JP2001508286A - 免疫原性の解毒変異体E.coli LT―A毒素 - Google Patents
免疫原性の解毒変異体E.coli LT―A毒素Info
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- JP2001508286A JP2001508286A JP52024098A JP52024098A JP2001508286A JP 2001508286 A JP2001508286 A JP 2001508286A JP 52024098 A JP52024098 A JP 52024098A JP 52024098 A JP52024098 A JP 52024098A JP 2001508286 A JP2001508286 A JP 2001508286A
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- C—CHEMISTRY; METALLURGY
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- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/245—Escherichia (G)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- 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
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- 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
- A61P37/04—Immunostimulants
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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
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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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.粘膜アジュバントとしての使用のための、E.coli熱不安定毒素(LT-A)のサ ブユニットA、またはそのフラグメントのアミノ酸配列を含む免疫原性解毒タン パク質であって、ここで該配列またはフラグメントにおけるアミノ酸Ala-72がア ルギニン残基で置換されている、タンパク質。 2.ワクチンとしての使用のための、(i)薬学的に受容可能なキャリアおよび (ii)E.coli熱不安定毒素(LT-A)のサブユニットAまたはそのフラグメントの アミノ酸配列を含む免疫原性解毒タンパク質、を含む免疫原性組成物であって、 該配列またはフラグメントにおけるアミノ酸Ala-72がアルギニン残基で置換され ている、免疫原性組成物。 3.第2の免疫原性抗原をさらに含む、請求項2に記載の免疫原性組成物。 4.ワクチン製造における、E.coli熱不安定毒素(LT-A)のサブユニットAまた はそのフラグメントのアミノ酸配列を含む免疫原性解毒タンパク質の使用であっ て、ここで該配列またはフラグメントにおけるアミノ酸Ala-72がアルギニン残基 で置換されている、使用。 5.前記ワクチンが第2の免疫原性抗原を含む、請求項4に記載の使用。 6.哺乳動物をワクチン接種する方法であって、(i)E.coli熱不安定毒素(LT -A)のサブユニットAまたはそのフラグメントのアミノ酸配列を含む有効量の免 疫原性解毒タンパク質であって、ここで該配列またはフラグメントにおけるアミ ノ酸Ala-72がアルギニン残基で置換されている、タンパク質の有効量、および必 要に応じて(ii)第2の免疫原性抗原とともに投与する工程を包含する、方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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GB9622660.0 | 1996-10-31 | ||
GBGB9622660.0A GB9622660D0 (en) | 1996-10-31 | 1996-10-31 | Immunogenic detoxified mutant toxin |
PCT/IB1997/001440 WO1998018928A1 (en) | 1996-10-31 | 1997-10-30 | Immunogenic detoxified mutant e. coli lt-a toxin |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2005141923A Division JP2005247868A (ja) | 1996-10-31 | 2005-05-13 | 免疫原性の解毒変異体E.coliLT−A毒素 |
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JP2001508286A true JP2001508286A (ja) | 2001-06-26 |
JP3715326B2 JP3715326B2 (ja) | 2005-11-09 |
Family
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JP52024098A Expired - Fee Related JP3715326B2 (ja) | 1996-10-31 | 1997-10-30 | 免疫原性の解毒変異体E.coli LT―A毒素 |
JP2005141923A Withdrawn JP2005247868A (ja) | 1996-10-31 | 2005-05-13 | 免疫原性の解毒変異体E.coliLT−A毒素 |
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JP2005141923A Withdrawn JP2005247868A (ja) | 1996-10-31 | 2005-05-13 | 免疫原性の解毒変異体E.coliLT−A毒素 |
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US (2) | US20030113338A1 (ja) |
EP (2) | EP1571214A3 (ja) |
JP (2) | JP3715326B2 (ja) |
AT (1) | ATE303441T1 (ja) |
CA (1) | CA2268758C (ja) |
DE (1) | DE69734110T2 (ja) |
DK (1) | DK0941333T3 (ja) |
ES (1) | ES2247622T3 (ja) |
GB (1) | GB9622660D0 (ja) |
WO (1) | WO1998018928A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013522360A (ja) * | 2010-03-23 | 2013-06-13 | 財團法人生物技術開發中心 | 解毒した大腸菌易熱性エンテロトキシンを用いたアレルギー治療法 |
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9326174D0 (en) * | 1993-12-22 | 1994-02-23 | Biocine Sclavo | Mucosal adjuvant |
US5925351A (en) | 1995-07-21 | 1999-07-20 | Biogen, Inc. | Soluble lymphotoxin-β receptors and anti-lymphotoxin receptor and ligand antibodies as therapeutic agents for the treatment of immunological disease |
EP1486215A3 (en) * | 1997-03-21 | 2006-04-12 | Chiron Corporation | Detoxified mutants of bacterial ADP-ribosylating toxins as parenteral adjuvants |
