[미국특허]
Lipidated glycosaminoglycan particles for the delivery of nucleic acids
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-009/16
A61K-048/00
A61K-047/18
A61K-047/36
C12N-015/88
A61K-009/51
A61K-031/713
C12N-015/113
A61K-009/127
A61K-047/54
A61K-047/69
출원번호
US-0395198
(2013-03-14)
등록번호
US-9925143
(2018-03-27)
국제출원번호
PCT/IL2013/050238
(2013-03-14)
국제공개번호
WO2013/156989
(2013-10-24)
발명자
/ 주소
Peer, Dan
Alpert, Evgenia
출원인 / 주소
RAMOT AT TEL-AVIV UNIVERSITY LTD.
대리인 / 주소
Browdy and Neimark, PLLC
인용정보
피인용 횟수 :
0인용 특허 :
70
초록
There are provided compositions comprising lipidated glycosaminoglycan particles, methods for their preparation and uses thereof for the efficient in-vivo and in-vitro delivery of nucleic acids, such as, siRNA molecules.
대표청구항▼
1. A composition comprising water insoluble lipidated glycosaminoglycan particles comprising (i) a plurality of lipids forming a particulate lipid composition, wherein the plurality of lipids comprises monocationic lipid N-[1-(2,3-Dioleoyloxy)]-N,N,N-trimethylammonium propane (DOTAP), 1,2-dilauroyl-
1. A composition comprising water insoluble lipidated glycosaminoglycan particles comprising (i) a plurality of lipids forming a particulate lipid composition, wherein the plurality of lipids comprises monocationic lipid N-[1-(2,3-Dioleoyloxy)]-N,N,N-trimethylammonium propane (DOTAP), 1,2-dilauroyl-Lphosphatidyl-ethanolamine (DLPE), and cholesterol, wherein the relative molar amount of DOTAP is greater than the relative molar amount of DLPE and the relative molar amount of cholesterol, and wherein the relative amount of DLPE in the composition is 11% to about 25%, and(ii) a nucleic acid encapsulated within the particles,wherein the weight ratio of the nucleic acid to lipids is less than 1:1, and wherein the composition is not a liposome. 2. The composition of claim 1, wherein the glycosaminoglycan is selected from hyaluronic acid, Chondroitin sulfate, Dermatan sulfate, Keratan sulfate, Heparin, Heparan sulfate, salts, and mixtures thereof. 3. The composition of claim 2, wherein the hyaluronic acid comprises high molecular weight hyaluronic acid. 4. The composition of claim 1, wherein the particulate lipid composition have a particle size of over about 200 nm. 5. The composition of claim 1, wherein the nucleic acid comprises DNA, RNA, modified forms thereof, and combinations thereof. 6. The composition of claim 5, wherein the RNA is selected from siRNA, miRNA, shRNA, antisense RNA and combinations thereof. 7. The composition of claim 1, wherein the weight ratio between the plurality of lipids and the nucleic acid is 10:1. 8. The composition of claim 1 further comprising a targeting moiety. 9. The composition of claim 1, wherein the particles are adapted to deliver the nucleic acid to a target site and wherein the target site is selected from the group consisting of a tumor, a cell, a tissue, an organ, and a microorganism. 10. A composition according to claim 1 in the form of freeze dried particles. 11. A pharmaceutical composition comprising the particles according to claim 1 in a dosage form suitable for administration via a route selected from oral, parenteral and topical. 12. The composition of claim 1, wherein the relative molar amount of DOTAP is about 30-80% and the relative molar amount of cholesterol is about 10-50%. 13. The composition of claim 1, wherein the relative molar amount of DOTAP is about 50% and the relative molar amount of cholesterol is about 35%. 14. The composition of claim 3, wherein the molecular weight of the hyaluronic acid is about 3.1×105 to about 1.5×106 daltons.
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