JP6084631B2 - Ｃｌｏｓｔｒｉｄｉｕｍｄｉｆｆｉｃｉｌｅ毒素ベースのワクチン - Google Patents
Ｃｌｏｓｔｒｉｄｉｕｍｄｉｆｆｉｃｉｌｅ毒素ベースのワクチン Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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)
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- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
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- A—HUMAN NECESSITIES
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
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- C—CHEMISTRY; METALLURGY
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Landscapes
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- Animal Behavior & Ethology (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| GB201121149A GB201121149D0 (en) | 2011-12-08 | 2011-12-08 | Clostridium difficile toxin-based vaccine |
| GB1121149.7 | 2011-12-08 | ||
| GBGB1217321.7A GB201217321D0 (en) | 2012-09-27 | 2012-09-27 | Vaccine |
| GB1217321.7 | 2012-09-27 | ||
| PCT/IB2012/002955 WO2013084071A2 (en) | 2011-12-08 | 2012-12-07 | Clostridium difficile toxin-based vaccine |
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| JP2015500827A5 JP2015500827A5 (enExample) | 2016-01-14 |
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| JP (1) | JP6084631B2 (enExample) |
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| ES (1) | ES2704069T3 (enExample) |
| IL (1) | IL232957A0 (enExample) |
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| MX (1) | MX2014006630A (enExample) |
| RU (1) | RU2014127714A (enExample) |
| SG (1) | SG11201402375VA (enExample) |
| WO (1) | WO2013084071A2 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI3505531T1 (sl) | 2011-04-22 | 2024-02-29 | Wyeth Llc | Kompozicije, povezane z mutantnim toksinom clostridium difficile in njegovimii metodami |
| EP2897637A1 (en) * | 2012-09-19 | 2015-07-29 | Novartis AG | Clostridium difficile polypeptides as vaccine |
| BR122016023101B1 (pt) | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| WO2014197651A1 (en) * | 2013-06-05 | 2014-12-11 | Tufts University | Atoxic recombinant holotoxins of clostridium difficile as immunogens |
| US10835595B2 (en) | 2014-01-06 | 2020-11-17 | The Trustees Of The University Of Pennsylvania | PD1 and PDL1 antibodies and vaccine combinations and use of same for immunotherapy |
| EP3160500B1 (en) * | 2014-06-25 | 2019-08-21 | GlaxoSmithKline Biologicals S.A. | Clostridium difficile immunogenic composition |
| US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
| US10668140B2 (en) | 2017-02-24 | 2020-06-02 | University Of South Floirida | Non-toxigenic Clostridium difficile spores for use in oral vaccination |
| US10555992B2 (en) | 2017-05-31 | 2020-02-11 | University Of South Florida | Immunogenic proteins against clostridium difficile |
| US10933126B2 (en) | 2018-05-03 | 2021-03-02 | The Board Of Regents Of The University Of Oklahoma | Clostridium difficile immunogenic compositions and methods of use |
| CA3141165A1 (en) * | 2019-05-21 | 2020-11-26 | The Regents Of The University Of California | Vaccine compositions for clostridium difficile |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US6090406A (en) | 1984-04-12 | 2000-07-18 | The Liposome Company, Inc. | Potentiation of immune responses with liposomal adjuvants |
| US5916588A (en) | 1984-04-12 | 1999-06-29 | The Liposome Company, Inc. | Peptide-containing liposomes, immunogenic liposomes and methods of preparation and use |
