CN104755622B - 用于稳健t细胞和抗体应答的pr13.5启动子 - Google Patents

用于稳健t细胞和抗体应答的pr13.5启动子 Download PDF

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CN104755622B
CN104755622B CN201380054013.0A CN201380054013A CN104755622B CN 104755622 B CN104755622 B CN 104755622B CN 201380054013 A CN201380054013 A CN 201380054013A CN 104755622 B CN104755622 B CN 104755622B
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CN104755622A (zh
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罗宾·施泰格瓦尔德
凯·布林克曼
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CN201380054013.0A 2012-10-28 2013-10-28 用于稳健t细胞和抗体应答的pr13.5启动子 Active CN104755622B (zh)

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US201261719429P 2012-10-28 2012-10-28
US61/719,429 2012-10-28
PCT/EP2013/003239 WO2014063832A1 (en) 2012-10-28 2013-10-28 Pr13.5 promoter for robust t-cell and antibody responses

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Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9828414B2 (en) * 2012-10-28 2017-11-28 Bavarian Nordic A/S Pr13.5 promoter for robust T-cell and antibody responses
FR3042121A1 (fr) 2015-10-08 2017-04-14 Jean-Marc Limacher Composition anti-tumorale
US10881725B2 (en) 2016-01-29 2021-01-05 Bavarian Nordic A/S Recombinant modified vaccinia virus Ankara (MVA) equine encephalitis virus vaccine
EP3452087A1 (en) 2016-05-02 2019-03-13 Janssen Vaccines & Prevention B.V. Therapeutic hpv vaccine combinations
CA3036799C (en) 2016-09-28 2025-05-13 Bavarian Nordic A/S COMPOSITIONS AND METHODS FOR IMPROVING THE STABILITY OF TRANSGENES IN POXVIRUSES
WO2018091680A1 (en) 2016-11-18 2018-05-24 Transgene Sa Cowpox-based oncolytic vectors
KR20190097240A (ko) 2016-12-28 2019-08-20 트랜스진 에스.에이. 종양용해성 바이러스 및 치료 분자
CN110958887B (zh) 2017-06-15 2023-10-31 扬森疫苗与预防公司 编码hiv抗原的痘病毒载体及其使用方法
WO2019020543A1 (en) 2017-07-28 2019-01-31 Transgene Sa ONCOLYTIC VIRUSES EXPRESSING AGENTS TARGETING METABOLIC IMMUNE MODULATORS
KR102754876B1 (ko) 2017-08-24 2025-01-13 버베리안 노딕 에이/에스 재조합 mva 및 항체의 정맥내 투여에 의한 암 치료를 위한 병용 요법
CN111741766A (zh) 2017-12-19 2020-10-02 杨森科学爱尔兰无限公司 用于诱导针对乙型肝炎病毒(hbv)的免疫应答的方法和组合物
GB201807932D0 (en) 2018-05-16 2018-06-27 Redchenko Irina Compositions and methods for inducing an immune response
WO2020011754A1 (en) 2018-07-09 2020-01-16 Transgene Chimeric vaccinia viruses
CN110904127B (zh) 2018-09-18 2024-09-20 瓦赫宁恩研究基金会 非洲猪瘟病毒疫苗
JP7555334B2 (ja) 2018-10-05 2024-09-24 バヴァリアン・ノルディック・アクティーゼルスカブ 組み換えmva、及び免疫チェックポイントアンタゴニストまたは免疫チェックポイントアゴニストの静脈内投与によって、がんを治療する併用療法
MX2021005560A (es) 2018-11-20 2021-06-23 Bavarian Nordic As Terapia para el tratamiento del cancer con administracion intratumoral y/o intravenosa de un virus vaccinia ankara (mva) recombinante que codifica ligando 4-1bbl (cd137l) y/o ligando del cumulo o grupo de diferenciacion 40 (cd40l).
CN114867491B (zh) 2019-11-20 2025-08-15 巴法里安诺迪克有限公司 用于肿瘤内和/或静脉内施用以治疗癌症的重组mva病毒
CA3181431A1 (en) 2020-06-10 2021-12-16 Jurgen Hausmann A recombinant modified vaccinia virus ankara (mva) vaccine against coronavirus disease
US20220118081A1 (en) 2020-10-20 2022-04-21 Janssen Vaccines & Prevention B.V. HIV vaccine regimens
IL311078A (en) 2021-09-03 2024-04-01 Bavarian Nordic As Use of microRNA to downregulate expression of cytotoxic transgenes by modified vicinia ankara virus (mva)
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JP2025525380A (ja) 2022-06-29 2025-08-05 バヴァリアン・ノルディック・アクティーゼルスカブ 組み換え改変saRNA(VRP)及びワクシニアウイルスアンカラ(MVA)プライム-ブーストレジメン
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FR3160186A1 (fr) 2024-03-13 2025-09-19 Odimma Therapeutics Vecteur non-viral pour transcription augmentee
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WO2026041811A1 (en) 2024-08-23 2026-02-26 Transgene Recombinant poxvirus and method for regulating the expression of toxic conditional gene products of said recombinant poxvirus in a producing cell

