ES2654613T3 - Promotores para una expresión aumentada de proteínas en meningococos - Google Patents
Promotores para una expresión aumentada de proteínas en meningococos Download PDFInfo
- Publication number
- ES2654613T3 ES2654613T3 ES13703562.2T ES13703562T ES2654613T3 ES 2654613 T3 ES2654613 T3 ES 2654613T3 ES 13703562 T ES13703562 T ES 13703562T ES 2654613 T3 ES2654613 T3 ES 2654613T3
- Authority
- ES
- Spain
- Prior art keywords
- promoters
- seq
- meningococci
- protein expression
- region
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000014509 gene expression Effects 0.000 title description 9
- 102000004169 proteins and genes Human genes 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 title 1
- 150000007523 nucleic acids Chemical class 0.000 abstract 1
- 102000039446 nucleic acids Human genes 0.000 abstract 1
- 108020004707 nucleic acids Proteins 0.000 abstract 1
- 101710186862 Factor H binding protein Proteins 0.000 description 8
- 230000002779 inactivation Effects 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 101150093941 PORA gene Proteins 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 108020004465 16S ribosomal RNA Proteins 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/095—Neisseria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- C07K14/22—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Neisseriaceae (F)
-
- 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/60—Vectors containing traps for, e.g. exons, promoters
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Public Health (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Abstract
Un ácido nucleico que comprende un promotor que tiene la SEQ ID NO: 32, la SEQ ID NO: 33 o la SEQ ID NO: 34.
Description
5
10
15
20
25
30
35
40
45
unidades arbitrarias.
La Figura 4 muestra los niveles de fHbp en vesículas aisladas de cepas con inactivación de (i) ΔpxL1ΔsynX y (ii) ΔlpxL1ΔsynXΔmltA. La Figura 4A muestra el rendimiento en mg/DO y la Figura 4B es una transferencia Western de vesículas de 0,5 µg.
La Figura 5 muestra la expresión de fHbp en dos cepas que sobreexpresan fHbp ya sea variante 1 o variante 2 en loci distintos (calles C y D) o una cepa que sobreexpresa tanto variante 1 como variante 2 en loci respectivos (calle e). La calle A es la cepa de tipo silvestre y la calle B es una inactivación de ΔfHbp de esa cepa.
La Figura 6 muestra una EGPA-DSS teñido con plata de vesículas purificadas a partir de la triple inactivación.
Las secuencias corriente arriba del sitio de inicio de la transcripción de dos variantes de fase del promotor porA meningocócico de tipo silvestre, que contienen 11 y 13 G consecutivas en la región espaciadora, son como se indica a continuación, con las regiones -35 y -10 subrayadas:
AAAAATGGTTTTTTGCGGGGGGGGGGGTATAATTGAAGAC (SEQ ID NO: 31) AAAAATGGTTTTTTGCGGGGGGGGGGGGGTATAATTGAAGAC (SEQ ID NO: 40)
La secuencia intermedia entre la regiones -35 y -10 incluye una secuencia de G11poli-G que está conectado a la variación de fase de la expresión de PorA. Para estabilizar la expresión de este promotor, se sometieron a ensayo tres modificaciones (modificaciones en minúsculas):
AAAAATGGTTTTTTGCGaGGGaGGtGGTATAATTGAAGAC ("ST1"; SEQ ID NO: 32) AAAAATtGacaTTTGCGaGGGaGGtGGTATAATTGAAGAC ("ST2"; SEQ ID NO: 33) AAAAtTGacaTTTTGCGaGGGaGGtGGTATAATTGAAGAC ("ST3"; SEQ ID NO: 34)
De este modo, en "ST1" la secuencia de G11 se interrumpió en tres lugares, dejando no más de 3 restos de G consecutivos. En "ST2" se usó la misma secuencia intermedia, pero la región -35 y se sustituyó por una región -35 de consenso TTGACA. En "ST3" se insertó un resto T adicional inmediatamente corriente abajo de la región -35.
