AU2013374345A1 - Signal-sensor polynucleotides for the alteration of cellular phenotypes - Google Patents
Signal-sensor polynucleotides for the alteration of cellular phenotypes Download PDFInfo
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- AU2013374345A1 AU2013374345A1 AU2013374345A AU2013374345A AU2013374345A1 AU 2013374345 A1 AU2013374345 A1 AU 2013374345A1 AU 2013374345 A AU2013374345 A AU 2013374345A AU 2013374345 A AU2013374345 A AU 2013374345A AU 2013374345 A1 AU2013374345 A1 AU 2013374345A1
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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|---|---|---|---|---|
| CA2782676C (en) | 2009-12-01 | 2021-06-15 | Shire Human Genetic Therapies, Inc. | Pharmaceutical compositions for intracellular delivery of nucleic acids and proteins and uses thereof for treatment of ureca cycle metabolic disorders |
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| US8853377B2 (en) | 2010-11-30 | 2014-10-07 | Shire Human Genetic Therapies, Inc. | mRNA for use in treatment of human genetic diseases |
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| DE12858350T1 (de) | 2011-12-16 | 2021-10-07 | Modernatx, Inc. | Modifizierte mrna zusammensetzungen |
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| US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| HK1206601A1 (en) | 2012-04-02 | 2016-01-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of biologics and proteins associated with human disease |
| CN108524919A (zh) | 2012-05-17 | 2018-09-14 | 延伸生物科学股份有限公司 | 用于改进的药物递送的载体 |
| JP6561378B2 (ja) | 2012-06-08 | 2019-08-21 | トランスレイト バイオ, インコーポレイテッド | 非肺標的細胞へのmRNAの経肺送達 |
| EP2859102A4 (en) | 2012-06-08 | 2016-05-11 | Shire Human Genetic Therapies | NUCLEASE RESISTANT POLYNUCLEOTIDES AND USES THEREOF |
| EP2885419A4 (en) | 2012-08-14 | 2016-05-25 | Moderna Therapeutics Inc | ENZYMES AND POLYMERASES FOR RNA SYNTHESIS |
| HRP20220607T1 (hr) | 2012-11-26 | 2022-06-24 | Modernatx, Inc. | Terminalno modificirana rna |
| WO2014113089A2 (en) | 2013-01-17 | 2014-07-24 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
| US20160024181A1 (en) | 2013-03-13 | 2016-01-28 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
| RS62565B1 (sr) | 2013-03-14 | 2021-12-31 | Translate Bio Inc | Metode i kompozicije za isporuku antitela kodiranih od strane irnk |
| MX365409B (es) | 2013-03-14 | 2019-05-31 | Shire Human Genetic Therapies | Composiciones de ácido ribonucleico mensajero del regulador transmembrana de fibrosis quística y métodos y usos relacionados. |
| WO2014152211A1 (en) | 2013-03-14 | 2014-09-25 | Moderna Therapeutics, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
| EA201591229A1 (ru) | 2013-03-14 | 2016-01-29 | Шир Хьюман Дженетик Терапис, Инк. | Способы очистки матричной рнк |
| EP2983804A4 (en) | 2013-03-15 | 2017-03-01 | Moderna Therapeutics, Inc. | Ion exchange purification of mrna |
| US10077439B2 (en) | 2013-03-15 | 2018-09-18 | Modernatx, Inc. | Removal of DNA fragments in mRNA production process |
| EP2971033B8 (en) * | 2013-03-15 | 2019-07-10 | ModernaTX, Inc. | Manufacturing methods for production of rna transcripts |
| US11377470B2 (en) | 2013-03-15 | 2022-07-05 | Modernatx, Inc. | Ribonucleic acid purification |
| HUE071526T2 (hu) | 2013-03-15 | 2025-09-28 | Translate Bio Inc | Nukleinsavak bejuttatásának szinergista fokozása kevert kiszerelésekkel |
| RS62529B1 (sr) | 2013-07-11 | 2021-11-30 | Modernatx Inc | Kompozicije koje sadrže sintetičke polinukleotide koji kodiraju proteine povezane sa crispr i sintetičke sgrnk i postupci upotrebe |
| WO2015048744A2 (en) | 2013-09-30 | 2015-04-02 | Moderna Therapeutics, Inc. | Polynucleotides encoding immune modulating polypeptides |
| WO2015051169A2 (en) | 2013-10-02 | 2015-04-09 | Moderna Therapeutics, Inc. | Polynucleotide molecules and uses thereof |
| WO2015051214A1 (en) | 2013-10-03 | 2015-04-09 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
| EP3060303B1 (en) | 2013-10-22 | 2018-11-14 | Translate Bio, Inc. | Mrna therapy for argininosuccinate synthetase deficiency |
| MX2016005239A (es) | 2013-10-22 | 2016-08-12 | Shire Human Genetic Therapies | Tratamiento con acido ribonucleico mensajero para la fenilcetonuria. |
| CA2928040A1 (en) | 2013-10-22 | 2015-04-30 | Shire Human Genetic Therapies, Inc. | Cns delivery of mrna and uses thereof |
| EP3871696B1 (en) | 2013-10-22 | 2025-03-19 | Translate Bio, Inc. | Lipid formulations for delivery of messenger rna |
| CN105939767B (zh) | 2014-01-08 | 2018-04-06 | 弗洛设计声能学公司 | 具有双声电泳腔的声电泳装置 |
| KR20250005450A (ko) | 2014-04-25 | 2025-01-09 | 샤이어 휴먼 지네틱 테라피즈 인크. | 메신저 rna 의 정제 방법 |
| BR112016027705A2 (pt) | 2014-05-30 | 2018-01-30 | Shire Human Genetic Therapies | lipídios biodegradáveis para distribuição de ácidos nucleicos |
| CN119842899A (zh) | 2014-06-18 | 2025-04-18 | 东丽株式会社 | 肝癌的检测试剂盒或装置以及检测方法 |
| US10286086B2 (en) | 2014-06-19 | 2019-05-14 | Modernatx, Inc. | Alternative nucleic acid molecules and uses thereof |
| PE20171238A1 (es) | 2014-06-24 | 2017-08-24 | Shire Human Genetic Therapies | Composiciones enriquecidas estereoquimicamente para administracion de acidos nucleicos |
| CN114146063A (zh) | 2014-07-02 | 2022-03-08 | 川斯勒佰尔公司 | 信使rna的包封 |
| EP3169335B8 (en) | 2014-07-16 | 2019-10-09 | ModernaTX, Inc. | Circular polynucleotides |
| EP3171895A1 (en) | 2014-07-23 | 2017-05-31 | Modernatx, Inc. | Modified polynucleotides for the production of intrabodies |
| US20180085391A1 (en) * | 2014-08-08 | 2018-03-29 | Modernatx, Inc. | Compositions and methods for the treatment of ophthalmic diseases and conditions |
| WO2016065042A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Therapeutic vitamin d conjugates |
| US9616109B2 (en) | 2014-10-22 | 2017-04-11 | Extend Biosciences, Inc. | Insulin vitamin D conjugates |
| US9789197B2 (en) | 2014-10-22 | 2017-10-17 | Extend Biosciences, Inc. | RNAi vitamin D conjugates |
| WO2016069752A1 (en) * | 2014-10-29 | 2016-05-06 | University Of Houston System | Nanovectors for penetrating brain tumor tissues to conduct gene therapy |
| WO2016090262A1 (en) | 2014-12-05 | 2016-06-09 | Shire Human Genetic Therapies, Inc. | Messenger rna therapy for treatment of articular disease |
| US20170362605A1 (en) * | 2014-12-19 | 2017-12-21 | Modernatx, Inc. | Terminal modifications of polynucleotides |
| WO2016130572A2 (en) * | 2015-02-10 | 2016-08-18 | Dana-Farber Cancer Institute, Inc. | Methods of determining levels of exposure to radiation and uses thereof |
| JP6895892B2 (ja) | 2015-03-19 | 2021-06-30 | トランスレイト バイオ, インコーポレイテッド | ポンペ病のmRNA治療 |
| EP3318630B1 (en) | 2015-04-22 | 2020-11-04 | iPS Academia Japan, Inc. | Method for sorting tissue cells |
| 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 |
| BR112017017949A2 (pt) * | 2015-05-15 | 2018-04-10 | Curevac Ag | regimes de iniciação-reforço envolvendo administração de pelo menos um constructo de mrna |
