CN109476713A - 工程改造的肉毒杆菌神经毒素 - Google Patents

工程改造的肉毒杆菌神经毒素 Download PDF

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Publication number
CN109476713A
CN109476713A CN201780035648.4A CN201780035648A CN109476713A CN 109476713 A CN109476713 A CN 109476713A CN 201780035648 A CN201780035648 A CN 201780035648A CN 109476713 A CN109476713 A CN 109476713A
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China
Prior art keywords
bont
polypeptide
seq
modified
modified bont
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CN201780035648.4A
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Chinese (zh)
Inventor
保罗·斯滕马克
张四才
董民
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Boston Childrens Hospital
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Boston Childrens Hospital
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
    • A61K38/4893—Botulinum neurotoxin (3.4.24.69)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/24—Metalloendopeptidases (3.4.24)
    • C12Y304/24069—Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • Y—GENERAL 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against 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)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Neurology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Neurosurgery (AREA)
  • Toxicology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Psychiatry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Hospice & Palliative Care (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
CN201780035648.4A 2016-06-08 2017-06-08 工程改造的肉毒杆菌神经毒素 Pending CN109476713A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662347579P 2016-06-08 2016-06-08
US62/347,579 2016-06-08
PCT/US2017/036628 WO2017214447A1 (en) 2016-06-08 2017-06-08 Engineered botulinum neurotoxins

Publications (1)

Publication Number Publication Date
CN109476713A true CN109476713A (zh) 2019-03-15

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CN201780035648.4A Pending CN109476713A (zh) 2016-06-08 2017-06-08 工程改造的肉毒杆菌神经毒素

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US (1) US11104891B2 (enExample)
EP (1) EP3468985A1 (enExample)
JP (2) JP7152392B2 (enExample)
KR (1) KR20190025906A (enExample)
CN (1) CN109476713A (enExample)
AU (1) AU2017277905B2 (enExample)
BR (1) BR112018075363A2 (enExample)
CA (1) CA3026492A1 (enExample)
EA (1) EA201892784A1 (enExample)
IL (1) IL263058B2 (enExample)
MX (1) MX2018015254A (enExample)
SG (2) SG10201912099TA (enExample)
WO (1) WO2017214447A1 (enExample)

Cited By (3)

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CN114369623A (zh) * 2022-01-12 2022-04-19 中国人民解放军空军军医大学 一种基于Cre-lox重组系统的Synaptotagmin2-RNAi及其应用
CN114410683A (zh) * 2022-01-12 2022-04-29 中国人民解放军空军军医大学 一种基于Cre-lox重组系统的RIM3-RNAi及其应用
WO2022179552A1 (zh) * 2021-02-26 2022-09-01 重庆誉颜制药有限公司 一种经修饰的神经毒素的单链多肽及其用途

