CN108367061A - 用于诱导免疫应答的新方法 - Google Patents
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- CN108367061A CN108367061A CN201680043249.8A CN201680043249A CN108367061A CN 108367061 A CN108367061 A CN 108367061A CN 201680043249 A CN201680043249 A CN 201680043249A CN 108367061 A CN108367061 A CN 108367061A
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112423786A (zh) * | 2018-08-10 | 2021-02-26 | 南特生物公司 | 用于病毒感染的细胞佐剂 |
| CN113088538A (zh) * | 2020-01-08 | 2021-07-09 | 怡道生物科技(苏州)有限公司 | 一种基于黑猩猩ChAd3型腺病毒的表达载体及其构建方法 |
| CN113088530A (zh) * | 2020-01-08 | 2021-07-09 | 怡道生物科技(苏州)有限公司 | 一种基于黑猩猩ChAd63型腺病毒的表达载体及其构建方法 |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6576326B2 (ja) | 2013-03-14 | 2019-09-18 | ソーク インスティテュート フォー バイオロジカル スタディーズ | 腫瘍溶解性アデノウイルス組成物 |
| GB201405921D0 (en) * | 2014-04-02 | 2014-05-14 | Glaxosmithkline Biolog Sa | Novel methods for inducing an immune response |
| AU2017222568B2 (en) | 2016-02-23 | 2020-09-10 | Salk Institute For Biological Studies | High throughput assay for measuring adenovirus replication kinetics |
| KR20220163505A (ko) | 2016-02-23 | 2022-12-09 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | 바이러스 동역학에 미치는 영향 최소화를 위한 치료용 아데노바이러스의 외인성 유전자 발현 |
| SMT202300106T1 (it) * | 2016-03-31 | 2023-05-12 | Centre Nat Rech Scient | Veicoli di rilascio derivati da proteine di rivestimento adenovirali |
| AU2017375633C1 (en) | 2016-12-12 | 2023-04-27 | Salk Institute For Biological Studies | Tumor-targeting synthetic adenoviruses and uses thereof |
| BR112020007238A2 (pt) * | 2017-10-16 | 2020-10-13 | Glaxosmithkline Biologicals S.A. | vetores adenovirais com replicação competente |
| EP3697919A1 (en) | 2017-10-16 | 2020-08-26 | GlaxoSmithKline Biologicals SA | Adenoviral vectors with two expression cassettes encoding rsv antigenic proteins or fragments thereof |
| BR112020007413A2 (pt) | 2017-10-16 | 2020-12-08 | Glaxosmithkline Biologicals S.A. | Vetores adenovirais com dois cassetes de expressão |
| CA3084358A1 (en) * | 2017-10-16 | 2019-04-25 | Glaxosmithkline Biologicals Sa | Enhanced promoter |
| GB201721069D0 (en) * | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B Immunisation regimen and compositions |
| CN112292449A (zh) | 2018-04-09 | 2021-01-29 | 萨克生物研究学院 | 具有增强的复制特性的溶瘤腺病毒组合物 |
| MX2020013553A (es) * | 2018-06-12 | 2021-02-26 | Glaxosmithkline Biologicals Sa | Polinucleotidos y polipeptidos de adenovirus. |
| TWI852977B (zh) * | 2019-01-10 | 2024-08-21 | 美商健生生物科技公司 | 前列腺新抗原及其用途 |
| CN110283766B (zh) * | 2019-05-13 | 2020-12-18 | 华中科技大学 | 一种重组卡介苗及其构建与应用 |
| CN110606875A (zh) * | 2019-09-20 | 2019-12-24 | 中国农业科学院兰州兽医研究所 | 一种用于制备口蹄疫疫苗的分子内佐剂及其应用和口蹄疫疫苗 |
| KR20220133854A (ko) * | 2019-09-30 | 2022-10-05 | 어플라이드 제네틱스 테크놀로지스 코퍼레이션 | 유전적 청력 상실 치료를 위한 아데노 관련 바이러스(aav) 시스템 |
| US12295997B2 (en) | 2020-07-06 | 2025-05-13 | Janssen Biotech, Inc. | Prostate neoantigens and their uses |
| CN114438128A (zh) * | 2020-10-30 | 2022-05-06 | 上海市公共卫生临床中心 | 一种增强型溶瘤腺病毒及其应用 |
