DK2529020T3 - SCALABLE PREPARATION PLATF FOR CLEANING VIRAL VECTORS AND CLEANED VIRAL VECTORS FOR USE IN GENTHERAPY - Google Patents
SCALABLE PREPARATION PLATF FOR CLEANING VIRAL VECTORS AND CLEANED VIRAL VECTORS FOR USE IN GENTHERAPY Download PDFInfo
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- DK2529020T3 DK2529020T3 DK11737508.9T DK11737508T DK2529020T3 DK 2529020 T3 DK2529020 T3 DK 2529020T3 DK 11737508 T DK11737508 T DK 11737508T DK 2529020 T3 DK2529020 T3 DK 2529020T3
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Families Citing this family (119)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9217155B2 (en) | 2008-05-28 | 2015-12-22 | University Of Massachusetts | Isolation of novel AAV'S and uses thereof |
| WO2010138263A2 (en) | 2009-05-28 | 2010-12-02 | University Of Massachusetts | Novel aav 's and uses thereof |
| MX340102B (es) * | 2010-01-28 | 2016-06-24 | The Children's Hospital Of Philadelphia * | Una plataforma de fabricacion ajustable en escala, para la purificacion de vector viral y vectores virales asi purificados para el uso en terapia de genes. |
| WO2011133874A1 (en) | 2010-04-23 | 2011-10-27 | University Of Massachusetts | Multicistronic expression constructs |
| US9102949B2 (en) | 2010-04-23 | 2015-08-11 | University Of Massachusetts | CNS targeting AAV vectors and methods of use thereof |
| WO2013036118A1 (en) * | 2011-09-08 | 2013-03-14 | Uniqure Ip B.V. | Removal of contaminating viruses from aav preparations |
| ES2949648T3 (es) | 2012-12-20 | 2023-10-02 | Purdue Research Foundation | Células T que expresan un receptor antigénico quimérico como terapia contra el cáncer |
| FR3002237B1 (fr) * | 2013-02-15 | 2017-12-15 | Genethon | Methodes pour la production de particules virales aav double brin |
| CA2930872C (en) | 2013-11-26 | 2022-05-31 | University Of Florida Research Foundation, Incorporated | Adeno-associated virus vectors for treatment of glycogen storage disease |
| GB201401707D0 (en) | 2014-01-31 | 2014-03-19 | Sec Dep For Health The | Adeno-associated viral vectors |
| WO2015127128A2 (en) | 2014-02-19 | 2015-08-27 | University Of Massachusetts | Recombinant aavs having useful transcytosis properties |
| AU2015231294B2 (en) | 2014-03-18 | 2020-10-29 | University Of Massachusetts | rAAV-based compositions and methods for treating amyotrophic lateral sclerosis |
| SI3119437T1 (sl) * | 2014-03-21 | 2020-01-31 | Genzyme Corporation | Genska terapija za retinitis pigmentoza |
| JP6741590B2 (ja) | 2014-04-25 | 2020-08-19 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | コレステロールレベルを低下させるためのldlr変異体および組成物中でのそれらの使用 |
| US10975391B2 (en) | 2014-04-25 | 2021-04-13 | University Of Massachusetts | Recombinant AAV vectors useful for reducing immunity against transgene products |
| US10689653B2 (en) | 2014-06-03 | 2020-06-23 | University Of Massachusetts | Compositions and methods for modulating dysferlin expression |
| WO2016054557A1 (en) | 2014-10-03 | 2016-04-07 | University Of Massachusetts | Novel high efficiency library-identified aav vectors |
| WO2016054554A1 (en) | 2014-10-03 | 2016-04-07 | University Of Massachusetts | Heterologous targeting peptide grafted aavs |
| CA2964272A1 (en) | 2014-10-21 | 2016-04-28 | Guangping Gao | Recombinant aav variants and uses thereof |
| WO2016083560A1 (en) * | 2014-11-28 | 2016-06-02 | Uniqure Ip B.V. | Dna impurities in a composition comprising a parvoviral virion |
