WO2021237051A1 - Anticorps anti-sars-cov-2 et méthodes associées - Google Patents

Anticorps anti-sars-cov-2 et méthodes associées Download PDF

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WO2021237051A1
WO2021237051A1 PCT/US2021/033594 US2021033594W WO2021237051A1 WO 2021237051 A1 WO2021237051 A1 WO 2021237051A1 US 2021033594 W US2021033594 W US 2021033594W WO 2021237051 A1 WO2021237051 A1 WO 2021237051A1
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seq
amino acid
acid sequence
antibody
cov
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PCT/US2021/033594
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English (en)
Inventor
Shusheng Wang
Xiaodong Xiao
Jianwei Zhu
Yueqing XIE
Kaiyong YANG
Lei Han
Haiqiu HUANG
Hua Jiang
Zhangyi SONG
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Jecho Laboratories, Inc.
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Publication of WO2021237051A1 publication Critical patent/WO2021237051A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983—Viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
    • C07K16/1002—Coronaviridae
    • C07K16/1003—Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2 or Covid-19]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08—RNA viruses
    • G01N2333/165—Coronaviridae, e.g. avian infectious bronchitis virus

Definitions

  • the coronavims disease 19 (COVID-19) pandemic first identified in 2019 has swept across the world and posed historic challenges to the health of the world population. In addition, the outbreak has disrupted the world economy.
  • the etiologic agent for COVID-19 is Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2). It shares homology with the SARS-CoV, which caused the SARS pandemic between 2002 and 2003. While interest is high and the need is immediate, none of the candidate therapeutics under investigation against either SARS-CoV or SARS-CoV-2 have received regulatory approval, other than under an emergency use authorization. Reports indicated that monoclonal antibodies could be especially efficacious in treating SARS-CoV infection in various animal models.
  • the present disclosure generally provides an antibody (i.e., isolated antibodies, and antigen binding fragments thereof), that can bind to the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  • an antibody, isolated antibodies, and antigen binding fragments thereof can bind to the spike protein of SARS-CoV-2, identified by the GenBank Accession No. QHR63290.2 (SEQ ID NO: 86; Table 1).
  • the present disclosure provides an antibody, isolated antibodies, and antigen binding fragments thereof that specifically bind to the spike protein including receptor binding domain (RBD) of the SARS- CoV-2 spike protein.
  • an antibody, isolated antibodies, and antigen binding fragments thereof can bind to the spike protein including receptor binding domain (RBD) of the SARS-CoV-2 spike protein that comprises SEQ ID NO: 84 (Table 1).
  • the disclosure provides an antibody, isolated antibodies, and antigen binding fragments thereof, that upon binding to the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevent, inhibit, or reduce interactions between the SARS-CoV-2 spike protein and the host transmembrane protein ACE2, which in turn provides a prevention, treatment, or neutralizing activity to the SARS-CoV-2.
  • the antibody, isolated antibody, and antigen binding fragment thereof has specific binding activity to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein.
  • the disclosure provides an antibody, isolated antibody, or antigen-binding fragment thereof that binds to the receptor binding domain of the SARS-CoV-2 spike protein.
  • the antibody, or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a Complementarity Determining Region 1 (HCDR1) having the amino acid sequence of SEQ ID NO: 3, a Complementarity Determining Region 2 (HCDR2) having the amino acid sequence of SEQ ID NO: 4, and a Complementarity Determining Region 3 (HCDR3) having the amino acid sequence of SEQ ID NO: 5; and (2) a light chain variable region having a Complementarity Determining Region 1 (LCDR1) having the amino acid sequence of SEQ ID NO: 7, a Complementarity Determining Region 2 (LCDR2) having the amino acid sequence of SEQ ID NO: 8, and a Complementarity Determining Region 3 (LCDR3) having the amino acid sequence of SEQ ID NO: 9.
  • HCDR1 Complementarity Determining Region 1
  • HCDR2 Complementarity Determining Region 2
  • HCDR3 Complementarity Determining Region 3
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 2, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 13.
  • the disclosure provides an antibody or isolated antibody, RBD-12.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a HCDR1 with the amino acid sequence of SEQ ID NO: 12, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR3 having the amino acid sequence of SEQ ID NO: 14; and (2) a light chain variable region having a LCDR1 having the amino acid sequence of SEQ ID NO: 16, a LCDR2 having the amino acid sequence of SEQ ID NO: 17, and a LCDR3 having the amino acid sequence of SEQ ID NO: 18.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 11, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 15.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 10 and a light chain comprising the amino acid sequence of SEQ ID NO: 43.
  • the disclosure provides antibody or isolated antibody RBD-18.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a HCDR1 with the amino acid sequence of SEQ ID NO: 21, a HCDR2 having the amino acid sequence of SEQ ID NO:22, and a HCDR3 having the amino acid sequence of SEQ ID NO: 23; and (2) a light chain variable region having a LCDR1 having the amino acid sequence of SEQ ID NO: 25, a LCDR2 having the amino acid sequence of SEQ ID NO: 26, and a LCDR3 having the amino acid sequence of SEQ ID NO: 27.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 20, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 24.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO: 44.
  • the disclosure provides antibody or isolated antibody RBD-20.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a HCDR1 with the amino acid sequence of SEQ ID NO: 30, a HCDR2 having the amino acid sequence of SEQ ID NO: 31, and a HCDR3 having the amino acid sequence of SEQ ID NO: 32; and (2) a light chain variable region having a LCDR1 having the amino acid sequence of SEQ ID NO: 34, a LCDR2 having the amino acid sequence of SEQ ID NO: 35, and a LCDR3 having the amino acid sequence of SEQ ID NO: 35.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 29, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 33.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 28 and a light chain comprising the amino acid sequence of SEQ ID NO: 48.
  • the disclosure provides antibody or isolated antibody RBD-21.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a HCDR1 with the amino acid sequence of SEQ ID NO: 39, a HCDR2 having the amino acid sequence of SEQ ID NO: 40, and a HCDR3 having the amino acid sequence of SEQ ID NO: 41; and (2) a light chain variable region having a LCDR1 having the amino acid sequence of SEQ ID NO: 25, a LCDR2 having the amino acid sequence of SEQ ID NO: 26, and a LCDR3 having the amino acid sequence of SEQ ID NO: 45.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 38, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 42.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 and a light chain comprising the amino acid sequence of SEQ ID NO: 49.
  • the disclosure provides antibody or isolated antibody RBD-24.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a HCDR1 with the amino acid sequence of SEQ ID NO: 3, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR3 having the amino acid sequence of SEQ ID NO: 50; and (2) a light chain variable region having a LCDR1 having the amino acid sequence of SEQ ID NO: 52, a LCDR2 having the amino acid sequence of SEQ ID NO: 8, and a LCDR3 having the amino acid sequence of SEQ ID NO: 9.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 47, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 51.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 46 and a light chain comprising the amino acid sequence of SEQ ID NO: 53.
  • the disclosure provides antibody or isolated antibody RBD-25.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a HCDR1 with the amino acid sequence of SEQ ID NO: 57, a HCDR2 having the amino acid sequence of SEQ ID NO: 58, and a HCDR3 having the amino acid sequence of SEQ ID NO: 59; and (2) a light chain variable region having a LCDR1 having the amino acid sequence of SEQ ID NO: 61, a LCDR2 having the amino acid sequence of SEQ ID NO: 62, and a LCDR3 having the amino acid sequence of SEQ ID NO: 63.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 56, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 60.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 55 and a light chain comprising the amino acid sequence of SEQ ID NO: 54.
  • the disclosure provides antibody or isolated antibody RBD-32.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a HCDR1 with the amino acid sequence of SEQ ID NO: 66, a HCDR2 having the amino acid sequence of SEQ ID NO: 67, and a HCDR3 having the amino acid sequence of SEQ ID NO: 68; and (2) a light chain variable region having a LCDR1 having the amino acid sequence of SEQ ID NO: 70, a LCDR2 having the amino acid sequence of SEQ ID NO: 71, and a LCDR3 having the amino acid sequence of SEQ ID NO: 72.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 65, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 69.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 64 and a light chain comprising the amino acid sequence of SEQ ID NO: 82.
  • the disclosure provides antibody or isolated antibody RBD-35.
  • the disclosure provides isolated antibodies, and antigen binding fragments thereof, that bind to the SD1 domain of the SARS-CoV-2 spike protein.
  • an antibody, isolated antibodies, and antigen binding fragments thereof can bind to the spike protein of the SARS-CoV-2 identified by GenBank Accession No. QHR63290.2 (SEQ ID NO: 86; Table 1).
  • the antibody or antigen-binding fragment thereof comprises: (1) a heavy chain variable region having a HCDR1 with the amino acid sequence of SEQ ID NO: 75, a HCDR2 having the amino acid sequence of SEQ ID NO: 76, and a HCDR3 having the amino acid sequence of SEQ ID NO: 77; and (2) a light chain variable region having a LCDR1 having the amino acid sequence of SEQ ID NO: 79, a LCDR2 having the amino acid sequence of SEQ ID NO: 80, and a LCDR3 having the amino acid sequence of SEQ ID NO: 81.
  • the antibody, isolated antibody, or antigen-binding fragment thereof comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 74, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 78.
  • the antibody or isolated antibody comprises a heavy chain comprising the amino acid sequence of the amino acid sequence of SEQ ID NO: 73 and a light chain comprising the amino acid sequence of SEQ ID NO: 83.
  • the disclosure provides scFv-Fc S 1-1.
  • the antibodies can be SARS-CoV-2 neutralizing agents and/or act to reduce, inhibit, or prevent SARS-CoV-2 binding activity with ACE2.
  • the disclosure provides methods for detecting, preventing, and/or treating SARS-CoV-2 viral infection in a subject, wherein the methods comprise administering or contacting an antibody, isolated antibody, or an antigen-binding fragment thereof, or any combination of two or more of the antibodies, isolated antibodies, or antigen-binding fragments thereof.
  • FIGS. 1A - IF illustrate the results of an ELISA for the binding of SARS-CoV-2
  • FIGS. 2A - 2F illustrate the results of an ELISA for cross -reactivity of SARS-
  • FIGS . 3 A - 3D illustrate the results of an ELISA for ACE2/S ARS-CoV-2 RBD binding inhibition by SARS-CoV-2 RBD scFv-Fc constructs.
  • FIGS. 4A - 4C illustrate the results of an ELISA for the binding of SARS-CoV-2
  • MERS Middle East respiratory syndrome
  • FIGS. 5A - 5D illustrate the results of a pharmacokinetic assay of SARS-CoV-2
  • RBD IgG monoclonal antibodies RBD-18, RBD-20, RBD-32, and RBD-35.