Estos tres promotores se usaron para impulsar la expresión de una secuencia de fHbp (fHbp variante 2) en la cepa NZ98/258. Los tres promotores modificados dieron como resultado una sobreexpresión de alto nivel de fHbp en la cepa en comparación con una cepa sobreexpresadora equivalente que se ha notificado en la bibliografía [103, 104]. La mejor expresión se observó con ST2 (Figuras 1 y 2).
En experimentos adicionales el promotor de ARNr 16S se fusionó al UTR 5' del gen porA:
ATATCTTGACAGGCGGAAGGAATACTTTATAATTCGCAAC... (SEQ ID NO: 35)
Este promotor se sometió a mutación y se secuenciaron tres variantes corriente abajo de la región -35 como se indica a continuación:
ATATCTTGACAGGCGGAAGGAATACTTTATAATTCGCAAC ("wt"; SEQ ID NO: 35) ATATCTTGACAGGCGGAAGGAATACTTTATATTCGCAAC... ("n.º 5"; SEQ ID NO: 36) ATATCTTGACAGGCGGAAGGAATACTTTTAATTCGCAC... ("n.º 6"; SEQ ID NO: 37) ATATCTTGACAGGCGGAAGGAAACTTTATAATTCGCAAC... ("n.º 8"; SEQ ID NO: 38)
De este modo, en las variantes n.º 5 y n.º 6 la secuencia -10 es un pentámero y la variante n.º 6 además perdió un nucleótido entre la región -10 y el sitio de inicio de la transcripción. En la variante n.º 8 la región -10 y su secuencia corriente abajo son iguales que en wt, pero la secuencia intermedia entre las regiones -35 y -10 es un nucleótido más corta que en wt.
Estos promotores se fusionan con la región 5'UTR del gen porA y se usan para impulsar la expresión de la secuencia codificante de fHbp. Como se observa en la Figura 2, las variantes n.º 5 y n.º 6 mostraron la expresión más fuerte, acercándose a los niveles observados con ST2.
La región completa que abarca el promotor de tipo silvestre (SEQ ID NO: 35), que se extiende corriente abajo en la región transcrita y también corriente arriba, era como se indica a continuación (SEQ ID NO: 41; de 358 monómeros), con las regiones -35 y -10 subrayadas y el nucleótido +1 (siguiente referencia 10) doblemente subrayado:
14
Claims (1)
-
imagen1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261594159P | 2012-02-02 | 2012-02-02 | |
| US201261594159P | 2012-02-02 | ||
| PCT/EP2013/052108 WO2013113917A1 (en) | 2012-02-02 | 2013-02-01 | Promoters for increased protein expression in meningococcus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2654613T3 true ES2654613T3 (es) | 2018-02-14 |
Family
ID=47683718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13703562.2T Active ES2654613T3 (es) | 2012-02-02 | 2013-02-01 | Promotores para una expresión aumentada de proteínas en meningococos |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US9657297B2 (es) |
| EP (2) | EP3299467B1 (es) |
| JP (2) | JP5957541B2 (es) |
| CN (1) | CN104114706A (es) |
| AU (1) | AU2013214105A1 (es) |
| BR (1) | BR112014019166A2 (es) |
| CA (1) | CA2861946A1 (es) |
| ES (1) | ES2654613T3 (es) |
| MX (1) | MX2014008988A (es) |
| RU (1) | RU2014135522A (es) |
| WO (1) | WO2013113917A1 (es) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160127104A (ko) | 2014-02-28 | 2016-11-02 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 변형된 수막구균 fhbp 폴리펩티드 |
| EP3607967A1 (en) | 2018-08-09 | 2020-02-12 | GlaxoSmithKline Biologicals S.A. | Modified meningococcal fhbp polypeptides |
| CN109485704B (zh) * | 2018-11-27 | 2022-04-19 | 温州大学 | 一种脑膜炎球菌fHbp蛋白的表达系统 |
