WO2021239014A1 - Anti-sars coronavirus-2 spike protein antibodies - Google Patents

Anti-sars coronavirus-2 spike protein antibodies Download PDF

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Publication number
WO2021239014A1
WO2021239014A1 PCT/CN2021/096185 CN2021096185W WO2021239014A1 WO 2021239014 A1 WO2021239014 A1 WO 2021239014A1 CN 2021096185 W CN2021096185 W CN 2021096185W WO 2021239014 A1 WO2021239014 A1 WO 2021239014A1
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Prior art keywords
seq
amino acid
acid sequence
chain variable
variable domain
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PCT/CN2021/096185
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French (fr)
Inventor
Leyan TANG
Allison SCHULKINS
Kimberly THAN
Chun-Nan Chen
Yiding CHEN
Jingyun MIAO
Lili QIN
Pingju GE
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Single Cell Technology, Inc.
Acrobiosystems, Inc.
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Publication of WO2021239014A1 publication Critical patent/WO2021239014A1/en

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    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/543—Mucosal route intranasal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • 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

Definitions

  • Coronaviruses are frequent causes of the common cold, causing upper respiratory tract infection throughout the world in all age groups (Greenberg, 2011) .
  • SARS-CoV severe acute respiratory syndrome coronavirus
  • MERS-CoV Middle East respiratory syndrome coronavirus
  • MERS emerged in 2012 in Jeddah, Saudi Arabia.
  • MERS-CoV infection has been identified in 1, 791 patients, with 640 deaths ( http: //www. who. int/emergencies/mers-cov/en/ ) .
  • no specific antivirals or approved vaccines are available to combat SARS nor MERS, and the SARS pandemic in 2002 and 2003 was finally stopped by conventional control measures and so was the MERS outbreaks.
  • SARS-CoV-2 SARS-coronavirus 2
  • SARS-CoV-2 SARS-coronavirus 2
  • Wei, 2020 presymptomatic transmission
  • SARS-CoV-2 peak viral load is reached by about 5-6 days post-infection, thus offering an opportunity for effective post-exposure treatment (Pan et al., 2020) .
  • One modality of treatment that may limit replication of the virus and thus its spread is passive immunization with neutralizing recombinant human monoclonal antibodies (mAbs) .
  • mAbs human monoclonal antibodies
  • Such a treatment during the prodromal phase of the disease could aid in rapid clearance of virus and limit poor clinical outcome and person to person spread, without the adverse effects associated with use of corticosteroids, animal sera, or human sera.
  • SARS-CoV-2 makes use of a densely glycosylated spike (S) protein to gain entry into host cells.
  • S protein is a trimeric class I fusion protein that exists in a metastable prefusion conformation that undergoes a dramatic structural rearrangement to fuse the viral membrane with the host-cell membrane (Li, 2016; Bosch et al., 2003) . This process is triggered when the Sl subunit binds to a host-cell receptor.
  • Receptor binding destabilizes the prefusion trimer, resulting in shedding of the S1 subunit and transition of the S2 subunit to a stable post-fusion conformation (Walls et al., 2017) .
  • the receptor-binding domain (RBD) of S1 undergoes hinge-like conformational movements that transiently hide or expose the determinants of receptor binding.
  • the S2 domain of the S protein contributes to infection of the target cell by mediating fusion of viral and host membranes through a conformational change in which two conserved helical regions (HR1 and HR2) of the S protein are brought together to form a six-helix bundle fusion core (He et al., 2005a) .
  • the S protein serves as the main antigen that elicits protective immune responses, including neutralizing antibodies in infected humans and animals (Bisht et al., 2004; Buchholz et al., 2004; Cheng et al., 2005; Greenough et al., 2005; He et al., 2005b; Hofmann et al., 2004) .
  • antibodies that recognize and specifically bind to SARS-CoV-2 S protein.
  • the disclosure provides an antibody that binds to SEQ ID NO: 1.
  • SCT-Ma054 mature heavy chain variable domain protein sequence 28 SCT-Ma125 mature heavy chain variable domain protein sequence 29 SCT-Ma015 mature heavy chain variable domain protein sequence 30 SCT-Ma052 mature heavy chain variable domain protein sequence 31 SCT-Ma094 mature heavy chain variable domain protein sequence 32 SCT-Ma126 mature heavy chain variable domain protein sequence 33 SCT-Ma100 mature heavy chain variable domain protein sequence 34 SCT-Ma103 mature heavy chain variable domain protein sequence 35 SCT-Ma123 mature heavy chain variable domain protein sequence 36 SCT-Ma077 mature heavy chain variable domain protein sequence 37 SCT-Ma099 mature heavy chain variable domain protein sequence 38 SCT-Ma067 mature heavy chain variable domain protein sequence 39 SCT-Ma095 mature heavy chain variable domain protein sequence 40 SCT-Ma004 mature heavy chain variable domain protein sequence 41 SCT-Ma050 mature heavy chain variable domain protein sequence 42 SCT-Ma068 mature heavy chain variable domain protein sequence 43 SCT-Ma072 mature heavy chain variable domain protein sequence 44 SCT-M
  • SCT-Ma133 mature heavy chain variable domain protein sequence 58
  • SCT-Ma120 mature heavy chain variable domain protein sequence 59
  • SCT-Ma086 mature heavy chain variable domain protein sequence 60
  • SCT-Ma019 mature heavy chain variable domain protein sequence 61
  • SCT-Ma016 mature heavy chain variable domain protein sequence 62
  • SCT-Ma025 mature heavy chain variable domain protein sequence 63
  • SCT-Ma046 mature heavy chain variable domain protein sequence 64
  • SCT-Ma129 mature heavy chain variable domain protein sequence 65
  • SCT-Ma117 mature heavy chain variable domain protein sequence 66
  • SCT-Ma098 mature heavy chain variable domain protein sequence 67
  • SCT-Ma006 mature heavy chain variable domain protein sequence 68
  • SCT-Ma121 mature heavy chain variable domain protein sequence 69
  • SCT-Ma008 mature heavy chain variable domain protein sequence 70
  • SCT-Ma128 mature heavy chain variable domain protein sequence 71
  • SCT-Ma032 mature heavy chain variable domain protein sequence 87 SCT-Ma066 mature heavy chain variable domain protein sequence 88 SCT-Ma122 mature heavy chain variable domain protein sequence 89 SCT-Ma003 mature heavy chain variable domain protein sequence 90 SCT-Ma115 mature heavy chain variable domain protein sequence 91 SCT-Ma074 mature heavy chain variable domain protein sequence 92 SCT-Ma083 mature heavy chain variable domain protein sequence 93 SCT-Ma109 mature heavy chain variable domain protein sequence 94 SCT-Ma009 mature heavy chain variable domain protein sequence 95 SCT-Ma044 mature heavy chain variable domain protein sequence 96 SCT-Ma088 mature heavy chain variable domain protein sequence 97 SCT-Ma030 mature heavy chain variable domain protein sequence 98 SCT-Ma007 mature heavy chain variable domain protein sequence 99 SCT-Ma013 mature heavy chain variable domain protein sequence 100 SCT-Ma023 mature heavy chain variable domain protein sequence 101 SCT-Ma060 mature heavy chain variable domain protein sequence 102 SCT-Ma
