RU2724840C2 - Способы гликоконъюгирования и композиции - Google Patents
Способы гликоконъюгирования и композиции Download PDFInfo
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- RU2724840C2 RU2724840C2 RU2016136630A RU2016136630A RU2724840C2 RU 2724840 C2 RU2724840 C2 RU 2724840C2 RU 2016136630 A RU2016136630 A RU 2016136630A RU 2016136630 A RU2016136630 A RU 2016136630A RU 2724840 C2 RU2724840 C2 RU 2724840C2
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- Prior art keywords
- saccharide
- kda
- polysaccharide
- glycoconjugate
- etec
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| KR20220080201A (ko) | 2014-01-21 | 2022-06-14 | 화이자 인코포레이티드 | 접합된 캡슐 사카라이드 항원을 포함하는 면역원성 조성물 및 그의 용도 |
| ES2930318T3 (es) | 2014-02-14 | 2022-12-09 | Pfizer | Conjugados glucoproteicos inmunogénicos |
| KR20160132034A (ko) | 2014-03-13 | 2016-11-16 | 우니페르시테트 바젤 | 미엘린-관련 당단백질에 대한 IgM 항체와 결합하는 탄수화물 리간드 |
| DK3244917T5 (da) | 2015-01-15 | 2024-10-14 | Pfizer | Immunogene sammensætninger til anvendelse i pneumokokvacciner |
| IL255106B2 (en) * | 2015-05-04 | 2023-04-01 | Pfizer | Protein-polysaccharide conjugates of group b streptococcus, methods for preparing conjugates, immunogenic preparations containing conjugates and their uses |
| MX2017015985A (es) * | 2015-06-08 | 2018-08-15 | Serum Inst Of India Private Ltd | Metodos para mejorar la adsorcion de conjugados de polisacarido-proteina y formulacion de vacuna multivalente obtenida con los mismos. |
| KR102800419B1 (ko) * | 2015-07-21 | 2025-04-25 | 화이자 인코포레이티드 | 접합된 캡슐형 사카라이드 항원을 포함하는 면역원성 조성물, 그를 포함하는 키트 및 그의 용도 |
| HK1252262A1 (zh) * | 2015-09-16 | 2019-05-24 | 巴塞尔大学 | 结合抗糖鞘脂糖蛋白表位抗体的碳水化合物配体 |
| CA3005524C (en) | 2015-11-20 | 2023-10-10 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
| 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 |
| KR20190044663A (ko) | 2016-09-02 | 2019-04-30 | 사노피 파스퇴르 인크 | 네이세리아 메닌기티디스 백신 |
| US11951165B2 (en) | 2016-12-30 | 2024-04-09 | Vaxcyte, Inc. | Conjugated vaccine carrier proteins |
| KR20190103256A (ko) | 2016-12-30 | 2019-09-04 | 수트로박스, 인코포레이티드 | 비자연 아미노산을 갖는 폴리펩타이드-항원 접합체 |
| MX392525B (es) | 2017-01-20 | 2025-03-12 | Pfizer | Composiciones inmunogenicas para su uso en vacunas neumococicas |
| CN111132691A (zh) | 2017-06-10 | 2020-05-08 | 创赏有限公司 | 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 |
| BR112020004396A8 (pt) | 2017-09-07 | 2023-01-31 | Merck Sharp & Dohme | Polissacarídeos pneumocócicos e uso dos mesmos em conjugados imunogênicos polissacarídeo-proteína carreadora |
| AU2018328040B2 (en) | 2017-09-07 | 2025-01-16 | Merck Sharp & Dohme Llc | Processes for the formulation of pneumococcal polysaccharides for conjugation to a carrier protein |
| 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 |
| AU2019239890B2 (en) * | 2018-03-23 | 2025-01-30 | Koranex Capital | Precision glycoconjugates as therapeutic tools |
| 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 |
| US11260119B2 (en) * | 2018-08-24 | 2022-03-01 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
| 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 |
| US20220184199A1 (en) | 2019-04-10 | 2022-06-16 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof |
| CN111024832B (zh) * | 2019-10-29 | 2022-05-03 | 北京成大天和生物科技有限公司 | 多糖结合疫苗中残余NaCNBH3的离子色谱检测方法 |
| MX2022005252A (es) | 2019-11-01 | 2022-06-08 | Pfizer | Composiciones de escherichia coli y metodos de las mismas. |
| US20230085173A1 (en) | 2020-02-21 | 2023-03-16 | Pfizer Inc. | Purification of saccharides |
| CA3173729A1 (en) | 2020-02-23 | 2021-08-26 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
| EP4192499A4 (en) | 2020-08-10 | 2024-09-25 | Inventprise, Inc. | Multivalent pneumococcal glycoconjugate vaccines containing emerging serotype 24f |
| KR20230043157A (ko) | 2020-09-17 | 2023-03-30 | 얀센 파마슈티칼즈, 인코포레이티드 | 다가 백신 조성물 및 이의 용도 |
