DK2436700T5 - Afkortet oprensningsfremgangsmåde til fremstilling af streptococcus pneumoniae-kapselpolysaccharider - Google Patents
Afkortet oprensningsfremgangsmåde til fremstilling af streptococcus pneumoniae-kapselpolysaccharider Download PDFInfo
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- DK2436700T5 DK2436700T5 DK11194173.8T DK11194173T DK2436700T5 DK 2436700 T5 DK2436700 T5 DK 2436700T5 DK 11194173 T DK11194173 T DK 11194173T DK 2436700 T5 DK2436700 T5 DK 2436700T5
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- Prior art keywords
- protein
- solution
- retentate
- polysaccharide
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Classifications
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- A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
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Claims (21)
1. Fremgangsmåde til fremstilling af oprensede kapselpolysaccharider ud fra et Streptococcus pneumoniae-ce\\e\ysat, hvilken fremgangsmåde omfatter trinnene: (a) at tilvejebringe en fermenteringssuppe omfattende bakterieceller, der producerer en udvalgt Streptococcus pneumoniae-serotype-, (b) at lysere bakteriecellerne fra trin (a) med et lytisk middel, hvorved der fremstilles et cellelysat omfattende celledebris, opløselige proteiner, nukleinsyrer og polysaccharider; (c) at klare cellelysatet fra trin (b) under anvendelse af centrifugering eller filtrering til fjernelse af celledebris, hvorved der fremstilles et klaret cellelysat; (d) at ultrafiltrere og diafiltrere det klarede cellelysat fra trin (c) til fjernelse af urenheder med lav molekylvægt og øgning af polysaccharidkoncentrationen, hvorved der fremstilles et retentat; (e) at sænke pH-værdien af retentatet fra trin (d) til mindre end 4,5 under anvendelse af en organisk syre eller en mineralsyre til udfældning af protein og nukleinsyrer, hvorved der dannes en forsuret retentatopløsning; (f) at fastholde den forsurede retentatopløsning dannet i trin (e) i et tidsrum, der er tilstrækkeligt til at muliggøre, at udfældningsproduktet bundfælder sig, efterfulgt af filtrering eller centrifugering af den forsurede retentatopløsning, hvorved der fremstilles en polysaccharidopløsning; (g) at filtrere den klarede polysaccharidopløsning fra trin (f) gennem et aktiveret kulfilter; (h) at ultrafiltrere og diafiltrere den filtrerede opløsning fremstillet ved trin (g), hvorved der fremstilles en koncentreret oprenset polysaccharidopløsning; og (i) at filtrere den koncentrerede oprensede polysaccharidopløsning fremstillet ved trin (h) under anvendelse af et sterilt filter; hvorved der fremstilles oprensede kapselpolysaccharider i form af en opløsning.
2. Fremgangsmåde ifølge krav 1, hvor den valgte Streptococcus pneumoniae-serotype udvælges fra gruppen bestående af 1,4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19Fog 23F.
3. Fremgangsmåde ifølge krav 1, omfattende trinnene: (a) at tilvejebringe en fermenteringssuppe omfattende bakterieceller, der producerer Streptococcus pneumoniae-serotype 1,4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F eller 23F; (b) at lysere bakteriecellerne fra trin (a) med et lytisk middel, hvorved der fremstilles et cellelysat omfattende celledebris, opløselige proteiner, nukleinsyrer og polysaccharider; (c) at klare cellelysatet fra trin (b) under anvendelse af centrifugering eller filtrering til fjernelse af celledebris, hvorved der fremstilles et klaret cellelysat; (d) at ultrafiltrere og diafiltrere det klarede cellelysat fra trin (c) ved rumtemperatur ved neutral pH i saltfri medier til fjernelse af urenheder med lav molekylvægt og øgning af polysaccharidkoncentrationen, hvorved der fremstilles et saltfrit retentat; (e) at sænke pH-værdien af det saltfri retentat fra trin (d) til mindre end 4,5 under anvendelse af en organisk syre eller en mineralsyre til udfældning af protein og nukleinsyrer, hvorved der dannes en forsuret retentatopløsning; (f) at fastholde den forsurede retentatopløsning dannet i trin (e) i mindst 2 timer ved rumtemperatur til muliggørelse af, at udfældningsproduktet bundfælder sig, efterfulgt af filtrering eller centrifugering af den forsurede retentatopløsning, hvorved der fremstilles en polysaccharidopløsning; (g) at filtrere den klarede polysaccharidopløsning fra trin (f) gennem et aktiveret kulfilter; (h) at ultrafiltrere og diafiltrere den filtrerede opløsning fremstillet ved trin (g), hvorved der fremstilles en koncentreret oprenset polysaccharidopløsning; og (i) at filtrere den koncentrerede oprensede polysaccharidopløsning fremstillet ved trin (h) under anvendelse af et sterilt filter; hvorved der fremstilles oprensede kapselpolysaccharider omfattende serotype 1,4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F eller 23F i form af en opløsning.
