WO2005021570A1 - N−0結合性架橋構造型新規人工核酸 - Google Patents
N−0結合性架橋構造型新規人工核酸 Download PDFInfo
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- WO2005021570A1 WO2005021570A1 PCT/JP2004/012173 JP2004012173W WO2005021570A1 WO 2005021570 A1 WO2005021570 A1 WO 2005021570A1 JP 2004012173 W JP2004012173 W JP 2004012173W WO 2005021570 A1 WO2005021570 A1 WO 2005021570A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- the present invention has stable and excellent antisense or antigene activity, or excellent activity as a detection agent for a specific gene or a primer for initiating amplification, etc.
- the present invention relates to oligonucleotide analogs and nucleoside analogs that are intermediates for producing the oligonucleotides, which are useful as materials for high-sensitivity analysis of components.
- antisense oligonucleotide inhibited infection of influenza virus. Since then, it has been reported that it inhibited oncogene expression and AIDS infection. Antisense oligonucleotides are one of the most promising fields in recent years as pharmaceuticals, as they specifically regulate the expression of unwanted genes.
- the antisense method is based on the concept of controlling a series of flows of so-called centralola red bears from DNA ⁇ mRNA ⁇ protein using antisense oligonucleotides.
- the inventors of the present invention provide various physiologically active substances, materials for pharmaceuticals, RNA interference method (Nature, Vol. 411, 494-498, 2001), double-stranded oligonucleotide for decoy, Functional materials, DNA chips targeting single-stranded nucleic acids such as cDNA, functional materials such as molecular beacons, various antisense methods (including ribozymes and DNAzymes), antigene methods, Nucleic acid analogs (artificial nucleic acids) with modified sugar moieties that would be useful as functional materials for gene homologous recombination methods, materials for high-sensitivity analysis of biological trace components by combining with fluorescent or luminescent substances, etc. We designed and synthesized it and confirmed its usefulness.
- R and R are hydrogen, R is hydrogen or methyl group
- DNA or RNA oligonucleotide analog ( ⁇ ⁇ ⁇ ) had the following excellent properties. That is, (1) The ability to form a duplex with a complementary RNA strand is extremely high.
- 2 ', 4'-BNA NC modified DNA oligonucleotides are distinguished in triplex-forming ability to double-stranded DNA strands.
- the Tm value power increases by 12 ° C in the formation of a triplex on a double-stranded DNA strand.
- the base sequence must be strictly identified and the sequence selectivity of binding only to the target sequence is required.
- the 2 ', 4'-BNA NC- modified DNA oligonucleotide matches the mismatch sequence with the mismatch sequence.
- the difference in the Tm value from the DNA is 25 ° C or more, and has excellent sequence selectivity over natural DNA oligonucleotides.
- 2 ', 4'-BNA NC- modified oligonucleotides have higher nuclease resistance than natural DNA oligonucleotides, but much lower than S-oligos (phosphorothioate-type oligonucleotides).
- the 2 ', 4, -BNA NC- modified oligonucleotide of the present invention is more excellent in nuclease resistance than S-oligo, which is highly evaluated for its nuclease resistance, as well as 2,4'_BNA modified oligonucleotide. And has the property of strongly resisting decomposition in vivo.
- the N_ ⁇ bond contained in the artificial nucleic acid 2 ′, 4′-BNA NG molecule of the present invention can be selectively cleaved under a mild condition by a reducing reagent, and the NH group and the OH group Release.
- a reducing reagent By bonding different functional molecules using the NH and OH groups as a foothold, It is easy to obtain various composites (conjugates) before and after the production.
- Other functional molecules include labeling molecules such as fluorescent molecules, chemiluminescent molecules, and molecular species containing radioisotopes, various DNA (RNA) -cleaving active molecules, intracellular and nuclear localization signal peptides, and the like. Is possible.
- [0012] or more, 2 ', to modify the 4'_BNA NC in various forms have DNA and RNA Origonukureo tide analog of the invention, antisense method, anti-gene method, decoy method, gene homologous recombination method, RNA interference Not only as a high-functional material for the creation of genetic medicines by methods and the like, but also as a base material for genetic diagnostic methods such as molecular beacons and DNA chips, and as a development material for research reagents for elucidation of gene function analysis etc. It is highly useful. Brief Description of Drawings
- FIG. 1 The time-dependent changes of the oligonucleotide analog (8) of the present invention and the natural and unnatural oligonucleotides analogs when degraded by exonuclease were determined by HPLC quantification for undegraded oligonucleotides.
- 3 is a graph shown as a residual ratio.
- the nucleoside analog of the present invention is a compound represented by the following general formula (I) and a salt thereof.
- Base represents an aromatic heterocyclic group or an aromatic hydrocarbon ring group which may have a substituent.
- R and R are the same or different and each are a hydrogen atom, a protecting group for a hydroxyl group in nucleic acid synthesis, an alkyl
- R is a hydrogen atom, an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group,
- m is an integer of 02 and n is an integer of 1 to 3.
- the oligonucleotide analog of the present invention is a DNA oligonucleotide or an RNA oligonucleotide analog containing one or two or more of four or more of the unit structures of the nucleoside analog represented by the following general formula (II): It is a pharmacologically acceptable salt. However, when two or more of these structures are contained, Base may be the same or different between the structures.
- the linkage between each nucleoside in the oligonucleotide analog is not limited to the same phosphodiester bond [1-OP (0-) ⁇ 1] as that of natural nucleic acid, but is also a phosphorothioate bond.
- the aromatic heterocyclic group of the base refers to a carbon atom that is a constituent atom of a hydrocarbon ring, which is a heteroatom such as one or more nitrogen, sulfur, or oxygen atoms. Any group having a 5- to 20-membered ring that has an aromatic structure and has a structure replaced with an atom, and includes a single ring and a condensed ring.
- a pyrimidine or purine nucleobase a pyrimidine or purine nucleobase optionally having one or more substituents selected from the following ⁇ group: Is mentioned.
- pyrimidine or purine nucleic acid bases include bases generally known as constituents of nucleic acids (eg, guanine, adenine, cytosine, thymine, peracil), and any other base that can act or substitute for nucleic acid components similar thereto. Includes chemical structures.
- it is a pyrimidine or purine nucleobase, a pyrimidine or purine nucleobase having one or more substituents selected from the following group, specifically, a purine nucleobase.
- Preferred are a 9-yl group, a 2-oxo-pyrimidine-11-yl group, or a purine-91-yl group or a 2-oxo-pyrimidine-11-yl group having a substituent selected from the following group.
- Group ⁇ hydroxyl group, hydroxyl group protected with a protecting group for nucleic acid synthesis, alkoxy group having 15 to 15 carbon atoms, mercapto group, mercapto group protected with a protecting group for nucleic acid synthesis, alkylthio group having 15 to 15 carbon atoms, An amino group, an amino group protected with a protecting group for nucleic acid synthesis, an amino group substituted with an alkyl group having 15 to 15 carbon atoms, an alkyl group having 15 to 15 carbon atoms, and a halogen atom.
- a group suitable as the “purine nucleobase optionally having a substituent” is 6-aminopurine-19-yl (that is, adenyl), in which the amino group is protected by a protecting group for nucleic acid synthesis.
- a group suitable as "a pyrimidine nucleobase having a substituent" is 2-oxo-4-amino-1,2-dihydropyrimidine-1-yl (ie, Cytosinyl), 2-amino-4-amino-1,2, -dihydropyrimidine-11-yl, 2-oxo-4-amino-4, amino-5-fluoro-1,2-, whose amino group is protected with a protecting group for nucleic acid synthesis.
- 6-aminopurine-19-yl ie, adenyl
- the amino group are protecting groups for nucleic acid synthesis.
- Protected 6-aminopurine-9-yl, 2,6-diaminopurine-9-yl, 2-amino-6-chloropurine-1-yl, the amino group is protected by a protecting group for nucleic acid synthesis.
- 2-dihydropyrimidine-1-yl, 2-oxo-4-amino-5-fluoro-1,2-dihydropyrimidine-1-yl, 2-oxo-1-amino group protected with a protecting group for nucleic acid synthesis 4_amino-5-fluoro-1,2-dihydropyrimidine-1-yl, 4-amino-1-oxo-5-chloro-1,2-dihydropyrimidine-1-yl, 2-oxo-4-methoxy-1 1,2-dihydropyrimidine-1-yl, 2-oxo-4-4-mercapto-1,2-dihydropyrimidine-1-yl, 2-oxo-1-hydroxy-1,2-dihydropyrimidine-1-yl (I.e., peracinyl), 2-oxo-1-hydroxy-5-methyl_1,2-dihydro Pyrimidine-1-yl (ie, thymnyl), 4-amino-5-methyl-2-oxo-1,2-di
- the aromatic hydrocarbon ring group of Base is a monovalent substituent obtained by removing one hydrogen atom from an aromatic hydrocarbon ring having 6 to 20 carbon atoms. It means a single ring and a condensed ring. Specifically, for example, phenyl, indenyl, naphthyl, pentalenyl, azulenyl, heptalenyl, biphenylenyl, indacenyl, fluorenyl, phenanthranol, anthryl, etc. All possible structures are included.
- the aromatic hydrocarbon ring is a hydroxyl group, a hydroxyl group protected with a protecting group for nucleic acid synthesis, an amino group, an amino group protected with a protecting group for nucleic acid synthesis, a halogen atom, a lower alkyl group, an alkoxy group, a carboxyl group
- the aromatic hydrocarbon group which may be substituted by one or more groups such as aryloxy group, nitro group, trifluoromethyl, phenyl group, etc.
- the optionally substituted aromatic hydrocarbon ring group is preferably a hydroxyl group, a hydroxyl group protected with a protecting group for nucleic acid synthesis, an amino group, an amino group protected with a protecting group for nucleic acid synthesis, or a lower group.
- the protecting group of the ⁇ hydroxyl group protected by the protecting group for nucleic acid synthesis '' in the group of 1 245 is not particularly limited as long as it can stably protect the hydroxyl group during nucleic acid synthesis.
- “Silyl groups” such as tri-lower alkylsilyl groups substituted by one or two aryl groups such as diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl, phenyldiisopropylsilyl; methoxy “Lower alkoxymethyl groups” such as methyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, t-butoxymethyl; “lower alkoxymethyl” groups such as 2-methoxyethoxymethyl "Norogeno lower alkoxymethyl group” such as 2,2,2_trichloroethoxymethyl and bis (2-chloroethoxymethyl); 1-ethoxyl, 1_ (isopropoxy) ethyl Such as “lower alkoxylated tyl group”; 2,2,2-trichloroethyl Una "Nono androgenic modified eth
- R and R hydroxyl protecting group for nucleic acid synthesis, preferably “aliphatic acyl group” is used.
- an “aliphatic acyl group”, an “aromatic acyl group”, or a “113 aryl group” is used.
- R 1, R 2 and the “alkyl group” of R are
- a linear or branched alkyl group having 116 carbon atoms such as butyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, and 2-ethylbutyl (in the present specification, And these are also referred to as lower alkyl groups
- the "alkenyl group" of R 1, R 2 and R is a group having 2 to 20 carbon atoms.
- R 1, R 2 and the “cycloalkyl group” of R are those having 31 carbon atoms
- the ⁇ cycloalkyl group '' also includes a heterocyclic group in which one or more methylene on the ring of the cycloalkyl group is substituted with an oxygen atom, a sulfur atom, or a nitrogen atom substituted with an alkyl group,
- a tetrahydrobiranyl group and the like can be mentioned.
- Power means a monovalent substituent having 6 to 14 carbon atoms excluding one hydrogen atom, and includes, for example, feninole, indul, naphthyl, phenanthrenyl, anthracenyl and the like.
- the aryl group may be substituted with one or more groups such as a halogen atom, a lower alkyl group, a hydroxyl group, an alkoxy group, an aryloxy group, an amino group, a nitro group, a trifluoromethyl group and a phenyl group.
- Such optionally substituted aryl groups include, for example, 2-methylphenyl, 2,6-dimethylphenyl, 2-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2,5- Examples thereof include dichlorophenyl, 2-bromophenyl, 4-methoxyphenyl, 4-chloro-2-nitrophenyl, 412-trophenyl, 2,4-dinitrophenyl, biphenylphenol, and the like.
- Preferable examples include a phenyl group and a phenyl group substituted with a halogen atom, a lower alkoxy group and a nitro group.
- an "aralkyl group” is substituted with an aryl group.
- Alkyl group " and the like.
- a ⁇ methyl group substituted by one to three aryl groups '' a ⁇ methyl group substituted by lower alkyl, lower alkoxy, halogen, or cyano group by one to three aryl groups substituted with one to three aryl groups '' Methyl group ", and more preferably, 4-methoxyphenyldiphenylmethyl and 4,4'-dimethoxytriphenylmethyl.
- R, R, and the “acyl group” of R include formyl, acetyl
- R, R, and the “sulfonyl group” of R are methanesulfo
- Aliphatic sulfonyl group '' such as a sulfonyl group in which a straight-chain or branched alkyl group having 16 carbon atoms is substituted, such as nyl and ethanesulfonyl, and various aryl groups such as benzenesulfonyl and p-toluenesulfonyl
- an “aromatic sulfonyl group” such as a substituted sulfonyl group, preferably a methanesulfonyl or p-toluenesulfonyl group.
- R and the “silyl group” of R include trimethylsilyl
- Tri-lower phenol silyl group such as triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-tert-butylsilyl, triisopropylsilinole, diphenylmethylsilyl, butyldiphenylbutylsilyl, diphenylsilyl
- Examples include ⁇ tri-lower alkylsilyl groups substituted with one to two aryl groups '' such as isopropylsilyl and phenyldiisopropylsilyl.
- protecting group is not particularly limited as long as it can stably protect a phosphate group during nucleic acid synthesis.Specifically, it is stable under acidic or neutral conditions, Refers to protecting groups that can be cleaved by chemical methods such as hydrogenolysis, hydrolysis, electrolysis, and photolysis.
- protecting groups include methinole, ethyl, n-propyl, isopropyl, n — Butyl, isobutyl, s-butyl, tert-butyl, n-pentyl, isopentyl, 2-methyl Rubutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1 "Lower alkyl groups" such as 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl; 2-cyanoethyl, 2-cyano-1,1-dimethylethyl "Ethyl group substituted by silyl group”
- the "functional molecular unit substituent" for R refers to a labeling molecule (for example, a fluorescent molecule, a chemiluminescent molecule, a molecular species containing a radioisotope atom, etc.), Includes DNA and RNA cleavage active molecules, and intracellular and nuclear translocation signal peptides.
- a labeling molecule for example, a fluorescent molecule, a chemiluminescent molecule, a molecular species containing a radioisotope atom, etc.
- the protecting group of R and R and the "mercapto group protected by a protecting group for nucleic acid synthesis" in the ⁇ group may be a mercapto group which is stably synthesized during nucleic acid synthesis.
- a protecting group for nucleic acid synthesis there is no particular limitation as long as it can protect the compound, but specifically, it is stable under acidic or neutral conditions, and is subjected to chemical methods such as hydrogenolysis, hydrolysis, electrolysis and photolysis.
- a protective group that can be cleaved for example, a group that forms a disulfide such as an alkylthio group such as methylthio, ethylthio, tert-butylthio, or an arylthio group such as benzylthio, in addition to those listed above as the protecting group for a hydroxyl group.
- a group that forms a disulfide such as an alkylthio group such as methylthio, ethylthio, tert-butylthio, or an arylthio group such as benzylthio, in addition to those listed above as the protecting group for a hydroxyl group.
- arylthio group such as benzylthio
- Is for example, methoxy, ethoxy, ⁇ -propoxy, isopropoxy, ⁇ -butoxy, isobutoxy, s-butoxy, tert-butoxy, n-pentoxy, and is preferably a methoxy or ethoxy group. .
- Examples thereof include methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, s-butylthio, tert_butylthio, and n-pentylthio, and preferably a methylthio or ethylthio group.
- a group substituted by a cyano group having "an alkoxy group having 1 to 5 carbon atoms" is, for example, cyanomethoxy, 2-cyanoethoxy, 3-cyanopropoxy, 4-cyanobutoxy, or 3_cyano. 2-methylpropoxy or 1-cyanomethinolate 1,1-dimethylmethoxy, preferably a 2-cyanoethoxy group.
- amino group substituted by an alkyl group of 45 to 15 examples include, for example, methinoleamino, ethylamino, isopropylamino-containing isopropylamino, butylamino, isobutylamino, s-butylamino, tert-butylamino, dimethylaminoamino, ethylamino, dipropylamino, Examples thereof include diisopropylamino, dibutylamino, diisobutylamido-containing di (s-butyl) amido-containing di (tert-butyl) amino, and preferably a methinoleamino, ethynoleamino, dimethylamino, getylamino or diisopropylamino group.
- alkyl group having 15 carbon atoms examples include methyl, ethyl, propyl, isopropyl, isopropyl, butyl, isobutyl, s-butyl, tert-butyl, n-pentyl and the like. And preferably a methyl or ethyl group.
- Examples of the "nitrogen atom" in group a include a fluorine atom, a chlorine atom, a bromine atom and a chlorine atom, and a fluorine atom or a chlorine atom is preferable.
- Phosphoramidite group refers to a group represented by the formula P ( ⁇ R) (NR) (wherein R is the number of carbon atoms
- R 1 represents an alkyl group or a C 17 alkyl group, and R represents 1 carbon atom.
- lb represents an alkyl group of 16.
- lb represents an alkyl group of 16.
- the protecting group for the “amino group protected by a protecting group for nucleic acid synthesis” in group a is not particularly limited as long as it can stably protect an amino group during nucleic acid synthesis.
- protective groups that are stable under acidic or neutral conditions and can be cleaved by chemical methods such as hydrogenolysis, hydrolysis, electrolysis and photolysis, for example, formyl, acetyl, propionyl, Butyrinole, Isobutyryl, Pentanoyl, Pivaloyl, Valerinole, Isovaleryl, Ottanoyl, Nonanoinole, Decanoyl, 3-Methinolenanoinole, 8-Methylnonanoyl, 3_Echilotanonoyl, 3,7_Dimethylocanodyl, 3,7_Dimethylotanoyl Toride canoy, tetradecanoyl, pentadecanoyl, hexade
- the aryl ring is substituted by one or two "lower alkoxy or nitro groups” such as 4-methoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, and 4-nitrobenzyloxycarbonyl.
- nucleoside analog refers to an unnatural type of "nucleoside” in which a purine or pyrimidine base is bonded to a sugar, and an aromatic heterocycle and an aromatic hydrocarbon ring other than purine and pyrimidine. Or, a substance in which a sugar is bonded to a substance that can be substituted for a pyrimidine base.
