JP7049262B2 - 結合組織成長因子を標的とするrna複合体を用いた特発性肺胞線維症の治療 - Google Patents
結合組織成長因子を標的とするrna複合体を用いた特発性肺胞線維症の治療 Download PDFInfo
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- JP7049262B2 JP7049262B2 JP2018553128A JP2018553128A JP7049262B2 JP 7049262 B2 JP7049262 B2 JP 7049262B2 JP 2018553128 A JP2018553128 A JP 2018553128A JP 2018553128 A JP2018553128 A JP 2018553128A JP 7049262 B2 JP7049262 B2 JP 7049262B2
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2818662C (en) | 2010-10-22 | 2021-07-06 | Sungkyunkwan University Foundation For Corporate Collaboration | Nucleic acid molecule inducing rna interference, and uses thereof |
| EP3514236A1 (en) * | 2012-05-22 | 2019-07-24 | Olix Pharmaceuticals, Inc. | Rna-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor |
| EP3377630A4 (en) | 2015-11-16 | 2020-01-01 | Olix Pharmaceuticals, Inc. | Treatment of age-related macular degeneration using rna complexes that target myd88 or tlr3 |
| CN108779463B (zh) | 2016-02-02 | 2022-05-24 | 奥利克斯医药有限公司 | 使用靶向IL4Rα、TRPA1或F2RL1的RNA复合物治疗特应性皮炎和哮喘 |
| WO2017134526A1 (en) | 2016-02-02 | 2017-08-10 | Olix Pharmaceuticals, Inc. | Treatment of angiogenesis-associated diseases using rna complexes that target angpt2 and pdgfb |
| WO2017178883A2 (en) * | 2016-04-11 | 2017-10-19 | Olix Pharmaceuticals, Inc. | Treatment of idiopathic pulmonary fibrosis using rna complexes that target connective tissue growth factor |
| KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| US11591600B2 (en) | 2017-02-10 | 2023-02-28 | OliX Pharmaceuticals. Inc. | Long double-stranded RNA for RNA interference |
| WO2020027640A1 (ko) * | 2018-07-31 | 2020-02-06 | 주식회사 레모넥스 | Ctgf 발현 억제용 조성물 |
| KR20200014684A (ko) * | 2018-07-31 | 2020-02-11 | 주식회사 레모넥스 | Ctgf 발현 억제용 조성물 |
| CN109402127B (zh) * | 2018-09-29 | 2021-12-10 | 复旦大学附属眼耳鼻喉科医院 | 一组与结缔组织生长因子特异性结合的高亲和力核酸适配体及其应用 |
| WO2020122534A1 (ko) * | 2018-12-10 | 2020-06-18 | 올릭스 주식회사 | Snai1의 발현을 억제하는 비대칭 sirna |
| KR102161041B1 (ko) | 2018-12-13 | 2020-10-05 | 영남대학교 산학협력단 | 살리노마이신을 유효성분으로 함유하는 세포노화 관련 질환 예방 또는 치료용 조성물 |
| CN111378655B (zh) * | 2018-12-28 | 2024-03-19 | 苏州瑞博生物技术股份有限公司 | 抑制CTGF基因表达的siRNA、含有该siRNA的药物组合物及其用途 |
| US20240093188A1 (en) * | 2020-05-26 | 2024-03-21 | Olix Pharmaceuticals, Inc. | RNAi AGENT TARGETING MYD88 AND USE THEREOF |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013094071A (ja) | 2011-10-28 | 2013-05-20 | Mie Univ | ヒトTGFβ1を発現するトランスジェニックマウス |
| JP2015518721A (ja) | 2012-05-22 | 2015-07-06 | オリックス ファーマシューティカルズ インコーポレイテッドOlix Pharmaceuticals Inc. | 細胞内貫通能を持ってrna干渉を誘導する核酸分子およびその用途 |
Family Cites Families (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5837258A (en) | 1991-08-30 | 1998-11-17 | University Of South Florida | Induction of tissue, bone or cartilage formation using connective tissue growth factor |
| DE10160151A1 (de) | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
| RU2322500C2 (ru) | 2000-12-01 | 2008-04-20 | Макс-Планк-Гезелльшафт Цур Фердерунг Дер Виссеншафтен Е.Ф. | Малые молекулы рнк, опосредующие интерференцию рнк |
| US20080188430A1 (en) | 2001-05-18 | 2008-08-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA) |