| US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
| NZ230423A (en) | 1988-08-25 | 1993-08-26 | Liposome Co Inc | A dosage form comprising an antigen and a multilamellar liposome comprising dimyristolyphosphatidylcholine (dmpc) and cholesterol |
| DE3841091A1 (de) | 1988-12-07 | 1990-06-13 | Behringwerke Ag | Synthetische antigene, verfahren zu ihrer herstellung und ihre verwendung |
| ES2055785T3 (es) | 1989-01-17 | 1994-09-01 | Eniricerche Spa | Peptidos sinteticos y su uso como vehiculos universales para la preparacion de conjugados inmunogenos aptos para el desarrollo de vacunas sinteticas. |
| JPH0832638B2 (ja) | 1989-05-25 | 1996-03-29 | カイロン コーポレイション | サブミクロン油滴乳剤を含んで成るアジュバント製剤 |
| AU651949B2 (en) | 1989-07-14 | 1994-08-11 | American Cyanamid Company | Cytokine and hormone carriers for conjugate vaccines |
| IT1237764B (it) | 1989-11-10 | 1993-06-17 | Eniricerche Spa | Peptidi sintetici utili come carriers universali per la preparazione di coniugati immunogenici e loro impiego per lo sviluppo di vaccini sintetici. |
| GB2276169A (en) | 1990-07-05 | 1994-09-21 | Celltech Ltd | Antibodies specific for carcinoembryonic antigen |
| IL98715A0 (en) | 1990-08-13 | 1992-07-15 | American Cyanamid Co | Filamentous hemaglutinin of bodetella pertussis as a carrier molecule for conjugate vaccines |
| IT1262896B (it) | 1992-03-06 | 1996-07-22 | Composti coniugati formati da proteine heat shock (hsp) e oligo-poli- saccaridi, loro uso per la produzione di vaccini. | |
| PT761231E (pt) | 1992-06-25 | 2000-06-30 | Smithkline Beecham Biolog | Composicao de vacina contendo adjuvantes |
| IL102687A (en) | 1992-07-30 | 1997-06-10 | Yeda Res & Dev | Conjugates of poorly immunogenic antigens and synthetic pepide carriers and vaccines comprising them |
| GB9326253D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6429199B1 (en) | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
| EP1041149B8 (en) | 1994-10-24 | 2007-10-03 | Allergan, Inc. | Vaccine and antitoxin for treatment and prevention of C. difficile disease |
| GB9513261D0 (en) | 1995-06-29 | 1995-09-06 | Smithkline Beecham Biolog | Vaccines |
| JPH11509200A (ja) | 1995-07-07 | 1999-08-17 | オラバックス インク． | 粘膜アジュバントとしてのクロストリジウム・ディフィシール（Ｃｌｏｓｔｒｉｄｉｕｍ Ｄｉｆｆｉｃｉｌｅ）トキシン |
| US5707829A (en) | 1995-08-11 | 1998-01-13 | Genetics Institute, Inc. | DNA sequences and secreted proteins encoded thereby |
| WO1998008540A1 (en) | 1996-08-28 | 1998-03-05 | Ophidian Pharmaceuticals, Inc. | Multivalent vaccine for clostridium botulinum neurotoxin |
| AU753688B2 (en) | 1997-03-10 | 2002-10-24 | Ottawa Civic Loeb Research Institute | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| GB9712347D0 (en) | 1997-06-14 | 1997-08-13 | Smithkline Beecham Biolog | Vaccine |
| GB9713156D0 (en) | 1997-06-20 | 1997-08-27 | Microbiological Res Authority | Vaccines |
| AU746859B2 (en) * | 1997-06-20 | 2002-05-02 | Imperial College Of Science, Technology And Medicine | Immonogenic fragments of toxin a of clostridium difficile |
| JP4426091B2 (ja) | 1997-09-05 | 2010-03-03 | 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 | サポニンを含有する水中油型エマルション |
| GB9725084D0 (en) | 1997-11-28 | 1998-01-28 | Medeva Europ Ltd | Vaccine compositions |
| CN1200730C (zh) | 1998-02-12 | 2005-05-11 | 惠氏控股有限公司 | 用白细胞介素－12配制的肺炎球菌和脑膜炎球菌疫苗 |