- oligonucleotide analog refers to a non-natural derivative of an "oligonucleotide” in which the same or different "nucleosides" or “nucleoside analogs” are bound by 2 to 50 phosphodiester bonds.
- Preferred analogs include a sugar derivative in which the sugar moiety is modified; a thioate derivative in which the phosphate diester moiety is thioated; an ester in which the terminal phosphate moiety is esterified; an amino acid on the purine base It is possible to raise the amide form in which the group is amidated, and more preferably, a sugar derivative in which the sugar moiety is modified
- the "salt” refers to the salt of the compound (1) of the present invention, since the compound can be converted into a salt.
- a salt is preferably a sodium salt, a potassium salt, a lithium salt
- Alkali metal salts such as calcium salts, alkaline earth metal salts such as magnesium salts, aluminum salts, metal salts such as iron salts, zinc salts, copper salts, nickel salts, cobalt salts
- inorganic salts such as ammonium salts Octylamine, dibenzylamine, monoreforin, dalcosamine, phenyldaricin alkyl ester, ethylenediamine, N-methyldalcamine, guanidine, getylamine, triethynoleamine, dicyclohexylamine, N, N'-dibenzylethylenediamine salt, black mouth pro-force salt, pro-force salt, diethanolamine salt, N-ben Amine salts such as organic salts such as zi crizethy
- the "pharmacologically acceptable salt” refers to a salt of the oligonucleotide analogue of the present invention, since the oligonucleotide can be converted to a salt.
- a salt is preferably a sodium salt, Metal salts such as alkali metal salts such as potassium salts and lithium salts, alkaline earth metal salts such as calcium salts and magnesium salts, aluminum salts, iron salts, zinc salts, copper salts, nickel salts and cobalt salts Inorganic salts such as ammonium salts, t-octylamine salts, dibenzylamine salts, monoreforin salts, dalcosamine salts, phenyldaricin alkyl ester salts, ethylenediamine salts, N-methyldalcamine salts, guanidine salts, getylamine salts, triethylamine salts, dicycloamine salts.
- suitable compounds include
- DR is hydrogen atom, aliphatic acyl group, aromatic acyl group, aliphatic or aromatic radical
- Norfonyl group methyl group substituted by one to three aryl groups, lower alkyl, lower alkyl
- a compound or a salt thereof which is a methyl group or a silyl group substituted with one to three aryl groups in which the aryl ring is substituted with a oxy, halogen or cyano group,
- R is a hydrogen atom, an aliphatic acid group, an aromatic acid group, an aliphatic or aromatic
- R hydrogen atom, alkyl group having 115 carbon atoms, alkenyl group having 115 carbon atoms, carbon
- Lower aliphatic or aromatic sulfonyl groups such as methyl group, methanesulfonyl group and P-toluenesulfonyl group substituted by aryl groups having 13 to 14 aryl groups;
- a compound having an aromatic acyl group such as an aliphatic acyl group having 1 to 5 carbon atoms, such as a phenoxy acetyl group and a benzoyl group, and a salt thereof;
- the compound according to claim 4, wherein the three molecular unit substituent is a fluorescent or chemiluminescent labeling molecule, a nucleic acid-cleaving active functional group, or a signal peptide for intracellular or nuclear translocation, and a salt thereof,
- Base is 6-aminopurine-9-yl (that is, adenyl), 6-aminopurine_9_yl, and 2,6-diaminopurine_9_yl in which the amino group is protected by a protecting group for nucleic acid synthesis.
- 2-amino-6-chloropurine, 2-amino-6-chloropurine-9-yl, 2-amino-6-chloropurine_9_yl whose amino group is protected by a protecting group for nucleic acid synthesis.
- 2-amino-6-fluoropurine _9_yl 2-amino-6-bromopurine in which the amino group is protected by a protecting group for nucleic acid synthesis 9-yl
- 2-amino-6-bromopurine-19-yl 2-amino-6-hydroxypurine-19-yl (i.e., guaninyl) in which the amino group is protected by a protecting group for nucleic acid synthesis, and the amino group is a nucleic acid.
- Base is benzoylaminopurine 9-yl, adenyl, 2-isobutyrylamino _6-hydroxyhydroxypurine 9-yl, guaninyl, 2-oxo_4_benzoylamino-1,2-dihydropyrimidine -1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-1,2, -dipyridin pyrimidine-11-yl, 5-methylcytosinyl, peracidil or thyminyl group, and salts thereof be able to.
- R represents (1) Select arbitrarily from one (2), R
- 1 2 can be arbitrarily selected from (3) and (4), R can be arbitrarily selected from (5), and Base can be selected from (6)-(7)
- R a hydrogen atom, an alkyl group having 15 to 15 carbon atoms, an aralkyl group such as a benzyl group,
- Oligonucleotide analogs which are lower aliphatic or aromatic acylone groups such as acetyl group and benzoyl group, and aliphatic or aromatic sulfonyl groups such as methanesnolephonyl group and p-toluenesulfonyl group, and pharmacologically acceptable salts thereof ,
- Base is 6-aminopurine-9-yl (ie, adenyl), 6-aminopurine_9_yl, 2,6-diaminopurine_9_yl in which the amino group is protected by a protecting group for nucleic acid synthesis.
- 2-amino-6-fluoropurine_9_yl, 2-amino-6-bromopurine-9-yl, and amino-amino groups are protecting groups for nucleic acid synthesis.
- Base is benzoylaminopurine-91-yl, adenyl, 2-isobutyrylamino-6-hydroxypurine-9-yl, guaninyl, 2-oxo-4_benzoylamino-1,2-dihydropyrimidine Oligonucleotide analogs which are 11-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-1,2-dihydropyrimidine-11-yl, 5-methylcytosinyl, peracinyl or thyminyl groups and the like Pharmaceutically acceptable salts can be mentioned.
- (9)-(10) indicates a more suitable oligonucleotide analog as the number increases, R is arbitrarily selected from (8), and Base is set to (9)-(10) Arbitrarily choose from these
- Oligonucleotide analogs obtained by arbitrarily combining and their pharmacologically acceptable salts are also suitable.
- Particularly preferred combinations in the general formula ( ⁇ ) are (8)-(9) and (8)-(10).
- nucleoside analogs and oligonucleotide analogs of the present invention can be synthesized based on the methods described in the Examples and conventional techniques in this field.
- the compound represented by the general formula (I) can be synthesized based on the methods described in Examples and conventional techniques in this field.
- the reaction conditions, the protecting group introduction reagent, and the reaction reagent can be specifically referred to the methods described in Examples, but are not limited thereto, and the reaction conditions that can be used based on common general technical knowledge in the art, Reagents can be appropriately employed.
- JP The methods described in JP-A-00-297097 and JP-A-10-304889 can be referred to.
- Japanese Patent Application Laid-Open No. Hei 10-304889 also describes the case where various bases in the general formula (I) or (II) have various natural and unnatural nucleobases and other aromatic heterocycles or aromatic hydrocarbon rings. With reference to the described method, it is possible to synthesize the raw material of the compound of the present invention.
- Oligonucleotide analogs containing the nucleoside analogs of the present invention can be variously synthesized using a known DNA synthesizer. Next, the resulting oligonucleotide analog is purified using a reversed-phase column, and the purity of the product is determined by reversed-phase HPLC or HPLC.
- nucleoside analogs of the present invention can be present in an oligonucleotide analog.
- the oligonucleotide analogue may be present at two or more positions of the oligonucleotide analog and isolated via one or more natural nucleotides. According to the present invention, it is possible to synthesize an oligonatalide analog in which the nucleoside analog of the present invention is introduced at a required position in a required number (length).
- the total length of the oligonucleotide analog is 2 to 50, preferably 8 to 30 nucleotide units.
- the oligonucleotide analogue of the present invention can exist in a living body for a long time after administration to a living body that is easily degraded by nucleases. Then, for example, it forms a duplex with sense RNA and inhibits transcription of a pathogenic in vivo component (protein) into mRNA. It is also thought to inhibit the growth of the infected virus.
- the oligonucleotide analogs of the present invention are expected to be useful as pharmaceuticals for treating diseases by inhibiting the functions of genes such as antitumor agents and antiviral agents. That is, according to the present invention, there are provided oligonucleotide analogs and intermediates for producing the same, which have stable and excellent antisense or antigenic activity, or excellent activity as a detection agent for specific genes or primers for starting amplification. Nucleoside analogs are provided.
- the 2 ', 4'-BNA NG monomer which is one of the nucleoside analogs of the present invention, is modified in various forms.
- Decorated DNA and RNA oligonucleotide analogs can be used for various physiologically active substances, materials for pharmaceuticals, functional materials for double-stranded oligonucleotides such as RNA interference and decoy methods, DNA chips targeting single-stranded nucleic acids such as cDNA, functional materials such as molecular beacons, various antisense methods (including ribozymes and DNAzymes), antigene methods and gene homologous recombination methods It is useful as a development material for functional materials, materials for high-sensitivity analysis of trace components of living organisms in combination with fluorescent or luminescent substances, and research reagents for elucidation of gene function analysis.
- nucleoside analogs and oligonucleotide analogs of the present invention can be formulated into parenteral administration preparations by blending conventional auxiliaries such as buffers and / or stabilizers.
- auxiliaries such as buffers and / or stabilizers.
- a common pharmaceutical carrier can be compounded to prepare an ointment, cream, liquid, salve or the like.
- nucleoside analog and the oligonucleotide analog of the present invention were synthesized according to the following synthesis scheme. These syntheses are described in more detail in the examples.
- Compounds 16, 21, 17, and 22 are amidites for introducing BNA NC (NMe) and BNA NC (NH) whose nucleobase moieties are thymine and methylcytosine into the oligonucleotide, respectively.
- an amidite 29 for introduction of a methylcytidine BNA NG (NH) derivative can be synthesized according to a conventional method (tritylation, amidite formation). Since nucleobase moiety are also known, instead adenine and a is derivative of the compound 1 Guanin to thymine, adenosine and guanosine BNA NG derivative by the synthetic routes also it is thought possible synthesis.
- nucleoside analog and the oligonucleotide analog of the present invention were synthesized according to the following synthesis scheme. These syntheses are described in more detail in the examples. In addition, the properties of the synthesized oligonucleotide analogs were measured by experimental examples.
- N-hydroxyphthalimide (67 mg, 0.41 mmol) 1,8-diazabicyclo [5.4.0] was added to a solution of crude product 7 (0.29 g) obtained in the previous reaction in acetonitrile solution (3 ml) at room temperature.
- 7-Pendecene (61 (1, 0.41 mmol) was added and stirred at room temperature for 12 hours.
- the reaction solution was extracted with dichloromethane, and the organic layer was washed with water and saturated saline, and then dried over anhydrous sodium sulfate.
- a 4,4′-dimethoxytritinol chloride (0.22 g, 0.64 mmol) was added to a pyridine solution (10 ml) of the compound 14 (0.16 g, 0.54 mmol), and the mixture was stirred at room temperature for 12 hours.
- a saturated aqueous sodium bicarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, and dried over anhydrous sodium sulfate.
- phosphoryl chloride (86 ml, 0.92 mmol) was added to a suspension of 1,2,4-triazole (278 mg, 4.03 mmol) in acetonitrile (9 ml) under ice cooling, and the mixture was vigorously stirred for 10 minutes. Triethylamine (0.64 ml, 4.62 mmol) was further added, and the mixture was stirred for 35 minutes. Under ice-cooling, a solution of compound 16 (95 mg, 0.12 mmol) in acetonitrile (3 ml) was added, and the mixture was stirred for 5.5 hours, and further stirred at room temperature for 2.5 hours.
- phosphoryl chloride (71 ml, 0.76 mmol) was added to a suspension of 1,2,4-triazole (229 mg, 3.32 mmol) in acetonitrile (10 ml) under ice cooling, and the mixture was vigorously stirred for 10 minutes. Triethylamine (0.53 ml, 3.81 mmol) was further added, and the mixture was stirred for 35 minutes. Under ice-cooling, a solution of compound 21 (90 mg, 0.10 mmol) in acetonitrile (2 ml) was prepared and stirred for 5 hours. Saturated aqueous sodium bicarbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate.
- Oligonucleotide analogs containing 2 ', 4'-BNA NC monomer units (1)-(22) were prepared using an automated nucleic acid synthesizer Expedite TM 8909 (ABI) according to a standard phosphoramidite protocol in an amount of 0.2 mmol. Synthesized on a scale. The coupling time between the amidite and the terminal hydroxyl group was set to 94 seconds for the native nucleoside amidite and 300 seconds for the 2 ', 4 and BNA NC amidites (16, 17 and 21).
- Tm Melting temperature
- the final concentrations were NaCl lOOmM, sodium phosphate buffer (pH 7.2) 10mM, A sample solution (500 L) containing 4 ⁇ m of antisense strand and 4 mm of sense strand was bathed in boiling water and cooled to room temperature over 10 hours. A nitrogen gas stream was passed through the cell chamber of the spectrophotometer (Beckman, DU-650) to prevent dew condensation, the sample solution was gradually cooled to 5 ° C, and further kept at 10 ° C for 2 ⁇ ⁇ minutes before measuring. Started. The temperature was increased by 0.5 ° C per minute to 90 ° C, and the ultraviolet absorption at 260 nm was measured.
- DNA g (5'-AGCAAAAAACGC-3 '): heavy chain-forming ability (Tm value evaluation): ° C
- Tm is the average of three or more experiments
- Tm is the average value of three or more experiments. Based on the above results, the nucleotide analogue of the present invention was found to be double-stranded with respect to single-stranded DNA (sense strand). Compared to the ability to form a strand, the ability to form a double strand for single-stranded RNA (sense strand) is significantly higher. This is considered to be suitable for the antisense method.
- Table 5 shows the results and the experimental conditions.
- Table 5-1 Table 5- 1. T m values of 2 ' , 4'-BNA N "oliaonucleotides with dsDNA.
- the oligonucleotide analogs (6)-(11) and (18)-(2 1) showed an excellent ability to form a triple chain.
- sequence selectivity is higher than that of nature, it is considered to be extremely useful for the anti-gene method and the like.
- X when X is a DNA monomer, it is a completely natural DNA oligonucleotide, and oligonucleotides containing other nucleotide analogs are partially unnatural oligonucleotides.
- X is 2 ′, 4 ′ oligonucleotide analogue is _BNA NC (N-Me) is an oligonucleotide analogue of the present invention.
- Table 6 and FIG. 1 show the change over time in the residual ratio of each oligonucleotide by HPLC.
