EA202190889A1 - Клостридиальные нейротоксины, содержащие экзогенную петлю активации - Google Patents

Клостридиальные нейротоксины, содержащие экзогенную петлю активации

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Publication number
EA202190889A1
EA202190889A1 EA202190889A EA202190889A EA202190889A1 EA 202190889 A1 EA202190889 A1 EA 202190889A1 EA 202190889 A EA202190889 A EA 202190889A EA 202190889 A EA202190889 A EA 202190889A EA 202190889 A1 EA202190889 A1 EA 202190889A1
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EA
Eurasian Patent Office
Prior art keywords
clostridial neurotoxin
activation
chain
chain clostridial
loop
Prior art date
Application number
EA202190889A
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English (en)
Inventor
Адам Купински
Лаура Лоувелок
Original Assignee
Ипсен Биофарм Лимитед
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Application filed by Ипсен Биофарм Лимитед filed Critical Ипсен Биофарм Лимитед
Publication of EA202190889A1 publication Critical patent/EA202190889A1/ru

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    • 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
    • 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)
    • 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
    • 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
    • C07K14/32—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Bacillus (G)
    • 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)
    • C—CHEMISTRY; METALLURGY
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
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    • 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)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6402—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from non-mammals
    • C12N9/6405—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from non-mammals not being snakes
    • C12N9/6408—Serine endopeptidases (3.4.21)
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    • 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)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
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    • C12P21/00—Preparation of peptides or proteins
    • C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
    • 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)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21009—Enteropeptidase (3.4.21.9), i.e. enterokinase
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Toxicology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Изобретение относится к способу протеолитического процессинга одноцепочечного клостридиального нейротоксина в соответствующий двухцепочечный клостридиальный нейротоксин, причем способ включает предоставление одноцепочечного клостридиального нейротоксина; и приведение одноцепочечного клостридиального нейротоксина в контакт с энтерокиназой или фактором Xa; где одноцепочечный клостридиальный нейротоксин имеет петлю активации, содержащую полипептидную последовательность Cys-(Xaa)a-Ile-Asp/Glu-Gly-Arg-(Yaa)b-Cys (SEQ ID NO: 1), где a=1-10 и b=4-15; и где энтерокиназа или фактор Xa гидролизует пептидную связь петли активации, тем самым продуцируя двухцепочечный клостридиальный нейротоксин. Изобретение также относится к сконструированным клостридиальным нейротоксинам и способам их изготовления, а также к родственным фармацевтическим композициям, нуклеотидным последовательностям и терапевтическим применениям.
EA202190889A 2018-09-28 2019-09-27 Клостридиальные нейротоксины, содержащие экзогенную петлю активации EA202190889A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB1815817.0A GB201815817D0 (en) 2018-09-28 2018-09-28 Clostridial neurotoxins comprising and exogenous activation loop
PCT/GB2019/052732 WO2020065336A1 (en) 2018-09-28 2019-09-27 Clostridial neurotoxins comprising an exogenous activation loop

Publications (1)

Publication Number Publication Date
EA202190889A1 true EA202190889A1 (ru) 2021-11-10

Family

ID=64108972

Family Applications (1)

Application Number Title Priority Date Filing Date
EA202190889A EA202190889A1 (ru) 2018-09-28 2019-09-27 Клостридиальные нейротоксины, содержащие экзогенную петлю активации

Country Status (15)

Country Link
US (1) US20220211823A1 (ru)
EP (1) EP3856232A1 (ru)
JP (2) JP2022512573A (ru)
KR (1) KR20210068476A (ru)
CN (1) CN113164565A (ru)
AU (1) AU2019348732B2 (ru)
BR (1) BR112021005017A2 (ru)
CA (1) CA3111962A1 (ru)
EA (1) EA202190889A1 (ru)
GB (1) GB201815817D0 (ru)
IL (1) IL281814A (ru)
MX (1) MX2021003261A (ru)
SG (1) SG11202102323TA (ru)
TW (1) TW202027782A (ru)
WO (1) WO2020065336A1 (ru)

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MX2019000151A (es) * 2016-07-08 2019-08-29 Childrens Medical Center Una neurotoxina botulinica novedosa y sus derivados.
GB202103372D0 (en) 2021-03-11 2021-04-28 Ipsen Biopharm Ltd Modified clostridial neurotoxins
GB202104294D0 (en) 2021-03-26 2021-05-12 Ipsen Biopharm Ltd Clostridial neurotoxins comprising an exogenous activation loop
BR112023020057A2 (pt) 2021-03-30 2024-03-12 Ipsen Biopharm Ltd Tratamento de dor e distúrbios inflamatórios
AU2021438810A1 (en) 2021-03-30 2023-09-21 Ipsen Biopharm Limited Catalytically inactive clostridial neurotoxins for the treatment of pain & inflammatory disorders
CN115785237B (zh) * 2022-09-01 2023-06-16 上海蓝晶生物科技有限公司 一种重组肉毒杆菌毒素及其制备方法
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GB202214229D0 (en) * 2022-09-28 2022-11-09 Ipsen Biopharm Ltd Clostridial neurotoxins comprising an activating endosomal protease cleavage site
GB202214232D0 (en) 2022-09-28 2022-11-09 Ispen Biopharm Ltd Clostridial neurotoxins comprising an activating exogenous protease cleavage site

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Also Published As

Publication number Publication date
CN113164565A (zh) 2021-07-23
SG11202102323TA (en) 2021-04-29
US20220211823A1 (en) 2022-07-07
AU2019348732A1 (en) 2021-04-15
MX2021003261A (es) 2021-05-12
EP3856232A1 (en) 2021-08-04
GB201815817D0 (en) 2018-11-14
TW202027782A (zh) 2020-08-01
IL281814A (en) 2021-05-31
JP2024012421A (ja) 2024-01-30
BR112021005017A2 (pt) 2021-06-08
AU2019348732B2 (en) 2024-02-15
WO2020065336A1 (en) 2020-04-02
CA3111962A1 (en) 2020-04-02
KR20210068476A (ko) 2021-06-09
JP2022512573A (ja) 2022-02-07

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