  • SCT-Ma081 mature heavy chain variable domain protein sequence 117 SCT-Ma028 mature heavy chain variable domain protein sequence 118 SCT-Ma055 mature heavy chain variable domain protein sequence 119 SCT-Ma085 mature heavy chain variable domain protein sequence 120 SCT-Ma080 mature heavy chain variable domain protein sequence 121 SCT-Ma124 mature heavy chain variable domain protein sequence 122 SCT-Ma063 mature heavy chain variable domain protein sequence 123 SCT-Ma111 mature heavy chain variable domain protein sequence 124 SCT-Ma035 mature heavy chain variable domain protein sequence 125 SCT-Ma037 mature heavy chain variable domain protein sequence 126 SCT-Ma036 mature heavy chain variable domain protein sequence 127 SCT-Ma017 mature heavy chain variable domain protein sequence 128 SCT-Ma079 mature heavy chain variable domain protein sequence 129 SCT-Ma110 mature heavy chain variable domain protein sequence 130 SCT-Ma024 mature heavy chain variable domain protein sequence 131 SCT-Ma027 mature light chain variable domain protein sequence 132 SCT
  • SCT-Ma009 mature light chain variable domain protein sequence 140 SCT-Ma044 mature light chain variable domain protein sequence 141 SCT-Ma028 mature light chain variable domain protein sequence 142 SCT-Ma055 mature light chain variable domain protein sequence 143 SCT-Ma053 mature light chain variable domain protein sequence 143 SCT-Ma056 mature light chain variable domain protein sequence 144 SCT-Ma131 mature light chain variable domain protein sequence 145 SCT-Ma033 mature light chain variable domain protein sequence 146 SCT-Ma103 mature light chain variable domain protein sequence 146 SCT-Ma132 mature light chain variable domain protein sequence 147 SCT-Ma080 mature light chain variable domain protein sequence 148 SCT-Ma124 mature light chain variable domain protein sequence 149 SCT-Ma077 mature light chain variable domain protein sequence 150 SCT-Ma099 mature light chain variable domain protein sequence 151 SCT-Ma089 mature light chain variable domain protein sequence 152 SCT-Ma081 mature light chain variable domain protein sequence 153 SCT-M
  • SCT-Ma021 mature light chain variable domain protein sequence 165 SCT-Ma006 mature light chain variable domain protein sequence 165 SCT-Ma116 mature light chain variable domain protein sequence 166 SCT-Ma008 mature light chain variable domain protein sequence 167 SCT-Ma046 mature light chain variable domain protein sequence 168 SCT-Ma120 mature light chain variable domain protein sequence 169 SCT-Ma098 mature light chain variable domain protein sequence 170 SCT-Ma016 mature light chain variable domain protein sequence 171 SCT-Ma129 mature light chain variable domain protein sequence 172 SCT-Ma117 mature light chain variable domain protein sequence 173 SCT-Ma086 mature light chain variable domain protein sequence 174 SCT-Ma054 mature light chain variable domain protein sequence 175 SCT-Ma018 mature light chain variable domain protein sequence 176 SCT-Ma082 mature light chain variable domain protein sequence 177 SCT-Ma076 mature light chain variable domain protein sequence 178 SCT-Ma064 mature light chain variable domain protein sequence 178 SCT
  • SCT-Ma115 mature light chain variable domain protein sequence 188
  • SCT-Ma122 mature light chain variable domain protein sequence 189
  • SCT-Ma041 mature light chain variable domain protein sequence 190
  • SCT-Ma007 mature light chain variable domain protein sequence 191
  • SCT-Ma083 mature light chain variable domain protein sequence 192
  • SCT-Ma001 mature light chain variable domain protein sequence 192
  • SCT-Ma061 mature light chain variable domain protein sequence 193
  • SCT-Ma078 mature light chain variable domain protein sequence 194
  • SCT-Ma084 mature light chain variable domain protein sequence 195
  • SCT-Ma014 mature light chain variable domain protein sequence 196
  • SCT-Ma092 mature light chain variable domain protein sequence 197
  • SCT-Ma019 mature light chain variable domain protein sequence 198
  • SCT-Ma025 mature light chain variable domain protein sequence 199
  • SCT-Ma085 mature light chain variable domain protein sequence 200
  • SCT-Ma059 mature light chain variable domain protein sequence 210 SCT-Ma070 mature light chain variable domain protein sequence 211 SCT-Ma043 mature light chain variable domain protein sequence 211 SCT-Ma049 mature light chain variable domain protein sequence 212 SCT-Ma108 mature light chain variable domain protein sequence 213 SCT-Ma073 mature light chain variable domain protein sequence 214 SCT-Ma094 mature light chain variable domain protein sequence 215 SCT-Ma034 mature light chain variable domain protein sequence 216 SCT-Ma045 mature light chain variable domain protein sequence 217 SCT-Ma123 mature light chain variable domain protein sequence 218 SCT-Ma100 mature light chain variable domain protein sequence 219 SCT-Ma111 mature light chain variable domain protein sequence 220 SCT-Ma133 mature light chain variable domain protein sequence 221 SCT-Ma063 mature light chain variable domain protein sequence 222 SCT-Ma079 mature light chain variable domain protein sequence 223 SCT-Ma036 mature light chain variable domain protein sequence 224 SCT
  • FIG. 1. shows a map of epitope bins for a select subset of the anti-SARS-CoV-2 antibodies.
  • Antibodies within a circle have either an identical epitope or epitopes that overlap to a substantial degree.
  • SCT-Ma009 and SCT-Ma058 may have identical or largely overlapping epitope whereas SCT-Ma087 definitely has an epitope distinct from that of SCT-Ma009.
  • FIG. 2. shows a titration plot of a select subset of antibodies with regards to their ability to inhibit the reporter virus particles (RVPs) to infect an appropriate host cell.
  • RVPs reporter virus particles
  • FIG. 3. shows a titration plot of a single antibody (SCT-Ma134) with regards to their ability to inhibit the RVPs representative of the South African SARS-CoV-2 variant (Benslimane et al., 2021) to infect an appropriate host cell.
  • Antibodies with their data points showing a significant level of inhibition at lower concentrations are more potency.
  • the antibodies each with an IC50 that can be reasonably calculated from the data points are shown.
  • SCT-Ma134 is compared to Casirivimab, a potent monoclonal antibody developed by Regeneron Pharmaceuticals, Inc. (US Patent No. 10,975,139) . It shows that the potency of SCT-Ma134 was not affected by the South African SARS-CoV-2 variant mutations whereas Casirivimab’s potency was reduced.
