Influenza hemagglutinin antibodies, compositions and related methods
Inventors
Yusibov, Vidadi • Mett, Vadim • Chichester, Jessica • Goldschmidt, Lauren
Assignees
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Abstract
Antibodies against influenza hemagglutinin, compositions containing the antibodies, and methods of using the antibodies are provided herein.
Core Innovation
The invention relates to influenza hemagglutinin (HA) monoclonal antibodies, including anti-H5N1 antibodies, that inhibit hemagglutination. The antibody light chain variable region and heavy chain variable region are defined by amino-acid ranges taken from SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:78, and SEQ ID NO:80, together with variants meeting specified minimum identity thresholds. The antibody sequence scope is tied to recombinant nucleic acid sequences encoding the light chain and/or heavy chain.
The invention further covers antibody formats and related constructs, including scFv, Fv, Fab, Fab’, F(ab’)2, and diabody, as well as fusion and bioconjugate constructs for therapeutic or diagnostic labeling. It also encompasses recombinant nucleic acids, expression vectors, and isolated host cells that express the defined antibody chains.
Plant-produced recombinant monoclonal antibody embodiments are described in plant systems, including transgenic plants and plant viral vector or transient expression approaches. The plant expression context also includes clonal plant/root/cell systems and sprouted seedling biomass production in contained growth systems.
The disclosed uses include treatment, risk of influenza infection determination, and influenza virus typing as H5 virus based on antibody binding. The document also describes pharmaceutical compositions, including encapsulated or liposomal formulations.
Claims Coverage
The independent claims focus on recombinant nucleic acids encoding defined influenza HA antibody light and/or heavy chain variable regions, including specific SEQ ID NO-derived amino-acid ranges and variants with minimum identity thresholds. Dependent claims add expression-vector and isolated host-cell limitations, and plant genus embodiments.
Recombinant nucleic acid encoding defined antibody light chain variable regions
A recombinant nucleic acid comprising a nucleotide sequence encoding an antibody light chain or an antibody heavy chain, wherein the antibody light chain comprises a light chain variable region amino acid sequence set forth in amino acids 1-97 of SEQ ID NO:79 or the light chain variable region amino acid sequence set forth in amino acids 1-97 of SEQ ID NO:79 with variants such that it is at least 95% identical, or the light chain variable region amino acid sequence set forth in amino acids 1-96 of SEQ ID NO:81 or the light chain variable region amino acid sequence set forth in amino acids 1-96 of SEQ ID NO:81 with variants such that it is at least 98% identical.
Recombinant nucleic acid encoding defined antibody heavy chain variable regions
A recombinant nucleic acid comprising a nucleotide sequence encoding an antibody light chain or an antibody heavy chain, wherein the antibody heavy chain comprises a heavy chain variable region amino acid sequence set forth in amino acids 1-115 of SEQ ID NO:78 or the heavy chain variable region amino acid sequence set forth in amino acids 1-115 of SEQ ID NO:78 with variants such that it is at least 95% identical, or the heavy chain variable region amino acid sequence set forth in amino acids 1-112 of SEQ ID NO:80 or the heavy chain variable region amino acid sequence set forth in amino acids 1-112 of SEQ ID NO:80 with variants such that it is at least 90% identical.
Expression vector and isolated host cell limitations
An expression vector including the recombinant nucleic acid; and an isolated host cell containing the expression vector.
Plant host embodiments with selected genera
A plant embodiment is specified to be from a selected genus chosen from Brassica, Nicotiana, Petunia, Lycopersicon, Solanum, Capsium, Daucus, Apium, Lactuca, Sinapis, or Arabidopsis.
The claim coverage centers on recombinant nucleic acids encoding antibody light and heavy chains with variable-region definitions by specified amino-acid ranges and identity thresholds. The coverage also extends to an expression vector, an isolated host cell containing the vector, and selected plant genera for plant embodiments.
Stated Advantages
Inhibits hemagglutination.
Enables risk of influenza infection determination based on antibody binding.
Enables influenza virus typing as H5 virus based on antibody binding.
Stable expression with high proportions of vector-containing cells.
Lower reversions versus transient plant infection.
Reduced culture cost (maintenance without hormones).
Rapid/transient protein expression timelines.
Documented Applications
Treatment.
Risk of influenza infection determination.
Influenza virus typing as H5 virus based on antibody binding.
Plant-based expression and production of HA polypeptides/antibodies using viral vector and agrobacterium-based systems.
Production of clonal root lines and clonal plants via viral inheritance through cell division.
Sprouted seedling systems in contained regulatable environments using inducible promoters, with viral or transgenic seed/sprout expression.
Use of antibody compositions including diagnostic, therapeutic, and vaccine compositions.
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