| ALNYLAM PHARMACEUTICALS, INC. Patent applications |
| Patent application number | Title | Published |
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| 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 |
| 20120116360 | TREATMENT OF NEUROLOGICAL DISORDERS - This invention provides treatment compositions as well as systems and methods of determining and administering an effective amount of treatment for a neurological disorder. The treatment composition can contain a labeled interfering RNA (iRNA) agent capable of decreasing expression of a target RNA associated with the neurological disorder. The methods of the invention include determining an effective amount of a therapeutic composition by introducing a solution containing a tracer into the brain of a mammal. The tracing solution is monitored until a target volume of distribution at steady state distribution is substantially achieved, and the rate of delivery of the therapeutic composition is determined. The therapeutic composition can then be administered at the rate determined by use of the tracing solution. | 05-10-2012 |
| 20120108646 | RNAi Modulation Of TGF-BETA And Therapeutic Uses Thereof - The present invention concerns methods of treatment using transforming growth factor beta (TGF-beta) modulators. More specifically, the invention concerns methods of treating disorders associated with undesirable TGF-beta signaling, by administering short interfering RNA which down-regulate the expression of TGF-beta, and agents useful therein. | 05-03-2012 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 20120046478 | LIPID CONTAINING FORMULATIONS - Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described. | 02-23-2012 |
| 20120035240 | CONSERVED HBV AND HCV SEQUENCES USEFUL FOR GENE SILENCING - Conserved consensus sequences from known hepatitis B virus strains and known hepatitis C virus strains, which are useful in inhibiting the expression of the viruses in mammalian cells, are provided. These sequences are useful to silence the genes of HBV and HCV, thereby providing therapeutic utility against HBV and HCV viral infection in humans. | 02-09-2012 |
| 20120035115 | CHEMICAL MODIFICATIONS OF MONOMERS AND OLIGONUCLEOTIDES WITH CYCLOADDITION - The invention features compounds of formula I or II: | 02-09-2012 |
| 20120028348 | MULTIPLE RNA POLYMERASE III PROMOTER EXPRESSION CONSTRUCTS - Expression constructs comprising at least two different RNA polymerase III promoters, wherein each promoter is operably linked to a nucleic acid sequence encoding an RNA effector molecule, are disclosed herein. Further provided are expression constructs comprising multiple polymerase III promoters operably linked to sequences encoding short hairpin RNA molecules, which may comprise single and/or multiple fingers. The provided constructs are useful for in vivo delivery of RNA molecules effective in gene silencing, including of viral genes including HBV and HCV. | 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 |
| 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 |
| 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 |
| 20110263684 | Lipid Formulated Compositions and Methods for Inhibiting Expression of Serum Amyloid A Gene - The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a Serum Amyloid A (SAA) gene, and methods of using the dsRNA to inhibit expression of SAA. | 10-27-2011 |
| 20110257247 | Method of Treating Neurodegenerative Disease - Aspects featured in the invention relate to compositions and methods for inhibiting alpha-synuclein (SNCA) gene expression, such as for the treatment of neurodegenerative disorders. An anti-SNCA agent featured herein that targets the SNCA gene can have been modified to alter distribution in favor of neural cells. | 10-20-2011 |
| 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 |
| 20110251262 | Compositions And Methods For Inhibiting Expression Of An RNA From West Nile Virus - This invention relates to double-stranded ribonucleic acid (dsRNA), and its use in mediating RNA interference to inhibit the expression of an RNA from the West Nile virus (WNV), and the use of the dsRNA to treat pathological processes mediated by WNV infection, such as viral encephalitis. | 10-13-2011 |
| 20110251259 | COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF CD274/PD-L1 GENE - The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the CD274/PD-L1 gene, and methods of using such dsRNA compositions to inhibit expression of CD274/PD-L1. | 10-13-2011 |
| 20110250138 | SINGLE-STRANDED AND DOUBLE-STRANDED OLIGONUCLEOTIDES COMPRISING A METAL-CHELATING LIGAND - The invention provides modified oligonucleotides of formula (I), comprising at least one metal chelator which provides a powerful tool for study of the pharmacokinetics of siRNA and its correlation with in vivo activity. The chelated metals provide luminescent properties enable detection of the oligonucleotides through the use of time-resolved fluorescent quenching based on energy transfer from the metal ion to a nonfluorescent quencher which can be used as non-isotopic labels of oligonucleotides for diagnostics and evaluation of cellular uptake. | 10-13-2011 |
