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RU2015119409A - Конъюгаты олигонуклеотидов - Google Patents

Конъюгаты олигонуклеотидов Download PDF

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RU2015119409A
RU2015119409A RU2015119409A RU2015119409A RU2015119409A RU 2015119409 A RU2015119409 A RU 2015119409A RU 2015119409 A RU2015119409 A RU 2015119409A RU 2015119409 A RU2015119409 A RU 2015119409A RU 2015119409 A RU2015119409 A RU 2015119409A
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oligomeric compound
group
compound according
phosphodiester
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RU2015119409A
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RU2653438C2 (ru
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Нанна Альбек
Хенрик Фрюденлунн ХАНСЕН
Сюзанн КАММЛЕР
Якоб Равн
Хенрик ЭРУМ
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Рош Инновейшен Сентер Копенгаген А/С
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Claims (46)

1. Олигомерное соединение длиной 8-35 нуклеотидов, включающее три области:
i) первую область (область А), которая представляет собой антисмысловой олигомер, содержащий 7-26 последовательных нуклеотидов, комплементарных нуклеиновокислотной мишени, где первая область содержит по меньшей мере один нуклеозидный аналог, и где межнуклеозидные связи первой области включают по меньшей мере 50% межнуклеозидных связей, отличных от фосфодиэфирной;
ii) вторую область (область В), которая содержит 1-10 нуклеотидов, ковалентно связанную с 5'- или 3'-нуклеотидом первой области, например, посредством межнуклеозидной связывающей группы, такой как фосфодиэфирная связь, где либо
a. межнуклеозидная связь между первой и второй областями является фосфодиэфирной связью, а нуклеозид второй области, примыкающий к первой области, представляет собой либо ДНК, либо РНК; и/или
b. по меньшей мере два нуклеозида второй области представляют собой связанные фосфодиэфирной связью ДНК- или РНК-нуклеозиды;
iii) третью область, которая содержит конъюгационную группировку, направляющую группировку или блокирующую группировку, где третья область ковалентно связана со второй областью.
2. Олигомерное соединение по п. 1, где межнуклеозидные связи первой области содержат по меньшей мере 75%, например, по меньшей мере 90%, например, 100% межнуклеозидных связей, отличных от фосфодиэфирной связи.
3. Олигомерное соединение по п. 1, где межнуклеозидные связи, отличные от фосфодиэфирных, выбраны из группы, состоящей из фосфоротиоатной, фосфородитиоатной и боранофосфатной групп.
4. Олигомерное соединение по п. 1, где нуклеиновокислотная мишень выбрана из группы, состоящей из микроРНК, мРНК, IncPHK (длинная некодирующая РНК), snPHK (малая ядерная РНК), snoPHK (малая ядрышковая РНК) и вирусной РНК.
5. Олигомерное соединение по п. 1, где олигомерное соединение, например, первая область, содержит химерный олигонуклеотид (гэпмер), миксмер или тоталмер.
6. Олигомерное соединение по п. 1, где олигомерное соединение, например, первая область, содержит по меньшей мере один бициклический нуклеотидный аналог (LNA).
7. Олигомерное соединение по п. 1, где первая область и вторая область образуют непрерывную нуклеотидную последовательность.
8. Олигомерное соединение по п. 1, где вторая область расположена с 5'-конца от первой области.
9. Олигомерное соединение по п. 1, где вторая область расположена с 3'-конца от первой области.
10. Олигомерное соединение по п. 1, где вторая область содержит по меньшей мере два, например, по меньшей мере три последовательных нуклеозидных звена, выбранных из группы ДНК- и РНК-звеньев, которые могут быть связаны фосфодиэфирными связями.
11. Олигомерное соединение по п. 1, где вторая область ковалентно связана с третьей областью на концевом нуклеозиде второй области (т.е. 3'- или 5'-конце в зависимости от положения первой области).
12. Олигомерное соединение по п. 1, где третья область содержит ненуклеотидную группировку, например, конъюгационную группу, такую как стерин, например холестерин, или углевод, такой как N-ацетилгалактозамин/N-ацетилгалактозамин (GalNac/GalNac)-кластер.
13. Олигомерное соединение по п. 12, где третья область включает группировку, выбранную из группы, состоящей из: липофильной группы (например, липида, жирной кислоты, стерина), белка, пептида, антитела или его фрагмента, полимера, репортерной группы, метки, рецепторного лиганда, низкомолекулярного препарата, пролекарства и витамина.
14. Олигомерное соединение по п. 1, где третья область содержит нуклеиновую кислоту или ее полимер, такой как аптамер, или блокирующую нуклеотидную последовательность.
15. Олигомерное соединение по п. 1, где третья область содержит направляющую группу.
16. Олигомерное соединение по п. 1, где третья область включает активированную группу.
17. Олигомерное соединение по п. 1, где вторая и третья области ковалентно соединены линкерной группой.
18. Олигомерное соединение по п. 17, где линкерная группа между второй и третьей областями включает группу, выбранную среди фосфодиэфирной, фосфоротиоатной и фосфородитиоатной или боранофосфатной групп, например, включает фосфодиэфирную группу.
19. Фармацевтическая композиция, содержащая олигомерное соединение по любому из пп. 1-18 и фармацевтически приемлемый разбавитель, носитель, соль или адъювант.
20. Олигомерное соединение по любому из пп. 1-18 для применения в ингибировании нуклеиновокислотной мишени в клетке.
21. Олигомерное соединение по любому из пп. 1-18 для применения в медицине.
22. Олигомерное соединение по любому из пп. 1-18 для применения в лечении медицинского заболевания или нарушения.
23. Применение олигомерного соединения по любому из пп. 1-18 для изготовления лекарственного средства для лечения заболевания или нарушения, такого как метаболическое заболевание или нарушение.
24. Способ синтеза олигомерного соединения, включающего первую область, вторую область и третью область и возможно линкерную область (Y), определенного в пп. 1-18, где указанный способ включает либо:
a) этап обеспечения подложки для олигонуклеотидного синтеза, к которой присоединена одна из следующих групп:
i) линкерная группа (-Y-)
ii) группа (Х-), выбранная из группы, состоящей из конъюгата, направляющей группы и блокирующей группы
iii) группа -Y-X
и
b) этап олигонуклеотидного синтеза области В, а затем области А, либо:
c) этап олигонуклеотидного синтеза первой области (А) и второй области (В), где после этапа синтеза следует
d) этап добавления третьей области
i) линкерной группы (-Y-)
ii) группы (Х-), выбранной из группы, состоящей из конъюгата, направляющей группы или блокирующей группы
iii) группы -Y-X,
а затем
е) отщепление олигомерного соединения от подложки, где возможно указанный способ также включает дополнительный этап,
где третья область является линкерной группой (Y),
этап добавления конъюгата, блокирующей или направляющей группы к линкерной группе (Y) выполняют либо до, либо после отщепления олигомерного соединения от подложки для олигонуклеотидного синтеза.
25. Способ лечения заболевания или нарушения у субъекта, нуждающегося в лечении, причем указанный способ включает этапы введения фармацевтической композиции, содержащей олигомерное соединение по любому из пп. 1-18, указанному субъекту в терапевтически эффективном количестве.
26. Способ ингибирования экспрессии гена-мишени в клетке, включающий введение олигомерного соединения по любому из пп. 1-18 в клетку, которая экспрессирует указанный ген-мишень, предпочтительно в количестве, эффективном для уменьшения экспрессии указанного гена-мишени в указанной клетке.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11413243B2 (en) 2017-11-06 2022-08-16 Nitto Denko Corporation Fusogenic compounds for delivery of biologically active molecules
RU2808990C2 (ru) * 2017-11-06 2023-12-05 Нитто Денко Корпорейшн Фузогенные соединения для доставки биологически активных молекул

Families Citing this family (296)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2752488T3 (da) 2002-11-18 2020-04-20 Roche Innovation Ct Copenhagen As Antisense-design
CN104212799B (zh) 2008-10-15 2018-11-23 Ionis制药公司 因子11表达的调节
RU2015151857A (ru) 2008-12-02 2019-01-15 Уэйв Лайф Сайенсес Джапан, Инк. Способ синтеза модифицированных по атому фосфора нуклеиновых кислот
MX342945B (es) 2009-07-06 2016-10-18 Ontorii Inc * Profármacos de ácido nucleico novedosos y métodos de uso de los mismos.