| EP3307305A4 (en) * | 2015-06-10 | 2019-05-22 | Modernatx, Inc. | TARGETED ADAPTIVE VACCINES |
| US11434486B2 (en) | 2015-09-17 | 2022-09-06 | Modernatx, Inc. | Polynucleotides containing a morpholino linker |
| CA2998370A1 (en) * | 2015-09-17 | 2017-03-23 | Moderna Therapeutics, Inc. | Polynucleotides containing a stabilizing tail region |
| CA3001003A1 (en) | 2015-10-05 | 2017-04-13 | Modernatx, Inc. | Methods for therapeutic administration of messenger ribonucleic acid drugs |
| ES2862412T3 (es) | 2015-10-14 | 2021-10-07 | Translate Bio Inc | Modificación de enzimas relacionados con el ARN para producción mejorada |
| KR101737706B1 (ko) | 2015-12-15 | 2017-05-18 | 한국원자력의학원 | miR-5582-5p를 포함하는 항암제 |
| WO2017106799A1 (en) | 2015-12-17 | 2017-06-22 | Modernatx, Inc. | POLYNUCLEOTIDES ENCODING METHYLMALONYL-CoA MUTASE |
| SI3394093T1 (sl) | 2015-12-23 | 2022-05-31 | Modernatx, Inc. | Metode uporabe liganda OX40, ki kodira polinukleotid |
| CN105483233B (zh) * | 2015-12-24 | 2018-07-20 | 北京大学第一医院 | 检测miR-3158-5p表达量的系统在预测阿司匹林对心血管疾病患者疗效中的应用 |
| US11021756B2 (en) * | 2016-01-04 | 2021-06-01 | Yang Zuozhang | MiRNA markers for the diagnosis of osteosarcoma |
| US20210206818A1 (en) * | 2016-01-22 | 2021-07-08 | Modernatx, Inc. | Messenger ribonucleic acids for the production of intracellular binding polypeptides and methods of use thereof |
| US20200330606A1 (en) * | 2016-03-29 | 2020-10-22 | Valkyrie Therapeutics Inc. | Modulation of structural maintenance of chromosome-1 expression |
| WO2017167910A1 (en) * | 2016-03-31 | 2017-10-05 | Ethris Gmbh | Novel minimal utr sequences |
| CA3020343A1 (en) | 2016-04-08 | 2017-10-12 | Translate Bio, Inc. | Multimeric coding nucleic acid and uses thereof |
| WO2017190061A1 (en) * | 2016-04-29 | 2017-11-02 | The University Of Chicago | Synthetic dna binding domain peptides and uses thereof |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| CA3024509A1 (en) * | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | Mrna combination therapy for the treatment of cancer |
| CA3024507A1 (en) | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | Polynucleotides encoding .alpha.-galactosidase a for the treatment of fabry disease |
| US12128113B2 (en) | 2016-05-18 | 2024-10-29 | Modernatx, Inc. | Polynucleotides encoding JAGGED1 for the treatment of Alagille syndrome |
| WO2017201349A1 (en) | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | Polynucleotides encoding citrin for the treatment of citrullinemia type 2 |
| EP3458105B1 (en) | 2016-05-18 | 2024-01-17 | Modernatx, Inc. | Polynucleotides encoding galactose-1-phosphate uridylyltransferase for the treatment of galactosemia type 1 |
| AU2017266948B2 (en) | 2016-05-18 | 2024-07-04 | Fundacion Para La Investigacion Medica Aplicada | Polynucleotides encoding porphobilinogen deaminase for the treatment of acute intermittent porphyria |
| JP7194594B2 (ja) | 2016-05-18 | 2022-12-22 | モデルナティエックス インコーポレイテッド | 免疫調節ポリペプチドをコードするmRNAの組み合わせ及びその使用 |
| JP7246930B2 (ja) | 2016-05-18 | 2023-03-28 | モデルナティエックス インコーポレイテッド | インターロイキン-12(il12)をコードするポリヌクレオチドおよびその使用 |
| US20190298657A1 (en) | 2016-05-18 | 2019-10-03 | Modernatx, Inc. | Polynucleotides Encoding Acyl-CoA Dehydrogenase, Very Long-Chain for the Treatment of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency |
| WO2017210735A1 (en) * | 2016-06-07 | 2017-12-14 | Garvan Institute Of Medical Research | Methods of treating neuroblastoma and reagents therefor |
| CN109312313A (zh) | 2016-06-13 | 2019-02-05 | 川斯勒佰尔公司 | 用于治疗鸟氨酸转氨甲酰酶缺乏症的信使rna疗法 |
| AU2017286606A1 (en) | 2016-06-14 | 2018-12-13 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
| US12385034B2 (en) | 2016-06-24 | 2025-08-12 | Modernatx, Inc. | Methods and apparatus for filtration |
| US20190161730A1 (en) | 2016-07-07 | 2019-05-30 | Rubius Therapeutics, Inc. | Compositions and methods related to therapeutic cell systems expressing exogenous rna |
| WO2018018077A1 (en) * | 2016-07-25 | 2018-02-01 | Garvan Institute Of Medical Research | Methods of treating breast cancer and reagents therefor |
| SG11201903674YA (en) | 2016-10-26 | 2019-05-30 | Modernatx Inc | Messenger ribonucleic acids for enhancing immune responses and methods of use thereof |
| EP3538067A1 (en) | 2016-11-08 | 2019-09-18 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
| WO2018094964A1 (zh) * | 2016-11-25 | 2018-05-31 | 武汉大学 | 一种以凋亡信号调节激酶1n端二聚化为靶点筛选用于治疗脂肪性肝炎药物的方法 |
| EA201991804A1 (ru) | 2017-02-01 | 2020-02-07 | МОДЕРНАТиЭкс, ИНК. | ИММУНОМОДУЛИРУЮЩИЕ ТЕРАПЕВТИЧЕСКИЕ КОМПОЗИЦИИ мРНК, КОДИРУЮЩЕЙ ПЕПТИДЫ С АКТИВИРУЮЩЕЙ ОНКОГЕННОЙ МУТАЦИЕЙ |
| EA201991747A1 (ru) | 2017-02-27 | 2020-06-04 | Транслейт Био, Инк. | НОВАЯ КОДОН-ОПТИМИЗИРОВАННАЯ мРНК CFTR |
| US11629340B2 (en) | 2017-03-03 | 2023-04-18 | Obsidian Therapeutics, Inc. | DHFR tunable protein regulation |
| WO2018172556A1 (en) | 2017-03-24 | 2018-09-27 | Curevac Ag | Nucleic acids encoding crispr-associated proteins and uses thereof |
| SI3612624T1 (sl) * | 2017-04-21 | 2025-03-31 | Ospedale San Raffaele S.R.L. | Genska terapija |
| CA3063531A1 (en) | 2017-05-16 | 2018-11-22 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of codon-optimized mrna encoding cftr |
| WO2018213789A1 (en) | 2017-05-18 | 2018-11-22 | Modernatx, Inc. | Modified messenger rna comprising functional rna elements |
| AU2018270111B2 (en) | 2017-05-18 | 2022-07-14 | Modernatx, Inc. | Polynucleotides encoding tethered interleukin-12 (IL12) polypeptides and uses thereof |
| CN118048460A (zh) * | 2017-06-29 | 2024-05-17 | 东丽株式会社 | 用于检测肺癌的试剂盒、装置和方法 |
| JP7318931B2 (ja) * | 2017-07-12 | 2023-08-01 | 国立大学法人京都大学 | 高発現性mRNAスイッチ |
| JP7275111B2 (ja) | 2017-08-31 | 2023-05-17 | モデルナティエックス インコーポレイテッド | 脂質ナノ粒子の生成方法 |
| EP3725092A4 (en) | 2017-12-14 | 2021-09-22 | FloDesign Sonics, Inc. | DRIVE AND CONTROL UNIT FOR ACOUSTIC CONVERTER |
| AU2018392716B2 (en) | 2017-12-20 | 2025-03-13 | Translate Bio, Inc. | Improved composition and methods for treatment of ornithine transcarbamylase deficiency |
| AU2019216307A1 (en) | 2018-01-30 | 2020-07-09 | Modernatx, Inc. | Compositions and methods for delivery of agents to immune cells |
| KR102141124B1 (ko) | 2018-01-30 | 2020-08-04 | (주)바이오니아 | 이중 가닥 miRNA를 포함하는 이중나선 올리고뉴클레오타이드 구조체 및 이의 용도 |
| WO2019199974A1 (en) * | 2018-04-10 | 2019-10-17 | Onconetics Pharmaceuticals, Inc. | Microrna regulated expression vectors, methods of making, and uses thereof |
| KR102070969B1 (ko) * | 2018-04-10 | 2020-01-29 | 한국한의학연구원 | 통증 판별용 마커 |
| US20210163928A1 (en) | 2018-04-11 | 2021-06-03 | Modernatx, Inc. | Messenger rna comprising functional rna elements |
| JP7462227B2 (ja) * | 2018-04-25 | 2024-04-05 | 東レ株式会社 | 膀胱がんの検出のためのキット、デバイス及び方法 |
| CN108760700A (zh) * | 2018-05-29 | 2018-11-06 | 云南健牛生物科技有限公司 | 一种荧光金纳米簇的制备及用于四环素及铜荧光探针 |
| AU2019319623A1 (en) | 2018-08-08 | 2021-02-25 | Theramir Ltd | Microrna-based therapy targeted against LCP-1 positive cancers |
