Elimination of hepatitis B virus with antiviral agents
Inventors
Schinazi, Raymond F. • BOUCLE, Sebastien • Amblard, Franck • SARI, Ozkan • BASSIT, Leda
Assignees
US Department of Veterans Affairs
Publication Number
US-10752584-B2
Publication Date
2020-08-25
Expiration Date
2037-03-09
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present invention is directed to compounds, compositions and methods for preventing, treating or curing Hepatitis B (HBV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment, prevention or eradication of HBV infection.
Core Innovation
The present invention is directed to compounds, compositions and methods for preventing, treating or curing Hepatitis B (HBV) infection in human subjects or other animal hosts. These compounds include pharmaceutically acceptable salts, prodrugs, and derivatives thereof as pharmaceutical compositions for treatment, prevention, or eradication of HBV infection.
Hepatitis B virus causes a serious human health problem, second only to tobacco as a cause of human cancer. Existing HBV treatments like 3TC (lamivudine), interferon alpha-2b, and others reduce viral load but do not provide a cure and are limited by drug resistance, low efficacy, and tolerability. The persistence of covalently closed circular DNA (cccDNA) is believed to contribute to low cure rates.
There is an urgent need for new drugs that are potent, safe, act by a different mechanism than nucleoside analogs, and can reduce cccDNA. The present invention provides new antiviral agents, compositions including these agents, and methods of treatment using them that address this need.
Claims Coverage
The patent includes multiple independent claims related to novel compounds, pharmaceutical compositions comprising these compounds, and methods of treatment for viral infections using these compounds. The main inventive features involve specific chemical structures, pharmaceutical formulations, and therapeutic applications against HBV and related viruses.
Compounds defined by specific chemical formulas and substitutions
The invention provides compounds of a general formula with defined moieties (such as I-VII) and specific ranges for substituents (e.g., R groups, ring systems, heteroatoms). These compounds are disclosed as pharmaceutically acceptable salts or prodrugs and include preferred embodiments with specific substitutions and configurations.
Pharmaceutical compositions comprising the compounds
Pharmaceutical compositions that include one or more compounds of the invention combined with pharmaceutically acceptable carriers. These compositions can be formulated for oral, injectable, transdermal, or nanoparticulate administration and may include additional antiviral agents active against HBV via different mechanisms.
Methods for treating HBV and other flaviviridae virus infections
Methods for treating hosts infected with HBV, West Nile Virus, or other flaviviridae viruses by administering an effective amount of the compounds of the invention to reduce viral activity, treat infection, or prevent infection. Such methods include suppression of hepatitis delta virus (HDV) infection due to reducing HBV cccDNA.
The independent claims cover novel chemical entities defined by detailed substituents and ring systems, their pharmaceutical formulations, and methods for treating HBV and related viral infections by administration of these compounds. The inventive features emphasize chemical novelty, combined therapeutic compositions, and antiviral methods targeting HBV and flaviviruses.
Stated Advantages
The compounds are potent in reducing HBV activity and can potentially cure HBV infection by targeting a different mechanism than existing nucleoside analogs.
The compounds disrupt HBV capsid assembly, reducing the latent form cccDNA, which is a key factor in persistent HBV infection and low cure rates.
The compounds can be used in combination with other antiviral agents to prevent drug resistance and improve efficacy.
Some compounds show activity against other flaviviridae viruses such as West Nile virus and potentially hepatitis C virus, showing broad antiviral potential.
The compounds demonstrate low cellular cytotoxicity and mitochondrial toxicity, indicating a favorable safety profile.
Documented Applications
Treating, preventing, or curing Hepatitis B virus (HBV) infections in humans or animal hosts.
Treating or reducing biological activity of West Nile Virus (WNV) infection and other flaviviridae viruses such as hepatitis C virus (HCV), Dengue fever, and Zika virus.
Suppressing or eliminating hepatitis delta virus (HDV) infection by reducing HBV cccDNA.
Combination therapy with approved HBV drugs, nucleoside analogs, and other antiviral agents including polymerase inhibitors, viral entry inhibitors, capsid assembly modulators, protease inhibitors, immune-based therapeutics, RNA interference agents, and gene editing approaches (e.g., CRISPR/Cas9).
Co-administration with HCV treatments to prevent reactivation of dormant HBV infection.
Formulations including oral, injectable, transdermal, and nanoparticulate drug delivery systems targeting liver infections and possibly liver cancer associated with chronic HBV infection.
Interested in licensing this patent?