| 20110245329 | DOUBLE-STRANDED RNA STRUCTURES AND CONSTRUCTS, AND METHODS FOR GENERATING AND USING THE SAME - The present invention relates to novel double-stranded RNA (dsRNA) structures and dsRNA expression constructs, methods for generating them, and methods of utilizing them for silencing genes. Desirably, these methods specifically inhibit the expression of one or more target genes in a cell or animal (e.g., a mammal such as a human) without inducing toxicity. These methods can be used to prevent or treat a disease or infection by silencing a gene associated with the disease or infection. The invention also provides methods for identifying nucleic acid sequences that modulate a detectable phenotype, such as the function of a cell, the expression of a gene, or the biological activity of a target polypeptide. | 10-06-2011 |
| 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 |
| 20110223665 | ENHANCEMENT OF siRNA SILENCING ACTIVITY USING UNIVERSAL BASES OR MISMATCHES IN THE SENSE STRAND - One aspect of the present invention relates to a double stranded nucleic acid useful as an siRNA, that has a sense strand and an antisense strand relative to a target nucleic acid, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one nucleoside comprising a non-natural nucleobase. Another aspect of the invention relates to a method of gene silencing, comprising administering to a mammal in need thereof a therapeutically effective amount of a double-stranded oligonucleotides containing a sense strand and an antisense strand, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand. | 09-15-2011 |
| 20110223634 | TRANSFECTION KINETICS AND STRUCTURAL PROMOTERS - The invention features methods of analyzing the kinetics properties of transfection reactions. Also featured are methods for creating structural promoters which are effectively unregulated by enhancers and repressors. The structural promoters are significantly more active than the native promoter sequences upon which they are based. | 09-15-2011 |
| 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 |
| 20110201671 | Compositions And Methods For Inhibiting Expression Of A Gene From The Ebola Virus - The invention relates to a double-stranded ribonucleic acid (dsRNA) FOR INHIBITING THE expression of a gene from the Ebola virus. | 08-18-2011 |
| 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 |
| 20110166198 | RNA COMPOSITIONS FOR MODULATING IMMUNE RESPONSE - This invention features modified iRNA agents that modulate an immune response, methods of making and identifying iRNA agents that modulate an immune response, and methods of using the iRNA agents to modulate an immune response. | 07-07-2011 |
| 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 |
| 20110124711 | COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF Nav1.8 GENE - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the Nav1.8 gene (Nav1.8 gene), comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of the Nav1.8 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of the Nav1.8 gene using the pharmaceutical composition; and methods for inhibiting the expression of the Nav1.8 gene in a cell. | 05-26-2011 |
| 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 |
| 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 |
| 20110112178 | Compositions And Methods For Inhibiting Expression Of IKK-B Gene - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the IKK-B gene, comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the IKK-B gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression or activation of the IKK-B gene using the pharmaceutical composition; and methods for inhibiting the expression of the IKK-B gene in a cell. | 05-12-2011 |
| 20110110860 | MODULATION OF LDL RECEPTOR GENE EXPRESSION WITH DOUBLE-STRANDED RNAS TARGETING THE LDL RECEPTOR GENE PROMOTER - Gene expression can be selectively regulated by double-stranded “antigene” RNAs that target regions of the low density lipoprotein receptor (LDL-R) promoter, thereby permitting modulation of LDL levels in vivo and subsequent effects on circulating LDL levels. | 05-12-2011 |
| 20110097720 | SCREENING METHOD FOR SELECTED AMINO LIPID-CONTAINING COMPOSITIONS - The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-Dilinoley 1-4-dimethylaminomethyl-[1,3]-dioxolane by screening for an effect of the agent on the liver of a model subject. | 04-28-2011 |
| 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 |
| 20110092565 | METHOD OF TREATING NEURODEGENERATIVE DISEASE - Aspects featured in the invention relate to compositions and methods for inhibiting alpha-synuclein (SNCA) gene expression, such as for the treatment of neurodegenerative disorders. An anti-SNCA agent featured herein that targets the SNCA gene can have been modified to alter distribution in favor of neural cells. | 04-21-2011 |
| 20110071209 | RNAi Modulation of the RHO-A Gene and Uses Thereof - The invention relates to compositions and methods for modulating the expression of the RhoA gene, and more particularly to the downregulation of RhoA by chemically modified oligonucleotides. | 03-24-2011 |