  • FIGS. 6A - 6D illustrate the results of an assay for RBD epitope binding of
  • SARS-CoV-2 RBD IgG monoclonal antibodies RBD-18, RBD-32, and RBD-35 and SARS- CoV-2 S 1 IgG (S1-C6).
  • FIGS . 7 A and 7B illustrate the results of an ELISA for ACE2/S ARS-CoV-2 RBD binding inhibition by SARS-CoV-2 RBD IgG monoclonal antibodies, RBD-12, RBD-18, RBD- 20, RBD-21, RBD-24, RBD-25, RBD-32, and RBD-35.
  • FIG. 8 illustrates the results of a pseudovims assay for ACE2/SARS-CoV-2 RBD binding inhibition by SARS-CoV-2 RBD IgG monoclonal antibodies RBD-32, RBD-35, and a combination of RBD-32 and RBD-35.
  • Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.
  • antibody or its plural, “antibodies”, also known as immunoglobulins, encompass full-length antibody sequences including, for example, monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, multispecific antibodies formed from at least two different epitope binding fragments, bispecific antibodies, human antibodies, and humanized antibodies.
  • Antibody “fragments” or “antigen binding fragments”, “binding fragments”, “epitope binding fragments”, and the like) as described herein typically refer to any antibody sequence that is less than the full-length antibody sequence, and still exhibits specific binding activity to the target antigen.
  • antibody fragments typically comprise at least a combination of three CDR sequences of a heavy chain variable domain (HCDR1, HCDR2, HCDR3) and at least three CDR sequences of a light chain variable domain (LCDR1, LCDR2, LCDR3).
  • Some non-limiting examples of antibody fragments include camelised antibodies, single-chain Fvs (scFv), single chain Fv-Fc (scFv-Fc), single-chain antibodies, single domain antibodies, domain antibodies,
  • the disclosure provides antibodies that include immunoglobulin molecules and immunologically active fragments of immunoglobulin molecules, i.e., molecules that contain at least one antigen-binding site.
  • Antibodies and fragments thereof may also include peptide fusions with antibodies or portions thereof such as a protein fused to an Fc domain.
  • Immunoglobulin molecules can be of any isotype (e.g., IgG, IgE, IgM, IgD, IgA and IgY), subisotype (e.g., IgGl, IgG2, IgG3, IgG4, IgAl and IgA2) or allotype (e.g., Gm, e.g., Glm(f, z, a or x), G2m(n), G3m(g, b, or c), Am, Em, and Km(l, 2 or 3)).
  • Antibodies and fragments thereof may be derived from any mammal, including, but not limited to, humans, monkeys, pigs, horses, rabbits, dogs, cats, mice, etc., or other animals such as birds (e.g. chickens).
  • the novel binding proteins are monoclonal antibodies (mAbs) or single chain Fv-Fc (scFv-Fc) antibodies.
  • mAbs monoclonal antibodies
  • scFv-Fc single chain Fv-Fc
  • a typical or conventional mAb comprises two heavy chain subunits and two light chain subunits.
  • Each mAb heavy chain contains one variable domain (VH) which contributes to antigen binding and a constant domain (CH) made up of three or four subregions (C H I, C H 2,
  • the VH comprises three complementarity-determining regions (CDRs), HCDR1, HCDR2, and HCDR3.
  • Each mAb light chain contains one variable domain (VL) and one constant domain (CL).
  • the VL comprises three CDRs, LCDR1, LCDR2, and LCDR3.
  • Disulfide bonds join each CHI domain to one CL domain, and join CH2 domains to one another.
  • Five types of heavy chains (a, d, e, g, and m) are found in different classes of antibodies (IgA, IgD, IgE, IgG, and IgM).
  • mAb heavy chains have hinge regions that confer structural flexibility and mobility.
  • the “Fc” region encompasses domains from the constant region of the heavy chain of an immunoglobulin, including a fragment, analog, variant, mutant, or derivative thereof. Suitable immunoglobulins include IgGl, IgG2, IgG3, IgG4, and other classes such as IgA, IgD, IgE and IgM.
  • the Fc region may be a native sequence Fc region or an altered Fc region.
  • the Fc region of an immunoglobulin generally comprises two constant domains, a CH2 domain and a CH3 domain.
  • the “Fv” region encompasses the VH and VL domains of an immunoglobulin.
  • scFv-Fc antibodies refer to a fusion protein of a single VH and a single VL domain, connected with a hinge region, and the CH2 domain and the CH3 domain of a single CH domain.
  • the antibodies and fragments thereof disclosed herein comprise binding domains that bind to the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2).
  • SARS- CoV-2 severe acute respiratory syndrome coronavirus 2
  • an antibody, isolated antibodies, and antigen binding fragments thereof can bind to the spike protein of SARS-CoV-2, identified by the GenBank Accession No. QHR63290.2 (SEQ ID NO: 86; Table 1).
  • Binding domain or “binding sequence” may be interchangeably used with an antibody fragment or “antigen binding fragment”, and as used herein refers to the portion of the antibody sequence that binds to or interacts with a target structure, antigen, or epitope.
  • the antibodies bind to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein.
  • RBD receptor binding domain
  • an antibody, isolated antibodies, and antigen binding fragments thereof bind to the RBD of the SARS-CoV-2 spike protein that comprises SEQ ID NO: 84 (Table 1).
  • the antibodies bind to the SD1 domain of the SARS-CoV-2 spike protein.
  • an antibody, isolated antibodies, and antigen binding fragments thereof bind to the SD1 domain of the SARS-CoV-2 spike protein having SEQ ID NO: 85 (Table 1), which, relative to the RBD, is toward the C-terminus of the spike protein.
  • the RBD of SARS-CoV-2 binds Angiotensin-Converting Enzyme 2 (ACE2) for host cellular entry.
  • ACE2 Angiotensin-Converting Enzyme 2
  • the antibodies or fragments thereof can prevent, inhibit, or reduce binding interactions between the SARS-CoV-2 spike protein and ACE2 on the host cell, and may provide neutralizing activity against SARS-CoV-2.
  • the antibodies disclosed herein can be characterized by one or more of the following structural and/or functional properties: a. an amino acid sequence comprising a VH domain and a VL domain, wherein the VH domain comprises an HCDR1 having SEQ ID NOs: 3, 12, 21, 30, 39, 57, or 66, an HCDR2 having SEQ ID NOs: 4, 22, 31, 40, 58, or 67, and an HCDR3 having SEQ ID NOs: 5, 14, 23, 32, 41, 50, 59, or 68; and wherein the VL domain comprises a LCDR1 having SEQ ID NOs: 7, 16, 25, 34, 52, 61, or 70, a LCDR2 having SEQ ID NOs: 8, 17, 26, 35, 62, or 71, and an LCDR3 having SEQ ID NOs: 9, 18, 27, 36, 45, 63, or 72; b.
  • the VH domain comprises an HCDR1 having SEQ ID NOs: 3, 12, 21, 30, 39, 57, or 66, an HCDR2 having SEQ
  • an amino acid sequence comprising a VH domain having the amino acid sequence of SEQ ID NOs: 2, 11, 20, 29, 38, 47, 56, or 65 and/or a VL domain having the amino acid sequence of SEQ ID NOs: 6, 15, 24, 33, 42, 51, 60, or 69; c.
  • binding specificity for SARS-CoV-2 spike protein e. with regard to SARS-CoV-2 spike protein, a dissociation constant (K d ) in the range of 1 - 500 nM, 1 - 450 nM, 1 - 400 nM, 1 - 300 nM, 1 - 200 nM, 1 - 100 nM, 1 - 50 nM, 1 - 25 nM, or 1 - 10 nM; f.
  • an antibody or antigen-binding fragment thereof capable of inhibiting, reducing, preventing, or disrupting the interaction of SARS-CoV-2 and ACE2, and/or capable of neutralizing the activity of the SARS-CoV-2, binds to an epitope present in the SARS-CoV-2 spike protein.
  • the epitope bound by the antibody or fragment thereof may be in the RBD.
  • the antibody or fragment thereof binds to an epitope on the SARS-CoV-2 spike protein that is not present in the RBD.
  • an antibody that binds SARS-CoV-2 RBD, or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD comprises a VH domain having the amino acid sequence of SEQ ID NOs: 2, 11, 20, 29, 38, 47, 56, or 65.
  • an antibody that binds SARS-CoV-2 RBD, or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD comprises a VL domain having the amino acid sequence of SEQ ID NOs: 6, 15, 24, 33, 42, 51, 60, or 69.
  • an antibody that binds SARS-CoV-2 that binds SARS-CoV-2
  • VH domain and VL domain combination selected from the following: i. a VH domain having the amino acid sequence of SEQ ID NO: 2 and a VL domain having the amino acid sequence of SEQ ID NO: 6; ii. a VH domain having the amino acid sequence of SEQ ID NO: 11 and a VL domain having the amino acid sequence of SEQ ID NO: 15; iii. a VH domain having the amino acid sequence of SEQ ID NO: 20 and a VL domain having the amino acid sequence of SEQ ID NO: 24; iv.
  • an antibody that binds SARS-CoV-2 RBD, or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD comprises a VH domain with a complementarity-determining region 1 (HCDR1) having SEQ ID NOs: 3, 12, 21, 30, 39, 57, or 66.
  • HCDR1 complementarity-determining region 1
  • an antibody that binds SARS-CoV-2 RBD, or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD comprises a VH domain with a complementarity-determining region 2 (HCDR2) having SEQ ID NOs: 4, 22, 31, 40, 58, or 67.
  • an antibody that binds SARS-CoV-2 RBD, or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD comprises a VH domain with a complementarity-determining region 3 (HCDR3) having SEQ ID NOs: 5, 14, 23, 32, 41, 50, 59, or 68.
  • HCDR3 complementarity-determining region 3
  • an antibody that binds SARS-CoV-2 RBD, or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD comprises a VL domain with a complementarity-determining region 1 (LCDR1) having SEQ ID NOs: 7, 16, 25, 34, 52, 61, or 70.
  • an antibody that binds SARS-CoV-2 RBD, or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD comprises a VL domain with a complementarity-determining region 2 (LCDR2) having SEQ ID NOs: 8, 17, 26, 35, 62, or 71.
  • LCDR2 complementarity-determining region 2
  • an antibody that binds SARS-CoV-2 RBD, or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD comprises a VL domain with a complementarity-determining region 3 (LCDR3) having SEQ ID NOs: 9, 18, 27, 36, 45, 63, or 72.
