CN112618732A - 用于递送信使rna的脂质制剂 - Google Patents
用于递送信使rna的脂质制剂 Download PDFInfo
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- CN112618732A CN112618732A CN202011525622.8A CN202011525622A CN112618732A CN 112618732 A CN112618732 A CN 112618732A CN 202011525622 A CN202011525622 A CN 202011525622A CN 112618732 A CN112618732 A CN 112618732A
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| WO2012075040A2 (en) * | 2010-11-30 | 2012-06-07 | Shire Human Genetic Therapies, Inc. | mRNA FOR USE IN TREATMENT OF HUMAN GENETIC DISEASES |
| US9238716B2 (en) | 2011-03-28 | 2016-01-19 | Massachusetts Institute Of Technology | Conjugated lipomers and uses thereof |
| EP3354644A1 (en) | 2011-06-08 | 2018-08-01 | Translate Bio, Inc. | Cleavable lipids |
| PL3586861T3 (pl) | 2011-06-08 | 2022-05-23 | Translate Bio, Inc. | Kompozycje nanocząstek lipidowych i sposoby dostarczania mrna |
| KR102451116B1 (ko) | 2011-10-27 | 2022-10-06 | 메사추세츠 인스티튜트 오브 테크놀로지 | 약물 캡슐화 마이크로스피어를 형성할 수 있는, ｎ-말단 상에 관능화된 아미노산 유도체 |
| JP2016538829A (ja) | 2013-10-03 | 2016-12-15 | モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | 低密度リポタンパク質受容体をコードするポリヌクレオチド |
| MX2016005238A (es) * | 2013-10-22 | 2016-08-12 | Shire Human Genetic Therapies | Formulaciones de lipidos para la administracion de acido ribonucleico mensajero. |
| ES2707966T3 (es) * | 2013-10-22 | 2019-04-08 | Translate Bio Inc | Terapia de ARNm para la deficiencia en síntesis de argininosuccinato |
| US20170143848A1 (en) * | 2014-03-24 | 2017-05-25 | Shire Human Genetic Therapies, Inc. | Mrna therapy for the treatment of ocular diseases |
| SG10201912038TA (en) | 2014-04-23 | 2020-02-27 | Modernatx Inc | Nucleic acid vaccines |
| US9840479B2 (en) | 2014-07-02 | 2017-12-12 | Massachusetts Institute Of Technology | Polyamine-fatty acid derived lipidoids and uses thereof |
| US11219634B2 (en) | 2015-01-21 | 2022-01-11 | Genevant Sciences Gmbh | Methods, compositions, and systems for delivering therapeutic and diagnostic agents into cells |
| ES2949540T3 (es) * | 2015-06-19 | 2023-09-29 | Massachusetts Inst Technology | 2,5-piperazinadionas sustituidas con alquenilo y su uso en composiciones para suministrar un agente a un sujeto o una célula |
| EP3364949A4 (en) | 2015-10-22 | 2019-07-31 | ModernaTX, Inc. | CANCER VACCINES |
| EP3364981A4 (en) | 2015-10-22 | 2019-08-07 | ModernaTX, Inc. | VACCINE AGAINST THE HUMAN CYTOMEGALOVIRUS |
| CN105200158B (zh) * | 2015-11-06 | 2018-09-21 | 中国医学科学院北京协和医院 | Ass1甲基化检测在骨性关节炎诊断中的应用 |
| WO2017165398A1 (en) * | 2016-03-21 | 2017-09-28 | Children's Medical Center Corporation | Compositions and methods for inhibiting wnt signaling |
| WO2017201347A1 (en) * | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | Polynucleotides encoding cystic fibrosis transmembrane conductance regulator for the treatment of cystic fibrosis |
| KR102469450B1 (ko) | 2016-05-18 | 2022-11-22 | 모더나티엑스, 인크. | 인터류킨-12 (il12)를 코딩하는 폴리뉴클레오티드 및 그의 용도 |
| WO2017205566A1 (en) * | 2016-05-27 | 2017-11-30 | Preceres Inc. | Oxidized aminolipidoids and uses thereof |
| WO2018035388A1 (en) | 2016-08-17 | 2018-02-22 | The Broad Institute, Inc. | Novel crispr enzymes and systems |
| CN110312799A (zh) | 2016-08-17 | 2019-10-08 | 博德研究所 | 新型crispr酶和系统 |
| MA46584A (fr) | 2016-10-21 | 2019-08-28 | Modernatx Inc | Vaccin contre le cytomégalovirus humain |
| MX2019005470A (es) | 2016-11-10 | 2019-11-21 | Translate Bio Inc | Formulación de nanopartículas lipídicas basadas en ice mejorada para el suministro de arnm. |
| KR102313431B1 (ko) | 2016-11-21 | 2021-10-18 | 나노스트링 테크놀로지스, 인크. | 화학적 조성물 및 이것을 사용하는 방법 |
| EP3544591B1 (en) * | 2016-11-23 | 2022-04-20 | Mayo Foundation for Medical Education and Research | Particle-mediated delivery of biologics |
| WO2018104540A1 (en) * | 2016-12-08 | 2018-06-14 | Curevac Ag | Rnas for wound healing |
| IL314915B1 (en) | 2017-01-23 | 2026-02-01 | Regeneron Pharma | Variants of 17-beta-hydroxysteroid dehydrogenase and their uses |
| WO2018157133A1 (en) | 2017-02-27 | 2018-08-30 | Translate Bio, Inc. | Methods for purification of messenger rna |
| EP3585892B8 (en) | 2017-02-27 | 2022-07-13 | Translate Bio, Inc. | Methods for purification of messenger rna |
| EA201991747A1 (ru) * | 2017-02-27 | 2020-06-04 | Транслейт Био, Инк. | НОВАЯ КОДОН-ОПТИМИЗИРОВАННАЯ мРНК CFTR |
| KR20190139869A (ko) | 2017-04-11 | 2019-12-18 | 리제너론 파마슈티칼스 인코포레이티드 | 하이드록시스테로이드 (17-베타) 탈수소효소(hsd17b) 패밀리의 구성원의 조절인자의 활성도를 스크리닝하기 위한 검정 |
| US12350368B2 (en) | 2017-04-14 | 2025-07-08 | The Broad Institute, Inc. | Delivery of large payloads |
| US10034951B1 (en) | 2017-06-21 | 2018-07-31 | New England Biolabs, Inc. | Use of thermostable RNA polymerases to produce RNAs having reduced immunogenicity |
| WO2019023179A1 (en) * | 2017-07-24 | 2019-01-31 | Modernatx, Inc. | MODIFIED mRNA ENCODING GLUCOSE-6-PHOSPHATASE AND USES THEREOF |
| US10961583B2 (en) | 2017-10-11 | 2021-03-30 | Regeneron Phramaceuticals, Inc. | Inhibition of HSD17B13 in the treatment of liver disease in patients expressing the PNPLA3 I148M variation |
| US12227742B2 (en) | 2017-10-23 | 2025-02-18 | The Broad Institute, Inc. | Nucleic acid modifiers |
| EP3710039A4 (en) | 2017-11-13 | 2021-08-04 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR TREATMENT OF CANCER BY TARGETING THE CLEC2D-KLRB1 PATH |
| JP7423521B2 (ja) | 2017-11-22 | 2024-01-29 | モダーナティエックス・インコーポレイテッド | フェニルケトン尿症の治療用のフェニルアラニンヒドロキシラーゼをコードするポリヌクレオチド |
| EP3714048B1 (en) | 2017-11-22 | 2025-04-09 | ModernaTX, Inc. | Polynucleotides encoding ornithine transcarbamylase for the treatment of urea cycle disorders |
| GB201800620D0 (en) | 2018-01-15 | 2018-02-28 | Univ Manchester | C3b Binding Polypeptide |
| WO2019143552A1 (en) | 2018-01-16 | 2019-07-25 | Children's Medical Center Corporation | Compositions and methods for inhibiting wnt signaling |
| JP7507093B2 (ja) | 2018-03-21 | 2024-06-27 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | １７β－水酸化ステロイド脱水素酵素１３型（ＨＳＤ１７Ｂ１３）ｉＲＮＡ組成物およびその使用方法 |
| US10968257B2 (en) | 2018-04-03 | 2021-04-06 | The Broad Institute, Inc. | Target recognition motifs and uses thereof |
| AU2019271028B2 (en) | 2018-05-14 | 2025-09-18 | Bruker Spatial Biology, Inc. | Chemical compositions and methods of using same |
| US20210220449A1 (en) * | 2018-05-15 | 2021-07-22 | Translate Bio, Inc. | Subcutaneous Delivery of Messenger RNA |
| CA3101454A1 (en) * | 2018-05-30 | 2019-12-05 | Translate Bio, Inc. | Messenger rna vaccines and uses thereof |
| AU2019320847A1 (en) * | 2018-08-14 | 2021-04-08 | Loxegen Holdings Pty Ltd | Nanoparticles for transfection |
| CA3108544A1 (en) | 2018-08-24 | 2020-02-27 | Translate Bio, Inc. | Methods for purification of messenger rna |
| KR20210091120A (ko) * | 2018-08-29 | 2021-07-21 | 트랜슬레이트 바이오 인코포레이티드 | Mrna-로딩된 지질 나노입자를 제조하는 개선된 공정 |
| EP3849597A1 (en) * | 2018-09-12 | 2021-07-21 | University of Florida Research Foundation, Inc. | Slow-cycling cell-rna based nanoparticle vaccine to treat cancer |
| WO2020072914A1 (en) | 2018-10-04 | 2020-04-09 | New England Biolabs, Inc. | Methods and compositions for increasing capping efficiency of transcribed rna |
| US11072808B2 (en) | 2018-10-04 | 2021-07-27 | New England Biolabs, Inc. | Methods and compositions for increasing capping efficiency of transcribed RNA |
| CN113166783B (zh) | 2018-10-09 | 2024-10-11 | 不列颠哥伦比亚大学 | 包含无有机溶剂和去污剂的转染活性囊泡的组合物和系统以及与之相关的方法 |
| KR20210089648A (ko) | 2018-11-08 | 2021-07-16 | 트랜슬레이트 바이오 인코포레이티드 | 메신저 rna 정제를 위한 방법 및 조성물 |
| AU2019378763B2 (en) | 2018-11-12 | 2025-06-26 | Translate Bio, Inc. | Methods for inducing immune tolerance |
| 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. |
| CA3118034A1 (en) | 2018-12-21 | 2020-06-25 | Curevac Ag | Rna for malaria vaccines |
| US20220133908A1 (en) | 2019-02-08 | 2022-05-05 | Curevac Ag | Coding rna administered into the suprachoroidal space in the treatment of ophthalmic diseases |
| US12215382B2 (en) | 2019-03-01 | 2025-02-04 | The General Hospital Corporation | Liver protective MARC variants and uses thereof |
| US12534714B2 (en) | 2019-03-18 | 2026-01-27 | The Broad Institute, Inc. | Type VII CRISPR proteins and systems |
| CN110244053B (zh) * | 2019-05-09 | 2022-03-11 | 北京大学第三医院（北京大学第三临床医学院） | 用于诊断狼疮肾炎并肺动脉高压疾病的分子标志物及其用途 |
| US20220313813A1 (en) | 2019-06-18 | 2022-10-06 | Curevac Ag | Rotavirus mrna vaccine |
| CN110302373A (zh) * | 2019-07-01 | 2019-10-08 | 大连民族大学 | 利用跨膜区定向排列病毒包膜蛋白疫苗及其制备方法 |
| US12589161B2 (en) | 2019-07-10 | 2026-03-31 | The University Of Hong Kong | PEGylated synthetic KL4 peptide, compositions and methods thereof |
| WO2021016075A1 (en) | 2019-07-19 | 2021-01-28 | Flagship Pioneering Innovations Vi, Llc | Recombinase compositions and methods of use |
| EP4003311A1 (en) * | 2019-07-23 | 2022-06-01 | Translate Bio, Inc. | Stable compositions of mrna-loaded lipid nanoparticles and processes of making |
