Abstract: The present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. The tight junction protein claudin-1 (CLDN1) is an essential entry factor for HCV and a promising target for therapy. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs). The inventors also demonstrate that anti-CLDN1 H3L3 cures persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy.

Abstract: The present disclosure relates to a method of a method of treating a cholangiopathy (e.g., Primary Sclerosing Cholangitis or Primary Biliary Cholangitis) in a human subject in need thereof, comprising administering a therapeutically effective amount of an anti-Claudin-1 antibody to the human subject.

Abstract: The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. The cellular model system for hepatocellular carcinoma (HCC)/cirrhosis development and progression may be used in the screening of compounds useful in the treatment and/or prevention of cirrhosis and/or HCC as well as in the identification biomarkers for the prediction of liver disease (especially cirrhosis) progression and HCC. The present invention also relates to specific compounds that have been identified, using such screening methods, as useful in the treatment and/or the prevention of HCC/cirrhosis.

Abstract: The present disclosure relates to a method of treating a cholangiocarcinoma in a human subject in need thereof, comprising administering a therapeutically effective amount of an anti-Claudin-1 antibody to the human subject.

Abstract: The present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. The tight junction protein claudin-1 (CLDN1) is an essential entry factor for HCV and a promising target for therapy. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs). The inventors also demonstrate that anti-CLDN1 H3L3 cures persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy.

Abstract: The present invention provides Histamine Receptor 2 antagonists and pharmaceutical compositions thereof for use in the treatment or prevention of liver disease, including liver fibrosis and hepato-biliary cancers. The present invention also relates to methods for identifying candidate compounds that are useful in the treatment or prevention of liver disease, including liver fibrosis and hepato-biliary cancers.

Abstract: The present invention relates to diagnosis and/or prognosis of liver disease progression and risk of hepatocellular carcinoma and the discovery of therapeutic compounds and targets to treat liver disease and cancer.

Abstract: The present invention concerns the use of anti-Claudin-1 monoclonal antibodies, and pharmaceutical compositions thereof, for the prevention and/or treatment of a fibrotic disease in a patient, in particular pulmonary fibrosis, kidney fibrosis or skin fibrosis. Methods of preventing and/or treating pulmonary fibrosis kidney fibrosis or skin fibrosis by administration of such a monoclonal antibody, or a pharmaceutical composition thereof, are also described.

Abstract: The present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. The tight junction protein claudin-1 (CLDN1) is an essential entry factor for HCV and a promising target for therapy. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs). The inventors also demonstrate that anti-CLDN1 H3L3 cures persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy.

Abstract: The present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs).

Abstract: The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. The cellular model system for hepatocellular carcinoma (HCC)/cirrhosis development and progression may be used in the screening of compounds useful in the treatment and/or prevention of cirrhosis and/or HCC as well as in the identification biomarkers for the prediction of liver disease (especially cirrhosis) progression and HCC. The present invention also relates to specific compounds that have been identified, using such screening methods, as useful in the treatment and/or the prevention of HCC/cirrhosis.

Abstract: The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. The cellular model system for hepatocellular carcinoma (HCC)/cirrhosis development and progression may be used in the screening of compounds useful in the treatment and/or prevention of cirrhosis and/or HCC as well as in the identification biomarkers for the prediction of liver disease (especially cirrhosis) progression and HCC. The present invention also relates to specific compounds that have been identified, using such screening methods, as useful in the treatment and/or the prevention of HCC/cirrhosis.

Abstract: Use of anti-Claudin 1 monoclonal antibodies and pharmaceutical compositions thereof, for the prevention and/or treatment of hepatocellular carcinoma in patients suffering from liver disease, in particular liver disease that is not associated with HCV infection or in patients who have been cured from HCV infection. Methods of preventing and/or treating hepatocellular carcinoma by administration of such a monoclonal antibody, or a pharmaceutical composition thereof, are also described. Experimental results with the hepatocarcinoma cell line HuH-7.5.1 are given.

Abstract: The present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs).

Abstract: The present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. The tight junction protein claudin-1 (CLDN1) is an essential entry factor for HCV and a promising target for therapy. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs). The inventors also demonstrate that anti-CLDN1 H3L3 cures persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy.

Abstract: Use of anti-Claudin 1 monoclonal antibodies and pharmaceutical compositions thereof, for the prevention and/or treatment of hepatocellular carcinoma in patients suffering from liver disease, in particular liver disease that is not associated with HCV infection or in patients who have been cured from HCV infection. Methods of preventing and/or treating hepatocellular carcinoma by administration of such a monoclonal antibody, or a pharmaceutical composition thereof, are also described. Experimental results with the hepatocarcinoma cell line HuH-7.5.1 are given.

Abstract: The present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. The tight junction protein claudin-1 (CLDN1) is an essential entry factor for HCV and a promising target for therapy. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs). The inventors also demonstrate that anti-CLDN1 H3L3 cures persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy.

Abstract: Use of anti-Claudin 1 monoclonal antibodies and pharmaceutical compositions thereof, for the prevention and/or treatment of hepatocellular carcinoma in patients suffering from liver disease, in particular liver disease that is not associated with HCV infection or in patients who have been cured from HCV infection. Methods of preventing and/or treating hepatocellular carcinoma by administration of such a monoclonal antibody, or a pharmaceutical composition thereof, are also described. Experimental results with the hepatocarcinoma cell line HuH-7.5.1 are given.

Abstract: The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. The cellular model system for hepatocellular carcinoma (HCC)/cirrhosis development and progression may be used in the screening of compounds useful in the treatment and/or prevention of cirrhosis and/or HCC as well as in the identification biomarkers for the prediction of liver disease (especially cirrhosis) progression and HCC. The present invention also relates to specific compounds that have been identified, using such screening methods, as useful in the treatment and/or the prevention of HCC/cirrhosis.

Abstract: Use of anti-Claudin 1 monoclonal antibodies and pharmaceutical compositions thereof, for the prevention and/or treatment of hepatocellular carcinoma in patients suffering from liver disease, in particular liver disease that is not associated with HCV infection or in patients who have been cured from HCV infection. Methods of preventing and/or treating hepatocellular carcinoma by administration of such a monoclonal antibody, or a pharmaceutical composition thereof, are also described. Experimental results with the hepatocarcinoma cell line HuH-7.5.1 are given.