公开(公告)号：BRPI0822472A2

公开(公告)日：2015-06-16

申请号：BRPI0822472

申请日：2008-05-29

Applicant: ACADEMIA SINICA

Inventor： HSIEH SHIE-LIANG ,  WONG CHI-HUEY ,  HSU TSUI-LING ,  CHEN SZU-TING

IPC: G01N33/53

公开(公告)号：AU2008353452A1

公开(公告)日：2009-10-01

申请号：AU2008353452

申请日：2008-05-29

Applicant: ACADEMIA SINICA

Inventor： WONG CHI-HUEY ,  HSIEH SHIE-LIANG ,  CHEN SZU-TING ,  HSU TSUI-LING

IPC: G01N33/53

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-alpha is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-alpha secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.

公开(公告)号：GB2458715A

公开(公告)日：2009-09-30

申请号：GB0812915

申请日：2008-07-15

Applicant: ACADEMIA SINICA

Inventor： WONG CHI-HUEY ,  HSIEH SHIE-LIANG ,  HSU TSUI-LING ,  CHEN SZU-TING

IPC: A61K39/395 ,  C07K16/28

Abstract: A pharmaceutical composition is disclosed comprising an effective amount of an antibody directed against at least one cellular receptor to modulate the effects of a pathogen infection, wherein the modulation comprises at least inhibition of pro-inflammatory cytokine secretion and does not affect secretion of cytokines that affect viral clearance. The cellular receptor may be the DLVR1 / CLEC5A (DVLR1, MDL-1) receptor. The pathogen may be a hepatitis virus or a flavivirus (e.g. Japanese encephalomyelitis virus or dengue virus). Use of an anti-DLVR1/CLEC5A antibody in the treatment of a flavivirus infection is claimed. A method comprising obtaining a fusion protein comprising a binding domain of a DLVR1/CLEC5A receptor and a domain that allows affixing to a substrate, contacting the fusion protein with a flavivirus to determine if the pathogen binds to the binding domain of the fusion, and detecting whether the pathogen is bound to the fusion protein, is also claimed.

公开(公告)号：EP2257806A4

公开(公告)日：2011-06-15

申请号：EP08873539

申请日：2008-05-29

Applicant: ACADEMIA SINICA

Inventor： HSIEH SHIE-LIANG ,  WONG CHI-HUEY ,  HSU TSUI-LING ,  CHEN SZU-TING

IPC: G01N33/53 ,  A61K39/395 ,  C12Q1/68

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

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%.