Broad spectrum immune and antiviral gene modulation by oral interferon
Inventors
Carter, William A. • Strayer, David R
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8075877-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 invention describes orally delivered natural human alpha-interferon (ALFERON N, a multi-species cocktail) to induce antiviral/immunomodulatory responses and prevent or mitigate lethal viral infections. It addresses the re-regulation of interferon-α pathways without significant inflammatory cytokine upregulation, including notably TNF, and contrasts this approach with recombinant single-species interferons, including differences in glycosylation.
The invention further reports broad gene induction, including interferon-related genes up to 385 genes. Alpha-interferon is administered orally, nasally, or via mucosa-related routes, and the administration induces innate immune responses. The described gene-expression effects include induction of alpha-interferon-related genes in peripheral blood leukocytes.
In example data, prophylactic efficacy is reported in cynomolgus macaques against H5N1 using oro-mucosal ALFERON, with dose-dependent reduction in lung pathology. Clinical gene-expression findings are also described in asymptomatic HIV+ subjects after oral dosing, including several TNF-related genes downregulated and mild tolerability findings.
Claims Coverage
The patent contains two independent claims, each centered on orally or nasally administering alpha-interferon at a body-weight-threshold amount to an infected animal to induce a biological response. Across the independent claims, the main inventive features are activation of an antiviral/immunomodulatory response and systemically activating an innate immune response, both tied to oral/nasal delivery and specified dosing thresholds, with dependent claims further defining the alpha-interferon preparation as a purified multi-species mixture from human white blood cells and adding human-route specific daily dose ranges.
Orally or nasally inducing an antiviral/immunomodulatory response in an infected animal
Orally or nasally administering alpha-interferon to an infected animal at an amount of at least 6.6 IU per round of the animal's body weight so that the antiviral/immunomodulatory response is induced.
Purified multi-species alpha-interferon from human white blood cells
Providing alpha-interferon that is purified as a mixture containing at least seven species of alpha-interferon produced by human white blood cells.
Oral dosing threshold and nasal dosing range for humans
Administering alpha-interferon species to a human by oral administration at a dose of at least 6.6 IU per pound of the human's body weight and by nasal administration at 1000-2000 IU per day.
Systemically activating an innate immune response
Orally or nasally administering alpha-interferon to an animal at an amount of at least 6.6 IU per pound of the animal's body weight so that the innate immune response is activated.
Overall, the claim coverage focuses on oral or nasal administration of alpha-interferon at body-weight-threshold amounts to induce either an antiviral/immunomodulatory response or systemically activate innate immune response, with key dependent refinements specifying a purified multi-species mixture produced by human white blood cells and adding human-route specific daily dose constraints.
Stated Advantages
Re-regulating interferon-α pathways without significant inflammatory cytokine upregulation, notably TNF.
Inducing a broad gene induction profile including interferon-related genes up to 385 genes.
Preventing or mitigating lethal viral infections, exemplified by prophylactic efficacy against H5N1 with dose-dependent reduction in lung pathology.
Downregulating several TNF-related genes after oral administration in asymptomatic HIV+ subjects.
Mild tolerability findings are reported in the clinical gene-expression study.
Documented Applications
Prophylactic efficacy against H5N1 in cynomolgus macaques using oro-mucosal ALFERON, with reduction in lung pathology.
Clinical gene-expression application in asymptomatic HIV+ subjects, where oral dosing induced alpha-interferon-related genes in peripheral blood leukocytes and included downregulation of several TNF-related genes.
Interested in licensing this patent?