranges from 40 to 50.

18. The method of claim 17 , wherein n is 45.

19. The method of claim 1 , having the following structure:

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

20. The method of claim 1 , having the following structure:

wherein n ranges from 40 to 50.

21. The method of claim 20 , wherein n is 45.

22. The method of claim 1 , having the following structure:

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

23. The method of claim 1 , having the following structure:

wherein n ranges from 40 to 50.

24. The method of claim 23 , wherein n is 45.

25. The method of claim 1 , having 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

• C12Y304/21022

  Coagulation factor IXa (3.4.21.22) · CPC title

• A61K9/1272 Primary

  comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) · CPC title

• C07D295/13

  to an acyclic saturated chain · 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

• C07C229/16

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