  • the disclosure provides antibodies that bind to SARS-CoV-2 S protein.
  • the disclosure provides an isolated antibody that binds to SEQ ID NO: 1.
  • the disclosure provides antibodies that bind specifically to SEQ ID NO: 1.
  • antibody as used herein, includes both full-length immunoglobulins and antibody fragments that bind to the same antigen.
  • the antibodies can be, e.g., a monoclonal, polyclonal, chimeric, humanized, or single chain antibody.
  • the terms “antigen binding fragment, ” “fragment, ” and “antibody fragment” are used interchangeably to refer to any fragment that comprises a portion of a full-length antibody, generally at least the antigen binding portion or the variable region thereof. Examples of antibody fragments include, but are not limited to, diabodies, single-chain antibody molecules, multi-specific antibodies, Fab, Fab’, F (ab') 2, Fv or scFv.
  • the term “excipient” refers to a natural or synthetic substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations, or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility.
  • terapéuticaally effective is intended to qualify the amount of active ingredients used in the treatment of a disease or disorder or on the effecting of a clinical endpoint.
  • terapéuticaally acceptable refers to those compounds (or salts, prodrugs, tautomers, zwitterionic forms, etc. ) which are suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit/risk ratio, and are effective for their intended use.
  • treating, ” “treatment, ” and the like, as used herein, mean ameliorating a disease, so as to reduce, ameliorate, or eliminate its cause, its progression, its severity, or one or more of its symptoms, or otherwise beneficially alter the disease in a subject.
  • Reference to “treating, ” or “treatment” of a patient is intended to include prophylaxis.
  • Treatment may also be preemptive in nature, i.e., it may include prevention of disease in a subject exposed to or at risk for the disease. Prevention of a disease may involve complete protection from disease, for example as in the case of prevention of infection with a pathogen, or may involve prevention of disease progression.
  • prevention of a disease may not mean complete foreclosure of any effect related to the diseases at any level, but instead may mean prevention of the symptoms of a disease to a clinically significant or detectable level. Prevention of diseases may also mean prevention of progression of a disease to a later stage of the disease.
  • subject and “patient” are used interchangeably herein to mean all mammals including humans. Examples of subjects include, but are not limited to, humans, monkeys, dogs, cats, horses, cows, goats, sheep, pigs, and rabbits. In one embodiment, the subject or patient is a human.
  • “moderate severity COVID-19” refers to individuals who have evidence of lower respiratory disease by clinical assessment or imaging and a saturation of oxygen (SpO 2 ) ⁇ 94%on room air at sea level. While the diagnosis can be made on clinical grounds; chest imaging (radiograph, CT scan, ultrasound) may assist in diagnosis and identify or exclude pulmonary complications.
  • standard of care refers to the diagnostic and treatment process that a clinician should follow for a certain type of patient, illness, or clinical circumstance.
  • SOC may include administration of drugs that are being used in clinical practice for the treatment of COVID-19 (e.g. lopinavir/ritonavir; darunavir/cobicistat; hydroxy/chloroquine, tocilizumab, etc. ) , other than those used as part of another clinical trial.
  • ARDS acute respiratory distress syndrome
  • provided antibodies disclosed herein can be used for identifying SARS-CoV-2 infected patients by specifically detecting the virus via its S protein. Such a test is necessary to help protect frontline healthcare workers to isolate those who are infected by the virus and treat them before their illness worsen. Epidemiologists can reliably identify infected subjects in hot spots to better measure the extent of the outbreaks, and government officials can use those results to help decide when and how to return residents to daily life. Most importantly, it is key to economic recovery because the infected population can be identified and quarantined to allow the rest of the society to function and operate.
  • the present disclosure provides a composition or kit comprising the antibody or antigen-binding fragment discussed above or herein in association with a further therapeutic agent.
  • the present disclosure provides a pharmaceutical composition comprising the antigen-binding protein, antibody or antigen-binding fragment discussed above or herein and a pharmaceutically acceptable carrier and, optionally, a further therapeutic agent.
  • the further therapeutic agent is an anti-viral drug or a vaccine.
  • the further therapeutic agent is selected from the group consisting of an anti-inflammatory agent, and an antimalarial agent.
  • the antimalarial agent is chloroquine or hydroxychloroquine.
  • the anti-inflammatory agent is an antibody, such as sarilumab, tocilizumab, or gimsilumab.
  • the further therapeutic agent is a second antibody or antigen-binding fragment comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences of Table 3.
  • the present disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising an isolated antibody as discussed above or herein, and a pharmaceutically acceptable carrier or diluent.
  • the pharmaceutical composition comprises one or more excipients.
  • the pharmaceutical composition further comprises a second therapeutic agent.
  • the second therapeutic agent is selected from the group consisting of: a second antibody, or an antigen-binding fragment thereof, that binds a SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 1, an anti-inflammatory agent, and an antimalarial agent.
  • the disclosure provides antibodies that bind specifically to SEQ ID NO: 1.
  • antibody as used herein, includes both full-length immunoglobulins and antibody fragments that bind to the same antigens.
  • the antibodies can be, e.g., a monoclonal, polyclonal, chimeric, humanized, or single chain antibody.
  • the provided antibodies may be used to diagnose, treat, or monitor infection by SARS-CoV-2 virus.
  • the antibodies or fragments thereof described herein may be used for various in vitro molecular biology applications such as, enzyme-linked immunosorbent assays (ELISA) , Western blots, immunohistochemistry, immunocytochemistry, flow cytometry and fluorescence-activated cell sorting (FACS) , immunoprecipitation, and/or enzyme-linked immunospot assays.
  • ELISA enzyme-linked immunosorbent assays
  • FACS fluorescence-activated cell sorting
  • the antibodies or fragments thereof may be packaged in kits with or without additional reagents known to those of skill in the art for practicing any of the molecular biology techniques disclosed above.
  • the present disclosure provides a method of preventing or treating SARS-CoV-2 infection in a subject in need thereof, comprising administering to the subject a therapeutically or prophylactically effective amount of a pharmaceutical composition comprising one or more of the antibodies described herein.
  • a method can comprise administration of any dose of the antibodies described herein effective for ameliorating or treating symptoms of SARS-CoV-2 infection.
  • administration of a pharmaceutical composition comprising one or more of the antibodies described herein can be made to a subject exposed to SARS-CoV-2.
  • the pharmaceutical compositions described herein can be administered alone or in combination with other therapies deemed appropriate by a clinician or practitioner.
  • the pharmaceutical compositions described herein may reduce the number of days of COVID-19 symptoms by one or more days, such as reducing symptoms by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 days.
  • the present disclosure provides a method of reducing, retarding, or otherwise inhibiting growth and/or replication of SARS-CoV-2 in an individual confirmed to have COVID-19 comprising administering a pharmaceutical composition comprising one or more of the antibodies described herein.