  • LCDR3 complementarity-determining region 3
  • an antibody that binds SARS-CoV-2 that binds SARS-CoV-2
  • RBD or an antigen-binding fragment thereof that binds SARS-CoV-2 RBD, comprises a VH domain and VL domain having the following combinations of CDRs: i. a VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 3, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR3 having the amino acid sequence of SEQ ID NO: 5; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 7, a LCDR2 having the amino acid sequence of SEQ ID NO: 8, and a LCDR3 having the amino acid sequence of SEQ ID NO: 9; ii.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 12, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR3 having the amino acid sequence of SEQ ID NO: 14; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 16, a LCDR2 having the amino acid sequence of SEQ ID NO: 17, and a LCDR3 having the amino acid sequence of SEQ ID NO: 18; iii.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 21, a HCDR2 having the amino acid sequence of SEQ ID NO: 22, and a HCDR3 having the amino acid sequence of SEQ ID NO: 23; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 25, a LCDR2 having the amino acid sequence of SEQ ID NO: 26, and a LCDR3 having the amino acid sequence of SEQ ID NO: 27; iv.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 30, a HCDR2 having the amino acid sequence of SEQ ID NO: 31, and a HCDR3 having the amino acid sequence of SEQ ID NO: 32 ; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 34, a LCDR2 having the amino acid sequence of SEQ ID NO: 35, and a LCDR3 having the amino acid sequence of SEQ ID NO: 36; v.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 39, a HCDR2 having the amino acid sequence of SEQ ID NO: 40, and a HCDR3 having the amino acid sequence of SEQ ID NO: 41; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 25, a LCDR2 having the amino acid sequence of SEQ ID NO: 26, and a LCDR3 having the amino acid sequence of SEQ ID NO: 45; vi.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 3, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR3 having the amino acid sequence of SEQ ID NO: 50; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 52, a LCDR2 having the amino acid sequence of SEQ ID NO: 8, and a LCDR3 having the amino acid sequence of SEQ ID NO: 9; vii.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 57, a HCDR2 having the amino acid sequence of SEQ ID NO: 58, and a HCDR3 having the amino acid sequence of SEQ ID NO: 59; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 61, a LCDR2 having the amino acid sequence of SEQ ID NO: 62, and a LCDR3 having the amino acid sequence of SEQ ID NO: 63; or viii.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 66, a HCDR2 having the amino acid sequence of SEQ ID NO: 67, and a HCDR3 having the amino acid sequence of SEQ ID NO: 68; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 70, a LCDR2 having the amino acid sequence of SEQ ID NO: 71, and a LCDR3 having the amino acid sequence of SEQ ID NO: 72.
  • an antibody that binds SARS-CoV-2 RBD comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 13.
  • an antibody that binds SARS-CoV-2 RBD comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 10 and a light chain comprising the amino acid sequence of SEQ ID NO: 43.
  • an antibody that binds SARS-CoV-2 RBD comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO: 44.
  • an antibody that binds SARS-CoV-2 RBD comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 28 and a light chain comprising the amino acid sequence of SEQ ID NO: 48.
  • an antibody that binds SARS-CoV-2 RBD comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 and a light chain comprising the amino acid sequence of SEQ ID NO: 49.
  • an antibody that binds SARS-CoV-2 RBD comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 46 and a light chain comprising the amino acid sequence of SEQ ID NO: 53.
  • an antibody that binds SARS-CoV-2 RBD comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 55 and a light chain comprising the amino acid sequence of SEQ ID NO: 54.
  • an antibody that binds SARS-CoV-2 RBD comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 64 and a light chain comprising the amino acid sequence of SEQ ID NO: 82.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • an antibody, or an antigen-binding fragment thereof comprises a
  • an antibody, or an antigen-binding fragment thereof comprises a VH domain and VL domain combination selected from the following: i. a VH domain having the amino acid sequence of SEQ ID NO: 2 and a VL domain having the amino acid sequence of SEQ ID NO: 6; ii. a VH domain having the amino acid sequence of SEQ ID NO: 11 and a VL domain having the amino acid sequence of SEQ ID NO: 15; iii.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VH domain with a complementarity-determining region 1 having SEQ ID NOs: 3, 12, 21, 30, 39, 57, or 66.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VH domain with a complementarity-determining region 2 having SEQ ID NOs: 4, 22, 31, 40, 58, or 67.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VH domain with a complementarity-determining region 3 having SEQ ID NOs: 5, 14, 23, 32, 41, 50, 59, or 68.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VL domain with a complementarity-determining region 1 having SEQ ID NOs: 7, 16, 25, 34, 52, 61, or 70.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VL domain with a complementarity-determining region 3 having SEQ ID NOs: 9, 18, 27, 36, 45, 63, or 72.
  • an antibody, or an antigen-binding fragment thereof comprises a VH domain and VL domain having the following combinations of CDRs: i. a VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 3, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR3 having the amino acid sequence of SEQ ID NO: 5; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 7, a LCDR2 having the amino acid sequence of SEQ ID NO: 8, and a LCDR3 having the amino acid sequence of SEQ ID NO: 9; ii.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 12, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR3 having the amino acid sequence of SEQ ID NO: 14; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 16, a LCDR2 having the amino acid sequence of SEQ ID NO: 17, and a LCDR3 having the amino acid sequence of SEQ ID NO: 18; iii.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 21, a HCDR2 having the amino acid sequence of SEQ ID NO: 22, and a HCDR3 having the amino acid sequence of SEQ ID NO: 23; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 25, a LCDR2 having the amino acid sequence of SEQ ID NO: 26, and a LCDR3 having the amino acid sequence of SEQ ID NO: 27; iv.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 30, a HCDR2 having the amino acid sequence of SEQ ID NO: 31, and a HCDR3 having the amino acid sequence of SEQ ID NO: 32 ; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 34, a LCDR2 having the amino acid sequence of SEQ ID NO: 35, and a LCDR3 having the amino acid sequence of SEQ ID NO: 36; v.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 39, a HCDR2 having the amino acid sequence of SEQ ID NO: 40, and a HCDR3 having the amino acid sequence of SEQ ID NO: 41; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 25, a LCDR2 having the amino acid sequence of SEQ ID NO: 26, and a LCDR3 having the amino acid sequence of SEQ ID NO: 45; vi.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 3, a HCDR2 having the amino acid sequence of SEQ ID NO: 4, and a HCDR3 having the amino acid sequence of SEQ ID NO: 50; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 52, a LCDR2 having the amino acid sequence of SEQ ID NO: 8, and a LCDR3 having the amino acid sequence of SEQ ID NO: 9; vii.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 57, a HCDR2 having the amino acid sequence of SEQ ID NO: 58, and a HCDR3 having the amino acid sequence of SEQ ID NO: 59; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 61, a LCDR2 having the amino acid sequence of SEQ ID NO: 62, and a LCDR3 having the amino acid sequence of SEQ ID NO: 63; or viii.
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 66, a HCDR2 having the amino acid sequence of SEQ ID NO: 67, and a HCDR3 having the amino acid sequence of SEQ ID NO: 68; and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 70, a LCDR2 having the amino acid sequence of SEQ ID NO: 71, and a LCDR3 having the amino acid sequence of SEQ ID NO: 72.
  • an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 13.
  • an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 10 and a light chain comprising the amino acid sequence of SEQ ID NO: 43. [0065] In some aspects, an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 19 and a light chain comprising the amino acid sequence of SEQ ID NO: 44.
  • an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 28 and a light chain comprising the amino acid sequence of SEQ ID NO: 48.
  • an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 and a light chain comprising the amino acid sequence of SEQ ID NO: 49.
  • an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 46 and a light chain comprising the amino acid sequence of SEQ ID NO: 53.
  • an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 55 and a light chain comprising the amino acid sequence of SEQ ID NO: 54.
  • an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 64 and a light chain comprising the amino acid sequence of SEQ ID NO: 82.
  • an antibody that binds SARS-CoV-2 SD1 which may be referred to herein as an “SD1 antibody” or an “S 1-1 antibody”, or an antigen-binding fragment thereof that binds SARS-CoV-2 SD1, comprises a VH domain having the amino acid sequence of SEQ ID NO: 74.
  • an antibody that binds SARS-CoV-2 SD1, or an antigen-binding fragment thereof that binds SARS-CoV-2 SD1, comprises a VL domain having the amino acid sequence of SEQ ID NO: 78.
  • an antibody that binds SARS-CoV-2 SD1, or an antigen binding fragment thereof that binds SARS-CoV-2 SD1 comprises a VH domain having the amino acid sequence of SEQ ID NO: 74 and a VL domain having the amino acid sequence of SEQ ID NO: 78.
  • an antibody that binds SARS-CoV-2 SD1, or an antigen-binding fragment thereof that binds SARS-CoV-2 SD1 comprises a VH domain with a HCDR1 having SEQ ID NO: 75.
  • an antibody that binds SARS-CoV-2 SD1, or an antigen-binding fragment thereof that binds SARS-CoV-2 SD1, comprises a VH domain with a HCDR2 having SEQ ID NO: 76.
  • an antibody that binds SARS-CoV-2 SD1, or an antigen-binding fragment thereof that binds SARS-CoV-2 SD1, comprises a VH domain with a HCDR3 having SEQ ID NO: 77.
  • an antibody that binds SARS-CoV-2 SD1, or an antigen-binding fragment thereof that binds SARS-CoV-2 SD1, comprises a VL domain with a LCDR1 having SEQ ID NO: 79.
  • an antibody that binds SARS-CoV-2 SD1, or an antigen-binding fragment thereof that binds SARS-CoV-2 SD1, comprises a VL domain with a LCDR2 having SEQ ID NO: 80.
  • an antibody that binds SARS-CoV-2 SD1, or an antigen-binding fragment thereof that binds SARS-CoV-2 SD1, comprises a VL domain with a LCDR3 having SEQ ID NO: 81.
  • an antibody that binds SARS-CoV-2 that binds SARS-CoV-2
  • VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 75, a HCDR2 having the amino acid sequence of SEQ ID NO: 76, and a HCDR3 having the amino acid sequence of SEQ ID NO: 77, and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 79, a LCDR2 having the amino acid sequence of SEQ ID NO: 80, and a LCDR3 having the amino acid sequence of SEQ ID NO: 81.
  • an antibody that binds SARS-CoV-2 SD1 comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 73 and a light chain comprising the amino acid sequence of SEQ ID NO: 83.
  • an antibody that binds SARS-CoV-2 SD1 has a K d in the range of 1 - 500 nM, 1 - 450 nM, 1 - 400 nM, 1 - 300 nM, 1 - 200 nM, 1 - 100 nM, 1 - 50 nM, 1 - 25 nM, or 1 - 10 nM.
  • a SARS-CoV-2 SD1 antibody has a K d of 39.8 nM.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VH domain having the amino acid sequence of SEQ ID NO: 74.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VL domain having the amino acid sequence of SEQ ID NO: 78.
  • an antibody, or an antigen-binding fragment thereof comprises a VH domain having the amino acid sequence of SEQ ID NO: 74 and a VL domain having the amino acid sequence of SEQ ID NO: 78.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VH domain with a HCDR1 having SEQ ID NO: 75 VH domain with a HCDR1 having SEQ ID NO: 75.
