Broad spectrum immune and antiviral gene modulation by oral interferon
Inventors
Carter, William A. • Strayer, David
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8075878-B2
Publication Date
2011-12-13
Expiration Date
Abstract
An antiviral/immunomodulatory response in an animal is induced by oral administration to an infected animal, including humans, of a human α-interferon. Methods of conferring resistance or mitigating the effects of exposure to a virus including avian influenza are described.
Core Innovation
The disclosed invention concerns a method of mitigating the effects of, or conferring resistance to, a susceptible viral infection by administering human b1-interferon. The method is applied prior to exposure to a virus or shortly after exposure to the virus, but prior to the development of symptoms, using oral or nasal administration to an animal or a human patient.
The invention is framed around re-regulating interferon-b1-driven immune pathways to prevent cytokine storm and inappropriate TNF-driven lung damage. The described mechanism links the b1-interferon administration to immune pathway modulation, including concurrent upregulation of antiviral interferon-stimulated genes and downregulation of TNF-related genes.
The patent further provides gene modulation results using oral ALFERON in HIV and healthy subjects, including cDNA microarray induction of 385+ genes and specific upregulation of antiviral ISGs such as OAS-like and PDZ-LIM5, together with downregulation of TNF-related genes. It also reports prophylactic non-human primate H5N1 studies using oro-mucosal dosing with ALFERON LDO/ALFERON, describing a dose-dependent reduction in gross/histopathology and pneumonia severity, and reporting no serious adverse effects observed.
Claims Coverage
The independent claims are two methods that each include administering b1-interferon, or multiple glycosylated b1-interferon species, orally or nasally before or shortly after viral exposure and prior to symptom development, in an amount of at least 6.6 IU per pound body weight, to confer resistance or mitigate effects. Across the independent claims, there are five main inventive features emphasized by the claim language and refined by dependent claims.
Timed oral or nasal b1-interferon administration relative to exposure and symptoms
Administering b1-interferon prior to exposure to a virus or shortly after exposure to the virus, but prior to the development of symptoms, so that the effects of the viral infection are mitigated or resistance is conferred.
Oral or nasal delivery to confer resistance or mitigate effects
Orally or nasally administering the b1-interferon to the animal or human patient as part of a method for conferring resistance to or mitigating the effects of the viral infection.
Influenza-like susceptible viral infection scope
Applying the method to any pathogen that replicates by a mechanism similar to human or avian influenza virus, as recited for the mitigation/resistance method.
Multiple glycosylated b1-interferon species to a human patient
Administering multiple, glycosylated b1-interferon species to a human patient so that resistance is conferred or effects are mitigated.
Abrogation of cytokine burst to prevent inappropriate immune response
Abrogating a cytokine burst that would otherwise lead to an inappropriate immune response as an outcome of the method.
Overall, the independent claim coverage centers on administering b1-interferon, including multiple glycosylated b1-interferon species, orally or nasally before or shortly after viral exposure and before symptom development, at least 6.6 IU per pound body weight, to confer resistance or mitigate effects. The claim set emphasizes an influenza-like or avian influenza virus scope and an immunological outcome directed to abrogating a cytokine burst or inappropriate immune response.
Stated Advantages
Mitigating the effects of a susceptible viral infection.
Conveying resistance to a susceptible viral infection.
Resistance conferred or effects mitigated in the context of an infectious, avian influenza virus.
Abrogating a cytokine burst to prevent an inappropriate immune response.
Documented Applications
Prophylactic non-human primate studies for H5N1 using oro-mucosal dosing with ALFERON LDO/ALFERON, describing dose-dependent reduction in gross/histopathology and pneumonia severity.
Gene modulation observed after oral ALFERON in HIV subjects and healthy subjects using cDNA microarray gene expression results.
Interested in licensing this patent?