DK2714910T3 - Immunogen sammensætning - Google Patents
Immunogen sammensætning Download PDFInfo
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- DK2714910T3 DK2714910T3 DK12724950.6T DK12724950T DK2714910T3 DK 2714910 T3 DK2714910 T3 DK 2714910T3 DK 12724950 T DK12724950 T DK 12724950T DK 2714910 T3 DK2714910 T3 DK 2714910T3
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- fragment
- polypeptide
- toxin
- repeat
- proximal end
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- 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
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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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)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
- C07K16/1282—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Clostridium (G)
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- 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
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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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
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- A61K2039/575—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response
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- C07K—PEPTIDES
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- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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- C07K2319/55—Fusion polypeptide containing a fusion with a toxin, e.g. diphteria toxin
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Claims (30)
1. Polypeptid omfattende et første fragment og et andet fragment, hvor (i) det første fragment er et toksin A-gentagelsesdomænefragment og omfatter mindst 100 aminosyrer; (ii) det andet fragment er et toksin B-gentagelsesdomænefragment og omfatter mindst 100 aminosyrer; (iii) den proksimale ende af det første fragmentet er placeret i en første gentagelsesdel; (iv) den proksimale ende af det andet fragment er placeret i en anden gentagelsesdel; og hvor det første fragment og det andet fragment er adskilt af mindre end eller præcis 5 aminosyrer i den primære struktur, hvor polypeptidet fremkalder antistoffer, som neutraliserer toksin A og toksin B, og hvor den første gentagelsesdel og den anden gentagelsesdel har mere end 50 % sekvenssimilaritet med hinanden.
2. Polypeptid ifølge krav 1, hvor den første gentagelsesdel og den anden gentagelsesdel har stor strukturlighed med hinanden, hvor de to sekvenser har stor strukturlighed, når deres procentiske similaritet er større end 70 %, 75 %, 80 %, 85 %, 90 %, 95 %, 98 % eller 99 % eller er 100 %.
3. Polypeptid ifølge et hvilket som helst af kravene 1-2, hvor polypeptidet fremkalder en beskyttende immunreaktion hos en pattedyrvært mod stammer af C. difficile.
4. Polypeptid ifølge et hvilket som helst af kravene 1-3, hvor det første fragment og det andet fragment omfatter mindre end 25 %, 20 %, 18 % eller 15 % alfahelix-struktur.
5. Polypeptid ifølge et hvilket som helst af kravene 1-4, hvor det første fragment og det andet fragment omfatter mere end 25 %, 30 %, 35 %, 38 % eller 40 % betaark-struktur.
6. Polypeptid ifølge et hvilket som helst af kravene 1-5, hvor den første proksimale ende er i gentagelsesdel VII eller gentagelsesdel VIII i toksin A.
7. Polypeptid ifølge et hvilket som helst af kravene 1-6, hvor den anden proksimale ende er i gentagelsesdel II eller gentagelsesdel I i toksin B.
8. Polypeptid ifølge krav 6, hvor den første proksimale ende er i gentagelsesdel VII i toksin A.
9. Polypeptid ifølge krav 7, hvor den anden proksimale ende er i gentagelsesdel II i toksin B.
10. Polypeptid ifølge et hvilket som helst af kravene 1-9, hvor den første proksimale ende er i en lang gentagelse.
11. Polypeptid ifølge et hvilket som helst af kravene 1-10, hvor den anden proksimale ende er i en lang gentagelse.
12. Polypeptid ifølge et hvilket som helst af kravene 1-11, hvor den første proksimale ende er i den lange gentagelse VII i toksin A (aminosyrer 2614-2644).
13. Polypeptid ifølge krav 12, hvor den første proksimale ende er indenfor aminosy- rerne 2620 og 2660 i toksin A.
14. Polypeptid ifølge et hvilket som helst af kravene 1-13, hvor den anden proksima-le ende er i den lange gentagelse II i toksin B (aminosyrerne 2028-2057).
15. Polypeptid ifølge krav 14, hvor den første proksimale ende er inden for aminosyrerne 2030 og 2050 i toksin B.
16. Polypeptid ifølge et hvilket som helst af de foregående krav, hvor polypeptidet er del af et større fusionsprotein.
17. Polynukleotid kodende for polypeptidet ifølge et hvilet som helst af kravene 1-16.
18. Vektor omfattende polynukleotidet ifølge krav 17.
19. Vektor ifølge krav 18 yderligere omfattende en inducerbar promotor.
20. Vektor ifølge krav 19, hvor den inducerbare promotor aktiveres ved tilsætning af en tilstrækkelig mængde IPTG.
21. Værtscelle omfattende vektoren ifølge et hvilket som helst af kravene 18-20 eller polynukleotidet ifølge krav 17.
22. Værtscelle ifølge krav 21, hvor værtscellen er en gramnegativ bakterie.
23. Værtcelle ifølge krav 22, hvor værtscellen er E. coli.
24. Immunogen sammensætning omfattende polypeptidet ifølge et hvilket som helst af kravene 1-16 og en farmaceutisk acceptabel excipiens.
