JP5766188B2 - 固形腫瘍に治療剤を送達するための脂質製剤 - Google Patents

固形腫瘍に治療剤を送達するための脂質製剤 Download PDF

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JP5766188B2
JP5766188B2 JP2012518706A JP2012518706A JP5766188B2 JP 5766188 B2 JP5766188 B2 JP 5766188B2 JP 2012518706 A JP2012518706 A JP 2012518706A JP 2012518706 A JP2012518706 A JP 2012518706A JP 5766188 B2 JP5766188 B2 JP 5766188B2
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lipid
nucleic acid
sirna
nucleotides
mol
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JP2012531469A (ja
JP2012531469A5 (cg-RX-API-DMAC7.html
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エド ジャウォースキー
エド ジャウォースキー
ステファン リード
ステファン リード
ジェームズ ヘイズ
ジェームズ ヘイズ
アダム ジャッジ
アダム ジャッジ
イアン マクラクラン
イアン マクラクラン
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プロチバ バイオセラピューティクス インコーポレイティッド
プロチバ バイオセラピューティクス インコーポレイティッド
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    • C12N2310/35—Nature of the modification
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JP2012518706A 2009-07-01 2010-06-30 固形腫瘍に治療剤を送達するための脂質製剤 Active JP5766188B2 (ja)

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Application Number Priority Date Filing Date Title
US22246909P 2009-07-01 2009-07-01
US61/222,469 2009-07-01
US29513410P 2010-01-14 2010-01-14
US61/295,134 2010-01-14
PCT/CA2010/001030 WO2011000107A1 (en) 2009-07-01 2010-06-30 Novel lipid formulations for delivery of therapeutic agents to solid tumors

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JP2012531469A JP2012531469A (ja) 2012-12-10
JP2012531469A5 JP2012531469A5 (cg-RX-API-DMAC7.html) 2013-08-08
JP5766188B2 true JP5766188B2 (ja) 2015-08-19

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US (9) US8283333B2 (cg-RX-API-DMAC7.html)
EP (1) EP2449114B9 (cg-RX-API-DMAC7.html)
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CA (1) CA2767127A1 (cg-RX-API-DMAC7.html)
ES (1) ES2613498T3 (cg-RX-API-DMAC7.html)
IL (3) IL292615B2 (cg-RX-API-DMAC7.html)
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Families Citing this family (416)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2338478B1 (en) 2002-06-28 2014-07-23 Protiva Biotherapeutics Inc. Method for producing liposomes
JP4951338B2 (ja) * 2003-07-16 2012-06-13 プロチバ バイオセラピューティクス インコーポレイティッド 脂質に封入された干渉ｒｎａ
EP1948674A4 (en) 2005-11-02 2009-02-04 Protiva Biotherapeutics Inc MODIFIED SIRNA MOLECULES AND APPLICATIONS THEREOF
AU2008342535B2 (en) * 2007-12-27 2015-02-05 Arbutus Biopharma Corporation Silencing of polo-like kinase expression using interfering RNA
JP5475753B2 (ja) 2008-04-15 2014-04-16 プロチバ バイオセラピューティクス インコーポレイティッド 核酸送達用の脂質製剤
EP3225621A1 (en) 2008-10-09 2017-10-04 Arbutus Biopharma Corporation Improved amino lipids and methods for the delivery of nucleic acids
MX338780B (es) 2008-11-10 2016-05-02 Alnylam Pharmaceuticals Inc Lipidos y composiciones novedosas para el suministro de terapeuticos.
EP2449106B1 (en) * 2009-07-01 2015-04-08 Protiva Biotherapeutics Inc. Compositions and methods for silencing apolipoprotein b
CA2767127A1 (en) 2009-07-01 2011-01-06 Protiva Biotherapeutics, Inc. Novel lipid formulations for delivery of therapeutic agents to solid tumors
EP3494963A1 (en) * 2009-12-18 2019-06-12 The University of British Columbia Methods and compositions for delivery of nucleic acids
EP2567952A4 (en) * 2010-04-28 2015-11-25 Kyowa Hakko Kirin Co Ltd CATIONIC LIPID
US9408914B2 (en) 2010-04-28 2016-08-09 Kyowa Hakko Kirin Co., Ltd. Cationic lipid
EP2569276B1 (en) 2010-05-12 2021-02-24 Arbutus Biopharma Corporation Novel cationic lipids and methods of use thereof
WO2011141704A1 (en) 2010-05-12 2011-11-17 Protiva Biotherapeutics, Inc Novel cyclic cationic lipids and methods of use
US9006417B2 (en) 2010-06-30 2015-04-14 Protiva Biotherapeutics, Inc. Non-liposomal systems for nucleic acid delivery
US11291635B2 (en) 2010-07-06 2022-04-05 Glaxosmithkline Biological Sa Virion-like delivery particles for self-replicating RNA molecules
LT3243526T (lt) 2010-07-06 2020-02-10 Glaxosmithkline Biologicals S.A. Rnr pristatymas, skirtas keleto imuninio atsako paleidimui
HRP20160805T1 (hr) 2010-07-06 2016-08-12 Glaxosmithkline Biologicals Sa Imuniziranje velikih sisavaca malim dozama rna
CA2804396C (en) 2010-07-06 2021-06-29 Novartis Ag Liposomes with lipids having an advantageous pka-value for rna delivery
WO2012019168A2 (en) 2010-08-06 2012-02-09 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
SI3981427T1 (sl) 2010-08-31 2022-08-31 Glaxosmithkline Biologicals S.A. Pegilirani liposomi za dostavo imunogen-kodirajoče RNA
ES3005233T3 (en) 2010-10-01 2025-03-14 Modernatx Inc Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
CN103269713B (zh) 2010-10-11 2016-01-20 诺华有限公司 抗原递送平台
DE12722942T1 (de) 2011-03-31 2021-09-30 Modernatx, Inc. Freisetzung und formulierung von manipulierten nukleinsäuren
WO2012162210A1 (en) * 2011-05-26 2012-11-29 Merck Sharp & Dohme Corp. Ring constrained cationic lipids for oligonucleotide delivery
EP3854413A1 (en) 2011-07-06 2021-07-28 GlaxoSmithKline Biologicals SA Immunogenic combination compositions and uses thereof
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
RU2648950C2 (ru) 2011-10-03 2018-04-02 Модерна Терапьютикс, Инк. Модифицированные нуклеозиды, нуклеотиды и нуклеиновые кислоты и их применение
EP2788006A1 (en) 2011-12-07 2014-10-15 Alnylam Pharmaceuticals, Inc. Biodegradable lipids for the delivery of active agents
AU2012352180A1 (en) 2011-12-16 2014-07-31 Moderna Therapeutics, Inc. Modified nucleoside, nucleotide, and nucleic acid compositions
US9035039B2 (en) * 2011-12-22 2015-05-19 Protiva Biotherapeutics, Inc. Compositions and methods for silencing SMAD4
CN104125826A (zh) * 2011-12-22 2014-10-29 努沃研究有限责任公司 亚氯酸盐或氯酸盐脂质体组合物
AU2013222179B2 (en) 2012-02-24 2017-08-24 Arbutus Biopharma Corporat ion Trialkyl cationic lipids and methods of use thereof
CA2868034C (en) 2012-03-29 2021-07-27 Shire Human Genetic Therapies, Inc. Ionizable cationic lipids
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
WO2013151663A1 (en) 2012-04-02 2013-10-10 modeRNA Therapeutics Modified polynucleotides for the production of membrane proteins
US9254311B2 (en) 2012-04-02 2016-02-09 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins
US10501513B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
AU2013243949A1 (en) 2012-04-02 2014-10-30 Moderna Therapeutics, Inc. Modified polynucleotides for the production of biologics and 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
HK1207977A1 (en) 2012-04-25 2016-02-19 Trustees Of Tufts College Silk microspheres and methods for surface lubrication
HRP20220607T1 (hr) 2012-11-26 2022-06-24 Modernatx, Inc. Terminalno modificirana rna
IL239317B (en) 2012-12-12 2022-07-01 Broad Inst Inc Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
WO2014164753A1 (en) * 2013-03-11 2014-10-09 Emory University Methods and compositions for managing vascular conditions
EP2971010B1 (en) 2013-03-14 2020-06-10 ModernaTX, Inc. Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
CN105793425B (zh) 2013-06-17 2021-10-26 布罗德研究所有限公司 使用病毒组分靶向障碍和疾病的crispr-cas系统和组合物的递送、用途和治疗应用
AU2014281028B2 (en) 2013-06-17 2020-09-10 Massachusetts Institute Of Technology Delivery and use of the CRISPR-Cas systems, vectors and compositions for hepatic targeting and therapy
EP3620524A1 (en) 2013-06-17 2020-03-11 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for targeting and modeling diseases and disorders of post mitotic cells
WO2015011633A1 (en) 2013-07-23 2015-01-29 Protiva Biotherapeutics, Inc. Compositions and methods for delivering messenger rna
EP3041938A1 (en) 2013-09-03 2016-07-13 Moderna Therapeutics, Inc. Circular polynucleotides
EP3041934A1 (en) 2013-09-03 2016-07-13 Moderna Therapeutics, Inc. Chimeric polynucleotides
EP3052106A4 (en) 2013-09-30 2017-07-19 ModernaTX, Inc. Polynucleotides encoding immune modulating polypeptides
KR20160067219A (ko) 2013-10-03 2016-06-13 모더나 세라퓨틱스, 인코포레이티드 저밀도 지단백질 수용체를 암호화하는 폴리뉴클레오타이드
EP3985118A1 (en) 2013-11-22 2022-04-20 MiNA Therapeutics Limited C/ebp alpha short activating rna compositions and methods of use
EP3080259B1 (en) 2013-12-12 2023-02-01 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
CN118813621A (zh) 2013-12-12 2024-10-22 布罗德研究所有限公司 用于基因组编辑的crispr-cas系统和组合物的递送、用途和治疗应用
WO2015089419A2 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using particle delivery components
WO2015089486A2 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems
EP3080257A1 (en) 2013-12-12 2016-10-19 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
MX374530B (es) 2013-12-12 2025-03-06 Broad Inst Inc Suministro, uso y aplicaciones terapeuticas de los sistemas y composiciones crispr-cas para actuar sobre hbv y trastornos y enfermedades virales.
