公开(公告)号：US20080292644A1

公开(公告)日：2008-11-27

申请号：US12079576

申请日：2008-03-27

Applicant: Shie-Liang Hsieh ,  Chi-Huey Wong ,  Tsui-Ling Hsu ,  Szu-Ting Chen

Inventor： Shie-Liang Hsieh ,  Chi-Huey Wong ,  Tsui-Ling Hsu ,  Szu-Ting Chen

IPC: A61K39/395 ,  G01N33/68 ,  C12Q1/70 ,  A01K67/027 ,  C12Q1/68

CPC classification number: C07K16/2851 ,  A61K2039/505 ,  C07K2317/56 ,  C07K2317/76 ,  C07K2319/30 ,  G01N2333/18 ,  G01N2333/185 ,  G01N2500/02 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/394

Abstract: Cellular receptors are identified that induce plasma leakage and other negative effects when infected with flaviviruses, such as dengue virus or Japanese encephamyelitis virus. Using fusion proteins disclosed herein, the receptors to which a pathogen, such as flavivirus, binds via glycan binding are determined. Once the receptors are determined, the effect of binding to a particular receptor may be determined, wherein targeting of the receptors causing a particular symptom may be targeted by agents that interrupt binding of the pathogen to the receptor. Accordingly, in the case of dengue virus and Japanese encephamyelitis virus, TNF-α is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-α secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.

Abstract translation: 鉴定当感染黄病毒如登革热病毒或日本脑炎病毒时诱导血浆渗漏和其它负面影响的细胞受体。 使用本文公开的融合蛋白，确定病原体（例如黄病毒）通过聚糖结合结合的受体。 一旦确定了受体，就可以确定与特定受体结合的作用，其中导致特定症状的受体的靶向可能被阻断病原体与受体结合的试剂所靶向。 因此，在登革热病毒和日本脑炎病毒的情况下，当病原体与DLVR1 / CLEC5A受体结合时，TNF-α被释放。 用单克隆抗体中断DLVR1 / CLEC5A受体降低TNF-α分泌，而不影响负责病毒清除的细胞因子分泌，从而将感染小鼠的存活率从零增加到约50％。

公开(公告)号：US20100055096A1

公开(公告)日：2010-03-04

申请号：US12533086

申请日：2009-07-31

Applicant: Chi-Huey Wong ,  Shie-Liang Hsieh ,  Tsui-Ling Hsu ,  Shih-Chin Cheng ,  Szu-Ting Chen

Inventor： Chi-Huey Wong ,  Shie-Liang Hsieh ,  Tsui-Ling Hsu ,  Shih-Chin Cheng ,  Szu-Ting Chen

IPC: A61K39/395

CPC classification number: C07K16/2851 ,  C07K2317/76 ,  C07K2319/30 ,  G01N33/56972 ,  G01N33/56983 ,  G01N2333/18 ,  G01N2500/02 ,  Y02A50/53

Abstract: The disclosure provides fusion proteins comprising a carbohydrate recognition domain of an innate immunity receptor and a heterologous polypeptide. The fusion proteins of the disclosure may be used, for example, to fingerprint polysaccharide compositions and to purify polysaccharide compositions. Polysaccharide compositions include those isolated from Ganoderma lucidum (Reishi). The methods and reagents of the disclosure may also be used to identify innate immunity receptors and cell types that bind to polysaccharide compositions (including polysaccharide compositions associated with pathogens), whereupon modulators of the identified receptors can then be obtained. The fusion proteins also may be used to inhibit the interaction between a polysaccharide composition and an innate immunity receptor on a cell surface. The methods and reagents of the disclosure are used in one example to determine that the DLVR1 innate immunity receptor on macrophages interacts with Dengue virus (DV), and that DLVR1 is responsible for DV-mediated secretion of proinflammatory cytokines from macrophages. The disclosure also provides DVLR1 antibodies that prevent the secretion of proinflammatory cytokines by DV-infected macrophages.

