Anti-SARS-Cov-2 antibodies derived from 3bgf
Inventors
Glanville, Jacob • Daraeikia, Shahrad • Wang, I-Chieh • Liao Chan, Sindy Andrea • Bürckert, Jean-Philippe • Youssef, Sawsan
Assignees
Distributed Bio Inc • Centivax Inc
Publication Number
US-11028167-B1
Publication Date
2021-06-08
Expiration Date
2040-05-14
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Abstract
This disclosure provides antibodies and antigen-binding fragments that are derived from 3bgf and that can be administered to an individual that is infected or suspected of being infected with a virus. Antibodies and antigen-binding fragments herein can be capable of treating or curing the virus, and which may provide protection against the virus for up to several weeks. Antibodies and antigen-binding fragments herein can be used to diagnose a SARS CoV-2 infection.
Core Innovation
The invention provides antibodies and antigen-binding fragments derived from the parental antibody clone 3bgf that selectively bind to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These 3bgf-derived antibodies or antigen-binding fragments are characterized by specific complementarity determining regions (CDRs) and can bind with high affinity (less than 200 nM, preferably less than 50 nM) to the receptor binding domain (RBD) of SARS-CoV-2. The antibodies and fragments described herein are capable of neutralizing the activity of SARS-CoV-2 and can be administered to an individual infected or suspected of being infected with the virus, or used in diagnostic assays.
The problem addressed by this invention is the lack of effective compositions for treating, preventing, or diagnosing SARS-CoV-2 infection, as there was no vaccine or treatment available for COVID-19 at the time of invention. There was an urgent need for new therapeutic and diagnostic tools to combat the rapid spread and significant morbidity and mortality associated with COVID-19.
The 3bgf-derived antibodies or antigen-binding fragments are defined by amino acid sequence identities in their variable heavy chain (VH) and variable light chain (VL) CDRs, with specified sequences and sequence identities provided in the specification. They can be formatted into various isotypes, subclasses, and fragment types (including IgG, IgM, Fab, scFv, etc.), and are useful both as therapeutics to treat or prevent COVID-19 and as reagents to diagnose the presence of SARS-CoV-2 infection by detecting viral antigens in samples through methods such as ELISA, lateral flow assay, flow cytometry, or immunohistochemistry.
Claims Coverage
The patent contains several independent claims describing core inventive features around 3bgf-derived antibodies and their applications.
3bgf-derived antibody or antigen-binding fragment with defined CDR sequences
An antibody or antigen-binding fragment that selectively binds to SARS-CoV-2 and comprises: - Variable heavy chain (VH) CDR1 with the amino acid sequence SEQ ID NO: 76 - VH CDR2 with the amino acid sequence SEQ ID NO: 102 - VH CDR3 with the amino acid sequence SEQ ID NO: 130 - Variable light chain (VL) CDR1 with the amino acid sequence SEQ ID NO: 13 - VL CDR2 with the amino acid sequence SEQ ID NO: 31 - VL CDR3 with the amino acid sequence SEQ ID NO: 48
3bgf-derived antibody or antigen-binding fragment with at least 90% VH and VL sequence identity
An antibody or antigen-binding fragment that comprises the above-defined CDRs and selectively binds to SARS-CoV-2, and further comprises: - VH having at least 90% sequence identity to SEQ ID NO: 155 - VL having at least 90% sequence identity to SEQ ID NO: 179
Antibody or antigen-binding fragment with specific isotypes or formats
An antibody or antigen-binding fragment defined as above, wherein the antibody is of class IgG, IgM, IgE, IgA, IgD (or derived therefrom), and may be selected from subclasses such as IgG1, IgG2a, IgG2b, IgG3, or IgG4. The antibody can also be a monoclonal, grafted, chimeric, human, or humanized antibody. The antigen-binding fragment may be a Fab, Fab′, F(ab′)2, variable fragment (Fv), triabody, tetrabody, minibody, bispecific F(ab′)2, trispecific F(ab′)2, diabody, bispecific diabody, scFv, scFv-Fc, Fab-Fc, VHH, or bispecific scFv.
