CN110499321A - 重组的肉毒梭菌神经毒素 - Google Patents

重组的肉毒梭菌神经毒素 Download PDF

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Publication number
CN110499321A
CN110499321A CN201910795176.3A CN201910795176A CN110499321A CN 110499321 A CN110499321 A CN 110499321A CN 201910795176 A CN201910795176 A CN 201910795176A CN 110499321 A CN110499321 A CN 110499321A
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CN
China
Prior art keywords
bont
protein
albumen
asn
chain
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Pending
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CN201910795176.3A
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English (en)
Chinese (zh)
Inventor
A·克辛斯
M·比尔得
P·马克斯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yi Pusen Biology Pharmacy Co Ltd
Syntaxin Ltd
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Yi Pusen Biology Pharmacy Co Ltd
Syntaxin Ltd
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Application filed by Yi Pusen Biology Pharmacy Co Ltd, Syntaxin Ltd filed Critical Yi Pusen Biology Pharmacy Co Ltd
Publication of CN110499321A publication Critical patent/CN110499321A/zh
Pending legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/164Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4886Metalloendopeptidases (3.4.24), e.g. collagenase
    • A61K38/4893Botulinum neurotoxin (3.4.24.69)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/33Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/24Metalloendopeptidases (3.4.24)
    • C12Y304/24069Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Toxicology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Dermatology (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201910795176.3A 2012-10-31 2013-10-31 重组的肉毒梭菌神经毒素 Pending CN110499321A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB201219602A GB201219602D0 (en) 2012-10-31 2012-10-31 Recombinant clostridium botulinum neurotoxins
GB1219602.8 2012-10-31
CN201380047542.8A CN104755098A (zh) 2012-10-31 2013-10-31 重组的肉毒梭菌神经毒素

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN201380047542.8A Division CN104755098A (zh) 2012-10-31 2013-10-31 重组的肉毒梭菌神经毒素

Publications (1)

Publication Number Publication Date
CN110499321A true CN110499321A (zh) 2019-11-26

Family

ID=47358958

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201910795176.3A Pending CN110499321A (zh) 2012-10-31 2013-10-31 重组的肉毒梭菌神经毒素
CN201380047542.8A Pending CN104755098A (zh) 2012-10-31 2013-10-31 重组的肉毒梭菌神经毒素

Family Applications After (1)

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CN201380047542.8A Pending CN104755098A (zh) 2012-10-31 2013-10-31 重组的肉毒梭菌神经毒素

Country Status (26)

