Compositions and methods for treating and preventing influenza
Inventors
Narayan, Kristin • Sloan, Susan • Yarbrough, Jill • Oldach, David William • Shriver, Zachary
Assignees
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Publication Number
US-11230593-B2
Publication Date
2022-01-25
Expiration Date
Abstract
This disclosure relates to binding agents, e.g., antibodies and antigen-binding fragments thereof, that bind hemagglutinin protein of influenza viruses, and methods of their use.
Core Innovation
The invention relates to treating or preventing an influenza virus infection, or a symptom thereof, in a human subject by administering an anti-HA antibody molecule. The anti-HA antibody molecule is defined by heavy-chain and light-chain immunoglobulin variable region segments including specific CDR1, CDR2, and CDR3 sequences, and the claims further include combination use with anti-viral agents comprising an endonuclease inhibitor, a neuraminidase inhibitor, a PB2 inhibitor, or combinations thereof.
The invention also includes responsive treatment based on a determination of influenza virus resistance to an antiviral agent, and evaluation or selection of a subject or therapy for anti-HA antibody treatment. The methods further include administering or modifying administration responsive to a change in cytokine levels comprising IL-6, IL-8, IL-10, IFN-b3, TNF-b1, or IL-33, and evaluating whether elevated cytokines indicate effectiveness or an adverse event.
The claims additionally include treatment of subjects with characteristics requiring hospitalization or ICU care and receiving, or being more likely to receive, oxygen therapy, positive pressure ventilation, and/or therapy to treat or prevent bacterial pneumonia, and/or being, or being more likely to be, incubated. The disclosed anti-HA antibody molecule is therefore used in influenza treatment, prevention, selection, and evaluation contexts tied to defined sequence features and clinical status.
Claims Coverage
The consolidated independent claim coverage identifies seven inventive features. Across the claims, the central subject matter is an anti-HA antibody molecule defined by specific heavy-chain and light-chain CDR sequences, used in influenza treatment or prevention, alone or with antiviral agents, and in resistance-guided, cytokine-guided, and severe-care subject selection contexts.
Combination anti-HA antibody with antiviral agents
Administering an anti-HA antibody molecule in combination with one or more anti-viral agents comprising an endonuclease inhibitor, a neuraminidase inhibitor, a PB2 inhibitor, or combinations thereof; the antibody molecule comprises specified heavy-chain and light-chain variable region CDR sequences.
Responsive anti-HA antibody administration for antiviral-resistant influenza
Administering an anti-HA antibody molecule responsive to a determination that the subject is infected with, or is at risk of being infected with, an influenza virus resistant to an antiviral agent; the resistant agent is chosen from an endonuclease inhibitor, a neuraminidase inhibitor, a PB2 inhibitor, or a combination thereof.
Selecting subject or therapy based on resistant influenza
Acquiring that a human subject is infected with, or is at risk of being infected with, an influenza virus resistant to an antiviral agent chosen from an endonuclease inhibitor, a neuraminidase inhibitor, a PB2 inhibitor, or a combination thereof, and selecting the subject or therapy for anti-HA antibody treatment.
Cytokine-responsive administering or modifying anti-HA antibody therapy
Administering an anti-HA antibody molecule, or modifying its administration, responsive to a change in one or more cytokines comprising IL-6, IL-8, IL-10, IFN-b3, TNF-b1, or IL-33.
Evaluating therapy using elevated cytokines as effectiveness indication
Acquiring that one or more cytokines is elevated after administration of an influenza therapy comprising an anti-HA antibody molecule, where the elevated cytokines indicate that the antibody is effective, and selecting the antibody as suitable or the subject as suitable for continued administration.
Evaluating adverse event risk using elevated cytokines
Acquiring that one or more cytokines is elevated after administration of an influenza therapy comprising an anti-HA antibody molecule, where the elevated cytokines indicate that the antibody is capable of causing an adverse event, and selecting the antibody as not suitable or the subject as not suitable for continued administration.
Treating severe-care influenza subjects with anti-HA antibody
Administering an anti-HA antibody molecule to a subject requiring hospitalization or ICU care and receiving, or more likely to receive, oxygen therapy, positive pressure ventilation, and/or therapy to treat or prevent bacterial pneumonia, and/or being, or more likely to be, incubated.
Across the independent claims, the core scope centers on an anti-HA antibody molecule defined by specific heavy-chain and light-chain CDR sequences. The inventive concepts include combination therapy with antiviral agents, resistance-guided administration and selection, cytokine-guided suitability or unsuitability determinations, and treatment of subjects with severe-care characteristics.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating or preventing an influenza virus infection, or a symptom thereof, in a human subject.
Combination therapy for influenza virus infection or symptoms using an anti-HA antibody molecule with anti-viral agents comprising an endonuclease inhibitor, a neuraminidase inhibitor, a PB2 inhibitor, or combinations thereof.
Treatment or prevention when the influenza virus is resistant to an antiviral agent chosen from an endonuclease inhibitor, a neuraminidase inhibitor, a PB2 inhibitor, or combinations thereof.
Evaluating a human subject or influenza therapy and selecting subjects or therapies for anti-HA antibody treatment based on antiviral resistance status.
Cytokine-guided evaluation to select suitable versus not suitable anti-HA antibody therapy based on elevated levels of IL-6, IL-8, IL-10, IFN-b3, TNF-b1, or IL-33.
Treating or preventing influenza in subjects requiring hospitalization or ICU care and with characteristics indicating receipt or likelihood of oxygen therapy, positive pressure ventilation, and/or therapy for bacterial pneumonia, and/or incubation.
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