Anti-influenza B virus neuraminidase antibodies and uses thereof
Inventors
Krammer, Florian • Wohlbold, Teddy John • Garcia-Sastre, Adolfo • Palese, Peter
Assignees
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Publication Number
US-12545718-B2
Publication Date
2026-02-10
Expiration Date
Abstract
Provided herein are antibodies that bind to neuraminidase (NA) of different strains of influenza B virus, host cells for producing such antibodies, and kits comprising such antibodies. Also provided herein are compositions comprising antibodies that bind to NA of different strains of influenza B virus and methods of using such antibodies to diagnose, prevent or treat influenza virus disease.
Core Innovation
The invention relates to an isolated antibody that binds to an influenza B virus neuraminidase (NA). The antibody comprises specific variable heavy chain and variable light chain complementarity determining regions (VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, VLCDR3) defined by SEQ ID NO amino acid sequences, together with variable heavy and variable light chain regions that are at least 95% identical to specified reference variable regions while retaining the defined CDR sequences.
The disclosed embodiments include multiple SEQ ID-defined VH and VL combinations and additional CDR-defined variants, including alternative heavy-chain and light-chain sequence pairings. The framework descriptions also reference human or primate antibody frameworks, constant regions or isotypes, and sequence variants while preserving the defined CDR regions.
The disclosure further describes cross-reactive influenza B virus NA-binding antibodies that inhibit influenza B NA enzymatic activity and bind across Victoria and Yamagata lineages. It also provides related antibody formats and variants, together with polynucleotides, expression vectors, and host cells for producing the antibodies.
Claims Coverage
The independent claim is directed to an isolated influenza B virus neuraminidase (NA)-binding antibody defined by SEQ ID-listed VHCDR and VLCDR amino acid sequences and variable-region sequence identity to specified reference variable regions. The claim coverage presents one core inventive feature set, broadened by multiple SEQ ID-defined heavy/light combinations and additional sequence-identity variants.
Isolated influenza B virus na-binding antibody with SEQ ID-defined VH and VL CDR sequences
An isolated antibody that binds to an influenza B virus neuraminidase (NA), comprising VHCDR1, VHCDR2, VHCDR3, VLCDR1, VLCDR2, and VLCDR3 amino acid sequences defined by SEQ ID NOs.
Variable heavy and light regions at least 95% identical to specified reference variable regions
A variable heavy chain region that is at least 95% identical to a specified reference variable region and comprises the defined VH CDR sequences, and a variable light chain region that is at least 95% identical to a specified reference variable region and comprises the defined VL CDR sequences.
Alternative SEQ ID-defined heavy and light chain pairings
Multiple SEQ ID-listed variable heavy chain and variable light chain combinations are included as embodiments of the antibody.
The claim coverage centers on an isolated NA-binding antibody with precisely defined VH and VL CDR sequences, supported by sequence-identity constraints to reference variable regions and enumerated alternative heavy/light pairings.
Stated Advantages
Inhibits influenza B NA enzymatic activity.
Cross-reacts across Victoria and Yamagata lineages.
Broad protection in BALB/c mouse challenge models across both Victoria and Yamagata lineages.
Reduction of lung viral titers.
Activity against an oseltamivir-resistant IBV strain carrying the D197E mutation.
Superiority of mAb 1F2 over oseltamivir when initiated late (72 hpi).
Binding stability ranking of humanized 1F2 variants is described.
In vivo dependence on Fc-effector functions is described.
Documented Applications
Detecting an influenza B virus in a sample by contacting cells or a biological sample with the antibody and detecting antibody binding to influenza B virus NA, where binding is greater than binding to non-influenza virus infected cells or a non-influenza-infected biological sample.
Formulating the antibody as a pharmaceutical composition including the antibody and a pharmaceutically acceptable carrier.
Treating an influenza virus infection or influenza virus disease by administering the antibody to a subject within 72 hours after onset of symptoms.
Combination with one or more antibodies that bind to an influenza virus hemagglutinin (HA) as part of administration to a subject.
In vivo efficacy for influenza B virus neuraminidase (IBV NA)-binding monoclonal antibodies in BALB/c mouse challenge models with prophylactic and therapeutic timing.
Production or expression by culturing a host cell and isolating the produced antibody from the host cell or its cell culture.
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