25. Immunogen sammensætning ifølge krav 24 yderligere omfattende en adjuvans.
26. Immunogen sammensætning ifølge et hvilket som helst af kravene 24-25 endvidere omfattende yderligere antigener.
27. Immunogen sammensætning ifølge krav 26, hvor de yderligere antigener er antigener afledt fra en bakterie udvalgt fra gruppen bestående af S. pneumoniae, H. influenzae, N. meningitidis, E. coli, M. cattarhalis, tetanus, diphtheria, pertussis, S. epidermidis, enterokokker, S. aureus og Pseudomonas aeruginosa.
28. Immunogen sammensætning ifølge et hvilket som helst af kravene 24-27 yderligere omfattende et saccharid fra C. difficile.
29. Vaccine omfattende den immunogene sammensætning ifølge et hvilket som helst af kravene 24-28 og en farmaceutisk acceptabel excipiens.
30. Immunogen sammensætning ifølge et hvilket som helst af kravene 24-28 eller vaccine ifølge krav 29 til anvendelse i behandling eller forebyggelse af C. d/ffic/'/e-sygdom.
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| US201161490734P | 2011-05-27 | 2011-05-27 | |
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| US201161490707P | 2011-05-27 | 2011-05-27 | |
| PCT/EP2012/059793 WO2012163811A1 (en) | 2011-05-27 | 2012-05-25 | Immunogenic composition |
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| LT2753352T (lt) | 2010-09-03 | 2017-05-25 | Valneva Austria Gmbh | Išskirtas toksino a ir toksino b baltymų polipeptidas iš c. difficile ir jo panaudojimas |
| EP4365196A3 (en) | 2011-04-22 | 2024-08-07 | Wyeth LLC | Compositions relating to a mutant clostridium difficile toxin and methods thereof |
| JP6084631B2 (ja) * | 2011-12-08 | 2017-02-22 | ノバルティス アーゲー | Ｃｌｏｓｔｒｉｄｉｕｍｄｉｆｆｉｃｉｌｅ毒素ベースのワクチン |
| BR122016023101B1 (pt) | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| DK2928489T3 (da) | 2012-12-05 | 2019-04-23 | Glaxosmithkline Biologicals Sa | Immunogen sammensætning |
| EP2988778A4 (en) * | 2013-04-22 | 2016-12-14 | Board Of Regents Of The Univ Of Oklahoma | CLOSTRIDIUM DIFFICILE IMPREGENT AND METHOD OF USE |
| US10533036B2 (en) | 2015-02-19 | 2020-01-14 | Immune Biosolutions Inc | Clostridium difficile toxins a and/or B antigen and epitope antibody, and pharmaceutical uses thereof |
| CN112703006A (zh) * | 2018-06-19 | 2021-04-23 | 葛兰素史密丝克莱恩生物有限公司 | 免疫原性组合物 |
| WO2023020992A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
| WO2023020993A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
| WO2023020994A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
| GB202205833D0 (en) | 2022-04-21 | 2022-06-08 | Glaxosmithkline Biologicals Sa | Bacteriophage |
| WO2023232901A1 (en) | 2022-06-01 | 2023-12-07 | Valneva Austria Gmbh | Clostridium difficile vaccine |
| WO2024160901A1 (en) | 2023-02-02 | 2024-08-08 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
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| US4235877A (en) | 1979-06-27 | 1980-11-25 | Merck & Co., Inc. | Liposome particle containing viral or bacterial antigenic subunit |
| US4751180A (en) | 1985-03-28 | 1988-06-14 | Chiron Corporation | Expression using fused genes providing for protein product |
| US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
| BR9509903A (pt) * | 1994-10-24 | 1997-11-25 | Ophidian Pharm Inc | Proteína de fusão proteína de fus o solúvel composição de matéria célula hospedeira processo para gerar uma antiotoxina neutralizante dirigida contra toxina tipo a de clostridium botulinum anticorpo processo para purificar uma proteina de fusão recombinante derivada de uma toxina tipo a de clostridium botulinum processo para gerar uma antitoxina neutralizante dirigida contra toxina tipo b de clostridium difficile anticorpo processo de tratemento processo para gerar uma antitoxina neutralizante dirigida contra toxina tipo a de clostridium difficile composição processo para vacinar um individuo para produzir antitoxina neutralizante dirigida contra toxina de clostridium difficile processo a detecção de antigenos de clostridium difficile em uma amosta processo de purificação de toxinas de clostridium difficile de uma cultura e processo de generação de uma forma dosagem sólida de uma antitoxina de ave dirigida contra uma proteina de toxina clostridial |
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