CN113797348A - 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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Publication number
CN113797348A
CN113797348A CN202110938247.8A CN202110938247A CN113797348A CN 113797348 A CN113797348 A CN 113797348A CN 202110938247 A CN202110938247 A CN 202110938247A CN 113797348 A CN113797348 A CN 113797348A
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expression
targeting ligand
targeting
rnai agent
oligomeric compound
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Chinese (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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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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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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CN202110938247.8A 2016-03-07 2017-03-07 用于治疗性化合物的靶向配体 Pending CN113797348A (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
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
CN201780016137.8A CN109069529B (zh) 2016-03-07 2017-03-07 用于治疗性化合物的靶向配体

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CN201780016137.8A Active CN109069529B (zh) 2016-03-07 2017-03-07 用于治疗性化合物的靶向配体

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EP (1) EP3426261A4 (enExample)
JP (4) JP6983797B2 (enExample)
KR (3) KR102515329B1 (enExample)
CN (2) CN113797348A (enExample)
AU (3) AU2017229469B2 (enExample)
BR (1) BR112018068230B1 (enExample)
CA (1) CA3011946A1 (enExample)
IL (3) IL296377A (enExample)
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114703184A (zh) * 2022-03-11 2022-07-05 厦门甘宝利生物医药有限公司 Lpa抑制剂及其用途

Families Citing this family (43)

* 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
KR102515329B1 (ko) 2016-03-07 2023-03-29 애로우헤드 파마슈티컬스 인코포레이티드 치료용 화합물을 위한 표적화 리간드
CN109526222B (zh) 2016-06-06 2022-04-29 箭头药业股份有限公司 5’-环膦酸酯修饰核苷酸
JOP20170161A1 (ar) 2016-08-04 2019-01-30 Arrowhead Pharmaceuticals Inc عوامل RNAi للعدوى بفيروس التهاب الكبد ب
JOP20170056B1 (ar) * 2016-09-02 2021-08-17 Arrowhead Pharmaceuticals Inc مركبات ترابطية مستهدفة
TW202436621A (zh) 2017-01-10 2024-09-16 美商愛羅海德製藥公司 α-1抗胰蛋白酶 (AAT) RNAi 藥劑、包含AAT RNAi 藥劑之組合物及使用方法
CA3048661A1 (en) 2017-01-30 2018-08-02 Arrowhead Pharmaceuticals Inc. Compositions and methods for inhibition of factor xii gene expression
CR20200108A (es) 2017-09-11 2020-06-28 Arrowhead Pharmaceuticals Inc Rnai agents and compositions for inhibiting expression of apolipoprotein c-iii (apoc3)
MX2020001912A (es) 2017-09-14 2020-03-24 Arrowhead Pharmaceuticals Inc Agentes de iarn y composiciones para inhibir la expresion de la angiopoyetina tipo 3 (angptl3) y metodos de uso.
EP3697909A4 (en) 2017-10-17 2021-10-13 Arrowhead Pharmaceuticals, Inc. RNAI-BASED AGENTS AND COMPOSITIONS INTENDED TO INHIBIT ASIALOGLYCOPROTEIN RECEPTOR 1 EXPRESSION