| EP3841208A1 (en) | 2018-08-24 | 2021-06-30 | Translate Bio, Inc. | Methods for purification of messenger rna |
| CA3110289A1 (en) * | 2018-08-30 | 2020-03-05 | The University Of North Carolina At Chapel Hill | Feedback enabled synthetic genes, target seed match cassettes, and their uses |
| 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 |
| US12090235B2 (en) | 2018-09-20 | 2024-09-17 | Modernatx, Inc. | Preparation of lipid nanoparticles and methods of administration thereof |
| CN109439749B (zh) * | 2018-09-26 | 2022-06-24 | 北京恩泽康泰生物科技有限公司 | 用于结直肠癌诊断的外泌体miRNA标志物及诊断试剂盒 |
| WO2020102609A1 (en) * | 2018-11-15 | 2020-05-22 | The Trustees Of The University Of Pennsylvania | Compositions and methods for the cytoplasmic delivery of antibodies and other proteins |
| MX2021005969A (es) | 2018-11-21 | 2021-09-14 | Translate Bio Inc | Tratamiento de la fibrosis quística mediante el suministro de arnm que codifica cftr nebulizado. |
| US12042527B2 (en) | 2019-01-08 | 2024-07-23 | Modernatx, Inc. | Use of mRNAs encoding OX40L, IL-23 and IL-36gamma in combination with immune checkpoint blockade for treating particular cancers |
| CA3128215A1 (en) | 2019-01-31 | 2020-08-06 | Modernatx, Inc. | Methods of preparing lipid nanoparticles |
| CN114174313A (zh) | 2019-04-09 | 2022-03-11 | 芝加哥大学 | 采用狄尔斯-阿尔德环加成反应的通用型肽和蛋白质的大环化和多聚化 |
| MA55896A (fr) | 2019-05-07 | 2022-03-16 | Modernatx Inc | Polynucléotides servant à perturber l'activité de cellule immunitaire et procédés pour les utiliser |
| WO2020246380A1 (ja) * | 2019-06-05 | 2020-12-10 | 株式会社キャンサーステムテック | 癌治療剤 |
| US20220372489A1 (en) * | 2019-06-21 | 2022-11-24 | Quralis Corporation | Ppm1a inhibitors and methods of using same |
| US20220387628A1 (en) | 2019-06-24 | 2022-12-08 | Modernatx, Inc. | Messenger rna comprising functional rna elements and uses thereof |
| EP3987027A1 (en) | 2019-06-24 | 2022-04-27 | ModernaTX, Inc. | Endonuclease-resistant messenger rna and uses thereof |
| CN110628907B (zh) * | 2019-09-09 | 2023-01-24 | 张宝华 | 一组胆囊癌血浆外泌体microRNAs标记物及其应用 |
| CN110845596B (zh) * | 2019-11-15 | 2021-09-03 | 上海交通大学 | 突变体xSUMO及其相关产品 |
| CN113134010B (zh) * | 2020-01-20 | 2023-09-01 | 上海市生物医药技术研究院 | 一种靶向雌激素受体α的微小RNA及其抗肿瘤用途 |
| TW202139976A (zh) | 2020-01-31 | 2021-11-01 | 美商現代公司 | 製備脂質奈米顆粒之方法 |
| CN111440802A (zh) * | 2020-03-16 | 2020-07-24 | 复旦大学附属妇产科医院 | 一种用于表达rp11-395g23.3的序列及其构建体和构建方法与应用 |
| CN113621708B (zh) * | 2020-03-30 | 2022-02-15 | 中国医学科学院肿瘤医院 | 用于肺癌诊断的试剂盒、装置及方法 |
| CA3178889A1 (en) * | 2020-03-31 | 2021-10-07 | Toray Industries, Inc. | Kit or device and method for detecting hippocampal atrophy |
| CA3182920A1 (en) | 2020-05-14 | 2021-11-18 | Modernatx, Inc. | Lnp compositions comprising an mrna therapeutic and an effector molecule |
| KR20230042005A (ko) | 2020-06-23 | 2023-03-27 | 모더나티엑스, 인크. | 반감기가 연장된 mrna 치료제를 포함하는 lnp 조성물 |
| PH12022553532A1 (en) * | 2020-07-10 | 2024-06-24 | SociaTa Des Produits Nestla S A | Nutritional composition comprising mir-3184 |
| CA3190790A1 (en) | 2020-08-06 | 2022-02-10 | Modernatx, Inc. | Methods of preparing lipid nanoparticles |
| CN113234782A (zh) * | 2020-08-20 | 2021-08-10 | 深圳市瑞吉生物科技有限公司 | 一种Cap2结构5′帽子类似物及其制备方法和应用 |
| EP4291165A1 (en) | 2021-02-12 | 2023-12-20 | ModernaTX, Inc. | Lnp compositions comprising payloads for in vivo therapy |
| EP4334446A1 (en) | 2021-05-03 | 2024-03-13 | CureVac SE | Improved nucleic acid sequence for cell type specific expression |
| US20240384277A1 (en) | 2021-06-15 | 2024-11-21 | Modernatx, Inc. | Engineered polynucleotides for cell-type or microenvironment-specific expression |
| WO2023277168A1 (ja) * | 2021-06-30 | 2023-01-05 | 協和キリン株式会社 | ポリヌクレオチド及び医薬組成物 |
| US20250281583A1 (en) | 2021-10-13 | 2025-09-11 | Modernatx, Inc. | Composition of mrna-encoded il15 fusion proteins and methods of use thereof |
| CN114107347B (zh) * | 2021-11-24 | 2022-10-28 | 中国人民解放军空军军医大学 | 一种基于具有按需抗炎功能、装载炎症响应型mRNA的工程化外泌体及其构建方法和应用 |
| CN114854740B (zh) * | 2022-03-29 | 2024-03-15 | 南京医科大学 | miR-483-5p海绵体及在制备抑制2型糖尿病β细胞去分化的药物中的用途 |
| US12325881B2 (en) * | 2022-04-04 | 2025-06-10 | Agency For Science, Technology And Research | Method of determining and treating breast cancer |
| US20250375389A1 (en) | 2022-07-29 | 2025-12-11 | Modernatx, Inc. | Lipid nanoparticle compositions comprising phospholipid derivatives and related uses |
| EP4561546A1 (en) | 2022-07-29 | 2025-06-04 | ModernaTX, Inc. | Lipid nanoparticle compositions comprising surface lipid derivatives and related uses |
| WO2024026475A1 (en) | 2022-07-29 | 2024-02-01 | Modernatx, Inc. | Compositions for delivery to hematopoietic stem and progenitor cells (hspcs) and related uses |
| IL319526A (en) | 2022-09-30 | 2025-05-01 | Extend Biosciences Inc | Long-acting parathyroid hormone |
| CN115261482B (zh) * | 2022-10-08 | 2022-12-09 | 暨南大学 | miR-4256在胃癌治疗、诊断以及预后评估中的应用 |
| CN115869332A (zh) * | 2022-10-27 | 2023-03-31 | 北京新合睿恩生物医疗科技有限公司 | 递送至体内后在肝脏少表达的mRNA药物及其制备方法 |
| WO2024178305A1 (en) | 2023-02-24 | 2024-08-29 | Modernatx, Inc. | Compositions of mrna-encoded il-15 fusion proteins and methods of use thereof for treating cancer |
| CN116286628B (zh) * | 2023-05-15 | 2023-07-28 | 四川大学华西医院 | 一种牙髓间充质干细胞培养基添加物、培养基及其应用 |
| WO2024259373A1 (en) | 2023-06-14 | 2024-12-19 | Modernatx, Inc. | Compounds and compositions for delivery of therapeutic agents |
| WO2025160381A1 (en) | 2024-01-26 | 2025-07-31 | Modernatx, Inc. | Methods of preparing lipid nanoparticles |
| WO2025166202A1 (en) | 2024-01-31 | 2025-08-07 | Modernatx, Inc. | Lipid nanoparticle compositions comprising sialic acid derivatives and the uses thereof |
| WO2025184429A1 (en) | 2024-02-28 | 2025-09-04 | Modernatx, Inc. | Bromodomain and extra-terminal domain (bet) epigenetic reader decoy |
| WO2025194138A1 (en) | 2024-03-14 | 2025-09-18 | Tessera Therapeutics, Inc. | St1cas9 compositions and methods for modulating a genome |
Family Cites Families (300)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2588623A (en) | 1948-05-10 | 1952-03-11 | Eliscu Frank | Surgical instrument for intradermal injection of fluids |
| US3467096A (en) | 1966-04-12 | 1969-09-16 | Ferrell S Horn | Multiple hypodermic syringe arrangement |
| US3572336A (en) | 1968-04-30 | 1971-03-23 | Daniel R Hershberg | Syringe |
| US4270537A (en) | 1979-11-19 | 1981-06-02 | Romaine Richard A | Automatic hypodermic syringe |
| JPS5927900A (ja) | 1982-08-09 | 1984-02-14 | Wakunaga Seiyaku Kk | 固定化オリゴヌクレオチド |
| FR2540122B1 (fr) | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
| US4605735A (en) | 1983-02-14 | 1986-08-12 | Wakunaga Seiyaku Kabushiki Kaisha | Oligonucleotide derivatives |
| US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
| US4824941A (en) | 1983-03-10 | 1989-04-25 | Julian Gordon | Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems |
| US4587044A (en) | 1983-09-01 | 1986-05-06 | The Johns Hopkins University | Linkage of proteins to nucleic acids |
| US5118802A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5430136A (en) | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
| US5258506A (en) | 1984-10-16 | 1993-11-02 | Chiron Corporation | Photolabile reagents for incorporation into oligonucleotide chains |
| US4828979A (en) | 1984-11-08 | 1989-05-09 | Life Technologies, Inc. | Nucleotide analogs for nucleic acid labeling and detection |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US4762779A (en) | 1985-06-13 | 1988-08-09 | Amgen Inc. | Compositions and methods for functionalizing nucleic acids |
| US5317098A (en) | 1986-03-17 | 1994-05-31 | Hiroaki Shizuya | Non-radioisotope tagging of fragments |
| US4695273A (en) | 1986-04-08 | 1987-09-22 | I-Flow Corporation | Multiple needle holder and subcutaneous multiple channel infusion port |
| JPS638396A (ja) | 1986-06-30 | 1988-01-14 | Wakunaga Pharmaceut Co Ltd | ポリ標識化オリゴヌクレオチド誘導体 |
| US4886499A (en) | 1986-12-18 | 1989-12-12 | Hoffmann-La Roche Inc. | Portable injection appliance |
| GB8704027D0 (en) | 1987-02-20 | 1987-03-25 | Owen Mumford Ltd | Syringe needle combination |
| US4904582A (en) | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US4940460A (en) | 1987-06-19 | 1990-07-10 | Bioject, Inc. | Patient-fillable and non-invasive hypodermic injection device assembly |
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US5525465A (en) | 1987-10-28 | 1996-06-11 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates and methods of production and applications of the same |
| DE3738460A1 (de) | 1987-11-12 | 1989-05-24 | Max Planck Gesellschaft | Modifizierte oligonukleotide |
| US5082830A (en) | 1988-02-26 | 1992-01-21 | Enzo Biochem, Inc. | End labeled nucleotide probe |
| US5339163A (en) | 1988-03-16 | 1994-08-16 | Canon Kabushiki Kaisha | Automatic exposure control device using plural image plane detection areas |
| US5109124A (en) | 1988-06-01 | 1992-04-28 | Biogen, Inc. | Nucleic acid probe linked to a label having a terminal cysteine |
| US5262536A (en) | 1988-09-15 | 1993-11-16 | E. I. Du Pont De Nemours And Company | Reagents for the preparation of 5'-tagged oligonucleotides |
| FR2638359A1 (fr) | 1988-11-03 | 1990-05-04 | Tino Dalto | Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau |
| US5512439A (en) | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
| US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
| US5599923A (en) | 1989-03-06 | 1997-02-04 | Board Of Regents, University Of Tx | Texaphyrin metal complexes having improved functionalization |
| US5391723A (en) | 1989-05-31 | 1995-02-21 | Neorx Corporation | Oligonucleotide conjugates |
| US4958013A (en) | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
| US5451463A (en) | 1989-08-28 | 1995-09-19 | Clontech Laboratories, Inc. | Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides |
| US5254469A (en) | 1989-09-12 | 1993-10-19 | Eastman Kodak Company | Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| AU658562B2 (en) | 1989-10-24 | 1995-04-27 | Isis Pharmaceuticals, Inc. | 2' modified oligonucleotides |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5292873A (en) | 1989-11-29 | 1994-03-08 | The Research Foundation Of State University Of New York | Nucleic acids labeled with naphthoquinone probe |
| US5486603A (en) | 1990-01-08 | 1996-01-23 | Gilead Sciences, Inc. | Oligonucleotide having enhanced binding affinity |
| US6783931B1 (en) | 1990-01-11 | 2004-08-31 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US5578718A (en) | 1990-01-11 | 1996-11-26 | Isis Pharmaceuticals, Inc. | Thiol-derivatized nucleosides |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US7037646B1 (en) | 1990-01-11 | 2006-05-02 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
| AU7579991A (en) | 1990-02-20 | 1991-09-18 | Gilead Sciences, Inc. | Pseudonucleosides and pseudonucleotides and their polymers |
| US5214136A (en) | 1990-02-20 | 1993-05-25 | Gilead Sciences, Inc. | Anthraquinone-derivatives oligonucleotides |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| ES2116977T3 (es) | 1990-05-11 | 1998-08-01 | Microprobe Corp | Soportes solidos para ensayos de hibridacion de acidos nucleicos y metodos para inmovilizar oligonucleotidos de modo covalente. |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5218105A (en) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5245022A (en) | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
| US5190521A (en) | 1990-08-22 | 1993-03-02 | Tecnol Medical Products, Inc. | Apparatus and method for raising a skin wheal and anesthetizing skin |
| US5512667A (en) | 1990-08-28 | 1996-04-30 | Reed; Michael W. | Trifunctional intermediates for preparing 3'-tailed oligonucleotides |
| CA2095212A1 (en) | 1990-11-08 | 1992-05-09 | Sudhir Agrawal | Incorporation of multiple reporter groups on synthetic oligonucleotides |
| US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| US5371241A (en) | 1991-07-19 | 1994-12-06 | Pharmacia P-L Biochemicals Inc. | Fluorescein labelled phosphoramidites |
| GB9118204D0 (en) | 1991-08-23 | 1991-10-09 | Weston Terence E | Needle-less injector |
| SE9102652D0 (sv) | 1991-09-13 | 1991-09-13 | Kabi Pharmacia Ab | Injection needle arrangement |
| EP0538194B1 (de) | 1991-10-17 | 1997-06-04 | Novartis AG | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| US5565552A (en) | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
| US5595726A (en) | 1992-01-21 | 1997-01-21 | Pharmacyclics, Inc. | Chromophore probe for detection of nucleic acid |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| US5328483A (en) | 1992-02-27 | 1994-07-12 | Jacoby Richard M | Intradermal injection device with medication and needle guard |
| DE69231123T2 (de) | 1992-03-25 | 2001-02-15 | Immunogen Inc | Konjugaten von Zell-bindender Mittel und Derivaten von CC-1065 |
| EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| US5272250A (en) | 1992-07-10 | 1993-12-21 | Spielvogel Bernard F | Boronated phosphoramidate compounds |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| US5569189A (en) | 1992-09-28 | 1996-10-29 | Equidyne Systems, Inc. | hypodermic jet injector |
| US5334144A (en) | 1992-10-30 | 1994-08-02 | Becton, Dickinson And Company | Single use disposable needleless injector |
| US5574142A (en) | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
| RU2143903C1 (ru) | 1993-02-19 | 2000-01-10 | Ниппон Синяку Ко., Лтд. | Фармацевтическая композиция, содержащая сополимер нуклеиновой кислоты |
| DK0691968T3 (da) | 1993-03-30 | 1998-02-23 | Sanofi Sa | Acykliske nukleosid-analoge og oligonukleotidsekvenser indeholdende disse |
| DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