| US10415044B2 (en) | 2014-12-23 | 2019-09-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Adeno-associated virus vectors encoding modified G6PC and uses thereof |
| EP3245218A4 (en) | 2015-01-13 | 2018-10-03 | Alfa Wassermann, Inc. | Methods of purifying adeno-associated virus (aav) and/or recombinant adeno-associated virus (raav) and gradients and flow-through buffers therefore |
| EP3054006A1 (en) | 2015-02-09 | 2016-08-10 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Recombinant adeno-associated virus particle purification with multiple-step anion exchange chromatography |
| EP3054007A1 (en) | 2015-02-09 | 2016-08-10 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Recombinant adeno-associated virus particle purification comprising an immuno-affinity purification step |
| US10584321B2 (en) | 2015-02-13 | 2020-03-10 | University Of Massachusetts | Compositions and methods for transient delivery of nucleases |
| EP3262162A4 (en) * | 2015-02-23 | 2018-08-08 | Voyager Therapeutics, Inc. | Regulatable expression using adeno-associated virus (aav) |
| CN108093639B (zh) | 2015-04-16 | 2022-07-19 | 埃默里大学 | 用于肝脏中蛋白质表达的重组启动子和载体及其用途 |
| ES2856936T3 (es) | 2015-04-23 | 2021-09-28 | Univ Washington State | Suministro del gen Smad7 como un agente terapéutico |
| CA3021949C (en) | 2015-04-24 | 2023-10-17 | University Of Massachusetts | Modified aav constructs and uses thereof |
| DK3364997T5 (da) | 2015-10-22 | 2024-09-30 | Univ Massachusetts | Aspartoacylase genterapi til behandling af canavans sygdom |
| CA3002980A1 (en) | 2015-10-22 | 2017-04-27 | University Of Massachusetts | Prostate-targeting adeno-associated virus serotype vectors |
| CN105420275A (zh) * | 2015-11-27 | 2016-03-23 | 中国科学院苏州生物医学工程技术研究所 | 制备外源功能基因定点整合的人神经干细胞的方法 |
| ES2918998T3 (es) | 2015-12-11 | 2022-07-21 | Univ Pennsylvania | Método de purificación escalable para AAVrh10 |
| MX2018007080A (es) * | 2015-12-11 | 2018-11-12 | Univ Pennsylvania | Terapia genica para tratar hipercolesterolemia familiar. |
| EP3387117B1 (en) * | 2015-12-11 | 2022-11-23 | The Trustees Of The University Of Pennsylvania | Scalable purification method for aav8 |
| WO2017100674A1 (en) * | 2015-12-11 | 2017-06-15 | The Trustees Of The University Of Pennsylvania | Scalable purification method for aav1 |
| US11098286B2 (en) | 2015-12-11 | 2021-08-24 | The Trustees Of The University Of Pennsylvania | Scalable purification method for AAV9 |
| WO2017106537A2 (en) | 2015-12-18 | 2017-06-22 | Sangamo Biosciences, Inc. | Targeted disruption of the mhc cell receptor |
| WO2017106528A2 (en) | 2015-12-18 | 2017-06-22 | Sangamo Biosciences, Inc. | Targeted disruption of the t cell receptor |
| CA3011939A1 (en) | 2016-02-02 | 2017-08-10 | University Of Massachusetts | Method to enhance the efficiency of systemic aav gene delivery to the central nervous system |
| EP3769775A3 (en) | 2016-02-02 | 2021-03-17 | Sangamo Therapeutics, Inc. | Compositions for linking dna-binding domains and cleavage domains |
| FI3411484T3 (fi) | 2016-02-05 | 2023-11-15 | Univ Emory | Yksisäikeisen tai itsekomplementaarisen adenoassosioidun viruksen 9 injektio serebrospinaaliseen fluidiin |
| WO2017139643A1 (en) | 2016-02-12 | 2017-08-17 | University Of Massachusetts | Anti-angiogenic mirna therapeutics for inhibiting corneal neovascularization |
