CA3042015A1 - Messenger ribonucleic acids for enhancing immune responses and methods of use thereof - Google Patents
Messenger ribonucleic acids for enhancing immune responses and methods of use thereof Download PDFInfo
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- CA3042015A1 CA3042015A1 CA3042015A CA3042015A CA3042015A1 CA 3042015 A1 CA3042015 A1 CA 3042015A1 CA 3042015 A CA3042015 A CA 3042015A CA 3042015 A CA3042015 A CA 3042015A CA 3042015 A1 CA3042015 A1 CA 3042015A1
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- antigen
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| MA52645B1 (fr) | 2015-10-22 | 2022-06-30 | Modernatx Inc | Vaccins contre le virus respiratoire |
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| EP3576780A1 (en) | 2017-02-01 | 2019-12-11 | Modernatx, Inc. | Immunomodulatory therapeutic mrna compositions encoding activating oncogene mutation peptides |
| MA47515A (fr) | 2017-02-16 | 2019-12-25 | Modernatx Inc | Compositions immunogènes très puissantes |
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| US11168326B2 (en) | 2017-07-11 | 2021-11-09 | Actym Therapeutics, Inc. | Engineered immunostimulatory bacterial strains and uses thereof |
| WO2019035901A1 (en) * | 2017-08-15 | 2019-02-21 | University Of Miami | COMPOSITIONS AND METHODS FOR STING PROTEIN MODULATION |
| US11866696B2 (en) | 2017-08-18 | 2024-01-09 | Modernatx, Inc. | Analytical HPLC methods |
| US11912982B2 (en) | 2017-08-18 | 2024-02-27 | Modernatx, Inc. | Methods for HPLC analysis |
| WO2019036682A1 (en) | 2017-08-18 | 2019-02-21 | Modernatx, Inc. | RNA VARIANTS POLYMERASE |
| MX2020002348A (es) | 2017-08-31 | 2020-10-08 | Modernatx Inc | Métodos de elaboración de nanopartículas lipídicas. |
| GB201714430D0 (en) | 2017-09-07 | 2017-10-25 | Micol Romain | Compositions and processes for targeted delivery and expression and modulation of therapeutic components in tissue |
| MA50253A (fr) | 2017-09-14 | 2020-07-22 | Modernatx Inc | Vaccins à arn contre le virus zika |
| JP7761994B2 (ja) | 2017-12-21 | 2025-10-29 | ベースクリック ゲーエムベーハー | クリック修飾ｍＲＮＡ |
| JP7355742B2 (ja) * | 2018-01-18 | 2023-10-03 | フレッド ハッチンソン キャンサー センター | 細胞活性状態を調節することにより免疫細胞の炎症状態をインビボで変更すること |
| US11911453B2 (en) | 2018-01-29 | 2024-02-27 | Modernatx, Inc. | RSV RNA vaccines |
| WO2019152557A1 (en) * | 2018-01-30 | 2019-08-08 | Modernatx, Inc. | Compositions and methods for delivery of agents to immune cells |
| WO2019191070A1 (en) * | 2018-03-26 | 2019-10-03 | University Of Miami | Recombinant viral vector and uses thereof |
| WO2019200171A1 (en) * | 2018-04-11 | 2019-10-17 | Modernatx, Inc. | Messenger rna comprising functional rna elements |
| CN112384205B (zh) | 2018-05-30 | 2024-05-03 | 川斯勒佰尔公司 | 信使rna疫苗及其用途 |
| BR112020024292A2 (pt) | 2018-06-06 | 2021-03-02 | Massachusetts Institute Of Technology | rna circular para translação em células eucarióticas |
| CN118147029A (zh) | 2018-07-11 | 2024-06-07 | 阿克蒂姆治疗有限公司 | 工程化的免疫刺激性细菌菌株及其用途 |
| US20210308214A1 (en) * | 2018-08-03 | 2021-10-07 | Board Of Trustees Of Michigan State University | Compositions of sting variants, combinations thereof, and methods for inducing and enhancing an immune response against infections, diseases, and disorders |
| WO2020041691A1 (en) * | 2018-08-24 | 2020-02-27 | City Of Hope | Oligonucleotide inhibitors of nuclear factor kappa-light-chain-enhancer |
