Claims for Patent: 8,492,359

Summary for Patent: 8,492,359

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:	Protiva Biotherapeutics, Inc. (Burnaby, BC, CA)
Application Number:	13/253,917
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,492,359
Patent Claims:	1. A nucleic acid-lipid particle comprising: (a) a nucleic acid; (b) a cationic lipid comprising from 50 mol % to 65 mol % of the total lipid present in the particle; (c) a non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof, wherein the phospholipid comprises from 3 mol % to 15 mol % of the total lipid present in the particle and the cholesterol or derivative thereof comprises from 30 mol % to 40 mol % of the total lipid present in the particle; and (d) a conjugated lipid that inhibits aggregation of particles comprising from 0.5 mol % to 2 mol % of the total lipid present in the particle. 2. The nucleic acid-lipid particle of claim 1, wherein the nucleic acid comprises a small interfering RNA (siRNA). 3. The nucleic acid-lipid particle of claim 2, wherein the siRNA comprises at least one modified nucleotide. 4. The nucleic acid-lipid particle of claim 2, wherein the siRNA comprises at least one 2'-O-methyl (2'OMe) nucleotide. 5. The nucleic acid-lipid particle of claim 2, wherein the siRNA is about 19 to about 25 base pairs in length. 6. The nucleic acid-lipid particle of claim 2, wherein the siRNA comprises 3' overhangs. 7. The nucleic acid-lipid particle of claim 1, wherein the cationic lipid comprises from 50 mol % to 60 mol % of the total lipid present in the particle. 8. The nucleic acid-lipid particle of claim 1, wherein the phospholipid comprises dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), or a mixture thereof. 9. The nucleic acid-lipid particle of claim 1, wherein the phospholipid comprises from 4 mol % to 15 mol % of the total lipid present in the particle. 10. The nucleic acid-lipid particle of claim 1, wherein the phospholipid comprises from 4 mol % to 12 mol % of the total lipid present in the particle. 11. The nucleic acid-lipid particle of claim 1, wherein the phospholipid comprises from 5 mol % to 12 mol % of the total lipid present in the particle. 12. The nucleic acid-lipid particle of claim 1, wherein the phospholipid comprises from 6 mol % to 12 mol % of the total lipid present in the particle. 13. The nucleic acid-lipid particle of claim 1, wherein the cholesterol or derivative thereof comprises from 30 mol % to 35 mol % of the total lipid present in the particle. 14. The nucleic acid-lipid particle of claim 1, wherein the conjugated lipid that inhibits aggregation of particles comprises a polyethyleneglycol (PEG)-lipid conjugate. 15. The nucleic acid-lipid particle of claim 14, wherein the PEG-lipid conjugate comprises a PEG-diacylglycerol (PEG-DAG) conjugate, a PEG-dialkyloxypropyl (PEG-DAA) conjugate, or a mixture thereof. 16. The nucleic acid-lipid particle of claim 15, wherein the PEG-DAA conjugate comprises a PEG-dimyristyloxypropyl (PEG-DMA) conjugate, a PEG-distearyloxypropyl (PEG-DSA) conjugate, or a mixture thereof. 17. The nucleic acid-lipid particle of claim 16, wherein the PEG has an average molecular weight of about 2,000 daltons. 18. The nucleic acid-lipid particle of claim 1, wherein the conjugated lipid that inhibits aggregation of particles comprises from 1 mol % to 2 mol % of the total lipid present in the particle. 19. The nucleic acid-lipid particle of claim 14, wherein the nucleic acid-lipid particle comprises about 55 mol % cationic lipid, about 11 mol % phospholipid, about 33 mol % cholesterol or a derivative thereof, and about 1.6 mol % PEG-lipid conjugate. 20. The nucleic acid-lipid particle of claim 1, wherein the nucleic acid is fully encapsulated in the nucleic acid-lipid particle. 21. A pharmaceutical composition comprising a nucleic acid-lipid particle of claim 1 and a pharmaceutically acceptable carrier.