EA201490994A1 - Функционально-модифицированные олигонуклеотиды и их субъединицы - Google Patents

Функционально-модифицированные олигонуклеотиды и их субъединицы

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Publication number
EA201490994A1
EA201490994A1 EA201490994A EA201490994A EA201490994A1 EA 201490994 A1 EA201490994 A1 EA 201490994A1 EA 201490994 A EA201490994 A EA 201490994A EA 201490994 A EA201490994 A EA 201490994A EA 201490994 A1 EA201490994 A1 EA 201490994A1
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EA
Eurasian Patent Office
Prior art keywords
modified oligonucleotide
sub
units
functionally modified
modified
Prior art date
Application number
EA201490994A
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English (en)
Other versions
EA035030B1 (ru
Inventor
Гуннар Дж. Хансон
Дуайт Д. Уэллер
Бао Чжун Цай
Мин Чжоу
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Сарепта Терапьютикс, Инк.
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Application filed by Сарепта Терапьютикс, Инк. filed Critical Сарепта Терапьютикс, Инк.
Publication of EA201490994A1 publication Critical patent/EA201490994A1/ru
Publication of EA035030B1 publication Critical patent/EA035030B1/ru

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
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    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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    • C07F9/02—Phosphorus compounds
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    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
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    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system
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    • 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
    • C12N15/1131—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 against viruses
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    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon

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Abstract

Представлены функционально-модифицированные аналоги олигонуклеотидов, включающие модифицированные межсубъединичные связи и/или модифицированные 3'- и/или 5'-концевые группы. Раскрытые соединения применимы для лечения заболеваний, где ингибирование экспрессии белков или коррекция продуктов сплайсинга искаженной мРНК создает благоприятные терапевтические эффекты.
EA201490994A 2011-11-18 2012-11-15 Модифицированные морфолиновые аналоги олигонуклеотидов EA035030B1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161561806P 2011-11-18 2011-11-18
PCT/US2012/065350 WO2013074834A1 (en) 2011-11-18 2012-11-15 Functionally-modified oligonucleotides and subunits thereof

Publications (2)

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EA201490994A1 true EA201490994A1 (ru) 2014-11-28
EA035030B1 EA035030B1 (ru) 2020-04-20

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Application Number Title Priority Date Filing Date
EA202090338A EA202090338A1 (ru) 2011-11-18 2012-11-15 Функционально-модифицированные олигонуклеотиды и их субъединицы
EA201490994A EA035030B1 (ru) 2011-11-18 2012-11-15 Модифицированные морфолиновые аналоги олигонуклеотидов

