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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| DK3402888T3 (da) * | 2016-01-12 | 2020-11-30 | Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Gesundheit & Umwelt Gmbh | Middel og fremgangsmåder til behandling af hbv |
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| US20190309326A1 (en) * | 2016-06-15 | 2019-10-10 | Oxford University Innovation Limited | Dual overlapping adeno-associated viral vector system for expressing abca4 |
| EP3276006A1 (en) * | 2016-07-27 | 2018-01-31 | Theravectys | Lentiviral vectors for expression of hepatitis b virus (hbv) antigens |
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| GB201721069D0 (en) | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B Immunisation regimen and compositions |
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| MX2021004032A (es) | 2018-10-08 | 2021-07-06 | Janssen Pharmaceuticals Inc | Replicones basados en alfavirus para la administracion de bioterapeuticos. |
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| 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 |
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| 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 |
| DE69231621T2 (de) | 1991-08-26 | 2001-05-31 | Epimmune, Inc. | Hepatitis-B-Virus-Epitope mit HLA-reduzierte CTL-Respons |
| 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 |
| KR960700745A (ko) | 1993-02-26 | 1996-02-24 | 더글라스 에이. 빙햄 | 비(b)형 간염 바이러스에 대한 세포독성 티(t) 임파세포 응답반응을 유도하는 펩티드(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. |
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| US5910488A (en) * | 1993-06-07 | 1999-06-08 | 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 |
| DE69638058D1 (de) | 1995-06-15 | 2009-11-26 | Crucell Holland Bv | Verpackungssysteme für humane rekombinante Adenoviren zur Gentherapie |
| 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 |
| WO1998000524A1 (fr) | 1996-07-01 | 1998-01-08 | Rhone-Poulenc Rorer S.A. | Procede de production d'adenovirus recombinants |
| US5981274A (en) * | 1996-09-18 | 1999-11-09 | Tyrrell; D. Lorne J. | Recombinant hepatitis virus vectors |
| EP1707631A3 (en) | 1996-11-20 | 2006-12-27 | Introgen Therapeutics, Inc. | An improved method for the production and purification of adenoviral vectors |
| JP2001506126A (ja) | 1996-12-13 | 2001-05-15 | シェーリング コーポレイション | ウイルスの精製方法 |
| 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 |
| 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 |
| HU229222B1 (en) | 1998-12-04 | 2013-09-30 | Biogen Idec Ma Inc Cambridge | 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 |
| AU779267B2 (en) | 1998-12-31 | 2005-01-13 | Centelion S.A.S. | Method for separating viral particles |
| ATE332364T1 (de) | 1999-02-22 | 2006-07-15 | Transgene Sa | Verfahren zur gewinnung von purifizierter virenzuammensetzung |
| DK1681353T3 (da) | 1999-05-17 | 2010-01-04 | Crucell Holland Bv | Af adenovirus afledte genoverförselsvehikler indeholdende mindste ét element af adenovirus type 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 |
| CA2407897A1 (en) * | 2000-05-05 | 2001-11-15 | Cytos Biotechnology Ag | Molecular antigen arrays and vaccines |
| US6858590B2 (en) * | 2000-08-17 | 2005-02-22 | Tripep Ab | Vaccines containing ribavirin and methods of use thereof |
| AU2002344190B2 (en) | 2001-05-30 | 2007-10-18 | Transgene S.A. | Adenovirus protein IX, Its domains involved in capsid assembly, transcriptional activity and nuclear reorganization |
| EP1476543B1 (en) * | 2002-02-07 | 2014-05-14 | Melbourne Health | Viral variants with altered susceptibility to nucleoside analogs and uses thereof |
| US7351413B2 (en) * | 2002-02-21 | 2008-04-01 | Lorantis, Limited | Stabilized HBc chimer particles as immunogens for chronic hepatitis |
| JP4495588B2 (ja) | 2002-04-25 | 2010-07-07 | クルセル ホランド ベー ヴェー | 安定なアデノウイルスベクターおよびその増殖方法 |