- % of intact oligonucleotidej refers to the residual ratio of undegraded oligonucleotide at the time of measurement relative to undegraded oligonucleotide at time 0 0 »(HPL
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ES04772134T ES2382807T3 (es) | 2003-08-28 | 2004-08-25 | Nuevos ácidos nucleicos artificiales del tipo de enlace N-O con reticulación |
EP04772134A EP1661905B9 (en) | 2003-08-28 | 2004-08-25 | Novel artificial nucleic acids of n-o bond crosslinkage type |
US10/569,949 US7427672B2 (en) | 2003-08-28 | 2004-08-25 | Artificial nucleic acids of n-o bond crosslinkage type |
DK04772134.5T DK1661905T3 (da) | 2003-08-28 | 2004-08-25 | Hidtil ukendte syntetiske nukleinsyrer af N-O-krydsbindingstype |
JP2005513440A JP4731324B2 (ja) | 2003-08-28 | 2004-08-25 | N−o結合性架橋構造型新規人工核酸 |
AT04772134T ATE555118T1 (de) | 2003-08-28 | 2004-08-25 | Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung |
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US9914922B2 (en) | 2012-04-20 | 2018-03-13 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
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WO2018143475A1 (ja) | 2017-02-06 | 2018-08-09 | 日産化学工業株式会社 | 一本鎖オリゴヌクレオチド |
WO2018169063A1 (ja) * | 2017-03-17 | 2018-09-20 | 国立大学法人千葉大学 | 構造強化されたS-TuDを用いた新規がん治療法 |
WO2018181428A1 (ja) | 2017-03-29 | 2018-10-04 | 塩野義製薬株式会社 | 核酸医薬及び多分岐脂質の複合体 |
US10190117B2 (en) | 2013-06-16 | 2019-01-29 | National University Corporation Tokyo Medical And Dental University | Double-stranded antisense nucleic acid with exon-skipping effect |
WO2019022196A1 (ja) | 2017-07-26 | 2019-01-31 | 日産化学株式会社 | 一本鎖オリゴヌクレオチド |
US10221414B2 (en) | 2013-10-11 | 2019-03-05 | Ionis Pharmaceuticals, Inc. | Compositions for modulating C9ORF72 expression |
WO2019045075A1 (ja) | 2017-08-31 | 2019-03-07 | 田辺三菱製薬株式会社 | Il-33アンタゴニストを含む子宮内膜症治療剤 |
EP3466960A2 (en) | 2011-04-01 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Modulation of signal transducer and activator of transcription 3 (stat3) expression |
US10273474B2 (en) | 2012-03-30 | 2019-04-30 | Washington University | Methods for modulating Tau expression for reducing seizure and modifying a neurodegenerative syndrome |
US10280423B2 (en) | 2014-05-01 | 2019-05-07 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating complement factor B expression |
US10294477B2 (en) | 2014-05-01 | 2019-05-21 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating PKK expression |
US10364433B2 (en) | 2014-11-14 | 2019-07-30 | The Regents Of The University Of California | Modulation of AGPAT5 expression |
WO2019165453A1 (en) | 2018-02-26 | 2019-08-29 | Synthorx, Inc. | Il-15 conjugates and uses thereof |
US10400243B2 (en) | 2014-11-25 | 2019-09-03 | Ionis Pharmaceuticals, Inc. | Modulation of UBE3A-ATS expression |
US10407680B2 (en) | 2016-09-29 | 2019-09-10 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing Tau expression |
US10415038B2 (en) | 2015-04-03 | 2019-09-17 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating TMPRSS6 expression |
WO2019182037A1 (ja) | 2018-03-20 | 2019-09-26 | 国立大学法人東京工業大学 | 毒性が低減されたアンチセンスオリゴヌクレオチド |
US10435430B2 (en) | 2013-07-31 | 2019-10-08 | Ionis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
US10443052B2 (en) | 2012-10-15 | 2019-10-15 | Ionis Pharmaceuticals, Inc. | Compositions for modulating C9ORF72 expression |
WO2019217459A1 (en) | 2018-05-07 | 2019-11-14 | Alnylam Pharmaceuticals, Inc. | Extrahepatic delivery |
US10513706B2 (en) | 2014-04-09 | 2019-12-24 | The Scripps Research Institute | Import of unnatural or modified nucleoside triphosphates into cells via nucleic acid triphosphate transporters |
EP3591054A1 (en) | 2013-06-27 | 2020-01-08 | Roche Innovation Center Copenhagen A/S | Antisense oligomers and conjugates targeting pcsk9 |
US10557137B2 (en) | 2015-11-06 | 2020-02-11 | Ionis Pharmaceuticals, Inc. | Modulating apolipoprotein (a) expression |
US10570169B2 (en) | 2014-05-22 | 2020-02-25 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
US10577604B2 (en) | 2012-10-15 | 2020-03-03 | Ionis Pharmaceuticals, Inc. | Methods for monitoring C9ORF72 expression |
US10590412B2 (en) | 2013-04-19 | 2020-03-17 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation nucleic acids through nonsense mediated decay |
WO2020069055A1 (en) | 2018-09-28 | 2020-04-02 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases |
US10610571B2 (en) | 2017-08-03 | 2020-04-07 | Synthorx, Inc. | Cytokine conjugates for the treatment of proliferative and infectious diseases |
US10626138B2 (en) | 2013-08-08 | 2020-04-21 | The Scripps Research Institute National Institutes Of Health (Nih), U.S. Dept Of Health And Human Services (Dhhs) | Method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides |
WO2020184700A1 (ja) | 2019-03-14 | 2020-09-17 | レナセラピューティクス株式会社 | Ihh発現を調節するための核酸複合体 |
WO2020203880A1 (ja) | 2019-03-29 | 2020-10-08 | 田辺三菱製薬株式会社 | Dux4の発現を調節するための化合物、方法及び医薬組成物 |
WO2020236600A1 (en) | 2019-05-17 | 2020-11-26 | Alnylam Pharmaceuticals, Inc. | Oral delivery of oligonucleotides |
EP3750997A1 (en) | 2013-12-02 | 2020-12-16 | Ionis Pharmaceuticals, Inc. | Antisense compounds and uses thereof |
WO2021020412A1 (ja) | 2019-07-30 | 2021-02-04 | 塩野義製薬株式会社 | Murf1を標的とする核酸医薬 |
US10912792B2 (en) | 2015-10-08 | 2021-02-09 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
EP3778618A1 (en) | 2013-02-04 | 2021-02-17 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
WO2021030706A1 (en) | 2019-08-15 | 2021-02-18 | Synthorx, Inc. | Immuno oncology combination therapies with il-2 conjugates |
WO2021041206A1 (en) | 2019-08-23 | 2021-03-04 | Synthorx, Inc. | Il-15 conjugates and uses thereof |
WO2021050554A1 (en) | 2019-09-10 | 2021-03-18 | Synthorx, Inc. | Il-2 conjugates and methods of use to treat autoimmune diseases |
EP3811977A1 (en) | 2014-05-01 | 2021-04-28 | Ionis Pharmaceuticals, Inc. | Method for synthesis of reactive conjugate clusters |
WO2021092145A1 (en) | 2019-11-06 | 2021-05-14 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna composition and methods of use thereof for treating or preventing ttr-associated ocular diseases |
WO2021091986A1 (en) | 2019-11-04 | 2021-05-14 | Synthorx, Inc. | Interleukin 10 conjugates and uses thereof |
WO2021092371A2 (en) | 2019-11-06 | 2021-05-14 | Alnylam Pharmaceuticals, Inc. | Extrahepatic delivery |
US11077195B2 (en) | 2019-02-06 | 2021-08-03 | Synthorx, Inc. | IL-2 conjugates and methods of use thereof |
WO2021153747A1 (ja) | 2020-01-31 | 2021-08-05 | 株式会社三和化学研究所 | Atn1のアンチセンスオリゴヌクレオチド |
WO2021177418A1 (ja) | 2020-03-04 | 2021-09-10 | 日産化学株式会社 | Calm2のアンチセンスオリゴヌクレオチド |
WO2021230286A1 (ja) | 2020-05-12 | 2021-11-18 | 田辺三菱製薬株式会社 | Ataxin 3発現を調節するための化合物、方法及び医薬組成物 |
WO2021263026A1 (en) | 2020-06-25 | 2021-12-30 | Synthorx, Inc. | Immuno oncology combination therapy with il-2 conjugates and anti-egfr antibodies |
WO2022011214A1 (en) | 2020-07-10 | 2022-01-13 | Alnylam Pharmaceuticals, Inc. | Circular sirnas |
US11230712B2 (en) | 2017-11-09 | 2022-01-25 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing SNCA expression |
US11261446B2 (en) | 2019-03-29 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating UBE3A-ATS |
US11260073B2 (en) | 2015-11-02 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating C90RF72 |
US11279932B2 (en) | 2019-02-27 | 2022-03-22 | Ionis Pharmaceuticals, Inc. | Modulators of MALAT1 expression |
WO2022065413A1 (ja) * | 2020-09-25 | 2022-03-31 | 株式会社理研ジェネシス | 新規人工核酸、その製造方法及び用途 |
WO2022076853A1 (en) | 2020-10-09 | 2022-04-14 | Synthorx, Inc. | Immuno oncology combination therapy with il-2 conjugates and pembrolizumab |
WO2022076859A1 (en) | 2020-10-09 | 2022-04-14 | Synthorx, Inc. | Immuno oncology therapies with il-2 conjugates |
US11359197B2 (en) | 2018-01-12 | 2022-06-14 | Bristol-Myers Squibb Company | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
WO2022147214A2 (en) | 2020-12-31 | 2022-07-07 | Alnylam Pharmaceuticals, Inc. | Cyclic-disulfide modified phosphate based oligonucleotide prodrugs |
WO2022147223A2 (en) | 2020-12-31 | 2022-07-07 | Alnylam Pharmaceuticals, Inc. | 2'-modified nucleoside based oligonucleotide prodrugs |
US11400161B2 (en) | 2016-10-06 | 2022-08-02 | Ionis Pharmaceuticals, Inc. | Method of conjugating oligomeric compounds |
WO2022174101A1 (en) | 2021-02-12 | 2022-08-18 | Synthorx, Inc. | Skin cancer combination therapy with il-2 conjugates and cemiplimab |
WO2022174102A1 (en) | 2021-02-12 | 2022-08-18 | Synthorx, Inc. | Lung cancer combination therapy with il-2 conjugates and an anti-pd-1 antibody or antigen-binding fragment thereof |
EP4056703A1 (en) | 2015-03-03 | 2022-09-14 | Ionis Pharmaceuticals, Inc. | Methods for modulating mecp2 expression |
US11447521B2 (en) | 2020-11-18 | 2022-09-20 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
WO2022213118A1 (en) | 2021-03-31 | 2022-10-06 | Entrada Therapeutics, Inc. | Cyclic cell penetrating peptides |
WO2022240721A1 (en) | 2021-05-10 | 2022-11-17 | Entrada Therapeutics, Inc. | Compositions and methods for modulating interferon regulatory factor-5 (irf-5) activity |
WO2022240760A2 (en) | 2021-05-10 | 2022-11-17 | Entrada Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR MODULATING mRNA SPLICING |
WO2022241408A1 (en) | 2021-05-10 | 2022-11-17 | Entrada Therapeutics, Inc. | Compositions and methods for modulating tissue distribution of intracellular therapeutics |
EP4092119A2 (en) | 2015-07-10 | 2022-11-23 | Ionis Pharmaceuticals, Inc. | Modulators of diacyglycerol acyltransferase 2 (dgat2) |
WO2022255273A1 (ja) | 2021-05-31 | 2022-12-08 | レナセラピューティクス株式会社 | リガンド結合核酸複合体 |
WO2022256538A1 (en) | 2021-06-03 | 2022-12-08 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and cetuximab |
US11530409B2 (en) | 2016-01-26 | 2022-12-20 | Nissan Chemical Corporation | Single-stranded oligonucleotide |
WO2022271818A1 (en) | 2021-06-23 | 2022-12-29 | Entrada Therapeutics, Inc. | Antisense compounds and methods for targeting cug repeats |
WO2023283403A2 (en) | 2021-07-09 | 2023-01-12 | Alnylam Pharmaceuticals, Inc. | Bis-rnai compounds for cns delivery |
WO2023287141A1 (ko) | 2021-07-12 | 2023-01-19 | 주식회사 씨젠 | 용기에 수용된 용액의 높이를 결정하는 방법 및 시스템 |
WO2023003922A1 (en) | 2021-07-21 | 2023-01-26 | Alnylam Pharmaceuticals, Inc. | Metabolic disorder-associated target gene irna compositions and methods of use thereof |
WO2023034817A1 (en) | 2021-09-01 | 2023-03-09 | Entrada Therapeutics, Inc. | Compounds and methods for skipping exon 44 in duchenne muscular dystrophy |
WO2023064530A1 (en) | 2021-10-15 | 2023-04-20 | Alnylam Pharmaceuticals, Inc. | Extra-hepatic delivery irna compositions and methods of use thereof |
US11634711B2 (en) | 2012-05-17 | 2023-04-25 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein (a) expression |
WO2023086295A2 (en) | 2021-11-10 | 2023-05-19 | University Of Rochester | Antisense oligonucleotides for modifying protein expression |
WO2023086292A2 (en) | 2021-11-10 | 2023-05-19 | University Of Rochester | Gata4-targeted therapeutics for treatment of cardiac hypertrophy |
WO2023122750A1 (en) | 2021-12-23 | 2023-06-29 | Synthorx, Inc. | Cancer combination therapy with il-2 conjugates and cetuximab |
WO2023122573A1 (en) | 2021-12-20 | 2023-06-29 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and pembrolizumab |
US11761007B2 (en) | 2015-12-18 | 2023-09-19 | The Scripps Research Institute | Production of unnatural nucleotides using a CRISPR/Cas9 system |
WO2023220744A2 (en) | 2022-05-13 | 2023-11-16 | Alnylam Pharmaceuticals, Inc. | Single-stranded loop oligonucleotides |
US11834689B2 (en) | 2017-07-11 | 2023-12-05 | The Scripps Research Institute | Incorporation of unnatural nucleotides and methods thereof |
WO2024006999A2 (en) | 2022-06-30 | 2024-01-04 | Alnylam Pharmaceuticals, Inc. | Cyclic-disulfide modified phosphate based oligonucleotide prodrugs |
US11879145B2 (en) | 2019-06-14 | 2024-01-23 | The Scripps Research Institute | Reagents and methods for replication, transcription, and translation in semi-synthetic organisms |
WO2024039776A2 (en) | 2022-08-18 | 2024-02-22 | Alnylam Pharmaceuticals, Inc. | Universal non-targeting sirna compositions and methods of use thereof |
WO2024050261A1 (en) | 2022-08-29 | 2024-03-07 | University Of Rochester | Antisense oligonucleotide-based anti-fibrotic therapeutics |
WO2024073732A1 (en) | 2022-09-30 | 2024-04-04 | Alnylam Pharmaceuticals, Inc. | Modified double-stranded rna agents |
Families Citing this family (281)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102005042073B4 (de) * | 2005-08-31 | 2010-11-11 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Faserlaser |
US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
US8084437B2 (en) * | 2006-11-27 | 2011-12-27 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
WO2009023855A2 (en) | 2007-08-15 | 2009-02-19 | Isis Pharmaceuticals, Inc. | Tetrahydropyran nucleic acid analogs |
EP2220230A2 (en) | 2007-11-09 | 2010-08-25 | Isis Pharmaceuticals, Inc. | Modulation of factor 9 expression |
KR20100105550A (ko) | 2007-11-09 | 2010-09-29 | 아이시스 파마수티컬즈 인코포레이티드 | 7 인자 발현 조절 |
WO2009100320A2 (en) | 2008-02-07 | 2009-08-13 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexitol nucleic acid analogs |
EP2282744B1 (en) * | 2008-03-21 | 2018-01-17 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising tricyclic nucleosides and methods for their use |
DK2285819T3 (da) | 2008-04-04 | 2013-12-02 | Isis Pharmaceuticals Inc | Oligomere forbindelser omfattende neutralt bundne, terminale bicykliske nukleosider |
US8541387B2 (en) * | 2008-05-22 | 2013-09-24 | Isis Pharmaceuticals, Inc. | Modulation of SMRT expression |
US8604192B2 (en) * | 2008-09-24 | 2013-12-10 | Isis Pharmaceuticals, Inc. | Cyclohexenyl nucleic acids analogs |
BRPI0920263B1 (pt) | 2008-10-15 | 2021-09-21 | Ionis Pharmaceuticals, Inc | Compostos compreendendo um oligonucleotídeo modificado, composição e uso dos mesmos |
WO2010048549A2 (en) | 2008-10-24 | 2010-04-29 | Isis Pharmaceuticals, Inc. | 5' and 2' bis-substituted nucleosides and oligomeric compounds prepared therefrom |
KR101881596B1 (ko) | 2008-12-02 | 2018-07-24 | 웨이브 라이프 사이언시스 재팬 인코포레이티드 | 인 원자 변형된 핵산의 합성 방법 |
WO2010090969A1 (en) | 2009-02-06 | 2010-08-12 | Isis Pharmaceuticals, Inc. | Tetrahydropyran nucleic acid analogs |
EP2414520A2 (en) | 2009-03-31 | 2012-02-08 | Altair Therapeutics, Inc. | Methods of modulating an immune response to a viral infection |
KR20210057223A (ko) | 2009-06-17 | 2021-05-20 | 바이오젠 엠에이 인코포레이티드 | 대상에게서 smn2 스플라이싱을 조정하기 위한 조성물 및 방법 |
SG10201403841QA (en) | 2009-07-06 | 2014-09-26 | Ontorii Inc | Novel nucleic acid prodrugs and methods of use thereof |
EP2462153B1 (en) | 2009-08-06 | 2015-07-29 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
SI2475675T1 (sl) | 2009-09-11 | 2017-03-31 | Ionis Pharmaceuticals, Inc. | Modulacija ekspresije huntingtina |
WO2011085102A1 (en) | 2010-01-11 | 2011-07-14 | Isis Pharmaceuticals, Inc. | Base modified bicyclic nucleosides and oligomeric compounds prepared therefrom |
EP2524038A4 (en) * | 2010-01-12 | 2013-11-20 | Isis Pharmaceuticals Inc | MODULATION OF TRANSFORMING A GROWTH FACTOR BETA-1 EXPRESSION |
EP2539356A4 (en) * | 2010-02-26 | 2014-03-05 | Isis Pharmaceuticals Inc | MODULATION OF SMAD3 EXPRESSION |
WO2011115817A1 (en) | 2010-03-16 | 2011-09-22 | Isis Pharmaceuticals, Inc. | Methods of preparing 2'-o-substituted purine nucleosides |
WO2011115818A1 (en) | 2010-03-17 | 2011-09-22 | Isis Pharmaceuticals, Inc. | 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom |
US10913767B2 (en) | 2010-04-22 | 2021-02-09 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
WO2011133868A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Conformationally restricted dinucleotide monomers and oligonucleotides |
AU2011261434B2 (en) | 2010-06-02 | 2015-11-26 | Alnylam Pharmaceuticals, Inc. | Compositions and methods directed to treating liver fibrosis |
WO2011159836A2 (en) | 2010-06-15 | 2011-12-22 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating interaction between proteins and target nucleic acids |
EP2620428B1 (en) | 2010-09-24 | 2019-05-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
US9193973B2 (en) | 2010-12-10 | 2015-11-24 | Alynylam Pharmaceuticals, Inc. | Compositions and methods for increasing erythropoietin (EPO) production |
EP2648763A4 (en) | 2010-12-10 | 2014-05-14 | Alnylam Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR EXPRESSION INHIBITION OF GENES KLF-1 AND BCL11A |
