Neutralizing anti-influenza B antibodies and uses thereof
Inventors
Kallewaard-LeLay, Nicole • Zhu, Qing • Benjamin, Ebony • Wachter, Leslie • Yuan, Andy • McAuliffe, Josephine Mary • Corti, Davide • Lanzavecchia, Antonio
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12325740-B2
Publication Date
2025-06-10
Expiration Date
Abstract
The invention relates to antibodies and antigen binding fragments thereof that are capable of binding to influenza B virus hemagglutinin (HA) and neutralizing influenza B virus in two phylogenetically distinct lineages. In one embodiment, the antibody or antigen binding fragment is capable of binding to influenza B virus hemagglutinin and neutralizing influenza B virus in Yamagata and Victoria lineages.
Core Innovation
The invention provides an isolated antibody or an antigen binding fragment thereof that binds to influenza B virus hemagglutinin (HA) and neutralizes influenza B virus in two phylogenetically distinct lineages, including the Yamagata lineage and the Victoria lineage, and pre-divergent influenza B strains. The antibody or binding fragment includes a set of six CDRs: HCDR-1, HCDR-2, HCDR-3, LCDR-1, LCDR-2, and LCDR-3, each defined by specified SEQ ID NOs.
The antibody or binding fragment is further defined by a variant IgG Fc region that comprises at least one substitution selected from 252Y, 254T and 256E as numbered by the EU index as set forth in Kabat. The disclosed Fc region variants are linked to Fc-effector-function modulation and are described in relation to ADCC, CDC, ADCP, binding, serum half-life, anti-inflammatory activity, and immunostimulatory properties.
The disclosure localizes the antibody epitope to the HA globular head region and identifies conservation of head-region contact residues between lineages. It also describes antibody variable-region specification, including VH and VL sequence identifier references, and references six CDR sets with Kabat and IMGT numbering.
Claims Coverage
Two inventive features are central to the claim set: an influenza B HA-binding neutralizing antibody or antigen binding fragment defined by a specific six-CDR set, and a variant IgG Fc region containing defined Kabat/EU-indexed substitutions.
Influenza B ha binding and neutralization across two phylogenetically distinct lineages
An isolated antibody or antigen binding fragment thereof that binds to influenza B virus hemagglutinin (HA) and neutralizes influenza B virus in two phylogenetically distinct lineages.
Defined six-cdr set for ha-directed antigen binding
The antibody or antigen binding fragment includes a set of six CDRs: HCDR-1, HCDR-2, HCDR-3, LCDR-1, LCDR-2, and LCDR-3, where HCDR-1 is of SEQ ID NO: 139, HCDR-2 is of SEQ ID NO: 140, HCDR-3 is of SEQ ID NO: 141, LCDR-1 is of SEQ ID NO: 142, LCDR-2 is of SEQ ID NO: 143 and LCDR-3 is of SEQ ID NO: 144.
Variant igg fc region with kabat/eu-indexed substitutions
The isolated antibody or binding fragment comprises a variant IgG Fc region that comprises at least one substitution selected from 252Y, 254T and 256E as numbered by the EU index as set forth in Kabat.
Overall claim coverage is directed to HA-binding, lineage-spanning influenza B neutralizing antibodies defined by a specific six-CDR set and refined by an Fc variant requiring at least one of the Kabat/EU-indexed substitutions 252Y, 254T, and 256E.
Stated Advantages
Neutralization of influenza B virus in two phylogenetically distinct lineages.
Modulation of IgG effector functions including ADCC mediated by NK cells.
Modulation of Fc-effector-function in relation to ADCC, CDC, ADCP, binding, and serum half-life.
Anti-inflammatory activity.
Immunostimulatory properties.
Documented Applications
Medical treatment of influenza B infection in a subject using an antibody or antigen-binding fragment specified in the claim.
Medical prophylaxis of influenza B infection in a subject using an antibody or antigen-binding fragment specified in the claim.
In vitro diagnostic detection of influenza B infection by contacting a subject sample with the antibody or antigen-binding fragment specified in the claim.
Detection, diagnosis, and prognosis use cases for influenza B infection.
Medical uses for influenza A infection, including cross-reactivity for certain influenza A H9 variants.
Interested in licensing this patent?