| 20110060031 | Compositions And Methods For Inhibiting Expression Of A Gene From The Ebola Virus - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a gene from the Ebola virus. | 03-10-2011 |
| 20110033859 | RNAi INHIBITION OF INFLUENZA VIRUS REPLICATION - The invention relates to compositions and methods for modulating the expression of influenza viral genes, and more particularly to the downregulation of influenza viral genes by chemically modified oligonucleotides. | 02-10-2011 |
| 20110003882 | RNAi Modulation of AHA and Therapeutic Uses Thereof - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of an Aha gene (Aha1 gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of an Aha gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by Aha1 expression and the expression of an Aha gene using the pharmaceutical composition; and methods for inhibiting the expression of an Aha gene in a cell. | 01-06-2011 |
| 20100324117 | HEPATITIS C DSRNA EFFECTOR MOLECULES, EXPRESSION CONSTRUCTS, COMPOSITIONS, AND METHODS OF USE - The present invention provides agents, compositions, constructs and methods for silencing HCV polynucleotides, as well as methods and compositions for treating or preventing HCV infection in a mammalian cell. In one aspect, the present invention provides an agent or composition comprising at least one double-stranded RNA effector molecule or complex. The double-stranded RNA effector molecule or complex comprises: (1) a sequence of at least 19 nucleotides having at least 90% identity with a nucleotide sequence within HCV Conserved Region 1 (SEQ ID NO: 2), HCV Conserved Region 2 (SEQ ID NO: 3), HCV Conserved Region 5 (SEQ ID NO: 4), (ATR)-1 (SEQ ID NO: 86), ATR-2 (SEQ ID NO: 87), ATR-3 (SEQ ID NO: 88), ATR-4 (SEQ ID NO: 89); and (2) its complementary sequence. In another aspect, the present invention provides a construct suitable for replication in a host cell, and/or suitable for expression of an RNA molecule or complex of the invention in vitro or in vivo. In a third aspect, the present invention provides a method for silencing HCV RNA in a mammalian cell, which comprises administering to the mammalian cell an agent, composition, or construct of the invention in a manner and amount effective to silence HCV RNA in the cell. In a related aspect, the invention provides a method for treating or preventing HCV infection in a patient, comprising administering to the patient an effective amount of an agent, composition, or construct of the invention as described herein. | 12-23-2010 |
| 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 |
| 20100267805 | TARGETING OPPOSITE STRAND REPLICATION INTERMEDIATES OF SINGLE-STRANDED VIRUSES BY RNAI - The invention relates to methods and compositions for modulating viral replication through double-stranded RNA-mediated gene silencing (RNAi), wherein the antiviral methods and compositions preferentially target opposite strand replication intermediates of single-stranded RNA viruses. | 10-21-2010 |
| 20100240881 | THERAPEUTIC COMPOSITIONS - This application relates to therapeutic siRNA agents and methods of making and using the agents. | 09-23-2010 |
| 20100222413 | Chemically Modified Oligonucleotides for Use in Modulating Micro RNA and Uses Thereof - This invention relates generally to chemically modified oligonuceotides useful for modulating expression of microRNAs and pre-microRNAs. More particularly, the invention relates to single stranded chemically modified oligonuceotides for inhibiting microRNA and pre-microRNA expression and to methods of making and using the modified oligonucleotides. Also included in the invention are compositions and methods for silencing microRNAs in the central nervous system. | 09-02-2010 |
| 20100216866 | RNAi Modulation of APOB and Uses Thereof - The invention relates to compositions and methods for modulating the expression of apolipoprotein B, and more particularly to the downregulation of apolipoprotein B by chemically modified oligonucleotides. | 08-26-2010 |
| 20100204306 | Method of Treating Neurodegenerative Disease - Aspects featured in the invention relate to compositions and methods for inhibiting alpha-synuclein (SNCA) gene expression, such as for the treatment of neurodegenerative disorders. An anti-SNCA agent featured herein that targets the SNCA gene can have been modified to alter distribution in favor of neural cells. | 08-12-2010 |
| 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 |
