JP5941926B2 - 酵素感受性連結を有するインビボポリヌクレオチド送達結合体 - Google Patents

酵素感受性連結を有するインビボポリヌクレオチド送達結合体 Download PDF

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JP5941926B2
JP5941926B2 JP2013547648A JP2013547648A JP5941926B2 JP 5941926 B2 JP5941926 B2 JP 5941926B2 JP 2013547648 A JP2013547648 A JP 2013547648A JP 2013547648 A JP2013547648 A JP 2013547648A JP 5941926 B2 JP5941926 B2 JP 5941926B2
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mmol
amino acid
product
group
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JP2014505685A5 (enExample
JP2014505685A (ja
Inventor
デイビッド ビー． ロゼマ
デイビッド ビー． ロゼマ
デイビッド エル． ルイス
デイビッド エル． ルイス
ダレン エイチ． ウェイクフィールド
ダレン エイチ． ウェイクフィールド
エリック エイ． キタス
エリック エイ． キタス
フィリップ ハドウィガー
フィリップ ハドウィガー
ジョン エイ． ウォルフ
ジョン エイ． ウォルフ
インゴ ローエル
インゴ ローエル
ピーター モーア
ピーター モーア
トルステン ホフマン
トルステン ホフマン
カースティン ヤン‐ホフマン
カースティン ヤン‐ホフマン
ハンス マーティン ミューラー
ハンス マーティン ミューラー
グエンテル オット
グエンテル オット
アンドレイ ブイ． ブローキン
アンドレイ ブイ． ブローキン
ジェフリー シー． カールソン
ジェフリー シー． カールソン
ジョナサン ディー． ベンソン
ジョナサン ディー． ベンソン
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アローヘッド リサーチ コーポレイション
アローヘッド リサーチ コーポレイション
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    • C07C233/05—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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JP2013547648A 2010-12-29 2011-12-28 酵素感受性連結を有するインビボポリヌクレオチド送達結合体 Expired - Fee Related JP5941926B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201061427936P 2010-12-29 2010-12-29
US61/427,936 2010-12-29
US13/336,028 US8426554B2 (en) 2010-12-29 2011-12-23 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages
US13/336,028 2011-12-23
PCT/US2011/067588 WO2012092373A2 (en) 2010-12-29 2011-12-28 In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

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JP2014505685A JP2014505685A (ja) 2014-03-06
JP2014505685A5 JP2014505685A5 (enExample) 2014-09-11
JP5941926B2 true JP5941926B2 (ja) 2016-06-29

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EP (1) EP2658579A4 (enExample)
JP (1) JP5941926B2 (enExample)
KR (1) KR20130136494A (enExample)
CN (1) CN103491982B (enExample)
AU (1) AU2011352204B2 (enExample)
BR (1) BR112013014115A2 (enExample)
CA (1) CA2816041C (enExample)
CL (2) CL2013001876A1 (enExample)
MX (2) MX347298B (enExample)
NZ (1) NZ611656A (enExample)
PE (1) PE20140198A1 (enExample)
RU (1) RU2619453C2 (enExample)
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WO (1) WO2012092373A2 (enExample)
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Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2889044A1 (en) 2012-11-15 2014-05-22 Roche Innovation Center Copenhagen A/S Anti apob antisense conjugate compounds
WO2015021092A1 (en) * 2013-08-07 2015-02-12 Arrowhead Research Corporation Polyconjugates for delivery of rnai triggers to tumor cells in vivo
JOP20160211B1 (ar) 2015-10-01 2021-08-17 Arrowhead Pharmaceuticals Inc تراكيب وأساليب لتثبيط تعبير جيني للـ lpa
KR102775461B1 (ko) * 2016-04-01 2025-02-28 어비디티 바이오사이언시스 인크. 핵산-폴리펩타이드 조성물 및 이의 용도
EP3630742B1 (en) * 2017-05-24 2023-08-16 Ramot at Tel-Aviv University Ltd. Chemiluminescent probes for imaging/detection of proteases
CN118638787A (zh) 2017-12-06 2024-09-13 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
AU2019416109A1 (en) * 2018-12-28 2021-07-22 Sirnaomics, Inc. Targeted delivery of therapeutic molecules
CN114450326B (zh) * 2019-06-24 2025-02-11 普罗美加公司 用于将生物分子递送到细胞中的改性聚胺聚合物
TW202144572A (zh) 2020-03-19 2021-12-01 美商亞維代堤生物科學公司 治療臉肩胛肱骨肌肉失養症之組合物及方法
CN115209922A (zh) * 2021-01-28 2022-10-18 南京桦冠生物技术有限公司 缀合物及其用途
KR20240024104A (ko) * 2021-06-24 2024-02-23 가부시키가이샤 토호쿠 테크노 아치 형광 프로브
KR102712976B1 (ko) * 2021-07-27 2024-10-07 국립안동대학교 산학협력단 등검은말벌 추출물을 유효성분으로 함유하는 혈전증의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품
CN113621003B (zh) * 2021-09-10 2023-02-03 国科温州研究院(温州生物材料与工程研究所) 一种制备有机分子共价修饰的功能化核酸材料的方法及其应用
EP4401792A4 (en) 2021-09-16 2025-12-03 Avidity Biosciences Inc COMPOSITIONS AND METHODS OF TREATMENT OF FACIO-SCAPULO-HUMERAL MUSCULAR DYSTROPHY
CN121079108A (zh) * 2023-05-12 2025-12-05 五稜化药株式会社 冻结干燥制剂、冻结干燥溶液和这些的制造方法、以及液剂

