CN109069529B - 用于治疗性化合物的靶向配体 - Google Patents

用于治疗性化合物的靶向配体 Download PDF

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CN109069529B
CN109069529B CN201780016137.8A CN201780016137A CN109069529B CN 109069529 B CN109069529 B CN 109069529B CN 201780016137 A CN201780016137 A CN 201780016137A CN 109069529 B CN109069529 B CN 109069529B
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expression
targeting ligand
linked
compound
oligomeric compound
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CN109069529A (zh
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D·B·罗泽玛
D·H·维基菲尔德
A·V·布罗金
J·D·本森
李
裴涛
F·弗雷兹
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Arrowhead Pharmaceuticals Inc
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
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CN201780016137.8A 2016-03-07 2017-03-07 用于治疗性化合物的靶向配体 Active CN109069529B (zh)

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US201662304652P 2016-03-07 2016-03-07
US62/304,652 2016-03-07
US201662370754P 2016-08-04 2016-08-04
US62/370,754 2016-08-04
US201662426916P 2016-11-28 2016-11-28
US62/426,916 2016-11-28
PCT/US2017/021175 WO2017156012A1 (en) 2016-03-07 2017-03-07 Targeting ligands for therapeutic compounds

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KR (3) KR102348425B1 (enExample)
CN (2) CN109069529B (enExample)
AU (3) AU2017229469B2 (enExample)
BR (1) BR112018068230B1 (enExample)
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Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201620526A (zh) 2014-06-17 2016-06-16 愛羅海德研究公司 用於抑制α－１抗胰蛋白酶基因表現之組合物及方法
JOP20210043A1 (ar) 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc تراكيب وأساليب لتثبيط تعبير جيني للـ lpa
KR102348425B1 (ko) * 2016-03-07 2022-01-10 애로우헤드 파마슈티컬스 인코포레이티드 치료용 화합물을 위한 표적화 리간드
IL290633B2 (en) 2016-06-06 2024-11-01 Arrowhead Pharmaceuticals Inc 5'-cyclo-phosphonate modified nucleotides, compositions comprising same and uses thereof
JOP20170161A1 (ar) 2016-08-04 2019-01-30 Arrowhead Pharmaceuticals Inc عوامل RNAi للعدوى بفيروس التهاب الكبد ب
US10294474B2 (en) 2016-09-02 2019-05-21 Arrowhead Pharmaceuticals, Inc. Targeting ligands
IL310548A (en) 2017-01-10 2024-03-01 Arrowhead Pharmaceuticals Inc Alpha-1 antitrypsin (aat) rnai agents, compositions including aat rnai agents, and methods of use
AU2018213379A1 (en) 2017-01-30 2019-07-18 Arrowhead Pharmaceuticals Inc. Compositions and methods for inhibition of factor XII gene expression
US10597657B2 (en) 2017-09-11 2020-03-24 Arrowhead Pharmaceuticals, Inc. RNAi agents and compositions for inhibiting expression of apolipoprotein C-III (APOC3)
CN111343994B (zh) 2017-09-14 2023-11-21 箭头药业股份有限公司 用于抑制血管生成素-样3 (ANGPTL3)的表达的RNAi剂和组合物以及使用方法
AU2018352379A1 (en) 2017-10-17 2020-06-04 Arrowhead Pharmaceuticals, Inc. RNAi agents and compositions for inhibiting expression of Asialoglycoprotein receptor 1
MY209138A (en) * 2018-09-19 2025-06-24 Arrowhead Pharmaceuticals Inc Rnai agents for inhibiting expression of 17beta-hsd type 13- (hsd17b13), compositions thereof, and methods of use
CN111377985B (zh) * 2018-12-29 2023-11-10 苏州瑞博生物技术股份有限公司 化合物和缀合物及其制备方法和用途
CA3141762A1 (en) 2019-06-06 2020-12-10 Arrowhead Pharmaceuticals, Inc. Methods for the treatment of alpha-1 antitrypsin deficiency (aatd)
CN114340664A (zh) 2019-06-18 2022-04-12 爱尔兰詹森科学公司 乙型肝炎病毒(HBV)疫苗和靶向HBV的RNAi的组合
US20220363711A1 (en) 2019-06-25 2022-11-17 Amgen Inc. Purification methods for carbohydrate-linked oligonucleotides
EP4025252A4 (en) 2019-09-03 2023-10-18 Arcturus Therapeutics, Inc. ASIALOGLYCOPROTEIN RECEPTOR-MEDIATED ADMINISTRATION OF THERAPEUTICALLY ACTIVE CONJUGATES
GB2629329B (en) * 2020-03-04 2025-02-26 Verve Therapeutics Inc Formulation comprising GalNAc-lipid nanoparticle
EP4126967A1 (en) 2020-03-23 2023-02-08 Amgen Inc. Monoclonal antibodies to chemically-modified nucleic acids and uses thereof
MX2022011907A (es) 2020-03-26 2023-01-05 Arrowhead Pharmaceuticals Inc Agentes de arni para inhibir la expresión de pnpla3, composiciones farmacéuticas de estos, y métodos de uso.