EP2495336B8 (en) | 2011-03-04 | 2014-07-23 | Roche Diagnostics GmbH | A new type of universal probes for the detection of genomic variants |
BR112013025006B1 (pt) | 2011-03-29 | 2021-06-15 | Alnylam Pharmaceuticals, Inc | Composição farmacêutica para inibir a expressão de um gene de tmprss6, método para inibição da expressão de tmprss6 em uma célula, e uso de ácidos ribonu-cleicos fita dupla |
EP3460064B8 (en) | 2011-04-03 | 2024-03-20 | The General Hospital Corporation d/b/a Massachusetts General Hospital | Efficient protein expression in vivo using modified rna (mod-rna) |
SG194636A1 (en) | 2011-04-25 | 2013-12-30 | Regulus Therapeutics Inc | Microrna compounds and methods for modulating mir-21 activity |
BR122019026068B8 (pt) | 2011-06-21 | 2022-10-18 | Alnylam Pharmaceuticals | Ácido ribonucleico de fita dupla (dsrna) para inibir a expressão de angptl3 e seu uso, composição farmacêutica e método in vitro para inibir a expressão de angptl3 em uma célula |
US20140235693A1 (en) | 2011-06-23 | 2014-08-21 | Alnylam Pharmaceuticals, Inc. | Serpina1 sirnas: compositions of matter and methods of treatment |
JP6128529B2 (ja) | 2011-07-19 | 2017-05-17 | ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. | 官能化核酸の合成のための方法 |
EP2739735A2 (en) | 2011-08-01 | 2014-06-11 | Alnylam Pharmaceuticals, Inc. | Method for improving the success rate of hematopoietic stem cell transplants |
US9243291B1 (en) | 2011-12-01 | 2016-01-26 | Isis Pharmaceuticals, Inc. | Methods of predicting toxicity |
US9133461B2 (en) | 2012-04-10 | 2015-09-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the ALAS1 gene |
KR20220028183A (ko) | 2012-04-25 | 2022-03-08 | 사노피 | 마이크로rna 화합물 및 mir-21 활성 조절 방법 |
US9127274B2 (en) | 2012-04-26 | 2015-09-08 | Alnylam Pharmaceuticals, Inc. | Serpinc1 iRNA compositions and methods of use thereof |
BR112015000723A2 (pt) | 2012-07-13 | 2017-06-27 | Shin Nippon Biomedical Laboratories Ltd | adjuvante de ácido nucléico quiral |
EP4219516A3 (en) | 2012-07-13 | 2024-01-10 | Wave Life Sciences Ltd. | Chiral control |
US9598458B2 (en) | 2012-07-13 | 2017-03-21 | Wave Life Sciences Japan, Inc. | Asymmetric auxiliary group |
AU2013337277B2 (en) | 2012-11-05 | 2018-03-08 | Foundation Medicine, Inc. | Novel NTRK1 fusion molecules and uses thereof |
WO2014093291A1 (en) | 2012-12-10 | 2014-06-19 | Advandx, Inc. | Use of probes for mass spectrometric identification of microorganisms or cells and associated conditions of interest |
CA2898326C (en) | 2013-01-18 | 2022-05-17 | Foundation Medicine, Inc. | Methods of treating cholangiocarcinoma |
WO2014130922A1 (en) | 2013-02-25 | 2014-08-28 | Trustees Of Boston University | Compositions and methods for treating fungal infections |
US20140249037A1 (en) | 2013-03-04 | 2014-09-04 | Fry Laboratories, LLC | Method and kit for characterizing microorganisms |
SG11201507400SA (en) | 2013-03-14 | 2015-10-29 | Alnylam Pharmaceuticals Inc | Complement component c5 irna compositions and methods of use thereof |
EP2978446B1 (en) | 2013-03-27 | 2020-03-04 | The General Hospital Corporation | Anti-cd33 antibody for use in treating alzheimer's disease |
EP2981617B1 (en) | 2013-04-04 | 2023-07-05 | President and Fellows of Harvard College | Therapeutic uses of genome editing with crispr/cas systems |
SG10201803157XA (en) | 2013-05-01 | 2018-05-30 | Regulus Therapeutics Inc | Microrna compounds and methods for modulating mir-122 |
EP2992096B1 (en) | 2013-05-01 | 2021-03-03 | Regulus Therapeutics Inc. | Compounds and methods for enhanced cellular uptake |
LT2999785T (lt) | 2013-05-22 | 2018-07-25 | Alnylam Pharmaceuticals, Inc. | Serpina1 irna kompozicijos ir jų panaudojimo būdai |
TW202342750A (zh) | 2013-05-22 | 2023-11-01 | 美商阿尼拉製藥公司 | TMPRSS6 iRNA組成物及其使用方法 |
EP3004396B1 (en) | 2013-06-06 | 2019-10-16 | The General Hospital Corporation | Compositions for the treatment of cancer |
US10077236B2 (en) | 2013-07-15 | 2018-09-18 | The Regents Of The University Of California | Azacyclic constrained analogs of FTY720 |
RU2662967C2 (ru) | 2013-09-13 | 2018-07-31 | Ионис Фармасьютикалз, Инк. | Модуляторы фактора в комплемента |
US10077444B2 (en) | 2013-10-02 | 2018-09-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the LECT2 gene |
IL282747B2 (en) | 2013-10-04 | 2023-10-01 | Alnylam Pharmaceuticals Inc | Preparations and methods for inhibiting expression of the ALAS1 gene |
US11162096B2 (en) | 2013-10-14 | 2021-11-02 | Ionis Pharmaceuticals, Inc | Methods for modulating expression of C9ORF72 antisense transcript |
EP3502270B1 (en) | 2013-10-21 | 2020-03-18 | The General Hospital Corporation | Methods relating to circulating tumor cell clusters and the treatment of cancer |
WO2015061536A1 (en) | 2013-10-25 | 2015-04-30 | Regulus Therapeutics Inc. | Microrna compounds and methods for modulating mir-21 activity |
IL294470A (en) | 2013-12-12 | 2022-09-01 | Alnylam Pharmaceuticals Inc | Complementary component irna compositions and methods for using them |
EP3082840B1 (en) | 2013-12-20 | 2021-03-24 | The General Hospital Corporation | Methods and assays relating to circulating tumor cells |
WO2015108048A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
WO2015108046A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
EP3095461A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
BR112016016400A2 (pt) | 2014-01-16 | 2017-10-03 | Wave Life Sciences Ltd | Composições de oligonucleotídeos quiralmente controlados, seu uso, sua composição farmacêutica, e métodos |
CA2938857A1 (en) | 2014-02-11 | 2015-08-20 | Alnylam Pharmaceuticals, Inc. | Ketohexokinase (khk) irna compositions and methods of use thereof |
US10006027B2 (en) | 2014-03-19 | 2018-06-26 | Ionis Pharmaceuticals, Inc. | Methods for modulating Ataxin 2 expression |
EP3131915A4 (en) | 2014-04-17 | 2017-11-29 | Biogen MA Inc. | Compositions and methods for modulation of smn2 splicing in a subject |
WO2015175510A1 (en) | 2014-05-12 | 2015-11-19 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating a serpinc1-associated disorder |
CN112301031A (zh) | 2014-05-22 | 2021-02-02 | 阿尔尼拉姆医药品有限公司 | 血管紧张素原(AGT)iRNA组合物及其使用方法 |
JP2017518307A (ja) | 2014-06-02 | 2017-07-06 | チルドレンズ メディカル センター コーポレーション | 免疫調節のための方法および組成物 |
CN106559995A (zh) | 2014-08-07 | 2017-04-05 | 莱古路斯治疗法股份有限公司 | 靶向代谢紊乱的微小rna |
EP4043567B1 (en) | 2014-08-29 | 2024-05-08 | The Children's Medical Center Corporation | Methods and compositions for the treatment of cancer |
EP3191591A1 (en) | 2014-09-12 | 2017-07-19 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting complement component c5 and methods of use thereof |
JOP20200115A1 (ar) | 2014-10-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات)) |
WO2016061487A1 (en) | 2014-10-17 | 2016-04-21 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof |
EP3212794B1 (en) | 2014-10-30 | 2021-04-07 | Genzyme Corporation | Polynucleotide agents targeting serpinc1 (at3) and methods of use thereof |
JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
US10287584B2 (en) | 2014-11-12 | 2019-05-14 | Ionis Pharmaceuticals, Inc. | Compounds and methods for the modulation of COMP |
EP3221451A1 (en) | 2014-11-17 | 2017-09-27 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof |
US10793855B2 (en) | 2015-01-06 | 2020-10-06 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of C9ORF72 antisense transcript |
WO2016115490A1 (en) | 2015-01-16 | 2016-07-21 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulation of dux4 |
CA2976445A1 (en) | 2015-02-13 | 2016-08-18 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
US11129844B2 (en) | 2015-03-03 | 2021-09-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating MECP2 expression |
US20160348073A1 (en) | 2015-03-27 | 2016-12-01 | President And Fellows Of Harvard College | Modified t cells and methods of making and using the same |
MX2017012610A (es) | 2015-04-08 | 2018-03-16 | Alnylam Pharmaceuticals Inc | Composiciones y metodos para inhibir la expresion del gen lect2. |
WO2016167780A1 (en) | 2015-04-16 | 2016-10-20 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
WO2016201301A1 (en) | 2015-06-12 | 2016-12-15 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions and methods of use thereof |
WO2016205323A1 (en) | 2015-06-18 | 2016-12-22 | Alnylam Pharmaceuticals, Inc. | Polynucleotde agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof |
WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
WO2017011286A1 (en) | 2015-07-10 | 2017-01-19 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof |
MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
US20180201937A1 (en) | 2015-08-04 | 2018-07-19 | The University Of Chicago | Inhibitors of cacna1a/alpha1a subunit internal ribosomal entry site (ires) and methods of treating spinocerebellar ataxia type 6 |
PE20181131A1 (es) | 2015-09-02 | 2018-07-17 | Alnylam Pharmaceuticals Inc | COMPOSICIONES DE ARNi PARA LIGANDO 1 DE MUERTE CELULAR PROGRAMADA 1 (PD-L1) Y METODOS DE USO DE LAS MISMAS |
WO2017053990A1 (en) | 2015-09-24 | 2017-03-30 | The Regents Of The University Of California | Synthetic sphingolipid-like molecules, drugs, methods of their synthesis and methods of treatment |
EP4285912A2 (en) | 2015-09-25 | 2023-12-06 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating ataxin 3 expression |
US20190046555A1 (en) | 2015-11-06 | 2019-02-14 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds for use in therapy |
EP3389670A4 (en) | 2015-12-04 | 2020-01-08 | Ionis Pharmaceuticals, Inc. | METHODS OF TREATING BREAST CANCER |
WO2017120365A1 (en) | 2016-01-05 | 2017-07-13 | Ionis Pharmaceuticals, Inc. | Methods for reducing lrrk2 expression |
AU2017229778A1 (en) | 2016-03-09 | 2018-08-16 | Ionis Pharmaceuticals, Inc. | Methods and compositions for inhibiting PMP22 expression |
WO2017161168A1 (en) | 2016-03-16 | 2017-09-21 | Ionis Pharmaceuticals, Inc. | Modulation of dyrk1b expression |
EP3429690A4 (en) | 2016-03-16 | 2019-10-23 | Ionis Pharmaceuticals, Inc. | METHOD FOR MODULATING KEAP1 |
WO2017180835A1 (en) | 2016-04-13 | 2017-10-19 | Ionis Pharmaceuticals, Inc. | Methods for reducing c9orf72 expression |
MA45295A (fr) | 2016-04-19 | 2019-02-27 | Alnylam Pharmaceuticals Inc | Composition d'arni de protéine de liaison de lipoprotéines haute densité (hdlbp/vigiline) et procédés pour les utiliser |
JP2019518028A (ja) | 2016-06-10 | 2019-06-27 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | 補体成分C5iRNA組成物及び発作性夜間血色素尿症(PNH)を処置するためのその使用方法 |
WO2017218454A1 (en) | 2016-06-14 | 2017-12-21 | Biogen Ma Inc. | Hydrophobic interaction chromatography for purification of oligonucleotides |
CA3023514A1 (en) | 2016-06-17 | 2017-12-21 | Ionis Pharmaceuticals, Inc. | Modulation of gys1 expression |
EP3507367A4 (en) | 2016-07-05 | 2020-03-25 | Aduro BioTech, Inc. | CYCLIC DINUCLEOTID COMPOUNDS WITH INCLUDED NUCLEIC ACIDS AND USES THEREOF |
CN109844115B (zh) | 2016-07-15 | 2023-06-30 | Ionis 制药公司 | 用于调节smn2的化合物和方法 |
CA3033756A1 (en) | 2016-09-02 | 2018-03-08 | Dicerna Pharmaceuticals, Inc. | 4'-phosphate analogs and oligonucleotides comprising the same |
JOP20190104A1 (ar) | 2016-11-10 | 2019-05-07 | Ionis Pharmaceuticals Inc | مركبات وطرق لتقليل التعبير عن atxn3 |
TWI788312B (zh) | 2016-11-23 | 2023-01-01 | 美商阿尼拉製藥公司 | 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法 |
US11033570B2 (en) | 2016-12-02 | 2021-06-15 | Cold Spring Harbor Laboratory | Modulation of Lnc05 expression |
JP7104703B2 (ja) | 2016-12-14 | 2022-07-21 | ヤンセン バイオテツク,インコーポレーテツド | Cd8a結合フィブロネクチンiii型ドメイン |
WO2018111978A1 (en) | 2016-12-14 | 2018-06-21 | Janssen Biotech, Inc. | Cd137 binding fibronectin type iii domains |
SG10201913552UA (en) | 2016-12-16 | 2020-03-30 | Alnylam Pharmaceuticals Inc | Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions |
US11180756B2 (en) | 2017-03-09 | 2021-11-23 | Ionis Pharmaceuticals | Morpholino modified oligomeric compounds |
JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
BR112019021852A2 (pt) | 2017-04-18 | 2020-06-02 | Alnylam Pharmaceuticals, Inc. | Agente de rnai e uma vacina contra hbv, uso ou método e kit para tratamento |
US11401519B2 (en) | 2017-06-07 | 2022-08-02 | University Of Massachusetts | Anti-ADAM33 oligonucleotides and related methods |
AU2018301477A1 (en) | 2017-07-13 | 2020-02-27 | Alnylam Pharmaceuticals Inc. | Lactate dehydrogenase a (LDHA) iRNA compositions and methods of use thereof |
US11197884B2 (en) | 2017-08-18 | 2021-12-14 | Ionis Pharmaceuticals, Inc. | Modulation of the notch signaling pathway for treatment of respiratory disorders |
WO2019051173A1 (en) | 2017-09-08 | 2019-03-14 | Ionis Pharmaceuticals, Inc. | MODULATORS OF SMAD7 EXPRESSION |
US11225660B2 (en) | 2017-10-12 | 2022-01-18 | Emory University | Methods and compositions for managing vascular conditions using miR-483 mimics and HIF1alpha pathway inhibitors |
CA3078971A1 (en) | 2017-11-01 | 2019-05-09 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof |
WO2019099610A1 (en) | 2017-11-16 | 2019-05-23 | Alnylam Pharmaceuticals, Inc. | Kisspeptin 1 (kiss1) irna compositions and methods of use thereof |
EP3714054A1 (en) | 2017-11-20 | 2020-09-30 | Alnylam Pharmaceuticals, Inc. | Serum amyloid p component (apcs) irna compositions and methods of use thereof |
US11725208B2 (en) | 2017-12-14 | 2023-08-15 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
MX2020006012A (es) | 2017-12-18 | 2020-09-14 | Alnylam Pharmaceuticals Inc | Composiciones de arni de la caja 1 del grupo de alta movilidad (hmgb1) y métodos de uso de las mismas. |
WO2019126641A2 (en) | 2017-12-21 | 2019-06-27 | Ionis Pharmaceuticals, Inc. | Modulation of frataxin expression |
MX2020007369A (es) | 2018-01-15 | 2020-10-28 | Ionis Pharmaceuticals Inc | Moduladores de la expresion de dnm2. |
JP7317029B2 (ja) | 2018-02-12 | 2023-07-28 | アイオーニス ファーマシューティカルズ, インコーポレーテッド | 修飾化合物及びその使用 |
WO2019169243A1 (en) | 2018-03-02 | 2019-09-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for the modulation of amyloid-beta precursor protein |
MX2020009147A (es) | 2018-03-02 | 2020-09-28 | Ionis Pharmaceuticals Inc | Moduladores de la expresion de irf4. |
EP3768694A4 (en) | 2018-03-22 | 2021-12-29 | Ionis Pharmaceuticals, Inc. | Methods for modulating fmr1 expression |
MX2020010721A (es) | 2018-04-11 | 2020-11-06 | Ionis Pharmaceuticals Inc | Moduladores de la expresion de ezh2. |
US20210355497A1 (en) | 2018-05-09 | 2021-11-18 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing fxi expression |
JP2021522800A (ja) | 2018-05-09 | 2021-09-02 | アイオーニス ファーマシューティカルズ, インコーポレーテッドIonis Pharmaceuticals,Inc. | Atxn3発現を低減するための化合物及び方法 |
TW202016304A (zh) | 2018-05-14 | 2020-05-01 | 美商阿尼拉製藥公司 | 血管收縮素原(AGT)iRNA組成物及其使用方法 |
US11833168B2 (en) | 2018-06-14 | 2023-12-05 | Ionis Pharmaceuticals, Inc. | Compounds and methods for increasing STMN2 expression |
MX2020013653A (es) | 2018-06-27 | 2021-03-02 | Ionis Pharmaceuticals Inc | Compuestos y metodos para la reduccion de la expresion de lrrk2. |
EP3826645A4 (en) | 2018-07-25 | 2023-05-17 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR REDUCING ATXN2 EXPRESSION |
EA202190528A1 (ru) | 2018-08-13 | 2021-04-23 | Элнилэм Фармасьютикалз, Инк. | КОМПОЗИЦИИ АГЕНТОВ дцРНК ВИРУСА ГЕПАТИТА B (HBV) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
KR20210043634A (ko) | 2018-08-15 | 2021-04-21 | 일루미나, 인코포레이티드 | 라이브러리 인리치먼트를 개선하기 위한 조성물 및 방법 |
TW202020157A (zh) | 2018-08-16 | 2020-06-01 | 美商艾爾妮蘭製藥公司 | 用於抑制lect2基因表現之組合物及方法 |
US11939582B2 (en) | 2018-08-20 | 2024-03-26 | Rogcon, Inc. | Antisense oligonucleotides targeting SCN2A for the treatment of SCN1A encephalopathies |
EP3620520A1 (en) | 2018-09-10 | 2020-03-11 | Universidad del Pais Vasco | Novel target to treat a metabolic disease in an individual |
JP2022500003A (ja) | 2018-09-18 | 2022-01-04 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | ケトヘキソキナーゼ(KHK)iRNA組成物およびその使用方法 |
TW202023573A (zh) | 2018-09-19 | 2020-07-01 | 美商Ionis製藥公司 | Pnpla3表現之調節劑 |
US10913951B2 (en) | 2018-10-31 | 2021-02-09 | University of Pittsburgh—of the Commonwealth System of Higher Education | Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure |
TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
JP2022509059A (ja) | 2018-11-15 | 2022-01-20 | アイオーニス ファーマシューティカルズ, インコーポレーテッド | Irf5発現の調節因子 |
EP4285929A3 (en) | 2018-12-20 | 2024-03-06 | Humabs Biomed SA | Combination hbv therapy |