4. Fremgangsmåde ifølge krav 1,2 eller 3, hvor pH-værdien fra trin (e) sænkes til ca. 3,5.
5. Fremgangsmåde ifølge krav 1,2, 3 eller 4, hvor diafiltreringen i trin (h) omfatter en pH-justering til mellem ca. 5,5 til ca. 7,5, fortrinsvis hvor diafiltreringen i trin (h) omfatter en pH-justering til mellem ca. 7,0 til ca. 7,5, endnu mere foretrukket hvor diafiltreringen i trin (h) omfatter en pH-justering til ca. 7,4.
6. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 5, hvor trin (e) fjerner mindst 98 % af protein fra retentatet fra trin (d).
7. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 6, hvor trin (g) fjerner mindst 90 % af proteinet fra den klarede polysaccharidopløsning fra trin (f)·
8. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 7, hvor det aktiverede kulfilter i trin (g) omfatter træbaseret phosphorsyreaktiveret kul.
9. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 8, hvor trin (f) omfatter at fastholde den forsurede retentatopløsning dannet i trin (e) i mindst 2 timer.
10. Fremgangsmåde ifølge krav 1, omfattende trinnene: (a) at tilvejebringe en fermenteringssuppe omfattende bakterieceller, der producerer Streptococcus pneumoniae-serotype 19A; (b) at lysere bakteriecellerne fra trin (a) med et lytisk middel, hvorved der fremstilles et cellelysat omfattende celledebris, opløselige proteiner, nukleinsyrer og polysaccharider; (c) at klare cellelysatet fra trin (b) under anvendelse af centrifugering eller filtrering til fjernelse af celledebris, hvorved der fremstilles et klaret cellelysat; (d) at ultrafiltrere og diafiltrere det klarede cellelysat fra trin (c) ved ca. 4 °C ved en pH-værdi på ca. 6 i natriumphosphatbuffer til fjernelse af urenheder med lav molekylvægt og øgning af polysaccharidkoncentrationen, hvorved der fremstilles et retentat; (e) at sænke pH-værdien af retentatet fra trin (d) til mindre end 4,5 under anvendelse af en organisk syre eller en mineralsyre til udfældning af protein og nukleinsyrer, hvorved der dannes en forsuret retentatopløsning; (f) at fastholde den forsurede retentatopløsning dannet i trin (e) i mindst 2 timer ved ca. 4 °C til muliggørelse af, at udfældningsproduktet bundfælder sig, efterfulgt af filtrering eller centrifugering af den forsurede retentatopløsning, hvorved der fremstilles en polysaccharidopløsning; (g) at justere pH-værdien af den klarede polysaccharidopløsning fra trin (f) til ca. 6, hvorved der fremstilles en pH-justeret klaret polysaccharidopløsning; (h) at filtrere den pH-justerede klarede polysaccharidopløsning fra trin (g) gennem et aktiveret kulfilter; (i) at ultrafiltrere og diafiltrere den filtrerede opløsning fremstillet ved trin (h), hvorved der fremstilles en koncentreret oprenset polysaccharidopløsning; og (j) at filtrere den koncentrerede oprensede polysaccharidopløsning fremstillet ved trin (i) under anvendelse af et sterilt filter; hvorved der fremstilles oprensede kapselpolysaccharider omfattende serotype 19A i form af en opløsning.
11. Fremgangsmåde ifølge krav 10, hvor pH-værdien fra trin (e) sænkestil ca. 3,5.
12. Fremgangsmåde ifølge krav 10 eller 11, hvor diafiltreringen i trin (i) omfatter en pH-justering til mellem ca. 5,5 til ca. 7,5, fortrinsvis hvor diafiltreringen i trin (i) omfatter en pH-justering til mellem ca. 7,0 til ca. 7,5, endnu mere foretrukket hvor diafiltreringen i trin (i) omfatter en pH-justering til ca. 7,4.
