Lipids and lipid nanoparticle formulations for delivery of nucleic acids
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.
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.