ES2941411T3 - Polinucleótidos que codifican interleucina-12 (IL12) y usos de los mismos - Google Patents
Polinucleótidos que codifican interleucina-12 (IL12) y usos de los mismos Download PDFInfo
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- ES2941411T3 ES2941411T3 ES17726458T ES17726458T ES2941411T3 ES 2941411 T3 ES2941411 T3 ES 2941411T3 ES 17726458 T ES17726458 T ES 17726458T ES 17726458 T ES17726458 T ES 17726458T ES 2941411 T3 ES2941411 T3 ES 2941411T3
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| EP3052521A1 (en) | 2013-10-03 | 2016-08-10 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
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| PL4023249T3 (pl) | 2014-04-23 | 2025-03-10 | Modernatx, Inc. | Szczepionki z kwasem nukleinowym |
| US11377651B2 (en) | 2016-10-19 | 2022-07-05 | Flodesign Sonics, Inc. | Cell therapy processes utilizing acoustophoresis |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
| MA42543A (fr) | 2015-07-30 | 2018-06-06 | Modernatx Inc | Arn épitope peptidiques concatémériques |
| JP6948313B6 (ja) | 2015-09-17 | 2022-01-14 | モデルナティエックス インコーポレイテッド | 治療剤の細胞内送達のための化合物および組成物 |
| EP4011451A1 (en) | 2015-10-22 | 2022-06-15 | ModernaTX, Inc. | Metapneumovirus mrna vaccines |
| LT3394030T (lt) | 2015-12-22 | 2022-04-11 | Modernatx, Inc. | Junginiai ir kompozicijos terapinei medžiagai teikti intraceliuliniu būdu |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| WO2017201342A1 (en) | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | Polynucleotides encoding jagged1 for the treatment of alagille syndrome |
| SI3458083T1 (sl) | 2016-05-18 | 2023-03-31 | Modernatx, Inc. | Polinukleotidi, ki kodirajo interlevkin-12 (IL12) in njihova uporaba |
| CA3036831A1 (en) | 2016-09-14 | 2018-03-22 | Modernatx, Inc. | High purity rna compositions and methods for preparation thereof |
| US11583504B2 (en) | 2016-11-08 | 2023-02-21 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
| MA46766A (fr) | 2016-11-11 | 2019-09-18 | Modernatx Inc | Vaccin antigrippal |
| WO2018107088A2 (en) * | 2016-12-08 | 2018-06-14 | Modernatx, Inc. | Respiratory virus nucleic acid vaccines |
| JP7724601B2 (ja) | 2017-02-03 | 2025-08-18 | ユニバーシティ オブ ピッツバーグ －オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション | 腫瘍溶解性ウイルス療法 |
| WO2018170322A1 (en) | 2017-03-15 | 2018-09-20 | Modernatx, Inc. | Crystal forms of amino lipids |
| EP4186888B1 (en) | 2017-03-15 | 2025-11-26 | ModernaTX, Inc. | Compound and compositions for intracellular delivery of therapeutic agents |
| CA3055653A1 (en) | 2017-03-15 | 2018-09-20 | Modernatx, Inc. | Lipid nanoparticle formulation |
| US11905525B2 (en) | 2017-04-05 | 2024-02-20 | Modernatx, Inc. | Reduction of elimination of immune responses to non-intravenous, e.g., subcutaneously administered therapeutic proteins |
| JP7285220B2 (ja) | 2017-05-18 | 2023-06-01 | モデルナティエックス インコーポレイテッド | 連結したインターロイキン－１２（ｉｌ１２）ポリペプチドをコードするポリヌクレオチドを含む脂質ナノ粒子 |
| WO2018232120A1 (en) | 2017-06-14 | 2018-12-20 | Modernatx, Inc. | Compounds and compositions for intracellular delivery of agents |
| MA49421A (fr) | 2017-06-15 | 2020-04-22 | Modernatx Inc | Formulations d'arn |
| EP3668979A4 (en) | 2017-08-18 | 2021-06-02 | Modernatx, Inc. | METHOD OF HPLC ANALYSIS |
| WO2019036682A1 (en) | 2017-08-18 | 2019-02-21 | Modernatx, Inc. | RNA VARIANTS POLYMERASE |
| MA49914A (fr) | 2017-08-18 | 2021-04-21 | Modernatx Inc | Procédés analytiques par hplc |
| KR102439221B1 (ko) | 2017-12-14 | 2022-09-01 | 프로디자인 소닉스, 인크. | 음향 트랜스듀서 구동기 및 제어기 |
| CN111712468A (zh) | 2017-12-22 | 2020-09-25 | 北卡罗莱纳州立大学 | 聚合物荧光团、包含其的组合物及制备和使用其的方法 |
| EP3746090A4 (en) | 2018-01-29 | 2021-11-17 | ModernaTX, Inc. | RSV RNA Vaccines |
| CA3101969A1 (en) * | 2018-05-31 | 2019-12-05 | Beth Israel Deaconess Medical Center | Rna-aided immunotherapeutics |
| CN112399860B (zh) | 2018-06-06 | 2024-08-16 | 麻省理工学院 | 用于在真核细胞中翻译的环状rna |
| WO2020051223A1 (en) | 2018-09-04 | 2020-03-12 | The Board Of Regents Of The University Of Texas System | Compositions and methods for organ specific delivery of nucleic acids |