| CN111321141B (zh) * | 2018-12-14 | 2021-02-26 | 上海凯赛生物技术股份有限公司 | 稳定期特异性启动子及其应用 |
| CN111850003A (zh) * | 2020-07-09 | 2020-10-30 | 华中农业大学 | 一种重组表达的多杀性巴氏杆菌硫胺素周质结合蛋白及应用 |
| MX2023004729A (es) * | 2020-10-23 | 2023-06-29 | Omvax Inc | Composiciones y metodos de vacunacion contra neisseria gonorrhoeae. |
| CN114854701B (zh) * | 2022-03-16 | 2023-09-22 | 福建福大百特生物科技有限公司 | 一种微泡菌超氧化物歧化酶及其编码基因 |
| CN119331872B (zh) * | 2024-12-23 | 2025-04-08 | 上海羽冠生物技术有限公司 | 一种启动子及其在增强脑膜炎球菌蛋白表达中的应用 |
Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2848965A1 (de) | 1978-11-11 | 1980-05-22 | Behringwerke Ag | Verfahren zur herstellung von membranproteinen aus neisseria meningitidis und diese enthaltende vaccine |
| US4551433A (en) | 1981-05-18 | 1985-11-05 | Genentech, Inc. | Microbial hybrid promoters |
| US5698438A (en) | 1994-10-18 | 1997-12-16 | Oregon Health Sciences University | Bacterial hemoglobin receptor gene |
| IL117483A (en) | 1995-03-17 | 2008-03-20 | Bernard Brodeur | MENINGITIDIS NEISSERIA shell protein is resistant to proteinase K. |
| US6180111B1 (en) | 1995-05-18 | 2001-01-30 | University Of Maryland | Vaccine delivery system |
| ES2301181T3 (es) | 1997-08-21 | 2008-06-16 | De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn, Volksgezondheid En Cultuur | Mutantes nuevos de bacterias mucosas gram negativas y su aplicacion en vacunas. |
| US6645503B1 (en) | 1998-03-10 | 2003-11-11 | Wyeth Holdings Corporation | Antigenic conjugates of conserved lipopolysaccharides of gram negative bacteria |
| EP2261338A3 (en) | 1998-05-01 | 2012-01-04 | Novartis Vaccines and Diagnostics, Inc. | Neisseria meningitidis antigens and compositions |
| GB9818004D0 (en) | 1998-08-18 | 1998-10-14 | Smithkline Beecham Biolog | Novel compounds |
| GB9820003D0 (en) | 1998-09-14 | 1998-11-04 | Smithkline Beecham Biolog | Novel compounds |
| WO2000023595A1 (en) | 1998-10-22 | 2000-04-27 | The University Of Montana | Omp85 proteins of neisseria gonorrhoeae and neisseria meningitidis, compositions containing same and methods of use thereof |
| GB9823978D0 (en) | 1998-11-02 | 1998-12-30 | Microbiological Res Authority | Multicomponent meningococcal vaccine |
| AU762369B2 (en) | 1998-11-03 | 2003-06-26 | De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn, Volksgezonheid En Cultuur | LPS with reduced toxicity from genetically modified gram negative bacteria |
| GB9826886D0 (en) | 1998-12-07 | 1999-01-27 | Smithkline Beecham Biolog | Novel compounds |
| AU1580300A (en) | 1998-12-08 | 2000-06-26 | Smithkline Beecham Biologicals (Sa) | Novel compounds |
| AU2288900A (en) | 1999-01-15 | 2000-08-01 | Smithkline Beecham Biologicals (Sa) | Novel compounds |
| EP1144643A1 (en) | 1999-01-15 | 2001-10-17 | SMITHKLINE BEECHAM BIOLOGICALS s.a. | Neisseria meningitidis antigen |
| AU2289000A (en) | 1999-01-15 | 2000-08-01 | Smithkline Beecham Biologicals (Sa) | (neisseria meningitidis) polypeptide basb052 |
| AU2292800A (en) | 1999-01-22 | 2000-08-07 | Smithkline Beecham Biologicals (Sa) | Neisseria meningitidis antigenic polypeptides, corresponding polynucleotides andprotective antibodies |
| HK1042515A1 (zh) | 1999-01-22 | 2002-08-16 | Smithkline Beecham Biologicals S.A. | 來自腦膜炎球菌的basb055多核苷酸和多肽，其使用法 |