US20230250125A1 (en) 2020-04-01 2023-08-10 Janssen Biopharma, Inc. Nucleic acid polymers
CN115443284A (zh) * 2020-04-10 2022-12-06 学校法人圣玛丽安娜医科大学 化合物、造影剂、及化合物的制造方法
WO2021254360A1 (zh) * 2020-06-16 2021-12-23 上海拓界生物医药科技有限公司 一种碳水化合物分子簇及其制备方法和医药用途
WO2022060721A2 (en) 2020-09-15 2022-03-24 Arrowhead Pharmaceuticals, Inc. Methods for the reduction of z-aat protein levels
KR20230104200A (ko) 2020-11-05 2023-07-07 암젠 인크 LPA-표적화된 RNAi 작제물을 이용하여 죽상경화성 심혈관질환을 치료하는 방법
CA3206285A1 (en) 2020-12-23 2022-06-30 Flagship Pioneering, Inc. Compositions of modified trems and uses thereof
KR20240028335A (ko) 2021-04-23 2024-03-05 간엔에이 바이오, 인크. 글리칸 변형 핵산, 제조 방법 및 치료 용도
US11629349B2 (en) 2021-06-21 2023-04-18 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of xanthine dehydrogenase (XDH), pharmaceutical compositions thereof, and methods of use
EP4365290A1 (en) * 2021-07-02 2024-05-08 Tuojie Biotech (Shanghai) Co., Ltd. Nucleic acid ligand and conjugate thereof, and preparation method therefor and use thereof
CN114703184B (zh) * 2022-03-11 2024-06-18 厦门甘宝利生物医药有限公司 Lpa抑制剂及其用途
CA3247602A1 (en) 2022-04-08 2023-10-12 Arrowhead Pharmaceuticals Inc TREATMENT OF NON-ALCOHOLIC HEPATIC STEATOSE
TW202406926A (zh) * 2022-05-02 2024-02-16 美商安進公司 用於製備碳水化合物靶向部分及其中間體之方法
WO2023233290A1 (en) 2022-05-31 2023-12-07 Janssen Sciences Ireland Unlimited Company Rnai agents targeting pd-l1
US20250179492A1 (en) 2022-06-22 2025-06-05 Flagship Pioneering Innovations Vi, Llc Compositions of modified trems and uses thereof
WO2024197017A2 (en) 2023-03-21 2024-09-26 Arrowhead Pharmaceuticals, Inc. Rnai agents for inhibiting expression of complement factor b (cfb) pharmaceutical compositions thereof, and methods of use
US20250051771A1 (en) 2023-07-24 2025-02-13 Astrazeneca Ab Multivalent cargo-carrying complexes and uses thereof
GB202311324D0 (en) 2023-07-24 2023-09-06 Astrazeneca Ab Multivalent cargo-carrying complexes and uses thereof
GB202311334D0 (en) 2023-07-24 2023-09-06 Astrazeneca Ab Multivalent cargo-carrying complexes and uses thereof
WO2025038661A1 (en) 2023-08-14 2025-02-20 Arrowhead Pharmaceuticals, Inc. Oligonucleotide synthesis methods
WO2025042786A1 (en) 2023-08-18 2025-02-27 Flagship Pioneering Innovations Vi, Llc Compositions comprising circular polyribonucleotides and uses thereof
WO2025074157A1 (en) 2023-10-06 2025-04-10 Glaxosmithkline Intellectual Property (No.3) Limited Treatment of a non-alcoholic fatty liver disease
US20250161347A1 (en) 2023-11-22 2025-05-22 Flagship Pioneering Innovations Vii, Llc Methods and compositions for treating non-alcoholic fatty liver disease
US20250333742A1 (en) 2024-04-25 2025-10-30 Insitro, Inc. Compositions and methods for treating metabolic dysfunction-associated steatotic liver disease
WO2025245188A2 (en) 2024-05-21 2025-11-27 Flagship Pioneering Innovations Vii, Llc Methods of treating liver steatosis and non-alcoholic fatty liver disease

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5885968A (en) * 1992-08-11 1999-03-23 Rijksuniversiteit Te Leiden Triantennary cluster glycosides, their preparation and use
CN1661044A (zh) * 1998-10-30 2005-08-31 第一制药株式会社 Dds化合物及其测定方法
CN103492568A (zh) * 2010-12-17 2014-01-01 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
CN103547272A (zh) * 2010-12-17 2014-01-29 箭头研究公司 基于肽的体内siRNA递送系统
CN103635576A (zh) * 2011-06-30 2014-03-12 箭头研究公司 用于抑制乙型肝炎病毒的基因表达的组合物和方法

