JP6045491B2 - 治療薬のｃｎｓ送達 - Google Patents
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2016037504A (ja) * | 2010-06-25 | 2016-03-22 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | 治療薬のｃｎｓ送達 |
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| AU2003222568B2 (en) | 2002-01-11 | 2009-05-07 | Bioasis Technologies, Inc. | Use of P97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes |
| NZ605874A (en) | 2010-06-25 | 2015-02-27 | Shire Human Genetic Therapies | Methods and compositions for cns delivery of heparan n-sulfatase |
| CN103179980B (zh) | 2010-06-25 | 2016-09-28 | 夏尔人类遗传性治疗公司 | 艾杜糖醛酸-2-硫酸酯酶的cns递送的方法和组合物 |
| NZ605873A (en) | 2010-06-25 | 2015-02-27 | Shire Human Genetic Therapies | Methods and compositions for cns delivery of arylsulfatase a |
| SMT201600385T1 (it) | 2010-06-25 | 2017-03-08 | Shire Human Genetic Therapies | Trasporto di agenti terapeutici all’snc |
| WO2012101671A1 (en) * | 2011-01-25 | 2012-08-02 | Jcr Pharmaceuticals Co., Ltd. | Method for production of human recombinant iduronate 2-sulfatase |
| ES2582869T3 (es) | 2011-07-05 | 2016-09-15 | Bioasis Technologies Inc | Conjugados de P97-anticuerpo |
| JP6329483B2 (ja) * | 2011-10-12 | 2018-05-23 | シナジェバ・バイオファーマ・コーポレイションＳｙｎａｇｅｖａ Ｂｉｏｐｈａｒｍａ Ｃｏｒｐ． | 組換えヒトｎａｇｌｕタンパク質およびその利用 |
| US20140377244A1 (en) | 2011-12-23 | 2014-12-25 | Shire Human Genetic Therapies, Inc. | Stable formulations for cns delivery of arylsulfatase a |
| EP2793933B1 (en) * | 2011-12-23 | 2019-04-17 | Shire Human Genetic Therapies, Inc. | Treatment of cognitive impairment of hunter syndrome by intrathecal delivery of iduronate-2-sulfatase |
| ES2647082T3 (es) * | 2012-07-31 | 2017-12-19 | Bioasis Technologies Inc | Proteínas desfosforiladas de la enfermedad de depósito lisosómico y métodos de uso de las mismas |
| AU2014205441B2 (en) | 2013-01-09 | 2019-12-12 | Takeda Pharmaceutical Company Limited | Methods for purification of arylsulfatase A |
| EP2981551B1 (en) | 2013-02-20 | 2020-06-03 | Valerion Therapeutics, LLC | Methods and compositions for treatment of pompe disease |
| JP6586412B2 (ja) | 2013-03-13 | 2019-10-02 | バイオアシス テクノロジーズ インコーポレイテッド | ｐ９７のフラグメントおよびその使用 |
| CN105377039A (zh) * | 2013-05-15 | 2016-03-02 | 明尼苏达大学董事会 | 腺相关病毒介导的基因向中枢神经系统转移 |
| JP6603227B2 (ja) | 2014-02-03 | 2019-11-06 | バイオアシス テクノロジーズ インコーポレイテッド | Ｐ９７融合タンパク質 |
| DK3107562T3 (da) | 2014-02-19 | 2019-12-16 | Bioasis Technologies Inc | P97-ids-fusionsproteiner |
| US10058619B2 (en) | 2014-05-01 | 2018-08-28 | Bioasis Technologies, Inc. | P97-polynucleotide conjugates |
| US10722559B2 (en) * | 2014-08-11 | 2020-07-28 | Shire Human Genetic Therapies, Inc. | Mannose-6-phosphate bearing peptides fused to lysosomal enzymes |
| US10413597B2 (en) | 2014-09-29 | 2019-09-17 | Alexion Pharmaceuticals, Inc. | Methods of treating Mucopolysaccharidosis IIIB (MPSIIIB) |
| WO2016100591A1 (en) * | 2014-12-19 | 2016-06-23 | Biogen Ma Inc. | Apparatus for compound dispersion |
| EP3292206B8 (en) | 2015-05-07 | 2022-02-09 | Takeda Pharmaceutical Company Limited | Glucocerebrosidase gene therapy for parkinson's disease |
| GB201508025D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Fabry disease gene therapy |
