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1. 发明申请

US20210047329A1 SUBSTITUTED 4,6-DIHYDROSPIRO[[1,2,3]TRIAZOLO[4,5-B]PYRIDINE-7,3'-INDOLINE]-2',5(3H)-DIONE ANALOGUES 有权
公开(公告)号：US20210047329A1
公开(公告)日：2021-02-18
申请号：US16938886
申请日：2020-07-24
申请人： Jia Zhou , Pei-Yong Shi , Jimin Xu , Xuping Xie
发明人： Jia Zhou , Pei-Yong Shi , Jimin Xu , Xuping Xie
IPC分类号： C07D471/20 , A61P31/14
摘要： A series of substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3′-indoline]-2′,5(3H)-dione analogues, the use thereof and the preparation thereof.

2. 发明授权

US11407752B2 Substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3′-indoline]-2′,5(3H)-dione analogues 有权
公开(公告)号：US11407752B2
公开(公告)日：2022-08-09
申请号：US16938886
申请日：2020-07-24
申请人： Jia Zhou , Pei-Yong Shi , Jimin Xu , Xuping Xie
发明人： Jia Zhou , Pei-Yong Shi , Jimin Xu , Xuping Xie
IPC分类号： C07D471/20 , C07D495/04 , A61P31/14
摘要： A series of substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3′-indoline]-2′,5(3H)-dione analogues, the use thereof and the preparation thereof.

3. 发明授权

US10533997B2 Reverse genetics system of Zika virus 有权
公开(公告)号：US10533997B2
公开(公告)日：2020-01-14
申请号：US16098401
申请日：2017-05-03
申请人： Pei-Yong Shi , Chao Shan , Xuping Xie
发明人： Pei-Yong Shi , Chao Shan , Xuping Xie
IPC分类号： A61K39/00 , A61K39/12 , C12N7/00 , A61K45/06 , C07H19/20 , G01N33/569 , C12Q1/70 , C12Q1/6897
摘要： Embodiments of the invention are directed to stable full-length cDNA clones of a clinical, Asian lineage ZIKV strain. Certain embodiments of the invention are directed to high-throughput assays for ZIKV and dengue virus (DENV) diagnosis.