| US6294664B1 (en) | 1993-07-29 | 2001-09-25 | Isis Pharmaceuticals, Inc. | Synthesis of oligonucleotides |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| WO1995024176A1 (en) | 1994-03-07 | 1995-09-14 | Bioject, Inc. | Ampule filling device |
| US5466220A (en) | 1994-03-08 | 1995-11-14 | Bioject, Inc. | Drug vial mixing and transfer device |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5464395A (en) | 1994-04-05 | 1995-11-07 | Faxon; David P. | Catheter for delivering therapeutic and/or diagnostic agents to the tissue surrounding a bodily passageway |
| US5597696A (en) | 1994-07-18 | 1997-01-28 | Becton Dickinson And Company | Covalent cyanine dye oligonucleotide conjugates |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5580731A (en) | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
| US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
| US5795587A (en) | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| US5730723A (en) | 1995-10-10 | 1998-03-24 | Visionary Medical Products Corporation, Inc. | Gas pressured needle-less injection device and method |
| US5713863A (en) | 1996-01-11 | 1998-02-03 | Interventional Technologies Inc. | Catheter with fluid medication injectors |
| US5893397A (en) | 1996-01-12 | 1999-04-13 | Bioject Inc. | Medication vial/syringe liquid-transfer apparatus |
| US5994316A (en) | 1996-02-21 | 1999-11-30 | The Immune Response Corporation | Method of preparing polynucleotide-carrier complexes for delivery to cells |
| GB9607549D0 (en) | 1996-04-11 | 1996-06-12 | Weston Medical Ltd | Spring-powered dispensing device |
| US20030073908A1 (en) | 1996-04-26 | 2003-04-17 | 2000 Injectx, Inc. | Method and apparatus for delivery of genes, enzymes and biological agents to tissue cells |
| EP0925088A2 (en) | 1996-06-28 | 1999-06-30 | Sontra Medical, L.P. | Ultrasound enhancement of transdermal transport |
| US6576752B1 (en) | 1997-02-14 | 2003-06-10 | Isis Pharmaceuticals, Inc. | Aminooxy functionalized oligomers |
| 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 |
| US6761726B1 (en) | 1998-05-15 | 2004-07-13 | Pyng Medical Corp. | Method and apparatus for the intraosseous introduction of a device such as an infusion tube |
| US5993412A (en) | 1997-05-19 | 1999-11-30 | Bioject, Inc. | Injection apparatus |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| CA2304982A1 (en) * | 1997-09-19 | 1999-03-25 | Sequitur, Inc. | Sense mrna therapy |
| US6077251A (en) | 1997-10-30 | 2000-06-20 | Ting; Windsor | Medicinal agent administration system |
| 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 |
| US6548633B1 (en) | 1998-12-22 | 2003-04-15 | Genset, S.A. | Complementary DNA's encoding proteins with signal peptides |
| US6517869B1 (en) | 1997-12-12 | 2003-02-11 | Expression Genetics, Inc. | Positively charged poly(alpha-(omega-aminoalkyl)lycolic acid) for the delivery of a bioactive agent via tissue and cellular uptake |
| WO1999029758A1 (en) | 1997-12-12 | 1999-06-17 | Samyang Corporation | Positively-charged poly[alpha-(omega-aminoalkyl)glycolic acid] for the delivery of a bioactive agent via tissue and cellular uptake |
| US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
| JP2002500075A (ja) | 1998-01-08 | 2002-01-08 | ソントラ メディカル, インコーポレイテッド | 超音波伝達で増強される経皮輸送 |
| IT1298087B1 (it) | 1998-01-08 | 1999-12-20 | Fiderm S R L | Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni |
| US8287483B2 (en) | 1998-01-08 | 2012-10-16 | Echo Therapeutics, Inc. | Method and apparatus for enhancement of transdermal transport |
| US6177274B1 (en) | 1998-05-20 | 2001-01-23 | Expression Genetics, Inc. | Hepatocyte targeting polyethylene glyco-grafted poly-L-lysine polymeric gene carrier |
| TR200100254T2 (tr) | 1998-07-13 | 2001-06-21 | Expression Genetics, Inc. | Eriyebilir ve bakterilerle ayrışabilir bir gen iletim taşıyıcısı olarak poly-l-lysine benzeri bir poliyester. |
| US20040171980A1 (en) | 1998-12-18 | 2004-09-02 | Sontra Medical, Inc. | Method and apparatus for enhancement of transdermal transport |
| JP2003535617A (ja) | 1999-03-01 | 2003-12-02 | プロ ダクト ヘルス インコーポレーティッド | 多数の乳管に物質を同時に送達するための装置、方法、およびキット |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| JP2002543214A (ja) | 1999-05-04 | 2002-12-17 | エクシコン エ/エス | L−リボ−lna類縁体 |
| US7171264B1 (en) | 1999-05-10 | 2007-01-30 | Genetronics, Inc. | Intradermal delivery of active agents by needle-free injection and electroporation |
| US6743211B1 (en) | 1999-11-23 | 2004-06-01 | Georgia Tech Research Corporation | Devices and methods for enhanced microneedle penetration of biological barriers |
| CA2311201A1 (en) | 1999-08-05 | 2001-02-05 | Genset S.A. | Ests and encoded human proteins |
| US6551338B1 (en) | 1999-09-01 | 2003-04-22 | Mcgill University | Method and device for myogenesis and angiogenesis of the heart |
| US20020198509A1 (en) | 1999-10-14 | 2002-12-26 | Mikszta John A. | Intradermal delivery of vaccines and gene therapeutic agents via microcannula |
| SE515932C2 (sv) | 1999-12-23 | 2001-10-29 | Prostalund Operations Ab | Sätt och anordning vid behandling av prostata |
| AU3117101A (en) | 2000-01-28 | 2001-08-07 | Scripps Research Inst | Synthetic internal ribosome entry sites and methods of identifying same |
| US7468275B2 (en) | 2000-01-28 | 2008-12-23 | The Scripps Research Institute | Synthetic internal ribosome entry sites and methods of identifying same |
| US6468247B1 (en) | 2000-04-21 | 2002-10-22 | Mark Zamoyski | Perfusion device for localized drug delivery |
| US6537242B1 (en) | 2000-06-06 | 2003-03-25 | Becton, Dickinson And Company | Method and apparatus for enhancing penetration of a member for the intradermal sampling or administration of a substance |
| US6607513B1 (en) | 2000-06-08 | 2003-08-19 | Becton, Dickinson And Company | Device for withdrawing or administering a substance and method of manufacturing a device |
| US20050181033A1 (en) | 2000-06-29 | 2005-08-18 | Dekker John P.Iii | Method for delivering interferons to the intradermal compartment |
| US20040142474A1 (en) | 2000-09-14 | 2004-07-22 | Expression Genetics, Inc. | Novel cationic lipopolymer as a biocompatible gene delivery agent |
| US6696038B1 (en) | 2000-09-14 | 2004-02-24 | Expression Genetics, Inc. | Cationic lipopolymer as biocompatible gene delivery agent |
| DE60119562T2 (de) | 2000-10-04 | 2007-05-10 | Santaris Pharma A/S | Verbesserte synthese von purin-blockierten nukleinsäure-analoga |
| US7628780B2 (en) | 2001-01-13 | 2009-12-08 | Medtronic, Inc. | Devices and methods for interstitial injection of biologic agents into tissue |
| US6652886B2 (en) | 2001-02-16 | 2003-11-25 | Expression Genetics | Biodegradable cationic copolymers of poly (alkylenimine) and poly (ethylene glycol) for the delivery of bioactive agents |
| US6625486B2 (en) | 2001-04-11 | 2003-09-23 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for intracellular delivery of an agent |
| ES2356934T3 (es) | 2001-06-05 | 2011-04-14 | Curevac Gmbh | ARNm ESTABILIZADO CON UN CONTENIDO DE G/C AUMENTADO QUE CODIFICA PARA UN ANTÍGENO VIRAL. |
