JP4378445B2 - 免疫調節化合物およびその使用方法 - Google Patents
免疫調節化合物およびその使用方法 Download PDFInfo
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- JP4378445B2 JP4378445B2 JP2003516455A JP2003516455A JP4378445B2 JP 4378445 B2 JP4378445 B2 JP 4378445B2 JP 2003516455 A JP2003516455 A JP 2003516455A JP 2003516455 A JP2003516455 A JP 2003516455A JP 4378445 B2 JP4378445 B2 JP 4378445B2
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- Prior art keywords
- alkyl
- alkoxy
- group
- added
- compound
- Prior art date
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- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
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- -1 methylene, amino Chemical group 0.000 claims description 33
- 238000009472 formulation Methods 0.000 claims description 25
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/918,849 US6551600B2 (en) | 1999-02-01 | 2001-07-31 | Immunological adjuvant compounds compositions and methods of use thereof |
| PCT/US2002/024258 WO2003011223A2 (en) | 2001-07-31 | 2002-07-31 | Immunomodulatory compounds and methods of use thereof |
Publications (3)
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| JP2005504749A JP2005504749A (ja) | 2005-02-17 |
| JP2005504749A5 JP2005504749A5 (https=) | 2006-01-19 |
| JP4378445B2 true JP4378445B2 (ja) | 2009-12-09 |
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| JP2003516455A Expired - Lifetime JP4378445B2 (ja) | 2001-07-31 | 2002-07-31 | 免疫調節化合物およびその使用方法 |
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| US (1) | US6551600B2 (https=) |
| EP (1) | EP1420825A4 (https=) |
| JP (1) | JP4378445B2 (https=) |
| AU (1) | AU2002330943A1 (https=) |
| WO (1) | WO2003011223A2 (https=) |
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| CA2611721C (en) | 2005-06-30 | 2014-04-22 | Eisai Co., Ltd. | Compounds for preparing immunological adjuvant |
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| JP5399410B2 (ja) * | 2007-12-18 | 2014-01-29 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 免疫アジュバントe6020への合成前駆体のベータ−ケトアミド合成のための試薬および方法 |
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| AR075437A1 (es) | 2009-02-17 | 2011-03-30 | Glaxosmithkline Biolog Sa | Composicion inmunogenica que comprende al menos un antigeno del virus del dengue inactivado y un adyuvante sin aluminio, metodo para producir dicha vacuna y su uso para preparar un medicamento |
| CA2754618A1 (en) | 2009-03-06 | 2010-09-10 | Novartis Ag | Chlamydia antigens |
| MX2011010735A (es) | 2009-04-14 | 2012-01-25 | Novartis Ag | Composiciones para inmunizacion contra staphylococcus aureus. |
| FR2949344A1 (fr) | 2009-04-27 | 2011-03-04 | Novartis Ag | Vaccins de protection contre la grippe |
| MX2012000035A (es) | 2009-06-24 | 2012-02-28 | Id Biomedical Corp Quebec | Antigenos de virus de sincicio respiratorio recombinantes. |
| AU2010264686A1 (en) | 2009-06-24 | 2012-01-19 | Glaxosmithkline Biologicals S.A. | Vaccine |
| US9907746B2 (en) | 2009-07-06 | 2018-03-06 | Variation Biotechnologies, Inc. | Methods for preparing vesicles and formulations produced therefrom |
| AU2010270722B2 (en) | 2009-07-06 | 2015-06-04 | Variation Biotechnologies, Inc. | Methods for preparing vesicles and formulations produced therefrom |
| WO2011004263A2 (en) | 2009-07-07 | 2011-01-13 | Novartis Ag | Conserved escherichia coli immunogens |
| EP4218799A1 (en) | 2009-07-15 | 2023-08-02 | GlaxoSmithKline Biologicals S.A. | Rsv f protein compositions and methods for making same |
| PL2464658T3 (pl) | 2009-07-16 | 2015-03-31 | Novartis Ag | Immunogeny z Escherichia coli o zniesionej toksyczności |
| GB0918392D0 (en) | 2009-10-20 | 2009-12-02 | Novartis Ag | Diagnostic and therapeutic methods |
| GB0919117D0 (en) | 2009-10-30 | 2009-12-16 | Glaxosmithkline Biolog Sa | Process |
| GB0919690D0 (en) | 2009-11-10 | 2009-12-23 | Guy S And St Thomas S Nhs Foun | compositions for immunising against staphylococcus aureus |