  • an antibody, or an antigen-binding fragment thereof comprises a VH domain with a HCDR2 having SEQ ID NO: 76.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VH domain with a HCDR3 having SEQ ID NO: 77 VH domain with a HCDR3 having SEQ ID NO: 77.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • an antibody, or an antigen-binding fragment thereof comprises a VL domain with a LCDR2 having SEQ ID NO: 80.
  • an antibody, or an antigen-binding fragment thereof comprises a
  • VL domain with a LCDR3 having SEQ ID NO: 81 VL domain with a LCDR3 having SEQ ID NO: 81.
  • an antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 73 and a light chain comprising the amino acid sequence of SEQ ID NO: 83.
  • an antibody, or an antigen-binding fragment thereof comprises a VH domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 75, a HCDR2 having the amino acid sequence of SEQ ID NO: 76, and a HCDR3 having the amino acid sequence of SEQ ID NO: 77, and a VL domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 79, a LCDR2 having the amino acid sequence of SEQ ID NO: 80, and a LCDR3 having the amino acid sequence of SEQ ID NO: 81.
  • the antibodies disclosed herein exhibit binding specificity for the SARS-CoV-2 spike protein, can inhibit, reduce, prevent, or disrupt SARS- CoV-2 - ACE2 interactions, and can be characterized by one or more of the following structural and/or functional properties: a.
  • VH domain comprises an HCDR1 having SEQ ID NO: 66, an HCDR2 having SEQ ID NO: 67, and an HCDR3 having SEQ ID NO: 68; and wherein the VL domain comprises a LCDR1 having SEQ ID NO: 70, a LCDR2 having SEQ ID NO: 71, and an LCDR3 having SEQ ID NO: 72; b. an amino acid sequence comprising a VH domain having the amino acid sequence of SEQ ID NO: 65 and/or a VL domain having the amino acid sequence of SEQ ID NO: 69; and c.
  • sequences disclosed herein can be modified to some degree without compromising the ability of the antibody or fragment thereof to interact with the target protein, i.e., SARS-CoV-2 spike protein.
  • antibody sequence variants retain the ability to interact with SARS-CoV-2 RBD such that the binding interaction between SARS-CoV-2 and ACE2 is disrupted, prevented, reduced, or inhibited.
  • sequence “variants” refer to an antibody amino acid sequence comprising at least one amino acid insertion, deletion, and/or substitution, wherein the resulting antibody maintains one or more of its functional characteristics as described herein.
  • a sequence variant maintains the ability to specifically bind the SARS-CoV-2 spike protein.
  • An amino acid insertion variant is characterized by the insertion of one or more amino acids between two existing amino acids.
  • An amino acid deletion variant is characterized by the deletion of one or more amino acids from the antibody sequence.
  • An amino acid substitution is characterized by at least one amino acid in the sequence being replaced by another amino acid.
  • the amino acid substitution(s) may be a conservative substitution, (i.e. an amino acid from one family of amino acids (acidic, basic, non polar, and uncharged, based on side chain characteristics, including size) is substituted with an amino acid from the same family).
  • sequence identity between the variant antibody sequence and the antibody sequences disclosed herein will be at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%.
  • sequence identity refers to the percentage of amino acid residues that are identical to the sequences being compared.
  • the antibodies or fragments thereof disclosed herein can be conjugated to a therapeutic agent, solid support, affinity agent, or a detectable agent.
  • Antibodies, and fragments, of the disclosure may be conjugated to labels for the purposes of diagnostics and other assays wherein the antibody and/or its associated targets(s) may be detected.
  • Labels include, without limitation, a chromophore, a fluorophore, a fluorescent protein, a phosphorescent dye, a tandem dye, a particle, a hapten, an enzyme and a radioisotope.
  • the antibodies are conjugated to a fluorophore.
  • the choice of the fluorophore attached to the antibody will determine the absorption and fluorescence emission properties of the conjugated antibody.
  • Physical properties of a fluorophore label that can be used for an antibody and antibody-bound ligands include, but are not limited to, spectral characteristics (absorption, emission and stokes shift), fluorescence intensity, lifetime, polarization and photo-bleaching rate, or combination thereof. All of these physical properties can be used to distinguish one fluorophore from another, and thereby allow for multiplexed analysis.
  • Other desirable properties of the fluorescent label may include cell permeability and low toxicity, for example if labeling of the antibody is to be performed in a cell or an organism (e.g., a living animal).
  • the conjugated label may comprise an enzyme.
  • Enzymes are desirable labels in some embodiments because amplification of the detectable signal can be obtained and result in increased assay sensitivity.
  • the enzyme itself does not produce a detectable response but functions to break down a substrate when it is contacted by an appropriate substrate such that the converted substrate produces a fluorescent, colorimetric or luminescent signal.
  • Enzymes may amplify the detectable signal because one enzyme on a labeling reagent can result in multiple substrates being converted to a detectable signal.
  • the enzyme substrate is selected to yield the preferred measurable product, e.g. colorimetric, fluorescent or chemiluminescence.
  • Such substrates are extensively used in the art and are well known by one skilled in the art and include for example, oxidoreductases such as horseradish peroxidase and a substrate such as 3,3’-diaminobenzidine (DAB); phosphatase enzymes such as an acid phosphatase, alkaline and a substrate such as 5-bromo-6-chloro-3-indolyl phosphate (BCIP); glycosidases, such as beta-galactosidase, beta-glucuronidase or beta-glucosidase and a substrate such as 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside (X-gal); additional enzymes include hydrolases such as cholinesterases and peptidases, oxidases such as glucose oxidase and cytochrome oxidases, and reductases for which suitable substrates are known.
  • DAB 3,3’-diaminobenz
  • Enzymes and their appropriate substrates that produce chemiluminescence are suitable for some assays. These include, but are not limited to, natural and recombinant forms of luciferases and aequorins. Chemiluminescence-producing substrates for phosphatases, glycosidases and oxidases such as those containing stable dioxetanes, luminol, isoluminol and acridinium esters are additionally useful.
  • haptens such as biotin
  • Biotin is useful because it can function in an enzyme system to further amplify the detectable signal, and it can function as a tag to be used in affinity chromatography for isolation purposes.
  • an enzyme conjugate that has affinity for biotin is used, such as avidin-HRP. Subsequently a peroxidase substrate is added to produce a detectable signal.
  • Haptens also include hormones, naturally occurring and synthetic drugs, pollutants, allergens, affector molecules, growth factors, chemokines, cytokines, lymphokines, amino acids, peptides, chemical intermediates, nucleotides and the like.
  • fluorescent proteins may be conjugated to the antibody as a label.
  • fluorescent proteins include green fluorescent protein (GFP) and the phycobiliproteins and the derivatives thereof.
  • the fluorescent proteins, especially phycobiliprotein, are particularly useful for creating tandem dye labeled labeling reagents. These tandem dyes comprise a fluorescent protein and a fluorophore for the purposes of obtaining a larger stokes shift wherein the emission spectra is farther shifted from the wavelength of the fluorescent protein’s absorption spectra.
  • the label is a radioactive isotope.
  • suitable radioactive materials include, but are not limited to, iodine ( 121 I, 123 I, 125 I, 131 I), carbon ( 14 C), sulfur ( 35 S), tritium ( 3 H), indium ( m In, 112 In, 113 mln, 115 mln,), technetium ( 99 Tc, 99 mTc), thallium ( 201 Ti), gallium ( 68 Ga, 67 Ga), palladium ( 103 Pd), molybdenum ( 99 Mo), xenon ( 135 Xe), fluorine ( 18 F), 153 SM, 177 LU, 159 Gd, 149 Pm, 140 La, 175 Yb, 166 Ho, 90 Y, 47 Sc, 186 Re, 188 Re, 142 Pr, 105 Rh and 97
  • drugs may be conjugated to the antibody.
  • an antibody may be conjugated to a therapeutic moiety or agent, such as a cytotoxic or antiviral drug.
  • the antibody may bind to a target antigen, and the antiviral drug is acts to inhibit, inactivate, or kill the virus. Any antiviral drug known in the art may be conjugated to an antibody.
  • drugs and other molecules may be conjugated to an antibody via site-specific conjugation.
  • the disclosure provides methods for producing antibodies and antibody fragments. In certain aspects, the disclosure provides for recombinant methods of generating the antibodies and/or fragments thereof.
  • recombinant nucleic acids encoding for the antibody or fragment thereof may be operably linked to one or more regulatory nucleotide sequences in an expression construct.
  • the nucleic acid sequences encoding the antibody light and heavy chains can be cloned in the same expression vector in any orientation (e.g., light chain in front of the heavy chain or vice versa) or can be cloned in two different vectors.
  • the two coding genes can have their own genetic elements (e.g., promoter, RBS, leader, stop, polyA, etc.) or they can be cloned with one single set of genetic elements, but connected with a cistron element.
  • Regulatory nucleotide sequences may be appropriate for a host cell used for expression. Numerous types of appropriate expression vectors and suitable regulatory sequences are known in the art for a variety of host cells.
  • one or more regulatory nucleotide sequences may include, but are not limited to, promoter sequences, leader or signal sequences, ribosomal binding sites, transcriptional start and termination sequences, translational start and termination sequences, and enhancer or activator sequences.
  • any known constitutive or inducible promoters are contemplated for use with the aspects and embodiments included in the disclosure.
  • the promoters may be either naturally occurring promoters, or hybrid promoters that combine elements of more than one promoter.
  • An expression construct may be present in a cell on an episome, such as a plasmid, or the expression construct may be inserted in a chromosome.
  • an expression vector contains a selectable marker gene to allow the selection of transformed host cells. Selectable marker genes are known and may vary with the host cell used.
  • the disclosure relates to an expression vector comprising a nucleotide sequence encoding a polypeptide that is operably linked to at least one regulatory sequence.
  • regulatory sequence includes promoters, enhancers, and other expression control elements. Exemplary, non-limiting regulatory sequences are described in Goeddel; Gene Expression Technology: Methods in Enzymology, Academic Press, San Diego, CA (1990). It should be understood that the design of the expression vector may depend on such factors as the choice of the host cell to be transformed and/or the type of protein (e.g., antibody or fragment thereof) to be expressed. Moreover, the vector's copy number, the ability to control that copy number and the expression of any other protein encoded by the vector, such as antibiotic markers, may be considered.
  • a host cell may be transfected with one or more expression vector(s) encoding an antibody or fragment thereof (e.g., a single vector encoding the heavy and the light chain or two vectors, one encoding the heavy chain and one encoding the light chain) and can be cultured under appropriate conditions to allow expression of the polypeptide to occur.