| US12357580B2 (en) | 2018-06-19 | 2025-07-15 | The Board Of Regents Of The University Of Texas System | Lipid nanoparticle compositions for delivery of mRNA and long nucleic acids |
| WO2020037102A1 (en) | 2018-08-15 | 2020-02-20 | University Of Florida Research Foundation, Inc. | Methods of sensitizing tumors to treatment with immune checkpoint inhibitors |
| EP3846857A4 (en) | 2018-09-04 | 2022-10-12 | The Board Of Regents Of The University Of Texas System | COMPOSITIONS AND METHODS FOR ORGAN-SPECIFIC DELIVERY OF NUCLEIC ACIDS |
| JP7556848B2 (ja) * | 2018-09-14 | 2024-09-26 | モデルナティエックス インコーポレイテッド | ｍＲＮＡ治療薬を使用したがんを治療するための方法及び組成物 |
| WO2020061295A1 (en) | 2018-09-19 | 2020-03-26 | Modernatx, Inc. | High-purity peg lipids and uses thereof |
| WO2020061367A1 (en) | 2018-09-19 | 2020-03-26 | Modernatx, Inc. | Compounds and compositions for intracellular delivery of therapeutic agents |
| CA3113025A1 (en) | 2018-09-19 | 2020-03-26 | Modernatx, Inc. | Peg lipids and uses thereof |
| KR102524247B1 (ko) * | 2018-12-21 | 2023-04-21 | 가톨릭대학교 산학협력단 | p40-EBI3의 복합체 및 이의 용도 |
| TWI852977B (zh) | 2019-01-10 | 2024-08-21 | 美商健生生物科技公司 | 前列腺新抗原及其用途 |
| WO2020146700A1 (en) * | 2019-01-10 | 2020-07-16 | Massachusetts Institute Of Technology | Lipid nanoparticles |
| CN113874502A (zh) | 2019-03-11 | 2021-12-31 | 摩登纳特斯有限公司 | 补料分批体外转录方法 |
| KR20210151822A (ko) * | 2019-03-14 | 2021-12-14 | 엔진 인코포레이티드 | 키토산-핵산 나노입자의 가역성 코팅 및 이의 사용 방법 |
| US12070495B2 (en) | 2019-03-15 | 2024-08-27 | Modernatx, Inc. | HIV RNA vaccines |
| CN109932511B (zh) * | 2019-03-22 | 2020-02-04 | 南昌大学第二附属医院 | 用于肝癌筛查的尿液外泌体磷脂标志物及其试剂盒 |
| WO2020209934A1 (en) * | 2019-04-11 | 2020-10-15 | Massachusetts Institute Of Technology | Novel chimeric antigen receptors and libraries |
| BR112021023411A2 (pt) | 2019-05-22 | 2022-02-01 | Massachusetts Inst Technology | Composições e métodos de rna circular |
| EP4009955A1 (en) * | 2019-08-07 | 2022-06-15 | ModernaTX, Inc. | Compositions and methods for enhanced delivery of agents |
| CA3155015A1 (en) | 2019-09-19 | 2021-03-25 | Modernatx, Inc. | Carbonate containing lipid compounds and compositions for intracellular delivery of therapeutic agents |
| AU2020350759A1 (en) | 2019-09-19 | 2022-03-31 | Modernatx, Inc. | Branched tail lipid compounds and compositions for intracellular delivery of therapeutic agents |
| CR20220220A (es) | 2019-11-18 | 2022-09-20 | Janssen Biotech Inc | Vacunas basadas en calr y jak2 mutantes y sus usos |
| CN121422256A (zh) | 2019-12-04 | 2026-01-30 | 奥纳治疗公司 | 环状rna组合物和方法 |
| EP4106730A4 (en) * | 2020-02-19 | 2024-03-27 | University of Florida Research Foundation, Incorporated | MULTILAMELLAR RNA NANOPARTICLES AND METHODS FOR SENSITIZING TUMORS TO TREATMENT WITH IMMUNE CHECKPOINT INHIBITORS |
| JP7539723B2 (ja) * | 2020-02-21 | 2024-08-26 | コンバインド セラピューティクス インコーポレイテッド | コード化リボ核酸の器官保護発現及び調節のための組成物並びに方法 |
| EP4132576A1 (en) | 2020-04-09 | 2023-02-15 | Suzhou Abogen Biosciences Co., Ltd. | Nucleic acid vaccines for coronavirus |
| WO2021204175A1 (en) | 2020-04-09 | 2021-10-14 | Suzhou Abogen Biosciences Co., Ltd. | Lipid nanoparticle composition |
| CN116648510A (zh) | 2020-05-17 | 2023-08-25 | 贝林格尔.英格海姆国际有限公司 | 用于受调控基因治疗的病毒载体和核酸 |
| EP4175664A2 (en) | 2020-07-06 | 2023-05-10 | Janssen Biotech, Inc. | Prostate neoantigens and their uses |
| EP4185274A1 (en) | 2020-07-24 | 2023-05-31 | Strand Therapeutics Inc. | Lipidnanoparticle comprising modified nucleotides |
| MX2023001187A (es) * | 2020-07-31 | 2023-04-04 | Combined Therapeutics Inc | Composiciones y métodos para una vacunación mejorada. |
| CZ310613B6 (cs) | 2020-09-23 | 2026-01-28 | Ústav organické chemie a biochemie AV ČR, v. v. i. | Lipidoidy pro transfekci nukleových kyselin a jejich použití |
| US12071633B2 (en) | 2020-10-13 | 2024-08-27 | Kriya Therapeutics, Inc. | Viral vector constructs for delivery of nucleic acids encoding cytokines and uses thereof for treating cancer |
| AR124599A1 (es) * | 2021-01-08 | 2023-04-12 | Strand Therapeutics Inc | Constructos de expresión y usos de estos |
| EP4274607A1 (en) | 2021-01-11 | 2023-11-15 | ModernaTX, Inc. | Seasonal rna influenza virus vaccines |
