TW201723176A - Kras表現之調節劑 - Google Patents
Kras表現之調節劑 Download PDFInfo
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- TW201723176A TW201723176A TW105130913A TW105130913A TW201723176A TW 201723176 A TW201723176 A TW 201723176A TW 105130913 A TW105130913 A TW 105130913A TW 105130913 A TW105130913 A TW 105130913A TW 201723176 A TW201723176 A TW 201723176A
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| WO (1) | WO2017053722A1 (OSRAM) |
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| HRP20191937T1 (hr) | 2012-09-25 | 2020-01-10 | F. Hoffmann - La Roche Ag | Derivati heksahidropirolo [3,4-c]pirola i srodni spojevi kao inhibitori autotaksina (atx) i kao inhibitori proizvodnje lizofosfatidne kiseline (lpa) za liječenje npr. bubrežnih bolesti |
| AR095079A1 (es) | 2013-03-12 | 2015-09-16 | Hoffmann La Roche | Derivados de octahidro-pirrolo[3,4-c]-pirrol y piridina-fenilo |
| LT3074400T (lt) | 2013-11-26 | 2018-02-12 | F. Hoffmann-La Roche Ag | Oktahidro-ciklobuta [1,2-c;3,4-c`]dipirolo dariniai kaip autotaksino inhibitoriai |
| PE20161223A1 (es) | 2014-03-26 | 2016-11-12 | Hoffmann La Roche | Compuestos condensados de [1,4]diazepina como inhibidores de la produccion de autotaxina (atx) y acido lisofosfatidico (lpa) |
| EA037928B1 (ru) | 2014-03-26 | 2021-06-08 | Ф. Хоффманн-Ля Рош Аг | Бициклические соединения в качестве ингибиторов продукции аутотаксина (atx) и лизофосфатидиловой кислоты (lpa) |
| MA41898A (fr) | 2015-04-10 | 2018-02-13 | Hoffmann La Roche | Dérivés de quinazolinone bicyclique |
| MX377277B (es) | 2015-09-04 | 2025-03-07 | Hoffmann La Roche | Derivados de fenoximetilo. |
| AU2016328535A1 (en) | 2015-09-24 | 2017-11-09 | F. Hoffmann-La Roche Ag | Bicyclic compounds as ATX inhibitors |
| EP3353178B1 (en) | 2015-09-24 | 2021-07-14 | F. Hoffmann-La Roche AG | Bicyclic compounds as dual atx/ca inhibitors |
| CA2991615A1 (en) | 2015-09-24 | 2017-03-30 | F. Hoffmann-La Roche Ag | Bicyclic compounds as atx inhibitors |
| AU2016328365B2 (en) | 2015-09-24 | 2020-04-23 | F. Hoffmann-La Roche Ag | New bicyclic compounds as dual ATX/CA inhibitors |
| US11180759B2 (en) * | 2016-01-19 | 2021-11-23 | The University Of North Carolina At Chapel Hill | Methods and compositions using RNA interference and antisense oligonucleotides for inhibition of KRAS |
| AU2017266911B2 (en) | 2016-05-18 | 2021-09-02 | Array Biopharma, Inc. | KRas G12C inhibitors |
| WO2018146316A1 (en) * | 2017-02-13 | 2018-08-16 | Astrazeneca Ab | Combination of a mapk pathway inhibitor and an antisense compound targeted to kras |
| WO2018155450A1 (ja) | 2017-02-21 | 2018-08-30 | 国立大学法人大阪大学 | アンチセンスオリゴ核酸 |
| JP7090099B2 (ja) | 2017-03-16 | 2022-06-23 | エフ.ホフマン-ラ ロシュ アーゲー | Atxインヒビターとしての新規二環式化合物 |
| BR112019019017A2 (pt) | 2017-03-16 | 2020-04-14 | Hoffmann La Roche | compostos heterocíclicos de utilidade como inibidores duplos de atx/ca |
| US10647715B2 (en) | 2017-11-15 | 2020-05-12 | Mirati Therapeutics, Inc. | KRas G12C inhibitors |
| SI3710439T1 (sl) | 2017-11-15 | 2023-06-30 | Mirati Therapeutics, Inc., | Zaviralci mutacije kras g12c |
