CA2770075C - Composition for treating hbv infection - Google Patents
Composition for treating hbv infection Download PDFInfo
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- CA2770075C CA2770075C CA2770075A CA2770075A CA2770075C CA 2770075 C CA2770075 C CA 2770075C CA 2770075 A CA2770075 A CA 2770075A CA 2770075 A CA2770075 A CA 2770075A CA 2770075 C CA2770075 C CA 2770075C
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- hbv
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| 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 |
| SG11201803474UA (en) * | 2015-11-04 | 2018-05-30 | Hookipa Biotech Ag | Vaccines against hepatitis b virus |
| CN108697775B (zh) | 2015-11-12 | 2023-05-09 | 霍欧奇帕生物科技有限公司 | 作为癌症疫苗的沙粒病毒颗粒 |
| US9963751B2 (en) | 2015-11-24 | 2018-05-08 | The Penn State Research Foundation | Compositions and methods for identifying agents to reduce hepatitis B virus covalently closed circular DNA |
| CA3002508A1 (en) * | 2016-01-12 | 2017-07-20 | Ulrike Protzer | Means and methods for treating hbv |
| 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 |
| CA3026054A1 (en) | 2016-05-30 | 2017-12-07 | Geovax Inc. | Compositions and methods for generating an immune response to hepatitis b virus |
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| EP3522920A2 (en) | 2016-10-10 | 2019-08-14 | Transgene SA | Immunotherapeutic product and mdsc modulator combination therapy |
| CN110073002B (zh) | 2016-10-17 | 2024-06-11 | 杨森制药公司 | 重组病毒复制子体系及其用途 |
| CA3045650A1 (en) | 2016-12-05 | 2018-06-14 | Synthetic Genomics, Inc. | Compositions and methods for enhancing gene expression |
| GB201705765D0 (en) * | 2017-04-10 | 2017-05-24 | Univ Oxford Innovation Ltd | HBV vaccine |
| AU2018269319A1 (en) | 2017-05-15 | 2019-11-07 | Janssen Vaccines & Prevention B.V. | Stable virus-containing composition |
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| EA202091517A1 (ru) | 2017-12-19 | 2020-11-03 | Янссен Сайенсиз Айрлэнд Анлимитед Компани | Способы и устройство для доставки вакцин против вируса гепатита b (hbv) |
| EA202091513A1 (ru) | 2017-12-19 | 2020-09-09 | Янссен Сайенсиз Айрлэнд Анлимитед Компани | Вакцины против вируса гепатита b (hbv) и их применение |
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| WO2019126120A1 (en) * | 2017-12-19 | 2019-06-27 | Janssen Sciences Ireland Unlimited Company | Methods and apparatus for the delivery of hepatitis b virus (hbv) vaccines |
| MX2020006471A (es) * | 2017-12-19 | 2020-09-22 | Janssen Sciences Ireland Unlimited Co | Metodos y composiciones para inducir una respuesta inmune contra el virus de hepatitis b (hbv). |
| KR20200111729A (ko) | 2018-01-19 | 2020-09-29 | 얀센 파마슈티칼즈, 인코포레이티드 | 재조합 레플리콘 시스템을 이용한 면역 반응 유도 및 증진 |
| AU2019231652B2 (en) * | 2018-03-06 | 2025-05-22 | Precigen, Inc. | Hepatitis B vaccines and uses of the same |
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| US12331076B2 (en) | 2018-10-08 | 2025-06-17 | Janssen Pharmaceuticals, Inc. | Alphavirus-based replicons for administration of biotherapeutics |
| CA3143679A1 (en) * | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and hbv-targeting rnai |
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| KR20220143812A (ko) | 2019-12-07 | 2022-10-25 | 아이에스에이 파마슈티컬즈 비.브이. | B형 간염 바이러스와 관련된 질병의 치료 |
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| CN114107377A (zh) * | 2020-08-31 | 2022-03-01 | 复旦大学附属华山医院 | 一种乙肝病毒载体及其应用 |
| WO2024223299A2 (en) | 2023-04-26 | 2024-10-31 | Isa Pharmaceuticals B.V. | Methods of treating cancer by administering immunogenic compositions and a pd-1 inhibitor |