Antibody or antigen-binding fragment with binding affinity and specificity
An antibody or antigen-binding fragment as above, with a binding affinity of less than 200 nM, and which selectively binds to a receptor binding domain (RBD) of SARS-CoV-2.
3bgf-derived antibody or antigen-binding fragment with alternate defined CDRs
An antibody or antigen-binding fragment that selectively binds to SARS-CoV-2 and comprises any of the following sets of CDR sequences: - (i) VH CDR1 SEQ ID NO: 78, VH CDR2 SEQ ID NO: 104, VH CDR3 SEQ ID NO: 132, VL CDR1 SEQ ID NO: 15, VL CDR2 SEQ ID NO: 30, VL CDR3 SEQ ID NO: 50 - (ii) VH CDR1 SEQ ID NO: 77, VH CDR2 SEQ ID NO: 103, VH CDR3 SEQ ID NO: 131, VL CDR1 SEQ ID NO: 14, VL CDR2 SEQ ID NO: 32, VL CDR3 SEQ ID NO: 49 - (iii) VH CDR1 SEQ ID NO: 66, VH CDR2 SEQ ID NO: 92, VH CDR3 SEQ ID NO: 120, VL CDR1 SEQ ID NO: 3, VL CDR2 SEQ ID NO: 29, VL CDR3 SEQ ID NO: 38 - (iv) VH CDR1 SEQ ID NO: 202, VH CDR2 SEQ ID NO: 203, VH CDR3 SEQ ID NO: 201, VL CDR1 SEQ ID NO: 204, VL CDR2 SEQ ID NO: 205, VL CDR3 SEQ ID NO: 206
3bgf-derived antibody or antigen-binding fragment with full-length VH and VL sequences
An antibody or antigen-binding fragment that selectively binds to SARS-CoV-2, comprising: - VH chain having the amino acid sequence SEQ ID NO: 155 - VL chain having the amino acid sequence SEQ ID NO: 179
Therapeutic method of treating or preventing SARS-CoV-2 infection
A method of preventing or treating a SARS-CoV-2 viral infection or COVID19 in a subject in need, by administering to the subject an antibody or antigen-binding fragment as defined above.
Therapeutic method in combination with additional therapies
The above therapeutic method wherein one or more additional therapies or drugs are also administered to the subject.
Diagnostic method for SARS-CoV-2 infection using 3bgf-derived antibody or fragment
A method of diagnosing a subject as being infected with SARS-CoV-2 or suspected of being infected, by contacting a sample (such as nasal swab, tissue sample, saliva, or blood) with the antibody or antigen-binding fragment as defined above, detecting its presence or absence, and diagnosing infection if detected. The detection can be via ELISA, immunospot assay, lateral flow assay, flow cytometry, immunohistochemistry, or western blot.
The inventive features cover specific 3bgf-derived antibodies or antigen-binding fragments defined by unique CDR and/or full-chain sequences, their high affinity and specificity for SARS-CoV-2 (especially RBD), various isotype and format options, as well as their use in therapeutic and diagnostic methods for COVID-19.
Stated Advantages
The antibodies or antigen-binding fragments are able to treat or cure SARS-CoV-2 infection and may provide protection against the virus for up to several weeks.
These antibodies or fragments can be used to diagnose a SARS-CoV-2 infection.
The invention addresses the urgent need for compositions useful in treating or preventing SARS-CoV-2 infection and for diagnosing exposure to the virus.
Antibodies and fragments have high specificity and binding affinity for SARS-CoV-2, enabling effective neutralization and diagnosis.
Therapeutic use of these antibodies may reduce symptoms, lower infection rates, reduce reproduction of the virus, and reduce death rates compared to untreated subjects.
Documented Applications
Treatment of individuals infected or suspected of being infected with SARS-CoV-2 or COVID-19.
Prevention of SARS-CoV-2 infection in individuals at risk.
Diagnostic detection of SARS-CoV-2 infection in samples such as nasal swab, tissue sample, saliva, or blood using methods including ELISA, immunospot assay, lateral flow assay, flow cytometry, immunohistochemistry, and western blot.
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