AU2014205441B2 - Methods for purification of arylsulfatase A - Google Patents
Methods for purification of arylsulfatase A Download PDFInfo
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- AU2014205441B2 AU2014205441B2 AU2014205441A AU2014205441A AU2014205441B2 AU 2014205441 B2 AU2014205441 B2 AU 2014205441B2 AU 2014205441 A AU2014205441 A AU 2014205441A AU 2014205441 A AU2014205441 A AU 2014205441A AU 2014205441 B2 AU2014205441 B2 AU 2014205441B2
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- chromatography
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- arylsulfatase
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/12—Purification
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
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| ES2625511T3 (es) * | 2011-07-08 | 2017-07-19 | Shire Human Genetic Therapies, Inc. | Métodos para la purificación de arylsulfatasa A |
| CN112126634A (zh) | 2013-01-09 | 2020-12-25 | 夏尔人类遗传性治疗公司 | 含用于纯化芳基硫酸酯酶a的方法 |
| WO2016106291A1 (en) * | 2014-12-22 | 2016-06-30 | Alexion Pharmaceuticals, Inc. | Methods of purifying recombinant proteins |
| WO2017031476A2 (en) * | 2015-08-20 | 2017-02-23 | Genentech, Inc. | Purification of fkpa and uses thereof for producing recombinant polypeptides |
| JP6985282B2 (ja) * | 2016-03-16 | 2021-12-22 | フェニックス ティシュー リペア インコーポレイテッドPhoenix Tissue Repair, Inc. | ７型コラーゲンの精製方法 |
| US11584777B2 (en) | 2017-08-31 | 2023-02-21 | Green Cross Corporation | Method for purifying a sulfatase protein |
| CN111699249A (zh) * | 2017-12-19 | 2020-09-22 | 夏尔人类遗传性治疗公司 | 纯化的芳基硫酸酯酶a及其组合物 |
| JP2021512853A (ja) * | 2018-02-02 | 2021-05-20 | エンジーヴァント セラピューティックス ゲーエムベーハー | ファーバー病を処置するための方法 |
| IL277797B1 (en) * | 2018-04-12 | 2024-11-01 | Amgen Inc | Methods for making stable protein compositions |
| CN112082832B (zh) * | 2019-06-12 | 2022-03-29 | 华南理工大学 | 一种保存城市污水中硫酸酯结合体和葡萄糖苷醛酸结合体的方法 |
| KR102286892B1 (ko) * | 2019-07-08 | 2021-08-06 | 삼천당제약주식회사 | 안과용 단백질 제제의 정제방법 |
| CN110632052A (zh) * | 2019-10-25 | 2019-12-31 | 山西师范大学 | 土壤芳基硫酸酯酶活性的荧光光谱检测法 |
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| CN112759643B (zh) * | 2021-03-17 | 2023-05-30 | 华兰生物工程股份有限公司 | 一种血清白蛋白的脱脂方法 |
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| EP0456229A2 (en) * | 1990-05-10 | 1991-11-13 | Bristol-Myers Squibb Company | Arylsulfatase |
| WO2002098455A2 (en) * | 2001-06-07 | 2002-12-12 | Hemebiotech A/S | Production of recombinant human arylsulfatase a |
| WO2005073367A1 (en) * | 2004-01-30 | 2005-08-11 | Zymenex A/S | Production and purification of recombinant arylsulfatase a |
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| US4314997A (en) | 1980-10-06 | 1982-02-09 | Edward Shanbrom | Purification of plasma protein products |
| US4315919A (en) | 1980-10-06 | 1982-02-16 | Edward Shanbrom | Depyrogenation process |
| US4764369A (en) | 1983-07-14 | 1988-08-16 | New York Blood Center Inc. | Undenatured virus-free biologically active protein derivatives |
| NO960163D0 (no) | 1996-01-15 | 1996-01-15 | Thomas Berg | Mutasjonsdeteksjon av bovin |
| ES2177240T3 (es) | 1998-01-27 | 2002-12-01 | Hemebiotech As | Tratamiento para la porfiria aguda intermitente (pai) y otras enfermedades porfiricas. |
| DK2270044T3 (en) | 1998-06-09 | 2015-01-26 | Csl Behring Ag | Liquid immunoglobulin G (IgG) product |
| SK288128B6 (sk) | 1998-06-09 | 2013-10-02 | Csl Behring Ag | Process for purifying immunoglobulin G (IgG), liquid immunoglobulin product and use thereof for the preparation of a medicament |
| AUPQ026799A0 (en) | 1999-05-10 | 1999-06-03 | Csl Limited | Method of increasing protein stability by removing immunoglobulin aggregates |
| EP1202744B1 (en) | 1999-07-27 | 2006-01-04 | Zymenex A/S | PRODUCTION OF rhPBGD |
| US6812339B1 (en) | 2000-09-08 | 2004-11-02 | Applera Corporation | Polymorphisms in known genes associated with human disease, methods of detection and uses thereof |
| WO2002040686A2 (en) | 2000-11-15 | 2002-05-23 | Genzyme Corporation | Expression system for recombinant proteins |
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| EP1402014A1 (en) | 2001-06-29 | 2004-03-31 | Hemebiotech A/S | A process for purification of recombinant porphobilinogen deaminase |
| US7232670B2 (en) | 2001-09-28 | 2007-06-19 | St. Jude Children's Research Hospital | Targeting proteins to cells expressing mannose receptors via expression in insect cells |
| EP1463512B1 (en) | 2002-01-11 | 2014-05-28 | biOasis Technologies Inc. | Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes |
| US7118675B2 (en) | 2002-02-04 | 2006-10-10 | Millipore Corporation | Process for removing protein aggregates and virus from a protein solution |
| EP1740204B1 (en) | 2004-04-01 | 2018-03-14 | Chiesi Farmaceutici S.p.A. | Medicinal use of alpha-mannosidase |
| US20060051347A1 (en) | 2004-09-09 | 2006-03-09 | Winter Charles M | Process for concentration of antibodies and therapeutic products thereof |
| BRPI0709737A2 (pt) | 2006-04-04 | 2011-07-26 | Zymenex As | processo para concentraÇço de um polipeptÍdeo |
| CA2739352C (en) * | 2008-10-29 | 2021-07-13 | Wyeth Llc | Methods for purification of single domain antigen binding molecules |
| US8945895B2 (en) * | 2009-07-31 | 2015-02-03 | Baxter International Inc. | Methods of purifying recombinant ADAMTS13 and other proteins and compositions thereof |
| CA2803003C (en) * | 2010-06-25 | 2022-11-22 | Shire Human Genetic Therapies, Inc. | Methods and compositions for cns delivery of arylsulfatase a |
| JP6045491B2 (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 | 治療薬のｃｎｓ送達 |
| GB201012603D0 (en) * | 2010-07-27 | 2010-09-08 | Ucb Pharma Sa | Protein purification |
| CN112126634A (zh) | 2013-01-09 | 2020-12-25 | 夏尔人类遗传性治疗公司 | 含用于纯化芳基硫酸酯酶a的方法 |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0456229A2 (en) * | 1990-05-10 | 1991-11-13 | Bristol-Myers Squibb Company | Arylsulfatase |
| WO2002098455A2 (en) * | 2001-06-07 | 2002-12-12 | Hemebiotech A/S | Production of recombinant human arylsulfatase a |
| WO2005073367A1 (en) * | 2004-01-30 | 2005-08-11 | Zymenex A/S | Production and purification of recombinant arylsulfatase a |
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