4. 发明申请

US20100279400A1 DIAGNOSTIC TEST FOR WEST NILE VIRUS 审中-公开
标题翻译：西尼病毒诊断测试
公开(公告)号：US20100279400A1
公开(公告)日：2010-11-04
申请号：US12060632
申请日：2008-04-01
申请人： Susan J. Wong , Pei-Yong Shi
发明人： Susan J. Wong , Pei-Yong Shi
IPC分类号： C12N5/16 , C07K16/08
CPC分类号： G01N33/56983 , C12Q1/04 , Y02A50/53
摘要： The present invention provides a rapid and sensitive method for the detection of a West Nile virus (WNV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV) and Dengue virus (DENV) and antibodies directed against thereof involving contacting a biological specimen suspected of being infected with WNV, JE, SLE or DEN with a substantially purified and isolated WNV E glycoprotein or subfragment thereof having a native conformation wherein the E glycoprotein or subfragment thereof has a reactivity with antibodies against WNV and a cross-reactivity with antibodies against JEV, SLEV and DENV. The instant invention further provides a rapid, sensitive, and consistent method for the specific detection of WNV by employing diagnostic assays having the antigen NS5 which is specifically reactive with anti-WNV antibodies but not cross-reactive with antibodies against other flaviviruses such as JEV, SLEV, or DENV. The present invention also provides a rapid, sensitive, and consistent method for the specific detection of DENV by employing diagnostic assays having the antigen NS5 which is specifically reactive with anti-DENV antibodies but do not cross-react with antibodies against other flaviviruses such as JEV, SLEV, or WNV. Further, the DENV NS5 antigens are serospecific and do not cross react with antibodies to other DENV strains. Thus, the method of the present invention provides a manner by which to discriminate infections by each DENV strain. Further, diagnostic kits for carrying out the methods are provided. The methods and kits for carrying out the methods of the invention are rapid and require as little as 10 minutes to detect a result. The invention also provides monoclonal antibodies against WNV NS5 and DENV NS5 antigen and their use in detecting WNV and DENV infections in a biological sample.
摘要翻译：本发明提供了用于检测西尼罗河病毒（WNV），日本脑炎病毒（JEV），圣路易斯脑炎病毒（SLEV）和登革热病毒（DENV））的快速和灵敏的方法以及针对其的抗体涉及使怀疑被WNV，JE，SLE或DEN感染的生物样品具有天然构象的基本纯化和分离的WNV E糖蛋白或其亚片段，其中E糖蛋白或其亚片段与针对WNV的抗体具有反应性和与针对JEV，SLEV和DENV的抗体。本发明进一步提供了通过采用具有与抗-WNV抗体特异性反应但不与抗其它黄病毒（例如JEV）的抗体交叉反应的抗原NS5的诊断试验来进行WNV的特异性检测的快速，灵敏和一致的方法， SLEV或DENV。本发明还提供了通过使用具有与抗DENV抗体特异性反应但不与抗其他黄病毒抗体（例如JEV）的抗体的抗原NS5的诊断测定法来快速，灵敏和一致的方法来进行DENV的特异性检测，SLEV或WNV。此外，DENV NS5抗原是血清特异性的，并且不与其他DENV毒株的抗体交叉反应。因此，本发明的方法提供了鉴别每种DENV毒株感染的方式。此外，提供了用于实施方法的诊断试剂盒。用于实施本发明方法的方法和试剂盒是快速的，并且需要少至10分钟来检测结果。本发明还提供针对WNV NS5和DENV NS5抗原的单克隆抗体及其在检测生物样品中的WNV和DENV感染中的用途。

5. 发明申请

US20110212986A1 ANTI-FLAVIVIRUS THERAPEUTIC 审中-公开
标题翻译：抗甲状腺炎治疗
公开(公告)号：US20110212986A1
公开(公告)日：2011-09-01
申请号：US13060035
申请日：2009-08-20
申请人： Pei-Yong Shi , Francesc Puig-Basagoiti , Krzysztof W. Pankiewicz , Krzysztof Felczak , Liqiang Chen
发明人： Pei-Yong Shi , Francesc Puig-Basagoiti , Krzysztof W. Pankiewicz , Krzysztof Felczak , Liqiang Chen
IPC分类号： A61K31/475 , C07D491/16 , A61P31/14 , C12N7/00
CPC分类号： A61K31/4741 , A61K31/4745 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/393 , Y02A50/395
摘要： The present invention relates to anti-flavivirus compounds, including lycorine and derivatives thereof, and their use in treating a subject infected by a flavivirus. The present invention also relates to the use of the anti-flavivirus compounds for the prophylaxis of flavivirus infection. The present invention further relates to a method of suppressing viral RNA synthesis of a flavivirus. Also described is a method of preparing an anti-flavivirus compound for use in the treatment or prophylaxis of flavivirus infection.
摘要翻译：本发明涉及抗黄病毒化合物，包括抗坏血酸及其衍生物，以及它们在治疗被黄病毒感染的受试者中的用途。本发明还涉及抗黄病毒化合物用于预防黄病毒感染的用途。本发明还涉及抑制黄病毒的病毒RNA合成的方法。还描述了一种制备用于治疗或预防黄病毒感染的抗黄病毒化合物的方法。