| WO2025226656A1 (en) * | 2024-04-23 | 2025-10-30 | Modernatx, Inc. | Hepatitis b virus mrna vaccines |
Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4711955A (en) | 1981-04-17 | 1987-12-08 | Yale University | Modified nucleotides and methods of preparing and using same |
| CA1223831A (en) | 1982-06-23 | 1987-07-07 | Dean Engelhardt | Modified nucleotides, methods of preparing and utilizing and compositions containing the same |
| FR2583429B1 (fr) | 1985-06-18 | 1989-11-03 | Transgene Sa | Vecteur d'expression de l'interferon u dans les cellules de mammifere, procede pour sa mise en oeuvre et produit obtenu et composition pharmaceutique contenant l'interferon u |
| 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 |
| NZ235315A (en) * | 1989-09-19 | 1991-09-25 | Wellcome Found | Chimaeric hepadnavirus core antigen proteins and their construction |
| EP0491077A1 (en) | 1990-12-19 | 1992-06-24 | Medeva Holdings B.V. | A composition used as a therapeutic agent against chronic viral hepatic diseases |
| EP0534615B1 (en) | 1991-08-26 | 2001-01-03 | Epimmune Inc. | HLA-restricted hepatitis B virus CTL epitopes |
| US6013638A (en) | 1991-10-02 | 2000-01-11 | The United States Of America As Represented By The Department Of Health And Human Services | Adenovirus comprising deletions on the E1A, E1B and E3 regions for transfer of genes to the lung |
| GB9223084D0 (en) | 1992-11-04 | 1992-12-16 | Imp Cancer Res Tech | Compounds to target cells |
| ES2204912T3 (es) | 1993-02-26 | 2004-05-01 | The Scripps Research Institute | Peptidos que inducen respuestas de linfoccitos t citotoxicos contra el virus de la hepatitis b. |
| FR2705686B1 (fr) | 1993-05-28 | 1995-08-18 | Transgene Sa | Nouveaux adénovirus défectifs et lignées de complémentation correspondantes. |
| US6133028A (en) | 1993-05-28 | 2000-10-17 | Transgene S.A. | Defective adenoviruses and corresponding complementation lines |
| WO1994029469A2 (en) * | 1993-06-07 | 1994-12-22 | Vical Incorporated | Plasmids suitable for gene therapy |
| US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| FR2727689A1 (fr) | 1994-12-01 | 1996-06-07 | Transgene Sa | Nouveau procede de preparation d'un vecteur viral |
| US5837520A (en) | 1995-03-07 | 1998-11-17 | Canji, Inc. | Method of purification of viral vectors |
| EP1445322B2 (en) | 1995-06-15 | 2012-06-06 | Crucell Holland B.V. | Packaging systems for human recombinant adenovirus to be used in gene therapy |
| CA2224477A1 (en) | 1995-06-20 | 1997-01-09 | Margherita Melegari | Inhibition of hepatitis b replication |
| UA68327C2 (en) * | 1995-07-04 | 2004-08-16 | Gsf Forschungszentrum Fur Unwe | A recombinant mva virus, an isolated eukaryotic cell, infected with recombinant mva virus, a method for production in vitro of polypeptides with use of said cell, a method for production in vitro of virus parts (variants), vaccine containing the recombinant mva virus, a method for immunization of animals |
| JP2000514290A (ja) | 1996-07-01 | 2000-10-31 | ローヌ―プーラン・ロレ・エス・アー | 組換えアデノウイルスの製造方法 |
| US5981274A (en) * | 1996-09-18 | 1999-11-09 | Tyrrell; D. Lorne J. | Recombinant hepatitis virus vectors |
| KR100503701B1 (ko) | 1996-11-20 | 2005-07-26 | 인트로겐 테라페티스, 인코퍼레이티드 | 아데노바이러스 벡터를 생산하고 정제하는 개선된 방법 |
| DE69739961D1 (de) | 1996-12-13 | 2010-09-23 | Schering Corp | Methoden zur Virus-Reinigung |
| EP0988053A1 (en) | 1997-06-11 | 2000-03-29 | 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 |
| US6596501B2 (en) * | 1998-02-23 | 2003-07-22 | Fred Hutchinson Cancer Research Center | Method of diagnosing autoimmune disease |