US10428019B2 (en) 2010-09-24 2019-10-01 Wave Life Sciences Ltd. Chiral auxiliaries
AU2011329777B2 (en) 2010-11-17 2016-06-09 Ionis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
EP3248982A1 (en) 2011-07-19 2017-11-29 Wave Life Sciences Ltd. Thiosulfonate reagents for the synthesis of functionalized nucleic acids
EP3533873A1 (en) 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
WO2013173638A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating smn gene family expression
EP2850188A4 (en) 2012-05-16 2016-01-20 Rana Therapeutics Inc COMPOSITIONS AND METHOD FOR MODULATING THE EXPRESSION OF THE HEMOGLOBIN GENE FAMILIES
CN104583401A (zh) 2012-05-16 2015-04-29 Rana医疗有限公司 用于调节atp2a2表达的组合物和方法
JP2015518712A (ja) 2012-05-16 2015-07-06 ラナ セラピューティクス インコーポレイテッド Ｍｅｃｐ２発現を調節するための組成物及び方法
JP2015518713A (ja) 2012-05-16 2015-07-06 ラナ セラピューティクス インコーポレイテッド Ｕｔｒｎ発現を調節するための組成物及び方法
CA2879023C (en) 2012-07-13 2017-03-28 Wave Life Sciences Japan Asymmetric auxiliary group
CN104661664B (zh) 2012-07-13 2020-07-03 波涛生命科学有限公司 手性控制
WO2014043544A1 (en) 2012-09-14 2014-03-20 Rana Therapeutics, Inc. Multimeric oligonucleotide compounds
SG11201503821YA (en) 2012-11-15 2015-06-29 Roche Innovation Ct Copenhagen As Oligonucleotide conjugates
RU2649367C2 (ru) * 2013-01-30 2018-04-02 Ф. Хоффманн-Ля Рош Аг Конъюгаты углевода и lna-олигонуклеотида
TW201446791A (zh) 2013-05-01 2014-12-16 Regulus Therapeutics Inc 用於調節mir-122之微小rna化合物及方法
CA2909868C (en) 2013-05-01 2021-10-19 Regulus Therapeutics Inc. Compounds and methods for enhanced cellular uptake
KR102482890B1 (ko) 2013-05-01 2022-12-30 아이오니스 파마수티컬즈, 인코포레이티드 아포지질단백질 (a) 발현을 조절하는 조성물 및 방법
US9943604B2 (en) 2013-09-20 2018-04-17 Ionis Pharmaceuticals, Inc. Targeted therapeutic nucleosides and their use
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
WO2015061536A1 (en) 2013-10-25 2015-04-30 Regulus Therapeutics Inc. Microrna compounds and methods for modulating mir-21 activity
US10144933B2 (en) 2014-01-15 2018-12-04 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator
JPWO2015108048A1 (ja) 2014-01-15 2017-03-23 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
MX2016009290A (es) 2014-01-16 2017-02-28 Wave Life Sciences Ltd Diseño quiral.
CA2935426C (en) * 2014-01-30 2023-07-25 F. Hoffmann-La Roche Ag Polyoligomer compound with biocleavable conjugates for reducing or inhibiting expression of a nucleic acid target
US10006027B2 (en) 2014-03-19 2018-06-26 Ionis Pharmaceuticals, Inc. Methods for modulating Ataxin 2 expression
WO2015143246A1 (en) 2014-03-19 2015-09-24 Isis Pharmaceuticals, Inc. Compositions for modulating ataxin 2 expression
MY192634A (en) 2014-04-01 2022-08-29 Biogen Ma Inc Compositions for modulating sod-1 expression
CN106232125B (zh) 2014-05-01 2020-10-16 Ionis制药公司 用于调节pkk表达的组合物和方法
CN110903337A (zh) 2014-05-01 2020-03-24 Ionis制药公司 用于调节生长激素受体表达的组合物和方法
SI3137605T1 (sl) 2014-05-01 2021-02-26 Ionis Pharmaceuticals, Inc. Sestavki in metode za modulacijo ekspresije angiopoetin 3-podobnega
PE20170010A1 (es) 2014-05-01 2017-03-04 Ionis Pharmaceuticals Inc Composiciones y metodos para modular la expresion del factor b del complemento
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
RU2017105342A (ru) * 2014-08-07 2018-09-13 Регулус Терапьютикс Инк. НАЦЕЛИВАНИЕ НА микроРНК ПРИ РАССТРОЙСТВАХ ОБМЕНА ВЕЩЕСТВ
US10436802B2 (en) 2014-09-12 2019-10-08 Biogen Ma Inc. Methods for treating spinal muscular atrophy
KR20170068469A (ko) 2014-10-10 2017-06-19 에프. 호프만-라 로슈 아게 ＧａｌＮＡｃ 포스포라미다이트, 그의 핵산 컨쥬게이트 및 그의 용도
JP2017534643A (ja) * 2014-11-10 2017-11-24 グラクソスミスクライン、インテレクチュアル、プロパティー、（ナンバー２）、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ （Ｎｏ．２） Ｌｉｍｉｔｅｄ Ｃ型肝炎のための組合せ長時間作用型組成物および方法
CN107208092B (zh) 2014-12-16 2021-09-10 罗氏创新中心哥本哈根有限公司 手性毒性筛选方法
WO2016100716A1 (en) 2014-12-18 2016-06-23 Vasant Jadhav Reversirtm compounds
WO2016112132A1 (en) 2015-01-06 2016-07-14 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
WO2016130943A1 (en) * 2015-02-13 2016-08-18 Rana Therapeutics, Inc. Hybrid oligonucleotides and uses thereof
US11129844B2 (en) 2015-03-03 2021-09-28 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating MECP2 expression
WO2016161388A1 (en) 2015-04-03 2016-10-06 University Of Massachusetts Fully stabilized asymmetric sirna
CN116004624A (zh) 2015-04-03 2023-04-25 马萨诸塞大学 用于靶向亨廷汀mRNA的寡核苷酸化合物
PT3277815T (pt) 2015-04-03 2021-11-11 Beth Israel Deaconess Medical Ct Inc Compostos de oligonucleótidos para o tratamento de pré-eclâmpsia e outros distúrbios angiogénicos
US10407678B2 (en) 2015-04-16 2019-09-10 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of C9ORF72 antisense transcript
WO2017030973A1 (en) * 2015-08-14 2017-02-23 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
DK3341479T3 (da) 2015-08-24 2020-02-24 Roche Innovation Ct Copenhagen As LNA-G-Proces
US20210052631A1 (en) * 2015-09-25 2021-02-25 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
EP3355932B1 (en) 2015-10-02 2023-04-12 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugation process
SG10201912902TA (en) 2015-10-09 2020-02-27 Wave Life Sciences Ltd Oligonucleotide compositions and methods thereof
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
DK4119569T3 (da) * 2015-11-06 2024-08-12 Ionis Pharmaceuticals Inc Konjugerede antisense-forbindelser til anvendelse i behandling
CA2999341A1 (en) 2015-11-06 2017-05-11 Ionis Pharmaceuticals, Inc. Modulating apolipoprotein (a) expression
UA125963C2 (uk) 2015-11-12 2022-07-20 Ф. Хоффманн-Ля Рош Аг Олігонуклеотид для індукції батьківської експресії ube3a
WO2017096395A1 (en) 2015-12-04 2017-06-08 Ionis Pharmaceuticals, Inc. Methods of treating breast cancer
EP3397288A4 (en) 2015-12-31 2019-09-11 Ionis Pharmaceuticals, Inc. PROCESS FOR REDUCING ATAXIN-2 EXPRESSION
EP3400300A4 (en) 2016-01-05 2019-08-07 Ionis Pharmaceuticals, Inc. PROCESS FOR REDUCING LRRK2 EXPRESSION
ES2858090T3 (es) * 2016-01-29 2021-09-29 Kyowa Kirin Co Ltd Complejo de ácidos nucleicos
JP7749201B6 (ja) 2016-01-31 2025-10-21 ユニバーシティー オブ マサチューセッツ 分岐オリゴヌクレオチド
CN109069529B (zh) 2016-03-07 2021-08-20 箭头药业股份有限公司 用于治疗性化合物的靶向配体
AR108038A1 (es) 2016-03-14 2018-07-11 Roche Innovation Ct Copenhagen As Oligonucleótidos para reducir la expresión de pd-l1 (ligando de muerte programada-1)
US10577607B2 (en) 2016-03-16 2020-03-03 Ionis Pharmaceuticals, Inc. Modulation of DYRK1B expression
EP3429690A4 (en) 2016-03-16 2019-10-23 Ionis Pharmaceuticals, Inc. METHOD FOR MODULATING KEAP1
MA45328A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Compositions acide nucléique-polypeptide et utilisations de celles-ci
EP3228326A1 (en) * 2016-04-05 2017-10-11 Silence Therapeutics GmbH Nucleic acid linked to a trivalent glycoconjugate
JP7150608B6 (ja) * 2016-04-08 2022-11-11 トランスレイト バイオ， インコーポレイテッド 多量体コード核酸及びその使用
EP3442983A1 (en) 2016-04-14 2019-02-20 H. Hoffnabb-La Roche Ag TRITYL-MONO-Ga1NAc COMPOUNDS AND THEIR USE
KR102608220B1 (ko) * 2016-05-06 2023-11-29 아이오니스 파마수티컬즈, 인코포레이티드 Glp-1 수용체 리간드 모이어티 컨쥬게이트된 올리고뉴클레오티드 및 이의 용도
WO2017219017A1 (en) 2016-06-17 2017-12-21 Ionis Pharmaceuticals, Inc. Modulation of gys1 expression
MA45496A (fr) 2016-06-17 2019-04-24 Hoffmann La Roche Molécules d'acide nucléique pour la réduction de l'arnm de padd5 ou pad7 pour le traitement d'une infection par l'hépatite b
WO2017220751A1 (en) 2016-06-22 2017-12-28 Proqr Therapeutics Ii B.V. Single-stranded rna-editing oligonucleotides
RU2019101298A (ru) 2016-07-01 2020-08-03 Ф. Хоффманн-Ля Рош Аг Антисмысловые олигонуклеотиды для модулирования экспрессии htra1
CA3033368A1 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
ES2837076T3 (es) 2016-09-01 2021-06-29 Proqr Therapeutics Ii Bv Oligonucleótidos para la edición de ARN de cadena sencilla modificados químicamente
CN109462981B (zh) 2016-09-02 2023-07-07 箭头药业股份有限公司 靶向配体
CN109661233A (zh) 2016-10-06 2019-04-19 Ionis 制药公司 缀合低聚化合物的方法
JOP20190104A1 (ar) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
WO2018102745A1 (en) 2016-12-02 2018-06-07 Cold Spring Harbor Laboratory Modulation of lnc05 expression