| MX2020008103A (es) * | 2018-02-12 | 2020-09-25 | Codiak Biosciences Inc | Metodos y composiciones para polarizacion de macrofagos. |
| AU2019218987B2 (en) | 2018-02-12 | 2025-04-24 | Ionis Pharmaceuticals, Inc. | Modified compounds and uses thereof |
| TWI840345B (zh) * | 2018-03-02 | 2024-05-01 | 美商Ionis製藥公司 | Irf4表現之調節劑 |
| WO2019217307A1 (en) | 2018-05-07 | 2019-11-14 | Mirati Therapeutics, Inc. | Kras g12c inhibitors |
| JP7247227B2 (ja) * | 2018-05-22 | 2023-03-28 | アイオニス・ファーマシューティカルズ・インコーポレイテッド | Apol1発現のモジュレーター |
| US11866705B2 (en) | 2018-07-31 | 2024-01-09 | Osaka Univerity | Small cell lung cancer therapeutic agent containing oligonucleotide |
| HRP20250059T1 (hr) | 2018-09-10 | 2025-03-28 | Mirati Therapeutics, Inc. | Kombinirane terapije |
| EP3849536A4 (en) | 2018-09-10 | 2022-06-29 | Mirati Therapeutics, Inc. | Combination therapies |
| EP3849538A4 (en) | 2018-09-10 | 2022-06-29 | Mirati Therapeutics, Inc. | Combination therapies |
| TW202028222A (zh) * | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
| EA202190630A1 (ru) | 2018-12-05 | 2021-10-11 | Мирати Терапьютикс, Инк. | Способы комбинированной терапии |
| WO2020146613A1 (en) | 2019-01-10 | 2020-07-16 | Mirati Therapeutics, Inc. | Kras g12c inhibitors |
| WO2020160453A1 (en) | 2019-01-31 | 2020-08-06 | Ionis Pharmaceuticals, Inc. | Modulators of yap1 expression |
| CN114641570A (zh) * | 2019-08-14 | 2022-06-17 | 科迪亚克生物科学公司 | 具有靶向kras的反义寡核苷酸的细胞外囊泡 |
| JP7622043B2 (ja) | 2019-08-29 | 2025-01-27 | ミラティ セラピューティクス, インコーポレイテッド | Kras g12d阻害剤 |
| CA3152025A1 (en) | 2019-09-24 | 2021-04-01 | David BRIERE | Combination therapies |
| CN110981943B (zh) * | 2019-12-02 | 2021-08-03 | 清华大学 | 多肽及其在制备药物中的用途和药物 |
| EP4076418A4 (en) | 2019-12-20 | 2024-01-24 | Mirati Therapeutics, Inc. | Sos1 inhibitors |
| JP7427227B2 (ja) * | 2020-01-21 | 2024-02-05 | 学校法人産業医科大学 | 腫瘍細胞の生存を低下させるkrasアンチセンスオリゴヌクレオチド及びその用途 |
| JP2023540809A (ja) | 2020-09-11 | 2023-09-26 | ミラティ セラピューティクス, インコーポレイテッド | Kras g12c阻害剤の結晶形態 |
| KR102574252B1 (ko) * | 2020-12-15 | 2023-09-07 | 주식회사 시선테라퓨틱스 | 펩티드 핵산 복합체를 유효성분으로 함유하는 췌장암 예방 또는 치료용 조성물 |
| IL303446A (en) | 2020-12-15 | 2023-08-01 | Mirati Therapeutics Inc | Azaquinazoline compounds as PAN-KRas inhibitors |
| WO2022133038A1 (en) | 2020-12-16 | 2022-06-23 | Mirati Therapeutics, Inc. | Tetrahydropyridopyrimidine pan-kras inhibitors |
| KR20240051272A (ko) * | 2021-09-02 | 2024-04-19 | 몰레큘라 악시옴, 엘엘씨 | Kras 발현을 조절하기 위한 조성물 및 방법 |
| WO2024155770A2 (en) * | 2023-01-18 | 2024-07-25 | Molecular Axiom, Llc | Compositions for modulating kras expression and uses thereof |
| CN119639745B (zh) * | 2024-12-12 | 2025-11-25 | 制能(北京)生物科技有限公司 | 一种靶向kras基因的反义核酸及其药物制剂和应用 |
Family Cites Families (114)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7666A (en) | 1850-09-24 | harris | ||
| US854A (en) | 1838-07-26 | Iixvi-lx n | ||
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
| FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
