JP2005520000A - クロストリジウム毒素のためのfretプロテアーゼアッセイ - Google Patents
クロストリジウム毒素のためのfretプロテアーゼアッセイ Download PDFInfo
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| PCT/US2002/027212 WO2004031773A1 (en) | 2001-08-28 | 2002-08-22 | Fret protease assays for clostridial toxins |
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| JP2008062974A Division JP2008174567A (ja) | 2001-08-28 | 2008-03-12 | クロストリジウム毒素のためのfretプロテアーゼアッセイ |
| JP2008062977A Division JP2008201786A (ja) | 2001-08-28 | 2008-03-12 | クロストリジウム毒素のためのfretプロテアーゼアッセイ |
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| JP2008062974A Pending JP2008174567A (ja) | 2001-08-28 | 2008-03-12 | クロストリジウム毒素のためのfretプロテアーゼアッセイ |
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| JP2008062977A Pending JP2008201786A (ja) | 2001-08-28 | 2008-03-12 | クロストリジウム毒素のためのfretプロテアーゼアッセイ |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012525563A (ja) * | 2009-04-27 | 2012-10-22 | メルツ ファルマ ゲーエムベーハー ウント コンパニー カーゲーアーアー | ニューロトキシンポリペプチドの量の測定とその触媒及びタンパク質分解活性の測定のための手段及び方法 |
| WO2018147018A1 (ja) * | 2017-02-08 | 2018-08-16 | 国立大学法人東京工業大学 | 抗原検出又は測定用キット |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060141572A1 (en) * | 1993-09-21 | 2006-06-29 | Smith Leonard A | Recombinant light chains of botulinum neurotoxins and light chain fusion proteins for use in research and clinical therapy |
| FR2809733B1 (fr) * | 2000-06-02 | 2004-04-30 | Inst Nat Sante Rech Med | Substrat peptidique reconnu par la toxine botulique de type bont/b et son utilisation pour doser et/ou detecter ladite toxine ou des inhibiteurs correspondants |
| US7354735B2 (en) * | 2001-05-24 | 2008-04-08 | Hong Kong University Of Science And Technology | Nucleic acid encoding fluorescent protein constructs and methods for detecting apoptosis |
| US7374896B2 (en) | 2001-08-28 | 2008-05-20 | Allergan, Inc. | GFP-SNAP25 fluorescence release assay for botulinum neurotoxin protease activity |
| US7332567B2 (en) * | 2001-08-28 | 2008-02-19 | Allergan, Inc. | Fret protease assays for clostridial toxins |
| US7208285B2 (en) * | 2001-08-28 | 2007-04-24 | Allergan, Inc. | Fret protease assays for botulinum serotype A/E toxins |
| US8022172B2 (en) * | 2001-08-28 | 2011-09-20 | Allergan, Inc. | Luminescence resonance energy transfer (LRET) assays for clostridial toxin activity |
| US20060063221A1 (en) * | 2004-09-21 | 2006-03-23 | Williams Dudley J | Lanthanide-based substrates and methods for determining clostridial toxin activity |
| US20080064054A1 (en) * | 2001-08-28 | 2008-03-13 | Ester Fernandez-Salas | Fluorescence resonance energy transfer (fret) assays for clostridial toxin activity |
| US7183066B2 (en) * | 2002-09-27 | 2007-02-27 | Allergan, Inc. | Cell-based fluorescence resonance energy transfer (FRET) assays for clostridial toxins |
| WO2004031355A2 (en) * | 2002-10-01 | 2004-04-15 | University Of Maryland | Methods for identifying inhibitors of botulinum neurotoxins |
| US20040115727A1 (en) * | 2002-12-11 | 2004-06-17 | Allergan, Inc., A Corporation | Evolved clostridial toxins with altered protease specificity |
| WO2005076785A2 (en) * | 2003-12-19 | 2005-08-25 | Wisconsin Alumni Research Foundation | Method and compositions for detecting botulinum neurotoxin |
