Compositions and methods for treating and preventing influenza
AssigneeVisterra, Inc.
InventorsKristin Narayan, Susan Sloan, Jill Yarbrough, David William Oldach, Zachary Shriver
Life of this patent
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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.
Claims20
A method of treating or preventing an influenza virus infection, or a symptom thereof, in a human subject, comprising administering to the subject a combination of an anti-HA antibody molecule, and one or more anti-viral agents comprising an endonuclease inhibitor, a polymerase basic protein 2 (PB2) inhibitor, or both,
- wherein the antibody molecule comprises:
- (a) a heavy chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 68)
- a CDR1 comprising the sequence
- S-Y-A-M-H;
- (SEQ ID NO:
- 69)
- a CDR2 comprising the sequence
- V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G;
- and
- (SEQ ID NO:
- 70)
- a CDR3 comprising the sequence
- D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P;
- and
- (b) a light chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 145)
- a CDR1 comprising the sequence
- Q-S-I-T-F-D-Y-K-N-Y-L-A;
- (SEQ ID NO:
- 72)
- a CDR2 comprising the sequence
- W-G-S-Y-L-E-S;
- and
- (SEQ ID NO:
- 73)
- a CDR3 comprising the sequence
- Q-Q-H-Y-R-T-P-P-S.
A method of treating or preventing an influenza virus infection, or a symptom thereof, in a human subject, comprising responsive to a determination of the presence of an influenza virus that is resistant to the antiviral agent administering to the subject an anti-HA antibody molecule,
- wherein the antibody molecule comprises:
- (a) a heavy chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 68)
- a CDR1 comprising the sequence
- S-Y-A-M-H;
- (SEQ ID NO:
- 69)
- a CDR2 comprising the sequence
- V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G;
- and
- (SEQ ID NO:
- 70)
- a CDR3 comprising the sequence
- D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P;
- and
- (b) a light chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 145)
- a CDR1 comprising the sequence
- Q-S-I-T-F-D-Y-K-N-Y-L-A;
- (SEQ ID NO:
- 72)
- a CDR2 comprising the sequence
- W-G-S-Y-L-E-S;
- and
- (SEQ ID NO:
- 73)
- a CDR3 comprising the sequence
- Q-Q-H-Y-R-T-P-P-S,
- and
- wherein the subject is infected with, or is at risk of being infected with, an influenza virus that is resistant to an antiviral agent chosen from an endonuclease inhibitor, a neuraminidase inhibitor, a PB2 inhibitor, or a combination thereof.
A method of evaluating a human subject or a therapy, the method comprising:
- acquiring acknowledge that a human subject is infected with, or is at risk of being infected with, an influenza virus that is resistant to an antiviral agent chosen from an endonuclease inhibitor, a neuraminidase inhibitor, a PB2 inhibitor, or a combination thereof;
- and
- selecting the subject for a therapy comprising an anti-HA antibody molecule, or selecting a therapy comprising an anti-HA antibody molecule for treating or preventing influenza in the subject,
- wherein the anti-HA antibody molecule comprises:
- (a) a heavy chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 68)
- a CDR1 comprising the sequence
- S-Y-A-M-H;
- (SEQ ID NO:
- 69)
- a CDR2 comprising the sequence
- V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G;
- and
- (SEQ ID NO:
- 70)
- a CDR3 comprising the sequence
- D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P;
- and
- (b) a light chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 145)
- a CDR1 comprising the sequence
- Q-S-I-T-F-D-Y-K-N-Y-L-A;
- (SEQ ID NO:
- 72)
- a CDR2 comprising the sequence
- W-G-S-Y-L-E-S;
- and
- (SEQ ID NO:
- 73)
- a CDR3 comprising the sequence
- Q-Q-H-Y-R-T-P-P-S.
A method of treating or preventing an influenza virus infection, or a symptom thereof, in a human subject, comprising administering to the subject an anti-HA antibody molecule or modifying the administration of an anti-HA antibody molecule to the subject, responsive to a change in the level of 1, 2, 3, 4, 5, or all of the cytokines comprising IL-6, IL-8, IL-10, IFN-γ, TNF-α, or IL-33 in the subject,
- wherein the antibody molecule comprises:
- (a) a heavy chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 68)
- a CDR1 comprising the sequence
- S-Y-A-M-H;
- (SEQ ID NO:
- 69)
- a CDR2 comprising the sequence
- V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G;
- (SEQ ID NO:
- 70)
- and a CDR3 comprising the sequence
- D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P;
- and
- (b) a light chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 145)
- a CDR1 comprising the sequence
- Q-S-I-T-F-D-Y-K-N-Y-L-A;
- (SEQ ID NO:
- 72)
- a CDR2 comprising the sequence
- W-G-S-Y-L-E-S;
- and
- (SEQ ID NO:
- 73)
- a CDR3 comprising the sequence
- Q-Q-H-Y-R-T-P-P-S.