Abstract translation: 本公开提供了包含先天免疫受体的碳水化合物识别结构域和异源多肽的融合蛋白。 本公开的融合蛋白可以用于例如指纹多糖组合物和纯化多糖组合物。 多糖组合物包括从灵芝（Reishi）分离的那些。 本公开的方法和试剂也可用于鉴定结合多糖组合物（包括与病原体相关的多糖组合物）的先天免疫受体和细胞类型，于是可以获得鉴定的受体的调节剂。 融合蛋白也可用于抑制多糖组合物和细胞表面上的先天免疫受体之间的相互作用。 在一个实例中使用本公开的方法和试剂来确定巨噬细胞上的DLVR1先天免疫受体与登革热病毒（DV）相互作用，并且DLVR1负责来自巨噬细胞的DV介导的促炎细胞因子的分泌。 本公开还提供DVLR1抗体，其防止DV感染的巨噬细胞分泌促炎细胞因子。

公开(公告)号：US08460669B2

公开(公告)日：2013-06-11

申请号：US13106046

申请日：2011-05-12

Applicant: Shie-Liang Hsieh ,  Chi-Huey Wong ,  Tsui-Ling Hsu ,  Szu-Ting Chen

Inventor： Shie-Liang Hsieh ,  Chi-Huey Wong ,  Tsui-Ling Hsu ,  Szu-Ting Chen

IPC: A61K39/395 ,  A61K39/285

CPC classification number: C07K16/2851 ,  A61K2039/505 ,  C07K2317/56 ,  C07K2317/76 ,  C07K2319/30 ,  G01N2333/18 ,  G01N2333/185 ,  G01N2500/02 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/394

Abstract: Cellular receptors are identified that induce plasma leakage and other negative effects when infected with flaviviruses, such as dengue virus or Japanese encephamyelitis virus. Using fusion proteins disclosed herein, the receptors to which a pathogen, such as flavivirus, binds via glycan binding are determined. Once the receptors are determined, the effect of binding to a particular receptor may be determined, wherein targeting of the receptors causing a particular symptom may be targeted by agents that interrupt binding of the pathogen to the receptor. Accordingly, in the case of dengue virus and Japanese encephamyelitis virus, TNF-α is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-α secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.

Abstract translation: 鉴定当感染黄病毒如登革热病毒或日本脑炎病毒时诱导血浆渗漏和其它负面影响的细胞受体。 使用本文公开的融合蛋白，确定病原体（例如黄病毒）通过聚糖结合结合的受体。 一旦确定了受体，就可以确定与特定受体结合的作用，其中导致特定症状的受体的靶向可能被阻断病原体与受体结合的试剂所靶向。 因此，在登革热病毒和日本脑炎病毒的情况下，当病原体与DLVR1 / CLEC5A受体结合时，TNF-α被释放。 用单克隆抗体中断DLVR1 / CLEC5A受体降低TNF-α分泌，而不影响负责病毒清除的细胞因子分泌，从而将感染小鼠的存活率从零增加到约50％。

公开(公告)号：US07998482B2

公开(公告)日：2011-08-16

申请号：US12533086

申请日：2009-07-31

Applicant: Chi-Huey Wong ,  Shie-Liang Hsieh ,  Tsui-Ling Hsu ,  Shih-Chin Cheng ,  Szu-Ting Chen

Inventor： Chi-Huey Wong ,  Shie-Liang Hsieh ,  Tsui-Ling Hsu ,  Shih-Chin Cheng ,  Szu-Ting Chen

IPC: A61K39/395 ,  C12N7/00 ,  A61K39/285

CPC classification number: C07K16/2851 ,  C07K2317/76 ,  C07K2319/30 ,  G01N33/56972 ,  G01N33/56983 ,  G01N2333/18 ,  G01N2500/02 ,  Y02A50/53

Abstract: The disclosure provides fusion proteins comprising a carbohydrate recognition domain of an innate immunity receptor and a heterologous polypeptide. The fusion proteins of the disclosure may be used, for example, to fingerprint polysaccharide compositions and to purify polysaccharide compositions. Polysaccharide compositions include those isolated from Ganoderma lucidum (Reishi). The methods and reagents of the disclosure may also be used to identify innate immunity receptors and cell types that bind to polysaccharide compositions (including polysaccharide compositions associated with pathogens), whereupon modulators of the identified receptors can then be obtained. The fusion proteins also may be used to inhibit the interaction between a polysaccharide composition and an innate immunity receptor on a cell surface. The methods and reagents of the disclosure are used in one example to determine that the DLVR1 innate immunity receptor on macrophages interacts with Dengue virus (DV), and that DLVR1 is responsible for DV-mediated secretion of proinflammatory cytokines from macrophages. The disclosure also provides DVLR1 antibodies that prevent the secretion of proinflammatory cytokines by DV-infected macrophages.