| US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
| 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 |
| AU2022268465A1 (en) * | 2021-05-06 | 2023-03-09 | Stemirna Therapeutics Co., Ltd. | A lipid |
| US20220363937A1 (en) | 2021-05-14 | 2022-11-17 | Armstrong World Industries, Inc. | Stabilization of antimicrobial coatings |
| JP2024521082A (ja) * | 2021-05-18 | 2024-05-28 | ユニバーシティ オブ テネシー リサーチ ファウンデーション | アミロイド障害を処置するための抗体－ペプチド融合タンパク質 |
| CZ310443B6 (cs) | 2021-07-19 | 2025-06-25 | Ústav organické chemie a biochemie AV ČR, v. v. i. | Cyklohexanové lipidoidy pro transfekci nukleových kyselin a jejich použití |
| US20240398940A1 (en) | 2021-09-03 | 2024-12-05 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids |
| CN116829578B (zh) * | 2021-10-08 | 2025-03-21 | 苏州艾博生物科技有限公司 | 编码白细胞介素-12(il-12)的多核苷酸以及其相关组合物和方法 |
| EP4422698A1 (en) | 2021-10-29 | 2024-09-04 | CureVac SE | Improved circular rna for expressing therapeutic proteins |
| CN116179549A (zh) | 2021-12-08 | 2023-05-30 | 南京吉迈生物技术有限公司 | 通过5’utr序列变体修饰基因转录和翻译效率 |
| US12529047B1 (en) | 2021-12-21 | 2026-01-20 | Modernatx, Inc. | mRNA quantification methods |
| CN114044741B (zh) | 2022-01-13 | 2022-04-15 | 北京悦康科创医药科技股份有限公司 | 一种阳离子脂质化合物、包含其的组合物及用途 |
| US20250099614A1 (en) | 2022-01-28 | 2025-03-27 | CureVac SE | Nucleic acid encoded transcription factor inhibitors |
| WO2023196988A1 (en) * | 2022-04-07 | 2023-10-12 | Modernatx, Inc. | Methods of use of mrnas encoding il-12 |
| CN116621965A (zh) * | 2022-05-06 | 2023-08-22 | 珠海丽凡达生物技术有限公司 | 治疗性核酸分子、混合物、药物及在治疗实体瘤中的应用 |
| CN114994331B (zh) * | 2022-05-17 | 2023-02-24 | 无锡科金生物科技有限公司 | 一种检测蛋白表达水平的试剂盒及其制备方法和应用 |
| US20250345407A1 (en) | 2022-05-25 | 2025-11-13 | CureVac SE | Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide |
| CN114773217B (zh) * | 2022-06-20 | 2022-10-18 | 深圳市瑞吉生物科技有限公司 | 用于递送核酸的阳离子脂质化合物和组合物及用途 |
| US12297285B2 (en) | 2022-06-24 | 2025-05-13 | Orna Therapeutics, Inc. | Circular RNA encoding chimeric antigen receptors targeting BCMA |
| WO2024020453A2 (en) * | 2022-07-20 | 2024-01-25 | Hdt Bio Corp. | Immune system modulators and uses thereof |
| EP4608442A1 (en) | 2022-10-28 | 2025-09-03 | GlaxoSmithKline Biologicals S.A. | Nucleic acid based vaccine |
| CN120112637A (zh) * | 2022-11-11 | 2025-06-06 | 斯微(上海)生物科技股份有限公司 | 人工核酸分子 |
| WO2024184500A1 (en) | 2023-03-08 | 2024-09-12 | CureVac SE | Novel lipid nanoparticle formulations for delivery of nucleic acids |
| WO2024230934A1 (en) | 2023-05-11 | 2024-11-14 | CureVac SE | Therapeutic nucleic acid for the treatment of ophthalmic diseases |
Family Cites Families (170)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5082767A (en) | 1989-02-27 | 1992-01-21 | Hatfield G Wesley | Codon pair utilization |
| US6140496A (en) | 1990-10-09 | 2000-10-31 | Benner; Steven Albert | Precursors for deoxyribonucleotides containing non-standard nucleosides |
| US5891680A (en) | 1995-02-08 | 1999-04-06 | Whitehead Institute For Biomedical Research | Bioactive fusion proteins comprising the p35 and p40 subunits of IL-12 |
| US5811097A (en) | 1995-07-25 | 1998-09-22 | The Regents Of The University Of California | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
| US5922685A (en) | 1996-06-05 | 1999-07-13 | Powderject Vaccines, Inc. | IL-12 gene therapy of tumors |
| JP2001503258A (ja) | 1996-10-18 | 2001-03-13 | バレンティス・インコーポレーテッド | 遺伝子発現および搬送系および用途 |
| US5994104A (en) | 1996-11-08 | 1999-11-30 | Royal Free Hospital School Of Medicine | Interleukin-12 fusion protein |
| CA2309535A1 (en) | 1997-11-12 | 1999-05-20 | Brigham And Women's Hospital, Inc. | The translation enhancer element of the human amyloid precursor protein gene |
| ATE550042T1 (de) | 1997-11-20 | 2012-04-15 | Vical Inc | Behandlung von krebs mithilfe cytokin- exprimierender polynukleotide und zusammensetzungen dafür |
| AU3534199A (en) | 1998-04-23 | 1999-11-08 | Takara Shuzo Co., Ltd. | Method For Synthesizing DNA |
| AU761520B2 (en) | 1998-09-15 | 2003-06-05 | Genetics Institute, Llc | Treatment of Kaposi's Sarcoma with IL-12 |
