Lipids and lipid nanoparticle formulations for delivery of nucleic acids

Patent metadata

Field	Value
Publication number	US-10723692-B2
Application number	US-201816132287-A
Country	US
Kind code	B2
Filing date	Sep 14, 2018
Priority date	Jun 25, 2014
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

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 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.

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

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

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

5. The compound of claim 1 , wherein z ranges from 30 to 60.

6. The compound of claim 1 , wherein z is 45.

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

8. The compound of claim 1 , having the following structure:

wherein n ranges from 40 to 50.

9. The compound of claim 8 , wherein n is 45.

10. The compound 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.

11. The compound of claim 1 , having the following structure:

wherein n ranges from 40 to 50.

12. The compound of claim 11 , wherein n is 45.

13. The compound 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.

14. The compound of claim 1 , having the following structure:

wherein n ranges from 40 to 50.

15. The compound of claim 14 , wherein n is 45.

16. The compound 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.

17. A lipid nanoparticle comprising the compound of claim 1 .

18. The lipid nanoparticle of claim 17 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 12 carbon atoms.

19. The lipid nanoparticle of claim 17 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 14 carbon atoms.

20. The lipid nanoparticle of claim 17 , wherein R 10 and R 11 are each straight, saturated alkyl chains containing 16 carbon atoms.

21. The lipid nanoparticle of claim 17 , wherein z ranges from 30 to 60.

22. The lipid nanoparticle of claim 17 , wherein z is 45.

23. The lipid nanoparticle of claim 17 , wherein z is selected such that an average molecular weight of structure (II) is about 2500 g/mol.

24. The lipid nanoparticle of claim 17 , wherein the compound has the following structure:

wherein n ranges from 40 to 50.

25. The lipid nanoparticle of claim 24 , wherein n is 45.

26. The lipid nanoparticle of claim 17 , 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.

27. The lipid nanoparticle of claim 17 , wherein the compound has the following structure:

wherein n ranges from 40 to 50.

28. The lipid nanoparticle of claim 27 , wherein n is 45.

29. The lipid nanoparticle of claim 17 , 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.

30. The lipid nanoparticle of claim 17 , wherein the compound has the following structure:

wherein n ranges from 40 to 50.

31. The lipid nanoparticle of claim 30 , wherein n is 45.

32. The lipid nanoparticle of claim 17 , 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.

33. The lipid nanoparticle of claim 17 , wherein the average molecular weight of the PEG portion,

of structure (II) is 2000 to 6000 g/mol.

34. The compound of claim 1 , wherein the average molecular weight of the PEG portion,

of structure (II) is 2000 to 6000 g/mol.

Assignees

• Acuitas Therapeutics Inc

Inventors

• Ansell Steven M
• Du Xinyao

Classifications

• C12Y304/21022

  Coagulation factor IXa (3.4.21.22) · CPC title

• C08G65/33306

  acyclic · CPC title

• C07D295/13

  to an acyclic saturated chain · CPC title

• C07C235/06

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07C229/24 Primary

  having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid · CPC title