13. fremgangsmåde ifølge et hvilket som helst af kravene 10 til 12, hvor trin (e) fjerner mindst 98 % af protein fra retentatet i trin (d).
14. Fremgangsmåde ifølge et hvilket som helst af kravene 10 til 13, hvor trin (h) fjerner mindst 90 % af proteinet fra den pH-justerede klarede polysaccharidopløsning fra trin (g).
15. Fremgangsmåde ifølge et hvilket som helst af kravene 10 til 13, hvor det aktiverede kulfilter i trin (h) omfatter træbaseret phosphorsyreaktiveret kul.
16. Fremgangsmåde ifølge et hvilket som helst af kravene 10 til 15, hvor natri-umphosphatbufferen i trin (d) er 25 mM natriumphosphat.
17. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 16, hvor det lytiske middel i trin (b) er deoxycholatnatrium.
18. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 16, hvor det lytiske middel i trin (b) er et lytisk middel af ikke-animalsk oprindelse, fortrinsvis hvor det lytiske middel af ikke-animalsk oprindelse er udvalgt fra gruppen bestående af: decansulfonsyre, tert-octylphenoxy-poly(oxyethylen)ethanoler, oc-tylphenolethylenoxidkondensater, N-lauryl-sarcosinnatrium (NLS), laurylimi-nodipropionat, natriumdodecylsulfat, chenodeoxycholat, hyodeoxycholat, gly-codeoxycholat, taurodeoxycholat, taurochenodeoxycholat og cholat, endnu mere foretrukket hvor det lytiske middel af ikke-animalsk oprindelse er N-lauryl-sarcosinnatrium.
19. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 18, hvor mineralsyren er udvalgt fra gruppen bestående af saltsyre, salpetersyre, phosphor-syre og svovlsyre.
20. Fremgangsmåde til fremstilling af en pneumokokvaccine, som omfatter at fremstille oprensede kapselpolysaccharider fra et Streptococcus pneumoniae-cellelysat ved en fremgangsmåde ifølge et hvilket som helst af kravene 1 til 19 og at anvende de oprensede kapselpolysaccharider til fremstilling af en pneumokokvaccine.
21. Fremgangsmåde ifølge krav 20, hvor pneumokokvaccinen indeholder po-lysaccharid konjugeret med en proteinbærer.
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| EP08732592.4A EP2129693B1 (en) | 2007-03-23 | 2008-03-20 | Shortened purification process for the production of capsular streptococcus pneumoniae polysaccharides |
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Families Citing this family (100)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3406635T3 (da) * | 2007-03-23 | 2022-05-30 | Wyeth Llc | Afkortet oprensningsmetode til fremstilling af Streptococcus Pneumoniae-kapselpolysaccharider |
| GB0818453D0 (en) * | 2008-10-08 | 2008-11-12 | Novartis Ag | Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom |
| ES2586308T3 (es) | 2008-10-27 | 2016-10-13 | Glaxosmithkline Biologicals Sa | Procedimiento de purificación de un hidrato de carbono de Streptococcus del grupo A |
| MX2011006432A (es) * | 2008-12-18 | 2011-09-29 | Wyeth Llc | Metodo para controlar el peso molecular del polisacarido streptococcus pneumoniae serotipo 19a. |
| CN102257127B (zh) | 2008-12-18 | 2014-01-01 | 惠氏有限责任公司 | 使用二氧化碳控制肺炎链球菌多糖分子量的方法 |
| CA2757620C (en) | 2009-04-30 | 2016-04-26 | Coley Pharmaceutical Group, Inc. | Pneumococcal vaccine and uses thereof |
| EP3238742A1 (en) | 2009-06-22 | 2017-11-01 | Wyeth LLC | Immunogenic compositions of staphylococcus aureus antigens |
| BRPI1011753B8 (pt) | 2009-06-22 | 2021-05-25 | Wyeth Llc | conjugados imunogênicos de polissacarídeo capsular de staphylococcus aureus de sorotipos 5 e 8, seu uso e composições que os compreendem |