| WO2020047161A2 (en) | 2018-08-28 | 2020-03-05 | Actym Therapeutics, Inc. | Engineered immunostimulatory bacterial strains and uses thereof |
| EP4509118A3 (en) | 2018-09-19 | 2025-05-14 | ModernaTX, Inc. | High-purity peg lipids and uses thereof |
| CA3113025A1 (en) | 2018-09-19 | 2020-03-26 | Modernatx, Inc. | Peg lipids and uses thereof |
| US12090235B2 (en) | 2018-09-20 | 2024-09-17 | Modernatx, Inc. | Preparation of lipid nanoparticles and methods of administration thereof |
| CA3123595A1 (en) * | 2018-12-21 | 2020-06-25 | Tiba Biotech Llc | Nanoparticle compositions for efficient nucleic acid delivery and methods of making and using the same |
| CN109762895A (zh) * | 2019-01-07 | 2019-05-17 | 中国医学科学院北京协和医院 | miR-146a在制备诊断激素性股骨头坏死产品中的应用 |
| EP3683229A1 (en) * | 2019-01-21 | 2020-07-22 | Charité - Universitätsmedizin Berlin | Specific t cell receptors against epitopes of mutant myd88l265p protein for adoptive t cell therapy |
| US11351242B1 (en) | 2019-02-12 | 2022-06-07 | Modernatx, Inc. | HMPV/hPIV3 mRNA vaccine composition |
| US11851694B1 (en) | 2019-02-20 | 2023-12-26 | Modernatx, Inc. | High fidelity in vitro transcription |
| JP2022521094A (ja) | 2019-02-20 | 2022-04-05 | モデルナティエックス インコーポレイテッド | 共転写キャッピング用ｒｎａポリメラーゼバリアント |
| CA3176660A1 (en) | 2019-02-27 | 2020-09-03 | Actym Therapeutics, Inc. | Immunostimulatory bacteria engineered to colonize tumors, tumor-resident immune cells, and the tumor microenvironment |
| US12024709B2 (en) | 2019-02-27 | 2024-07-02 | Actym Therapeutics, Inc. | Immunostimulatory bacteria engineered to colonize tumors, tumor-resident immune cells, and the tumor microenvironment |
| EP3938507A4 (en) | 2019-03-11 | 2023-02-22 | ModernaTX, Inc. | PROCEDURE FOR IN VITRO FED BATCH TRANSCRIPTION |
| MA55321A (fr) | 2019-03-15 | 2022-01-19 | Modernatx Inc | Vaccins à base d'arn contre le vih |
| KR20220019660A (ko) | 2019-04-02 | 2022-02-17 | 이뮨튠 비.브이. | 면역-자극성 조성물 및 이의 용도 |
| IL288284B2 (en) | 2019-05-22 | 2024-06-01 | Massachusetts Inst Technology | Circular rna compositions and methods |
| AU2020299636A1 (en) * | 2019-07-03 | 2022-02-24 | The Walter And Eliza Hall Institute Of Medical Research | Compositions and methods of use |
| US11666624B2 (en) | 2019-09-24 | 2023-06-06 | Auburn University | Phage-peptide constructs for stimulating an immune response against CD47 |
| JP7650873B2 (ja) | 2019-10-09 | 2025-03-25 | トランスレイト バイオ， インコーポレイテッド | メッセンジャーｒｎａの組成物、方法および使用 |
| US20220373548A1 (en) * | 2019-10-24 | 2022-11-24 | Arizona Board Of Regents On Behalf Of Arizona State University | Novel antibodies for detecting epstein barr virus-positive gastric cancer |
| EP4058578A2 (en) | 2019-11-12 | 2022-09-21 | Actym Therapeutics, Inc. | Immunostimulatory bacteria delivery platforms and their use for delivery of therapeutic products |
| CN114641315A (zh) * | 2019-11-14 | 2022-06-17 | 博阿济吉大学 | 癌症免疫疗法中的asc斑点 |
| AU2020382378A1 (en) * | 2019-11-15 | 2022-06-30 | Daiichi Sankyo Company, Limited | Nucleic acid lipid particle vaccine encapsulating HPV mRNA |
| US20210154281A1 (en) * | 2019-11-26 | 2021-05-27 | Massachusetts Institute Of Technology | Cell-based cancer vaccines and cancer therapies |
| JP2023504568A (ja) | 2019-12-04 | 2023-02-03 | オルナ セラピューティクス インコーポレイテッド | 環状ｒｎａ組成物及び方法 |
