ZA201503375B - Oligonucleotide conjugates - Google Patents

Oligonucleotide conjugates

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Publication number
ZA201503375B
ZA201503375B ZA2015/03375A ZA201503375A ZA201503375B ZA 201503375 B ZA201503375 B ZA 201503375B ZA 2015/03375 A ZA2015/03375 A ZA 2015/03375A ZA 201503375 A ZA201503375 A ZA 201503375A ZA 201503375 B ZA201503375 B ZA 201503375B
Authority
ZA
South Africa
Prior art keywords
oligonucleotide conjugates
conjugates
oligonucleotide
Prior art date
Application number
ZA2015/03375A
Other languages
English (en)
Inventor
HENRIK øRUM
Jacob Ravn
Susanne Kammler
Henrik Frydenlund Hansen
Nanna Albæk
Original Assignee
Roche Innovation Ct Copenhagen As
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Roche Innovation Ct Copenhagen As filed Critical Roche Innovation Ct Copenhagen As
Publication of ZA201503375B publication Critical patent/ZA201503375B/en

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    • C12N15/113Non-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
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    • C12N2310/32Chemical structure of the sugar
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    • C12N2310/34Spatial arrangement of the modifications
    • C12N2310/341Gapmers, i.e. of the type ===---===
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ZA2015/03375A 2012-11-15 2015-05-14 Oligonucleotide conjugates ZA201503375B (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP12192773 2012-11-15
EP13153296 2013-01-30
EP13157237 2013-02-28
EP13174092 2013-06-27
PCT/EP2013/073858 WO2014076195A1 (en) 2012-11-15 2013-11-14 Oligonucleotide conjugates

Publications (1)

Publication Number Publication Date
ZA201503375B true ZA201503375B (en) 2016-02-24

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ID=49584733

Family Applications (1)

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ZA2015/03375A ZA201503375B (en) 2012-11-15 2015-05-14 Oligonucleotide conjugates

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US (4) US20150291958A1 (enExample)
EP (3) EP3406718A1 (enExample)
JP (3) JP6452614B2 (enExample)
KR (2) KR102112892B1 (enExample)
CN (3) CN104884618A (enExample)
AU (2) AU2013346767B2 (enExample)
BR (2) BR112015011112A2 (enExample)
CA (2) CA2889044A1 (enExample)
DK (2) DK2920307T3 (enExample)
ES (1) ES2724853T3 (enExample)
HK (2) HK1214297A1 (enExample)
HR (1) HRP20190826T1 (enExample)
IL (2) IL238448B (enExample)
MX (2) MX363068B (enExample)
MY (1) MY173826A (enExample)
NZ (1) NZ708171A (enExample)
PL (1) PL2920304T3 (enExample)
RU (3) RU2015119411A (enExample)
SG (2) SG11201503821YA (enExample)
SI (1) SI2920304T1 (enExample)
WO (2) WO2014076196A1 (enExample)
ZA (1) ZA201503375B (enExample)

Families Citing this family (302)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2141233B1 (en) 2002-11-18 2016-10-19 Roche Innovation Center Copenhagen A/S Antisense design
DK2379084T3 (en) 2008-10-15 2018-01-22 Ionis Pharmaceuticals Inc MODULATION OF FACTOR 11 EXPRESSION
SG171914A1 (en) 2008-12-02 2011-07-28 Chiralgen Ltd Method for the synthesis of phosphorus atom modified nucleic acids
US9744183B2 (en) 2009-07-06 2017-08-29 Wave Life Sciences Ltd. Nucleic acid prodrugs and methods of use thereof
US11083444B2 (en) 2010-03-11 2021-08-10 Globus Medical, Inc. Tissue retractor and methods of use
DK2620428T3 (da) 2010-09-24 2019-07-01 Wave Life Sciences Ltd Asymmetrisk hjælpegruppe
AU2011329777B2 (en) 2010-11-17 2016-06-09 Ionis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
RU2014105311A (ru) 2011-07-19 2015-08-27 Уэйв Лайф Сайенсес Пте. Лтд. Способы синтеза функционализованных нуклеиновых кислот
EP2756080B1 (en) 2011-09-14 2019-02-20 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
WO2013173599A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating hemoglobin gene family expression
EA201492116A1 (ru) 2012-05-16 2015-05-29 Рана Терапьютикс, Инк. Композиции и способы для модулирования экспрессии mecp2
AU2013262656A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating UTRN expression
AU2013262649A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating smn gene family expression
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
EP2850182A4 (en) 2012-05-16 2016-01-20 Rana Therapeutics Inc COMPOSITIONS AND METHODS FOR MODULATING ATP2A2 GENE EXPRESSION
KR102712879B1 (ko) 2012-07-13 2024-10-04 웨이브 라이프 사이언시스 리미티드 키랄 제어
PT2872485T (pt) 2012-07-13 2021-03-05 Wave Life Sciences Ltd Grupo auxiliar assimétrico
CA2884608C (en) 2012-09-14 2025-05-20 Translate Bio Ma, Inc. MULTIMERIC OLIGONUCLEOTIDE COMPOUNDS
JP6452614B2 (ja) 2012-11-15 2019-01-16 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 オリゴヌクレオチドコンジュゲート
EP2951305B1 (en) * 2013-01-30 2018-08-15 F.Hoffmann-La Roche Ag Lna oligonucleotide carbohydrate conjugates
NZ630890A (en) 2013-05-01 2017-09-29 Regulus Therapeutics Inc Microrna compounds and methods for modulating mir-122
PL2992098T3 (pl) 2013-05-01 2019-09-30 Ionis Pharmaceuticals, Inc. Kompozycje i sposoby modulowania ekspresji hbv i ttr
TWI680767B (zh) 2013-05-01 2020-01-01 美商雷格勒斯治療公司 用於增強的細胞攝取之化合物及方法
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
US9994846B2 (en) 2013-10-25 2018-06-12 Regulus Therapeutics Inc. MicroRNA compounds and methods for modulating miR-21 activity
JPWO2015108047A1 (ja) 2014-01-15 2017-03-23 株式会社新日本科学 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤
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
PT3094728T (pt) 2014-01-16 2022-05-19 Wave Life Sciences Ltd Desenho quiral
US10358643B2 (en) 2014-01-30 2019-07-23 Hoffmann-La Roche, Inc. Poly oligomer compound with biocleavable conjugates
EP3119888B1 (en) 2014-03-19 2021-07-28 Ionis Pharmaceuticals, Inc. Compositions for modulating ataxin 2 expression
US10006027B2 (en) 2014-03-19 2018-06-26 Ionis Pharmaceuticals, Inc. Methods for modulating Ataxin 2 expression
WO2015153800A2 (en) 2014-04-01 2015-10-08 Isis Pharmaceuticals, Inc. Compositions for modulating sod-1 expression
KR102369736B1 (ko) 2014-05-01 2022-03-02 아이오니스 파마수티컬즈, 인코포레이티드 보체 인자 b 발현을 조절하기 위한 조성물 및 방법
ES2812099T3 (es) 2014-05-01 2021-03-16 Ionis Pharmaceuticals Inc Composiciones y métodos para modular la expresión del receptor de la hormona del crecimiento
KR102366078B1 (ko) 2014-05-01 2022-02-21 아이오니스 파마수티컬즈, 인코포레이티드 Pkk 발현을 조절하는 조성물 및 방법
KR102356388B1 (ko) 2014-05-01 2022-01-26 아이오니스 파마수티컬즈, 인코포레이티드 안지오포이에틴-유사 3 발현을 조절하기 위한 조성물 및 방법
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
AU2015301057A1 (en) 2014-08-07 2017-01-19 Regulus Therapeutics Inc. Targeting micrornas for metabolic disorders
WO2016040748A1 (en) 2014-09-12 2016-03-17 Ionis Pharmaceuticals, Inc. Compositions and methods for detection of smn protein in a subject and treatment of a subject
MX2017004039A (es) 2014-10-10 2017-07-24 Hoffmann La Roche Fosforamiditas de n-acetilgalactosamina (galnac), conjugados de acido nucleico de las mismas y su uso.