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US (5) US9278987B2 (ru)
EP (1) EP2780299A4 (ru)
JP (4) JP2015500204A (ru)
KR (4) KR102271212B1 (ru)
CN (3) CN108864192A (ru)
AU (4) AU2012340390B2 (ru)
BR (1) BR112014011875B1 (ru)
CA (1) CA2854907C (ru)
EA (2) EA202090338A1 (ru)
HK (2) HK1201514A1 (ru)
IL (3) IL232651B (ru)
MX (1) MX354940B (ru)
WO (1) WO2013074834A1 (ru)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006086667A2 (en) 2005-02-09 2006-08-17 Avi Bio Pharma, Inc. Antisense composition and method for treating muscle atrophy
US8067571B2 (en) 2005-07-13 2011-11-29 Avi Biopharma, Inc. Antibacterial antisense oligonucleotide and method
TWI620756B (zh) 2010-05-28 2018-04-11 薩羅塔治療公司 具有經修飾之單元間連結及／或末端基團之寡核苷酸類似物
WO2012031243A2 (en) 2010-09-03 2012-03-08 Avi Biopharma, Inc. dsRNA MOLECULES COMPRISING OLIGONUCLEOTIDE ANALOGS HAVING MODIFIED INTERSUBUNIT LINKAGES AND/OR TERMINAL GROUPS
US20130085139A1 (en) 2011-10-04 2013-04-04 Royal Holloway And Bedford New College Oligomers
CA2854907C (en) * 2011-11-18 2020-03-10 Sarepta Therapeutics, Inc. Functionally-modified oligonucleotides and subunits thereof
RS57467B1 (sr) 2011-12-08 2018-09-28 Sarepta Therapeutics Inc Oligonukleotidni analozi koji ciljaju humani lmna
CN105228999B (zh) 2013-05-24 2021-03-02 味之素株式会社 吗啉代寡核苷酸的制备方法
JP6618910B2 (ja) 2013-09-05 2019-12-11 サレプタ セラピューティクス，インコーポレイテッド 酸性α−グルコシダーゼにおけるアンチセンス誘導エクソン２包含
WO2016060135A1 (ja) * 2014-10-14 2016-04-21 味の素株式会社 モルフォリノオリゴヌクレオチドの製造方法
EP3240794A4 (en) * 2014-12-31 2018-10-31 Oregon State University Antisense antibacterial compounds and methods
PL3244891T3 (pl) 2015-01-16 2022-12-27 The General Hospital Corporation Związki poprawiające splicing mRNA
WO2016138534A2 (en) * 2015-02-27 2016-09-01 Sarepta Therapeutics, Inc. Antisense-induced exon2 inclusion in acid alpha-glucosidase
MA41795A (fr) 2015-03-18 2018-01-23 Sarepta Therapeutics Inc Exclusion d'un exon induite par des composés antisens dans la myostatine
US10849917B2 (en) 2015-06-01 2020-12-01 Sarepta Therapeutics, Inc. Antisense-induced exon exclusion in type VII collagen
WO2016196897A1 (en) 2015-06-04 2016-12-08 Sarepta Therapeutics, Inc. Methods and compounds for treatment of lymphocyte-related diseases and conditions
ES2907629T3 (es) 2015-08-05 2022-04-25 Eisai R&D Man Co Ltd Un método para preparar un oligómero de fosforodiamidato sustancialmente puro diastereoisoméricamente, un oligómero de fosforodiamidato preparado mediante dicho método y una composición farmacéutica que comprende dicho oligómero de fosforodiamidato
CN108699555A (zh) 2015-10-09 2018-10-23 萨勒普塔医疗公司 用于治疗杜兴肌营养不良和相关病症的组合物和方法
EP3389719B1 (en) * 2015-12-15 2021-11-17 Sarepta Therapeutics, Inc. Peptide oligonucleotide conjugates
EA201892366A1 (ru) 2016-04-18 2019-03-29 Сарепта Терапьютикс, Инк. Антисмысловые олигомеры и способы их применения для лечения заболеваний, связанных с геном кислой альфа-глюкозидазы
MA45616A (fr) 2016-04-29 2019-03-06 Sarepta Therapeutics Inc Analogues d'oligonucléotide ciblant lmna humain
US11472824B2 (en) 2016-05-24 2022-10-18 Sarepta Therapeutics, Inc. Processes for preparing phosphorodiamidate morpholino oligomers
SG10202101830WA (en) 2016-05-24 2021-04-29 Sarepta Therapeutics Inc Processes for preparing oligomers
AU2017270975B2 (en) * 2016-05-24 2021-04-15 Sarepta Therapeutics, Inc. Processes for preparing phosphorodiamidate morpholino oligomers
FI3464306T3 (fi) 2016-05-24 2024-05-16 Sarepta Therapeutics Inc Menetelmiä fosforodiamidaattimorfolino-oligomeerien valmistamiseksi
MA45362A (fr) 2016-05-24 2019-04-10 Sarepta Therapeutics Inc Procédés de préparation d'oligomères morpholino de phosphorodiamidate
US11767520B2 (en) 2017-04-20 2023-09-26 Atyr Pharma, Inc. Compositions and methods for treating lung inflammation
CN107589189B (zh) * 2017-09-06 2018-07-10 中国农业科学院饲料研究所 一种氟甲喹的手性对映体的检测方法
JP7394753B2 (ja) 2017-10-18 2023-12-08 サレプタ セラピューティクス， インコーポレイテッド アンチセンスオリゴマー化合物
JP7394749B2 (ja) * 2018-05-10 2023-12-08 日本新薬株式会社 オリゴ核酸化合物の製造方法
US10765760B2 (en) 2018-05-29 2020-09-08 Sarepta Therapeutics, Inc. Exon skipping oligomer conjugates for muscular dystrophy
EP4059943A4 (en) * 2019-11-13 2024-01-31 Nippon Shinyaku Co., Ltd. METHOD FOR PRODUCING OLIGONUCLEIC ACID COMPOUND
CN114981281A (zh) * 2019-11-13 2022-08-30 日本新药株式会社 寡核苷酸化合物的制造方法
CN115894392A (zh) * 2022-12-02 2023-04-04 中国科学院福建物质结构研究所 (c3h8n6i6)·3h2o化合物、双折射晶体及其制法和用途

