CA2946392A1 - Ldlr variants and their use in compositions for reducing cholesterol levels - Google Patents
Ldlr variants and their use in compositions for reducing cholesterol levels Download PDFInfo
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- A61P3/06—Antihyperlipidemics
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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| CN110769845A (zh) * | 2017-04-21 | 2020-02-07 | 精密生物科学公司 | 对pcsk9基因中的识别序列具有特异性的工程化大范围核酸酶 |
Families Citing this family (47)
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| EP3052521A1 (en) | 2013-10-03 | 2016-08-10 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
| ES2876409T3 (es) | 2014-04-25 | 2021-11-12 | Univ Pennsylvania | Variantes del RLBD y su uso en composiciones para reducir los niveles de colesterol |
| EP3151866B1 (en) | 2014-06-09 | 2023-03-08 | Voyager Therapeutics, Inc. | Chimeric capsids |
| BR112017009497A2 (pt) | 2014-11-05 | 2018-02-06 | Voyager Therapeutics, Inc. | polinucleotídeos de aadc para o tratamento da doença de parkinson |
| CA2967367C (en) | 2014-11-14 | 2023-05-16 | Voyager Therapeutics, Inc. | Compositions and methods of treating amyotrophic lateral sclerosis (als) |
| US10570395B2 (en) | 2014-11-14 | 2020-02-25 | Voyager Therapeutics, Inc. | Modulatory polynucleotides |
| HK1245326A1 (zh) | 2014-12-12 | 2018-08-24 | Voyager Therapeutics, Inc. | 用於生产scaav的组合物和方法 |
| WO2016164762A1 (en) * | 2015-04-08 | 2016-10-13 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor egf-a and intracellular domain mutants and methods of using the same |
| US11535665B2 (en) | 2015-05-13 | 2022-12-27 | The Trustees Of The University Of Pennsylvania | AAV-mediated expression of anti-influenza antibodies and methods of use thereof |
| MX2018007080A (es) | 2015-12-11 | 2018-11-12 | Univ Pennsylvania | Terapia genica para tratar hipercolesterolemia familiar. |
| IL262207B1 (en) | 2016-04-15 | 2025-09-01 | Univ Pennsylvania | Compositions for treatment of wet age-related macular degeneration |
| WO2017189964A2 (en) | 2016-04-29 | 2017-11-02 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
| WO2017189959A1 (en) | 2016-04-29 | 2017-11-02 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
| RU2764587C2 (ru) | 2016-05-18 | 2022-01-18 | Вояджер Терапьютикс, Инк. | Способы и композиции для лечения хореи гентингтона |
| JP7066635B2 (ja) | 2016-05-18 | 2022-05-13 | ボイジャー セラピューティクス インコーポレイテッド | 調節性ポリヌクレオチド |
| WO2018022511A1 (en) | 2016-07-25 | 2018-02-01 | The Trustees Of The University Of Pennsylvania | Compositions comprising a lecithin cholesterol acyltransferase variant and uses thereof |
| US11298041B2 (en) | 2016-08-30 | 2022-04-12 | The Regents Of The University Of California | Methods for biomedical targeting and delivery and devices and systems for practicing the same |
| BR112019013576A2 (pt) * | 2016-12-30 | 2020-02-04 | Univ Pennsylvania | terapia genica para o tratamento da fenilcetonuria |
| AU2018220212A1 (en) * | 2017-02-20 | 2019-08-08 | The Trustees Of The University Of Pennsylvania | Gene therapy for treating familial hypercholesterolemia |
| JOP20190200A1 (ar) | 2017-02-28 | 2019-08-27 | Univ Pennsylvania | تركيبات نافعة في معالجة ضمور العضل النخاعي |
| LT3589730T (lt) | 2017-02-28 | 2024-03-12 | The Trustees Of The University Of Pennsylvania | Adenoasocijuoto viruso (aav) monofiletinės grupės f vektorius, ir jo panaudojimo būdai |
| SG10201913833PA (en) | 2017-02-28 | 2020-03-30 | Univ Pennsylvania | Influenza vaccines based on aav vectors |
| EP3618839A4 (en) | 2017-05-05 | 2021-06-09 | Voyager Therapeutics, Inc. | Compositions and methods of treating amyotrophic lateral sclerosis (als) |
| SG11201909868YA (en) | 2017-05-05 | 2019-11-28 | Voyager Therapeutics Inc | Compositions and methods of treating huntington's disease |