| JP5781542B2 (ja) | 2009-12-30 | 2015-09-24 | ノバルティス アーゲー | E.coliキャリアタンパク質に結合体化した多糖免疫原 |
| KR20130121699A (ko) | 2010-05-28 | 2013-11-06 | 테트리스 온라인, 인코포레이티드 | 상호작용 혼성 비동기 컴퓨터 게임 기반구조 |
| CA2801151A1 (en) | 2010-06-01 | 2011-12-08 | Novartis Ag | Concentration of vaccine antigens with lyophilization |
| EP2575872B1 (en) | 2010-06-01 | 2020-08-19 | Seqirus UK Limited | Concentration of influenza vaccine antigens without lyophilization |
| GB201009861D0 (en) | 2010-06-11 | 2010-07-21 | Novartis Ag | OMV vaccines |
| US9192661B2 (en) | 2010-07-06 | 2015-11-24 | Novartis Ag | Delivery of self-replicating RNA using biodegradable polymer particles |
| MX342138B (es) | 2010-07-06 | 2016-09-14 | Variation Biotechnologies Inc | Composiciones y metodos para el tratamiento de influenza. |
| ES2531577T3 (es) | 2010-08-20 | 2015-03-17 | Novartis Ag | Conjuntos de agujas para la administración de vacuna soluble contra la gripe |
| PL2651436T3 (pl) | 2010-12-14 | 2016-10-31 | Kompozycja antygenów mykobakteryjnych | |
| CA2862864C (en) | 2011-01-13 | 2018-12-11 | Variation Biotechnologies Inc. | Compositions and methods for treating viral infections |
| AU2012211278B2 (en) | 2011-01-26 | 2016-11-10 | Glaxosmithkline Biologicals Sa | RSV immunization regimen |
| DK2707385T3 (da) | 2011-05-13 | 2017-11-20 | Glaxosmithkline Biologicals Sa | RSV-F-præfusionsantigener |
| WO2012167088A1 (en) | 2011-06-03 | 2012-12-06 | 3M Innovative Properties Company | Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom |
| EP3153180A1 (en) | 2011-06-03 | 2017-04-12 | 3M Innovative Properties Company | Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom |
| WO2013009564A1 (en) | 2011-07-08 | 2013-01-17 | Novartis Ag | Tyrosine ligation process |
| EP2776069A1 (en) | 2011-11-07 | 2014-09-17 | Novartis AG | Carrier molecule comprising a spr0096 and a spr2021 antigen |
| US20140356399A1 (en) | 2012-01-12 | 2014-12-04 | Variation Biotechnologies, Inc. | Compositions and methods for treating viral infections |
| US20150079077A1 (en) | 2012-01-27 | 2015-03-19 | Variation Biotechnologies, Inc. | Methods and compositions for therapeutic agents |
| CN104159603A (zh) | 2012-03-08 | 2014-11-19 | 诺华股份有限公司 | 带有tlr4激动剂的联合疫苗 |
| MX372965B (es) | 2012-03-08 | 2020-04-01 | Glaxosmithkline Biologicals Sa | Formulaciones adyuvadas de vacunas de difteria, tetanos y tos ferina (dtp) de refuerzo. |
| WO2013139744A1 (en) | 2012-03-18 | 2013-09-26 | Glaxosmithkline Biologicals S.A. | Method of vaccination against human papillomavirus |
| WO2014024026A1 (en) | 2012-08-06 | 2014-02-13 | Glaxosmithkline Biologicals S.A. | Method for eliciting in infants an immune response against rsv and b. pertussis |
| US20140037680A1 (en) | 2012-08-06 | 2014-02-06 | Glaxosmithkline Biologicals, S.A. | Novel method |
| US9526776B2 (en) | 2012-09-06 | 2016-12-27 | Glaxosmithkline Biologicals Sa | Combination vaccines with serogroup B meningococcus and D/T/P |
| WO2014053521A2 (en) | 2012-10-02 | 2014-04-10 | Novartis Ag | Nonlinear saccharide conjugates |
| US20150273036A1 (en) | 2012-10-12 | 2015-10-01 | Glaxosmithkline Biologicals Sa | Non-cross-linked acellular pertussis antigens for use in combination vaccines |
| RS56886B1 (sr) | 2012-11-30 | 2018-04-30 | Glaxosmithkline Biologicals Sa | Antigeni pseudomonasa i kombinacije antigena |
| JP6411378B2 (ja) | 2013-02-01 | 2018-10-24 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | Toll様受容体アゴニストを含む免疫学的組成物の皮内送達 |
| FI2970398T3 (fi) | 2013-03-13 | 2024-08-06 | Us Health | Rsv f -prefuusioproteiineja ja niiden käyttö |
| UY35418A (es) | 2013-03-15 | 2014-10-31 | Glaxosmithkline Biolog Sa | Vacuna que proporciona protección frente a diferentes Picornavirus humanos. |
| AU2014304545A1 (en) | 2013-08-05 | 2016-02-25 | Glaxosmithkline Biologicals S.A. | Combination immunogenic compositions |
| EP2870974A1 (en) | 2013-11-08 | 2015-05-13 | Novartis AG | Salmonella conjugate vaccines |