| TW201136603A (en) * | 2010-02-09 | 2011-11-01 | Merck Sharp & Amp Dohme Corp | 15-valent pneumococcal polysaccharide-protein conjugate vaccine composition |
| US20110262989A1 (en) | 2010-04-21 | 2011-10-27 | Nanomr, Inc. | Isolating a target analyte from a body fluid |
| US8841104B2 (en) | 2010-04-21 | 2014-09-23 | Nanomr, Inc. | Methods for isolating a target analyte from a heterogeneous sample |
| US9476812B2 (en) | 2010-04-21 | 2016-10-25 | Dna Electronics, Inc. | Methods for isolating a target analyte from a heterogeneous sample |
| WO2011145108A2 (en) * | 2010-05-15 | 2011-11-24 | Serum Institute Of India Ltd. | Purification of capsular polysaccharides |
| EP2688573B1 (en) * | 2011-03-22 | 2016-11-30 | Serum Institute of India Private Limited | A novel process for preparation of polysaccharides |
| CN102660601B (zh) * | 2012-04-17 | 2015-10-28 | 江苏康泰生物医学技术有限公司 | 快速纯化细菌荚膜多糖的方法 |
| CN102660603B (zh) * | 2012-04-17 | 2015-03-25 | 江苏康泰生物医学技术有限公司 | 一种快速纯化细菌荚膜多糖的方法 |
| CN102660602B (zh) * | 2012-04-17 | 2015-03-25 | 江苏康泰生物医学技术有限公司 | 快速纯化细菌荚膜多糖的方法 |
| US9650411B2 (en) * | 2012-08-07 | 2017-05-16 | Kyowa Hakko Kirin Co., Ltd. | Method of purifying protein |
| AU2013313794B2 (en) * | 2012-09-07 | 2016-10-20 | Sk Bioscience Co., Ltd. | Production method for capsular polysaccharide having pneumococcal serotype |
| ES2773954T3 (es) | 2012-10-03 | 2020-07-15 | Glaxosmithkline Biologicals Sa | Composición inmunogénica |
| US10000557B2 (en) | 2012-12-19 | 2018-06-19 | Dnae Group Holdings Limited | Methods for raising antibodies |
| US9804069B2 (en) | 2012-12-19 | 2017-10-31 | Dnae Group Holdings Limited | Methods for degrading nucleic acid |
| US9599610B2 (en) | 2012-12-19 | 2017-03-21 | Dnae Group Holdings Limited | Target capture system |
| US9995742B2 (en) | 2012-12-19 | 2018-06-12 | Dnae Group Holdings Limited | Sample entry |
| US9551704B2 (en) | 2012-12-19 | 2017-01-24 | Dna Electronics, Inc. | Target detection |
| US9434940B2 (en) | 2012-12-19 | 2016-09-06 | Dna Electronics, Inc. | Methods for universal target capture |
| JP2016529885A (ja) | 2013-07-12 | 2016-09-29 | イー・エム・デイー・ミリポア・コーポレイシヨン | 活性炭を使用して標的タンパク質を含む試料からのウイルス除去を決定する方法 |
| 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 |
| US11160855B2 (en) | 2014-01-21 | 2021-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| IL311385A (en) | 2014-01-21 | 2024-05-01 | Pfizer | Streptococcus pneumoniae capsular polysaccharides and conjugates thereof |
| JP6612260B2 (ja) | 2014-01-21 | 2019-11-27 | ファイザー・インク | 肺炎連鎖球菌（Ｓｔｒｅｐｔｏｃｏｃｃｕｓ ｐｎｅｕｍｏｎｉａｅ）莢膜多糖およびそのコンジュゲート |
| KR20230021167A (ko) | 2014-01-21 | 2023-02-13 | 화이자 인코포레이티드 | 접합된 캡슐 사카라이드 항원을 포함하는 면역원성 조성물 및 그의 용도 |
| US9107906B1 (en) | 2014-10-28 | 2015-08-18 | Adma Biologics, Inc. | Compositions and methods for the treatment of immunodeficiency |
| MX395525B (es) | 2015-01-15 | 2025-03-25 | Pfizer | Composiciones inmunogenicas para usar en vacunas neumococicas. |
| SG10202101887WA (en) | 2015-05-04 | 2021-03-30 | Pfizer | Group b streptococcus polysaccharide-protein conjugates, methods for producing conjugates, immunogenic compositions comprising conjugates, and uses thereof |
| JPWO2016204265A1 (ja) * | 2015-06-18 | 2018-06-14 | 一般財団法人阪大微生物病研究会 | 肺炎球菌補体依存性殺菌能測定方法 |
| NZ739007A (en) | 2015-07-21 | 2022-08-26 | Pfizer | Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof |
| CN105131139B (zh) * | 2015-07-31 | 2018-02-13 | 兰州生物制品研究所有限责任公司 | 一种肺炎链球菌荚膜多糖的纯化方法 |
| CA3005524C (en) | 2015-11-20 | 2023-10-10 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
| MX2019001342A (es) | 2016-08-05 | 2019-07-04 | Sanofi Pasteur Inc | Composicion de conjugado de proteina-polisacarido de neumococo multivalente. |
| AU2017306708B2 (en) | 2016-08-05 | 2021-08-26 | Sk Bioscience Co., Ltd. | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| US10751402B2 (en) | 2016-11-09 | 2020-08-25 | Pfizer Inc. | Immunogenic compositions and uses thereof |
| MX2019007910A (es) | 2016-12-30 | 2019-12-05 | Sutrovax Inc | Conjugados de polipeptido-antigeno con aminoacidos no naturales. |
| US11951165B2 (en) | 2016-12-30 | 2024-04-09 | Vaxcyte, Inc. | Conjugated vaccine carrier proteins |
| MX392525B (es) | 2017-01-20 | 2025-03-12 | Pfizer | Composiciones inmunogenicas para su uso en vacunas neumococicas |
| KR102650073B1 (ko) | 2017-01-31 | 2024-03-20 | 머크 샤프 앤드 돔 엘엘씨 | 스트렙토코커스 뉴모니아 혈청형 19f 유래의 협막 다당류 단백질 접합체의 제조 방법 |
| US11197921B2 (en) | 2017-01-31 | 2021-12-14 | Merck Sharp & Dohme Corp. | Methods for making polysaccharide-protein conjugates |
| BR112019017390A2 (pt) | 2017-02-24 | 2020-03-31 | Merck Sharp & Dohme Corp. | Formulações de vacina pneumocócica conjugada e uso das mesmas |
| BR112019017560A2 (pt) | 2017-02-24 | 2020-04-07 | Merck Sharp & Dohme | intensificação da imunogenicidade dos conjugados de polissacarídeo-proteína de streptococcus pneumoniae |
| US10259865B2 (en) | 2017-03-15 | 2019-04-16 | Adma Biologics, Inc. | Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection |
| CN118356485A (zh) | 2017-06-10 | 2024-07-19 | 创赏公司 | 提供改善的免疫原性和亲合力的具有二价或多价缀合物多糖的多价缀合物疫苗 |
| US10729763B2 (en) | 2017-06-10 | 2020-08-04 | Inventprise, Llc | Mixtures of polysaccharide-protein pegylated compounds |
| MX2020000224A (es) * | 2017-07-05 | 2020-08-17 | Inventprise Llc | Purificacion de polisacárido para la produccion de vacuna utilizando enzimas líticas, filtración de flujo tangencial y cromatografía multimodal. |
| US10702596B2 (en) | 2017-07-05 | 2020-07-07 | Inventprise, Llc | Polysaccharide purification for vaccine production using lytic enzymes, tangential flow filtration, and multimode chromatography |
| WO2019050813A1 (en) | 2017-09-07 | 2019-03-14 | Merck Sharp & Dohme Corp. | ANTI-PNEUMOCOCCAL POLYSACCHARIDES AND THEIR USE IN IMMUNOGENIC CONJUGATES POLYSACCHARIDE-PROTEIN CARRIER |
| SI3678654T1 (sl) | 2017-09-07 | 2024-10-30 | Merck Sharp & Dohme Llc | Pnevmokokni polisaharidi in njihova uporaba v imunogenih polisaharidnih nosilnih proteinskih konjugatih |
| 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 |
| CN107936128B (zh) * | 2017-11-22 | 2020-07-03 | 成都欧林生物科技股份有限公司 | 一种简便有效的细菌疫苗纯化方法 |
| EP3720483A2 (en) | 2017-12-06 | 2020-10-14 | Merck Sharp&Dohme Corp. | Compositions comprising streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof |
| EP3787673A4 (en) | 2018-04-30 | 2022-04-27 | Merck Sharp & Dohme Corp. | METHODS FOR PRODUCING CAPSULAR CARRIER PROTEIN-POLYSACCHARIDE CONJUGATES OF STREPTOCOCCUS PNEUMONIAE |
| US11896656B2 (en) | 2018-04-30 | 2024-02-13 | Merck Sharp & Dohme Llc | Methods for providing a homogenous solution of lyophilized mutant diptheria toxin in dimethylsulfoxide |