MX2017006140A (es) * 2014-11-10 2017-11-16 Glaxosmithkline Intellectual Property (No 2) Ltd Composiciones de accion prolongada de combinacion y métodos para hepatitis c.
EP3234131B1 (en) 2014-12-16 2020-04-22 Roche Innovation Center Copenhagen A/S Chiral toxicity screening method
US20170369872A1 (en) * 2014-12-18 2017-12-28 Alnylam Pharmaceuticals, Inc. Reversir tm compounds
WO2016112132A1 (en) 2015-01-06 2016-07-14 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
US10538763B2 (en) 2015-01-16 2020-01-21 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
JP6892433B2 (ja) 2015-04-03 2021-06-23 ユニバーシティ・オブ・マサチューセッツUniversity Of Massachusetts 十分に安定化された非対称sirna
KR102539587B1 (ko) 2015-04-03 2023-06-01 아이오니스 파마수티컬즈, 인코포레이티드 Tmprss6 발현을 조절하기 위한 화합물 및 방법들
SI3277815T1 (sl) 2015-04-03 2022-01-31 University Of Massachusetts Ologonukleotidne spojine za zdravljenje preeklampsije in drugih angiogeneznih motenj
EP3766973A1 (en) 2015-04-03 2021-01-20 University Of Massachusetts Oligonucleotide compounds for targeting huntingtin mrna
WO2016167780A1 (en) 2015-04-16 2016-10-20 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
CA2995110A1 (en) 2015-08-14 2017-02-23 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
KR20180043819A (ko) 2015-08-24 2018-04-30 로슈 이노베이션 센터 코펜하겐 에이/에스 Lna-g 방법
EP3353305A4 (en) * 2015-09-25 2019-09-18 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
KR20180073584A (ko) 2015-10-02 2018-07-02 로슈 이노베이션 센터 코펜하겐 에이/에스 올리고뉴클레오타이드 접합 방법
US20190127733A1 (en) 2015-10-09 2019-05-02 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
EP4119569B1 (en) * 2015-11-06 2024-07-31 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds for use in therapy
MY203086A (en) 2015-11-06 2024-06-07 Ionis Pharmaceuticals Inc Modulating apolipoprotein (a) expression
CN108350431A (zh) 2015-11-12 2018-07-31 豪夫迈·罗氏有限公司 用于确定候选药物的功效特征的方法
EP3389670A4 (en) 2015-12-04 2020-01-08 Ionis Pharmaceuticals, Inc. METHODS OF TREATING BREAST CANCER
US20190002887A1 (en) 2015-12-31 2019-01-03 Ionis Pharmaceuticals, Inc. Methods for reducing ataxin-2 expression
EP3400300A4 (en) 2016-01-05 2019-08-07 Ionis Pharmaceuticals, Inc. PROCESS FOR REDUCING LRRK2 EXPRESSION
SG11201806372UA (en) * 2016-01-29 2018-08-30 Kyowa Hakko Kirin Co Ltd Nucleic acid conjugate
US10478503B2 (en) 2016-01-31 2019-11-19 University Of Massachusetts Branched oligonucleotides
KR102348425B1 (ko) 2016-03-07 2022-01-10 애로우헤드 파마슈티컬스 인코포레이티드 치료용 화합물을 위한 표적화 리간드
SG11201807854SA (en) 2016-03-14 2018-10-30 Hoffmann La Roche Oligonucleotides for reduction of pd-l1 expression
WO2017161168A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Modulation of dyrk1b expression
EP3429690A4 (en) 2016-03-16 2019-10-23 Ionis Pharmaceuticals, Inc. METHOD FOR MODULATING KEAP1
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
AU2017248189B2 (en) * 2016-04-08 2021-04-29 Translate Bio, Inc. Multimeric coding nucleic acid and uses thereof
US11248019B2 (en) 2016-04-14 2022-02-15 Hoffmann-La Roche Inc. Trityl-mono-GalNAc compounds and their use
IL262728B2 (en) * 2016-05-06 2023-10-01 Astrazeneca Ab Oligonucleotides conjugated to the GLP-1 receptor ligand complex and their uses
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
CN109477103A (zh) 2016-06-22 2019-03-15 ProQR治疗上市公司Ⅱ 单链rna-编辑寡核苷酸
SG10202005885VA (en) 2016-07-01 2020-07-29 Hoffmann La Roche Antisense oligonucleotides for modulating htra1 expression
CA3033368A1 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
KR102501980B1 (ko) 2016-09-01 2023-02-20 프로큐알 테라퓨틱스 Ⅱ 비.브이. 화학적으로 변형된 단일 가닥 rna-편집 올리고뉴클레오타이드
SG11201901841TA (en) 2016-09-02 2019-03-28 Arrowhead Pharmaceuticals Inc Targeting ligands
US11400161B2 (en) 2016-10-06 2022-08-02 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
JOP20190104A1 (ar) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
US11033570B2 (en) 2016-12-02 2021-06-15 Cold Spring Harbor Laboratory Modulation of Lnc05 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
WO2018130581A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
WO2018130583A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb1 expression
US20190338286A1 (en) 2017-01-13 2019-11-07 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
WO2018164275A1 (ja) 2017-03-10 2018-09-13 国立研究開発法人国立成育医療研究センター アンチセンスオリゴヌクレオチドおよび糖原病Ia型予防または治療用組成物
US11512312B2 (en) 2017-03-10 2022-11-29 The Board Of Regents Of The University Of Texas System Treatment of Fuchs' endothelial corneal dystrophy
SG11201909433XA (en) * 2017-04-11 2019-11-28 Arbutus Biopharma Corp Targeted compositions
WO2018215049A1 (en) * 2017-05-23 2018-11-29 F. Hoffmann-La Roche Ag Process for galnac oligonucleotide conjugates