| AU6270499A (en) | 1998-09-29 | 2000-04-17 | Phylos, Inc. | Synthesis of codon randomized nucleic acids |
| EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| ATE305801T1 (de) * | 2000-01-20 | 2005-10-15 | Univ Zuerich Inst Fuer Medizin | Intratumorale verabreichung nackter il-12 codierender nukleinsäuremoleküle |
| CA2398790A1 (en) | 2000-01-28 | 2001-08-02 | The Scripps Research Institute | Methods of identifying synthetic transcriptional and translational regulatory elements, and compositions relating to same |
| US7468275B2 (en) | 2000-01-28 | 2008-12-23 | The Scripps Research Institute | Synthetic internal ribosome entry sites and methods of identifying same |
| ES2164011B1 (es) | 2000-02-25 | 2003-05-16 | Inst Cientifico Tecnol Navarra | Uso combinado de la quimiocina ip-10 y la interleucina-12 en la preparacion de composiciones para el tratamiento de tumores malignos. |
| AU3958101A (en) | 2000-03-15 | 2001-09-24 | Univ Pohang | Genes of il-12p40 subunit mutated for improving the activity of il-12 and use thereof for dna vaccine adjuvant |
| KR20020010206A (ko) | 2000-07-27 | 2002-02-04 | 이시우 | 인터루킨 12와 보조활성인자 ｂ7.1 유전자를 함유하는ｄｎａ 벡터 및 이벡터가 도입된 항암 세포백신 |
| ES2340499T3 (es) | 2001-06-05 | 2010-06-04 | Curevac Gmbh | Arnm de antigeno tumoral estabilizado con un contenido de g/c aumentado. |
| AU2002354799A1 (en) | 2001-07-03 | 2003-01-21 | University Of Utah Research Foundation | Soluble steroidal peptides for nucleic acid delivery |
| EP2447370B1 (en) | 2001-09-28 | 2018-07-18 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | MicroRNA molecules |
| ATE427992T1 (de) | 2001-11-14 | 2009-04-15 | Toyo Boseki | Dna-synthesepromotoren, mit dna-polymerase assoziierte faktoren und nutzung davon |
| CA2409775C (en) | 2001-12-03 | 2010-07-13 | F. Hoffmann-La Roche Ag | Reversibly modified thermostable enzymes for dna synthesis and amplification in vitro |
| EP1490494A1 (en) | 2002-04-01 | 2004-12-29 | Walter Reed Army Institute of Research | Method of designing synthetic nucleic acid sequences for optimal protein expression in a host cell |
| US7595303B1 (en) | 2002-09-05 | 2009-09-29 | University Of South Florida | Genetic adjuvants for immunotherapy |
| DE10248141B4 (de) | 2002-10-11 | 2007-04-19 | Universitätsklinikum Hamburg-Eppendorf | Nukleinsäuren und deren Verwendung für die Gentherapie |
| DE10260805A1 (de) | 2002-12-23 | 2004-07-22 | Geneart Gmbh | Verfahren und Vorrichtung zum Optimieren einer Nucleotidsequenz zur Expression eines Proteins |
| CN1798502A (zh) | 2003-05-30 | 2006-07-05 | 南佛罗里达大学 | 治疗恶性肿瘤的方法 |
| US7683036B2 (en) | 2003-07-31 | 2010-03-23 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding RNAs |
| GB0329146D0 (en) | 2003-12-16 | 2004-01-21 | Glaxosmithkline Biolog Sa | Vaccine |
| DE102004042546A1 (de) | 2004-09-02 | 2006-03-09 | Curevac Gmbh | Kombinationstherapie zur Immunstimulation |
| EP1640018A1 (en) | 2004-09-24 | 2006-03-29 | Universität Zürich | Combinational therapy for treating cancer |
| DK2439273T3 (da) | 2005-05-09 | 2019-06-03 | Ono Pharmaceutical Co | Humane monoklonale antistoffer til programmeret død-1(pd-1) og fremgangsmåder til behandling af cancer ved anvendelse af anti-pd-1- antistoffer alene eller i kombination med andre immunterapeutika |
| US7550264B2 (en) | 2005-06-10 | 2009-06-23 | Datascope Investment Corporation | Methods and kits for sense RNA synthesis |
| CA2613442C (en) | 2005-06-30 | 2016-08-23 | Archemix Corp. | Materials and methods for the generation of fully 2'-modified nucleic acid transcripts |
| US8101385B2 (en) | 2005-06-30 | 2012-01-24 | Archemix Corp. | Materials and methods for the generation of transcripts comprising modified nucleotides |
| PT1907424E (pt) | 2005-07-01 | 2015-10-09 | Squibb & Sons Llc | Anticorpos monoclonais humanos para o ligando 1 de morte programada (pd-l1) |
| US9012219B2 (en) | 2005-08-23 | 2015-04-21 | The Trustees Of The University Of Pennsylvania | RNA preparations comprising purified modified RNA for reprogramming cells |
| PL2578685T3 (pl) | 2005-08-23 | 2020-01-31 | The Trustees Of The University Of Pennsylvania | Rna zawierający zmodyfikowane nukleozydy i sposoby jego zastosowania |