| HUE056854T2 (hu) | 2016-03-31 | 2022-03-28 | Spark Therapeutics Inc | Oszlop alapú, teljes mértékben méretezhetõ rAAV elõállítási eljárás |
| US11207426B2 (en) | 2016-04-05 | 2021-12-28 | University Of Massachusetts | Compositions and methods for selective inhibition of grainyhead-like protein expression |
| JP7282521B2 (ja) | 2016-04-08 | 2023-05-29 | パーデュー・リサーチ・ファウンデイション | Car t細胞療法のための方法および組成物 |
| US11413356B2 (en) | 2016-04-15 | 2022-08-16 | University Of Massachusetts | Methods and compositions for treating metabolic imbalance |
| US11882815B2 (en) | 2016-06-15 | 2024-01-30 | University Of Massachusetts | Recombinant adeno-associated viruses for delivering gene editing molecules to embryonic cells |
| GB201612248D0 (en) | 2016-07-14 | 2016-08-31 | Puridify Ltd | New process |
| US20190284576A1 (en) * | 2016-07-21 | 2019-09-19 | Spark Therapeutics, Inc. | SCALABLE HIGH RECOVERY METHODS FOR PRODUCING HIGH YIELD RECOMBINANT ADENO-ASSOCIATED VIRAL (rAAV) VECTOR AND RECOMBINANT ADENO-ASSOCIATED VIRAL (rAAV) VECTORS PRODUCED THEREBY |
| US11883470B2 (en) | 2016-07-25 | 2024-01-30 | The Trustees Of The University Of Pennsylvania | Compositions comprising a lecithin cholesterol acyltransferase variant and uses thereof |
| CA3034527A1 (en) | 2016-08-23 | 2018-03-01 | Emmanuel John Simons | Compositions and methods for treating non-age-associated hearing impairment in a human subject |
| WO2018039448A1 (en) | 2016-08-24 | 2018-03-01 | Sangamo Therapeutics, Inc. | Engineered target specific nucleases |
| HRP20212025T1 (hr) | 2016-08-24 | 2022-04-01 | Sangamo Therapeutics, Inc. | Regulacija ekspresije gena pomoću projektiranih nukleaza |
| US10457940B2 (en) | 2016-09-22 | 2019-10-29 | University Of Massachusetts | AAV treatment of Huntington's disease |
| WO2018071831A1 (en) | 2016-10-13 | 2018-04-19 | University Of Massachusetts | Aav capsid designs |
| MX2019004784A (es) * | 2016-11-04 | 2019-08-12 | Baxalta Inc | Metodos de purificacion del virus adeno-asociado. |
| EP3321357A1 (en) | 2016-11-09 | 2018-05-16 | Deutsches Krebsforschungszentrum | Scalable process for oncolytic rat parvovirus h-1 production and purification based on isoelectric point-based elimination of empty particles |
| US20190367944A1 (en) | 2017-01-30 | 2019-12-05 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Recombinant virus vectors for the treatment of glycogen storage disease |
| CN110612119B (zh) | 2017-02-07 | 2024-10-29 | 西雅图儿童医院(Dba西雅图儿童研究所) | 磷脂醚(ple)car t细胞肿瘤靶向(ctct)剂 |
| JP2020510648A (ja) | 2017-02-20 | 2020-04-09 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 家族性高コレステロール血症を処置するための遺伝子治療 |
| US11850262B2 (en) | 2017-02-28 | 2023-12-26 | Purdue Research Foundation | Compositions and methods for CAR T cell therapy |
| CA3059213A1 (en) | 2017-05-09 | 2018-11-15 | University Of Massachusetts | Methods of treating amyotrophic lateral sclerosis (als) |
| WO2018208973A1 (en) | 2017-05-09 | 2018-11-15 | Emory University | Clotting factor variants and their use |
| BR112019025792A2 (pt) | 2017-06-07 | 2020-07-07 | Spark Therapeutics, Inc. | agentes de aperfeiçoamento para transfecção de células melhoradas e/ou produção de vetor raav |
| SG11201913157RA (en) * | 2017-06-30 | 2020-01-30 | Spark Therapeutics Inc | Aav vector column purification methods |
| WO2019060686A1 (en) | 2017-09-22 | 2019-03-28 | University Of Massachusetts | NEW DUAL EXPRESSION VECTORS OF SOD1 AND USES THEREOF |