US20220056455A1 (en) | 2018-12-20 | 2022-02-24 | Praxis Precision Medicines, Inc. | Compositions and methods for the treatment of kcnt1 related disorders |
MX2021008628A (es) | 2019-01-16 | 2021-11-17 | Genzyme Corp | Composiciones de arni para serpinc1 y metodos de uso de las mismas. |
US11214803B2 (en) | 2019-01-31 | 2022-01-04 | Ionis Pharmaceuticals, Inc. | Modulators of YAP1 expression |
EP3941483A4 (en) | 2019-03-21 | 2023-10-18 | Arnay Sciences, Llc | ANTISEN OLIGONUCLEOTIDES FOR ALLEL SPECIFICITY |
JP7413362B2 (ja) * | 2019-03-29 | 2024-01-15 | シスメックス株式会社 | 新規人工核酸、その製造方法及び用途 |
CA3134486A1 (en) | 2019-03-29 | 2020-10-08 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for the treatment of kras associated diseases or disorders |
CN113795581A (zh) | 2019-05-03 | 2021-12-14 | 迪克纳制药公司 | 具有缩短的有义链的双链核酸抑制剂分子 |
EP3966328A4 (en) | 2019-05-06 | 2023-10-18 | University Of Massachusetts | ANTI-C9ORF72 OLIGONUCLEOTIDES AND RELATED METHODS |
SG11202112240VA (en) | 2019-05-13 | 2021-12-30 | Vir Biotechnology Inc | Compositions and methods for treating hepatitis b virus (hbv) infection |
WO2020243292A1 (en) | 2019-05-28 | 2020-12-03 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing fus expression |
EP3956450A4 (en) | 2019-07-26 | 2022-11-16 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR MODULATION OF GFAP |
EP4007812A1 (en) | 2019-08-01 | 2022-06-08 | Alnylam Pharmaceuticals, Inc. | Serpin family f member 2 (serpinf2) irna compositions and methods of use thereof |
EP4007811A2 (en) | 2019-08-01 | 2022-06-08 | Alnylam Pharmaceuticals, Inc. | Carboxypeptidase b2 (cpb2) irna compositions and methods of use thereof |
EP4013870A1 (en) | 2019-08-13 | 2022-06-22 | Alnylam Pharmaceuticals, Inc. | Small ribosomal protein subunit 25 (rps25) irna agent compositions and methods of use thereof |
KR20220062517A (ko) | 2019-08-15 | 2022-05-17 | 아이오니스 파마수티컬즈, 인코포레이티드 | 결합 변형된 올리고머 화합물 및 이의 용도 |
MX2022002689A (es) | 2019-09-03 | 2022-04-07 | Alnylam Pharmaceuticals Inc | Composiciones y metodos para inhibir la expresion del gen de quimiotaxina derivada de celulas de leucocitos 2 (lect2). |
EP4038189A1 (en) | 2019-10-04 | 2022-08-10 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing ugt1a1 gene expression |
US11628222B2 (en) | 2019-10-14 | 2023-04-18 | Aro Biotherapeutics Company | CD71 binding fibronectin type III domains |
US11781138B2 (en) | 2019-10-14 | 2023-10-10 | Aro Biotherapeutics Company | FN3 domain-siRNA conjugates and uses thereof |
WO2021074772A1 (en) | 2019-10-14 | 2021-04-22 | Astrazeneca Ab | Modulators of pnpla3 expression |
US20240141358A1 (en) | 2019-10-18 | 2024-05-02 | Alnylam Pharmaceuticals, Inc. | Solute carrier family member irna compositions and methods of use thereof |
KR20220084399A (ko) | 2019-10-22 | 2022-06-21 | 알닐람 파마슈티칼스 인코포레이티드 | 보체 성분 C3 iRNA 조성물 및 이의 사용 방법 |
MX2022004388A (es) | 2019-11-01 | 2022-05-06 | Alnylam Pharmaceuticals Inc | Composiciones de agentes de arni de huntingtina (htt) y metodos de uso de las mismas. |
EP4051796A1 (en) | 2019-11-01 | 2022-09-07 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing dnajb1-prkaca fusion gene expression |
EP4058577A1 (en) | 2019-11-13 | 2022-09-21 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating an angiotensinogen- (agt-) associated disorder |
US20230056569A1 (en) | 2019-11-22 | 2023-02-23 | Alnylam Pharmaceuticals, Inc. | Ataxin3 (atxn3) rnai agent compositions and methods of use thereof |
IL293824A (en) | 2019-12-13 | 2022-08-01 | Alnylam Pharmaceuticals Inc | Compositions of RNA material (c9orf72) human chromosome 9 open reading frame 72 and methods of using them |
WO2021126734A1 (en) | 2019-12-16 | 2021-06-24 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
JP2023511082A (ja) | 2020-01-15 | 2023-03-16 | ディセルナ ファーマシューティカルズ インコーポレイテッド | 4’-o-メチレンホスホネート核酸及びその類似体 |
WO2021154941A1 (en) | 2020-01-31 | 2021-08-05 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als) |
JP2023514190A (ja) | 2020-02-10 | 2023-04-05 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | Vegf-a発現をサイレンシングするための組成物および方法 |
KR20220143106A (ko) | 2020-02-18 | 2022-10-24 | 알닐람 파마슈티칼스 인코포레이티드 | 아포지질단백질 C3 (APOC3) iRNA 조성물 및 이의 사용 방법 |
WO2021174019A1 (en) | 2020-02-28 | 2021-09-02 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating smn2 |
TW202146651A (zh) | 2020-03-02 | 2021-12-16 | 日商田邊三菱製藥股份有限公司 | miR-33b阻礙物質所致之動脈瘤的預防或治療 |
WO2021178607A1 (en) | 2020-03-05 | 2021-09-10 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases |
MX2022011009A (es) | 2020-03-06 | 2022-10-07 | Alnylam Pharmaceuticals Inc | Composiciones de acido ribonucleico de interferencia (arni) de ketohexocinasa (khk) y metodos de uso de las mismas. |
IL296106A (en) | 2020-03-06 | 2022-11-01 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of transthyretin (ttr) |
WO2021188611A1 (en) | 2020-03-18 | 2021-09-23 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant |
TW202204615A (zh) | 2020-03-26 | 2022-02-01 | 美商阿尼拉製藥公司 | 冠狀病毒iRNA組成物及其使用方法 |
WO2021202443A2 (en) | 2020-03-30 | 2021-10-07 | Alnylam Pharmaceucticals, Inc. | Compositions and methods for silencing dnajc15 gene expression |
CA3179411A1 (en) | 2020-04-06 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing myoc expression |
EP4133076A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Angiotensin-converting enzyme 2 (ace2) irna compositions and methods of use thereof |
EP4133077A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof |
CN116134135A (zh) | 2020-04-07 | 2023-05-16 | 阿尔尼拉姆医药品有限公司 | 用于沉默scn9a表达的组合物和方法 |
EP4143319A1 (en) | 2020-04-27 | 2023-03-08 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein e (apoe) irna agent compositions and methods of use thereof |
IL297680A (en) | 2020-04-30 | 2022-12-01 | Alnylam Pharmaceuticals Inc | IRNA compounds complement factor b (cfb) and methods of using them |
EP4143321A2 (en) | 2020-05-01 | 2023-03-08 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating atxn1 |
EP4150089A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of retinoschisin 1 (rs1) |
EP4150086A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2) |
WO2021231692A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of otoferlin (otof) |
CA3162416C (en) | 2020-05-15 | 2023-07-04 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1) |
WO2021231679A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2) |
EP4150076A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2) |
EP4150078A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl) |
EP4150077A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1) |
WO2021237097A1 (en) | 2020-05-21 | 2021-11-25 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting marc1 gene expression |
US11408000B2 (en) | 2020-06-03 | 2022-08-09 | Triplet Therapeutics, Inc. | Oligonucleotides for the treatment of nucleotide repeat expansion disorders associated with MSH3 activity |
EP4162050A1 (en) | 2020-06-09 | 2023-04-12 | Alnylam Pharmaceuticals, Inc. | Rnai compositions and methods of use thereof for delivery by inhalation |
WO2021257782A1 (en) | 2020-06-18 | 2021-12-23 | Alnylam Pharmaceuticals, Inc. | XANTHINE DEHYDROGENASE (XDH) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
KR20230042023A (ko) | 2020-06-24 | 2023-03-27 | 비르 바이오테크놀로지, 인코포레이티드 | 조작된 b형 간염 바이러스 중화 항체 및 이의 용도 |
WO2022006134A2 (en) | 2020-06-29 | 2022-01-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating plp1 |
EP4183416A1 (en) | 2020-07-17 | 2023-05-24 | Mitsubishi Tanabe Pharma Corporation | Agent for preventing or treating muscular disease |
KR20230061389A (ko) | 2020-08-04 | 2023-05-08 | 다이서나 파마수이티컬, 인크. | 올리고뉴클레오티드의 전신 전달 |
TW202227102A (zh) | 2020-09-22 | 2022-07-16 | 瑞典商阿斯特捷利康公司 | 治療脂肪肝病之方法 |
EP4217489A1 (en) | 2020-09-24 | 2023-08-02 | Alnylam Pharmaceuticals, Inc. | Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof |
EP4225917A1 (en) | 2020-10-05 | 2023-08-16 | Alnylam Pharmaceuticals, Inc. | G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof |
AU2021365822A1 (en) | 2020-10-21 | 2023-06-08 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating primary hyperoxaluria |
EP4232582A1 (en) | 2020-10-23 | 2023-08-30 | Alnylam Pharmaceuticals, Inc. | Mucin 5b (muc5b) irna compositions and methods of use thereof |
CA3200595A1 (en) | 2020-11-13 | 2022-05-19 | Alnylam Pharmaceuticals, Inc. | Coagulation factor v (f5) irna compositions and methods of use thereof |
EP4247950A1 (en) | 2020-11-18 | 2023-09-27 | Lemba BV | Umlilo antisense transcription inhibitors |
US20240002853A1 (en) | 2020-11-23 | 2024-01-04 | Alpha Anomeric Sas | Nucleic acid duplexes |
AU2021393417A1 (en) | 2020-12-01 | 2023-06-29 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression |
EP4259795A1 (en) | 2020-12-08 | 2023-10-18 | Alnylam Pharmaceuticals, Inc. | Coagulation factor x (f10) irna compositions and methods of use thereof |
GB2603454A (en) | 2020-12-09 | 2022-08-10 | Ucl Business Ltd | Novel therapeutics for the treatment of neurodegenerative disorders |
CA3206285A1 (en) | 2020-12-23 | 2022-06-30 | Flagship Pioneering, Inc. | Compositions of modified trems and uses thereof |
EP4274896A1 (en) | 2021-01-05 | 2023-11-15 | Alnylam Pharmaceuticals, Inc. | Complement component 9 (c9) irna compositions and methods of use thereof |
EP4291654A2 (en) | 2021-02-12 | 2023-12-20 | Alnylam Pharmaceuticals, Inc. | Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases |
JP2024509783A (ja) | 2021-02-25 | 2024-03-05 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | プリオンタンパク質(prnp)irna組成物およびその使用方法 |
TW202302847A (zh) | 2021-02-26 | 2023-01-16 | 美商艾拉倫製藥股份有限公司 | 己酮糖激酶(KHK)iRNA組成物及其使用方法 |
IL305442A (en) | 2021-03-04 | 2023-10-01 | Alnylam Pharmaceuticals Inc | Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them |
EP4305169A1 (en) | 2021-03-12 | 2024-01-17 | Alnylam Pharmaceuticals, Inc. | Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof |
CA3214499A1 (en) | 2021-03-29 | 2022-10-06 | Alnylam Pharmaceuticals, Inc. | Huntingtin (htt) irna agent compositions and methods of use thereof |
EP4314293A1 (en) | 2021-04-01 | 2024-02-07 | Alnylam Pharmaceuticals, Inc. | Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof |
TW202309291A (zh) | 2021-04-07 | 2023-03-01 | 法商新植物Sas公司 | 用於室內空氣修復之組合物及方法 |
BR112023022284A2 (pt) | 2021-04-26 | 2023-12-26 | Alnylam Pharmaceuticals Inc | Composições de irna de protease transmembrana, serina 6 (tmprss6) e métodos de uso da mesma |
JP2024519293A (ja) | 2021-04-29 | 2024-05-10 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | シグナル伝達兼転写活性化因子6(STAT6)iRNA組成物およびその使用方法 |
JPWO2022230987A1 (ja) | 2021-04-30 | 2022-11-03 | ||
EP4341401A1 (en) | 2021-05-18 | 2024-03-27 | Alnylam Pharmaceuticals, Inc. | Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof |
WO2022246023A1 (en) | 2021-05-20 | 2022-11-24 | Korro Bio, Inc. | Methods and compositions for adar-mediated editing |
CA3221935A1 (en) | 2021-05-29 | 2022-12-08 | 1Globe Health Institute Llc | Asymmetric short duplex dna as a novel gene silencing technology and use thereof |
EP4347828A1 (en) | 2021-05-29 | 2024-04-10 | 1Globe Health Institute LLC | Short duplex dna as a novel gene silencing technology and use thereof |
WO2022256283A2 (en) | 2021-06-01 | 2022-12-08 | Korro Bio, Inc. | Methods for restoring protein function using adar |
TW202317762A (zh) | 2021-06-02 | 2023-05-01 | 美商艾拉倫製藥股份有限公司 | 含有類PATATIN磷脂酶結構域3(PNPLA3)的iRNA組成物及其使用方法 |
CN117561334A (zh) | 2021-06-04 | 2024-02-13 | 阿尔尼拉姆医药品有限公司 | 人染色体9开放阅读框72(C9ORF72)iRNA药剂组合物和其使用方法 |
EP4351541A2 (en) | 2021-06-08 | 2024-04-17 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders |
CA3223192A1 (en) | 2021-06-18 | 2022-12-22 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing ifnar1 expression |
US20230194709A9 (en) | 2021-06-29 | 2023-06-22 | Seagate Technology Llc | Range information detection using coherent pulse sets with selected waveform characteristics |
EP4363574A1 (en) | 2021-06-29 | 2024-05-08 | Korro Bio, Inc. | Methods and compositions for adar-mediated editing |
CA3225469A1 (en) | 2021-06-30 | 2023-01-05 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating an angiotensinogen- (agt-) associated disorder |
EP4373934A1 (en) | 2021-07-19 | 2024-05-29 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating subjects having or at risk of developing a non-primary hyperoxaluria disease or disorder |
IL309905A (en) | 2021-07-23 | 2024-03-01 | Alnylam Pharmaceuticals Inc | IRNA compositions in β-catenin (CTNNB1) and methods of using them |
WO2023009687A1 (en) | 2021-07-29 | 2023-02-02 | Alnylam Pharmaceuticals, Inc. | 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof |
WO2023014677A1 (en) | 2021-08-03 | 2023-02-09 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna compositions and methods of use thereof |
TW202337474A (zh) | 2021-08-04 | 2023-10-01 | 美商艾拉倫製藥股份有限公司 | 用於緘默血管收縮素原(AGT)的iRNA組成物及方法 |
AR126771A1 (es) | 2021-08-13 | 2023-11-15 | Alnylam Pharmaceuticals Inc | COMPOSICIONES DE ARNi CONTRA EL FACTOR XII (F12) Y SUS MÉTODOS DE USO |
US11833221B2 (en) | 2021-09-01 | 2023-12-05 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds for reducing DMPK expression |
WO2023044370A2 (en) | 2021-09-17 | 2023-03-23 | Alnylam Pharmaceuticals, Inc. | Irna compositions and methods for silencing complement component 3 (c3) |
WO2023044094A1 (en) | 2021-09-20 | 2023-03-23 | Alnylam Pharmaceuticals, Inc. | Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof |
WO2023056329A1 (en) | 2021-09-30 | 2023-04-06 | Akouos, Inc. | Compositions and methods for treating kcnq4-associated hearing loss |
AU2022370009A1 (en) | 2021-10-22 | 2024-05-16 | Korro Bio, Inc. | Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing |
AR127477A1 (es) | 2021-10-29 | 2024-01-31 | Alnylam Pharmaceuticals Inc | COMPOSICIONES DE ARNi CONTRA EL FACTOR B DEL COMPLEMENTO (CFB) Y MÉTODOS DE USO DE LAS MISMAS |
WO2023076450A2 (en) | 2021-10-29 | 2023-05-04 | Alnylam Pharmaceuticals, Inc. | HUNTINGTIN (HTT) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF |
GB202117758D0 (en) | 2021-12-09 | 2022-01-26 | Ucl Business Ltd | Therapeutics for the treatment of neurodegenerative disorders |
WO2023122762A1 (en) | 2021-12-22 | 2023-06-29 | Camp4 Therapeutics Corporation | Modulation of gene transcription using antisense oligonucleotides targeting regulatory rnas |
WO2023141314A2 (en) | 2022-01-24 | 2023-07-27 | Alnylam Pharmaceuticals, Inc. | Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof |
WO2023177866A1 (en) | 2022-03-18 | 2023-09-21 | Dicerna Pharmaceuticals, Inc. | Decarboxylative acetoxylation using mn(ii) or mn(iii) reagent for synthesis of 4'-acetoxy- nucleoside and use thereof for synthesis of corresponding 4'-(dimethoxyphosphoryl)methoxy- nucleotide |
WO2023240277A2 (en) | 2022-06-10 | 2023-12-14 | Camp4 Therapeutics Corporation | Methods of modulating progranulin expression using antisense oligonucleotides targeting regulatory rnas |
WO2024040041A1 (en) | 2022-08-15 | 2024-02-22 | Dicerna Pharmaceuticals, Inc. | Regulation of activity of rnai molecules |
WO2024042489A1 (en) | 2022-08-25 | 2024-02-29 | LifeEDIT Therapeutics, Inc. | Chemical modification of guide rnas with locked nucleic acid for rna guided nuclease-mediated gene editing |
WO2024059165A1 (en) | 2022-09-15 | 2024-03-21 | Alnylam Pharmaceuticals, Inc. | 17b-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002516256A (ja) * | 1998-05-26 | 2002-06-04 | アイ・シー・エヌ・フアーマシユーテイカルズ・インコーポレイテツド | 二環式糖成分を有する新規ヌクレオシド |
JP2002521310A (ja) * | 1997-09-12 | 2002-07-16 | エクシコン エ/エス | オリゴヌクレオチド類似体 |
WO2003068795A1 (fr) * | 2002-02-13 | 2003-08-21 | Takeshi Imanishi | Analogues de nucleoside et derive d'oligonucleotide comprenant un analogue nucleotidique de ces composes |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
US6833361B2 (en) | 1998-05-26 | 2004-12-21 | Ribapharm, Inc. | Nucleosides having bicyclic sugar moiety |
TR200604211T1 (tr) * | 1999-02-12 | 2007-02-21 | Daiichi Sankyo Company Limiteddaiichi Sankyo Company Limited | Yeni nükleosid ve oligonükleotid analoglarıYeni nükleosid ve oligonükleotid analogları |
-
2004
- 2004-08-25 DK DK04772134.5T patent/DK1661905T3/da active
- 2004-08-25 ES ES04772134T patent/ES2382807T3/es active Active
- 2004-08-25 EP EP04772134A patent/EP1661905B9/en active Active
- 2004-08-25 JP JP2005513440A patent/JP4731324B2/ja active Active
- 2004-08-25 US US10/569,949 patent/US7427672B2/en active Active
- 2004-08-25 AT AT04772134T patent/ATE555118T1/de active
