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21. 发明公开

EP2864338A2 7-OXO-THIAZOLOPYRIDINE CARBONIC ACID DERIVATIVES AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF A VIRAL DISEASE 有权
标题翻译： 7-氧代THIAZOLOPYRIDINKOHLENSÄUREDERIVATE及其用途用于治疗，减轻或预防一种疾病病毒的
公开(公告)号：EP2864338A2
公开(公告)日：2015-04-29
申请号：EP13730130.5
申请日：2013-05-23
申请人： Savira Pharmaceuticals GmbH , F.Hoffmann-La Roche AG , European Molecular Biology Laboratory (EMBL)
发明人： WOLKERSTORFER, Andrea , SZOLAR, Oliver , HANDLER, Norbert , CUSACK, Stephen , SAUVAÎTRE, Thibault , MICHAUT-SIMON, Céline , MORICE, Christophe , GIETHLEN, Bruno , LANGER, Thierry , SMITH, Mark , SO, Sung-Sau , CLASSEN-HOUBEN, Dirk , BUSCHMANN, Helmut
IPC分类号： C07D513/04 , A61K31/429 , A61P31/12
CPC分类号： C07D513/04 , A61K31/437 , A61K31/4545 , A61K31/496 , A61K31/519 , A61K31/5377 , A61K45/06 , C07D487/04
摘要： The present invention relates to a compound having the general formula (A), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diasiereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

22. 发明公开

EP2776396A2 HETEROARYL HYDROXAMIC ACID DERIVATIVES AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF A VIRAL DISEASE 审中-公开
标题翻译： HETEROARYLHYDROXAMSÄUREDERIVATE及其用途用于治疗，减轻或预防疾病病毒的
公开(公告)号：EP2776396A2
公开(公告)日：2014-09-17
申请号：EP12786860.2
申请日：2012-10-19
申请人： F.Hoffmann-La Roche AG , Savira Pharmaceuticals GmbH , European Molecular Biology Laboratory
发明人： CLASSEN-HOUBEN, Dirk , WOLKERSTORFER, Andrea , SZOLAR, Oliver , SMITH, Mark , SO, Sung-Sau , CUSACK, Stephen , LANGER, Thierry , GIETHLEN, Bruno , MORICE, Christophe , MICHAUT-SIMON, Céline , ZUBIETA, Chloe
IPC分类号： C07D213/81 , C07D217/26 , C07D401/04 , C07D401/12 , C07D401/14 , C07D405/08 , C07D413/04 , C07D471/04 , C07D495/04 , A61K31/44 , A61P31/16
CPC分类号： C07D213/81 , A61K31/44 , A61K31/4439 , A61K31/444 , A61K31/4545 , A61K31/47 , A61K31/472 , A61K31/496 , A61K31/519 , A61K31/5377 , A61K45/06 , C07D215/48 , C07D217/26 , C07D401/04 , C07D401/12 , C07D401/14 , C07D405/04 , C07D405/08 , C07D413/04 , C07D471/04 , C07D493/10 , C07D495/04
摘要： The present invention relates to a compound having the general formula I, optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, tautomer, racemate, enantiomer, or dsasiereomer or mixture thereof, which is useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.
摘要翻译：本发明涉及具有通式I，任选呈其药学上可接受的盐，溶剂合物，多晶型物，前药，互变异构体，外消旋体，对映体，或对映异构体或其混合物的形式，其可用于治疗，改善或预防有用的化合物，在所有病毒性疾病。进一步，特定的组合疗法是游离缺失盘。

23. 发明公开

EP3166951A1 DIHYDROPYRIDOPYRAZINE-1,8-DIONES AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF VIRAL DISEASES 无效
标题翻译： DIHYDROPYRIDOPYRAZIN -1,8-二酮和它们在治疗中，RELIEF或预防病毒病
公开(公告)号：EP3166951A1
公开(公告)日：2017-05-17
申请号：EP15745155.0
申请日：2015-07-06
申请人： Savira Pharmaceuticals GmbH , European Molecular Biology Laboratory
发明人： SCHULZ-GASCH, Tanja , WEIKERT, Robert , NEIDHART, Werner , BUSCHMANN, Helmut , SZOLAR, Oliver , WOLKERSTORFER, Andrea , HANDLER, Norbert , ROCH, Franz-Ferdinand , CUSACK, Stephen
IPC分类号： C07D519/00 , A61K31/499 , A61P31/12
CPC分类号： A61K31/506 , A61K31/4985 , A61K45/06 , C07D471/04 , C07D519/00
摘要： The present invention relates to a compound having the general formula (V), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.
摘要翻译：本发明涉及具有通式（V）中，任选地在药学上可接受的盐，溶剂合物，多晶型物，共药物，共结晶体，前药，互变异构体，外消旋体，对映异构体，或非对映体或混合物的形式存在的化合物，这是有用在治疗，预防或ameloriating病毒性疾病。进一步，特定的组合疗法是游离缺失盘。

