KR20140108519A - 재조합 인간 naglu 단백질 및 이의 용도 - Google Patents
재조합 인간 naglu 단백질 및 이의 용도 Download PDFInfo
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- KR20140108519A KR20140108519A KR1020147012617A KR20147012617A KR20140108519A KR 20140108519 A KR20140108519 A KR 20140108519A KR 1020147012617 A KR1020147012617 A KR 1020147012617A KR 20147012617 A KR20147012617 A KR 20147012617A KR 20140108519 A KR20140108519 A KR 20140108519A
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| JP5901877B2 (ja) | 2007-07-27 | 2016-04-13 | アーメイゲン・テクノロジーズ・インコーポレイテッドＡｒｍａｇｅｎ Ｔｅｃｈｎｏｌｏｇｉｅｓ， Ｉｎｃ． | 中枢神経系のα−Ｌ−イデュロニダーゼ活性を増加させるための方法および組成物 |
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| NZ715014A (en) | 2010-09-09 | 2018-10-26 | Synageva Biopharma Corp | Use of lysosomal acid lipase for treating lysosomal acid lipase deficiency in patients |
| WO2012112681A1 (en) | 2011-02-15 | 2012-08-23 | Shire Human Genetic Therapies, Inc. | Methods for treating lysosomal acid lipase deficiency |
| AU2012322811A1 (en) * | 2011-10-12 | 2014-05-01 | Synageva Biopharma Corp. | Recombinant human NaGlu protein and uses thereof |
| EP4338797A3 (en) | 2011-12-02 | 2024-06-12 | Armagen, Inc. | Methods and compositions for increasing arylsulfatase a activity in the cns |
| CA2912678C (en) | 2013-05-15 | 2023-10-10 | Regents Of The University Of Minnesota | Adeno-associated virus mediated gene transfer to the central nervous system |
| TWI793159B (zh) * | 2013-10-23 | 2023-02-21 | 美商健臻公司 | 重組醣蛋白及其用途 |
| KR102446169B1 (ko) * | 2014-05-14 | 2022-09-22 | 에스테베 파마슈티칼스 에스에이 | 리소좀 저장 장애의 치료를 위한 아데노연관 바이러스 벡터 |
| US20170267986A1 (en) * | 2014-06-25 | 2017-09-21 | Shire Human Genetic Therapies, Inc. | Generation of mannose-6-phosphate containing recombinant alpha-n-acetyl glucosaminidase |
| BR112017002741A2 (pt) | 2014-08-11 | 2018-02-27 | Shire Human Genetic Therapies, Inc | peptídeos contendo manose-6-fosfato fundidos a enzimas lisossômicas |
| AU2015323966A1 (en) | 2014-09-29 | 2017-03-16 | Alexion Pharmaceuticals, Inc. | Methods of treating mucopolysaccharidosis IIIB (MPSIIIB) |
| CN104524662B (zh) * | 2014-12-31 | 2017-02-22 | 迈得医疗工业设备股份有限公司 | 一种医用针座组装的上料机构 |
| US10538589B2 (en) * | 2015-01-14 | 2020-01-21 | Armagen Inc. | Methods and compositions for increasing N-acetylglucosaminidase (NAGLU) activity in the CNS using a fusion antibody comprising an anti-human insulin receptor antibody and NAGLU |
| US20190083583A1 (en) * | 2016-01-29 | 2019-03-21 | Alexion Pharmaceuticals, Inc. | Enzyme replacement therapy in mucopolysaccharidosis iiib patients |
| WO2017181113A1 (en) | 2016-04-15 | 2017-10-19 | The Trustees Of The University Of Pennsyvania | Gene therapy for treating mucopolysaccharidosis type ii |
| US10633705B2 (en) * | 2016-10-14 | 2020-04-28 | Alexion Pharmaceuticals, Inc. | N-acetyl-alpha-D-glucosaminidase deficiency compositions and methods |
| WO2019060662A1 (en) | 2017-09-22 | 2019-03-28 | The Trustees Of The University Of Pennsylvania | GENE THERAPY FOR THE TREATMENT OF MUCOPOLYSACCHARIDOSE TYPE II |
| MA50746A (fr) | 2017-10-02 | 2020-08-12 | Denali Therapeutics Inc | Protéines de fusion comprenant des enzymes d'enzymothérapie substitutive |
| WO2021194915A1 (en) * | 2020-03-23 | 2021-09-30 | The University Of North Carolina At Chapel Hill | Aav-naglu vectors for treatment of mucopolysaccharidosis iiib |
| CN111718947B (zh) * | 2020-06-18 | 2022-08-23 | 舒泰神（北京）生物制药股份有限公司 | 用于治疗ⅲa或ⅲb型粘多糖贮积症的腺相关病毒载体及用途 |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6825396B2 (en) | 1996-06-12 | 2004-11-30 | Board Of Trustees Operating Michigan State University | Methods for tissue specific synthesis of protein in eggs of transgenic hens |
| US5897998A (en) | 1997-08-04 | 1999-04-27 | The University Of Georgia Research Foundation, Inc. | Method for manipulating avian eggs |
| US7511120B2 (en) | 1997-10-16 | 2009-03-31 | Synageva Biopharma Corp. | Glycosylated G-CSF obtained from a transgenic chicken |
| JP2001520009A (ja) | 1997-10-16 | 2001-10-30 | ユニバーシティ・オブ・ジョージア・リサーチ・ファウンデイション・インコーポレイテッド | 鳥の導入遺伝子についてのマグナム特異的プロモーターを含むベクター |