| JOP20190269A1 (ar) | 2017-06-15 | 2019-11-20 | Voyager Therapeutics Inc | بولي نوكليوتيدات aadc لعلاج مرض باركنسون |
| JP7229989B2 (ja) | 2017-07-17 | 2023-02-28 | ボイジャー セラピューティクス インコーポレイテッド | 軌道アレイガイドシステム |
| AU2018311069A1 (en) | 2017-08-03 | 2020-02-20 | Voyager Therapeutics, Inc. | Compositions and methods for delivery of AAV |
| EP3687582A4 (en) | 2017-09-29 | 2021-07-14 | Voyager Therapeutics, Inc. | RESCUE OF CENTRAL AND PERIPHERAL NEUROLOGICAL PHENOTYPE OF FRIEDREICH ATAXIA BY INTRAVENOUS ADMINISTRATION |
| US20200237799A1 (en) | 2017-10-16 | 2020-07-30 | Voyager Therapeutics, Inc. | Treatment of amyotrophic lateral sclerosis (als) |
| TW202413649A (zh) | 2017-10-16 | 2024-04-01 | 美商航海家醫療公司 | 肌萎縮性脊髓側索硬化症(als)之治療 |
| JP2021523914A (ja) | 2018-05-15 | 2021-09-09 | ボイジャー セラピューティクス インコーポレイテッドＶｏｙａｇｅｒ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | パーキンソン病を治療するための組成物および方法 |
| EP3856762A1 (en) | 2018-09-28 | 2021-08-04 | Voyager Therapeutics, Inc. | Frataxin expression constructs having engineered promoters and methods of use thereof |
| JP2022518354A (ja) * | 2018-12-20 | 2022-03-15 | 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治療するための遺伝子療法 |
| WO2021188892A1 (en) * | 2020-03-19 | 2021-09-23 | Ultragenyx Pharmaceutical Inc. | Compositions and methods for reducing reverse packaging of cap and rep sequences in recombinant aav |
| KR20230002594A (ko) * | 2020-04-29 | 2023-01-05 | 살리오젠 테라퓨틱스 인코포레이티드 | 가족성 고콜레스테롤혈증 및 상승된 저밀도 지단백질 콜레스테롤의 치료를 위한 조성물 및 방법 |
| CN115803064A (zh) | 2020-05-12 | 2023-03-14 | 宾夕法尼亚州大学信托人 | 用于drg特异性降低转基因表达的组合物 |
| US20230287451A1 (en) | 2020-08-14 | 2023-09-14 | The Trustees Of The University Of Pennsylvania | Novel aav capsids and compositions containing same |
| TW202233844A (zh) | 2020-10-29 | 2022-09-01 | 賓州大學委員會 | Aav衣殼及含有其之組成物 |
| JP2023551903A (ja) | 2020-12-01 | 2023-12-13 | 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 | 組織特異的標的化モチーフを有する新規組成物及びそれを含有する組成物 |
| MX2023012513A (es) | 2021-04-23 | 2023-12-15 | Univ Pennsylvania | Nuevas composiciones con motivos selectivos para el cerebro y composiciones que las contienen. |
| TW202309066A (zh) | 2021-04-27 | 2023-03-01 | 賓州大學委員會 | 衍生自豬的腺相關病毒衣殼及其用途 |
| CN113684215A (zh) * | 2021-09-07 | 2021-11-23 | 华中科技大学同济医学院附属协和医院 | 高胆固醇血症相关的新突变基因及其应用 |
| TW202325845A (zh) | 2021-10-02 | 2023-07-01 | 賓州大學委員會 | 新穎aav衣殼及含其之組成物 |
| WO2023087019A2 (en) | 2021-11-15 | 2023-05-19 | The Trustees Of The University Of Pennsylvania | Compositions for drg-specific reduction of transgene expression |
| WO2024015966A2 (en) | 2022-07-15 | 2024-01-18 | The Trustees Of The University Of Pennsylvania | Recombinant aav having aav clade d and clade e capsids and compositions containing same |
| AR133098A1 (es) | 2023-06-29 | 2025-08-27 | Univ Pennsylvania | Aav mutante con motivos dirigidos al sistema nervioso central y composiciones que lo contienen |
| WO2025231085A1 (en) | 2024-04-30 | 2025-11-06 | Airna Corporation | Site-directed editing of rna |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| US5436146A (en) | 1989-09-07 | 1995-07-25 | The Trustees Of Princeton University | Helper-free stocks of recombinant adeno-associated virus vectors |
| US6268213B1 (en) | 1992-06-03 | 2001-07-31 | Richard Jude Samulski | Adeno-associated virus vector and cis-acting regulatory and promoter elements capable of expressing at least one gene and method of using same for gene therapy |
| US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
| US5869305A (en) | 1992-12-04 | 1999-02-09 | The University Of Pittsburgh | Recombinant viral vector system |
| US6204059B1 (en) | 1994-06-30 | 2001-03-20 | University Of Pittsburgh | AAV capsid vehicles for molecular transfer |
| US5817789A (en) * | 1995-06-06 | 1998-10-06 | Transkaryotic Therapies, Inc. | Chimeric proteins for use in transport of a selected substance into cells |
| US5741683A (en) | 1995-06-07 | 1998-04-21 | The Research Foundation Of State University Of New York | In vitro packaging of adeno-associated virus DNA |