| AU2020405068A1 (en) | 2019-12-18 | 2022-07-07 | Stinginn Llc | Substituted 1,2, 4-triazoles and methods of use |
| CN110974954B (zh) * | 2019-12-24 | 2021-03-16 | 珠海丽凡达生物技术有限公司 | 一种用于增强核酸疫苗免疫效果的脂质纳米颗粒及其制备方法 |
| IL295724A (en) * | 2020-02-21 | 2022-10-01 | Combined Therapeutics Inc | Compositions and methods for organ-protective expression and modulation of coding ribonucleic acids |
| WO2021168266A1 (en) * | 2020-02-21 | 2021-08-26 | Temple University - Of The Commonwealth System Of Higher Education | Eradication of merkel cell polyomavirus |
| WO2021197589A1 (en) * | 2020-03-31 | 2021-10-07 | BioNTech SE | Treatment involving non-immunogenic rna for antigen vaccination |
| JP2023522249A (ja) | 2020-04-22 | 2023-05-29 | ビオンテック・ソシエタス・エウロパエア | コロナウイルスワクチン |
| EP4139044A4 (en) | 2020-04-22 | 2025-01-01 | Nutcracker Therapeutics, Inc. | MRNA PROCESSING NANOPARTICLES |
| US11897888B1 (en) | 2020-04-30 | 2024-02-13 | Stinginn Llc | Small molecular inhibitors of sting signaling compositions and methods of use |
| MX2023000197A (es) * | 2020-07-07 | 2023-02-22 | BioNTech SE | Arn terapeutico para el cancer positivo para vph. |
| WO2022035621A1 (en) * | 2020-07-31 | 2022-02-17 | Combined Therapeutics, Inc. | Compositions and methods for improved vaccination |
| CA3187258A1 (en) * | 2020-08-06 | 2022-02-10 | Karin Jooss | Multiepitope vaccine cassettes |
| EP4196139A2 (en) | 2020-08-12 | 2023-06-21 | Actym Therapeutics, Inc. | Immunostimulatory bacteria-based vaccines, therapeutics, and rna delivery platforms |
| US11406703B2 (en) | 2020-08-25 | 2022-08-09 | Modernatx, Inc. | Human cytomegalovirus vaccine |
| JP2023546133A (ja) * | 2020-10-14 | 2023-11-01 | アールエヌエーイミューン、インコーポレイテッド | 汎ＲＡＳ ｍＲＮＡがんワクチン |
| GB202017119D0 (en) * | 2020-10-28 | 2020-12-09 | Oxford Vacmedix Uk Ltd | Polypeptides for cancer treatment |
| US11058751B1 (en) | 2020-11-20 | 2021-07-13 | Think Therapeutics, Inc. | Compositions for optimized RAS peptide vaccines |
| JP2023551204A (ja) * | 2020-11-20 | 2023-12-07 | シンク・セラピューティクス・インコーポレイテッド | 最適化ペプチドワクチンの組成物および方法 |
| CN116710115A (zh) | 2020-11-20 | 2023-09-05 | 思维疗法股份有限公司 | 用于优化的肽疫苗的组合物和方法 |
| GB202020063D0 (en) * | 2020-12-17 | 2021-02-03 | Imperial College Innovations Ltd | RNA construct |
| WO2022140588A1 (en) * | 2020-12-23 | 2022-06-30 | Kernal Biologics, Inc. | Constitutively active payloads |
| US12329811B2 (en) | 2021-01-11 | 2025-06-17 | Modernatx, Inc. | Seasonal RNA influenza virus vaccines |
| JP2024504640A (ja) * | 2021-01-15 | 2024-02-01 | ユニバーシティ オブ ロチェスター | Ｓｔａｐｈｙｌｏｃｏｃｃｕｓ ａｕｒｅｕｓ抗原系核酸ワクチン |
| US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
| CA3214085A1 (en) * | 2021-03-31 | 2022-10-06 | Darby Rye Schmidt | Thanotransmission polypeptides and their use in treating cancer |
| CN113509542A (zh) * | 2021-04-20 | 2021-10-19 | 嘉晨西海(杭州)生物技术有限公司 | 一种基于mRNA的表达白介素12针对肿瘤的药物及其制备方法 |
| US20220363937A1 (en) | 2021-05-14 | 2022-11-17 | Armstrong World Industries, Inc. | Stabilization of antimicrobial coatings |
| EP4342993A4 (en) * | 2021-05-19 | 2025-05-28 | Daiichi Sankyo Company, Limited | Hpv infectious disease vaccine |
| WO2022256637A2 (en) * | 2021-06-03 | 2022-12-08 | David Weiner | Synthetic dna vaccine immunogenic improvements |