CR20210186A (es) * 2018-09-19 2021-06-14 Arrowhead Pharmaceuticals Inc Agentes de arni para inhibir la expresión de 17beta-hsd tipo 13 (hsd17b13), composiciones de dichos agentes, y métodos de uso
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)
TW202114731A (zh) 2019-06-18 2021-04-16 愛爾蘭商健生科學愛爾蘭無限公司 B型肝炎病毒(HBV)疫苗與靶向HBV之RNAi之組合
JP7720788B2 (ja) 2019-06-25 2025-08-08 アムジエン・インコーポレーテツド 炭水化物に連結されたオリゴヌクレオチドのための精製方法
CA3152529A1 (en) 2019-09-03 2021-03-11 Arcturus Therapeutics, Inc. Asialoglycoprotein receptor mediated delivery of therapeutically active conjugates
IL296133A (en) * 2020-03-04 2022-11-01 Verve Therapeutics Inc Preparations and methods for administering targeted RNA
MX2022011801A (es) * 2020-03-23 2022-10-07 Amgen Inc Anticuerpos monoclonales contra acidos nucleicos modificados quimicamente y usos de los mismos.
IL296718A (en) 2020-03-26 2022-11-01 Arrowhead Pharmaceuticals Inc RNAi agents for inhibiting expression of pnpla3, their pharmaceutical compositions and methods of use
US20230250125A1 (en) 2020-04-01 2023-08-10 Janssen Biopharma, Inc. Nucleic acid polymers
EP4148059A4 (en) * 2020-04-10 2024-02-21 St. Marianna University School of Medicine COMPOUND, CONTRAST AGENT AND METHOD FOR PRODUCING COMPOUND
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
CA3192372A1 (en) 2020-09-15 2022-03-24 Dawn CHRISTIANSON 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
KR20230135585A (ko) 2020-12-23 2023-09-25 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 변형된 trem의 조성물 및 이의 용도
MX2023012605A (es) 2021-04-23 2024-02-23 Ganna Bio Inc Acidos nucleicos modificados con glicano, metodos de preparacion y usos terapeuticos.
US11549112B1 (en) 2021-06-21 2023-01-10 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of xanthine dehydrogenase (XDH), pharmaceutical compositions thereof, and methods of use
CN117377765A (zh) * 2021-07-02 2024-01-09 上海拓界生物医药科技有限公司 一种核酸配体及其缀合物、其制备方法和用途
JP2025511854A (ja) 2022-04-08 2025-04-16 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 非アルコール性脂肪肝疾患の治療
CA3256663A1 (en) * 2022-05-02 2023-11-09 Amgen Inc. METHODS FOR MANUFACTURING A CARBOHYDRATE TARGETING FRACTION AND ITS INTERMEDIARIES
WO2023233290A1 (en) 2022-05-31 2023-12-07 Janssen Sciences Ireland Unlimited Company Rnai agents targeting pd-l1
WO2023250112A1 (en) 2022-06-22 2023-12-28 Flagship Pioneering Innovations Vi, Llc Compositions of modified trems and uses thereof
US12378558B2 (en) 2023-03-21 2025-08-05 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of complement factor B (CFB), pharmaceutical compositions thereof, and methods of use
GB202311334D0 (en) 2023-07-24 2023-09-06 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
US20250051771A1 (en) 2023-07-24 2025-02-13 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

