CA3031797A1 - Multivalent pneumococcal polysaccharide-protein conjugate composition - Google Patents
Multivalent pneumococcal polysaccharide-protein conjugate composition Download PDFInfo
- Publication number
- CA3031797A1 CA3031797A1 CA3031797A CA3031797A CA3031797A1 CA 3031797 A1 CA3031797 A1 CA 3031797A1 CA 3031797 A CA3031797 A CA 3031797A CA 3031797 A CA3031797 A CA 3031797A CA 3031797 A1 CA3031797 A1 CA 3031797A1
- Authority
- CA
- Canada
- Prior art keywords
- serotypes
- conjugated
- serotype
- capsular polysaccharides
- mixed carrier
- 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.)
- Pending
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| US11160855B2 (en) | 2014-01-21 | 2021-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| CA3031797A1 (en) | 2016-08-05 | 2018-02-08 | Sanofi Pasteur, Inc. | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| KR102437120B1 (ko) | 2016-08-05 | 2022-08-25 | 사노피 파스퇴르 인코포레이티드 | 다가 폐렴구균 다당류-단백질 접합체 조성물 |
| US10729763B2 (en) | 2017-06-10 | 2020-08-04 | Inventprise, Llc | Mixtures of polysaccharide-protein pegylated compounds |
| CN111417884B (zh) * | 2017-12-01 | 2022-07-29 | 浜松光子学株式会社 | 致动器装置 |
| MX2020005779A (es) | 2017-12-06 | 2020-10-28 | Merck Sharp & Dohme | Composiciones que comprenden conjugados de polisacarido de streptococcus pneumoniae con proteina y metodos de uso de estos. |
| BR112020014978A2 (pt) * | 2018-02-05 | 2020-12-22 | Sanofi Pasteur, Inc. | Composição de conjugado polissacarídeo-proteína pneumocócico multivalente |
| CA3089007A1 (en) * | 2018-02-05 | 2019-08-08 | Sanofi Pasteur Inc. | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| TW202011985A (zh) | 2018-04-18 | 2020-04-01 | 韓商Ｓｋ生物科學股份有限公司 | 肺炎鏈球菌的莢膜多醣類以及其免疫原性接合體 |
| KR20240169145A (ko) | 2018-12-19 | 2024-12-02 | 머크 샤프 앤드 돔 엘엘씨 | 스트렙토코쿠스 뉴모니아에 폴리사카라이드-단백질 접합체를 포함하는 조성물 및 그의 사용 방법 |
| MX2022001241A (es) * | 2019-07-31 | 2022-04-20 | Sanofi Pasteur Inc | Composiciones de conjugados neumococicos multivalentes polisacarido - proteina y metodos para usar los mismos. |
| KR20230047827A (ko) * | 2021-10-01 | 2023-04-10 | 에스케이바이오사이언스(주) | 향상된 효능을 갖는 알루미늄계 애주번트를 제조하는 방법 |
Family Cites Families (98)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0027888B1 (en) | 1979-09-21 | 1986-04-16 | Hitachi, Ltd. | Semiconductor switch |
| US4270537A (en) | 1979-11-19 | 1981-06-02 | Romaine Richard A | Automatic hypodermic syringe |
| US4673574A (en) | 1981-08-31 | 1987-06-16 | Anderson Porter W | Immunogenic conjugates |
| US4902506A (en) | 1983-07-05 | 1990-02-20 | The University Of Rochester | Immunogenic conjugates |
| US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US4886499A (en) | 1986-12-18 | 1989-12-12 | Hoffmann-La Roche Inc. | Portable injection appliance |
| GB8704027D0 (en) | 1987-02-20 | 1987-03-25 | Owen Mumford Ltd | Syringe needle combination |
| US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US4940460A (en) | 1987-06-19 | 1990-07-10 | Bioject, Inc. | Patient-fillable and non-invasive hypodermic injection device assembly |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US5339163A (en) | 1988-03-16 | 1994-08-16 | Canon Kabushiki Kaisha | Automatic exposure control device using plural image plane detection areas |