| JP2024525578A (ja) * | 2021-07-06 | 2024-07-12 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | Ｃ型肝炎ウイルスのためのＰ７含有ヌクレオシド－改変されたｍＲＮＡ－脂質ナノ粒子系統ワクチン |
| CN113616793B (zh) * | 2021-08-20 | 2023-07-04 | 南方海洋科学与工程广东省实验室(湛江) | Traf6抑制剂在作为和/或制备铁死亡诱导剂中的应用 |
| WO2023076131A2 (en) * | 2021-10-25 | 2023-05-04 | The Regents Of The University Of California | Kaposi sarcoma associated herpesvirus gene function |
| JP2024542173A (ja) | 2021-11-09 | 2024-11-13 | アクティム・セラピューティクス・インコーポレイテッド | マクロファージを処置に適している表現型に変換するための免疫刺激細菌および処置のための対象の同定のためのコンパニオン診断法 |
| CN113952359A (zh) * | 2021-11-19 | 2022-01-21 | 大连理工大学盘锦产业技术研究院 | 顺铂与Tri-1的联合抗肺癌药物组合物及其应用 |
| US12186387B2 (en) | 2021-11-29 | 2025-01-07 | BioNTech SE | Coronavirus vaccine |
| CN116376942A (zh) * | 2021-12-31 | 2023-07-04 | 广州国家实验室 | mRNA疫苗 |
| WO2023135305A1 (en) * | 2022-01-17 | 2023-07-20 | Sanofi | Lipidic compounds, and uses thereof |
| JP2025507571A (ja) * | 2022-02-18 | 2025-03-21 | モデルナティエックス インコーポレイテッド | チェックポイントがんワクチンをコードするｍＲＮＡ及びその使用 |
| US12297285B2 (en) | 2022-06-24 | 2025-05-13 | Orna Therapeutics, Inc. | Circular RNA encoding chimeric antigen receptors targeting BCMA |
| US11878055B1 (en) | 2022-06-26 | 2024-01-23 | BioNTech SE | Coronavirus vaccine |
| CN115089588A (zh) * | 2022-08-22 | 2022-09-23 | 云南大学 | 达沙布韦作为e3连接酶新型配体构建protac的应用 |
| WO2025087250A1 (en) * | 2023-10-23 | 2025-05-01 | Abogen Biosciences (Shanghai) Co., Ltd. | Therapeutic mrna cancer vaccine targeting hpv-associated cancers |
| WO2025087266A1 (en) * | 2023-10-23 | 2025-05-01 | Abogen Biosciences (Shanghai) Co., Ltd. | Immunomodulatory mrna cassettes, and uses thereof |
| CN119662655A (zh) * | 2023-12-04 | 2025-03-21 | 武汉厚先生物医药有限公司 | Rna分子及其组合物在肿瘤免疫治疗中的应用 |
| WO2025153053A1 (en) * | 2024-01-17 | 2025-07-24 | Abogen Biosciences (Shanghai) Co., Ltd. | Composition and methods for inducing antigen specific immunity against kras mutant cells |
| CN118839285B (zh) * | 2024-08-05 | 2025-03-18 | 洛阳莱普生信息科技有限公司 | 基于智能耳标的畜牧生物资产监管方法及系统 |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| AU3559695A (en) | 1994-09-30 | 1996-04-26 | Inex Pharmaceuticals Corp. | Glycosylated protein-liposome conjugates and methods for their preparation |
| EP2390328A1 (en) | 2001-09-28 | 2011-11-30 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | MicroRNA molecules |
| US20050222064A1 (en) | 2002-02-20 | 2005-10-06 | Sirna Therapeutics, Inc. | Polycationic compositions for cellular delivery of polynucleotides |
| EP1648914A4 (en) | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
| DE102004035227A1 (de) * | 2004-07-21 | 2006-02-16 | Curevac Gmbh | mRNA-Gemisch zur Vakzinierung gegen Tumorerkrankungen |
| US7404969B2 (en) | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
| ES2524018T3 (es) | 2006-01-05 | 2014-12-03 | The Ohio State University Research Foundation | Anomalías de la expresión de microARN en tumores pancreáticos endocrinos y acinares |
| EP2487260B1 (en) | 2006-01-05 | 2015-07-08 | The Ohio State University Research Foundation | Microrna-based methods and compositions for the diagnosis and treatment of solid cancers |
| EP2522747A1 (en) | 2006-03-02 | 2012-11-14 | The Ohio State University | MicroRNA expression profile associated with pancreatic cancer |
| AU2007299828C1 (en) | 2006-09-19 | 2014-07-17 | Interpace Diagnostics, Llc | MicroRNAs differentially expressed in pancreatic diseases and uses thereof |