| US12144855B2 (en) | 2018-04-30 | 2024-11-19 | Merck Sharp & Dohme Llc | Methods for producing streptococcus pneumoniae capsular polysaccharide carrier protein conjugates from lyospheres |
| WO2020010016A1 (en) | 2018-07-04 | 2020-01-09 | Sutrovax, Inc. | Self-adjuvanted immunogenic conjugates |
| WO2020010000A1 (en) | 2018-07-04 | 2020-01-09 | Sutrovax, Inc. | Improved methods for the preparation of immunogenic conjugates |
| EP3817775B1 (en) | 2018-07-04 | 2024-09-04 | Vaxcyte, Inc. | Improvements in immunogenic conjugates |
| MX2021000548A (es) * | 2018-07-19 | 2021-07-02 | Glaxosmithkline Biologicals Sa | Procesos para preparar polisacáridos en seco. |
| EP3893926A1 (en) | 2018-12-12 | 2021-10-20 | Pfizer Inc. | Immunogenic multiple hetero-antigen polysaccharide-protein conjugates and uses thereof |
| PE20211888A1 (es) | 2018-12-19 | 2021-09-22 | Merck Sharp & Dohme | Composiciones que comprenden conjugados de polisacarido de streptococcus pneumoniae con proteina y sus metodos de uso |
| JP7239509B6 (ja) * | 2019-02-22 | 2023-03-28 | ファイザー・インク | 細菌多糖類を精製するための方法 |
| WO2020208502A1 (en) | 2019-04-10 | 2020-10-15 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof |
| CN114728050A (zh) | 2019-07-31 | 2022-07-08 | 圣诺菲·帕斯图尔公司 | 多价肺炎球菌多糖-蛋白质缀合物组合物及其使用方法 |
| US20210070890A1 (en) * | 2019-09-06 | 2021-03-11 | Serum Institute Of India Private Limited | Method for obtaining purified bacterial polysaccharides |
| CA3171864A1 (en) * | 2020-02-21 | 2021-08-26 | Pfizer Inc. | Purification of saccharides |
| CN116075517A (zh) * | 2020-06-12 | 2023-05-05 | 巴斯夫欧洲公司 | 改进的发酵液的脱矿化与诸如寡糖的精细化学品的纯化 |
| US12053515B2 (en) | 2020-08-10 | 2024-08-06 | Inventprise, Inc. | Multivalent pneumococcal glycoconjugate vaccines containing emerging serotype 24F |
| 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 |
| GB202016165D0 (en) | 2020-10-12 | 2020-11-25 | Optivalent Ltd | Vaccine |
| WO2022084852A1 (en) | 2020-10-22 | 2022-04-28 | Pfizer Inc. | Methods for purifying bacterial polysaccharides |
| KR20230097160A (ko) | 2020-11-04 | 2023-06-30 | 화이자 인코포레이티드 | 폐렴구균 백신에 사용하기 위한 면역원성 조성물 |
| WO2022101745A2 (en) | 2020-11-10 | 2022-05-19 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| 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 |
| CA3218544A1 (en) | 2021-05-03 | 2022-11-10 | Pfizer Inc. | Vaccination against bacterial and betacoronavirus infections |
| WO2022234416A1 (en) | 2021-05-03 | 2022-11-10 | Pfizer Inc. | Vaccination against pneumoccocal and covid-19 infections |
| CA3221075A1 (en) | 2021-05-28 | 2022-12-01 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| EP4346892A2 (en) | 2021-05-28 | 2024-04-10 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| MX2024008039A (es) | 2022-01-13 | 2024-07-10 | Pfizer | Composiciones inmunogenicas que comprenden antigenos de sacaridos capsulares conjugados y usos de los mismos. |
| GB2614916A (en) | 2022-01-25 | 2023-07-26 | Optivalent Ltd | Intradermal vaccine complement |
| WO2023161817A1 (en) | 2022-02-25 | 2023-08-31 | Pfizer Inc. | Methods for incorporating azido groups in bacterial capsular polysaccharides |
| WO2024084397A1 (en) | 2022-10-19 | 2024-04-25 | Pfizer Inc. | Vaccination against pneumoccocal and covid-19 infections |
| WO2024110827A1 (en) | 2022-11-21 | 2024-05-30 | Pfizer Inc. | Methods for preparing conjugated capsular saccharide antigens and uses thereof |
| KR20250107930A (ko) | 2022-11-22 | 2025-07-14 | 화이자 인코포레이티드 | 접합된 피막 사카라이드 항원을 포함하는 면역원성 조성물 및 그의 용도 |