Family Cites Families (97)

* 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
NL9201440A (nl) 1992-08-11 1994-03-01 Univ Leiden Triantennaire clusterglycosiden, hun bereiding en toepassing.
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
US20030119724A1 (en) 1995-11-22 2003-06-26 Ts`O Paul O.P. Ligands to enhance cellular uptake of biomolecules
AU1039397A (en) 1995-11-22 1997-06-27 Johns Hopkins University, The 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
HK1042438A1 (zh) * 1998-10-30 2002-08-16 第一制药株式会社 Dds化合物及其测定方法
US6383812B1 (en) 1999-05-28 2002-05-07 Academia Sinica Anti liver disease drug R-YEEE and method of synthesizing branched galactose-terminal glycoproteins
US8541548B2 (en) 1999-06-07 2013-09-24 Arrowhead Madison Inc. Compounds and methods for reversible modification of biologically active molecules
US20080281041A1 (en) 1999-06-07 2008-11-13 Rozema David B Reversibly Masked Polymers
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
EP1309726B2 (en) 2000-03-30 2018-10-03 Whitehead Institute For Biomedical Research Rna sequence-specific mediators of rna interference
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
US20040259247A1 (en) 2000-12-01 2004-12-23 Thomas Tuschl 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
US7875612B2 (en) 2001-04-24 2011-01-25 Purdue Research Foundation Folate mimetics and folate-receptor binding conjugates thereof
EP2415486B1 (en) 2001-05-18 2017-02-22 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US7109165B2 (en) 2001-05-18 2006-09-19 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)
EP1543019A2 (en) 2002-09-11 2005-06-22 Santaris Pharma A/S Modified pna molecules
EP2216407B1 (en) 2003-03-07 2016-01-13 Alnylam Pharmaceuticals, Inc. Therapeutic compositions
EP1608735A4 (en) 2003-04-03 2008-11-05 Alnylam Pharmaceuticals RNAI CONJUGATES
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
CA2522637C (en) 2003-04-17 2014-01-21 Alnylam Pharmaceuticals, Inc. Modified irna agents
WO2004101619A1 (ja) 2003-05-15 2004-11-25 Shionogi Co., Ltd. 機能的糖ペプチドの合理的設計および合成
EP1791567B1 (en) 2004-08-10 2015-07-29 Alnylam Pharmaceuticals Inc. Chemically modified oligonucleotides
US20090203132A1 (en) 2004-09-09 2009-08-13 Swayze Eric E 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
US20080206869A1 (en) 2005-01-24 2008-08-28 Avaris Ab Nucleic Acid Complex
JP5274461B2 (ja) 2006-08-18 2013-08-28 アローヘッド リサーチ コーポレイション ポリヌクレオチドのインビボ送達のためのポリ結合体
US8658211B2 (en) 2006-08-18 2014-02-25 Arrowhead Madison Inc. Polyconjugates for in vivo delivery of polynucleotides
US9216228B2 (en) 2007-02-16 2015-12-22 KTB Tumorforschungsgesellschaft MBM Receptor and antigen targeted prodrug
US8877917B2 (en) 2007-04-23 2014-11-04 Alnylam Pharmaceuticals, Inc. Glycoconjugates of RNA interference agents
EP2231194B1 (en) 2007-12-04 2017-02-22 Alnylam Pharmaceuticals Inc. Folate-irna conjugates
CA2930393C (en) * 2007-12-04 2022-11-29 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
AU2009241591A1 (en) 2008-01-31 2009-11-05 Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of DSRNA targeting the PCSK9 gene
WO2009120878A2 (en) 2008-03-26 2009-10-01 Alnylam Pharmaceuticals, Inc. Non-natural ribonucleotides, and methods of use thereof
EP3604533A1 (en) 2008-04-11 2020-02-05 Arbutus Biopharma Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
AU2009298802A1 (en) 2008-09-23 2010-04-08 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
HUE026604T2 (hu) 2008-10-20 2016-06-28 Alnylam Pharmaceuticals Inc Transztiretin-expresszió gátlására szolgáló készítmények és eljárások
EP2358398A2 (en) 2008-10-24 2011-08-24 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
EP3757090B1 (en) 2008-11-10 2024-06-12 Arbutus Biopharma Corporation Novel lipids and compositions for the delivery of therapeutics
KR102229618B1 (ko) 2009-05-05 2021-03-18 알닐람 파마슈티칼스 인코포레이티드 지질 조성물
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