  • the antibody or fragment thereof may be secreted and isolated from cells and/or cell culture media containing the antibody or fragment thereof.
  • the antibody may be retained in the cytoplasm or in a membrane fraction and the harvested cells, which may be lysed subsequently purified and isolated.
  • a cell culture includes host cells, media and other byproducts.
  • Antibodies and antibody fragments can be isolated from cell culture medium, host cells, or both using common techniques for purifying proteins, and antibodies in particular, including, for example, ion-exchange chromatography, gel filtration chromatography, ultrafiltration, electrophoresis, and immunoaffinity purification.
  • the antibody may be produced as a fusion protein containing a domain (e.g., a His-tag) which may facilitate its purification.
  • a recombinant nucleic acid can be produced by ligating the cloned gene, or a portion thereof, into a vector suitable for expression in either prokaryotic cells, eukaryotic cells (yeast, avian, insect or mammalian), or both.
  • Expression vehicles for production of a recombinant polypeptide include plasmids and other vectors.
  • suitable vectors include plasmids of the types: pBR322-derived plasmids, pEMBL-derived plasmids, pEX- derived plasmids, pBTac-derived plasmids and pUC-derived plasmids for expression in prokaryotic cells, such as E. coli.
  • mammalian expression vectors contain both prokaryotic sequences to facilitate the propagation of the vector in bacteria, and one or more eukaryotic transcription units that are expressed in eukaryotic cells.
  • the pcDNAI/amp, pcDNAEneo, pRc/CMV, pSV2gpt, pSV2neo, pSV2-dhfr, pTk2, pRSVneo, pMSG, pSVT7, pko- neo and pHyg derived vectors are examples of mammalian expression vectors suitable for transfection of eukaryotic cells.
  • vectors are modified with sequences from bacterial plasmids, such as pBR322, to facilitate replication and drug resistance selection in both prokaryotic and eukaryotic cells.
  • derivatives of viruses such as the bovine papilloma virus (BPV-1), or Epstein-Barr virus (pHEBo, pREP-derived and p205) can be used for transient expression of proteins in eukaryotic cells.
  • BBV-1 bovine papilloma virus
  • pHEBo Epstein-Barr virus
  • the various methods employed in the preparation of the plasmids and transformation of host organisms are well known in the art.
  • suitable expression systems for both prokaryotic and eukaryotic cells, as well as general recombinant procedures see Molecular Cloning A Laboratory Manual , 2nd Ed., ed.
  • baculovirus expression systems include pVL- derived vectors (such as pVL1392, pVL1393 and pVL941), pAcUW-derived vectors (such as pAcUWl), and pBlueBac-derived vectors (such as the B-gal containing pBlueBac III).
  • fusion genes Techniques for making fusion genes are well known. Essentially, the joining of various nucleic acid fragments coding for different polypeptide sequences is performed in accordance with conventional techniques, employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation.
  • the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers.
  • PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive nucleic acid fragments which can subsequently be annealed to generate a chimeric gene sequence (see, for example, Current Protocols in Molecular Biology, eds. Ausubel et al., John Wiley & Sons: 1992).
  • an expression vector expressing any of the nucleic acids described above may be used to express an antibody in a host cell.
  • an antibody may be expressed in bacterial cells such as E. coll, insect cells (e.g., using a baculovirus expression system), yeast, or mammalian cells. Other suitable host cells are known to those skilled in the art.
  • the expression vector is transferred to a host cell by conventional techniques, the transfected cells are then cultured by conventional techniques to produce an antibody.
  • the disclosure includes host cells containing a polynucleotide encoding an antibody or antigen-binding fragments thereof, operably linked to a heterologous promoter.
  • both the heavy chain and the light chain may be co-expressed (from the same or different vectors) in the host cell for expression of the entire antibody.
  • both the heavy and light chains of the antibody are expressed from a single promoter.
  • the heavy and light chains of the antibody are expressed from multiple promoters.
  • the heavy and light chains of the antibody are encoded on a single vector. In certain aspects, the heavy and light chains of the antibody are encoded on multiple vectors.
  • Mammalian cell lines available as hosts for expression of recombinant antibodies are well known in the art and include many immortalized cell lines available from the American Type Culture Collection (ATCC), including but not limited to Chinese hamster ovary (CHO) cells, HeLa cells, baby hamster kidney (BHK) cells, monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), human epithelial kidney 293 cells, and a number of other cell lines.
  • ATCC American Type Culture Collection
  • CHO Chinese hamster ovary
  • HeLa cells HeLa cells
  • BHK baby hamster kidney
  • COS monkey kidney cells
  • human hepatocellular carcinoma cells e.g., Hep G2
  • human epithelial kidney 293 cells e.g., Hep G2
  • Different host cells have characteristic and specific mechanisms for the post- translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the antibody or portion thereof expressed
  • eukaryotic host cells that possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used.
  • mammalian host cells include but are not limited to CHO, HEK293, VERY, BHK, Hela, COS, MDCK, 293, 3T3, W138, BT483, Hs578T, HTB2, BT20 and T47D, NS0 (a murine myeloma cell line that does not endogenously produce any functional immunoglobulin chains), SP20, CRL7030 and HsS78Bst cells.
  • NS0 a murine myeloma cell line that does not endogenously produce any functional immunoglobulin chains
  • SP20 CRL7030 and HsS78Bst cells.
  • Stable expression can be used for long-term, high-yield production of recombinant proteins.
  • cell lines that stably express the antibody molecule may be generated.
  • Host cells can be transformed with an appropriately engineered vector comprising expression control elements (e.g., promoter, enhancer, transcription terminators, polyadenylation sites, etc.), and a selectable marker gene.
  • expression control elements e.g., promoter, enhancer, transcription terminators, polyadenylation sites, etc.
  • selectable marker gene e.g., promoter, enhancer, transcription terminators, polyadenylation sites, etc.
  • the selectable marker in the recombinant plasmid confers resistance to the selection and allows cells that stably integrated the plasmid into their chromosomes to grow and form foci, which in turn can be cloned and expanded into cell lines. Methods for producing stable cell lines with a high yield are well known in the art and reagents are generally available commercially.
  • antibodies and antibody fragments of the disclosure are transiently expressed in a cell line. Transient transfection is a process in which the nucleic acid introduced into a cell does not integrate into the genome or chromosomal DNA of that cell, but is maintained as an extrachromosomal element, e.g. as an episome, in the cell. Transcription processes of the nucleic acid of the episome are not affected and a protein encoded by the nucleic acid of the episome is produced.
  • the cell line is maintained in cell culture medium and conditions well known in the art resulting in the expression and production of monoclonal antibodies.
  • the mammalian cell culture media is based on commercially available media formulations, including, for example, DMEM or Ham's F12.
  • the cell culture media is modified to support increases in both cell growth and biologic protein expression.
  • the terms “cell culture medium,” “culture medium,” and “medium formulation” refer to a nutritive solution for the maintenance, growth, propagation, or expansion of cells in an artificial in vitro environment outside of a multicellular organism or tissue.
  • Cell culture medium may be optimized for a specific cell culture use, including, for example, cell culture growth medium that is formulated to promote cellular growth, or cell culture production medium which is formulated to promote recombinant protein production.
  • the terms nutrient, ingredient, and component are used interchangeably herein to refer to the constituents that make up a cell culture medium.
  • an antibody Once an antibody has been produced, it may be purified by any method known in the art for purification of an immunoglobulin molecule or other multimeric molecules, for example, by chromatography (e.g., ion exchange, affinity, particularly by affinity for the specific antigens Protein A or Protein G, and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for the purification of proteins.
  • the antibody and antibody fragment can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the molecule is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration. Carter et ah, Bio/Technology , 10:163-167 (1992) describe a procedure for isolating antibodies, which are secreted into the periplasmic space of E. coli.
  • supernatants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit.
  • a protease inhibitor such as PMSF may be included in any of the foregoing steps to inhibit proteolysis and antibiotics may be included to prevent the growth of adventitious contaminants.
  • composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, hydrophobic interaction chromatography, ion exchange chromatography, gel electrophoresis, dialysis, and/or affinity chromatography either alone or in combination with other purification steps.
  • the suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domain, if present, in the molecule and will be understood by one of skill in the art.
  • the matrix to which the affinity ligand is attached is most often agarose, but other matrices are available.
  • Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene allow for faster flow rates and shorter processing times than can be achieved with agarose.
  • Other techniques for protein purification such as fractionation on an ion-exchange column, ethanol precipitation, Reverse Phase HPLC, chromatography on silica, chromatography on heparin, SEPHAROSE chromatography on an anion or cation exchange resin (such as a polyaspartic acid column), chromatofocusing, SDS-PAGE, and ammonium sulfate precipitation are also available depending on the molecule to be recovered.
  • binding assays may be performed (before and/or after purification).
  • ELISA assays including dual ELISA assays may be used.
  • a first antigen is coated on a well, and binding to this antigen immobilizes the antibody.
  • a tagged second antigen is added to the well, and detected. Only antibodies that are both immobilized via binding to the first antigen and bound to the second antigen will be detected.
  • the disclosure provides for recombinant cell lines that may be deposited and maintained with an international depository institution that is authorized under the provisions of the Budapest Treaty (i.e., an International Depositary Authority, IDA).
  • the disclosure provides pharmaceutical compositions.
  • Such pharmaceutical compositions may also be compositions comprising an antibody and/or an antibody fragment as disclosed herein and a pharmaceutically acceptable excipient.
  • the pharmaceutical compositions of the disclosure are used as a medicament (i.e., in methods of treating or preventing a disease or condition (e.g., COVID-19 or a clinically related symptom thereof), in a subject in need of treatment or preventative treatment).
  • pharmaceutical compositions may be compositions comprising a nucleic acid molecule that encodes an antibody as disclosed herein.
  • an antibody (or nucleic acid molecules encoding an antibody) may be formulated with a pharmaceutically acceptable carrier, excipient or stabilizer, as pharmaceutical compositions.
  • a pharmaceutically acceptable carrier such as one or more non-toxic materials that do not interfere with the effectiveness of the biological activity of the active ingredients.
  • Such preparations may routinely contain salts, buffering agents, preservatives, compatible carriers, and optionally other therapeutic agents.
  • Such pharmaceutically acceptable preparations may also contain compatible solid or liquid fillers, diluents or encapsulating substances, which are suitable for administration into a human.
  • suitable solid or liquid fillers, diluents or encapsulating substances which are suitable for administration into a human.
  • Other contemplated carriers, excipients, and/or additives, which may be utilized in the formulations described herein include, for example, flavoring agents, antimicrobial agents, sweeteners, antioxidants, antistatic agents, lipids, protein excipients such as serum albumin, gelatin, casein, salt-forming counterions such as sodium and the like.