| EP2479254A1 (en) | 2005-08-24 | 2012-07-25 | The Scripps Research Institute | Translation enhancer-element dependent vector systems |
| DE102005046490A1 (de) | 2005-09-28 | 2007-03-29 | Johannes-Gutenberg-Universität Mainz | Modifikationen von RNA, die zu einer erhöhten Transkriptstabilität und Translationseffizienz führen |
| PL1966238T3 (pl) | 2005-12-30 | 2012-09-28 | Merck Patent Gmbh | Warianty interleukiny-12p40 o polepszonej stabilności |
| US7670840B2 (en) | 2006-01-05 | 2010-03-02 | The Ohio State University Research Foundation | Micro-RNA expression abnormalities of pancreatic, endocrine and acinar tumors |
| EP1969147B1 (en) | 2006-01-05 | 2014-07-30 | The Ohio State University Research Foundation | microRNA-based methods for the diagnosis of stomach cancer |
| US7833754B2 (en) | 2006-01-13 | 2010-11-16 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | IL-12 for expression in mammalian cell |
| KR101241477B1 (ko) | 2006-01-27 | 2013-03-08 | 엘지이노텍 주식회사 | 질화물 반도체 발광소자 및 그 제조 방법 |
| EP2522746B1 (en) | 2006-03-02 | 2014-11-12 | The Ohio State University Research Foundation | MicroRNA expression profile associated with pancreatic cancer |
| US7919079B2 (en) | 2006-03-31 | 2011-04-05 | Biosante Pharmaceuticals, Inc. | Cancer immunotherapy compositions and methods of use |
| WO2007113648A2 (en) | 2006-04-05 | 2007-10-11 | Pfizer Products Inc. | Ctla4 antibody combination therapy |
| US20080046192A1 (en) | 2006-08-16 | 2008-02-21 | Richard Lathrop | Polypepetide-encoding nucleotide sequences with refined translational kinetics and methods of making same |
| US20090131348A1 (en) | 2006-09-19 | 2009-05-21 | Emmanuel Labourier | Micrornas differentially expressed in pancreatic diseases and uses thereof |
| DE102006051516A1 (de) | 2006-10-31 | 2008-05-08 | Curevac Gmbh | (Basen-)modifizierte RNA zur Expressionssteigerung eines Proteins |
| US8252538B2 (en) | 2006-11-01 | 2012-08-28 | The Ohio State University | MicroRNA expression signature for predicting survival and metastases in hepatocellular carcinoma |
| WO2008073915A2 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Micrornas differentially expressed in leukemia and uses thereof |
| WO2008078180A2 (en) | 2006-12-22 | 2008-07-03 | Archemix Corp. | Materials and methods for the generation of transcripts comprising modified nucleotides |
| WO2008134879A1 (en) | 2007-05-04 | 2008-11-13 | University Health Network | Il-12 immunotherapy for cancer |
| WO2008147974A1 (en) | 2007-05-23 | 2008-12-04 | University Of South Florida | Micro-rnas modulating immunity and inflammation |
| US20090099034A1 (en) | 2007-06-07 | 2009-04-16 | Wisconsin Alumni Research Foundation | Reagents and Methods for miRNA Expression Analysis and Identification of Cancer Biomarkers |
| BR122017025062B8 (pt) | 2007-06-18 | 2021-07-27 | Merck Sharp & Dohme | anticorpo monoclonal ou fragmento de anticorpo para o receptor de morte programada humano pd-1, polinucleotídeo e composição compreendendo o referido anticorpo ou fragmento |
| WO2009014708A2 (en) | 2007-07-23 | 2009-01-29 | Cell Genesys, Inc. | Pd-1 antibodies in combination with a cytokine-secreting cell and methods of use thereof |
| TWI359030B (en) | 2007-08-24 | 2012-03-01 | Univ Nat Taiwan | Treatment of cellular proliferative disorders |
| US8476419B2 (en) | 2007-09-14 | 2013-07-02 | Vrije Universiteit Brussel | Enhancing the T-cells stimulatory capacity of human antigen presenting cells and their use in vaccination |
| US20110086904A1 (en) | 2007-09-17 | 2011-04-14 | The Trustees Of The University Of Pennsylvania | GENERATION OF HYPERSTABLE mRNAs |
| WO2009040811A2 (en) * | 2007-09-24 | 2009-04-02 | Bar-Ilan University | Polymer nanoparticles coated by magnetic metal oxide and uses thereof |
| CA2715078C (en) | 2007-09-26 | 2019-07-23 | Intrexon Corporation | Synthetic 5'utrs, expression vectors, and methods for increasing transgene expression |
| CN101918594A (zh) | 2007-11-30 | 2010-12-15 | 俄亥俄州立大学研究基金会 | 肺癌中外周血中的微rna表达特征谱和靶向 |
