Superhuman anti-SARS-CoV-2 antibodies and uses thereof
Inventors
Glanville, Jacob • Daraeikia, Shahrad • Wang, I-Chieh • Liao-Chan, Sindy Andrea
Assignees
Distributed Bio Inc • Centivax Inc
Publication Number
US-11021532-B1
Publication Date
2021-06-01
Expiration Date
2040-05-14
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Abstract
This disclosure provides superhuman antibodies and antigen-binding fragments that can be administered to an individual that is infected or suspected of being infected with a virus. Superhuman antibodies and antigen-binding fragments provided herein can be capable of treating or curing the virus, and which may provide protection against the virus for up to at least several weeks. Superhuman antibodies and antigen-binding fragments provided herein can be used to diagnose a SARS Cov-2 infection.
Core Innovation
The invention provides superhuman (SH) antibodies and antigen-binding fragments that selectively bind to the SARS-CoV-2 virus. These antibodies are characterized by specific combinations of complementarity determining regions (CDRs) in the variable heavy (VH) and variable light (VL) chains, including specified amino acid sequences with defined levels of identity. The antibodies demonstrate strong binding affinity, with KD values of less than 50 nanomolar, and are capable of neutralizing SARS-CoV-2 by binding the receptor binding domain (RBD) of the virus.
The disclosed SH antibodies are derived from parental antibody frameworks known to bind to SARS-CoV-1 or MERS but are engineered to selectively and strongly bind to SARS-CoV-2, without comprising amino acid sequences 100% identical to the parental CDRs. The invention covers numerous sequence variants and engineered frameworks, providing a range of antibodies and fragments that conform to specified CDR and framework identities and combinations. The antibodies described encompass various formats, including full-length antibodies and antigen-binding fragments such as Fab, F(ab')2, scFv, VHH, and others.
The problem being addressed by this invention is the urgent global need for new compositions for treating, preventing, or diagnosing infection with SARS-CoV-2, the coronavirus responsible for COVID-19, for which at the time of invention there was no effective vaccine or treatment available. The antibodies of this invention can be administered to infected or exposed individuals for treatment or prevention of infection, and can also be used as diagnostic reagents to detect SARS-CoV-2 infection in patient samples.
Claims Coverage
The independent claims cover several inventive features relating to antibody compositions, engineered sequences, and therapeutic and diagnostic uses against SARS-CoV-2.
Antibody with defined CDR sequences for specific SARS-CoV-2 binding
An antibody or antigen-binding fragment that selectively binds to SARS-CoV-2, comprising: - VH CDR1: SEQ ID NO: 214 - VH CDR2: SEQ ID NO: 262 - VH CDR3: SEQ ID NO: 310 - VL CDR1: SEQ ID NO: 46 - VL CDR2: SEQ ID NO: 94 - VL CDR3: SEQ ID NO: 142 This configuration ensures selective binding to SARS-CoV-2.
Method of preventing or treating SARS-CoV-2 infection using the antibody
A method for preventing or treating SARS-CoV-2 viral infection or COVID19 in a subject in need thereof, comprising administering the antibody or antigen-binding fragment as described with the specified CDR sequences.
Method for diagnosing SARS-CoV-2 infection using the antibody
A method for diagnosing a subject as being infected with or suspected of being infected with SARS-CoV-2, comprising: 1. Contacting a biological sample from the subject with the specified antibody or antigen-binding fragment. 2. Detecting the presence or absence of an antibody/SARS-CoV-2 virus complex or antigen-binding fragment/SARS-CoV-2 virus complex. 3. Diagnosing infection upon detection of such complexes. The claim also specifies acceptable sample types and detection methods.
Antibody composition with alternative defined CDR combinations for SARS-CoV-2 binding
An antibody or antigen-binding fragment selectively binding to SARS-CoV-2, comprising any one of the following CDR sets: - (i) VH CDR1: SEQ ID NO: 200, VH CDR2: SEQ ID NO: 248, VH CDR3: SEQ ID NO: 296; VL CDR1: SEQ ID NO: 32, VL CDR2: SEQ ID NO: 80, VL CDR3: SEQ ID NO: 128 - (ii) VH CDR1: SEQ ID NO: 430, VH CDR2: SEQ ID NO: 431, VH CDR3: SEQ ID NO: 429; VL CDR1: SEQ ID NO: 432, VL CDR2: SEQ ID NO: 433, VL CDR3: SEQ ID NO: 441 - (iii) VH CDR1: SEQ ID NO: 215, VH CDR2: SEQ ID NO: 263, VH CDR3: SEQ ID NO: 311; VL CDR1: SEQ ID NO: 47, VL CDR2: SEQ ID NO: 95, VL CDR3: SEQ ID NO: 143 These defined sets provide alternative antibody configurations for binding SARS-CoV-2.
Antibody with full variable region sequences for SARS-CoV-2 binding
An antibody or antigen-binding fragment that selectively binds to SARS-CoV-2, comprising: - VH having amino acid sequence of SEQ ID NO: 358 - VL having amino acid sequence of SEQ ID NO: 382
The inventive features claim specific antibodies with defined CDR or variable region sequences for binding and neutralizing SARS-CoV-2, as well as methods of using these antibodies for treatment and diagnosis of SARS-CoV-2 infection.
Stated Advantages
The antibodies can treat or cure SARS-CoV-2 infection and may provide protection against the virus for several weeks.
These antibodies can be used to diagnose SARS-CoV-2 infection via binding to the virus in biological samples.
Antibodies selectively bind with high affinity (less than 50 nM) to SARS-CoV-2, enabling potent neutralization.
Treatment with the antibodies can reduce SARS-CoV-2 infection rates, death rates, viral reproduction, and the severity or duration of COVID-19 symptoms.
The antibodies can be used prophylactically in high-risk or asymptomatic subjects to prevent infection.
The antibodies are engineered to avoid 100% sequence identity with parental clones, minimizing cross-reactivity with related coronaviruses.
Documented Applications
Administering the antibodies or fragments to individuals for treatment or prophylaxis of SARS-CoV-2 (COVID-19) infection.
Using the antibodies or fragments in diagnostic assays, including ELISA, immunospot, lateral flow, flow cytometry, immunohistochemistry, or western blot, for detection of SARS-CoV-2 in patient samples such as nasal swab, tissue, saliva, or blood.
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