Ha binding agents
Inventors
Shriver, Zachary • Viswanathan, Karthik • Subramanian, Vidya • Raguram, Sasisekharan
Assignees
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Publication Number
US-12024552-B2
Publication Date
2024-07-02
Expiration Date
Abstract
This disclosure relates to novel peptide agents, e.g., antibodies and antigen-binding fragments thereof, that bind hemagglutinin protein of influenza viruses, and methods of their use.
Core Innovation
The disclosure relates to contacting a biological sample with an antibody molecule and detecting binding of the antibody molecule to the sample to detect an influenza virus. The antibody molecule comprises a heavy chain immunoglobulin variable region segment and a light chain immunoglobulin variable region segment, each including defined CDR1, CDR2, and CDR3 sequences.
The document also describes novel anti-influenza hemagglutinin (HA) binding agents, including peptide and antibody formats, that target conserved HA epitopes and bind the HA trimer interface. The agents neutralize multiple influenza subtypes, inhibit HA fusogenic activity, and limit escape, including failure to generate escape mutants after serial infections in cell culture and improved escape mutant frequency versus reference antibodies.
The disclosure further describes amino-acid sequences of influenza HA regions H3 HA1/HA2 and H1 HA1/HA2, epitope footprint mapping for Ab044 and FI6, and 3D epitope representations that highlight Ab044-unique versus FI6-unique residues. It also transitions into diagnostic methods and kits for detecting influenza virus in biological samples using HA-binding antibody molecules.
Claims Coverage
The consolidated claim coverage identifies two independent claims centered on the same antibody-defined CDR sequence sets. The claims cover antibody-mediated influenza detection in a biological sample and patient infection determination based on whether the antibody binds a polypeptide in the sample.
Antibody-defined influenza detection by binding detection
A method of detecting an influenza virus in a biological sample by contacting the sample with an antibody molecule comprising a heavy chain immunoglobulin variable region segment with CDR1, CDR2, and CDR3 sequences (SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70) and a light chain immunoglobulin variable region segment with CDR1, CDR2, and CDR3 sequences (SEQ ID NO:145, SEQ ID NO:72, SEQ ID NO:73), and detecting binding of the antibody molecule to the sample.
Patient infection determination based on antibody binding to sample polypeptide
A method comprising providing a sample from a patient, contacting the sample with an antibody molecule comprising a heavy chain immunoglobulin variable region segment with CDR1, CDR2, and CDR3 sequences (SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70) and a light chain immunoglobulin variable region segment with CDR1, CDR2, and CDR3 sequences (SEQ ID NO:145, SEQ ID NO:72, SEQ ID NO:73), determining whether the antibody molecule binds a polypeptide in the sample, and determining the patient is infected with influenza if binding occurs.
Across the independent claims, influenza detection is defined by contacting a sample with an antibody molecule specified by heavy- and light-chain variable region CDR sequences and detecting whether binding occurs, either as a virus detection outcome or as a patient infection determination outcome.
Stated Advantages
The agents are said to neutralize multiple influenza subtypes.
The agents are said to inhibit HA fusogenic activity.
The agents are said to limit escape, including failure to generate escape mutants after serial infections in cell culture and improved escape mutant frequency versus reference antibodies.
High-affinity HA binding across influenza groups/subtypes.
Broad treatment and prevention coverage for influenza Group 1 and Group 2, and influenza B.
Binding that competes for the hemagglutinin trimer interface/epitopes and is distinct from reference antibodies via competition assays.
Enables detection of an influenza virus in a biological sample by detecting binding of an antibody molecule.
Determines whether a patient is infected with influenza based on antibody binding to a polypeptide in the sample.
Documented Applications
Diagnostic methods and kits for detecting influenza virus in biological samples using HA-binding antibody molecules, with detection including ELISA, Western blot, and immunohistochemistry.
Prevention and treatment across influenza subtypes.
Detection of an influenza virus in a biological sample by contacting the sample with an antibody molecule and detecting binding.
Determining whether a patient is infected with influenza by providing a patient sample, contacting it with the antibody molecule, and determining infection status based on antibody binding to a polypeptide in the sample.
Diagnostic/therapeutic kit formulations are described.
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