Family Cites Families (122)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
ATE171185T1 (de) 1985-03-15 1998-10-15 Antivirals Inc Immunotestmittel für polynukleotid und verfahren
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5217866A (en) 1985-03-15 1993-06-08 Anti-Gene Development Group Polynucleotide assay reagent and method
US5521063A (en) 1985-03-15 1996-05-28 Antivirals Inc. Polynucleotide reagent containing chiral subunits and methods of use
US5749847A (en) 1988-01-21 1998-05-12 Massachusetts Institute Of Technology Delivery of nucleotides into organisms by electroporation
US5223168A (en) 1989-12-12 1993-06-29 Gary Holt Surface cleaner and treatment
JP3398378B2 (ja) 1989-12-20 2003-04-21 アンチビラルス・インコーポレイテツド リン含有キラルインターサブユニットリンケージを有する非電荷モルホリノ―基体ポリマー
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5852188A (en) 1990-01-11 1998-12-22 Isis Pharmaceuticals, Inc. Oligonucleotides having chiral phosphorus linkages
US5506351A (en) 1992-07-23 1996-04-09 Isis Pharmaceuticals Process for the preparation of 2'-O-alkyl guanosine and related compounds
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5212295A (en) 1990-01-11 1993-05-18 Isis Pharmaceuticals Monomers for preparation of oligonucleotides having chiral phosphorus linkages
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US6262241B1 (en) 1990-08-13 2001-07-17 Isis Pharmaceuticals, Inc. Compound for detecting and modulating RNA activity and gene expression
HUT69956A (en) 1990-08-14 1995-09-28 Isis Pharmaceuticals Inc Methode for inhibition of influenza virus by antiseuse oligonucleotides
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
JPH07501204A (ja) 1991-06-28 1995-02-09 マサチューセッツ インスティテュート オブ テクノロジー 局所的オリゴヌクレオチド療法
US6030954A (en) 1991-09-05 2000-02-29 University Of Connecticut Targeted delivery of poly- or oligonucleotides to cells
US5599797A (en) 1991-10-15 1997-02-04 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5576302A (en) 1991-10-15 1996-11-19 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity
WO1993013226A1 (en) 1991-12-23 1993-07-08 Chiron Corporation Hav probes for use in solution phase sandwich hybridization assays
US6391542B1 (en) 1992-09-10 2002-05-21 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of Hepatitis C virus-associated diseases
US6174868B1 (en) 1992-09-10 2001-01-16 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of hepatitis C virus-associated diseases
US5571902A (en) 1993-07-29 1996-11-05 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides
US5801154A (en) 1993-10-18 1998-09-01 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of multidrug resistance-associated protein
US6060456A (en) 1993-11-16 2000-05-09 Genta Incorporated Chimeric oligonucleoside compounds
US5554746A (en) 1994-05-16 1996-09-10 Isis Pharmaceuticals, Inc. Lactam nucleic acids
US5734039A (en) 1994-09-15 1998-03-31 Thomas Jefferson University Antisense oligonucleotides targeting cooperating oncogenes
GB9510718D0 (en) 1995-05-26 1995-07-19 Sod Conseils Rech Applic Antisense oligonucleotides
US5955318A (en) 1995-08-14 1999-09-21 Abbott Laboratories Reagents and methods useful for controlling the translation of hepatitis GBV proteins