- 2004-08-25 WO PCT/JP2004/012173 patent/WO2005021570A1/ja active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002521310A (ja) * | 1997-09-12 | 2002-07-16 | エクシコン エ/エス | オリゴヌクレオチド類似体 |
JP2002516256A (ja) * | 1998-05-26 | 2002-06-04 | アイ・シー・エヌ・フアーマシユーテイカルズ・インコーポレイテツド | 二環式糖成分を有する新規ヌクレオシド |
WO2003068795A1 (fr) * | 2002-02-13 | 2003-08-21 | Takeshi Imanishi | Analogues de nucleoside et derive d'oligonucleotide comprenant un analogue nucleotidique de ces composes |
Cited By (403)
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---|---|---|---|---|
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EP2505647A1 (en) | 2006-05-05 | 2012-10-03 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of DGAT2 |
EP2397551A1 (en) | 2006-05-05 | 2011-12-21 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of PCSK9 |
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EP2363481A1 (en) | 2006-05-05 | 2011-09-07 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating gene expression |
EP2363482A1 (en) | 2006-05-05 | 2011-09-07 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating gene expression |
WO2007146511A2 (en) | 2006-05-05 | 2007-12-21 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating gene expression |
EP2410054A1 (en) | 2006-10-18 | 2012-01-25 | Isis Pharmaceuticals, Inc. | Antisense compounds |
EP2410053A1 (en) | 2006-10-18 | 2012-01-25 | Isis Pharmaceuticals, Inc. | Antisense compounds |
EP3916095A1 (en) | 2006-10-18 | 2021-12-01 | Ionis Pharmaceuticals, Inc. | Antisense compounds |
EP3202905A1 (en) | 2006-10-18 | 2017-08-09 | Ionis Pharmaceuticals, Inc. | Antisense compounds |
US9550988B2 (en) | 2006-10-18 | 2017-01-24 | Ionis Pharmaceuticals, Inc. | Antisense compounds |
US8846639B2 (en) | 2008-04-04 | 2014-09-30 | Isis Pharmaceutical, Inc. | Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity |
WO2009149182A1 (en) | 2008-06-04 | 2009-12-10 | The Board Of Regents Of The University Of Texas System | Modulation of gene expression through endogenous small rna targeting of gene promoters |
WO2010014592A1 (en) | 2008-07-29 | 2010-02-04 | The Board Of Regents Of The University Of Texas Sytem | Selective inhibition of polyglutamine protein expression |
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WO2010091308A2 (en) | 2009-02-06 | 2010-08-12 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
US8653254B2 (en) | 2009-03-31 | 2014-02-18 | Takeda Pharmaceutical Company Limited | Process for producing nucleoside |
WO2010113937A1 (ja) | 2009-03-31 | 2010-10-07 | 武田薬品工業株式会社 | ヌクレオシドの製造方法 |
JP5685526B2 (ja) * | 2009-03-31 | 2015-03-18 | 武田薬品工業株式会社 | ヌクレオシドの製造方法 |
WO2010124231A2 (en) | 2009-04-24 | 2010-10-28 | The Board Of Regents Of The University Of Texas System | Modulation of gene expression using oligomers that target gene regions downstream of 3' untranslated regions |
WO2010150789A1 (ja) | 2009-06-23 | 2010-12-29 | 武田薬品工業株式会社 | 核酸の合成法 |
WO2011010583A1 (ja) | 2009-07-22 | 2011-01-27 | 株式会社Galaxy Pharma | オリゴヌクレオチドのスクリーニング方法及びオリゴヌクレオチドライブラリー |
WO2011010706A1 (ja) | 2009-07-23 | 2011-01-27 | 武田薬品工業株式会社 | Fgf21シスエレメント結合物質 |
WO2011052436A1 (ja) | 2009-10-29 | 2011-05-05 | 国立大学法人大阪大学 | 架橋型人工ヌクレオシドおよびヌクレオチド |
US8541562B2 (en) | 2009-10-29 | 2013-09-24 | Osaka University | Bridged artificial nucleoside and nucleotide |
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WO2011053994A1 (en) | 2009-11-02 | 2011-05-05 | Alnylam Pharmaceuticals, Inc. | Modulation of ldl receptor gene expression with double-stranded rnas targeting the ldl receptor gene promoter |
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WO2011090052A1 (ja) | 2010-01-20 | 2011-07-28 | 国立大学法人 東京大学 | リン酸化試薬 |
WO2011097388A1 (en) | 2010-02-03 | 2011-08-11 | Alnylam Pharmaceuticals, Inc. | Selective inhibition of polyglutamine protein expression |
EP3561060A1 (en) | 2010-02-08 | 2019-10-30 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
WO2011097643A1 (en) | 2010-02-08 | 2011-08-11 | Isis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
EP3208347A1 (en) | 2010-02-08 | 2017-08-23 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
EP3628750A1 (en) | 2010-02-08 | 2020-04-01 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
EP3321361A1 (en) | 2010-02-08 | 2018-05-16 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
WO2011139699A2 (en) | 2010-04-28 | 2011-11-10 | Isis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
WO2011139695A2 (en) | 2010-04-28 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Modified 5' diphosphate nucleosides and oligomeric compounds prepared therefrom |
EP3173419A1 (en) | 2010-04-28 | 2017-05-31 | Ionis Pharmaceuticals, Inc. | Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom |
EP3091027A1 (en) | 2010-04-28 | 2016-11-09 | Ionis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
WO2011139702A2 (en) | 2010-04-28 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Modified nucleosides and oligomeric compounds prepared therefrom |
WO2011139917A1 (en) | 2010-04-29 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Modulation of transthyretin expression |
US11535849B2 (en) | 2010-04-29 | 2022-12-27 | Ionis Pharmaceuticals, Inc. | Modulation of transthyretin expression |
WO2011139911A2 (en) | 2010-04-29 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
US9061044B2 (en) | 2010-04-29 | 2015-06-23 | Isis Pharmaceuticals, Inc. | Modulation of transthyretin expression |
US9399774B2 (en) | 2010-04-29 | 2016-07-26 | Ionis Pharmaceuticals, Inc. | Modulation of transthyretin expression |
WO2011156278A1 (en) | 2010-06-07 | 2011-12-15 | Isis Pharmaceuticals, Inc. | Bicyclic nucleosides and oligomeric compounds prepared therefrom |
WO2011156202A1 (en) | 2010-06-08 | 2011-12-15 | Isis Pharmaceuticals, Inc. | Substituted 2 '-amino and 2 '-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom |
EP3633038A2 (en) | 2010-07-19 | 2020-04-08 | Ionis Pharmaceuticals, Inc. | Modulation of dystrophia myotonica-protein kinase (dmpk) expression |
EP3031920A1 (en) | 2010-07-19 | 2016-06-15 | Ionis Pharmaceuticals, Inc. | Modulation of dystrophia myotonica-protein kinase (dmpk) expression |
WO2012012443A2 (en) | 2010-07-19 | 2012-01-26 | Bennett C Frank | Modulation of dystrophia myotonica-protein kinase (dmpk) expression |
EP3489360A2 (en) | 2010-07-19 | 2019-05-29 | Ionis Pharmaceuticals, Inc. | Modulation of nuclear-retained rna |
WO2012029870A1 (ja) * | 2010-08-31 | 2012-03-08 | 国立大学法人大阪大学 | オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する脂質異常症治療剤 |
JP5875006B2 (ja) * | 2010-08-31 | 2016-03-02 | 国立大学法人大阪大学 | オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する脂質異常症治療剤 |
US9127280B2 (en) | 2010-08-31 | 2015-09-08 | Osaka University | Oligonucleotide, and therapeutic agent for dyslipidemia containing oligonucleotide as active ingredient |
US9556434B2 (en) | 2010-10-20 | 2017-01-31 | Rosalind Franklin University Of Medicine And Science | Antisense oligonucleotides that target a cryptic splice site in Ush1c as a therapeutic for usher syndrome |
US9150864B2 (en) | 2010-11-08 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Methods for modulating factor 12 expression |
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WO2012068405A2 (en) | 2010-11-17 | 2012-05-24 | Isis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
US9663783B2 (en) | 2010-11-17 | 2017-05-30 | Ionis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
EP3067421A1 (en) | 2011-02-08 | 2016-09-14 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
WO2012109395A1 (en) | 2011-02-08 | 2012-08-16 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
US10017764B2 (en) | 2011-02-08 | 2018-07-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
EP3467109A1 (en) | 2011-02-08 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
EP3466960A2 (en) | 2011-04-01 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Modulation of signal transducer and activator of transcription 3 (stat3) expression |
WO2012142458A1 (en) | 2011-04-13 | 2012-10-18 | Isis Pharmaceuticals, Inc. | Antisense modulation of ptp1b expression |
EP3816288A2 (en) | 2011-04-21 | 2021-05-05 | Glaxo Group Limited | Modulation of hepatitis b virus (hbv) expression |
EP3312189A1 (en) | 2011-04-21 | 2018-04-25 | Ionis Pharmaceuticals, Inc. | Modulation of hepatitis b virus (hbv) expression |
EP3505528A1 (en) | 2011-04-21 | 2019-07-03 | Ionis Pharmaceuticals, Inc. | Modulation of hepatitis b virus (hbv) expression |
EP3357497A1 (en) | 2011-04-27 | 2018-08-08 | Ionis Pharmaceuticals, Inc. | Modulation of apolipoprotein ciii (apociii) expression |
WO2012149495A1 (en) | 2011-04-27 | 2012-11-01 | Isis Pharmaceuticals, Inc. | Modulation of apolipoprotein ciii (apociii) expression |
US9353371B2 (en) | 2011-05-02 | 2016-05-31 | Ionis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with usher syndrome |
WO2012170347A1 (en) | 2011-06-09 | 2012-12-13 | Isis Pharmaceuticals, Inc. | Bicyclic nucleosides and oligomeric compounds prepared therefrom |
EP3320922A1 (en) | 2011-06-10 | 2018-05-16 | Ionis Pharmaceuticals, Inc. | Methods for modulating kallikrein (klkb1) expression |
US9187749B2 (en) | 2011-06-10 | 2015-11-17 | Isis Pharmaceuticals, Inc. | Methods for modulating factor 12 expression |
US9315811B2 (en) | 2011-06-10 | 2016-04-19 | Ionis Pharmaceuticals, Inc. | Methods for modulating kallikrein (KLKB1) expression |
WO2012174476A2 (en) | 2011-06-16 | 2012-12-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of fibroblast growth factor receptor 4 expression |
US9322021B2 (en) | 2011-06-29 | 2016-04-26 | Ionis Pharmaceuticals, Inc. | Methods for modulating kallikrein (KLKB1) expression |
WO2013003808A1 (en) | 2011-06-29 | 2013-01-03 | Isis Pharmaceuticals, Inc. | Methods for modulating kallikrein (klkb1) expression |
WO2013022967A1 (en) | 2011-08-11 | 2013-02-14 | Isis Pharmaceuticals, Inc. | Gapped oligomeric compounds comprising 5'-modified deoxyribonucleosides in the gap and uses thereof |
EP3556859A1 (en) | 2011-08-11 | 2019-10-23 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
US9752142B2 (en) | 2011-08-11 | 2017-09-05 | Ionis Pharmaceuticals, Inc. | Gapped oligomeric compounds comprising 5′-modified deoxyribonucleosides in the gap and uses thereof |
WO2013022966A1 (en) | 2011-08-11 | 2013-02-14 | Isis Pharmaceuticals, Inc. | Linkage modified gapped oligomeric compounds and uses thereof |
US11732261B2 (en) | 2011-08-11 | 2023-08-22 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
EP3205725A1 (en) | 2011-08-11 | 2017-08-16 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
EP4269584A2 (en) | 2011-08-11 | 2023-11-01 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
US10202599B2 (en) | 2011-08-11 | 2019-02-12 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
EP3922722A1 (en) | 2011-08-11 | 2021-12-15 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
US9976138B2 (en) | 2011-08-29 | 2018-05-22 | Ionis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
EP3453761A1 (en) | 2011-08-29 | 2019-03-13 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
US10023861B2 (en) | 2011-08-29 | 2018-07-17 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
EP3640332A1 (en) | 2011-08-29 | 2020-04-22 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
WO2013043817A1 (en) | 2011-09-20 | 2013-03-28 | Isis Phamaceuticals, Inc. | Antisense modulation of gcgr expression |
US9404114B2 (en) | 2011-09-20 | 2016-08-02 | Ionis Pharmaceuticals, Inc. | Antisense modulation of GCGR expression |
EP3401401A1 (en) | 2011-09-20 | 2018-11-14 | Ionis Pharmaceuticals, Inc. | Antisense modulation of gcgr expression |
US8865674B2 (en) | 2011-09-20 | 2014-10-21 | Isis Pharmaceuticals, Inc. | Antisense modulation of GCGR expression |
WO2013063313A1 (en) | 2011-10-25 | 2013-05-02 | Isis Pharmaceuticals, Inc. | Antisense modulation of gccr expression |
EP3650544A1 (en) | 2011-11-07 | 2020-05-13 | Ionis Pharmaceuticals, Inc. | Modulation of tmprss6 expression |
US9725722B2 (en) | 2011-11-07 | 2017-08-08 | Ionis Pharmaceuticals, Inc. | Modulation of TMPRSS6 expression |
WO2013070786A1 (en) | 2011-11-07 | 2013-05-16 | Isis Pharmaceuticals, Inc. | Modulation of tmprss6 expression |
US9816089B2 (en) | 2011-12-16 | 2017-11-14 | National University Corporation Tokyo Medical And Dental University | Chimeric double-stranded nucleic acid |
US11034955B2 (en) | 2011-12-16 | 2021-06-15 | National University Corporation Tokyo Medical And Dental University | Chimeric double-stranded nucleic acid |
US10337006B2 (en) | 2011-12-16 | 2019-07-02 | Osaka University | Chimeric double-stranded nucleic acid |
US10329567B2 (en) | 2011-12-16 | 2019-06-25 | Osaka University | Chimeric double-stranded nucleic acid |
US9546368B2 (en) | 2011-12-22 | 2017-01-17 | Ionis Pharmaceuticals, Inc. | Methods for modulating metastasis-associated-in-lung-adenocarcinoma-transcript-1 (MALAT-1) expression |
WO2013096837A1 (en) | 2011-12-22 | 2013-06-27 | Isis Pharmaceuticals, Inc. | Methods for modulating metastasis-associated-in-lung-adenocarcinoma-transcript-1(malat-1) expression |
WO2013106770A1 (en) | 2012-01-11 | 2013-07-18 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulation of ikbkap splicing |
US11066668B2 (en) | 2012-01-11 | 2021-07-20 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of IKBKAP splicing |
EP3330278A1 (en) | 2012-02-08 | 2018-06-06 | Ionis Pharmaceuticals, Inc. | Modulation of rna by repeat targeting |
WO2013120003A1 (en) | 2012-02-08 | 2013-08-15 | Isis Pharmaceuticals, Inc. | Modulation of rna by repeat targeting |
US9340784B2 (en) | 2012-03-19 | 2016-05-17 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating alpha-1-antitrypsin expression |
US10273474B2 (en) | 2012-03-30 | 2019-04-30 | Washington University | Methods for modulating Tau expression for reducing seizure and modifying a neurodegenerative syndrome |
US11781135B2 (en) | 2012-03-30 | 2023-10-10 | Washington University | Methods for treating Alzheimer's disease |
US9221864B2 (en) | 2012-04-09 | 2015-12-29 | Isis Pharmaceuticals, Inc. | Tricyclic nucleic acid analogs |
WO2013154799A1 (en) | 2012-04-09 | 2013-10-17 | Isis Pharmaceuticals, Inc. | Tricyclic nucleosides and oligomeric compounds prepared therefrom |
WO2013154798A1 (en) | 2012-04-09 | 2013-10-17 | Isis Pharmaceuticals, Inc. | Tricyclic nucleic acid analogs |
EP3336189A1 (en) | 2012-04-20 | 2018-06-20 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
US9914922B2 (en) | 2012-04-20 | 2018-03-13 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
US11566245B2 (en) | 2012-04-20 | 2023-01-31 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
US9574193B2 (en) | 2012-05-17 | 2017-02-21 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein (a) expression |
US11859180B2 (en) | 2012-05-17 | 2024-01-02 | Ionis Pharmaceuticals, Inc. | Antisense oligonucleotide compositions |
US11634711B2 (en) | 2012-05-17 | 2023-04-25 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein (a) expression |
WO2013177248A2 (en) | 2012-05-22 | 2013-11-28 | Isis Pharmaceuticals, Inc. | Modulation of enhancer rna mediated gene expression |
US9518261B2 (en) | 2012-05-22 | 2016-12-13 | Ionis Pharmaceuticals, Inc. | Modulation of enhancer RNA mediated gene expression |
EP3822352A2 (en) | 2012-05-24 | 2021-05-19 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein(a) expression |
EP3825403A2 (en) | 2012-05-24 | 2021-05-26 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein(a) expression |
WO2013177468A2 (en) | 2012-05-24 | 2013-11-28 | Isis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein(a) expression |
US9828602B2 (en) | 2012-06-01 | 2017-11-28 | Ionis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with fibronectin |
US9487780B2 (en) | 2012-06-01 | 2016-11-08 | Ionis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with fibronectin |
EP3770258A1 (en) | 2012-06-25 | 2021-01-27 | Ionis Pharmaceuticals, Inc. | Modulation of ube3a-ats expression |
EP3461895A1 (en) | 2012-06-25 | 2019-04-03 | Ionis Pharmaceuticals, Inc. | Modulation of ube3a-ats expression |
US9617539B2 (en) | 2012-06-25 | 2017-04-11 | Ionis Pharmaceuticals, Inc. | Modulation of UBE3A-ATS expression |
WO2014004572A2 (en) | 2012-06-25 | 2014-01-03 | Isis Pharmaceuticals, Inc. | Modulation of ube3a-ats expression |
WO2014018930A1 (en) | 2012-07-27 | 2014-01-30 | Isis Pharmaceuticals. Inc. | Modulation of renin-angiotensin system (ras) related diseases by angiotensinogen |