| US20050282188A1 (en) | 2001-05-18 | 2005-12-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
| JP2005506087A (ja) | 2001-10-26 | 2005-03-03 | リボファーマ アーゲー | プラス鎖rnaウイルスによる感染症を処置するための2本鎖リボ核酸の使用 |
| US20040138163A1 (en) | 2002-05-29 | 2004-07-15 | Mcswiggen James | RNA interference mediated inhibition of vascular edothelial growth factor and vascular edothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| ES2280826T5 (es) | 2002-08-05 | 2017-08-03 | Silence Therapeutics Gmbh | Nuevas formas adicionales de moléculas de ARN de interferencia |
| DK2284266T3 (da) | 2002-11-14 | 2014-01-13 | Thermo Fisher Scient Biosciences Inc | sIRNA-MOLEKYLE MOD TP53 |
| WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| EP3450559A1 (en) | 2003-03-07 | 2019-03-06 | Alnylam Pharmaceuticals, Inc. | Therapeutic compositions |
| US20040198640A1 (en) | 2003-04-02 | 2004-10-07 | Dharmacon, Inc. | Stabilized polynucleotides for use in RNA interference |
| US20050136437A1 (en) * | 2003-08-25 | 2005-06-23 | Nastech Pharmaceutical Company Inc. | Nanoparticles for delivery of nucleic acids and stable double-stranded RNA |
| WO2005062937A2 (en) | 2003-12-22 | 2005-07-14 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended sirna |
| US20060134787A1 (en) | 2004-12-22 | 2006-06-22 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended siRNA |
| WO2005079533A2 (en) | 2004-02-17 | 2005-09-01 | University Of Massachusetts | Methods and compositions for mediating gene silencing |
| AU2005222902B2 (en) | 2004-03-12 | 2010-06-10 | Alnylam Pharmaceuticals, Inc. | iRNA agents targeting VEGF |
| KR101147147B1 (ko) | 2004-04-01 | 2012-05-25 | 머크 샤프 앤드 돔 코포레이션 | Rna 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드 |
| JP2008512500A (ja) | 2004-09-10 | 2008-04-24 | ソマジェニックス インコーポレーティッド | ウィルス遺伝子発現を効率的に阻害する低分子干渉rnaおよびその使用方法 |
| US20060142228A1 (en) | 2004-12-23 | 2006-06-29 | Ambion, Inc. | Methods and compositions concerning siRNA's as mediators of RNA interference |
| TWI386225B (zh) | 2004-12-23 | 2013-02-21 | Alcon Inc | 用於治療眼睛病症的結締組織生長因子(CTGF)RNA干擾(RNAi)抑制技術 |
| KR20070118703A (ko) | 2005-04-08 | 2007-12-17 | 나스텍 파마수티컬 컴퍼니 인코포레이티드 | 호흡기 바이러스 감염을 치료하는 알엔에이 아이 |
| US8067572B2 (en) | 2005-05-25 | 2011-11-29 | The University Of York | Hybrid interfering RNA |
| US8048429B2 (en) | 2005-06-24 | 2011-11-01 | Intervet International B.V. | Inactivated chimeric flavivirus |
| FR2890859B1 (fr) | 2005-09-21 | 2012-12-21 | Oreal | Oligonucleotide d'arn double brin inhibant l'expression de la tyrosinase |
| US7825099B2 (en) | 2006-01-20 | 2010-11-02 | Quark Pharmaceuticals, Inc. | Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes |
| CA2638906A1 (en) | 2006-01-26 | 2007-08-16 | University Of Massachusetts | Rna interference agents for therapeutic use |
| WO2007089601A2 (en) | 2006-01-27 | 2007-08-09 | Biogen Idec Ma Inc. | Nogo receptor antagonists |
| US20070218495A1 (en) | 2006-03-16 | 2007-09-20 | Dharmacon, Inc. | Methods, libraries and computer program products for gene silencing with reduced off-target effects |
| US7700541B2 (en) | 2006-04-06 | 2010-04-20 | Nitto Denko Corporation | Biodegradable cationic polymers |
| GB0608838D0 (en) | 2006-05-04 | 2006-06-14 | Novartis Ag | Organic compounds |
