Patent application number | Description | Published |
20090281298 | OLIGONUCLEOTIDES COMPRISING A MODIFIED OR NON-NATURAL NUCLEOBASE - One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage. | 11-12-2009 |
20090281299 | OLIGONUCLEOTIDES COMPRISING A NON-PHOSPHATE BACKBONE LINKAGE - One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety. | 11-12-2009 |
20090286973 | LIGAND-CONJUGATED MONOMERS - This invention relates composition and methods for making and using chemically modified oligonucleotides agents for inhibiting gene expression. | 11-19-2009 |
20090312531 | OLIGNUCLEOTIDES COMPRISING A LIGAND TETHERED TO A MODIFIED OR NON-NATURAL NUCLEOBASE - One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage. | 12-17-2009 |
20090318676 | OLIGONUCLEOTIDES COMPRISING A NON-PHOSPHATE BACKBONE LINKAGE - One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety. | 12-24-2009 |
20100069471 | CHEMICALLY MODIFIED OLIGONUCLEOTIDES - This invention relates composition and methods for making and using chemically modified oligonucleotides agents for inhibiting gene expression. | 03-18-2010 |
20100076056 | MODIFIED iRNA AGENTS - The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent. | 03-25-2010 |
20100179309 | MODIFIED iRNA AGENTS - The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a carbohydrate; or a steroid, e.g., cholesterol, which is optionally substituted with at least one carbohydrate. is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents. | 07-15-2010 |
20100197899 | SINGLE-STRANDED AND DOUBLE-STRANDED OLIGONUCLEOTIDES COMPRISING A 2-ARYLPROPYL MOIETY - The present invention provides single-stranded and double-stranded oligonucleotides comprising at least one aralkyl ligand that improvise the pharmacokinetic properties of the oligonucleotide. The aralkyl ligands of the present invention include naproxen, ibuprofen, and derivatives thereof. The present invention also provides method for modulating gene expression using the modified oligonucleotide compounds and compositions comprising those modified oligonucleotides. | 08-05-2010 |
20100240881 | THERAPEUTIC COMPOSITIONS - This application relates to therapeutic siRNA agents and methods of making and using the agents. | 09-23-2010 |
20100267941 | IRNA AGENTS WITH BIOCLEAVABLE TETHERS - The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent. | 10-21-2010 |
20100292455 | MODIFIED iRNA AGENTS - The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents. | 11-18-2010 |
20100324120 | LIPID FORMULATION - The invention features a cationic lipid of formula I, | 12-23-2010 |
20110097707 | RNAi Agents Comprising Universal Nucleobases - One aspect of the present invention relates to an oligonucleotide agent comprising at least one universal nucleobase. In certain embodiments, the universal nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the universal nucleobase is difluorotolyl. In certain embodiments, the oligonucleotide is double-stranded. In certain embodiments, the oligonucleotide is single-stranded. Another aspect of the present invention relates to a method of altering the expression level of a target in the presence of target sequence polymorphism. In a preferred embodiment, the oligonucleotide agent alters the expression of different alleles of a gene. In another preferred embodiment, the oligonucleotide agent alters the expression level of two or more genes. In another embodiment, the oligonucleotide agent alters the expression level of a viral gene from different strains of the virus. In another embodiment, the oligonucleotide agent alters the expression level of genes from different species. | 04-28-2011 |
20110118339 | CHEMICALLY MODIFIED OLIGONUCLEOTIDES AND USES THEREOF - This invention relates generally to chemically modified oligonuceotides useful for augmenting activity of microRNAs and pre-microRNAs. E.g., the invention relates to single stranded chemically modified oligonuceotides for augmenting microRNA and pre-microRNA expression and to methods of making and using the modified oligonucleotides. | 05-19-2011 |
20110118340 | DELIVERY OF RNAI CONSTRUCTS TO OLIGODENDROCYTES - The invention provides methods for delivering a double-stranded nbonucleic acid (dsRNA) to the central nervous system of a subject, and particularly, to oligodendrocytes of a subject by localized delivery to the brain, e.g., to the corpus caïlosum. For example, the dsRNA molecules can include a first sequence that is selected from the Sroup consisting of the sense sequences of Tables 8, 10, 13-16, and a second sequence selected from the group consisting of the antisense sequences of Tables 8, 10, and 13-16. The dsRNA molecules can include naturally occurring nucleotides or can include at least one modified nucleotide, such as a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, or a terminal nucleotide linked to a conjugate group, such as to a cholesteryl derivative or a vitamin E group. Alternatively, the modified nucleotide may be chosen from the group consisting of a 2f-deoxy-2′-fliιioro modified nucleotide, a 2′-de-oxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural bas comprising nucleotide. Generally, such modified sequences will be based on a first sequence of a dsRNA selected from the group consisting of the sense sequences of Tables 8, 10, and 13-16, and a second sequence selected from the group consisting of the antisense sequences of Tables 8 10, and 13-16. | 05-19-2011 |
