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-11447541-B1
Publication Date
2022-09-20
Expiration Date
2041-03-04
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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 fully human anti-coronavirus antibodies, particularly anti-SARS-CoV and anti-SARS-CoV-2 antibodies that bind the Spike protein of these viruses. These antibodies, derived from convalescent patients infected with coronaviruses, are converted to full-length IgG1 isotypes and produced recombinantly. The antibodies specifically bind the Spike protein of SARS-CoV-2 and some cross-react with Spike proteins of other coronaviruses.
The disclosed antibody library comprises one thousand three hundred twenty nine anti-coronavirus antibodies annotated as antibodies 258 to 577 and 589 to 1587, detailed by their nucleic acid and amino acid sequences. The antibodies or antigen-binding fragments contain variable heavy and light chain regions defined by complementarity determining regions (CDRs) according to Kabat, Chothia, and MacCallum numbering systems. The antibodies include neutralizing and depleting types, some of which are conjugated to immunomodulators, cytokines, cytotoxic agents, chemotherapeutic agents, diagnostic agents, antiviral or antimicrobial agents, or drugs, and can be formulated as pharmaceutical compositions with carriers and excipients.
The problem addressed is the urgent need for antibody-based therapeutics, prophylactics, and diagnostics to treat, prevent, and detect SARS-CoV and SARS-CoV-2 infections amid the global COVID-19 pandemic. Existing vaccines have limitations against high antigenic diversity and fast-moving outbreaks. Isolation of potent human antibodies from convalescent patients expedites development of countermeasures with specific properties needed for these applications. The invention provides a large, diverse antibody library enabling rapid screening and selection for suitable antibodies with developed affinity, specificity, and epitope recognition.
Claims Coverage
The patent claims a set of independent features centered on antibodies specifically binding to SARS-CoV-2 Spike protein, with detailed structural and compositional features including CDR sequences and isotypes, as well as methods and compositions involving these antibodies.
Antibody comprising specific CDR sequences binding SARS-CoV-2 Spike protein
An antibody that specifically binds to the SARS-CoV-2 Spike protein, comprising three complementarity determining regions (CDRs) of the heavy chain variable region set forth as SEQ ID NO: 4949 and three CDRs of the light chain variable region set forth as SEQ ID NO: 4950, having an IgG1m3 allotype.
Variant CDR numbering schemes for antibody CDR domains
The antibody CDRs are defined by residues 31-35, 50-65, and 95-102 for heavy chain and 24-34, 50-56, and 89-97 for light chain (Kabat numbering), or alternatively residues 26-32, 50-58, 95-102 (Chothia), or residues 30-35, 47-58, 93-101 (heavy chain) and 30-36, 46-55, 89-96 (light chain) according to MacCallum numbering.
Antibody comprising specified full-length variable region sequences
An antibody comprising a heavy chain variable region and a light chain variable region set forth as SEQ ID NOs: 4949 and 4950 respectively.
Antibody comprising defined heavy and light chain amino acid sequences
An antibody comprising a heavy chain comprising SEQ ID NO: 5735 and a light chain comprising SEQ ID NO: 5736.
Pharmaceutical compositions comprising the claimed antibodies
Pharmaceutical compositions comprising the antibodies with pharmaceutically acceptable carriers, diluents, or excipients, optionally including additional antibodies binding the SARS-CoV-2 Spike protein, buffer components like histidine, sodium chloride, sucrose, polysorbate 80, with a pH of about 6.0 and antibody concentrations from about 35 to about 125 mg/mL.
Methods of treatment of SARS-CoV-2 linked disease using the claimed antibodies
Methods of treating SARS-CoV-2-linked diseases, including COVID-19, by administering therapeutically effective amounts of the claimed antibodies intravenously or subcutaneously, with possible co-administration of other SARS-CoV-2 Spike binding antibodies.
Conjugated antibody forms
Antibodies of the invention conjugated to an immunomodulator, cytokine, cytotoxic agent, chemotherapeutic agent, diagnostic agent, antiviral agent, antimicrobial agent, or drug.
The claims extensively cover human antibodies specifically binding the SARS-CoV-2 Spike protein, defined structurally at the CDR and full variable region sequence levels, and embrace pharmaceutical compositions containing these antibodies. Methods of treatment using these antibodies for SARS-CoV-2 infections, including COVID-19, are claimed. Conjugated antibody forms and antibody combinations with other antibodies are also claimed.
Stated Advantages
Availability of a large and diverse library of human antibodies specific to coronaviruses enables rapid response to emerging outbreaks by screening and selecting antibodies suitable for therapeutics, prophylactics, and diagnostics.
Antibody-based therapies provide immediate passive immunity, which is critical in fast-moving pandemics where vaccine-induced immunity is too slow.
Use of recombinant antibodies and nucleic acid-encoded versions can alleviate limitations in large-scale manufacturing, reduce costs, and enable easier distribution and administration globally.
The antibodies disclosed have specific desirable properties including high affinity, specificity, cross-reactivity, neutralizing and depleting functions, and compatibility with conjugation to various agents, enhancing therapeutic potential.
Documented Applications
Use in diagnosis of SARS-CoV-2 or SARS-CoV infections by contacting patient samples with the antibodies conjugated to detectable agents followed by detecting antigen binding.
Methods for identifying SARS-CoV-2 infected cells through antibody binding.
Methods for treating or preventing SARS-CoV or SARS-CoV-2-linked diseases such as COVID-19 by administering therapeutically effective amounts of the antibodies or pharmaceutical compositions comprising them.
Use of the antibodies or antigen-binding fragments as test reagents for development and production of vaccines against SARS-CoV-2.
Formulation and administration of the antibodies in pharmaceutical compositions intravenously or subcutaneously, including in combination therapies with other antibodies.
Use as reagents to screen for compounds affecting coronavirus infection or viral propagation.
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