| IL290078B2 (en) | 2019-07-30 | 2025-09-01 | Translate Bio Inc | Treatment of cystic fibrosis by administering mRNA encoding CFTR in the form of a fine spray |
| EP4013880A1 (en) | 2019-08-14 | 2022-06-22 | CureVac AG | Rna combinations and compositions with decreased immunostimulatory properties |
| KR20220046693A (ko) | 2019-08-23 | 2022-04-14 | 뉴 잉글랜드 바이오랩스, 인크 | 효소학적 rna 캡핑 방법 |
| WO2021041267A1 (en) | 2019-08-23 | 2021-03-04 | New England Biolabs, Inc. | Enzymatic rna capping method |
| US12398173B2 (en) | 2019-08-23 | 2025-08-26 | New England Biolabs, Inc. | Enzymatic RNA capping method |
| KR102164218B1 (ko) * | 2019-09-24 | 2020-10-12 | 코스맥스 주식회사 | 피부 흡수 증진을 위한 다중층 양이온성 리포좀 및 이의 제조방법 |
| WO2021064998A1 (ja) * | 2019-10-04 | 2021-04-08 | 国立大学法人北海道大学 | ３次元流路構造体およびこれを用いたナノ粒子の製造方法 |
| WO2021072172A1 (en) * | 2019-10-09 | 2021-04-15 | Translate Bio, Inc. | Compositions, methods and uses of messenger rna |
| US20230051811A1 (en) * | 2019-12-20 | 2023-02-16 | Translate Bio, Inc | Rectal delivery of messenger rna |
| KR102198736B1 (ko) | 2020-01-15 | 2021-01-05 | 이화여자대학교 산학협력단 | 생체 내 약물 전달을 위한 지질 나노입자 및 이의 용도 |
| MX2022009460A (es) | 2020-02-04 | 2022-12-16 | Curevac Ag | Vacuna contra el coronavirus. |
| JP7744354B2 (ja) | 2020-02-25 | 2025-09-25 | トランスレイト バイオ， インコーポレイテッド | Ｍｒｎａ担持脂質ナノ粒子を調製する改善された方法 |
| MX2022011805A (es) | 2020-03-24 | 2023-01-11 | Generation Bio Co | Vectores de adn no virales y usos de estos para expresar agentes terapéuticos con factor ix. |
| AU2021244559A1 (en) | 2020-03-24 | 2022-11-17 | Generation Bio Co. | Non-viral DNA vectors and uses thereof for expressing Gaucher therapeutics |
| US12605395B2 (en) | 2020-04-01 | 2026-04-21 | University Of Cincinnati | Materials and methods for immunosuppressive tumor microenvironment-targeted cancer therapy |
| CN116096430A (zh) * | 2020-04-27 | 2023-05-09 | 衣阿华大学研究基金会 | 用于治疗囊性纤维化的组合物和方法 |
| US12605399B2 (en) | 2020-05-07 | 2026-04-21 | Translate Bio, Inc. | Compositions for CFTR MRNA therapy |
| IL298363A (en) | 2020-05-20 | 2023-01-01 | Flagship Pioneering Innovations Vi Llc | Immunogenic compositions and uses thereof |
| CA3179420A1 (en) | 2020-05-20 | 2021-11-25 | Avak Kahvejian | Coronavirus antigen compositions and their uses |
| CA3182026A1 (en) | 2020-05-29 | 2021-12-02 | Flagship Pioneering Innovations Vi, Llc. | Trem compositions and methods relating thereto |
| MX2022015132A (es) | 2020-05-29 | 2023-03-08 | CureVac SE | Vacunas combinadas a base de acidos nucleicos. |
| CA3180101A1 (en) | 2020-05-29 | 2021-12-02 | Flagship Pioneering Innovations Vi, Llc | Trem compositions and methods relating thereto |
| CN111658782A (zh) * | 2020-06-10 | 2020-09-15 | 深圳近邻生物科技有限公司 | mRNA疫苗递送载体及制备方法、mRNA疫苗及制备方法 |
| WO2025056938A1 (en) | 2023-09-11 | 2025-03-20 | BioNTech SE | Rna compositions for delivery of incretin agents |
| US11788074B2 (en) | 2020-06-23 | 2023-10-17 | New England Biolabs, Inc. | Vaccinia capping enzyme compositions and methods |
| CN111635937B (zh) * | 2020-06-29 | 2021-10-08 | 江苏省中医院 | Ass1或bckdk抑制剂在制备治疗溃疡性结肠炎的药物中的应用 |
| CN116234917A (zh) | 2020-07-27 | 2023-06-06 | 安杰瑞姆生物科学公司 | Dna分子组合物及其制备方法和使用方法 |
| WO2022023559A1 (en) | 2020-07-31 | 2022-02-03 | Curevac Ag | Nucleic acid encoded antibody mixtures |
| US11406703B2 (en) | 2020-08-25 | 2022-08-09 | Modernatx, Inc. | Human cytomegalovirus vaccine |
| CA3170743A1 (en) | 2020-08-31 | 2022-03-03 | Susanne RAUCH | Multivalent nucleic acid based coronavirus vaccines |
| MX2023002439A (es) | 2020-09-03 | 2023-05-09 | Flagship Pioneering Innovations Vi Llc | Composiciones immunogénicas y usos de las mismas. |
| CA3193347A1 (en) * | 2020-09-23 | 2022-03-31 | Saswata KARMAKAR | Piperazine-based cationic lipids |
| JP2023546175A (ja) | 2020-10-14 | 2023-11-01 | ジョージ・メイソン・リサーチ・ファウンデーション・インコーポレイテッド | 脂質ナノ粒子製造の方法及びそれに由来する組成物 |
| WO2022099003A1 (en) | 2020-11-06 | 2022-05-12 | Sanofi | Lipid nanoparticles for delivering mrna vaccines |
| JP2023548587A (ja) * | 2020-11-09 | 2023-11-17 | トランスレイト バイオ， インコーポレイテッド | コドン最適化したｍＲＮＡの送達のための改善された組成物 |
| WO2022135993A2 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Pharmaceutical composition comprising lipid-based carriers encapsulating rna for multidose administration |
| WO2022137133A1 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Rna vaccine against sars-cov-2 variants |
| IL303886A (en) | 2020-12-23 | 2023-08-01 | Flagship Pioneering Inc | Compositions of modified trems and uses thereof |
| WO2022155195A1 (en) * | 2021-01-12 | 2022-07-21 | Peranteau William | Ionizable lipid nanoparticles for in utero mrna delivery |
| WO2022162027A2 (en) | 2021-01-27 | 2022-08-04 | Curevac Ag | Method of reducing the immunostimulatory properties of in vitro transcribed rna |
| WO2022164428A1 (en) | 2021-01-27 | 2022-08-04 | New England Biolabs, Inc. | Faustovirus capping enzyme, mrna capping enzyme compositions, methods and kits |
| US11028379B1 (en) | 2021-01-27 | 2021-06-08 | New England Biolabs, Inc. | FCE mRNA capping enzyme compositions, methods and kits |
| US20240148897A1 (en) * | 2021-03-08 | 2024-05-09 | Eyegene Inc. | Composition for in vivo delivery of rna and preperation method therefor |
| JP2024511463A (ja) | 2021-03-22 | 2024-03-13 | リコード セラピューティクス，インク． | 細胞への標的送達のための組成物および方法 |
| US20240181037A1 (en) | 2021-03-26 | 2024-06-06 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
| EP4312988A2 (en) | 2021-03-31 | 2024-02-07 | CureVac SE | Syringes containing pharmaceutical compositions comprising rna |
| JP2024512669A (ja) | 2021-03-31 | 2024-03-19 | フラグシップ パイオニアリング イノベーションズ ブイ，インコーポレーテッド | タノトランスミッションポリペプチド及び癌の処置におけるそれらの使用 |
| AU2022260111A1 (en) | 2021-04-20 | 2023-11-30 | Anjarium Biosciences Ag | Compositions of dna molecules encoding amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase, methods of making thereof, and methods of use thereof |
| WO2022226313A1 (en) * | 2021-04-23 | 2022-10-27 | University Of Cincinnati | Therapeutics for hyponatremia and polycystic kidney disease |
| CN117881786A (zh) | 2021-04-27 | 2024-04-12 | 世代生物公司 | 表达治疗性抗体的非病毒dna载体及其用途 |
| EP4329884A1 (en) | 2021-04-27 | 2024-03-06 | Generation Bio Co. | Non-viral dna vectors expressing anti-coronavirus antibodies and uses thereof |
| CA3171589A1 (en) | 2021-05-03 | 2022-11-03 | Moritz THRAN | Improved nucleic acid sequence for cell type specific expression |
| AU2022273530A1 (en) | 2021-05-12 | 2023-11-23 | Massachusetts Institute Of Technology | Modified mrna, modified non-coding rna, and uses thereof |
| WO2023009547A1 (en) | 2021-07-26 | 2023-02-02 | Flagship Pioneering Innovations Vi, Llc | Trem compositions and uses thereof |
| JP2024534915A (ja) | 2021-09-03 | 2024-09-26 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | 自己増幅性メッセンジャーリボ核酸におけるヌクレオチド塩基の置換 |
| WO2023031392A2 (en) | 2021-09-03 | 2023-03-09 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids comprising phosphatidylserine |
| MX2024002726A (es) | 2021-09-03 | 2024-03-20 | CureVac SE | Nuevas nanoparticulas lipidicas para la administracion de acidos nucleicos. |
| ES2994006T3 (en) | 2021-09-17 | 2025-01-16 | Flagship Pioneering Innovations Vi Llc | Compositions and methods for producing circular polyribonucleotides |
| WO2023059806A1 (en) | 2021-10-06 | 2023-04-13 | Massachusetts Institute Of Technology | Lipid nanoparticles for drug delivery to microglia in the brain |
| JP2024538144A (ja) | 2021-10-18 | 2024-10-18 | フラッグシップ パイオニアリング イノベーションズ シックス，エルエルシー | ポリリボヌクレオチドを精製するための組成物及び方法 |
| WO2023073228A1 (en) | 2021-10-29 | 2023-05-04 | CureVac SE | Improved circular rna for expressing therapeutic proteins |
| EP4430024A1 (en) | 2021-11-08 | 2024-09-18 | Orna Therapeutics, Inc. | Lipid nanoparticle compositions for delivering circular polynucleotides |
| EP4436984A1 (en) | 2021-11-24 | 2024-10-02 | Flagship Pioneering Innovations VI, LLC | Coronavirus immunogen compositions and their uses |
| MX2024006440A (es) | 2021-11-24 | 2024-08-19 | Flagship Pioneering Innovations Vi Llc | Composiciones inmunogenicas y sus usos. |
| AU2022397292A1 (en) | 2021-11-24 | 2024-05-30 | Flagship Pioneering Innovations Vi, Llc | Varicella-zoster virus immunogen compositions and their uses |
| JP2024546855A (ja) | 2021-12-17 | 2024-12-26 | フラッグシップ パイオニアリング イノベーションズ シックス，エルエルシー | 変性条件下での環状ｒｎａの濃縮方法 |
| KR20240117149A (ko) | 2021-12-22 | 2024-07-31 | 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 | 폴리리보뉴클레오티드를 정제하기 위한 조성물 및 방법 |
| MX2024007870A (es) | 2021-12-23 | 2024-08-15 | Flagship Pioneering Innovations Vi Llc | Polirribonucleotidos circulares que codifican polipeptidos antifusogenicos. |
| JP2025504404A (ja) | 2022-01-14 | 2025-02-12 | アンジャリウム バイオサイエンシズ エージー | Ｖｉｉｉ因子をコードするｄｎａ分子の組成物、それを作製する方法、及びその使用方法 |