20110123520 | SITE-SPECIFIC DELIVERY OF NUCLEIC ACIDS BY COMBINING TARGETING LIGANDS WITH ENDOSOMOLYTIC COMPONENTS - The invention relates to compositions and methods for site-specific delivery of nucleic acids by combining them with targeting ligands and endosomolytic components. | 05-26-2011 |
20110130440 | NON-NATURAL RIBONUCLEOTIDES, AND METHODS OF USE THEREOF - One aspect of the present invention relates to modified nucleosides and oligonucleotides comprising such modified nucleosides. Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. | 06-02-2011 |
20110196145 | PROCESS FOR DESILYLATION OF OLIGONUCLEOTIDES - The present invention relates to processes and reagents for oligonucleotide synthesis and purification. One aspect of the present invention relates to compounds useful for activating phosphoramidites in oligonucleotide synthesis. Another aspect of the present invention relates to a method of preparing oligonucleotides via the phosphoramidite method using an activator of the invention. Another aspect of the present invention relates to sulfur-transfer agents. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to a method of preparing a phosphorothioate by treating a phosphite with a sulfur-transfer reagent of the invention. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to compounds that scavenge acrylonitrile produced during the deprotection of phosphate groups bearing ethylnitrile protecting groups. In a preferred embodiment, the acrylonitrile scavenger is a polymer-bound thiol. Another aspect of the present invention relates to agents used to oxidize a phosphite to a phosphate. In a preferred embodiment, the oxidizing agent is sodium chlorite, chloroamine, or pyridine-N-oxide. Another aspect of the present invention relates to methods of purifying an oligonucleotide by annealing a first single-stranded oligonucleotide and second single-stranded oligonucleotide to form a double-stranded oligonucleotide; and subjecting the double-stranded oligonucleotide to chromatographic purification. In a preferred embodiment, the chromatographic purification is high-performance liquid chromatography. | 08-11-2011 |
20110218334 | PHOSPHOROTHIOATE OLIGONUCLEOTIDES AND NON-NUCLEOSIDIC PHOSPHOROTHIOATES AS DELIVERY AGENTS FOR iRNA AGENTS - The invention relates to use of single-stranded phosphorothioate oligonucleotides or non-nucleosidic phosphrothiaote as vehicles or carriers to modulate the biodistribution of iRNA agents. | 09-08-2011 |
20110245320 | NUCLEASE RESISTANT DOUBLE-STRANDED RIBONUCLEIC ACID - This invention relates to modified double-stranded oligoribonucleic acid (dsRNA) having improved stability in cells and biological fluids, and methods of making and identifying dsRNA having improved stability, and of using the dsRNA to inhibit the expression or function of a target gene. | 10-06-2011 |
20110257244 | CHEMICALLY MODIFIED OLIGONUCLEOTIDES AND SMALL MOLECULES FOR USE IN REDUCING MICRO RNA ACTIVITY LEVELS AND USES THEREOF - This invention relates generally to chemically modified oligonucleotides useful for modulating activity of microRNAs and pre-microRNAs. More particularly, the invention relates to single stranded chemically modified oligonucleotides for inhibiting microRNA and pre-microRNA activity and to methods of making and using the modified oligonucleotides. | 10-20-2011 |
20110269814 | 2'-F MODIFIED RNA INTERFERENCE AGENTS - This invention relates to a method of modulating the expression of a target gene in an organism comprising administering an iRNA agent, wherein the iRNA comprises at least one 2′-deoxy-2′-fluoro (2′-F) nucleotide in the antisense strand and at least one modified nucleotide in the sense strand. The invention also relates to compositions comprising a single-stranded oligonucleotide that contains at least one 2′-deoxy-2′-fluoro (2′-F) nucleotide. siRNA molecule containing these oligonucleotides have decreased immunogenicity. | 11-03-2011 |
20110311582 | NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS - 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: R | 12-22-2011 |
