NO304117B1 - Konjugat av pneumokokkpolysakkarid og immunogent protein, fremgangsmÕte for fremstilling av konjugatet, samt vaksine som inneholder konjugatet - Google Patents
Konjugat av pneumokokkpolysakkarid og immunogent protein, fremgangsmÕte for fremstilling av konjugatet, samt vaksine som inneholder konjugatet Download PDFInfo
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- NO304117B1 NO304117B1 NO920350A NO920350A NO304117B1 NO 304117 B1 NO304117 B1 NO 304117B1 NO 920350 A NO920350 A NO 920350A NO 920350 A NO920350 A NO 920350A NO 304117 B1 NO304117 B1 NO 304117B1
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- polysaccharide
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- A—HUMAN NECESSITIES
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- A61K39/02—Bacterial antigens
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
- A61K39/092—Streptococcus
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- A—HUMAN NECESSITIES
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- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6068—Other bacterial proteins, e.g. OMP
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K2039/62—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier
- A61K2039/627—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier characterised by the linker
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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US64657091A | 1991-01-28 | 1991-01-28 | |
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EP (1) | EP0497525B2 (da) |
JP (1) | JPH0794472B2 (da) |
KR (1) | KR100243958B1 (da) |
CN (1) | CN1080124C (da) |
AT (1) | ATE169825T1 (da) |
AU (1) | AU651656B2 (da) |
CA (1) | CA2059692C (da) |
CZ (1) | CZ283284B6 (da) |
DE (1) | DE69226668T3 (da) |
DK (1) | DK0497525T4 (da) |
ES (1) | ES2121820T5 (da) |
FI (1) | FI107370B (da) |
HU (1) | HU216101B (da) |
IE (1) | IE920244A1 (da) |
IL (5) | IL119961A (da) |
LV (1) | LV12309B (da) |
MX (1) | MX9200328A (da) |
NO (1) | NO304117B1 (da) |
NZ (1) | NZ241367A (da) |
SI (1) | SI9210081B (da) |
SK (1) | SK280659B6 (da) |
YU (1) | YU49068B (da) |
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CA2059693C (en) * | 1991-01-28 | 2003-08-19 | Peter J. Kniskern | Polysaccharide antigens from streptococcus pneumoniae |
US5445817A (en) * | 1992-08-21 | 1995-08-29 | The United States Of America As Represented By The Department Of Health And Human Services | Pertussis toxin used as a carrier protein with non-charged saccharides in conjugate vaccines |
US5439808A (en) * | 1993-07-23 | 1995-08-08 | North American Vaccine, Inc. | Method for the high level expression, purification and refolding of the outer membrane group B porin proteins from Neisseria meningitidis |
US5565204A (en) * | 1994-08-24 | 1996-10-15 | American Cyanamid Company | Pneumococcal polysaccharide-recombinant pneumolysin conjugate vaccines for immunization against pneumococcal infections |
US5681570A (en) * | 1995-01-12 | 1997-10-28 | Connaught Laboratories Limited | Immunogenic conjugate molecules |
US5747287A (en) * | 1995-04-28 | 1998-05-05 | North American Vaccine, Inc. | Method for the high level expression, purification and refolding of the outer membrane group B porin proteins from Neisseria meningitidis |
IL121585A0 (en) * | 1995-06-07 | 1998-02-08 | Alberta Res Council | Immunogenic and immunostimulatory oligosaccharide compositions and methods of preparing and using them |
US5695768A (en) * | 1995-06-07 | 1997-12-09 | Alberta Research Council | Immunostimulating activity of Streptococcus pneumoniae serotype 8 oligosaccharides |