24. 发明授权

EP2864338B1 7-OXO-THIAZOLOPYRIDINE CARBONIC ACID DERIVATIVES AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF A VIRAL DISEASE 有权
标题翻译： 7-氧代THIAZOLOPYRIDINKOHLENSÄUREDERIVATE及其用途用于治疗，减轻或预防一种疾病病毒的
公开(公告)号：EP2864338B1
公开(公告)日：2016-12-14
申请号：EP13730130.5
申请日：2013-05-23
申请人： Savira Pharmaceuticals GmbH , F.Hoffmann-La Roche AG , European Molecular Biology Laboratory (EMBL)
发明人： WOLKERSTORFER, Andrea , SZOLAR, Oliver , HANDLER, Norbert , CUSACK, Stephen , SAUVAÎTRE, Thibault , MICHAUT-SIMON, Céline , MORICE, Christophe , GIETHLEN, Bruno , LANGER, Thierry , SMITH, Mark , SO, Sung-Sau , CLASSEN-HOUBEN, Dirk , BUSCHMANN, Helmut
IPC分类号： C07D513/04 , A61K31/429 , A61P31/12
CPC分类号： C07D513/04 , A61K31/437 , A61K31/4545 , A61K31/496 , A61K31/519 , A61K31/5377 , A61K45/06 , C07D487/04

25. 发明公开

EP2794616A1 PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF A VIRAL DISEASE 有权
标题翻译：嘧啶-4- ON衍生物及其在治疗，减轻或预防一种疾病病毒的
公开(公告)号：EP2794616A1
公开(公告)日：2014-10-29
申请号：EP12787384.2
申请日：2012-10-19
申请人： F.Hoffmann-La Roche AG , Savira Pharmaceuticals GmbH , European Molecular Biology Laboratory
发明人： CLASSEN-HOUBEN, Dirk , WOLKERSTORFER, Andrea , SZOLAR, Oliver , SMITH, Mark , SO, Sung-Sau , CUSACK, Stephen , LANGER, Thierry , GIETHLEN, Bruno , MORICE, Christophe , MICHAUT-SIMON, Céline , JUNG, Laurence
IPC分类号： C07D495/04 , A61K31/519 , A61P31/12
CPC分类号： C07D495/04 , A61K31/519 , A61K31/5377 , A61K45/06
摘要： The present invention relates to a compound having the general formula (II), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, Formula (II) which is useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

26. 发明申请

WO2020239822A1 NUCLEIC ACID CONSTRUCT BINDING TO INFLUENZA POLYMERASE PB1 RNA SYNTHESIS ACTIVE SITE 审中-公开
公开(公告)号：WO2020239822A1
公开(公告)日：2020-12-03
申请号：PCT/EP2020/064674
申请日：2020-05-27
申请人： THE EUROPEAN MOLECULAR BIOLOGY LABORATORY
发明人： CUSACK, Stephen , DRNCOVA, Petra , KOUBA, Tomas
IPC分类号： C12N15/11 , C12N9/12 , C07K14/005 , C30B29/58
摘要： The present invention relates to a new nucleic acid construct capable of binding to the PB1 RNA synthesis active site of influenza polymerase. The nucleic acid construct allows capturing the structure of the transcription initiation state of influenza polymerase. The present invention further pertains to methods for obtaining images or crystallography data on an influenza polymerase in a functional or active state, methods for identifying, selecting or designing a compound which inhibits influenza RNA polymerase, and to such compounds per se. Further provided are pharmaceutical compositions comprising such compounds and the compounds or pharmaceutical compositions for use in treating, ameliorating, or preventing a disease caused by viral infections with negative-sense single stranded RNA viruses.