| US20080274480A1 (en) * | 2004-08-04 | 2008-11-06 | Allergan, Inc. | Botulinum Toxin Type a Immunoresistant Assay |
| US8617838B2 (en) * | 2004-09-20 | 2013-12-31 | University Of Massachusetts | Fluorescent proteins and related methods and compounds |
| US7399607B2 (en) * | 2004-09-22 | 2008-07-15 | Allergan, Inc. | Fluorescence polarization assays for determining clostridial toxin activity |
| WO2006068794A2 (en) | 2004-11-22 | 2006-06-29 | New York University | Genetically engineered clostridial genes, proteins encoded by the engineered genes, and uses thereof |
| CA2605160A1 (en) | 2005-04-05 | 2006-10-05 | Allergan, Inc. | Clostridial toxin activity assays |
| EP2293064B1 (en) * | 2005-04-05 | 2012-04-04 | Allergan, Inc. | Lipophilic dye-based FRET assays for clostridial toxin activity |
| ATE518882T1 (de) * | 2005-09-19 | 2011-08-15 | Allergan Inc | Mit clostridientoxin aktivierbare clostridientoxine |
| CA2602972C (en) * | 2005-10-12 | 2013-09-24 | Allergan, Inc. | Assays of molecular or subcellular interactivity using depolarization after resonance energy transfer (daret) |
| US8753831B2 (en) * | 2007-06-05 | 2014-06-17 | City Of Hope | Methods for detection of botulinum neurotoxin |
| WO2009035476A1 (en) | 2007-09-14 | 2009-03-19 | Biosentinel, Llc | Resonance energy transfer assay with cleavage sequence and spacer |
| KR101604515B1 (ko) | 2008-03-14 | 2016-03-17 | 알러간, 인코포레이티드 | 면역-기반 보툴리눔 독소 세로타입 a 활성 검정 |
| PT2271670E (pt) | 2008-03-14 | 2014-11-28 | Allergan Inc | Ensaio imunobaseado da atividade do serotipo a da toxina botulínica |
| CN105833254A (zh) | 2008-12-10 | 2016-08-10 | 阿勒根公司 | 梭菌毒素药物组合物 |
| KR101923847B1 (ko) | 2009-03-13 | 2018-11-29 | 알러간, 인코포레이티드 | 면역 기반 재표적화된 엔도펩티다제 활성 검정 |
| BRPI1008940A2 (pt) | 2009-03-13 | 2020-10-27 | Allergan, Inc. | linhagem de célula clonal estabelecida suscetível à intoxicação por bont/a |
| US8129139B2 (en) | 2009-07-13 | 2012-03-06 | Allergan, Inc. | Process for obtaining botulinum neurotoxin |
| EP2483666A1 (en) | 2009-10-02 | 2012-08-08 | Allergan, Inc. | In vitro method of determining changes in a protein environment |
| ES2676277T3 (es) * | 2009-10-16 | 2018-07-18 | Biomadison, Inc. | Células modificadas genéticamente para el ensayo de transferencia de energía por resonancia con el resto del sustrato de sinaptobrevina |
| EP2528941A4 (en) * | 2010-01-25 | 2013-05-29 | Univ New York | FOR TRANSPORT STUDIES AND NEURONAL ADMINISTRATION, MANIPULATED RECOMBINANT DERIVATIVES FROM BOTULINUM NEUROTOXINES |
| US8569254B2 (en) | 2010-12-10 | 2013-10-29 | National Yang Ming University | Methods for modulating the expression and aggregation of CAG-expanded gene product in cells and methods for identifying agents useful for doing the same |
| ES2653249T3 (es) | 2011-09-29 | 2018-02-06 | Cellsnap, Llc | Composiciones y métodos para ensayos de toxigenicidad |
| EP2798077A2 (en) | 2011-12-31 | 2014-11-05 | Allergan, Inc. | Highly Sensitive Cell-Based Assay to Detect the Presence of Active Botulinum Neurotoxin Serotype-A |
| US8962340B2 (en) | 2012-12-03 | 2015-02-24 | Src, Inc. | Real-time assay for the detection of botulinum toxin |
| GB2512691B (en) * | 2012-12-03 | 2016-06-29 | Src Inc | Real-time assay for the detection of botulinum toxin |