  • the COVID-19 is of moderate severity.
  • administration of a prophylactic or therapeutic dose of one or more of the antibodies described herein is initiated within the earlier of 24 to 72 hours of illness onset or confirmation of the individual having COVID-19. In some embodiments, administration is initiated within the earlier of 24 hours of illness onset or confirmation of the individual having COVID-19.
  • the individual is at an elevated risk of exposure to SARS-CoV-2. In some embodiments, the individual is a health care worker. In some embodiments, the individual is located in an area where ongoing community spread of SARS-CoV-2 has been reported. In some embodiments, the individual has been in close contacts with one or more persons with COVID-19.
  • the individual is at an elevated risk of severe illness. In some embodiments, the individual is 60 years of age or older. In some embodiments, the individual has a serious chronic medical condition. In some embodiments, the chronic medical condition is chosen from pulmonary disease, diabetes mellitus (type 2) , requiring oral medication or insulin for treatment, hypertension, cardiovascular disease.
  • the individual has a baseline blood pressure under 110 mmHg systolic at rest. In some embodiments, the individual has a body mass index ⁇ 30.
  • the method further comprises testing the individual for SARS-CoV-2 infection.
  • testing comprises testing nasopharyngeal and oropharyngeal swabs by real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay.
  • rRT-PCR real-time reverse-transcriptase–polymerase-chain-reaction
  • the antibodies disclosed herein can be genetically engineered to enhance binding to a major component, mucin, of the mucosal membrane to enable a prophylactic application. This is accomplished by coating the upper airways of a subject with a single anti-SARS-CoV-2 neutralizing antibody or a panel of anti-SARS-CoV-2 antibodies disclosed herein to prevent the virus from reaching its target or directly neutralize infectious virus.
  • the disclosure provides the antibodies SCT-Ma001, SCT-Ma002, SCT-Ma003, SCT-Ma004, SCT-Ma005, SCT-Ma006, SCT-Ma007, SCT-Ma008, SCT-Ma009, SCT-Ma010, SCT-Ma011, SCT-Ma012, SCT-Ma013, SCT-Ma014, SCT-Ma015, SCT-Ma016, SCT-Ma017, SCT-Ma018, SCT-Ma019, SCT-Ma020, SCT-Ma021, SCT-Ma022, SCT-Ma023, SCT-Ma024, SCT-Ma025, SCT-Ma026, SCT-Ma027, SCT-Ma028, SCT-Ma029, SCT-Ma030, SCT-Ma031, SCT-Ma032, SCT-Ma033, SCT-Ma034, SCT
  • recombinant anti-SARS-CoV-2 S protein antibodies such as chimeric and humanized monoclonal antibodies, comprising both human and non-human portions, which can be made using standard recombinant DNA techniques, are within the scope of the disclosure.
  • Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques such as, for example, the methods described in U.S. Pat. No. 7,112,421; Better et al. (1988) Science 240: 1041-1043; or Liu et al. (1987) Proc. Natl. Acad. Sci. USA 84: 3439-3443.
  • the antibodies of the disclosure may comprise the heavy chain variable domain sequences of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, S
  • the heavy chain variable domain sequences may consist essentially of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO
  • the antibodies of the disclosure may comprise the light chain variable domain sequences of ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO:
  • the light chain variable domain sequences may consist essentially of ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, S
  • variable domain sequence comprising a sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to a sequence selected from SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 31, S
  • variable domain sequence comprising a sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to a sequence selected from ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO:
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 81 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 192.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 53 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 134.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 89 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 40 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 6 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 210.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 67 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 165.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 98 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 190.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 69 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 166.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 94 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 140.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 11 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 203.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 74 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 155.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 49 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 134.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 99 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 184.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 111 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 195.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 29 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 204.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 61 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 170.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 127 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 158.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 51 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 175.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 60 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 197.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 18 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 230.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 71 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 164.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 24 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 210.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 100 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 130 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 158.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 62 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 198.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 10 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 208.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 52 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 131.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 117 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 141.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 24 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 205.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 97 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 50 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 86 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 185.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 85 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 145.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 80 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 215.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 124 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 156.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 126 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 223.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 125 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 158.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 13 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 209.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 73 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 154.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 75 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 157.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 76 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 189.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 47 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 135.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 14 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 211.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 95 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 140.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 79 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 216.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 63 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 167.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 112 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 225.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 20 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 206.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 15 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 211.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 41 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 132.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 102 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 184.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 30 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 204.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 46 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 143.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 27 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 174.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 118 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 142.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 45 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 143.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 107 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 182.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 48 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 135.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 19 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 210.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 101 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 82 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 192.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 83 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 179.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 122 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 221.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 105 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 178.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 103 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 133.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 87 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 38 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 201.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 42 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 137.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 8 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 226.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 23 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 210.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 17 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 209.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 43 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 9 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 213.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 91 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 21 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 207.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 5 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 177.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 36 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 149.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 84 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 193.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 128 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 222.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 120 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 147.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 116 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 152.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 4 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 176.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 92 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 191.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 110 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 194.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 119 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 199.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 59 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 173.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 109 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 183.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 96 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 113 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 151.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 12 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 209.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 54 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 49 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 196.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 22 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 227.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 31 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 214.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 39 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 224.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 108 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 180.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 78 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 153.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 66 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 169.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 37 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 150.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 33 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 218.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 56 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 161.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 25 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 231.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 34 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 146.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 77 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 153.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 55 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 160.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 7 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 200.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 104 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 178.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 72 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 212.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 93 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 136.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 129 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 158.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 123 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 219.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 16 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 229.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 15 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 204.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 107 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 181.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 90 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 187.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 71 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 165.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 65 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 172.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 71 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 159.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 26 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 228.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 58 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 168.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 68 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 163.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 88 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 188.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 35 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 217.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 121 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 148.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 28 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 204.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 32 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 202.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 44 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 139.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 70 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 162.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 64 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 171.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 106 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 178.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 114 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 144.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 115 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 146.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 57 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 220.
  • the disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 542 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 543.
  • the provided antibodies disclosed herein when appropriately humanized can be used to treat and prevent infection by SARS-CoV-2 by blocking binding of the S protein to human angiotensin converting enzyme 2 (huACE2) . It was shown that such a binding event is a part of a multi-step process for a virus to enter cells and multiply (Hoffmann et al., 2020) .
  • the provided antibodies disclosed herein when appropriately humanized can be used to provide passive immunity to frontline healthcare workers to prevent infection.
  • compositions comprising the antibodies or antibody fragments of the present disclosure are also contemplated and can be used in the methods disclosed herein.
  • Pharmaceutical compositions can comprise one or more of the antibodies or antibody fragments described herein and a pharmaceutically acceptable carrier or excipient.
  • the carrier or excipient may facilitate administration, it should not itself induce the production of antibodies harmful to the subject or individual receiving the composition; nor should it be toxic.