US6245747B1 (en) 1996-03-12 2001-06-12 The Board Of Regents Of The University Of Nebraska Targeted site specific antisense oligodeoxynucleotide delivery method
WO1997040854A2 (en) 1996-05-01 1997-11-06 Antivirals Inc. Polypeptide conjugates for transporting substances across cell membranes
US20040161844A1 (en) 1996-06-06 2004-08-19 Baker Brenda F. Sugar and backbone-surrogate-containing oligomeric compounds and compositions for use in gene modulation
AU734827B2 (en) 1997-05-21 2001-06-21 Board Of Trustees Of The Leland Stanford Junior University Composition and method for enhancing transport across biological membranes
US6133246A (en) 1997-08-13 2000-10-17 Isis Pharmaceuticals Inc. Antisense oligonucleotide compositions and methods for the modulation of JNK proteins
US6228579B1 (en) 1997-11-14 2001-05-08 San Diego State University Foundation Method for identifying microbial proliferation genes
US6548651B1 (en) 1998-11-11 2003-04-15 Pantheco A/S Modified peptide nucleic acid (PNA) molecules
JP2002535015A (ja) 1999-01-29 2002-10-22 エイブイアイ バイオファーマ， インコーポレイテッド 標的ｒｎａを検出するための非侵襲性方法
US7094765B1 (en) 1999-01-29 2006-08-22 Avi Biopharma, Inc. Antisense restenosis composition and method
AU778741B2 (en) 1999-03-19 2004-12-16 Cambrex Bio Science Rockland, Inc. Boronic acid containing reagents and oligonucleotides
US6521438B1 (en) 1999-11-05 2003-02-18 North Carolina State University Chemoreceptors in plant parasitic nematodes
US20030095953A1 (en) 1999-11-12 2003-05-22 Myles C. Cabot Methods of reversing drug resistance in cancer cells
CA2392685C (en) 1999-11-29 2011-02-22 Avi Biopharma, Inc. Antisense antibacterial method and composition
WO2001049775A2 (en) 2000-01-04 2001-07-12 Avi Biopharma, Inc. Antisense antibacterial cell division composition and method
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
WO2001076636A2 (en) 2000-04-06 2001-10-18 Pantheco A/S Pharmaceutical composition of modified pna molecules
US6784291B2 (en) 2000-05-04 2004-08-31 Avi Biopharma, Inc. Splice-region antisense composition and method
AU2001271873A1 (en) 2000-07-06 2002-01-21 Avi Biopharma, Inc. Transforming growth factor beta (TGF-beta) blocking agent-treated stem cell composition and method
EP1328543B1 (en) 2000-10-27 2009-08-12 Novartis Vaccines and Diagnostics S.r.l. Nucleic acids and proteins from streptococcus groups a & b
WO2002079467A2 (en) 2001-03-29 2002-10-10 Københavns Universitet Antibiotic-free bacterial strain selection with antisense molecules
JP4489356B2 (ja) 2001-05-11 2010-06-23 メリオン リサーチ スリー リミテッド 浸透促進剤
KR20040004629A (ko) 2001-05-17 2004-01-13 에이브이아이 바이오파마 인코포레이티드 ｃ-ｍｙｃ 안티센스 올리고머를 사용한 암치료를 위한조합 접근법
AU2002317437A1 (en) 2001-05-18 2002-12-03 Cureon A/S Therapeutic uses of lna-modified oligonucleotides in infectious diseases
CN100547071C (zh) 2001-10-16 2009-10-07 Avi生物制药公司 用于治疗单链rna病毒感染的抗病毒反义核酸的试剂和方法
US20030224353A1 (en) 2001-10-16 2003-12-04 Stein David A. Antisense antiviral agent and method for treating ssRNA viral infection
EA008940B1 (ru) 2002-09-13 2007-10-26 Репликор, Инк. Антивирусные олигонуклеотиды, не связанные с комплементарностью последовательностей
CA2868618C (en) 2002-10-16 2017-05-23 Gen-Probe Incorporated Compositions and methods for detecting west nile virus