| CA3242744A1 (en) | 2022-01-27 | 2023-08-03 | The Trustees Of The University Of Pennsylvania | Pharmaceutical compositions for the administration of herpes simplex virus antigens and associated methods |
| US20250099614A1 (en) | 2022-01-28 | 2025-03-27 | CureVac SE | Nucleic acid encoded transcription factor inhibitors |
| EP4490285A1 (en) | 2022-03-11 | 2025-01-15 | New England Biolabs, Inc. | Immobilized enzyme compositions and methods |
| WO2023177655A1 (en) | 2022-03-14 | 2023-09-21 | Generation Bio Co. | Heterologous prime boost vaccine compositions and methods of use |
| EP4499607A1 (en) | 2022-03-25 | 2025-02-05 | Sail Biomedicines, Inc. | Novel ionizable lipids and lipid nanoparticles and methods of using the same |
| JP2025511756A (ja) | 2022-04-08 | 2025-04-16 | フラッグシップ パイオニアリング イノベーションズ セブン，エルエルシー | ワクチン及び関連する方法 |
| US20250295687A1 (en) | 2022-05-09 | 2025-09-25 | Flagship Pioneering Innovations Vi, Llc | Trem compositions and methods of use for treating proliferative disorders |
| JP2025516638A (ja) | 2022-05-13 | 2025-05-30 | フラッグシップ パイオニアリング イノベーションズ セブン，エルエルシー | 二本鎖ｄｎａ組成物及び関連する方法 |
| WO2023227608A1 (en) | 2022-05-25 | 2023-11-30 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide |
| EP4536197A1 (en) | 2022-06-07 | 2025-04-16 | Generation Bio Co. | Lipid nanoparticle compositions and uses thereof |
| FR3136367A1 (fr) * | 2022-06-09 | 2023-12-15 | Damien SULEIMAN | Compositions et méthodes concernant des molécules d’ARN messager codant le facteur V encapsulées dans des nanoparticules lipidiques |
| WO2023242817A2 (en) | 2022-06-18 | 2023-12-21 | Glaxosmithkline Biologicals Sa | Recombinant rna molecules comprising untranslated regions or segments encoding spike protein from the omicron strain of severe acute respiratory coronavirus-2 |
| US20250179492A1 (en) | 2022-06-22 | 2025-06-05 | Flagship Pioneering Innovations Vi, Llc | Compositions of modified trems and uses thereof |
| JP2025525778A (ja) | 2022-08-01 | 2025-08-07 | フラッグシップ パイオニアリング イノベーションズ セブン，エルエルシー | 免疫調節タンパク質及び関連方法 |
| EP4569112A1 (en) | 2022-08-12 | 2025-06-18 | Remix Therapeutics Inc. | Methods and compositions for modulating splicing at alternative splice sites |
| WO2024040222A1 (en) | 2022-08-19 | 2024-02-22 | Generation Bio Co. | Cleavable closed-ended dna (cedna) and methods of use thereof |
| AU2023334610A1 (en) | 2022-08-31 | 2025-03-13 | Sail Biomedicines, Inc. | Novel ionizable lipids and lipid nanoparticles and methods of using the same |
| KR102785258B1 (ko) * | 2022-09-07 | 2025-03-26 | 아이진 주식회사 | 변형핵산 함유 mRNA의 체내 전달용 조성물 |
| AU2023274159A1 (en) * | 2022-09-07 | 2024-03-21 | Eyegene Inc. | COMPOSITION FOR IN-VIVO DELIVERING mRNA CONTAINING MODIFIED NUCLEOTIDE |
| EP4590331A1 (en) | 2022-09-23 | 2025-07-30 | BioNTech SE | Compositions for delivery of plasmodium csp antigens and related methods |
| JP2025533541A (ja) | 2022-09-23 | 2025-10-07 | ビオンテック・ソシエタス・エウロパエア | 肝病期抗原の送達のための組成物及び関連方法 |
| WO2024063789A1 (en) | 2022-09-23 | 2024-03-28 | BioNTech SE | Compositions for delivery of malaria antigens and related methods |
| WO2024063788A1 (en) | 2022-09-23 | 2024-03-28 | BioNTech SE | Compositions for delivery of malaria antigens and related methods |
| CN119947747A (zh) | 2022-09-26 | 2025-05-06 | 葛兰素史克生物有限公司 | 流感病毒疫苗 |
| WO2024077191A1 (en) | 2022-10-05 | 2024-04-11 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additionalpolypeptides and their use in treating cancer |
| WO2024089638A1 (en) | 2022-10-28 | 2024-05-02 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine |
| AU2023372397A1 (en) | 2022-10-31 | 2025-05-08 | Flagship Pioneering Innovations Vi, Llc | Compositions and methods for purifying polyribonucleotides |
| CN120390656A (zh) | 2022-11-08 | 2025-07-29 | 欧纳医疗公司 | 环状rna组合物 |
| EP4615465A1 (en) | 2022-11-08 | 2025-09-17 | Flagship Pioneering Innovations VI, LLC | Compositions and methods for producing circular polyribonucleotides |
| TW202425959A (zh) | 2022-11-08 | 2024-07-01 | 美商歐納醫療公司 | 遞送多核苷酸的脂質及奈米顆粒組合物 |
| WO2024102762A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Lipids and lipid nanoparticle compositions for delivering polynucleotides |
| KR20250114116A (ko) | 2022-12-01 | 2025-07-28 | 제너레이션 바이오 컴퍼니 | 세포 표적화를 위한 스텔스 지질 나노입자 조성물 |
| WO2024119103A1 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Lipid nanoparticles comprising nucleic acids and lipid-anchored polymers |
| KR20250131271A (ko) | 2022-12-01 | 2025-09-02 | 제너레이션 바이오 컴퍼니 | 신규한 폴리글리세롤-접합된 지질 및 이를 포함하는 지질 나노입자 조성물 |
| JP2025540076A (ja) | 2022-12-01 | 2025-12-11 | ジェネレーション バイオ カンパニー | 核酸、イオン化可能な脂質、ステロール、脂質アンカーポリマー、及びヘルパー脂質を含む脂質ナノ粒子、それらの使用 |
| TW202430215A (zh) | 2022-12-14 | 2024-08-01 | 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 | 用於將治療劑遞送至骨之組成物和方法 |
| CN120435560A (zh) * | 2022-12-16 | 2025-08-05 | 深圳深信生物科技有限公司 | 提高rna分子翻译效率和/或稳定性的utr及其应用 |
| WO2024133160A1 (en) | 2022-12-19 | 2024-06-27 | Glaxosmithkline Biologicals Sa | Hepatitis b compositions |
| US20240252520A1 (en) | 2023-01-09 | 2024-08-01 | Beth Israel Deaconess Medical Center, Inc. | Therapeutic agents and their use for treating chronic wounds |
| WO2024151583A2 (en) | 2023-01-09 | 2024-07-18 | Flagship Pioneering Innovations Vii, Llc | Vaccines and related methods |
| US20240238473A1 (en) * | 2023-01-09 | 2024-07-18 | Beth Israel Deaconess Medical Center, Inc. | Recombinant nucleic acid molecules and their use in wound healing |
| WO2024151687A1 (en) | 2023-01-09 | 2024-07-18 | Flagship Pioneering Innovations V, Inc. | Genetic switches and their use in treating cancer |
| EP4654996A1 (en) | 2023-01-27 | 2025-12-03 | BioNTech SE | Pharmaceutical compositions for delivery of herpes simplex virus glycoprotein c, glycoprotein d, and glycoprotein e antigens and related methods |
| CN116047082B (zh) * | 2023-01-31 | 2023-09-15 | 江苏品升医学科技有限公司 | 一种fgl1蛋白用于制备诊断慢性肾脏病的试剂盒的用途 |
| WO2024160936A1 (en) | 2023-02-03 | 2024-08-08 | Glaxosmithkline Biologicals Sa | Rna formulation |
| WO2024167885A1 (en) | 2023-02-06 | 2024-08-15 | Flagship Pioneering Innovations Vii, Llc | Immunomodulatory compositions and related methods |
| IL322468A (en) | 2023-02-13 | 2025-09-01 | Flagship Pioneering Innovations Vii Llc | Ionizable lipids containing degradable crosslinkers and lipid carriers for therapeutic compositions |
| GB202302092D0 (en) | 2023-02-14 | 2023-03-29 | Glaxosmithkline Biologicals Sa | Analytical method |
| IL322378A (en) | 2023-02-17 | 2025-09-01 | Flagship Pioneering Innovations Vii Llc | DNA compositions containing modified cytosine |
| JP2026507513A (ja) | 2023-02-17 | 2026-03-04 | フラッグシップ パイオニアリング イノベーションズ セブン，エルエルシー | 修飾されたウラシルを含むｄｎａ組成物 |
| KR20250153298A (ko) | 2023-03-08 | 2025-10-24 | 큐어백 에스이 | 핵산 전달을 위한 신규의 지질 나노입자 제형 |
| EP4680276A1 (en) | 2023-03-15 | 2026-01-21 | Flagship Pioneering Innovations VI, LLC | Immunogenic compositions and uses thereof |
| WO2024192420A1 (en) | 2023-03-15 | 2024-09-19 | Flagship Pioneering Innovations Vi, Llc | Compositions comprising polyribonucleotides and uses thereof |
| WO2024205657A2 (en) | 2023-03-29 | 2024-10-03 | Orna Therapeutics, Inc. | Lipids and lipid nanoparticle compositions for delivering polynucleotides |
| WO2024216191A1 (en) | 2023-04-12 | 2024-10-17 | Flagship Pioneering Innovations Vi, Llc | Modified trems, compositions, and related methods thereof |
| WO2024216128A1 (en) | 2023-04-12 | 2024-10-17 | Flagship Pioneering Innovations Vi, Llc | Trems for use in correction of missense mutations |
| WO2024220746A2 (en) | 2023-04-21 | 2024-10-24 | Flagship Pioneering Innovations Vii, Llc | Rnai agents targeting fatty acid synthase and related methods |
| WO2024223724A1 (en) | 2023-04-27 | 2024-10-31 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
| EP4701658A1 (en) | 2023-04-27 | 2026-03-04 | GlaxoSmithKline Biologicals S.A. | Influenza virus vaccines |
| WO2024228044A1 (en) | 2023-05-03 | 2024-11-07 | BioNTech SE | Optimized csp variants and related methods |
| WO2024228150A1 (en) | 2023-05-03 | 2024-11-07 | BioNTech SE | Optimized csp variants and related methods |
| WO2024233308A2 (en) | 2023-05-05 | 2024-11-14 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
| WO2024230934A1 (en) | 2023-05-11 | 2024-11-14 | CureVac SE | Therapeutic nucleic acid for the treatment of ophthalmic diseases |
| WO2024258829A1 (en) | 2023-06-12 | 2024-12-19 | Flagship Pioneering Innovations Vii, Llc | Sars-cov-2 vaccine compositions and related methods |
| WO2025006684A1 (en) | 2023-06-28 | 2025-01-02 | Flagship Pioneering Innovations Vi, Llc | Circular polyribonucleotides encoding antifusogenic polypeptides |
| WO2025011529A2 (en) | 2023-07-07 | 2025-01-16 | Shanghai Circode Biomed Co., Ltd. | Circular rna vaccines for seasonal flu and methods of uses |
| CN121816193A (zh) | 2023-07-21 | 2026-04-07 | 生物技术欧洲股份公司 | 用于递送疟原虫抗原的组合物及相关方法 |
