Monoclonal antibodies against the hemagglutinin (HA) and neuraminidase (NA) of in-fluenza H3N2 viruses
Inventors
Kobie, James J. • Martinez-Sobrido, Luis • Piepenbrink, Michael • Nogales, Aitor
Assignees
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Publication Number
US-12516108-B2
Publication Date
2026-01-06
Expiration Date
Abstract
The present disclosure relates to neutralizing anti-influenza monoclonal antibodies. The disclosure further relates to therapeutic uses of the isolated antibody. The antibodies are either directed against Hemagglutinin (HA) and Neuraminidase (NA) of Influenza H3N2.
Core Innovation
The invention relates to isolated antibodies or antigen-binding fragments thereof that specifically bind to influenza virus hemagglutinin (HA) or neuraminidase (NA). For HA-binding, the antibodies comprise a heavy chain variable region and a light chain variable region with HCDR1, HCDR2, HCDR3 and LCDR1, LCDR2, LCDR3 defined using selected HCDR and LCDR sets from specified SEQ ID NOs. For NA-binding, the antibodies similarly comprise heavy and light chain variable regions in which the HCDRs and LCDRs are defined using selected SEQ ID NO groups.
The invention further includes antibodies that are broadly neutralizing against influenza H3N2, with cross-blocking and competitive binding properties described for the antibody binding behavior. Variant Fc constant regions are included as an option, and antibody formats can include chimeric, humanized, or human antibodies and antibody fragments. The antibodies may also be conjugated to payloads, including a polymer such as PEG or cytotoxic agents, and may be encoded by nucleic acids and expressed from expression vectors.
The invention also encompasses treatment and prophylaxis of influenza virus infection by administering an isolated antibody or antigen-binding fragment. Pharmaceutical compositions are described as including an antibody or antigen-binding fragment and a pharmaceutically acceptable carrier. The disclosed examples describe generation of human monoclonal antibodies, measurement of binding and neutralization activity, and evaluation of prophylactic and therapeutic activity in a mouse protection setting.
Claims Coverage
Two independent claims are provided. Each independent claim defines an isolated antibody or antigen-binding fragment by the specific CDR composition of the heavy and light chain variable regions using selected SEQ ID NO sets, one directed to HA and the other directed to NA. Across the dependent claim set, additional inventive feature refinements include variant Fc constant regions, conjugation to payloads, and therapeutic use via administration in a pharmaceutical composition.
H3 hemagglutinin-binding antibody with defined heavy/light CDR sets
An isolated antibody or antigen-binding fragment thereof that specifically binds to a hemagglutinin (HA) of influenza virus, comprising a heavy chain variable region that comprises HCDR1, HCDR2, and HCDR3 comprising the respective sequences of a HCDR set selected from the group consisting of SEQ ID NOs: 1-3, and SEQ ID NOs: 7-9, and SEQ ID NOs: 7, 8, and 12, and a light chain variable region that comprises LCDR1, LCDR2 and LCDR3 comprising the respective sequences of a LCDR set selected from the group consisting of SEQ ID NOs: 4-6 and SEQ ID NOs: 10, 5, and 11.
H3 neuraminidase-binding antibody with defined heavy/light CDR sets
An isolated antibody or antigen-binding fragment thereof that specifically binds to a neuraminidase (NA) of influenza virus, comprising a heavy chain variable region that comprises HCDR1, HCDR2, and HCDR3 comprising the respective sequences of a HCDR set selected from the group consisting of SEQ ID NOs: 13-15 and SEQ ID NOs: 19-21, and a light chain variable region that comprises LCDR1, LCDR2 and LCDR3 comprising the respective sequences of a LCDR set selected from the group consisting of SEQ ID NOs: 16-18, and SEQ ID NOs: 22-24.
The claim coverage is centered on isolated anti-influenza antibodies defined by specific heavy- and light-chain variable region CDR sets selected from numbered SEQ ID NO groups, with separate HA-directed and NA-directed independent claim scopes. Dependent claims additionally refine antibody composition, antibody payload conjugation, and therapeutic use for treating or neutralizing influenza virus infection via administration in a pharmaceutical composition.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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