US5866132A (en) * | 1995-06-07 | 1999-02-02 | Alberta Research Council | Immunogenic oligosaccharide compositions |
US6410025B1 (en) | 1996-02-14 | 2002-06-25 | Merck & Co., Inc. | Polysaccharide precipitation process |
SE9601158D0 (sv) * | 1996-03-26 | 1996-03-26 | Stefan Svenson | Method of producing immunogenic products and vaccines |
US6207157B1 (en) | 1996-04-23 | 2001-03-27 | The United States Of America As Represented By The Department Of Health And Human Services | Conjugate vaccine for nontypeable Haemophilus influenzae |
DE69708318T3 (de) * | 1996-08-27 | 2006-11-16 | Novartis Vaccines and Diagnostics, Inc., Emeryville | Neisseria meningitidis serogruppe b glykokonjugate und verfahren zu deren verwendung |
FR2763244B1 (fr) * | 1997-05-14 | 2003-08-01 | Pasteur Merieux Serums Vacc | Composition vaccinale multivalente a porteur mixte |
AU740956B2 (en) | 1997-07-21 | 2001-11-15 | Baxter Healthcare Sa | Modified immunogenic pneumolysin compositions as vaccines |
US6224880B1 (en) | 1997-09-24 | 2001-05-01 | Merck & Co., Inc. | Immunization against Streptococcus pneumoniae using conjugated and unconjugated pneumoccocal polysaccharide vaccines |
US6756361B1 (en) * | 1997-10-14 | 2004-06-29 | Nabi | Enterococcus antigens and vaccines |
GB9727262D0 (en) * | 1997-12-24 | 1998-02-25 | Smithkline Beecham Biolog | Vaccine |
AU759391B2 (en) * | 1998-02-12 | 2003-04-10 | Wyeth Holdings Corporation | Pneumococcal and meningococcal vaccines formulated with interleukin-12 |
US7018637B2 (en) * | 1998-02-23 | 2006-03-28 | Aventis Pasteur, Inc | Multi-oligosaccharide glycoconjugate bacterial meningitis vaccines |
EP1073667A2 (en) * | 1998-04-28 | 2001-02-07 | Galenica Pharmaceuticals, Inc. | Polysaccharide-antigen conjugates |
GB9816337D0 (en) * | 1998-07-27 | 1998-09-23 | Cortecs Uk Ltd | Proteins |
US20080096236A1 (en) * | 1998-08-25 | 2008-04-24 | Binax, Inc. | Method for Detecting the Presence of Target Bacteria or a Target Component Carbohydrate Antigen Thereof |
US9134303B1 (en) | 1998-08-25 | 2015-09-15 | Alere Scarborough, Inc. | ICT immunoassay for Legionella pneumophila serogroup 1 antigen employing affinity purified antibodies thereto |
US6824997B1 (en) * | 1998-09-18 | 2004-11-30 | Binax, Inc. | Process and materials for the rapid detection of streptococcus pneumoniae employing purified antigen-specific antibodies |
US6146902A (en) * | 1998-12-29 | 2000-11-14 | Aventis Pasteur, Inc. | Purification of polysaccharide-protein conjugate vaccines by ultrafiltration with ammonium sulfate solutions |
GB9906437D0 (en) * | 1999-03-19 | 1999-05-12 | Smithkline Beecham Biolog | Vaccine |
HU228499B1 (en) * | 1999-03-19 | 2013-03-28 | Smithkline Beecham Biolog | Streptococcus vaccine |
US20040191834A1 (en) * | 1999-10-28 | 2004-09-30 | Laferriere Craig Antony Joseph | Novel method |
AP1695A (en) * | 2000-06-29 | 2006-12-17 | Glaxosmithkline Biologicals Sa | Multivalent vaccine composition. |
GB0108364D0 (en) | 2001-04-03 | 2001-05-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
GB0022742D0 (en) * | 2000-09-15 | 2000-11-01 | Smithkline Beecham Biolog | Vaccine |
GB0115176D0 (en) * | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
CA2508539A1 (en) * | 2002-12-03 | 2004-06-17 | Sloan-Kettering Institute For Cancer Research | Gp120 specific antigens and uses thereof |
US7369578B2 (en) * | 2003-07-01 | 2008-05-06 | Nortel Networks Limited | Digital processing of SONET pointers |