| FR2638359A1 (fr) | 1988-11-03 | 1990-05-04 | Tino Dalto | Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5190521A (en) | 1990-08-22 | 1993-03-02 | Tecnol Medical Products, Inc. | Apparatus and method for raising a skin wheal and anesthetizing skin |
| NZ239643A (en) * | 1990-09-17 | 1996-05-28 | North American Vaccine Inc | Vaccine containing bacterial polysaccharide protein conjugate and adjuvant (c-nd-che-a-co-b-r) with a long chain alkyl group. |
| US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
| CA2059693C (en) | 1991-01-28 | 2003-08-19 | Peter J. Kniskern | Polysaccharide antigens from streptococcus pneumoniae |
| GB9118204D0 (en) | 1991-08-23 | 1991-10-09 | Weston Terence E | Needle-less injector |
| SE9102652D0 (sv) | 1991-09-13 | 1991-09-13 | Kabi Pharmacia Ab | Injection needle arrangement |
| KR950700081A (ko) | 1992-02-11 | 1995-01-16 | W 로우 죤 | 이중 캐리어 면역원성 구성물 |
| US5328483A (en) | 1992-02-27 | 1994-07-12 | Jacoby Richard M | Intradermal injection device with medication and needle guard |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| US5569189A (en) | 1992-09-28 | 1996-10-29 | Equidyne Systems, Inc. | hypodermic jet injector |
| US5334144A (en) | 1992-10-30 | 1994-08-02 | Becton, Dickinson And Company | Single use disposable needleless injector |
| ATE280235T1 (de) | 1993-03-05 | 2004-11-15 | Wyeth Corp | Plasmid zur herstellung von crm-protein und diphtherie-toxin |
| ATE254475T1 (de) | 1993-09-22 | 2003-12-15 | Jackson H M Found Military Med | Verfahren zur aktivierung von löslichem kohlenhydraten durch verwendung von neuen cyanylierungsreagenzien, zur herstellung von immunogenischen konstrukten |
| WO1995024176A1 (en) | 1994-03-07 | 1995-09-14 | Bioject, Inc. | Ampule filling device |
| US5466220A (en) | 1994-03-08 | 1995-11-14 | Bioject, Inc. | Drug vial mixing and transfer device |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| EP0772619B2 (en) | 1994-07-15 | 2010-12-08 | The University of Iowa Research Foundation | Immunomodulatory oligonucleotides |
| US6429199B1 (en) | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
| WO1996025425A1 (en) | 1995-02-16 | 1996-08-22 | Massachusetts Health Research Institute, Inc. | Purified tetanus toxoid and toxin |
| EP0814833B1 (en) | 1995-03-22 | 2003-05-28 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Producing immunogenic constructs using soluble carbohydrates activated via organic cyanylating reagents |
| US5730723A (en) | 1995-10-10 | 1998-03-24 | Visionary Medical Products Corporation, Inc. | Gas pressured needle-less injection device and method |
| CA2153730A1 (en) | 1995-07-12 | 1997-01-13 | Andrew J. Malcolm | Immunostimulating activity of streptococcus pneumoniae serotype 8 oligosaccharides |
| 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 |
| CA2153733A1 (en) | 1995-07-12 | 1997-01-13 | Andrew J. Malcolm | Immunogenic oligosaccharide compositions |
