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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| CN106148404B (zh) * | 2015-03-25 | 2020-01-24 | 复旦大学 | 一种人乙型肝炎病毒重组载体及其应用 |
| 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 |
| EP4177348A1 (en) * | 2015-11-04 | 2023-05-10 | Hookipa Biotech GmbH | Vaccines against hepatitis b virus |
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| CA3002508A1 (en) * | 2016-01-12 | 2017-07-20 | Ulrike Protzer | Means and methods for treating hbv |
| WO2017180770A1 (en) | 2016-04-13 | 2017-10-19 | Synthetic Genomics, Inc. | Recombinant arterivirus replicon systems and uses thereof |
| US11052148B2 (en) | 2016-05-30 | 2021-07-06 | Geo Vax, Inc. | Compositions and methods for generating an immune response to hepatitis B virus |
| KR20190020745A (ko) * | 2016-06-15 | 2019-03-04 | 옥스포드 유니버시티 이노베이션 리미티드 | Abc4a를 발현시키기 위한 이중 중첩 아데노-관련 바이러스 벡터 시스템 |
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| EP3522920A2 (en) | 2016-10-10 | 2019-08-14 | Transgene SA | Immunotherapeutic product and mdsc modulator combination therapy |
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| BR112019011661A2 (pt) | 2016-12-05 | 2020-01-07 | Synthetic Genomics, Inc. | Composições e métodos para aumentar expressão de gene |
| GB201705765D0 (en) | 2017-04-10 | 2017-05-24 | Univ Oxford Innovation Ltd | HBV vaccine |
| CN110769850A (zh) | 2017-05-15 | 2020-02-07 | 扬森疫苗与预防公司 | 稳定的含病毒组合物 |
| EP3624851A1 (en) | 2017-05-15 | 2020-03-25 | Janssen Vaccines & Prevention B.V. | Stable virus-containing composition |
| GB201721069D0 (en) | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B Immunisation regimen and compositions |
| 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) |
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| SG11202005710YA (en) * | 2017-12-19 | 2020-07-29 | Janssen Sciences Ireland Unlimited Co | Methods and compositions for inducing an immune response against hepatitis b virus (hbv) |
| KR20200111729A (ko) | 2018-01-19 | 2020-09-29 | 얀센 파마슈티칼즈, 인코포레이티드 | 재조합 레플리콘 시스템을 이용한 면역 반응 유도 및 증진 |
| IL277128B2 (en) | 2018-03-06 | 2025-11-01 | Precigen Inc | Hepatitis b vaccines and uses of the same |
| KR102234027B1 (ko) * | 2018-05-09 | 2021-03-31 | 서울대학교산학협력단 | B형 간염 바이러스 유래 폴리펩티드 및 이의 항바이러스 용도 |
| KR20210074314A (ko) | 2018-10-08 | 2021-06-21 | 얀센 파마슈티칼즈, 인코포레이티드 | 생체치료제의 투여를 위한 알파바이러스 기반 레플리콘 |
| CN114340663A (zh) * | 2019-06-18 | 2022-04-12 | 爱尔兰詹森科学公司 | 乙型肝炎病毒(HBV)疫苗和靶向HBV的RNAi的组合 |
| US20220296703A1 (en) * | 2019-06-18 | 2022-09-22 | Janssen Sciences Ireland Unlimited Company | Cobmination of hepatitis b virus (hbv) vaccines and anti-pd-1 or anti-pd-l1 antibody |
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| JP2023505304A (ja) | 2019-12-07 | 2023-02-08 | アイエスエー ファーマシューティカルズ ビー．ヴイ． | Ｂ型肝炎ウイルスに関連する疾患の治療 |
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| 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 |
| NZ270605A (en) | 1991-08-26 | 1997-07-27 | Cytel Corp | Cytotoxic t lymphocyte inducing peptides (6-19 amino acids) and pharmaceutical compositions thereof |
| 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 |
| AU695261B2 (en) | 1993-02-26 | 1998-08-13 | Scripps Research Institute, The | Peptides for inducing cytotoxic T lymphocyte responses to hepatitis B virus |
| 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 |
| US5994128A (en) | 1995-06-15 | 1999-11-30 | Introgene B.V. | Packaging systems for human recombinant adenovirus to be used in gene therapy |
| EP0833668A4 (en) * | 1995-06-20 | 2001-12-12 | Gen Hospital Corp | INHIBITATION OF THE HEPATITIS B VIRUS 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 |
| US6485958B2 (en) | 1996-07-01 | 2002-11-26 | Gencell Sa | Method for producing recombinant adenovirus |
| US5981274A (en) * | 1996-09-18 | 1999-11-09 | Tyrrell; D. Lorne J. | Recombinant hepatitis virus vectors |
| WO1998022588A2 (en) | 1996-11-20 | 1998-05-28 | Introgen Therapeutics, Inc. | An improved method for the production and purification of adenoviral vectors |
| ATE353956T1 (de) | 1996-12-13 | 2007-03-15 | 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 |
| SK7602001A3 (en) | 1998-12-04 | 2002-03-05 | 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 |