| WO2014108480A1 (en) * | 2013-01-09 | 2014-07-17 | Friedrich-Alexander-Universitaet Erlangen-Nuernberg | Method for in vitro detection and monitoring of a disease by measuring disease-associated protease activity in extracellular vesicles |
| US9315549B2 (en) | 2013-01-28 | 2016-04-19 | New York University | Treatment methods using atoxic neurotoxin derivatives |
| AU2014301116B2 (en) | 2013-06-28 | 2019-11-14 | Merz Pharma Gmbh & Co. Kgaa | Means and methods for the determination of the biological activity of Neurotoxin polypeptides in cells |
| KR20170026624A (ko) | 2014-07-07 | 2017-03-08 | 알러간, 인코포레이티드 | 조직 샘플에서 절단된 snap25를 검출하는 방법 |
| PT3177640T (pt) | 2014-08-08 | 2020-08-31 | Univ Leland Stanford Junior | Agentes pd-1 de alta afinidade e métodos de utilização |
| AU2015301737B2 (en) * | 2014-08-12 | 2021-01-28 | Biomadison, Inc. | Botulinum neurotoxins with modified light chain specifity and methods for producing same |
| US11897921B2 (en) | 2014-12-09 | 2024-02-13 | New York University | Propeptide fusion comprising a mutated clostridium botulinum neurotoxin and a VHH domain |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| CN106117525B (zh) * | 2016-06-27 | 2018-01-05 | 温州医科大学 | pH敏感嵌段聚合物、FRET复合物及其制备方法 |
| KR102480965B1 (ko) | 2016-09-13 | 2022-12-26 | 알레간 인코포레이티드 | 안정화된 비단백질 클로스트리듐 독소 조성물 |
| WO2018073370A1 (en) * | 2016-10-21 | 2018-04-26 | Toxogen Gmbh | A functional detection assay devoid of antibodies for serotyping of botulinum neurotoxins |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| GB201702500D0 (en) | 2017-02-16 | 2017-04-05 | Univ Sheffield | Stable vamp reporter assay |
| CN109211863B (zh) * | 2018-10-26 | 2021-04-20 | 大连民族大学 | 利用Eu2+f-f跃迁光谱检测爆炸物TNP的方法 |
Family Cites Families (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5804604A (en) * | 1989-12-21 | 1998-09-08 | Biogen, Inc. | Tat-derived transport polypeptides and fusion proteins |
| CA2082770A1 (en) | 1992-02-25 | 1993-08-26 | Denis Banville | Engineered protein chelates suitable for fluorescent lanthanide (e.g. terbium (iii)) based time resolved fluorescence assays |
| GB9310978D0 (en) * | 1993-05-27 | 1993-07-14 | Zeneca Ltd | Compounds |
| US7214787B1 (en) * | 1993-09-21 | 2007-05-08 | United States Of America As Represented By The Secretary Of The Army | Recombinant vaccine against botulinum neurotoxin |
| US7227010B2 (en) * | 1993-09-21 | 2007-06-05 | United States Of America As Represented By The Secretary Of The Army | Recombinant light chains of botulinum neurotoxins and light chain fusion proteins for use in research and clinical therapy |
| US5962637A (en) | 1994-06-03 | 1999-10-05 | Microbiological Research Authority | Toxin assay |
| GB9411138D0 (en) | 1994-06-03 | 1994-07-27 | Microbiological Res Authority | Toxin assay |
| US5693476A (en) * | 1995-02-24 | 1997-12-02 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of screening for compounds capable of modulating vesicular release |
| US5650280A (en) * | 1995-03-23 | 1997-07-22 | Incyte Pharmaceuticals, Inc. | Cellubrevin homolog |
| GB9508204D0 (en) | 1995-04-21 | 1995-06-07 | Speywood Lab Ltd | A novel agent able to modify peripheral afferent function |