| KR20240164969A (ko) | 2017-10-20 | 2024-11-21 | 더 리서치 인스티튜트 앳 네이션와이드 칠드런스 하스피탈 | Nt-3 유전자 치료를 위한 방법 및 물질 |
| EP3707264A1 (en) * | 2017-11-08 | 2020-09-16 | Avexis Inc. | Means and method for preparing viral vectors and uses of same |
| BR112020014913A2 (pt) | 2018-01-22 | 2020-12-08 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Métodos para uso de células t car |
| PE20212076A1 (es) | 2018-02-01 | 2021-10-26 | Homology Medicines Inc | Composiciones de virus adeno-asociado para restaurar la funcion del gen pah y metodos de uso de las mismas |
| US10610606B2 (en) | 2018-02-01 | 2020-04-07 | Homology Medicines, Inc. | Adeno-associated virus compositions for PAH gene transfer and methods of use thereof |
| SG11202007426XA (en) | 2018-02-06 | 2020-09-29 | Seattle Childrens Hospital Dba Seattle Childrens Res Inst | Fluorescein-specific cars exhibiting optimal t cell function against fl-ple labelled tumors |
| US11306329B2 (en) | 2018-02-19 | 2022-04-19 | City Of Hope | Adeno-associated virus compositions for restoring F8 gene function and methods of use thereof |
| CA3091674A1 (en) | 2018-02-23 | 2019-08-29 | Endocyte, Inc. | Sequencing method for car t cell therapy |
| CA3091810A1 (en) | 2018-03-02 | 2019-09-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Use of il-34 to treat retinal inflammation and neurodegeneration |
| BR112020020174A2 (pt) * | 2018-04-05 | 2021-01-19 | Nightstarx Limited | Composições de aav, métodos de fabricação e métodos de uso |
| US12228571B2 (en) | 2018-06-08 | 2025-02-18 | Novartis Ag | Cell-based assay for measuring drug product potency |
| US12163129B2 (en) | 2018-06-08 | 2024-12-10 | University Of Massachusetts | Antisense oligonucleotides to restore dysferlin protein expression in dysferlinopathy patient cells |
| CA3103740A1 (en) | 2018-06-29 | 2020-01-02 | Wuhan Neurophth Biotechnology Limited Company | Compositions and methods for treating leber's hereditary optic neuropathy |
| EP3840785A4 (en) | 2018-08-20 | 2022-07-13 | Wuhan Neurophth Biotechnology Limited Company | COMPOSITIONS AND METHODS FOR THE TREATMENT OF LEBERIAN OPTIC ATROPHY |
| IL322436A (en) | 2018-09-21 | 2025-09-01 | Acuitas Therapeutics Inc | Systems and methods for producing lipid nanoparticles and liposomes |
| TWI897418B (zh) * | 2018-11-30 | 2025-09-11 | 瑞士商諾華公司 | Aav病毒載體及其用途 |
| ES2969222T3 (es) | 2018-12-18 | 2024-05-17 | Ultragenyx Pharmaceutical Inc | Métodos y composiciones para el tratamiento de enfermedades del almacenamiento de glucógeno |
| TWI848038B (zh) | 2019-01-04 | 2024-07-11 | 美商奧崔基尼克斯製藥公司 | 用於治療威爾森氏症之基因療法構築體 |
| WO2020146805A1 (en) | 2019-01-11 | 2020-07-16 | Acuitas Therapeutics, Inc. | Lipids for lipid nanoparticle delivery of active agents |
| AU2020208467A1 (en) * | 2019-01-18 | 2021-08-05 | Voyager Therapeutics, Inc. | Methods and systems for producing AAV particles |
| WO2020264254A1 (en) | 2019-06-28 | 2020-12-30 | Crispr Therapeutics Ag | Materials and methods for controlling gene editing |
| KR20220035937A (ko) | 2019-07-25 | 2022-03-22 | 노파르티스 아게 | 조절 가능한 발현 시스템 |
| WO2021062012A1 (en) | 2019-09-25 | 2021-04-01 | Emory University | Use of klk10 and engineered derivatizations thereof |
| CN113025633B (zh) | 2019-12-09 | 2024-08-27 | 武汉纽福斯生物科技有限公司 | 编码人nadh脱氢酶亚单位1蛋白的核酸及其应用 |
| WO2021124152A1 (en) | 2019-12-19 | 2021-06-24 | Pfizer Inc. | Compositions and methods for nucleic acid transfection using cationic polymers and stabilizers |
