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-11414479-B2
Publication Date
2022-08-16
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 disclosure describes anti-coronavirus spike antibodies and antigen-binding fragments that bind to a spike protein of a coronavirus. The antibodies are defined by heavy chain variable region and light chain variable region complementarity-determining regions, including VH CDR1, VH CDR2, VH CDR3 and VL CDR1, VL CDR2, VL CDR3, each associated with specified SEQ ID NOs.
The specific CDR amino-acid sequences are provided for the antibody, including SEQ ID NOs corresponding to the heavy-chain CDR1, CDR2, and CDR3 and the light-chain CDR1, CDR2, and CDR3. The disclosure also includes anti-CoV-S antibody designations such as ADI-55688, ADI-55689, ADI-55690, and post-affinity-maturation SARS-CoV-2 antibodies including ADI-58120/24/26 and engineered Fc variants such as ADI-58125.
The invention further contemplates therapeutic, prophylactic, and diagnostic use, including treatment, prophylaxis, and disease diagnosis/assessment based on the described antibodies. It also includes antibody conjugates with functional or detectable moieties, polynucleotides encoding the antibodies, vectors and host cells, and binding-based embodiments including competitive binding.
Claims Coverage
The document provides independent claim coverage centered on treating a coronavirus infection by administering a coronavirus spike-binding antibody or antigen-binding fragment. The core inventive feature set specifies six CDR sequences by SEQ ID NO for VH CDR1/2/3 and VL CDR1/2/3.
Treating coronavirus infection with defined spike-binding CDR-defined antibody
A method of treating an infection of a subject by a coronavirus by administering an antibody, or antigen-binding fragment thereof, which binds to a spike protein of the coronavirus, where the antibody comprises a heavy chain variable region (VH) comprising VH CDR1 comprising SEQ ID NO:22304, VH CDR2 comprising SEQ ID NO:22306, and VH CDR3 comprising SEQ ID NO:22308; and a light chain variable region (VL) comprising VL CDR1 comprising SEQ ID NO:22314, VL CDR2 comprising SEQ ID NO:22316, and VL CDR3 comprising SEQ ID NO:22318.
The claim set is anchored on administering a coronavirus spike-binding antibody or antigen-binding fragment defined by specific VH and VL CDR sequence identity assignments via SEQ ID NOs 22304/22306/22308 and 22314/22316/22318.
Stated Advantages
Enhanced neutralization potency and cross-neutralization breadth across sarbecoviruses and variants.
Low polyreactivity, low hydrophobicity, and low self-interaction.
Favorable Fab thermal stability.
Fc engineering that does not disrupt FcgR binding while preserving or adjusting FcRn binding at pH 6.0 and maintaining C1q binding.
Strong Fc-mediated effector functions including ADCP/ADNP, complement deposition, NK degranulation, and ADCC.
In vivo protection in mice without ADE.
No cross-tissue reactivity in human tissue IHC.
Documented Applications
Treating an infection of a subject by a coronavirus by administering a spike-binding antibody or antigen-binding fragment defined by specified CDR sequences.
Prophylaxis based on the described antibodies and antigen-binding fragments.
Disease diagnosis/assessment based on the described antibodies.
Evaluating and developing post-affinity-maturation SARS-CoV-2 antibodies, including ADI-58125, with cross-neutralization breadth across sarbecoviruses and variants and variant escape/escape-resistance characterization.
In vivo assessment of protection in mice using mouse-adapted SARS-CoV-2 MA10 and mouse-adapted SARS-CoV MA15, with evaluation for ADE in THP-1/Raji using pseudovirus.
Preclinical evaluation in Syrian hamsters and non-human primates, including safety/PK/PD and efficacy, and human tissue cross-reactivity assessment by IHC.
Clinical development planning for ADI-58125, including proposed Phase 2/3 and Phase 1/2/3 clinical trials.
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