US11273222B2 (en) 2017-05-26 2022-03-15 National Cerebral And Cardiovascular Center Antisense nucleic acid targeting PCSK9
US20190055564A1 (en) 2017-06-01 2019-02-21 F. Hoffmann-La Roche Ag Antisense oligonucleotides for modulating htra1 expression
US20210198305A1 (en) * 2017-06-02 2021-07-01 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
EP3642341A4 (en) 2017-06-23 2021-06-16 University Of Massachusetts TWO-DAY SELF-RELEASING SIRNA AND RELATED PROCEDURES
TW201919712A (zh) 2017-08-10 2019-06-01 法商塞勒尼斯醫療控股公司 運送子(cargomers)
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
AU2018318230B2 (en) 2017-08-17 2024-10-03 Alnylam Pharmaceuticals, Inc. Tunable REVERSIRTM compounds
EP3668984A4 (en) 2017-08-18 2021-09-08 Ionis Pharmaceuticals, Inc. MODULATION OF THE NOTCH SIGNALING PATH FOR THE TREATMENT OF RESPIRATORY DISORDERS
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. MODULATORS OF SMAD7 EXPRESSION
JP2020537518A (ja) 2017-10-12 2020-12-24 ウェーブ ライフ サイエンシーズ リミテッド オリゴヌクレオチド組成物及びその方法
EP3694995A1 (en) 2017-10-13 2020-08-19 Roche Innovation Center Copenhagen A/S Methods for identifying improved stereodefined phosphorothioate oligonucleotide variants of antisense oligonucleotides utilising sub-libraries of partially stereodefined oligonucleotides
TW202424191A (zh) 2017-10-16 2024-06-16 瑞士商赫孚孟拉羅股份公司 用於降低PAPD5及PAPD7 mRNA以治療B型肝炎感染之核酸分子
CN111386105B (zh) 2017-11-06 2023-09-15 日东电工株式会社 用于递送生物活性分子的膜融合化合物
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
WO2019105419A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN110944675B9 (zh) 2017-12-01 2024-08-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
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
WO2019105414A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
WO2019105437A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
SG11202005022YA (en) 2017-12-06 2020-06-29 Avidity Biosciences Inc Compositions and methods of treating muscle atrophy and myotonic dystrophy
EP3724333A2 (en) 2017-12-11 2020-10-21 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating fndc3b expression
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
WO2019121838A1 (en) 2017-12-21 2019-06-27 F. Hoffmann-La Roche Ag Companion diagnostic for htra1 rna antagonists
JP2021508327A (ja) 2017-12-22 2021-03-04 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 新規のチオホスホラミダイト
BR112020012427A8 (pt) 2017-12-22 2024-04-02 Roche Innovation Ct Copenhagen As Oligonucleotídeos, sal farmaceuticamente aceitável, conjugado, composição farmacêutica e processo para a fabricação de um oligonucleotídeo
EP4092117A1 (en) 2017-12-22 2022-11-23 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
KR102617947B1 (ko) * 2017-12-29 2023-12-27 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 접합체와 제조 및 그 용도
JP2021511022A (ja) 2018-01-10 2021-05-06 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 Pias4発現を調節するためのオリゴヌクレオチド
BR112020012921A2 (pt) 2018-01-12 2020-12-08 Roche Innovation Center Copenhagen A/S Oligonucleotídeos antissenso de alfa-sinucleína e usos dos mesmos
CA3088112A1 (en) 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
BR112020014011A2 (pt) 2018-01-12 2020-12-08 Bristol-Myers Squibb Company Oligonucleotídeos antissenso dirigidos à alfa-sinucleína e usos dos mesmos
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
CN111902537A (zh) 2018-01-15 2020-11-06 Ionis制药公司 Dnm2表达的调节剂
JP2021510525A (ja) 2018-01-17 2021-04-30 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 Erc1発現を調節するためのオリゴヌクレオチド
US20210095277A1 (en) 2018-01-18 2021-04-01 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
CA3085407A1 (en) * 2018-01-26 2019-08-01 F. Hoffmann-La Roche Ag Radiolabelled oligonucleotides and process for their preparation
CN111868245B (zh) 2018-02-09 2024-11-19 豪夫迈·罗氏有限公司 用于调节tmem106b表达的寡核苷酸
WO2019169243A1 (en) 2018-03-02 2019-09-06 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of 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
EP3763815A4 (en) 2018-03-09 2021-12-15 Daiichi Sankyo Company, Limited THERAPEUTIC FOR GLYCOGEN STORAGE DISEASE OF TYPE IA
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
KR20200141481A (ko) 2018-04-11 2020-12-18 아이오니스 파마수티컬즈, 인코포레이티드 Ezh2 발현의 조절제
EP3790991A1 (en) 2018-05-07 2021-03-17 Roche Innovation Center Copenhagen A/S Massively parallel discovery methods for oligonucleotide therapeutics
JP7279081B2 (ja) 2018-05-08 2023-05-22 レグルス セラピューティクス インコーポレイテッド Mir-122を調節するためのマイクロrna化合物及び方法
WO2019215175A1 (en) 2018-05-08 2019-11-14 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating myh7 expression
MX2020011911A (es) 2018-05-09 2021-01-29 Ionis Pharmaceuticals Inc Compuestos y metodos para reducir de la expresion de atxn3.
