JP2004502456A - 組換えα−Ｌ−イズロニダーゼ、その生成及び精製方法及びその欠失により引き起こされる疾病の処理方法 - Google Patents
組換えα−Ｌ−イズロニダーゼ、その生成及び精製方法及びその欠失により引き起こされる疾病の処理方法 Download PDFInfo
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- JP2004502456A JP2004502456A JP2002509470A JP2002509470A JP2004502456A JP 2004502456 A JP2004502456 A JP 2004502456A JP 2002509470 A JP2002509470 A JP 2002509470A JP 2002509470 A JP2002509470 A JP 2002509470A JP 2004502456 A JP2004502456 A JP 2004502456A
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- iduronidase
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- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01014—Chitinase (3.2.1.14)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01075—Glucan endo-1,6-beta-glucosidase (3.2.1.75)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01076—L-Iduronidase (3.2.1.76)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y402/00—Carbon-oxygen lyases (4.2)
- C12Y402/02—Carbon-oxygen lyases (4.2) acting on polysaccharides (4.2.2)
- C12Y402/02004—Chondroitin ABC lyase (4.2.2.4), i.e. chondroitinase
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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| Application Number | Priority Date | Filing Date | Title |
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| US09/439,923 US6426208B1 (en) | 1999-11-12 | 1999-11-12 | Recombinant α-L-iduronidase, methods for producing and purifying the same and methods for treating diseases caused by deficiencies thereof |
| 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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| JP2004242343A Division JP3857705B2 (ja) | 1999-11-12 | 2004-08-23 | 組換えα−Ｌ−イズロニダーゼ、その生成及び精製方法及びその欠失により引き起こされる疾病の処理方法 |
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| JP2004502456A true JP2004502456A (ja) | 2004-01-29 |
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| JP2004242343A Expired - Lifetime JP3857705B2 (ja) | 1999-11-12 | 2004-08-23 | 組換えα−Ｌ−イズロニダーゼ、その生成及び精製方法及びその欠失により引き起こされる疾病の処理方法 |
| JP2006215076A Pending JP2006312648A (ja) | 1999-11-12 | 2006-08-07 | 組換えα−Ｌ−イズロニダーゼ、その生成及び精製方法及びその欠失により引き起こされる疾病の処理方法 |
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| JP2006215076A Pending JP2006312648A (ja) | 1999-11-12 | 2006-08-07 | 組換えα−Ｌ−イズロニダーゼ、その生成及び精製方法及びその欠失により引き起こされる疾病の処理方法 |
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| JP (3) | JP2004502456A (enExample) |
| CN (2) | CN101407796A (enExample) |
| AT (2) | ATE430193T1 (enExample) |
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| DE (2) | DE60042137D1 (enExample) |
| ES (2) | ES2273748T3 (enExample) |
| IL (3) | IL149568A0 (enExample) |
| MX (1) | MXPA02004742A (enExample) |
| WO (1) | WO2002004616A1 (enExample) |
| ZA (1) | ZA200203619B (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JP2022105471A (ja) * | 2021-01-04 | 2022-07-14 | 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 |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JP2004522763A (ja) * | 2001-02-20 | 2004-07-29 | ユーエイビー リサーチ ファンデーション | リソソーム蓄積症のアミノグリコシド治療 |
| 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 |
| CA2535816A1 (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 |
| EP2132224B1 (en) * | 2007-03-21 | 2011-12-28 | Raptor Pharmaceutical Inc | Cyclic receptor-associated protein (rap) peptides |
| PL3327026T3 (pl) | 2007-07-09 | 2020-02-28 | 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 |
| HUE034850T2 (en) | 2008-05-07 | 2018-03-28 | Biomarin Pharm Inc | Lysosomal targeting peptides and their use |
| EP3679942A1 (en) | 2009-06-17 | 2020-07-15 | 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 |
| HK1209633A1 (en) | 2012-06-19 | 2016-04-08 | University Of Florida Research Foundation, Inc. | Compositions and methods for treating diabetes |
| IN2015KN00596A (enExample) | 2012-08-10 | 2015-07-17 | Osio Corp D B A Yolia Health | |
| MX386059B (es) * | 2013-03-15 | 2025-03-18 | Univ Pennsylvania | COMPOSICIONES Y SUS usos EN EL TRATAMIENTO DE LA MUCOPOLISACARIDOSIS TIPO I. |
| IL260959B2 (en) | 2016-02-03 | 2024-09-01 | Univ Pennsylvania | Gene therapy for treating mucopolysaccharidosis type i |
| WO2018144441A1 (en) * | 2017-01-31 | 2018-08-09 | Regenxbio Inc. | Treatment of mucopolysaccharidosis i with fully-human glycosylated human alpha-l-iduronidase (idua) |
| BR112020000063A2 (pt) | 2017-07-06 | 2020-07-14 | The Trustees Of The University Of Pennsylvania | terapia gênica mediada por aav9 para tratamento de mucopolissacaridose tipo i |
| AU2018335752B2 (en) | 2017-09-22 | 2025-04-10 | Christian HINDERER | Gene therapy for treating Mucopolysaccharidosis type ii |
| 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 |
| WO2020132100A1 (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 |
| 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 |
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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 |
| AU649897B2 (en) | 1991-11-14 | 1994-06-02 | Women's And Children's Hospital | Synthetic alpha-L-iduronidase and genetic sequences encoding same |
| US5278051A (en) * | 1991-12-12 | 1994-01-11 | New York University | Construction of geometrical objects from polynucleotides |
| ATE426031T1 (de) | 1995-09-14 | 2009-04-15 | Virginia Tech Intell Prop | Produktion von lysosomalen enzymen in pflanzlichen expressionssystemen |
| GB9807464D0 (en) | 1998-04-07 | 1998-06-10 | Pharming Bv | Purification of human acid µ-glucosidase |
| IL139616A0 (en) | 1998-05-13 | 2002-02-10 | 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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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JP2022105471A (ja) * | 2021-01-04 | 2022-07-14 | 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 |
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