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Compositions and methods for treating hepatitis b virus infection

A hepatitis B virus and residue technology, applied in the direction of antiviral agents, virus antigen components, sugar derivatives, etc., can solve the problems of HbsAg loss and poor treatment tolerance

Pending Publication Date: 2022-05-13
UNIV OF WASHINGTON
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Problematically, IFN-based therapy of chronic HBV is poorly tolerated and only a low frequency of treated patients shows complete loss of HbsAg that defines clinical HBV cure

Method used

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  • Compositions and methods for treating hepatitis b virus infection
  • Compositions and methods for treating hepatitis b virus infection
  • Compositions and methods for treating hepatitis b virus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] This example describes the demonstration that induction of the RIG-I signaling pathway destabilizes cccDNA and prevents the formation of new cccDNA in hepatocytes, providing a strategy for the eradication of cccDNA and corresponding hepatitis B virus infection.

[0113] introduction

[0114] Acute viral infection often triggers the activation of intracellular innate immunity, leading to the induction of intracellular antiviral defenses. This process serves to control viral replication and spread from the site of infection, and to modulate the adaptive immune response for systemic viral control. Activation of innate immunity occurs through host cell perception of viral pathogen-associated molecular patterns (PAMPs) embedded in viral replication products, including viral nucleic acids. PAMPs are sensed by cellular pattern recognition receptors (PRRs). PRRs that sense viral infection include Toll-like receptors (TLRs), NOD-like receptors (NLRs), intracellular DNA senso...

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Abstract

The present disclosure provides compositions and methods for inhibiting hepatitis B virus (HBV) in infected cells. Exemplary methods include contacting an infected cell with one or more agents that induce interferon regulatory factor 3 (IRF3) activation in the infected cell. In some embodiments, one or more agents include a nucleic acid molecule comprising a pathogen-related molecular pattern (PAMP), a small molecule agent (e.g., a benzothiazole derivative molecule), or a combination thereof. In some embodiments, the method further comprises contacting the infected cells with an NRTI. The method may be an in vivo method of treating a subject suffering from HBV infection comprising administering a therapeutically related amount of one or more agents formulated in one or more therapeutically effective compositions. An exemplary composition is formulated for treating hepatitis B virus (HBV) infection in a subject, comprising a RIG-I agonist, a vehicle for intracellular delivery, and a pharmaceutically acceptable carrier.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 909,321, filed October 2, 2019, which is hereby incorporated by reference in its entirety. [0003] Statement Regarding Sequence Listing [0004] The Sequence Listing related to this application is provided in text format in lieu of a paper copy and is hereby incorporated by reference into this specification. The name of the text file containing the sequence listing is 72750_Sequence_Listing_final_2020-09-28.txt. The text file is 31KB; created on September 28, 2020; and is being submitted via EFS-Web along with the specification submission. [0005] Statement of Government Licensing Rights [0006] This invention was made with government support under Grant Nos. R01 AI118916 and R01 AI127463 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0007] Hepatitis B virus (HBV) ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/12A61K39/29C07H21/04
CPCA61K31/7105A61K31/428A61P31/20A61P31/12A61K31/7115A61K39/39A61K2039/55561A61K2039/55555A61K45/06A61K31/506A61K31/522A61K31/675A61K31/7072A61K31/7088
Inventor M·J·小加勒S·李
Owner UNIV OF WASHINGTON
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