IL277970B2 (en) 2018-05-09 2025-03-01 Ionis Pharmaceuticals Inc Oligomeric compounds comprising modified oligonucleotides and conjugated groups for use in the treatment of end-stage renal disease, chronic kidney disease and coronary artery disease
BR112020022620A2 (pt) * 2018-05-11 2021-02-17 Alpha Anomeric Sas conjugados de oligonucleotídeos que compreendem nucleosídeos de açúcar 7'-5'-alfa-anomérico-bicíclicos
JP7427608B2 (ja) 2018-05-11 2024-02-05 ウェイブ ライフ サイエンシズ リミテッド オリゴヌクレオチド組成物及びその使用方法
GB201808146D0 (en) 2018-05-18 2018-07-11 Proqr Therapeutics Ii Bv Stereospecific Linkages in RNA Editing Oligonucleotides
EP3802824A1 (en) 2018-06-05 2021-04-14 F. Hoffmann-La Roche AG Oligonucleotides for modulating atxn2 expression
US11833168B2 (en) 2018-06-14 2023-12-05 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
WO2020007772A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting gbp-1
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
RU2768285C1 (ru) 2018-07-03 2022-03-23 Ф. Хоффманн-Ля Рош Аг Олигонуклеотиды для модуляции экспрессии тау-белка
WO2020007889A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting stat1
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
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
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
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
KR20210033004A (ko) 2018-07-13 2021-03-25 에프. 호프만-라 로슈 아게 Rtel1의 발현을 조절하기 위한 올리고뉴클레오티드
US12496311B2 (en) 2018-07-17 2025-12-16 Aronora, Inc. Methods for safely reducing thrombopoietin
AU2019310097A1 (en) 2018-07-25 2021-02-04 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing ATXN2 expression
MX2020013270A (es) 2018-07-31 2021-02-18 Roche Innovation Ct Copenhagen As Oligonucleotidos que comprenden enlace internucleosidico de fosforotritioato.
ES2924362T3 (es) 2018-07-31 2022-10-06 Roche Innovation Ct Copenhagen As Oligonucleótidos que comprenden un enlace internucleosídico fosforotritioato
KR20210093227A (ko) 2018-08-10 2021-07-27 유니버시티 오브 매사추세츠 Snp를 표적화하는 변형된 올리고뉴클레오티드
US11918600B2 (en) 2018-08-21 2024-03-05 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof
JP7627042B2 (ja) 2018-08-23 2025-02-05 ユニバーシティー オブ マサチューセッツ O-メチルリッチ完全安定化オリゴヌクレオチド
WO2020038973A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting sptlc1
WO2020038976A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting usp8
WO2020038968A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Microrna-134 biomarker
WO2020038971A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting vcan
JP2021536239A (ja) 2018-08-28 2021-12-27 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 スプライス調節化合物を使用したネオアンチゲン操作
EP3620519A1 (en) 2018-09-04 2020-03-11 F. Hoffmann-La Roche AG Use of isolated milk extracellular vesicles for delivering oligonucleotides orally
WO2020051398A1 (en) * 2018-09-06 2020-03-12 Aptamir Therapeutics, Inc. Metabolic benefits of short mir-22 mirna antagomir therapies
WO2020063198A1 (zh) 2018-09-30 2020-04-02 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
WO2020089260A1 (en) 2018-11-01 2020-05-07 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
US11208650B2 (en) 2018-11-15 2021-12-28 Ionis Pharmaceuticals, Inc. Modulators of IRF5 expression
WO2020106996A1 (en) 2018-11-21 2020-05-28 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing prion expression
EP3894559A4 (en) 2018-12-03 2023-04-05 Triplet Therapeutics, Inc. METHODS OF TREATMENT OF TRINUCLEOTIDE REPEAT EXPANSION DISORDERS RELATED TO MLH3 ACTIVITY
US20220056455A1 (en) 2018-12-20 2022-02-24 Praxis Precision Medicines, Inc. Compositions and methods for the treatment of kcnt1 related disorders
JP2022514648A (ja) 2018-12-21 2022-02-14 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Card9を標的とするアンチセンスオリゴヌクレオチド
EP3903830A4 (en) 2018-12-28 2023-04-26 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, COMPOSITION AND CONJUGATE WITH NUCLEIC ACID, PROCESS FOR THEIR PREPARATION AND ITS USE
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
CN113365607A (zh) * 2019-01-25 2021-09-07 豪夫迈·罗氏有限公司 用于口服药物递送的脂质囊泡
KR20210122809A (ko) 2019-01-31 2021-10-12 아이오니스 파마수티컬즈, 인코포레이티드 Yap1 발현의 조절인자
KR20210132681A (ko) 2019-02-20 2021-11-04 로슈 이노베이션 센터 코펜하겐 에이/에스 신규 포스포라미디트
JP2022521510A (ja) 2019-02-20 2022-04-08 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 ホスホノアセテートギャップマー型オリゴヌクレオチド
EP3931348B1 (en) 2019-02-26 2023-08-09 Roche Innovation Center Copenhagen A/S Oligonucleotide formulation method
BR112021015323A2 (pt) 2019-02-27 2021-10-05 Ionis Pharmaceuticals, Inc. Moduladores de expressão de malat1
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
TW202536179A (zh) 2019-03-29 2025-09-16 美商Ionis製藥公司 用於調節ube3a-ats之化合物及方法
EP3947678A1 (en) 2019-04-02 2022-02-09 ProQR Therapeutics II B.V. Antisense oligonucleotides for immunotherapy
CN113906139A (zh) 2019-04-03 2022-01-07 百时美施贵宝公司 Angptl2反义寡核苷酸及其用途
WO2020201339A1 (en) 2019-04-04 2020-10-08 F. Hoffmann-La Roche Ag Oligonucleotides for modulating atxn2 expression
US11286485B2 (en) 2019-04-04 2022-03-29 Hoffmann-La Roche Inc. Oligonucleotides for modulating ATXN2 expression
AU2020280438B2 (en) 2019-05-22 2025-03-06 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
MX2021014206A (es) 2019-05-31 2022-01-06 Aligos Therapeutics Inc Oligonucleotidos gapmer modificados y metodos de uso.