| CA3199094A1 (en) | 2020-10-22 | 2022-04-28 | Pfizer Inc. | Methods for purifying bacterial polysaccharides |
| TW202227467A (zh) | 2020-10-27 | 2022-07-16 | 美商輝瑞大藥廠 | 大腸桿菌組合物及其方法 |
| US12138302B2 (en) | 2020-10-27 | 2024-11-12 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
| EP4240410A1 (en) | 2020-11-04 | 2023-09-13 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
| US12357681B2 (en) | 2020-12-23 | 2025-07-15 | Pfizer Inc. | E. coli FimH mutants and uses thereof |
| 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 |
| WO2022249107A2 (en) | 2021-05-28 | 2022-12-01 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| JP7714690B2 (ja) | 2021-05-28 | 2025-07-29 | ファイザー・インク | コンジュゲートさせた莢膜糖抗原を含む免疫原性組成物およびその使用 |
| WO2024084397A1 (en) | 2022-10-19 | 2024-04-25 | Pfizer Inc. | Vaccination against pneumoccocal and covid-19 infections |
| IL321062A (en) | 2022-11-22 | 2025-07-01 | Pfizer | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| IL321069A (en) | 2022-12-01 | 2025-07-01 | Pfizer | Pneumococcal conjugate vaccine preparations |
| AU2024246082A1 (en) | 2023-03-30 | 2025-10-16 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| CN121057590A (zh) | 2023-04-14 | 2025-12-02 | 辉瑞公司 | 包含缀合荚膜糖抗原的免疫原性组合物及其用途 |
| WO2024224266A1 (en) | 2023-04-24 | 2024-10-31 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| 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 |
| TW202527906A (zh) | 2023-09-14 | 2025-07-16 | 美商輝瑞股份有限公司 | 包含經結合之肺炎鏈球菌莢膜醣抗原之佐劑化致免疫性組成物及其用途 |
| WO2025186705A2 (en) | 2024-03-06 | 2025-09-12 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
| WO2025191415A1 (en) | 2024-03-11 | 2025-09-18 | Pfizer Inc. | Immunogenic compositions comprising conjugated escherichia coli saccharides and uses thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007071707A2 (en) * | 2005-12-22 | 2007-06-28 | Glaxosmithkline Biologicals Sa | Pneumococcal polysaccharide conjugate vaccine |
| WO2007141077A1 (de) * | 2006-06-07 | 2007-12-13 | Continental Aktiengesellschaft | Verfahren und messfahrzeug zur ermittlung objektiver reifeneigenschaften auf einer fahrbahnoberfläche |
| WO2008157590A1 (en) * | 2007-06-20 | 2008-12-24 | Baxter International Inc. | Modified polysaccharides for conjugate vaccines |
| RU2378015C2 (ru) * | 2008-04-02 | 2010-01-10 | Равшан Иноятович Атауллаханов | Конъюгат для иммунизации и вакцинации и способ повышения иммуногенности |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US578573A (en) | 1897-03-09 | Brake-actuating mechanism | ||
| US4708871A (en) | 1983-03-08 | 1987-11-24 | Commonwealth Serum Laboratories Commission | Antigenically active amino acid sequences |
| US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
| US4912094B1 (en) | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
| HU212924B (en) | 1989-05-25 | 1996-12-30 | Chiron Corp | Adjuvant formulation comprising a submicron oil droplet emulsion |
| IL101715A (en) | 1991-05-02 | 2005-06-19 | Amgen Inc | Recombinant dna-derived cholera toxin subunit analogs |
| WO1993013302A1 (de) | 1991-12-23 | 1993-07-08 | Michael Zoche | Motor mit einer vorrichtung zur entölung |
| ATE280235T1 (de) | 1993-03-05 | 2004-11-15 | Wyeth Corp | Plasmid zur herstellung von crm-protein und diphtherie-toxin |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6113918A (en) | 1997-05-08 | 2000-09-05 | Ribi Immunochem Research, Inc. | Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors |
| AU8070898A (en) | 1997-06-12 | 1998-12-30 | Shin-Etsu Bio, Inc. | Production of non-native bacterial exopolysaccharide in a recombinant bacteri al host |
| ES2293735T3 (es) | 1998-09-30 | 2008-03-16 | Wyeth Holdings Corporation | Holotoxina del colera mutante como coadyuvante. |
| US6936258B1 (en) | 1999-03-19 | 2005-08-30 | Nabi Biopharmaceuticals | Staphylococcus antigen and vaccine |
| DE19926475A1 (de) * | 1999-06-10 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Träger-Pharmaka-Konjugate |
