Antibodies useful in passive influenza immunization
Inventors
Kauvar, Lawrence M. • ELLSWORTH, STOTE • Usinger, William • McCutcheon, Krista M. • PARK, MINHA • Chen, Bo • Jiang, Ying-Ping
Assignees
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Publication Number
US-10676520-B2
Publication Date
2020-06-09
Expiration Date
Abstract
Monoclonal antibodies and fragments thereof that are crossreactive with multiple clades of influenza virus including both Group 1 and Group 2 representatives are disclosed. These antibodies are useful in controlling influenza epidemics and pandemics as well as in providing prophylactic or therapeutic protection against seasonal influenza.
Core Innovation
The invention relates to monoclonal antibodies and antigen-binding fragments that specifically bind the HA0 protein from influenza A viral clades H1, H5, H7 and H9, including fully human antibodies. The binding is described as occurring on native HA trimers at an epitope near the HA0 maturation cleavage-site consensus, with cross-reactivity across multiple influenza A clades.
The invention further includes monoclonal antibodies or antigen-binding fragments that specifically bind HA0 and HA2 proteins from influenza A viral clades H1, H5, H7 and H9, including single-chain antibody formats. The antibodies are defined by heavy-chain and light-chain variable region sequences and/or by specific CDR1, CDR2 and CDR3 sequences identified by SEQ ID NOs.
The invention also includes antigen epitope identification using peptide binding around the HA0 cleavage consensus, including binary logic peptide binding and optional CellSpot™ cell screening. The document reports characterization and functional performance for antibodies such as MAB53 and MAB8, including binding across clades, epitope mapping, competition, affinity characterization, in vitro neutralization, and mouse survival data after H1N1 and H5N1 challenge.
Claims Coverage
The provided independent claims define isolated recombinant monoclonal antibodies and antigen-binding fragments with specific binding targets across influenza A viral clades H1, H5, H7 and H9. Across the independent claims, there are 5 inventive feature groupings based on CDR-defined antibody fragments, HA0/HA2 binding with single-chain and sequence-defined variable regions, bispecific binding, and recombinant production by a nonhuman host cell with operably linked expression sequences.
CDR-defined recombinant monoclonal antibody or fragment binding HA0 across clades
An isolated recombinant monoclonal antibody or an antigen binding fragment thereof that specifically binds the HA0 protein from influenza A viral clades H1, H5, H7 and H9, the monoclonal antibody or antigen binding fragment thereof comprising a heavy chain variable region comprising specified CDR1, CDR2, and CDR3 sequences and a light chain variable region comprising specified CDR1, CDR2, and CDR3 sequences, with the antibody or fragment being a single-chain antibody or fragment.
HA0 and HA2 binding single-chain antibody with defined heavy chain variable region
An isolated recombinant monoclonal antibody or an antigen binding fragment thereof that specifically binds the HA0 and HA2 protein from influenza A viral clades H1, H5, H7 and H9, the antibody being a single chain antibody, the antigen binding region comprising a heavy chain variable region comprising a specified amino-acid sequence.
Bispecific monoclonal antibody binding HA0 and HA2 across clades
A monoclonal antibody or an antigen binding fragment thereof that specifically binds the HA0 and HA2 protein from influenza A viral clades H1, H5, H7 and H9, comprising a heavy chain variable region comprising a specified amino-acid sequence and optionally further comprising a light chain variable region comprising a specified amino-acid sequence, wherein the monoclonal antibody or the antigen binding fragment thereof is a bispecific antibody.
Recombinant monoclonal antibody produced by modified nonhuman host cell with defined variable regions
A monoclonal antibody produced recombinantly by a nonhuman host cell modified to contain a nucleotide sequence encoding a heavy chain variable region comprising a specified amino-acid sequence and a light chain variable region comprising a specified amino-acid sequence operably linked to control sequences for expression, said antibody specifically binding to the HA0 protein from influenza A viral clades H1, H5, H7 and H9.
Recombinant monoclonal antibody with CDR-defined variable regions produced by modified nonhuman host cell
A monoclonal antibody produced recombinantly by a nonhuman host cell modified to contain a nucleotide sequence operably linked to control sequences for expression, encoding a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences and a light chain variable region comprising CDR1, CDR2, and CDR3 sequences, said antibody specifically binding to the HA0 protein from influenza A viral clades H1, H5, H7 and H9.
Taken together, the independent claims cover isolated recombinant monoclonal antibodies or antigen-binding fragments that bind HA0, and in some claims both HA0 and HA2, across influenza A clades H1, H5, H7 and H9. The binding antibodies are defined by either CDR sequences or full variable region sequences, include single-chain and bispecific formats, and can be produced recombinantly by a nonhuman host cell with operably linked expression control sequences.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Passive prophylaxis and therapy against seasonal influenza, epidemics, and pandemics.
Passive immunity administration to subjects at risk or exposed to or infected with influenza A for prophylactic or treating influenza A infection.
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