RU2625021C2 - Мутантные полимеразы вируса гепатита В - Google Patents
Мутантные полимеразы вируса гепатита В Download PDFInfo
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- RU2625021C2 RU2625021C2 RU2014104360A RU2014104360A RU2625021C2 RU 2625021 C2 RU2625021 C2 RU 2625021C2 RU 2014104360 A RU2014104360 A RU 2014104360A RU 2014104360 A RU2014104360 A RU 2014104360A RU 2625021 C2 RU2625021 C2 RU 2625021C2
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| EP12305450 | 2012-04-18 | ||
| PCT/EP2012/063640 WO2013007772A1 (en) | 2011-07-12 | 2012-07-12 | Hbv polymerase mutants |
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Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3339321T3 (da) | 2008-08-28 | 2021-06-21 | Taiga Biotechnologies Inc | Modulatorer af myc, fremgangsmåder til anvendelse af samme og fremgangsmåder til at identificere stoffer der modulerer myc |
| TWI623618B (zh) * | 2011-07-12 | 2018-05-11 | 傳斯堅公司 | Ｈｂｖ聚合酶突變體 |
| TWI690322B (zh) | 2012-10-02 | 2020-04-11 | 法商傳斯堅公司 | 含病毒的調配物及其使用 |
| JP2015128397A (ja) * | 2014-01-08 | 2015-07-16 | 国立大学法人広島大学 | 亜リン酸デヒドロゲナーゼ遺伝子、および、当該遺伝子を用いた出芽酵母の選択的培養方法 |
| WO2016020538A1 (en) * | 2014-08-08 | 2016-02-11 | Transgene Sa | Hbv vaccine and antibody combination therapy to treat hbv infections |
| WO2016131945A1 (en) | 2015-02-20 | 2016-08-25 | Transgene Sa | Combination product with autophagy modulator |
| JP6566368B2 (ja) * | 2015-04-16 | 2019-08-28 | 国立研究開発法人産業技術総合研究所 | Ｂ型肝炎ウイルス分泌阻害剤 |
| AU2016306275A1 (en) | 2015-08-07 | 2018-02-08 | Arrowhead Pharmaceuticals, Inc. | RNAi therapy for Hepatitis B virus infection |
| JP7250520B2 (ja) | 2016-04-13 | 2023-04-03 | ヤンセン ファーマシューティカルズ，インコーポレーテッド | 組換えアルテリウイルスレプリコン系およびその使用 |
| CA3023022A1 (en) | 2016-05-04 | 2017-11-09 | Transgene Sa | Combination therapy with cpg tlr9 ligand |
| JOP20190015A1 (ar) | 2016-08-04 | 2019-02-04 | Arrowhead Pharmaceuticals Inc | عوامل (ار ان ايه آي) لعدوى فيروس الالتهاب الكبدي الوبائي ب |
| WO2018069316A2 (en) | 2016-10-10 | 2018-04-19 | Transgene Sa | Immunotherapeutic product and mdsc modulator combination therapy |
| KR102718353B1 (ko) | 2016-10-17 | 2024-10-15 | 얀센 파마슈티칼즈, 인코포레이티드 | 재조합 바이러스 레플리콘 시스템 및 그의 용도 |
| EP3548425B1 (en) * | 2016-12-02 | 2023-03-29 | Taiga Biotechnologies, Inc. | Nanoparticle formulations |
| CA3045650A1 (en) | 2016-12-05 | 2018-06-14 | Janssen Pharmaceuticals, Inc. | Compositions and methods for enhancing gene expression |
| GB201705765D0 (en) * | 2017-04-10 | 2017-05-24 | Univ Oxford Innovation Ltd | HBV vaccine |
| CA3062549A1 (en) | 2017-05-15 | 2018-11-22 | Janssen Vaccines & Prevention B.V. | Stable virus-containing composition |
| EP3624851A1 (en) | 2017-05-15 | 2020-03-25 | Janssen Vaccines & Prevention B.V. | Stable virus-containing composition |
| EA202091517A1 (ru) | 2017-12-19 | 2020-11-03 | Янссен Сайенсиз Айрлэнд Анлимитед Компани | Способы и устройство для доставки вакцин против вируса гепатита b (hbv) |