Abstract translation: 本公开提供了包含先天免疫受体的碳水化合物识别结构域和异源多肽的融合蛋白。 本公开的融合蛋白可以用于例如指纹多糖组合物和纯化多糖组合物。 多糖组合物包括从灵芝（Reishi）分离的那些。 本公开的方法和试剂也可用于鉴定结合多糖组合物（包括与病原体相关的多糖组合物）的先天免疫受体和细胞类型，于是可以获得鉴定的受体的调节剂。 融合蛋白也可用于抑制多糖组合物和细胞表面上的先天免疫受体之间的相互作用。 在一个实例中使用本公开的方法和试剂来确定巨噬细胞上的DLVR1先天免疫受体与登革热病毒（DV）相互作用，并且DLVR1负责来自巨噬细胞的DV介导的促炎细胞因子的分泌。 本公开还提供DVLR1抗体，其防止DV感染的巨噬细胞分泌促炎细胞因子。

公开(公告)号：US07943134B2

公开(公告)日：2011-05-17

申请号：US12079576

申请日：2008-03-27

Applicant: Shie-Liang Hsieh ,  Chi-Huey Wong ,  Tsui-Ling Hsu ,  Szu-Ting Chen

Inventor： Shie-Liang Hsieh ,  Chi-Huey Wong ,  Tsui-Ling Hsu ,  Szu-Ting Chen

IPC: A61K39/395 ,  A61K39/00 ,  A61K39/193 ,  A61K45/00 ,  C12N7/00 ,  C07K16/00 ,  C12P21/08 ,  A61K39/285

CPC classification number: C07K16/2851 ,  A61K2039/505 ,  C07K2317/56 ,  C07K2317/76 ,  C07K2319/30 ,  G01N2333/18 ,  G01N2333/185 ,  G01N2500/02 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/394

Abstract: Cellular receptors are identified that induce plasma leakage and other negative effects when infected with flaviviruses, such as dengue virus or Japanese encephamyelitis virus. Using fusion proteins disclosed herein, the receptors to which a pathogen, such as flavivirus, binds via glycan binding are determined. Once the receptors are determined, the effect of binding to a particular receptor may be determined, wherein targeting of the receptors causing a particular symptom may be targeted by agents that interrupt binding of the pathogen to the receptor. Accordingly, in the case of dengue virus and Japanese encephamyelitis virus, TNF-α is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-α secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.

Abstract translation: 鉴定当感染黄病毒如登革热病毒或日本脑炎病毒时诱导血浆渗漏和其它负面影响的细胞受体。 使用本文公开的融合蛋白，确定病原体（例如黄病毒）通过聚糖结合结合的受体。 一旦确定了受体，就可以确定与特定受体结合的作用，其中导致特定症状的受体的靶向可能被阻断病原体与受体结合的试剂所靶向。 因此，在登革热病毒和日本脑炎病毒的情况下，当病原体与DLVR1 / CLEC5A受体结合时，TNF-α被释放。 用单克隆抗体中断DLVR1 / CLEC5A受体降低TNF-α分泌，而不影响负责病毒清除的细胞因子分泌，从而将感染小鼠的存活率从零增加到约50％。

公开(公告)号：US20120213770A1

公开(公告)日：2012-08-23

申请号：US13106046

申请日：2011-05-12

Applicant: Shie-Liang Hsieh ,  Chi-Huey Wong ,  Tsui-Ling Hsu ,  Szu-Ting Chen

Inventor： Shie-Liang Hsieh ,  Chi-Huey Wong ,  Tsui-Ling Hsu ,  Szu-Ting Chen

IPC: A61K39/395 ,  A61P31/14 ,  A61P31/12

CPC classification number: C07K16/2851 ,  A61K2039/505 ,  C07K2317/56 ,  C07K2317/76 ,  C07K2319/30 ,  G01N2333/18 ,  G01N2333/185 ,  G01N2500/02 ,  Y02A50/386 ,  Y02A50/388 ,  Y02A50/39 ,  Y02A50/394

