Claims for Patent: 11,141,378

Summary for Patent: 11,141,378

Title:	Lipid formulations for nucleic acid delivery
Abstract:	The present invention provides novel, stable lipid particles comprising one or more active agents or therapeutic agents, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles. More particularly, the present invention provides stable nucleic acid-lipid particles (SNALP) comprising a nucleic acid (such as one or more interfering RNA), methods of making the SNALP, and methods of delivering and/or administering the SNALP.
Inventor(s):	Yaworski; Edward (Maple Ridge, CA), Lam; Kieu (Surrey, CA), Jeffs; Lloyd (Delta, CA), Palmer; Lorne (Vancouver, CA), MacLachlan; Ian (Mission, CA)
Assignee:	ARBUTUS BIOPHARMA CORPORATION (Vancouver, CA)
Application Number:	17/227,802
Patent Claims:	1. A nucleic acid-lipid particle consisting essentially of: (a) an RNA; (b) a cationic lipid having a protonatable tertiary amine; (c) a mixture of a phospholipid and cholesterol of from 30 mol % to 55 mol % of the total lipid present in the particle, wherein the phospholipid consists of from 3 mol % to 15 mol % of the total lipid present in the particle; and (d) a polyethyleneglycol (PEG)-lipid conjugate consisting of from 0.1 mol % to 2 mol % of the total lipid present in the particle. 2. The nucleic acid-lipid particle of claim 1, wherein the cholesterol consists of from 25 mol % to 45 mol % of the total lipid present in the particle. 3. The nucleic acid-lipid particle of claim 2, wherein the phospholipid is distearoylphosphatidylcholine (DSPC). 4. The nucleic acid-lipid particle of claim 3, wherein the PEG has an average molecular weight of about 2,000 daltons. 5. The nucleic acid-lipid particle of claim 4, wherein the PEG has a terminal methoxy group. 6. The nucleic acid-lipid particle of claim 5, wherein the PEG-lipid conjugate is a PEG-diacylglycerol (PEG-DAG) conjugate having the same saturated acyl groups. 7. The nucleic acid-lipid particle of claim 6, wherein the cholesterol consists of from 35 mol % to 45 mol % of the total lipid present in the particle. 8. A pharmaceutical composition comprising a nucleic acid-lipid particle of claim 6 and a pharmaceutically acceptable carrier. 9. The pharmaceutical composition of claim 8, wherein the RNA is fully encapsulated in the nucleic acid-lipid particle. 10. A pharmaceutical composition comprising a nucleic acid-lipid particle of claim 7 and a pharmaceutically acceptable carrier. 11. The pharmaceutical composition of claim 10, wherein the RNA is fully encapsulated in the nucleic acid-lipid particle. 12. The nucleic acid-lipid particle of claim 1, wherein the RNA is an mRNA. 13. The nucleic acid-lipid particle of claim 12, wherein the cholesterol consists of from 25 mol % to 45 mol % of the total lipid present in the particle. 14. The nucleic acid-lipid particle of claim 13, wherein the phospholipid is DSPC. 15. The nucleic acid-lipid particle of claim 14, wherein the PEG has an average molecular weight of about 2,000 daltons. 16. The nucleic acid-lipid particle of claim 15, wherein the PEG has a terminal methoxy group. 17. The nucleic acid-lipid particle of claim 16, wherein the PEG-lipid conjugate is a PEG-DAG conjugate having the same saturated acyl groups. 18. The nucleic acid-lipid particle of claim 17, wherein the cholesterol consists of from 35 mol % to 45 mol % of the total lipid present in the particle. 19. A pharmaceutical composition comprising a nucleic acid-lipid particle of claim 17 and a pharmaceutically acceptable carrier. 20. The pharmaceutical composition of claim 19, wherein the mRNA is fully encapsulated in the nucleic acid-lipid particle. 21. A pharmaceutical composition comprising a nucleic acid-lipid particle of claim 18 and a pharmaceutically acceptable carrier. 22. The pharmaceutical composition of claim 21, wherein the mRNA is fully encapsulated in the nucleic acid-lipid particle. 23. The nucleic acid-lipid particle of claim 5, wherein the PEG-lipid conjugate comprises an amido linker moiety. 24. The nucleic acid-lipid particle of claim 3, wherein the cholesterol consists of from 35 mol % to 45 mol % of the total lipid present in the particle. 25. The nucleic acid-lipid particle of claim 24, wherein the PEG-lipid conjugate consists of from 0.5 mol % to 2 mol % of the total lipid present in the particle. 26. A pharmaceutical composition comprising a nucleic acid-lipid particle of claim 25 and a pharmaceutically acceptable carrier. 27. The pharmaceutical composition of claim 26, wherein the RNA is fully encapsulated in the nucleic acid-lipid particle. 28. The nucleic acid-lipid particle of claim 16, wherein the PEG-lipid conjugate comprises an amido linker moiety. 29. The nucleic acid-lipid particle of claim 28, wherein the DSPC consists of from 4 mol % to 10 mol % of the total lipid present in the particle. 30. A pharmaceutical composition comprising a nucleic acid-lipid particle of claim 29 and a pharmaceutically acceptable carrier.