20110311583 | NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS - (A1) Translate this text 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 provides lipids having the following structure (I) 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, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, ?-aminoalkyls, ?-(substituted)aminoalkyls, ?-phosphoalkyls, ?-thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; E is O, S, N(Q), C(O), N(Q)C(O), C(0)N(Q), (Q)N(CO)O, O(CO)N(Q), S(O), NS(O)2N(Q), S(O)2, N(Q)S(O)2, SS, O═N, aryl, heteroaryl, cyclic or heterocycle; and, Q is H, alkyl, ?-aminoalkyl, ?-(substituted)aminoalky, ?-phosphoalkyl or ?-thiophosphoalkyl. | 12-22-2011 |
20120027796 | NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS - 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 provides lipids having the following structures: (Formula (I) or (XXXV)). | 02-02-2012 |
20120027803 | BIODEGRADABLE LIPIDS FOR THE DELIVERY OF ACTIVE AGENTS - The present invention relates to a cationic lipid having one or more biodegradable groups located in the mid- or distal section of a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid. | 02-02-2012 |
20120035115 | CHEMICAL MODIFICATIONS OF MONOMERS AND OLIGONUCLEOTIDES WITH CYCLOADDITION - The invention features compounds of formula I or II: | 02-09-2012 |
20120058144 | LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS - 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 provides lipids having the following structures XIV or XVII. | 03-08-2012 |
20120071641 | NUCLEIC ACID CHEMICAL MODIFICATIONS - The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least one nucleoside of formula (2): Another aspect of the invention relates to a method of inhibiting the expression of a gene in cell, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. | 03-22-2012 |
20120095075 | NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS - 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 provides lipids having the following structure: | 04-19-2012 |
20120101148 | LIPID FORMULATION - 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 R | 04-26-2012 |
20120107272 | SYNTHETIC METHODS AND DERIVATIVES OF TRIPHOSPHATE OLIGONUCLEOTIDES - The invention features a oligonucleotide of formula I, or pharmaceutically acceptable salts, or prodrugs thereof: | 05-03-2012 |
20120128760 | LIPID COMPOSITIONS - Disclosed herein are lipid compositions comprising a cationic lipid of formula (I), a neutral lipid, a sterol and a PEG or PEG-modified lipid, wherein formula (I) is (F). Also disclosed are methods of producing the cationic lipid of formula (I). | 05-24-2012 |
20120136042 | CARBOHYDRATE CONJUGATES AS DELIVERY AGENTS FOR OLIGONUCLEOTIDES - The present invention provides iRNA agents comprising at least one subunit of the formula (I): | 05-31-2012 |
20120142101 | OLIGONUCLEOTIDE END CAPS - Modified nucleic acids are described herein, including pharmaceutical compositions comprising the modified nucleic acids, and methods of using the modified nucleic acids. | 06-07-2012 |
20120157511 | 5' PHOSPHATE MIMICS - The present invention provides nucleosides and oligonucleotides comprising a 5′ phosphate mimics of formula (IVc) or (Vc). One aspect of the present invention relates to modified nucleosides and oligonucleotides comprising such dinucleotide of formula (Ia). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. | 06-21-2012 |
20120183602 | LIPID FORMULATION - The invention features a cationic lipid of formula I, | 07-19-2012 |
20130017223 | METHODS AND COMPOSITIONS FOR DELIVERY OF NUCLEIC ACIDS - A lipid particle can include a plurality of cationic lipids, such as a first cationic lipid and a second cationic lipid. The first cationic lipid can be selected on the basis of a first property and the second cationic can be selected on the basis of a second property. The first and second properties are complementary. The attributes of the lipid particle can reflect the selected properties of the cationic lipids, and the complementary nature of those properties. | 01-17-2013 |
20130129785 | METHODS AND COMPOSITIONS FOR DELIVERY OF ACTIVE AGENTS - A lipid particle can include a cationic lipid. Synthesis of the cationic lipid can include a ylide-based reaction, such as a Wittig reaction or sulfur ylide reaction. In some cases, the synthesis can also include a Michael addition or a related addition reaction. | 05-23-2013 |
20130130378 | OLIGONUCLEOTIDES COMPRISING ACYCLIC AND ABASIC NUCLEOSIDES AND ANALOGS - This invention relates to acyclic and abasic nucleosides and oligonucleotides prepared therefrom. For instance, oligonucleotides can be prepared having one or more of the following formulas (I-III):, or isomers thereof. | 05-23-2013 |
20130144048 | THERAPEUTIC COMPOSITIONS - This application relates to therapeutic siRNA agents and methods of making and using the agents. | 06-06-2013 |
20130150570 | NUCLEASE RESISTANT DOUBLE-STRANDED RIBONUCLEIC ACID - This invention relates to modified double-stranded oligoribonucleic acid (dsRNA) having improved stability in cells and biological fluids, and methods of making and identifying dsRNA having improved stability, and of using the dsRNA to inhibit the expression or function of a target gene. | 06-13-2013 |
