Compounds specific to coronavirus S protein and uses thereof
Inventors
Walker, Laura • Deveau, Laura • Belk, Jonathan • Wec, Anna • Rappazzo, C. Garrett
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11192940-B2
Publication Date
2021-12-07
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 provides an isolated antibody, or antigen-binding fragment thereof, that specifically binds to the spike protein of a coronavirus (CoV-S). The antibody comprises a heavy chain variable region (VH) with specified VH CDR1, VH CDR2, and VH CDR3 sequence identities, and a light chain variable region (VL) with specified VL CDR1, VL CDR2, and VL CDR3 sequence identities. The nucleic-acid embodiments include nucleic acids encoding the VH and VL as defined by the stated SEQ ID numbers.
The disclosed antibodies and antigen-binding fragments are associated with coronavirus spike binding, including epitopes described as linear and conformational. Related embodiments describe antibodies that share specified CDR identities, target the same CoV-S epitope, and permit affinity maturation while maintaining VH/VL sequence identity thresholds, with reference to SARS-CoV-S and/or SARS-CoV-2-S and extensive sequence-based characterization.
The scope further includes binding antibodies, neutralizing antibodies, epitope-competition antibodies, antibody fragment conjugates, optional Fc variants, polynucleotides, vectors, host cells, and broader construct formats such as antibody-drug conjugates and CAR constructs. The disclosure also contemplates pharmaceutical and diagnostic compositions, therapeutic, diagnostic, and prophylactic uses, and functional performance parameters such as K_D and IC50 thresholds and cross-reactivity.
Claims Coverage
The independent claims center on a CoV-S-specific isolated antibody, or antigen-binding fragment thereof, defined by specified VH and VL CDR sequence identities. The claim family includes dependent refinements for target spike identity, neutralization behavior, potency and binding thresholds, and antigen-binding fragment format limitations, for a total of six inventive features.
Coronavirus spike-specific antibody defined by specified VH/VL CDR identities
An isolated antibody, or antigen-binding fragment thereof, specifically binding to the spike protein of a coronavirus (CoV-S), wherein the antibody comprises a heavy chain variable region (VH) with VH CDR1, VH CDR2, and VH CDR3 comprising the specified SEQ ID numbers, and a light chain variable region (VL) with VL CDR1, VL CDR2, and VL CDR3 comprising the specified SEQ ID numbers.
Targeting SARS-CoV spike and/or SARS-CoV-2 spike
The isolated antibody, or antigen-binding fragment thereof, binds an antigen that is specifically either the SARS-CoV spike protein (SARS-CoV-S) or the spike protein of SARS-CoV-2 (SARS-CoV-2-S).
Neutralizing SARS-CoV and/or SARS-CoV-2
An isolated antibody, or antigen-binding fragment thereof, that neutralizes SARS-CoV and/or SARS-CoV-2.
Potent neutralization threshold by IC50
An isolated antibody, or antigen-binding fragment thereof, that neutralizes SARS-CoV and/or SARS-CoV-2 with an IC50 of about 100 nM or lower.
High-affinity binding threshold by KD
An isolated antibody, or antigen-binding fragment thereof, that binds to SARS-CoV-S with a K_D of about 100 nM or lower.
Antigen-binding fragment formats
An isolated antibody, or antigen-binding fragment thereof, whose antigen-binding portion is a Fab, Fab2, or scFv.
Coverage centers on a CoV-S-specific isolated antibody defined by specified VH and VL CDR sequence identities, with dependent refinements for targeted spike protein, neutralization, potency thresholds, binding affinity, and allowed antigen-binding fragment formats.
Stated Advantages
Improved SARS-CoV-2 neutralization IC50s versus parental clones.
Broadened neutralization across sarbecoviruses.
Neutralization breadth against SARS-CoV-2 variants including D614G and variants such as UK, South Africa, and P.1.
Reduced escape/resistance profiles for certain antibodies.
Engineered antibodies lack polyreactivity and have low hydrophobicity/self-interaction.
Clinically comparable Fab thermal stability.
Demonstrated ACE2 blocking via competition ELISA.
Yeast-display RBD binding breadth measured across multiple sarbecovirus RBDs and multiple circulating SARS-CoV-2 RBD variants.
Fc-mediated effector functions assessed by binding and functional assays, with reported no ADE in phagocyte uptake assays.
Prophylactic and therapeutic mouse efficacy, with extension to hamster and non-human primate models, showing reductions in viral replication and disease burden.
Specifically binds to the spike protein of a coronavirus (CoV-S).
Includes antibodies that neutralize SARS-CoV and/or SARS-CoV-2.
Defines neutralization potency by an IC50 threshold of about 100 nM or lower.
Defines binding affinity by a KD threshold of about 100 nM or lower for SARS-CoV-S.
Allows restriction of the antigen-binding portion to Fab, Fab2, or scFv.
Documented Applications
Prophylactic and therapeutic efficacy in mouse models (MA15/MA10), with reported reductions in viral replication and disease burden.
Evaluation in hamster model, reported as reductions in viral replication and disease burden.
Evaluation in non-human primate model (rhesus macaques), reported as reductions in viral replication and disease burden.
Therapeutic use.
Diagnostic use.
Prophylactic use.
Receptor blocking of ACE2 and related receptors mentioned in the document, including CD209L (L-SIGN), DPP4 (CD26), and TMPRSS2.
Antibody-drug conjugates (ADCs) and CAR constructs.
Interested in licensing this patent?