| TW202237164A (zh) * | 2020-12-04 | 2022-10-01 | 美商磨石生物公司 | 組合物及其使用方法 |
| JP2024534178A (ja) * | 2021-08-31 | 2024-09-18 | ヴィア・バイオテクノロジー・インコーポレイテッド | 結核ワクチン |
| CN118662620A (zh) * | 2023-03-15 | 2024-09-20 | 康希诺生物股份公司 | 一种肺结核疫苗及其制备方法和应用 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101014613A (zh) * | 2004-01-23 | 2007-08-08 | P·安杰莱蒂分子生物学研究所 | 黑猩猩腺病毒疫苗载运体 |
| CN101213204A (zh) * | 2005-06-17 | 2008-07-02 | P.安杰莱蒂分子生物学研究所 | 丙型肝炎病毒核酸疫苗 |
| CN101273055A (zh) * | 2005-04-29 | 2008-09-24 | 葛兰素史密丝克莱恩生物有限公司 | 用于预防或治疗结核分枝杆菌感染的新方法 |
| WO2011130627A2 (en) * | 2010-04-16 | 2011-10-20 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Chimpanzee adenoviral vector-based filovirus vaccines |
| CN102666575A (zh) * | 2009-10-16 | 2012-09-12 | 艾西斯创新有限公司 | 分枝杆菌疫苗 |
| CN103260642A (zh) * | 2010-12-14 | 2013-08-21 | 葛兰素史密丝克莱恩生物有限公司 | 分枝杆菌抗原组合物 |
| WO2013123579A1 (en) * | 2012-02-24 | 2013-08-29 | Mcmaster University | Adenovirus-based tuberculosis vaccine and its use |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ319377A (en) | 1995-09-01 | 2000-01-28 | Corixa Corp | polypeptides comprising a portion of a soluble M tuberculosis antigen |
| US6350456B1 (en) | 1997-03-13 | 2002-02-26 | Corixa Corporation | Compositions and methods for the prevention and treatment of M. tuberculosis infection |
| US5981225A (en) | 1998-04-16 | 1999-11-09 | Baylor College Of Medicine | Gene transfer vector, recombinant adenovirus particles containing the same, method for producing the same and method of use of the same |
| US7083796B2 (en) * | 2000-06-20 | 2006-08-01 | Corixa Corporation | Fusion proteins of mycobacterium tuberculosis |
| AU2003213118A1 (en) * | 2002-02-15 | 2003-09-09 | Corixa Corporation | Fusion proteins of mycobacterium tuberculosis |
| CA2563500C (en) * | 2004-04-28 | 2016-06-28 | The Trustees Of The University Of Pennsylvania | Immunization regimen with e4-deleted adenovirus prime and e1-deleted adenovirus boost |
| AU2008223951B2 (en) | 2007-03-02 | 2014-03-27 | Glaxosmithkline Biologicals S.A. | Novel method and compositions |
| MX2010005860A (es) | 2007-11-28 | 2010-06-22 | Univ Pennsylvania | Adenovirus simianos de la subfamilia c sadv-40, sadv-31 y sadv-34 y usos de los mismos. |
| GB0815872D0 (en) | 2008-09-01 | 2008-10-08 | Pasteur Institut | Novel method and compositions |
| EP3385387B1 (en) * | 2009-02-02 | 2021-08-25 | GlaxoSmithKline Biologicals SA | Simian adenovirus nucleic acid- and amino acid-sequences, vectors containing same, and uses thereof |
| CN102869372B (zh) * | 2010-01-27 | 2016-01-20 | 葛兰素史密丝克莱恩生物有限公司 | 经修饰的结核抗原 |
| KR102535670B1 (ko) | 2015-06-12 | 2023-05-22 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 아데노바이러스 폴리뉴클레오티드 및 폴리펩티드 |
-
2015
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2016
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- 2016-07-25 KR KR1020187005661A patent/KR20180034589A/ko not_active Withdrawn
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-
2021
