SE2050326A1 - Engineered botulinum neurotoxin serotype E - Google Patents
Engineered botulinum neurotoxin serotype EInfo
- Publication number
- SE2050326A1 SE2050326A1 SE2050326A SE2050326A SE2050326A1 SE 2050326 A1 SE2050326 A1 SE 2050326A1 SE 2050326 A SE2050326 A SE 2050326A SE 2050326 A SE2050326 A SE 2050326A SE 2050326 A1 SE2050326 A1 SE 2050326A1
- Authority
- SE
- Sweden
- Prior art keywords
- bont
- amino acid
- substitution
- acid sequence
- replaces
- Prior art date
Links
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Classifications
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
- C07K2319/43—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation containing a FLAG-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
Claims (11)
1. En modifierad botulinum-neurotoxin serotyp E (BoNT/E) Heavy Chain Binding domän (HC), SEQ ID NO: 3, innefattande multipla aminosyra substitutioneri BoNT/E HC sekvensen, SEQ ID NO: 2, utgörande en synaptisk associerad vesikel 2C (SV2C) receptor bindingssite i den modifierade BoNT/E HC, varvid de multipla aminosyra substitutionerna in den modifierade BoNT/E HC sekvensen innefattar följande substitutioner med aminosyrarest numrering av den nativa BoNT/E fullängds aminosyrasekvensen, SEQ ID NO: 7,: substitution 2a eller substitution 2b, vari substitution 2a ersätter aminosyror påpositioner 925-933 och innefattar en aminosyrasekvens: Lys Tyr Phe Asn Ser Ile SerLeu, och substitution 2b ersätter aminosyror på positioner 925-932 och innefattar enaminosyrasekvens: Lys Tyr Phe Asn Ser Ile Ser; substitution 3, vari substitution 3 ersätter aminosyror 956-957 och innefattar enaminosyrasekvens: Tyr Gly; substitution 4a eller substitution 4b, vari substitution 4a ersätter aminosyror 978-982och innefattar en aminosyrasekvens: Ser Gln Met Ile Asn, och substitution 4b ersätteraminosyror 980-981 och innefattar en aminosyrasekvens: I\/Iet Ile; substitution 5a eller substitution 5b1 och 5b2, vari substitution 5a ersätter aminosyror1033-1039 och innefattar en aminosyrasekvens: Leu Asp Gly Cys Arg Asp Thr His, substitution 5b1 ersätter aminosyra 1035 och innefattar en aminosyra: Gly, och substitution 5b2 ersätter aminosyror 1037-1039 a och innefattar en aminosyrasekvens: Arg Asp Thr His; substitution 7a eller substitution 7b1, 7b2, 7b3 och 7b4, vari substitution 7a ersätteraminosyror 1109-1123 och innefattar en aminosyrasekvens: Lys Gly Pro Arg Gly Ser ValI\/Iet ThrThr Asn Ile Tyr Leu Asn Ser Ser Leu Tyr Arg, substitution 7b1 ersätteraminosyror 1110-1111 och innefattar en aminosyrasekvens: Gly Pro, substitution 7b2ersätter aminosyra 1113 och innefattar en aminosyra: Gly, substitution 7b3 ersätteraminosyror 1115-1120 och innefattar en aminosyrasekvens: Met Thr Thr Asn Ile TyrLeu Asn Ser Ser, och substitution 7b4 ersätter aminosyra 1123 och innefattar enaminosyra: Arg; substitution 8a eller substitution 8b1, 8b2, 8b3 och 8b4, vari substitution 8a ersätter aminosyror 1244-1252 och innefattar en aminosyrasekvens: Pro Val Asp Asp Gly Trp 2Gly Glu Arg Pro Leu, substitution 8b1 ersätter aminosyra 1245 och innefattar enaminosyra: Val, substitution 8b2 ersätter aminosyra 1247 och innefattar enaminosyras: Asp, substitution 8b3 ersätter aminosyra 1250 och innefattar enaminosyra: Gly, och substitution 8b4 ersätter aminosyra 1252 och innefattar en aminosyrasekvens: Arg Pro Leu.
2. Den modifierade BoNT/E HC enligt patentkrav 1, vari de multipla aminosyrasubstitutionerna vidare innefattar följande substitutioner med aminosyrarestnumrering av den nativa BoNT/E fullängds aminosyrasekvensen: - substitution 1, vari substitution 1 ersätter aminosyror 891-896 och innefattar enaminosyrasekvens: Phe Asn Leu Glu Ser, and/or- substitution 6, vari substitution 6 ersätter aminosyra 1097 och innefattar en aminosyra: Tyr.
3. Den modifierade BoNT/E HC enligt patentkrav 1 eller 2, vari BoNT/E är selekterad ifrånnågon av subtyp E1, E2, E3, E4, E5, E6, E7, E8, E9, E10, E11 eller E12.
4. Den modifierade BoNT/E HC enligt något av föregående patentkrav kopplad till någotett eller flera protein, polypeptid, aminosyrasekvens, eller fluorescerande markör direkt eller via en länk.