SG182189A1 (en) | 2003-12-17 | 2012-07-30 | Elan Pharma Int Ltd | A(beta) immunogenic peptide carrier conjugates and methods of producing same |
HUE026000T2 (en) * | 2003-12-17 | 2016-04-28 | Wyeth Llc | Immunogenic peptide-bearing conjugates and methods for their preparation |
EP2305294B1 (en) | 2004-09-22 | 2015-04-01 | GlaxoSmithKline Biologicals SA | Immunogenic composition for use in vaccination against staphylococcei |
EP2425855A1 (en) * | 2005-04-08 | 2012-03-07 | Wyeth LLC | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US20070184072A1 (en) | 2005-04-08 | 2007-08-09 | Wyeth | Multivalent pneumococcal polysaccharide-protein conjugate composition |
AU2011253684B8 (en) * | 2005-04-08 | 2013-07-11 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US7955605B2 (en) | 2005-04-08 | 2011-06-07 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US7709001B2 (en) * | 2005-04-08 | 2010-05-04 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
PT2351578T (pt) | 2005-06-27 | 2017-04-07 | Glaxosmithkline Biologicals Sa | Processo para o fabrico de vacinas |
TWI457133B (zh) | 2005-12-13 | 2014-10-21 | Glaxosmithkline Biolog Sa | 新穎組合物 |
GB0607088D0 (en) | 2006-04-07 | 2006-05-17 | Glaxosmithkline Biolog Sa | Vaccine |
LT3017827T (lt) | 2005-12-22 | 2019-01-10 | Glaxosmithkline Biologicals S.A. | Pneumokokinė polisacharidinė konjuguota vakcina |
CN101024079B (zh) * | 2006-02-17 | 2012-02-01 | 福州昌晖生物工程有限公司 | 肺炎链球菌多糖-外膜蛋白结合疫苗及制备方法 |
KR101541383B1 (ko) | 2006-03-30 | 2015-08-03 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 면역원성 조성물 |
AU2013200552B9 (en) * | 2006-04-07 | 2014-07-03 | Glaxosmithkline Biologicals S.A. | Conjugate vaccines |
TW200806315A (en) * | 2006-04-26 | 2008-02-01 | Wyeth Corp | Novel formulations which stabilize and inhibit precipitation of immunogenic compositions |
US8808707B1 (en) | 2006-05-08 | 2014-08-19 | Wyeth Llc | Pneumococcal dosing regimen |
CN110064053A (zh) * | 2006-08-07 | 2019-07-30 | 哈佛大学校长及研究员协会 | 蛋白质基质疫苗及这种疫苗的制备和给药方法 |
MX2009002560A (es) | 2006-09-07 | 2009-03-20 | Glaxosmithkline Biolog Sa | Vacuna. |
ATE473289T1 (de) * | 2006-10-10 | 2010-07-15 | Wyeth Llc | Verbesserte verfahren zur trennung von streptococcus pneumoniae-3-polysacchariden |
CN1963500B (zh) * | 2006-12-06 | 2010-05-12 | 云南沃森生物技术股份有限公司 | 一种肺炎链球菌荚膜多糖结合物中游离多糖含量的测定方法 |
GB0700136D0 (en) | 2007-01-04 | 2007-02-14 | Glaxosmithkline Biolog Sa | Process for manufacturing vaccines |
CA2681570C (en) * | 2007-03-23 | 2016-05-03 | Wyeth | Shortened purification process for the production of capsular streptococcus pneumoniae polysaccharides |
EP2155244B1 (en) | 2007-04-23 | 2017-03-22 | Serum Institute of India Private Limited | Antigenic polysaccharides and process for their preparation |
EA201490303A1 (ru) | 2007-05-02 | 2014-05-30 | Глаксосмитклайн Байолоджикалс С.А. | Вакцина |
KR20100045445A (ko) | 2007-06-26 | 2010-05-03 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 스트렙토코쿠스 뉴모니애 캡슐 다당류 컨쥬게이트를 포함하는 백신 |
AU2009302582A1 (en) | 2008-10-06 | 2010-04-15 | University Of Chicago | Compositions and methods related to bacterial Eap, Emp, and/or AdsA proteins |
HUE046859T2 (hu) * | 2008-12-18 | 2020-03-30 | Wyeth Llc | Eljárás Streptococcus pneumoniae poliszacharid molekulatömegének szabályozására szén alkalmazásával |
WO2010080486A2 (en) * | 2008-12-18 | 2010-07-15 | Wyeth Llc | Method for controlling streptococcus pneumoniae serotype 19a polysaccharide molecular weight |
US9050283B2 (en) | 2009-01-16 | 2015-06-09 | University Of Maryland, Baltimore | Broad spectrum vaccine against non-typhoidal Salmonella |