Abstract: Cellular receptors are identified that induce plasma leakage and other negative effects when infected with flaviviruses, such as dengue virus or Japanese encephamyelitis virus. Using fusion proteins disclosed herein, the receptors to which a pathogen, such as flavivirus, binds via glycan binding are determined. Once the receptors are determined, the effect of binding to a particular receptor may be determined, wherein targeting of the receptors causing a particular symptom may be targeted by agents that interrupt binding of the pathogen to the receptor. Accordingly, in the case of dengue virus and Japanese encephamyelitis virus, TNF-α is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-α secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.

Abstract translation: 鉴定当感染黄病毒如登革热病毒或日本脑炎病毒时诱导血浆渗漏和其它负面影响的细胞受体。 使用本文公开的融合蛋白，确定病原体（例如黄病毒）通过聚糖结合结合的受体。 一旦确定了受体，就可以确定与特定受体结合的作用，其中导致特定症状的受体的靶向可能被阻断病原体与受体结合的试剂所靶向。 因此，在登革热病毒和日本脑炎病毒的情况下，当病原体与DLVR1 / CLEC5A受体结合时，TNF-α被释放。 用单克隆抗体中断DLVR1 / CLEC5A受体降低TNF-α分泌，而不影响负责病毒清除的细胞因子分泌，从而将感染小鼠的存活率从零增加到约50％。

公开(公告)号：US20070072247A1

公开(公告)日：2007-03-29

申请号：US11469270

申请日：2006-08-31

Applicant: Chie-Huey Wong ,  Shie-Liang Hsieh ,  Tsui-Ling Hsu ,  Shih-Chin Cheng ,  Szu-Ting Chen

Inventor： Chie-Huey Wong ,  Shie-Liang Hsieh ,  Tsui-Ling Hsu ,  Shih-Chin Cheng ,  Szu-Ting Chen

IPC: G01N33/567 ,  C07H21/04 ,  C12P21/04 ,  C07K16/46

CPC classification number: C07K16/2851 ,  C07K2317/76 ,  C07K2319/30 ,  G01N33/56972 ,  G01N33/56983 ,  G01N2333/18 ,  G01N2500/02 ,  Y02A50/53

Abstract: The disclosure provides fusion proteins comprising a carbohydrate recognition domain of an innate immunity receptor and a heterologous polypeptide. The fusion proteins of the disclosure may be used, for example, to fingerprint polysaccharide compositions and to purify polysaccharide compositions. Polysaccharide compositions include those isolated from Ganoderma lucidum (Reishi). The methods and reagents of the disclosure may also be used to identify innate immunity receptors and cell types that bind to polysaccharide compositions (including polysaccharide compositions associated with pathogens), whereupon modulators of the identified receptors can then be obtained. The fusion proteins also may be used to inhibit the interaction between a polysaccharide composition and an innate immunity receptor on a cell surface. The methods and reagents of the disclosure are used in one example to determine that the DLVR1 innate immunity receptor on macrophages interacts with Dengue virus (DV), and that DLVR1 is responsible for DV-mediated secretion of proinflammatory cytokines from macrophages. The disclosure also provides DVLR1 antibodies that prevent the secretion of proinflammatory cytokines by DV-infected macrophages.

Abstract translation: 本公开提供了包含先天免疫受体的碳水化合物识别结构域和异源多肽的融合蛋白。 本公开的融合蛋白可以用于例如指纹多糖组合物和纯化多糖组合物。 多糖组合物包括从灵芝（Reishi）分离的那些。 本公开的方法和试剂也可用于鉴定结合多糖组合物（包括与病原体相关的多糖组合物）的先天免疫受体和细胞类型，于是可以获得鉴定的受体的调节剂。 融合蛋白也可用于抑制多糖组合物和细胞表面上的先天免疫受体之间的相互作用。 在一个实例中使用本公开的方法和试剂来确定巨噬细胞上的DLVR1先天免疫受体与登革热病毒（DV）相互作用，并且DLVR1负责来自巨噬细胞的DV介导的促炎细胞因子的分泌。 本公开还提供DVLR1抗体，其防止DV感染的巨噬细胞分泌促炎细胞因子。