  • Suitable carriers may be large, slowly metabolized macromolecules such as proteins, polypeptides, liposomes, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers and inactive virus particles, and are known to one of skill in the art.
  • the antibodies or an antigen binding fragments described herein, or the pharmaceutical compositions disclosed herein may be administered by any number of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intraperitoneal, intrathecal, intraventricular, transdermal, transcutaneous, topical, subcutaneous, intranasal, enteral, sublingual, intravaginal or rectal routes.
  • the therapeutic compositions may be prepared as injectables, either as liquid solutions or suspensions. Solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection may also be prepared.
  • the antibody, or an antigen binding fragment thereof, or pharmaceutical composition is administered intravenously. In another embodiment, the antibody, or an antigen binding fragment thereof, or pharmaceutical composition is administered by intravenous infusion.
  • Direct delivery of the compositions will generally be accomplished by injection, subcutaneously, intraperitoneally, intravenously or intramuscularly, or delivered to the interstitial space of a tissue.
  • the compositions can also be administered into a lesion.
  • Dosage treatment may be a single dose schedule or a multiple dose schedule.
  • Known antibody-based pharmaceuticals provide guidance relating to frequency of administration e.g., whether a pharmaceutical should be delivered daily, weekly, monthly, etc. Frequency and dosage may also depend on the severity of symptoms.
  • the active ingredient in the composition will be an antibody molecule, an antibody fragment or variants and derivatives thereof. As such, it will be susceptible to degradation in the gastrointestinal tract. Thus, if the composition is to be administered by a route using the gastrointestinal tract, the composition will need to contain agents which protect the antibody from degradation but which release the antibody once it has been absorbed from the gastrointestinal tract.
  • the methods of the present disclosure can use an antibody, or an antigen binding fragment thereof, as described above, alone or in combination with other pharmaceutically active compounds, to treat conditions such as those disclosed hereinabove.
  • the additional pharmaceutically active compound (s) can be administered simultaneously (either in the same dosage form or in separate dosage forms) or sequentially.
  • the present disclosure comprises methods for treating a condition by administering to the subject a therapeutically-effective amount of an antibody, or an antigen binding fragment thereof, of the present disclosure and one or more additional pharmaceutically active compounds.
  • provided antibodies disclosed herein can be used for identifying SARS-CoV-2 infected patients by specifically detecting the virus via its S protein.
  • Such a test is absolutely necessary to help protect frontline healthcare workers to isolate those who are infected by the virus and treat them before their illness worsen.
  • Epidemiologists can reliably identify infected subjects in hot spots to better measure the extent of the outbreaks, and government officials can use those results to help decide when and how to return residents to daily life.
  • Table 1 provides a summary of the SARS-CoV-2 S protein-specific antibodies described herein.
  • Example 1 Isolation of murine anti-SARS-CoV-2 S protein antibodies
  • Recombinant SARS-CoV-2 S protein (R683A, R685A) His tagged catalog no: SPN-C52H4 (ACROBiosystems, Beijing, China, SEQ ID NO: 2) was used to immunize young CD-1 mice each with 80 ⁇ g of the protein in Sigma Adjuvant (Sigma-Aldrich, St. Louis, MO) over a period of 35 days using a rapid immunization protocol of Antibody Solutions (Santa Clara, CA) . The lymph nodes were harvested on day 35. Single cell suspension of the lymph node was generated, and the suspension was filtered through a 70 ⁇ m mesh (BD Bioscience) to remove clumps.
  • the filtered lymphocyte suspension was enriched for plasma cells actively secreting IgGs using a kit based on cell surface expression of CD138 (Miltenyi, Auburn, CA) .
  • a kit based on cell surface expression of CD138 Miltenyi, Auburn, CA
  • freshly enriched plasma cells were deposited on a PDMS device to allow a single cell settled in the microwells on the device.
  • Antibody secreted from each plasma cell was captured on a derivatized microscope slide.
  • Antigen-specific antibody secreting cells were identified by interrogating the antibody capture slide with varying concentrations of fluorescently labeled full-length SARS-CoV-2 S protein tagged with His (ACROBiosystems, Beijing, China, catalog no: SPN-C52H4, SEQ ID NO: 2) and counter-screen with fluorescently labeled SARS-CoV-2 S protein RBD, His, Avitag (ACROBiosystems, Beijing, China, catalog no: SPD-C82E9, SEQ ID NO: 3) to detect recognizing and/or neutralizing antibodies. Labeling was done using a kit (AnaSpec, Fremont, CA, AS-72046, AnaTag TM HiLyte TM Fluor 555 Microscale Protein Labeling Kit *Ultra Convenient*) .
  • oligonucleotide microarray (Agilent, Santa Clara, CA) . This procedure was previously described in U.S. Patent No. 9,328,172.
  • the custom oligonucleotide microarray is prepared such that each feature contains not only a unique tag specifying its coordinate but also capture probes for all subclasses (1, 2a, 2b, and 3) of murine IgG heavy chain, murine Ig kappa light chain.
  • Captured mRNA on the custom microarray was further processed to synthesize cDNA of each mRNA incorporating the unique tag originally on each feature.
  • the cDNA is then amplify using a Taq polymerase (Promega, Madison, WI) and appropriate set of primers to allow amplification of the following genes: variable domain of IgG heavy chain subclasses and variable domain of Ig kappa light chain. Though now released from cells, these fragments of each gene are now labeled with the unique tag from the custom oligonucleotide microarray manifesting their originating locations.
  • the amplicons were further manipulated to have appropriate sequence attached at both ends to enable sequencing on an Illumina MiSeq instrument using 2 x 250 bp chemistry at SeqMatic LLC (Fremont, CA) .
  • V H or V L sequence containing the identified CDR3s was identified and the associated sequencing reads were assembled into full-length cDNA sequences for V H and V L .
  • the pair of full-length cDNA was correlated with the affinity measurements associated with each of the antigen-specific antibody spot.
  • Example 2 Molecular reconstruction and recombinant expression of anti-SARS-CoV-2 S antibodies
  • the paired V H and V L anti-SARS-CoV-2 S antibody sequences were used to synthesize corresponding gene fragments by a service provider according to the known art.
  • the resulting gene fragments were cloned into an appropriate plasmid vector and transfected into an appropriate mammalian host, such as HEK293, for recombinant expression to produce an antibody preparation in full-IgG format.
  • the antibody preparations were characterized by measurements at OD280 to assess the amount produced and by gel electrophoresis on PAGE to assess the size of the antibody chains produced.
  • Example 3 Characterization of recombinant anti-SARS-CoV-2 S antibodies
  • a select subset of anti-SARS-CoV-2 S antibodies were recombinantly expressed and used to assess affinity of the antibodies on a biolayer interferometry (BLI) instrument, such as an Octet RED96e, against recombinant SARS-CoV-2 S protein RBD His-tagged (catalog no: SPD-S52H6, ACROBiosystems, Beijing, China, SEQ ID NO: 3) by a method known in the art.