WO2020245233A1 (en) 2019-06-06 2020-12-10 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting atxn3
EP3956450B1 (en) 2019-07-26 2025-08-13 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating gfap
CN114466929A (zh) * 2019-07-30 2022-05-10 Mpeg La有限责任公司 具有增强的生物活性的多聚体寡核苷酸的皮下递送
CA3149835A1 (en) 2019-08-09 2021-02-18 University Of Massachusetts Chemically modified oligonucleotides targeting snps
TWI896556B (zh) 2019-09-10 2025-09-11 日商第一三共股份有限公司 用於肝臟遞送之GalNAc-寡核苷酸結合物
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
EP4038187A4 (en) * 2019-10-02 2023-06-07 Sirnaomics, Inc. OLIGONUCLEOTIDES INCLUDING 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
WO2021122921A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of cops3 inhibitors for treating hepatitis b virus infection
WO2021122735A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of sept9 inhibitors for treating hepatitis b virus infection
WO2021122869A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of scamp3 inhibitors for treating hepatitis b virus infection
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
WO2021127650A1 (en) * 2019-12-19 2021-06-24 Entrada Therapeutics, Inc. Compositions for delivery of antisense compounds
EP4077672A1 (en) 2019-12-20 2022-10-26 F. Hoffmann-La Roche AG Enhanced oligonucleotides for inhibiting scn9a expression
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
EP4081639A1 (en) 2019-12-24 2022-11-02 F. Hoffmann-La Roche AG Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist 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
BR112022016238A2 (pt) 2020-02-28 2022-10-11 Ionis Pharmaceuticals Inc Compostos e métodos para modular smn2
CN115176010A (zh) 2020-02-28 2022-10-11 豪夫迈·罗氏有限公司 用于调节cd73外显子7剪接的寡核苷酸
MX2022010980A (es) 2020-03-04 2022-12-02 Verve Therapeutics Inc Composiciones y metodos para el suministro de arn dirigido.
JP7788060B2 (ja) 2020-03-19 2025-12-18 アビディティー バイオサイエンシーズ,インク. 顔面肩甲上腕型筋ジストロフィーを処置するための組成物および方法
CA3176210A1 (en) * 2020-04-21 2021-10-28 Nathan Wilson STEBBINS Bifunctional molecules and methods of using thereof
EP4143321A4 (en) 2020-05-01 2025-02-19 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating atxn1
WO2021231211A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component c1s inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
WO2021231204A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component 4 inhibitors for treating neurological diseases, and related compositons, systems and methods of using same
CN115605592A (zh) 2020-05-11 2023-01-13 基因泰克公司(Us) 用于治疗神经系统疾病的补体组分c1r抑制剂以及相关的组合物、系统和使用它们的方法
WO2021229036A1 (en) 2020-05-13 2021-11-18 F. Hoffmann-La Roche Ag Oligonucleotide agonists targeting progranulin
EP4150090A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of otoferlin (otof)
WO2021231685A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1)
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)
WO2021231679A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2)
EP4150088A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1)
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)
WO2021231691A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of retinoschisin 1 (rsi)
EP4150078A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl)
US20230193269A1 (en) 2020-05-22 2023-06-22 Boehringer Ingelheim International Gmbh Oligonucleotides for splice modulation of card9
US11408000B2 (en) 2020-06-03 2022-08-09 Triplet Therapeutics, Inc. Oligonucleotides for the treatment of nucleotide repeat expansion disorders associated with MSH3 activity
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
IL298530A (en) 2020-06-29 2023-01-01 Ionis Pharmaceuticals Inc Compounds and methods for modulating plp1
TW202219273A (zh) 2020-07-23 2022-05-16 瑞士商赫孚孟拉羅股份公司 靶向rna結合蛋白位點之寡核苷酸
WO2022018155A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Lna oligonucleotides for splice modulation of stmn2
AU2021315992A1 (en) 2020-07-28 2023-02-09 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing app expression
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
KR20230048052A (ko) 2020-08-07 2023-04-10 아이오니스 파마수티컬즈, 인코포레이티드 Scn2a를 조절하는 화합물 및 방법
CN116157522A (zh) 2020-08-21 2023-05-23 豪夫迈·罗氏有限公司 A1cf抑制剂用于治疗乙型肝炎病毒感染的用途
WO2022072950A1 (en) * 2020-10-02 2022-04-07 Sirnaomics, Inc. NUCLEOSIDE CONTAINING siRNAS FOR TREAT VIRAL DISEASES
MX2023005736A (es) 2020-11-18 2023-05-25 Ionis Pharmaceuticals Inc Compuestos y metodos para modular la expresion de angiotensinogeno.
AR124227A1 (es) 2020-12-03 2023-03-01 Hoffmann La Roche Oligonucleótidos antisentido que actúan sobre atxn3
TW202237842A (zh) 2020-12-03 2022-10-01 瑞士商赫孚孟拉羅股份公司 靶向atxn3之反義寡核苷酸
US12018261B2 (en) 2020-12-18 2024-06-25 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating factor XII
CN116583603A (zh) 2020-12-18 2023-08-11 豪夫迈·罗氏有限公司 靶向颗粒蛋白前体的反义寡核苷酸
EP4267734A1 (en) 2020-12-22 2023-11-01 F. Hoffmann-La Roche AG Oligonucleotides targeting xbp1
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
EP4284513A1 (en) 2021-01-26 2023-12-06 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
WO2022189363A1 (en) 2021-03-08 2022-09-15 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
KR20240019228A (ko) 2021-06-08 2024-02-14 에프. 호프만-라 로슈 아게 올리고뉴클레오티드 프로그래눌린 효현제
US12378267B2 (en) 2021-06-17 2025-08-05 Entrada Therapeutics, Inc. Synthesis of FMOC-protected morpholino monomers and oligomers
EP4355759A1 (en) 2021-06-18 2024-04-24 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing ifnar1 expression