| SG10201408162PA (en) | 2007-12-11 | 2015-01-29 | Scripps Research Inst | Compositions and methods related to mrna translational enhancer elements |
| EP2072618A1 (en) | 2007-12-14 | 2009-06-24 | Johannes Gutenberg-Universität Mainz | Use of RNA for reprogramming somatic cells |
| WO2009086558A1 (en) * | 2008-01-02 | 2009-07-09 | Tekmira Pharmaceuticals Corporation | Improved compositions and methods for the delivery of nucleic acids |
| EP2260110B1 (en) | 2008-02-08 | 2014-11-12 | Asuragen, INC. | miRNAs DIFFERENTIALLY EXPRESSED IN LYMPH NODES FROM CANCER PATIENTS |
| CA2717026A1 (en) | 2008-02-28 | 2009-09-03 | The Ohio State University Research Foundation | Microrna signatures associated with human chronic lymphocytic leukemia (ccl) and uses thereof |
| CA2721333C (en) * | 2008-04-15 | 2020-12-01 | Protiva Biotherapeutics, Inc. | Novel lipid formulations for nucleic acid delivery |
| 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 |
| US8715964B2 (en) | 2008-05-11 | 2014-05-06 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Expression of IL-12 family heterodimers |
| US8401798B2 (en) | 2008-06-06 | 2013-03-19 | Dna Twopointo, Inc. | Systems and methods for constructing frequency lookup tables for expression systems |
| PL215513B1 (pl) | 2008-06-06 | 2013-12-31 | Univ Warszawski | Nowe boranofosforanowe analogi dinukleotydów, ich zastosowanie, czasteczka RNA, sposób otrzymywania RNA oraz sposób otrzymywania peptydów lub bialka |
| US7561973B1 (en) | 2008-07-31 | 2009-07-14 | Dna Twopointo, Inc. | Methods for determining properties that affect an expression property value of polynucleotides in an expression system |
| US8126653B2 (en) | 2008-07-31 | 2012-02-28 | Dna Twopointo, Inc. | Synthetic nucleic acids for expression of encoded proteins |
| 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 |
| AU2009288730B2 (en) | 2008-08-25 | 2013-06-20 | Amplimmune, Inc. | Compositions of PD-1 antagonists and methods of use |
| US9074206B2 (en) | 2008-11-13 | 2015-07-07 | Fudan University | Compositions and methods for micro-RNA expression profiling of colorectal cancer |
| EP3255060A1 (en) | 2008-12-09 | 2017-12-13 | F. Hoffmann-La Roche AG | Anti-pd-l1 antibodies and their use to enhance t-cell function |
| EP2358902A1 (en) | 2008-12-10 | 2011-08-24 | Universität Regensburg | Compositions and methods for micro-rna expression profiling of cancer stem cells |
| WO2010126766A1 (en) * | 2009-04-30 | 2010-11-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Inducible interleukin-12 |
| 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 |
| KR101766408B1 (ko) | 2009-06-10 | 2017-08-10 | 알닐람 파마슈티칼스 인코포레이티드 | 향상된 지질 조성물 |
| CA2769670C (en) | 2009-07-31 | 2018-10-02 | Ethris Gmbh | Rna with a combination of unmodified and modified nucleotides for protein expression |
| EP2281579A1 (en) | 2009-08-05 | 2011-02-09 | BioNTech AG | Vaccine composition comprising 5'-Cap modified RNA |
| US20110082055A1 (en) | 2009-09-18 | 2011-04-07 | Codexis, Inc. | Reduced codon mutagenesis |
| WO2011066342A2 (en) | 2009-11-24 | 2011-06-03 | Amplimmune, Inc. | Simultaneous inhibition of pd-l1/pd-l2 |
| EP3318248B1 (en) | 2009-12-01 | 2019-04-10 | Translate Bio, Inc. | Delivery of mrna for the augmentation of proteins and enzymes in human genetic diseases |
| 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 |
| US20130059015A1 (en) | 2010-03-11 | 2013-03-07 | 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 |
| US20130230884A1 (en) | 2010-07-16 | 2013-09-05 | John Chaput | Methods to Identify Synthetic and Natural RNA Elements that Enhance Protein Translation |
| US20130183718A1 (en) | 2010-09-21 | 2013-07-18 | RibpxX GmbH | Method for Synthesizing RNA using DNA Template |
| WO2012072096A1 (en) | 2010-12-03 | 2012-06-07 | Biontech Ag | Method for cellular rna expression |
| KR20120066952A (ko) | 2010-12-15 | 2012-06-25 | 주식회사 롤팩 | 7층 구조의 공압출 항균 진공포장 필름 및 그 제조방법 |
| EP2651445A2 (en) | 2010-12-16 | 2013-10-23 | SPRNA GmbH | Pharmaceutical composition consisting of rna having alkali metal as counter ion and formulated with dications |