  • BLI biolayer interferometry
  • a subset of the recombinantly expressed anti-SARS-CoV-2 S antibodies were further characterized by epitope binning by BLI assay using a method known in the art.
  • a map of the epitope bins is shown in FIG. 1.
  • a subset of the recombinantly expressed anti-SARS-CoV-2 S antibodies were further characterized by assessing their neutralization activity using a preparation of SARS-CoV-2 reporter virus particles (RVPs, Integral Molecular, Philadelphia, PA, USA) representative of the D614G variant.
  • the RVPs are replication-incompetent pseudotyped virus particles that enable safe viral infectivity and neutralization assays.
  • These RVPs carry luciferase that acts as a reporter gene where infection of an appropriate host cell (a stable 293 cells stably transfected with a human ACE2 gene construct) will display bioluminescence.
  • Antibodies capable of blocking RVPs from entering the host cells showed no signals. The results of such neutralization assays are shown in FIG. 2.
  • a subset of the antibodies from the present disclosure will be modified to enhance binding to mucin glycoproteins produced by mucus-producing cells in the epithelium or submucosal glands.
  • One of the modifications is to remove terminal galactose from the antibodies by enzymatic digestion with beta1, 4-galactosidase (Gunn et al., 2016) .
  • beta1, 4-galactosidase Gibn et al., 2016
  • MUC16 Cat. No. 5609-MU-050, R&D Systems, Minneapolis, MN, USA
  • mice transgenic mouse line: K18-hACE2
  • SARS-CoV-2 spike pseudotyped lentivirus harboring a reporter luciferase gene mRNA (Cat. No. RVP-706, Integral Molecular, Philadelphia, PA, USA) representing the UK variant will be administered to the said treated mice intranasally (20 ⁇ L per nostril) .
  • bioluminescent imaging will be performed for each of the treated mouse. After bioluminescence measurement, the lungs will be dissected and also imaged. A separate cohort of transgenic mice will be similarly treated with only saline solution followed by intranasal administration of the pseudotyped lentivirus carrying the luciferase gene mRNA. The expected outcome will be that the group of mice treated with the enzyme digested antibodies will show no bioluminescence whereas the saline treated mice will show bioluminescence.
  • Antibodies recovered from the antibody campaign described above are listed herein.
  • the CDR sequences and the V H and V L sequences for the anti-SARS-CoV-2 S antibodies described herein are depicted in Tables 3 and 4, respectively.
  • a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission a study of a family cluster. The Lancet 395, 514–523.
  • Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. J. Immunol. Baltim. Md 1950 174, 4908–4915.
  • a DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 428, 561–564.

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Abstract

Provided are antibodies that specifically recognize SARS-CoV-2 S protein.

Description

ANTI-SARS CORONAVIRUS-2 SPIKE PROTEIN ANTIBODIES
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority to U.S. Provisional Application No. 63/030,016 filed 26 May 2020, which is incorporated herein by reference in its entirety for all purposes.
INCORPORATION OF SEQUENCE LISTING
The instant application contains a Sequence Listing which has been submitted via EFS-Web and is hereby incorporated by reference in its entirety. The ASCII copy, created on 25 0D\, 2021, is named ACB0014-401-PC_Sequence_Listing_ST25. txt, and is 305 kilobytes in size.
BACKGROUND
Coronaviruses (CoV) are frequent causes of the common cold, causing upper respiratory tract infection throughout the world in all age groups (Greenberg, 2011) . In contrast, the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic and cause severe respiratory diseases in afflicted individuals, SARS and MERS, respectively (Fehr et al., 2017) . MERS emerged in 2012 in Jeddah, Saudi Arabia. As of August 11, 2016, MERS-CoV infection has been identified in 1, 791 patients, with 640 deaths ( http: //www. who. int/emergencies/mers-cov/en/) . At present, no specific antivirals or approved vaccines are available to combat SARS nor MERS, and the SARS pandemic in 2002 and 2003 was finally stopped by conventional control measures and so was the MERS outbreaks.
A novel coronavirus, SARS-coronavirus 2 (SARS-CoV-2) , which is closely related to SARS-CoV, was detected in patients and is believed to be the etiologic agent of COVID-19 (Zhu et al., 2020) . Several factors, including symptoms similar to common old, government and public not taking the spread seriously, and presymptomatic transmission (Wei, 2020) , among others, contributed to the rapid transmission of COVID-19 throughout the world. As of April 15, 2020, there are 1,918,138 confirmed cases and 123, 126 associated deaths worldwide ( https: //covid19. who. int/) .
During the 2002-2003 SARS outbreak, isolation measures proved effective in bringing the outbreak under control and it appears the same strategy is going to work for the COVID-19 pandemic but very likely with grave economic consequences. Though there are a great number of interventions for COVID-19 under intense development (Zhang and Liu, 2020) , there are no established treatments available as of April 2020. Therefore, a targeted and effective treatment for COVID-19 remains highly desirable.
SARS-CoV-2 peak viral load is reached by about 5-6 days post-infection, thus offering an opportunity for effective post-exposure treatment (Pan et al., 2020) . One modality of treatment that may limit replication of the virus and thus its spread is passive immunization with neutralizing recombinant human monoclonal antibodies (mAbs) . Such a treatment during the prodromal phase of the disease could aid in rapid clearance of virus and limit poor clinical outcome and person to person spread, without the adverse effects associated with use of corticosteroids, animal sera, or human sera.
SARS-CoV-2 makes use of a densely glycosylated spike (S) protein to gain entry into host cells. The followings are findings with SARS-CoV but based on the close relatedness on the DNA sequence level, a lot of them will be relevant to SARS-CoV-2. The S protein is a trimeric class I fusion protein that exists in a metastable prefusion conformation that undergoes a dramatic structural rearrangement to fuse the viral membrane with the host-cell membrane (Li, 2016; Bosch et al., 2003) . This process is triggered when the Sl subunit binds to a host-cell receptor. Receptor binding destabilizes the prefusion trimer, resulting in shedding of the S1 subunit and transition of the S2 subunit to a stable post-fusion conformation (Walls et al., 2017) . In order to engage a host-cell receptor, the receptor-binding domain (RBD) of S1 undergoes hinge-like conformational movements that transiently hide or expose the determinants of receptor binding. The S2 domain of the S protein contributes to infection of the target cell by mediating fusion of viral and host membranes through a conformational change in which two conserved helical regions (HR1 and HR2) of the S protein are brought together to form a six-helix bundle fusion core (He et al., 2005a) .