US6219776B1 (en) | 1998-03-10 | 2001-04-17 | Billions Of Operations Per Second | Merged array controller and processing element |
DE69931944T2 (de) | 1998-10-09 | 2007-02-08 | Biogen Idec Ma Inc., Cambridge | Umkehr des viral-induzierten systemischen schocks und des atemnotsyndroms durch blockierung des lymphotoxin-beta- aktivierungsweges |
KR100649286B1 (ko) * | 1998-10-21 | 2006-11-24 | 샤단호칭키타사토겐큐쇼 | 감독화톡신을 포함하는 백신제제 |
BR9916515A (pt) * | 1998-12-22 | 2001-11-06 | Thompson Boyce Plant Res | Polinucleotìdeo, vetor de expressão, células de e. coli e de agrobacterium tumefaciens transformadas com o vetor de expressão, célula de planta transgênica, semente de planta transgênica, célula eucariótica transgênica, composição imunogênica, método de evocar uma resposta imune em um animal ou ser humano, planta transgênica, e, adjuvante |
DE60239317D1 (de) | 2001-01-12 | 2011-04-14 | Novartis Vaccines & Diagnostic | Nukleinsäure mukosale immunisierung |
MX339524B (es) | 2001-10-11 | 2016-05-30 | Wyeth Corp | Composiciones inmunogenicas novedosas para la prevencion y tratamiento de enfermedad meningococica. |
US20060035242A1 (en) | 2004-08-13 | 2006-02-16 | Michelitsch Melissa D | Prion-specific peptide reagents |
EP2382988A1 (en) | 2006-03-31 | 2011-11-02 | Novartis AG | Combined mucosal and parenteral immunization against HIV |
KR20090083958A (ko) | 2006-10-20 | 2009-08-04 | 바이오겐 아이덱 엠에이 인코포레이티드 | 가용성 림프독소-베타-수용체를 이용한 탈수초성 장애의 치료 |
US8338376B2 (en) | 2006-10-20 | 2012-12-25 | Biogen Idec Ma Inc. | Compositions comprising variant LT-B-R-IG fusion proteins |
KR20110031343A (ko) | 2008-06-20 | 2011-03-25 | 와이어쓰 엘엘씨 | 베타-용혈성 스트렙토코커스 균주로부터 유래된 orf1358을 사용하는 조성물 및 방법 |
AU2010203223B9 (en) | 2009-01-05 | 2015-10-08 | Epitogenesis Inc. | Adjuvant compositions and methods of use |
JP2012530785A (ja) | 2009-06-22 | 2012-12-06 | ワイス・エルエルシー | 組成物および黄色ブドウ球菌(Staphylococcusaureus)血清型5および8莢膜多糖コンジュゲート免疫原性組成物を調製するための方法 |
WO2010151544A1 (en) | 2009-06-22 | 2010-12-29 | Wyeth Llc | Immunogenic compositions of staphylococcus aureus antigens |
ES2850973T3 (es) | 2010-08-23 | 2021-09-01 | Wyeth Llc | Formulaciones estables de antígenos rLP2086 de Neisseria meningitidis |
WO2012032489A1 (en) | 2010-09-10 | 2012-03-15 | Wyeth Llc | Non-lipidated variants of neisseria meningitidis orf2086 antigens |
US8822427B2 (en) | 2010-10-27 | 2014-09-02 | Harrisvaccines | Methods and compositions to protect aquatic invertebrates from disease |
US10004797B2 (en) | 2010-10-27 | 2018-06-26 | Harrisvaccines, Inc. | Method of rapidly producing improved vaccines for animals |
WO2012058073A2 (en) | 2010-10-27 | 2012-05-03 | Harrisvaccines, Inc. | Methods and compositions to protect aquatic invertebrates from disease |
DK3150222T3 (da) | 2010-12-22 | 2020-01-27 | Wyeth Llc | Stabile immunogene sammensætninger af staphylococcus aureus-antigener |
BR112013032410A2 (pt) | 2011-06-24 | 2017-01-17 | Epitogenesis Inc | composições farmacêuticas compreendendo uma combinação de veículos, vitaminas, taninos e flavonoides de seleção como imunomoduladores específicos de antígeno |
WO2013103434A1 (en) | 2011-10-19 | 2013-07-11 | Harrisvaccines, Inc. | Methods and compositions to protect aquatic invertebrates from disease |
NZ628449A (en) | 2012-03-09 | 2016-04-29 | Pfizer | Neisseria meningitidis compositions and methods thereof |
SA115360586B1 (ar) | 2012-03-09 | 2017-04-12 | فايزر انك | تركيبات لعلاج الالتهاب السحائي البكتيري وطرق لتحضيرها |
WO2014097099A2 (en) | 2012-12-20 | 2014-06-26 | Pfizer Inc. | Glycoconjugation process |
CN105188747A (zh) | 2013-02-01 | 2015-12-23 | 葛兰素史密斯克莱生物公司 | 包含toll样受体激动剂的免疫组合物的皮内递送 |
JP6446377B2 (ja) | 2013-03-08 | 2018-12-26 | ファイザー・インク | 免疫原性融合ポリペプチド |
CA2923129C (en) | 2013-09-08 | 2020-06-09 | Pfizer Inc. | Neisseria meningitidis compositions and methods thereof |