| 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 |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| JP2828642B2 (ja) | 1987-06-24 | 1998-11-25 | ハワード フローレイ インスティテュト オブ イクスペリメンタル フィジオロジー アンド メディシン | ヌクレオシド誘導体 |
| US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
| US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
| US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5457191A (en) | 1990-01-11 | 1995-10-10 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| JPH0874B2 (ja) | 1990-07-27 | 1996-01-10 | アイシス・ファーマシューティカルス・インコーポレーテッド | 遺伝子発現を検出および変調するヌクレアーゼ耐性、ピリミジン修飾オリゴヌクレオチド |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| US5948903A (en) | 1991-01-11 | 1999-09-07 | Isis Pharmaceuticals, Inc. | Synthesis of 3-deazapurines |
| US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| TW393513B (en) | 1991-11-26 | 2000-06-11 | Isis Pharmaceuticals Inc | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| DE637965T1 (de) | 1991-11-26 | 1995-12-14 | Gilead Sciences Inc | Gesteigerte bildung von triple- und doppelhelices aus oligomeren mit modifizierten pyrimidinen. |
| US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
| US6784290B1 (en) | 1992-10-05 | 2004-08-31 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide inhibition of ras |
| US5872242A (en) * | 1992-10-05 | 1999-02-16 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide inhibition of ras |
| JPH08504559A (ja) | 1992-12-14 | 1996-05-14 | ハネウエル・インコーポレーテッド | 個別に制御される冗長巻線を有するモータシステム |
| US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
| US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| US6172045B1 (en) | 1994-12-07 | 2001-01-09 | Neorx Corporation | Cluster clearing agents |
| US6908903B1 (en) | 1994-12-07 | 2005-06-21 | Aletheon Pharmaceuticals, Inc. | Cluster clearing agents |
| JP2000501414A (ja) | 1995-11-22 | 2000-02-08 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 生体分子の細胞取り込みを高めるリガンド |
| US20030119724A1 (en) | 1995-11-22 | 2003-06-26 | Ts`O Paul O.P. | Ligands to enhance cellular uptake of biomolecules |
| WO1998013381A1 (fr) | 1996-09-26 | 1998-04-02 | Ajinomoto Co., Inc. | Proteines modifiees physiologiquement actives et compositions medicamenteuses les contenant |
| 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 |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| US6300319B1 (en) | 1998-06-16 | 2001-10-09 | Isis Pharmaceuticals, Inc. | Targeted oligonucleotide conjugates |
| KR20010112944A (ko) | 1999-04-21 | 2001-12-22 | 이곤 이 버그 | 폴리뉴클레오티드 서열의 기능을 억제하기 위한 방법 및조성물 |
| AU776362B2 (en) | 1999-05-04 | 2004-09-09 | Roche Innovation Center Copenhagen A/S | L-ribo-LNA analogues |
| US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| 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 |
| US7491805B2 (en) | 2001-05-18 | 2009-02-17 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
| US6906182B2 (en) | 2000-12-01 | 2005-06-14 | Cell Works Therapeutics, Inc. | Conjugates of glycosylated/galactosylated peptide, bifunctional linker, and nucleotidic monomers/polymers, and related compositions and method of use |