EP3693460A1 (en) | 2012-07-27 | 2020-08-12 | Ionis Pharmaceuticals, Inc. | Modulation of renin-angiotensin system (ras) related diseases by angiotensinogen |
US9403865B2 (en) | 2012-08-15 | 2016-08-02 | Ionis Pharmaceuticals, Inc. | Method of preparing oligomeric compounds using modified capping protocols |
WO2014045126A2 (en) | 2012-09-18 | 2014-03-27 | Uti Limited Partnership | Treatment of pain by inhibition of usp5 de-ubiquitinase |
KR20150056647A (ko) | 2012-09-21 | 2015-05-26 | 고꾸리쯔 다이가꾸 호우징 오사까 다이가꾸 | 구아니딘 가교를 갖는 인공 뉴클레오시드 및 올리고뉴클레오티드 |
WO2014046212A1 (ja) | 2012-09-21 | 2014-03-27 | 国立大学法人大阪大学 | グアニジン架橋を有する人工ヌクレオシドおよびオリゴヌクレオチド |
WO2014051076A1 (ja) | 2012-09-28 | 2014-04-03 | 株式会社Bna | Bnaクランプ法 |
US9175291B2 (en) | 2012-10-11 | 2015-11-03 | Isis Pharmaceuticals Inc. | Modulation of androgen receptor expression |
EP4052709A1 (en) | 2012-10-11 | 2022-09-07 | Ionis Pharmaceuticals, Inc. | Methods of treating kennedy's disease |
US9695418B2 (en) | 2012-10-11 | 2017-07-04 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleosides and uses thereof |
WO2014059238A2 (en) | 2012-10-11 | 2014-04-17 | Isis Pharmaceuticals Inc | Modulation of androgen receptor expression |
US9523094B2 (en) | 2012-10-11 | 2016-12-20 | Ionis Pharmaceuticals, Inc. | Methods of treating kennedy's disease |
EP3459549A1 (en) | 2012-10-12 | 2019-03-27 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
WO2014059356A2 (en) | 2012-10-12 | 2014-04-17 | Isis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
WO2014059341A2 (en) | 2012-10-12 | 2014-04-17 | Isis Pharmaceuticals, Inc. | Antisense compounds and uses thereof |
US11236335B2 (en) | 2012-10-12 | 2022-02-01 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
EP4144845A1 (en) | 2012-10-12 | 2023-03-08 | Ionis Pharmaceuticals, Inc. | Antisense compounds and uses thereof |
EP4086347A2 (en) | 2012-10-12 | 2022-11-09 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
WO2014062686A1 (en) | 2012-10-15 | 2014-04-24 | Isis Pharmaceuticals, Inc. | Methods for modulating c9orf72 expression |
US9963699B2 (en) | 2012-10-15 | 2018-05-08 | Ionis Pharmaceuticals, Inc. | Methods for modulating C9ORF72 expression |
US10443052B2 (en) | 2012-10-15 | 2019-10-15 | Ionis Pharmaceuticals, Inc. | Compositions for modulating C9ORF72 expression |
US10577604B2 (en) | 2012-10-15 | 2020-03-03 | Ionis Pharmaceuticals, Inc. | Methods for monitoring C9ORF72 expression |
US9029335B2 (en) | 2012-10-16 | 2015-05-12 | Isis Pharmaceuticals, Inc. | Substituted 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom |
WO2014070868A1 (en) | 2012-10-31 | 2014-05-08 | Isis Pharmaceuticals Inc | Cancer treatment |
EP3483273A1 (en) | 2012-10-31 | 2019-05-15 | Ionis Pharmaceuticals, Inc. | Cancer treatment |
EP3406718A1 (en) | 2012-11-15 | 2018-11-28 | Roche Innovation Center Copenhagen A/S | Oligonucleotide conjugates |
WO2014076195A1 (en) | 2012-11-15 | 2014-05-22 | Santaris Pharma A/S | Oligonucleotide conjugates |
US11155816B2 (en) | 2012-11-15 | 2021-10-26 | Roche Innovation Center Copenhagen A/S | Oligonucleotide conjugates |
WO2014076196A1 (en) | 2012-11-15 | 2014-05-22 | Santaris Pharma A/S | Anti apob antisense conjugate compounds |
US10077443B2 (en) | 2012-11-15 | 2018-09-18 | Roche Innovation Center Copenhagen A/S | Oligonucleotide conjugates |
WO2014080004A1 (en) | 2012-11-26 | 2014-05-30 | Santaris Pharma A/S | Compositions and methods for modulation of fgfr3 expression |
US9695475B2 (en) | 2012-12-11 | 2017-07-04 | Ionis Pharmaceuticals, Inc. | Competitive modulation of microRNAs |
JPWO2014112463A1 (ja) * | 2013-01-15 | 2017-01-19 | 国立大学法人大阪大学 | スルホンアミド構造を有するヌクレオシドおよびヌクレオチド |
WO2014112463A1 (ja) * | 2013-01-15 | 2014-07-24 | 国立大学法人大阪大学 | スルホンアミド構造を有するヌクレオシドおよびヌクレオチド |
WO2014118272A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Antimir-122 oligonucleotide carbohydrate conjugates |
WO2014118267A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Lna oligonucleotide carbohydrate conjugates |
US9701708B2 (en) | 2013-01-31 | 2017-07-11 | Ionis Pharmaceuticals, Inc. | Method of preparing oligomeric compounds using modified coupling protocols |
EP3778618A1 (en) | 2013-02-04 | 2021-02-17 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
EP3400947A1 (en) | 2013-02-14 | 2018-11-14 | Ionis Pharmaceuticals, Inc. | Modulation of apolipoprotein c-iii (apociii) expression in lipoprotein lipase deficient (lpld) populations |
US9593333B2 (en) | 2013-02-14 | 2017-03-14 | Ionis Pharmaceuticals, Inc. | Modulation of apolipoprotein C-III (ApoCIII) expression in lipoprotein lipase deficient (LPLD) populations |
WO2014126229A1 (ja) | 2013-02-18 | 2014-08-21 | 塩野義製薬株式会社 | 含窒素複素環構造を有するヌクレオシド及びヌクレオチド |
US9315535B2 (en) | 2013-02-18 | 2016-04-19 | Shionogi & Co., Ltd. | Nucleoside and nucleotide having nitrogen-containing heterocycle structure |
JPWO2014126229A1 (ja) * | 2013-02-18 | 2017-02-02 | 塩野義製薬株式会社 | 含窒素複素環構造を有するヌクレオシド及びヌクレオチド |
WO2014134179A1 (en) | 2013-02-28 | 2014-09-04 | The Board Of Regents Of The University Of Texas System | Methods for classifying a cancer as susceptible to tmepai-directed therapies and treating such cancers |
WO2014132671A1 (en) | 2013-03-01 | 2014-09-04 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
US10844374B2 (en) | 2013-03-01 | 2020-11-24 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
US11155815B2 (en) | 2013-03-14 | 2021-10-26 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating Tau expression |
EP3766974A1 (en) | 2013-03-14 | 2021-01-20 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating tau expression |
US9644207B2 (en) | 2013-03-14 | 2017-05-09 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating Tau expression |
WO2014153236A1 (en) | 2013-03-14 | 2014-09-25 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating tau expression |
US10590412B2 (en) | 2013-04-19 | 2020-03-17 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation nucleic acids through nonsense mediated decay |
US9127276B2 (en) | 2013-05-01 | 2015-09-08 | Isis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
US9181550B2 (en) | 2013-05-01 | 2015-11-10 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein (a) expression |
WO2014179627A2 (en) | 2013-05-01 | 2014-11-06 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating hbv and ttr expression |
US9163239B2 (en) | 2013-05-01 | 2015-10-20 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein C-III expression |
EP3524680A1 (en) | 2013-05-01 | 2019-08-14 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating ttr expression |
US11851655B2 (en) | 2013-05-01 | 2023-12-26 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein (a) expression |
EP3690049A1 (en) | 2013-05-01 | 2020-08-05 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein c-iii expression |
US9145558B2 (en) | 2013-05-01 | 2015-09-29 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating HBV expression |
WO2014179625A1 (en) | 2013-05-01 | 2014-11-06 | Isis Pharmaceuticals, Inc. | COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION |
WO2014179629A2 (en) | 2013-05-01 | 2014-11-06 | Isis Pharmaceuticals, Inc. | Compositions and methods |
US9957504B2 (en) | 2013-05-01 | 2018-05-01 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein (a) expression |
US11299736B1 (en) | 2013-05-01 | 2022-04-12 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
US9932580B2 (en) | 2013-05-01 | 2018-04-03 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating HBV expression |
US9932581B2 (en) | 2013-05-01 | 2018-04-03 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein C-III expression |
US9181549B2 (en) | 2013-05-01 | 2015-11-10 | Isis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
EP3828275A1 (en) | 2013-05-01 | 2021-06-02 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating ttr expression |
US10883104B2 (en) | 2013-05-01 | 2021-01-05 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein (a) expression |
US10683499B2 (en) | 2013-05-01 | 2020-06-16 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating TTR expression |
US9714421B2 (en) | 2013-05-01 | 2017-07-25 | Ionis Pharmaceuticals, Inc. | Compositions and methods |
WO2014179626A2 (en) | 2013-05-01 | 2014-11-06 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein c-iii expression |
EP3633039A1 (en) | 2013-05-01 | 2020-04-08 | Ionis Pharmaceuticals, Inc. | Compositions and methods |
WO2014192310A1 (en) | 2013-05-30 | 2014-12-04 | National University Corporation Tokyo Medical And Dental University | Double-stranded agents for delivering therapeutic oligonucleotides |
US11028387B2 (en) | 2013-05-30 | 2021-06-08 | National University Corporation Tokyo Medical And Dental University | Double-stranded agents for delivering therapeutic oligonucleotides |
US10190117B2 (en) | 2013-06-16 | 2019-01-29 | National University Corporation Tokyo Medical And Dental University | Double-stranded antisense nucleic acid with exon-skipping effect |
US9909124B2 (en) | 2013-06-21 | 2018-03-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating apolipoprotein C-III expression for improving a diabetic profile |
WO2014205449A2 (en) | 2013-06-21 | 2014-12-24 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile |
WO2014205451A2 (en) | 2013-06-21 | 2014-12-24 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
EP3656386A1 (en) | 2013-06-21 | 2020-05-27 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile |
EP3564374A1 (en) | 2013-06-21 | 2019-11-06 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
EP3730619A1 (en) | 2013-06-21 | 2020-10-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
EP3591054A1 (en) | 2013-06-27 | 2020-01-08 | Roche Innovation Center Copenhagen A/S | Antisense oligomers and conjugates targeting pcsk9 |
EP3730614A2 (en) | 2013-07-02 | 2020-10-28 | Ionis Pharmaceuticals, Inc. | Modulators of growth hormone receptor |
WO2015002971A2 (en) | 2013-07-02 | 2015-01-08 | Isis Pharmaceuticals, Inc. | Modulators of growth hormone receptor |
US9683235B2 (en) | 2013-07-19 | 2017-06-20 | Ionis Pharmaceuticals, Inc. | Compositions for modulating Tau expression |
WO2015010135A2 (en) | 2013-07-19 | 2015-01-22 | Isis Pharmaceuticals, Inc. | Compositions for modulating tau expression |
EP3910060A1 (en) | 2013-07-19 | 2021-11-17 | Biogen MA Inc. | Compositions for modulating tau expression |
US11591595B2 (en) | 2013-07-19 | 2023-02-28 | Biogen Ma Inc. | Compositions for modulating Tau expression |
US10793856B2 (en) | 2013-07-19 | 2020-10-06 | Biogen Ma Inc. | Compositions for modulating Tau expression |
US10435430B2 (en) | 2013-07-31 | 2019-10-08 | Ionis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
US10626138B2 (en) | 2013-08-08 | 2020-04-21 | The Scripps Research Institute National Institutes Of Health (Nih), U.S. Dept Of Health And Human Services (Dhhs) | Method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides |
US11634451B2 (en) | 2013-08-08 | 2023-04-25 | The Scripps Research Institute | Method for the site-specific enzymatic labelling of nucleic acids in vitro by incorporation of unnatural nucleotides |
WO2015021457A2 (en) | 2013-08-09 | 2015-02-12 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulation of dystrophia myotonica-protein kinase (dmpk) expression |
EP3995580A2 (en) | 2013-08-09 | 2022-05-11 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulation of dystrophia myotonica-protein kinase (dmpk) expression |
US11840686B2 (en) | 2013-08-28 | 2023-12-12 | Ionis Pharmaceuticals, Inc. | Modulation of prekallikrein (PKK) expression |
EP3715457A2 (en) | 2013-08-28 | 2020-09-30 | Ionis Pharmaceuticals, Inc. | Modulation of prekallikrein (pkk) expression |
US9670492B2 (en) | 2013-08-28 | 2017-06-06 | Ionis Pharmaceuticals, Inc. | Modulation of prekallikrein (PKK) expression |
US11053500B2 (en) | 2013-08-28 | 2021-07-06 | lonis Pharmaceuticals, Inc. | Modulation of prekallikrein (PKK) expression |
WO2015031679A2 (en) | 2013-08-28 | 2015-03-05 | Isis Pharmaceuticals, Inc. | Modulation of prekallikrein (pkk) expression |
US9943604B2 (en) | 2013-09-20 | 2018-04-17 | Ionis Pharmaceuticals, Inc. | Targeted therapeutic nucleosides and their use |
US10221414B2 (en) | 2013-10-11 | 2019-03-05 | Ionis Pharmaceuticals, Inc. | Compositions for modulating C9ORF72 expression |
EP4166667A2 (en) | 2013-10-11 | 2023-04-19 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
US11339393B2 (en) | 2013-10-11 | 2022-05-24 | Ionis Pharmaceuticals, Inc. | Compositions for modulating C9ORF72 expression |
US9758546B2 (en) | 2013-10-21 | 2017-09-12 | Ionis Pharmaceuticals, Inc. | Method for solution phase detritylation of oligomeric compounds |
EP3750997A1 (en) | 2013-12-02 | 2020-12-16 | Ionis Pharmaceuticals, Inc. | Antisense compounds and uses thereof |
EP3770259A1 (en) | 2013-12-24 | 2021-01-27 | Ionis Pharmaceuticals, Inc. | Modulation of angiopoietin-like 3 expression |
US11118183B2 (en) | 2013-12-24 | 2021-09-14 | Ionis Pharmaceuticals, Inc. | Modulation of angiopoietin-like 3 expression |
WO2015100394A1 (en) | 2013-12-24 | 2015-07-02 | Isis Pharmaceuticals, Inc. | Modulation of angiopoietin-like 3 expression |
JPWO2015125783A1 (ja) * | 2014-02-18 | 2017-03-30 | 国立大学法人大阪大学 | 架橋型ヌクレオシドおよびヌクレオチド |
WO2015125783A1 (ja) * | 2014-02-18 | 2015-08-27 | 国立大学法人大阪大学 | 架橋型ヌクレオシドおよびヌクレオチド |
US10036019B2 (en) | 2014-03-17 | 2018-07-31 | Ionis Pharmaceuticals, Inc. | Bicyclic carbocyclic nucleosides and oligomeric compounds prepared therefrom |
EP3978610A2 (en) | 2014-03-19 | 2022-04-06 | Ionis Pharmaceuticals, Inc. | Compositions for modulating ataxin 2 expression |
WO2015143246A1 (en) | 2014-03-19 | 2015-09-24 | Isis Pharmaceuticals, Inc. | Compositions for modulating ataxin 2 expression |
EP3757214A1 (en) | 2014-04-01 | 2020-12-30 | Biogen MA Inc. | Compositions for modulating sod-1 expression |
WO2015153800A2 (en) | 2014-04-01 | 2015-10-08 | Isis Pharmaceuticals, Inc. | Compositions for modulating sod-1 expression |
EP4137573A2 (en) | 2014-04-01 | 2023-02-22 | Biogen MA Inc. | Compositions for modulating sod-1 expression |
EP3943607A1 (en) | 2014-04-09 | 2022-01-26 | The Scripps Research Institute | Import of unnatural or modified nucleoside triphosphates into cells via nucleic acid triphosphate transporters |
US11466279B2 (en) | 2014-04-09 | 2022-10-11 | The Scripps Research Institute | Import of unnatural or modified nucleoside triphosphates into cells via nucleic acid triphosphate transporters |
US10513706B2 (en) | 2014-04-09 | 2019-12-24 | The Scripps Research Institute | Import of unnatural or modified nucleoside triphosphates into cells via nucleic acid triphosphate transporters |
WO2015164693A1 (en) | 2014-04-24 | 2015-10-29 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising alpha-beta-constrained nucleic acid |
US10221416B2 (en) | 2014-04-24 | 2019-03-05 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising alpha-beta-constrained nucleic acid |
EP3647318A1 (en) | 2014-04-28 | 2020-05-06 | Ionis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
US9926556B2 (en) | 2014-04-28 | 2018-03-27 | Ionis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
WO2015168172A1 (en) | 2014-04-28 | 2015-11-05 | Isis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
US10294477B2 (en) | 2014-05-01 | 2019-05-21 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating PKK expression |
US11732265B2 (en) | 2014-05-01 | 2023-08-22 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating complement factor B expression |
EP3974534A1 (en) | 2014-05-01 | 2022-03-30 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating growth hormone receptor expression |
US9994855B2 (en) | 2014-05-01 | 2018-06-12 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating growth hormone receptor expression |
EP4219718A2 (en) | 2014-05-01 | 2023-08-02 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating complement factor b expression |
US11312964B2 (en) | 2014-05-01 | 2022-04-26 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating growth hormone receptor expression |
EP3862362A2 (en) | 2014-05-01 | 2021-08-11 | Ionis Pharmaceuticals, Inc. | Conjugates of modified antisense oligonucleotides and their use for modulating pkk expression |
US9382540B2 (en) | 2014-05-01 | 2016-07-05 | Isis Pharmaceuticals, Inc | Compositions and methods for modulating angiopoietin-like 3 expression |