| KR20170004814A (ko) * | 2015-07-02 | 2017-01-11 | 주식회사 녹십자 | 헌터증후군 치료제 |
| WO2017062666A2 (en) * | 2015-10-06 | 2017-04-13 | Patricia Dickson | Enzyme replacement therapy for mucopolysaccharidosis iiid |
| US10123969B2 (en) | 2015-10-15 | 2018-11-13 | Wisconsin Alumni Research Foundation | Osmotic enhancement of drug/therapeutic delivery to the brain following infusion or injection into the cerebrospinal fluid |
| IL259964B (en) * | 2015-12-15 | 2022-09-01 | Genzyme Corp | Adenovirus-associated vectors for the treatment of mucolipodosis type ii |
| WO2017116066A1 (en) | 2015-12-30 | 2017-07-06 | Green Cross Corporation | Methods and compositions for treating hunter syndrome |
| EP3416678A1 (en) * | 2016-02-17 | 2018-12-26 | Shire Human Genetic Therapies, Inc. | Methods and compositions for cns delivery of arylsulfatase a |
| IL305449B2 (en) | 2016-04-15 | 2026-01-01 | Univ Pennsylvania | Gene therapy for the treatment of mucocutaneous type ii diabetes |
| AU2017342555A1 (en) | 2016-10-14 | 2019-05-30 | Children's Medical Center Corporation | Compositions and methods for treating diseases and disorders of the central nervous system |
| WO2018136434A1 (en) | 2017-01-17 | 2018-07-26 | Children's Medical Center Corporation | Compositions and methods for diagnosing and treating peroxisomal diseases |
| GB201709459D0 (en) | 2017-06-14 | 2017-07-26 | Intrabio Ltd | Treatment for migraine |
| KR102655498B1 (ko) | 2017-09-07 | 2024-04-11 | 제이씨알 파마 가부시키가이샤 | 수성 의약 조성물 |
| TWI835747B (zh) | 2017-09-22 | 2024-03-21 | 賓州大學委員會 | 用於治療黏多醣病 ii 型之基因治療 |
| AU2018345303B2 (en) | 2017-10-02 | 2025-09-18 | Denali Therapeutics Inc. | Fusion proteins comprising enzyme replacement therapy enzymes |
| LT3697399T (lt) | 2017-10-18 | 2026-01-12 | Intrabio Ltd | Terapiniai agentai, skirti panaudoti gydant neramių kojų sindromą |
| US12458614B2 (en) | 2017-10-18 | 2025-11-04 | Intrabio Ltd | Therapeutic agents for improved mobility and cognitive function and for treating neurodegenerative diseases and lysosomal storage disorders |
| WO2019126376A1 (en) | 2017-12-19 | 2019-06-27 | Shire Human Genetic Therapies, Inc. | Purified arylsulfatase a and compositons thereof |
| JP7337081B2 (ja) | 2018-02-15 | 2023-09-01 | イントラバイオ リミティド | レストレスレッグズ症候群を治療するための治療薬 |
| WO2020004368A1 (ja) | 2018-06-25 | 2020-01-02 | Ｊｃｒファーマ株式会社 | 蛋白質含有水性液剤 |
| WO2020178721A1 (en) | 2019-03-02 | 2020-09-10 | Intrabio Ltd. | Leucine, acetyl leucine, and related analogs for treating disease |
| SI3989962T1 (sl) | 2019-06-28 | 2025-11-28 | Intrabio Ltd | Kombinirano zdravljenje z acetil-levcinom in miglustatom za zdravljenje lizosomske bolezni kopičenja |
| AU2020336984B2 (en) * | 2019-08-29 | 2026-04-23 | Biomarin Pharmaceutical Inc. | Methods for treating CLN2 disease in pediatric subjects |
| US20230051742A1 (en) | 2020-01-13 | 2023-02-16 | Intrabio Ltd. | Treatment of late-onset neurodegenerative diseases in heterozygous npc1 gene mutation carriers |
| JP2023526517A (ja) | 2020-05-22 | 2023-06-21 | イントラビオ エルティーディー | 運動失調症を治療するためのアセチルロイシンと４－アミノピリジン又はアセタゾラミドとの組合せ |
| JP2025538189A (ja) * | 2022-11-09 | 2025-11-26 | ジーエムピー・バイオテクノロジー・リミテッド | Ｃｎｓ疾患のための組成物および方法 |
| WO2024176112A1 (en) | 2023-02-21 | 2024-08-29 | Takeda Pharmaceutical Company Limited | Large scale production of recombinant arylsulfatase a and compositions thereof |
