TWI667037B - 於腦脊髓膜內遞送芳基硫酸酯酶ａ之方法及組合物 - Google Patents
於腦脊髓膜內遞送芳基硫酸酯酶ａ之方法及組合物 Download PDFInfo
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/06—Sulfuric ester hydrolases (3.1.6)
- C12Y301/06013—Iduronate-2-sulfatase (3.1.6.13)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Biochemistry (AREA)
- Inorganic Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
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- Psychiatry (AREA)
- Hematology (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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|---|---|---|---|
| US35885710P | 2010-06-25 | 2010-06-25 | |
| US61/358,857 | 2010-06-25 | ||
| US36078610P | 2010-07-01 | 2010-07-01 | |
| US61/360,786 | 2010-07-01 | ||
| US38786210P | 2010-09-29 | 2010-09-29 | |
| US61/387,862 | 2010-09-29 | ||
| US201161435710P | 2011-01-24 | 2011-01-24 | |
| US61/435,710 | 2011-01-24 | ||
| US201161442115P | 2011-02-11 | 2011-02-11 | |
| US61/442,115 | 2011-02-11 | ||
| US201161476210P | 2011-04-15 | 2011-04-15 | |
| US61/476,210 | 2011-04-15 | ||
| US201161495268P | 2011-06-09 | 2011-06-09 | |
| PCT/US2011/041926 WO2011163650A2 (en) | 2010-06-25 | 2011-06-25 | Methods and compositions for cns delivery of arylsulfatase a |
| US61/495,268 | 2012-06-09 |
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| TW201206464A TW201206464A (en) | 2012-02-16 |
| TWI667037B true TWI667037B (zh) | 2019-08-01 |
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|---|---|---|---|---|
| BR112012033214B1 (pt) | 2010-06-25 | 2020-11-03 | Shire Human Genetic Therapies, Inc. | uso de uma formulação estável compreendendo uma proteína de iduronato-2-sulfatase (i2s), formulação compreendendo a mesma e recipiente |
| JP6073783B2 (ja) | 2010-06-25 | 2017-02-01 | 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 | ヘパランｎ−スルファターゼのｃｎｓ送達のための方法および組成物 |
| CA2803166C (en) | 2010-06-25 | 2023-03-07 | Shire Human Genetic Therapies, Inc. | Cns delivery of therapeutic agents |
| JP6045493B2 (ja) | 2010-06-25 | 2016-12-14 | 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 | アリールスルファターゼａのｃｎｓ送達の方法および組成物 |
| KR20130043165A (ko) | 2010-06-25 | 2013-04-29 | 샤이어 휴먼 지네틱 테라피즈 인크. | 이듀로네이트-2-설파타제의 cns 전달을 위한 방법들 및 조성물들 |
| US20140377244A1 (en) | 2011-12-23 | 2014-12-25 | Shire Human Genetic Therapies, Inc. | Stable formulations for cns delivery of arylsulfatase a |
| WO2014110246A1 (en) | 2013-01-09 | 2014-07-17 | Shire Human Genetic Therapies, Inc. | Methods for purification of arylsulfatase a |
| JP2016523835A (ja) * | 2013-05-15 | 2016-08-12 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 中枢神経系へのアデノ随伴ウイルスを介した遺伝子導入 |
| US10208734B2 (en) * | 2015-04-23 | 2019-02-19 | Continuum Dynamics, Inc. | Lift-driven wind turbine with force canceling blade configuration |
| RU2687237C1 (ru) * | 2015-07-10 | 2019-05-08 | Синтон Байофармасьютикалс Б. В. | Композиции, содержащие конъюгаты антитело-лекарственное средство дуокармицин |
| BR112018016874A2 (pt) * | 2016-02-17 | 2019-02-05 | Shire Human Genetic Therapies, Inc. | métodos e composições para distribuição de arilsulfatase a no sistema nervoso central (snc) |
| DK3463308T4 (da) * | 2016-06-01 | 2026-02-09 | Servier Ip Uk Ltd | Formuleringer af polyalkylenoxid-asparaginase og fremgangsmåder til fremstilling og anvendelse deraf |