WO2004041854A2 (en) 2002-11-05 2004-05-21 Affinium Pharmaceuticals, Inc. Essential novel bacterial polypeptides
WO2004058794A1 (en) 2002-12-31 2004-07-15 Proligo Llc Methods and compositions for the tandem synthesis of two or more oligonuleotides on the same solid support
WO2004097017A2 (en) 2003-04-29 2004-11-11 Avi Biopharma, Inc. Compositions for enhancing transport and antisense efficacy of nucleic acid analog into cells
CN1826527B (zh) 2003-05-23 2010-11-24 瑞士联邦理工大学.洛桑（Epfl） 基于酰基载体蛋白的蛋白标记方法
AU2004276226B2 (en) 2003-08-05 2009-07-30 Avi Biopharma, Inc. Oligonucleotide analog and method for treating flavivirus infections
KR20060096487A (ko) * 2003-10-27 2006-09-11 진랩스 테크놀러지스, 인크. 바이러스 감염증들을 치료하기 위한 뉴클레오시드 화합물
US20050171044A1 (en) 2003-12-24 2005-08-04 Stein David A. Oligonucleotide compound and method for treating nidovirus infections
CA2553104A1 (en) 2004-01-23 2005-08-11 Avi Biopharma, Inc. Antisense oligomers and methods for inducing immune tolerance and immunosuppression
US7402574B2 (en) 2004-03-12 2008-07-22 Avi Biopharma, Inc. Antisense composition and method for treating cancer
US20050288246A1 (en) 2004-05-24 2005-12-29 Iversen Patrick L Peptide conjugated, inosine-substituted antisense oligomer compound and method
EP2206781B1 (en) 2004-06-28 2015-12-02 The University Of Western Australia Antisense oligonucleotides for inducing exon skipping and methods of use thereof
DK1766012T3 (da) 2004-07-02 2011-09-19 Avi Biopharma Inc Antisense-antibakteriel fremgangsmåde og forbindelse
US8129352B2 (en) 2004-09-16 2012-03-06 Avi Biopharma, Inc. Antisense antiviral compound and method for treating ssRNA viral infection
US8357664B2 (en) 2004-10-26 2013-01-22 Avi Biopharma, Inc. Antisense antiviral compound and method for treating influenza viral infection
US7524829B2 (en) 2004-11-01 2009-04-28 Avi Biopharma, Inc. Antisense antiviral compounds and methods for treating a filovirus infection
US7838657B2 (en) 2004-12-03 2010-11-23 University Of Massachusetts Spinal muscular atrophy (SMA) treatment via targeting of SMN2 splice site inhibitory sequences
GB0501944D0 (en) 2005-01-31 2005-03-09 Univ Cambridge Tech Compounds for use in chemical detection and/or quantitation
WO2006086667A2 (en) 2005-02-09 2006-08-17 Avi Bio Pharma, Inc. Antisense composition and method for treating muscle atrophy
US20060293268A1 (en) 2005-05-05 2006-12-28 Rieder Aida E Antisense antiviral compounds and methods for treating foot and mouth disease
HUE027486T2 (en) 2005-06-23 2016-09-28 Isis Pharmaceuticals Inc Preparations and methods for modifying SMN2-Splicing
WO2007009094A2 (en) 2005-07-13 2007-01-18 Avi Biopharma, Inc. Antisense antibacterial method and compound
US7790694B2 (en) 2005-07-13 2010-09-07 Avi Biopharma Inc. Antisense antibacterial method and compound
US8067571B2 (en) 2005-07-13 2011-11-29 Avi Biopharma, Inc. Antibacterial antisense oligonucleotide and method
CA2621964A1 (en) 2005-09-08 2007-03-15 Avi Biopharma, Inc. Antisense antiviral compound and method for treating picornavirus infection
US8524676B2 (en) 2005-09-08 2013-09-03 Sarepta Therapeutics, Inc. Method for treating enterovirus or rhinovirus infection using antisense antiviral compounds