Country Link
US (1) US10030238B2 (OSRAM)
EP (3) EP3673914B1 (OSRAM)
JP (2) JP2019068823A (OSRAM)
KR (2) KR102188539B1 (OSRAM)
CN (2) CN110499321A (OSRAM)
AR (2) AR093309A1 (OSRAM)
AU (3) AU2013340610B2 (OSRAM)
BR (1) BR112015005384A2 (OSRAM)
CA (1) CA2885519A1 (OSRAM)
DK (2) DK2914282T3 (OSRAM)
EA (1) EA201590794A8 (OSRAM)
ES (2) ES2788199T3 (OSRAM)
GB (1) GB201219602D0 (OSRAM)
HU (2) HUE048802T2 (OSRAM)
IL (1) IL237623B (OSRAM)
IN (1) IN2015MN00436A (OSRAM)
MX (2) MX367080B (OSRAM)
NO (1) NO2914282T3 (OSRAM)
NZ (1) NZ705575A (OSRAM)
PL (2) PL2914282T3 (OSRAM)
PT (2) PT2914282T (OSRAM)
SG (2) SG11201502372SA (OSRAM)
TW (3) TWI626307B (OSRAM)
UA (1) UA118837C2 (OSRAM)
WO (1) WO2014068317A1 (OSRAM)
ZA (1) ZA201501449B (OSRAM)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201219602D0 (en) * 2012-10-31 2012-12-12 Syntaxin Ltd Recombinant clostridium botulinum neurotoxins
HK1248737A1 (zh) * 2015-03-26 2018-10-19 哈佛大学校长及研究员协会 工程改造的肉毒桿菌神經毒素
WO2017063743A1 (en) 2015-10-14 2017-04-20 Merz Pharma Gmbh & Co. Kgaa Improvements to ultrasound-based therapy of photoaged tissue
WO2017148915A1 (en) 2016-03-02 2017-09-08 Merz Pharma Gmbh & Co. Kgaa Composition comprising botulinum toxin
EP3263710A1 (en) * 2016-07-01 2018-01-03 Ipsen Biopharm Limited Production of activated clostridial neurotoxins
JP7100020B2 (ja) 2016-08-24 2022-07-12 プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ 操作されたボツリヌス神経毒素
AU2017326253B2 (en) 2016-09-13 2021-10-21 Allergan, Inc. Stabilized non-protein clostridial toxin compositions
US11952601B2 (en) 2017-06-20 2024-04-09 Merz Pharma Gmbh & Co. Kgaa Recombinant botulinum toxin with increased duration of effect
US11155802B2 (en) 2017-07-06 2021-10-26 Merz Pharma Gmbh & Co. Kgaa Recombinant botulinum neurotoxins with increased duration of effect
US20190105261A1 (en) 2017-10-11 2019-04-11 Illustris Pharmaceuticals, Inc. Methods and compositions for topical delivery
UA128185C2 (uk) * 2018-01-29 2024-05-01 Іпсен Біофарм Лімітед Ботулінічний нейротоксин, який розщеплює ненейронний snare
US11707510B2 (en) * 2018-02-16 2023-07-25 Preclinics Discovery Gmbh Nucleic acid-based botulinum neurotoxin for therapeutic use
GB201815844D0 (en) 2018-09-28 2018-11-14 Ipsen Biopharm Ltd Therapeutic & comestic uses of botulinum neurotoxin serotype e
GB202011055D0 (en) 2020-07-17 2020-09-02 Ipsen Bioinnovation Ltd Treatment of post-operative pain
GB202015618D0 (en) 2020-10-01 2020-11-18 Ipsen Biopharm Ltd Method for producing beta-trypsin
CN115819526A (zh) * 2022-12-02 2023-03-21 海雅美生物技术(珠海)有限公司 一种重组肉毒杆菌神经毒素及其制备方法和应用

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1184504A (zh) * 1995-05-17 1998-06-10 纳幕尔杜邦公司 重组杆状病毒杀虫剂
US20050238665A1 (en) * 1995-03-16 2005-10-27 Allergan, Inc., Allergan Botox Limited Soluble recombinant botulinum toxin proteins
WO2006011966A1 (en) * 2004-06-30 2006-02-02 Allergan, Inc. Optimizing expression of active botulinum toxin type e
US20060099672A1 (en) * 1999-08-25 2006-05-11 Allergan, Inc. Activatable recombinant neurotoxins
US20070218084A1 (en) * 2005-12-30 2007-09-20 Fondazione Pierfranco E Luisa Mariani- Onlus Method for the Mapping of the Epileptogenic Focus in the Pre-Surgical Evaluation of Patients with Intractable Epilepsy
CN101107361A (zh) * 2005-01-21 2008-01-16 比奥泰康医疗有限责任公司 二硫桥连双链形式的蛋白质的重组表达
US20110111483A1 (en) * 2004-06-30 2011-05-12 Allergan, Inc. Optimizing Expression of Active Botulinum Toxin Type E
CN104755098A (zh) * 2012-10-31 2015-07-01 突触融合蛋白有限公司 重组的肉毒梭菌神经毒素
CN106414759A (zh) * 2014-04-29 2017-02-15 益普生生物创新有限公司 重组肉毒梭菌神经毒素的制造
CN110072880A (zh) * 2016-08-24 2019-07-30 哈佛大学校长及研究员协会 工程化肉毒杆菌神经毒素