WO2016130569A1 (en) | 2015-02-09 | 2016-08-18 | Mj Biologics, Inc. | A composition comprising pedv antigens and methods for making and using the composition |
US10034934B2 (en) | 2014-03-11 | 2018-07-31 | Regents Of The University Of Minnesota | Porcine epidemic diarrhea virus vaccines and methods of use thereof |
BR112017017460A2 (pt) | 2015-02-19 | 2018-04-10 | Pfizer Inc. | composições de neisseria meningitidis e métodos das mesmas |
IL297740A (en) | 2015-05-04 | 2022-12-01 | Pfizer | Protein-polysaccharide conjugates of group b streptococcus, methods for preparing the conjugates, immunogenic preparations containing conjugates and their uses |
US10751402B2 (en) | 2016-11-09 | 2020-08-25 | Pfizer Inc. | Immunogenic compositions and uses thereof |
CN110234658B (zh) | 2017-01-31 | 2024-03-12 | 辉瑞大药厂 | 脑膜炎奈瑟菌组合物及其使用方法 |
US20210187064A1 (en) * | 2018-05-07 | 2021-06-24 | Administrators Of The Tulane Educational Fund | Mutated e. coli enterotoxins as anti-inflammatory agents |
US20230146256A1 (en) | 2020-04-17 | 2023-05-11 | Regents Of The University Of Minnesota | SARS-CoV-2 SPIKE RECEPTOR BINDING DOMAIN AND COMPOSITIONS AND METHODS THEREOF |
EP4203995A1 (en) | 2020-08-26 | 2023-07-05 | Pfizer Inc. | Group b streptococcus polysaccharide-protein conjugates, methods for producing conjugates, immunogenic compositions comprising conjugates, and uses thereof |
KR20230171941A (ko) * | 2021-03-19 | 2023-12-21 | 고쿠리츠다이가쿠호진 미에다이가쿠 | 급성 폐손상 및 폐섬유증의 급성 악화를 개선하기 위한 의약 조성물 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8333131D0 (en) * | 1983-12-12 | 1984-01-18 | Glaxo Group Ltd | Microbiological process |
JP2849632B2 (ja) * | 1988-04-08 | 1999-01-20 | 社団法人北里研究所 | ワクチン製剤 |
DK0396964T3 (da) | 1989-04-28 | 1995-10-30 | Sclavo Spa | Pertussistoxin-mutanter, Bordetella-stammer, der er i stand til at producere sådanne mutanter, samt deres anvendelse til udvikling af antipertussis-vacciner |
IT1248735B (it) | 1990-06-21 | 1995-01-26 | Sclavo Spa | Vaccini acellulari contro la pertosse |
IL101715A (en) | 1991-05-02 | 2005-06-19 | Amgen Inc | Recombinant dna-derived cholera toxin subunit analogs |
GB9513371D0 (en) | 1995-06-30 | 1995-09-06 | Biocine Spa | Immunogenic detoxified mutant toxins |
IT1253009B (it) * | 1991-12-31 | 1995-07-10 | Sclavo Ricerca S R L | Mutanti immunogenici detossificati della tossina colerica e della tossina lt, loro preparazione ed uso per la preparazione di vaccini |
GB9326174D0 (en) * | 1993-12-22 | 1994-02-23 | Biocine Sclavo | Mucosal adjuvant |
US20030072774A1 (en) | 1994-06-10 | 2003-04-17 | Diane M. Gajewczyk | Proteinaceous adjuvants |
US6019982A (en) * | 1994-08-26 | 2000-02-01 | The Administrators Of The Tulane Educational Fund | Mutant enterotoxin effective as a non-toxic oral adjuvant |
HUP0104842A3 (en) | 1998-05-08 | 2002-12-28 | Univ Bristol Bristol | Vaccine |
DK1117435T3 (da) | 1998-09-30 | 2008-03-17 | Wyeth Corp | Muteret cholera-holotoxin som adjuvans |
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Cited By (1)
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JP2013522360A (ja) * | 2010-03-23 | 2013-06-13 | 財團法人生物技術開發中心 | 解毒した大腸菌易熱性エンテロトキシンを用いたアレルギー治療法 |
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WO1998018928A1 (en) | 1998-05-07 |
US20030170262A1 (en) | 2003-09-11 |
ES2247622T3 (es) | 2006-03-01 |
EP1571214A3 (en) | 2006-03-29 |
JP3715326B2 (ja) | 2005-11-09 |
DK0941333T3 (da) | 2006-01-02 |
EP0941333A1 (en) | 1999-09-15 |
DE69734110D1 (de) | 2005-10-06 |
ATE303441T1 (de) | 2005-09-15 |
CA2268758A1 (en) | 1998-05-07 |
GB9622660D0 (en) | 1997-01-08 |
EP0941333B1 (en) | 2005-08-31 |
JP2005247868A (ja) | 2005-09-15 |
US20030113338A1 (en) | 2003-06-19 |
CA2268758C (en) | 2007-05-29 |
EP1571214A2 (en) | 2005-09-07 |
DE69734110T2 (de) | 2006-06-29 |
US7291588B2 (en) | 2007-11-06 |
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