| US6303114B1 (en) | 1998-03-05 | 2001-10-16 | The Medical College Of Ohio | IL-12 enhancement of immune responses to T-independent antigens |
| KR20010042573A (ko) | 1998-04-09 | 2001-05-25 | 장 스테판느 | 애쥬번트 조성물 |
| US20020009429A1 (en) * | 1999-01-29 | 2002-01-24 | Galagen, Inc. | Pharmaceutical composition comprising a selected antigen and candida species antigen and methods |
| MY125387A (en) | 1999-03-19 | 2006-07-31 | Smithkline Beecham Biologicals S A | Vaccine |
| US6733760B1 (en) * | 1999-04-09 | 2004-05-11 | Techlab, Inc. | Recombinant toxin A/toxin B vaccine against Clostridium difficile |
| EP1165796A2 (en) | 1999-04-09 | 2002-01-02 | Techlab, Inc. | Recombinant clostridium toxin a protein carrier for polysaccharide conjugate vaccines |
| WO2000061762A1 (en) | 1999-04-09 | 2000-10-19 | Techlab, Inc. | RECOMBINANT TOXIN A/TOXIN B VACCINE AGAINST $i(CLOSTRIDIUM DIFFICILE) |
| GB0007432D0 (en) | 2000-03-27 | 2000-05-17 | Microbiological Res Authority | Proteins for use as carriers in conjugate vaccines |
| CA2409672A1 (en) * | 2000-05-10 | 2001-11-15 | Glycodesign Inc. | Designing modulators for glycosyltransferases |
| AU1412702A (en) | 2000-10-27 | 2002-05-06 | Chiron Spa | Nucleic acids and proteins from streptococcus groups a and b |
| US20040107461A1 (en) * | 2001-03-30 | 2004-06-03 | Padma Commuri | Glucan chain length domains |
| US20030099668A1 (en) | 2001-09-14 | 2003-05-29 | Cytos Biotechnology Ag | Packaging of immunostimulatory substances into virus-like particles: method of preparation and use |
| US20030091593A1 (en) | 2001-09-14 | 2003-05-15 | Cytos Biotechnology Ag | In vivo activation of antigen presenting cells for enhancement of immune responses induced by virus like particles |
| AU2003299527A1 (en) | 2002-06-17 | 2004-06-07 | Jimmy D. Ballard | Mutant of clostridium difficile toxin b and methods of use |
| US20040235139A1 (en) * | 2002-12-23 | 2004-11-25 | Demain Arnold L. | Clostridium difficile culture and toxin production methods |
| SI2857418T1 (en) | 2004-02-06 | 2018-01-31 | University Of Massachusetts | Antibodies against Clostridium difficile toxins and uses thereof |
| US20090087478A1 (en) | 2004-12-27 | 2009-04-02 | Progenics Pharmaceuticals (Nevada), Inc. | Orally Deliverable and Anti-Toxin Antibodies and Methods for Making and Using Them |
| US20060228369A1 (en) | 2005-04-11 | 2006-10-12 | Program For Appropriate Technology In Health | Stabilization and preservation of temperature-sensitive vaccines |
| WO2007146139A2 (en) | 2006-06-08 | 2007-12-21 | Cornell Research Foundation, Inc. | Codon-optimized dna molecules encoding the receptor binding domains of clostridium difficile toxins a and b |
| EP2054044B1 (de) | 2006-08-02 | 2014-07-23 | Johannes Gutenberg-Universität Mainz | Arzneimittel gegen lct-vergiftungen |
| WO2008152429A1 (en) | 2007-06-14 | 2008-12-18 | Health Protection Agency | Chemically modified peptides with improved immunogenicity |
| WO2008156676A1 (en) * | 2007-06-15 | 2008-12-24 | President And Fellows Of Harvard College | Methods and compositions for detecting and modulating o-glycosylation |
| WO2010017383A1 (en) * | 2008-08-06 | 2010-02-11 | Emergent Product Development Uk Limited | Vaccines against clostridium difficile and methods of use |
| JP5740714B2 (ja) | 2009-02-20 | 2015-06-24 | ヘルス プロテクション エージェンシー | クロストリジウム・ディフィシル（Ｃｌｏｓｔｒｉｄｉｕｍｄｉｆｆｉｃｉｌｅ）毒素に対する抗体 |
