Cationic lipids and transfection methods

• US 10,556,855 B1
• Filed: 10/22/2019
• Issued: 02/11/2020
• Est. Priority Date: 07/30/2019
• Status: Active Grant

• Current Assignee: Factor Bioscience Inc
• Original Assignee: Factor Bioscience Inc
• Inventors: Angel, Matthew, Kostas, Franklin, Rohde, Christopher
• Primary Examiner(s): Davis, Brian J
• Application Number:
  US16/660,299
• Time in Patent Office: 112 Days
• Field of Search: None
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: C07C 215/14 the nitrogen atom of the amino group being further bound to hydrocarbon groups substituted by amino groups
• CPC Class Codes: C07C 215/24 and acyclic

Abstract

The present invention relates in part to novel cationic lipids and their use, e.g., in delivering nucleic acids to cells.

Claims

1. A compound of the formula:

2. A pharmaceutical composition comprising the compound of claim 1.

3. A lipid aggregate comprising the compound of claim 1.

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

5. A liposome comprising the compound of claim 1.

6. A lipid carrier comprising the compound of claim 1.

7. A composition comprising the compound of claim 1, and a nucleic acid.

8. The composition of claim 7, wherein the nucleic acid comprises DNA.

9. The composition of claim 7, wherein the nucleic acid comprises RNA.

10. The composition of claim 7, wherein the nucleic acid is an in vitro transcribed mRNA.

11. The composition of claim 10, wherein the in vitro transcribed mRNA comprises a non-canonical nucleotide.

12. The composition of claim 7, wherein the nucleic acid is an siRNA.

13. The composition of claim 7, wherein the nucleic acid is an antisense oligonucleotide.

14. The pharmaceutical composition of claim 2, further comprising an additional lipid.

15. The lipid aggregate of claim 3, further comprising an additional lipid.

16. The lipid nanoparticle of claim 4, further comprising an additional lipid.

17. The liposome of claim 5, further comprising an additional lipid.

18. The lipid carrier of claim 6, further comprising an additional lipid.

19. The composition of claim 7, further comprising an additional lipid.

20. The composition of claim 9, further comprising an additional lipid.

21. The composition of claim 10, further comprising an additional lipid.

22. The pharmaceutical composition of claim 14, wherein the additional lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.

23. The lipid aggregate of claim 15, wherein the additional lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.

24. The lipid nanoparticle of claim 16, wherein the additional lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.

25. The liposome of claim 17, wherein the additional lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.

26. The lipid carrier of claim 18, wherein the additional lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.

27. The composition of claim 19, wherein the additional lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.

28. The composition of claim 20, wherein the additional lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.

29. The composition of claim 21, wherein the additional lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.

30. The composition of claim 11, further comprising an additional lipid or helper, wherein the additional or helper lipid is selected from dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), cholesterol, and a polyethylene glycol (PEG)-modified lipid.