| US6093570A (en) | 1995-06-07 | 2000-07-25 | The University Of North Carolina At Chapel Hill | Helper virus-free AAV production |
| WO1998046728A1 (en) | 1997-04-14 | 1998-10-22 | Cell Genesys, Inc. | Methods for increasing the efficiency of recombinant aav product |
| EP1080218A1 (en) | 1998-05-27 | 2001-03-07 | University of Florida | Method of preparing recombinant adeno-associated virus compositions by using an iodixanol gradient |
| ATE454445T1 (de) | 1998-11-10 | 2010-01-15 | Univ North Carolina | Virusvektoren und verfahren für ihre herstellung und verabreichung. |
| CA2379166C (en) | 1999-08-09 | 2013-03-26 | Targeted Genetics Corporation | Enhancement of expression of a single-stranded, heterologous nucleotide sequence from recombinant viral vectors by designing the sequence such that it forms instrastrand base pairs |
| EP1224312A1 (en) * | 1999-10-12 | 2002-07-24 | The University of North Carolina at Chapel Hill | Adeno-associated virus vectors encoding factor viii and methods of using the same |
| ES2327609T3 (es) | 2000-06-01 | 2009-11-02 | University Of North Carolina At Chapel Hill | Procedimientos y compuestos para controlar la liberacion de vectores de parvovirus reconbinantes. |
| BR122016004546B8 (pt) | 2001-11-13 | 2021-07-27 | Univ Pennsylvania | vírus adenoassociado recombinante, método de geração do referido vírus e composição compreendendo o referido vírus |
| DK1453547T3 (en) | 2001-12-17 | 2016-12-05 | Univ Pennsylvania | ADENOASSOCATED VIRUS (AAV) SEROTYPE 8 SEQUENCES, VECTORS CONTAINING THESE AND APPLICATIONS THEREOF |
| US20070015238A1 (en) | 2002-06-05 | 2007-01-18 | Snyder Richard O | Production of pseudotyped recombinant AAV virions |
| CA3072423A1 (en) | 2003-09-30 | 2005-04-14 | The Trustees Of The University Of Pennsylvania | Adeno-associated virus (aav) clades, sequences, vectors containing same, and uses therefor |
| CN101018858A (zh) | 2004-06-01 | 2007-08-15 | 建新公司 | 防止aav载体聚集的组合物和方法 |
| EP3409296A1 (en) | 2005-04-07 | 2018-12-05 | The Trustees of the University of Pennsylvania | Method of increasing the function of an aav vector |
| EP1777906A1 (en) | 2005-06-09 | 2007-04-25 | Matsushita Electric Industrial Co., Ltd. | Amplitude error compensating apparatus and orthogonality error compensating apparatus |
| US7943374B2 (en) * | 2005-08-21 | 2011-05-17 | Markus Hildinger | Super-size adeno-associated viral vector harboring a recombinant genome larger than 5.7 kb |
| US7535296B2 (en) | 2006-02-24 | 2009-05-19 | Kenergy, Inc. | Class-E radio frequency power amplifier with feedback control |
| EP2007795B1 (en) | 2006-03-30 | 2016-11-16 | The Board Of Trustees Of The Leland Stanford Junior University | Aav capsid proteins |
| KR101010352B1 (ko) | 2008-05-30 | 2011-01-25 | 삼성중공업 주식회사 | 전력 제어 장치 및 방법 |
| US11305022B2 (en) | 2009-01-29 | 2022-04-19 | The Regents Of The University Of California | Methods for distributing high levels of therapeutic agent throughout the cortex to treat neurological disorders |
| WO2011020118A1 (en) | 2009-08-14 | 2011-02-17 | Theramind Research, Llc | Methods and compositions for treatment of tuberous sclerosis complex |
| PT2529020T (pt) | 2010-01-28 | 2018-07-30 | Childrens Hospital Philadelphia | Plataforma de fabrico escalável para purificação de vetor viral e vetores virais assim purificados para utilização na terapia génica |
| CN102869779A (zh) | 2010-03-29 | 2013-01-09 | 宾夕法尼亚大学托管会 | 药理学诱导的转基因消融系统 |
| US9315825B2 (en) | 2010-03-29 | 2016-04-19 | The Trustees Of The University Of Pennsylvania | Pharmacologically induced transgene ablation system |
| EP2721063A4 (en) * | 2011-06-20 | 2015-01-14 | Hoffmann La Roche | PCSK9 BINDING POLYPEPTIDES AND METHOD OF USE THEREOF |
| FR2977562B1 (fr) | 2011-07-06 | 2016-12-23 | Gaztransport Et Technigaz | Cuve etanche et thermiquement isolante integree dans une structure porteuse |