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EP3372239B1 (en) 2012-05-30 2020-11-11 President and Fellows of Harvard College Engineered botulinum neurotoxin
WO2016154534A1 (en) * 2015-03-26 2016-09-29 President And Fellows Of Harvard College Engineered botulinum neurotoxin
US10676723B2 (en) 2015-05-11 2020-06-09 David Gordon Bermudes Chimeric protein toxins for expression by therapeutic bacteria
TW201718627A (zh) 2015-06-11 2017-06-01 梅茲製藥有限兩合公司 重組梭菌神經毒素及其使用與形成方法、包括其之醫藥組合物及對應其之前驅物、編碼前驅物之核酸序列及其獲得方法與前驅物之形成方法、載體與包括核酸序列之重組宿主細胞
GB201607901D0 (en) * 2016-05-05 2016-06-22 Ipsen Biopharm Ltd Chimeric neurotoxins
CA3024331A1 (en) * 2016-05-16 2017-11-23 President And Fellows Of Harvard College Method for purification and activation of botulinum neurotoxin
PL3481852T3 (pl) * 2016-07-08 2023-07-24 Children's Medical Center Corporation Nowa neurotoksyna botulinowa i jej pochodne
CN110072880B (zh) 2016-08-24 2025-02-18 哈佛大学校长及研究员协会 工程化肉毒杆菌神经毒素
US11129906B1 (en) 2016-12-07 2021-09-28 David Gordon Bermudes Chimeric protein toxins for expression by therapeutic bacteria
EP3687566A2 (en) 2017-09-29 2020-08-05 Children's Medical Center Corporation A neurotoxin-like toxin and uses thereof
TWI810228B (zh) * 2017-12-20 2023-08-01 英商艾普森生物製藥有限公司 自主神經系統障礙之治療
US20210040467A1 (en) * 2018-01-30 2021-02-11 Children's Medical Center Corporation Production of botulinum neurotoxins using bacillus systems
EP3752128B1 (de) * 2018-02-16 2025-01-15 preclinics discovery GmbH Nukleinsäure-basiertes botulinum neurotoxin zur therapeutischen anwendung
SE542539C2 (en) * 2018-02-26 2020-06-02 Toxotech Ab Chimeric botulinum neurotoxin heavy chain binding domain
KR20230001260A (ko) 2021-06-28 2023-01-04 (주)메디톡스 재조합 보툴리눔 독소 타입 a 경쇄, 재조합 보툴리눔 독소 및 이의 조성물, 용도 및 방법
KR20230001254A (ko) 2021-06-28 2023-01-04 (주)메디톡스 재조합 보툴리눔 독소 타입 a 경쇄, 재조합 보툴리눔 독소 및 이의 조성물, 용도 및 방법
US20250255941A1 (en) * 2021-10-22 2025-08-14 Bpmed Co., Ltd. Composition for ameliorating hair loss comprising botulinum-derived peptide
CA3234608A1 (en) * 2021-11-22 2023-05-25 Ipsen Biopharm Limited Treatment of pain
GB202206348D0 (en) * 2022-04-29 2022-06-15 Ipsen Biopharm Ltd Treatment of limb spasticity
KR102728382B1 (ko) * 2022-10-12 2024-11-14 주식회사 알케미어 보툴리눔 독소의 경쇄 변이체
WO2025065012A1 (en) * 2023-09-21 2025-03-27 The Medical College Of Wisconsin, Inc. Botulinum neurotoxin variants, constructs, compositions, and methods of use

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Publication number Priority date Publication date Assignee Title
WO2022179552A1 (zh) * 2021-02-26 2022-09-01 重庆誉颜制药有限公司 一种经修饰的神经毒素的单链多肽及其用途
CN114369623A (zh) * 2022-01-12 2022-04-19 中国人民解放军空军军医大学 一种基于Cre-lox重组系统的Synaptotagmin2-RNAi及其应用
CN114410683A (zh) * 2022-01-12 2022-04-29 中国人民解放军空军军医大学 一种基于Cre-lox重组系统的RIM3-RNAi及其应用
CN114369623B (zh) * 2022-01-12 2023-07-07 中国人民解放军空军军医大学 一种基于Cre-lox重组系统的Synaptotagmin2-RNAi及其应用
CN114410683B (zh) * 2022-01-12 2023-11-28 中国人民解放军空军军医大学 一种基于Cre-lox重组系统的RIM3-RNAi及其应用

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AU2017277905B2 (en) 2022-04-14
CA3026492A1 (en) 2017-12-14
JP2022112031A (ja) 2022-08-01
BR112018075363A2 (pt) 2019-03-19
WO2017214447A1 (en) 2017-12-14
EP3468985A1 (en) 2019-04-17
IL263058A (en) 2018-12-31
IL263058B1 (en) 2023-07-01
EA201892784A1 (ru) 2019-05-31
SG10201912099TA (en) 2020-02-27
AU2017277905A1 (en) 2018-12-20
JP7152392B2 (ja) 2022-10-12
MX2018015254A (es) 2019-08-16
SG11201810210UA (en) 2018-12-28
JP2019523015A (ja) 2019-08-22
US11104891B2 (en) 2021-08-31
IL263058B2 (en) 2023-11-01
KR20190025906A (ko) 2019-03-12
US20190300869A1 (en) 2019-10-03

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