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2336587A1 (en) 1998-07-10 2000-01-20 U.S. Medical Research Institute Of Infectious Diseases Botulinum neurotoxin vaccine
US7374896B2 (en) 2001-08-28 2008-05-20 Allergan, Inc. GFP-SNAP25 fluorescence release assay for botulinum neurotoxin protease activity
US7514088B2 (en) * 2005-03-15 2009-04-07 Allergan, Inc. Multivalent Clostridial toxin derivatives and methods of their use
GB2416122A (en) * 2004-07-12 2006-01-18 Ipsen Ltd Botulinum neurotoxin composition
DE102004043009A1 (de) * 2004-09-06 2006-03-23 Toxogen Gmbh Transportprotein zum Einbringen chemischer Verbindungen in Nervenzellen
BRPI0508374A (pt) * 2005-03-03 2007-07-31 Allergan Inc meios para bactéria clostrìdio e processo para obtenção de uma toxina clostrìdica
AU2006339490B2 (en) * 2005-09-19 2011-12-08 Allergan, Inc. Clostridial toxin activatable clostridial toxins
CA2657521A1 (en) 2006-07-11 2008-01-17 Allergan, Inc. Modified clostridial toxins with enhanced translocation capabilities and altered targeting activity for non-clostridial toxin target cells
EP2178905B1 (en) 2007-07-26 2013-11-06 Allergan, Inc. Methods of activiting clostridial toxins
CA2746425C (en) 2008-12-10 2016-05-03 Allergan, Inc. Clostridial toxin pharmaceutical compositions
GB0903006D0 (en) * 2009-02-23 2009-04-08 Syntaxin Ltd Modified non-cytotoxic proteases
EP2419128B1 (en) * 2009-04-14 2018-06-06 Medical College of Wisconsin, Inc. Engineered botulinum neurotoxin
RU2012129557A (ru) * 2009-12-16 2014-01-27 Аллерган, Инк. МОДИФИЦИРОВАННЫЕ ТОКСИНЫ Clostridial, СОДЕРЖАЩИЕ ИНТЕГРИРОВАННЫЙ САЙТ-СВЯЗЫВАЮЩИЙ ДОМЕН ПРОТЕАЗНОГО РАСЩЕПЛЕНИЯ
WO2012112434A1 (en) 2011-02-14 2012-08-23 Allergan, Inc. Inhibiting aberrant blood vessel formation using retargeted endopeptidases

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050238665A1 (en) * 1995-03-16 2005-10-27 Allergan, Inc., Allergan Botox Limited Soluble recombinant botulinum toxin proteins
CN1184504A (zh) * 1995-05-17 1998-06-10 纳幕尔杜邦公司 重组杆状病毒杀虫剂
US20060099672A1 (en) * 1999-08-25 2006-05-11 Allergan, Inc. Activatable recombinant neurotoxins
WO2006011966A1 (en) * 2004-06-30 2006-02-02 Allergan, Inc. Optimizing expression of active botulinum toxin type e
US20110111483A1 (en) * 2004-06-30 2011-05-12 Allergan, Inc. Optimizing Expression of Active Botulinum Toxin Type E
CN101107361A (zh) * 2005-01-21 2008-01-16 比奥泰康医疗有限责任公司 二硫桥连双链形式的蛋白质的重组表达
US20070218084A1 (en) * 2005-12-30 2007-09-20 Fondazione Pierfranco E Luisa Mariani- Onlus Method for the Mapping of the Epileptogenic Focus in the Pre-Surgical Evaluation of Patients with Intractable Epilepsy
CN104755098A (zh) * 2012-10-31 2015-07-01 突触融合蛋白有限公司 重组的肉毒梭菌神经毒素
EP3673914A1 (en) * 2012-10-31 2020-07-01 Ipsen Bioinnovation Limited Solid compositions comprising recombinant clostridium botulinum neurotoxins
CN106414759A (zh) * 2014-04-29 2017-02-15 益普生生物创新有限公司 重组肉毒梭菌神经毒素的制造
CN110072880A (zh) * 2016-08-24 2019-07-30 哈佛大学校长及研究员协会 工程化肉毒杆菌神经毒素