6. 发明授权

US07351547B2 Diagnostic test for West Nile virus 有权
标题翻译：西尼罗河病毒诊断试验
公开(公告)号：US07351547B2
公开(公告)日：2008-04-01
申请号：US10699550
申请日：2003-10-31
申请人： Susan J. Wong , Pei-Yong Shi
发明人： Susan J. Wong , Pei-Yong Shi
IPC分类号： G01N33/00 , G01N33/53 , C12Q1/70 , A61K39/193
CPC分类号： G01N33/56983 , C12Q1/04 , Y02A50/53
摘要： The present invention provides a rapid and sensitive method for the detection of a West Nile virus (WNV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV) and Dengue virus (DENV) and antibodies directed against thereof involving contacting a biological specimen suspected of being infected with WNV, JE, SLE or DEN with a substantially purified and isolated WNV E glycoprotein or subfragment thereof having a native conformation wherein the E glycoprotein or subfragment thereof has a reactivity with antibodies against WNV and a cross-reactivity with antibodies against JEV, SLEV and DENV. The instant invention further provides a rapid, sensitive, and consistent method for the specific detection of WNV by employing diagnostic assays having the antigen NS5 which is specifically reactive with anti-WNV antibodies but not cross-reactive with antibodies against other flaviviruses such as JEV, SLEV, or DENV. The present invention also provides a rapid, sensitive, and consistent method for the specific detection of DENV by employing diagnostic assays having the antigen NS5 which is specifically reactive with anti-DENV antibodies but do not cross-react with antibodies against other flaviviruses such as JEV, SLEV, or WNV. Further, the DENV NS5 antigens are serospecific and do not cross react with antibodies to other DENV strains. Thus, the method of the present invention provides a manner by which to discriminate infections by each DENV strain. Further, diagnostic kits for carrying out the methods are provided. The methods and kits for carrying out the methods of the invention are rapid and require as little as 10 minutes to detect a result.
摘要翻译：本发明提供了用于检测西尼罗河病毒（WNV），日本脑炎病毒（JEV），圣路易斯脑炎病毒（SLEV）和登革热病毒（DENV））的快速和灵敏的方法以及针对其的抗体涉及使怀疑被WNV，JE，SLE或DEN感染的生物样品具有天然构象的基本纯化和分离的WNV E糖蛋白或其亚片段，其中E糖蛋白或其亚片段与针对WNV的抗体具有反应性和与针对JEV，SLEV和DENV的抗体。本发明进一步提供了通过采用具有与抗-WNV抗体特异性反应但不与抗其它黄病毒（例如JEV）的抗体交叉反应的抗原NS5的诊断试验来进行WNV的特异性检测的快速，灵敏和一致的方法， SLEV或DENV。本发明还提供了通过使用具有与抗DENV抗体特异性反应但不与抗其他黄病毒抗体（例如JEV）的抗体的抗原NS5的诊断测定法来快速，灵敏和一致的方法来进行DENV的特异性检测，SLEV或WNV。此外，DENV NS5抗原是血清特异性的，并且不与其他DENV毒株的抗体交叉反应。因此，本发明的方法提供了鉴别每种DENV毒株感染的方式。此外，提供了用于实施方法的诊断试剂盒。用于实施本发明方法的方法和试剂盒是快速的，并且需要少至10分钟来检测结果。

