- Lipid nanoparticle formulations of non-viral capsid-free DNA vectors
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Provided herein are lipid nanoparticle formulations that comprise an ionizable lipid and non-viral, capsid-free DNA vectors with covalently-closed ends.
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- LINOLEIC ACID DERIVATIVES, PHARMACEUTICAL COMPOSITION OR FOOD COMPOSITION COMPRISING SAID LINOLEIC ACID DERIVATIVES, AND THEIR USES
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This invention relates to linoleic acid derivative of Formula (I) below comprising a hydrophobic part C17H31 linked to a polar head part "A": wherein said polar head part A is selected from A1 to A4 below: wherein R1 and R2 are independently selected from the group composed of H or a saturated or unsaturated, straight or branched alkyl group containing 1 to 8 carbon atoms, or R1 and R2 are linked together to form a divalent radical of formula -R1-R2-, wherein -R1-R2- is preferably -CH2-CH2- or-(CH2)3-; R3 is independently selected from the group composed of:
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Paragraph 0137; 0139-0140; 0145
(2019/12/16)
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- 3 - (1 - Piperazine - 4 - yl uncle ding yangtang acid radical) propionic acid amphiphilic derivatives and use thereof (by machine translation)
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The invention relates to an amphiphilic derivative of 3-(1-tert-butoxycarbonylpiperazin-4-yl)propionic acid, and a use thereof, and also relates to a liposome prepared from the amphiphilic derivative. The use is the use of the liposome as a drug carrier delivery system. The liposome prepared from the amphiphilic derivative can be compounded with gene drug siRNA to form a compound with small particle size and uniform particle size distribution. The amphiphilic derivative is electrically neutral in environment with the pH value of 7.4, increases the in vivo stability of the lipid compound and reduces cytotoxicity caused by too many positive charges. The liposome can specifically inhibit gene expression in human non-small cell lung cancer H1299-Pg13 cells in vitro, and can specifically transship fluorescence gene drugs into normal mouse liver cells in vivo.
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- COMPOUNDS AND COMPOSITIONS FOR INTRACELLULAR DELIVERY OF AGENTS
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The disclosure features amino lipids and compositions involving the same. Nanoparticle compositions include an amino lipid as well as additional lipids such as phospholipids, structural lipids, PEG lipids, or a combination thereof. Nanoparticle compositions further including therapeutic and/or prophylactic agents such as RNA are useful in the delivery of therapeutic and/or prophylactic agents to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
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- COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS
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This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.
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Page/Page column 337-338
(2017/07/18)
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- OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF
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Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.
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- COMPOUNDS AND COMPOSITIONS FOR INTRACELLULAR DELIVERY OF AGENTS
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The disclosure features amino lipids and compositions involving the same. Nanoparticle compositions include an amino lipid as well as additional lipids such as phospholipids, structural lipids, PEG lipids, or a combination thereof. Nanoparticle compositions further including therapeutic and/or prophylactic agents such as RNA are useful in the delivery of therapeutic and/or prophylactic agents to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
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- Di-aliphatic substituted pegylated lipids
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The disclosure relates to di-aliphatic substituted PEGylated lipids and to methods of their preparation. The disclosure also relates to lipid conjugates containing di-aliphatic substituted PEGylated lipids, and to the use of di-aliphatic substituted PEGylated-lipid conjugates in drug delivery.
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- LIPID MEMBRANE STRUCTURE FOR siRNA INTRACELLULAR DELIVERY
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A lipid membrane structure encapsulating an siRNA inside thereof and containing a lipid compound of the formula (I) as a lipid component (R1 and R2 represent CH3—(CH2)n—CH═CH—CH2—CH═CH—(CH2)m—, n represents an integer of 3 to 5, m represents an integer of 6 to 10, p represents an integer of 2 to 7, and R3 and R4 represent a C1-4 alkyl group or a C2-4 alkenyl group.
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- OLIGONUCLEOTIDES, COMPOSITIONS AND METHODS THEREOF
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The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described. In some embodiments, no immune modulation is desired, and the present disclosure provides methods of identifying chirally controlled oligonucleotide compositions which have decreased immune modulation.
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- 3 - ((2 - (Dimethylamino) ethyl) (methyl) amino) propionic acid amphiphilic derivatives and use thereof
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The invention relates to an amphiphilic derivative of 3-((2-dimethylamino)ethyl(methyl)amino)propionic acid, and a use thereof, and also relates to a liposome prepared from the above amphiphilic compound. The use is the use of the liposome as a drug carrier delivery system. The liposome prepared from the amphiphilic compound has many positive charges in acidic environment, and can be well compounded with gene drug siRNA to form a compound with small particle size and uniform particle size distribution. The amphiphilic compound is electrically neutral in environment with the pH value of 7.4, increases the in vivo stability of the lipid compound and reduces cytotoxicity caused by too many positive charges. The liposome can specifically inhibit gene expression in human non-small cell lung cancer H1299-Pg13 cells in vitro, and can specifically transship fluorescence gene drugs into normal mouse liver cells in vivo.