US20190367920A1 (en) 2017-01-13 2019-12-05 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb1 expression
EP3568480A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
EP3568481A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
US20190338286A1 (en) 2017-01-13 2019-11-07 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
WO2018130581A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
CN110536964A (zh) 2017-03-10 2019-12-03 国立研究开发法人国立成育医疗研究中心 反义寡核苷酸和糖原贮积病Ia型预防或治疗用组合物
WO2018165541A1 (en) * 2017-03-10 2018-09-13 The Board Of Regents Of The University Of Texas System Treatment of fuchs' endothelial corneal dystrophy
KR20250145702A (ko) 2017-04-11 2025-10-13 아뷰터스 바이오파마 코포레이션 표적화 조성물
WO2018215049A1 (en) * 2017-05-23 2018-11-29 F. Hoffmann-La Roche Ag Process for galnac oligonucleotide conjugates
EP3633036A4 (en) 2017-05-26 2021-03-17 National Cerebral and Cardiovascular Center NUCLEIC ACID TARGETING ANTI-SENSES PCSK9
US20190055564A1 (en) 2017-06-01 2019-02-21 F. Hoffmann-La Roche Ag Antisense oligonucleotides for modulating htra1 expression
WO2018223073A1 (en) * 2017-06-02 2018-12-06 Wave Life Sciences Ltd. Oligonucleotide compositions and methods of use thereof
WO2018226788A1 (en) 2017-06-07 2018-12-13 University Of Massachusetts Anti-adam33 oligonucleotides and related methods
CN110799647A (zh) 2017-06-23 2020-02-14 马萨诸塞大学 双尾自递送sirna及相关的方法
WO2019030574A1 (en) 2017-08-10 2019-02-14 Cerenis Therapeutics Holding Cargomers
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
WO2019036612A1 (en) 2017-08-17 2019-02-21 Alnylam Pharmaceuticals, Inc. ADJUSTABLE REVERSIR TM COMPOUNDS
US11197884B2 (en) 2017-08-18 2021-12-14 Ionis Pharmaceuticals, Inc. Modulation of the notch signaling pathway for treatment of respiratory disorders
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
US10517889B2 (en) 2017-09-08 2019-12-31 Ionis Pharmaceuticals, Inc. Modulators of SMAD7 expression
WO2019075357A1 (en) * 2017-10-12 2019-04-18 Wave Life Sciences Ltd. OLIGONUCLEOTIDE COMPOSITIONS AND RELATED METHODS
JP2021502059A (ja) 2017-10-13 2021-01-28 ロシュ イノベーション センター コペンハーゲン エーエス 部分的に立体定義されたオリゴヌクレオチドのサブライブラリーを使用することによる、アンチセンスオリゴヌクレオチドの、改良された立体定義されたホスホロチオエートオリゴヌクレオチド変異体を同定するための方法
AU2018350693B2 (en) 2017-10-16 2021-03-04 F. Hoffmann-La Roche Ag Nucleic acid molecule for reduction of PAPD5 and PAPD7 mRNA for treating hepatitis B infection
TWI809004B (zh) 2017-11-09 2023-07-21 美商Ionis製藥公司 用於降低snca表現之化合物及方法
US11414661B2 (en) 2017-12-01 2022-08-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof
WO2019105418A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 双链寡核苷酸、含双链寡核苷酸的组合物与缀合物及制备方法和用途
US11414665B2 (en) 2017-12-01 2022-08-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof
JP7365052B2 (ja) 2017-12-01 2023-10-19 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用
KR102834361B1 (ko) 2017-12-01 2025-07-17 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 핵산, 이를 포함하는 조성물과 컨쥬게이트, 및 그의 제조 방법과 용도
CN118667812A (zh) 2017-12-06 2024-09-20 艾维迪提生物科学公司 治疗肌萎缩和强直性肌营养不良的组合物和方法
CN111344408A (zh) 2017-12-11 2020-06-26 哥本哈根罗氏创新中心 用于调控fndc3b表达的寡核苷酸
WO2019115417A2 (en) 2017-12-12 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating rb1 expression
WO2019126641A2 (en) 2017-12-21 2019-06-27 Ionis Pharmaceuticals, Inc. Modulation of frataxin expression
CN111512160B (zh) 2017-12-21 2024-04-09 豪夫迈·罗氏有限公司 Htra1 rna拮抗剂的伴随诊断
CN111757936B (zh) 2017-12-22 2025-07-04 罗氏创新中心哥本哈根有限公司 包含二硫代磷酸酯核苷间连接的寡核苷酸
US20200332289A1 (en) 2017-12-22 2020-10-22 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
US11597926B2 (en) 2017-12-22 2023-03-07 Roche Innovation Center Copenhagen A/S Thiophosphoramidites
CA3087106A1 (en) * 2017-12-29 2019-07-04 Suzhou Ribo Life Science Co., Ltd. Conjugates and preparation and use thereof
WO2019137883A1 (en) 2018-01-10 2019-07-18 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating pias4 expression
KR102839166B1 (ko) 2018-01-12 2025-07-28 브리스톨-마이어스 스큅 컴퍼니 알파-시누클레인을 표적화하는 안티센스 올리고뉴클레오티드 및 그의 용도
JP2021510295A (ja) 2018-01-12 2021-04-22 ロシュ イノベーション センター コペンハーゲン エーエス Ｇｓｋ３ｂ発現を調節するためのオリゴヌクレオチド
CA3088112A1 (en) 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
JP2021511027A (ja) * 2018-01-12 2021-05-06 ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブＲｏｃｈｅ Ｉｎｎｏｖａｔｉｏｎ Ｃｅｎｔｅｒ Ｃｏｐｅｎｈａｇｅｎ Ａ／Ｓ アルファ−シヌクレインアンチセンスオリゴヌクレオチド及びその使用
AU2019206731A1 (en) 2018-01-15 2020-07-30 Ionis Pharmaceuticals, Inc. Modulators of DNM2 expression
EP3740574A1 (en) 2018-01-17 2020-11-25 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating erc1 expression
WO2019141723A1 (en) 2018-01-18 2019-07-25 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting srebp1
WO2019145386A1 (en) 2018-01-26 2019-08-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating csnk1d expression
EP3743116B1 (en) * 2018-01-26 2024-07-10 F. Hoffmann-La Roche AG Radiolabelled oligonucleotides and process for their preparation
MA51795A (fr) * 2018-02-09 2020-12-16 Hoffmann La Roche Oligonucléotides pour moduler l'expression de tmem106b
IL320427A (en) 2018-02-21 2025-06-01 Bristol Myers Squibb Co CAMK2D antisense oligonucleotides and their uses
EP3759127A4 (en) 2018-03-02 2022-03-30 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR MODULATING AMYLOID BETA PRECURSOR PROTEIN
TWI840345B (zh) 2018-03-02 2024-05-01 美商Ionis製藥公司 Irf4表現之調節劑
CN115976028B (zh) 2018-03-09 2025-03-25 第一三共株式会社 糖原病Ia型治疗药
WO2019183440A1 (en) 2018-03-22 2019-09-26 Ionis Pharmaceuticals, Inc. Methods for modulating fmr1 expression
EP3775208A1 (en) 2018-04-05 2021-02-17 F. Hoffmann-La Roche AG Use of fubp1 inhibitors for treating hepatitis b virus infection
US11365416B2 (en) 2018-04-11 2022-06-21 Ionis Pharmaceuticals, Inc. Modulators of EZH2 expression
EP3790990A1 (en) 2018-05-07 2021-03-17 Roche Innovation Center Copenhagen A/S Quality control of lna oligonucleotide therapeutics using massively parallel sequencing
CN112400020B (zh) 2018-05-08 2024-11-19 莱古路斯治疗法股份有限公司 作为具有hcv抗病毒活性与降低的高胆红素血症副作用的mir-122抑制剂的galnac缀合的经修饰的寡核苷酸
WO2019215175A1 (en) 2018-05-08 2019-11-14 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating myh7 expression
US20210355497A1 (en) 2018-05-09 2021-11-18 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing fxi expression
WO2019217708A1 (en) 2018-05-09 2019-11-14 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing atxn3 expression
SG11202010841QA (en) * 2018-05-11 2020-11-27 Alpha Anomeric Sas Oligonucleotides conjugates comprising 7'-5'-alpha-anomeric-bicyclic sugar nucleosides
CA3098624A1 (en) 2018-05-11 2019-11-14 Wave Life Sciences Ltd. Oligonucleotide compositions and methods of use thereof
GB201808146D0 (en) 2018-05-18 2018-07-11 Proqr Therapeutics Ii Bv Stereospecific Linkages in RNA Editing Oligonucleotides
WO2019233922A1 (en) 2018-06-05 2019-12-12 F. Hoffmann-La Roche Ag Oligonucleotides for modulating atxn2 expression
WO2019241648A1 (en) 2018-06-14 2019-12-19 Ionis Pharmaceuticals, Inc. Compounds and methods for increasing stmn2 expression
TWI833770B (zh) 2018-06-27 2024-03-01 美商Ionis製藥公司 用於減少 lrrk2 表現之化合物及方法
WO2020007702A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting bcl2l11
WO2020007700A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting spi1
WO2020007772A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting gbp-1
MY206038A (en) 2018-07-03 2024-11-26 Hoffmann La Roche Oligonucleotides for modulating tau expression
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
WO2020007889A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting stat1
WO2020011743A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mafb
WO2020011653A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting kynu
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
WO2020011869A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting tlr2
WO2020011744A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
MX2021000404A (es) 2018-07-13 2021-03-25 Hoffmann La Roche Oligonucleotidos para modular la expresion de rtel1.