KR101773368B1 (ko) | 2009-04-03 | 2017-08-31 | 유니버시티 오브 시카고 | 단백질 A(SpA) 변이체와 관련된 조성물 및 방법 |
WO2010141312A2 (en) | 2009-06-01 | 2010-12-09 | Wake Forest University Health Sciences | Flagellin fusion proteins and conjugates comprising pneumococcus antigens and methods of using the same |
CN107126557A (zh) * | 2009-06-29 | 2017-09-05 | 健诺西生物科学公司 | 抗肺炎链球菌的疫苗和组合物 |
GB0913681D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
GB0913680D0 (en) | 2009-08-05 | 2009-09-16 | Glaxosmithkline Biolog Sa | Immunogenic composition |
GB201003922D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Conjugation process |
GB201003924D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Immunogenic composition |
JP2013523818A (ja) | 2010-04-05 | 2013-06-17 | ザ・ユニバーシティー・オブ・シカゴ | 免疫反応のエンハンサーとしてのプロテインA(SpA)抗体に関連する組成物および方法 |
WO2011148382A1 (en) | 2010-05-28 | 2011-12-01 | Biological E Limited | An improved process for the purification of capsular polysaccharides of haemophilus influenza - b, neisseria meningitis such as serotypes a, c, y and w-135, and other similar related capsular polysaccharides produced from both gram negative and gram positive microorganisms using aluminium phosphate with alcohol. |
CN103037885B (zh) | 2010-07-02 | 2015-08-26 | 芝加哥大学 | 与蛋白A(SpA)变体相关的组合物和方法 |
JP5793194B2 (ja) | 2010-09-09 | 2015-10-14 | ザ・ユニバーシティ・オブ・シカゴThe University Of Chicago | 感染防御ブドウ球菌抗原が関与する方法および組成物 |
AU2012207089B2 (en) | 2011-01-20 | 2016-04-14 | Children's Medical Center Corporation | Vaccines and compositions against Streptococcus pneumoniae |
GB201103836D0 (en) | 2011-03-07 | 2011-04-20 | Glaxosmithkline Biolog Sa | Conjugation process |
JP5944480B2 (ja) | 2011-03-22 | 2016-07-05 | セルム・インスティテュート・オブ・インディア・ピーブイティー.・リミテッド | 多糖を調製するための新規な方法 |
US8945588B2 (en) | 2011-05-06 | 2015-02-03 | The University Of Chicago | Methods and compositions involving protective staphylococcal antigens, such as EBH polypeptides |
DK2788023T3 (da) | 2011-12-06 | 2016-12-19 | Valneva Austria Gmbh | Aluminiumforbindelser til anvendelse i terapeutiske midler og vacciner |
EP2804627B1 (en) | 2012-01-20 | 2019-08-14 | Genocea Biosciences Inc. | Fused antigen vaccines and compositions against streptococcus pneumoniae |
EP2844275B1 (en) | 2012-04-26 | 2020-05-13 | University of Chicago | Staphylococcal coagulase antigens and methods of their use |
ITMI20121597A1 (it) * | 2012-09-25 | 2014-03-26 | Beta Pharma S A | Coniugato tra frammento di parete cellulare batterica ed un veicolo mucopolisaccaridico e suoi usi in ambito medico |
EP4272750A3 (en) | 2013-02-07 | 2024-01-24 | Children's Medical Center, Corp. | Protein antigens that provide protection against pneumococcal colonization and/or disease |
US10328141B2 (en) * | 2013-07-07 | 2019-06-25 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Synthetic vaccines against Streptococcus pneumoniae type 1 |
US11708411B2 (en) | 2013-12-20 | 2023-07-25 | Wake Forest University Health Sciences | Methods and compositions for increasing protective antibody levels induced by pneumococcal polysaccharide vaccines |
EP3096785B1 (en) * | 2014-01-21 | 2020-09-09 | Pfizer Inc | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
US11160855B2 (en) | 2014-01-21 | 2021-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
EP3583947B1 (en) * | 2014-01-21 | 2023-10-11 | Pfizer Inc. | Streptococcus pneumoniae capsular polysaccharides and conjugates thereof |
US10668164B2 (en) * | 2014-02-14 | 2020-06-02 | Pfizer Inc. | Immunogenic glycoprotein conjugates |
US9107906B1 (en) | 2014-10-28 | 2015-08-18 | Adma Biologics, Inc. | Compositions and methods for the treatment of immunodeficiency |