JP6779866B2 (ja) 2014-06-13 2020-11-04 チルドレンズ メディカル センター コーポレイション ミトコンドリアを単離するための製品および方法
CN106795096B (zh) 2014-06-25 2020-05-29 爱康泰生治疗公司 用于递送核酸的新型脂质和脂质纳米颗粒制剂
US10583084B2 (en) 2014-06-26 2020-03-10 Ramot At Tel-Aviv University Ltd. Liposomal formulations for delivery of nucleic acids
US20170204152A1 (en) 2014-07-16 2017-07-20 Moderna Therapeutics, Inc. Chimeric polynucleotides
US20170210788A1 (en) 2014-07-23 2017-07-27 Modernatx, Inc. Modified polynucleotides for the production of intrabodies
EP3686279B1 (en) 2014-08-17 2023-01-04 The Broad Institute, Inc. Genome editing using cas9 nickases
WO2016049163A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Use and production of chd8+/- transgenic animals with behavioral phenotypes characteristic of autism spectrum disorder
WO2016049258A2 (en) 2014-09-25 2016-03-31 The Broad Institute Inc. Functional screening with optimized functional crispr-cas systems
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
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
EP3230452B1 (en) 2014-12-12 2025-06-11 The Broad Institute, Inc. Dead guides for crispr transcription factors
WO2016094880A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Delivery, use and therapeutic applications of crispr systems and compositions for genome editing as to hematopoietic stem cells (hscs)
EP3889260A1 (en) 2014-12-12 2021-10-06 The Broad Institute, Inc. Protected guide rnas (pgrnas)
EP3234192B1 (en) 2014-12-19 2021-07-14 The Broad Institute, Inc. Unbiased identification of double-strand breaks and genomic rearrangement by genome-wide insert capture sequencing
WO2016106236A1 (en) 2014-12-23 2016-06-30 The Broad Institute Inc. Rna-targeting system
AU2015369725A1 (en) 2014-12-24 2017-06-29 Massachusetts Institute Of Technology CRISPR having or associated with destabilization domains
WO2016197132A1 (en) 2015-06-04 2016-12-08 Protiva Biotherapeutics Inc. Treating hepatitis b virus infection using crispr
CA3012631A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Novel crispr enzymes and systems
WO2016205613A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Crispr enzyme mutations reducing off-target effects
WO2016205745A2 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Cell sorting
WO2016205749A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Novel crispr enzymes and systems
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems
HRP20240865T1 (hr) 2015-06-29 2024-10-11 Acuitas Therapeutics Inc. Lipidi i formulacije lipidnih nanočestica za isporuku nukleinskih kiselina
WO2017019891A2 (en) 2015-07-29 2017-02-02 Protiva Biotherapeutics, Inc. Compositions and methods for silencing hepatitis b virus gene expression
WO2017031370A1 (en) 2015-08-18 2017-02-23 The Broad Institute, Inc. Methods and compositions for altering function and structure of chromatin loops and/or domains
ES2910425T3 (es) 2015-09-17 2022-05-12 Modernatx Inc Compuestos y composiciones para la administración intracelular de agentes terapéuticos
US12241053B2 (en) 2015-10-09 2025-03-04 The Brigham And Women's Hospital, Inc. Modulation of novel immune checkpoint targets
CN109153980B (zh) 2015-10-22 2023-04-14 布罗德研究所有限公司 Vi-b型crispr酶和系统
CA3002922A1 (en) 2015-10-22 2017-04-27 Modernatx, Inc. Human cytomegalovirus vaccine
MD3718565T2 (ro) 2015-10-22 2022-09-30 Modernatx Inc Vaccinuri împotriva virusului respirator
WO2017074788A1 (en) 2015-10-27 2017-05-04 The Broad Institute Inc. Compositions and methods for targeting cancer-specific sequence variations
AU2016343803B2 (en) 2015-10-28 2021-04-29 Acuitas Therapeutics, Inc. Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids
WO2017075465A1 (en) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses by detecting and targeting gata3
WO2017075478A2 (en) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses by use of immune cell gene signatures
WO2017075451A1 (en) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses by detecting and targeting pou2af1
WO2017095946A1 (en) 2015-11-30 2017-06-08 Flagship Pioneering, Inc. Methods and compositions relating to chondrisomes
AU2016366978B2 (en) 2015-12-10 2022-07-28 Modernatx, Inc. Compositions and methods for delivery of therapeutic agents
WO2017106657A1 (en) 2015-12-18 2017-06-22 The Broad Institute Inc. Novel crispr enzymes and systems
SMT202200252T1 (it) 2015-12-22 2022-07-21 Modernatx Inc Composti e composizioni per il rilascio intracellulare di agenti
HRP20220525T1 (hr) 2015-12-23 2022-05-27 Modernatx, Inc. Postupci uporabe polinukleotida koji kodiraju ligand ox40
MA43587A (fr) 2016-01-10 2018-11-14 Modernatx Inc Arnm thérapeutiques codant pour des anticorps anti-ctla-4
JP7185527B2 (ja) 2016-01-15 2022-12-07 ザ チルドレンズ メディカル センター コーポレーション ミトコンドリアおよび組み合わされたミトコンドリア剤の治療的使用
KR102424476B1 (ko) 2016-04-19 2022-07-25 더 브로드 인스티튜트, 인코퍼레이티드 신규한 crispr 효소 및 시스템
EP3445856A1 (en) 2016-04-19 2019-02-27 The Broad Institute Inc. Novel crispr enzymes and systems
US11286478B2 (en) 2016-04-19 2022-03-29 The Broad Institute, Inc. Cpf1 complexes with reduced indel activity
CN109642231A (zh) 2016-06-17 2019-04-16 博德研究所 Vi型crispr直向同源物和系统
WO2018005873A1 (en) 2016-06-29 2018-01-04 The Broad Institute Inc. Crispr-cas systems having destabilization domain
MX2018016389A (es) * 2016-06-30 2019-08-16 Arbutus Biopharma Corp Composiciones y metodos para suministro de arn mensajero.
EP3500671B1 (en) 2016-08-17 2024-07-10 The Broad Institute, Inc. Method of selecting target sequences for the design of guide rnas
US20200283743A1 (en) 2016-08-17 2020-09-10 The Broad Institute, Inc. Novel crispr enzymes and systems
EP3500294A4 (en) 2016-08-22 2020-07-29 Arbutus Biopharma Corporation ANTI-PD-1 ANTIBODIES, OR THEIR FRAGMENTS, FOR THE TREATMENT OF HEPATITIS B
WO2018049025A2 (en) 2016-09-07 2018-03-15 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses
US12499971B2 (en) 2016-09-28 2025-12-16 The Broad Institute, Inc. Systematic screening and mapping of regulatory elements in non-coding genomic regions, methods, compositions, and applications thereof
WO2018067991A1 (en) 2016-10-07 2018-04-12 The Brigham And Women's Hospital, Inc. Modulation of novel immune checkpoint targets
EP3532103B1 (en) 2016-10-26 2025-12-03 Acuitas Therapeutics, Inc. Lipid nanoparticle formulations
US12491261B2 (en) 2016-10-26 2025-12-09 Acuitas Therapeutics, Inc. Lipid nanoparticle formulations
US11583504B2 (en) 2016-11-08 2023-02-21 Modernatx, Inc. Stabilized formulations of lipid nanoparticles
CA3056133A1 (en) 2017-03-15 2018-09-20 Modernatx, Inc. Crystal forms of amino lipids
SI3596041T1 (sl) 2017-03-15 2023-02-28 Modernatx, Inc. Spojina in sestavki za intracelično dostavljanje terapevtskih sredstev
US11739308B2 (en) 2017-03-15 2023-08-29 The Broad Institute, Inc. Cas13b orthologues CRISPR enzymes and systems
CA3055653A1 (en) 2017-03-15 2018-09-20 Modernatx, Inc. Lipid nanoparticle formulation
EP3596112A2 (en) 2017-03-17 2020-01-22 Newcastle University Adeno-associated virus vector delivery of a fragment of micro-dystrophin to treat muscular dystrophy
EP3610009A1 (en) 2017-04-12 2020-02-19 The Broad Institute, Inc. Novel type vi crispr orthologs and systems
WO2018191719A1 (en) 2017-04-13 2018-10-18 Acuitas Therapeutics, Inc. Lipid delivery of therapeutic agents to adipose tissue
WO2018191657A1 (en) 2017-04-13 2018-10-18 Acuitas Therapeutics, Inc. Lipids for delivery of active agents
WO2018191750A2 (en) 2017-04-14 2018-10-18 The Broad Institute Inc. Novel delivery of large payloads
EP4410317A3 (en) 2017-04-28 2024-10-30 Acuitas Therapeutics Inc. Novel carbonyl lipids and lipid nanoparticle formulations for delivery of nucleic acids
US11591601B2 (en) 2017-05-05 2023-02-28 The Broad Institute, Inc. Methods for identification and modification of lncRNA associated with target genotypes and phenotypes
CA3062426A1 (en) 2017-05-08 2018-11-15 Flagship Pioneering Innovations V, Inc. Compositions for facilitating membrane fusion and uses thereof
EP3625246A1 (en) 2017-05-18 2020-03-25 ModernaTX, Inc. Polynucleotides encoding tethered interleukin-12 (il12) polypeptides and uses thereof
EP3625342B1 (en) 2017-05-18 2022-08-24 The Broad Institute, Inc. Systems, methods, and compositions for targeted nucleic acid editing
JP2020524993A (ja) 2017-06-13 2020-08-27 フラッグシップ パイオニアリング イノベーションズ ブイ， インコーポレイテッド クロンを含む組成物及びその使用
WO2018232006A1 (en) 2017-06-14 2018-12-20 Modernatx, Inc. Polynucleotides encoding coagulation factor viii
EP3638678B1 (en) 2017-06-14 2025-12-03 ModernaTX, Inc. Compounds and compositions for intracellular delivery of agents
EP3638215A4 (en) 2017-06-15 2021-03-24 Modernatx, Inc. RNA FORMULATIONS
WO2019036008A1 (en) 2017-08-16 2019-02-21 Acuitas Therapeutics, Inc. LIPIDS FOR USE IN LIPID NANOPARTICULAR FORMULATIONS
US11542225B2 (en) 2017-08-17 2023-01-03 Acuitas Therapeutics, Inc. Lipids for use in lipid nanoparticle formulations
WO2019036030A1 (en) 2017-08-17 2019-02-21 Acuitas Therapeutics, Inc. LIPIDS FOR USE IN LIPID NANOPARTICLE FORMULATIONS
EP3668834B1 (en) 2017-08-17 2024-10-02 Acuitas Therapeutics, Inc. Lipids for use in lipid nanoparticle formulations
WO2019046809A1 (en) 2017-08-31 2019-03-07 Modernatx, Inc. METHODS OF MANUFACTURING LIPID NANOPARTICLES
EP4219715A3 (en) 2017-09-08 2023-09-06 MiNA Therapeutics Limited Stabilized cebpa sarna compositions and methods of use
US11447773B2 (en) 2017-09-08 2022-09-20 Mina Therapeutics Limited Stabilized HNF4A saRNA compositions and methods of use
AU2018338318B2 (en) 2017-09-21 2022-12-22 Massachusetts Institute Of Technology Systems, methods, and compositions for targeted nucleic acid editing
US20200255828A1 (en) 2017-10-04 2020-08-13 The Broad Institute, Inc. Methods and compositions for altering function and structure of chromatin loops and/or domains
US12227742B2 (en) 2017-10-23 2025-02-18 The Broad Institute, Inc. Nucleic acid modifiers
WO2019089828A1 (en) 2017-10-31 2019-05-09 Acuitas Therapeutics, Inc. Lamellar lipid nanoparticles
US11547614B2 (en) 2017-10-31 2023-01-10 The Broad Institute, Inc. Methods and compositions for studying cell evolution
WO2019094648A1 (en) 2017-11-08 2019-05-16 L.E.A.F. Holdings Group Llc Platinum complexes and uses thereof
WO2019094983A1 (en) 2017-11-13 2019-05-16 The Broad Institute, Inc. Methods and compositions for treating cancer by targeting the clec2d-klrb1 pathway