| WO2012116714A1 (en) | 2011-03-02 | 2012-09-07 | Curevac Gmbh | Vaccination in elderly patients |
| CA2828940C (en) | 2011-03-10 | 2024-04-16 | Provectus Pharmaceuticals, Inc. | Combination of local and systemic immunomodulative therapies for enhanced treatment of cancer |
| AU2012236099A1 (en) | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
| WO2012151212A1 (en) | 2011-05-01 | 2012-11-08 | University Of Rochester | Multifocal hepatocellular carcinoma microrna expression patterns and uses thereof |
| WO2012150807A2 (ko) | 2011-05-02 | 2012-11-08 | 엘지전자 주식회사 | 무선 접속 시스템에서 데이터 송수신 방법 및 이를 위한 기지국 |
| EP2705370A2 (en) | 2011-05-06 | 2014-03-12 | Xentech | Markers for cancer prognosis and therapy and methods of use |
| RU2013154295A (ru) | 2011-06-08 | 2015-07-20 | Шир Хьюман Дженетик Терапис, Инк. | КОМПОЗИЦИИ ЛИПИДНЫХ НАНОЧАСТИЦ И СПОСОБЫ ДЛЯ ДОСТАВКИ мРНК |
| DK2732052T3 (en) | 2011-07-15 | 2017-02-20 | Leo Pharma As | Diagnostic microRNA profiling in cutaneous T cell lymphoma (CTCL) |
| EP2751292A4 (en) | 2011-09-01 | 2015-05-20 | Allegro Diagnostics Corp | METHOD AND COMPOSITIONS FOR DETECTING CANCER BASED ON MIRNA EXPRESSION PROFILES |
| EP2755986A4 (en) | 2011-09-12 | 2015-05-20 | Moderna Therapeutics Inc | MANIPULATED NUCLEIC ACIDS AND METHOD OF APPLICATION THEREFOR |
| DE19216461T1 (de) | 2011-10-03 | 2021-10-07 | Modernatx, Inc. | Modifizierte nukleoside, nukleotide und nukleinsäuren und verwendungen davon |
| EP2766035B1 (en) * | 2011-10-11 | 2018-03-28 | Universität Zürich Prorektorat MNW | Combination medicament comprising il-12 and an agent for blockade of t-cell inhibitory molecules for tumour therapy |
| US20140243240A1 (en) | 2011-10-26 | 2014-08-28 | Georgetown University | microRNA EXPRESSION PROFILING OF THYROID CANCER |
| KR101764096B1 (ko) | 2011-11-28 | 2017-08-02 | 메르크 파텐트 게엠베하 | 항-ｐｄ-ｌ1 항체 및 그의 용도 |
| JP6333730B2 (ja) | 2011-12-12 | 2018-05-30 | 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 | 改善されたｉｌ−１２遺伝子構築物を含む組成物、及びそれを用いたワクチン、免疫治療剤及び方法 |
| EP2623121A1 (en) | 2012-01-31 | 2013-08-07 | Bayer Innovation GmbH | Pharmaceutical composition comprising a polymeric carrier cargo complex and an antigen |
| WO2013143555A1 (en) | 2012-03-26 | 2013-10-03 | Biontech Ag | Rna formulation for immunotherapy |
| WO2013151665A2 (en) | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of proteins associated with human disease |
| HK1203971A1 (en) | 2012-05-15 | 2015-11-06 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
| EP2672197A1 (de) | 2012-06-06 | 2013-12-11 | Hörmann Energietechnik GmbH & Co. KG | Montageanordnung zur dachseitigen Montage von Flächenkörpern an einem Bauwerk |
| WO2013185067A1 (en) | 2012-06-08 | 2013-12-12 | Shire Human Genetic Therapies, Inc. | Nuclease resistant polynucleotides and uses thereof |
| EP2858679B2 (en) | 2012-06-08 | 2024-06-05 | Translate Bio, Inc. | Pulmonary delivery of mrna to non-lung target cells |
| US20140020675A1 (en) | 2012-07-18 | 2014-01-23 | Chandrashekhar Sonwane | Solar receiver |
| WO2014028429A2 (en) | 2012-08-14 | 2014-02-20 | Moderna Therapeutics, Inc. | Enzymes and polymerases for the synthesis of rna |
| CN102876684B (zh) * | 2012-09-17 | 2014-10-08 | 青岛康立泰药业有限公司 | 人白细胞介素-12的编码基因、真核宿主细胞和表达方法 |
| WO2014093924A1 (en) | 2012-12-13 | 2014-06-19 | Moderna Therapeutics, Inc. | Modified nucleic acid molecules and uses thereof |
| WO2014071963A1 (en) | 2012-11-09 | 2014-05-15 | Biontech Ag | Method for cellular rna expression |
| PL2922554T3 (pl) * | 2012-11-26 | 2022-06-20 | Modernatx, Inc. | Na zmodyfikowany na końcach |
| EP4331620A3 (en) | 2012-12-07 | 2024-12-04 | Translate Bio, Inc. | Lipidic nanoparticles for mrna delivery |
| AU2013374345A1 (en) | 2013-01-17 | 2015-08-06 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
| US9974845B2 (en) | 2013-02-22 | 2018-05-22 | Curevac Ag | Combination of vaccination and inhibition of the PD-1 pathway |
| CN107879960B (zh) | 2013-03-08 | 2021-06-22 | 诺华股份有限公司 | 用于传递活性成分的脂质和脂质组合物 |
| US20160022840A1 (en) | 2013-03-09 | 2016-01-28 | Moderna Therapeutics, Inc. | Heterologous untranslated regions for mrna |