| FR2777570A1 (fr) | 1998-04-17 | 1999-10-22 | Transgene Sa | Mutant ayant une activite phosphoribosyl transferase |
| 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 |
| WO2000032625A1 (en) | 1998-12-04 | 2000-06-08 | Biogen, Inc. | Hbv core antigen particles with multiple immunogenic components attached via peptide ligands |
| FR2787465A1 (fr) | 1998-12-21 | 2000-06-23 | Transgene Sa | Procede d'inactivation des virus enveloppes dans une preparation virale de virus non enveloppes |
| KR100762033B1 (ko) | 1998-12-31 | 2007-10-04 | 아방티 파르마 소시에테 아노님 | 바이러스 입자의 분리방법 |
| EP1155120B1 (fr) | 1999-02-22 | 2006-07-05 | Transgene S.A. | Procede d'obtention d'une preparation virale purifiee |
| DK1550722T3 (da) | 1999-05-17 | 2007-10-08 | Crucell Holland Bv | Rekombinant human adenovirus serotype 35 |
| US6492169B1 (en) | 1999-05-18 | 2002-12-10 | Crucell Holland, B.V. | Complementing cell lines |
| FR2803599B1 (fr) * | 2000-01-06 | 2004-11-19 | Inst Nat Sante Rech Med | Nouveau virus mute de l'hepatite b, ses constituants nucleiques et proteiques et leurs applications |
| CA2341356C (en) | 2000-04-14 | 2011-10-11 | Transgene S.A. | Poxvirus with targeted infection specificity |
| EP1278542A2 (en) * | 2000-05-05 | 2003-01-29 | Cytos Biotechnology AG | Molecular antigen arrays and vaccines |
| RU2286172C2 (ru) * | 2000-08-17 | 2006-10-27 | Трипеп Аб | Вакцины, содержащие рибавирин, и способы их использования |
| WO2002096939A2 (en) | 2001-05-30 | 2002-12-05 | Transgene S.A. | Adenovirus protein ix, its domains involved in capsid assembly, transcriptional activity and nuclear reorganization |
| CN100497604C (zh) * | 2002-02-07 | 2009-06-10 | 墨尔本保健公司 | 对核苷类似物具有改变的敏感性的病毒变体及其应用 |
| US7351413B2 (en) * | 2002-02-21 | 2008-04-01 | Lorantis, Limited | Stabilized HBc chimer particles as immunogens for chronic hepatitis |
| WO2004001032A2 (en) | 2002-04-25 | 2003-12-31 | Crucell Holland B.V. | Stable adenoviral vectors and methods for propagation thereof |
| AU2003262790A1 (en) | 2003-03-17 | 2004-10-11 | Merck & Co., Inc. | Adenovirus serotype 24 vectors, nucleic acids and virus produced thereby |
| AU2003298554A1 (en) | 2003-03-28 | 2004-11-23 | Merck & Co., Inc. | Adenovirus serotype 34 vectors, nucleic acids and virus produced thereby |
| US7695960B2 (en) | 2003-06-05 | 2010-04-13 | Transgene S.A. | Composition comprising the polyprotein NS3/NS4 and the polypeptide NS5B of HCV, expression vectors including the corresponding nucleic sequences and their therapeutic use |
| FR2855758B1 (fr) * | 2003-06-05 | 2005-07-22 | Biomerieux Sa | Composition comprenant la polyproteine ns3/ns4 et le polypeptide ns5b du vhc, vecteurs d'expression incluant les sequences nucleiques correspondantes et leur utilisation en therapeutique |
| CA2529997A1 (en) | 2003-06-20 | 2004-12-29 | Dade Behring Marburg Gmbh | Novel surface protein (hbsag) variant of hepatitis b virus |
| WO2005010149A2 (en) | 2003-07-18 | 2005-02-03 | Onyx Pharmaceuticals, Inc. | Subgroup b adenoviral vectors for treating disease |
| WO2005014642A2 (en) | 2003-07-21 | 2005-02-17 | Transgene S.A. | Novel multifunctional cytokines |
| US8007805B2 (en) * | 2003-08-08 | 2011-08-30 | Paladin Labs, Inc. | Chimeric antigens for breaking host tolerance to foreign antigens |
| DE10339927A1 (de) * | 2003-08-29 | 2005-03-24 | Rhein Biotech Gesellschaft für neue Biotechnologische Prozesse und Produkte mbH | Zusammensetzung zur Prophylaxe/Therapie von HBV-Infektionen und HBV-vermittelten Erkrankungen |
| CA2543538A1 (en) * | 2003-10-21 | 2005-05-12 | Melbourne Health | Hbv variants detection and application |
