BR112022007795A2 - Administração extra-hepática - Google Patents

Administração extra-hepática

Info

Publication number
BR112022007795A2
BR112022007795A2 BR112022007795A BR112022007795A BR112022007795A2 BR 112022007795 A2 BR112022007795 A2 BR 112022007795A2 BR 112022007795 A BR112022007795 A BR 112022007795A BR 112022007795 A BR112022007795 A BR 112022007795A BR 112022007795 A2 BR112022007795 A2 BR 112022007795A2
Authority
BR
Brazil
Prior art keywords
extrahepatic
administration
lipophilic
complementary
conjugated
Prior art date
Application number
BR112022007795A
Other languages
English (en)
Inventor
K Nair Jayaprakash
A Maier Martin
C Salinas Juan
Matsuda Shigeo
V Kel'in Alexander
P Lentini Scott
He Guo
H Jung Michelle
M Pierson Justin
Manohaean Muthiah
Guenther Dale
Zlatev Ivan
S Theile Christopher
R Jadhav Vasant
Milstein Stuart
Datta Dhrubajyoti
Janas Maja
Original Assignee
Alnylam Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alnylam Pharmaceuticals Inc filed Critical Alnylam Pharmaceuticals Inc
Publication of BR112022007795A2 publication Critical patent/BR112022007795A2/pt

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • C12N2310/3535—Nitrogen
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications

Abstract

ADMINISTRAÇÃO EXTRA-HEPÁTICA. A presente invenção refere-se a um composto compreendendo uma fita antissenso que é complementar a um gene-alvo; uma fita senso que é complementar a dita fita antissenso; e um ou mais monômeros lipofílicos, contendo uma ou mais porções lipofílicas, conjugados a uma ou mais posições em pelo menos uma fita, opcionalmente por meio de um ligante ou veículo. Um outro aspecto da invenção se refere a um método de silenciamento de gene, o qual compreende administrar a uma célula ou um indivíduo com necessidade do mesmo uma quantidade terapeuticamente eficaz do composto conjugado a monômero lipofílico.
BR112022007795A 2019-11-06 2020-11-06 Administração extra-hepática BR112022007795A2 (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201962931631P 2019-11-06 2019-11-06
PCT/US2020/059399 WO2021092371A2 (en) 2019-11-06 2020-11-06 Extrahepatic delivery

Publications (1)

Publication Number Publication Date
BR112022007795A2 true BR112022007795A2 (pt) 2022-07-05

Family

ID=73646550

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112022007795A BR112022007795A2 (pt) 2019-11-06 2020-11-06 Administração extra-hepática

Country Status (10)

Country Link
US (1) US20230016929A1 (pt)
EP (1) EP4055166A2 (pt)
JP (1) JP2023500681A (pt)
KR (1) KR20220110749A (pt)
CN (1) CN114945669A (pt)
AU (1) AU2020378414A1 (pt)
BR (1) BR112022007795A2 (pt)
CA (1) CA3160329A1 (pt)
MX (1) MX2022005220A (pt)
WO (1) WO2021092371A2 (pt)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024508714A (ja) 2021-02-12 2024-02-28 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 スーパーオキシドジスムターゼ１－（ＳＯＤ１－）関連神経変性疾患を治療または予防するためのスーパーオキシドジスムターゼ１（ＳＯＤ１）ｉＲＮＡ組成物およびその使用方法
WO2022260939A2 (en) * 2021-06-08 2022-12-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
CN114891509B (zh) * 2021-12-14 2023-05-05 湖北兴福电子材料股份有限公司 一种高选择性的缓冲氧化物蚀刻液
US20230304008A1 (en) * 2022-03-28 2023-09-28 Empirico Inc. Modified oligonucleotides
WO2024073732A1 (en) 2022-09-30 2024-04-04 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents

Family Cites Families (141)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5218A (en) 1847-08-07 Improvement in plows
US105A (en) 1836-12-15 knight
US2816110A (en) 1956-11-23 1957-12-10 Merck & Co Inc Methods for the production of substituted pteridines
GB971700A (en) 1961-02-02 1964-09-30 Boots Pure Drug Co Ltd Anti-Inflammatory Agents
US4009197A (en) 1967-01-13 1977-02-22 Syntex Corporation 2-(6-Substituted-2'-naphthyl) acetic acid derivatives and the salts and esters thereof
US3904682A (en) 1967-01-13 1975-09-09 Syntex Corp 2-(6{40 -Methoxy-2{40 -naphthyl)acetic acid
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5149782A (en) 1988-08-19 1992-09-22 Tanox Biosystems, Inc. Molecular conjugates containing cell membrane-blending agents
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
EP0942000B1 (en) 1989-10-24 2004-06-23 Isis Pharmaceuticals, Inc. 2'-Modified oligonucleotides
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US6153737A (en) 1990-01-11 2000-11-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
WO1991013080A1 (en) 1990-02-20 1991-09-05 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
DK0455905T3 (da) 1990-05-11 1998-12-07 Microprobe Corp Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
KR930702373A (ko) 1990-11-08 1993-09-08 안토니 제이. 페이네 합성 올리고누클레오티드에 대한 다중 리포터(Reporter)그룹의 첨합
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
EP0538194B1 (de) 1991-10-17 1997-06-04 Novartis AG Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US6335434B1 (en) 1998-06-16 2002-01-01 Isis Pharmaceuticals, Inc., Nucleosidic and non-nucleosidic folate conjugates
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5159079A (en) 1991-12-20 1992-10-27 Eli Lilly And Company 2-piperidones as intermediates for 5-deaza-10-oxo- and 5-deaza-10-thio-5,6,7,8-tetrahydrofolic acids
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
WO1993023569A1 (en) 1992-05-11 1993-11-25 Ribozyme Pharmaceuticals, Inc. Method and reagent for inhibiting viral replication
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US6172208B1 (en) 1992-07-06 2001-01-09 Genzyme Corporation Oligonucleotides modified with conjugate groups
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
JPH08504559A (ja) 1992-12-14 1996-05-14 ハネウエル・インコーポレーテッド 個別に制御される冗長巻線を有するモータシステム
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
EP0691968B1 (en) 1993-03-30 1997-07-16 Sanofi Acyclic nucleoside analogs and oligonucleotide sequences containing them
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
ATE247128T1 (de) 1993-09-03 2003-08-15 Isis Pharmaceuticals Inc Aminoderivatisierte nukleoside und oligonukleoside
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
PL181064B1 (pl) 1994-03-07 2001-05-31 Dendritech Inc Kompleks polimeru typu gęstej gwiazdy, kompozycja do przenoszenia materiału genetycznego i sposób wytwarzania kompleksu polimeru typu gęstej gwiazdy
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5792747A (en) 1995-01-24 1998-08-11 The Administrators Of The Tulane Educational Fund Highly potent agonists of growth hormone releasing hormone
US5801155A (en) 1995-04-03 1998-09-01 Epoch Pharmaceuticals, Inc. Covalently linked oligonucleotide minor grove binder conjugates
US5672662A (en) 1995-07-07 1997-09-30 Shearwater Polymers, Inc. Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications
US7144869B2 (en) 1995-12-13 2006-12-05 Mirus Bio Corporation Nucleic acid injected into hapatic vein lumen and delivered to primate liver
US8217015B2 (en) 2003-04-04 2012-07-10 Arrowhead Madison Inc. Endosomolytic polymers
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
US6444806B1 (en) 1996-04-30 2002-09-03 Hisamitsu Pharmaceutical Co., Inc. Conjugates and methods of forming conjugates of oligonucleotides and carbohydrates
US6001311A (en) 1997-02-05 1999-12-14 Protogene Laboratories, Inc. Apparatus for diverse chemical synthesis using two-dimensional array
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
CA2303299C (en) 1997-09-12 2016-02-23 Exiqon A/S Oligonucleotide analogues
EP1071753A2 (en) 1998-04-20 2001-01-31 Ribozyme Pharmaceuticals, Inc. Nucleic acid molecules with novel chemical compositions capable of modulating gene expression
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6043352A (en) 1998-08-07 2000-03-28 Isis Pharmaceuticals, Inc. 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides
US6335437B1 (en) 1998-09-07 2002-01-01 Isis Pharmaceuticals, Inc. Methods for the preparation of conjugated oligomers
CA2361201A1 (en) 1999-01-28 2000-08-03 Medical College Of Georgia Research Institute, Inc. Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna
EP1152009B2 (en) 1999-02-12 2017-09-06 Daiichi Sankyo Company, Limited Novel nucleosides and oligonucleotide analogues
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
ATE356824T1 (de) 1999-05-04 2007-04-15 Santaris Pharma As L-ribo-lna analoge
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US20080281041A1 (en) 1999-06-07 2008-11-13 Rozema David B Reversibly Masked Polymers
US8211468B2 (en) 1999-06-07 2012-07-03 Arrowhead Madison Inc. Endosomolytic polymers
JP4151751B2 (ja) 1999-07-22 2008-09-17 第一三共株式会社 新規ビシクロヌクレオシド類縁体
US6395437B1 (en) 1999-10-29 2002-05-28 Advanced Micro Devices, Inc. Junction profiling using a scanning voltage micrograph
GB9927444D0 (en) 1999-11-19 2000-01-19 Cancer Res Campaign Tech Inhibiting gene expression
US6559279B1 (en) 2000-09-08 2003-05-06 Isis Pharmaceuticals, Inc. Process for preparing peptide derivatized oligomeric compounds
US8138383B2 (en) 2002-03-11 2012-03-20 Arrowhead Madison Inc. Membrane active heteropolymers
US8008355B2 (en) 2002-03-11 2011-08-30 Roche Madison Inc. Endosomolytic poly(vinyl ether) polymers
PT2151250E (pt) 2002-05-06 2013-12-09 Endocyte Inc Agentes de formação de imagem direccionados para vitamina
US7569575B2 (en) 2002-05-08 2009-08-04 Santaris Pharma A/S Synthesis of locked nucleic acid derivatives
US20040219565A1 (en) 2002-10-21 2004-11-04 Sakari Kauppinen Oligonucleotides useful for detecting and analyzing nucleic acids of interest
AU2003291753B2 (en) 2002-11-05 2010-07-08 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP2664672A1 (en) 2003-04-17 2013-11-20 Alnylam Pharmaceuticals Inc. Modified iRNA agents
US8017762B2 (en) 2003-04-17 2011-09-13 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
US7851615B2 (en) * 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
US7427672B2 (en) 2003-08-28 2008-09-23 Takeshi Imanishi Artificial nucleic acids of n-o bond crosslinkage type
CA2554212A1 (en) 2004-02-10 2005-08-25 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using multifunctional short interfering nucleic acid (multifunctional sina)
CA2562685C (en) 2004-04-27 2013-09-17 Alnylam Pharmaceuticals, Inc. Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety
AU2005252662B2 (en) 2004-06-03 2011-08-18 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
EP1924692A2 (en) * 2005-09-16 2008-05-28 Coley Pharmaceutical GmbH Modulation of immunostimulatory properties of short interfering ribonucleic acid (sirna) by nucleotide modification
EP1989307B1 (en) 2006-02-08 2012-08-08 Quark Pharmaceuticals, Inc. NOVEL TANDEM siRNAS
MX2008012993A (es) 2006-04-07 2008-12-18 Idera Pharmaceuticals Inc Compuestos de acido ribonucleico inmunomodulador estabilizado para receptores tipo toll-7 y receptores tipo toll-8.
US8017109B2 (en) 2006-08-18 2011-09-13 Roche Madison Inc. Endosomolytic poly(acrylate) polymers
AU2007285782B2 (en) 2006-08-18 2010-06-24 Arrowhead Research Corporation Polyconjugates for in vivo delivery of polynucleotides
CN101795715A (zh) 2007-07-09 2010-08-04 艾德拉药物股份有限公司 稳定化免疫调控性rna(simra)化合物
CA2910760C (en) * 2007-12-04 2019-07-09 Muthiah Manoharan Targeting lipids
US8507455B2 (en) * 2007-12-04 2013-08-13 Alnylam Pharmaceuticals, Inc. Folate conjugates
CA2721183C (en) * 2008-04-11 2019-07-16 Alnylam Pharmaceuticals, Inc. Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
EP2321414B1 (en) 2008-07-25 2018-01-10 Alnylam Pharmaceuticals, Inc. Enhancement of sirna silencing activity using universal bases or mismatches in the sense strand
JP2012502991A (ja) * 2008-09-22 2012-02-02 アールエックスアイ ファーマシューティカルズ コーポレーション 皮膚適用におけるｒｎａ干渉
PL2396038T3 (pl) * 2009-02-12 2016-05-31 Curna Inc Leczenie chorób związanych z neurotropowym czynnikiem pochodzenia mózgowego (bdnf) poprzez zahamowanie naturalnego antysensownego transkryptu bdnf
CN102575252B (zh) 2009-06-01 2016-04-20 光环生物干扰疗法公司 用于多价rna干扰的多核苷酸、组合物及其使用方法
EP2264169A1 (en) * 2009-06-15 2010-12-22 Qiagen GmbH Modified siNA
ES2538347T3 (es) 2009-08-27 2015-06-19 Idera Pharmaceuticals, Inc. Composiciones para inhibir expresión genética y usos de las mismas
US10913767B2 (en) 2010-04-22 2021-02-09 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
AU2011296268A1 (en) * 2010-08-31 2013-02-21 Merck Sharp & Dohme Corp. Novel single chemical entities and methods for delivery of oligonucleotides
DK3019200T3 (da) * 2013-07-11 2022-06-20 Alnylam Pharmaceuticals Inc Oligonukleotid-ligand-konjugater og fremgangsmåde til fremstiling deraf
SG10201913791QA (en) * 2014-08-20 2020-03-30 Alnylam Pharmaceuticals Inc Modified double-stranded rna agents
EP3323893A4 (en) * 2015-07-16 2019-03-27 Kyowa Hakko Kirin Co., Ltd. BETA2GPI GENE EXPRESSION-INHIBITING NUCLEIC ACID COMPLEX
EP3353306A4 (en) * 2015-09-25 2019-06-05 Ionis Pharmaceuticals, Inc. ANTISENSE CONJUGATED COMPOUNDS AND THEIR USE