MX2021000922A (es) 2018-07-25 2021-03-31 Ionis Pharmaceuticals Inc Compuestos y metodos para reducir la expresion de la atxn2.
CN112513060B (zh) 2018-07-31 2024-08-06 罗氏创新中心哥本哈根有限公司 包含三硫代磷酸酯核苷间键的寡核苷酸
US20210221837A1 (en) * 2018-07-31 2021-07-22 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
EP3833763A4 (en) 2018-08-10 2023-07-19 University of Massachusetts MODIFIED OLIGONUCLEOTIDES FOR TARGETING SNPS
JP2021533800A (ja) 2018-08-21 2021-12-09 スーチョウ リボ ライフ サイエンス カンパニー、リミテッドSuzhou Ribo Life Science Co., Ltd. 核酸、当該核酸を含む薬物組成物及び複合体ならびにその使用
WO2020038971A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting vcan
US11279930B2 (en) 2018-08-23 2022-03-22 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
EP3841220A1 (en) 2018-08-23 2021-06-30 Roche Innovation Center Copenhagen A/S Microrna-134 biomarker
WO2020038976A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting usp8
WO2020038973A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting sptlc1
EP3844274A1 (en) 2018-08-28 2021-07-07 Roche Innovation Center Copenhagen A/S Neoantigen engineering using splice modulating compounds
EP3620519A1 (en) 2018-09-04 2020-03-11 F. Hoffmann-La Roche AG Use of isolated milk extracellular vesicles for delivering oligonucleotides orally
US20220056443A1 (en) * 2018-09-06 2022-02-24 Aptamir Therapeutics, Inc. Metabolic benefits of short mir-22 mirna antagomir therapies
CN111655297A (zh) 2018-09-30 2020-09-11 苏州瑞博生物技术有限公司 一种siRNA缀合物及其制备方法和用途
EP3873920A1 (en) 2018-11-01 2021-09-08 F. Hoffmann-La Roche AG Antisense oligonucleotides targeting tia1
TW202028222A (zh) 2018-11-14 2020-08-01 美商Ionis製藥公司 Foxp3表現之調節劑
WO2020102630A1 (en) 2018-11-15 2020-05-22 Ionis Pharmaceuticals, Inc. Modulators of irf5 expression
MY205095A (en) 2018-11-21 2024-10-01 Ionis Pharmaceuticals Inc Compounds and methods for reducing prion expression
US12485136B2 (en) 2018-12-03 2025-12-02 Takeda Pharmaceuticals U.S.A., Inc. Methods for the treatment of trinucleotide repeat expansion disorders associated with MLH3 activity
CN113631709A (zh) 2018-12-20 2021-11-09 普拉克西斯精密药物股份有限公司 用于治疗kcnt1相关病症的组合物和方法
WO2020136125A2 (en) 2018-12-21 2020-07-02 Boehringer Ingelheim International Gmbh Antisense oligonucleotides targeting card9
JP2022523467A (ja) 2019-01-18 2022-04-25 ユニバーシティ・オブ・マサチューセッツ 動的な薬物動態を修飾するアンカー
JP2022518500A (ja) * 2019-01-25 2022-03-15 エフ．ホフマン－ラ ロシュ アーゲー 経口薬物送達のための脂質小胞
US11214803B2 (en) 2019-01-31 2022-01-04 Ionis Pharmaceuticals, Inc. Modulators of YAP1 expression
CN113490742A (zh) * 2019-02-20 2021-10-08 罗氏创新中心哥本哈根有限公司 膦酰基乙酸酯缺口聚物寡核苷酸
CA3129646A1 (en) 2019-02-20 2020-08-27 Roche Innovation Center Copenhagen A/S Novel phosphoramidites
CN113474633A (zh) 2019-02-26 2021-10-01 罗氏创新中心哥本哈根有限公司 寡核苷酸配制方法
KR20210134686A (ko) 2019-02-27 2021-11-10 아이오니스 파마수티컬즈, 인코포레이티드 Malat1 발현의 조절인자
JP2022522898A (ja) * 2019-03-05 2022-04-20 エフ．ホフマン－ラ ロシュ アーゲー 分子の細胞内標的化
CN117431244A (zh) 2019-03-29 2024-01-23 Ionis制药公司 用于调节ube3a-ats的化合物和方法
CA3132178A1 (en) 2019-04-02 2020-10-08 Aliye Seda Yilmaz-Elis Antisense oligonucleotides for immunotherapy
BR112021019182A2 (pt) 2019-04-03 2022-05-31 Bristol Myers Squibb Co Oligonucleotídeos angptl2 antissenso e seus usos
US11286485B2 (en) 2019-04-04 2022-03-29 Hoffmann-La Roche Inc. Oligonucleotides for modulating ATXN2 expression
JP7499267B2 (ja) 2019-04-04 2024-06-13 エフ． ホフマン－ラ ロシュ アーゲー Ａｔｘｎ２発現を調節するためのオリゴヌクレオチド
SG11202112741XA (en) 2019-05-31 2021-12-30 Aligos Therapeutics Inc Modified gapmer oligonucleotides and methods of use
CN113950529A (zh) 2019-06-06 2022-01-18 豪夫迈·罗氏有限公司 靶向atxn3的反义寡核苷酸
EP4660307A2 (en) 2019-07-26 2025-12-10 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating gfap
CA3144467A1 (en) * 2019-07-30 2021-02-04 Jonathan Miles Brown Subcutaneous delivery of multimeric oligonucleotides with enhanced bioactivity
CN114502730A (zh) 2019-08-09 2022-05-13 马萨诸塞大学 经化学修饰的靶向snp的寡核苷酸
CA3150715A1 (en) 2019-09-10 2021-03-18 Makoto Koizumi Conjugate of galnac-oligonucleotide for delivery to liver and manufacturing method thereof
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
AU2020356931A1 (en) * 2019-10-02 2022-05-26 Sirnaomics, Inc. Oligonucleotides with nucleoside analogs
JP2023506954A (ja) 2019-12-19 2023-02-20 エフ． ホフマン－ラ ロシュ エージー． Ｂ型肝炎ウイルス感染を処置するためのｓａｒａｆ阻害剤の使用
CN114829599A (zh) 2019-12-19 2022-07-29 豪夫迈·罗氏有限公司 Scamp3抑制剂用于治疗乙型肝炎病毒感染的用途
EP4077670A1 (en) 2019-12-19 2022-10-26 F. Hoffmann-La Roche AG Use of cops3 inhibitors for treating hepatitis b virus infection
WO2021127650A1 (en) * 2019-12-19 2021-06-24 Entrada Therapeutics, Inc. Compositions for delivery of antisense compounds
CN114901821A (zh) * 2019-12-19 2022-08-12 豪夫迈·罗氏有限公司 Sept9抑制剂用于治疗乙型肝炎病毒感染的用途
JP2023506550A (ja) 2019-12-19 2023-02-16 エフ． ホフマン－ラ ロシュ エージー． Ｂ型肝炎ウイルス感染症を処置するためのｓｂｄｓ阻害剤の使用
US20210214727A1 (en) 2019-12-20 2021-07-15 Hoffmann-La Roche Inc. Enhanced oligonucleotides for inhibiting scn9a expression
CA3163490A1 (en) 2019-12-24 2021-07-01 F. Hoffman-La Roche Ag Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv
WO2021130270A1 (en) 2019-12-24 2021-07-01 F. Hoffmann-La Roche Ag Pharmaceutical combination of antiviral agents targeting hbv and/or an immune modulator for treatment of hbv
EP4097234A1 (en) 2020-01-28 2022-12-07 Université de Strasbourg Antisense oligonucleotide targeting linc00518 for treating melanoma
WO2021158810A1 (en) 2020-02-05 2021-08-12 Bristol-Myers Squibb Company Oligonucleotides for splice modulation of camk2d
JP2023516142A (ja) 2020-02-28 2023-04-18 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト Ｃｄ７３エクソン７スプライシングを調節するためのオリゴヌクレオチド
AR121446A1 (es) 2020-02-28 2022-06-08 Ionis Pharmaceuticals Inc Compuestos y métodos para modular smn2
MX2022010980A (es) 2020-03-04 2022-12-02 Verve Therapeutics Inc Composiciones y metodos para el suministro de arn dirigido.