| CA2356373A1 (fr) | 1998-12-31 | 2000-07-13 | Aventis Pharma S.A. | Methode de separation de particules virales |
| AU774437B2 (en) | 1999-02-22 | 2004-06-24 | Transgene S.A. | Method for obtaining a purified viral preparation |
| ES2289426T3 (es) | 1999-05-17 | 2008-02-01 | Crucell Holland B.V. | Adenovirus recombinante humano de serotipo 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 |
| AU2001252458A1 (en) * | 2000-05-05 | 2001-11-20 | Martin Bachmann | Molecular antigen arrays and vaccines |
| RU2286172C2 (ru) * | 2000-08-17 | 2006-10-27 | Трипеп Аб | Вакцины, содержащие рибавирин, и способы их использования |
| EP1390398A2 (en) | 2001-05-30 | 2004-02-25 | Transgene S.A. | Adenovirus protein ix, its domains involved in capsid assembly, transcriptional activity and nuclear reorganization |
| JP4502642B2 (ja) * | 2002-02-07 | 2010-07-14 | メルボルン ヘルス | ヌクレオシドアナログに対する感受性の変化を有するウイルス変種およびその使用 |
| 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 |
| WO2004083418A1 (en) | 2003-03-17 | 2004-09-30 | Merck & Co., Inc. | Adenovirus serotype 24 vectors, nucleic acids and virus produced thereby |
| CA2519207A1 (en) | 2003-03-28 | 2004-11-11 | 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 |
| WO2004113370A1 (de) * | 2003-06-20 | 2004-12-29 | Dade Behring Marburg Gmbh | NEUE OBERFLÄCHENPROTEIN-(HBsAG-) VARIANTE DES HEPATITIS B VIRUS |
| AU2004260044B2 (en) | 2003-07-18 | 2009-04-23 | Onyx Pharmaceuticals, Inc. | Subgroup B adenoviral vectors for treating disease |
| DK1648931T3 (da) | 2003-07-21 | 2011-03-07 | Transgene Sa | Multifunktionelle cytokiner |
| 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 |
| AU2004285983B2 (en) * | 2003-10-21 | 2012-06-28 | Alfred Health | HBV variants detection and application |
| GB0328753D0 (en) | 2003-12-11 | 2004-01-14 | Royal Veterinary College The | Hepatitis B vaccines |
| US8470591B2 (en) | 2004-11-08 | 2013-06-25 | Transgene S.A. | Kit of parts designed for implementing an antitumoral or antiviral treatment in a mammal |
| 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 |
| JP5188400B2 (ja) * | 2006-03-09 | 2013-04-24 | トランスジーン エス．エー． | Ｃ型肝炎ウイルスの非構造融合タンパク質 |
| US20100129403A1 (en) | 2006-06-20 | 2010-05-27 | Transgene S.A. | Recombinant viral vaccine |
| WO2008020656A1 (en) * | 2006-08-14 | 2008-02-21 | Postech Foundation | A dna vaccine for curing chronic hepatitis b and a method of preparing same |
| US8337859B2 (en) * | 2007-05-15 | 2012-12-25 | Transgene S.A. | Vectors for multiple gene expression |
| CN102015753A (zh) * | 2008-01-25 | 2011-04-13 | 海德堡吕布莱希特-卡尔斯大学 | 乙肝病毒(HBV)的疏水性修饰的preS-衍生肽及其作为载体将化合物特异性递送到肝脏的用途 |
| CA2770075C (en) * | 2009-08-07 | 2021-08-24 | Perrine Martin | Composition for treating hbv infection |
| US10076570B2 (en) * | 2009-08-07 | 2018-09-18 | Transgene S.A. | Composition for treating HBV infection |
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- 2010-08-06 WO PCT/EP2010/061492 patent/WO2011015656A2/en not_active Ceased
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- 2010-08-06 TW TW099126293A patent/TWI555531B/zh active
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| Publication number | Publication date |
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| JP2013501038A (ja) | 2013-01-10 |
| IL217926A (en) | 2016-07-31 |
| HK1223295A1 (zh) | 2017-07-28 |
| MX2012001592A (es) | 2012-05-22 |
| JP5897464B2 (ja) | 2016-03-30 |
| CN102573903B (zh) | 2015-12-02 |
| ZA201200899B (en) | 2012-10-31 |
| CN105535960B (zh) | 2019-06-04 |
| RU2555346C2 (ru) | 2015-07-10 |
| TW201106967A (en) | 2011-03-01 |
| CN102573903A (zh) | 2012-07-11 |
| WO2011015656A3 (en) | 2011-03-31 |
| KR20120052352A (ko) | 2012-05-23 |
| US20170072047A1 (en) | 2017-03-16 |
| JP2016074707A (ja) | 2016-05-12 |
| SG178254A1 (en) | 2012-03-29 |
| US9393299B2 (en) | 2016-07-19 |
| CN105535960A (zh) | 2016-05-04 |
| JP6246778B2 (ja) | 2017-12-13 |
| EP2461826A2 (en) | 2012-06-13 |
| WO2011015656A2 (en) | 2011-02-10 |
| TWI555531B (zh) | 2016-11-01 |
| IL217926A0 (en) | 2012-03-29 |
| BR112012002628B1 (pt) | 2021-09-08 |
| CA2770075A1 (en) | 2011-02-10 |
| BR112012002628A2 (pt) | 2016-11-08 |
| NZ598000A (en) | 2013-10-25 |
| AU2010280710A1 (en) | 2012-03-01 |
| RU2012107671A (ru) | 2013-09-20 |
| US20130011435A1 (en) | 2013-01-10 |
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