| 20100190842 | INFLUENZA POLYNUCLEOTIDES, EXPRESSION CONSTRUCTS, COMPOSITIONS, AND METHODS OF USE - The invention provides isolated RNA molecules containing a stretch of nucleotides from a conserved Influenza sequence, and provides complementary RNA molecules thereto. The RNA molecules of the invention are also substantially non-homologous to human sequences. The RNA molecules of the invention include double-stranded RNAs comprising a first region that is a conserved Influenza sequence, and a second region that is at least substantially complementary to the first region. Such double-stranded RNAs include single short hairpin RNAs (shRNAs) as well as multi-target hairpin RNAs containing a plurality, or several, stem-loop structures. The present invention further provides expression constructs that provide for expression of one, or a plurality, of RNA molecules of the invention. The RNA molecules, expression constructs, and compositions of the present invention find use in reducing levels of Influenza A RNA, in reducing Influenza A virus titer, and in treating or preventing Influenza virus infection. The invention is effective against at least human, swine and avian originating strains of Influenza A, and makes gene-silencing therapeutic strategies for combating Influenza A infection feasible. | 07-29-2010 |
| 20100172976 | METHODS AND COMPOSITIONS FOR INHIBITING THE FUNCTION OF POLYNUCLEOTIDE SEQUENCES - A therapeutic composition for inhibiting the function of a target polynucleotide sequence in a mammalian cell includes an agent that provides to a mammalian cell an at least partially double-stranded RNA molecule comprising a polynucleotide sequence of at least about 200 nucleotides in length, said polynucleotide sequence being substantially homologous to a target polynucleotide sequence. This RNA molecule desirably does not produce a functional protein. The agents useful in the composition can be RNA molecules made by enzymatic synthetic methods or chemical synthetic methods in vitro; or made in recombinant cultures of microorganisms and isolated therefrom, or alternatively, can be capable of generating the desired RNA molecule in vivo after delivery to the mammalian cell. In methods of treatment of prophylaxis of virus infections, other pathogenic infections or certain cancers, these compositions are administered in amounts effective to reduce or inhibit the function of the target polynucleotide sequence, which can be of pathogenic origin or produced in response to a tumor or other cancer, among other sources. | 07-08-2010 |
| 20100168205 | Methods and Compositions for Prevention or Treatment of RSV Infection Using Modified Duplex RNA Molecules - Methods and compositions are provided for the prevention or treatment of RSV infection in a human. The methods include administering one or more doses of a composition comprising an siRNA. The dose can be formulated for topical or parenteral administration. Topical administration includes administration as a nasal spray, or by inhalation of respirable particles or droplets. The siRNA preferably comprises a sense strand and antisense strand with modified nucleotides. | 07-01-2010 |
| 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 |
| 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 |
| 20100069461 | COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF FACTOR V LEIDEN MUTANT GENE - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the Factor V Leiden mutant gene (Factor V Leiden mutant gene), comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of the Factor V Leiden mutant gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of the Factor V Leiden mutant gene using the pharmaceutical composition; and methods for inhibiting the expression of the Factor V Leiden mutant gene in a cell. | 03-18-2010 |
| 20100029747 | METHODS AND COMPOSITIONS FOR INHIBITING THE FUNCTION OF POLYNUCLEOTIDE SEQUENCES - A therapeutic composition for inhibiting the function of a target polynucleotide sequence in a mammalian cell includes an agent that provides to a mammalian cell an at least partially double-stranded RNA molecule comprising a polynucleotide sequence of at least about 200 nucleotides in length, said polynucleotide sequence being substantially homologous to a target polynucleotide sequence. This RNA molecule desirably does not produce a functional protein. The agents useful in the composition can be RNA molecules made by enzymatic synthetic methods or chemical synthetic methods in vitro; or made in recombinant cultures of microorganisms and isolated therefrom, or alternatively, can be capable of generating the desired RNA molecule in vivo after delivery to the mammalian cell. In methods of treatment of prophylaxis of virus infections, other pathogenic infections or certain cancers, these compositions are administered in amounts effective to reduce or inhibit the function of the target polynucleotide sequence, which can be of pathogenic origin or produced in response to a tumor or other cancer, among other sources. | 02-04-2010 |
| 20100016405 | Compositions and Methods for Inhibiting Expression of the MYC Gene - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the MYC gene (MYC gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the MYC gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by MYC gene expression and the expression of the MYC gene using the pharmaceutical composition. | 01-21-2010 |
| 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 |
| 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 |
| 20090312397 | RNAi Modulation Of ApoB And Uses Thereof - The invention relates to compositions and methods for modulating the expression of apolipoprotein B, and more particularly to the downregulation of apolipoprotein B by chemically modified oligonucleotides. | 12-17-2009 |