EP4121063A4 (en) 2020-03-19 2024-07-03 Avidity Biosciences, Inc. COMPOSITIONS AND METHODS FOR TREATING FACIO-SCAPULO-HUMERAL MUSCULAR DYSTROPHY
EP4138858A4 (en) * 2020-04-21 2024-07-03 Flagship Pioneering, Inc. BIFUNCTIONAL MOLECULES AND METHODS OF USE THEREOF
JP7738573B2 (ja) 2020-05-01 2025-09-12 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 Ａｔｘｎ１を調節するための化合物及び方法
EP4150085A1 (en) 2020-05-11 2023-03-22 Genentech, Inc. Complement component c1r inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
EP4150084A1 (en) 2020-05-11 2023-03-22 Genentech, Inc. Complement component 4 inhibitors for treating neurological diseases, and related compositons, systems and methods of using same
EP4149486A1 (en) 2020-05-11 2023-03-22 Genentech, Inc. Complement component c1s inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
TW202208628A (zh) 2020-05-13 2022-03-01 瑞士商赫孚孟拉羅股份公司 靶向顆粒蛋白前體之寡核苷酸促效劑
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)
CA3162416C (en) 2020-05-15 2023-07-04 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1)
EP4150087A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2)
WO2021231698A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl)
WO2021231680A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2)
WO2021231692A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of otoferlin (otof)
EP4150089A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of retinoschisin 1 (rs1)
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)
CN115884777A (zh) 2020-05-22 2023-03-31 豪夫迈·罗氏有限公司 用于card9的剪接调节的寡核苷酸
AR122534A1 (es) 2020-06-03 2022-09-21 Triplet Therapeutics Inc Métodos para el tratamiento de los trastornos de expansión por repetición de nucleótidos asociados con la actividad de msh3
US20230212572A1 (en) 2020-06-09 2023-07-06 Roche Innovation Center Copenhagen A/S Guanosine Analogues for Use in Therapeutics Polynucleotides
AR122731A1 (es) 2020-06-26 2022-10-05 Hoffmann La Roche Oligonucleótidos mejorados para modular la expresión de fubp1
CN116096899A (zh) 2020-06-29 2023-05-09 Ionis制药公司 调节plp1的化合物和方法
JP2023534557A (ja) 2020-07-23 2023-08-09 エフ． ホフマン－ラ ロシュ アーゲー Ｒｎａ結合タンパク質部位を標的とするオリゴヌクレオチド
WO2022018155A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Lna oligonucleotides for splice modulation of stmn2
UY39344A (es) 2020-07-28 2022-02-25 Ionis Pharmaceuticals Inc Compuestos y métodos para reducir la expresión de app
CN111671913B (zh) * 2020-07-30 2022-02-08 四川大学 一种量子点-小核酸偶联物及其用途
CA3186935A1 (en) 2020-08-07 2022-02-10 Paymaan JAFAR-NEJAD Compounds and methods for modulating scn2a
EP4200419A2 (en) 2020-08-21 2023-06-28 F. Hoffmann-La Roche AG Use of a1cf inhibitors for treating hepatitis b virus infection
CA3194161A1 (en) * 2020-10-02 2022-04-07 David M. Evans Nucleoside containing sirnas for treating viral diseases
TW202227101A (zh) 2020-11-18 2022-07-16 美商Ionis製藥公司 用於調節血管收縮素原表現之化合物及方法
AR124227A1 (es) 2020-12-03 2023-03-01 Hoffmann La Roche Oligonucleótidos antisentido que actúan sobre atxn3
AR124229A1 (es) 2020-12-03 2023-03-01 Hoffmann La Roche Oligonucleótidos antisentido que actúan sobre atxn3
EP4263831A1 (en) 2020-12-18 2023-10-25 F. Hoffmann-La Roche AG Antisense oligonucleotides for targeting progranulin
TW202242111A (zh) 2020-12-18 2022-11-01 美商Ionis製藥公司 用於調節因子ｘｉｉ之化合物及方法
JP2024501662A (ja) 2020-12-22 2024-01-15 エフ． ホフマン－ラ ロシュ アーゲー Ｘｂｐ１を標的とするオリゴヌクレオチド
CN114716518A (zh) * 2021-01-06 2022-07-08 圣诺制药公司 一种能够抑制pcsk9表达的分子构造及药物组合物
US20240083990A1 (en) 2021-01-26 2024-03-14 Universite Brest Bretagne Occidentale Novel stim1 splicing variants and uses thereof
TW202246500A (zh) 2021-02-02 2022-12-01 瑞士商赫孚孟拉羅股份公司 用於抑制 ｒｔｅｌ１ 表現之增強型寡核苷酸
AU2022234522A1 (en) 2021-03-08 2023-10-26 Les Laboratoires Servier Antisense oligonucleotides for inhibiting alpha-synuclein expression
WO2022232650A1 (en) * 2021-04-30 2022-11-03 Ionis Pharmaceuticals, Inc. Methods for reducing agt expression
EP4341405A1 (en) 2021-05-20 2024-03-27 Korro Bio, Inc. Methods and compositions for adar-mediated editing
WO2022256283A2 (en) 2021-06-01 2022-12-08 Korro Bio, Inc. Methods for restoring protein function using adar
WO2022258555A1 (en) 2021-06-08 2022-12-15 F. Hoffmann-La Roche Ag Oligonucleotide progranulin agonists
US12378267B2 (en) 2021-06-17 2025-08-05 Entrada Therapeutics, Inc. Synthesis of FMOC-protected morpholino monomers and oligomers
MX2023015230A (es) 2021-06-18 2024-01-18 Ionis Pharmaceuticals Inc Compuestos y metodos para reducir la expresion de ifnar1.
EP4359539A4 (en) 2021-06-23 2025-05-14 University Of Massachusetts ANTI-FLT1 OLIGONUCLEOTIDE COMPOUNDS OPTIMIZED FOR THE TREATMENT OF PREECLAMPSIA AND OTHER ANGIOGENIC DISORDERS
WO2023278410A1 (en) 2021-06-29 2023-01-05 Korro Bio, Inc. Methods and compositions for adar-mediated editing
US20230194709A9 (en) 2021-06-29 2023-06-22 Seagate Technology Llc Range information detection using coherent pulse sets with selected waveform characteristics
US20250188455A1 (en) * 2021-09-02 2025-06-12 Vanderbilt University Lipophilic oligonucleotide conjugates
KR20240055874A (ko) 2021-09-16 2024-04-29 어비디티 바이오사이언시스 인크. 안면견갑상완 근이영양증을 치료하는 조성물 및 방법
CA3234835A1 (en) 2021-10-22 2023-04-27 Korro Bio, Inc. Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing
JP2024540271A (ja) 2021-11-03 2024-10-31 エフ． ホフマン－ラ ロシュ アーゲー アポリポタンパク質ｅ４発現を調節するためのオリゴヌクレオチド
KR20240101580A (ko) 2021-11-11 2024-07-02 에프. 호프만-라 로슈 아게 Hbv 치료를 위한 약학 조합물
CA3241316A1 (en) * 2021-12-03 2023-06-08 Quralis Corporation Gapmer antisense oligonucleotides with modified backbone chemistries
CN118434858A (zh) 2021-12-07 2024-08-02 豪夫迈·罗氏有限公司 靶向actl6b的反义寡核苷酸
JP2024546887A (ja) 2021-12-17 2024-12-26 ジェネンテック， インコーポレイテッド オリゴヌクレオチドｇｂａアゴニスト
JP2024546993A (ja) 2021-12-17 2024-12-26 エフ． ホフマン－ラ ロシュ アーゲー Ｒｔｅｌ１及びｆｕｂｐ１を調節するためのオリゴヌクレオチドの組み合わせ
JP2024547071A (ja) 2021-12-20 2024-12-26 エフ． ホフマン－ラ ロシュ アーゲー トレオース核酸アンチセンスオリゴヌクレオチドおよびその方法
CN118613268A (zh) 2022-01-20 2024-09-06 基因泰克公司 用于调节tmem106b表达的反义寡核苷酸
AR128558A1 (es) 2022-02-21 2024-05-22 Hoffmann La Roche Oligonucleótido antisentido
CN118871585A (zh) 2022-03-16 2024-10-29 第一三共株式会社 具有RNAi活性的化学-修饰的寡核苷酸
CN118891366A (zh) 2022-03-16 2024-11-01 第一三共株式会社 抑制转铁蛋白受体2的表达的siRNA
WO2023217890A1 (en) 2022-05-10 2023-11-16 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting cfp-elk1 intergene region
JP2025518522A (ja) 2022-05-18 2025-06-17 エフ． ホフマン－ラ ロシュ アーゲー Ｒｎａ結合タンパク質部位を標的とする改善されたオリゴヌクレオチド
EP4282964A1 (en) * 2022-05-23 2023-11-29 Universitat de Valéncia Oligonucleotides conjugated to oleic acid and uses thereof
JP2025520514A (ja) 2022-06-17 2025-07-03 エフ． ホフマン－ラ ロシュ アーゲー プログラニュリンを標的とするためのアンチセンスオリゴヌクレオチド
EP4332221A1 (en) 2022-08-29 2024-03-06 Roche Innovation Center Copenhagen A/S Threose nucleic acid antisense oligonucleotides and methods thereof
TW202421206A (zh) 2022-09-06 2024-06-01 瑞士商赫孚孟拉羅股份公司 用於投予至眼睛之雙股ｒｎａ分子
KR20250075637A (ko) 2022-09-23 2025-05-28 아이오니스 파마수티컬즈, 인코포레이티드 Mecp2 발현을 감소시키기 위한 화합물 및 방법(compounds and methods for reducing mecp2 expression)
CN120529923A (zh) * 2022-11-21 2025-08-22 肽世代公司 细胞穿透肽、其缀合物及其使用方法
WO2024126654A1 (en) 2022-12-14 2024-06-20 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting actl6b
EP4652273A1 (en) 2023-01-16 2025-11-26 Institut National de la Recherche pour l'Agriculture, l'Alimentation et l'Environnement Antisense molecules and their uses for the treatment of coronavirus infection, in particular the treatment of covid-19 related to sars-cov-2 infection
WO2024155957A1 (en) 2023-01-19 2024-07-25 Altos Labs, Inc. Use of regeneration factors in organ transplantation
WO2024196893A1 (en) * 2023-03-17 2024-09-26 Camford Labs Inc. Chemically modified nucleotides
CN121002179A (zh) * 2023-03-30 2025-11-21 中美瑞康核酸技术(南通)研究院有限公司 寡核苷酸的递送载体及其使用方法
WO2024227765A2 (en) 2023-05-04 2024-11-07 F. Hoffmann-La Roche Ag Oligonucleotides capable of upregulating glucocerebrosidase expression
TW202508607A (zh) * 2023-05-19 2025-03-01 大陸商北京炫景瑞醫藥科技有限公司 雙股寡核苷酸及其共軛物和用途
TW202516004A (zh) 2023-06-16 2025-04-16 瑞士商赫孚孟拉羅股份公司 調節ｊａｋ１表現之雙股寡核苷酸
