Compounds specific to coronavirus S protein and uses thereof
Inventors
Walker, Laura • Deveau, Laura • Belk, Jonathan • Wec, Anna • Rappazzo, C. Garrett
Assignees
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Publication Number
US-11220536-B1
Publication Date
2022-01-11
Expiration Date
Abstract
The present disclosure is directed to antibodies, and antigen binding fragments thereof, having binding specificity for the S protein of coronaviruses (CoV-S), such as the S protein of the SARS coronavirus (SARS-CoV-S) and/or the S protein of the SARS coronavirus 2 (SARS-CoV-2-S), including neutralizing antibodies and antibodies that bind to and/or compete for binding to the same linear or conformational epitope(s) on CoV-S. Further disclosed are conjugates of anti-CoV-S antibodies, and binding fragments thereof, conjugated to one or more functional or detectable moieties. Methods of making said anti-CoV-S antibodies and antigen binding fragments thereof are also contemplated. Other embodiments of the disclosure include the use of anti-CoV-S antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with coronaviruses, or the S protein thereof, and conditions where neutralization or inhibition of coronaviruses, or the S protein thereof, would be therapeutically and/or prophylactically beneficial.
Core Innovation
The invention concerns isolated antibodies, or antigen-binding fragments thereof, that specifically bind the spike protein of a coronavirus (CoV-S). The antibodies are defined by heavy chain variable region (VH) and light chain variable region (VL) CDRs, including VH CDR1, VH CDR2, VH CDR3 and VL CDR1, VL CDR2, VL CDR3, each assigned by SEQ ID NOs. The disclosed material focuses on SARS-CoV-S and SARS-CoV-2-S binding antibodies and characterizes binding behavior against coronaviruses using BLI and SPR.
The invention includes affinity-matured anti-SARS-CoV-2 antibodies, including ADI-58120, ADI-58124, ADI-58125, and ADI-55689, and related variants. The antibodies specifically bind coronavirus spike proteins and are characterized for neutralization potency and breadth across authentic sarbecoviruses, including SARS-CoV and bat sarbecoviruses. Resistance and escape behavior is described by characterizing binding and escape using multiple RBD variants and mapping conserved epitope residues on the spike.
Developability and biophysical and functional properties are described, including low polyreactivity, low hydrophobicity, and favorable thermal stability. Fc-related binding and effector activities are characterized, including ACE2 competition, FcRn and FcgR binding, C1q binding, ADCC, ADCP, ADCD, NK degranulation, and evaluation of ADE absence in vitro. The disclosure also includes antibody formats including Fab, Fab2, scFv, humanized/chimeric forms, expression vectors and host cells, ADC and CAR constructs targeting CoV-S, and diagnostic and therapeutic compositions.
Claims Coverage
The provided claims show one independent claim directed to an isolated coronavirus spike (CoV-S) binding antibody defined by specified VH and VL CDR SEQ ID identities. Coverage is further refined by dependent claims that specify antibody format, targeted spike, and quantitative binding and neutralization thresholds, and by dependent claims that add a second specified antibody in a pharmaceutical composition. The claim set covers 6 inventive features.
CoV-S specific isolated antibody defined by VH/VL CDR SEQ IDs
An isolated antibody, or antigen-binding fragment thereof, which specifically binds the spike protein of a coronavirus (CoV-S), comprising a heavy chain variable region (VH) with VH CDR1 SEQ ID NO:21904, VH CDR2 SEQ ID NO:21906, VH CDR3 SEQ ID NO:21908, and a light chain variable region (VL) with VL CDR1 SEQ ID NO:21914, VL CDR2 SEQ ID NO:21916, and VL CDR3 SEQ ID NO:21918.
Quantified spike binding affinity threshold
The isolated antibody, or antigen-binding fragment, binds SARS-CoV-S with a KD value of about 100 nM or lower.
Quantified neutralization potency against SARS-CoV and/or SARS-CoV-2
The isolated antibody, or antigen-binding fragment, neutralizes SARS-CoV and/or SARS-CoV-2 with an IC50 of about 100 nM or lower.
Specified coronavirus spike target scope
The CoV-S target is either the SARS-CoV spike protein (SARS-CoV-S) or a spike protein of SARS-CoV-2 (SARS-CoV-2-S).
Antigen-binding fragment format defined as Fab, Fab2, or scFv
The antigen-binding fragment is a Fab, Fab2, or scFv.
Pharmaceutical composition including a second specified antibody
A pharmaceutical composition includes a second antibody, or an antigen-binding fragment, in addition to the composition of claim 12, wherein the second antibody has heavy and light chain variable regions containing specified CDRs defined by given SEQ ID numbers.
Claim coverage centers on a CoV-S-binding isolated antibody or antigen-binding fragment defined by specified VH and VL CDR sequence identities. The dependent claims refine the target scope, format, and quantitative binding or neutralization thresholds, and extend to a pharmaceutical composition that includes a second specified antibody.
Stated Advantages
Provides antibodies that specifically bind the coronavirus spike protein (CoV-S).
Includes sequence-defined antibodies with specified VH/VL CDRs via SEQ ID numbers.
Supports binding affinity characterization with a KD threshold of about 100 nM or lower.
Supports neutralization potency characterization with an IC50 threshold of about 100 nM or lower.
Improved neutralization and cross-neutralization across authentic sarbecoviruses, including SARS-CoV and bat viruses.
Low polyreactivity, low hydrophobicity, and favorable thermal stability.
Fc-function activity including ACE2 competition, FcRn/FcgR/C1q binding, and Fc-mediated effector functions (ADCC, ADCP, ADCD, NK degranulation).
In vivo prophylactic and therapeutic protection in mouse hamster and non-human primate models.
Absence of ADE in vitro.
Documented Applications
Therapeutic and diagnostic compositions are described, including pharmaceutical and diagnostic compositions.
Antibody-drug conjugates (ADCs) are mentioned within the general scope of the disclosed anti-CoV-S antibodies.
Chimeric antigen receptor (CAR) use is mentioned within the general scope of the disclosed anti-CoV-S antibodies.
Prophylactic protection and therapeutic protection in mouse hamster and non-human primate models.
Diagnosis use with receptor-binding inhibition context involving ACE2, L-SIGN (CD209L), DPP4, CD26, and priming protein TMPRSS2, as described in the partial content.
Treatment use via compositions and constructs including antibodies and antigen-binding fragments, and downstream modalities such as ADC and CAR constructs targeting CoV-S, as described in the partial content.
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