27. 发明申请

WO2018007615A1 VIRAL POLYPEPTIDE FRAGMENTS THAT BIND CELLULAR POL II C-TERMINAL DOMAIN (CTD) AND THEIR USES 审中-公开
标题翻译：结合细胞pol II C-端结构域（CTD）的病毒多肽片段及其用途
公开(公告)号：WO2018007615A1
公开(公告)日：2018-01-11
申请号：PCT/EP2017/067144
申请日：2017-07-07
申请人： THE EUROPEAN MOLECULAR BIOLOGY LABORATORY
发明人： CUSACK, Stephen , PFLUG, Alexander , LUKARSKA, Maria
IPC分类号： C12N9/12 , G06F19/16
摘要： The present invention relates to in silico methods for identifying compounds which decrease or prevent the binding of the viral RNA-dependent RNA polymerase from the Orthomyxoviridae family or variant thereof, to its ligand, (preferably to cellular Pol II, more preferably to CTD), as well as methods of producing the identified compounds. The present invention also relates to a compounds identifiable and/or producible by said methods. The present invention also relates to antibodies directed against the binding site of the RNA-dependent RNA polymerase, to its ligand (in particular to cellular Pol II, in particular to CTD of Pol II) as well as nucleic acids encoding said antibodies and vectors comprising the nucleic acid. The present invention relates to a pharmaceutical composition producible according to said method, and/or comprising said compound, said antibody, said nucleic acid, or said vector. The present invention also relates to the use of said compound, said antibody, said nucleic acid, said vector or said pharmaceutical in treating, ameliorating, or preventing disease conditions caused by viral infections with viruses of the Orthomyxoviridae family.
摘要翻译：本发明涉及用于鉴定减少或防止病毒RNA依赖性RNA聚合酶从正粘病毒科或其变体与其变体结合的化合物的计算机方法，配体（优选转化为细胞Pol II，更优选转化为CTD），以及生产所鉴定的化合物的方法。本发明还涉及可通过所述方法鉴定和/或生产的化合物。本发明还涉及针对所述RNA依赖性RNA聚合酶的结合位点的抗体，其配体（尤其是对细胞RNA聚合酶II，特别是RNA聚合酶II的CTD）以及核酸编码所述抗体和载体，其包括核酸。本发明涉及根据所述方法可产生的和/或包含所述化合物，所述抗体，所述核酸或所述载体的药物组合物。本发明还涉及所述化合物，所述抗体，所述核酸，所述载体或所述药物在治疗，改善或预防由正粘病毒科病毒感染病毒引起的疾病中的用途。

28. 发明申请

WO2010069600A2 POLYPEPTIDE FRAGMENTS COMPRISING ENDONUCLEASE ACTIVITY AND THEIR USE 审中-公开
标题翻译：包含内切酶活性的多肽片段及其使用
公开(公告)号：WO2010069600A2
公开(公告)日：2010-06-24
申请号：PCT/EP2009/009161
申请日：2009-12-18
申请人： EUROPEAN MOLECULAR BIOLOGY LABORATORY (EMBL) , UNIVERSITY JOSEPH FOURIER FILIALE , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE� , BOUVIER, Denis , CREPIN, Thibaut , RUIGROK, Rob , DIAS, Alexander , CUSACK, Stephen
发明人： BOUVIER, Denis , CREPIN, Thibaut , RUIGROK, Rob , DIAS, Alexander , CUSACK, Stephen
IPC分类号： C12N9/12
CPC分类号： C12N9/22 , A61K31/192 , C07K2299/00 , C12N9/127 , C12Q1/44 , G01N2333/922 , G01N2500/02 , G06F19/12 , G06F19/16
摘要： The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.
摘要翻译：本发明涉及包含病毒RNA依赖性RNA聚合酶的PA亚基的氨基末端片段或其具有核酸内切酶活性的变体的多肽片段，其中所述PA亚单位来自属于正粘病毒科的病毒。本发明还涉及（i）适合于使用X射线晶体学结构测定所述多肽片段的多肽片段的晶体，以及（ii）使用所述多肽的结构坐标筛选和设计调节的化合物的计算方法，优选抑制多肽片段内的核内解离活性位点。此外，本发明涉及鉴定结合具有核酸内切酶活性的PA多肽片段的化合物的方法，优选抑制所述内切核酸酶活性，优选以高通量设置。本发明还涉及包含鉴定的化合物的化合物和药物组合物，用于治疗由正粘病毒科家族病毒引起的病毒感染引起的疾病状况。