| EP1149164A2 (en) | 1999-01-22 | 2001-10-31 | SmithKline Beecham Biologics SA | Neisseria meningitidis polypeptides |
| GB9902084D0 (en) | 1999-01-29 | 1999-03-24 | Smithkline Beecham Biolog | Novel compounds |
| GB9902070D0 (en) | 1999-01-29 | 1999-03-24 | Smithkline Beecham Biolog | Novel compounds |
| GB9902937D0 (en) | 1999-02-10 | 1999-03-31 | Smithkline Beecham Biolog | Novel compounds |
| EP1163343B1 (en) | 1999-03-12 | 2009-12-09 | GlaxoSmithKline Biologicals S.A. | Neisseria meningitidis antigenic polypeptides, corresponding polynucleotides and protective antibodies |
| WO2000066741A2 (en) | 1999-04-30 | 2000-11-09 | Chiron S.P.A. | Conserved neisserial antigens |
| NZ515935A (en) * | 1999-05-19 | 2004-01-30 | Chiron S | Combination Neisserial compositions and vaccines for the prevention of infections due to Neisseria bacteria such as meningococcal meningitis |
| GB9918319D0 (en) * | 1999-08-03 | 1999-10-06 | Smithkline Beecham Biolog | Vaccine composition |
| GB9918206D0 (en) | 1999-08-03 | 1999-10-06 | Smithkline Beecham Biolog | Novel compounds |
| US6531131B1 (en) | 1999-08-10 | 2003-03-11 | The United States Of America As Represented By The Department Of Health And Human Services | Conjugate vaccine for Neisseria meningitidis |
| GB9925559D0 (en) | 1999-10-28 | 1999-12-29 | Smithkline Beecham Biolog | Novel method |
| AU1917501A (en) | 1999-11-12 | 2001-06-06 | University Of Iowa Research Foundation, The | Control of neisserial membrane synthesis |
| BR0015961A (pt) | 1999-11-29 | 2003-06-10 | Chiron Spa | Antìgeno de neisseria de 85kda |
| NZ520445A (en) | 2000-01-25 | 2004-02-27 | Univ Queensland | Proteins comprising conserved regions of neisseria meningitidis surface antigen NhhA |
| NO20002828D0 (no) | 2000-06-02 | 2000-06-02 | Statens Inst For Folkehelse | Proteinholdig vaksine mot Neisseria meningtidis serogruppe samt fremgangsmÕte ved fremstilling derav |
| ES2519440T3 (es) | 2000-07-27 | 2014-11-07 | Children's Hospital & Research Center At Oakland | Vacunas para la protección de amplio espectro contra enfermedades causadas por Neisseria meningitidis |
| GB0103170D0 (en) | 2001-02-08 | 2001-03-28 | Smithkline Beecham Biolog | Vaccine composition |
| GB0103171D0 (en) | 2001-02-08 | 2001-03-28 | Smithkline Beecham Biolog | Vaccine composition |
| GB0109289D0 (en) | 2001-04-12 | 2001-05-30 | Glaxosmithkline Biolog Sa | Novel compounds |
| MX339524B (es) | 2001-10-11 | 2016-05-30 | Wyeth Corp | Composiciones inmunogenicas novedosas para la prevencion y tratamiento de enfermedad meningococica. |
| GB0213622D0 (en) | 2002-06-13 | 2002-07-24 | Glaxosmithkline Biolog Sa | Vaccine Corporation |
| US20060057160A1 (en) | 2002-08-02 | 2006-03-16 | Ralph Biemans | Vaccine composition |
| GB0220194D0 (en) | 2002-08-30 | 2002-10-09 | Chiron Spa | Improved vesicles |
| GB0227346D0 (en) | 2002-11-22 | 2002-12-31 | Chiron Spa | 741 |
| GB0316560D0 (en) | 2003-07-15 | 2003-08-20 | Chiron Srl | Vesicle filtration |
| JP5173194B2 (ja) | 2003-12-23 | 2013-03-27 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | ワクチン |
| GB0419627D0 (en) | 2004-09-03 | 2004-10-06 | Chiron Srl | Immunogenic bacterial vesicles with outer membrane proteins |