| WO2025024324A1 (en) | 2023-07-21 | 2025-01-30 | BioNTech SE | Compositions for delivery of plasmodium antigens and related methods |
| IL325898A (en) | 2023-07-24 | 2026-03-01 | BioNTech SE | Compositions for administering Plasmodium antigens and related methods |
| AU2024299627A1 (en) | 2023-07-25 | 2026-01-22 | Flagship Pioneering Innovations Vii, Llc | Cas endonucleases and related methods |
| WO2025030154A1 (en) | 2023-08-03 | 2025-02-06 | The Trustees Of The University Of Pennsylvania | Pharmaceutical compositions for delivery of herpes simplex virus glycoprotein b antigens and related methods |
| CN121772938A (zh) | 2023-08-03 | 2026-03-31 | 百欧恩泰欧洲股份公司 | 用于递送单纯疱疹病毒抗原的药物组合物及相关方法 |
| WO2025042786A1 (en) | 2023-08-18 | 2025-02-27 | Flagship Pioneering Innovations Vi, Llc | Compositions comprising circular polyribonucleotides and uses thereof |
| WO2025049690A1 (en) | 2023-08-29 | 2025-03-06 | Orna Therapeutics, Inc. | Circular polyethylene glycol lipids |
| CN121752588A (zh) | 2023-08-29 | 2026-03-27 | 上海环码生物医药有限公司 | 编码vegf多肽的环状rna、制剂和使用方法 |
| WO2025054236A2 (en) | 2023-09-06 | 2025-03-13 | Flagship Pioneering Innovations Vii, Llc | Sars-cov-2 vaccine compositions and related methods |
| WO2025052180A2 (en) | 2023-09-07 | 2025-03-13 | Axelyf ehf. | Lipids and lipid nanoparticles |
| WO2025054556A1 (en) | 2023-09-07 | 2025-03-13 | BioNTech SE | Rna compositions for delivery of mpox antigens and related methods |
| CN121844046A (zh) | 2023-09-11 | 2026-04-10 | C·米库尔卡 | 用于递送肠促胰岛素剂的rna组合物 |
| WO2025059500A1 (en) | 2023-09-14 | 2025-03-20 | New England Biolabs, Inc. | Rna polymerases |
| AU2024344058A1 (en) | 2023-09-18 | 2026-04-02 | Flagship Pioneering Innovations Vii, Llc | Ionizable lipidoid compositions and therapeutic uses thereof |
| WO2025072331A1 (en) | 2023-09-26 | 2025-04-03 | Flagship Pioneering Innovations Vii, Llc | Cas nucleases and related methods |
| WO2025096807A2 (en) | 2023-10-31 | 2025-05-08 | Flagship Pioneering Innovations Vii, Llc | Novel therapeutic dna forms |
| WO2025101501A1 (en) | 2023-11-07 | 2025-05-15 | Orna Therapeutics, Inc. | Circular rna compositions |
| WO2025106670A1 (en) | 2023-11-14 | 2025-05-22 | Flagship Pioneering Innovations Vii, Llc | Ionizable lipidoid compositions and therapeutic uses thereof |
| US20250161347A1 (en) | 2023-11-22 | 2025-05-22 | Flagship Pioneering Innovations Vii, Llc | Methods and compositions for treating non-alcoholic fatty liver disease |
| WO2025117877A2 (en) | 2023-12-01 | 2025-06-05 | Flagship Pioneering Innovations Vii, Llc | Cas nucleases and related methods |
| CN119662655A (zh) * | 2023-12-04 | 2025-03-21 | 武汉厚先生物医药有限公司 | Rna分子及其组合物在肿瘤免疫治疗中的应用 |
| WO2025132839A1 (en) | 2023-12-21 | 2025-06-26 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
| CN121015605A (zh) * | 2024-01-19 | 2025-11-28 | 晟迪生物医药(苏州)有限公司 | 含有可电离脂质的肺部递送系统、其制备方法和应用 |
| TW202545974A (zh) | 2024-01-26 | 2025-12-01 | 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 | 免疫受體抑制蛋白及相關方法 |
| WO2025194120A1 (en) * | 2024-03-14 | 2025-09-18 | Massachusetts Institute Of Technology | Zwitterionic polymer functionalized lipid nanoparticles for delivery of nucleic acids |
| WO2025194019A1 (en) | 2024-03-14 | 2025-09-18 | Flagship Pioneering Innovations Vii, Llc | Methods for treating liver fibrosis and non-alcoholic fatty liver disease |
| WO2025194138A1 (en) | 2024-03-14 | 2025-09-18 | Tessera Therapeutics, Inc. | St1cas9 compositions and methods for modulating a genome |
| WO2025202937A1 (en) | 2024-03-26 | 2025-10-02 | BioNTech SE | Cancer vaccines |
| GB202404607D0 (en) | 2024-03-29 | 2024-05-15 | Glaxosmithkline Biologicals Sa | RNA formulation |
| US12492420B2 (en) | 2024-03-29 | 2025-12-09 | New England Biolabs, Inc. | Compositions, kits, and methods for in vitro transcription |
| WO2025213131A1 (en) | 2024-04-05 | 2025-10-09 | BioNTech SE | Rna compositions for delivery of orthopox antigens and related methods |
| WO2025217275A2 (en) | 2024-04-10 | 2025-10-16 | Flagship Pioneering Innovations Vii, Llc | Immune cell targeted compositions and related methods |
| WO2025229572A1 (en) | 2024-05-01 | 2025-11-06 | Glaxosmithkline Biologicals Sa | Epstein-barr virus antigen-encoding messenger ribonucleic acid and antigen protein vaccines |
| WO2025240680A1 (en) | 2024-05-16 | 2025-11-20 | Flagship Pioneering Innovations Vii, Llc | Immunoreceptor inhibitory proteins and related methods |
| WO2025245188A2 (en) | 2024-05-21 | 2025-11-27 | Flagship Pioneering Innovations Vii, Llc | Methods of treating liver steatosis and non-alcoholic fatty liver disease |
| WO2025245111A1 (en) | 2024-05-22 | 2025-11-27 | Flagship Pioneering Innovations Vii, Llc | Immunoreceptor targeting proteins and related methods |
| US20260000702A1 (en) | 2024-06-26 | 2026-01-01 | Flagship Pioneering Innovations Vii, Llc | Therapeutic circular dna forms |
| WO2026003582A2 (en) | 2024-06-27 | 2026-01-02 | Axelyf ehf. | Lipids and lipid nanoparticles |
| WO2026015882A1 (en) | 2024-07-12 | 2026-01-15 | BioNTech SE | Hsv antigen fragments and related methods |
| WO2026055543A1 (en) | 2024-09-06 | 2026-03-12 | Flagship Pioneering Innovations Vii, Llc | Modified dna compositions and related methods |
| WO2026055547A1 (en) | 2024-09-06 | 2026-03-12 | Flagship Pioneering Innovations Vii, Llc | Dna compositions and related methods |
| WO2026064313A1 (en) | 2024-09-17 | 2026-03-26 | Flagship Pioneering Innovations Vii, Llc | Rna compositions and related methods |
| WO2026064512A1 (en) | 2024-09-18 | 2026-03-26 | Generation Bio Co. | Polyglycerol-conjugated lipids and lipid nanoparticle compositions comprising the same |
Family Cites Families (323)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2647121A (en) | 1951-02-02 | 1953-07-28 | Ruth P Jacoby | Diamine-bis-acetamides |
| US2819718A (en) | 1953-07-16 | 1958-01-14 | Isidore H Goldman | Drainage tube |
| US2717909A (en) | 1953-09-24 | 1955-09-13 | Monsanto Chemicals | Hydroxyethyl-keryl-alkylene-ammonium compounds |
| US2844629A (en) | 1956-04-25 | 1958-07-22 | American Home Prod | Fatty acid amides and derivatives thereof |
| US3096560A (en) | 1958-11-21 | 1963-07-09 | William J Liebig | Process for synthetic vascular implants |
| GB1072118A (en) | 1962-12-01 | 1967-06-14 | Sandoz Ag | Amides of aminopropionic acid |
| FR1378382A (fr) | 1962-12-01 | 1964-11-13 | Sandoz Sa | Amides de l'acide amino-propionique, utilisables en particulier pour le traitement des fibres textiles |
| JPS5141663B1 (https=) | 1966-03-12 | 1976-11-11 | ||
| JPS4822365B1 (https=) | 1968-10-25 | 1973-07-05 | ||
| NL143127B (nl) | 1969-02-04 | 1974-09-16 | Rhone Poulenc Sa | Versterkingsorgaan voor een defecte hartklep. |
| US3614954A (en) | 1970-02-09 | 1971-10-26 | Medtronic Inc | Electronic standby defibrillator |
| US3614955A (en) | 1970-02-09 | 1971-10-26 | Medtronic Inc | Standby defibrillator and method of operation |
| JPS5024216B1 (https=) | 1970-12-29 | 1975-08-14 | ||
| JPS5012146Y2 (https=) | 1971-07-27 | 1975-04-15 | ||
| US3945052A (en) | 1972-05-01 | 1976-03-23 | Meadox Medicals, Inc. | Synthetic vascular graft and method for manufacturing the same |
| US3805301A (en) | 1972-07-28 | 1974-04-23 | Meadox Medicals Inc | Tubular grafts having indicia thereon |
| JPS49127908A (https=) | 1973-04-20 | 1974-12-07 | ||
| JPS5624664B2 (https=) | 1973-06-28 | 1981-06-08 | ||
| US4013507A (en) | 1973-09-18 | 1977-03-22 | California Institute Of Technology | Ionene polymers for selectively inhibiting the vitro growth of malignant cells |
| JPS5123537A (ja) | 1974-04-26 | 1976-02-25 | Adeka Argus Chemical Co Ltd | Kasozaisoseibutsu |
| GB1527592A (en) | 1974-08-05 | 1978-10-04 | Ici Ltd | Wound dressing |
| US3995623A (en) | 1974-12-23 | 1976-12-07 | American Hospital Supply Corporation | Multipurpose flow-directed catheter |
| JPS5813576B2 (ja) | 1974-12-27 | 1983-03-14 | アデカ ア−ガスカガク カブシキガイシヤ | 安定化された合成高分子組成物 |
| DE2520814A1 (de) | 1975-05-09 | 1976-11-18 | Bayer Ag | Lichtstabilisierung von polyurethanen |
| US4281669A (en) | 1975-05-09 | 1981-08-04 | Macgregor David C | Pacemaker electrode with porous system |
| JPS5210847A (en) | 1975-07-16 | 1977-01-27 | Nippon Steel Corp | Pinch roll |
| US4096860A (en) | 1975-10-08 | 1978-06-27 | Mclaughlin William F | Dual flow encatheter |
| CA1069652A (en) | 1976-01-09 | 1980-01-15 | Alain F. Carpentier | Supported bioprosthetic heart valve with compliant orifice ring |
| US4134402A (en) | 1976-02-11 | 1979-01-16 | Mahurkar Sakharam D | Double lumen hemodialysis catheter |
| US4072146A (en) | 1976-09-08 | 1978-02-07 | Howes Randolph M | Venous catheter device |
| US4335723A (en) | 1976-11-26 | 1982-06-22 | The Kendall Company | Catheter having inflatable retention means |
| US4099528A (en) | 1977-02-17 | 1978-07-11 | Sorenson Research Co., Inc. | Double lumen cannula |