Family Cites Families (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4751219A (en) 1985-02-05 1988-06-14 Nederlandse Centrale Organisatie Voor Toegepast-Natuur-Wetenschappelijk Onderzoek Synthetic glycolipides, a process for the preparation thereof and several uses for these synthetic glycolipides
US6908903B1 (en) 1994-12-07 2005-06-21 Aletheon Pharmaceuticals, Inc. Cluster clearing agents
US6172045B1 (en) 1994-12-07 2001-01-09 Neorx Corporation Cluster clearing agents
EP0862439A4 (en) 1995-11-22 2001-01-10 O Paul O P Ts LIGANDS FOR INCREASING THE CELLULAR UPtake OF BIOMOLECULES
US20030119724A1 (en) 1995-11-22 2003-06-26 Ts`O Paul O.P. Ligands to enhance cellular uptake of biomolecules
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
CN1231675A (zh) 1996-09-26 1999-10-13 味之素株式会社 修饰的生理活性蛋白及含有该蛋白的药物组合物
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6383812B1 (en) 1999-05-28 2002-05-07 Academia Sinica Anti liver disease drug R-YEEE and method of synthesizing branched galactose-terminal glycoproteins
US20080281041A1 (en) 1999-06-07 2008-11-13 Rozema David B Reversibly Masked Polymers
US8541548B2 (en) 1999-06-07 2013-09-24 Arrowhead Madison Inc. Compounds and methods for reversible modification of biologically active molecules
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
PT1309726E (pt) 2000-03-30 2010-03-08 Whitehead Biomedical Inst Mediadores de interferência por rna específicos de sequência de rna
EP1355672A2 (en) 2000-12-01 2003-10-29 Cell Works Inc. Conjugates of glycosylated/galactosylated peptide, bifunctional linker, and nucleotidic monomers/polymers, and related compositions and methods of use
DK1407044T4 (en) 2000-12-01 2017-12-04 Max-Planck-Gesellschaft Zur Förderung Der Wss E V RNA interference mediating small RNA molecules
EP1386004A4 (en) 2001-04-05 2005-02-16 Ribozyme Pharm Inc MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID
EP1389209B1 (en) 2001-04-24 2009-04-08 Purdue Research Foundation Folate mimetics and folate-receptor binding conjugates thereof
US7109165B2 (en) 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
EP3231445A1 (en) 2001-05-18 2017-10-18 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US20030148928A1 (en) 2001-07-20 2003-08-07 Leonid Beigelman Enzymatic nucleic acid peptide conjugates
US7439043B2 (en) 2001-10-10 2008-10-21 Neose Technologies, Inc. Galactosyl nucleotide sugars
US20100240730A1 (en) 2002-02-20 2010-09-23 Merck Sharp And Dohme Corp. RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA)
WO2004024757A2 (en) 2002-09-11 2004-03-25 Santaris Pharma A/S Modified pna molecules
WO2004080406A2 (en) 2003-03-07 2004-09-23 Alnylam Pharmaceuticals Therapeutic compositions
EP1608735A4 (en) 2003-04-03 2008-11-05 Alnylam Pharmaceuticals RNAI CONJUGATES
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
JP4597976B2 (ja) 2003-04-17 2010-12-15 アルナイラム ファーマシューティカルズ インコーポレイテッド 修飾ｉＲＮＡ剤
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
JPWO2004101619A1 (ja) 2003-05-15 2006-10-26 塩野義製薬株式会社 機能的糖ペプチドの合理的設計および合成
JP5192234B2 (ja) 2004-08-10 2013-05-08 アルナイラム ファーマシューティカルズ， インコーポレイテッド 化学修飾オリゴヌクレオチド
WO2006031461A2 (en) 2004-09-09 2006-03-23 Isis Pharmaceuticals, Inc. Pyrrolidinyl groups for attaching conjugates to oligomeric compounds
US20060148740A1 (en) 2005-01-05 2006-07-06 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