The S protein serves as the main antigen that elicits protective immune responses, including neutralizing antibodies in infected humans and animals (Bisht et al., 2004; Buchholz et al., 2004; Cheng et al., 2005; Greenough et al., 2005; He et al., 2005b; Hofmann et al., 2004) . Immunization of mice with a DNA vaccine encoding the S sequence, devoid of the cytoplasmic  domain and/or the transmembrane domain, results in the development of neutralizing antibodies as well as both CD4+ and CD8+ T cell responses (Yang et al., 2004) . However, it is not the cellular, but the humoral (IgG) component of immunity that inhibits viral replication (Yang et al., 2004) . In fact, use of convalescent plasma has been quite successful in China (Duan et al., 2020) . Together, these studies show that primarily antibodies are responsible for protection against SARS-CoV replication and indicate the potential therapeutic value of passive transfer of neutralizing Abs against SARS-CoV. The immunogenic property of the S protein, including its ability to induce neutralizing antibodies and its essential role in viral attachment and fusion, make it an ideal target for developing effective immunotherapy against SARS-CoV-2 infection.
During an outbreak, the coronavirus can mutate and exhibit antigenic variation. In fact, sequence analysis indicated that the clinical isolates could be divided into early, middle, and late isolates (Sui et al., 2005) . The significance of this is demonstrated in the ability of later isolates to escape neutralization by a monoclonal antibody that effectively neutralized an earlier isolate (Yang et al., 2005) . Therefore, it is important to produce neutralizing mAbs that are effective against a wide range of clinical isolates with antigenic diversity. Because of the potential evolution of antigenic variants an effective passive therapy against SARS-CoV-2 will likely contain a cocktail of neutralizing Abs that target different epitopes and/or steps in the entry process, such as blocking receptor binding and fusion or Fc signaling.
Passive therapy with the appropriate anti-virus immunoglobulins-such as the ones disclosed herein-when appropriately humanized, can confer immediate protection. Accordingly, there remains an urgent need for potent, broad spectrum antibody therapeutics for use in treating SARS-CoV-2 infection.
SUMMARY
Provided are antibodies that recognize and specifically bind to SARS-CoV-2 S protein. In one embodiment, the disclosure provides an antibody that binds to SEQ ID NO: 1.
BRIEF DESCRIPTION OF THE SEQUENCES
TABLE 1.
SEQ ID NO. Description of sequence
1 SARS-CoV-2 S protein sequence
2 SARS-CoV-2 S protein S1 subunit His tagged protein sequence
3 SARS-CoV-2 S protein RBD, His tagged and Avitag protein sequence
4 SCT-Ma082 mature heavy chain variable domain protein sequence
5 SCT-Ma076 mature heavy chain variable domain protein sequence
6 SCT-Ma005 mature heavy chain variable domain protein sequence
7 SCT-Ma106 mature heavy chain variable domain protein sequence
8 SCT-Ma069 mature heavy chain variable domain protein sequence
9 SCT-Ma073 mature heavy chain variable domain protein sequence
10 SCT-Ma026 mature heavy chain variable domain protein sequence
11 SCT-Ma010 mature heavy chain variable domain protein sequence
12 SCT-Ma090 mature heavy chain variable domain protein sequence
13 SCT-Ma038 mature heavy chain variable domain protein sequence
14 SCT-Ma043 mature heavy chain variable domain protein sequence
15 SCT-Ma049 mature heavy chain variable domain protein sequence
15 SCT-Ma113 mature heavy chain variable domain protein sequence
16 SCT-Ma112 mature heavy chain variable domain protein sequence
17 SCT-Ma071 mature heavy chain variable domain protein sequence
18 SCT-Ma020 mature heavy chain variable domain protein sequence
19 SCT-Ma059 mature heavy chain variable domain protein sequence
20 SCT-Ma048 mature heavy chain variable domain protein sequence
21 SCT-Ma075 mature heavy chain variable domain protein sequence
22 SCT-Ma093 mature heavy chain variable domain protein sequence
23 SCT-Ma070 mature heavy chain variable domain protein sequence
24 SCT-Ma022 mature heavy chain variable domain protein sequence
24 SCT-Ma029 mature heavy chain variable domain protein sequence
25 SCT-Ma102 mature heavy chain variable domain protein sequence
26 SCT-Ma119 mature heavy chain variable domain protein sequence
27 SCT-Ma054 mature heavy chain variable domain protein sequence
28 SCT-Ma125 mature heavy chain variable domain protein sequence
29 SCT-Ma015 mature heavy chain variable domain protein sequence
30 SCT-Ma052 mature heavy chain variable domain protein sequence
31 SCT-Ma094 mature heavy chain variable domain protein sequence
32 SCT-Ma126 mature heavy chain variable domain protein sequence
33 SCT-Ma100 mature heavy chain variable domain protein sequence
34 SCT-Ma103 mature heavy chain variable domain protein sequence
35 SCT-Ma123 mature heavy chain variable domain protein sequence
36 SCT-Ma077 mature heavy chain variable domain protein sequence
37 SCT-Ma099 mature heavy chain variable domain protein sequence
38 SCT-Ma067 mature heavy chain variable domain protein sequence
39 SCT-Ma095 mature heavy chain variable domain protein sequence
40 SCT-Ma004 mature heavy chain variable domain protein sequence
41 SCT-Ma050 mature heavy chain variable domain protein sequence
42 SCT-Ma068 mature heavy chain variable domain protein sequence
43 SCT-Ma072 mature heavy chain variable domain protein sequence
44 SCT-Ma127 mature heavy chain variable domain protein sequence
45 SCT-Ma056 mature heavy chain variable domain protein sequence
46 SCT-Ma053 mature heavy chain variable domain protein sequence
47 SCT-Ma042 mature heavy chain variable domain protein sequence
48 SCT-Ma058 mature heavy chain variable domain protein sequence
49 SCT-Ma012 mature heavy chain variable domain protein sequence
49 SCT-Ma092 mature heavy chain variable domain protein sequence
50 SCT-Ma031 mature heavy chain variable domain protein sequence
51 SCT-Ma018 mature heavy chain variable domain protein sequence
52 SCT-Ma027 mature heavy chain variable domain protein sequence
53 SCT-Ma002 mature heavy chain variable domain protein sequence
54 SCT-Ma091 mature heavy chain variable domain protein sequence
55 SCT-Ma105 mature heavy chain variable domain protein sequence
56 SCT-Ma101 mature heavy chain variable domain protein sequence
57 SCT-Ma133 mature heavy chain variable domain protein sequence
58 SCT-Ma120 mature heavy chain variable domain protein sequence
59 SCT-Ma086 mature heavy chain variable domain protein sequence
60 SCT-Ma019 mature heavy chain variable domain protein sequence
61 SCT-Ma016 mature heavy chain variable domain protein sequence
62 SCT-Ma025 mature heavy chain variable domain protein sequence
63 SCT-Ma046 mature heavy chain variable domain protein sequence