| JP2013503198A (ja) * | 2009-08-27 | 2013-01-31 | シナプティック リサーチ，リミテッド ライアビリティ カンパニー | 人工多能性幹（ｉＰＳ）細胞または組織特異的細胞を誘導するための新規タンパク質送達系 |
| WO2011060431A2 (en) | 2009-11-16 | 2011-05-19 | University Of Maryland Baltimore | Multivalent live vector vaccine against clostridium difficile-associated disease |
| US20120282274A1 (en) | 2009-11-20 | 2012-11-08 | Northshore University Health System Research Institute | Targeting of the c-terminal segment of c.difficile toxin b for improved clinical diagnosis, prevention, and treatment |
| WO2011068953A2 (en) * | 2009-12-02 | 2011-06-09 | Tufts University | Atoxic recombinant holotoxins of clostridium difficile as immunogens |
| GB0921288D0 (en) | 2009-12-04 | 2010-01-20 | Health Prot Agency | Therapies for preventing or suppressing clostridium difficile infection |
| AU2011238711B2 (en) | 2010-03-30 | 2015-06-18 | Pelican Technology Holdings, Inc. | High level expression of recombinant toxin proteins |
| MX339253B (es) * | 2010-04-15 | 2016-05-18 | Progenics Pharm Inc | Anticuerpos para el tratamiento de infeccion y enfermedad asociadas con clostridium dificile. |
| CN103957931B (zh) | 2010-09-03 | 2017-10-24 | 瓦尔内瓦奥地利有限责任公司 | 艰难梭状芽胞杆菌毒素a和毒素b蛋白的分离多肽及其用途 |
| US8431361B2 (en) | 2010-09-17 | 2013-04-30 | Board Of Regents Of The University Of Oklahoma | Bacterial cells, optimized nucleotide sequences and methods for improved expression of recombinant Clostridium difficile toxin B |
| GB201016742D0 (en) * | 2010-10-05 | 2010-11-17 | Health Prot Agency | Clostridium difficile antigens |
| WO2012118693A1 (en) | 2011-02-28 | 2012-09-07 | Northshore University Healthsystem | Methods of diagnosing clostridium difficile infection |
| SI3505531T1 (sl) * | 2011-04-22 | 2024-02-29 | Wyeth Llc | Kompozicije, povezane z mutantnim toksinom clostridium difficile in njegovimii metodami |
| CN103732750A (zh) | 2011-05-27 | 2014-04-16 | 葛兰素史密丝克莱恩生物有限公司 | 免疫原性组合物 |
| AR087716A1 (es) * | 2011-08-31 | 2014-04-09 | Valent Biosciences Corp | Composiciones reguladoras del crecimiento de plantas, metodos de preparacion y usos de las mismas |
| AR089797A1 (es) * | 2012-01-27 | 2014-09-17 | Merck Sharp & Dohme | Vacunas contra clostridum difficile que comprenden toxinas recombinantes |
| GB201223342D0 (en) * | 2012-12-23 | 2013-02-06 | Glaxosmithkline Biolog Sa | Immunogenic composition |
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- 2012-12-07 KR KR1020147018480A patent/KR20140101835A/ko not_active Withdrawn
- 2012-12-07 SG SG11201402375VA patent/SG11201402375VA/en unknown
- 2012-12-07 RU RU2014127714A patent/RU2014127714A/ru not_active Application Discontinuation
-
2014
- 2014-06-05 IL IL232957A patent/IL232957A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20140101835A (ko) | 2014-08-20 |
| JP2015500827A (ja) | 2015-01-08 |
| IN2014CN04071A (enExample) | 2015-10-23 |
| WO2013084071A3 (en) | 2013-11-07 |
| SG11201402375VA (en) | 2014-10-30 |
| WO2013084071A2 (en) | 2013-06-13 |
| CA2858519A1 (en) | 2013-06-13 |
| US9694063B2 (en) | 2017-07-04 |
| BR112014013876A2 (pt) | 2019-09-24 |
| EP2788022B1 (en) | 2018-10-31 |
| EP2788022A2 (en) | 2014-10-15 |
| MX2014006630A (es) | 2014-07-09 |
| US20150132333A1 (en) | 2015-05-14 |
| AU2012349753A1 (en) | 2014-06-19 |
| ES2704069T3 (es) | 2019-03-14 |
| IL232957A0 (en) | 2014-07-31 |
| CN103974718A (zh) | 2014-08-06 |
| RU2014127714A (ru) | 2016-01-27 |
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