| US4140126A (en) | 1977-02-18 | 1979-02-20 | Choudhury M Hasan | Method for performing aneurysm repair |
| US4265745A (en) | 1977-05-25 | 1981-05-05 | Teijin Limited | Permselective membrane |
| US4182833A (en) | 1977-12-07 | 1980-01-08 | Celanese Polymer Specialties Company | Cationic epoxide-amine reaction products |
| US4180068A (en) | 1978-04-13 | 1979-12-25 | Motion Control, Incorporated | Bi-directional flow catheter with retractable trocar/valve structure |
| EP0005035B1 (en) | 1978-04-19 | 1981-09-23 | Imperial Chemical Industries Plc | A method of preparing a tubular product by electrostatic spinning |
| US4284459A (en) | 1978-07-03 | 1981-08-18 | The Kendall Company | Method for making a molded catheter |
| US4227533A (en) | 1978-11-03 | 1980-10-14 | Bristol-Myers Company | Flushable urinary catheter |
| US4375817A (en) | 1979-07-19 | 1983-03-08 | Medtronic, Inc. | Implantable cardioverter |
| US5132418A (en) | 1980-02-29 | 1992-07-21 | University Patents, Inc. | Process for preparing polynucleotides |
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4500707A (en) | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
| DE3010841A1 (de) | 1980-03-21 | 1981-10-08 | Ulrich Dr.med. 6936 Haag Uthmann | Katheder |
| US4308085A (en) | 1980-07-28 | 1981-12-29 | Jenoptik Jena Gmbh | Process for the preparation of high molecular thermoplastic epoxide-amine-polyadducts |
| US4973679A (en) | 1981-03-27 | 1990-11-27 | University Patents, Inc. | Process for oligonucleo tide synthesis using phosphormidite intermediates |
| US4415732A (en) | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
| US4668777A (en) | 1981-03-27 | 1987-05-26 | University Patents, Inc. | Phosphoramidite nucleoside compounds |
| US4339369A (en) | 1981-04-23 | 1982-07-13 | Celanese Corporation | Cationic epoxide-amine reaction products |
| US4401796A (en) | 1981-04-30 | 1983-08-30 | City Of Hope Research Institute | Solid-phase synthesis of polynucleotides |
| US4373071A (en) | 1981-04-30 | 1983-02-08 | City Of Hope Research Institute | Solid-phase synthesis of polynucleotides |
| US4406656A (en) | 1981-06-01 | 1983-09-27 | Brack Gillium Hattler | Venous catheter having collapsible multi-lumens |
| US4475972A (en) | 1981-10-01 | 1984-10-09 | Ontario Research Foundation | Implantable material |
| US4401472A (en) | 1982-02-26 | 1983-08-30 | Martin Marietta Corporation | Hydraulic cement mixes and processes for improving hydraulic cement mixes |
| US4568329A (en) | 1982-03-08 | 1986-02-04 | Mahurkar Sakharam D | Double lumen catheter |
| US4546499A (en) | 1982-12-13 | 1985-10-15 | Possis Medical, Inc. | Method of supplying blood to blood receiving vessels |
| US4530113A (en) | 1983-05-20 | 1985-07-23 | Intervascular, Inc. | Vascular grafts with cross-weave patterns |
| US4647416A (en) | 1983-08-03 | 1987-03-03 | Shiley Incorporated | Method of preparing a vascular graft prosthesis |
| US4550447A (en) | 1983-08-03 | 1985-11-05 | Shiley Incorporated | Vascular graft prosthesis |
| US5104399A (en) | 1986-12-10 | 1992-04-14 | Endovascular Technologies, Inc. | Artificial graft and implantation method |
| US4571241A (en) | 1983-12-16 | 1986-02-18 | Christopher T Graham | Urinary catheter with collapsible urethral tube |
| US4710169A (en) | 1983-12-16 | 1987-12-01 | Christopher T Graham | Urinary catheter with collapsible urethral tube |
| US4737518A (en) | 1984-04-03 | 1988-04-12 | Takeda Chemical Industries, Ltd. | Lipid derivatives, their production and use |
| US4562596A (en) | 1984-04-25 | 1986-01-07 | Elliot Kornberg | Aortic graft, device and method for performing an intraluminal abdominal aortic aneurysm repair |
| US4782836A (en) | 1984-05-24 | 1988-11-08 | Intermedics, Inc. | Rate adaptive cardiac pacemaker responsive to patient activity and temperature |
| US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4662382A (en) | 1985-01-16 | 1987-05-05 | Intermedics, Inc. | Pacemaker lead with enhanced sensitivity |
| US4762915A (en) | 1985-01-18 | 1988-08-09 | Liposome Technology, Inc. | Protein-liposome conjugates |
| US4860751A (en) | 1985-02-04 | 1989-08-29 | Cordis Corporation | Activity sensor for pacemaker control |
| CA1320724C (en) | 1985-07-19 | 1993-07-27 | Koichi Kanehira | Terpene amino alcohols and medicinal uses thereof |
| US4701162A (en) | 1985-09-24 | 1987-10-20 | The Kendall Company | Foley catheter assembly |
| US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
| US5153319A (en) | 1986-03-31 | 1992-10-06 | University Patents, Inc. | Process for preparing polynucleotides |
| DE3616824A1 (de) | 1986-05-17 | 1987-11-19 | Schering Ag | Verwendung von haertbaren kunstharzmischungen fuer oberflaechenbeschichtungen und druckfarben und verfahren zu ihrer herstellung |
| EP0255899B1 (de) | 1986-07-31 | 1992-07-15 | Werner Prof. Dr.-Ing. Irnich | Frequenzadaptierender Herzschrittmacher |
| US4960409A (en) | 1986-09-11 | 1990-10-02 | Catalano Marc L | Method of using bilumen peripheral venous catheter with adapter |
| JPH0829776B2 (ja) | 1986-10-29 | 1996-03-27 | 東燃化学株式会社 | 合成樹脂製容器及びその製造用金型 |
| US4720517A (en) | 1986-11-24 | 1988-01-19 | Ciba-Geigy Corporation | Compositions stabilized with N-hydroxyiminodiacetic and dipropionic acids and esters thereof |
| DE3728917A1 (de) | 1987-08-29 | 1989-03-09 | Roth Hermann J | Neue lipide mit unsymmetrisch substituierter disulfidbruecke |
| US5047540A (en) | 1987-12-17 | 1991-09-10 | Shionogi & Co., Ltd. | Lipid derivatives |
| US5138067A (en) | 1987-12-17 | 1992-08-11 | Shionogi & Co. Ltd. | Lipid derivatives |
| US4892540A (en) | 1988-04-21 | 1990-01-09 | Sorin Biomedica S.P.A. | Two-leaflet prosthetic heart valve |
| US5176661A (en) | 1988-09-06 | 1993-01-05 | Advanced Cardiovascular Systems, Inc. | Composite vascular catheter |
| US5024671A (en) | 1988-09-19 | 1991-06-18 | Baxter International Inc. | Microporous vascular graft |
| US5200395A (en) | 1988-10-18 | 1993-04-06 | Ajinomoto Company, Inc. | Pharmaceutical composition of BUF-5 for treating anemia |
| CA2001401A1 (en) | 1988-10-25 | 1990-04-25 | Claude Piantadosi | Quaternary amine containing ether or ester lipid derivatives and therapeutic compositions |
| US5047524A (en) | 1988-12-21 | 1991-09-10 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
| US5262530A (en) | 1988-12-21 | 1993-11-16 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
| FR2645866B1 (fr) | 1989-04-17 | 1991-07-05 | Centre Nat Rech Scient | Nouvelles lipopolyamines, leur preparation et leur emploi |
| US5101824A (en) | 1990-04-16 | 1992-04-07 | Siemens-Pacesetter, Inc. | Rate-responsive pacemaker with circuitry for processing multiple sensor inputs |
| WO1992001425A1 (en) | 1990-07-26 | 1992-02-06 | Rodney James Lane | Self expanding vascular endoprosthesis for aneurysms |
| US5693338A (en) * | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
| DE9117152U1 (de) | 1990-10-09 | 1996-07-11 | Cook Inc., Bloomington, Ind. | Stent |
| ATE120971T1 (de) | 1990-12-19 | 1995-04-15 | Osypka Peter | Herzschrittmacherleitung mit einem inneren kanal und mit einem elektrodenkopf. |
| US5116360A (en) | 1990-12-27 | 1992-05-26 | Corvita Corporation | Mesh composite graft |
| US5405363A (en) | 1991-03-15 | 1995-04-11 | Angelon Corporation | Implantable cardioverter defibrillator having a smaller displacement volume |
| US5330768A (en) | 1991-07-05 | 1994-07-19 | Massachusetts Institute Of Technology | Controlled drug delivery using polymer/pluronic blends |
| US5545449A (en) | 1991-10-02 | 1996-08-13 | Weyerhaeuser Company | Polyether-reinforced fiber-based materials |
| US5151105A (en) | 1991-10-07 | 1992-09-29 | Kwan Gett Clifford | Collapsible vessel sleeve implant |
| US5284491A (en) | 1992-02-27 | 1994-02-08 | Medtronic, Inc. | Cardiac pacemaker with hysteresis behavior |
| US5352461A (en) | 1992-03-11 | 1994-10-04 | Pharmaceutical Discovery Corporation | Self assembling diketopiperazine drug delivery system |
| SE9200951D0 (sv) | 1992-03-27 | 1992-03-27 | Kabi Pharmacia Ab | Pharmaceutical composition containing a defined lipid system |
| EP0657534A4 (en) | 1992-08-04 | 1997-06-04 | Green Cross Corp | ANTIALLERGIC AGING. |
| US5334761A (en) | 1992-08-28 | 1994-08-02 | Life Technologies, Inc. | Cationic lipids |
| US5461223A (en) | 1992-10-09 | 1995-10-24 | Eastman Kodak Company | Bar code detecting circuitry |
| US5300022A (en) | 1992-11-12 | 1994-04-05 | Martin Klapper | Urinary catheter and bladder irrigation system |
| US5496362A (en) | 1992-11-24 | 1996-03-05 | Cardiac Pacemakers, Inc. | Implantable conformal coil patch electrode with multiple conductive elements for cardioversion and defibrillation |
| US5716395A (en) | 1992-12-11 | 1998-02-10 | W.L. Gore & Associates, Inc. | Prosthetic vascular graft |