WO2019126709A1 (en) 2017-12-22 2019-06-27 The Broad Institute, Inc. Cas12b systems, methods, and compositions for targeted dna base editing
CN111954531A (zh) 2018-02-07 2020-11-17 L.E.A.F.控股集团公司 α聚谷氨酸化培美曲塞及其用途
CN111954530A (zh) 2018-02-07 2020-11-17 L.E.A.F.控股集团公司 γ聚谷氨酸化培美曲塞及其用途
WO2019197845A1 (en) 2018-04-12 2019-10-17 Mina Therapeutics Limited Sirt1-sarna compositions and methods of use
US12458597B2 (en) 2018-05-03 2025-11-04 L.E.A.F. Holdings Group Llc Carotenoid compositions and uses thereof
EP3807413B1 (en) 2018-06-18 2025-05-21 Research Institute at Nationwide Children's Hospital Adeno-associated virus vector delivery of muscle specific micro-dystrophin to treat muscular dystrophy
EP3833761A1 (en) 2018-08-07 2021-06-16 The Broad Institute, Inc. Novel cas12b enzymes and systems
EP3833762A4 (en) 2018-08-09 2022-09-28 Verseau Therapeutics, Inc. Oligonucleotide compositions for targeting ccr2 and csf1r and uses thereof
US12421507B2 (en) 2018-08-20 2025-09-23 The Broad Institute, Inc. Methods and compositions for optochemical control of CRISPR-CAS9
US12263248B2 (en) 2018-09-19 2025-04-01 Modernatx, Inc. Compounds and compositions for intracellular delivery of therapeutic agents
AU2019345067A1 (en) 2018-09-19 2021-04-08 Modernatx, Inc. High-purity peg lipids and uses thereof
MA53650A (fr) 2018-09-19 2021-07-28 Modernatx Inc Lipides peg et leurs utilisations
WO2020061457A1 (en) 2018-09-20 2020-03-26 Modernatx, Inc. Preparation of lipid nanoparticles and methods of administration thereof
IL322436A (en) 2018-09-21 2025-09-01 Acuitas Therapeutics Inc Systems and methods for producing lipid nanoparticles and liposomes
AU2019347774A1 (en) 2018-09-28 2021-03-25 Nutcracker Therapeutics, Inc. Lipid nanoparticle formulations comprising lipidated cationic peptide compounds for nucleic acid delivery
EP4379053A3 (en) 2018-10-09 2024-09-18 The University of British Columbia Compositions and systems comprising transfection-competent vesicles free of organic-solvents and detergents and methods related thereto
WO2020097540A1 (en) 2018-11-09 2020-05-14 Arbutus Biopharma Corporation Lipid nanoparticle formulations
US11166996B2 (en) 2018-12-12 2021-11-09 Flagship Pioneering Innovations V, Inc. Anellovirus compositions and methods of use
AU2019410737A1 (en) 2018-12-21 2021-06-10 CureVac SE RNA for malaria vaccines
US11453639B2 (en) 2019-01-11 2022-09-27 Acuitas Therapeutics, Inc. Lipids for lipid nanoparticle delivery of active agents
CA3125511A1 (en) 2019-02-08 2020-08-13 Curevac Ag Coding rna administered into the suprachoroidal space in the treatment of ophthalmic diseases
WO2020191102A1 (en) 2019-03-18 2020-09-24 The Broad Institute, Inc. Type vii crispr proteins and systems
US20220211740A1 (en) 2019-04-12 2022-07-07 Mina Therapeutics Limited Sirt1-sarna compositions and methods of use
US20220220469A1 (en) 2019-05-20 2022-07-14 The Broad Institute, Inc. Non-class i multi-component nucleic acid targeting systems
JP7744011B2 (ja) 2019-06-07 2025-09-25 スクライブ・セラピューティクス・インコーポレイテッド 操作されたｃａｓｘシステム
EP3986452A1 (en) 2019-06-18 2022-04-27 CureVac AG Rotavirus mrna vaccine
ES2982157T3 (es) 2019-07-18 2024-10-14 Institut Nat De La Sante Et De Larecherche Medicale Inserm Mutante de RAC2 para su uso en la ablación de la hematopoyesis y en el tratamiento de neoplasias malignas hematopoyéticas
EP3999642A1 (en) 2019-07-19 2022-05-25 Flagship Pioneering Innovations VI, LLC Recombinase compositions and methods of use
EP4010031A1 (en) 2019-08-06 2022-06-15 L.E.A.F Holdings Group LLC Processes of preparing polyglutamated antifolates and uses of their compositions
HRP20241255T1 (hr) 2019-08-14 2024-12-06 Acuitas Therapeutics, Inc. Poboljšane lipidne nanočestice za isporuku nukleinskih kiselina
CA3144902A1 (en) 2019-08-14 2022-01-19 Andreas Thess Rna combinations and compositions with decreased immunostimulatory properties
CN110564729A (zh) * 2019-09-17 2019-12-13 四川大学 一种对PLK1基因具有沉默活性且具有高血清稳定性的siRNA及其应用
CN120423969A (zh) 2019-09-19 2025-08-05 摩登纳特斯有限公司 用于治疗剂的细胞内递送的支链尾端脂质化合物和组合物
JP2022548399A (ja) 2019-09-23 2022-11-18 オメガ セラピューティクス， インコーポレイテッド 肝細胞核因子４－アルファ（ＨＮＦ４α）遺伝子発現をモジュレートするための組成物および方法
AU2020355000A1 (en) 2019-09-23 2022-03-17 Omega Therapeutics, Inc. Compositions and methods for modulating apolipoprotein B (APOB) gene expression
CA3160511A1 (en) 2020-02-04 2021-08-12 Susanne RAUCH Coronavirus vaccine
US11965161B2 (en) 2020-03-04 2024-04-23 Regeneron Pharmaceuticals, Inc. Methods and compositions for sensitization of tumor cells to immune therapy
JP2023517326A (ja) 2020-03-11 2023-04-25 オメガ セラピューティクス， インコーポレイテッド フォークヘッドボックスｐ３（ｆｏｘｐ３）遺伝子発現をモジュレートするための組成物および方法
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.
CN115667531A (zh) 2020-03-24 2023-01-31 世代生物公司 非病毒DNA载体和其用于表达戈谢（Gaucher）治疗剂的用途
WO2021198157A1 (en) 2020-03-30 2021-10-07 BioNTech SE Rna compositions targeting claudin-18.2
CN116322760A (zh) 2020-05-20 2023-06-23 旗舰创业创新第六有限责任公司 冠状病毒抗原组合物及其用途
IL298363A (en) 2020-05-20 2023-01-01 Flagship Pioneering Innovations Vi Llc Immunogenic compositions and uses thereof
EP4158032A2 (en) 2020-05-29 2023-04-05 Flagship Pioneering Innovations VI, LLC Trem compositions and methods relating thereto
CA3170740A1 (en) 2020-05-29 2021-12-02 Curevac Ag Nucleic acid based combination vaccines
IL298539A (en) 2020-05-29 2023-01-01 Flagship Pioneering Innovations Vi Llc Trem compositions and methods relating thereto
MX2022016332A (es) 2020-06-15 2023-04-03 Res Inst Nationwide Childrens Hospital Administracion de vectores de virus adenoasociados para distrofias musculares.
WO2025056938A1 (en) 2023-09-11 2025-03-20 BioNTech SE Rna compositions for delivery of incretin agents
FI4182297T3 (fi) 2020-07-16 2025-12-05 Acuitas Therapeutics Inc Kationisia lipidejä käytettäväksi lipidinanohiukkasissa
BR112023001648A2 (pt) 2020-07-27 2023-04-04 Anjarium Biosciences Ag Moléculas de dna de fita dupla, veículo de entrega e método para preparar uma molécula de dna com extremidade em grampo
EP4172194A1 (en) 2020-07-31 2023-05-03 CureVac SE Nucleic acid encoded antibody mixtures
CA3189854A1 (en) 2020-08-06 2022-02-10 Modernatx, Inc. Compositions for the delivery of payload molecules to airway epithelium
EP4157344A2 (en) 2020-08-31 2023-04-05 CureVac SE Multivalent nucleic acid based coronavirus vaccines
IL300947A (en) 2020-09-03 2023-04-01 Flagship Pioneering Innovations Vi Llc Immunogenic compositions and uses thereof
JP2023549011A (ja) 2020-09-15 2023-11-22 ヴァーヴ・セラピューティクス，インコーポレーテッド 遺伝子編集のための脂質製剤
MX2023004371A (es) 2020-10-14 2023-07-26 George Mason Res Foundation Inc Lípidos ionizables, y métodos de fabricación y uso de los mismos.
WO2022099003A1 (en) 2020-11-06 2022-05-12 Sanofi Lipid nanoparticles for delivering mrna vaccines
CN117098541A (zh) 2020-11-25 2023-11-21 阿卡格拉医药公司 用于递送核酸的脂质纳米粒及相关使用方法
GB2616584A (en) 2020-12-03 2023-09-13 Scribe Therapeutics Inc Engineered class 2 type V CRISPR systems
PH12023500013A1 (en) * 2020-12-04 2024-03-11 Tidal Therapeutics Inc Ionizable cationic lipids and lipi nanoparticles, and methods of synthesis and use thereof
GB2603454A (en) 2020-12-09 2022-08-10 Ucl Business Ltd Novel therapeutics for the treatment of neurodegenerative disorders
WO2022137133A1 (en) 2020-12-22 2022-06-30 Curevac Ag Rna vaccine against sars-cov-2 variants
WO2022135993A2 (en) 2020-12-22 2022-06-30 Curevac Ag Pharmaceutical composition comprising lipid-based carriers encapsulating rna for multidose administration
US20240175020A1 (en) 2020-12-23 2024-05-30 Flagship Pioneering Innovations Vi, Llc Compositions of modified trems and uses thereof
US20240102065A1 (en) 2021-01-27 2024-03-28 CureVac SE Method of reducing the immunostimulatory properties of in vitro transcribed rna
US11524023B2 (en) 2021-02-19 2022-12-13 Modernatx, Inc. Lipid nanoparticle compositions and methods of formulating the same
EP4314292A1 (en) 2021-03-26 2024-02-07 MiNA Therapeutics Limited Tmem173 sarna compositions and methods of use
JP2024511206A (ja) 2021-03-26 2024-03-12 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 免疫原性組成物
CA3214085A1 (en) 2021-03-31 2022-10-06 Darby Rye Schmidt Thanotransmission polypeptides and their use in treating cancer
WO2022207862A2 (en) 2021-03-31 2022-10-06 Curevac Ag Syringes containing pharmaceutical compositions comprising rna
WO2022215036A1 (en) 2021-04-08 2022-10-13 Vaxthera Sas Coronavirus vaccine comprising a mosaic protein
JP2024517427A (ja) 2021-04-20 2024-04-22 アンジャリウム バイオサイエンシズ エージー アミロ－α－１，６－グルコシダーゼ、４－α－グルカノトランスフェラーゼをコードするＤＮＡ分子の組成物、その作製の方法、及びその使用の方法
CA3216585A1 (en) 2021-04-27 2022-11-03 Nathaniel SILVER Non-viral dna vectors expressing therapeutic antibodies and uses thereof
US20240216535A1 (en) 2021-04-27 2024-07-04 Generation Bio Co. Non-viral dna vectors expressing anti-coronavirus antibodies and uses thereof
WO2022233880A1 (en) 2021-05-03 2022-11-10 Curevac Ag Improved nucleic acid sequence for cell type specific expression
EP4352215A1 (en) 2021-06-11 2024-04-17 LifeEDIT Therapeutics, Inc. Rna polymerase iii promoters and methods of use
EP4367242A2 (en) 2021-07-07 2024-05-15 Omega Therapeutics, Inc. Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression
EP4377457A1 (en) 2021-07-26 2024-06-05 Flagship Pioneering Innovations VI, LLC Trem compositions and uses thereof
WO2023014974A1 (en) 2021-08-06 2023-02-09 University Of Iowa Research Foundation Double stranded mrna vaccines
WO2023023055A1 (en) 2021-08-16 2023-02-23 Renagade Therapeutics Management Inc. Compositions and methods for optimizing tropism of delivery systems for rna
IL309505A (en) 2021-09-03 2024-02-01 CureVac SE Novel lipid nanoparticles for delivery of nucleic acids
AU2022336664A1 (en) 2021-09-03 2024-01-18 CureVac SE Novel lipid nanoparticles for delivery of nucleic acids comprising phosphatidylserine
JP2024533865A (ja) 2021-09-14 2024-09-12 レナゲード セラピューティクス マネージメント インコーポレイテッド 環状脂質及びその使用方法
TW202325263A (zh) 2021-09-14 2023-07-01 美商雷納嘉德醫療管理公司 非環狀脂質及其使用方法
JP2024534428A (ja) 2021-09-17 2024-09-20 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 環状ポリリボヌクレオチドを生成するための組成物及び方法
US20240392271A1 (en) 2021-09-21 2024-11-28 Scribe Therapeutics Inc. Engineered casx repressor systems
MX2024004618A (es) 2021-10-18 2024-07-12 Flagship Pioneering Innovations Vi Llc Composiciones y metodos para purificar polirribonucleotidos.