Also Published As

Publication number Publication date
KR20220110749A (ko) 2022-08-09
JP2023500681A (ja) 2023-01-10
WO2021092371A3 (en) 2021-06-17
AU2020378414A1 (en) 2022-05-26
EP4055166A2 (en) 2022-09-14
CN114945669A (zh) 2022-08-26
WO2021092371A2 (en) 2021-05-14
CA3160329A1 (en) 2021-05-14
US20230016929A1 (en) 2023-01-19
MX2022005220A (es) 2022-08-11

Similar Documents

Publication Publication Date Title
BR112022007795A2 (pt) Administração extra-hepática
BR112020022546A8 (pt) Entrega extra-hepática
Chen et al. MiR-3662 suppresses hepatocellular carcinoma growth through inhibition of HIF-1α-mediated Warburg effect
Leidgens et al. Ibuprofen and diclofenac restrict migration and proliferation of human glioma cells by distinct molecular mechanisms
BR112014019988A8 (pt) Forma de dosagem resistente a socamento compreendendo um composto farmacologicamente ativo e um polímero aniônico
Jara et al. Metformin and cancer: between the bioenergetic disturbances and the antifolate activity
BR112015029616A2 (pt) forma de dosagem resistente à adulteração com perfil de liberação bimodal
CY1117033T1 (el) Αγωγη εναντι οξειας λεμφοβλαστικης λευχαιμιας
CY1118625T1 (el) Παραγωγα πολυμυξινης με βραχεια ουρα λιπαρου οξεος και χρησεις αυτων
CY1118350T1 (el) Μορφες δοσολογιας για ληψη απο το στομα που περιλαμβανουν οξεικη λικαρβαζεπινη
Schrör et al. Aspirin and lipid mediators in the cardiovascular system
CY1115862T1 (el) Θεραπεια με πιρφενιδονη για ασθενεις με μη φυσιολογικη ηπατικη λειτουργια
Ishikawa et al. Synergistic anti-AML effects of the LSD1 inhibitor T-3775440 and the NEDD8-activating enzyme inhibitor pevonedistat via transdifferentiation and DNA rereplication
CY1114215T1 (el) Φαρμακευτικες συνθεσεις διαλυματος για υπο πιεση εισπνευστηρες μετρουμενης δοσης
BRPI0615860B8 (pt) composição farmacêutica de liberação prolongada monolítica sólida
BR112013005195A2 (pt) forma de dosagem resistente à violação compreendendo um polímero aniônico
BRPI0409945A (pt) forma de dosagem resistente à alteração
BRPI0922796A2 (pt) Comprimido farmacêutico para administração por via oral e método de fabricação do mesmo
BR112012020270A2 (pt) sistema e método para administrar medicamentos com base em valores de urina.
Tan et al. Circ_0001971 regulates oral squamous cell carcinoma progression and chemosensitivity by targeting miR-194/miR-204 in vitro and in vivo.
Zhang et al. Nuclear receptor SHP inhibition of Dnmt1 expression via ERRγ
Chen et al. MicroRNA-134 regulates lung cancer cell H69 growth and apoptosis by targeting WWOX gene and suppressing the ERK1/2 signaling pathway
BR112014018135A8 (pt) Produto farmacêutico e uso do produto farmacêutico
Yang et al. Long non-coding RNA Snhg3 protects against hypoxia/ischemia-induced neonatal brain injury
Kiran et al. Lactate metabolism and signaling in tuberculosis and cancer: a comparative review