29. 发明申请

WO2011113579A2 INFLUENZA A 2009 PANDEMIC H1N1 POLYPEPTIDE FRAGMENTS COMPRISING ENDONUCLEASE ACTIVITY AND THEIR USE 审中-公开
标题翻译： INFLUENZA A 2009大流行H1N1多肽片段包含内切酶活性及其使用
公开(公告)号：WO2011113579A2
公开(公告)日：2011-09-22
申请号：PCT/EP2011/001274
申请日：2011-03-15
申请人： EUROPEAN MOLECULAR BIOLOGY LABORATORY (EMBL) , CUSACK, Stephen , KOWALINSKI, Eva , ZUBIETA, Chloe
发明人： CUSACK, Stephen , KOWALINSKI, Eva , ZUBIETA, Chloe
IPC分类号： C07K14/11
CPC分类号： C12N9/22 , A61K31/33 , A61K38/00 , C07D211/32 , C07D211/96 , C07D311/62 , C07H19/10 , C07K14/005 , C07K16/40 , C07K2299/00 , C07K2317/34 , C12N2760/16122 , G06F19/16
摘要： The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase possessing endonuclease activity, wherein said PA subunit is from Influenza A 2009 pandemic HlNl virus or is a variant thereof. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds which are able to modulate, preferably to inhibit, the endonuclease activity of the PA subunit polypeptide fragment or variant thereof of the present invention and pharmaceutical compositions comprising said compounds for the treatment of disease conditions caused by viral infections with viruses of the Orthomyxoviridae family, Bunyaviridae family and/or Arenviridae family, preferably caused by viral infections with Influenza A 2009 pandemic HlNl virus. Preferably, said compounds are identifiable by the methods disclosed herein or said pharmaceutical compositions are producible by the methods disclosed herein.
摘要翻译：本发明涉及包含具有核酸内切酶活性的病毒RNA依赖性RNA聚合酶的PA亚单位的氨基末端片段的多肽片段，其中所述PA亚单位来自A流感大流行H1N1病毒，或其变体。本发明还涉及（i）适合于使用X射线晶体学结构测定所述多肽片段的多肽片段的晶体，以及（ii）使用所述多肽的结构坐标筛选和设计调节的化合物的计算方法，优选抑制多肽片段内的核内解离活性位点。此外，本发明涉及鉴定结合具有核酸内切酶活性的PA多肽片段的化合物的方法，优选抑制所述内切核酸酶活性，优选以高通量设置。本发明还涉及能够调节，优选抑制本发明的PA亚基多肽片段或其变体的内切核酸酶活性的化合物和包含所述化合物的药物组合物，用于治疗由病毒感染引起的疾病状况的正粘病毒科，布尼亚病毒科和/或球虫病科，优选由2009年流感大流行H1N1流感病毒感染引起。优选地，所述化合物可以通过本文公开的方法鉴定，或者所述药物组合物可通过本文公开的方法生产。

30. 发明申请

WO2009046983A1 SOLUBLE FRAGMENTS OF INFLUENZA VIRUS PB2 PROTEIN CAPABLE OF BINDING RNA-CAP 审中-公开
标题翻译：可溶性片段的流感病毒PB2蛋白能够结合RNA-CAP
公开(公告)号：WO2009046983A1
公开(公告)日：2009-04-16
申请号：PCT/EP2008/008543
申请日：2008-10-09
申请人： EUROPEAN MOLECULAR BIOLOGY LABORATORY (EMBL) , CUSACK, Stephen , GUILLIGAY, Delphine , HART, Darren , TARENDEAU, Franck
发明人： CUSACK, Stephen , GUILLIGAY, Delphine , HART, Darren , TARENDEAU, Franck
IPC分类号： C07K14/11 , C12Q1/18 , A61K38/00 , C07K14/16
CPC分类号： B65D1/0223 , B65D79/005 , B65D2501/0036 , C07K14/005 , C07K2299/00 , C12N2760/16122 , G01N2333/11 , G01N2500/04
摘要： The present invention relates to soluble fragments of the Influenza virus RNA dependent RNA polymerase subunit PB2 and variants thereof, and crystallized complexes thereof comprising an RNA cap analog. This invention also relates to computational methods using the structural coordinates of said complex to screen for and design compounds that interact with the RNA cap binding pocket. In addition, this invention relates to methods identifying compounds that bind to PB2 polypeptide fragments comprising the RNA cap binding pocket, preferably inhibit the interaction with RNA caps or analogs thereof, by using said PB2 polypeptide fragments, preferably in a high-throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by negative-sense single stranded RNA viruses.
摘要翻译：本发明涉及流感病毒RNA依赖性RNA聚合酶亚基PB2及其变体的可溶性片段及其包含RNA帽类似物的结晶复合物。本发明还涉及使用所述复合物的结构坐标筛选和设计与RNA帽结合口袋相互作用的化合物的计算方法。此外，本发明涉及通过使用所述PB2多肽片段，优选以高通量设置，鉴定结合含有RNA帽结合口袋的PB2多肽片段的化合物的方法，优选抑制与RNA帽或其类似物的相互作用。本发明还涉及包含用于治疗由负义单链RNA病毒引起的病毒感染的疾病状况的鉴定化合物的化合物和药物组合物。

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