| CZ327897A3 (cs) | 1995-06-07 | 1998-02-18 | Alberta Research Council | Imunogenní a imunostimulační oligosacharidové kompozice, způsoby jejich přípravy a použití |
| US5893397A (en) | 1996-01-12 | 1999-04-13 | Bioject Inc. | Medication vial/syringe liquid-transfer apparatus |
| GB9607549D0 (en) | 1996-04-11 | 1996-06-12 | Weston Medical Ltd | Spring-powered dispensing device |
| AU738513B2 (en) | 1997-02-28 | 2001-09-20 | University Of Iowa Research Foundation, The | Use of nucleic acids containing unmethylated CpG dinucleotide in the treatment of LPS-associated disorders |
| US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| US6299881B1 (en) | 1997-03-24 | 2001-10-09 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Uronium salts for activating hydroxyls, carboxyls, and polysaccharides, and conjugate vaccines, immunogens, and other useful immunological reagents produced using uronium salts |
| FR2763244B1 (fr) * | 1997-05-14 | 2003-08-01 | Pasteur Merieux Serums Vacc | Composition vaccinale multivalente a porteur mixte |
| US5993412A (en) | 1997-05-19 | 1999-11-30 | Bioject, Inc. | Injection apparatus |
| DE69838294T2 (de) | 1997-05-20 | 2009-08-13 | Ottawa Health Research Institute, Ottawa | Verfahren zur Herstellung von Nukleinsäurekonstrukten |
| IT1298087B1 (it) | 1998-01-08 | 1999-12-20 | Fiderm S R L | Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni |
| ES2284247T3 (es) | 1998-04-03 | 2007-11-01 | University Of Iowa Research Foundation | Metodos y productos para estimular el sistema inmunitario usando oligonucleotidos y citoquinas inmunoterapeuticos. |
| EP1162999B1 (en) | 1999-03-19 | 2006-11-29 | Glaxosmithkline Biologicals S.A. | Vaccine against Streptococcus pneumoniae |
| FR2806304B1 (fr) * | 2000-03-17 | 2002-05-10 | Aventis Pasteur | Conjugues polysaccharidiques du pneumocoque a usage vaccinal contre le tetanos et la diphterie |
| GB0108364D0 (en) | 2001-04-03 | 2001-05-23 | Glaxosmithkline Biolog Sa | Vaccine composition |
| CZ20024224A3 (cs) | 2000-06-29 | 2003-05-14 | Glaxosmithkline Biologicals S. A. | Farmaceutický prostředek |
| MXPA03005386A (es) | 2000-12-28 | 2004-04-20 | Wyeth Corp | Proteina protectora recombinante de streptococcus pneumoniae. |
| AU2007200116A1 (en) | 2001-04-03 | 2007-02-01 | Glaxosmithkline Biologicals S.A. | Vaccine composition |
| KR100886095B1 (ko) | 2001-04-16 | 2009-02-27 | 와이어쓰 홀딩스 코포레이션 | 폴리펩티드 항원을 암호화하는 신규한 스트렙토코쿠스 뉴모니애 개방형 판독 프레임 및 이를 포함하는 조성물 |
| TWI341210B (en) | 2002-04-01 | 2011-05-01 | Glaxosmithkline Biolog Sa | Vaccine kit |
| TWI346555B (en) | 2002-04-01 | 2011-08-11 | Glaxosmithkline Biolog Sa | Vaccine composition |
| DE602004010376T2 (de) | 2003-03-13 | 2008-10-23 | Glaxosmithkline Biologicals S.A. | Verfahren zur reinigung von bakteriellem cytolysin |
| US7320874B2 (en) | 2003-07-08 | 2008-01-22 | Aventis Pasteur Sa | Assaying the teichoic acids of gram+ bacteria |
| GB0421083D0 (en) | 2004-09-22 | 2004-10-27 | Glaxosmithkline Biolog Sa | Purification process |