WO2025036916A1 (en) 2023-08-16 2025-02-20 Les Laboratoires Servier Oligonucleotides for modulating kcnt1 expression

Family Cites Families (207)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US603095A (en) 1898-04-26 Machine for dishing metal
US2699808A (en) 1944-10-06 1955-01-18 Mark W Lowe Apparatus for peeling tomatoes
US2699508A (en) 1951-12-21 1955-01-11 Selectronics Inc Method of mounting and construction of mounting for low frequency piezoelectric crystals
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
US4962029A (en) 1987-10-02 1990-10-09 Cetus Corporation Covalent oligonucleotide-horseradish peroxidase conjugate
US4914210A (en) 1987-10-02 1990-04-03 Cetus Corporation Oligonucleotide functionalizing reagents
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
US5354844A (en) 1989-03-16 1994-10-11 Boehringer Ingelheim International Gmbh Protein-polycation conjugates
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
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
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US6395492B1 (en) 1990-01-11 2002-05-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
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
DE4104186A1 (de) 1991-02-12 1992-08-13 Genentech Inc Neue, ueber endozytose in hoehere eukaryotische zellen aufnehmbare, nukleinsaeure enthaltende komplexe
DE4110409C2 (de) 1991-03-29 1999-05-27 Boehringer Ingelheim Int Neue Protein-Polykation-Konjugate
KR950014915B1 (ko) 1991-06-19 1995-12-18 주식회사녹십자 탈시알로당단백-포함화합물
ATE239484T1 (de) 1991-10-24 2003-05-15 Isis Pharmaceuticals Inc Derivatisierte oligonukleotide mit verbessertem aufnahmevermögen
WO2002081494A1 (en) 2001-03-26 2002-10-17 Sirna Therapeutics, Inc. Oligonucleotide mediated inhibition of hepatitis b virus and hepatitis c virus replication
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
NL9201440A (nl) 1992-08-11 1994-03-01 Univ Leiden Triantennaire clusterglycosiden, hun bereiding en toepassing.
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
DE69433036T2 (de) 1993-09-03 2004-05-27 Isis Pharmaceuticals, Inc., Carlsbad Aminoderivatisierte nukleoside und oligonukleoside
PL182237B1 (pl) 1994-03-07 2001-11-30 Dow Chemical Co Sposób przeprowadzania transfekcji komórek i osiagniecia biodostepnosci materialu genetycznego in vitro i ex vivo PL PL
US5646262A (en) 1994-07-28 1997-07-08 Georgetown University Antisense oligonucleotides against hepatitis B viral replication
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
JP3307945B2 (ja) 1994-10-06 2002-07-29 アイシス・ファーマシューティカルス・インコーポレーテッド ペプチド核酸コンジュゲート
US5684142A (en) 1995-06-07 1997-11-04 Oncor, Inc. Modified nucleotides for nucleic acid labeling
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
US5985662A (en) 1995-07-13 1999-11-16 Isis Pharmaceuticals Inc. Antisense inhibition of hepatitis B virus replication
EP0862439A4 (en) 1995-11-22 2001-01-10 O Paul O P Ts LIGANDS FOR INCREASING THE CELLULAR UPtake OF BIOMOLECULES
US6344436B1 (en) 1996-01-08 2002-02-05 Baylor College Of Medicine Lipophilic peptides for macromolecule delivery
US5656408A (en) 1996-04-29 1997-08-12 Xerox Corporation Coated carrier particles
US5776907A (en) 1996-05-20 1998-07-07 Texas Biotechnology Corporation Mitomycin oligonucleotide conjugates
US6001991A (en) * 1996-10-04 1999-12-14 Isis Pharmaceuticals Inc. Antisense oligonucleotide modulation of MDR P-glycoprotein gene expression
US20030014318A1 (en) 1996-11-08 2003-01-16 Matthew Byrne International trading system and method
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
US5770716A (en) 1997-04-10 1998-06-23 The Perkin-Elmer Corporation Substituted propargylethoxyamido nucleosides, oligonucleotides and methods for using same
WO1998050540A1 (en) 1997-05-05 1998-11-12 Hoechst Marion Roussel Deutschland Gmbh MODIFIED ANTISENSE NUCLEOTIDES COMPLEMENTARY TO A SECTION OF THE HUMAN Ha-Ras GENE
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
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
KR100414936B1 (ko) 1997-09-12 2004-01-13 엑시콘 에이/에스 이환 및 삼환 뉴클레오시드, 뉴클레오타이드 및올리고뉴클레오타이드 동족체
US6096875A (en) 1998-05-29 2000-08-01 The Perlein-Elmer Corporation Nucleotide compounds including a rigid linker
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6335432B1 (en) 1998-08-07 2002-01-01 Bio-Red Laboratories, Inc. Structural analogs of amine bases and nucleosides
US6335437B1 (en) 1998-09-07 2002-01-01 Isis Pharmaceuticals, Inc. Methods for the preparation of conjugated oligomers
US6365379B1 (en) 1998-10-06 2002-04-02 Isis Pharmaceuticals, Inc. Zinc finger peptide cleavage of nucleic acids
CA2348823A1 (en) 1998-12-02 2000-06-08 I.D.M. Immuno-Designed Molecules New oligomeric conjugates liable to transfer biological molecules into cells
PT1178999E (pt) 1999-05-04 2007-06-26 Santaris Pharma As Análogos de l-ribo-lna
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US6656730B1 (en) * 1999-06-15 2003-12-02 Isis Pharmaceuticals, Inc. Oligonucleotides conjugated to protein-binding drugs
US20040146516A1 (en) 1999-06-17 2004-07-29 Utah Ventures Ii L.P. Lumen-exposed molecules and methods for targeted delivery
US6617442B1 (en) 1999-09-30 2003-09-09 Isis Pharmaceuticals, Inc. Human Rnase H1 and oligonucleotide compositions thereof
CA2385853A1 (en) 1999-10-04 2001-04-12 Exiqon A/S Design of high affinity rnase h recruiting oligonucleotide
US20080039414A1 (en) 2002-02-20 2008-02-14 Sima Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US6559279B1 (en) 2000-09-08 2003-05-06 Isis Pharmaceuticals, Inc. Process for preparing peptide derivatized oligomeric compounds
EP1572067A4 (en) 2001-05-18 2009-05-13 Sirna Therapeutics Inc CONJUGATES AND COMPOSITIONS FOR CELLULAR RELEASE
US7407943B2 (en) 2001-08-01 2008-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein B expression
US7259150B2 (en) 2001-08-07 2007-08-21 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein (a) expression
US7227014B2 (en) 2001-08-07 2007-06-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (a) expression
US20030191075A1 (en) * 2002-02-22 2003-10-09 Cook Phillip Dan Method of using modified oligonucleotides for hepatic delivery
AU2003237875A1 (en) 2002-05-15 2003-12-02 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein b expression
GB2389824B (en) 2002-06-21 2005-08-24 Paul Sinclair Improvements in or relating to funeral vehicles
US7655790B2 (en) 2002-07-12 2010-02-02 Sirna Therapeutics, Inc. Deprotection and purification of oligonucleotides and their derivatives
US7087229B2 (en) 2003-05-30 2006-08-08 Enzon Pharmaceuticals, Inc. Releasable polymeric conjugates based on aliphatic biodegradable linkers
US6878805B2 (en) 2002-08-16 2005-04-12 Isis Pharmaceuticals, Inc. Peptide-conjugated oligomeric compounds
EP1560840B1 (en) 2002-11-05 2015-05-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
AU2003295389A1 (en) 2002-11-05 2004-06-03 Isis Pharmaceuticals, Inc. Conjugated oligomeric compounds and their use in gene modulation
EP1569695B1 (en) 2002-11-13 2013-05-15 Genzyme Corporation Antisense modulation of apolipoprotein b expression
US7511131B2 (en) 2002-11-13 2009-03-31 Genzyme Corporation Antisense modulation of apolipoprotein B expression
DK2752488T3 (da) 2002-11-18 2020-04-20 Roche Innovation Ct Copenhagen As Antisense-design
US7816337B2 (en) 2003-02-18 2010-10-19 Roche Madison Inc. Reversible attachment of a membrane active polymer to a polynucleotide
WO2004087931A1 (en) 2003-04-03 2004-10-14 Korea Advanced Institute Of Science And Technology Conjugate for gene transfer comprising oligonucleotide and hydrophilic polymer, polyelectrolyte complex micelles formed from the conjugate, and methods for preparation thereof
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
US7541344B2 (en) * 2003-06-03 2009-06-02 Eli Lilly And Company Modulation of survivin expression
ES2302898T3 (es) 2003-07-11 2008-08-01 Lbr Medbiotech B.V. Transferencia de genes a celulas musculares mediada por el receptor de manosa-6-fosfato.