| US6586524B2 (en) | 2001-07-19 | 2003-07-01 | Expression Genetics, Inc. | Cellular targeting poly(ethylene glycol)-grafted polymeric gene carrier |
| EP2428568B1 (en) | 2001-09-28 | 2018-04-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Microrna molecules |
| US7429258B2 (en) | 2001-10-26 | 2008-09-30 | Massachusetts Institute Of Technology | Microneedle transport device |
| WO2003094995A1 (en) | 2002-05-06 | 2003-11-20 | Becton, Dickinson And Company | Method and device for controlling drug pharmacokinetics |
| BR0311849A (pt) | 2002-05-08 | 2005-04-05 | Univ California | Sistema para formar um bloqueio de condução em uma estrutura de tecido cardìaco para tratar uma arritmia cardìaca em um coração de um paciente, métodos para tratar uma arritmia cardìaca em um coração de um paciente e para montar um sistema de tratamento de arritmia cardìaca a partir de uma pluralidade de sistemas de distribuição cardìacos, e, sistema para tratar uma arritmia cardìaca em um coração de um paciente |
| US7374930B2 (en) | 2002-05-21 | 2008-05-20 | Expression Genetics, Inc. | GLP-1 gene delivery for the treatment of type 2 diabetes |
| US20040009180A1 (en) | 2002-07-11 | 2004-01-15 | Allergan, Inc. | Transdermal botulinum toxin compositions |
| CA2492639C (en) | 2002-08-01 | 2013-06-18 | Abbott Laboratories Vascular Enterprises, Limited | Apparatus for sealing a puncture by causing a reduction in the circumference of the puncture |
| JP2006508056A (ja) * | 2002-08-28 | 2006-03-09 | イミュネックス・コーポレーション | 心臓血管疾患を治療するための組成物および方法 |
| MXPA05002270A (es) | 2002-08-30 | 2005-06-08 | Becton Dickinson Co | Metodo para controlar farmacocineticos de compuestos inmunomoduladores. |
| US6896666B2 (en) | 2002-11-08 | 2005-05-24 | Kochamba Family Trust | Cutaneous injection delivery under suction |
| JP4959136B2 (ja) | 2002-12-13 | 2012-06-20 | イミューノメディクス、インコーポレイテッド | 細胞内で開裂可能な結合を有する免疫接合体 |
| KR20050115231A (ko) * | 2003-02-10 | 2005-12-07 | 내셔날 인스티튜트 오브 어드밴스드 인더스트리얼 사이언스 앤드 테크놀로지 | 포유동물 세포의 조절 |
| US20040226556A1 (en) | 2003-05-13 | 2004-11-18 | Deem Mark E. | Apparatus for treating asthma using neurotoxin |
| EP2530157B1 (en) | 2003-07-31 | 2016-09-28 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of miRNAs |
| US7998119B2 (en) | 2003-11-18 | 2011-08-16 | Nano Pass Technologies Ltd. | System and method for delivering fluid into flexible biological barrier |
| US7150726B2 (en) | 2004-01-23 | 2006-12-19 | Norfolk Medical | Device for subcutaneous infusion of fluids |
| EP1713514B1 (en) | 2004-01-28 | 2021-11-24 | Johns Hopkins University | Drugs and gene carrier particles that rapidly move through mucous barriers |
| CA2562643A1 (en) | 2004-04-12 | 2005-11-24 | Allergan, Inc. | Multi-site injection system |
| US20080103053A1 (en) | 2005-11-22 | 2008-05-01 | Helicos Biosciences Corporation | Methods and compositions for sequencing a nucleic acid |
| US8338648B2 (en) | 2004-06-12 | 2012-12-25 | Signum Biosciences, Inc. | Topical compositions and methods for epithelial-related conditions |
| US7527947B2 (en) | 2004-06-14 | 2009-05-05 | Novozymes A/S | Signal peptide for producing a polypeptide |
| EP1768742A4 (en) | 2004-07-06 | 2007-10-17 | Transpharma Medical Ltd | ADMINISTRATION SYSTEM FOR TRANSDERMAL IMMUNIZATION |
| JPWO2006028245A1 (ja) | 2004-09-07 | 2008-05-08 | 河淳株式会社 | 商品自動前出し棚装置 |
| US8057821B2 (en) | 2004-11-03 | 2011-11-15 | Egen, Inc. | Biodegradable cross-linked cationic multi-block copolymers for gene delivery and methods of making thereof |
| WO2006054280A2 (en) | 2004-11-18 | 2006-05-26 | Nanopass Technologies Ltd. | System and method for delivering fluid into flexible biological barrier |
| US7964571B2 (en) | 2004-12-09 | 2011-06-21 | Egen, Inc. | Combination of immuno gene therapy and chemotherapy for treatment of cancer and hyperproliferative diseases |
| CA2590098C (en) | 2004-12-10 | 2015-03-31 | Justin Hanes | Functionalized poly (ether-anhydride) block copolymers |
| US20060263338A1 (en) | 2005-03-04 | 2006-11-23 | Jacoby Douglas B | Catheter-based delivery of Skeletal Myoblasts to the Myocardium of Damaged Hearts |
| JP4793806B2 (ja) | 2005-03-22 | 2011-10-12 | Tti・エルビュー株式会社 | イオントフォレーシス装置 |
| EP1874936B1 (en) * | 2005-04-19 | 2013-10-30 | BASF Plant Science GmbH | Improved methods controlling gene expression |
| US7850656B2 (en) | 2005-04-29 | 2010-12-14 | Warsaw Orthopedic, Inc. | Devices and methods for delivering medical agents |
| CA2609142C (en) * | 2005-05-27 | 2016-02-09 | Fondazione Centro San Raffaele Del Monte Tabor | Therapeutic gene vectors comprising mirna target sequences |
| US7691086B2 (en) | 2005-06-14 | 2010-04-06 | Tengiz Tkebuchava | Catheter for introduction of medications to the tissues of a heart or other organ |
| MX2007016561A (es) | 2005-06-30 | 2008-03-10 | Archemix Corp | Materiales y metodos para la generacion de transcriptos de acido nucleico completamente modificados en la posicion 2. |
| US8101385B2 (en) | 2005-06-30 | 2012-01-24 | Archemix Corp. | Materials and methods for the generation of transcripts comprising modified nucleotides |
| EP4174179B1 (en) * | 2005-08-23 | 2025-05-07 | The Trustees of the University of Pennsylvania | Rna containing modified nucleosides and methods of use thereof |
| WO2007025008A2 (en) | 2005-08-24 | 2007-03-01 | The Scripps Research Institute | Translation enhancer-element dependent vector systems |
| US20070185432A1 (en) | 2005-09-19 | 2007-08-09 | Transport Pharmaceuticals, Inc. | Electrokinetic system and method for delivering methotrexate |
| DE102005046490A1 (de) | 2005-09-28 | 2007-03-29 | Johannes-Gutenberg-Universität Mainz | Modifikationen von RNA, die zu einer erhöhten Transkriptstabilität und Translationseffizienz führen |
| US8012096B2 (en) | 2005-10-17 | 2011-09-06 | Cardiogenesis Corporation | Surgical device and method for performing combination revascularization and therapeutic substance delivery to tissue |
| JP5490413B2 (ja) | 2006-01-05 | 2014-05-14 | 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 | 膵内分泌腫瘍及び膵腺房腫瘍におけるマイクロrna発現異常 |
| ES2508893T3 (es) | 2006-01-05 | 2014-10-16 | The Ohio State University Research Foundation | Métodos basados en microARN para el diagnóstico de cánceres de estómago |
| US7399845B2 (en) | 2006-01-27 | 2008-07-15 | Isis Pharmaceuticals, Inc. | 6-modified bicyclic nucleic acid analogs |
| CA2638844C (en) | 2006-03-02 | 2016-05-03 | Thomas D. Schmittgen | Microrna expression profile associated with pancreatic cancer |
| US7361908B2 (en) | 2006-04-13 | 2008-04-22 | The Hong Kong Polytechnic University | Radiation dose estimation for radiochromic films based on measurements at multiple absorption peaks |
| DE602007012559D1 (de) | 2006-09-08 | 2011-03-31 | Univ Johns Hopkins | H die schleimhaut |