| US20040185555A1 (en) | 2003-03-17 | 2004-09-23 | Emini Emilio A. | Adenovirus serotype 24 vectors, nucleic acids and virus produced thereby |
| EP1611237A1 (en) | 2003-03-28 | 2006-01-04 | 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 |
| EP1638995B1 (de) | 2003-06-20 | 2015-08-26 | Siemens Healthcare Diagnostics Products GmbH | Neue oberflächenprotein-(hbsag-) variante des hepatitis b virus |
| CN1934253A (zh) | 2003-07-18 | 2007-03-21 | 昂尼克斯药物公司 | 用于治疗疾病的b亚组腺病毒载体 |
| JP4842128B2 (ja) | 2003-07-21 | 2011-12-21 | トランジェーヌ、ソシエテ、アノニム | 新規多機能性サイトカイン |
| 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 |
| CN1934248B (zh) * | 2003-10-21 | 2012-08-22 | 墨尔本保健公司 | Hbv变异体的检测和应用 |
| 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 |
| ES2387321T3 (es) * | 2006-03-09 | 2012-09-20 | Transgene Sa | Proteína de fusión no estructural del virus de la hepatitis C |
| CA2656266C (en) * | 2006-06-20 | 2012-07-31 | Transgene S.A. | Recombinant viral vaccine |
| EP2057268B1 (en) * | 2006-08-14 | 2014-08-13 | Postech Foundation | A dna vaccine for curing chronic hepatitis b and a method of preparing same |
| EP2162544B1 (en) * | 2007-05-15 | 2013-04-17 | Transgene SA | Vectors for multiple gene expression |
| JP5686468B2 (ja) * | 2008-01-25 | 2015-03-18 | ルプレヒト−カールス−ウニヴェルジテート ハイデルベルクＲｕｐｒｅｃｈｔ−Ｋａｒｌｓ−Ｕｎｉｖｅｒｓｉｔａｅｔ Ｈｅｉｄｅｌｂｅｒｇ | Ｂ型肝炎ウイルス（ＨＢＶ）の疎水性修飾されたｐｒｅＳ由来ペプチド及び肝臓に化合物を特異的に送達するためのビヒクルとしてのそれらの使用 |
| US10076570B2 (en) * | 2009-08-07 | 2018-09-18 | Transgene S.A. | Composition for treating HBV infection |
| SG178254A1 (en) * | 2009-08-07 | 2012-03-29 | Transgene Sa | Composition for treating hbv infection |
-
2010
- 2010-08-06 SG SG2012007845A patent/SG178254A1/en unknown
- 2010-08-06 MX MX2012001592A patent/MX2012001592A/es active IP Right Grant
- 2010-08-06 CN CN201080042650.2A patent/CN102573903B/zh active Active
- 2010-08-06 EP EP10737945A patent/EP2461826A2/en not_active Ceased
- 2010-08-06 CA CA2770075A patent/CA2770075C/en active Active
- 2010-08-06 KR KR1020127005033A patent/KR20120052352A/ko not_active Ceased
- 2010-08-06 CN CN201510884240.7A patent/CN105535960B/zh active Active
- 2010-08-06 TW TW099126293A patent/TWI555531B/zh active
- 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
- 2010-08-06 JP JP2012523352A patent/JP5897464B2/ja not_active Expired - Fee Related
- 2010-08-06 RU RU2012107671/15A patent/RU2555346C2/ru active
- 2010-08-06 US US13/388,826 patent/US9393299B2/en not_active Expired - Fee Related
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- 2012-02-07 ZA ZA2012/00899A patent/ZA201200899B/en unknown
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2015
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2016
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Also Published As
| Publication number | Publication date |
|---|---|
| RU2555346C2 (ru) | 2015-07-10 |
| SG178254A1 (en) | 2012-03-29 |
| TW201106967A (en) | 2011-03-01 |
| AU2010280710A1 (en) | 2012-03-01 |
| NZ598000A (en) | 2013-10-25 |
| JP5897464B2 (ja) | 2016-03-30 |
| CN105535960B (zh) | 2019-06-04 |
| TWI555531B (zh) | 2016-11-01 |
| CA2770075A1 (en) | 2011-02-10 |
| BR112012002628B1 (pt) | 2021-09-08 |
| US9393299B2 (en) | 2016-07-19 |
| US20130011435A1 (en) | 2013-01-10 |
| IL217926A (en) | 2016-07-31 |
| WO2011015656A3 (en) | 2011-03-31 |
| IL217926A0 (en) | 2012-03-29 |
| HK1223295A1 (zh) | 2017-07-28 |
| JP2016074707A (ja) | 2016-05-12 |
| CN105535960A (zh) | 2016-05-04 |
| KR20120052352A (ko) | 2012-05-23 |
| ZA201200899B (en) | 2012-10-31 |
| EP2461826A2 (en) | 2012-06-13 |
| CN102573903A (zh) | 2012-07-11 |
| WO2011015656A2 (en) | 2011-02-10 |
| JP2013501038A (ja) | 2013-01-10 |
| MX2012001592A (es) | 2012-05-22 |
| RU2012107671A (ru) | 2013-09-20 |
| JP6246778B2 (ja) | 2017-12-13 |
| BR112012002628A2 (pt) | 2016-11-08 |
| CN102573903B (zh) | 2015-12-02 |
| US20170072047A1 (en) | 2017-03-16 |
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