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- IMPROVED LIPID FORMULATION
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The invention features an improved lipid formulation comprising a cationic lipid of formula (A), a neutral lipid, a sterol and a PEG or PEG-modified lipid, where R1 and R2 are independently alkyl, alkenyl or alkynyl, each can be optionally substituted, and R3 and R4 are independently lower alkyl or R3 and R4 can be taken together to form an optionally substituted heterocyclic ring. In one embodiment, R1 and R2 are independently selected from oleoyl, pamitoyl, steroyl, linoleyl and R3 and R4 are methyl. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.
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Paragraph 0255; 0256
(2017/11/28)
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- Lipid formulations
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The invention features a cationic lipid of formula I, an improved lipid formulation comprising a cationic lipid of formula I and corresponding methods of use. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.
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- The lipid membrane structure (by machine translation)
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PROBLEM TO BE SOLVED: siRNA of Hepatocytic nucleic acid or the like can be efficiently deliver glycolipid film structure of the carrier. SOLUTION: eq. (I) (R the eq. (A) or eq. (B) a group represented by (n is 2 from 4 integer, m is an integer of from 2 5)) as a compound represented by structure including glycolipid glycolipid film. Selected drawing: no (by machine translation)
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- IMPROVED COMPOSITIONS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS
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The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
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Paragraph 0203-0204
(2016/08/17)
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- NON-LIPOSOMAL SYSTEMS FOR NUCLEIC ACID DELIVERY
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The present invention provides novel, stable lipid particles having a non-lamellar structure and comprising one or more active agents or therapeutic agents, methods of making such lipid particles, and methods of delivering and/or administering such lipid particles. More particularly, the present invention provides stable nucleic acid-lipid particles (SNALP) that have a non-lamellar structure and that comprise a nucleic acid (such as one or more interfering RNA), methods of making the SNALP, and methods of delivering and/or administering the SNALP.
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Page/Page column 0551; 0552
(2016/02/22)
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- Polymerizable organoboron alkyd resin anti fouling coatings
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A compound includes a boron atom attached to at least one C8-C26 fatty acid residue having at least one C═C moiety. Such compounds are polymerizable through the at least one C═C moiety. Polymers thus formed exhibit anti-fouling properties when used as coatings.
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- LIPIDOSOME PREPARATION, PREPARATION METHOD AND APPLICATION THEREOF
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The present invention discloses a liposome formulation, its preparation method, and its application in the treatment of diseases caused by abnormal gene expression. The liposome formulation comprises complementary cationic lipid pairs, phospholipids, and long-circulating lipids. The method of preparing the liposome formulation comprises: mixing the complementary cationic lipid pairs with the phospholipid and the long-circulating lipid to generate pre-formed vesicles; and then mixing the pre-formed vesicles with the nucleic acid solution to generate the liposome-nucleic acid formulation. This liposome formulation provided by the present invention is easily prepared; and in the treatment of diseases caused by abnormal gene expression, the liposome formulation can be used to deliver in vivo therapeutic agents, including nucleic acids.
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- Lipids and compositions for the delivery of therapeutics
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The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention formula (I) provides lipids having the following structure XXXIII wherein: R1 and R2 are each independently for each occurrence optionally substituted C10-C30 alkyl, optionally substituted C10-C30 alkenyl, optionally substituted C10-C30 alkynyl, optionally substituted C10-C30 acyl, or -linker-ligand; R3 is H, optionally substituted C1-C10 alkyl, optionally substituted C2-C10 alkenyl, optionally substituted C2-C10 alkynyl, alky lhetro cycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ω-aminoalkyls, ω-(substituted)aminoalkyls, ω-phosphoalkyls, ω-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).
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- Improved glycolipid preparation
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The invention features a cationic lipid of formula (I), an improved lipid formulation comprising a cationic lipid of formula I and corresponding methods of use. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.
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Paragraph 0447; 0449
(2016/12/12)
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- LEPTIN mRNA COMPOSITIONS AND FORMULATIONS
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A formulation comprising a modified synthetic messenger RNA and a delivery agent. The modified synthetic messenger RNA encodes a leptin protein, is non-replicating and is translation-ready. The formulation can be delivered to a subject with congenital leptin deficiency, lipodystrophy or other condition where circulating leptin level is low.