US20250027108A1 (en) 2021-10-29 2025-01-23 CureVac SE Improved circular rna for expressing therapeutic proteins
WO2023081756A1 (en) 2021-11-03 2023-05-11 The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone Precise genome editing using retrons
WO2023081526A1 (en) 2021-11-08 2023-05-11 Orna Therapeutics, Inc. Lipid nanoparticle compositions for delivering circular polynucleotides
CN118829423A (zh) 2021-11-12 2024-10-22 摩登纳特斯有限公司 用于将有效载荷分子递送至气道上皮的组合物
CN118829625A (zh) 2021-11-16 2024-10-22 赛欧生物医药股份有限公司 新型可电离脂质和脂质纳米颗粒以及它们的使用方法
JP2024542260A (ja) 2021-11-22 2024-11-13 セイル バイオメディシンズ インコーポレイテッド 新規イオン化可能な脂質および脂質ナノ粒子ならびにそれらを使用する方法
KR20240125931A (ko) 2021-11-24 2024-08-20 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 수두-대상포진 바이러스 면역원 조성물 및 이의 용도
MX2024006440A (es) 2021-11-24 2024-08-19 Flagship Pioneering Innovations Vi Llc Composiciones inmunogenicas y sus usos.
US20250352638A1 (en) 2021-11-24 2025-11-20 Flagship Pioneering Innovations Vi, Llc Coronavirus immunogen compositions and their uses
WO2023099884A1 (en) 2021-12-01 2023-06-08 Mina Therapeutics Limited Pax6 sarna compositions and methods of use
GB202117758D0 (en) 2021-12-09 2022-01-26 Ucl Business Ltd Therapeutics for the treatment of neurodegenerative disorders
US12129223B2 (en) 2021-12-16 2024-10-29 Acuitas Therapeutics, Inc. Lipids for use in lipid nanoparticle formulations
TW202340460A (zh) 2021-12-17 2023-10-16 美商旗艦先鋒創新有限責任公司 用於在變性條件下富集環狀ｒｎａ之方法
KR20240117149A (ko) 2021-12-22 2024-07-31 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 폴리리보뉴클레오티드를 정제하기 위한 조성물 및 방법
CA3243054A1 (en) 2021-12-23 2025-04-08 Renagade Therapeutics Management Inc. Constrained Lipids and Associated Utilization Processes
EP4452337A1 (en) 2021-12-23 2024-10-30 Flagship Pioneering Innovations VI, LLC Circular polyribonucleotides encoding antifusogenic polypeptides
EP4463475A2 (en) 2022-01-14 2024-11-20 Anjarium Biosciences AG Compositions of dna molecules encoding factor viii, methods of making thereof, and methods of use thereof
JP2025502257A (ja) 2022-01-17 2025-01-24 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル 固形腫瘍細胞の集団の細胞死を誘導する方法
WO2023141602A2 (en) 2022-01-21 2023-07-27 Renagade Therapeutics Management Inc. Engineered retrons and methods of use
EP4469063A1 (en) 2022-01-27 2024-12-04 BioNTech SE Pharmaceutical compositions for delivery of herpes simplex virus antigens and related methods
EP4469091A1 (en) 2022-01-28 2024-12-04 CureVac SE Nucleic acid encoded transcription factor inhibitors
EP4475882A1 (en) 2022-02-09 2024-12-18 ModernaTX, Inc. Mucosal administration methods and formulations
WO2023152365A1 (en) 2022-02-14 2023-08-17 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of the 15-lipoxygenase for the treatment of lymphedema
US20250327041A1 (en) 2022-02-24 2025-10-23 Io Biotech Aps Nucleotide delivery of cancer therapy
WO2023170435A1 (en) 2022-03-07 2023-09-14 Mina Therapeutics Limited Il10 sarna compositions and methods of use
KR20240161965A (ko) 2022-03-14 2024-11-13 제너레이션 바이오 컴퍼니 이종 프라임 부스트 백신 조성물 및 사용 방법
WO2023178425A1 (en) 2022-03-23 2023-09-28 Nanovation Therapeutics Inc. High sterol-containing lipid nanoparticles
KR20240166554A (ko) 2022-03-25 2024-11-26 세일 바이오메디슨스, 인크. 신규한 이온화 가능 지질 및 지질 나노입자, 및 이를 사용하는 방법
CA3255116A1 (en) 2022-04-01 2023-10-05 Nanovation Therapeutics Inc. METHOD FOR ADMINISTRATING RNA AND ASSOCIATED COMPOSITION
WO2023196818A1 (en) 2022-04-04 2023-10-12 The Regents Of The University Of California Genetic complementation compositions and methods
AU2023251104A1 (en) 2022-04-07 2024-10-17 Renagade Therapeutics Management Inc. Cyclic lipids and lipid nanoparticles (lnp) for the delivery of nucleic acids or peptides for use in vaccinating against infectious agents
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
AU2023260227A1 (en) 2022-04-27 2024-11-21 Shanghai Regenelead Therapies Co., Ltd Nucleic acid construct and use thereof
WO2023220083A1 (en) 2022-05-09 2023-11-16 Flagship Pioneering Innovations Vi, Llc Trem compositions and methods of use for treating proliferative disorders
JP2025515206A (ja) 2022-05-13 2025-05-13 上海瑞宏迪医薬有限公司 Ｕｔｒを含む核酸構築物及びその使用
EP4522753A2 (en) 2022-05-13 2025-03-19 Flagship Pioneering Innovations VII, LLC Double stranded dna compositions and related methods
WO2023218431A1 (en) 2022-05-13 2023-11-16 BioNTech SE Rna compositions targeting hiv
US20250345407A1 (en) 2022-05-25 2025-11-13 CureVac SE Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide
CA3256897A1 (en) 2022-05-25 2023-11-30 Akagera Medicines, Inc. Lipid nanoparticles for the administration of nucleic acids and their methods of use
WO2023230295A1 (en) 2022-05-25 2023-11-30 BioNTech SE Rna compositions for delivery of monkeypox antigens and related methods
CN119562807A (zh) 2022-05-30 2025-03-04 生物技术公司 用于递送核酸的复合物
JP2025520127A (ja) 2022-06-02 2025-07-01 スクライブ・セラピューティクス・インコーポレイテッド 操作されたクラス２タイプｖ ｃｒｉｓｐｒ系
CA3258303A1 (en) 2022-06-07 2023-12-14 Generation Bio Co. Compositions of lipid nanoparticles and their uses
CA3257914A1 (en) 2022-06-07 2023-12-14 Scribe Therapeutics Inc. COMPOSITIONS AND METHODS FOR TARGETING PCSK9
EP4536819A1 (en) 2022-06-07 2025-04-16 Scribe Therapeutics Inc. Compositions and methods for the targeting of pcsk9
US20250179492A1 (en) 2022-06-22 2025-06-05 Flagship Pioneering Innovations Vi, Llc Compositions of modified trems and uses thereof
WO2024023034A1 (en) 2022-07-25 2024-02-01 Institut National de la Santé et de la Recherche Médicale Use of apelin for the treatment of lymphedema
TW202413424A (zh) 2022-08-01 2024-04-01 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 免疫調節蛋白及相關方法
EP4569112A1 (en) 2022-08-12 2025-06-18 Remix Therapeutics Inc. Methods and compositions for modulating splicing at alternative splice sites
AU2023323547A1 (en) 2022-08-12 2025-03-20 Life Edit Therapeutics, Inc. Rna-guided nucleases and active fragments and variants thereof and methods of use
WO2024040222A1 (en) 2022-08-19 2024-02-22 Generation Bio Co. Cleavable closed-ended dna (cedna) and methods of use thereof
WO2024049979A2 (en) 2022-08-31 2024-03-07 Senda Biosciences, Inc. Novel ionizable lipids and lipid nanoparticles and methods of using the same
WO2024047247A1 (en) 2022-09-02 2024-03-07 Institut National de la Santé et de la Recherche Médicale Base editing approaches for the treatment of amyotrophic lateral sclerosis
EP4342460A1 (en) 2022-09-21 2024-03-27 NovoArc GmbH Lipid nanoparticle with nucleic acid cargo
IL319414A (en) 2022-09-23 2025-05-01 BioNTech SE Compositions for delivering antigens at the liver level and related methods
WO2024064910A1 (en) 2022-09-23 2024-03-28 Chroma Medicine, Inc. Compositions and methods for epigenetic regulation of hbv gene expression
WO2024063788A1 (en) 2022-09-23 2024-03-28 BioNTech SE Compositions for delivery of malaria antigens and related methods
AU2023347390A1 (en) 2022-09-23 2025-04-10 BioNTech SE Compositions for delivery of plasmodium csp antigens and related methods
WO2024063789A1 (en) 2022-09-23 2024-03-28 BioNTech SE Compositions for delivery of malaria antigens and related methods
AU2023353931A1 (en) 2022-09-26 2025-03-20 Glaxosmithkline Biologicals Sa Influenza virus vaccines
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
WO2024074211A1 (en) 2022-10-06 2024-04-11 BioNTech SE Rna compositions targeting claudin-18.2
AU2023357320A1 (en) 2022-10-06 2025-04-17 BioNTech SE Rna compositions targeting claudin-18.2
US12186389B2 (en) 2022-10-28 2025-01-07 Glaxosmithkline Biologicals Sa Nucleic acid base vaccine against emerging SARS-CoV-2 variants
KR20250099195A (ko) 2022-10-31 2025-07-01 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 폴리리보뉴클레오티드를 정제하기 위한 조성물 및 방법
WO2024102730A1 (en) 2022-11-08 2024-05-16 Orna Therapeutics, Inc. Lipids and nanoparticle compositions for delivering polynucleotides
AU2023375897A1 (en) 2022-11-08 2025-06-12 Orna Therapeutics, Inc. Circular rna compositions
AR131008A1 (es) 2022-11-08 2025-02-05 Flagship Pioneering Innovations Vi Llc Composiciones y métodos para producir polirribonucleótidos circulares
WO2024102762A1 (en) 2022-11-08 2024-05-16 Orna Therapeutics, Inc. Lipids and lipid nanoparticle compositions for delivering polynucleotides
JP2025541726A (ja) 2022-12-01 2025-12-23 ジェネレーション バイオ カンパニー 細胞標的化のためのステルス脂質ナノ粒子組成物
KR20250129819A (ko) 2022-12-01 2025-08-29 제너레이션 바이오 컴퍼니 핵산, 이온화 가능한 지질, 스테롤, 지질에 고정된 중합체, 및 헬퍼 지질을 포함하는 지질 나노입자 및 이의 용도
EP4626402A1 (en) 2022-12-01 2025-10-08 Generation Bio Co. Lipid nanoparticles comprising nucleic acids and lipid-anchored polymers
WO2024119051A1 (en) 2022-12-01 2024-06-06 Generation Bio Co. Novel polyglycerol-conjugated lipids and lipid nanoparticle compositions comprising the same
WO2024123633A1 (en) 2022-12-08 2024-06-13 Recode Therapeutics, Inc. Lipid nanoparticle compositions and uses thereof
EP4630033A1 (en) 2022-12-09 2025-10-15 Institut National de la Santé et de la Recherche Médicale Novel human antiviral genes related to the eleos and lamassu prokaryotic systems
WO2024125597A1 (en) 2022-12-14 2024-06-20 Providence Therapeutics Holdings Inc. Compositions and methods for infectious diseases
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
WO2024134199A1 (en) 2022-12-22 2024-06-27 Mina Therapeutics Limited Chemically modified sarna compositions and methods of use
CN121127490A (zh) 2022-12-28 2025-12-12 生物技术欧洲股份公司 靶向hiv的rna组合物
WO2024151673A2 (en) 2023-01-09 2024-07-18 President And Fellows Of Harvard College Recombinant nucleic acid molecules and their use in wound healing
EP4648789A1 (en) 2023-01-09 2025-11-19 Institut National de la Santé et de la Recherche Médicale Use of the recombinant fibrinogen-like domain of angiopoietin-like 4 for treating adverse post-ischemic cardiac remodeling in a patient who experienced a myocardial infarction