  • compositions described herein are known in the art, e.g., as listed in “Remington: The Science & Practice of Pharmacy”, 21 st ed., Lippincott Williams & Wilkins, (2005), and in the “Physician’s Desk Reference”, 60 th ed., Medical Economics, Montvale, N.J. (2005).
  • Pharmaceutically acceptable carriers can be selected that are suitable for the mode of administration, solubility and/or stability desired or required.
  • the formulations described herein comprise active agents (i.e., one or more antibody or fragments thereof as disclosed herein) in a concentration resulting in a w/v appropriate for a desired dose.
  • the active agent is present in a formulation at a concentration of about 1 mg/ml to about 200 mg/ml, about 1 mg/ml to about 100 mg/ml, about 1 mg/ml to about 50 mg/ml, or about 1 mg/ml to about 25 mg/ml.
  • the concentration of the active agent in a formulation may vary from about 0.1% to about 75% by total weight.
  • the concentration of the active agent is in the range of 0.003 to 1.0 molar.
  • the formulations When used for in vivo administration, the formulations should be sterile. Formulations may be sterilized by various sterilization methods, including sterile filtration, radiation, etc. In one aspect, the formulation is filter- sterilized with a presterilized 0.22-micron filter. Sterile compositions for injection can be formulated according to conventional pharmaceutical practice as described in “Remington: The Science & Practice of Pharmacy”, 21 st ed., Lippincott Williams & Wilkins, (2005).
  • compositions are encompassed by the pharmaceutical formulations described herein, and may formulated for particular routes of administration, such as oral, nasal, pulmonary, topical (including buccal and sublingual), rectal, vaginal and/or parenteral administration.
  • routes of administration such as oral, nasal, pulmonary, topical (including buccal and sublingual), rectal, vaginal and/or parenteral administration.
  • parenteral administration and “administered parenterally” as used herein refer to modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal injection and infusion.
  • the formulations may be in unit dosage form and may be prepared by any known method. Actual dosage levels of the active ingredients in the pharmaceutical compositions may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient (e.g., “a therapeutically effective amount”).
  • the selected dosage level will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions employed, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.
  • Suitable dosages may range from about 0.0001 to about 100 mg/kg of body weight or greater, for example about 0.1, 1, 10, or 50 mg/kg of body weight, with about 1 to about 10 mg/kg of body weight being suitable.
  • the formulations may be suitable for diagnostic and research use.
  • concentration of active agent in such formulations, as well as the presence or absence of excipients and/or pyrogens, can be modified or selected based on the particular application and intended use.
  • the antibodies and fragments thereof, as described herein, can be used in methods that prevent, inhibit, or reduce interactions between SARS-CoV-2 spike protein and a host ACE2, thereby disrupting or inhibiting viral entry into the host cell and viral infection.
  • the antibodies and fragments thereof disclosed herein can provide a neutralizing effect against SARS-CoV-2.
  • the antibodies or fragments of the disclosure can be used to treat a SARS-CoV-2 infection in a subject in need of treatment.
  • the antibodies and fragments disclosed herein can be used to prevent a SARS-CoV-2 infection in a subject, who may be at risk of exposure and/or of developing an infection.
  • the antibodies can be used to treat the respiratory illness coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, in a subject in need of treatment.
  • COVID-19 respiratory illness coronavirus disease 2019
  • the antibodies can be used to prevent COVID-19 in a subject at risk of developing COVID-19.
  • Such methods can be carried out by administering to the patient a therapeutically effective dose of an antibody or antibody fragment of the disclosure, or pharmaceutical compositions comprising such an antibody or antibody fragment.
  • the disclosure relates to methods of treating, preventing, diagnosing, or monitoring, a disease characterized by an infection by a virus, and particularly a coronavirus (e.g., SARS-CoV-2).
  • a coronavirus e.g., SARS-CoV-2
  • the antibodies, compositions and methods described herein can be used to treat a subject with a viral disease, e.g., a disease (COVID-19) characterized by infection with SARS-CoV-2.
  • a viral disease e.g., a disease (COVID-19) characterized by infection with SARS-CoV-2.
  • the term "disease” refers to any pathological state arising from viral infection, such as coronavirus infection, and in particular embodiments, the diseases and clinical symptoms associated with SARS-CoV-2 infection (COVID-19).
  • the disease or clinical symptom may include fever, cough, in particular a dry cough, shortness of breath, myalgia, stroke, cardiac events, acute respiratory distress syndrome (ARDS), and/or fatigue.
  • Additional COVID-19 symptoms can include pharyngitis (sore throat), headache, productive cough (i.e. a cough producing mucus or phlegm), hemoptysis, loss of appetite, nausea, diarrhea, and/or skin rash.
  • a “viral infection” may be determined or identified based on any available and/or accepted test that can detect the presence or absence of virus in a subject or a sample obtained from a subject, wherein the test indicates the presence of viral infection.
  • a viral infection may be determined based on detecting any one or more of viral load, viremia, viral sequence (e.g., nucleic acid or amino acid), as well as clinical manifestations of infection (e.g., fever, immune response, and other symptoms described herein). Commonly used clinical diagnostic tests may include immunoassays and PCR assays.
  • treat refers to administering an antibody or antigen binding fragment thereof, or compositions as described herein to a subject in order to eliminate or reduce the clinical signs of viral infection; arrest, inhibit, or slow the progression of viral infection in a subject; and/or decrease the number, frequency, or severity of clinical symptoms and/or recurrence of infection in a subject who currently has or who previously has had an infection or disease (e.g., COVID-19).
  • an infection or disease e.g., COVID-19
  • treatment of a disease includes curing, shortening the duration, ameliorating, slowing down, or inhibiting progression or worsening, or delaying the onset of a disease or the symptoms thereof in a subject who has the disease.
  • the disclosure provides methods for preventing disease (i.e., preventing viral infection, preventing the onset of a disease or the clinical symptoms of disease) in a subject.
  • the subject may be at risk of viral infection.
  • being at risk or having an “increased risk” a subject is identified as having a higher than normal chance of viral infection and/or developing a disease and/or clinical symptoms associated with viral infection, in particular COVID-19, compared to the general population.
  • a subject who has had, or who currently has, a disease or viral infection, or who is of a certain age is a subject who has an increased risk for developing viral infection or associated disease.
  • an immunocompromised subject can also be considered as having an increased risk for developing a viral infection or associated disease.
  • immunocompromised refers to a subject having a weakened immune system or a reduced ability to fight infections or other diseases, due to a genetic disorder or disease, an infection, an environmental disorder or disease, or other environmental factors.
  • a subject at risk of viral infection may be a subject who has not previously been infected, or who has not previously been vaccinated or immunized against viral infection.
  • immunotherapy relates to a treatment involving a specific immune reaction.
  • terms such as “protect”, “prevent”, “prophylactic”, “preventive”, or “protective” relate to the prevention of the occurrence and/or the propagation of a viral infection or associated disease and clinical symptoms in an individual and, in some embodiments, to minimizing the chance that a subject will develop a viral infection.
  • a person at risk for viral infection and associated disease, as described above, would be a candidate for preventative therapy to prevent a viral infection.
  • a prophylactic administration of an immunotherapy for example, a prophylactic administration of an antibody or a composition comprising the antibody or fragment thereof as disclosed herein, can in certain embodiments protect the recipient from a viral infection.
  • a prophylactic administration may reduce the severity of a future infection in the recipient (e.g., the subject may be asymptomatic or experience milder clinical symptoms associated with disease/infection).
  • a therapeutic administration of an immunotherapy may lead to the inhibition of the progress of the infection, viral load, and/or clinical symptoms associated with the viral infection.
  • Such methods may include embodiments that comprise the reduction or inhibition of the progress of infection/propagation of the virus, which preferably leads to elimination of the disease and associated clinical symptoms.
  • subject is interchangeable, and relate to vertebrates, preferably mammals.
  • mammals in the context of the disclosure are humans, non-human primates, domesticated animals such as dogs, cats, sheep, cattle, goats, pigs, horses etc., laboratory animals such as mice, rats, rabbits, guinea pigs, etc., as well as animals in captivity such as animals in zoos.
  • animal as used herein also includes humans.
  • subject may also include a patient, i.e., an animal, an in particular embodiments a human having a disease associated with viral infection, in particular SARS-CoV-2 infection and related disease, such as COVID-19.
  • Subjects may also include a patient who may be at risk of exposure to the vims and/or at higher risk of developing viral infection.
  • the antibodies or fragments thereof, and compositions described herein may be administered via any conventional route, including by injection or infusion.
  • the administration may be carried out, for example, orally, intravenously, intraperitonealy, intramuscularly, subcutaneously, or transdermally.
  • antibodies, fragments thereof, or compositions comprising them may be administered by way of a lung aerosol.
  • the antibodies, fragments thereof, and the compositions comprising them are administered in effective amounts.
  • An "effective amount” includes an amount that achieves a desired reaction or a desired effect and may be in the form of a single dose or as multiple doses.
  • the desired reaction relates to inhibition of the course of the disease or symptom. Such inhibition can include slowing down the progression of the disease/clinical symptoms and, in some embodiments, interrupting or reversing the progression of the disease/clinical symptoms.
  • the treatment of a disease or of a condition may also be delay of the onset or a prevention of the onset of said disease or said condition in a subject who has active viral infection.
  • An effective amount of a composition of the invention will depend on the condition to be treated, the severity of the disease, the individual parameters of the patient, including age, physiological condition, size and weight, the duration of treatment, the type of an accompanying therapy (if present), the specific route of administration and similar factors. Accordingly, the doses of the compositions of the invention administered may depend on various combinations of such parameters. In embodiments in which an initial amount administered to a patient is insufficient, further administration with higher amounts, more frequent doses, or a different/more localized route of administration may be used.
  • the disclosure relates to methods of diagnosing and/or methods of monitoring a viral infection or disease associated with a viral infection in a subject, wherein the methods comprise the detection and/or the determination or the monitoring of the quantity of (i) a nucleic acid associated with SARS-CoV-2, (ii) a SARS-CoV-2-associated antigen or a part thereof, (iii) an antibody against one or more SARS-CoV-2-associated antigens or a part thereof, and/or (iv) a vims, viral particle, or virus-like particle, in a biologic sample isolated from a patient.
  • the methods comprise the detection and/or the determination or the monitoring of the quantity of (i) a nucleic acid associated with SARS-CoV-2, (ii) a SARS-CoV-2-associated antigen or a part thereof, (iii) an antibody against one or more SARS-CoV-2-associated antigens or a part thereof, and/or (iv) a vims, viral particle
  • the invention relates to a method of diagnosing an infection, or a disease characterized by infection of SARS-CoV-2.