20130156845 | LIPID FORMULATED SINGLE STRANDED RNA - 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. | 06-20-2013 |
20130178512 | CARBOHYDRATE CONJUGATES AS DELIVERY AGENTS FOR OLIGONUCLEOTIDES - The present invention provides iRNA agents comprising at least one subunit of the formula (I): | 07-11-2013 |
20130184328 | LIGAND-CONJUGATED MONOMERS - This invention relates composition and methods for making and using chemically modified oligonucleotides agents for inhibiting gene expression. | 07-18-2013 |
20130195920 | BIODEGRADABLE LIPIDS FOR THE DELIVERY OF ACTIVE AGENTS - The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid. | 08-01-2013 |
20130202652 | METHODS AND COMPOSITIONS FOR DELIVERY OF ACTIVE AGENTS - A targeting lipid can have the formula (I) in which T4 is a targeting moiety. The targeting moiety can be chosen to favor the lipid being localized with a desired organ, tissue, cell, cell type or subtype, or organelle. The targeting moiety can include, for example, transferrin, anisamide, an RGD peptide, prostate specific membrane antigen (PSMA), fucose, an antibody, or an aptamer. | 08-08-2013 |
20130203836 | 2' AND 5' MODIFIED MONOMERS AND OLIGONUCLEOTIDES - The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least on nucleoside of formula (2):Formula (1) and Formula (2). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene. | 08-08-2013 |
20130236968 | MULTIFUNCTIONAL COPOLYMERS FOR NUCLEIC ACID DELIVERY - The present invention relates to multifunctional polymers represented by the following formula: | 09-12-2013 |
20130281685 | iRNA AGENTS WITH BIOCLEAVABLE TETHERS - The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent. | 10-24-2013 |
20130317080 | MODIFIED iRNA AGENTS - The present invention provides effective motifs for RNA agents conjugated to at least one ligand, which are advantageous for the in vivo delivery of iRNA duplex agents. Additionally, the present invention provides methods of making these compositions, as well as methods of introducing these iRNA duplex agents into cells using these compositions, e.g., for the treatment of various disease conditions. | 11-28-2013 |
20130317081 | SERPINC1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF - The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the Serpinc1 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of Serpinc1 and methods of treating subjects having a bleeding disorder, such as a hemophilia. | 11-28-2013 |
20140045919 | Folate Conjugates - The present invention provides iRNA agent including at least one monomer having the structure shown in formula (I′) | 02-13-2014 |
20140121393 | LIPID CONTAINING FORMULATIONS - Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described. | 05-01-2014 |
20140179761 | TARGETING LIPIDS - The present invention provides targeting lipids of structure | 06-26-2014 |
20140200257 | PEGYLATED LIPIDS AND THEIR USE FOR DRUG DELIVERY - The invention provides poly(ethylene glycol)-lipid conjugates for use in drug delivery. | 07-17-2014 |
20140256785 | SITE SPECIFIC DELIVERY OF NUCLEIC ACIDS BY COMBINING TARGETING LIGANDS WITH ENDOSOMOLYTIC COMPONENTS - The invention relates to compositions and methods for site-specific delivery of nucleic acids by combining them with targeting ligands and endosomolytic components. | 09-11-2014 |
20140288158 | MODIFIED RNAi AGENTS - One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene. The dsRNA duplex comprises one or more motifs of three identical modifications on three consecutive nucleotides in one or both strand, particularly at or near the cleavage site of the strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions. | 09-25-2014 |
20140308304 | LIPIDS FOR THE DELIVERY OF ACTIVE AGENTS - The present invention relates to novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides, to facilitate the cellular uptake and endosomal escape, and to knockdown target mRNA both in vitro and in vivo. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid. | 10-16-2014 |
20140309411 | THERAPEUTIC COMPOSITIONS - This application relates to therapeutic siRNA agents and methods of making and using the agents. | 10-16-2014 |
20140315835 | RNAI AGENTS, COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING TRANSTHYRETIN (TTR) ASSOCIATED DISEASES - The present invention provides RNAi agents, e.g., double stranded RNAi agents, that target the transthyretin (TTR) gene and methods of using such RNAi agents for treating or preventing TTR-associated diseases. | 10-23-2014 |
20150073133 | iRNA AGENTS WITH BIOCLEAVABLE TETHERS - The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent. | 03-12-2015 |
20150080457 | 5' PHOSPHATE MIMICS - The present invention provides nucleosides and oligonucleotides comprising a 5′ phosphate mimics of formula (IVc) or (Vc), | 03-19-2015 |