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Paragraph 0372; 0373
(2015/07/07)
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- LIPIDS AND LIPID COMPOSITIONS FOR THE DELIVERY OF ACTIVE AGENTS
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This invention provides for a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1-R3, n, p, L1 and L2 are defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.
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Page/Page column 208
(2015/07/07)
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- LIPID FORMULATED SINGLE STRANDED RNA
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The present invention provides compositions comprising a nucleic acid lipid particle and an oligomeric compound and uses thereof. In certain embodiments, such compositions are useful as antisense compounds. Certain such antisense compounds are useful as RNase H antisense compounds or as RNAi compounds.
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Paragraph 0835-0836
(2013/06/28)
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- DI-ALIPHATIC SUBSTITUTED PEGYLATED LIPIDS
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The disclosure relates to di-aliphatic substituted PEGylated lipids and to methods of their preparation. The disclosure also relates to lipid conjugates containing di-aliphatic substituted PEGylated lipids, and to the use of di-aliphatic substituted PEGylated-lipid conjugates in drug delivery.
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Page/Page column 122; 123; 124
(2013/04/13)
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- COMPOSITIONS AND METHODS FOR SILENCING APOLIPOPROTEIN B
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The present invention provides compositions and methods for the delivery of interfering RNAs such as siRNAs that silence APOB expression in cells such as liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells such as liver cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
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Paragraph 0545-0547
(2013/05/22)
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- Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo
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Special (lipid) delivery: The role of the ionizable lipid pKa in the in?vivo delivery of siRNA by lipid nanoparticles has been studied with a large number of head group modifications to the lipids. A tight correlation between the lipid pKa?value and silencing of the mouse FVII gene (FVII ED50) was found, with an optimal pKa range of 6.2-6.5 (see graph). The most potent cationic lipid from this study has ED50 levels around 0.005?mg?kg?1 in mice and less than 0.03?mg?kg?1 in non-human primates.
- Jayaraman, Muthusamy,Ansell, Steven M.,Mui, Barbara L.,Tam, Ying K.,Chen, Jianxin,Du, Xinyao,Butler, David,Eltepu, Laxman,Matsuda, Shigeo,Narayanannair, Jayaprakash K.,Rajeev, Kallanthottathil G.,Hafez, Ismail M.,Akinc, Akin,Maier, Martin A.,Tracy, Mark A.,Cullis, Pieter R.,Madden, Thomas D.,Manoharan, Muthiah,Hope, Michael J.
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p. 8529 - 8533
(2012/10/18)
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- COMPOSITIONS AND METHODS FOR ENHANCING CELLULAR UPTAKE AND INTRACELLULAR DELIVERY OF LIPID PARTICLES
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Compositions, methods and compounds useful for enhancing the uptake of a lipid particle b\ a cell are described In particular embodiments, the methods of the invention include contacting a cell with a lipid particle and a compound that binds a Na+/K+ ATPase to enhance uptake of the lipid particle b\ the cell Related compositions useful in practicing methods include lipid particles comprising a conjugated compound that enhances uptake of the lipid particles b\ the cell The methods and compositions are useful in delivering a therapeutic agent to a cell, e g for the treatment of a disease or disorder in a subject
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Page/Page column 42
(2012/10/23)
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- NOVEL CATIONIC LIPIDS AND METHODS OF USE THEREOF
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The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
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Page/Page column 77
(2011/12/02)
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- NOVEL CYCLIC CATIONIC LIPIDS AND METHODS OF USE
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The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid- lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
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Page/Page column 108
(2011/12/02)
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- COMPOSITIONS AND METHODS FOR SILENCING APOLIPOPROTEIN B
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The present invention provides compositions and methods for the delivery of interfering RNAs that silence APOB expression to liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
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- IMPROVED AMINO LIPIDS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS
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The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
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Page/Page column 86-87
(2010/04/28)
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- AMINO LIPID BASED IMPROVED LIPID FORMULATION
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The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic aicd to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art. Formulae (I), (II), (III), (IV).
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Page/Page column 94
(2009/12/05)
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- Synthesis of Very Long Fatty Acid Methyl Esters
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Phosphoranes, produced by treating alkyltriphenylphosphonium bromides with lithium hexamethyldisilazide, reacted with ω-oxo esters to give modest yields of the corresponding methyl cis-alkenoates.By an alternative method, treatment of ω-iodo esters with the complexes formed from reactions of alkylcopper(I) and Grignard reagents gave methyl alkanoates, cis-alkenoates, and methylene-interrupted cis,cis-alka-dienoates and cis,cis,cis-trienoates.The stereochemical integrity of the esters was determined by 13C NMR spectroscopy.
- Kling, Marcel R.,Easton, Christopher J.,Poulos, Alf
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p. 1183 - 1190
(2007/10/02)
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