| US6803188B1 (en) | 1996-01-31 | 2004-10-12 | The Regents Of The University Of California | Tandem fluorescent protein constructs |
| US6169074B1 (en) * | 1996-03-18 | 2001-01-02 | The Regents Of The University Of California | Peptide inhibitors of neurotransmitter secretion by neuronal cells |
| US5965699A (en) * | 1996-11-06 | 1999-10-12 | The United States Of America As Represented By The Secretary Of The Army | Assay for the proteolytic activity of serotype a from clostridium botulinum |
| US6197928B1 (en) * | 1997-03-14 | 2001-03-06 | The Regents Of The University Of California | Fluorescent protein sensors for detection of analytes |
| US6180340B1 (en) | 1997-10-31 | 2001-01-30 | Gen-Probe Incorporated | Extended dynamic range assays |
| WO1999029721A1 (en) | 1997-12-10 | 1999-06-17 | Washington University | Anti-pathogen system and methods of use thereof |
| EP1073763A4 (en) | 1998-04-28 | 2002-08-07 | Univ Washington | METHODS FOR TRANSDUCING FUSION MOLECULES |
| DE69941085D1 (de) * | 1998-07-17 | 2009-08-20 | Univ Maryland | Manipulierte proteine zum analyten nachweis |
| JP2002531113A (ja) | 1998-12-10 | 2002-09-24 | ワシントン大学 | 蛋白質の形質導入システムおよびその使用法 |
| ES2160485B1 (es) * | 1999-04-23 | 2002-05-16 | Lipotec Sa | Peptidos inhibidores de la exocitosis neuronal, composiciones cosmeticas y farmaceuticas que los contienen. |
| US6713444B1 (en) * | 1999-05-14 | 2004-03-30 | The United States Of America As Represented By The Secretary Of The Army | Buforin I as a specific inhibitor and therapeutic agent for botulinum toxin B and tetanus neurotoxins |
| US6573244B1 (en) * | 1999-05-17 | 2003-06-03 | The United States Of America As Represented By The Secretary Of The Army | Previns as specific inhibitors and therapeutic agents for Botulinum toxin B and Tetanus neurotoxins |
| US7235521B1 (en) * | 1999-05-17 | 2007-06-26 | United States Of America As Represented By The Secretary Of The Army | Previns as specific inhibitors and therapeutic agents for botulinum toxin B and tetanus neurotoxins |
| US6469154B1 (en) * | 1999-05-21 | 2002-10-22 | The Regents Of The University Of California | Fluorescent protein indicators |
| WO2001018038A2 (en) * | 1999-08-20 | 2001-03-15 | Imperial College Innovations Limited | Isoforms of snare molecules and the uses thereof in modulation of cellular exocytosis |
| US7740868B2 (en) * | 1999-08-25 | 2010-06-22 | Allergan, Inc. | Activatable clostridial toxins |
| ATE348178T1 (de) * | 1999-08-25 | 2007-01-15 | Allergan Inc | Aktivierbare rekombinante neurotoxine |
| US20030219462A1 (en) * | 2000-07-21 | 2003-11-27 | Allergan Sales, Inc | Clostridial neurotoxin compositions and modified clostridial neurotoxins |
| US6903187B1 (en) * | 2000-07-21 | 2005-06-07 | Allergan, Inc. | Leucine-based motif and clostridial neurotoxins |
| US7491799B2 (en) * | 2000-07-21 | 2009-02-17 | Allergan, Inc. | Modified botulinum neurotoxins |
| US7691983B2 (en) * | 2000-07-21 | 2010-04-06 | Allergan, Inc. | Chimera botulinum toxin type E |
| DE60131468D1 (de) * | 2000-09-25 | 2007-12-27 | U S Medical Res Inst Of Infect | Hoch-durchsatz assays für proteolytische aktivitäten von clostridium neurotoxinen |