| WO2025264957A2 (en) | 2024-06-20 | 2025-12-26 | Intrabio Inc. | Acetyl leucine for treating neurodevelopmental disorders |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4743265A (en) * | 1986-04-23 | 1988-05-10 | Dij Catheter Corp | Articulated catheter placement device |
| US5863782A (en) | 1995-04-19 | 1999-01-26 | Women's And Children's Hospital | Synthetic mammalian sulphamidase and genetic sequences encoding same |
| US6118045A (en) | 1995-08-02 | 2000-09-12 | Pharming B.V. | Lysosomal proteins produced in the milk of transgenic animals |
| ES2185117T3 (es) | 1997-08-22 | 2003-04-16 | Seikagaku Kogyo Co Ltd | Agente terapeutico para disco intervertebral herniado. |
| DK1137762T3 (da) | 1998-12-07 | 2009-02-02 | Genzyme Corp | Behandling af Pompes sygdom |
| US6217552B1 (en) | 1999-03-01 | 2001-04-17 | Coaxia, Inc. | Medical device for selective intrathecal spinal cooling in aortic surgery and spinal trauma |
| US20020052311A1 (en) | 1999-09-03 | 2002-05-02 | Beka Solomon | Methods and compostions for the treatment and/or diagnosis of neurological diseases and disorders |
| US6537785B1 (en) | 1999-09-14 | 2003-03-25 | Genzyme Glycobiology Research Institute, Inc. | Methods of treating lysosomal storage diseases |
| US20020099025A1 (en) * | 1999-12-30 | 2002-07-25 | Heywood James A. | Treatment of neurological disorders |
| US7560424B2 (en) | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US20040005309A1 (en) | 2002-05-29 | 2004-01-08 | Symbiontics, Inc. | Targeted therapeutic proteins |
| ATE384736T1 (de) | 2001-04-30 | 2008-02-15 | Zystor Therapeutics Inc | Subzelluläres targeting von therapeutischen proteinen |
| US7629309B2 (en) | 2002-05-29 | 2009-12-08 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| WO2003032913A2 (en) | 2001-10-16 | 2003-04-24 | Symbiontics Inc. | Methods and compositions for targeting proteins across the blood brain barrier |
| US20030072761A1 (en) | 2001-10-16 | 2003-04-17 | Lebowitz Jonathan | Methods and compositions for targeting proteins across the blood brain barrier |
| EP1503788B1 (en) * | 2002-04-25 | 2011-06-29 | Shire Human Genetic Therapies, Inc. | Treatment of alpha-galactosidase a deficiency |
| CA2487815A1 (en) | 2002-05-29 | 2003-12-11 | Biomarin Pharmaceutical Inc. | Targeted therapeutic proteins |
| ATE521701T1 (de) | 2003-01-22 | 2011-09-15 | Univ Duke | Verbesserte konstrukte zur expression lysosomaler polypeptide |
| US20050026823A1 (en) * | 2003-06-20 | 2005-02-03 | Biomarin Pharmaceutical Inc. | Use of the chaperone receptor-associated protein (RAP) for the delivery of therapeutic compounds to the brain and other tissues |
| CA2525236C (en) | 2003-06-20 | 2015-03-24 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| US7442372B2 (en) | 2003-08-29 | 2008-10-28 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| US8536315B2 (en) | 2004-01-30 | 2013-09-17 | Shire Pharmaceuticals Ireland Limited | Production and purification of recombinant arylsulftase |
| US20060029656A1 (en) | 2004-02-03 | 2006-02-09 | Biodelivery Sciences International, Inc. | Replacement enzyme cochleates |