WO2007103529A2 (en) 2006-03-07 2007-09-13 Avi Biopharma, Inc. Antisense antiviral compound and method for treating arenavirus infection
US8785407B2 (en) 2006-05-10 2014-07-22 Sarepta Therapeutics, Inc. Antisense antiviral agent and method for treating ssRNA viral infection
LT2024499T (lt) * 2006-05-10 2018-02-26 Sarepta Therapeutics, Inc. Oligonukleotido analogai, turintys katijonines jungtis tarp subvienetų
ATE502122T1 (de) * 2006-06-01 2011-04-15 Trilink Biotechnologies Chemisch modifizierte oligonukleotidprimer zur nukleinsäureamplifikation
NZ574807A (en) 2006-08-11 2011-01-28 Prosensa Technologies Bv Methods and means for treating dna repeat instability associated genetic disorders
CA2981308C (en) 2006-09-21 2020-12-22 University Of Rochester Compositions and methods related to protein displacement therapy for myotonic dystrophy
US20100016215A1 (en) 2007-06-29 2010-01-21 Avi Biopharma, Inc. Compound and method for treating myotonic dystrophy
BRPI0819828A8 (pt) * 2007-11-15 2022-12-27 Avi Biopharma Inc Processo de síntese de oligômeros de morfolino
US8299206B2 (en) 2007-11-15 2012-10-30 Avi Biopharma, Inc. Method of synthesis of morpholino oligomers
US8076476B2 (en) 2007-11-15 2011-12-13 Avi Biopharma, Inc. Synthesis of morpholino oligomers using doubly protected guanine morpholino subunits
JP5712125B2 (ja) * 2008-05-27 2015-05-07 トリリンク バイオテクノロジーズ 高温で開始される核酸増幅のための、化学修飾されたヌクレオシド５’−三リン酸
US9000142B2 (en) 2008-07-07 2015-04-07 Syntrix Biosystems, Inc. Photocleavable sense-antisense complex
SI3133160T1 (sl) 2008-10-24 2019-05-31 Sarepta Therapeutics, Inc. Sestavki, ki preskakujejo ekson za DMD
WO2010120820A1 (en) 2009-04-13 2010-10-21 Isis Pharmaceuticals, Inc. Compositions and methods for modulation of smn2 splicing
DK3449926T3 (da) 2009-06-17 2019-11-11 Biogen Ma Inc Sammensætninger og fremgangsmåder til modulering af smn2-splejsning hos et individ
JP5991922B2 (ja) 2009-11-13 2016-09-14 サレプタ セラピューティクス， インコーポレイテッド アンチセンス抗ウイルス性化合物およびインフルエンザウイルス感染を処置するための方法
EP2545173A2 (en) 2010-03-12 2013-01-16 Sarepta Therapeutics, Inc. Antisense modulation of nuclear hormone receptors
TWI620756B (zh) 2010-05-28 2018-04-11 薩羅塔治療公司 具有經修飾之單元間連結及／或末端基團之寡核苷酸類似物
US8198429B2 (en) 2010-08-09 2012-06-12 Avi Biopharma, Inc. Antisense antiviral compounds and methods for treating a filovirus infection
WO2012031243A2 (en) 2010-09-03 2012-03-08 Avi Biopharma, Inc. dsRNA MOLECULES COMPRISING OLIGONUCLEOTIDE ANALOGS HAVING MODIFIED INTERSUBUNIT LINKAGES AND/OR TERMINAL GROUPS
CN103154009B (zh) 2010-09-30 2015-06-10 日本新药株式会社 吗啉基核酸衍生物
EP3067420A1 (en) 2010-11-12 2016-09-14 Sarepta Therapeutics, Inc. Antisense antibacterial compounds and methods
KR102339196B1 (ko) * 2011-05-05 2021-12-15 사렙타 쎄러퓨틱스, 인코퍼레이티드 펩타이드 올리고뉴클레오타이드 접합체
US9161948B2 (en) 2011-05-05 2015-10-20 Sarepta Therapeutics, Inc. Peptide oligonucleotide conjugates
CA2854907C (en) * 2011-11-18 2020-03-10 Sarepta Therapeutics, Inc. Functionally-modified oligonucleotides and subunits thereof
RS57467B1 (sr) 2011-12-08 2018-09-28 Sarepta Therapeutics Inc Oligonukleotidni analozi koji ciljaju humani lmna
KR102079284B1 (ko) 2012-03-20 2020-02-19 사렙타 쎄러퓨틱스, 인코퍼레이티드 올리고뉴클레오티드 유사체의 보론산 접합체

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