DE60031456T2 - Rekombinante alpha-l-iduronisase, deren herstellungs- und aufreinigungsverfahren, und behandlung von durch diese hervorgerufene mangelerkrankungen - Google Patents
Rekombinante alpha-l-iduronisase, deren herstellungs- und aufreinigungsverfahren, und behandlung von durch diese hervorgerufene mangelerkrankungen Download PDFInfo
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- DE60031456T2 DE60031456T2 DE60031456T DE60031456T DE60031456T2 DE 60031456 T2 DE60031456 T2 DE 60031456T2 DE 60031456 T DE60031456 T DE 60031456T DE 60031456 T DE60031456 T DE 60031456T DE 60031456 T2 DE60031456 T2 DE 60031456T2
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- iduronidase
- recombinant
- enzyme
- medium
- cells
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| PCT/US2000/031293 WO2002004616A1 (en) | 1999-11-12 | 2000-11-09 | RECOMBINANT α-L-IDURONIDASE, METHODS FOR PRODUCING AND PURIFYING THE SAME AND METHODS FOR TREATING DISEASES CAUSED BY DEFICIENCIES THEREOF |
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| DE60031456T Expired - Lifetime DE60031456T2 (de) | 1999-11-12 | 2000-11-09 | Rekombinante alpha-l-iduronisase, deren herstellungs- und aufreinigungsverfahren, und behandlung von durch diese hervorgerufene mangelerkrankungen |
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| US6585971B1 (en) * | 1999-11-12 | 2003-07-01 | Harbor-Ucla Research And Education Institute | Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating disease caused by deficiencies thereof |
| US6569661B1 (en) * | 1999-11-12 | 2003-05-27 | Biomarin Pharmaceutical Inc. | Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof |
| CA2438750A1 (en) * | 2001-02-20 | 2002-08-29 | Uab Research Foundation | Aminoglycoside treatment for lysosomal storage diseases |
| 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 |
| US7485314B2 (en) * | 2002-05-06 | 2009-02-03 | Los Angeles Biomedical Research Institute At Harbor-Ucla Medical Center | Induction of antigen specific immunologic tolerance |
| 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 |
| WO2005021716A2 (en) * | 2003-08-21 | 2005-03-10 | Q Therapeutics, Inc. | Genetically modified somatic cells for sustained secretion of lysosomal proenzymes deficient in lysosomal storage disorders |
| US7442372B2 (en) | 2003-08-29 | 2008-10-28 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| MXPA03011987A (es) * | 2003-12-19 | 2005-06-23 | Osio Sancho Alberto | Metodo para el tratamiento de la presbicia induciendo cambios en el poder y fisiologia corneal. |
| US9062126B2 (en) | 2005-09-16 | 2015-06-23 | Raptor Pharmaceuticals Inc. | Compositions comprising receptor-associated protein (RAP) variants specific for CR-containing proteins and uses thereof |
| WO2007065273A1 (en) * | 2005-12-08 | 2007-06-14 | The University Of British Columbia | Mucopolysaccharidosis (mps) diagnostic methods, systems, kits and assays associated therewith |
| KR20100015786A (ko) * | 2007-03-21 | 2010-02-12 | 랩터 파마슈티컬 인코포레이티드 | 환형의 수용체-연관된 단백질(ｒａｐ) 펩티드 |
| PL2188302T3 (pl) | 2007-07-09 | 2018-04-30 | Genentech, Inc. | Zapobieganie redukcji wiązań disiarczkowych podczas rekombinacyjnego wytwarzania polipeptydów |
| ES2387251T3 (es) * | 2008-02-21 | 2012-09-19 | Fiat Group Automobiles S.P.A. | Conjunto de soporte de vidrio para una puerta de vehículo a motor con un borde superior sin armazón |
| BRPI0912225A2 (pt) | 2008-05-07 | 2018-03-20 | Zystor Therapeutics, Inc. | peptídeos de direcionamento lisossomais e usos dos mesmos |
| EP3075386B1 (en) | 2009-06-17 | 2019-10-16 | BioMarin Pharmaceutical Inc. | Formulations for lysosomal enzymes |