| CA2556245A1 (en) | 2004-02-06 | 2005-08-25 | Biomarin Pharmaceutical Inc. | Manufacture of highly phosphorylated lysosomal enzymes and uses thereof |
| CN1922313B (zh) | 2004-02-10 | 2011-10-26 | 生物马林医药公司 | 酸性α-糖苷酶及其片段 |
| US20050208090A1 (en) * | 2004-03-18 | 2005-09-22 | Medtronic, Inc. | Methods and systems for treatment of neurological diseases of the central nervous system |
| WO2006121199A1 (ja) | 2005-05-11 | 2006-11-16 | Oxygenix Co., Ltd. | 脂質小胞体組成物 |
| CN101541172A (zh) | 2005-06-08 | 2009-09-23 | 阿米库斯治疗学公司 | 溶酶体酶编码基因突变相关的cns紊乱的治疗 |
| AR059089A1 (es) | 2006-01-20 | 2008-03-12 | Genzyme Corp | Administracion intraventricular de una enzima para enfermedades de almacenamiento lisosomal |
| ES2928096T3 (es) | 2006-04-04 | 2022-11-15 | Takeda Pharmaceuticals Co | Un proceso para la concentración de un polipéptido |
| GB0611463D0 (en) | 2006-06-09 | 2006-07-19 | Novartis Ag | Organic compounds |
| WO2008070769A1 (en) | 2006-12-06 | 2008-06-12 | Medtronic, Inc. | Intrathecal catheter |
| WO2008109677A2 (en) | 2007-03-06 | 2008-09-12 | Saint Louis University | Modified enzyme and treatment method |
| EP2174661B1 (en) * | 2007-06-29 | 2012-12-19 | National University Corporation Nagoya University | Agent for improving neuropathic pain |
| WO2009017005A1 (ja) | 2007-07-27 | 2009-02-05 | Sharp Kabushiki Kaisha | 移動局装置、基地局装置、通信システム及びプログラム |
| US8933197B2 (en) | 2007-08-15 | 2015-01-13 | Amunix Operating Inc. | Compositions comprising modified biologically active polypeptides |
| TWI543768B (zh) | 2007-11-30 | 2016-08-01 | 艾伯維生物技術有限責任公司 | 蛋白質調配物及製造其之方法 |
| US7722865B2 (en) | 2008-01-18 | 2010-05-25 | Biomarin Pharmaceutical Inc. | Manufacture of active highly phosphorylated human lysosomal sulfatase enzymes and uses thereof |
| HRP20170698T1 (hr) | 2008-05-07 | 2017-09-22 | Biomarin Pharmaceutical Inc. | Lizosomski usmjereni peptidi i njihove uporabe |
| US8436489B2 (en) | 2009-06-29 | 2013-05-07 | Lightsail Energy, Inc. | Compressed air energy storage system utilizing two-phase flow to facilitate heat exchange |
| NZ605874A (en) | 2010-06-25 | 2015-02-27 | Shire Human Genetic Therapies | Methods and compositions for cns delivery of heparan n-sulfatase |
| NZ605873A (en) | 2010-06-25 | 2015-02-27 | Shire Human Genetic Therapies | Methods and compositions for cns delivery of arylsulfatase a |
| SMT201600385T1 (it) | 2010-06-25 | 2017-03-08 | Shire Human Genetic Therapies | Trasporto di agenti terapeutici all’snc |
| EP2588132A4 (en) | 2010-06-25 | 2014-10-15 | Shire Human Genetic Therapies | METHOD AND COMPOSITIONS FOR DELIVERING BETA GALACTOCEREBROSIDASE INTO THE CNS |
| RS62620B1 (sr) | 2010-06-25 | 2021-12-31 | Shire Human Genetic Therapies | Metode i kompozicije za isporuku cns akrilsulfataze a |
| CA2805449A1 (en) | 2010-06-25 | 2011-12-29 | Shire Human Genetic Therapies, Inc. | Treatment of sanfilippo syndrome type b |
| CN103179980B (zh) | 2010-06-25 | 2016-09-28 | 夏尔人类遗传性治疗公司 | 艾杜糖醛酸-2-硫酸酯酶的cns递送的方法和组合物 |
| JP2012062312A (ja) | 2010-08-19 | 2012-03-29 | Yoshikatsu Eto | ハンター症候群の治療剤 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016037504A (ja) * | 2010-06-25 | 2016-03-22 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | 治療薬のｃｎｓ送達 |
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