| BR112015022505A2 (pt) | 2013-03-14 | 2017-10-24 | Shire Human Genetic Therapies | avaliação quantitativa para eficiência do cap de rna mensageiro |
| BR112015022855A2 (pt) | 2013-03-14 | 2017-11-07 | Shire Human Genetic Therapies | composições e método para produção de um anticorpo in vitro |
| RS57739B1 (sr) | 2013-03-14 | 2018-12-31 | Translate Bio Inc | Kompozicije cftr irnk i postupci i upotrebe u vezi sa njima |
| ES2708562T3 (es) | 2013-03-14 | 2019-04-10 | Translate Bio Inc | Evaluación cuantitativa de la eficacidad de tapa de ARN mensajero |
| EP3750903A1 (en) | 2013-03-14 | 2020-12-16 | Translate Bio, Inc. | Ribonucleic acids with 4'-thio-modified nucleotides and related methods |
| JP6586075B2 (ja) | 2013-03-14 | 2019-10-02 | 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の精製方法 |
| EP2970940B1 (en) | 2013-03-14 | 2018-07-25 | Translate Bio, Inc. | Mrna therapeutic compositions and use to treat diseases and disorders |
| EP3388834B1 (en) | 2013-03-15 | 2020-04-15 | Translate Bio, Inc. | Synergistic enhancement of the delivery of nucleic acids via blended formulations |
| KR102354389B1 (ko) | 2013-08-21 | 2022-01-20 | 큐어백 아게 | Rna―암호화된 단백질의 발현을 증가시키는 방법 |
| CN112552401B (zh) | 2013-09-13 | 2023-08-25 | 广州百济神州生物制药有限公司 | 抗pd1抗体及其作为治疗剂与诊断剂的用途 |
| US20160367651A1 (en) | 2013-10-01 | 2016-12-22 | Mie University | T cell inducing vaccine containing an interepitope sequence that promotes antigen presentation |
| AU2014337156A1 (en) | 2013-10-18 | 2016-05-12 | Modernatx, Inc. | Compositions and methods for tolerizing cellular systems |
| JP6506749B2 (ja) | 2013-10-22 | 2019-04-24 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | フェニルケトン尿症のためのｍＲＮＡ療法 |
| ES3032935T3 (en) | 2013-10-22 | 2025-07-29 | Translate Bio Inc | Lipid formulations for delivery of messenger rna |
| WO2015062738A1 (en) | 2013-11-01 | 2015-05-07 | Curevac Gmbh | Modified rna with decreased immunostimulatory properties |
| WO2015095423A2 (en) * | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
| JP2017501712A (ja) * | 2013-12-18 | 2017-01-19 | イントレキソン コーポレーション | 単鎖ｉｌ−１２核酸、ポリペプチド、およびそれらの使用 |
| CN111304231A (zh) | 2013-12-30 | 2020-06-19 | 库瑞瓦格股份公司 | 人工核酸分子 |
| CA2927254C (en) | 2013-12-30 | 2023-10-24 | Curevac Ag | Artificial nucleic acid molecules |
| PL4023249T3 (pl) | 2014-04-23 | 2025-03-10 | Modernatx, Inc. | Szczepionki z kwasem nukleinowym |
| HUE060907T2 (hu) * | 2014-06-25 | 2023-04-28 | Acuitas Therapeutics Inc | Új lipidek és lipid nanorészecske formulációk nukleinsavak bevitelére |
| EP3197911A4 (en) | 2014-09-22 | 2018-06-20 | Intrexon Corporation | Improved therapeutic control of heterodimeric and single chain forms of interleukin-12 |
| US11786457B2 (en) | 2015-01-30 | 2023-10-17 | President And Fellows Of Harvard College | Peritumoral and intratumoral materials for cancer therapy |
| CN108064176A (zh) | 2015-04-22 | 2018-05-22 | 库瑞瓦格股份公司 | 用于治疗肿瘤疾病的含有rna的组合物 |
| US10682401B2 (en) | 2015-05-19 | 2020-06-16 | Morphogenesis, Inc. | Multi-indication mRNA cancer immunotherapy |
| WO2016187407A1 (en) | 2015-05-19 | 2016-11-24 | Morphogenesis, Inc. | Cancer vaccine comprising mrna encoding a m-like-protein |
| JP6948313B6 (ja) * | 2015-09-17 | 2022-01-14 | モデルナティエックス インコーポレイテッド | 治療剤の細胞内送達のための化合物および組成物 |
| EP3205356A1 (en) | 2016-02-10 | 2017-08-16 | Onkoloski Institut Ljubljana | Plasmid expression vector encoding human interleukin 12 under transcriptional control of p21 promoter and without antibiotic resistance for cancer gene therapy and other uses thereof |
| EP3211000B1 (en) | 2016-02-25 | 2019-01-30 | Provecs Medical GmbH | Novel immunostimulating vector system |
| SI3458083T1 (sl) | 2016-05-18 | 2023-03-31 | Modernatx, Inc. | Polinukleotidi, ki kodirajo interlevkin-12 (IL12) in njihova uporaba |
| CN109715205A (zh) | 2016-08-19 | 2019-05-03 | 库瑞瓦格股份公司 | 用于癌症治疗的rna |
| EP3523323A4 (en) | 2016-10-07 | 2020-06-17 | Board of Regents, The University of Texas System | T-CELLS WITH EXPRESSION OF MEMBRANE-ANCHORED IL-12 FOR THE TREATMENT OF CANCER |
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