| US20040019923A1 (en) | 1997-10-16 | 2004-01-29 | Ivarie Robert D. | Exogenous proteins expressed in avians and their eggs |
| US6217552B1 (en) | 1999-03-01 | 2001-04-17 | Coaxia, Inc. | Medical device for selective intrathecal spinal cooling in aortic surgery and spinal trauma |
| US6534300B1 (en) | 1999-09-14 | 2003-03-18 | Genzyme Glycobiology Research Institute, Inc. | Methods for producing highly phosphorylated lysosomal hydrolases |
| US7138262B1 (en) | 2000-08-18 | 2006-11-21 | Shire Human Genetic Therapies, Inc. | High mannose proteins and methods of making high mannose proteins |
| US7001994B2 (en) | 2001-01-18 | 2006-02-21 | Genzyme Corporation | Methods for introducing mannose 6-phosphate and other oligosaccharides onto glycoproteins |
| US7294507B2 (en) | 2001-11-30 | 2007-11-13 | Avigenics, Inc. | Ovomucoid promoters and methods of use |
| US6875588B2 (en) | 2001-11-30 | 2005-04-05 | Avigenics, Inc. | Ovomucoid promoter and methods of use |
| US6679165B2 (en) | 2002-05-22 | 2004-01-20 | Shiny Shih | Window adapted to a dater |
| US20050142141A1 (en) * | 2002-11-27 | 2005-06-30 | Pardridge William M. | Delivery of enzymes to the brain |
| EP1587923B1 (en) * | 2003-01-22 | 2011-08-24 | Duke University | Improved constructs for expressing lysosomal polypeptides |
| US7442372B2 (en) * | 2003-08-29 | 2008-10-28 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| US20050090001A1 (en) | 2003-10-07 | 2005-04-28 | Parker Stephen H. | Cell lines and methods for producing proteins |
| US20050208090A1 (en) * | 2004-03-18 | 2005-09-22 | Medtronic, Inc. | Methods and systems for treatment of neurological diseases of the central nervous system |
| US20090166224A1 (en) * | 2004-05-05 | 2009-07-02 | Ziping Yang | Multi-lectin affinity chromatography and uses thereof |
| EP1981546B1 (en) | 2006-02-06 | 2014-06-04 | The Medical Research and Infrastructure Fund of the Tel-Aviv Sourasky Medical Center | Enzyme replacement therapy for treating lysosomal storage diseases |
| 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 |
| CA2671570A1 (en) | 2007-01-26 | 2008-07-31 | Synageva Biopharma Corp. | Transgene expression in avians |
| US8431770B2 (en) * | 2008-01-07 | 2013-04-30 | Synageva Biopharma Corp. | Method of producing sialytransferase-modified proteins |
| WO2009131698A2 (en) * | 2008-04-23 | 2009-10-29 | Iowa State University Research Foundation, Inc. | PHOSPHORYLATED RECOMBINANT N-ACETYL-alpha-D- GLUCOSAMINIDASE (NaGlu) AND USES THEREOF |
| ES2576853T3 (es) * | 2009-07-03 | 2016-07-11 | Inserm - Institut National De La Santé Et De La Recherche Médicale | Compuestos dirigidos al receptor del manosa 6-fosfato independiente de cationes |
| UA115648C2 (uk) * | 2010-06-25 | 2017-12-11 | Шае Хюмен Дженетік Терапіс, Інк. | Доставка терапевтичних агентів до цнс |
| NZ702801A (en) | 2010-06-25 | 2016-08-26 | Shire Human Genetic Therapies | Treatment of sanfilippo syndrome type b |
| WO2012012742A2 (en) * | 2010-07-22 | 2012-01-26 | Shire Human Genetic Therapies, Inc. | Crystal structure of human alpha-n-acetylglucosaminidase |
| NZ715014A (en) | 2010-09-09 | 2018-10-26 | Synageva Biopharma Corp | Use of lysosomal acid lipase for treating lysosomal acid lipase deficiency in patients |
| AU2012322811A1 (en) * | 2011-10-12 | 2014-05-01 | Synageva Biopharma Corp. | Recombinant human NaGlu protein and uses thereof |
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| US9579366B2 (en) | 2017-02-28 |
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| US20170216412A1 (en) | 2017-08-03 |
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| US20140255383A1 (en) | 2014-09-11 |
| JP2014534962A (ja) | 2014-12-25 |
| JP6329483B2 (ja) | 2018-05-23 |
| IL232073A0 (en) | 2014-05-28 |
| MX2014004359A (es) | 2014-05-28 |
| US20130095092A1 (en) | 2013-04-18 |
| TW201321515A (zh) | 2013-06-01 |
| SG11201401457SA (en) | 2014-05-29 |
| EP2766477A4 (en) | 2015-07-15 |
| EP2766477A2 (en) | 2014-08-20 |
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