| US7709001B2 (en) | 2005-04-08 | 2010-05-04 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| US20070184072A1 (en) | 2005-04-08 | 2007-08-09 | Wyeth | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| CN104815327A (zh) | 2005-04-08 | 2015-08-05 | 惠氏有限责任公司 | 多价肺炎球菌多糖-蛋白质缀合物组合物 |
| AU2006234984B2 (en) | 2005-04-08 | 2011-10-13 | Wyeth | Separation of contaminants from Streptococcus pneumoniae polysaccharide by pH manipulation |
| US7955605B2 (en) | 2005-04-08 | 2011-06-07 | Wyeth Llc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| PL3017827T3 (pl) * | 2005-12-22 | 2019-04-30 | Glaxosmithkline Biologicals Sa | Szczepionka z koniugatem polisacharydu pneumokokowego |
| US8808707B1 (en) | 2006-05-08 | 2014-08-19 | Wyeth Llc | Pneumococcal dosing regimen |
| PT2074221E (pt) | 2006-10-10 | 2010-09-06 | Wyeth Llc | Métodos melhorados para a separação de polissacáridos tipo 3 de streptococcus pneumoniae |
| PT2129693T (pt) | 2007-03-23 | 2017-02-14 | Wyeth Llc | Processo de purificação abreviado para a produção de polissacáridos capsulares de streptococcus pneumoniae |
| US9610339B2 (en) | 2007-06-26 | 2017-04-04 | Glaxosmithkline Biologicals, S.A. | Vaccine comprising Streptococcus pneumoniae capsular polysaccharide conjugates |
| KR101450958B1 (ko) | 2009-04-30 | 2014-10-15 | 콜레이 파마시티컬 그룹, 인코포레이티드 | 폐렴구균 백신 및 그의 용도 |
| TW201136603A (en) | 2010-02-09 | 2011-11-01 | Merck Sharp & Amp Dohme Corp | 15-valent pneumococcal polysaccharide-protein conjugate vaccine composition |
| CN101785857B (zh) | 2010-03-05 | 2012-09-26 | 成都安特金生物技术有限公司 | 一种新的肺炎球菌结合疫苗及其制备方法 |
| GB201003920D0 (en) | 2010-03-09 | 2010-04-21 | Glaxosmithkline Biolog Sa | Method of treatment |
| CN102068690A (zh) | 2010-12-31 | 2011-05-25 | 北京民海生物科技有限公司 | 多价肺炎球菌荚膜多糖结合疫苗及其制备方法 |
| KR102057217B1 (ko) | 2012-06-20 | 2020-01-22 | 에스케이바이오사이언스 주식회사 | 다가 폐렴구균 다당류-단백질 접합체 조성물 |
| IN2015DN00694A (enExample) | 2012-08-16 | 2015-06-26 | Pfizer | |
| CN103656631B (zh) * | 2012-09-24 | 2015-08-19 | 北京科兴中维生物技术有限公司 | 多价肺炎球菌荚膜多糖-蛋白缀合物组合物及其制备方法 |
| CN103656632B (zh) | 2012-09-24 | 2016-01-13 | 北京科兴中维生物技术有限公司 | 多价肺炎球菌荚膜多糖组合物、其制备方法及应用 |
| KR20140075196A (ko) | 2012-12-11 | 2014-06-19 | 에스케이케미칼주식회사 | 다가 폐렴구균 다당류-단백질 접합체 조성물 |
| ITMI20130142A1 (it) | 2013-01-31 | 2014-08-01 | Biosynth Srl | Vaccini glicoconiugati comprendenti unita' di base di un costrutto molecolare esprimente epitopi multipli incorporati |
| BR112016015835B1 (pt) | 2014-01-21 | 2023-12-26 | Pfizer Inc | Processo de preparação de conjugados compreendendo polissacarídeos capsulares de streptococcus pneumoniae |
| CA2937190A1 (en) | 2014-01-21 | 2015-07-30 | Pfizer Inc. | Streptococcus pneumoniae capsular polysaccharides and conjugates thereof |
| KR20220080201A (ko) * | 2014-01-21 | 2022-06-14 | 화이자 인코포레이티드 | 접합된 캡슐 사카라이드 항원을 포함하는 면역원성 조성물 및 그의 용도 |
| CN107029225B (zh) | 2014-07-25 | 2020-08-11 | 武汉博沃生物科技有限公司 | 一种缀合疫苗及其制备方法 |
| DK3244917T5 (da) | 2015-01-15 | 2024-10-14 | Pfizer | Immunogene sammensætninger til anvendelse i pneumokokvacciner |