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1266459A (zh) * 1997-06-09 2000-09-13 奥克松药品有限公司 用于产生cd8t细胞免疫应答的接种方法和试剂
CN1391609A (zh) * 1999-09-21 2003-01-15 埃西斯创新有限公司 用复制缺陷腺病毒载体加强cd8+t细胞对抗原的免疫应答
WO2006073431A2 (en) * 2004-06-25 2006-07-13 Merial Limited Avipox recombinants expressing foot and mouth disease virus genes

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL212047B1 (pl) 2000-11-23 2012-08-31 Bavarian Nordic As Zmodyfikowany wirus krowianki szczepu Ankara MVA-BN i jego pochodna, genom i zawierające je kompozycja farmaceutyczna, zwłaszcza szczepionka oraz ich zastosowania
JP2008301792A (ja) 2007-06-11 2008-12-18 National Univ Corp Shizuoka Univ 改変ポリヘドリンプロモーター、バクミド変異体及び目的タンパク質の製造方法
JP2012509678A (ja) 2008-11-27 2012-04-26 バヴァリアン・ノルディック・アクティーゼルスカブ 組換えウイルス発現のためのプロモーター
US8394385B2 (en) * 2009-03-13 2013-03-12 Bavarian Nordic A/S Optimized early-late promoter combined with repeated vaccination favors cytotoxic T cell response against recombinant antigen in MVA vaccines
US9828414B2 (en) * 2012-10-28 2017-11-28 Bavarian Nordic A/S Pr13.5 promoter for robust T-cell and antibody responses

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1266459A (zh) * 1997-06-09 2000-09-13 奥克松药品有限公司 用于产生cd8t细胞免疫应答的接种方法和试剂
CN1391609A (zh) * 1999-09-21 2003-01-15 埃西斯创新有限公司 用复制缺陷腺病毒载体加强cd8+t细胞对抗原的免疫应答
WO2006073431A2 (en) * 2004-06-25 2006-07-13 Merial Limited Avipox recombinants expressing foot and mouth disease virus genes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Immediate-Early Expression of a Recombinant Antigen by Modified Vaccinia Virus Ankara Breaks the Immunodominance of Strong Vector-Specific B8R Antigen in Acute and Memory CD8 T-Cell Responses;Karen Baur等;《JOURNAL OF VIROLOGY》;20100930;第84卷(第17期);8743-8744 *

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JP2019131572A (ja) 2019-08-08
BR112015009320A2 (pt) 2017-10-17
US11028130B2 (en) 2021-06-08
ZA201502892B (en) 2020-08-26
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KR102135818B1 (ko) 2020-07-22
CA2887623A1 (en) 2014-05-01
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US9828414B2 (en) 2017-11-28
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EA201990114A1 (ru) 2019-09-30
MY194609A (en) 2022-12-06
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