| US20030077829A1 (en) | 2001-04-30 | 2003-04-24 | Protiva Biotherapeutics Inc.. | Lipid-based formulations |
| US20030158403A1 (en) | 2001-07-03 | 2003-08-21 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
| US20030175906A1 (en) | 2001-07-03 | 2003-09-18 | Muthiah Manoharan | Nuclease resistant chimeric oligonucleotides |
| 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 |
| AU2003291753B2 (en) | 2002-11-05 | 2010-07-08 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| EP2957568B1 (en) | 2002-11-05 | 2016-12-21 | Ionis Pharmaceuticals, Inc. | Compositions comprising alternating 2'-modified nucleosides for use in gene modulation |
| US6673661B1 (en) | 2002-12-20 | 2004-01-06 | Taiwan Semiconductor Manufacturing Co., Ltd. | Self-aligned method for forming dual gate thin film transistor (TFT) device |
| CA2522637C (en) | 2003-04-17 | 2014-01-21 | Alnylam Pharmaceuticals, Inc. | Modified irna agents |
| US7851615B2 (en) | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
| US7723509B2 (en) | 2003-04-17 | 2010-05-25 | Alnylam Pharmaceuticals | IRNA agents with biocleavable tethers |
| 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 |
| WO2004106356A1 (en) | 2003-05-27 | 2004-12-09 | Syddansk Universitet | Functionalized nucleotide derivatives |
| ATE555118T1 (de) | 2003-08-28 | 2012-05-15 | Takeshi Imanishi | Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung |
| 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 |
| WO2006020768A2 (en) | 2004-08-10 | 2006-02-23 | 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 |
| 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 |
| EP1984381B1 (en) | 2006-01-27 | 2010-09-29 | Isis Pharmaceuticals, Inc. | 6-modified bicyclic nucleic acid analogs |
| US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
| ES2389737T3 (es) | 2006-05-11 | 2012-10-31 | Isis Pharmaceuticals, Inc. | Análogos de ácidos nucleicos bicíclicos modificados en 5' |
| US8658211B2 (en) | 2006-08-18 | 2014-02-25 | Arrowhead Madison Inc. | Polyconjugates for in vivo delivery of polynucleotides |
| WO2008022309A2 (en) | 2006-08-18 | 2008-02-21 | F. Hoffmann-La Roche Ag | Polyconjugates for in vivo delivery of polynucleotides |
| EP2125852B1 (en) | 2007-02-15 | 2016-04-06 | Ionis Pharmaceuticals, Inc. | 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom |
| EP2606911A1 (en) | 2007-02-16 | 2013-06-26 | KTB Tumorforschungsgesellschaft mbH | Receptor And Antigen Targeted Prodrug |
| US8877917B2 (en) | 2007-04-23 | 2014-11-04 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of RNA interference agents |
| US8278425B2 (en) | 2007-05-30 | 2012-10-02 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
| DK2173760T4 (en) | 2007-06-08 | 2016-02-08 | Isis Pharmaceuticals Inc | Carbocyclic bicyclic nukleinsyreanaloge |
| US8278283B2 (en) | 2007-07-05 | 2012-10-02 | Isis Pharmaceuticals, Inc. | 6-disubstituted or unsaturated bicyclic nucleic acid analogs |
| CN101821277B (zh) | 2007-08-15 | 2014-05-07 | Isis制药公司 | 四氢吡喃核酸类似物 |