| JP5501766B2 (ja) | 2006-11-01 | 2014-05-28 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | 肝細胞癌における生存および転移を予測するためのマイクロｒｎａ発現サイン |
| CN101622350A (zh) | 2006-12-08 | 2010-01-06 | 奥斯瑞根公司 | 作为干预治疗靶标的miR-126调控基因和通路 |
| WO2008147974A1 (en) | 2007-05-23 | 2008-12-04 | University Of South Florida | Micro-rnas modulating immunity and inflammation |
| WO2008154098A2 (en) | 2007-06-07 | 2008-12-18 | Wisconsin Alumni Research Foundation | Reagents and methods for mirna expression analysis and identification of cancer biomarkers |
| HUE029164T2 (hu) * | 2007-09-14 | 2017-02-28 | Univ Brussel Vrije | Humán antigén-prezentáló sejtek T-sejteket stimuláló képességének fokozása és azok alkalmazása vakcinázásra |
| US20100323357A1 (en) | 2007-11-30 | 2010-12-23 | The Ohio State University Research Foundation | MicroRNA Expression Profiling and Targeting in Peripheral Blood in Lung Cancer |
| US20090263803A1 (en) | 2008-02-08 | 2009-10-22 | Sylvie Beaudenon | Mirnas differentially expressed in lymph nodes from cancer patients |
| US20110052502A1 (en) | 2008-02-28 | 2011-03-03 | The Ohio State University Research Foundation | MicroRNA Signatures Associated with Human Chronic Lymphocytic Leukemia (CCL) and Uses Thereof |
| EP2112235A1 (en) | 2008-04-24 | 2009-10-28 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Compositions and methods for microRNA expression profiling of nasopharyngeal carcinoma |
| WO2009149539A1 (en) * | 2008-06-10 | 2009-12-17 | Université de Montréal | Enhancing antigen-specific cd8+ t cell response using irf-7 mrna |
| WO2010018563A2 (en) | 2008-08-12 | 2010-02-18 | Rosetta Genomics Ltd. | Compositions and methods for the prognosis of lymphoma |
| WO2010037408A1 (en) * | 2008-09-30 | 2010-04-08 | Curevac Gmbh | Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof |
| WO2010055487A2 (en) | 2008-11-13 | 2010-05-20 | Koninklijke Philips Electronics N.V. | Compositions and methods for micro-rna expession profiling of colorectal cancer |
| US20120053224A1 (en) | 2008-12-10 | 2012-03-01 | Universitat Regensburg | Compositions and methods for micro-rna expression profiling of cancer stem cells |
| EP2427574A2 (en) | 2009-05-08 | 2012-03-14 | The Ohio State University Research Foundation | Microrna expression profiling and targeting in chronic obstructive pulmonary disease (copd) lung tissue and methods of use thereof |
| KR20230098713A (ko) | 2009-06-10 | 2023-07-04 | 알닐람 파마슈티칼스 인코포레이티드 | 향상된 지질 조성물 |
| WO2011076142A1 (en) | 2009-12-24 | 2011-06-30 | Fudan University | Compositions and methods for microrna expession profiling in plasma of colorectal cancer |
| WO2011076143A1 (en) | 2009-12-24 | 2011-06-30 | Fudan University | Compositions and methods for microrna expression profiling of lung cancer |
| EP2341145A1 (en) | 2009-12-30 | 2011-07-06 | febit holding GmbH | miRNA fingerprint in the diagnosis of diseases |
| WO2011094683A2 (en) | 2010-01-29 | 2011-08-04 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Method of identifying myelodysplastic syndromes |
| EP2354246A1 (en) | 2010-02-05 | 2011-08-10 | febit holding GmbH | miRNA in the diagnosis of ovarian cancer |
| WO2011113030A2 (en) | 2010-03-11 | 2011-09-15 | H.Lee Moffitt Cancer Center & Research Institute | Human cancer micro-rna expression profiles predictive of chemo-response |