| 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 |
| 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 |
| 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 |
| 20090264511 | COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF FACTOR VII GENE - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the Factor VII gene. | 10-22-2009 |
| 20090258934 | COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF Nav1.8 GENE - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the Nav1.8 gene (Nav1.8 gene), comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of the Nav1.8 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of the Nav1.8 gene using the pharmaceutical composition; and methods for inhibiting the expression of the Nav1.8 gene gene in a cell. | 10-15-2009 |
| 20090247614 | Folate Conjugates - The present invention provides iRNA agent including at least one monomer having the structure shown in formula (I′) | 10-01-2009 |
| 20090247608 | Targeting Lipids - The present invention provides targeting lipids of structure | 10-01-2009 |
| 20090240043 | RNAi MODULATION OF RSV AND THERAPEUTIC USES THEREOF - The present invention is based on the in vivo demonstration that RSV can be inhibited through intranasal administration of iRNA agents as well as by parenteral administration of such agents. Further, it is shown that effective viral reduction can be achieved with more than one virus being treated concurrently. Based on these findings, the present invention provides general and specific compositions and methods that are useful in reducing RSV mRNA levels, RSV protein levels and viral titers in a subject, e.g., a mammal, such as a human. These findings can be applied to other respiratory viruses. | 09-24-2009 |
| 20090239814 | Carbohydrate Conjugates as Delivery Agents for Oligonucleotides - The present invention provides iRNA agents comprising at least one subunit of the formula (I): | 09-24-2009 |
| 20090238772 | METHODS AND COMPOSITIONS FOR PREVENTION OR TREATMENT OF RSV INFECTION - Methods and compositions are provided for the prevention or treatment of RSV infection in a human. The methods include administering one or more doses of a composition comprising an siRNA. The dose can be formulated for topical or parenteral administration. Topical administration includes administration as a nasal spray, or by inhalation of respirable particles or droplets. The siRNA comprises a sense strand of ALN-RSV01 and an antisense strand of ALN-RSV01. | 09-24-2009 |
| 20090203135 | Glycoconjugates of RNA Interference Agents - The present invention relates to agents, compositions and methods for inhibiting the expression of a target gene, comprising an RNAi agent bearing at least one galactosyl moiety. These are useful for delivering the gene expression inhibiting activity to cells, particularly hepatocytes, and more particularly in therapeutic applications. | 08-13-2009 |
| 20090187027 | PROCESSES AND REAGENTS FOR SULFURIZATION 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, chloramine, 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. | 07-23-2009 |
| 20090176729 | METHOD OF TREATING NEURODEGENERATIVE DISEASE - Aspects featured in the invention relate to compositions and methods for inhibiting alpha-synuclein (SNCA) gene expression, such as for the treatment of neurodegenerative disorders. An anti-SNCA agent featured herein that targets the SNCA gene can have been modified to alter distribution in favor of neural cells. | 07-09-2009 |
| 20090163705 | CATIONIC LIPIDS - Cyclic lipid moieties are described herein. | 06-25-2009 |
| 20090143323 | COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF A GENE FROM THE EBOLA - The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a gene from the Ebola virus. | 06-04-2009 |
| 20090053808 | COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF ANTI-APOPTOPIC GENES - The present invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of an anti-apoptotic gene, comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of an apoptotic gene, such as a Bcl gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of an anti-apoptotic gene using the pharmaceutical composition; and methods for inhibiting the expression of an anti-apoptotic gene in a cell. | 02-26-2009 |
| 20090005549 | Processes and Reagents 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. | 01-01-2009 |
| 20080293662 | RNAi MODULATION OF THE BCR-ABL FUSION GENE AND USES THEREOF - The invention relates to compositions and methods for modulating the expression of Bcr-Abl, and more particularly to the down-regulation of Bcr-Abl mRNA and Bcr-Abl protein levels by oligonucleotides via RNA interference, e.g., chemically modified oligonucleotides. | 11-27-2008 |
| 20080233584 | RNAi MODULATION OF MLL-AF4 AND USES THEREOF - The invention relates to compositions and methods for modulating the expression of the MLL-AF4 fusion gene, and more particularly to the downregulation of MLL-AF4 by chemically modified oligonucleotides. | 09-25-2008 |
| 20080213891 | 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. | 09-04-2008 |