| BE1022857A1 (fr) | 2014-03-26 | 2016-09-27 | Glaxosmithkline Biologicals Sa | Immunisation contre staphylococcus aureus |
| CN106659777A (zh) | 2014-06-13 | 2017-05-10 | 葛兰素史密丝克莱恩生物有限公司 | 免疫原性组合产品 |
| AU2015384786B2 (en) | 2015-03-03 | 2020-08-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Display platform from bacterial spore coat proteins |
| US10065978B2 (en) | 2015-11-24 | 2018-09-04 | University Of South Carolina | Cysteine-modifying substrate analogue inhibitors of ribose 5-phosphate isomerase for parasitic diseases, along with methods of their formation and use |
| GB201616904D0 (en) | 2016-10-05 | 2016-11-16 | Glaxosmithkline Biologicals Sa | Vaccine |
| BR112019011286A2 (pt) | 2016-12-07 | 2019-10-15 | Glaxosmithkline Biologicals S.A. | métodos para produzir uma composição de lipossoma, para preparar uma composição de vacina e para preparar um kit de vacina. |
| US11084850B2 (en) | 2016-12-16 | 2021-08-10 | The Pirbright Institute | Recombinant prefusion RSV F proteins and uses thereof |
| US10682359B2 (en) | 2017-03-31 | 2020-06-16 | University Of South Carolina | Inhibitors of glucose kinases, along with methods of their formation and use |
| UA129243C2 (uk) | 2017-04-19 | 2025-02-26 | Інстітьют Фо Рісьорч Ін Біомедцін | Антитіло, що зв'язується зі спорозоїтами p. falciparum |
| EP3615061A1 (en) | 2017-04-28 | 2020-03-04 | GlaxoSmithKline Biologicals S.A. | Vaccination |
| GB201707700D0 (en) | 2017-05-12 | 2017-06-28 | Glaxosmithkline Biologicals Sa | Dried composition |
| EP3581201A1 (en) | 2018-06-15 | 2019-12-18 | GlaxoSmithKline Biologicals S.A. | Escherichia coli o157:h7 proteins and uses thereof |
| WO2020010016A1 (en) | 2018-07-04 | 2020-01-09 | Sutrovax, Inc. | Self-adjuvanted immunogenic conjugates |
| US11059842B2 (en) | 2019-04-29 | 2021-07-13 | University Of South Carolina | Monosaccharide amine and 3-nitro-2-phenyl-2H-chromene based inhibitors of glucose kinases |
| US11555047B2 (en) | 2019-10-31 | 2023-01-17 | University Of South Carolina | One-step synthesis of phosphate-based inhibitors and applications thereof |
| EP4158352A1 (en) | 2020-06-01 | 2023-04-05 | Loop Diagnostics, S.L. | Method and kit for the early detection of sepsis |
| CA3202549A1 (en) | 2020-12-02 | 2022-06-09 | Glaxosmithkline Biologicals Sa | Novel antigens |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5484911A (en) * | 1993-04-01 | 1996-01-16 | Health Research, Inc. | Nucleoside 5'-diphosphate conjugates of ether lipids |
| US5961970A (en) | 1993-10-29 | 1999-10-05 | Pharmos Corporation | Submicron emulsions as vaccine adjuvants |
| AU1218295A (en) | 1993-12-09 | 1995-06-27 | Heinrich Exner | Adjuvant for antigens, process for producing the same and its use |
| GB9326253D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
| US6180111B1 (en) | 1995-05-18 | 2001-01-30 | University Of Maryland | Vaccine delivery system |
| US5958901A (en) * | 1995-06-07 | 1999-09-28 | Genta Incorporated | Phosphonic acid-based cationic lipids |
| TW343975B (en) * | 1995-12-15 | 1998-11-01 | Boehringer Mannheim Gmbh | New phospholipid derivatives of phosphonocarboxylic acids, the production thereof as well as their use as antiviral pharmaceutical agents |
| US5834015A (en) | 1996-09-11 | 1998-11-10 | Albany Medical College | Protein-lipid vesicles and autogenous vaccine comprising the same |
| US6355257B1 (en) * | 1997-05-08 | 2002-03-12 | Corixa Corporation | Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors |
| ES2223464T3 (es) * | 1999-02-01 | 2005-03-01 | Eisai Co., Ltd. | Compuestos adyuvantes inmunologicos. |
| DE60016205T2 (de) * | 1999-05-28 | 2005-12-01 | Vical, Inc., San Diego | Cytofectin-dimere und verfahren zu ihrer anwendung |
| EP1307466B1 (en) * | 2000-07-31 | 2005-11-16 | Eisai Co., Ltd. | Immunological adjuvant compounds |
| WO2002018395A1 (en) * | 2000-08-31 | 2002-03-07 | Merck & Co., Inc. | Phosphate derivatives as immunoregulatory agents |
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