7. 发明授权

US07355033B2 Screening for West Nile Virus antiviral therapy 有权
标题翻译：筛选西尼罗病毒抗病毒治疗
公开(公告)号：US07355033B2
公开(公告)日：2008-04-08
申请号：US10706892
申请日：2003-11-13
申请人： Pei-Yong Shi , Michael Lo , Mark Tilgner
发明人： Pei-Yong Shi , Michael Lo , Mark Tilgner
IPC分类号： C12N15/40 , C12N5/10 , C12Q1/18
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2770/24122 , C12N2770/24162 , C12N2840/203 , C12Q1/701
摘要： The instant invention provides stable and novel lineage I WNV reverse genetics systems, and methods for making the reverse genetics systems, specifically, a fully-infectious lineage I WNV cDNA or replicon system engineered with one or more nucleotide sequences each encoding a reporter gene to be used in high throughput cell-based screening assays for the identification of novel antiflaviviral chemotherapeutics and/or vaccines effective to treat and/or immunize against infections by WNV and other emerging flaviviruses, such as, for example, JEV, SLEV, AV, KV, JV, CV, YV, TBEV, DENV-1, DENV-2, DENV-3, DENV-4, YFV and MVEV. The present invention further provides methods of high throughput screening of antiflaviviral compounds or improved derivatives thereof using novel lineage I WNV reverse genetics systems and/or cell lines stably containing the reverse genetics systems. Also, the invention provides novel pharmaceutical compositions comprising an attenuated lineage I WNV that is less virulent but similarly immunogenic as the parent WNV and is capable of providing a protective immune response in a host.
摘要翻译：本发明提供了稳定和新颖的谱系I WNV反向遗传学系统，以及用于制作反向遗传学系统的方法，具体地说，是一种完全感染谱系I WNV cDNA或复制子系统，每个编码一个或多个编码报告基因的核苷酸序列被编码为用于鉴定可有效治疗和/或免疫WNV和其它新出现的黄病毒感染的新型抗玻璃病毒化学治疗剂和/或疫苗的高通量细胞筛选试验，例如JEV，SLEV，AV，KV， JV，CV，YV，TBEV，DENV-1，DENV-2，DENV-3，DENV-4，YFV和MVEV。本发明进一步提供使用新的谱系IWNV反向遗传学系统和/或稳定含有反向遗传学系统的细胞系，抗冻病毒化合物或其改进的衍生物的高通量筛选方法。此外，本发明提供新的药物组合物，其包含与母体WNV相比毒性较低但相似的免疫原性并且能够在宿主中提供保护性免疫应答的减毒谱系WNV。

8. 发明申请

US20050058987A1 Screening for west nile virus antiviral therapy 有权
标题翻译：筛选西尼罗病毒抗病毒治疗
公开(公告)号：US20050058987A1
公开(公告)日：2005-03-17
申请号：US10706892
申请日：2003-11-13
申请人： Pei-Yong Shi , Michael Lo , Mark Tilgner
发明人： Pei-Yong Shi , Michael Lo , Mark Tilgner
IPC分类号： C07K14/18 , C12N7/04 , C12N15/86 , C12Q1/68 , C12Q1/70
CPC分类号： C07K14/005 , C12N7/00 , C12N15/86 , C12N2770/24122 , C12N2770/24162 , C12N2840/203 , C12Q1/701
摘要： The instant invention provides stable and novel lineage I WNV reverse genetics systems, and methods for making the reverse genetics systems, specifically, a fully-infectious lineage I WNV cDNA or replicon system engineered with one or more nucleotide sequences each encoding a reporter gene to be used in high throughput cell-based screening assays for the identification of novel antiflaviviral chemotherapeutics and/or vaccines effective to treat and/or immunize against infections by WNV and other emerging flaviviruses, such as, for example, JEV, SLEV, AV, KV, JV, CV, YV, TBEV, DENV-1, DENV-2, DENV-3, DENV-4, YFV and MVEV. The present invention further provides methods of high throughput screening of antiflaviviral compounds or improved derivatives thereof using novel lineage I WNV reverse genetics systems and/or cell lines stably containing the reverse genetics systems. Also, the invention provides novel pharmaceutical compositions comprising an attenuated lineage I WNV that is less virulent but similarly immunogenic as the parent WNV and is capable of providing a protective immune response in a host.
摘要翻译：本发明提供了稳定和新颖的谱系I WNV反向遗传学系统，以及用于制作反向遗传学系统的方法，具体地说，是一种完全感染谱系I WNV cDNA或复制子系统，每个编码一个或多个编码报告基因的核苷酸序列被编码为用于鉴定可有效治疗和/或免疫WNV和其它新出现的黄病毒感染的新型抗玻璃病毒化学治疗剂和/或疫苗的高通量细胞筛选试验，例如JEV，SLEV，AV，KV， JV，CV，YV，TBEV，DENV-1，DENV-2，DENV-3，DENV-4，YFV和MVEV。本发明进一步提供使用新的谱系IWNV反向遗传学系统和/或稳定含有反向遗传学系统的细胞系，抗冻病毒化合物或其改进的衍生物的高通量筛选方法。此外，本发明提供新的药物组合物，其包含与母体WNV相比毒性较低但相似的免疫原性并且能够在宿主中提供保护性免疫应答的减毒谱系WNV。