| WO2011157294A1 (en) | 2010-06-16 | 2011-12-22 | Universita' Degli Studi Di Padova | Compositions for use in treating or preventing cancer, breast cancer, lung cancer, ovarian cancer, metastasis, heart failure, cardiac remodelling, dilated cardiomyopathy, autoimmune diseases, or diseases or disorders related thereto |
| EP3431485B2 (en) | 2010-10-01 | 2024-09-04 | ModernaTX, Inc. | Engineered nucleic acids and methods of use thereof |
| PL2633034T3 (pl) * | 2010-10-26 | 2018-05-30 | Friedrich-Alexander-Universität Erlangen-Nürnberg | KOMÓRKI DENDRYTYCZNE Z PODDANYM MANIPULACJI SZLAKIEM SYGNAŁOWYM NFkB |
| AU2012207606B2 (en) | 2011-01-11 | 2017-02-23 | Alnylam Pharmaceuticals, Inc. | Pegylated lipids and their use for drug delivery |
| US9085631B2 (en) | 2011-04-08 | 2015-07-21 | Nov Vac APS | Proteins and nucleic acids useful in vaccines targeting Staphylococcus aureus |
| US20140113978A1 (en) | 2011-05-01 | 2014-04-24 | University Of Rochester | Multifocal hepatocellular carcinoma microrna expression patterns and uses thereof |
| US20130042333A1 (en) | 2011-05-06 | 2013-02-14 | Jean-Gabriel JUDDE | Markers for cancer prognosis and therapy and methods of use |
| US8691750B2 (en) | 2011-05-17 | 2014-04-08 | Axolabs Gmbh | Lipids and compositions for intracellular delivery of biologically active compounds |
| CA3198966A1 (en) | 2011-06-08 | 2012-12-13 | Translate Bio, Inc. | Cleavable lipids |
| ES2610245T3 (es) | 2011-07-15 | 2017-04-26 | Leo Pharma A/S | Perfilado de microARN para el diagnóstico en linfoma cutáneo de células T (CTCL) |
| WO2013033640A1 (en) | 2011-09-01 | 2013-03-07 | Allegro Diagnostics Corp. | Methods and compositions for detecting cancer based on mirna expression profiles |
| WO2013066678A1 (en) | 2011-10-26 | 2013-05-10 | Georgetown University | Microrna expression profiling of thyroid cancer |
| CA2856742A1 (en) | 2011-12-07 | 2013-06-13 | Alnylam Pharmaceuticals, Inc. | Biodegradable lipids for the delivery of active agents |
| WO2013103659A1 (en) | 2012-01-04 | 2013-07-11 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Stabilizing rna by incorporating chain-terminating nucleosides at the 3'-terminus |
| WO2013116126A1 (en) | 2012-02-01 | 2013-08-08 | Merck Sharp & Dohme Corp. | Novel low molecular weight, biodegradable cationic lipids for oligonucleotide delivery |
| WO2013134225A1 (en) | 2012-03-05 | 2013-09-12 | University Of Maryland, Baltimore | Multivalent vaccine protection from staphylococcus aureus infection |
| DE18200782T1 (de) * | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
| WO2014039961A1 (en) * | 2012-09-07 | 2014-03-13 | University Of Miami | Fusion proteins for promoting an immune response, nucleic acids encoding same, and methods of making and use thereof |
| WO2014093924A1 (en) | 2012-12-13 | 2014-06-19 | Moderna Therapeutics, Inc. | Modified nucleic acid molecules and uses thereof |
| CA2892529C (en) | 2012-11-26 | 2023-04-25 | Moderna Therapeutics, Inc. | Terminally modified rna |
| HK1217215A1 (zh) | 2013-01-17 | 2016-12-30 | Modernatx, Inc. | 用於改变细胞表型的信号传感器多核苷酸 |
| US20160022840A1 (en) | 2013-03-09 | 2016-01-28 | Moderna Therapeutics, Inc. | Heterologous untranslated regions for mrna |
| US20160024181A1 (en) | 2013-03-13 | 2016-01-28 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