US10280423B2 (en) | 2014-05-01 | 2019-05-07 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating complement factor B expression |
US10793862B2 (en) | 2014-05-01 | 2020-10-06 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating growth hormone receptor expression |
US10875884B2 (en) | 2014-05-01 | 2020-12-29 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
EP3757215A2 (en) | 2014-05-01 | 2020-12-30 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating growth hormone receptor expression |
US9957292B2 (en) | 2014-05-01 | 2018-05-01 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
EP3845547A1 (en) | 2014-05-01 | 2021-07-07 | Ionis Pharmaceuticals, Inc. | Galnac3 conjugated modified oligonucleotide for modulating angiopoietin-like 3 expression |
EP3811977A1 (en) | 2014-05-01 | 2021-04-28 | Ionis Pharmaceuticals, Inc. | Method for synthesis of reactive conjugate clusters |
EP3608406A1 (en) | 2014-05-01 | 2020-02-12 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating complement factor b expression |
WO2015168589A2 (en) | 2014-05-01 | 2015-11-05 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
EP4223315A2 (en) | 2014-05-01 | 2023-08-09 | Ionis Pharmaceuticals, Inc. | Method for synthesis of reactive conjugate clusters |
US11613752B2 (en) | 2014-05-01 | 2023-03-28 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating PKK expression |
WO2015168618A2 (en) | 2014-05-01 | 2015-11-05 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating growth hormone receptor expression |
US10570169B2 (en) | 2014-05-22 | 2020-02-25 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
US10364433B2 (en) | 2014-11-14 | 2019-07-30 | The Regents Of The University Of California | Modulation of AGPAT5 expression |
US10400243B2 (en) | 2014-11-25 | 2019-09-03 | Ionis Pharmaceuticals, Inc. | Modulation of UBE3A-ATS expression |
EP4088741A1 (en) | 2014-12-08 | 2022-11-16 | The Board of Regents of the University of Texas System | Lipocationic polymers and uses thereof |
WO2016094342A1 (en) | 2014-12-08 | 2016-06-16 | The Board Of Regents Of The University Of Texas System | Lipocationic polymers and uses thereof |
WO2016100716A1 (en) | 2014-12-18 | 2016-06-23 | Vasant Jadhav | Reversirtm compounds |
US9688707B2 (en) | 2014-12-30 | 2017-06-27 | Ionis Pharmaceuticals, Inc. | Bicyclic morpholino compounds and oligomeric compounds prepared therefrom |
WO2016138353A1 (en) | 2015-02-26 | 2016-09-01 | Ionis Pharmaceuticals, Inc. | Allele specific modulators of p23h rhodopsin |
WO2016141236A1 (en) | 2015-03-03 | 2016-09-09 | Ionis Pharmaceuticals, Inc. | Compositions for modulating mecp2 expression |
EP4056703A1 (en) | 2015-03-03 | 2022-09-14 | Ionis Pharmaceuticals, Inc. | Methods for modulating mecp2 expression |
US10415038B2 (en) | 2015-04-03 | 2019-09-17 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating TMPRSS6 expression |
US9605263B2 (en) | 2015-04-16 | 2017-03-28 | Ionis Pharmaceuticals, Inc. | Compositions for modulating C9ORF72 expression |
WO2016168592A2 (en) | 2015-04-16 | 2016-10-20 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
EP3722424A1 (en) | 2015-04-16 | 2020-10-14 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
WO2017004261A1 (en) | 2015-06-29 | 2017-01-05 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
EP4092119A2 (en) | 2015-07-10 | 2022-11-23 | Ionis Pharmaceuticals, Inc. | Modulators of diacyglycerol acyltransferase 2 (dgat2) |
WO2017015109A1 (en) | 2015-07-17 | 2017-01-26 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
EP3919619A1 (en) | 2015-07-17 | 2021-12-08 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
KR20180052722A (ko) | 2015-09-14 | 2018-05-18 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 지질양이온성 덴드리머 및 이의 용도 |
EP3950003A1 (en) | 2015-09-14 | 2022-02-09 | The Board of Regents of the University of Texas System | Lipocationic dendrimers and uses thereof |
WO2017048789A1 (en) | 2015-09-14 | 2017-03-23 | The Board Of Regents Of The University Of Texas System | Lipocationic dendrimers and uses thereof |
KR20240027890A (ko) | 2015-09-14 | 2024-03-04 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 지질양이온성 덴드리머 및 이의 용도 |
JPWO2017047097A1 (ja) * | 2015-09-18 | 2018-07-05 | 国立大学法人 東京大学 | 構造強化されたmiRNA阻害剤S−TuD |
JP2022033869A (ja) * | 2015-09-18 | 2022-03-02 | 田辺三菱製薬株式会社 | 架橋型核酸GuNA、その製造方法および中間体化合物 |
US10961269B2 (en) | 2015-09-18 | 2021-03-30 | Mitsubishi Tanabe Pharma Corporation | Bridged nucleic acid GuNA, method for producing same, and intermediate compound |
WO2017047816A1 (ja) * | 2015-09-18 | 2017-03-23 | 田辺三菱製薬株式会社 | 架橋型核酸GuNA、その製造方法および中間体化合物 |
WO2017047097A1 (ja) * | 2015-09-18 | 2017-03-23 | 国立大学法人 東京大学 | 構造強化されたmiRNA阻害剤S-TuD |
JPWO2017047816A1 (ja) * | 2015-09-18 | 2018-07-05 | 田辺三菱製薬株式会社 | 架橋型核酸GuNA、その製造方法および中間体化合物 |
US10844376B2 (en) | 2015-09-18 | 2020-11-24 | University Of Tokyo | Structurally-enhanced miRNA inhibitor S-TuD |
EP3974436A1 (en) | 2015-09-18 | 2022-03-30 | Mitsubishi Tanabe Pharma Corporation | Crosslinked nucleic acid guna method for producing same, and intermediate compound |
JP6994197B2 (ja) | 2015-09-18 | 2022-01-14 | 田辺三菱製薬株式会社 | 架橋型核酸GuNA、その製造方法および中間体化合物 |
WO2017053722A1 (en) | 2015-09-24 | 2017-03-30 | Ionis Pharmaceuticals, Inc. | Modulators of kras expression |
US10912792B2 (en) | 2015-10-08 | 2021-02-09 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
US11260073B2 (en) | 2015-11-02 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating C90RF72 |
US11319536B2 (en) | 2015-11-06 | 2022-05-03 | Ionis Pharmacueticals, Inc. | Modulating apolipoprotein (a) expression |
US10557137B2 (en) | 2015-11-06 | 2020-02-11 | Ionis Pharmaceuticals, Inc. | Modulating apolipoprotein (a) expression |
US11761007B2 (en) | 2015-12-18 | 2023-09-19 | The Scripps Research Institute | Production of unnatural nucleotides using a CRISPR/Cas9 system |
US11530409B2 (en) | 2016-01-26 | 2022-12-20 | Nissan Chemical Corporation | Single-stranded oligonucleotide |
WO2017142054A1 (ja) | 2016-02-17 | 2017-08-24 | 国立大学法人東京工業大学 | 人工ヌクレオシド及び人工ヌクレオチド並びに人工オリゴヌクレオチド |
WO2017201076A1 (en) | 2016-05-16 | 2017-11-23 | The Board Of Regents Of The University Of Texas System | Cationic sulfonamide amino lipids and amphiphilic zwitterionic amino lipids |
US10696719B2 (en) | 2016-06-24 | 2020-06-30 | The Scripps Research Institute | Nucleoside triphosphate transporter and uses thereof |
WO2017223528A1 (en) | 2016-06-24 | 2017-12-28 | The Scripps Research Institute | Novel nucleoside triphosphate transporter and uses thereof |
US11834479B2 (en) | 2016-06-24 | 2023-12-05 | The Scripps Research Institute | Nucleoside triphosphate transporter and uses thereof |
US10696720B2 (en) | 2016-06-24 | 2020-06-30 | The Scripps Research Institute | Nucleoside triphosphate transporter and uses thereof |
EP4163293A1 (en) | 2016-06-24 | 2023-04-12 | The Scripps Research Institute | Novel nucleoside triphosphate transporter and uses thereof |
US11053498B2 (en) | 2016-09-29 | 2021-07-06 | Biogen Ma Inc. | Compounds and methods for reducing Tau expression |
US10407680B2 (en) | 2016-09-29 | 2019-09-10 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing Tau expression |
US11400161B2 (en) | 2016-10-06 | 2022-08-02 | Ionis Pharmaceuticals, Inc. | Method of conjugating oligomeric compounds |
WO2018143475A1 (ja) | 2017-02-06 | 2018-08-09 | 日産化学工業株式会社 | 一本鎖オリゴヌクレオチド |
US11572558B2 (en) | 2017-02-06 | 2023-02-07 | Nissan Chemical Corporation | Single-stranded oligonucleotide |
US11479769B2 (en) | 2017-03-17 | 2022-10-25 | National University Corporation Chiba University | Technique for treating cancer using structurally-reinforced S-TuD |
JP7306653B2 (ja) | 2017-03-17 | 2023-07-11 | 国立大学法人千葉大学 | 構造強化されたS-TuDを用いた新規がん治療法 |
CN110650742A (zh) * | 2017-03-17 | 2020-01-03 | 国立大学法人千叶大学 | 使用经结构强化的S-TuD的新的癌症治疗方法 |
WO2018169063A1 (ja) * | 2017-03-17 | 2018-09-20 | 国立大学法人千葉大学 | 構造強化されたS-TuDを用いた新規がん治療法 |
JPWO2018169063A1 (ja) * | 2017-03-17 | 2020-01-23 | 国立大学法人千葉大学 | 構造強化されたS−TuDを用いた新規がん治療法 |
WO2018181428A1 (ja) | 2017-03-29 | 2018-10-04 | 塩野義製薬株式会社 | 核酸医薬及び多分岐脂質の複合体 |
US11834689B2 (en) | 2017-07-11 | 2023-12-05 | The Scripps Research Institute | Incorporation of unnatural nucleotides and methods thereof |
US11555188B2 (en) | 2017-07-26 | 2023-01-17 | Nissan Chemical Corporation | Single-stranded oligonucleotide |
WO2019022196A1 (ja) | 2017-07-26 | 2019-01-31 | 日産化学株式会社 | 一本鎖オリゴヌクレオチド |
US11701407B2 (en) | 2017-08-03 | 2023-07-18 | Synthorx, Inc. | Cytokine conjugates for the treatment of proliferative and infectious diseases |
US11622993B2 (en) | 2017-08-03 | 2023-04-11 | Synthorx, Inc. | Cytokine conjugates for the treatment of autoimmune diseases |
US10610571B2 (en) | 2017-08-03 | 2020-04-07 | Synthorx, Inc. | Cytokine conjugates for the treatment of proliferative and infectious diseases |
WO2019045075A1 (ja) | 2017-08-31 | 2019-03-07 | 田辺三菱製薬株式会社 | Il-33アンタゴニストを含む子宮内膜症治療剤 |
US11230712B2 (en) | 2017-11-09 | 2022-01-25 | Ionis Pharmaceuticals, Inc. | Compounds and methods for reducing SNCA expression |
US11359197B2 (en) | 2018-01-12 | 2022-06-14 | Bristol-Myers Squibb Company | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
US11447775B2 (en) | 2018-01-12 | 2022-09-20 | Bristol-Myers Squibb Company | Antisense oligonucleotides targeting alpha-synuclein and uses thereof |
WO2019165453A1 (en) | 2018-02-26 | 2019-08-29 | Synthorx, Inc. | Il-15 conjugates and uses thereof |
US11919934B2 (en) | 2018-02-26 | 2024-03-05 | Synthorx, Inc. | IL-15 conjugates and uses thereof |
WO2019182037A1 (ja) | 2018-03-20 | 2019-09-26 | 国立大学法人東京工業大学 | 毒性が低減されたアンチセンスオリゴヌクレオチド |
WO2019217459A1 (en) | 2018-05-07 | 2019-11-14 | Alnylam Pharmaceuticals, Inc. | Extrahepatic delivery |
WO2020069055A1 (en) | 2018-09-28 | 2020-04-02 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases |
US11077195B2 (en) | 2019-02-06 | 2021-08-03 | Synthorx, Inc. | IL-2 conjugates and methods of use thereof |
US11279932B2 (en) | 2019-02-27 | 2022-03-22 | Ionis Pharmaceuticals, Inc. | Modulators of MALAT1 expression |
WO2020184700A1 (ja) | 2019-03-14 | 2020-09-17 | レナセラピューティクス株式会社 | Ihh発現を調節するための核酸複合体 |
WO2020203880A1 (ja) | 2019-03-29 | 2020-10-08 | 田辺三菱製薬株式会社 | Dux4の発現を調節するための化合物、方法及び医薬組成物 |
US11261446B2 (en) | 2019-03-29 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating UBE3A-ATS |
WO2020236600A1 (en) | 2019-05-17 | 2020-11-26 | Alnylam Pharmaceuticals, Inc. | Oral delivery of oligonucleotides |
US11879145B2 (en) | 2019-06-14 | 2024-01-23 | The Scripps Research Institute | Reagents and methods for replication, transcription, and translation in semi-synthetic organisms |
WO2021020412A1 (ja) | 2019-07-30 | 2021-02-04 | 塩野義製薬株式会社 | Murf1を標的とする核酸医薬 |
WO2021030706A1 (en) | 2019-08-15 | 2021-02-18 | Synthorx, Inc. | Immuno oncology combination therapies with il-2 conjugates |
WO2021041206A1 (en) | 2019-08-23 | 2021-03-04 | Synthorx, Inc. | Il-15 conjugates and uses thereof |
WO2021050554A1 (en) | 2019-09-10 | 2021-03-18 | Synthorx, Inc. | Il-2 conjugates and methods of use to treat autoimmune diseases |
WO2021091986A1 (en) | 2019-11-04 | 2021-05-14 | Synthorx, Inc. | Interleukin 10 conjugates and uses thereof |
WO2021092145A1 (en) | 2019-11-06 | 2021-05-14 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna composition and methods of use thereof for treating or preventing ttr-associated ocular diseases |
WO2021092371A2 (en) | 2019-11-06 | 2021-05-14 | Alnylam Pharmaceuticals, Inc. | Extrahepatic delivery |
WO2021153747A1 (ja) | 2020-01-31 | 2021-08-05 | 株式会社三和化学研究所 | Atn1のアンチセンスオリゴヌクレオチド |
WO2021177418A1 (ja) | 2020-03-04 | 2021-09-10 | 日産化学株式会社 | Calm2のアンチセンスオリゴヌクレオチド |
WO2021230286A1 (ja) | 2020-05-12 | 2021-11-18 | 田辺三菱製薬株式会社 | Ataxin 3発現を調節するための化合物、方法及び医薬組成物 |
WO2021263026A1 (en) | 2020-06-25 | 2021-12-30 | Synthorx, Inc. | Immuno oncology combination therapy with il-2 conjugates and anti-egfr antibodies |
WO2022011214A1 (en) | 2020-07-10 | 2022-01-13 | Alnylam Pharmaceuticals, Inc. | Circular sirnas |
WO2022065413A1 (ja) * | 2020-09-25 | 2022-03-31 | 株式会社理研ジェネシス | 新規人工核酸、その製造方法及び用途 |
WO2022076859A1 (en) | 2020-10-09 | 2022-04-14 | Synthorx, Inc. | Immuno oncology therapies with il-2 conjugates |
WO2022076853A1 (en) | 2020-10-09 | 2022-04-14 | Synthorx, Inc. | Immuno oncology combination therapy with il-2 conjugates and pembrolizumab |
US11447521B2 (en) | 2020-11-18 | 2022-09-20 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
WO2022147214A2 (en) | 2020-12-31 | 2022-07-07 | Alnylam Pharmaceuticals, Inc. | Cyclic-disulfide modified phosphate based oligonucleotide prodrugs |
WO2022147223A2 (en) | 2020-12-31 | 2022-07-07 | Alnylam Pharmaceuticals, Inc. | 2'-modified nucleoside based oligonucleotide prodrugs |
WO2022174102A1 (en) | 2021-02-12 | 2022-08-18 | Synthorx, Inc. | Lung cancer combination therapy with il-2 conjugates and an anti-pd-1 antibody or antigen-binding fragment thereof |
WO2022174101A1 (en) | 2021-02-12 | 2022-08-18 | Synthorx, Inc. | Skin cancer combination therapy with il-2 conjugates and cemiplimab |
WO2022213118A1 (en) | 2021-03-31 | 2022-10-06 | Entrada Therapeutics, Inc. | Cyclic cell penetrating peptides |
WO2022240721A1 (en) | 2021-05-10 | 2022-11-17 | Entrada Therapeutics, Inc. | Compositions and methods for modulating interferon regulatory factor-5 (irf-5) activity |
WO2022241408A1 (en) | 2021-05-10 | 2022-11-17 | Entrada Therapeutics, Inc. | Compositions and methods for modulating tissue distribution of intracellular therapeutics |
WO2022240760A2 (en) | 2021-05-10 | 2022-11-17 | Entrada Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR MODULATING mRNA SPLICING |
WO2022255273A1 (ja) | 2021-05-31 | 2022-12-08 | レナセラピューティクス株式会社 | リガンド結合核酸複合体 |
WO2022256538A1 (en) | 2021-06-03 | 2022-12-08 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and cetuximab |
WO2022256534A1 (en) | 2021-06-03 | 2022-12-08 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and pembrolizumab |
WO2022271818A1 (en) | 2021-06-23 | 2022-12-29 | Entrada Therapeutics, Inc. | Antisense compounds and methods for targeting cug repeats |
WO2023283403A2 (en) | 2021-07-09 | 2023-01-12 | Alnylam Pharmaceuticals, Inc. | Bis-rnai compounds for cns delivery |
WO2023287141A1 (ko) | 2021-07-12 | 2023-01-19 | 주식회사 씨젠 | 용기에 수용된 용액의 높이를 결정하는 방법 및 시스템 |
WO2023003922A1 (en) | 2021-07-21 | 2023-01-26 | Alnylam Pharmaceuticals, Inc. | Metabolic disorder-associated target gene irna compositions and methods of use thereof |
WO2023034817A1 (en) | 2021-09-01 | 2023-03-09 | Entrada Therapeutics, Inc. | Compounds and methods for skipping exon 44 in duchenne muscular dystrophy |
WO2023064530A1 (en) | 2021-10-15 | 2023-04-20 | Alnylam Pharmaceuticals, Inc. | Extra-hepatic delivery irna compositions and methods of use thereof |
WO2023086292A2 (en) | 2021-11-10 | 2023-05-19 | University Of Rochester | Gata4-targeted therapeutics for treatment of cardiac hypertrophy |
WO2023086295A2 (en) | 2021-11-10 | 2023-05-19 | University Of Rochester | Antisense oligonucleotides for modifying protein expression |
WO2023122573A1 (en) | 2021-12-20 | 2023-06-29 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and pembrolizumab |
WO2023122750A1 (en) | 2021-12-23 | 2023-06-29 | Synthorx, Inc. | Cancer combination therapy with il-2 conjugates and cetuximab |
WO2023220744A2 (en) | 2022-05-13 | 2023-11-16 | Alnylam Pharmaceuticals, Inc. | Single-stranded loop oligonucleotides |
WO2024006999A2 (en) | 2022-06-30 | 2024-01-04 | Alnylam Pharmaceuticals, Inc. | Cyclic-disulfide modified phosphate based oligonucleotide prodrugs |
WO2024039776A2 (en) | 2022-08-18 | 2024-02-22 | Alnylam Pharmaceuticals, Inc. | Universal non-targeting sirna compositions and methods of use thereof |
WO2024050261A1 (en) | 2022-08-29 | 2024-03-07 | University Of Rochester | Antisense oligonucleotide-based anti-fibrotic therapeutics |
WO2024073732A1 (en) | 2022-09-30 | 2024-04-04 | Alnylam Pharmaceuticals, Inc. | Modified double-stranded rna agents |
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US7427672B2 (en) | 2008-09-23 |
EP1661905A1 (en) | 2006-05-31 |
EP1661905B9 (en) | 2012-12-19 |
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US20070167387A1 (en) | 2007-07-19 |
ES2382807T3 (es) | 2012-06-13 |
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EP1661905B1 (en) | 2012-04-25 |
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ATE555118T1 (de) | 2012-05-15 |
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