| AU2018390825A1 (en) * | 2017-12-19 | 2020-06-18 | Ichor Medical Systems, Inc. | Methods and apparatus for the delivery of hepatitis B virus (HBV) vaccines |
| US11021692B2 (en) | 2017-12-19 | 2021-06-01 | Janssen Sciences Ireland Unlimited Company | Hepatitis B virus (HBV) vaccines and uses thereof |
| EA202091516A1 (ru) | 2017-12-19 | 2020-11-03 | Янссен Сайенсиз Айрлэнд Анлимитед Компани | Способы и композиции для индукции иммунного ответа против вируса гепатита b (hbv) |
| CN111836641A (zh) * | 2017-12-19 | 2020-10-27 | 杨森科学爱尔兰无限公司 | 乙型肝炎病毒(hbv)疫苗及其用途 |
| JP7494117B2 (ja) | 2018-01-19 | 2024-06-03 | ヤンセン ファーマシューティカルズ，インコーポレーテッド | 組換えレプリコン系を使用する免疫応答の誘導および増強 |
| IL277128B2 (en) * | 2018-03-06 | 2025-11-01 | Precigen Inc | Hepatitis b vaccines and uses of the same |
| CA3093093A1 (en) | 2018-03-07 | 2019-09-12 | Transgene | Parapoxvirus vectors |
| WO2020076775A1 (en) | 2018-10-08 | 2020-04-16 | Janssen Pharmaceuticals, Inc. | Alphavirus-based replicons for administration of biotherapeutics |
| CN113874033A (zh) | 2019-04-08 | 2021-12-31 | 泰加生物工艺学公司 | 用于冷冻保存免疫细胞的组合物和方法 |
| EP3969041A4 (en) | 2019-05-14 | 2023-05-10 | Taiga Biotechnologies, Inc. | COMPOSITIONS AND METHODS FOR TREATMENT OF T-CELL DEPLETION |
| CA3141003A1 (en) * | 2019-06-18 | 2020-12-24 | Helen Horton | Combination of hepatitis b virus (hbv) vaccines and pd-l1 inhibitors |
| KR20220042116A (ko) * | 2019-06-18 | 2022-04-04 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | B형 간염 바이러스(HBV) 백신 및 HBV-타케팅 RNAi의 조합 |
| CA3143679A1 (en) * | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and hbv-targeting rnai |
| KR20220041080A (ko) * | 2019-06-18 | 2022-03-31 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | B형 간염 바이러스(hbv) 백신 및 항-pd-1 또는 항-pc-l1 항체의 조합 |
| WO2020255018A1 (en) * | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Hepatitis b virus (hbv) vaccines and uses thereof |
| EP3986457A1 (en) * | 2019-06-20 | 2022-04-27 | Janssen Sciences Ireland Unlimited Company | Carbohydrate nanocarrier delivery of hepatitis b virus (hbv) vaccines |
| AU2020298267A1 (en) * | 2019-06-20 | 2022-02-17 | Janssen Sciences Ireland Unlimited Company | Self-replicating RNA molecules for hepatitis B virus (HBV) vaccines and uses thereof |
| DK4037708T3 (da) * | 2019-09-30 | 2024-09-30 | Gilead Sciences Inc | HBV-vacciner og fremgangsmåder til at behandle HBV |
| CN111548395A (zh) * | 2020-05-25 | 2020-08-18 | 中国农业科学院兰州兽医研究所 | 一种口蹄疫病毒二价多表位重组病毒样颗粒及其应用 |
| KR20220117627A (ko) * | 2021-02-17 | 2022-08-24 | 주식회사 녹십자 | 백신 조성물과의 병용을 위한 hbv 특이적 항체를 포함하는 b형 간염 치료용 조성물 |
| CN115851656A (zh) * | 2021-09-24 | 2023-03-28 | 中国科学院生物物理研究所 | 一种乙肝病毒聚合酶的制备方法 |
| CN116333170B (zh) * | 2023-03-28 | 2026-02-17 | 陇东学院 | 一种用于免疫治疗胃癌的重组病毒样纳米颗粒及其应用 |
| WO2025022515A1 (ja) * | 2023-07-24 | 2025-01-30 | 株式会社日立製作所 | 細胞培養容器、細胞培養装置及び細胞シートの作製方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2295536C2 (ru) * | 2001-02-05 | 2007-03-20 | Стрессджен Байотекнолоджиз Корп. | Композиции на основе белка вируса гепатита в и стрессового белка и их применение |