SG183374A1 (en) 2010-02-24 2012-09-27 Arrowhead Res Corp Compositions for targeted delivery of sirna
JP2013528665A (ja) 2010-03-26 2013-07-11 メルサナ セラピューティックス， インコーポレイテッド ポリヌクレオチドの送達のための修飾ポリマー、その製造方法、およびその使用方法
US20130236968A1 (en) 2010-06-21 2013-09-12 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
WO2012037254A1 (en) 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. MODIFIED iRNA AGENTS
US8987377B2 (en) * 2010-11-19 2015-03-24 Alnylam Pharmaceuticals, Inc. Poly(amide) polymers for the delivery of oligonucleotides
US8501930B2 (en) * 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
EP3192800A1 (en) * 2010-12-17 2017-07-19 Arrowhead Pharmaceuticals, Inc. Galactose cluster-pharmacokinetic modulator targeting moiety for sirna
BR122020024388B1 (pt) 2010-12-29 2021-09-21 F. Hoffmann-La Roche Ag Oligonucleotídeo e composição farmacêutica
EP3505528B1 (en) 2011-04-21 2020-11-25 Ionis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
KR102434346B1 (ko) * 2011-06-30 2022-08-18 애로우헤드 파마슈티컬스 인코포레이티드 B형 간염 바이러스의 유전자 발현 저해용 조성물 및 방법
PH12014500214A1 (en) 2011-08-26 2019-03-22 Arrowhead Res 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
JP2015515530A (ja) * 2012-04-18 2015-05-28 アローヘッド リサーチ コーポレイション インビボ核酸送達のためのポリ（アクリラート）ポリマー
EP3358013B1 (en) 2012-05-02 2020-06-24 Sirna Therapeutics, Inc. 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
AR090906A1 (es) 2012-05-02 2014-12-17 Merck Sharp & Dohme Conjugados que contienen tetragalnac y procedimientos para la administracion de oligonucleotidos
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
EP4253395A3 (en) 2012-08-06 2023-11-29 Alnylam Pharmaceuticals, Inc. Processes for the preparation of carbohydrate conjugated rna agents
US20150291958A1 (en) 2012-11-15 2015-10-15 Roche Innovation Center Copenhagen A/S Anti apob antisense conjugate compounds
US20150368642A1 (en) 2013-01-30 2015-12-24 Hoffmann-La Roche Inc. Lna oligonucleotide carbohydrate conjugates
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
US9127276B2 (en) 2013-05-01 2015-09-08 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
EP2992095B1 (en) 2013-05-01 2019-01-09 Regulus Therapeutics Inc. Microrna compounds and methods for modulating mir-122
US10808246B2 (en) 2013-07-11 2020-10-20 Alnylam Pharmaceuticals, Inc. Oligonucleotide-ligand conjugates and process for their preparation
US10239957B2 (en) 2013-11-06 2019-03-26 Merck Sharp & Dohme Corp. Peptide containing conjugates for dual molecular delivery of oligonucleotides
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
EP3151839A4 (en) * 2014-06-06 2018-02-28 Ionis 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
CN107074433A (zh) 2014-07-01 2017-08-18 Gima Tt 股份有限责任公司 吸烟制品的包装
EP3195107A4 (en) 2014-09-15 2018-03-07 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
US20160272970A1 (en) * 2015-03-17 2016-09-22 Arrowhead Madison Inc. RNA Interference Agents
EP3271482A4 (en) * 2015-03-17 2019-02-13 Arrowhead Pharmaceuticals, Inc. COMPOSITIONS AND METHODS FOR INHIBITING THE GENE EXPRESSION OF FACTOR XII
EP3332007A4 (en) * 2015-08-07 2019-07-17 Arrowhead Pharmaceuticals, Inc. RNAi Therapy Against Infection with Hepatitis B Virus
JOP20210043A1 (ar) * 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc تراكيب وأساليب لتثبيط تعبير جيني للـ lpa
KR102515329B1 (ko) * 2016-03-07 2023-03-29 애로우헤드 파마슈티컬스 인코포레이티드 치료용 화합물을 위한 표적화 리간드
JOP20170056B1 (ar) 2016-09-02 2021-08-17 Arrowhead Pharmaceuticals Inc مركبات ترابطية مستهدفة
TW202436621A (zh) 2017-01-10 2024-09-16 美商愛羅海德製藥公司 α-1抗胰蛋白酶 (AAT) RNAi 藥劑、包含AAT RNAi 藥劑之組合物及使用方法
CA3048661A1 (en) 2017-01-30 2018-08-02 Arrowhead Pharmaceuticals Inc. Compositions and methods for inhibition of factor xii gene expression

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114703184A (zh) * 2022-03-11 2022-07-05 厦门甘宝利生物医药有限公司 Lpa抑制剂及其用途

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