EP1648914A4 (en) 2003-07-31 2009-12-16 Regulus Therapeutics Inc OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA
US8969314B2 (en) 2003-07-31 2015-03-03 Regulus Therapeutics, Inc. Methods for use in modulating miR-122a
US7825235B2 (en) 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
JP4731324B2 (ja) 2003-08-28 2011-07-20 武 今西 Ｎ−ｏ結合性架橋構造型新規人工核酸
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
AU2004275876B2 (en) * 2003-09-25 2011-03-31 Coley Pharmaceutical Gmbh Nucleic acid-lipophilic conjugates
CN100569945C (zh) 2003-12-23 2009-12-16 桑塔里斯制药公司 用于调节bcl-2的寡聚化合物
JP2007524412A (ja) 2004-01-22 2007-08-30 イムノメディクス， インコーポレイテッド 葉酸コンジュゲートおよびコンプレックス
DK1713912T3 (da) 2004-01-30 2013-12-16 Santaris Pharma As Modificerede Korte Interfererende RNA (Modificerede siRNA)
US20050244869A1 (en) 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
US20060105975A1 (en) 2004-04-19 2006-05-18 Shannon Pendergrast Aptamer-mediated intracellular delivery of therapeutic oligonucleotides
US20050288246A1 (en) 2004-05-24 2005-12-29 Iversen Patrick L Peptide conjugated, inosine-substituted antisense oligomer compound and method
WO2006112872A2 (en) * 2004-08-04 2006-10-26 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
AU2005272912A1 (en) 2004-08-10 2006-02-23 Genzyme Corporation Antisense modulation of apolipoprotein B expression
AU2005289588B2 (en) * 2004-09-24 2011-12-22 Alnylam Pharmaceuticals, Inc. RNAi modulation of ApoB and uses thereof
US20060154888A1 (en) * 2004-11-09 2006-07-13 Santaris Pharma A/S LNA oligonucleotides and the treatment of cancer
NZ555644A (en) * 2004-11-09 2009-04-30 Santaris Pharma As Potent LNA oligonucleotides for the inhibition of HIF-1A expression
US20120122801A1 (en) 2005-01-05 2012-05-17 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
JP2008527993A (ja) 2005-01-24 2008-07-31 アヴァリス・アクチエボラーグ 特異性及び送達の改善のためのｓｉＲＮＡ分子、ｓｈＲＮＡ分子又はアンチセンス分子及び機能的実体を含む複合体
US20070213292A1 (en) 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
WO2007027894A2 (en) 2005-08-29 2007-03-08 Isis Pharmaceuticals, Inc. Antisense compounds having enhanced anti-microrna activity
KR20080068019A (ko) * 2005-09-15 2008-07-22 산타리스 팔마 에이/에스 아포지단백질-ｂ100 발현 억제용 ｒｎａ 길항제 화합물
WO2007031091A2 (en) 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
CA2623772A1 (en) 2005-09-19 2007-03-29 Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Modulation of glucocorticoid receptor expression
KR101789603B1 (ko) 2005-11-10 2017-11-21 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 Ｔｎｆ 수퍼패밀리 수용체에 대한 스플라이스 스위칭올리고머 및 염증성 질환 치료용 약제학적 조성물
ES2516815T3 (es) 2006-01-27 2014-10-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos modificados en la posición 6
CA2638837A1 (en) 2006-01-27 2007-08-02 Santaris Pharma A/S Lna modified phosphorothiolated oligonucleotides
EP2089521A1 (en) 2006-02-08 2009-08-19 Ercole Biotech, Inc. Soluble tnf receptors and their use in treatment of disease
WO2007107162A2 (en) 2006-03-23 2007-09-27 Santaris Pharma A/S Small internally segmented interfering rna
GB0606415D0 (en) 2006-03-31 2006-05-10 Univ Southampton Topical drug delivery
US8163708B2 (en) * 2006-04-03 2012-04-24 Santaris Pharma A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotide
KR101407707B1 (ko) 2006-04-03 2014-06-19 산타리스 팔마 에이/에스 Ａｎｔｉ-ｍｉｒｎａ 안티센스 올리고뉴클레오타이드를 함유하는 약학적 조성물
WO2007136989A2 (en) * 2006-05-05 2007-11-29 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of dgat2
CA2651453C (en) 2006-05-11 2014-10-14 Isis Pharmaceuticals, Inc. 5'-modified bicyclic nucleic acid analogs
EP2076257A4 (en) 2006-09-15 2014-04-16 Belrose Pharma Inc POLYMER CONJUGATES WITH POSITIVELY LOADED PARTS
CN101534643A (zh) 2006-09-15 2009-09-16 安佐制药股份有限公司 用于递送寡核苷酸的基于位阻酯的生物可降解连接体
MX2009003398A (es) 2006-09-27 2009-08-12 Coley Pharm Gmbh Analogos de oligonucleotidos cpg que contienen analogos t hidrofobos con actividad inmunoestimuladora mejorada.
WO2008040355A2 (en) 2006-10-06 2008-04-10 Exiqon A/S Novel methods for quantification of micrornas and small interfering rnas
MX2009003729A (es) 2006-10-09 2009-04-22 Santaris Pharma As Copuestos antagonistas de acido ribonucleico para la modulacion de proproteina convertasa subtilisina/kexina tipo 9a.
JP2010510807A (ja) 2006-11-27 2010-04-08 アイシス ファーマシューティカルズ， インコーポレーテッド 高コレステロール血症を治療するための方法
US20100190837A1 (en) 2007-02-15 2010-07-29 Isis Pharmaceuticals, Inc. 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom
WO2008109369A2 (en) 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting tnf gene expression and uses thereof
DE102007012908A1 (de) 2007-03-19 2008-09-25 Momentive Performance Materials Gmbh Neue Polyamid-Polysiloxan-Verbindungen
EP2126079A1 (en) 2007-03-22 2009-12-02 Santaris Pharma A/S Rna antagonist compounds for the inhibition of apo-b100 expression
DK2149605T3 (da) 2007-03-22 2013-09-30 Santaris Pharma As Korte RNA antagonist forbindelser til modulering af det ønskede mRNA
RU2559536C2 (ru) 2007-03-24 2015-08-10 Джензим Корпорейшн Введение антисмысловых олигонуклеотидов, комплементарных человеческому аполипопротеину в
AU2007352163A1 (en) 2007-05-01 2008-11-06 Ercole Biotech, Inc. Splice switching oligomers for TNF superfamily receptors and their use in treatment of disease
CA2685444A1 (en) 2007-05-01 2008-11-06 Jesper Worm Rna antagonist compounds for the modulation of beta-catenin
WO2008150729A2 (en) 2007-05-30 2008-12-11 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
EP2173760B2 (en) 2007-06-08 2015-11-04 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
JP5864100B2 (ja) 2007-06-29 2016-02-17 サレプタ セラピューティクス インコーポレイテッド 組織特異的ペプチドコンジュゲートおよび方法
AU2008272918B2 (en) 2007-07-05 2012-09-13 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
US20090140837A1 (en) 2007-07-19 2009-06-04 Glen Eric Jennings RF Token and Receptacle System and Method
WO2009025669A1 (en) 2007-08-20 2009-02-26 Enzon Pharmaceuticals, Inc. Polymeric linkers containing pyridyl disulfide moieties
WO2009046141A2 (en) 2007-10-01 2009-04-09 Isis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
US8288356B2 (en) 2007-10-04 2012-10-16 Santaris Pharma A/S MicroRNAs
US20100280098A1 (en) 2007-10-05 2010-11-04 Juliano Rudolph L Receptor targeted oligonucleotides
KR20100110298A (ko) 2007-11-26 2010-10-12 산타리스 팔마 에이/에스 안드로겐 수용체를 표적화하는 ｌｎａ 길항제
KR20100105648A (ko) 2007-12-03 2010-09-29 엔즌 파마슈티칼스, 인코포레이티드 Ｐｉｋ３ｃａ 발현 조절용 ｒｎａ 길항제 화합물
EP3705125B1 (en) 2007-12-04 2023-07-05 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
US8530640B2 (en) 2008-02-07 2013-09-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
EP2268811A1 (en) 2008-03-07 2011-01-05 Santaris Pharma A/S Pharmaceutical compositions for treatment of microrna related diseases
EP2285819B1 (en) 2008-04-04 2013-10-16 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising neutrally linked terminal bicyclic nucleosides
AU2009234266B2 (en) 2008-04-11 2015-08-06 Tekmira Pharmaceuticals Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