US10729780B2 (en) * | 2015-06-08 | 2020-08-04 | Serum Institute Of India Private Ltd. | Methods for improving the adsorption of polysaccharide-protein conjugates and multivalent vaccine formulation obtained thereof |
US11058757B2 (en) | 2016-03-31 | 2021-07-13 | Pogona, LLC | Saccharide-polypeptide conjugate compositions and methods of use thereof |
US11191822B2 (en) | 2016-06-22 | 2021-12-07 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Pneumococcal polysaccharide-protein conjugate composition |
EP3269385A1 (en) | 2016-07-12 | 2018-01-17 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Pneumococcal polysaccharide-protein conjugate composition |
US11951165B2 (en) | 2016-12-30 | 2024-04-09 | Vaxcyte, Inc. | Conjugated vaccine carrier proteins |
CN118662649A (zh) | 2016-12-30 | 2024-09-20 | Vaxcyte公司 | 具有非天然氨基酸的多肽-抗原缀合物 |
KR102650073B1 (ko) | 2017-01-31 | 2024-03-20 | 머크 샤프 앤드 돔 엘엘씨 | 스트렙토코커스 뉴모니아 혈청형 19f 유래의 협막 다당류 단백질 접합체의 제조 방법 |
US11246918B2 (en) | 2017-02-03 | 2022-02-15 | Eva Barbara Schadeck | Haemophilus influenzae saccharide-carrier conjugate compositions and uses thereof |
EP3585427A4 (en) * | 2017-02-24 | 2020-12-30 | Merck Sharp & Dohme Corp. | METHODS FOR IMPROVING THE FILTRABILITY OF POLYSACCHARIDE CONJUGATE WITH PROTEIN REACTIONS |
US11400162B2 (en) | 2017-02-24 | 2022-08-02 | Merck Sharp & Dohme Llc | Processes for the formulation of pneumococcal polysaccharides for conjugation to a carrier protein |
US10259865B2 (en) | 2017-03-15 | 2019-04-16 | Adma Biologics, Inc. | Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection |
US10688170B2 (en) | 2017-06-10 | 2020-06-23 | Inventprise, Llc | Multivalent conjugate vaccines with bivalent or multivalent conjugate polysaccharides that provide improved immunogenicity and avidity |
US10729763B2 (en) | 2017-06-10 | 2020-08-04 | Inventprise, Llc | Mixtures of polysaccharide-protein pegylated compounds |
CA3074703A1 (en) | 2017-09-07 | 2019-03-14 | Merck Sharp & Dohme Corp. | Pneumococcal polysaccharides and their use in immunogenic polysaccharide-carrier protein conjugates |
JP7218358B2 (ja) | 2017-09-07 | 2023-02-06 | メルク・シャープ・アンド・ドーム・エルエルシー | 肺炎球菌多糖体および免疫原性多糖体-キャリアタンパク質コンジュゲートでのその使用 |
DK3678654T3 (da) | 2017-09-07 | 2024-09-02 | Merck Sharp & Dohme Llc | Pneumokokpolysaccharider og anvendelse deraf i immunogene polysaccharid-bærerprotein-konjugater |
CN117736348A (zh) | 2017-09-07 | 2024-03-22 | 默沙东有限责任公司 | 肺炎球菌多糖及其在免疫原性多糖-载体蛋白缀合物中的用途 |
US11524076B2 (en) | 2017-09-07 | 2022-12-13 | Merck Sharp & Dohme Llc | Pneumococcal polysaccharides and their use in immunogenic polysaccharide-carrier protein conjugates |
TWI725359B (zh) | 2017-12-06 | 2021-04-21 | 美商默沙東藥廠 | 包含肺炎鏈球菌多醣-蛋白結合物之組合物及其使用方法 |
CN108079286B (zh) * | 2018-01-19 | 2020-07-31 | 云南沃森生物技术股份有限公司 | 一种13价肺炎球菌多糖-蛋白结合物组合物及其制备方法和应用 |
US11530432B2 (en) | 2018-03-19 | 2022-12-20 | Northwestern University | Compositions and methods for rapid in vitro synthesis of bioconjugate vaccines in vitro via production and N-glycosylation of protein carriers in detoxified prokaryotic cell lysates |
JOP20210148A1 (ar) | 2018-12-19 | 2023-01-30 | Merck Sharp & Dohme | تركيبات تشتمل على متقارنات بولي سكاريد-بروتين للمكورات العقدية الرئوية وطرق استخدامها |
CN113966234A (zh) | 2019-05-10 | 2022-01-21 | 葛兰素史克生物有限公司 | 缀合物的产生 |
CN114728051A (zh) | 2019-11-22 | 2022-07-08 | 葛兰素史克生物有限公司 | 细菌糖糖缀合物疫苗的剂量和施用 |
EP3900739A1 (en) | 2020-04-21 | 2021-10-27 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Synthetic streptococcus pneumoniae saccharide conjugates to conserved membrane protein |