| GB0328753D0 (en) | 2003-12-11 | 2004-01-14 | Royal Veterinary College The | Hepatitis B vaccines |
| DE602005012535D1 (de) | 2004-11-08 | 2009-03-12 | Transgene Sa | Aus teilen bestehendes kit für die durchführung einer antitumorbehandlung oder antiviralen behandlung in einem säugetier |
| EP1764369A1 (de) | 2005-09-16 | 2007-03-21 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Vakzine enthaltend trunkiertes HBV core protein plus Saponin-basierendes Adjuvants |
| GB0522578D0 (en) | 2005-11-04 | 2005-12-14 | King S College London | Ribozymal nucleic acid |
| ES2387321T3 (es) | 2006-03-09 | 2012-09-20 | Transgene Sa | Proteína de fusión no estructural del virus de la hepatitis C |
| US20100129403A1 (en) | 2006-06-20 | 2010-05-27 | Transgene S.A. | Recombinant viral vaccine |
| CN101573449B (zh) | 2006-08-14 | 2013-09-18 | 浦项工大产学协力团 | 用于治疗慢性乙型肝炎的dna疫苗及其制备方法 |
| CA2686772C (en) * | 2007-05-15 | 2015-03-24 | Transgene S.A. | Vectors for multiple gene expression |
| WO2009092612A1 (en) * | 2008-01-25 | 2009-07-30 | Universitätsklinikum Heidelberg | Hydrophobic modified pres-derived peptides of hepatitis b virus (hbv) and their use as vehicles for the specific delivery of compounds to the liver |
| US10076570B2 (en) * | 2009-08-07 | 2018-09-18 | Transgene S.A. | Composition for treating HBV infection |
| US9393299B2 (en) * | 2009-08-07 | 2016-07-19 | Transgene S.A. | Composition for treating HBV infection |
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2010
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- 2010-08-06 CA CA2770075A patent/CA2770075C/en active Active
- 2010-08-06 SG SG2012007845A patent/SG178254A1/en unknown
- 2010-08-06 EP EP10737945A patent/EP2461826A2/en not_active Ceased
- 2010-08-06 WO PCT/EP2010/061492 patent/WO2011015656A2/en not_active Ceased
- 2010-08-06 MX MX2012001592A patent/MX2012001592A/es active IP Right Grant
- 2010-08-06 RU RU2012107671/15A patent/RU2555346C2/ru active
- 2010-08-06 CN CN201080042650.2A patent/CN102573903B/zh active Active
- 2010-08-06 TW TW099126293A patent/TWI555531B/zh active
- 2010-08-06 CN CN201510884240.7A patent/CN105535960B/zh active Active
- 2010-08-06 KR KR1020127005033A patent/KR20120052352A/ko not_active Ceased
- 2010-08-06 BR BR112012002628-3A patent/BR112012002628B1/pt not_active IP Right Cessation
- 2010-08-06 NZ NZ598000A patent/NZ598000A/xx not_active IP Right Cessation
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Also Published As
| Publication number | Publication date |
|---|---|
| CN102573903A (zh) | 2012-07-11 |
| CN102573903B (zh) | 2015-12-02 |
| SG178254A1 (en) | 2012-03-29 |
| EP2461826A2 (en) | 2012-06-13 |
| CN105535960B (zh) | 2019-06-04 |
| US20170072047A1 (en) | 2017-03-16 |
| HK1223295A1 (zh) | 2017-07-28 |
| JP2016074707A (ja) | 2016-05-12 |
| BR112012002628B1 (pt) | 2021-09-08 |
| IL217926A0 (en) | 2012-03-29 |
| US9393299B2 (en) | 2016-07-19 |
| US20130011435A1 (en) | 2013-01-10 |
| WO2011015656A3 (en) | 2011-03-31 |
| RU2012107671A (ru) | 2013-09-20 |
| ZA201200899B (en) | 2012-10-31 |
| MX2012001592A (es) | 2012-05-22 |
| CN105535960A (zh) | 2016-05-04 |
| TWI555531B (zh) | 2016-11-01 |
| RU2555346C2 (ru) | 2015-07-10 |
| JP2013501038A (ja) | 2013-01-10 |
| TW201106967A (en) | 2011-03-01 |
| KR20120052352A (ko) | 2012-05-23 |
| JP6246778B2 (ja) | 2017-12-13 |
| NZ598000A (en) | 2013-10-25 |
| AU2010280710A1 (en) | 2012-03-01 |
| JP5897464B2 (ja) | 2016-03-30 |
| IL217926A (en) | 2016-07-31 |
| WO2011015656A2 (en) | 2011-02-10 |
| CA2770075A1 (en) | 2011-02-10 |
| BR112012002628A2 (pt) | 2016-11-08 |
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