| GB201518684D0 (en) | 2015-10-21 | 2015-12-02 | Glaxosmithkline Biolog Sa | Vaccine |
| CA3005524C (en) | 2015-11-20 | 2023-10-10 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
| CN106140046B (zh) | 2016-07-06 | 2019-02-22 | 江南大学 | 阵列式感应电场流体反应系统及其应用 |
| KR102437120B1 (ko) | 2016-08-05 | 2022-08-25 | 사노피 파스퇴르 인코포레이티드 | 다가 폐렴구균 다당류-단백질 접합체 조성물 |
| CA3031797A1 (en) | 2016-08-05 | 2018-02-08 | Sanofi Pasteur, Inc. | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| CA3089007A1 (en) | 2018-02-05 | 2019-08-08 | Sanofi Pasteur Inc. | Multivalent pneumococcal polysaccharide-protein conjugate composition |
| BR112020014978A2 (pt) | 2018-02-05 | 2020-12-22 | Sanofi Pasteur, Inc. | Composição de conjugado polissacarídeo-proteína pneumocócico multivalente |
| MX2022001241A (es) | 2019-07-31 | 2022-04-20 | Sanofi Pasteur Inc | Composiciones de conjugados neumococicos multivalentes polisacarido - proteina y metodos para usar los mismos. |
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2017
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- 2017-08-04 MX MX2019001341A patent/MX2019001341A/es unknown
- 2017-08-04 WO PCT/US2017/045479 patent/WO2018027123A1/en not_active Ceased
- 2017-08-04 JP JP2019527779A patent/JP7001686B2/ja active Active
- 2017-08-04 CN CN201780061960.0A patent/CN109890415B/zh active Active
- 2017-08-04 AR ARP170102206A patent/AR109290A1/es not_active Application Discontinuation
- 2017-08-04 SG SG11201900789VA patent/SG11201900789VA/en unknown
- 2017-08-04 EA EA201990126A patent/EA039427B1/ru unknown
- 2017-08-04 BR BR112019001995-2A patent/BR112019001995A2/pt unknown
- 2017-08-04 EP EP17837752.9A patent/EP3493840B1/en active Active
- 2017-08-04 US US16/322,698 patent/US11224652B2/en active Active
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2019
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- 2019-03-04 ZA ZA2019/01345A patent/ZA201901345B/en unknown
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| CN109890415B (zh) | 2023-04-04 |
| KR102467074B1 (ko) | 2022-11-11 |
| AU2017306708A1 (en) | 2019-02-14 |
| IL264553A (en) | 2019-02-28 |
| CN109890415A (zh) | 2019-06-14 |
| SG11201900789VA (en) | 2019-02-27 |
| TWI770044B (zh) | 2022-07-11 |
| TW201811362A (zh) | 2018-04-01 |
| EP3493840A4 (en) | 2020-04-08 |
| KR20190051945A (ko) | 2019-05-15 |
| IL264553B (en) | 2022-12-01 |
| AR109290A1 (es) | 2018-11-14 |
| SA519401028B1 (ar) | 2023-10-01 |
| AU2017306708B2 (en) | 2021-08-26 |
| EA201990126A1 (ru) | 2019-08-30 |
| PH12019500238B1 (en) | 2023-05-10 |
| EP3493840B1 (en) | 2022-08-24 |
| EA039427B1 (ru) | 2022-01-26 |
| JP7001686B2 (ja) | 2022-02-04 |
| WO2018027123A1 (en) | 2018-02-08 |
| MY199342A (en) | 2023-10-24 |
| US20200230233A1 (en) | 2020-07-23 |
| US11224652B2 (en) | 2022-01-18 |
| BR112019001995A2 (pt) | 2019-05-07 |
| EP3493840A1 (en) | 2019-06-12 |
| MX2019001341A (es) | 2019-07-04 |
| IL264553B2 (en) | 2023-04-01 |
| PH12019500238A1 (en) | 2019-10-21 |
| ZA201901345B (en) | 2024-09-25 |
| JP2019526620A (ja) | 2019-09-19 |
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