Neutralizing anti-influenza A antibodies and uses thereof
Inventors
Benjamin, Ebony • Kallewaard-LeLay, Nicole • McAuliffe, Josephine Mary • Palmer-Hill, Frances • Wachter, Leslie • Yuan, Andy • Zhu, Qing • Corti, Davide • Lanzavecchia, Antonio • Guarino, Barbara • DeMarco, Anna
Assignees
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Publication Number
US-11932682-B2
Publication Date
2024-03-19
Expiration Date
Abstract
The invention relates to antibodies and binding fragments thereof that are capable of binding to influenza A virus hemagglutinin and neutralizing at least one group 1 subtype and at least 1 group 2 subtype of influenza A virus.
Core Innovation
The invention relates to an isolated antibody or a binding fragment thereof that binds to influenza A virus hemagglutinin and neutralizes at least one group 1 subtype and at least one group 2 subtype of influenza A virus. The antibody or fragment includes a set of six CDRs consisting of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, comprising HCDR1 of SEQ ID NO.:103, HCDR2 of SEQ ID NO.:104, HCDR3 of SEQ ID NO.:105, LCDR1 of SEQ ID NO.:108, LCDR2 of SEQ ID NO.:109, and LCDR3 of SEQ ID NO.:110.
The described approach addresses the need for influenza A virus neutralizing antibodies that act across influenza A group 1 and group 2 subtypes. By specifying the six CDRs with particular SEQ ID NO. references, the invention defines a binding and neutralizing antibody having a defined HA-binding specificity. The antibody is further described as capable of neutralizing influenza A virus subtypes and variants belonging to both group 1 and group 2.
The document also includes pharmaceutical composition or medicament formulations for treatment, prevention, and diagnostic detection of influenza A infection or antigen-antibody complexes. The medical use description includes administration timing relative to exposure and considers subject serostatus, while the antibody specificity is grounded in the defined HA-binding and neutralizing CDR set.
Claims Coverage
The claim coverage centers on a CDR-defined isolated antibody or binding fragment that binds influenza A HA and neutralizes across influenza A group 1 and group 2 subtypes, with dependent refinements specifying subtype/variant scope, VH/VL sequence identity, selectable antibody formats, variant Fc for enhanced serum half-life, and a specified formulation buffer.
Cdr-defined influenza a ha-binding and cross-group neutralization
An isolated antibody or a binding fragment thereof capable of binding to influenza A virus hemagglutinin and neutralizing at least one group 1 subtype and at least one group 2 subtype of influenza A virus, where the antibody or fragment includes a set of six CDRs comprising HCDR1 of SEQ ID NO.:103, HCDR2 of SEQ ID NO.:104, HCDR3 of SEQ ID NO.:105, LCDR1 of SEQ ID NO.:108, LCDR2 of SEQ ID NO.:109, and LCDR3 of SEQ ID NO.:110.
Subtype and variant neutralization of influenza a group 1 and group 2
The antibody or binding fragment capable of neutralizing specified influenza A virus group 1 and group 2 subtypes and their variants.
Sequence-identity threshold to specified vh/vl sequences
The antibody or binding fragment includes a VH and/or VL with at least 75% sequence identity to specified VH and VL sequences (SEQ ID NO.:102 and SEQ ID NO.:107).
Selected antibody and binding-fragment formats
The antibody or binding fragment is selected from a listed group of antibody and antibody-fragment formats, including monoclonal, chimeric, CDR-grafted, humanized, Fab, Fab', F(ab')2, Fv, disulfide linked Fv, scFv, single domain antibody, diabody, multispecific antibody, dual-specific antibody, and bispecific antibody.
Variant fc region associated with enhanced serum half-life
The antibody or binding fragment includes a variant Fc region that provides an enhanced serum half-life compared to a native Fc antibody.
Composition formulated with specified buffer components and ph
A composition includes the antibody or binding fragment formulated with 25 mM His and 0.15 M NaCl at pH 6.0.
The coverage is centered on a CDR-defined isolated antibody or binding fragment that binds influenza A HA and neutralizes at least one group 1 and at least one group 2 subtype, with dependent refinements specifying subtype/variant scope, VH/VL sequence identity, selectable antibody formats, variant Fc for enhanced serum half-life, and a specified formulation buffer.
Stated Advantages
Broad cross-reactivity and neutralization across influenza A group 1 and group 2 subtypes, through defined HA stalk/HA2 targeting.
Enhanced serum half-life via a variant Fc region.
Documented Applications
Therapeutic, prophylactic, and diagnostic uses are described for the antibodies, binding fragments, and related compositions, including in vitro diagnosis.
Use of nucleic acids encoding the antibodies, vectors, and host cells for expression is described.
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