WO2022271786A1 (en) 2021-06-23 2022-12-29 University Of Massachusetts Optimized anti-flt1 oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
EP4363574A1 (en) 2021-06-29 2024-05-08 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
WO2023034561A2 (en) * 2021-09-02 2023-03-09 Vanderbilt University Lipophilic oligonucleotide conjugates
US11912779B2 (en) 2021-09-16 2024-02-27 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy
US20250352667A1 (en) 2021-10-22 2025-11-20 Korro Bio, Inc. Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing
EP4426833A1 (en) 2021-11-03 2024-09-11 F. Hoffmann-La Roche AG Oligonucleotides for modulating apolipoprotein e4 expression
WO2023083906A2 (en) 2021-11-11 2023-05-19 F. Hoffmann-La Roche Ag Pharmaceutical combinations for treatment of hbv
WO2023102188A1 (en) * 2021-12-03 2023-06-08 Quralis Corporation Gapmer antisense oligonucleotides with modified backbone chemistries
EP4444882A1 (en) 2021-12-07 2024-10-16 F. Hoffmann-La Roche AG Antisense oligonucleotides targeting actl6b
CN119095603A (zh) 2021-12-17 2024-12-06 豪夫迈·罗氏有限公司 用于调节rtel1和fubp1的寡核苷酸的组合
CN118489009A (zh) 2021-12-17 2024-08-13 豪夫迈·罗氏有限公司 寡核苷酸gba激动剂
CN118434860A (zh) 2021-12-20 2024-08-02 豪夫迈·罗氏有限公司 苏糖核酸反义寡核苷酸及其方法
WO2023141507A1 (en) 2022-01-20 2023-07-27 Genentech, Inc. Antisense oligonucleotides for modulating tmem106b expression
US20240167040A1 (en) 2022-02-21 2024-05-23 Hoffmann-La Roche Inc. Antisense oligonucleotide
AU2023234185A1 (en) 2022-03-16 2024-10-03 Daiichi Sankyo Company, Limited siRNA FOR SUPPRESSING EXPRESSION OF TRANSFERRIN RECEPTOR-2
TW202400786A (zh) 2022-03-16 2024-01-01 日商第一三共股份有限公司 具有RNAi活性的化學修飾寡核苷酸
WO2023217890A1 (en) 2022-05-10 2023-11-16 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting cfp-elk1 intergene region
EP4526445A1 (en) 2022-05-18 2025-03-26 F. Hoffmann-La Roche AG Improved oligonucleotides targeting rna binding protein sites
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
KR20250059413A (ko) 2022-09-06 2025-05-02 에프. 호프만-라 로슈 아게 눈에 투여하기 위한 이중 가닥 rna 분자
CN120239607A (zh) 2022-09-23 2025-07-01 Ionis制药公司 用于降低mecp2表达的化合物和方法
WO2024112809A2 (en) * 2022-11-21 2024-05-30 Pepgen Inc. Cell-penetrating peptides, conjugates thereof, and methods of their use
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
KR20250162631A (ko) 2023-01-19 2025-11-18 알토스 랩스, 인크. 장기 이식에서의 재생 인자의 용도
WO2024196893A1 (en) * 2023-03-17 2024-09-26 Camford Labs Inc. Chemically modified nucleotides
WO2024199445A1 (en) * 2023-03-30 2024-10-03 Ractigen Therapeutics Vehicles for delivering oligonucleotides and methods of use thereof
CN121263524A (zh) 2023-05-04 2026-01-02 豪夫迈·罗氏有限公司 能够上调葡糖脑苷脂酶表达的寡核苷酸
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
US20250034576A1 (en) 2023-06-16 2025-01-30 Hoffmann-La Roche Inc. Double Stranded Oligonucleotide For Modulating JAK1 Expression
WO2025036916A1 (en) 2023-08-16 2025-02-20 Les Laboratoires Servier Oligonucleotides for modulating kcnt1 expression
WO2026006436A1 (en) 2024-06-25 2026-01-02 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of tar dna binding protein 43 kda (tdp43)

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
WO1992008728A1 (en) 1990-11-08 1992-05-29 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
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
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.
EP0673559A1 (en) 1992-12-14 1995-09-27 Honeywell Inc. Motor system with individually controlled redundant windings
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
EP0728139B1 (en) 1993-09-03 2003-08-13 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
CA2161684C (en) 1994-03-07 2010-11-09 Larry R. Wilson Bioactive and/or targeted dendrimer conjugates
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
AU3999495A (en) 1994-10-06 1996-05-02 Buchardt, Dorte Peptide nucleic acid conjugates
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
US5994517A (en) 1995-11-22 1999-11-30 Paul O. P. Ts'o Ligands to enhance 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
KR100518108B1 (ko) * 1997-05-05 2005-10-04 아벤티스 파마 도이칠란트 게엠베하 사람 Ha-ras 유전자 절편에 상보적인 변형된 안티센스 뉴클레오티드
US6306993B1 (en) 1997-05-21 2001-10-23 The Board Of Trustees Of The Leland Stanford, Jr. University Method and composition for enhancing transport across biological membranes
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
CA2303299C (en) 1997-09-12 2016-02-23 Exiqon A/S Oligonucleotide analogues
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
DE60033927T2 (de) 1999-05-04 2007-11-29 Santaris Pharma A/S L-ribo-lna analoge
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
AU7406700A (en) 1999-10-04 2001-05-10 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)
WO2002094185A2 (en) 2001-05-18 2002-11-28 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US6559279B1 (en) 2000-09-08 2003-05-06 Isis Pharmaceuticals, Inc. Process for preparing peptide derivatized oligomeric compounds
EP1383782A1 (en) 2001-03-26 2004-01-28 Sirna Therpeutics, Inc. Oligonucleotide mediated inhibition of hepatitis b virus and hepatitis c virus replication
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
AU2003290596B2 (en) 2002-11-05 2011-05-12 Isis Pharmaceuticals, Inc. Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
WO2004044141A2 (en) 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. Conjugated oligomeric compounds and their use in gene modulation
WO2004041889A2 (en) 2002-11-05 2004-05-21 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP2336318B1 (en) 2002-11-13 2013-04-24 Genzyme Corporation Antisense modulation of apolipoprotein b expression