EP1841867A1 (en) 2005-01-24 2007-10-10 Avaris AB COMPLEX CONTAINING SiRNA, ShRNA OR ANTISENSE MOLECULE AND FUNCTIONAL ENTITY, FOR IMPROVED SPECIFICITY AND DELIVERY
US8658211B2 (en) 2006-08-18 2014-02-25 Arrowhead Madison Inc. Polyconjugates for in vivo delivery of polynucleotides
EP2061443A4 (en) 2006-08-18 2013-07-24 Arrowhead Res Corp POLYCONJUGATE FOR IN VIVO ADMINISTRATION OF POLYNUCLEOTIDES
US9216228B2 (en) 2007-02-16 2015-12-22 KTB Tumorforschungsgesellschaft MBM Receptor and antigen targeted prodrug
WO2008131419A2 (en) 2007-04-23 2008-10-30 Alnylam Pharmaceuticals, Inc. Glycoconjugates of rna interference agents
AU2008340354B2 (en) 2007-12-04 2014-04-17 Alnylam Pharmaceuticals, Inc. Folate-iRNA conjugates
US20090247608A1 (en) 2007-12-04 2009-10-01 Alnylam Pharmaceuticals, Inc. Targeting Lipids
BRPI0907008A2 (pt) 2008-01-31 2015-07-07 Alnylam Pharmaceuticals Inc Métodos otimizados para liberação de dsrna alvejando o gene pcsk9
WO2009120878A2 (en) 2008-03-26 2009-10-01 Alnylam Pharmaceuticals, Inc. Non-natural ribonucleotides, and methods of use thereof
AU2009234266B2 (en) 2008-04-11 2015-08-06 Tekmira Pharmaceuticals Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
CA2737661C (en) 2008-09-23 2019-08-20 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
CN106834291B (zh) 2008-10-20 2020-09-29 阿尔尼拉姆医药品有限公司 抑制运甲状腺素蛋白表达的组合物和方法
WO2010048585A2 (en) 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
JP5832898B2 (ja) 2008-11-10 2015-12-16 テクミラ ファーマシューティカルズ コーポレイションＴｅｋｍｉｒａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｃｏｒｐｏｒａｔｉｏｎ 治療薬を送達するための新規な脂質及び組成物
SG10201911942UA (en) 2009-05-05 2020-02-27 Muthiah Manoharan Lipid compositions
SG10201912450XA (en) 2009-06-10 2020-03-30 Arbutus Biopharma Corp Improved lipid formulation
WO2011005980A1 (en) 2009-07-09 2011-01-13 Intradigm Corporation Novel heterobifunctional polyethylene glycol reagents, their preparation and uses thereof
TWI458493B (zh) 2009-09-25 2014-11-01 Iner Aec Executive Yuan 新穎肝標靶藥劑與合成方法
TWI391144B (zh) 2009-10-26 2013-04-01 Iner Aec Executive Yuan 一種定量肝殘餘功能的檢驗方法與其新穎肝受體造影檢驗藥劑
TWI388338B (zh) 2009-10-26 2013-03-11 Iner Aec Executive Yuan 對聚合醣鏈進行放射標誌以作為肝受體造影劑之方法
WO2011072290A2 (en) 2009-12-11 2011-06-16 The Regents Of The University Of Michigan Targeted dendrimer-drug conjugates
JP6137834B2 (ja) * 2010-02-24 2017-05-31 アローヘッド ファーマシューティカルズ インコーポレイテッド ｓｉＲＮＡの標的化送達のための組成物
EP2553019A1 (en) 2010-03-26 2013-02-06 Mersana Therapeutics, Inc. Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof
US20130236968A1 (en) 2010-06-21 2013-09-12 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
JP2013541334A (ja) 2010-09-15 2013-11-14 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 修飾されたｉＲＮＡ剤
US8987377B2 (en) * 2010-11-19 2015-03-24 Alnylam Pharmaceuticals, Inc. Poly(amide) polymers for the delivery of oligonucleotides
EP2658981B1 (en) 2010-12-29 2016-09-28 F.Hoffmann-La Roche Ag Small molecule conjugates for intracellular delivery of nucleic acids
SG194555A1 (en) 2011-04-21 2013-12-30 Isis Pharmaceuticals Inc Modulation of hepatitis b virus (hbv) expression
CA2842039A1 (en) 2011-08-26 2013-03-07 Arrowhead Research Corporation Poly(vinyl ester) polymers for in vivo nucleic acid delivery
US10023861B2 (en) 2011-08-29 2018-07-17 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
US8933047B2 (en) * 2012-04-18 2015-01-13 Arrowhead Madison Inc. Poly(acrylate) polymers for in vivo nucleic acid delivery