| WO2008029408A1 (en) | 2006-09-08 | 2008-03-13 | Arbel Medical Ltd. | Method and device for combined treatment |
| JP5520605B2 (ja) | 2006-09-19 | 2014-06-11 | アシュラジェン インコーポレイテッド | 膵臓疾患で差次的に発現されるマイクロrnaおよびその使用 |
| WO2008054828A2 (en) | 2006-11-01 | 2008-05-08 | The Ohio State University Research Foundation | Microrna expression signature for predicting survival and metastases in hepatocellular carcinoma |
| 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 |
| WO2008078180A2 (en) | 2006-12-22 | 2008-07-03 | Archemix Corp. | Materials and methods for the generation of transcripts comprising modified nucleotides |
| US8057426B2 (en) | 2007-01-03 | 2011-11-15 | Medtronic Vascular, Inc. | Devices and methods for injection of multiple-component therapies |
| WO2008091799A2 (en) * | 2007-01-22 | 2008-07-31 | The Trustees Of Columbia University In The City Of New York | Cell-based methods for identifying inhibitors of parkinson's disease-associated lrrk2 mutants |
| US8029496B2 (en) | 2007-03-05 | 2011-10-04 | Ebrahim Versi | Method and device for delivering drug to the trigone of the bladder |
| AU2008245585B2 (en) | 2007-04-27 | 2011-10-06 | Echo Therapeutics, Inc. | Skin permeation device for analyte sensing or transdermal drug delivery |
| 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 |
| WO2009015071A1 (en) * | 2007-07-23 | 2009-01-29 | Dharmacon, Inc. | Screening of micro-rna cluster inhibitor pools |
| US20090042825A1 (en) | 2007-08-06 | 2009-02-12 | Majed Matar | Composition, method of preparation & application of concentrated formulations of condensed nucleic acids with a cationic lipopolymer |
| CN103083794B (zh) | 2007-08-14 | 2016-03-02 | 弗雷德哈钦森癌症研究中心 | 用于递送治疗药物的针阵列组件和方法 |
| US20130108663A1 (en) | 2007-09-14 | 2013-05-02 | Vrije Universiteit Brussel | Enhancing the t-cell stimulatory capacity of human antigen presenting cells in vitro and in vivo and their use in vaccination |
| US20090137945A1 (en) | 2007-11-28 | 2009-05-28 | Claire Marquez | Electro Collagen Induction Therapy Device |
| AU2008329755A1 (en) | 2007-11-30 | 2009-06-04 | The Ohio State University Research Foundation | MicroRNA expression profiling and targeting in peripheral blood in lung cancer |
| US8785611B2 (en) | 2007-12-11 | 2014-07-22 | The Scripps Research Institute | Compositions and methods related to mRNA translational enhancer elements |
| WO2009093384A1 (ja) * | 2008-01-24 | 2009-07-30 | National Institute Of Advanced Industrial Science And Technology | ポリヌクレオチド及びポリヌクレオチド類似体並びにこれらを用いた遺伝子発現制御方法 |
| 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 |
| WO2009108891A2 (en) | 2008-02-29 | 2009-09-03 | Egen, Inc. | Modified poloxamers for gene expression and associated methods |
| US20100004315A1 (en) | 2008-03-14 | 2010-01-07 | Gregory Slobodkin | Biodegradable Cross-Linked Branched Poly(Alkylene Imines) |
| 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 |
| US9394538B2 (en) * | 2008-05-07 | 2016-07-19 | Shi-Lung Lin | Development of universal cancer drugs and vaccines |
| US8540678B2 (en) | 2008-06-06 | 2013-09-24 | Wockhardt Ltd. | Device and a system for delivery of biological material |
| US7799016B2 (en) | 2008-06-20 | 2010-09-21 | Pharmaco-Kinesis Corporation | Magnetic breather pump and a method for treating a brain tumor using the same |
| WO2009158032A1 (en) | 2008-06-25 | 2009-12-30 | Fe2, Inc. | Patches and methods for the transdermal delivery of a therapeutically effective amount of iron |
| US20100009424A1 (en) | 2008-07-14 | 2010-01-14 | Natasha Forde | Sonoporation systems and methods |
| WO2010018563A2 (en) | 2008-08-12 | 2010-02-18 | Rosetta Genomics Ltd. | Compositions and methods for the prognosis of lymphoma |
| EP2328650B1 (en) | 2008-08-26 | 2016-04-06 | Cook Medical Technologies LLC | Balloon catheters having a plurality of needles for the injection of one or more therapeutic agents |
| US20120100558A1 (en) * | 2008-09-08 | 2012-04-26 | Hanash Samir M | Lung cancer diagnosis |
| CN105056336B (zh) | 2008-10-10 | 2019-09-13 | 医树专利有限公司 | 药物输注 |
| ITVI20080239A1 (it) | 2008-10-14 | 2010-04-15 | Antoine Assaf | Apparato medicale per iniezioni multiple. |
| HUE026604T2 (hu) | 2008-10-20 | 2016-06-28 | Alnylam Pharmaceuticals Inc | Transztiretin-expresszió gátlására szolgáló készítmények és eljárások |
| EP2364362B1 (en) | 2008-11-12 | 2015-10-21 | Ospedale San Raffaele S.r.l. | Gene vector for inducing transgene-specific immune tolerance |
| US20120053224A1 (en) | 2008-12-10 | 2012-03-01 | Universitat Regensburg | Compositions and methods for micro-rna expression profiling of cancer stem cells |
| US8669085B2 (en) | 2009-02-05 | 2014-03-11 | Ut-Battelle, Llc | Transformation of gram positive bacteria by sonoporation |
| KR101800833B1 (ko) | 2009-03-20 | 2017-11-23 | 씨엘에스엔 래버러토리스, 인코퍼레이티드 | 폴리아민 유도체 |
| WO2010129860A2 (en) | 2009-05-08 | 2010-11-11 | The Ohio State University Research Foundation | Microrna expression profiling and targeting in chronic obstructive pulmonary disease (copd) lung tissue and methods of use thereof |
| SG10201912450XA (en) | 2009-06-10 | 2020-03-30 | Arbutus Biopharma Corp | Improved lipid formulation |
| EP2451823A4 (en) | 2009-07-06 | 2013-07-03 | Alnylam Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR ENHANCING THE PRODUCTION OF A BIOLOGICAL PRODUCT |
| EP3581197A1 (de) | 2009-07-31 | 2019-12-18 | ethris GmbH | Rna mit einer kombination aus unmodifizierten und modifizierten nucleotiden zur proteinexpression |
| WO2011028175A1 (en) | 2009-09-01 | 2011-03-10 | Agency For Science, Technology And Research | Terminal device and method for processing an encrypted bit stream |
| CA2782676C (en) | 2009-12-01 | 2021-06-15 | Shire Human Genetic Therapies, Inc. | Pharmaceutical compositions for intracellular delivery of nucleic acids and proteins and uses thereof for treatment of ureca cycle metabolic disorders |
| SG10201407996PA (en) | 2009-12-23 | 2015-01-29 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
| WO2011076143A1 (en) | 2009-12-24 | 2011-06-30 | Fudan University | Compositions and methods for microrna expression profiling of lung cancer |
| WO2011076142A1 (en) | 2009-12-24 | 2011-06-30 | Fudan University | Compositions and methods for microrna expession profiling in plasma of colorectal cancer |
| EP2341145A1 (en) | 2009-12-30 | 2011-07-06 | febit holding GmbH | miRNA fingerprint in the diagnosis of diseases |
| WO2011088309A1 (en) * | 2010-01-14 | 2011-07-21 | Regulus Therapeutics Inc. | Microrna compositions and methods |
| 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 |
| US9149432B2 (en) | 2010-03-19 | 2015-10-06 | Massachusetts Institute Of Technology | Lipid vesicle compositions and methods of use |
| CA2795695A1 (en) * | 2010-04-09 | 2011-10-13 | The University Of Tokyo | Microrna-controlled recombinant vaccinia virus and use thereof |