US20240252520A1 (en) 2023-01-09 2024-08-01 Beth Israel Deaconess Medical Center, Inc. Therapeutic agents and their use for treating chronic wounds
US20240269251A1 (en) 2023-01-09 2024-08-15 Flagship Pioneering Innovations V, Inc. Genetic switches and their use in treating cancer
TW202438673A (zh) 2023-01-09 2024-10-01 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 疫苗及相關方法
WO2024153636A1 (en) 2023-01-17 2024-07-25 Institut National de la Santé et de la Recherche Médicale Vasorin as a biomarker and biotarget in nephrology
EP4654984A1 (en) 2023-01-27 2025-12-03 Institut National de la Santé et de la Recherche Médicale Use of amphiregulin (areg) in methods of treating vascular hyperpermeability
EP4658239A1 (en) 2023-02-03 2025-12-10 GlaxoSmithKline Biologicals S.A. 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
EP4665405A1 (en) 2023-02-17 2025-12-24 Flagship Pioneering Innovations VII, LLC Dna compositions comprising modified uracil
AU2024220221A1 (en) 2023-02-17 2025-08-07 Flagship Pioneering Innovations Vii, Llc Dna compositions comprising modified cytosine
DE112024001143T5 (de) 2023-03-08 2025-12-18 CureVac SE Neue lipid-nanopartikel-formeln für die abgabe von nukleinsäuren
WO2024192422A1 (en) 2023-03-15 2024-09-19 Flagship Pioneering Innovations Vi, Llc Immunogenic compositions and uses thereof
KR20250162610A (ko) 2023-03-15 2025-11-18 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 폴리리보뉴클레오티드를 포함하는 조성물 및 이의 용도
WO2024194484A1 (en) 2023-03-23 2024-09-26 Institut National de la Santé et de la Recherche Médicale Modulating the expression and/or activity of gas7 for modulating viral replication
TW202444914A (zh) 2023-03-29 2024-11-16 美商斯奎柏治療公司 抑制子融合蛋白系統
TW202444906A (zh) 2023-03-29 2024-11-16 美商斯奎柏治療公司 用於靶向pcsk9之組合物及方法
WO2024205657A2 (en) 2023-03-29 2024-10-03 Orna Therapeutics, Inc. Lipids and lipid nanoparticle compositions for delivering polynucleotides
TW202444921A (zh) 2023-03-29 2024-11-16 美商斯奎柏治療公司 用於靶向lpa之組合物及方法
TW202444910A (zh) 2023-03-29 2024-11-16 美商斯奎柏治療公司 編碼casx之信使rna
AU2024255972A1 (en) 2023-04-12 2025-10-23 Flagship Pioneering Innovations Vi, Llc Modified trems, compositions, and related methods thereof
AU2024252590A1 (en) 2023-04-12 2025-10-23 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
WO2024223728A1 (en) 2023-04-27 2024-10-31 Glaxosmithkline Biologicals Sa Influenza virus vaccines
WO2024229309A2 (en) 2023-05-03 2024-11-07 Manifold Biotechnologies, Inc. Methodsand compositions for high-throughput protein delivery, screening, and detection
CN121038807A (zh) 2023-05-03 2025-11-28 生物技术欧洲股份公司 优化的csp变体及相关方法
WO2024228044A1 (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
WO2024238700A1 (en) 2023-05-15 2024-11-21 Chroma Medicine, Inc. Compositions and methods for epigenetic regulation of hbv gene expression
AU2024270764A1 (en) 2023-05-15 2025-12-04 Nchroma Bio, Inc. Compositions and methods for epigenetic regulation of hbv gene expression
WO2024243438A2 (en) 2023-05-23 2024-11-28 Omega Therapeutics, Inc. Compositions and methods for reducing cxcl9, cxcl10, and cxcl11 gene expression
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
WO2025024324A1 (en) 2023-07-21 2025-01-30 BioNTech SE Compositions for delivery of plasmodium antigens and related methods
WO2025024335A2 (en) 2023-07-21 2025-01-30 BioNTech SE Compositions for delivery of plasmodium antigens and related methods
WO2025024337A1 (en) 2023-07-24 2025-01-30 BioNTech SE Compositions for delivery of plasmodium antigens and related methods
WO2025021083A1 (en) * 2023-07-24 2025-01-30 National Institute Of Biological Sciences, Beijing Lipid nanoparticle compositions for localized treatment of skin diseases
TW202516001A (zh) 2023-07-25 2025-04-16 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 Ｃａｓ內切酶及相關方法
WO2025022367A2 (en) 2023-07-27 2025-01-30 Life Edit Therapeutics, Inc. Rna-guided nucleases and active fragments and variants thereof and methods of use
WO2025026545A1 (en) 2023-08-01 2025-02-06 BioNTech SE Ionizable thioplipids and uses thereof
TW202519509A (zh) 2023-08-01 2025-05-16 德商拜恩技術股份公司 可離子化硫脂質及其用途
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
WO2025027576A2 (en) 2023-08-03 2025-02-06 BioNTech SE Rna compositions targeting hiv
WO2025027579A2 (en) 2023-08-03 2025-02-06 BioNTech SE Rna compositions targeting hiv
WO2025030097A2 (en) 2023-08-03 2025-02-06 BioNTech SE Pharmaceutical compositions for delivery of herpes simplex virus antigens and related methods
WO2025042786A1 (en) 2023-08-18 2025-02-27 Flagship Pioneering Innovations Vi, Llc Compositions comprising circular polyribonucleotides and uses thereof
WO2025045142A1 (en) 2023-08-29 2025-03-06 Shanghai Circode Biomed Co., Ltd. Circular rna encoding vegf polypeptides, formulations, and methods of uses
WO2025049690A1 (en) 2023-08-29 2025-03-06 Orna Therapeutics, Inc. Circular polyethylene glycol lipids
WO2025046121A1 (en) 2023-09-01 2025-03-06 Novoarc Gmbh Lipid nanoparticle with nucleic acid cargo and ionizable lipid
WO2025054236A2 (en) 2023-09-06 2025-03-13 Flagship Pioneering Innovations Vii, Llc Sars-cov-2 vaccine compositions and related methods
EP4520345A1 (en) 2023-09-06 2025-03-12 Myneo Nv Product
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
WO2025057088A1 (en) 2023-09-11 2025-03-20 BioNTech SE Rna compositions for delivery of incretin agents
TW202525266A (zh) 2023-09-18 2025-07-01 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 可電離類脂質組成物及其治療用途
WO2025072383A1 (en) 2023-09-25 2025-04-03 The Broad Institute, Inc. Viral open reading frames, uses thereof, and methods of detecting the same
WO2025072331A1 (en) 2023-09-26 2025-04-03 Flagship Pioneering Innovations Vii, Llc Cas nucleases and related methods
WO2025072293A1 (en) 2023-09-27 2025-04-03 Scribe Therapeutics Inc. Optimized mrnas encoding casx proteins
WO2025081042A1 (en) 2023-10-12 2025-04-17 Renagade Therapeutics Management Inc. Nickase-retron template-based precision editing system and methods of use
WO2025083619A1 (en) 2023-10-18 2025-04-24 Life Edit Therapeutics, Inc. Rna-guided nucleases and acive fragments and variants thereof and methods of use
WO2025083211A1 (en) 2023-10-20 2025-04-24 Institut National de la Santé et de la Recherche Médicale Use of factor h for the treatment of dementia
WO2025096807A2 (en) 2023-10-31 2025-05-08 Flagship Pioneering Innovations Vii, Llc Novel therapeutic dna forms
WO2025097055A2 (en) 2023-11-02 2025-05-08 The Broad Institute, Inc. Compositions and methods of use of t cells in immunotherapy
WO2025101501A1 (en) 2023-11-07 2025-05-15 Orna Therapeutics, Inc. Circular rna compositions
TW202535835A (zh) 2023-11-14 2025-09-16 美商旗艦先鋒創新有限責任（Ｖｉｉ）公司 可電離類脂質組成物及其治療用途
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
US12364773B2 (en) 2023-12-01 2025-07-22 Recode Therapeutics, Inc. Lipid nanoparticle compositions and uses thereof
WO2025124711A1 (en) 2023-12-13 2025-06-19 BioNTech SE Glycolipid compositions
WO2025129128A1 (en) 2023-12-15 2025-06-19 Vivasor, Inc. Compositions and methods for non-viral delivery of therapeutic compounds
WO2025129158A1 (en) 2023-12-15 2025-06-19 The Broad Institute, Inc. Engineered arc delivery vesicles and uses thereof
WO2025132839A1 (en) 2023-12-21 2025-06-26 Glaxosmithkline Biologicals Sa Influenza virus vaccines
WO2025134066A1 (en) 2023-12-21 2025-06-26 Biontech Delivery Technologies Gmbh Ionizable lipids
WO2025134062A2 (en) 2023-12-21 2025-06-26 Biontech Delivery Technologies Gmbh Ionizable lipids
WO2025133105A1 (en) 2023-12-21 2025-06-26 Biontech Delivery Technologies Gmbh Compositions and methods
WO2025137646A1 (en) 2023-12-22 2025-06-26 Recode Therapeutics, Inc. Gene editing methods and compositions for treating cystic fibrosis
WO2025155753A2 (en) 2024-01-17 2025-07-24 Renagade Therapeutics Management Inc. Improved gene editing system, guides, and methods
US20250375499A1 (en) 2024-01-26 2025-12-11 Flagship Pioneering Innovations Vii, Llc Immunoreceptor inhibitory proteins and related methods
WO2025166325A1 (en) 2024-02-02 2025-08-07 Editas Medicine, Inc. MODIFIED GUIDE RNAs
WO2025174908A1 (en) 2024-02-12 2025-08-21 Life Edit Therapeutics, Inc. Novel rna-guided nucleases and proteins for polymerase editing
WO2025184508A1 (en) 2024-03-01 2025-09-04 Acuitas Therapeutics, Inc. Materials and methods for encapsulating therapeutics in lipid nanoparticles
WO2025194019A1 (en) 2024-03-14 2025-09-18 Flagship Pioneering Innovations Vii, Llc Methods for treating liver fibrosis and non-alcoholic fatty liver disease
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
WO2025213138A1 (en) 2024-04-05 2025-10-09 Editas Medicine, Inc. Crispr/rna-guided nuclease related methods and compositions for treating primary open angle glaucoma
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
WO2025215072A1 (en) 2024-04-10 2025-10-16 Institut National de la Santé et de la Recherche Médicale Class i lanthipeptides with anti-viral function
WO2025240680A1 (en) 2024-05-16 2025-11-20 Flagship Pioneering Innovations Vii, Llc Immunoreceptor inhibitory proteins and related methods
WO2025240940A1 (en) 2024-05-17 2025-11-20 Scribe Therapeutics Inc. Compositions and methods for the targeting of apolipoprotein c3
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
WO2025250808A1 (en) 2024-05-29 2025-12-04 The Brigham And Women’S Hospital, Inc. Anti-crispr delivery compositions and methods
WO2025248096A1 (en) 2024-05-31 2025-12-04 Institut National de la Santé et de la Recherche Médicale Antimicrobial peptides having liquid-liquid phase separation activities
WO2025259931A1 (en) 2024-06-14 2025-12-18 Orbital Therapeutics, Inc. Compositions and methods for rna circularization

Family Cites Families (244)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL154598B (nl) 1970-11-10 1977-09-15 Organon Nv Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking.