9. 发明授权

US07384785B2 Diagnostic test for West Nile virus 有权
标题翻译：西尼罗河病毒诊断试验
公开(公告)号：US07384785B2
公开(公告)日：2008-06-10
申请号：US10839442
申请日：2004-05-04
申请人： Susan J. Wong , Pei-Yong Shi
发明人： Susan J. Wong , Pei-Yong Shi
IPC分类号： C12N5/06 , C12Q1/70 , G01N33/53 , G01N33/567 , A61K39/12
CPC分类号： G01N33/56983 , C12Q1/04 , Y02A50/53
摘要： The present invention provides a rapid and sensitive method for the detection of a West Nile virus (WNV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV) and Dengue virus (DENV) and antibodies directed against thereof involving contacting a biological specimen suspected of being infected with WNV, JE, SLE or DEN with a substantially purified and isolated WNV E glycoprotein or subfragment thereof having a native conformation wherein the E glycoprotein or subfragment thereof has a reactivity with antibodies against WNV and a cross-reactivity with antibodies against JEV, SLEV and DENV. The instant invention further provides a rapid, sensitive, and consistent method for the specific detection of WNV by employing diagnostic assays having the antigen NS5 which is specifically reactive with anti-WNV antibodies but not cross-reactive with antibodies against other flaviviruses such as JEV, SLEV, or DENV. The present invention also provides a rapid, sensitive, and consistent method for the specific detection of DENV by employing diagnostic assays having the antigen NS5 which is specifically reactive with anti-DENV antibodies but do not cross-react with antibodies against other flaviviruses such as JEV, SLEV, or WNV. Further, the DENV NS5 antigens are serospecific and do not cross react with antibodies to other DENV strains. Thus, the method of the present invention provides a manner by which to discriminate infections by each DENV strain. Further, diagnostic kits for carrying out the methods are provided. The methods and kits for carrying out the methods of the invention are rapid and require as little as 10 minutes to detect a result. The invention also provides monoclonal antibodies against WNV NS5 and DENV NS5 antigen and their use in detecting WNV and DENV infections in a biological sample.
摘要翻译：本发明提供了用于检测西尼罗河病毒（WNV），日本脑炎病毒（JEV），圣路易斯脑炎病毒（SLEV）和登革热病毒（DENV））的快速和灵敏的方法以及针对其的抗体涉及使怀疑被WNV，JE，SLE或DEN感染的生物样品具有天然构象的基本纯化和分离的WNV E糖蛋白或其亚片段，其中E糖蛋白或其亚片段与针对WNV的抗体具有反应性和与针对JEV，SLEV和DENV的抗体。本发明进一步提供了通过采用具有与抗-WNV抗体特异性反应但不与抗其它黄病毒（例如JEV）的抗体交叉反应的抗原NS5的诊断试验来进行WNV的特异性检测的快速，灵敏和一致的方法， SLEV或DENV。本发明还提供了通过使用具有与抗DENV抗体特异性反应但不与抗其他黄病毒抗体（例如JEV）的抗体的抗原NS5的诊断测定法来快速，灵敏和一致的方法来进行DENV的特异性检测，SLEV或WNV。此外，DENV NS5抗原是血清特异性的，并且不与其他DENV毒株的抗体交叉反应。因此，本发明的方法提供了鉴别每种DENV毒株感染的方式。此外，提供了用于实施方法的诊断试剂盒。用于实施本发明方法的方法和试剂盒是快速的，并且需要少至10分钟来检测结果。本发明还提供针对WNV NS5和DENV NS5抗原的单克隆抗体及其在检测生物样品中的WNV和DENV感染中的用途。