| MX2019007824A (es) * | 2016-12-28 | 2019-09-09 | Japan Chem Res | Preparacion liofilizada. |
| EP3684938A1 (en) | 2017-09-22 | 2020-07-29 | The Trustees of the University of Pennsylvania | Gene therapy for treating mucopolysaccharidosis type ii |
| CA3086181A1 (en) | 2017-12-19 | 2019-06-27 | Shire Human Genetic Therapies, Inc. | Purified arylsulfatase a and compositons thereof |
| CN112566652A (zh) * | 2018-06-25 | 2021-03-26 | Jcr制药股份有限公司 | 含有蛋白的水性液体制剂 |
| JP7715640B2 (ja) | 2019-05-03 | 2025-07-30 | 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 | 異染性白質ジストロフィーの治療に有用な組成物 |
| US20220348981A1 (en) * | 2019-09-23 | 2022-11-03 | University Of Washington | Assay of arylsulfatase a enzymatic activity in dried blood spots by mass spectrometry and fluorometry |
| WO2024176112A1 (en) | 2023-02-21 | 2024-08-29 | Takeda Pharmaceutical Company Limited | Large scale production of recombinant arylsulfatase a and compositions thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090017005A1 (en) * | 2003-08-29 | 2009-01-15 | Biomarion Pharmaceutical Inc. | Delivery of Therapeutic Compounds to the Brain and Other Tissues |
Family Cites Families (47)
| 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. |
| DK2020438T3 (en) | 1998-12-07 | 2018-07-23 | Genzyme Corp | Treatment of Pompe disease |
| 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 |
| US6534300B1 (en) | 1999-09-14 | 2003-03-18 | Genzyme Glycobiology Research Institute, Inc. | Methods for producing highly phosphorylated lysosomal hydrolases |
| US20020099025A1 (en) | 1999-12-30 | 2002-07-25 | Heywood James A. | Treatment of neurological disorders |
| US6866844B2 (en) | 2002-11-07 | 2005-03-15 | Biomarin Pharmaceutical Inc. | Precursor N-acetylgalactosamine-4-sulfatase, methods of treatment using said enzyme and methods for producing and purifying said enzyme |
| US7560424B2 (en) | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US7629309B2 (en) | 2002-05-29 | 2009-12-08 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| EP1436316B1 (en) | 2001-04-30 | 2008-01-23 | ZyStor Therapeutics , Inc. | Subcellular targeting of therapeutic proteins |
| US20040005309A1 (en) | 2002-05-29 | 2004-01-08 | Symbiontics, Inc. | Targeted therapeutic proteins |
| WO2003102583A1 (en) | 2002-05-29 | 2003-12-11 | Symbiontics, 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 |
| DK1503788T3 (da) | 2002-04-25 | 2011-10-17 | Shire Human Genetic Therapies | Behandling af alpha-galactosidase A-deficiens |
| PT1587923E (pt) | 2003-01-22 | 2011-12-07 | Univ Duke | Construções melhoradas para a expressão de polipéptidos lisossomais |
| WO2005002515A2 (en) | 2003-06-20 | 2005-01-13 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| 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 |
| NZ576986A (en) * | 2004-01-30 | 2010-12-24 | Shire Pharmaceuticals Ireland Ltd | Production and purification of recombinant arylsulfatase A |
| WO2005074888A2 (en) | 2004-02-03 | 2005-08-18 | Biodelivery Sciences International, Inc. | Replacement enzyme cochleates |
| US20080014188A1 (en) | 2004-02-06 | 2008-01-17 | Zankel Todd C | Manufacture of Highly Phosphorylated Lysosomal Enzymes and Uses Thereof |
| DE602005020745D1 (de) | 2004-02-10 | 2010-06-02 | Zystor Therapeutics Inc | Saure alpha-glukosidase und fragmente davon |