| GB0424092D0 (en) | 2004-10-29 | 2004-12-01 | Chiron Srl | Immunogenic bacterial vesicles with outer membrane proteins |
| WO2006081259A2 (en) | 2005-01-27 | 2006-08-03 | Children's Hospital & Research Center At Oakland | Gna1870-based vesicle vaccines for broad spectrum protection against diseases caused by neisseria meningitidis |
| PE20110072A1 (es) | 2005-06-27 | 2011-02-04 | Glaxosmithkline Biolog Sa | Composicion inmunogenica |
| KR101515078B1 (ko) | 2005-12-22 | 2015-04-24 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 백신 |
| US7943554B2 (en) | 2006-06-26 | 2011-05-17 | Bp Exploration Operating Company Limited | Wellbore fluid comprising at least one polymer containing pendant alkyl groups |
| CA2695467A1 (en) | 2007-08-02 | 2009-03-26 | Children's Hospital & Research Center At Oakland | Fhbp- and lpxl1-based vesicle vaccines for broad spectrum protection against diseases caused by neisseria meningitidis |
| CN102356089B (zh) | 2008-02-21 | 2014-02-19 | 诺华股份有限公司 | 脑膜炎球菌fHBP多肽 |
| AU2009223613B2 (en) | 2008-03-10 | 2014-09-25 | Children's Hospital & Research Center At Oakland | Chimeric factor H binding proteins (fHBP) containing a heterologous B domain and methods of use |
| UA99659C2 (uk) | 2008-05-30 | 2012-09-10 | Дзе Ю.Ес.Ей., Ес Репрезентед Бай Дзе Секретарі Оф Дзе Армі, Он Бехаф Оф Уолтер Рід Армі | Мультивалентна вакцина з нативних везикул зовнішньої мембрани менінгококів, способи її застосування |
| GB0816447D0 (en) | 2008-09-08 | 2008-10-15 | Glaxosmithkline Biolog Sa | Vaccine |
| GB0819633D0 (en) | 2008-10-25 | 2008-12-03 | Isis Innovation | Composition |
| WO2010070453A2 (en) | 2008-12-17 | 2010-06-24 | Novartis Ag | Meningococcal vaccines including hemoglobin receptor |
| CA2759400A1 (en) | 2009-04-30 | 2010-11-04 | Children's Hospital & Research Center At Oakland | Chimeric factor h binding proteins (fhbp) and methods of use |
| GB0917003D0 (en) | 2009-09-28 | 2009-11-11 | Novartis Vaccines Inst For Global Health Srl | Purification of bacterial vesicles |
| TR201802933T4 (tr) | 2010-03-30 | 2018-03-21 | Childrens Hospital & Res Center At Oakland | Özellikleri değiştirilmiş faktör h bağlama proteinleri (fhbp) ve bunların kullanım yöntemi. |
| US9260489B2 (en) * | 2011-08-31 | 2016-02-16 | Children's Hospital & Research Center Oakland | Engineered sequences to facilitate expression of antigens in Neisseria and methods of use |
-
2013
- 2013-02-01 EP EP17199436.1A patent/EP3299467B1/en active Active
- 2013-02-01 BR BR112014019166A patent/BR112014019166A2/pt not_active IP Right Cessation
- 2013-02-01 CA CA2861946A patent/CA2861946A1/en not_active Abandoned
- 2013-02-01 MX MX2014008988A patent/MX2014008988A/es unknown
- 2013-02-01 US US14/375,222 patent/US9657297B2/en active Active
- 2013-02-01 WO PCT/EP2013/052108 patent/WO2013113917A1/en not_active Ceased
- 2013-02-01 ES ES13703562.2T patent/ES2654613T3/es active Active
- 2013-02-01 AU AU2013214105A patent/AU2013214105A1/en not_active Abandoned
- 2013-02-01 RU RU2014135522A patent/RU2014135522A/ru not_active Application Discontinuation
- 2013-02-01 JP JP2014555238A patent/JP5957541B2/ja not_active Expired - Fee Related
- 2013-02-01 EP EP13703562.2A patent/EP2809785B1/en active Active
- 2013-02-01 CN CN201380007752.4A patent/CN104114706A/zh active Pending
