Anti-coronavirus antibodies and methods of use
Inventors
WESTENDORF, Kathryn • ZENTELIS, Stefanie • MUTHURAMAN, Krithika • JEPSON, Kevin • FALCONER, Ester • Mascola, John • Graham, Barney • Corbett, Kizzmekia • Ledgerwood, Julie • Wang, Lingshu • ABIONA, Olubukola • Shi, Wei • Kong, Wing-pui • Zhang, Yi • Jones, Bryan Edward • FOSTER, Denisa • Davies, Julian • Chai, Qing • Frye, Christopher Carl • Gopalrathnam, Ganapathy • HENDLE, Jörg • SAUDER, John Michael • Boyles, Jeffrey Streetman • PUSTILNIK, Anna
Assignees
AbCellera Biologics Inc • United States, REPRESENTED BY SECRETARY Department Of Health And Human Svcs AS • Eli Lilly and Co • US Department of Health and Human Services
Publication Number
US-11370828-B2
Publication Date
2022-06-28
Expiration Date
2040-12-09
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Abstract
Antibodies that bind SARS-CoV spike protein, SARS-CoV-2 spike protein, and methods of using same for treating or preventing conditions associated with SARS or COVID-19 and for detecting SARS-CoV or SARS-CoV-2.
Core Innovation
The invention relates to anti-coronavirus antibodies, specifically anti-SARS-CoV and anti-SARS-CoV-2 antibodies that bind the spike protein of these viruses. The invention includes large libraries of fully human recombinant antibodies obtained from convalescent patients, with characterized variable heavy (VH) and light (VL) chain sequences. These antibodies can be used for treating or preventing diseases associated with these viruses such as COVID-19, for detecting infection, or as research reagents in vaccine development.
The problem being addressed arises from the severe global health emergency caused by rapidly spreading and mutating viruses like SARS-CoV-2, which places immense burden on healthcare systems and economy. Existing treatments like vaccines have limitations against rapidly evolving viruses and emerging strains due to the time lag in immunity development and the challenge of producing broad-spectrum antibodies. Monoclonal antibody therapeutics face scale-up and specificity challenges, necessitating a rapid pipeline for the discovery and delivery of potent therapeutic antibodies with ideal properties including affinity, specificity, and manufacturability.
Claims Coverage
The patent claims are centered on the antibody comprising specific complementarity determining regions (CDRs), heavy and light chain variable regions, and full heavy and light chain sequences that specifically bind to the SARS-CoV-2 spike protein with IgG1m3 allotype and possess neutralizing activity and additional functional properties.
Antibody specificity to SARS-CoV-2 spike protein with defined CDRs and allotype
An antibody that specifically binds to the SARS-CoV-2 spike protein, comprising three CDRs from heavy chain variable region SEQ ID NO: 1255 and light chain variable region SEQ ID NO: 1256, having an IgG1m3 allotype.
Antibody comprising defined CDR residues according to Kabat, Chothia, or MacCallum numbering
The antibody or antigen-binding fragment contains specific CDR residues defined by Kabat (residues 31-35, 50-65, 95-102 for heavy chain and 24-34, 50-56, 89-97 for light chain), Chothia, or MacCallum schemes as detailed in claims 2-4.
Antibody variable region sequence identity variants
Antibodies comprising heavy and light chain variable regions with at least 95% sequence identity to sequences set forth in SEQ ID NOs: 1255 and 1256 respectively, along with the exact sequences themselves.
Antibody with specified full heavy and light chain sequences
An antibody comprising a heavy chain of SEQ ID NO: 5363 and a light chain of SEQ ID NO: 5364.
Neutralizing activity and conjugation
The antibody neutralizes SARS-CoV-2, and may be conjugated to immunomodulators, cytokines, cytotoxic agents, chemotherapeutics, diagnostics, antiviral or antimicrobial agents, or drugs.
Pharmaceutical formulations
Pharmaceutical compositions comprising the antibody with pharmaceutically acceptable carriers, diluents or excipients, optionally containing additional antibodies against SARS-CoV-2 spike protein and specific excipients (histidine, sodium chloride, sucrose, polysorbate 80) with defined pH and concentration ranges.
Methods for treating SARS-CoV, SARS-CoV-2, and COVID-19
Methods comprising administering a therapeutically effective amount of the antibody or pharmaceutical composition to treat, inhibit or prevent SARS-CoV, SARS-CoV-2, or COVID-19, with dosing regimens involving intravenous or subcutaneous routes at specified doses and optionally combined with additional antibodies targeting SARS-CoV-2 spike protein.
The claims cover novel antibodies specifically targeting SARS-CoV-2 spike protein characterized by defined CDRs, variable and full-length sequences, with IgG1m3 isotype, exhibiting neutralizing activity, and optionally conjugated to therapeutic or diagnostic agents. Also claimed are compositions and methods for treatment or prevention of COVID-19 using these antibodies and their pharmaceutical formulations.
Stated Advantages
Facilitates rapid response to emerging coronavirus outbreaks through a large diverse library of human antibodies.
Antibodies exhibit specificity, high affinity, neutralizing, and cross-reactive properties against SARS-CoV and SARS-CoV-2 spike proteins.
Availability of nucleic acid-encoded antibodies for direct administration reduces production scale limitations of protein therapeutics.
Antibodies suitable for diagnostics, prophylaxis, and therapeutics with optimized properties like solubility, affinity, and manufacturability.
Use of antibody cocktails and multispecific antibody constructs provide enhanced therapeutic potential.
Engineering of antibodies to improve serum half-life, effector functions, and reduce immunogenicity.
Documented Applications
Treatment or prevention of SARS-CoV or SARS-CoV-2-linked diseases such as COVID-19 in human patients.
Diagnostic assays for detecting SARS-CoV or SARS-CoV-2 infection by detecting viral antigens using the antibodies or antigen-binding fragments conjugated to detectable agents.
Monitoring or screening coronavirus infection progression in vivo or in vitro, including binding and quantification of virus.
Use as reagents for vaccine development and production, including testing vaccine preparations comprising coronavirus subunits or fragments.
Combination therapies involving administration of two or more antibodies binding distinct epitopes of SARS-CoV-2 spike protein.
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