US7511131B2 (en) 2002-11-13 2009-03-31 Genzyme Corporation Antisense modulation of apolipoprotein B expression
EP2141233B1 (en) 2002-11-18 2016-10-19 Roche Innovation Center Copenhagen A/S Antisense design
US7816337B2 (en) 2003-02-18 2010-10-19 Roche Madison Inc. Reversible attachment of a membrane active polymer to a polynucleotide
AU2003219576A1 (en) 2003-04-03 2004-10-25 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
EP1633307A4 (en) * 2003-06-03 2009-06-24 Isis Pharmaceuticals Inc Modulation of survivin expression
EP1495769B1 (en) 2003-07-11 2008-02-27 LBR Medbiotech B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
US7825235B2 (en) 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
DK1661905T3 (da) 2003-08-28 2012-07-23 Takeshi Imanishi Hidtil ukendte syntetiske nukleinsyrer af N-O-krydsbindingstype
JP5379347B2 (ja) 2003-09-18 2013-12-25 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 4’−チオヌクレオシドおよびオリゴマー化合物
US7615539B2 (en) * 2003-09-25 2009-11-10 Coley Pharmaceutical Group, Inc. Nucleic acid-lipophilic conjugates
JP4642775B2 (ja) 2003-12-23 2011-03-02 サンタリス ファーマ アー/エス Bcl−2のモデュレーションのためのオリゴマー化合物
EP1732608A2 (en) 2004-01-22 2006-12-20 Immunomedics, Inc. Folate conjugates and complexes
US20080249039A1 (en) 2004-01-30 2008-10-09 Santaris Pharma A/S Modified Short Interfering Rna (Modified Sirna)
US20050244869A1 (en) 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
EP1737879B1 (en) 2004-04-19 2012-10-10 Archemix LLC 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
CA2574603C (en) 2004-08-04 2014-11-04 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
US20060035858A1 (en) 2004-08-10 2006-02-16 Geary Richard S Methods for modulating lipoprotein and cholesterol levels in humans
EP1802644B1 (en) 2004-09-24 2012-11-07 Alnylam Pharmaceuticals Inc. Rnai modulation of apob and uses thereof
EP1833840B9 (en) * 2004-11-09 2010-11-10 Santaris Pharma A/S Potent lna oligonucleotides for the inhibition of hif-1a
NZ555645A (en) * 2004-11-09 2009-08-28 Santaris Pharma As LNA oligonucleotides and the treatment of cancer
US20120122801A1 (en) 2005-01-05 2012-05-17 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
WO2006078217A1 (en) 2005-01-24 2006-07-27 Avaris Ab COMPLEX CONTAINING SiRNA, ShRNA OR ANTISENSE MOLECULE AND FUNCTIONAL ENTITY, FOR IMPROVED SPECIFICITY AND DELIVERY
US20070213292A1 (en) 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
ATE494372T1 (de) 2005-08-29 2011-01-15 Regulus Therapeutics Inc Verfahren für mir-122a-modulation
DK1931780T3 (en) 2005-08-29 2016-01-25 Regulus Therapeutics Inc Antisense-forbindelser med forøget anti-microrna-aktivitet
WO2007031091A2 (en) 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
EA200800823A1 (ru) * 2005-09-15 2008-10-30 Сантарис Фарма А/С Соединения-антагонисты рнк для ингибирования экспрессии аро-в100
EP1941040A1 (en) 2005-09-19 2008-07-09 Johnson & Johnson Pharmaceutical Research & Development L.L.C. Modulation of glucocorticoid receptor expression
WO2007058894A2 (en) 2005-11-10 2007-05-24 The University Of North Carolina At Chapel Hill Splice switching oligomers for tnf superfamily receptors and their use in treatment of disease
WO2007085485A2 (en) 2006-01-27 2007-08-02 Santaris Pharma A/S Lna modified phosphorothiolated oligonucleotides
PL2314594T3 (pl) 2006-01-27 2014-12-31 Isis Pharmaceuticals Inc Zmodyfikowane w pozycji 6 analogi bicykliczne kwasów nukleinowych
AU2007309650A1 (en) 2006-02-08 2008-05-02 Ercole Biotech, Inc. Soluble TNF receptors and their use in treatment of disease
DK2002004T3 (en) 2006-03-23 2015-11-30 Roche Innovation Ct Copenhagen As LITTLE INTERNAL SEGMENTED INTERFERENCE RNA
GB0606415D0 (en) 2006-03-31 2006-05-10 Univ Southampton Topical drug delivery
CA2649045C (en) 2006-04-03 2019-06-11 Santaris Pharma A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
ES2569558T3 (es) * 2006-04-03 2016-05-11 Roche Innovation Center Copenhagen A/S Composición farmacéutica que comprende oligonucleótidos antisentido anti-ARNmi
DK2363481T3 (en) 2006-05-05 2017-06-26 Ionis Pharmaceuticals Inc Compounds and methods for modulating gene expression
CA2651453C (en) 2006-05-11 2014-10-14 Isis Pharmaceuticals, Inc. 5'-modified bicyclic nucleic acid analogs
AU2007296055A1 (en) 2006-09-15 2008-03-20 Enzon Pharmaceuticals, Inc. Polymeric conjugates containing positively-charged moieties
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
KR101251707B1 (ko) * 2006-09-27 2013-04-11 콜리 파마슈티칼 게엠베하 면역 자극 활성이 증강된 소수성 T 유사체를 함유하는 CpG 올리고뉴클레오티드 유사체
WO2008040355A2 (en) 2006-10-06 2008-04-10 Exiqon A/S Novel methods for quantification of micrornas and small interfering rnas
US20100216864A1 (en) 2006-10-09 2010-08-26 Ellen Marie Straarup RNA Antagonist Compounds for the Modulation of PCSK9
KR20090103894A (ko) 2006-11-27 2009-10-01 아이시스 파마수티컬즈 인코포레이티드 고콜레스테롤혈증을 치료하는 방법
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
US8580756B2 (en) 2007-03-22 2013-11-12 Santaris Pharma A/S Short oligomer antagonist compounds for the modulation of target mRNA
US8470791B2 (en) 2007-03-22 2013-06-25 Santaris Pharma A/S RNA antagonist compounds for the inhibition of Apo-B100 expression
AU2008230886B9 (en) * 2007-03-24 2014-09-04 Kastle Therapeutics, Llc Administering antisense oligonucleotides complementary to human apolipoprotein B
CA2685444A1 (en) 2007-05-01 2008-11-06 Jesper Worm Rna antagonist compounds for the modulation of beta-catenin
MX346434B (es) 2007-05-01 2017-03-21 Santaris Pharma As Oligómeros de cambio de empalme de receptores de la superfamilia tnf y su uso en el tratamiento de enfermedades.