EP3919076A1 (en) | 2020-06-02 | 2021-12-08 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Synthetic oligosaccharide vaccines against streptococcus pneumoniae with microparticle adjuvant formulations |
EP4165064A2 (en) | 2020-06-12 | 2023-04-19 | GlaxoSmithKline Biologicals S.A. | Dock tag system |
JP2023537945A (ja) | 2020-08-10 | 2023-09-06 | インベントプライズ・インコーポレイテッド | 出現血清型24fを含む多価肺炎球菌複合糖質ワクチン |
TW202245835A (zh) | 2021-02-04 | 2022-12-01 | 美商默沙東有限責任公司 | 用於肺炎球菌結合物疫苗之奈米乳化液佐劑組合物 |
WO2022180648A1 (en) | 2021-02-26 | 2022-09-01 | Biological E Limited | Activated-quenched polysaccharide and improved methods for quantification of polysaccharide in a vaccine composition |
EP4169513A1 (en) | 2021-10-19 | 2023-04-26 | GlaxoSmithKline Biologicals S.A. | Adjuvant composition comprising sting agonists |
WO2024062494A1 (en) | 2022-09-19 | 2024-03-28 | Biological E Limited | Method for the purification of capsular polysaccharides |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4324887A (en) * | 1978-08-16 | 1982-04-13 | President And Fellows Of Harvard College | Type II group B Streptococci polysaccharide |
US4221906A (en) * | 1979-03-19 | 1980-09-09 | American Cyanamid Company | Stabilization of pneumococcal polysaccharides |
US4242501A (en) * | 1979-08-08 | 1980-12-30 | American Cyanamid Company | Purification of pneumococcal capsular polysaccharides |
US4271147A (en) * | 1980-01-10 | 1981-06-02 | Behringwerke Aktiengesellschaft | Process for the isolation of membrane proteins from Neisseria meningitidis and vaccines containing same |
IE51174B1 (en) * | 1980-04-14 | 1986-10-29 | Merck & Co Inc | Group b streptococcal capsular polysaccharides |
FR2495939B1 (fr) * | 1980-12-11 | 1985-10-11 | Merieux Inst | Procede de purification de polyosides de streptococcus pneumoniae et vaccin a base de polyosides ainsi purifies |
NL8202527A (nl) * | 1982-06-22 | 1984-01-16 | Univ Utrecht | Vaccins tegen door bacterien met kapsel-polysacchariden verwekte ziekten en werkwijze voor het bereiden daarvan. |
US4496538A (en) * | 1982-07-06 | 1985-01-29 | Connaught Laboratories, Inc. | Haemophilus influenzae b polysaccharide-diphtheria toxoid conjugate vaccine |
US4619828A (en) * | 1982-07-06 | 1986-10-28 | Connaught Laboratories, Inc. | Polysaccharide exotoxoid conjugate vaccines |
US4644059A (en) * | 1982-07-06 | 1987-02-17 | Connaught Laboratories, Inc. | Haemophilus influenzae B polysaccharide-diptheria toxoid conjugate vaccine |
US4459286A (en) * | 1983-01-31 | 1984-07-10 | Merck & Co., Inc. | Coupled H. influenzae type B vaccine |
US4686102A (en) * | 1984-04-12 | 1987-08-11 | American Cyanamid Company | Multivalent pneumococcal vaccine and preparation thereof |
US4695624A (en) * | 1984-05-10 | 1987-09-22 | Merck & Co., Inc. | Covalently-modified polyanionic bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins with bigeneric spacers, and methods of preparing such polysaccharides and conjugates and of confirming covalency |
US4882317A (en) * | 1984-05-10 | 1989-11-21 | Merck & Co., Inc. | Covalently-modified bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins with bigeneric spacers and methods of preparing such polysaccharides and conjugataes and of confirming covalency |
NZ214503A (en) * | 1984-12-20 | 1990-02-26 | Merck & Co Inc | Covalently-modified neutral bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins, and methods of preparing such polysaccharides and conjugates |
IT1187753B (it) * | 1985-07-05 | 1987-12-23 | Sclavo Spa | Coniugati glicoproteici ad attivita' immunogenica trivalente |