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
ABDOULREZA AGHELI MANSOUR 等: "Cloning, high level expression and immunogenicity of 1163-1256 residues of C-terminal heavy chain of C. botulinum neurotoxin type E", 《BIOLOGICALS》 *
GILMORE MA等: "Fully active recombinant Bont/E purified from E. coli in high yield", 《TOXICON》 *
KUMARAN,D.等: "Chain A, Domain Organization In Clostridium Butulinum Neurotoxin Type E Is Unique: Its Implication In Faster Translocation", 《GENBANK》 *
SHUNJI KOZAKI等: "Immunological Characterization of Clostridium butyricum Neurotoxin and Its Trypsin-Induced Fragment by Use of Monoclonal Antibodies against Clostridium botulinum Type E Neurotoxin", 《INFECTION AND IMMUNITY》 *
古月有心: "大肠杆菌偏好密码子表", 《道客巴巴在线文档分享平台》 *
贾宏丽等: "重组肉毒毒素E(BoNT/E)重链C端的表达、纯化及其抗原性分析", 《军事医学科学院院刊》 *

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JP2019068823A (ja) 2019-05-09
AU2013340610A1 (en) 2015-03-19
IN2015MN00436A (OSRAM) 2015-09-04
WO2014068317A1 (en) 2014-05-08
KR20200110470A (ko) 2020-09-23
GB201219602D0 (en) 2012-12-12
AR093309A1 (es) 2015-05-27
PT3326644T (pt) 2020-05-29
EP3673914B1 (en) 2021-10-27
NO2914282T3 (OSRAM) 2018-05-19
SG10201701140WA (en) 2017-04-27
PL3326644T3 (pl) 2020-08-24
EP3673914A1 (en) 2020-07-01
TWI626307B (zh) 2018-06-11
ZA201501449B (en) 2016-08-31
NZ705575A (en) 2019-08-30
US10030238B2 (en) 2018-07-24
EA201590794A8 (ru) 2016-01-29
IL237623A0 (en) 2015-04-30
KR20150094590A (ko) 2015-08-19
DK2914282T3 (en) 2018-02-26
ES2788199T3 (es) 2020-10-20
PL2914282T3 (pl) 2018-07-31
HUE048802T2 (hu) 2020-08-28
SG11201502372SA (en) 2015-05-28
EP3326644A1 (en) 2018-05-30
EA201590794A1 (ru) 2015-08-31
ES2662402T3 (es) 2018-04-06
HUE036764T2 (hu) 2018-07-30
TWI673361B (zh) 2019-10-01
AU2018203556A1 (en) 2018-06-07
UA118837C2 (uk) 2019-03-25
AR117738A2 (es) 2021-08-25
AU2013340610B2 (en) 2018-02-22
PT2914282T (pt) 2018-03-13
MX2015005156A (es) 2015-09-23
DK3326644T3 (da) 2020-05-11
EP2914282B1 (en) 2017-12-20
TW201825680A (zh) 2018-07-16
KR102188539B1 (ko) 2020-12-09
KR102264478B1 (ko) 2021-06-15
CA2885519A1 (en) 2014-05-08
BR112015005384A2 (pt) 2017-08-08
JP2020078321A (ja) 2020-05-28
EP2914282A1 (en) 2015-09-09
CN104755098A (zh) 2015-07-01
IL237623B (en) 2019-05-30
TW202012622A (zh) 2020-04-01
US20150247139A1 (en) 2015-09-03
EP3326644B1 (en) 2020-03-04
MX367080B (es) 2019-08-05
MX2019009222A (es) 2019-11-21
AU2020244481A1 (en) 2020-10-29
AU2018203556B2 (en) 2020-08-20
HK1208359A1 (en) 2016-03-04
TW201435084A (zh) 2014-09-16

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