WO2013165816A2 (en) 2012-05-02 2013-11-07 Merck Sharp & Dohme Corp. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
AR090905A1 (es) 2012-05-02 2014-12-17 Merck Sharp & Dohme Conjugados que contienen tetragalnac y peptidos y procedimientos para la administracion de oligonucleotidos, composicion farmaceutica
TWI595885B (zh) 2012-05-02 2017-08-21 喜納製藥公司 包含四ｇａｌｎａｃ之新穎結合物及傳送寡核苷酸之方法
US9150602B2 (en) * 2012-07-24 2015-10-06 Atomic Energy Council, Institute Of Nuclear Energy Research Precursor used for labeling hepatorcyte receptor and containing trisaccharide and diamide demercaptide ligand, method for preparing the same, radiotracer and pharmaceutical composition of the same
CN104717982B (zh) 2012-08-06 2018-08-28 阿尔尼拉姆医药品有限公司 碳水化合物共轭物及其制备改进工艺
EP3406718A1 (en) 2012-11-15 2018-11-28 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
RU2649367C2 (ru) 2013-01-30 2018-04-02 Ф. Хоффманн-Ля Рош Аг Конъюгаты углевода и lna-олигонуклеотида
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
CN105378082B (zh) 2013-05-01 2020-06-09 Ionis制药公司 组合物和方法
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
EP3019200B1 (en) 2013-07-11 2022-03-23 Alnylam Pharmaceuticals, Inc. Oligonucleotide-ligand conjugates and process for their preparation
EP3610884B1 (en) 2013-11-06 2021-08-18 Merck Sharp & Dohme Corp. Peptide containing conjugates for dual molecular delivery of oligonucleotides
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
WO2015188194A1 (en) 2014-06-06 2015-12-10 Isis Pharmaceuticals, Inc. Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds
TW201620526A (zh) 2014-06-17 2016-06-16 愛羅海德研究公司 用於抑制α－１抗胰蛋白酶基因表現之組合物及方法
RU2017101140A (ru) 2014-07-01 2018-08-02 Джима Тт С.П.А. Упаковка для курительных изделий
AU2015317958A1 (en) 2014-09-15 2017-05-04 Qubole, Inc. Systems and methods for providing metadata-aware background caching in data analysis
SG11201702877TA (en) 2014-10-10 2017-05-30 Hoffmann La Roche Galnac phosphoramidites, nucleic acid conjugates thereof and their use
CN113493789A (zh) * 2015-03-17 2021-10-12 箭头药业股份有限公司 用于抑制因子xii的基因表达的组合物和方法
WO2016149020A1 (en) 2015-03-17 2016-09-22 Arrowhead Research Corporation Rna interference agents
WO2017027350A2 (en) * 2015-08-07 2017-02-16 Arrowhead Pharmaceuticals, Inc. Rnai therapy for hepatitis b virus infection
JOP20210043A1 (ar) * 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc تراكيب وأساليب لتثبيط تعبير جيني للـ lpa
KR102348425B1 (ko) * 2016-03-07 2022-01-10 애로우헤드 파마슈티컬스 인코포레이티드 치료용 화합물을 위한 표적화 리간드
US10294474B2 (en) 2016-09-02 2019-05-21 Arrowhead Pharmaceuticals, Inc. Targeting ligands
IL310548A (en) * 2017-01-10 2024-03-01 Arrowhead Pharmaceuticals Inc Alpha-1 antitrypsin (aat) rnai agents, compositions including aat rnai agents, and methods of use
AU2018213379A1 (en) 2017-01-30 2019-07-18 Arrowhead Pharmaceuticals Inc. Compositions and methods for inhibition of factor XII gene expression

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5885968A (en) * 1992-08-11 1999-03-23 Rijksuniversiteit Te Leiden Triantennary cluster glycosides, their preparation and use
CN1661044A (zh) * 1998-10-30 2005-08-31 第一制药株式会社 Dds化合物及其测定方法
CN103492568A (zh) * 2010-12-17 2014-01-01 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
CN103547272A (zh) * 2010-12-17 2014-01-29 箭头研究公司 基于肽的体内siRNA递送系统
CN103635576A (zh) * 2011-06-30 2014-03-12 箭头研究公司 用于抑制乙型肝炎病毒的基因表达的组合物和方法

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