| TW202140791A (zh) | 2020-01-13 | 2021-11-01 | 美商霍蒙拉奇醫藥公司 | 治療苯酮尿症之方法 |
| CA3165922A1 (en) | 2020-01-17 | 2021-07-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Gene therapy for treatment of crx-autosomal dominant retinopathies |
| CA3164714A1 (en) | 2020-02-14 | 2021-08-19 | Ultragenyx Pharmaceutical Inc. | Gene therapy for treating cdkl5 deficiency disorder |
| BR112022016596A2 (pt) | 2020-02-21 | 2022-11-16 | Akouos Inc | Composições e métodos para o tratamento de debilitação auditiva não associada à idade em um indivíduo humano |
| TW202208632A (zh) | 2020-05-27 | 2022-03-01 | 美商同源醫藥公司 | 用於恢復pah基因功能的腺相關病毒組成物及其使用方法 |
| BR112023000327A2 (pt) | 2020-07-16 | 2023-01-31 | Acuitas Therapeutics Inc | Lipídeos catiônicos para o uso em nanopartículas lipídicas |
| CN116261483A (zh) * | 2020-08-18 | 2023-06-13 | 赛多利斯比亚分离有限责任公司 | 多模式金属亲和加工衣壳 |
| US20230383278A1 (en) | 2020-09-18 | 2023-11-30 | The United States Of America,As Represented By The Secretary,Department Of Health And Human Services | Novel adeno-associated viral (aav) vectors to treat hereditary methylmalonic acidemia (mma) caused by methylmalonyl-coa mutase (mmut) deficiency |
| EP4229204A1 (en) | 2020-10-15 | 2023-08-23 | F. Hoffmann-La Roche AG | Nucleic acid constructs for simultaneous gene activation |
| JP2023546116A (ja) | 2020-10-15 | 2023-11-01 | エフ. ホフマン-ラ ロシュ アーゲー | Va rna転写のための核酸構築物 |
| CN117980484A (zh) | 2021-09-16 | 2024-05-03 | 诺华股份有限公司 | 新颖的转录因子 |
| KR20240123832A (ko) | 2021-12-16 | 2024-08-14 | 아퀴타스 테라퓨틱스 인크. | 지질 나노입자 제형에 사용하기 위한 지질 |
| WO2023196898A1 (en) | 2022-04-07 | 2023-10-12 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Beta globin mimetic peptides and their use |
| CN118974274A (zh) | 2022-04-13 | 2024-11-15 | 豪夫迈·罗氏有限公司 | 用于确定aav基因组的方法 |
| JP2025517628A (ja) | 2022-05-06 | 2025-06-10 | ノバルティス アーゲー | 新規の組換えaav vp2融合ポリペプチド |
| JP2025517987A (ja) | 2022-05-23 | 2025-06-12 | エフ. ホフマン-ラ ロシュ アーゲー | Aav粒子血清型およびaav粒子負荷状態の識別のためのラマンベースの方法 |
| AU2023278422A1 (en) | 2022-06-03 | 2024-11-14 | F. Hoffmann-La Roche Ag | Method for producing recombinant aav particles |
| CA3261054A1 (en) | 2022-07-14 | 2024-01-18 | F. Hoffmann-La Roche Ag | PROCESS FOR THE PRODUCTION OF RECOMBINANT ADENO-ASSOCIATED VIRUS PARTICLES |
| KR20250067819A (ko) | 2022-09-12 | 2025-05-15 | 에프. 호프만-라 로슈 아게 | 핵산 포함 및 핵산 비포함 aav 입자를 분리하는 방법 |
| EP4662490A1 (en) | 2023-02-07 | 2025-12-17 | F. Hoffmann-La Roche AG | Method for the detection of anti-aav particle antibodies |
| WO2024168358A1 (en) | 2023-02-10 | 2024-08-15 | Expression Therapeutics, Llc | Lentiviral system |
| WO2024178113A1 (en) | 2023-02-22 | 2024-08-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Recombinant adeno-associated virus vectors lacking an immunodominant t cell epitope and use thereof |
| AU2024240009A1 (en) | 2023-03-17 | 2025-09-18 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods for treatment of age-related macular degeneration |
| CN120835797A (zh) | 2023-03-21 | 2025-10-24 | 豪夫迈·罗氏有限公司 | 用于产生重组aav颗粒制备物的方法 |
| WO2025090942A1 (en) * | 2023-10-26 | 2025-05-01 | University Of Notre Dame Du Lac | Gene therapy for treatment of neurometabolic disease |
| WO2025168663A1 (en) | 2024-02-09 | 2025-08-14 | F. Hoffmann-La Roche Ag | Method for producing recombinant adeno-associated viral particles |
