Compounds and methods for treating influenza
Inventors
Rossignol, Jean-Francois • Semple, J. Edward
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11850237-B2
Publication Date
2023-12-26
Expiration Date
Abstract
This invention is directed to methods for treating and preventing influenza infection by inhibiting influenza virus HA maturation processes employing compounds of formula I. It is also directed to combinations for treating and preventing influenza infection comprising compounds of formula I and other agents.
Core Innovation
The invention relates to reducing a time to resolution of one or more symptoms of an influenza-like illness in a patient suffering from the influenza-like illness, by administering a therapeutically effective amount of nitazoxanide, tizoxanide, a mixture thereof, or a pharmaceutically acceptable salt. The patient does not test positive for specified viruses, including Adenovirus, RSV, Influenza A, and Parainfluenza 1, with further refinements for additional viruses.
The symptoms targeted are selected from nasal secretion, nasal obstruction, sneezing, sore throat, fever, cough, malaise, headache, and chills, and additionally include respiratory symptom sets selected from erythematous oropharynx, hypertrophic tonsils, nasal congestion, rhonchi, and adenomegaly. The time-to-resolution endpoint is addressed for one or more selected symptoms.
The disclosed invention also relates to thiazolide compounds of formula I, including nitazoxanide and tizoxanide, for treating and preventing influenza by selectively blocking influenza hemagglutinin (HA) maturation at an endoglycosidase-resistant stage prior to resistance to Endo-H digestion. Mechanistic and experimental evidence indicates inhibition of influenza A/B replication after entry, interference with HA N-glycosylation processing, blockade of HA trafficking from ER toward/through the Golgi, and reduced plasma-membrane HA and virus egress, resulting in reduced virion production.
The disclosure further describes synergistic and greater-than-additive antiviral effects when these compounds are combined with neuraminidase inhibitors such as zanamivir or oseltamivir. It also references clinical/ILI symptom-resolution data in patients negative for multiple respiratory viruses and outlines combination products including NTZ plus a neuraminidase inhibitor, an immunostimulant, PEGylated interferon, or a vaccine.
Claims Coverage
The independent claims cover methods for reducing time to resolution of influenza-like illness symptoms by administering nitazoxanide or tizoxanide, or a mixture thereof, or a pharmaceutically acceptable salt. Four inventive features are presented across the independent claims, centered on symptom selection, respiratory symptom selection, and patient exclusion based on viral test positivity criteria.
Influenza-like illness time-to-resolution with nitazoxanide or tizoxanide
A method of reducing a time to resolution of one or more symptoms of an influenza-like illness by administering to a patient a therapeutically effective amount of nitazoxanide, tizoxanide, a mixture thereof, or a pharmaceutically acceptable salt.
Symptom selection for influenza-like illness resolution
The one or more symptoms are selected from nasal secretion, nasal obstruction, sneezing, sore throat, fever, cough, malaise, headache, and chills.
Respiratory symptom time-to-resolution with nitazoxanide or tizoxanide
A method of reducing a time to resolution of one or more respiratory symptoms of an influenza-like illness by administering to a patient a therapeutically effective amount of nitazoxanide, tizoxanide, a mixture thereof, or a pharmaceutically acceptable salt.
Respiratory symptom selection set
The one or more respiratory symptoms are selected from erythematous oropharynx, hypertrophic tonsils, nasal congestion, rhonchi, and adenomegaly.
Overall, the claim coverage focuses on time-to-resolution endpoints for defined symptom sets during an influenza-like illness, using nitazoxanide or tizoxanide, or mixtures and salts, as the therapeutic agent. Patient selection based on not testing positive for specified respiratory viruses is included in the claims, with dependent refinements further constraining symptom-count thresholds and dosing duration.
Stated Advantages
Reducing a time to resolution of one or more influenza-like illness symptoms.
Reducing a time to resolution of one or more respiratory symptoms of an influenza-like illness.
Providing reduced virus production and reduced virus egress.
Providing synergistic and greater-than-additive antiviral effects when combined with neuraminidase inhibitors such as zanamivir and oseltamivir.
Treating and preventing influenza by selectively blocking influenza hemagglutinin maturation at an endoglycosidase-resistant stage.
Documented Applications
Reducing time to resolution of symptoms or respiratory symptoms of an influenza-like illness in a patient suffering from the influenza-like illness.
Treating and preventing influenza by selectively blocking influenza hemagglutinin maturation at an endoglycosidase-resistant stage prior to resistance to Endo-H digestion.
Combination use with neuraminidase inhibitors such as zanamivir and oseltamivir for enhanced antiviral effects.
Use in patients negative for multiple respiratory viruses, including referenced clinical/ILI symptom-resolution data.
Combination products including NTZ plus a neuraminidase inhibitor, an immunostimulant, PEGylated interferon, or a vaccine.
Interested in licensing this patent?