EP2170917B1 (en) 2007-05-30 2012-06-27 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
US8278426B2 (en) 2007-06-08 2012-10-02 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
EP3443976A1 (en) 2007-06-29 2019-02-20 Sarepta Therapeutics, Inc. Tissue specific peptide conjugates and methods
CA2692579C (en) 2007-07-05 2016-05-03 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
CN101816010A (zh) 2007-07-19 2010-08-25 数据匙电子有限公司 Rf令牌和接纳器系统与方法
CA2695532A1 (en) 2007-08-20 2009-02-26 Enzon Pharmaceuticals, Inc. Polymeric linkers containing pyridyl disulfide moieties
KR101660989B1 (ko) 2007-10-01 2016-09-28 아이오니스 파마수티컬즈, 인코포레이티드 섬유아세포 성장 인자 수용체 4 발현의 안티센스 조절
EP3492594A1 (en) * 2007-10-04 2019-06-05 Roche Innovation Center Copenhagen A/S Micromirs
WO2009045536A2 (en) 2007-10-05 2009-04-09 The University Of North Carolina At Chapel Hill Receptor targeted oligonucleotides
DK2225377T3 (da) 2007-11-26 2014-04-07 Santaris Pharma As Lna-antagonister, der er målrettet mod androgenreceptoren
CA2707539A1 (en) * 2007-12-03 2009-06-11 Santaris Pharma A/S Rna antagonist compounds for the modulation of pik3ca expression
EP3156077B1 (en) * 2007-12-04 2022-03-09 Arbutus Biopharma Corporation Targeting lipids
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
EP2265627A2 (en) 2008-02-07 2010-12-29 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
US9290534B2 (en) 2008-04-04 2016-03-22 Ionis Pharmaceuticals, Inc. Oligomeric compounds having at least one neutrally linked terminal bicyclic nucleoside
JP5788312B2 (ja) 2008-04-11 2015-09-30 アルニラム ファーマスーティカルズ インコーポレイテッドAlnylam Pharmaceuticals, Inc. 標的リガンドをエンドソーム分解性成分と組み合わせることによる核酸の部位特異的送達
WO2009148605A2 (en) 2008-06-04 2009-12-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
CA2729897A1 (en) 2008-07-03 2010-01-07 Santaris Pharma A/S Rna antagonist compounds for the inhibition of expression of mitochondrial glycerol-3-phosphate acyltransferase 1 (mtgpat1)
US8703730B2 (en) 2008-07-10 2014-04-22 Regenesance B.V. Complement antagonists and uses thereof
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
US20120022245A1 (en) 2008-10-17 2012-01-26 Purdue Research Foundation Folate targeting of nucleotides
JP5793423B2 (ja) * 2008-12-31 2015-10-14 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 急性冠症候群の治療のためのLNAApoBアンチセンスオリゴマーの使用
AT507215B1 (de) 2009-01-14 2010-03-15 Boehler Edelstahl Gmbh & Co Kg Verschleissbeständiger werkstoff
EP2414521B1 (en) 2009-03-31 2016-10-26 The General Hospital Corporation Regulation of mir-33 micrornas in the treatment of cholesterol-related disorders
US9034837B2 (en) 2009-04-24 2015-05-19 Roche Innovation Center Copenhagen A/S Pharmaceutical compositions for treatment of HCV patients that are poor-responders to interferon
WO2010142805A1 (en) 2009-06-12 2010-12-16 Santaris Pharma A/S New potent anti apob antisense compounds
US8563528B2 (en) 2009-07-21 2013-10-22 Santaris Pharma A/S Antisense oligomers targeting PCSK9
NZ598943A (en) 2009-10-16 2014-09-26 Glaxo Group Ltd 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
US8653047B2 (en) 2010-01-08 2014-02-18 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
US8846631B2 (en) 2010-01-14 2014-09-30 Regulus Therapeutics Inc. MicroRNA compositions and methods
NZ601737A (en) 2010-02-24 2013-06-28 Arrowhead Res Corp Compositions for targeted delivery of sirna
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
EP3231446B1 (en) 2010-04-19 2026-01-07 Palomo Limited Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types
WO2011133871A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
ES2625689T3 (es) 2010-04-29 2017-07-20 Ionis Pharmaceuticals, Inc. Modulación de la expresión de transtiretina
WO2012012716A2 (en) 2010-07-23 2012-01-26 Regulus Therapeutics, Inc. Targeting micrornas for the treatment of fibrosis
JP5875006B2 (ja) * 2010-08-31 2016-03-02 国立大学法人大阪大学 オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する脂質異常症治療剤
US10378016B2 (en) 2010-12-06 2019-08-13 Children's Medical Center Corporation Composition and method for oligonucleotide delivery
EP3226459B1 (en) 2010-12-13 2020-11-25 Telefonaktiebolaget LM Ericsson (publ) Exchange of parameters relating to measurement periods
CN103492568B (zh) 2010-12-17 2017-04-12 箭头研究公司 用于siRNA的半乳糖簇‑药代动力学调节剂靶向部分
KR20130136494A (ko) 2010-12-29 2013-12-12 애로우헤드 리서치 코오포레이션 효소 민감성 결합을 갖는 In Vivo 폴리뉴클레오티드 전달 컨쥬게이트
BR122020024394B1 (pt) * 2010-12-29 2021-05-11 F. Hoffmann-La Roche Ag conjugado e composição farmacêutica
DK2663548T3 (en) 2011-01-11 2017-07-24 Alnylam Pharmaceuticals Inc PEGYLED LIPIDS AND THEIR USE FOR PHARMACEUTICAL SUPPLY
TW201303013A (zh) 2011-04-21 2013-01-16 Isis Pharmaceuticals Inc B型肝炎病毒(hbv)表現之調節
SI3505528T1 (sl) 2011-04-21 2021-04-30 Glaxo Group Limited Modulacija izražanja virusa hepatitisa B (HBV)
US20120270928A1 (en) 2011-04-25 2012-10-25 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
AU2012271357A1 (en) 2011-06-16 2013-05-02 Ionis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
EA202090994A1 (ru) 2011-06-30 2020-08-31 Эрроухэд Фармасьютикалс, Инк. Композиции и способы ингибирования экспрессии генов вируса гепатита в
EP3640332A1 (en) 2011-08-29 2020-04-22 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EP2756080B1 (en) * 2011-09-14 2019-02-20 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
AU2012327227A1 (en) 2011-11-07 2013-05-23 Isis Pharmaceuticals, Inc. Administration of Factor XI antisense oligonucleotides
WO2013068348A1 (en) 2011-11-07 2013-05-16 Santaris Pharma A/S Lna oligomers for improvement in hepatic function
AU2013216852A1 (en) 2012-02-08 2014-08-21 Isis Pharmaceuticals, Inc. Methods and compositions for modulating 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
JP6452614B2 (ja) 2012-11-15 2019-01-16 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 オリゴヌクレオチドコンジュゲート
EP2951305B1 (en) 2013-01-30 2018-08-15 F.Hoffmann-La Roche Ag Lna oligonucleotide carbohydrate conjugates
PL2992098T3 (pl) 2013-05-01 2019-09-30 Ionis Pharmaceuticals, Inc. Kompozycje i sposoby modulowania ekspresji hbv i ttr
KR20160083876A (ko) 2013-11-14 2016-07-12 로슈 이노베이션 센터 코펜하겐 에이/에스 ApoB 안티센스 접합체 화합물
US9778708B1 (en) 2016-07-18 2017-10-03 Lenovo Enterprise Solutions (Singapore) Pte. Ltd. Dual sided latching retainer for computer modules

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