| WO2025252480A1 (en) | 2024-06-07 | 2025-12-11 | F. Hoffmann-La Roche Ag | Method for purifying plasmid dna |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6001650A (en) | 1995-08-03 | 1999-12-14 | Avigen, Inc. | High-efficiency wild-type-free AAV helper functions |
| US6004797A (en) | 1995-11-09 | 1999-12-21 | Avigen, Inc. | Adenovirus helper-free recombinant AAV Virion production |
| JP4289687B2 (ja) * | 1997-03-14 | 2009-07-01 | ザ チルドレンズ ホスピタル オブ フィラデルフィア | 血友病の治療のための遺伝子治療で使用する方法と組成物 |
| US6989264B2 (en) * | 1997-09-05 | 2006-01-24 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| DE69941905D1 (de) * | 1998-11-10 | 2010-02-25 | Univ North Carolina | Virusvektoren und verfahren für ihre herstellung und verabreichung. |
| DK1190055T3 (da) * | 1999-06-30 | 2008-09-22 | Univ Tulane | Human endogen retrovirus |
| AU2001249389A1 (en) * | 2000-03-22 | 2001-10-03 | The Children's Hospital Of Philadelphia | Modified blood clotting factors and methods of use |
| US6593123B1 (en) | 2000-08-07 | 2003-07-15 | Avigen, Inc. | Large-scale recombinant adeno-associated virus (rAAV) production and purification |
| AU2003253595A1 (en) * | 2002-04-05 | 2003-11-03 | The Children's Hospital Of Philadelphia | Methods for the production of chimeric adeno-associated virus (aav) vectors, compositions of chimeric aav vectors, and methods of use thereof |
| DK2277996T3 (da) * | 2003-05-21 | 2014-10-20 | Genzyme Corp | Fremgangsmåder til fremstilling af præparationer af rekombinante aav-virioner, der i hovedsagen er fri for tomme capsider |
| JP2008501339A (ja) * | 2004-06-01 | 2008-01-24 | ジェンザイム・コーポレイション | Aavベクターの凝集を防ぐための組成物およびその方法 |
| CN1873012A (zh) * | 2005-06-01 | 2006-12-06 | 上海二医新生基因科技有限公司 | 重组腺相关病毒(rAAV)载体大规模生产新工艺 |
| CN101528916B (zh) * | 2006-04-28 | 2013-09-04 | 宾夕法尼亚大学托管会 | 规模可调的aav生产方法 |
| WO2008128251A1 (en) * | 2007-04-17 | 2008-10-23 | The Children's Hospital Of Philadelphia | Humanized viral vectors and methods of use thereof |
| US9169491B2 (en) * | 2008-06-18 | 2015-10-27 | Oxford Biomedica (Uk) Limited | Virus purification |
| MX340102B (es) * | 2010-01-28 | 2016-06-24 | The Children's Hospital Of Philadelphia * | Una plataforma de fabricacion ajustable en escala, para la purificacion de vector viral y vectores virales asi purificados para el uso en terapia de genes. |
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| IL221158B (en) | 2018-07-31 |
| US11878056B2 (en) | 2024-01-23 |
| EP2529020A1 (en) | 2012-12-05 |
| JP2013517798A (ja) | 2013-05-20 |
| EP2529020B1 (en) | 2018-04-25 |
| US20130072548A1 (en) | 2013-03-21 |
| CN105838737A (zh) | 2016-08-10 |
| MX2012008757A (es) | 2012-11-06 |
| AU2011209743A1 (en) | 2012-08-23 |
| JP6991095B2 (ja) | 2022-01-12 |
| US20190321463A1 (en) | 2019-10-24 |
| US9408904B2 (en) | 2016-08-09 |
| JP2018046820A (ja) | 2018-03-29 |
| US20160206706A1 (en) | 2016-07-21 |
| CA2787827C (en) | 2020-11-10 |
| PT2529020T (pt) | 2018-07-30 |
| WO2011094198A1 (en) | 2011-08-04 |
| US10328145B2 (en) | 2019-06-25 |
| CN102947453A (zh) | 2013-02-27 |
| AU2011209743B2 (en) | 2016-03-10 |
| JP2018121653A (ja) | 2018-08-09 |
| EP2529020A4 (en) | 2013-10-16 |
| IN2012DN06629A (enExample) | 2015-10-23 |
| US20200405845A1 (en) | 2020-12-31 |
| CA2787827A1 (en) | 2011-08-04 |
| JP2016185153A (ja) | 2016-10-27 |
| MX340102B (es) | 2016-06-24 |
| BR112012018899A2 (pt) | 2015-09-15 |
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