Use of liposomes in a carrier comprising a continuous hydrophobic phase for delivery of polynucleotides in vivo
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/20
A61K-039/39
A61K-048/00
A61K-009/127
A61K-031/7088
C12N-015/88
A61K-009/107
C12N-015/113
A61K-039/00
출원번호
US-0290567
(2016-10-11)
등록번호
US-10232052
(2019-03-19)
발명자
/ 주소
Mansour, Marc
Karkada, Mohan
Weir, Genevieve Mary
출원인 / 주소
IMMUNOVACCINE TECHNOLOGIES INC.
대리인 / 주소
Troutman Sanders LLP
인용정보
피인용 횟수 :
0인용 특허 :
81
초록
The invention provides compositions comprising a carrier comprising a continuous phase of a hydrophobic substance, liposomes, and a polynucleotide, and methods for using such compositions for delivering a polynucleotide to a subject.
대표청구항▼
1. An injectable composition comprising: a carrier comprising a continuous phase of oil;liposomes comprising a saturated or unsaturated phospholipid; anda polynucleotide encapsulated within said liposomes, said polynucleotide encoding a polypeptide and being operably linked to a promoter functional
1. An injectable composition comprising: a carrier comprising a continuous phase of oil;liposomes comprising a saturated or unsaturated phospholipid; anda polynucleotide encapsulated within said liposomes, said polynucleotide encoding a polypeptide and being operably linked to a promoter functional in mammalian cells,wherein said carrier and said liposomes are present in a ratio of 1:1 by volume. 2. The composition according to claim 1, wherein the composition is a water-in-oil emulsion. 3. The composition according to claim 1, wherein said carrier is free of water. 4. The composition according to claim 1, wherein said oil comprises a natural oil, a synthetic oil, or a combination thereof. 5. The composition according to claim 1, wherein said liposomes comprise cholesterol, dioleoyl phosphatidylcholine (DOPC), phosphoglycerol, phosphoethanolamine, phosphoserine, phosphocholine, phosphoinositol, phosphatidylcholine, lecithin, phosphatidylcholine and ascorbyl palmitate, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazolinium chloride (DOTIM), or combinations thereof. 6. The composition according to claim 1, further comprising an emulsifier. 7. The composition according to claim 6, wherein said emulsifier comprises mannide oleate, mannide monooleate, lecithin, polysorbate 80, sorbitan laurate, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, or combinations thereof. 8. The composition according to claim 1, further comprising an adjuvant. 9. The composition according to claim 8, wherein said adjuvant is present: (a) within said liposomes; (b) exterior to said liposomes; or (c) both within said liposomes and exterior to said liposomes. 10. The composition according to claim 1, wherein said polynucleotide is inserted in an expression plasmid or is contained in a bacterial or viral vector. 11. The composition according to claim 1, wherein said polynucleotide is present both encapsulated within said liposomes and exterior to said liposomes. 12. The composition according to claim 1, wherein said polypeptide is an antigen, an antibody or antibody fragment, an enzyme, a cytokine, a therapeutic protein, a chemokine, a regulatory protein, a structural protein, a chimeric protein, a nuclear protein, a transcription factor, a viral protein, a TLR protein, an interferon regulatory factor, an angiostatic or angiogenic protein, an apoptotic protein, an Fc gamma receptor, a hematopoietic protein, a tumor suppressor, a cytokine receptor, or a chemokine receptor. 13. A method for delivering a polynucleotide to a subject, comprising administering the composition of claim 1 to said subject. 14. The method according to claim 13, wherein said subject is a human. 15. The composition according to claim 1, wherein said oil comprises, a vegetable oil, mineral oil, a nut oil, soybean oil, peanut oil, or combinations thereof. 16. A method for making a composition comprising: (a) providing a polynucleotide that encodes a polypeptide and that is operably linked to a promoter functional in mammalian cells;(b) encapsulating said polynucleotide in liposomes comprising a saturated or unsaturated phospholipid; and(c) combining said liposomes with a carrier comprising a continuous phase of oil in a ratio of 1:1 by volume. 17. The method according to claim 16, wherein said liposomes are dehydrated before they are combined with said carrier. 18. The method according to claim 16, wherein said carrier is a water-in-oil emulsion. 19. The method according to claim 16, wherein said carrier is free of water. 20. The method according to claim 16, wherein said oil comprises a natural oil, a synthetic oil, or a combination thereof. 21. The method according to claim 16 wherein said liposomes comprise cholesterol, dioleoyl phosphatidylcholine (DOPC), phosphoglycerol, phosphoethanolamine, phosphoserine, phosphocholine, phosphoinositol, phosphatidylcholine, lecithin, phosphatidylcholine and ascorbyl palmitate, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazolinium chloride (DOTIM), or combinations thereof. 22. The method according to claim 16, wherein said carrier comprises an emulsifier. 23. The method according to claim 22, wherein said emulsifier comprises mannide oleate, mannide monooleate, lecithin, polysorbate 80, sorbitan laurate, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, or combinations thereof. 24. The method according to claim 16, further comprising combining an adjuvant with said polynucleotides, said liposomes, or said carrier. 25. The method according to claim 16, wherein said polypeptide is an antigen, an antibody or antibody fragment, an enzyme, a cytokine, a therapeutic protein, a chemokine, a regulatory protein, a structural protein, a chimeric protein, a nuclear protein, a transcription factor, a viral protein, a TLR protein, an interferon regulatory factor, an angiostatic or angiogenic protein, an apoptotic protein, an Fc gamma receptor, a hematopoietic protein, a tumor suppressor, a cytokine receptor, or a chemokine receptor. 26. A composition produced by the method according to claim 16. 27. The method according to claim 16, wherein said oil comprises, a vegetable oil, mineral oil, a nut oil, soybean oil, peanut oil, or combinations thereof.
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