| US7273722B2 (en) * | 2000-11-29 | 2007-09-25 | Allergan, Inc. | Neurotoxins with enhanced target specificity |
| JP4686906B2 (ja) * | 2001-06-04 | 2011-05-25 | 株式会社日立製作所 | 波長多重用光伝送装置 |
| US8022172B2 (en) * | 2001-08-28 | 2011-09-20 | Allergan, Inc. | Luminescence resonance energy transfer (LRET) assays for clostridial toxin activity |
| US20060063221A1 (en) * | 2004-09-21 | 2006-03-23 | Williams Dudley J | Lanthanide-based substrates and methods for determining clostridial toxin activity |
| US7374896B2 (en) * | 2001-08-28 | 2008-05-20 | Allergan, Inc. | GFP-SNAP25 fluorescence release assay for botulinum neurotoxin protease activity |
| US20080064054A1 (en) * | 2001-08-28 | 2008-03-13 | Ester Fernandez-Salas | Fluorescence resonance energy transfer (fret) assays for clostridial toxin activity |
| US7332567B2 (en) * | 2001-08-28 | 2008-02-19 | Allergan, Inc. | Fret protease assays for clostridial toxins |
| US7208285B2 (en) * | 2001-08-28 | 2007-04-24 | Allergan, Inc. | Fret protease assays for botulinum serotype A/E toxins |
| US6504006B1 (en) * | 2001-10-12 | 2003-01-07 | Nancy Rose Shine | Substrate peptides and assays for detecting and measuring proteolytic activity of serotype A neurotoxin from clostridium botulinum |
| US7183066B2 (en) * | 2002-09-27 | 2007-02-27 | Allergan, Inc. | Cell-based fluorescence resonance energy transfer (FRET) assays for clostridial toxins |
| WO2004031355A2 (en) | 2002-10-01 | 2004-04-15 | University Of Maryland | Methods for identifying inhibitors of botulinum neurotoxins |
| US20040115727A1 (en) * | 2002-12-11 | 2004-06-17 | Allergan, Inc., A Corporation | Evolved clostridial toxins with altered protease specificity |
| US7611856B2 (en) * | 2003-11-05 | 2009-11-03 | Los Alamos National Security, Llc | Mass spectrometry-based methods for detection and differentiation of botulinum neurotoxins |
| WO2005076785A2 (en) | 2003-12-19 | 2005-08-25 | Wisconsin Alumni Research Foundation | Method and compositions for detecting botulinum neurotoxin |
| ES2374822T3 (es) * | 2004-02-24 | 2012-02-22 | Allergan, Inc. | Ensayo de selección de toxinas botul�?nicas. |
| US7514088B2 (en) * | 2005-03-15 | 2009-04-07 | Allergan, Inc. | Multivalent Clostridial toxin derivatives and methods of their use |
| US7811584B2 (en) * | 2004-06-30 | 2010-10-12 | Allergan, Inc. | Multivalent clostridial toxins |
| US20060024331A1 (en) * | 2004-08-02 | 2006-02-02 | Ester Fernandez-Salas | Toxin compounds with enhanced membrane translocation characteristics |
| DE602005011458D1 (de) * | 2004-09-01 | 2009-01-15 | Allergan Inc | Abbaubare clostridientoxine |
| US7399607B2 (en) * | 2004-09-22 | 2008-07-15 | Allergan, Inc. | Fluorescence polarization assays for determining clostridial toxin activity |
| CA2605160A1 (en) * | 2005-04-05 | 2006-10-05 | Allergan, Inc. | Clostridial toxin activity assays |
| EP2293064B1 (en) * | 2005-04-05 | 2012-04-04 | Allergan, Inc. | Lipophilic dye-based FRET assays for clostridial toxin activity |
| ATE518882T1 (de) * | 2005-09-19 | 2011-08-15 | Allergan Inc | Mit clostridientoxin aktivierbare clostridientoxine |
| CA2602972C (en) * | 2005-10-12 | 2013-09-24 | Allergan, Inc. | Assays of molecular or subcellular interactivity using depolarization after resonance energy transfer (daret) |