| CA2679867A1 (en) | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting vegf family gene expression and uses thereof |
| US20100105134A1 (en) | 2007-03-02 | 2010-04-29 | Mdrna, Inc. | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| PT2164967E (pt) | 2007-05-31 | 2015-10-27 | Univ Iowa Res Found | Redução da toxicidade não dirigida do arn de interferência |
| US20090004668A1 (en) | 2007-06-22 | 2009-01-01 | The Board Of Trustees Of The Leland Stanford Junior University | Pre-miRNA loop-modulated target regulation |
| WO2009020344A2 (en) | 2007-08-06 | 2009-02-12 | Postech Acad Ind Found | Small interfering rnas (sirnas) controlling multiple target genes and method for preparing the same |
| ES2873350T3 (es) | 2007-08-27 | 2021-11-03 | 1Globe Health Inst Llc | Composiciones de ARN interferente asimétrico y usos de las mismas |
| DK2195428T3 (en) | 2007-09-19 | 2014-03-03 | Applied Biosystems Llc | SIRNA SEQUENCE-INDEPENDENT MODIFICATION FORMS TO REDUCE TARGET-FAILING PHENOTYPIC EFFECTS OF RNAI, AND STABILIZED FORMS THEREOF |
| CA2701845A1 (en) | 2007-10-03 | 2009-04-09 | Quark Pharmaceuticals, Inc. | Novel sirna structures |
| US8614311B2 (en) | 2007-12-12 | 2013-12-24 | Quark Pharmaceuticals, Inc. | RTP801L siRNA compounds and methods of use thereof |
| KR100949791B1 (ko) | 2007-12-18 | 2010-03-30 | 이동기 | 오프-타겟 효과를 최소화하고 RNAi 기구를 포화시키지않는 신규한 siRNA 구조 및 그 용도 |
| AU2009215795A1 (en) | 2008-02-21 | 2009-08-27 | University Of Kentucky Research Foundation | Ultra-small RNAs as toll-like receptor-3 antagonists |
| WO2010011346A1 (en) | 2008-07-24 | 2010-01-28 | Rxi Pharmaceuticals Corporation | Rnai constructs and uses therof |
| JP5294344B2 (ja) | 2008-09-08 | 2013-09-18 | 学校法人福岡大学 | 白血病治療用医薬組成物 |
| CN108165548B (zh) | 2008-09-22 | 2022-10-14 | 菲奥医药公司 | 减小大小的自递送RNAi化合物 |
| US20100227920A1 (en) | 2008-09-29 | 2010-09-09 | The Regents Of The University Of California | Aldehyde dehydrogenase inhibitors as novel depigmenting agents |
| US9745574B2 (en) | 2009-02-04 | 2017-08-29 | Rxi Pharmaceuticals Corporation | RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| JP2012517815A (ja) | 2009-02-18 | 2012-08-09 | サイレンス・セラピューティクス・アーゲー | Ang2の発現を阻害するための手段 |
| EP2408916A2 (en) * | 2009-03-19 | 2012-01-25 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF CONNECTIVE TISSUE GROWTH FACTOR (CTGF) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| KR101207561B1 (ko) | 2009-12-15 | 2012-12-04 | 주식회사 코리아나화장품 | 티로시나제의 발현을 저해하는 siRNA 올리고뉴클레오타이드 및 이를 함유하는 화장료 조성물 |
| WO2011084193A1 (en) | 2010-01-07 | 2011-07-14 | Quark Pharmaceuticals, Inc. | Oligonucleotide compounds comprising non-nucleotide overhangs |
| CN103200945B (zh) | 2010-03-24 | 2016-07-06 | 雷克西制药公司 | 眼部症候中的rna干扰 |
| KR102453078B1 (ko) * | 2010-03-24 | 2022-10-11 | 피오 파마슈티칼스 코프. | 진피 및 섬유증성 적응증에서의 rna 간섭 |
| WO2011140659A1 (en) | 2010-05-12 | 2011-11-17 | Centre Hospitalier De L'universite De Montreal | Screening assays based on mag and/or abhd6 for selecting insulin secretion promoting agents |
| EP2616543A1 (en) | 2010-09-15 | 2013-07-24 | Alnylam Pharmaceuticals, Inc. | MODIFIED iRNA AGENTS |