| CA3122219A1 (en) | 2010-04-16 | 2011-10-20 | The Children's Hospital Corporation | Sustained polypeptide expression from synthetic, modified rnas and uses thereof |
| US9629979B2 (en) | 2010-04-28 | 2017-04-25 | Sanovas, Inc. | Pressure/Vacuum actuated catheter drug delivery probe |
| 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 |
| US20120158100A1 (en) | 2010-06-21 | 2012-06-21 | Kevin Schomacker | Driving Microneedle Arrays into Skin and Delivering RF Energy |
| US8351828B2 (en) | 2010-06-30 | 2013-01-08 | Eastman Kodak Company | Printer having an alternate scavenger geometry |
| US8353871B2 (en) | 2010-07-05 | 2013-01-15 | Roller Jet Ltd. | Drug delivery device with needles and roller |
| AU2011276234B2 (en) | 2010-07-06 | 2016-02-25 | Glaxosmithkline Biologicals S.A. | Liposomes with lipids having an advantageous pKa- value for RNA delivery |
| FI4005592T3 (fi) | 2010-07-06 | 2023-01-13 | Virionin kaltaisia kuljetuspartikkeleita itsereplikoituville rna-molekyyleille | |
| CN103327963A (zh) | 2010-07-06 | 2013-09-25 | 诺华股份有限公司 | 阳离子水包油乳液 |
| US20130230884A1 (en) | 2010-07-16 | 2013-09-05 | John Chaput | Methods to Identify Synthetic and Natural RNA Elements that Enhance Protein Translation |
| US8822663B2 (en) * | 2010-08-06 | 2014-09-02 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| WO2012019630A1 (en) | 2010-08-13 | 2012-02-16 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded protein |
| PT3981427T (pt) | 2010-08-31 | 2022-06-27 | Glaxosmithkline Biologicals Sa | Lipossomas peguilados para entrega de arn codificador de imunogénio |
| AU2011295938B2 (en) | 2010-08-31 | 2016-01-14 | Glaxosmithkline Biologicals S.A. | Lipids suitable for liposomal delivery of protein-coding RNA |
| RS63430B1 (sr) | 2010-10-01 | 2022-08-31 | Modernatx Inc | Ribonukleinske kiseline koje sadrže n1-metil-pseudouracile i njihove primene |
| US10078075B2 (en) | 2011-12-09 | 2018-09-18 | Vanderbilt University | Integrated organ-on-chip systems and applications of the same |
| CA2816977C (en) | 2010-11-05 | 2019-10-29 | The Johns Hopkins University | Compositions and methods relating to reduced mucoadhesion |
| US10364440B2 (en) | 2011-01-04 | 2019-07-30 | Brown University | Nanotubes as carriers of nucleic acids into cells |
| US9999673B2 (en) | 2011-01-11 | 2018-06-19 | Alnylam Pharmaceuticals, Inc. | PEGylated lipids and their use for drug delivery |
| WO2012099805A2 (en) | 2011-01-19 | 2012-07-26 | Ocean Nanotech, Llc | Nanoparticle based immunological stimulation |
| EP2691101A2 (en) * | 2011-03-31 | 2014-02-05 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
| JP2014511694A (ja) | 2011-04-03 | 2014-05-19 | ザ ジェネラル ホスピタル コーポレーション ドゥーイング ビジネス アズ マサチューセッツ ジェネラル ホスピタル | 修飾型rna(mod−rna)を使用する効率的なインビボタンパク質発現 |
| WO2012151212A1 (en) | 2011-05-01 | 2012-11-08 | University Of Rochester | Multifocal hepatocellular carcinoma microrna expression patterns and uses thereof |
| EP2944961A1 (en) | 2011-05-06 | 2015-11-18 | XenTech | Markers for cancer prognosis and therapy and methods of use |
| JP5965481B2 (ja) | 2011-07-15 | 2016-08-03 | レオ ファーマ アクティーゼルスカブ | 皮膚t細胞リンパ腫(ctcl)の診断用マイクロrnaプロファイリング |
| US20150080243A1 (en) | 2011-09-01 | 2015-03-19 | Allegro Diagnostics Corp. | Methods and compositions for detecting cancer based on mirna expression profiles |
| DK3682905T3 (da) | 2011-10-03 | 2022-02-28 | Modernatx Inc | Modificerede nukleosider, nukleotider og nukleinsyrer og anvendelser deraf |
| WO2013066678A1 (en) | 2011-10-26 | 2013-05-10 | Georgetown University | Microrna expression profiling of thyroid cancer |
| TR201111743A2 (tr) | 2011-11-28 | 2012-04-24 | Nesl�Han G�Rsoy Reyhan | Kanser tedavisinde kullanılmak üzere yağ bazlı nanotaşıyıcı sistemler. |
| US10087422B2 (en) | 2011-12-09 | 2018-10-02 | President And Fellows Of Harvard College | Organ chips and uses thereof |
| WO2013086486A1 (en) | 2011-12-09 | 2013-06-13 | President And Fellows Of Harvard College | Integrated human organ-on-chip microphysiological systems |
| DE12858350T1 (de) | 2011-12-16 | 2021-10-07 | Modernatx, Inc. | Modifizierte mrna zusammensetzungen |
| 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 |
| US20150064255A1 (en) | 2012-02-22 | 2015-03-05 | Northwestern University | Nanostructures for treating cancers and other conditions |
| EP2819652A1 (en) | 2012-02-27 | 2015-01-07 | Epitarget As | Use of a particulate immunomodulator in cancer therapy |
| EP2819651A1 (en) | 2012-02-27 | 2015-01-07 | Epitarget AS | Use of an antibody and a particulate immunomodulator in therapy |
| US20130236504A1 (en) | 2012-03-06 | 2013-09-12 | Medical University Of South Carolina | Delivery System for Enhancing Drug Efficacy |
| CN104411338A (zh) * | 2012-04-02 | 2015-03-11 | 现代治疗公司 | 用于产生与人类疾病相关的生物制剂和蛋白质的修饰多核苷酸 |
| HK1206601A1 (en) * | 2012-04-02 | 2016-01-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of biologics and proteins associated with human disease |
| HRP20220607T1 (hr) * | 2012-11-26 | 2022-06-24 | Modernatx, Inc. | Terminalno modificirana rna |
| WO2014113089A2 (en) | 2013-01-17 | 2014-07-24 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
| WO2015007871A2 (en) | 2013-07-17 | 2015-01-22 | Ospedale San Raffaele S.R.L. | Micrornas and autoimmune-immune mediated inflammatory disease |
| WO2015048744A2 (en) | 2013-09-30 | 2015-04-02 | Moderna Therapeutics, Inc. | Polynucleotides encoding immune modulating polypeptides |
| EP3169783A4 (en) | 2014-07-17 | 2018-10-03 | Modernatx, Inc. | Terminal modifications of polynucleotides |
| EP3461904A1 (en) | 2014-11-10 | 2019-04-03 | ModernaTX, Inc. | Alternative nucleic acid molecules containing reduced uracil content and uses thereof |
| 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 |
| SI3394093T1 (sl) | 2015-12-23 | 2022-05-31 | Modernatx, Inc. | Metode uporabe liganda OX40, ki kodira polinukleotid |
-
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- 2013-09-30 EP EP13779972.2A patent/EP2946014A2/en not_active Withdrawn
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- 2013-09-30 CA CA2897941A patent/CA2897941A1/en not_active Abandoned
- 2013-09-30 JP JP2015553717A patent/JP2016504050A/ja active Pending
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2021
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| JP2017113010A (ja) | 2017-06-29 |
| US20190185529A1 (en) | 2019-06-20 |
| WO2014113089A2 (en) | 2014-07-24 |
| JP2018183181A (ja) | 2018-11-22 |
| US20140200261A1 (en) | 2014-07-17 |
| AU2017219054A1 (en) | 2017-09-14 |
| US20140206852A1 (en) | 2014-07-24 |
| EP3434774A1 (en) | 2019-01-30 |
| US11708396B2 (en) | 2023-07-25 |
| WO2014113089A3 (en) | 2014-09-12 |
| JP6726711B2 (ja) | 2020-07-22 |
| CA2897941A1 (en) | 2014-07-24 |
| US20230013773A1 (en) | 2023-01-19 |
| EP2946014A2 (en) | 2015-11-25 |
| AU2017219054B2 (en) | 2019-09-26 |
| JP2016504050A (ja) | 2016-02-12 |
| HK1217215A1 (zh) | 2016-12-30 |
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