  • the method comprises the detection, and/or the determination of the quantity, of (i) a nucleic acid associated with SARS-CoV-2, (ii) a SARS-CoV-2-associated antigen or a part thereof, (iii) an antibody against one or more SARS-CoV-2-associated antigens or a part thereof, and/or (iv) a virus, viral particle, or virus-like particle comprising a portion of SARS-Cov-2, in a biologic sample isolated from a patient.
  • detection comprises (i) contacting the biological sample with an antibody or antigen-binding fragment thereof as disclosed herein, which binds specifically to a SARS-CoV-2-associated antigen or a part thereof, an antibody against one or more SARS-CoV-2-associated antigens or a part thereof, and/or a vims, viral particle, or virus-like particle comprising a portion of SARS-CoV-2 antigen, and (ii) detecting the formation of a complex between the antibody or antigen-binding fragment thereof and the SARS-CoV-2-associated antigen or the part thereof, the antibody against one or more SARS- CoV-2-associated antigens or a part thereof, and/or a vims, viral particle, or virus-like particle comprising a portion of SARS-CoV-2 antigen.
  • the biological sample isolated from the patient is compared to a reference sample, e.g., a comparable biological sample obtained from a patient who is not in
  • the disclosure relates to a method for determining regression, course, or onset of a disease characterized by viral infection (i.e., SARS-CoV-2) identified according to the disclosure, which method comprises monitoring a sample from a patient who has said disease or is suspected of falling ill with said disease, for one or more parameters selected from the group consisting of (i) the amount of nucleic acid associated with SARS-CoV- 2, (ii) the amount of SARS-CoV-2-associated antigen or a part thereof, (iii) the amount of an antibody against one or more SARS-CoV-2-associated antigens or a part thereof, and/or (iv) the amount of a vims, viral particle, or vims-like particle comprising a portion of SARS-Cov-2.
  • the method comprises determining the parameter(s) in a first sample at a first point in time and in a further sample at a second point in time and in which the course of the disease is
  • sample can include any sample that is useful or usable in accordance with the methods described herein.
  • a sample can be a biological sample, such a sample from a tissue, which may include, for example, bodily fluids, and/or cellular samples that may be obtained by any conventional method (e.g., by tissue biopsy, taking blood, bronchial aspirate, sputum, urine, feces or other body fluids).
  • sample may include processed samples such as fractions or isolates of biological samples, e.g. nucleic acid and peptide/protein isolates.
  • detection of a SARS-Cov-2-associated antigen or of a part thereof, or determining or monitoring the amount of a SARS-Cov-2-associated antigen or of a part thereof may be carried out using one or more antibodies or fragments thereof as described herein.
  • the methods comprising detection that incorporate an antibody or fragment thereof as disclosed herein may comprise a detectable label.
  • the detectable label or marker is a fluorescent, colorimetric, radioactive, or an enzymatic marker, or other markers as disclosed herein or otherwise known in the art.
  • kits comprises any of the compositions or pharmaceutical compositions of a nucleic acid, polypeptide, expression vector, or host cell described above, and instructions or a label directing appropriate use or administration.
  • a kit may also include one or more containers and/or a syringe or other device to facilitate delivery or use. The disclosure contemplates that all or any subset of the components for conducting research assays, diagnostic assays and/or for administering therapeutically effective amounts may be enclosed in the kit.
  • the kit may include instructions for making a polypeptide by, for example culturing a host cell that expresses a nucleic acid that encodes an antibody of the disclosure under suitable conditions.
  • a kit for therapeutic administration of an antibody of the disclosure may comprise a solution containing a pharmaceutical formulation of the antibody, or a lyophilized preparation of the antibody, and instructions for administering the composition to a patient in need thereof and/or for reconstituting the lyophilized product.
  • the present disclosure also encompasses a finished packaged and labeled pharmaceutical product.
  • This article of manufacture includes the appropriate unit dosage form in an appropriate vessel or container such as a glass vial or other container that is hermetically sealed.
  • the active ingredient e.g., an above-described antibody
  • the formulation is suitable for intravenous administration, such as for intravenous infusion to a human or animal.
  • the formulations of the disclosure are formulated in single dose vials as a sterile liquid.
  • Exemplary containers include, but are not limited to, vials, bottles, pre-filled syringes, IV bags, and blister packs (comprising one or more pills).
  • Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human diagnosis and/or administration.
  • the packaging material and container are designed to protect the stability of the product during storage and shipment.
  • the products of the disclosure include instructions for use or other informational material that advise the physician, technician or patient on how to appropriately prevent or treat the disease or disorder in question.
  • the article of manufacture includes instruction means indicating or suggesting a dosing regimen including, but not limited to, actual doses, monitoring procedures, etc., and other monitoring information.
  • a kit for diagnostic assays may comprise a solution containing an antibody or a lyophilized preparation of an antibody of the disclosure, wherein the antibody binds specifically to one or more targets, as well as reagents for detecting such antibodies.
  • the antibody may be labeled according to methods known in the art and described herein, including but not limited to labels such as small molecule fluorescent tags, proteins such as biotin, GFP or other fluorescent proteins, or epitope sequences such as his or myc.
  • primary antibodies used for detecting the antibody may be included in the kit.
  • Primary antibodies may be directed to sequences on the antibody or to labels, tags, or epitopes with which the antibodies are labeled.
  • Primary antibodies may, in turn, be labeled for detection, or, if further amplification of the signal is desired, the primary antibodies may be detected by secondary antibodies, which may also be included in the kit.
  • Kits for research use are also contemplated. Such kits may, for example, resemble kits intended for diagnostic or therapeutic uses but further include a label specifying that the kit and its use is restricted to research purposes only.
  • antibodies and/or antigen binding fragments thereof include, without limitation, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a scFv, a single domain antibody, a diabody, a multispecific antibody, a dual-specific antibody, and a bispecific antibody.
  • the disclosed antibodies, and antigen binding fragments thereof can also be used to generate fusion proteins and/or for antibody-targeted cell fusion, such as with stem cells.
  • the disclosed antibodies, and antigen binding fragments thereof can also be used to produce therapeutic immunoconjugates, wherein the disclosed antibodies, or antigen binding fragments thereof, are conjugated with one or more therapeutic agents.
  • disclosed antibodies, or antigen binding fragments thereof can be used in the production of Antibody- Drug-Conjugates (ADC).
  • ADC Antibody- Drug-Conjugates
  • Drugs that can be used include, without limitation, antiviral drugs that treat, prevent, or otherwise neutralize the Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2).
  • Example drugs include, for example: Remdesivir; Baricitinib; Bemcentinib; Chloroquine phosphate; Colchicine; EIDD-2801; Favipiravir; Fingolimod; Hydroxychloroquine; Azithromycin; Ivermectin; and combinations thereof.
  • Antibody discovery was performed using scFv phage display libraries derived from IgG and IgM antibody sequences from healthy human donors.
  • the RBD region (Sino Biological, Cat#: 40592-V05H) or SI region (Sino Biological, Cat# 40591-V08H) of the SARS- CoV-2 spike protein was used as a panning antigen.
  • the RBD or SI region was first biotinylated and then mixed with IgG and IgM phage libraries.
  • the protein-phage complexes were incubated with Dynabead M-280 Streptavidin beads.
  • Tables 2 and 3 detail sequence information for exemplary monoclonal IgG and scFv-Fc antibodies in accordance with example embodiments as disclosed herein.
  • Table 2 Full Heavy and Light Chain Amino Acid Sequences for Representative anti- SARS-CoV-2 RBD and anti- SARS-CoV-2 SD1
  • Table 3 Amino Acid Sequences for Representative anti-SARS-CoV-2 RBD and anti- SARS-CoV-2 SD1 in accordance with example embodiments of the disclosure.
  • SARS-CoV-2 RBD scFv-Fc constructs Human IgGl Fc was fused with the C-terminus of each of the identified scFv regions (SARS-CoV-2 RBD scFv-Fc constructs) and transiently transfected into HEK293F cells to generate conditioned media/supematant.
  • the SARS-CoV-2 RBD scFv-Fc constructs were screened via a direct ELISA for binding to in-house SARS-CoV-2 RBD or commercially available SARS-CoV-2 RBD-mFc (Sino Biological, Cat#: 40592-V05H).
  • a 96-well plate was coated with 1 pg/inL of SARS-CoV-2 RBD in Phosphate Buffered Saline (PBS) and incubated at 4°C overnight.
  • the SARS-CoV-2 RBD scFv-Fc-containing supernatant was serially diluted 1/3 in PBS + 0.1% Tween (PBS-T) and 3% dry milk into the coated wells.
  • ACE-2-Fc served as a positive control for RBD-binding. The plate was incubated for 1 hour at room temperature and then washed three times with PBS-T.
  • the wells were incubated with 0.5 ug/mL goat anti-human Fc-HRP secondary antibody, diluted in PBS-T + 3% dry milk, (Invitrogen, Cat# A18829). The plate was incubated for 1 hour at room temperature and then washed three times with PBS-T. HRP substrate 1-step Ultra TMB -ELISA (Thermo Fisher, Cat# 34029) was added to the wells. The color reactions were stopped by adding 2 M sulfuric acid to each well. The resulting optical density of the plate was read at 450 nm (OD450) using a SpectraMax M3 plate reader (Molecular devices, CA, USA). The results of Example 2 are shown in FIGS. 1A-1F.
  • SARS-CoV-2 RBD scFv-Fc constructs were also screened by direct ELISA for cross-reactivity with SARS-CoV RBD.
  • a 96-well plate was coated with 1 ug/mL of SARS-CoV RBD (Sino Biological 40150-V08B2) in PBS and incubated at 4°C overnight.
  • SARS-CoV-2 RBD scFv-Fc-containing supernatant was serially diluted 1/3 in PBS-T and 3% dry milk into the coated wells.
  • ACE-2-Fc served as a positive control for RBD-binding. The plate was incubated for 1 hour at room temperature and then washed three times with PBS-T.
  • SARS-CoV-2 RBD scFv-Fc constructs were selected to examine ACE-2/SARS-CoV-2 RBD binding inhibition using an ELISA.
  • SARS-CoV-2 Sl-RBD- Fc was biotinylated using a biotinylation kit (Thermo Fisher, Cat # A39257) according to the manufacturer’s instructions. Briefly, lyophilized SARS-CoV-2 RBD-Fc protein (Sino Biologicals, Cat # 40592-V05H) was dissolved in water to 500 pg/mL (9.7 pM).
  • Sulfo-NHS- biotin was dissolved in water to 10 mM, and immediately mixed with the reconstituted SARS- CoV-2 RBD-Fc protein at a 10:1 molar ratio. The mixture was incubated at room temperature for 45 minutes, resulting in SARS-CoV-2 Sl-RBD-Fc-biotin.