| US6020317A (en) | 1993-02-19 | 2000-02-01 | Nippon Shinyaku Co. Ltd. | Glycerol derivative, device and pharmaceutical composition |
| US5395619A (en) | 1993-03-03 | 1995-03-07 | Liposome Technology, Inc. | Lipid-polymer conjugates and liposomes |
| US5697953A (en) | 1993-03-13 | 1997-12-16 | Angeion Corporation | Implantable cardioverter defibrillator having a smaller displacement volume |
| US5624976A (en) | 1994-03-25 | 1997-04-29 | Dentsply Gmbh | Dental filling composition and method |
| US5314430A (en) | 1993-06-24 | 1994-05-24 | Medtronic, Inc. | Atrial defibrillator employing transvenous and subcutaneous electrodes and method of use |
| DE4325848A1 (de) | 1993-07-31 | 1995-02-02 | Basf Ag | Verfahren zur Herstellung von N-(2-Hydroxyethyl)-piperazin |
| EP0647462A1 (en) | 1993-10-06 | 1995-04-12 | The Kansai Electric Power Co., Inc. | Method for removing carbon dioxide from combustion exhaust gas |
| US5609624A (en) | 1993-10-08 | 1997-03-11 | Impra, Inc. | Reinforced vascular graft and method of making same |
| SE9303481L (sv) | 1993-10-22 | 1995-04-23 | Berol Nobel Ab | Hygienkomposition |
| WO1995013033A1 (en) | 1993-11-08 | 1995-05-18 | Lazarus Harrison M | Intraluminal vascular graft and method |
| NZ277614A (en) | 1993-11-24 | 1998-05-27 | Megabios Corp | Piperazine-containing amphiphiles and their use in liposomes for delivering genetic material intracellularly |
| US5464924A (en) | 1994-01-07 | 1995-11-07 | The Dow Chemical Company | Flexible poly(amino ethers) for barrier packaging |
| US5840576A (en) | 1994-07-20 | 1998-11-24 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
| US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
| US5965434A (en) | 1994-12-29 | 1999-10-12 | Wolff; Jon A. | Amphipathic PH sensitive compounds and delivery systems for delivering biologically active compounds |
| US5830430A (en) | 1995-02-21 | 1998-11-03 | Imarx Pharmaceutical Corp. | Cationic lipids and the use thereof |
| EP0822835A1 (en) | 1995-04-17 | 1998-02-11 | Imarx Pharmaceutical Corp. | Hybrid magnetic resonance contrast agents |
| US5772694A (en) | 1995-05-16 | 1998-06-30 | Medical Carbon Research Institute L.L.C. | Prosthetic heart valve with improved blood flow |
| US5700642A (en) | 1995-05-22 | 1997-12-23 | Sri International | Oligonucleotide sizing using immobilized cleavable primers |
| ATE285477T1 (de) | 1995-06-07 | 2005-01-15 | Inex Pharmaceutical Corp | Herstellung von lipid-nukleinsäure partikeln duch ein hydrophobische lipid-nukleinsäuree komplexe zwischenprodukt und zur verwendung in der gentransfer |
| US5609629A (en) | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
| US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
| US7422902B1 (en) | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| US5705385A (en) | 1995-06-07 | 1998-01-06 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| US5607385A (en) | 1995-08-17 | 1997-03-04 | Medtronic, Inc. | Device and algorithm for a combined cardiomyostimulator and a cardiac pacer-carioverter-defibrillator |
| US5744335A (en) | 1995-09-19 | 1998-04-28 | Mirus Corporation | Process of transfecting a cell with a polynucleotide mixed with an amphipathic compound and a DNA-binding protein |
| FR2740978B1 (fr) | 1995-11-10 | 1998-01-02 | Ela Medical Sa | Dispositif medical actif du type defibrillateur/cardioverteur implantable |
| US5874105A (en) | 1996-01-31 | 1999-02-23 | Collaborative Laboratories, Inc. | Lipid vesicles formed with alkylammonium fatty acid salts |
| US5913848A (en) | 1996-06-06 | 1999-06-22 | Luther Medical Products, Inc. | Hard tip over-the-needle catheter and method of manufacturing the same |
| US5736573A (en) | 1996-07-31 | 1998-04-07 | Galat; Alexander | Lipid and water soluble derivatives of drugs |
| TW520297B (en) | 1996-10-11 | 2003-02-11 | Sequus Pharm Inc | Fusogenic liposome composition and method |
| JPH10129797A (ja) | 1996-10-25 | 1998-05-19 | Toshiba Mach Co Ltd | 生ビール注出弁及び注出ノズルからの泡の排出方法 |
| US6887665B2 (en) | 1996-11-14 | 2005-05-03 | Affymetrix, Inc. | Methods of array synthesis |
| US6204297B1 (en) | 1996-11-26 | 2001-03-20 | Rhodia Inc. | Nonionic gemini surfactants |
| JPH10197978A (ja) | 1997-01-09 | 1998-07-31 | Mitsubishi Paper Mills Ltd | ハロゲン化銀写真感光材料 |
| FR2760193B1 (fr) | 1997-02-28 | 1999-05-28 | Transgene Sa | Lipides et complexes de lipides cationiques et de substances actives, notamment pour la transfection de cellules |
| US5837283A (en) | 1997-03-12 | 1998-11-17 | The Regents Of The University Of California | Cationic lipid compositions targeting angiogenic endothelial cells |
| US5945326A (en) | 1997-03-20 | 1999-08-31 | New England Biolabs, Inc. | Method for cloning and producing the Spel restriction endonuclease |
| JPH115786A (ja) | 1997-06-13 | 1999-01-12 | Pola Chem Ind Inc | 新規アミノヒドロキシプロピルピペラジン誘導体 |
| US6067471A (en) | 1998-08-07 | 2000-05-23 | Cardiac Pacemakers, Inc. | Atrial and ventricular implantable cardioverter-defibrillator and lead system |
| JPH1180142A (ja) | 1997-09-05 | 1999-03-26 | Pola Chem Ind Inc | ジフェニルアルキル化合物の製造法 |
| US20030083272A1 (en) * | 1997-09-19 | 2003-05-01 | Lahive & Cockfield, Llp | Sense mrna therapy |
| US6096075A (en) | 1998-01-22 | 2000-08-01 | Medical Carbon Research Institute, Llc | Prosthetic heart valve |
| US6271209B1 (en) | 1998-04-03 | 2001-08-07 | Valentis, Inc. | Cationic lipid formulation delivering nucleic acid to peritoneal tumors |
| US6176877B1 (en) | 1998-04-20 | 2001-01-23 | St. Jude Medical, Inc. | Two piece prosthetic heart valve |
| DE19822602A1 (de) | 1998-05-20 | 1999-11-25 | Goldschmidt Ag Th | Verfahren zur Herstellung von Polyaminosäureestern durch Veresterung von sauren Polyaminosäuren oder Umesterung von Polyaminosäureestern |
| NO313244B1 (no) | 1998-07-08 | 2002-09-02 | Crew Dev Corp | Fremgangsmåte for isolering og produksjon av magnesitt eller magnesiumklorid |
| US6055454A (en) | 1998-07-27 | 2000-04-25 | Cardiac Pacemakers, Inc. | Cardiac pacemaker with automatic response optimization of a physiologic sensor based on a second sensor |
| CA2340652C (en) | 1998-08-20 | 2013-09-24 | Cook Incorporated | Coated implantable medical device comprising paclitaxel |
| US6379698B1 (en) | 1999-04-06 | 2002-04-30 | Isis Pharmaceuticals, Inc. | Fusogenic lipids and vesicles |
| US6169923B1 (en) | 1999-04-23 | 2001-01-02 | Pacesetter, Inc. | Implantable cardioverter-defibrillator with automatic arrhythmia detection criteria adjustment |
| KR100669053B1 (ko) | 1999-04-23 | 2007-01-15 | 알자 코포레이션 | 리포좀에 사용하기 위한 절단가능 결합을 갖는 콘쥬게이트 |
| US6696424B1 (en) | 1999-05-28 | 2004-02-24 | Vical Incorporated | Cytofectin dimers and methods of use thereof |
| EP1202714A1 (en) | 1999-07-16 | 2002-05-08 | Purdue Research Foundation | Vinyl ether lipids with cleavable hydrophilic headgroups |
| DE19937275C2 (de) | 1999-08-06 | 2003-10-30 | Framatome Anp Gmbh | Verfahren und Datenverarbeitungsprogramm zur Ermittlung einer Kenngröße eines Nuklearreaktors |
| US6358278B1 (en) | 1999-09-24 | 2002-03-19 | St. Jude Medical, Inc. | Heart valve prosthesis with rotatable cuff |
| US6371983B1 (en) | 1999-10-04 | 2002-04-16 | Ernest Lane | Bioprosthetic heart valve |
| CN101041079A (zh) | 1999-12-30 | 2007-09-26 | 诺瓦提斯公司 | 用于基因治疗的新的胶体合成载体 |
| US6370434B1 (en) | 2000-02-28 | 2002-04-09 | Cardiac Pacemakers, Inc. | Cardiac lead and method for lead implantation |
| US6565960B2 (en) | 2000-06-01 | 2003-05-20 | Shriners Hospital Of Children | Polymer composite compositions |
| WO2002000870A2 (en) | 2000-06-26 | 2002-01-03 | Christian Plank | Method for transfecting cells using a magnetic field |
| IL138474A0 (en) | 2000-09-14 | 2001-10-31 | Epox Ltd | Highly branched water-soluble polyamine oligomers, process for their preparation and applications thereof |
| US7427394B2 (en) | 2000-10-10 | 2008-09-23 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| US6998115B2 (en) | 2000-10-10 | 2006-02-14 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| USRE43612E1 (en) | 2000-10-10 | 2012-08-28 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| US20020094528A1 (en) | 2000-11-29 | 2002-07-18 | Salafsky Joshua S. | Method and apparatus using a surface-selective nonlinear optical technique for detection of probe-target interations |
| JP2002167368A (ja) | 2000-12-01 | 2002-06-11 | Nitto Denko Corp | アルキル置換デンドリマーおよびその製造法 |
| US20020192721A1 (en) | 2001-03-28 | 2002-12-19 | Engeneos, Inc. | Modular molecular clasps and uses thereof |
| US7084303B2 (en) | 2001-04-23 | 2006-08-01 | Shin-Etsu Chemical Co., Ltd. | Tertiary amine compounds having an ester structure and processes for preparing same |
| EP2390331B1 (en) | 2001-09-28 | 2018-04-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | MicroRNA molecules |
| WO2003040288A2 (de) | 2001-11-09 | 2003-05-15 | Bayer Healthcare Ag | Isotopencodierte affinitätsmarker 3 |