| AU2023403045A1 (en) | 2022-12-01 | 2025-06-12 | Pfizer Inc. | Pneumococcal conjugate vaccine formulations |
| WO2024166008A1 (en) | 2023-02-10 | 2024-08-15 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| WO2024201324A2 (en) | 2023-03-30 | 2024-10-03 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| WO2024214016A1 (en) | 2023-04-14 | 2024-10-17 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| WO2024224266A1 (en) | 2023-04-24 | 2024-10-31 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| AR132702A1 (es) | 2023-05-18 | 2025-07-23 | Merck Sharp & Dohme Llc | Compuestos y formulaciones adyuvantes útiles en vacunas neumocócicas |
| WO2024241172A2 (en) | 2023-05-19 | 2024-11-28 | Glaxosmithkline Biologicals Sa | Methods for eliciting an immune response to respiratory syncycial virus and streptococcus pneumoniae infection |
| WO2025057078A1 (en) | 2023-09-14 | 2025-03-20 | Pfizer Inc. | Adjuvanted immunogenic compositions comprising conjugated pneumococcal capsular saccharide antigens and uses thereof |
| WO2025133971A1 (en) | 2023-12-23 | 2025-06-26 | Pfizer Inc. | Improved methods for producing bacterial capsular saccharide glycoconjugates |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0002004B1 (en) | 1977-11-07 | 1982-03-24 | Ciba-Geigy Ag | Process for the manufacture of fluorinated cationic compounds and their use as surfactants |
| CA1115210A (en) * | 1977-11-28 | 1981-12-29 | Dennis J. Carlo | Pneumococcal vaccine |
| 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 |
| 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 |
| US4686102A (en) * | 1984-04-12 | 1987-08-11 | American Cyanamid Company | Multivalent pneumococcal vaccine and preparation thereof |
| JPS6170994A (ja) * | 1984-09-14 | 1986-04-11 | Daikin Ind Ltd | 環状（１→２）−β−Ｄ−グルカンの製法 |
| IT1187753B (it) * | 1985-07-05 | 1987-12-23 | Sclavo Spa | Coniugati glicoproteici ad attivita' immunogenica trivalente |
| CA2059692C (en) * | 1991-01-28 | 2004-11-16 | Peter J. Kniskern | Pneumoccoccal polysaccharide conjugate vaccine |
| US5714354A (en) * | 1995-06-06 | 1998-02-03 | American Home Products Corporation | Alcohol-free pneumococcal polysaccharide purification process |
| RU2087156C1 (ru) * | 1995-06-22 | 1997-08-20 | Леонид Николаевич Падюков | Вакцина против пневмококковой инфекции |
| KR100641490B1 (ko) * | 1997-12-23 | 2006-10-31 | 박스터 헬쓰케어 에스.에이. | 백신용도이거나 결합백신으로서 단백질에 결합되는 세균성 캡슐형 다당류의 추출 및 단리방법 |
| US6146902A (en) * | 1998-12-29 | 2000-11-14 | Aventis Pasteur, Inc. | Purification of polysaccharide-protein conjugate vaccines by ultrafiltration with ammonium sulfate solutions |
| GB0108079D0 (en) * | 2001-03-30 | 2001-05-23 | Microbial Technics Ltd | Protein |
| GB0115176D0 (en) * | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
| ES2808126T3 (es) * | 2005-04-08 | 2021-02-25 | Wyeth Llc | Separación de contaminantes de polisacárido de Streptococcus pneumoniae por manipulación del pH |
| US7709001B2 (en) * | 2005-04-08 | 2010-05-04 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| EP3311836A1 (en) * | 2005-04-08 | 2018-04-25 | Wyeth LLC | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| DK3406635T3 (da) * | 2007-03-23 | 2022-05-30 | Wyeth Llc | Afkortet oprensningsmetode til fremstilling af Streptococcus Pneumoniae-kapselpolysaccharider |
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