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214345B1 (en) * 1993-05-14 2001-04-10 Bristol-Myers Squibb Co. Lysosomal enzyme-cleavable antitumor drug conjugates
US6180095B1 (en) * 1997-12-17 2001-01-30 Enzon, Inc. Polymeric prodrugs of amino- and hydroxyl-containing bioactive agents
EP1242609A2 (en) * 1999-12-30 2002-09-25 Novartis AG Novel colloid synthetic vectors for gene therapy
HUP0300024A2 (en) * 2000-02-24 2003-05-28 Genentech Inc Caspase activated prodrugs therapy
EP1243276A1 (en) * 2001-03-23 2002-09-25 Franciscus Marinus Hendrikus De Groot Elongated and multiple spacers containing activatible prodrugs
US7091186B2 (en) * 2001-09-24 2006-08-15 Seattle Genetics, Inc. p-Amidobenzylethers in drug delivery agents
US7541330B2 (en) * 2004-06-15 2009-06-02 Kosan Biosciences Incorporated Conjugates with reduced adverse systemic effects
US20080171067A1 (en) * 2007-01-17 2008-07-17 Immunomedics, Inc. Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites
WO2007059404A2 (en) * 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
CN101500548A (zh) * 2006-08-18 2009-08-05 弗·哈夫曼-拉罗切有限公司 用于体内递送多核苷酸的多缀合物
RU2430740C2 (ru) * 2006-08-18 2011-10-10 Ф.Хоффманн-Ля Рош Аг Поликонъюгаты для введения in vivo полинуклеотидов
TW201004647A (en) * 2008-05-20 2010-02-01 Sigma Tau Ind Farmaceuti Novel dual targeting antitumoural conjugates
US8501930B2 (en) * 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system

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RU2013117286A (ru) 2015-03-10
BR112013014115A2 (pt) 2019-09-24
MX341118B (es) 2016-08-09
MX2013007316A (es) 2013-07-29
MX347298B (es) 2017-04-21
WO2012092373A3 (en) 2013-10-24
CA2816041A1 (en) 2012-07-05
AU2011352204A1 (en) 2013-05-02
KR20130136494A (ko) 2013-12-12
CN103491982B (zh) 2017-09-12
JP2014505685A (ja) 2014-03-06
PE20140198A1 (es) 2014-02-21
EP2658579A2 (en) 2013-11-06
CN103491982A (zh) 2014-01-01
CL2015003580A1 (es) 2016-07-15
AU2011352204B2 (en) 2015-05-21
CA2816041C (en) 2019-01-08
EP2658579A4 (en) 2015-07-22
ZA201302896B (en) 2014-07-25
WO2012092373A2 (en) 2012-07-05
RU2619453C2 (ru) 2017-05-16
NZ611656A (en) 2014-10-31
CL2013001876A1 (es) 2014-04-11
SG189942A1 (en) 2013-06-28

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