| CA2818662C (en) | 2010-10-22 | 2021-07-06 | Sungkyunkwan University Foundation For Corporate Collaboration | Nucleic acid molecule inducing rna interference, and uses thereof |
| EP2649181B1 (en) | 2010-12-06 | 2016-04-27 | Quark Pharmaceuticals, Inc. | Double stranded oligonucleotide compounds comprising positional modifications |
| CN102719432B (zh) | 2011-03-29 | 2013-10-23 | 南京大学 | 特异性抑制肿瘤凋亡抑制基因Bcl2的双链不对称小核酸干扰分子asiRNA及其应用 |
| KR101590586B1 (ko) | 2011-05-30 | 2016-02-01 | 성균관대학교산학협력단 | 표적 유전자 발현 억제 및 면역 반응을 동시에 유발하는 이중가닥의 긴 간섭 rna |
| US9611473B2 (en) | 2012-09-12 | 2017-04-04 | Quark Pharmaceuticals, Inc. | Double-stranded nucleic acid compounds |
| KR101867414B1 (ko) * | 2013-07-05 | 2018-06-14 | (주)바이오니아 | 호흡기 질환 연관 유전자 특이적 siRNA, 그러한 siRNA를 포함하는 이중나선 올리고 RNA 구조체 및 이를 포함하는 호흡기 질환 예방 또는 치료용 조성물 |
| US20160208247A1 (en) | 2013-07-31 | 2016-07-21 | Qbi Enterprises Ltd. | Methods of use of sphingolipid polyalkylamine oligonucleotide compounds |
| US9790506B2 (en) | 2013-10-02 | 2017-10-17 | The Regents Of The University Of California | Diagnostic and screening methods for atopic dermatitis |
| US8980273B1 (en) | 2014-07-15 | 2015-03-17 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
| KR102279110B1 (ko) * | 2014-04-30 | 2021-07-20 | 올릭스 주식회사 | LasiRNA를 유효성분으로 포함하는 피부 미백용 조성물 |
| US20170226507A1 (en) | 2014-05-05 | 2017-08-10 | The Brigham And Women's Hospital, Inc. | Coordinate control of pathogenic signaling by the mir-130/301 family in pulmonary hypertension and fibroproliferative diseases |
| WO2016161388A1 (en) | 2015-04-03 | 2016-10-06 | University Of Massachusetts | Fully stabilized asymmetric sirna |
| WO2017017523A1 (en) | 2015-07-27 | 2017-02-02 | Olix Pharmaceuticals, Inc. | Rna complexes that inhibit melanin production |
| EP3377630A4 (en) | 2015-11-16 | 2020-01-01 | Olix Pharmaceuticals, Inc. | Treatment of age-related macular degeneration using rna complexes that target myd88 or tlr3 |
| CN108779463B (zh) | 2016-02-02 | 2022-05-24 | 奥利克斯医药有限公司 | 使用靶向IL4Rα、TRPA1或F2RL1的RNA复合物治疗特应性皮炎和哮喘 |
| WO2017134526A1 (en) | 2016-02-02 | 2017-08-10 | Olix Pharmaceuticals, Inc. | Treatment of angiogenesis-associated diseases using rna complexes that target angpt2 and pdgfb |
| WO2017178883A2 (en) | 2016-04-11 | 2017-10-19 | Olix Pharmaceuticals, Inc. | Treatment of idiopathic pulmonary fibrosis using rna complexes that target connective tissue growth factor |
| KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| US11591600B2 (en) | 2017-02-10 | 2023-02-28 | OliX Pharmaceuticals. Inc. | Long double-stranded RNA for RNA interference |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013094071A (ja) | 2011-10-28 | 2013-05-20 | Mie Univ | ヒトTGFβ1を発現するトランスジェニックマウス |
| JP2015518721A (ja) | 2012-05-22 | 2015-07-06 | オリックス ファーマシューティカルズ インコーポレイテッドOlix Pharmaceuticals Inc. | 細胞内貫通能を持ってrna干渉を誘導する核酸分子およびその用途 |
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| US10301628B2 (en) | 2019-05-28 |
| JP2019513384A (ja) | 2019-05-30 |
| KR20180128423A (ko) | 2018-12-03 |
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| US10829761B2 (en) | 2020-11-10 |
| KR102339886B1 (ko) | 2021-12-17 |
| WO2017178883A3 (en) | 2018-08-23 |
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