| DE10207178A1 (de) | 2002-02-19 | 2003-09-04 | Novosom Ag | Komponenten für die Herstellung amphoterer Liposomen |
| US20030215395A1 (en) | 2002-05-14 | 2003-11-20 | Lei Yu | Controllably degradable polymeric biomolecule or drug carrier and method of synthesizing said carrier |
| US7601367B2 (en) | 2002-05-28 | 2009-10-13 | Mirus Bio Llc | Compositions and processes using siRNA, amphipathic compounds and polycations |
| US7901708B2 (en) | 2002-06-28 | 2011-03-08 | Protiva Biotherapeutics, Inc. | Liposomal apparatus and manufacturing methods |
| US20040028804A1 (en) | 2002-08-07 | 2004-02-12 | Anderson Daniel G. | Production of polymeric microarrays |
| WO2004018654A2 (en) | 2002-08-22 | 2004-03-04 | Celltran Limited | Cell culture surface |
| CN100457804C (zh) | 2002-11-04 | 2009-02-04 | Ge拜尔硅股份有限公司 | 线性聚氨基-和/或聚铵聚硅氧烷共聚物ⅰ |
| CA2506843A1 (en) | 2002-11-22 | 2004-06-10 | Novo-Nordisk A/S | 2,5-diketopiperazines for the treatment of obesity |
| US7135575B2 (en) * | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
| US7619017B2 (en) | 2003-05-19 | 2009-11-17 | Wacker Chemical Corporation | Polymer emulsions resistant to biodeterioration |
| EP1644479A4 (en) | 2003-06-16 | 2008-04-23 | Mark W Grinstaff | FUNCTIONAL SYNTHETIC MOLECULES AND MACROMOLECULES FOR GENERAL FEEDING |
| WO2005028619A2 (en) | 2003-09-15 | 2005-03-31 | Massachusetts Institute Of Technology | Nanoliter-scale synthesis of arrayed biomaterials and screening thereof |
| NZ592917A (en) | 2003-09-15 | 2012-12-21 | Protiva Biotherapeutics Inc | Stable polyethyleneglycol (PEG) dialkyloxypropyl (DAA) lipid conjugates |
| US20050069590A1 (en) | 2003-09-30 | 2005-03-31 | Buehler Gail K. | Stable suspensions for medicinal dosages |
| KR20060111471A (ko) | 2003-11-10 | 2006-10-27 | 니폰 가야꾸 가부시끼가이샤 | 디이모늄염 화합물 및 그의 용도 |
| US7022214B2 (en) | 2004-01-21 | 2006-04-04 | Bio-Rad Laboratories, Inc. | Carrier ampholytes of high pH range |
| US7556684B2 (en) | 2004-02-26 | 2009-07-07 | Construction Research & Technology Gmbh | Amine containing strength improvement admixture |
| US20060228404A1 (en) | 2004-03-04 | 2006-10-12 | Anderson Daniel G | Compositions and methods for treatment of hypertrophic tissues |
| CN1981044B (zh) * | 2004-06-07 | 2010-05-05 | 普洛体维生物治疗公司 | 包封干扰rna的脂质 |
| US7799565B2 (en) | 2004-06-07 | 2010-09-21 | Protiva Biotherapeutics, Inc. | Lipid encapsulated interfering RNA |
| US7745651B2 (en) | 2004-06-07 | 2010-06-29 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods of use |
| DE102004043342A1 (de) | 2004-09-08 | 2006-03-09 | Bayer Materialscience Ag | Blockierte Polyurethan-Prepolymere als Klebstoffe |
| GB0502482D0 (en) | 2005-02-07 | 2005-03-16 | Glaxo Group Ltd | Novel compounds |
| JP5042863B2 (ja) | 2005-02-14 | 2012-10-03 | サーナ・セラピューティクス・インコーポレイテッド | 生物学的に活性な分子をデリバリーするための脂質ナノ粒子系組成物および方法 |
| EP1869106B1 (en) | 2005-03-28 | 2014-06-25 | Dendritic Nanotechnologies, Inc. | Janus dendrimers and dendrons |
| US9006487B2 (en) | 2005-06-15 | 2015-04-14 | Massachusetts Institute Of Technology | Amine-containing lipids and uses thereof |
| EP3611266B1 (en) | 2005-08-23 | 2022-11-09 | The Trustees of the University of Pennsylvania | Rna containing modified nucleosides and methods of use thereof |
| WO2007031091A2 (en) | 2005-09-15 | 2007-03-22 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of p21 ras expression |
| US8101741B2 (en) | 2005-11-02 | 2012-01-24 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
| WO2007073489A2 (en) | 2005-12-22 | 2007-06-28 | Trustees Of Boston University | Molecules for gene delivery and gene therapy, and methods of use thereof |
| CN100569877C (zh) | 2005-12-30 | 2009-12-16 | 财团法人工业技术研究院 | 含多uv交联反应基的分枝状结构化合物及其应用 |
| US20070275923A1 (en) | 2006-05-25 | 2007-11-29 | Nastech Pharmaceutical Company Inc. | CATIONIC PEPTIDES FOR siRNA INTRACELLULAR DELIVERY |
| WO2007143659A2 (en) | 2006-06-05 | 2007-12-13 | Massachusetts Institute Of Technology | Crosslinked, degradable polymers and uses thereof |
| ES2293834B1 (es) | 2006-07-20 | 2009-02-16 | Consejo Superior Investig. Cientificas | Compuesto con actividad inhibidora de las interacciones ubc13-uev, composiciones farmaceuticas que lo comprenden y sus aplicaciones terapeuticas. |
| CA2658768C (en) | 2006-07-21 | 2016-05-17 | Massachusetts Institute Of Technology | End-modified poly(beta-amino esters) and uses thereof |
| EP2049665A2 (en) | 2006-07-28 | 2009-04-22 | Applera Corporation | Dinucleotide mrna cap analogs |
| EP3192788A1 (en) | 2006-10-03 | 2017-07-19 | Arbutus Biopharma Corporation | Lipid containing formulations |
| WO2008113364A2 (en) | 2007-03-20 | 2008-09-25 | Recepticon Aps | Amino derivatives to prevent nephrotoxicity and cancer |
| JP5186126B2 (ja) | 2007-03-29 | 2013-04-17 | 公益財団法人地球環境産業技術研究機構 | 新規トリアジン誘導体ならびにその製法およびそのガス分離膜としての用途 |
| US8678686B2 (en) | 2007-05-01 | 2014-03-25 | Pgr-Solutions | Multi-chain lipophilic polyamines |
| CA2701274A1 (en) | 2007-10-02 | 2009-04-09 | Mdrna, Inc. | Lipopeptides for delivery of nucleic acids |
| WO2009058911A2 (en) | 2007-10-31 | 2009-05-07 | Applied Biosystems Inc. | Preparation and isolation of 5' capped mrna |
| WO2009082607A2 (en) | 2007-12-04 | 2009-07-02 | Alnylam Pharmaceuticals, Inc. | Targeting lipids |
| WO2009082817A1 (en) | 2007-12-27 | 2009-07-09 | Protiva Biotherapeutics, Inc. | Silencing of polo-like kinase expression using interfering rna |
| WO2009126933A2 (en) | 2008-04-11 | 2009-10-15 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
| AU2009238175C1 (en) | 2008-04-15 | 2023-11-30 | Arbutus Biopharma Corporation | Novel lipid formulations for nucleic acid delivery |
| US20090263407A1 (en) | 2008-04-16 | 2009-10-22 | Abbott Laboratories | Cationic Lipids and Uses Thereof |
| WO2009127230A1 (en) | 2008-04-16 | 2009-10-22 | Curevac Gmbh | MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION |
| JP5024216B2 (ja) | 2008-07-23 | 2012-09-12 | トヨタ自動車株式会社 | 内燃機関の点火時期制御装置及び点火時期制御方法 |
| WO2010037408A1 (en) | 2008-09-30 | 2010-04-08 | Curevac Gmbh | Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof |
| CN104119242B (zh) | 2008-10-09 | 2017-07-07 | 泰米拉制药公司 | 改善的氨基脂质和递送核酸的方法 |
| CN102231979B (zh) | 2008-10-16 | 2014-10-29 | 玛瑞纳生物技术有限公司 | 基因沉默治疗剂的脂质体有效递送方法和组合物 |
| WO2010062322A2 (en) | 2008-10-27 | 2010-06-03 | Massachusetts Institute Of Technology | Modulation of the immune response |
| ES2646630T3 (es) | 2008-11-07 | 2017-12-14 | Massachusetts Institute Of Technology | Lipidoides aminoalcohólicos y usos de los mismos |
| HUE037082T2 (hu) | 2008-11-10 | 2018-08-28 | Arbutus Biopharma Corp | Új lipidek és készítmények terápiás hatóanyagok szállítására |
| TW201019969A (en) * | 2008-11-17 | 2010-06-01 | Enzon Pharmaceuticals Inc | Branched cationic lipids for nucleic acids delivery system |
| CA2750561C (en) | 2009-01-26 | 2017-10-10 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein c-iii expression |
| US20100222489A1 (en) | 2009-02-27 | 2010-09-02 | Jiang Dayue D | Copolymer composition, membrane article, and methods thereof |
| WO2010114789A1 (en) | 2009-04-02 | 2010-10-07 | The Siemon Company | Telecommunications patch panel |
| KR20180094137A (ko) | 2009-05-05 | 2018-08-22 | 알닐람 파마슈티칼스 인코포레이티드 | 지질 조성물 |
| MX342785B (es) | 2009-06-10 | 2016-10-12 | Alnylam Pharmaceuticals Inc | Formulacion mejorada de lipido. |
| WO2010147992A1 (en) | 2009-06-15 | 2010-12-23 | Alnylam Pharmaceuticals, Inc. | Methods for increasing efficacy of lipid formulated sirna |
| US8569256B2 (en) | 2009-07-01 | 2013-10-29 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
| US9018187B2 (en) | 2009-07-01 | 2015-04-28 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
| US8236943B2 (en) | 2009-07-01 | 2012-08-07 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein B |
| WO2011011447A1 (en) | 2009-07-20 | 2011-01-27 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing ebola virus gene expression |
| BR112012002134B8 (pt) | 2009-07-30 | 2021-05-25 | Salvat Lab Sa | compostos inibidores de apaf-1 |
| BR112012002291A2 (pt) | 2009-07-31 | 2016-11-29 | Ethris Gmbh | "polirribonucleotídeo com uma sequência que codifica uma proteína ou fragmento de proteína, implante, e, processo para a seleção de sequências de nucleotídeos" |
| DE102009043342A1 (de) | 2009-09-29 | 2011-03-31 | Bayer Technology Services Gmbh | Stoffe für selbstorganisierte Träger zur kontrollierten Freisetzung eines Wirkstoffs |
| HUE042177T2 (hu) | 2009-12-01 | 2019-06-28 | Translate Bio Inc | Szteroidszármazék mRNS szállítására humán genetikai betegségekben |
| EP2338520A1 (de) | 2009-12-21 | 2011-06-29 | Ludwig Maximilians Universität | Konjugat mit Zielfindungsligand und dessen Verwendung |
| WO2011076807A2 (en) | 2009-12-23 | 2011-06-30 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