| JP2005504718A (ja) * | 2001-01-23 | 2005-02-17 | アヴェンティス パストゥール | 多価髄膜炎菌多糖−タンパク質複合ワクチン |
| US7285281B2 (en) | 2001-06-07 | 2007-10-23 | Wyeth Holdings Corporation | Mutant forms of cholera holotoxin as an adjuvant |
| CN1541111A (zh) | 2001-06-07 | 2004-10-27 | ���Ͽع�����˾ | 作为佐剂的霍乱全毒素的突变形式 |
| CN1394867A (zh) * | 2001-07-06 | 2003-02-05 | 中国科学院生态环境研究中心 | 可作药物的寡糖和其制备方法及含该寡糖的药物组合物 |
| AU2003277139A1 (en) * | 2002-10-03 | 2004-04-23 | Wyeth Holdings Corporation | Process for preparing monoprotected diols from symmetric diols |
| CA2517439C (en) * | 2003-03-07 | 2013-07-23 | Wyeth Holdings Corporation | Polysaccharide - staphylococcal surface adhesin carrier protein conjugates for immunization against nosocomial infections |
| EP1603950A2 (en) | 2003-03-17 | 2005-12-14 | Wyeth Holdings Corporation | Mutant cholera holotoxin as an adjuvant and an antigen carrier protein |
| GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
| CA2562962A1 (en) * | 2004-04-14 | 2005-11-10 | Wyeth | Process for preparing rapamycin 42-esters and fk-506 32-esters with dicarboxylic acid, precursors for rapamycin conjugates and antibodies |
| US7910753B2 (en) * | 2004-09-10 | 2011-03-22 | Anaspec Incorporated | Cyanine dyes and their applications as luminescence quenching compounds |
| 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 |
| GB0513069D0 (en) * | 2005-06-27 | 2005-08-03 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| TWI457133B (zh) * | 2005-12-13 | 2014-10-21 | Glaxosmithkline Biolog Sa | 新穎組合物 |
| TW200806685A (en) * | 2006-02-21 | 2008-02-01 | Wyeth Corp | Processes for the convergent synthesis of calicheamicin derivatives |
| EP1993610A2 (en) * | 2006-03-07 | 2008-11-26 | Wyeth | Process for preparing water-soluble polyethylene glycol conjugates of macrolide immunosuppressants |
| WO2007127668A2 (en) | 2006-04-26 | 2007-11-08 | Wyeth | Novel processes for coating container means which inhibit precipitation of polysaccharide-protein conjugate formulations |
| EP3461496B1 (en) * | 2009-06-22 | 2023-08-23 | Wyeth LLC | Compositions and methods for preparing staphylococcus aureus serotype 5 and 8 capsular polysaccharide conjugate immunogenic compositions |
| CA2766614C (en) * | 2009-07-03 | 2018-06-19 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Compounds targeting the cation-independent mannose 6-phosphate receptor |
| KR101567901B1 (ko) * | 2009-11-24 | 2015-11-10 | 그리폴스 테라퓨틱스 인코포레이티드 | 동결건조 방법, 조성물, 및 키트 |
| US20130273098A1 (en) * | 2010-12-10 | 2013-10-17 | Jeffrey T. Blue | Novel formulations which mitigate agitation-induced aggregation of immunogenic compositions |
| CA2848142C (en) * | 2011-09-07 | 2021-05-18 | Prolynx Llc | Hydrogels with biodegradable crosslinking |
| IN2015DN00694A (enExample) | 2012-08-16 | 2015-06-26 | Pfizer | |
| KR20220080201A (ko) | 2014-01-21 | 2022-06-14 | 화이자 인코포레이티드 | 접합된 캡슐 사카라이드 항원을 포함하는 면역원성 조성물 및 그의 용도 |
| ES2930318T3 (es) | 2014-02-14 | 2022-12-09 | Pfizer | Conjugados glucoproteicos inmunogénicos |
-
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-
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- 2023-06-21 US US18/338,961 patent/US12447203B2/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007071707A2 (en) * | 2005-12-22 | 2007-06-28 | Glaxosmithkline Biologicals Sa | Pneumococcal polysaccharide conjugate vaccine |
| WO2007141077A1 (de) * | 2006-06-07 | 2007-12-13 | Continental Aktiengesellschaft | Verfahren und messfahrzeug zur ermittlung objektiver reifeneigenschaften auf einer fahrbahnoberfläche |
| WO2008157590A1 (en) * | 2007-06-20 | 2008-12-24 | Baxter International Inc. | Modified polysaccharides for conjugate vaccines |
| RU2378015C2 (ru) * | 2008-04-02 | 2010-01-10 | Равшан Иноятович Атауллаханов | Конъюгат для иммунизации и вакцинации и способ повышения иммуногенности |
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