WO2009148605A2 (en) 2008-06-04 2009-12-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
KR20110031368A (ko) 2008-07-03 2011-03-25 산타리스 팔마 에이/에스 미토콘드리아의 글리세롤-3-포스페이트 아실트랜스페라제 1 (ｍｔｇｐａｔ1)의 발현을 억제하기 위한 ｒｎａ 안타고니스트 화합물
SI2320925T1 (sl) 2008-07-10 2016-05-31 Regenesance B.V. Komplement antagonisti in njih uporaba
US9033197B2 (en) 2008-07-17 2015-05-19 Nir Bar Spool holder
US7932256B2 (en) 2008-07-31 2011-04-26 Bristol-Myers Squibb Company (S)-4-(1-cyclopropyl-2-methoxyethyl)-6-(6-(difluoromethoxy)-2,5-dimethylpyridin-3-ylamino)-5-oxo-4,5-dihydropyrazine-2-carbonitrile: a pyrazinone modulator of corticotropin-releasing factor receptor activity
WO2010017509A1 (en) 2008-08-07 2010-02-11 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression for the treatment of cns related disorders
WO2010045584A1 (en) 2008-10-17 2010-04-22 Endocyte, Inc. Folate targeting of nucleotides
ES2572361T3 (es) * 2008-12-31 2016-05-31 Roche Innovation Ct Copenhagen As Utilización de oligómeros de ANB antisentido de ApoB para el tratamiento de síndromes coronarios agudos
AT507215B1 (de) 2009-01-14 2010-03-15 Boehler Edelstahl Gmbh & Co Kg Verschleissbeständiger werkstoff
WO2010120508A2 (en) 2009-03-31 2010-10-21 The General Hospital Corporation Regulation of mir-33 micrornas in the treatment of cholesterol-related disorders
JP5773535B2 (ja) * 2009-04-24 2015-09-02 ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブＲｏｃｈｅ Ｉｎｎｏｖａｔｉｏｎ Ｃｅｎｔｅｒ Ｃｏｐｅｎｈａｇｅｎ Ａ／Ｓ インターフェロンに非応答性のｈｃｖ患者の治療のための医薬組成物
EP2440215B1 (en) 2009-06-12 2015-10-21 Roche Innovation Center Copenhagen A/S New potent anti apob antisense compounds
WO2011009697A1 (en) 2009-07-21 2011-01-27 Santaris Pharma A/S Antisense oligomers targeting pcsk9
EP2512491B1 (en) 2009-10-16 2017-10-11 Glaxo Group Limited Hbv antisense inhibitors
KR101663617B1 (ko) 2009-10-29 2016-10-07 엘지전자 주식회사 하향링크 기준신호 송수신 방법 및, 이를 이용한 기지국 및 사용자기기
US20130023578A1 (en) * 2009-12-31 2013-01-24 Samyang Biopharmaceuticals Corporation siRNA for inhibition of c-Met expression and anticancer composition containing the same
CN106146591B (zh) 2010-01-08 2020-07-31 Ionis制药公司 血管生成素样3表达的调节
US8846631B2 (en) 2010-01-14 2014-09-30 Regulus Therapeutics Inc. MicroRNA compositions and methods
ES2562817T3 (es) 2010-02-24 2016-03-08 Arrowhead Research Corporation Composiciones para el suministro dirigido de ARNip
US9102938B2 (en) 2010-04-01 2015-08-11 Alnylam Pharmaceuticals, Inc. 2′ and 5′ modified monomers and oligonucleotides
WO2011126937A1 (en) 2010-04-06 2011-10-13 The University Of North Carolina At Chapel Hill Targeted intracellular delivery of oligonucleotides via conjugation with small molecule ligands
WO2011130458A2 (en) 2010-04-13 2011-10-20 John Rossi Rna aptamers against baff-r as cell-type specific delivery agents and methods for their use
DK2560687T3 (en) 2010-04-19 2017-09-18 Nlife Therapeutics S L Preparations and Methods for Selective Delivery of Oligonucleotide Molecules to Specific Neuron Types
US9725479B2 (en) 2010-04-22 2017-08-08 Ionis Pharmaceuticals, Inc. 5′-end derivatives
NZ603339A (en) 2010-04-29 2015-01-30 Isis Pharmaceuticals Inc Modulation of transthyretin expression
US8815826B2 (en) 2010-07-23 2014-08-26 Regulus Therapeutics, Inc. Targeting microRNAs for the treatment of fibrosis
EP2612914B1 (en) * 2010-08-31 2017-06-21 Osaka University Oligonucleotide, and therapeutic agent for dyslipidemia containing oligonucleotide as active ingredient
WO2012078637A2 (en) 2010-12-06 2012-06-14 Immune Disease Institute, Inc. Composition and method for oligonucleotide delivery
EP3843313A1 (en) 2010-12-13 2021-06-30 Telefonaktiebolaget LM Ericsson (publ) Exchange of parameters relating to measurement periods
KR20130132475A (ko) 2010-12-17 2013-12-04 애로우헤드 리서치 코오포레이션 ｓｉＲＮＡ의 갈락토오스 클러스터-약동학적 조절제 표적 물질
MX347298B (es) 2010-12-29 2017-04-21 Arrowhead Res Corp Conjugados de suministro de polinucleotidos in vivo que tienen acoplamientos sensibles a enzima.
RU2582235C2 (ru) * 2010-12-29 2016-04-20 Ф.Хоффманн-Ля Рош Аг Низкомолекулярные конъюгаты для внутриклеточной доставки нуклеиновых кислот
AU2012207606B2 (en) 2011-01-11 2017-02-23 Alnylam Pharmaceuticals, Inc. Pegylated lipids and their use for drug delivery
JP6042871B2 (ja) 2011-04-21 2016-12-14 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． Ｂ型肝炎ウイルス（ｈｂｖ）発現の調節
TW201303013A (zh) 2011-04-21 2013-01-16 Isis Pharmaceuticals Inc Ｂ型肝炎病毒（ｈｂｖ）表現之調節
EP2702155B9 (en) 2011-04-25 2020-01-01 Regulus Therapeutics Inc. Microrna compounds and methods for modulating mir-21 activity
CN102226185A (zh) * 2011-05-09 2011-10-26 华中科技大学同济医学院附属同济医院 靶向肝细胞的rna适配子及其核苷酸序列
WO2012174154A1 (en) 2011-06-13 2012-12-20 Isis Pharmaceuticals, Inc. Modulation of inflammatory responses by factor vii
CA2839437A1 (en) 2011-06-16 2012-12-20 Isis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
CN106434665B (zh) 2011-06-30 2021-06-08 箭头药业股份有限公司 用于抑制乙型肝炎病毒的基因表达的组合物和方法
EP2751270B1 (en) 2011-08-29 2018-08-22 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EP3533873A1 (en) * 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
WO2013068348A1 (en) 2011-11-07 2013-05-16 Santaris Pharma A/S Lna oligomers for improvement in hepatic function
AU2012327227A1 (en) 2011-11-07 2013-05-23 Isis Pharmaceuticals, Inc. Administration of Factor XI antisense oligonucleotides
EP2812433A4 (en) 2012-02-08 2016-01-20 Isis Pharmaceuticals Inc METHOD AND COMPOSITIONS FOR MODULATING THE FACTOR VII EXPRESSION
WO2013142514A1 (en) 2012-03-19 2013-09-26 Isis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
US9221864B2 (en) 2012-04-09 2015-12-29 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
WO2013159109A1 (en) 2012-04-20 2013-10-24 Isis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
US9984408B1 (en) 2012-05-30 2018-05-29 Amazon Technologies, Inc. Method, medium, and system for live video cooperative shopping
SG11201503821YA (en) 2012-11-15 2015-06-29 Roche Innovation Ct Copenhagen As Oligonucleotide conjugates
RU2649367C2 (ru) 2013-01-30 2018-04-02 Ф. Хоффманн-Ля Рош Аг Конъюгаты углевода и lna-олигонуклеотида
KR102482890B1 (ko) 2013-05-01 2022-12-30 아이오니스 파마수티컬즈, 인코포레이티드 아포지질단백질 (a) 발현을 조절하는 조성물 및 방법
JP2017501684A (ja) 2013-11-14 2017-01-19 ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブＲｏｃｈｅ Ｉｎｎｏｖａｔｉｏｎ Ｃｅｎｔｅｒ Ｃｏｐｅｎｈａｇｅｎ Ａ／Ｓ Ａｐｏｂアンチセンスコンジュゲート化合物
US9778708B1 (en) 2016-07-18 2017-10-03 Lenovo Enterprise Solutions (Singapore) Pte. Ltd. Dual sided latching retainer for computer modules

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11413243B2 (en) 2017-11-06 2022-08-16 Nitto Denko Corporation Fusogenic compounds for delivery of biologically active molecules
RU2808990C2 (ru) * 2017-11-06 2023-12-05 Нитто Денко Корпорейшн Фузогенные соединения для доставки биологически активных молекул
US12440445B2 (en) 2017-11-06 2025-10-14 Nitto Denko Corporation Fusogenic compounds for delivery of biologically active molecules

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