| WO2011141705A1 (en) | 2010-05-12 | 2011-11-17 | Protiva Biotherapeutics, Inc. | Novel cationic lipids and methods of use thereof |
| CN101863544B (zh) | 2010-06-29 | 2011-09-28 | 湖南科技大学 | 一种氰尿酸基重金属螯合絮凝剂及其制备方法 |
| WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP2609135A4 (en) | 2010-08-26 | 2015-05-20 | Massachusetts Inst Technology | POLY (BETA AMINO ALCOHOLS), THEIR PREPARATION AND USES THEREOF |
| RU2013120302A (ru) | 2010-10-01 | 2014-11-20 | Модерна Терапьютикс, Инк. | Сконструированные нуклеиновые кислоты и способы их применения |
| WO2012075040A2 (en) | 2010-11-30 | 2012-06-07 | Shire Human Genetic Therapies, Inc. | mRNA FOR USE IN TREATMENT OF HUMAN GENETIC DISEASES |
| US9238716B2 (en) | 2011-03-28 | 2016-01-19 | Massachusetts Institute Of Technology | Conjugated lipomers and uses thereof |
| EP2691101A2 (en) | 2011-03-31 | 2014-02-05 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
| WO2012133737A1 (ja) | 2011-03-31 | 2012-10-04 | 公益財団法人地球環境産業技術研究機構 | 架橋性アミン化合物、該化合物を用いた高分子膜及びその製造方法 |
| WO2012158736A1 (en) | 2011-05-17 | 2012-11-22 | modeRNA Therapeutics | Engineered nucleic acids and methods of use thereof for non-human vertebrates |
| EP2532649B1 (en) | 2011-06-07 | 2015-04-08 | Incella GmbH | Amino lipids, their synthesis and uses thereof |
| EP3354644A1 (en) | 2011-06-08 | 2018-08-01 | Translate Bio, Inc. | Cleavable lipids |
| PL3586861T3 (pl) * | 2011-06-08 | 2022-05-23 | Translate Bio, Inc. | Kompozycje nanocząstek lipidowych i sposoby dostarczania mrna |
| EP2755986A4 (en) | 2011-09-12 | 2015-05-20 | Moderna Therapeutics Inc | MANIPULATED NUCLEIC ACIDS AND METHOD OF APPLICATION THEREFOR |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP3384938A1 (en) | 2011-09-12 | 2018-10-10 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| US8999950B2 (en) | 2011-10-05 | 2015-04-07 | Protiva Biotherapeutics Inc. | Compositions and methods for silencing aldehyde dehydrogenase |
| KR102451116B1 (ko) | 2011-10-27 | 2022-10-06 | 메사추세츠 인스티튜트 오브 테크놀로지 | 약물 캡슐화 마이크로스피어를 형성할 수 있는, ｎ-말단 상에 관능화된 아미노산 유도체 |
| WO2013090186A1 (en) | 2011-12-14 | 2013-06-20 | modeRNA Therapeutics | Modified nucleic acids, and acute care uses thereof |
| US20140378538A1 (en) | 2011-12-14 | 2014-12-25 | Moderma Therapeutics, Inc. | Methods of responding to a biothreat |
| CN104114572A (zh) | 2011-12-16 | 2014-10-22 | 现代治疗公司 | 经修饰的核苷、核苷酸和核酸组合物 |
| JP2015510495A (ja) | 2011-12-21 | 2015-04-09 | モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | 器官または器官移植片の生存可能性または寿命を延長する方法 |
| EP2797634A4 (en) | 2011-12-29 | 2015-08-05 | Moderna Therapeutics Inc | MODIFIED MRNAS FOR THE CODING OF CELL-PENETRATING POLYPEPTIDES |
| SG11201405157PA (en) | 2012-02-24 | 2014-10-30 | Protiva Biotherapeutics Inc | Trialkyl cationic lipids and methods of use thereof |
| CA2868391A1 (en) | 2012-04-02 | 2013-10-10 | Stephane Bancel | Polynucleotides comprising n1-methyl-pseudouridine and methods for preparing the same |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| US20140275229A1 (en) | 2012-04-02 | 2014-09-18 | Moderna Therapeutics, Inc. | Modified polynucleotides encoding udp glucuronosyltransferase 1 family, polypeptide a1 |
| US20150050354A1 (en) | 2012-04-02 | 2015-02-19 | Moderna Therapeutics, Inc. | Modified polynucleotides for the treatment of otic diseases and conditions |
| AU2013243948A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins associated with human disease |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| US9254311B2 (en) | 2012-04-02 | 2016-02-09 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
| EP2882706A1 (en) | 2012-08-13 | 2015-06-17 | Massachusetts Institute of Technology | Amine-containing lipidoids and uses thereof |
| WO2014081507A1 (en) | 2012-11-26 | 2014-05-30 | Moderna Therapeutics, Inc. | Terminally modified rna |
| EP4331620A3 (en) | 2012-12-07 | 2024-12-04 | Translate Bio, Inc. | Lipidic nanoparticles for mrna delivery |
| WO2014093574A1 (en) | 2012-12-13 | 2014-06-19 | Moderna Therapeutics, Inc. | Modified polynucleotides for altering cell phenotype |
| US20140200261A1 (en) | 2013-01-17 | 2014-07-17 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
| US20160022774A1 (en) | 2013-03-12 | 2016-01-28 | Moderna Therapeutics, Inc. | Diagnosis and treatment of fibrosis |
| EP2968391A1 (en) | 2013-03-13 | 2016-01-20 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
| EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
| DK2970456T3 (da) | 2013-03-14 | 2021-07-05 | Translate Bio Inc | Fremgangsmåder og sammensætninger til levering af mrna-kodede antistoffer |
| KR20210122917A (ko) * | 2013-03-14 | 2021-10-12 | 샤이어 휴먼 지네틱 테라피즈 인크. | Cftr mrna 조성물 및 관련 방법 및 사용 |
| WO2014152031A1 (en) | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Ribonucleic acid purification |
| WO2014144711A1 (en) | 2013-03-15 | 2014-09-18 | Moderna Therapeutics, Inc. | Analysis of mrna heterogeneity and stability |
| WO2014152030A1 (en) | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Removal of dna fragments in mrna production process |
| WO2014152027A1 (en) | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Manufacturing methods for production of rna transcripts |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| WO2014144767A1 (en) | 2013-03-15 | 2014-09-18 | Moderna Therapeutics, Inc. | Ion exchange purification of mrna |
| US20160032273A1 (en) | 2013-03-15 | 2016-02-04 | Moderna Therapeutics, Inc. | Characterization of mrna molecules |
| WO2014179562A1 (en) | 2013-05-01 | 2014-11-06 | Massachusetts Institute Of Technology | 1,3,5-triazinane-2,4,6-trione derivatives and uses thereof |
| US9895443B2 (en) | 2013-06-26 | 2018-02-20 | Massachusetts Institute Of Technology | Multi-tailed lipids and uses thereof |
| SMT202100691T1 (it) | 2013-07-11 | 2022-01-10 | Modernatx Inc | Composizioni 5 comprendenti polinucleotidi sintetici che codificano proteine correlate a crispr e sgrna sintetici e metodi d'uso |
| WO2015011633A1 (en) | 2013-07-23 | 2015-01-29 | Protiva Biotherapeutics, Inc. | Compositions and methods for delivering messenger rna |
| US20160194368A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Circular polynucleotides |
| US20160194625A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| WO2015051169A2 (en) | 2013-10-02 | 2015-04-09 | Moderna Therapeutics, Inc. | Polynucleotide molecules and uses thereof |
| EP3052479A4 (en) | 2013-10-02 | 2017-10-25 | Moderna Therapeutics, Inc. | Polynucleotide molecules and uses thereof |
| AU2014337156A1 (en) | 2013-10-18 | 2016-05-12 | Modernatx, Inc. | Compositions and methods for tolerizing cellular systems |
| EA034103B1 (ru) * | 2013-10-22 | 2019-12-27 | Транслейт Био, Инк. | СПОСОБ ЛЕЧЕНИЯ ФЕНИЛКЕТОНУРИИ С ПРИМЕНЕНИЕМ мРНК |
| ES2707966T3 (es) * | 2013-10-22 | 2019-04-08 | Translate Bio Inc | Terapia de ARNm para la deficiencia en síntesis de argininosuccinato |
| MX2016005238A (es) * | 2013-10-22 | 2016-08-12 | Shire Human Genetic Therapies | Formulaciones de lipidos para la administracion de acido ribonucleico mensajero. |
| EP3160959B1 (en) * | 2014-06-24 | 2023-08-30 | Translate Bio, Inc. | Stereochemically enriched compositions for delivery of nucleic acids |
| BR112017006679A2 (pt) | 2014-10-02 | 2017-12-26 | Protiva Biotherapeutics Inc | moléculas, composição, partícula, composição farmacêutica, métodos para silenciar a expressão de um gene, usos de uma partícula, métodos para melhorar um ou mais sintomas, métodos para tratar uma infecção, usos de uma composição, método para inibir a replicação do vírus da hepatite d |
| WO2016071857A1 (en) | 2014-11-07 | 2016-05-12 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing ebola virus expression |
| EP3461904A1 (en) | 2014-11-10 | 2019-04-03 | ModernaTX, Inc. | Alternative nucleic acid molecules containing reduced uracil content and uses thereof |
| WO2016077123A1 (en) | 2014-11-10 | 2016-05-19 | Moderna Therapeutics, Inc. | Multiparametric nucleic acid optimization |
| WO2016090262A1 (en) * | 2014-12-05 | 2016-06-09 | Shire Human Genetic Therapies, Inc. | Messenger rna therapy for treatment of articular disease |
| US20180000953A1 (en) | 2015-01-21 | 2018-01-04 | Moderna Therapeutics, Inc. | Lipid nanoparticle compositions |
| WO2016118725A1 (en) | 2015-01-23 | 2016-07-28 | Moderna Therapeutics, Inc. | Lipid nanoparticle compositions |
| EP3727428A1 (en) * | 2017-12-20 | 2020-10-28 | Translate Bio, Inc. | Improved composition and methods for treatment of ornithine transcarbamylase deficiency |
| MX2020011166A (es) | 2018-04-25 | 2022-10-19 | Ethris Gmbh | Agentes crioprotectores para formulaciones en forma de particulas. |
| CA3101454A1 (en) * | 2018-05-30 | 2019-12-05 | Translate Bio, Inc. | Messenger rna vaccines and uses thereof |
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