| WO2015082536A1 (en) | 2013-12-03 | 2015-06-11 | Evaxion Biotech Aps | Proteins and nucleic acids useful in vaccines targeting staphylococcus aureus |
| US10821175B2 (en) | 2014-02-25 | 2020-11-03 | Merck Sharp & Dohme Corp. | Lipid nanoparticle vaccine adjuvants and antigen delivery systems |
| DK4023249T3 (da) * | 2014-04-23 | 2025-01-13 | Modernatx Inc | Nukleinsyrevacciner |
| CN106414493A (zh) | 2014-05-06 | 2017-02-15 | 塔格瓦克斯公司 | 包含突变的ras肽和化疗剂的肽疫苗 |
| HRP20221536T1 (hr) | 2014-06-25 | 2023-02-17 | Acuitas Therapeutics Inc. | Novi lipidi i formulacije lipidnih nanočestica za isporuku nukleinskih kiselina |
| AU2016251687C1 (en) * | 2015-04-22 | 2023-07-27 | CureVac SE | RNA containing composition for treatment of tumor diseases |
| EP3289083A4 (en) * | 2015-04-27 | 2018-12-19 | The Trustees Of The University Of Pennsylvania | Nucleoside-modified rna for inducing an adaptive immune response |
| US12150980B2 (en) * | 2015-07-30 | 2024-11-26 | Modernatx, Inc. | Concatemeric peptide epitope RNAs |
| PT3368507T (pt) | 2015-10-28 | 2023-02-07 | Acuitas Therapeutics Inc | Novos lípidos e formulações de nanopartículas lipídicas para distribuição de ácidos nucleicos |
-
2017
- 2017-10-26 RU RU2019116006A patent/RU2765874C2/ru active
- 2017-10-26 CA CA3042015A patent/CA3042015A1/en active Pending
- 2017-10-26 KR KR1020197014935A patent/KR20190086681A/ko not_active Withdrawn
- 2017-10-26 CN CN201780080846.2A patent/CN110402145A/zh active Pending
- 2017-10-26 JP JP2019522512A patent/JP2019532657A/ja active Pending
- 2017-10-26 EP EP17808634.4A patent/EP3532070A1/en not_active Withdrawn
- 2017-10-26 BR BR112019008369A patent/BR112019008369A2/pt not_active Application Discontinuation
- 2017-10-26 AU AU2017347837A patent/AU2017347837A1/en not_active Abandoned
- 2017-10-26 SG SG11201903674YA patent/SG11201903674YA/en unknown
- 2017-10-26 MX MX2019004810A patent/MX2019004810A/es unknown
- 2017-10-26 WO PCT/US2017/058585 patent/WO2018081459A1/en not_active Ceased
-
2018
- 2018-06-01 US US15/995,519 patent/US20180311343A1/en not_active Abandoned
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2019
- 2019-04-24 IL IL266222A patent/IL266222A/en unknown
- 2019-11-01 US US16/671,921 patent/US20200261572A1/en not_active Abandoned
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2022
- 2022-09-09 JP JP2022143786A patent/JP2022184924A/ja active Pending
-
2024
- 2024-06-27 US US18/756,934 patent/US20250170235A1/en not_active Abandoned
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| Publication number | Publication date |
|---|---|
| MX2019004810A (es) | 2019-10-15 |
| US20200261572A1 (en) | 2020-08-20 |
| RU2765874C2 (ru) | 2022-02-04 |
| RU2019116006A3 (enExample) | 2021-07-30 |
| EP3532070A1 (en) | 2019-09-04 |
| KR20190086681A (ko) | 2019-07-23 |
| WO2018081459A9 (en) | 2018-11-22 |
| IL266222A (en) | 2019-06-30 |
| AU2017347837A1 (en) | 2019-06-06 |
| BR112019008369A2 (pt) | 2019-10-01 |
| US20250170235A1 (en) | 2025-05-29 |
| JP2022184924A (ja) | 2022-12-13 |
| JP2019532657A (ja) | 2019-11-14 |
| SG11201903674YA (en) | 2019-05-30 |
| CN110402145A (zh) | 2019-11-01 |
| RU2019116006A (ru) | 2020-11-27 |
| WO2018081459A1 (en) | 2018-05-03 |
| US20180311343A1 (en) | 2018-11-01 |
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