Patent · US Active

Humanized anti-claudin-1 antibodies and uses thereof

US10851160B2 · kind B2 · utility

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12Claims
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Key dates

Filing dateMar 21, 2017
Grant dateDec 1, 2020
Priority date
Expiry dateMar 21, 2037

Classification

  • Technology area (CPC C)Chemistry; Metallurgy
  • CPC primaryC07K2317/567
  • WIPO fieldPharmaceuticals
  • WIPO sectorChemistry

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. Thus, the present invention relates to humanized anti-claudin-1 antibodies and uses thereof, in particular for the prevention and treatment of hepatitis C virus infection, virus-induced liver diseases, hepatocellular carcinoma (HC…

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