US4707543A (en) * | 1985-09-17 | 1987-11-17 | The United States Of America As Represented By The Secretary Of The Army | Process for the preparation of detoxified polysaccharide-outer membrane protein complexes, and their use as antibacterial vaccines |
US4727136A (en) * | 1985-10-01 | 1988-02-23 | Canadian Patents And Development Ltd. | Modified meningococcal group B polysaccharide for conjugate vaccine |
ES2000034A6 (es) * | 1985-11-26 | 1987-10-01 | Schweiz Serum & Impfinst | Procedimiento para la preparacion de una vacuna viva contra paperas |
US4755381A (en) * | 1986-03-27 | 1988-07-05 | Swiss Serum And Vaccine Institute Berne | Klebsiella capsular polysaccharide vaccine |
EP0302887B1 (en) * | 1986-04-16 | 1994-06-22 | The Brigham And Women's Hospital, Inc. | Bacterial antigens, antibodies, vaccines, and methods of manufacture |
NZ223009A (en) * | 1986-12-31 | 1990-06-26 | Nl Rivm Of Thoven | Oligosaccharides containing d-ribose d-ribitol and phosphate units mimicing haemophilus influenzae type b antigens |
EP0338265B1 (en) * | 1988-04-19 | 1994-05-04 | American Cyanamid Company | Haemophilus influenzae type B polysaccharide-outer membrane protein conjugate vaccine |
US5091300A (en) * | 1989-08-03 | 1992-02-25 | Merck & Co., Inc. | Radio-immuno assay for hepatitis b virus pres2 antibodies |
CA2059693C (en) * | 1991-01-28 | 2003-08-19 | Peter J. Kniskern | Polysaccharide antigens from streptococcus pneumoniae |
JP2636128B2 (ja) * | 1993-02-03 | 1997-07-30 | 株式会社アマダメトレックス | パンチング金型 |
-
1992
- 1992-01-20 CA CA002059692A patent/CA2059692C/en not_active Expired - Lifetime
- 1992-01-21 IL IL11996192A patent/IL119961A/xx not_active IP Right Cessation
- 1992-01-21 IL IL11996292A patent/IL119962A/xx not_active IP Right Cessation
- 1992-01-21 IL IL10071692A patent/IL100716A/en not_active IP Right Cessation
- 1992-01-22 NZ NZ241367A patent/NZ241367A/en not_active IP Right Cessation
- 1992-01-23 SK SK199-92A patent/SK280659B6/sk not_active IP Right Cessation
- 1992-01-23 CZ CS92199A patent/CZ283284B6/cs not_active IP Right Cessation
- 1992-01-24 AU AU10467/92A patent/AU651656B2/en not_active Expired
- 1992-01-27 MX MX9200328A patent/MX9200328A/es unknown
- 1992-01-27 AT AT92300655T patent/ATE169825T1/de not_active IP Right Cessation
- 1992-01-27 DE DE69226668T patent/DE69226668T3/de not_active Expired - Lifetime
- 1992-01-27 HU HUP9200252A patent/HU216101B/hu unknown
- 1992-01-27 IE IE024492A patent/IE920244A1/en unknown
- 1992-01-27 YU YU8192A patent/YU49068B/sh unknown
- 1992-01-27 CN CN92100700A patent/CN1080124C/zh not_active Expired - Lifetime
- 1992-01-27 KR KR1019920001108A patent/KR100243958B1/ko not_active IP Right Cessation
- 1992-01-27 NO NO920350A patent/NO304117B1/no not_active IP Right Cessation
- 1992-01-27 FI FI920353A patent/FI107370B/fi active
- 1992-01-27 ES ES92300655T patent/ES2121820T5/es not_active Expired - Lifetime
- 1992-01-27 EP EP92300655A patent/EP0497525B2/en not_active Expired - Lifetime
- 1992-01-27 DK DK92300655.5T patent/DK0497525T4/da active
- 1992-01-27 SI SI9210081A patent/SI9210081B/sl unknown
- 1992-01-28 JP JP4012941A patent/JPH0794472B2/ja not_active Expired - Lifetime
-
1994
- 1994-05-20 US US08/246,394 patent/US5623057A/en not_active Expired - Lifetime
-
1997
- 1997-01-03 IL IL11996197A patent/IL119961A0/xx unknown
- 1997-01-03 IL IL11996297A patent/IL119962A0/xx unknown
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1999
- 1999-04-26 LV LVP-99-69A patent/LV12309B/en unknown
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