| WO2009082607A2 (en) | 2007-12-04 | 2009-07-02 | Alnylam Pharmaceuticals, Inc. | Targeting lipids |
| EP2245039A4 (en) | 2008-01-31 | 2012-06-06 | Alnylam Pharmaceuticals Inc | OPTIMIZED METHODS FOR EXPORING DSRNA TO TARGET THE PCSK9 GEN |
| WO2009142822A2 (en) | 2008-03-26 | 2009-11-26 | Alnylam Pharmaceuticals, Inc. | 2-f modified rna interference agents |
| US8575123B2 (en) | 2008-04-11 | 2013-11-05 | Tekmira Pharmaceuticals Corporation | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
| US8962580B2 (en) | 2008-09-23 | 2015-02-24 | Alnylam Pharmaceuticals, Inc. | Chemical modifications of monomers and oligonucleotides with cycloaddition |
| WO2010054406A1 (en) | 2008-11-10 | 2010-05-14 | Alnylam Pharmaceuticals, Inc. | Novel lipids and compositions for the delivery of therapeutics |
| WO2010088537A2 (en) | 2009-01-29 | 2010-08-05 | Alnylam Pharmaceuticals, Inc. | Improved lipid formulation |
| WO2010115202A2 (en) * | 2009-04-03 | 2010-10-07 | Dicerna Pharmaceuticals, Inc. | Methods and compositions for the specific inhibition of kras by blunt ended double-stranded rna |
| NZ711583A (en) | 2009-05-05 | 2017-03-31 | Arbutus Biopharma Corp | Lipid compositions |
| KR102066189B1 (ko) | 2009-06-10 | 2020-01-14 | 알닐람 파마슈티칼스 인코포레이티드 | 향상된 지질 조성물 |
| EA201270019A1 (ru) | 2009-06-15 | 2012-06-29 | Элнилэм Фармасьютикалз, Инк. | Двуцепочечная рнк, включенная в липидный состав и мишенью которой является ген pcsk9 |
| 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 |
| US9198972B2 (en) | 2010-01-28 | 2015-12-01 | Alnylam Pharmaceuticals, Inc. | Monomers and oligonucleotides comprising cycloaddition adduct(s) |
| RS54578B1 (sr) | 2010-02-24 | 2016-06-30 | Arrowhead Research Corporation | Preparati za ciljano dopremanje sirnk |
| US20130109817A1 (en) | 2010-03-26 | 2013-05-02 | Mersana Therapeutics, Inc. | Modified Polymers for Delivery of Polynucleotides, Method of Manufacture, and Methods of Use Thereof |
| CA2794307A1 (en) | 2010-03-26 | 2011-09-29 | Mersana Therapeutics, Inc. | Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof |
| WO2011133876A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
| US20130236968A1 (en) | 2010-06-21 | 2013-09-12 | Alnylam Pharmaceuticals, Inc. | Multifunctional copolymers for nucleic acid delivery |
| EP2616543A1 (en) | 2010-09-15 | 2013-07-24 | Alnylam Pharmaceuticals, Inc. | MODIFIED iRNA AGENTS |
| WO2012068187A1 (en) | 2010-11-19 | 2012-05-24 | Merck Sharp & Dohme Corp. | 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 |
| JP2014504295A (ja) | 2010-12-17 | 2014-02-20 | アローヘッド リサーチ コーポレイション | siRNA用ガラクトースクラスター−薬物動態調節剤標的指向部分 |
| CN103282503B (zh) | 2010-12-29 | 2015-12-02 | 弗·哈夫曼-拉罗切有限公司 | 用于细胞内递送核酸的小分子缀合物 |
| RU2631805C2 (ru) | 2011-06-21 | 2017-09-26 | Элнилэм Фармасьютикалз, Инк. | Композиции и способы ингибирования экспрессии генов аполипопротеина с-iii (арос3) |
| CN104024328A (zh) | 2011-08-26 | 2014-09-03 | 箭头研究公司 | 用于体内核酸递送的聚(乙烯基酯)聚合物 |
| EP2751270B1 (en) | 2011-08-29 | 2018-08-22 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