- 2021-08-09 US US17/397,379 patent/US20210386846A1/en not_active Abandoned
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101014613A (zh) * | 2004-01-23 | 2007-08-08 | P·安杰莱蒂分子生物学研究所 | 黑猩猩腺病毒疫苗载运体 |
| CN101273055A (zh) * | 2005-04-29 | 2008-09-24 | 葛兰素史密丝克莱恩生物有限公司 | 用于预防或治疗结核分枝杆菌感染的新方法 |
| CN101213204A (zh) * | 2005-06-17 | 2008-07-02 | P.安杰莱蒂分子生物学研究所 | 丙型肝炎病毒核酸疫苗 |
| CN102666575A (zh) * | 2009-10-16 | 2012-09-12 | 艾西斯创新有限公司 | 分枝杆菌疫苗 |
| WO2011130627A2 (en) * | 2010-04-16 | 2011-10-20 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Chimpanzee adenoviral vector-based filovirus vaccines |
| CN103260642A (zh) * | 2010-12-14 | 2013-08-21 | 葛兰素史密丝克莱恩生物有限公司 | 分枝杆菌抗原组合物 |
| WO2013123579A1 (en) * | 2012-02-24 | 2013-08-29 | Mcmaster University | Adenovirus-based tuberculosis vaccine and its use |
Non-Patent Citations (1)
| Title |
|---|
| NEHA DALMIA等: "Prime–boost approaches to tuberculosis vaccine development", 《EXPERT REV VACCINES》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112423786A (zh) * | 2018-08-10 | 2021-02-26 | 南特生物公司 | 用于病毒感染的细胞佐剂 |
| CN112423786B (zh) * | 2018-08-10 | 2024-03-22 | 南特生物公司 | 用于病毒感染的细胞佐剂 |
| US12329809B2 (en) | 2018-08-10 | 2025-06-17 | Nantbio, Inc. | Cellular adjuvants for viral infection |
| US12350323B2 (en) | 2018-08-10 | 2025-07-08 | Nantbio, Inc. | Cellular adjuvants for viral infection |
| CN113088538A (zh) * | 2020-01-08 | 2021-07-09 | 怡道生物科技(苏州)有限公司 | 一种基于黑猩猩ChAd3型腺病毒的表达载体及其构建方法 |
| CN113088530A (zh) * | 2020-01-08 | 2021-07-09 | 怡道生物科技(苏州)有限公司 | 一种基于黑猩猩ChAd63型腺病毒的表达载体及其构建方法 |
| WO2021139547A1 (zh) * | 2020-01-08 | 2021-07-15 | 怡道生物科技(苏州)有限公司 | 一种基于黑猩猩ChAd3型腺病毒的表达载体及其构建方法 |
| WO2021139548A1 (zh) * | 2020-01-08 | 2021-07-15 | 怡道生物科技(苏州)有限公司 | 一种基于黑猩猩ChAd63型腺病毒的表达载体及其构建方法 |
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| US11110159B2 (en) | 2021-09-07 |
| AR105470A1 (es) | 2017-10-04 |
| CA2993371A1 (en) | 2017-02-02 |
| EP3328420A1 (en) | 2018-06-06 |
| MX2018001215A (es) | 2018-04-13 |
| GB201513176D0 (en) | 2015-09-09 |
| US20180250375A1 (en) | 2018-09-06 |
| BE1023915A9 (fr) | 2018-01-24 |
| BR112018001572A2 (pt) | 2018-11-06 |
| EA201890355A1 (ru) | 2018-08-31 |
| BE1023915B1 (fr) | 2018-01-31 |
| JP2018521666A (ja) | 2018-08-09 |
| JP2018524393A (ja) | 2018-08-30 |
| BR112018001683A2 (pt) | 2018-09-18 |
| US20210386846A1 (en) | 2021-12-16 |
| AU2016301029A1 (en) | 2018-02-01 |
| US20180216081A1 (en) | 2018-08-02 |
| BE1023916A1 (fr) | 2017-09-12 |
| MX2018001213A (es) | 2018-04-13 |
| BE1023916A9 (fr) | 2018-02-12 |
| US20210060150A1 (en) | 2021-03-04 |
| BE1023915A1 (fr) | 2017-09-12 |
| BE1023916B1 (fr) | 2018-01-22 |
| WO2017017050A1 (en) | 2017-02-02 |
| EP3328421A1 (en) | 2018-06-06 |
| CA2993277A1 (en) | 2017-02-02 |
| KR20180034589A (ko) | 2018-04-04 |
| IL257071A (en) | 2018-03-29 |
| CN108135991A (zh) | 2018-06-08 |
| WO2017017049A1 (en) | 2017-02-02 |
| AU2016301029B2 (en) | 2019-08-22 |
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