US3901654A (en) 1971-06-21 1975-08-26 Biological Developments Receptor assays of biologically active compounds employing biologically specific receptors
US3817827A (en) 1972-03-30 1974-06-18 Scott Paper Co Soft absorbent fibrous webs containing elastomeric bonding material and formed by creping and embossing
US3935074A (en) 1973-12-17 1976-01-27 Syva Company Antibody steric hindrance immunoassay with two antibodies
US3996345A (en) 1974-08-12 1976-12-07 Syva Company Fluorescence quenching with immunological pairs in immunoassays
US4034074A (en) 1974-09-19 1977-07-05 The Board Of Trustees Of Leland Stanford Junior University Universal reagent 2-site immunoradiometric assay using labelled anti (IgG)
US3993754A (en) 1974-10-09 1976-11-23 The United States Of America As Represented By The United States Energy Research And Development Administration Liposome-encapsulated actinomycin for cancer chemotherapy
US3984533A (en) 1975-11-13 1976-10-05 General Electric Company Electrophoretic method of detecting antigen-antibody reaction
US4086257A (en) 1976-10-12 1978-04-25 Sears Barry D Phosphatidyl quaternary ammonium compounds
US4098876A (en) 1976-10-26 1978-07-04 Corning Glass Works Reverse sandwich immunoassay
CH624011A5 (cg-RX-API-DMAC7.html) 1977-08-05 1981-07-15 Battelle Memorial Institute
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4394448A (en) 1978-02-24 1983-07-19 Szoka Jr Francis C Method of inserting DNA into living cells
EP0032578B1 (de) 1980-01-16 1984-07-25 Hans Georg Prof. Dr. Weder Verfahren und Dialysiereinrichtung zur Herstellung von Bilayer-Vesikeln und Verwendung der Bilayer-Vesikel
US4598051A (en) 1980-03-12 1986-07-01 The Regents Of The University Of California Liposome conjugates and diagnostic methods therewith
US4452901A (en) 1980-03-20 1984-06-05 Ciba-Geigy Corporation Electrophoretically transferring electropherograms to nitrocellulose sheets for immuno-assays
US4376110A (en) 1980-08-04 1983-03-08 Hybritech, Incorporated Immunometric assays using monoclonal antibodies
US4522803A (en) 1983-02-04 1985-06-11 The Liposome Company, Inc. Stable plurilamellar vesicles, their preparation and use
US4588578A (en) 1983-08-08 1986-05-13 The Liposome Company, Inc. Lipid vesicles prepared in a monophase
US4515736A (en) 1983-05-12 1985-05-07 The Regents Of The University Of California Method for encapsulating materials into liposomes
US5208036A (en) 1985-01-07 1993-05-04 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
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
US5545412A (en) 1985-01-07 1996-08-13 Syntex (U.S.A.) Inc. N-[1, (1-1)-dialkyloxy]-and N-[1, (1-1)-dialkenyloxy]-alk-1-yl-n,n,n-tetrasubstituted ammonium lipids and uses therefor
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4737323A (en) 1986-02-13 1988-04-12 Liposome Technology, Inc. Liposome extrusion method
US5453566A (en) 1986-03-28 1995-09-26 Calgene, Inc. Antisense regulation of gene expression in plant/cells
US4987071A (en) 1986-12-03 1991-01-22 University Patents, Inc. RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods
US5320906A (en) 1986-12-15 1994-06-14 Vestar, Inc. Delivery vehicles with amphiphile-associated active ingredient
WO1994003198A1 (en) 1992-07-31 1994-02-17 Genentech, Inc. Human growth hormone aqueous formulation
CA1340323C (en) 1988-09-20 1999-01-19 Arnold E. Hampel Rna catalyst for cleaving specific rna sequences
GB8822492D0 (en) 1988-09-24 1988-10-26 Considine J Apparatus for removing tumours from hollow organs of body
US5703055A (en) 1989-03-21 1997-12-30 Wisconsin Alumni Research Foundation Generation of antibodies through lipid mediated DNA delivery
FR2645866B1 (fr) 1989-04-17 1991-07-05 Centre Nat Rech Scient Nouvelles lipopolyamines, leur preparation et leur emploi
US5725871A (en) 1989-08-18 1998-03-10 Danbiosyst Uk Limited Drug delivery compositions comprising lysophosphoglycerolipid
JP3058686B2 (ja) 1989-08-31 2000-07-04 シティ・オブ・ホープ キメラｄｎａ―ｒｎａ触媒活性配列
US5286634A (en) 1989-09-28 1994-02-15 Stadler Joan K Synergistic method for host cell transformation
JPH03126211A (ja) 1989-10-12 1991-05-29 Nippon Chemicon Corp 電解コンデンサ用電解液
US5225212A (en) 1989-10-20 1993-07-06 Liposome Technology, Inc. Microreservoir liposome composition and method
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5707644A (en) 1989-11-04 1998-01-13 Danbiosyst Uk Limited Small particle compositions for intranasal drug delivery
US6753423B1 (en) 1990-01-11 2004-06-22 Isis Pharmaceuticals, Inc. Compositions and methods for enhanced biostability and altered biodistribution of oligonucleotides in mammals
US5279833A (en) 1990-04-04 1994-01-18 Yale University Liposomal transfection of nucleic acids into animal cells
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
US6465188B1 (en) 1990-06-11 2002-10-15 Gilead Sciences, Inc. Nucleic acid ligand complexes
US6365730B1 (en) 1990-06-19 2002-04-02 Gene Shears Pty. Limited DNA-Armed ribozymes and minizymes
US5789573A (en) 1990-08-14 1998-08-04 Isis Pharmaceuticals, Inc. Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2
WO1992007065A1 (en) 1990-10-12 1992-04-30 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Modified ribozymes
DE4114491A1 (de) * 1991-05-03 1992-11-05 Henkel Kgaa Fluessigwaschmittel
DE4216134A1 (de) 1991-06-20 1992-12-24 Europ Lab Molekularbiolog Synthetische katalytische oligonukleotidstrukturen
JP2774417B2 (ja) 1991-08-07 1998-07-09 株式会社ディ・ディ・エス研究所 ペプチド骨格を有する分枝鎖型糖複合体及び微粒子キャリヤー
US5283185A (en) 1991-08-28 1994-02-01 University Of Tennessee Research Corporation Method for delivering nucleic acids into cells
US6831166B2 (en) 1992-10-23 2004-12-14 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
CA2126101A1 (en) 1991-12-17 1993-06-24 Robert J. Debs Gene therapy for cystic fibrosis transmembrane conductance regulator activity (cftr)
US5858784A (en) 1991-12-17 1999-01-12 The Regents Of The University Of California Expression of cloned genes in the lung by aerosol- and liposome-based delivery
US5756353A (en) 1991-12-17 1998-05-26 The Regents Of The University Of California Expression of cloned genes in the lung by aerosol-and liposome-based delivery
US5652094A (en) 1992-01-31 1997-07-29 University Of Montreal Nucleozymes
EP0672178A4 (en) 1992-02-19 1996-03-20 Baylor College Medicine CELL GROWTH MODULATION WITH OLIGONUCLEOTIDS.
WO1993023569A1 (en) 1992-05-11 1993-11-25 Ribozyme Pharmaceuticals, Inc. Method and reagent for inhibiting viral replication
WO1993023011A1 (en) 1992-05-18 1993-11-25 Minnesota Mining And Manufacturing Company Transmucosal drug delivery device
IL105914A0 (en) 1992-06-04 1993-10-20 Univ California Methods and compositions for in vivo gene therapy
US5792451A (en) 1994-03-02 1998-08-11 Emisphere Technologies, Inc. Oral drug delivery compositions and methods
JPH07509133A (ja) 1992-07-17 1995-10-12 リボザイム・ファーマシューティカルズ・インコーポレイテッド 動物疾患の処置のための方法および剤
US5334761A (en) 1992-08-28 1994-08-02 Life Technologies, Inc. Cationic lipids
JP2854203B2 (ja) 1992-09-03 1999-02-03 株式会社ディ・ディ・エス研究所 リポソームの製造法
IL108367A0 (en) 1993-01-27 1994-04-12 Hektoen Inst For Medical Resea Antisense polynzcleotide inhibition of human growth factor-sensitive cancer cells
WO1995002698A1 (en) 1993-07-12 1995-01-26 Life Technologies, Inc. Composition and methods for transfecting eukaryotic cells
US5426039A (en) 1993-09-08 1995-06-20 Bio-Rad Laboratories, Inc. Direct molecular cloning of primer extended DNA containing an alkane diol
US5801154A (en) 1993-10-18 1998-09-01 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of multidrug resistance-associated protein
US5674908A (en) 1993-12-20 1997-10-07 Life Technologies, Inc. Highly packed polycationic ammonium, sulfonium and phosphonium lipids
FR2714830B1 (fr) 1994-01-10 1996-03-22 Rhone Poulenc Rorer Sa Composition contenant des acides nucléiques, préparation et utilisations.