| WO2011015656A2 (en) * | 2009-08-07 | 2011-02-10 | Transgene Sa | Composition for treating hbv infection |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2650838A1 (fr) | 1989-08-09 | 1991-02-15 | Transgene Sa | Vecteurs d'expression du facteur ix dans une cellule eucaryote superieure, procede de preparation de facteur ix par des animaux transgeniques et facteur ix obtenu |
| EP0534615B1 (en) | 1991-08-26 | 2001-01-03 | Epimmune Inc. | HLA-restricted hepatitis B virus CTL epitopes |
| WO1995003777A1 (en) | 1993-08-02 | 1995-02-09 | The Scripps Research Institute | Peptides for inducing cytotoxic t lymphocyte responses to hepatitis b virus |
| JP3657603B2 (ja) | 1993-02-26 | 2005-06-08 | ザ スクリップス リサーチ インスティテュート | Ｂ型肝炎のウイルスに対する細胞障害性ｔリンパ球の応答を誘発するペプチド |
| FR2705686B1 (fr) | 1993-05-28 | 1995-08-18 | Transgene Sa | Nouveaux adénovirus défectifs et lignées de complémentation correspondantes. |
| IL112820A0 (en) | 1994-03-07 | 1995-05-26 | Merck & Co Inc | Coordinate in vivo gene expression |
| US5837520A (en) | 1995-03-07 | 1998-11-17 | Canji, Inc. | Method of purification of viral vectors |
| IL160406A0 (en) | 1995-06-15 | 2004-07-25 | Crucell Holland Bv | A cell harbouring nucleic acid encoding adenoritus e1a and e1b gene products |
| IL127692A0 (en) | 1996-07-01 | 1999-10-28 | Rhone Poulenc Rorer Sa | Method for producing recombinant adenovirus |
| WO1998022588A2 (en) | 1996-11-20 | 1998-05-28 | Introgen Therapeutics, Inc. | An improved method for the production and purification of adenoviral vectors |
| AU5370598A (en) | 1996-12-13 | 1998-07-03 | Schering Corporation | Methods for purifying viruses |
| WO1998056415A1 (en) | 1997-06-11 | 1998-12-17 | Aquila Biopharmaceuticals, Inc. | Purified saponins as oral adjuvants |
| FR2766091A1 (fr) | 1997-07-18 | 1999-01-22 | Transgene Sa | Composition antitumorale a base de polypeptide immunogene de localisation cellulaire modifiee |
| JP3864610B2 (ja) | 1998-05-21 | 2007-01-10 | 旭硝子株式会社 | 水分散型撥水撥油剤組成物およびその製造方法 |
| US7462354B2 (en) * | 1999-12-28 | 2008-12-09 | Pharmexa Inc. | Method and system for optimizing minigenes and peptides encoded thereby |
| KR20040043129A (ko) | 2001-06-22 | 2004-05-22 | 더 위스타 인스티튜트 오브 아나토미 앤드 바이올로지 | 세포독성 면역 반응을 유도하는 방법과 그에 유용한재조합체 원숭이 아데노바이러스 조성물 |
| AU2002365366B2 (en) | 2001-11-21 | 2007-05-10 | The Trustees Of The University Of Pennsylvania | Simian adenovirus nucleic acid and amino acid sequences, vectors containing same, and methods of use |
| FR2836924B1 (fr) | 2002-03-08 | 2005-01-14 | Vivalis | Lignees de cellules aviaires utiles pour la production de substances d'interet |
| GB0328753D0 (en) | 2003-12-11 | 2004-01-14 | Royal Veterinary College The | Hepatitis B vaccines |
| DE602005017743D1 (de) | 2004-01-23 | 2009-12-31 | Angeletti P Ist Richerche Bio | Impfstoffträger für schimpansen-adenovirus |