10. 发明申请

US20060115896A1 Diagnostic test for west nile virus 有权
标题翻译：西尼罗病毒诊断试验
公开(公告)号：US20060115896A1
公开(公告)日：2006-06-01
申请号：US10839442
申请日：2004-05-04
申请人： Susan Wong , Pei-Yong Shi
发明人： Susan Wong , Pei-Yong Shi
IPC分类号： C12P21/06 , C12N5/06 , C12N5/16
CPC分类号： G01N33/56983 , C12Q1/04 , Y02A50/53
摘要： The present invention provides a rapid and sensitive method for the detection of a West Nile virus (WNV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV) and Dengue virus (DENV) and antibodies directed against thereof involving contacting a biological specimen suspected of being infected with WNV, JE, SLE or DEN with a substantially purified and isolated WNV E glycoprotein or subfragment thereof having a native conformation wherein the E glycoprotein or subfragment thereof has a reactivity with antibodies against WNV and a cross-reactivity with antibodies against JEV, SLEV and DENV. The instant invention further provides a rapid, sensitive, and consistent method for the specific detection of WNV by employing diagnostic assays having the antigen NS5 which is specifically reactive with anti-WNV antibodies but not cross-reactive with antibodies against other flaviviruses such as JEV, SLEV, or DENV. The present invention also provides a rapid, sensitive, and consistent method for the specific detection of DENV by employing diagnostic assays having the antigen NS5 which is specifically reactive with anti-DENV antibodies but do not cross-react with antibodies against other flaviviruses such as JEV, SLEV, or WNV. Further, the DENV NS5 antigens are serospecific and do not cross react with antibodies to other DENV strains. Thus, the method of the present invention provides a manner by which to discriminate infections by each DENV strain. Further, diagnostic kits for carrying out the methods are provided. The methods and kits for carrying out the methods of the invention are rapid and require as little as 10 minutes to detect a result. The invention also provides monoclonal antibodies against WNV NS5 and DENV NS5 antigen and their use in detecting WNV and DENV infections in a biological sample.
摘要翻译：本发明提供了用于检测西尼罗河病毒（WNV），日本脑炎病毒（JEV），圣路易斯脑炎病毒（SLEV）和登革热病毒（DENV））的快速和灵敏的方法以及针对其的抗体涉及使怀疑被WNV，JE，SLE或DEN感染的生物样品具有天然构象的基本纯化和分离的WNV E糖蛋白或其亚片段，其中E糖蛋白或其亚片段与针对WNV的抗体具有反应性和与针对JEV，SLEV和DENV的抗体。本发明进一步提供了通过采用具有与抗-WNV抗体特异性反应但不与抗其它黄病毒（例如JEV）的抗体交叉反应的抗原NS5的诊断试验来进行WNV的特异性检测的快速，灵敏和一致的方法， SLEV或DENV。本发明还提供了通过使用具有与抗DENV抗体特异性反应但不与抗其他黄病毒抗体（例如JEV）的抗体的抗原NS5的诊断测定法来快速，灵敏和一致的方法来进行DENV的特异性检测，SLEV或WNV。此外，DENV NS5抗原是血清特异性的，并且不与其他DENV毒株的抗体交叉反应。因此，本发明的方法提供了鉴别每种DENV毒株感染的方式。此外，提供了用于实施方法的诊断试剂盒。用于实施本发明方法的方法和试剂盒是快速的，并且需要少至10分钟来检测结果。本发明还提供针对WNV NS5和DENV NS5抗原的单克隆抗体及其在检测生物样品中的WNV和DENV感染中的用途。

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