5. Polypeptiden enligt patentkrav 4, vari nämnda polypeptid utöver HC innefattar enHeavy Chain Translocation domän (HN), en Lätt kedja (LC) och en proteas-site positioneradmellan LC och HN i polypeptid-sekvensen, vari HN och LC, respektive och oberoendehärstammar ifrån någon av BoNT serotyperna A, B, C, D, DC, E, En, F, G, Wo ellerX eller deras subtyper.
6. En vektor innefattandes en nukleinsyrasekvens som kodar den modifierade BoNT/E HC enligt någon av patentkrav 1-3 eller polypeptiden enligt patentkrav 4 eller 5.
7. Den modifierade BoNT/E HC enligt något av patentkrav 1-3 eller polypeptiden enligt patentkrav 4 eller 5 för användning i en terapeutisk eller kosmetisk metod.
8. Den modifierade BoNT/E HC eller polypeptiden för användning enligt patentkrav 7, varisjukdomen är vald från en grupp innefattande spasmodisk dysfoni, spastisk torticollis,laryngeal dystoni, oromandibulär dystoni, tungdystoni, cervikal dystoni, fokal handdystoni,blefarospasm, skelning, hemifacial spasm, ögonlocksstörning, cerebral pares, fokalspasticitetoch andra röststörningar, spasmodisk kolit, neurogen blåsstörning, obstipation, lemspasticitet,tick, darrningar, tandgnissling, analfissur, akalasi, sväljningssvårigheter och andramuskeltoniska störningar och andra störningar vilka kännetecknas av ofrivilliga rörelser förmuskelgrupper, tårbildning, hyperhidros, överdriven salivutsöndring, överdrivnagastrointestinala utsöndringar, sekretoriska störningar, smärta från muskelspasmer, huvudvärksmärta, idrottsskador, och depression.
9. En farmaceutisk eller kosmetisk sammansättning innefattande den modifierade BoNT/E HC enligt något av patentkrav 1-3 eller polypeptiden enligt patentkrav 4 eller 5.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE2050326A SE2050326A1 (en) | 2020-03-25 | 2020-03-25 | Engineered botulinum neurotoxin serotype E |
| PCT/EP2021/056595 WO2021190987A1 (en) | 2020-03-25 | 2021-03-16 | Engineered botulinum neurotoxin serotype e |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE2050326A SE2050326A1 (en) | 2020-03-25 | 2020-03-25 | Engineered botulinum neurotoxin serotype E |
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| Publication Number | Publication Date |
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| SE543726C2 SE543726C2 (en) | 2021-06-29 |
| SE2050326A1 true SE2050326A1 (en) | 2021-06-29 |
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| SE2050326A SE2050326A1 (en) | 2020-03-25 | 2020-03-25 | Engineered botulinum neurotoxin serotype E |
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| Country | Link |
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| SE (1) | SE2050326A1 (sv) |
| WO (1) | WO2021190987A1 (sv) |
Citations (6)
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| US20060024794A1 (en) * | 2004-07-30 | 2006-02-02 | Shengwen Li | Novel methods for production of di-chain botulinum toxin |
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| WO2013068476A1 (en) * | 2011-11-09 | 2013-05-16 | Merz Pharma Gmbh & Co. Kgaa | Neurotoxins exhibiting shortened biological activity |
| AU2012201518B2 (en) * | 2004-02-24 | 2014-06-12 | Allergan, Inc. | Botulinum toxin screening assays |
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| US10266816B2 (en) * | 2005-04-26 | 2019-04-23 | Ipsen Bioinnovation Limited | Carrier for targeting nerve cells |
-
2020
- 2020-03-25 SE SE2050326A patent/SE2050326A1/en unknown
-
2021
- 2021-03-16 WO PCT/EP2021/056595 patent/WO2021190987A1/en active Application Filing
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| AU2012201518B2 (en) * | 2004-02-24 | 2014-06-12 | Allergan, Inc. | Botulinum toxin screening assays |
| US20060024794A1 (en) * | 2004-07-30 | 2006-02-02 | Shengwen Li | Novel methods for production of di-chain botulinum toxin |
| US20100041098A1 (en) * | 2005-03-15 | 2010-02-18 | Allergan, Inc. | Modified clostridial toxins with altered targeting capabilities for clostridial toxin target cells |
| US10266816B2 (en) * | 2005-04-26 | 2019-04-23 | Ipsen Bioinnovation Limited | Carrier for targeting nerve cells |
| WO2013068476A1 (en) * | 2011-11-09 | 2013-05-16 | Merz Pharma Gmbh & Co. Kgaa | Neurotoxins exhibiting shortened biological activity |
| EP2934571A1 (en) * | 2012-12-18 | 2015-10-28 | Allergan, Inc. | Prophylactic treatment of herpes recurrence |
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2021190987A1 (en) | 2021-09-30 |
| SE543726C2 (en) | 2021-06-29 |
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