| WO2012101671A1 (en) * | 2011-01-25 | 2012-08-02 | Jcr Pharmaceuticals Co., Ltd. | Method for production of human recombinant iduronate 2-sulfatase |
| DE102011102170B4 (de) | 2011-05-20 | 2024-06-06 | Vitesco Technologies GmbH | Einspritzvorrichtung zur Einspritzung eines Fluids |
| HUE051632T2 (hu) | 2012-06-19 | 2021-03-29 | Univ Florida | Betegségek kezelésére szolgáló készítmények és eljárások |
| AU2013299415B2 (en) | 2012-08-10 | 2017-07-13 | Osio Corporation d/b/a Yolia Health | Contact lens use in the treatment of an ophthalmologic condition |
| KR102346455B1 (ko) * | 2013-03-15 | 2022-01-04 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | Ｍｐｓｉ 치료를 위한 조성물 및 방법 |
| KR20180121899A (ko) | 2016-02-03 | 2018-11-09 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | I형 점액다당류증을 치료하기 위한 유전자 요법 |
| UY37587A (es) * | 2017-01-31 | 2018-08-31 | Regenxbio Inc | Tratamiento de mucopolisacaridosis i con alfa-l-iduronidasa (idua) humana glicosilada completamente humana |
| WO2019010335A1 (en) | 2017-07-06 | 2019-01-10 | The Trustees Of The University Of Pennsylvania | AAV9 MEDIATED GENE THERAPY FOR TREATING MUCOPOLYSACCHARIDOSIS TYPE I |
| 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 |
| CN107699590A (zh) * | 2017-10-13 | 2018-02-16 | 成都中医药大学 | 一种制备重组人α‑L‑艾杜糖醛酸酶的方法 |
| CA3123086A1 (en) | 2018-12-19 | 2020-06-25 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules for lysosomal targeting and related compositions and methods |
| CN110577559B (zh) * | 2019-08-19 | 2023-02-17 | 江西科技师范大学 | α-L-艾杜糖醛酸酶测定用荧光糖苷酶底物的合成方法 |
| WO2022145449A1 (ja) * | 2021-01-04 | 2022-07-07 | 国立大学法人徳島大学 | ライソゾームを標的とした新規ｄｄｓの開発 |
| JP7791517B2 (ja) * | 2021-01-04 | 2025-12-24 | 国立大学法人徳島大学 | ライソゾームを標的とした新規ｄｄｓの開発 |
| CN115109790A (zh) * | 2021-03-23 | 2022-09-27 | 北京据德医药科技有限公司 | 一种重组a-L-艾杜糖醛酸普酶及其制备方法 |
| WO2023288033A1 (en) | 2021-07-14 | 2023-01-19 | Lycia Therapeutics, Inc. | Asgpr cell surface receptor binding compounds and conjugates |
| CN114181318B (zh) * | 2021-11-08 | 2023-08-01 | 四川大学 | 一种组织特异性表达穿透血脑屏障的idua融合蛋白的重组腺相关病毒及应用 |
| CN115161284B (zh) * | 2022-07-04 | 2024-07-09 | 无锡多宁生物科技有限公司 | 一种lmh悬浮细胞复苏培养方法及其应用 |
Family Cites Families (11)
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| GB1029548A (en) | 1963-07-17 | 1966-05-11 | Amagasaki Iron & Steel Mfg Co | Corrugated roofing sheet |
| US3472931A (en) | 1969-01-17 | 1969-10-14 | Foster Milburn Co | Percutaneous absorption with lower alkyl amides |
| US3891757A (en) | 1971-11-11 | 1975-06-24 | Alza Corp | Anaesthetic topical and percutaneous administration with selected promoters |
| US5270051A (en) | 1991-10-15 | 1993-12-14 | Harris Donald H | Enzyme-orthokeratology |
| US6149909A (en) | 1995-06-23 | 2000-11-21 | Women's And Children's Hospital | Synthetic α-L-iduronidase and genetic sequences encoding same |
| EP0578790A4 (en) | 1991-11-14 | 1994-11-02 | Womens & Childrens Hospital | SYNTHETIC ALPHA-L-IDURONIDASE AND THESE ENCODING GENETIC SEQUENCES. |
| US5278051A (en) * | 1991-12-12 | 1994-01-11 | New York University | Construction of geometrical objects from polynucleotides |
| EP0865499B1 (en) | 1995-09-14 | 2009-03-18 | Virginia Tech Intellectual Properties, Inc. | Production of lysosomal enzymes in plant-based expression systems |
| GB9807464D0 (en) | 1998-04-07 | 1998-06-10 | Pharming Bv | Purification of human acid µ-glucosidase |
| CA2328518A1 (en) | 1998-05-13 | 1999-11-18 | Harbor-Ucla | Recombinant (alpha)-l-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof |
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