DNA monoclonal antibodies targeting influenza virus
Inventors
Weiner, David B. • Patel, Ami • Yan, Jian • ELLIOTT, Sarah
Assignees
University of Pennsylvania • The Wistar Institute • Inovio Pharmaceuticals Inc
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Publication Number
US-11851477-B2
Publication Date
2023-12-26
Expiration Date
Abstract
Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an anti-influenza-hemagglutinin synthetic antibody. The disclosure also provides a method of preventing and/or treating influenza in a subject using said composition and method of generation.
Core Innovation
The disclosure concerns recombinant nucleic acid molecules encoding synthetic anti-influenza hemagglutinin antibodies or functional fragments thereof. The constructs comprise antibody variable regions, human IgG1κ constant regions, and a cleavage domain associated with heavy- and light-chain expression. The encoded antibodies comprise amino acid sequences at least 90% identical to specified sequences such as SEQ ID NOs:1–8 or functional fragments thereof, including 5J8 binding the globular-head receptor-binding pocket and F16 binding a conserved fusion subdomain.
The disclosure reports antibody expression, secretion, hemagglutinin binding, and neutralization, as well as protection in challenge studies against influenza A and B following plasmid delivery. Evaluated outcomes include serum human IgG levels, hemagglutinin reactivity, survival, body weight, and lung viral titers. The described molecules exhibit cross-reactivity and neutralization across influenza strains, supporting nucleic-acid delivery of anti-hemagglutinin antibodies for influenza treatment, including co-administered combinations.
Claims Coverage
The claim coverage includes five inventive features directed to nucleic acid molecules encoding synthetic anti-influenza hemagglutinin antibodies, structural domains, and therapeutic uses.
Nucleic acid encoding synthetic anti-influenza hemagglutinin antibodies or fragments
The independent claim recites a nucleic acid molecule comprising a nucleotide sequence encoding an anti-influenza hemagglutinin synthetic antibody or a fragment thereof.
Specified antibody sequences and functional fragments
The claim specifies an encoded anti-influenza hemagglutinin synthetic antibody comprising an amino acid sequence at least 90% identical to one of SEQ ID NOs:1–8, or a functional fragment thereof, with a dependent claim specifying an identity threshold of at least 95%.
Hemagglutinin binding regions
A dependent claim specifies that the encoded anti-influenza hemagglutinin synthetic antibody binds either the globular head or the fusion subdomain of influenza hemagglutinin.
Antibody chain regions and cleavage domain
A claim recites human IgG1κ constant heavy- and light-chain regions and a polypeptide architecture containing anti-influenza hemagglutinin variable heavy- and light-chain regions and a cleavage domain.
Treatment of influenza infection
A claim recites treating influenza infection, including influenza A or B, in a subject by administering the claimed nucleic acid molecule.
The independent claim covers nucleic acid molecules encoding synthetic anti-influenza hemagglutinin antibodies or functional fragments, while dependent claims refine sequence identity thresholds, structural domains, binding regions, and methods of treating influenza infection.
Stated Advantages
The described 5J8 antibody cross-reacts with multiple H1 viruses.
The described F16 antibody neutralizes influenza A Group 1 and Group 2 viruses.
The reported results provide evidence of antibody expression, hemagglutinin reactivity, and protective efficacy in influenza A and B challenge models, including combination-treatment results.
Documented Applications
Nucleic-acid delivery of anti-hemagglutinin antibodies for the treatment of influenza infection, including influenza A and influenza B, in a subject.
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