| ES2857773T5 (es) | 2011-08-24 | 2024-06-04 | Univ Leland Stanford Junior | Nuevas proteínas de la cápside de AAV para la transferencia de ácidos nucleicos |
| HRP20241450T1 (hr) | 2011-09-16 | 2025-01-03 | Regeneron Pharmaceuticals, Inc. | Postupci za smanjivanje razina lipoproteina(a) putem primjene inhibitora proproteinske konvertaze suptilizin keksin 9 (pcsk9) |
| US9821114B2 (en) * | 2012-02-07 | 2017-11-21 | Global Bio Therapeutics, Inc. | Compartmentalized method of nucleic acid delivery and compositions and uses thereof |
| MX367100B (es) | 2012-02-17 | 2019-08-05 | The Children´S Hospital Of Philadelphia | Composiciones del vector aav y metodos para su transferencia genetica a celulas, organos y tejidos. |
| WO2014089212A1 (en) * | 2012-12-05 | 2014-06-12 | Sangamo Biosciences, Inc. | Methods and compositions for regulation of metabolic disorders |
| DK2954051T3 (da) | 2013-02-08 | 2019-07-08 | Univ Pennsylvania | Modificeret kapsid til genoverførsel til behandling af nethinden |
| US9873893B2 (en) | 2013-02-15 | 2018-01-23 | The United States Of America As Represented By The Secretary, Dept. Of Health And Human Services | Methods and compositions for treating genetically linked diseases of the eye |
| SG11201507507PA (en) * | 2013-03-15 | 2015-10-29 | Univ Pennsylvania | Compositions and methods for treating mpsi |
| US9254332B2 (en) | 2013-03-15 | 2016-02-09 | Arecor Limited | Stable aqueous formulations of adenovirus vectors |
| US9719106B2 (en) | 2013-04-29 | 2017-08-01 | The Trustees Of The University Of Pennsylvania | Tissue preferential codon modified expression cassettes, vectors containing same, and uses thereof |
| US20150065556A1 (en) * | 2013-08-05 | 2015-03-05 | Whitehead Institute For Biomedical Research | Therapeutic targets for mitochondrial disorders |
| EP3052521A1 (en) * | 2013-10-03 | 2016-08-10 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
| ES2876409T3 (es) | 2014-04-25 | 2021-11-12 | Univ Pennsylvania | Variantes del RLBD y su uso en composiciones para reducir los niveles de colesterol |
| EP4215605A1 (en) | 2015-12-11 | 2023-07-26 | The Trustees of The University of Pennsylvania | Scalable purification method for aav8 |
| MX2018007080A (es) | 2015-12-11 | 2018-11-12 | Univ Pennsylvania | Terapia genica para tratar hipercolesterolemia familiar. |
| AU2018220212A1 (en) | 2017-02-20 | 2019-08-08 | The Trustees Of The University Of Pennsylvania | Gene therapy for treating familial hypercholesterolemia |
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- 2015-04-24 BR BR112016024379A patent/BR112016024379A2/pt active Search and Examination
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- 2015-04-24 CA CA2946392A patent/CA2946392A1/en active Pending
- 2015-04-24 EP EP21166865.2A patent/EP3919508A1/en not_active Withdrawn
- 2015-04-24 US US15/306,419 patent/US11555059B2/en active Active
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2020
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110769845A (zh) * | 2017-04-21 | 2020-02-07 | 精密生物科学公司 | 对pcsk9基因中的识别序列具有特异性的工程化大范围核酸酶 |
| CN110769845B (zh) * | 2017-04-21 | 2023-08-15 | 精密生物科学公司 | 对pcsk9基因中的识别序列具有特异性的工程化大范围核酸酶 |
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| Publication number | Publication date |
|---|---|
| EP3919508A1 (en) | 2021-12-08 |
| US11555059B2 (en) | 2023-01-17 |
| JP2023100960A (ja) | 2023-07-19 |
| BR112016024379A2 (pt) | 2017-10-10 |
| JP7280853B2 (ja) | 2023-05-24 |
| EP3134431B1 (en) | 2021-04-07 |
| JP2020120673A (ja) | 2020-08-13 |
| ES2876409T3 (es) | 2021-11-12 |
| US20230272032A1 (en) | 2023-08-31 |
| JP6741590B2 (ja) | 2020-08-19 |
| EP3134431A1 (en) | 2017-03-01 |
| JP2017513504A (ja) | 2017-06-01 |
| US20170101458A1 (en) | 2017-04-13 |
| WO2015164778A1 (en) | 2015-10-29 |
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