| US20050208090A1 (en) | 2004-03-18 | 2005-09-22 | Medtronic, Inc. | Methods and systems for treatment of neurological diseases of the central nervous system |
| EP1889628B1 (en) | 2005-05-11 | 2013-12-11 | JCR PHARMACEUTICALS Co., LTD. | Lipid liposome composition |
| ES2485369T3 (es) | 2005-06-08 | 2014-08-13 | Amicus Therapeutics, Inc. | Tratamiento de trastornos del SNC asociados con mutaciones en genes que codifican enzimas lisosómicas |
| AR059089A1 (es) * | 2006-01-20 | 2008-03-12 | Genzyme Corp | Administracion intraventricular de una enzima para enfermedades de almacenamiento lisosomal |
| CN101410408A (zh) * | 2006-04-04 | 2009-04-15 | 希尔制药爱尔兰有限责任公司 | 用于浓缩多肽的方法 |
| NO347673B1 (no) | 2006-04-04 | 2024-02-19 | Takeda Pharmaceuticals Co | En sammensetning som omfatter konsentrert polypeptide og bruk derav. |
| GB0611463D0 (en) | 2006-06-09 | 2006-07-19 | Novartis Ag | Organic compounds |
| US8419710B2 (en) | 2006-12-06 | 2013-04-16 | Medtronic, Inc. | Methods for infusing fluids via an implantable infusion system |
| WO2008109677A2 (en) | 2007-03-06 | 2008-09-12 | Saint Louis University | Modified enzyme and treatment method |
| CA2695374A1 (en) | 2007-08-15 | 2009-02-19 | Amunix, Inc. | Compositions and methods for modifying properties of biologically active polypeptides |
| US8420081B2 (en) | 2007-11-30 | 2013-04-16 | Abbvie, Inc. | Antibody formulations and methods of making same |
| US7722865B2 (en) | 2008-01-18 | 2010-05-25 | Biomarin Pharmaceutical Inc. | Manufacture of active highly phosphorylated human lysosomal sulfatase enzymes and uses thereof |
| WO2009137721A2 (en) | 2008-05-07 | 2009-11-12 | Zystor Therapeutics, Inc. | Lysosomal targeting peptides and uses thereof |
| US8436489B2 (en) | 2009-06-29 | 2013-05-07 | Lightsail Energy, Inc. | Compressed air energy storage system utilizing two-phase flow to facilitate heat exchange |
| EP2588132A4 (en) | 2010-06-25 | 2014-10-15 | Shire Human Genetic Therapies | METHOD AND COMPOSITIONS FOR DELIVERING BETA GALACTOCEREBROSIDASE INTO THE CNS |
| JP6073783B2 (ja) | 2010-06-25 | 2017-02-01 | 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 | ヘパランｎ−スルファターゼのｃｎｓ送達のための方法および組成物 |
| CA2803166C (en) | 2010-06-25 | 2023-03-07 | Shire Human Genetic Therapies, Inc. | Cns delivery of therapeutic agents |
| CN103269709A (zh) | 2010-06-25 | 2013-08-28 | 夏尔人类遗传性治疗公司 | Sanfilippo综合症类型B的治疗 |
| JP6045493B2 (ja) | 2010-06-25 | 2016-12-14 | 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 | アリールスルファターゼａのｃｎｓ送達の方法および組成物 |
| BR112012033214B1 (pt) | 2010-06-25 | 2020-11-03 | Shire Human Genetic Therapies, Inc. | uso de uma formulação estável compreendendo uma proteína de iduronato-2-sulfatase (i2s), formulação compreendendo a mesma e recipiente |
| KR20130043165A (ko) | 2010-06-25 | 2013-04-29 | 샤이어 휴먼 지네틱 테라피즈 인크. | 이듀로네이트-2-설파타제의 cns 전달을 위한 방법들 및 조성물들 |
| 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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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090017005A1 (en) * | 2003-08-29 | 2009-01-15 | Biomarion Pharmaceutical Inc. | Delivery of Therapeutic Compounds to the Brain and Other Tissues |
Non-Patent Citations (1)
| Title |
|---|
| Matzner U et al. Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy. Hum Mol Genet. 2005 May 1;14(9):1139-52. Epub 2005 Mar 16. * |
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