  • Immulon 4HBX plates (Thermo Fisher, Cat # 3855) were coated with 1 ug/mL ACE2-Fc (Jecho Labs) in 0.2 M carbonate buffer (Thermo Fisher, Cat # 28382) and incubated overnight at 4°C overnight. Each plate included one positive control (SARS-CoV-2 Sl-RBD-Fc-biotin) and one negative control (sample diluent). The plates were washed with PBS-T and blocked with sample diluent (BD, Cat # 555213) for 1 hour at room temperature.
  • SARS-CoV-2 Sl-RBD-Fc-biotin positive control
  • sample diluent sample diluent
  • SARS-CoV-2 RBD scFv-Fc-containing supernatant was serially diluted 1 to 4, and incubated with 5 ng/mL (IC50 of RBD/ACE2 interaction) of SARS-CoV-2 Sl-RBD-Fc-biotin at room temperature for 45 minutes. The resulting mixtures were loaded onto the ACE2-Fc coated plate. The plates were shaken at 500 rpm for 1 hour at room temperature to allow SARS-CoV-2 Sl- RBD-Fc-biotin to bind to ACE2-Fc.
  • the plates were washed three times with PBS-T and 0.5 ug/mL HRP-streptavidin (Jackson Immuno Research Lab, Cat # 016-030-084) was loaded onto the plate to detect bound SARS-CoV-2 Sl-RBD-Fc-biotin.
  • the plates were shaken at 500 rpm for 1 hour at room temperature.
  • peroxidase substrate (Thermo Fisher, Cat # 34028) was added to the plate, and the colorimetric reaction eventually stopped by 2 M sulfuric acid.
  • the OD450 values were measured by the SpectraMax M3 plate reader.
  • Reduced HRP signal indicated the interruption of ACE-2-RBD interactions.
  • the results of Example 4, illustrated as % inhibition, are shown in FIGS. 3A-3D.
  • IC50 was calculated using 4-parameter curve fit by SoftMax software (Table 4).
  • Table 4 Titer, IC50, and ACE-2/SARS-CoV-2 RBD maximum binding inhibition of SARS- CoV-2 RBD scFv-Fc
  • SARS-CoV-2 RBD scFv-Fc constructs were converted into fully human IgG mAbs. Binding specificity to SARS-CoV-2 (Sino Biological, Cat# 40591-V08H) and cross reactivity to SARS-CoV (Sino Biological, Cat# 40150-V08B1) and Middle East respiratory syndrome (MERS) -related coronavims spike protein (Sino Biological, Cat#40069-V08B1) were examined by ELISA. A 96-well plate was coated with 1 pg/inL SARS-CoV-2, SARS-CoV, or MERS-related coronavims in PBS and incubated at 4°C overnight.
  • SARS-CoV-2 RBD scFv-Fc constructs were converted into fully human IgG mAbs. Binding specificity to SARS-CoV-2 (Sino Biological, Cat# 40591-V08H) and cross reactivity to SARS-CoV
  • the SARS-CoV-2 RBD IgG- containing supernatant was serially diluted 1/4 in PBS-T and 3% dry milk into the coated wells.
  • ACE-2-Fc served as a positive control for RBD-binding for SARS-CoV-2 and SARS-CoV.
  • the plate was incubated for 1 hour at room temperature and then washed three times with PBS-T.
  • the wells were incubated with 0.5 ug/mL goat anti-human Fc-HRP secondary, incubated for 1 hour at room temperature, and washed three times with PBS-T.
  • HRP substrate was added to the wells, and the color reaction stopped by adding 2 M sulfuric acid to each well. The resulting optical density of the plate was read at 450 nm.
  • Example 5 The results of Example 5 are shown in FIGS. 4A-4C.
  • RBD-18 IgG, RBD-20 IgG, RBD-21 IgG, RBD-32 IgG, and RBD-35 IgG exhibited SARS-CoV-2 binding.
  • RBD-32 IgG showed cross -reactivity to SARS-CoV. None of the antibodies cross-reacted with MERS-related coronavims.
  • the loaded probes were dipped into wells containing 0 nM, 6.25 nM, 12.5 nM, 25 nM, 100 nM, or 200 nM of a monomeric RBD of the SARS-CoV-2 spike protein.
  • the reference probe was dipped into 200 nM of monomeric RBD.
  • the association reaction was monitored for 300 seconds.
  • the probes were transferred into buffer solutions to initiate a disassociation reaction, which was monitored for 300 seconds. After measurement, the probes were regenerated according to manufacturer’s instructions and steps 1- 3 repeated for RBD-20 IgG, RBD-32 IgG, and RBD-35 IgG. The resulting data were fit to a 1:1 binding model using Octet data analysis software.
  • Example 6 The results of Example 6 are shown in FIGS. 5A-5D.
  • the resulting dissociation constant (K d ) of RBD-18 IgG, RBD-20 IgG, RBD-21 IgG, RBD-32 IgG, and RBD-35 IgG are shown in Table 5.
  • RBD- 18 IgG, RBD-32 IgG, and RBD-35 IgG were analyzed as well as SI IgG, which is downstream of the RBD domain of the SARS-CoV-2 spike protein.
  • An epitope binning experiment was performed using the Octet Qke.
  • an anti-His probe/biosensor was loaded with 1 pg/inL His-tagged SARS-CoV-2 RBD.
  • the loaded probe was dipped into a well containing 2.5 pg/inL of RBD- 18 IgG to initiate phase I association.
  • the probe was dipped into a well containing 2.5 pg/inL of RBD-32 IgG, RBD-35 IgG, or SI IgG to initiate phase II association.
  • a probe dipped into a well containing 2.5 pg/inL RBD- 18 IgG served as a control.
  • Epitope binning was analyzed by comparing association rates in phase II between the control and RBD-32 IgG, RBD-35 IgG, or SI IgG. Steps 1-3 were repeated for RBD-32 IgG, RBD-35 IgG, and SI IgG.
  • Phase II IgGs having different epitopes result in increased signal while phase II IgGs having identical or similar epitopes to the RBD or S 1 IgG show decreased signal, depending on the degree to epitope overlap.
  • the results of Example 7 are shown in FIGS. 6A-6D.
  • SI IgG S1-C6
  • RBD- 18 IgG and RBD-32 IgG which both showed some degree of cross-reactivity to SARS-CoV RBD, shared a similar epitope.
  • RBD-35 IgG which did not cross-react with SARS-CoV RBD, possesses a unique epitope.
  • RBD- 12 IgG, RBD- 18 IgG, RBD-20 IgG, RBD-21, RBD-24, RBD-25, RBD-32, and RBD-35 IgG were analyzed for ACE-2/SARS-CoV-2 RBD binding inhibition as described in Example 4.
  • the results of Example 8, illustrated as percent inhibition, are shown in FIGS. 7A and 7B.
  • the percent inhibition was calculated and plotted.
  • IC50 was calculated using 4-parameter curve fit by SoftMax software (Table 6).
  • RBD-35 IgG, RBD-32 IgG, and a combination of RBD-35 IgG and RBD-32 IgG were analyzed for ACE-2/SARS-CoV-2 binding inhibition using a SARS-CoV-2 pseudovirus (Virongy, Cat# CoV2LUC-02) and NR-52511, an HEK293T cell line that stably expresses ACE- 2 (BEI resources). Analysis was carried out as described in Example 4. The results of Example 9, illustrated as percent inhibition, are shown in FIG. 8. For each SARS-CoV-2 RBD IgG, the percent inhibition was calculated and plotted. The IC50 values of RBD-35 IgG, RBD-32 IgG, and the RBD-35 IgG and RBD-32 IgG combination are shown in Table 7.
  • RBD-35 IgG and RBD-32 IgG were further tested in vitro.
  • Vero cells lxlO 5 cell/mL
  • Vero cells were infected with 100 TCID50 of SARS-CoV-2 in the presence of serially diluted RBD-35 IgG, RBD-32 IgG, or the RBD-35 IgG and RBD-32 IgG combination.
  • Infected cells were cultured at 37°C for 3-5 days and Cytopathic effect (CPE) evaluated via microscopic analysis.
  • CPE Cytopathic effect
  • the resulting IC50 values are shown in Table 8.
  • the data of Examples 9 and 10 demonstrate that antibodies falling within the scope of the disclosure can inhibit ACE-2/SARS-CoV-2 binding interaction.
  • RBD-35 IgG robustly inhibits ACE-2/SARS- CoV-2 binding.
  • Table 8 IC50 of SARS-CoV-2 RBD IgG tested in real virus neutralization assay

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Abstract

La divulgation concerne des anticorps dirigés contre le coronavirus 2 responsable du syndrome respiratoire aigu sévère (SARS-CoV-2), ainsi que des compositions les comprenant. Plus particulièrement, la divulgation concerne des anticorps anti-SARS-CoV-2 et des fragments associés qui se lient à la protéine de spicule du SARS-CoV-2, y compris des anticorps et des fragments qui se lient au domaine SD1 ou au domaine de liaison aux récepteurs (RBD) de la protéine de spicule du SARS-CoV-2. La divulgation concerne aussi des méthodes de détection, de traitement et/ou de prévention d'une infection à SARS-CoV-2 chez un sujet, les méthodes comprenant les anticorps ou les fragments associés qui sont décrits dans la description.
PCT/US2021/033594 2020-05-22 2021-05-21 Anticorps anti-sars-cov-2 et méthodes associées WO2021237051A1 (fr)

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Citations (3)

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Publication number Priority date Publication date Assignee Title
WO2008060331A2 (fr) * 2006-05-19 2008-05-22 Amgen Inc. Anticorps au coronavirus sras
WO2015057942A1 (fr) * 2013-10-18 2015-04-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anticorps monoclonaux humains contre le coronavirus du syndrome respiratoire du moyen-orient (mers-cov) et fusions bispécifiques modifiées avec peptides inhibiteurs
WO2017066714A1 (fr) * 2015-10-16 2017-04-20 Compugen Ltd. Conjugués d'anticorps anti-vsig1 et de médicaments

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008060331A2 (fr) * 2006-05-19 2008-05-22 Amgen Inc. Anticorps au coronavirus sras
WO2015057942A1 (fr) * 2013-10-18 2015-04-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anticorps monoclonaux humains contre le coronavirus du syndrome respiratoire du moyen-orient (mers-cov) et fusions bispécifiques modifiées avec peptides inhibiteurs
WO2017066714A1 (fr) * 2015-10-16 2017-04-20 Compugen Ltd. Conjugués d'anticorps anti-vsig1 et de médicaments

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Title
CHEN: "Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor", CELLULAR & MOLECULAR IMMUNOLOGY, vol. 17, 20 April 2020 (2020-04-20), pages 647 - 649, XP037433894, DOI: 10.1038/s41423-020-0426-7 *

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