A method of evaluating an influenza therapy or a human subject, the method comprising:
- acquiring acknowledge that the level of one or more cytokines is elevated in a human subject after administration of an influenza therapy comprising an anti-HA antibody molecule,
- wherein an elevated level of one or more cytokines is indicative that the anti-HA antibody molecule is effective in treating or preventing an influenza infection, or a symptom thereof, and
- selecting the anti-HA antibody molecule as suitable for treating or preventing an influenza infection, or a symptom thereof, in the subject, or selecting the subject as suitable for continued administration of the anti-HA antibody molecule,
- wherein the antibody molecule comprises:
- (a) a heavy chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 68)
- a CDR1 comprising the sequence
- S-Y-A-M-H;
- (SEQ ID NO:
- 69)
- a CDR2 comprising the sequence
- V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G;
- and
- (SEQ ID NO:
- 70)
- a CDR3 comprising the sequence
- D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P;
- and
- (b) a light chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 145)
- a CDR1 comprising the sequence
- Q-S-I-T-F-D-Y-K-N-Y-L-A;
- (SEQ ID NO:
- 72)
- a CDR2 comprising the sequence
- W-G-S-Y-L-E-S;
- and
- (SEQ ID NO:
- 73)
- a CDR3 comprising the sequence
- Q-Q-H-Y-R-T-P-P-S.
A method of evaluating an influenza therapy or a human subject, the method comprising:
- acquiring acknowledge that the level of one or more cytokines is elevated in a human subject after administration of an influenza therapy comprising an anti-HA antibody molecule,
- wherein an elevated level of one or more cytokines is indicative that the anti-HA antibody molecule is capable of causing an adverse event in the subject, and
- selecting the anti-HA antibody molecule as not suitable for treating or preventing an influenza infection, or a symptom thereof, in the subject, or selecting the subject as not suitable for continued administration of the anti-HA antibody molecule,
- wherein the antibody molecule comprises:
- (a) a heavy chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 68)
- a CDR1 comprising the sequence
- S-Y-A-M-H;
- (SEQ ID NO:
- 69)
- a CDR2 comprising the sequence
- V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G;
- and
- (SEQ ID NO:
- 70)
- a CDR3 comprising the sequence
- D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P;
- and
- (b) a light chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 145)
- a CDR1 comprising the sequence
- Q-S-I-T-F-D-Y-K-N-Y-L-A;
- (SEQ ID NO:
- 72)
- a CDR2 comprising the sequence
- W-G-S-Y-L-E-S;
- and
- a CDR3 comprising the sequence
- (SEQ ID NO:
- 73)
- Q-Q-H-Y-R-T-P-P-S.
A method of treating or preventing an influenza virus infection, or a symptom thereof, in a subject, comprising administering to the subject an anti-HA antibody molecule,
- wherein the antibody molecule comprises:
- (a) a heavy chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 68)
- a CDR1 comprising the sequence
- S-Y-A-M-H;
- (SEQ ID NO:
- 69)
- a CDR2 comprising the sequence
- V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G;
- and
- (SEQ ID NO:
- 70)
- a CDR3 comprising the sequence
- D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P;
- and
- (b) a light chain immunoglobulin variable region
- segment comprising:
- (SEQ ID NO:
- 145)
- a CDR1 comprising the sequence
- Q-S-I-T-F-D-Y-K-N-Y-L-A;
- (SEQ ID NO:
- 72)
- a CDR2 comprising the sequence
- W-G-S-Y-L-E-S;
- and
- (SEQ ID NO:
- 73)
- a CDR3 comprising the sequence
- Q-Q-H-Y-R-T-P-P-S,
- and
- wherein the subject has the following characteristics:
- (i) requires hospitalization or intensive care unit (ICU) care;
- and
- (ii) receives, or is more likely to receive, an oxygen therapy, positive pressure ventilation, and/or a therapy to treat or prevent bacterial pneumonia;
- and/or is, or is more likely to be, incubated.
Dependencies are inferred from the claim text.