US6075012A (en) 1994-02-11 2000-06-13 Life Technologies, Inc. Reagents for intracellular delivery of macromolecules
US6989434B1 (en) 1994-02-11 2006-01-24 Invitrogen Corporation Reagents for intracellular delivery of macromolecules
US5591317A (en) 1994-02-16 1997-01-07 Pitts, Jr.; M. Michael Electrostatic device for water treatment
US5631359A (en) 1994-10-11 1997-05-20 Ribozyme Pharmaceuticals, Inc. Hairpin ribozymes
CA2194221C (en) 1994-06-22 2001-01-02 Timothy D. Heath Cationic amphiphiles
FR2722506B1 (fr) 1994-07-13 1996-08-14 Rhone Poulenc Rorer Sa Composition contenant des acides nucleiques, preparation et utilisations
US5885613A (en) 1994-09-30 1999-03-23 The University Of British Columbia Bilayer stabilizing components and their use in forming programmable fusogenic liposomes
US5820873A (en) 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
US5753613A (en) 1994-09-30 1998-05-19 Inex Pharmaceuticals Corporation Compositions for the introduction of polyanionic materials into cells
CA2200952C (en) 1994-09-30 2006-04-11 Inex Pharmaceuticals Corp. Novel compositions comprising quaternary ammonium compounds and neutral lipids for the introduction of polyanionic materials into cells
WO1996011266A2 (en) 1994-10-05 1996-04-18 Amgen Inc. Method for inhibiting smooth muscle cell proliferation and oligonucleotides for use therein
US5627159A (en) 1994-10-27 1997-05-06 Life Technologies, Inc. Enhancement of lipid cationic transfections in the presence of serum
US5783683A (en) 1995-01-10 1998-07-21 Genta Inc. Antisense oligonucleotides which reduce expression of the FGFRI gene
US5580579A (en) 1995-02-15 1996-12-03 Nano Systems L.L.C. Site-specific adhesion within the GI tract using nanoparticles stabilized by high molecular weight, linear poly (ethylene oxide) polymers
IE80468B1 (en) 1995-04-04 1998-07-29 Elan Corp Plc Controlled release biodegradable nanoparticles containing insulin
US6051429A (en) 1995-06-07 2000-04-18 Life Technologies, Inc. Peptide-enhanced cationic lipid transfections
JPH11507815A (ja) 1995-06-07 1999-07-13 ジンタ・インコーポレイテッド ホスホン酸基本カチオン性脂質
JPH11507352A (ja) 1995-06-07 1999-06-29 ジンタ・インコーポレイテッド 新規カルバメート基本カチオン性脂質
AU723163B2 (en) 1995-06-07 2000-08-17 Tekmira Pharmaceuticals Corporation Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US5811406A (en) 1995-06-07 1998-09-22 Regents Of The University Of California Dry powder formulations of polynucleotide complexes
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
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
US20030069173A1 (en) 1998-03-16 2003-04-10 Life Technologies, Inc. Peptide-enhanced transfections
US5747470A (en) 1995-06-07 1998-05-05 Gen-Probe Incorporated Method for inhibiting cellular proliferation using antisense oligonucleotides to gp130 mRNA
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
US5736392A (en) 1995-06-07 1998-04-07 Life Technologies, Inc. Peptide-enhanced cationic lipid transfections
US6339173B1 (en) 1996-07-22 2002-01-15 Promega Biosciences, Inc. Amide-based cationic lipids
JPH11510489A (ja) 1995-07-21 1999-09-14 ジンタ・インコーポレイテッド 新規アミド基本カチオン性脂質
US20040142895A1 (en) 1995-10-26 2004-07-22 Sirna Therapeutics, Inc. Nucleic acid-based modulation of gene expression in the vascular endothelial growth factor pathway
US20030216335A1 (en) 2001-11-30 2003-11-20 Jennifer Lockridge Method and reagent for the modulation of female reproductive diseases and conditions
US6330349B1 (en) 1995-11-30 2001-12-11 Chromavision Medical Systems, Inc. Automated method for image analysis of residual protein
US5817856A (en) 1995-12-11 1998-10-06 Yissum Research Development Company Of The Hebrew University Of Jerusalem Radiation-protective phospholipid and method
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
US6713069B1 (en) 1996-04-16 2004-03-30 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Compositions and methods for detecting, preventing, and treating African Hemorrhagic Fever
US20050119470A1 (en) 1996-06-06 2005-06-02 Muthiah Manoharan Conjugated oligomeric compounds and their use in gene modulation
US6284267B1 (en) 1996-08-14 2001-09-04 Nutrimed Biotech Amphiphilic materials and liposome formulations thereof
US6111085A (en) 1996-09-13 2000-08-29 Isis Pharmaceuticals, Inc. Carbamate-derivatized nucleosides and oligonucleosides
US6210707B1 (en) 1996-11-12 2001-04-03 The Regents Of The University Of California Methods of forming protein-linked lipidic microparticles, and compositions thereof
US5739119A (en) 1996-11-15 1998-04-14 Galli; Rachel L. Antisense oligonucleotides specific for the muscarinic type 2 acetylcholine receptor MRNA
US5877220A (en) 1997-03-06 1999-03-02 Genta, Incorporated Amide-based oligomeric cationic lipids
US6034135A (en) 1997-03-06 2000-03-07 Promega Biosciences, Inc. Dimeric cationic lipids
US6406705B1 (en) 1997-03-10 2002-06-18 University Of Iowa Research Foundation Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant
DE69841002D1 (de) 1997-05-14 2009-09-03 Univ British Columbia Hochwirksame verkapselung von nukleinsäuren in lipidvesikeln
WO1998051285A2 (en) 1997-05-15 1998-11-19 Genzyme Corporation Cationic amphiphile formulations
US20030073640A1 (en) 1997-07-23 2003-04-17 Ribozyme Pharmaceuticals, Inc. Novel compositions for the delivery of negatively charged molecules
US6110745A (en) 1997-07-24 2000-08-29 Inex Pharmaceuticals Corp. Preparation of lipid-nucleic acid particles using a solvent extraction and direct hydration method
CA2309727C (en) 1997-10-10 2012-12-04 Inex Pharmaceuticals Corporation Methods for encapsulating nucleic acids in lipid bilayers
US6320017B1 (en) 1997-12-23 2001-11-20 Inex Pharmaceuticals Corp. Polyamide oligomers
US6410328B1 (en) 1998-02-03 2002-06-25 Protiva Biotherapeutics Inc. Sensitizing cells to compounds using lipid-mediated gene and compound delivery
CA2271582A1 (en) 1998-05-14 1999-11-14 Sean C. Semple Method for administration of therapeutic agents, including antisense, with repeat dosing
US6429200B1 (en) 1998-07-17 2002-08-06 Mirus Corporation Reverse micelles for delivery of nucleic acids
ATE237312T1 (de) 1998-07-20 2003-05-15 Protiva Biotherapeutics Inc In liposomen verkapselte nukleinsäurekomplexe
US6900049B2 (en) 1998-09-10 2005-05-31 Cell Genesys, Inc. Adenovirus vectors containing cell status-specific response elements and methods of use thereof
ATE383331T1 (de) 1998-11-12 2008-01-15 Invitrogen Corp Transportreagentien
US6649780B1 (en) 1998-12-22 2003-11-18 Valentis, Inc. Cationic lipids
CA2362485A1 (en) 1999-03-02 2000-09-08 The Liposome Company, Inc. Encapsulation of bioactive complexes in liposomes
EP1173600A2 (en) 1999-04-20 2002-01-23 The University Of British Columbia Cationic peg-lipids and methods of use
US6852334B1 (en) 1999-04-20 2005-02-08 The University Of British Columbia Cationic peg-lipids and methods of use
US6696424B1 (en) 1999-05-28 2004-02-24 Vical Incorporated Cytofectin dimers and methods of use thereof
US20010048940A1 (en) 1999-06-18 2001-12-06 Jennifer D. Tousignant Cationic amphiphile micellar complexes
WO2001005873A1 (en) 1999-07-14 2001-01-25 Alza Corporation Neutral lipopolymer and liposomal compositions containing same
AU771706B2 (en) 1999-07-15 2004-04-01 University Of British Columbia, The Methods and apparatus for preparation of lipid vesicles
DE60036950T2 (de) 1999-08-27 2008-08-07 Inex Pharmaceuticals Corp., Burnaby Zusammensetzungen zur stimulation der zytokin sekretion und zur induktion einer immunantwort
US6458382B1 (en) 1999-11-12 2002-10-01 Mirus Corporation Nucleic acid transfer complexes
EP2845596A3 (en) 2000-01-10 2015-07-15 Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Use of lipid conjugates in the treatment of disease
US8202979B2 (en) 2002-02-20 2012-06-19 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US20070026394A1 (en) 2000-02-11 2007-02-01 Lawrence Blatt Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies
AU2001249622B2 (en) 2000-03-30 2007-06-07 Massachusetts Institute Of Technology RNA sequence-specific mediators of RNA interference
US7189705B2 (en) 2000-04-20 2007-03-13 The University Of British Columbia Methods of enhancing SPLP-mediated transfection using endosomal membrane destabilizers
US20030072794A1 (en) 2000-06-09 2003-04-17 Teni Boulikas Encapsulation of plasmid DNA (lipogenes™) and therapeutic agents with nuclear localization signal/fusogenic peptide conjugates into targeted liposome complexes
EP1292284A2 (en) 2000-06-09 2003-03-19 Teni Boulikas Encapsulation of polynucleotides and drugs into targeted liposomes
US20030082103A1 (en) 2000-10-11 2003-05-01 Targesome, Inc. Targeted therapeutic lipid constructs having cell surface targets
JP2004511572A (ja) 2000-10-25 2004-04-15 ザ　ユニバーシティ　オブ　ブリティッシュ　コロンビア 標的化送達のための脂質製剤
AU2002232387A1 (en) 2000-10-27 2002-05-06 Invitrogen Corporation Method for introducing antisense oligonucleotides into eucaryotic cells
US20020081736A1 (en) 2000-11-03 2002-06-27 Conroy Susan E. Nucleic acid delivery
EP1873259B1 (en) 2000-12-01 2012-01-25 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. RNA interference mediated by 21 and 22nt RNAs
EP1350262B8 (en) 2000-12-08 2008-08-13 Coley Pharmaceuticals GmbH Cpg-like nucleic acids and methods of use thereof
US7053150B2 (en) 2000-12-18 2006-05-30 Nektar Therapeutics Al, Corporation Segmented polymers and their conjugates
TW593427B (en) 2000-12-18 2004-06-21 Nektar Therapeutics Al Corp Synthesis of high molecular weight non-peptidic polymer derivatives
US20030026831A1 (en) 2001-04-20 2003-02-06 Aparna Lakkaraju Anionic liposomes for delivery of bioactive agents
US20030077829A1 (en) 2001-04-30 2003-04-24 Protiva Biotherapeutics Inc.. Lipid-based formulations
US20040142892A1 (en) 2001-04-30 2004-07-22 The University Of British Columbia Autogene nucleic acids encoding a secretable RNA polymerase
US20030130186A1 (en) 2001-07-20 2003-07-10 Chandra Vargeese Conjugates and compositions for cellular delivery
US20050282188A1 (en) 2001-05-18 2005-12-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US7109165B2 (en) 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US20070173473A1 (en) 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
DE10163098B4 (de) 2001-10-12 2005-06-02 Alnylam Europe Ag Verfahren zur Hemmung der Replikation von Viren
US20040063654A1 (en) 2001-11-02 2004-04-01 Davis Mark E. Methods and compositions for therapeutic use of RNA interference
EP1432724A4 (en) 2002-02-20 2006-02-01 Sirna Therapeutics Inc INTERFERENCE MEDIATION INHIBITION OF GENE RNA FROM MAP KINASE
EP1476552A2 (en) 2002-02-22 2004-11-17 Strebhardt, Klaus, Prof. Dr. Agent for inhibiting development or progress of proliferative diseases and especially cancer diseases and pharmaceutical composition containing said agent
CA2752143C (en) 2002-05-15 2014-09-23 Sutter West Bay Hospitals Delivery of nucleic acid-like compounds
EP2338478B1 (en) 2002-06-28 2014-07-23 Protiva Biotherapeutics Inc. Method for producing liposomes
ES2322145T3 (es) 2002-07-26 2009-06-17 Novartis Vaccines And Diagnostics, Inc. Moleculas pequeñas modificadas de adn inerferente y procedimiento de uso.