| AU2012340159B2 (en) | 2011-11-18 | 2017-09-07 | Alnylam Pharmaceuticals, Inc. | RNAi agents, compositions and methods of use thereof for treating transthyretin (TTR) associated diseases |
| TW201808342A (zh) | 2012-05-02 | 2018-03-16 | 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 |
| EP3453762B1 (en) | 2012-05-02 | 2021-04-21 | Sirna Therapeutics, Inc. | Short interfering nucleic acid (sina) compositions |
| BR112015027322A8 (pt) | 2013-05-01 | 2018-01-02 | Isis Pharmaceuticals Inc | Compostos antissenso conjugados e sua utilização |
-
2016
- 2016-09-23 EP EP16849701.4A patent/EP3353328A4/en not_active Withdrawn
- 2016-09-23 JP JP2018515292A patent/JP6877414B2/ja not_active Expired - Fee Related
- 2016-09-23 SG SG10201913209WA patent/SG10201913209WA/en unknown
- 2016-09-23 MX MX2018003472A patent/MX2018003472A/es unknown
- 2016-09-23 CN CN201680053233.5A patent/CN108513588A/zh active Pending
- 2016-09-23 CA CA2998382A patent/CA2998382A1/en not_active Abandoned
- 2016-09-23 AR ARP160102916A patent/AR106135A1/es unknown
- 2016-09-23 AU AU2016326619A patent/AU2016326619B2/en not_active Ceased
- 2016-09-23 WO PCT/US2016/053334 patent/WO2017053722A1/en not_active Ceased
- 2016-09-23 KR KR1020187010307A patent/KR20180051626A/ko not_active Withdrawn
- 2016-09-23 HK HK18111182.5A patent/HK1251624A1/zh unknown
- 2016-09-23 US US15/762,616 patent/US20180273577A1/en not_active Abandoned
- 2016-09-23 TW TW105130913A patent/TW201723176A/zh unknown
- 2016-09-23 BR BR112018004620-5A patent/BR112018004620A2/pt active Search and Examination
- 2016-09-23 RU RU2018113709A patent/RU2018113709A/ru not_active Application Discontinuation
- 2016-09-23 HK HK18114849.4A patent/HK1255699A1/zh unknown
-
2018
- 2018-02-16 CL CL2018000429A patent/CL2018000429A1/es unknown
- 2018-03-11 IL IL258013A patent/IL258013A/en unknown
- 2018-03-23 CO CONC2018/0003168A patent/CO2018003168A2/es unknown
- 2018-04-20 ZA ZA2018/02663A patent/ZA201802663B/en unknown
-
2020
- 2020-10-28 AU AU2020260436A patent/AU2020260436A1/en not_active Abandoned
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|---|---|
| MX2018003472A (es) | 2018-07-06 |
| AR106135A1 (es) | 2017-12-13 |
| AU2016326619A1 (en) | 2018-05-10 |
| AU2020260436A1 (en) | 2020-11-26 |
| CN108513588A (zh) | 2018-09-07 |
| WO2017053722A1 (en) | 2017-03-30 |
| JP6877414B2 (ja) | 2021-05-26 |
| HK1255699A1 (zh) | 2019-08-23 |
| RU2018113709A3 (OSRAM) | 2020-05-29 |
| KR20180051626A (ko) | 2018-05-16 |
| RU2018113709A (ru) | 2019-10-30 |
| IL258013A (en) | 2018-05-31 |
| CA2998382A1 (en) | 2017-03-30 |
| HK1251624A1 (zh) | 2019-02-01 |
| ZA201802663B (en) | 2019-01-30 |
| JP2018528781A (ja) | 2018-10-04 |
| CL2018000429A1 (es) | 2018-08-10 |
| CO2018003168A2 (es) | 2018-06-20 |
| BR112018004620A2 (pt) | 2018-09-25 |
| AU2016326619B2 (en) | 2020-07-30 |
| EP3353328A4 (en) | 2019-06-12 |
| US20180273577A1 (en) | 2018-09-27 |
| EP3353328A1 (en) | 2018-08-01 |
| SG10201913209WA (en) | 2020-02-27 |
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