| US8273865B2 (en) * | 2006-03-15 | 2012-09-25 | Allergan, Inc. | Multivalent clostridial toxins |
| US20080118532A1 (en) * | 2006-06-01 | 2008-05-22 | Atassi M Zouhair | Determining and reducing immunoresistance to a botulinum toxin therapy using botulinum toxin b peptides |
| AU2007272515B2 (en) * | 2006-07-11 | 2013-09-26 | Allergan, Inc. | Modified clostridial toxins with enhanced translocation capabilities and altered targeting activity for clostridial toxin target cells |
| US8067192B2 (en) * | 2007-06-05 | 2011-11-29 | City Of Hope | Methods for detection of botulinum neurotoxin |
| SG181772A1 (en) * | 2009-12-16 | 2012-07-30 | Allergan Inc | Modified clostridial toxins comprising an integrated protease cleavage site-binding domain |
-
2001
- 2001-08-28 US US09/942,098 patent/US7332567B2/en not_active Expired - Lifetime
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2002
- 2002-08-22 AU AU2002368109A patent/AU2002368109B8/en not_active Expired
- 2002-08-22 WO PCT/US2002/027212 patent/WO2004031773A1/en not_active Ceased
- 2002-08-22 BR BRPI0212140A patent/BRPI0212140B8/pt not_active IP Right Cessation
- 2002-08-22 DK DK02807745.1T patent/DK1438586T3/da active
- 2002-08-22 DK DK07023843.1T patent/DK1901069T3/da active
- 2002-08-22 EP EP02807745A patent/EP1438586B1/en not_active Revoked
- 2002-08-22 AT AT02807745T patent/ATE541213T1/de active
- 2002-08-22 JP JP2004541415A patent/JP2005520000A/ja active Pending
- 2002-08-22 CA CA2462686A patent/CA2462686C/en not_active Expired - Lifetime
- 2002-08-22 AT AT07023843T patent/ATE540317T1/de active
- 2002-08-22 EP EP07023843A patent/EP1901069B1/en not_active Revoked
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2007
- 2007-07-20 US US11/780,872 patent/US20080032318A1/en not_active Abandoned
- 2007-07-20 US US11/780,925 patent/US20080038756A1/en not_active Abandoned
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2008
- 2008-03-12 JP JP2008062974A patent/JP2008174567A/ja active Pending
- 2008-03-12 JP JP2008062977A patent/JP2008201786A/ja active Pending
- 2008-10-21 US US12/192,798 patent/US20090042231A1/en not_active Abandoned
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2009
- 2009-11-17 US US12/620,388 patent/US8048643B2/en not_active Expired - Fee Related
- 2009-11-17 US US12/620,337 patent/US20100075346A1/en not_active Abandoned
- 2009-11-17 US US12/620,370 patent/US8003753B2/en not_active Expired - Fee Related
- 2009-11-17 US US12/620,417 patent/US8053209B2/en not_active Expired - Fee Related
- 2009-11-17 US US12/620,434 patent/US8013113B2/en not_active Expired - Fee Related
- 2009-11-17 US US12/620,400 patent/US8053208B2/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012525563A (ja) * | 2009-04-27 | 2012-10-22 | メルツ ファルマ ゲーエムベーハー ウント コンパニー カーゲーアーアー | ニューロトキシンポリペプチドの量の測定とその触媒及びタンパク質分解活性の測定のための手段及び方法 |
| WO2018147018A1 (ja) * | 2017-02-08 | 2018-08-16 | 国立大学法人東京工業大学 | 抗原検出又は測定用キット |
| JPWO2018147018A1 (ja) * | 2017-02-08 | 2019-12-12 | 国立大学法人東京工業大学 | 抗原検出又は測定用キット |
| US11499965B2 (en) | 2017-02-08 | 2022-11-15 | Tokyo Institute Of Technology | Kit for detecting antigen or measuring its amount |
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