-
2016
- 2016-02-22 JP JP2016030838A patent/JP2016093202A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2861946A1 (en) | 2013-08-08 |
| RU2014135522A (ru) | 2016-03-27 |
| MX2014008988A (es) | 2014-08-27 |
| US9657297B2 (en) | 2017-05-23 |
| US20150218566A1 (en) | 2015-08-06 |
| EP3299467B1 (en) | 2021-08-11 |
| EP3299467A2 (en) | 2018-03-28 |
| EP2809785B1 (en) | 2017-11-01 |
| JP2016093202A (ja) | 2016-05-26 |
| BR112014019166A2 (pt) | 2017-07-04 |
| JP2015506693A (ja) | 2015-03-05 |
| EP3299467A3 (en) | 2018-05-30 |
| CN104114706A (zh) | 2014-10-22 |
| WO2013113917A1 (en) | 2013-08-08 |
| EP2809785A1 (en) | 2014-12-10 |
| JP5957541B2 (ja) | 2016-07-27 |
| AU2013214105A1 (en) | 2014-07-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2654613T3 (es) | Promotores para una expresión aumentada de proteínas en meningococos | |
| US12397048B2 (en) | Bunyavirales vaccine | |
| AU2019254591B2 (en) | Novel RSV RNA molecules and compositions for vaccination | |
| US12201682B2 (en) | Henipavirus vaccine | |
| JP2012519484A5 (es) | ||
| ES2986334T3 (es) | Gen modificado que confiere resistencia al virus | |
| WO2013151670A3 (en) | Modified polynucleotides for the production of nuclear proteins | |
| WO2016077938A1 (es) | Plásmidos y método para obtener partículas virales | |
| BRPI0416916A (pt) | promotores para expressão em vìrus de vacìnia modificada ankara | |
| AR065533A1 (es) | Metodos de transcripcion, constructos de adn de repeticion en tandem, productores de proteinas que atacan geminivirus patogenos de plantas a traves de la interrupcion de los factores de transcripcion esenciales de los agentes patogenos | |
| JP4665122B2 (ja) | 組み換えウイルスおよびその用途 | |
| MX2021009161A (es) | Acidos nucleicos recombinantes que contienen secuencias promotoras de alfaherpesvirus. | |
| ÇETİN et al. | Development of a Novel Plasmid-based Eukaryotic Model to Investigate Crimean-Congo Hemorrhagic Fever Virus | |
| ES3061718T3 (en) | Increase in meiotic recombination in plants by inhibiting an recq4 or top3a protein of the rtr complex | |
| AR125354A1 (es) | Vacuna contra el virus de la pseudorabia | |
| AR065746A1 (es) | Constructos de adn de repeticion en tandem, productores de proteinas que atacan virus, hongos y bacterias patogenos de plantas a traves de la interrupcion de los factores de transcripcion esenciales para que los mencionados agentes patogenos hagan su replicacion en las plantas | |
| Elvira-González et al. | Transposable element-derived siRNAs control viral disease in Arabidopsis | |
| RU2013148606A (ru) | Универсальный промотор для экспрессии терапевтических генов в клетках млекопитающих | |
| AR132118A1 (es) | Activadores de vías sintéticas | |
| AR065534A1 (es) | Constructos de adn de repeticion en tandem, productores de proteinas que atacan virus, hongos y bacterias patogenos de plantas a traves de la interrupcion de los factores de transcripcion esenciales para que los mencionados agentes patogenos hagan su replicacion en las plantas | |
| Finch | Reverse genetics of influenza B and the development of a novel LAIV vaccine | |
| RU2019106796A (ru) | Композиции, содержащие слитый белок альбумина и его аналогов, способы их получения и применение |