| CN100339488C (zh) * | 2004-12-07 | 2007-09-26 | 中山大学达安基因股份有限公司 | 乙型肝炎病毒基因组耐药突变检测方法 |
| CN1313483C (zh) * | 2005-12-12 | 2007-05-02 | 浙江大学 | 鸭乙型肝炎病毒多聚酶蛋白ymdd功能区的抑制肽及应用 |
| MX2008016036A (es) | 2006-06-20 | 2009-04-07 | Transgene Sa | Vacuna viral recombinante. |
| WO2008020656A1 (en) | 2006-08-14 | 2008-02-21 | Postech Foundation | A dna vaccine for curing chronic hepatitis b and a method of preparing same |
| KR20080086687A (ko) | 2007-03-23 | 2008-09-26 | 주식회사 파나진 | 라미부딘 내성 ｂ형 간염바이러스 검출을 위한 ρνα프로브, 키트 및 방법 |
| TW200844230A (en) | 2007-05-15 | 2008-11-16 | Transgene Sa | Signaling peptides |
| JP5421250B2 (ja) | 2007-07-03 | 2014-02-19 | トランスジーン ソシエテ アノニム | トリ不死化細胞株 |
| US8357531B2 (en) | 2007-07-03 | 2013-01-22 | Transgene S.A. | Immortalized avian cell lines |
| AU2008331905B2 (en) | 2007-11-28 | 2014-09-18 | The Trustees Of The University Of Pennsylvania | Simian subfamily B adenovirus SAdV-28 and uses thereof |
| CN102131920B (zh) | 2007-11-28 | 2013-11-06 | 宾夕法尼亚大学托管会 | 猿猴亚家族C腺病毒SAdV-40、-31和-34及其应用 |
| CN101883858B (zh) | 2007-11-28 | 2015-07-22 | 宾夕法尼亚大学托管会 | 猿猴亚家族E腺病毒SAdV-39、-25.2、-26、-30、-37和-38及其应用 |
| JP5661476B2 (ja) | 2008-03-04 | 2015-01-28 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | サルアデノウイルスＳＡｄＶ−３６、−４２．１、−４２．２および−４４ならびにそれらの用途 |
| PL2391638T3 (pl) | 2009-02-02 | 2018-11-30 | Glaxosmithkline Biologicals Sa | Sekwencje nukleotydowe i aminokwasowe małpiego adenowirusa, zawierające je wektory i ich zastosowania |
| US8609392B2 (en) | 2009-05-12 | 2013-12-17 | Transgene S.A. | Method for orthopoxvirus production and purification |
| WO2011001565A1 (ja) | 2009-07-01 | 2011-01-06 | シャープ株式会社 | 液晶表示素子及び液晶表示装置 |
| TWI623618B (zh) * | 2011-07-12 | 2018-05-11 | 傳斯堅公司 | Ｈｂｖ聚合酶突變體 |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2295536C2 (ru) * | 2001-02-05 | 2007-03-20 | Стрессджен Байотекнолоджиз Корп. | Композиции на основе белка вируса гепатита в и стрессового белка и их применение |
| WO2011015656A2 (en) * | 2009-08-07 | 2011-02-10 | Transgene Sa | Composition for treating hbv infection |
Non-Patent Citations (1)
| Title |
|---|
| ZAJAKINA A., et al., Translation of hepatitis B virus (HBV) surface proteins from the HBV pregenome and precore RNAs in Semliki forest virus-driven expression, J Gen Virol., 2004, 85, pp.3343-3351. CHANG LUNG-JI, et al., Effects of insertional and point mutations on the functions of the duck hepatitis B virus polymerase, Journal of virology, 1990, Vol.64, No.11, pp.5553-5558. KIM Y., et al., Hepatitis b virus: DNA polymerase activity of deletion mutants, Biochemistry and molecular biology international, 1999, Vol.47, No.2, pp.30-308. АБДУРАХМАНОВ Д.Т., и др., Резистентность вируса гепатита В к противовирусной терапии: диагностика, профилактика и лечение, Клиническая гепатология, 2009, No.1, с.25-30. * |
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