WO2006006948A2 (en) 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
EP2314691A3 (en) 2002-11-14 2012-01-18 Dharmacon, Inc. Fuctional and hyperfunctional siRNA
EP1604010B1 (en) 2003-01-16 2010-08-11 The Trustees of The University of Pennsylvania COMPOSITIONS AND METHODS FOR siRNA INHIBITION OF ICAM-1
US20040167090A1 (en) 2003-02-21 2004-08-26 Monahan Sean D. Covalent modification of RNA for in vitro and in vivo delivery
US7803781B2 (en) 2003-02-28 2010-09-28 Isis Pharmaceuticals, Inc. Modulation of growth hormone receptor expression and insulin-like growth factor expression
EP1604022A2 (en) 2003-03-06 2005-12-14 Oligo Engine, Inc. Modulation of gene expression using dna-rna hybrids
WO2004090108A2 (en) 2003-04-03 2004-10-21 Alnylam Pharmaceuticals Irna conjugates
US20040185559A1 (en) 2003-03-21 2004-09-23 Isis Pharmaceuticals Inc. Modulation of diacylglycerol acyltransferase 1 expression
WO2004091515A2 (en) 2003-04-09 2004-10-28 Alnylam Pharmaceuticals, Inc. iRNA CONJUGATES
DK1620544T3 (en) 2003-04-17 2019-01-14 Alnylam Pharmaceuticals Inc MODIFIED iRNA AGENTS
US20050148531A1 (en) 2003-05-15 2005-07-07 Todd Hauser Modulation of gene expression using DNA-DNA hybrids
AU2004246905B2 (en) 2003-06-18 2010-01-21 Biolab Ltd. Sphingoid polyalkylamine conjugates for vaccination
JP4951338B2 (ja) 2003-07-16 2012-06-13 プロチバ バイオセラピューティクス インコーポレイティッド 脂質に封入された干渉ｒｎａ
US7825235B2 (en) 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
JP4842821B2 (ja) 2003-09-15 2011-12-21 プロチバ バイオセラピューティクス インコーポレイティッド ポリエチレングリコール修飾脂質化合物およびその使用
CN100368423C (zh) 2003-11-21 2008-02-13 杭州新瑞佳生物医药技术开发有限公司 有效杀伤肿瘤细胞的针对PLK1 mRNA的小干扰核糖核酸分子（SiRNA）、其混合物及用途
EP2514758B2 (en) 2004-03-15 2021-06-23 City of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
US20070265220A1 (en) 2004-03-15 2007-11-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
AU2005252273B2 (en) 2004-06-07 2011-04-28 Arbutus Biopharma Corporation Lipid encapsulated interfering RNA
US7745651B2 (en) 2004-06-07 2010-06-29 Protiva Biotherapeutics, Inc. Cationic lipids and methods of use
CA2572439A1 (en) 2004-07-02 2006-01-12 Protiva Biotherapeutics, Inc. Immunostimulatory sirna molecules and uses therefor
EP1793835A4 (en) 2004-09-10 2010-12-01 Somagenics Inc SMALL INTERFERING RNA EFFECTIVELY INHIBITING VIRAL GENE EXPRESSION AND METHODS OF USE THEREOF
CN101133074B (zh) 2004-09-24 2012-05-30 阿尔尼拉姆医药品有限公司 APOB的RNAi调节及其用途
WO2006035515A1 (ja) 2004-09-28 2006-04-06 Univ Kyoto 膀胱表在性癌の治療又は予防用医薬組成物､及びその利用
US20060134189A1 (en) 2004-11-17 2006-06-22 Protiva Biotherapeutics, Inc siRNA silencing of apolipoprotein B
WO2006074108A2 (en) 2004-12-30 2006-07-13 Hauser Todd M Compositions and methods for modulating gene expression using self-protected oligonucleotides
US7404969B2 (en) 2005-02-14 2008-07-29 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules
WO2007086881A2 (en) 2005-02-14 2007-08-02 Sirna Therapeutics, Inc. Cationic lipids and formulated molecular compositions containing them
US20060228406A1 (en) 2005-03-17 2006-10-12 Invitrogen Corporation Transfection reagent for non-adherent suspension cells
EP1937213B1 (en) 2005-07-27 2017-10-25 Protiva Biotherapeutics Inc. Systems and methods for manufacturing liposomes
JP2007052863A (ja) * 2005-08-18 2007-03-01 Toshiba Corp 光ディスク、光ディスク作製方法、光ディスク装置
US20070054873A1 (en) 2005-08-26 2007-03-08 Protiva Biotherapeutics, Inc. Glucocorticoid modulation of nucleic acid-mediated immune stimulation
WO2007048046A2 (en) 2005-10-20 2007-04-26 Protiva Biotherapeutics, Inc. Sirna silencing of filovirus gene expression
EP1948674A4 (en) * 2005-11-02 2009-02-04 Protiva Biotherapeutics Inc MODIFIED SIRNA MOLECULES AND APPLICATIONS THEREOF
WO2007056861A1 (en) 2005-11-18 2007-05-24 Protiva Biotherapeutics, Inc. Sirna silencing of influenza virus gene expression
JP2009523823A (ja) 2006-01-23 2009-06-25 アボット・ラボラトリーズ ｓｉＲＮＡ送達のための化学的に修飾されたポリカチオンポリマー
EP2835429B1 (en) 2006-05-11 2017-12-13 Alnylam Pharmaceuticals Inc. Compositions and methods for inhibiting expression of the PCSK9 gene
US8598333B2 (en) * 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
US7915399B2 (en) 2006-06-09 2011-03-29 Protiva Biotherapeutics, Inc. Modified siRNA molecules and uses thereof
US20080311040A1 (en) 2007-03-06 2008-12-18 Flagship Ventures METHODS AND COMPOSITIONS FOR IMPROVED THERAPEUTIC EFFECTS WITH siRNA
AU2008247488B2 (en) 2007-05-04 2014-02-27 Marina Biotech, Inc. Amino acid lipids and uses thereof
US20110159586A1 (en) 2007-12-07 2011-06-30 Halo-Bio Rnai Therapeutics, Inc. Compositions and methods for modulating gene expression using asymmetrically-active precursor polynucleotides
US7871985B2 (en) 2007-12-10 2011-01-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of factor VII gene
AU2008342535B2 (en) 2007-12-27 2015-02-05 Arbutus Biopharma Corporation Silencing of polo-like kinase expression using interfering RNA
EP3100718B1 (en) 2008-01-02 2019-11-27 Arbutus Biopharma Corporation Improved compositions and methods for the delivery of nucleic acids
EA201301171A1 (ru) 2008-03-05 2014-10-30 Элнилэм Фармасьютикалз, Инк. Композиции и способы ингибирования экспрессии генов eg5 и vegf
CA2721380A1 (en) 2008-04-15 2009-10-22 Protiva Biotherapeutics, Inc. Silencing of csn5 gene expression using interfering rna
JP5475753B2 (ja) 2008-04-15 2014-04-16 プロチバ バイオセラピューティクス インコーポレイティッド 核酸送達用の脂質製剤
US9006193B2 (en) * 2008-05-13 2015-04-14 University Of Washington Polymeric carrier
WO2010006282A2 (en) 2008-07-10 2010-01-14 Serina Therapeutics, Inc. Polyoxazolines with inert terminating groups, polyoxazolines prepared from protected initiating groups and related compounds
EP3225621A1 (en) 2008-10-09 2017-10-04 Arbutus Biopharma Corporation Improved amino lipids and methods for the delivery of nucleic acids
JP5791505B2 (ja) 2008-10-20 2015-10-07 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． トランスチレチンの発現を阻害するための組成物および方法
US8722082B2 (en) 2008-11-10 2014-05-13 Tekmira Pharmaceuticals Corporation Lipids and compositions for the delivery of therapeutics
MX338780B (es) 2008-11-10 2016-05-02 Alnylam Pharmaceuticals Inc Lipidos y composiciones novedosas para el suministro de terapeuticos.
EP3243504A1 (en) 2009-01-29 2017-11-15 Arbutus Biopharma Corporation Improved lipid formulation
CA2754043A1 (en) 2009-03-12 2010-09-16 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of eg5 and vegf genes
PL2440183T3 (pl) 2009-06-10 2019-01-31 Arbutus Biopharma Corporation Ulepszona formulacja lipidowa
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation 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
CA2767127A1 (en) 2009-07-01 2011-01-06 Protiva Biotherapeutics, Inc. Novel lipid formulations for delivery of therapeutic agents to solid tumors
EP2449106B1 (en) * 2009-07-01 2015-04-08 Protiva Biotherapeutics Inc. Compositions and methods for silencing apolipoprotein b
US9018187B2 (en) * 2009-07-01 2015-04-28 Protiva Biotherapeutics, Inc. Cationic lipids and methods for the delivery of therapeutic agents
WO2011011447A1 (en) * 2009-07-20 2011-01-27 Protiva Biotherapeutics, Inc. Compositions and methods for silencing ebola virus gene expression
EP3118334A1 (en) * 2009-11-04 2017-01-18 DiamiR, LLC Methods of using small rna from bodily fluids for diagnosis and monitoring of neurodegenerative diseases
US8455455B1 (en) * 2010-03-31 2013-06-04 Protiva Biotherapeutics, Inc. Compositions and methods for silencing genes involved in hemorrhagic fever
WO2011141704A1 (en) 2010-05-12 2011-11-17 Protiva Biotherapeutics, Inc Novel cyclic cationic lipids and methods of use
WO2011141703A1 (en) 2010-05-12 2011-11-17 Protiva Biotherapeutics Inc. Compositions and methods for silencing apolipoprotein b
US9006417B2 (en) 2010-06-30 2015-04-14 Protiva Biotherapeutics, Inc. Non-liposomal systems for nucleic acid delivery
US8466122B2 (en) * 2010-09-17 2013-06-18 Protiva Biotherapeutics, Inc. Trialkyl cationic lipids and methods of use thereof
WO2012068176A1 (en) 2010-11-15 2012-05-24 Life Technologies Corporation Amine-containing transfection reagents and methods for making and using same
US9126966B2 (en) 2011-08-31 2015-09-08 Protiva Biotherapeutics, Inc. Cationic lipids and methods of use thereof
AU2012318249B2 (en) 2011-10-05 2016-04-21 Protiva Biotherapeutics Inc. Compositions and methods for silencing aldehyde dehydrogenase
AU2012352180A1 (en) 2011-12-16 2014-07-31 Moderna Therapeutics, Inc. Modified nucleoside, nucleotide, and nucleic acid compositions
US9035039B2 (en) 2011-12-22 2015-05-19 Protiva Biotherapeutics, Inc. Compositions and methods for silencing SMAD4
CN107106874B (zh) 2014-08-29 2021-08-31 阿尔尼拉姆医药品有限公司 治疗甲状腺素运载蛋白(ttr)介导的淀粉样变性的方法
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
US20200315967A1 (en) 2016-06-24 2020-10-08 Modernatx, Inc. Lipid nanoparticles
EP3638215A4 (en) 2017-06-15 2021-03-24 Modernatx, Inc. RNA FORMULATIONS

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