64 SCT-Ma129 mature heavy chain variable domain protein sequence
65 SCT-Ma117 mature heavy chain variable domain protein sequence
66 SCT-Ma098 mature heavy chain variable domain protein sequence
67 SCT-Ma006 mature heavy chain variable domain protein sequence
68 SCT-Ma121 mature heavy chain variable domain protein sequence
69 SCT-Ma008 mature heavy chain variable domain protein sequence
70 SCT-Ma128 mature heavy chain variable domain protein sequence
71 SCT-Ma021 mature heavy chain variable domain protein sequence
71 SCT-Ma116 mature heavy chain variable domain protein sequence
71 SCT-Ma118 mature heavy chain variable domain protein sequence
72 SCT-Ma108 mature heavy chain variable domain protein sequence
73 SCT-Ma039 mature heavy chain variable domain protein sequence
74 SCT-Ma011 mature heavy chain variable domain protein sequence
75 SCT-Ma040 mature heavy chain variable domain protein sequence
76 SCT-Ma041 mature heavy chain variable domain protein sequence
77 SCT-Ma104 mature heavy chain variable domain protein sequence
78 SCT-Ma097 mature heavy chain variable domain protein sequence
79 SCT-Ma045 mature heavy chain variable domain protein sequence
80 SCT-Ma034 mature heavy chain variable domain protein sequence
81 SCT-Ma001 mature heavy chain variable domain protein sequence
82 SCT-Ma061 mature heavy chain variable domain protein sequence
83 SCT-Ma062 mature heavy chain variable domain protein sequence
84 SCT-Ma078 mature heavy chain variable domain protein sequence
85 SCT-Ma033 mature heavy chain variable domain protein sequence
86 SCT-Ma032 mature heavy chain variable domain protein sequence
87 SCT-Ma066 mature heavy chain variable domain protein sequence
88 SCT-Ma122 mature heavy chain variable domain protein sequence
89 SCT-Ma003 mature heavy chain variable domain protein sequence
90 SCT-Ma115 mature heavy chain variable domain protein sequence
91 SCT-Ma074 mature heavy chain variable domain protein sequence
92 SCT-Ma083 mature heavy chain variable domain protein sequence
93 SCT-Ma109 mature heavy chain variable domain protein sequence
94 SCT-Ma009 mature heavy chain variable domain protein sequence
95 SCT-Ma044 mature heavy chain variable domain protein sequence
96 SCT-Ma088 mature heavy chain variable domain protein sequence
97 SCT-Ma030 mature heavy chain variable domain protein sequence
98 SCT-Ma007 mature heavy chain variable domain protein sequence
99 SCT-Ma013 mature heavy chain variable domain protein sequence
100 SCT-Ma023 mature heavy chain variable domain protein sequence
101 SCT-Ma060 mature heavy chain variable domain protein sequence
102 SCT-Ma051 mature heavy chain variable domain protein sequence
103 SCT-Ma065 mature heavy chain variable domain protein sequence
104 SCT-Ma107 mature heavy chain variable domain protein sequence
105 SCT-Ma064 mature heavy chain variable domain protein sequence
106 SCT-Ma130 mature heavy chain variable domain protein sequence
107 SCT-Ma057 mature heavy chain variable domain protein sequence
107 SCT-Ma114 mature heavy chain variable domain protein sequence
108 SCT-Ma096 mature heavy chain variable domain protein sequence
109 SCT-Ma087 mature heavy chain variable domain protein sequence
110 SCT-Ma084 mature heavy chain variable domain protein sequence
111 SCT-Ma014 mature heavy chain variable domain protein sequence
112 SCT-Ma047 mature heavy chain variable domain protein sequence
113 SCT-Ma089 mature heavy chain variable domain protein sequence
114 SCT-Ma131 mature heavy chain variable domain protein sequence
115 SCT-Ma132 mature heavy chain variable domain protein sequence
116 SCT-Ma081 mature heavy chain variable domain protein sequence
117 SCT-Ma028 mature heavy chain variable domain protein sequence
118 SCT-Ma055 mature heavy chain variable domain protein sequence
119 SCT-Ma085 mature heavy chain variable domain protein sequence
120 SCT-Ma080 mature heavy chain variable domain protein sequence
121 SCT-Ma124 mature heavy chain variable domain protein sequence
122 SCT-Ma063 mature heavy chain variable domain protein sequence
123 SCT-Ma111 mature heavy chain variable domain protein sequence
124 SCT-Ma035 mature heavy chain variable domain protein sequence
125 SCT-Ma037 mature heavy chain variable domain protein sequence
126 SCT-Ma036 mature heavy chain variable domain protein sequence
127 SCT-Ma017 mature heavy chain variable domain protein sequence
128 SCT-Ma079 mature heavy chain variable domain protein sequence
129 SCT-Ma110 mature heavy chain variable domain protein sequence
130 SCT-Ma024 mature heavy chain variable domain protein sequence
131 SCT-Ma027 mature light chain variable domain protein sequence
132 SCT-Ma050 mature light chain variable domain protein sequence
133 SCT-Ma065 mature light chain variable domain protein sequence
134 SCT-Ma002 mature light chain variable domain protein sequence
134 SCT-Ma012 mature light chain variable domain protein sequence
135 SCT-Ma042 mature light chain variable domain protein sequence
135 SCT-Ma058 mature light chain variable domain protein sequence
136 SCT-Ma109 mature light chain variable domain protein sequence
137 SCT-Ma068 mature light chain variable domain protein sequence
138 SCT-Ma004 mature light chain variable domain protein sequence
138 SCT-Ma030 mature light chain variable domain protein sequence
138 SCT-Ma031 mature light chain variable domain protein sequence
138 SCT-Ma072 mature light chain variable domain protein sequence
138 SCT-Ma088 mature light chain variable domain protein sequence
138 SCT-Ma091 mature light chain variable domain protein sequence
139 SCT-Ma127 mature light chain variable domain protein sequence
140 SCT-Ma009 mature light chain variable domain protein sequence
140 SCT-Ma044 mature light chain variable domain protein sequence
141 SCT-Ma028 mature light chain variable domain protein sequence
142 SCT-Ma055 mature light chain variable domain protein sequence
143 SCT-Ma053 mature light chain variable domain protein sequence
143 SCT-Ma056 mature light chain variable domain protein sequence
144 SCT-Ma131 mature light chain variable domain protein sequence
145 SCT-Ma033 mature light chain variable domain protein sequence
146 SCT-Ma103 mature light chain variable domain protein sequence
146 SCT-Ma132 mature light chain variable domain protein sequence
147 SCT-Ma080 mature light chain variable domain protein sequence
148 SCT-Ma124 mature light chain variable domain protein sequence
149 SCT-Ma077 mature light chain variable domain protein sequence
150 SCT-Ma099 mature light chain variable domain protein sequence
151 SCT-Ma089 mature light chain variable domain protein sequence
152 SCT-Ma081 mature light chain variable domain protein sequence
153 SCT-Ma097 mature light chain variable domain protein sequence
153 SCT-Ma104 mature light chain variable domain protein sequence
154 SCT-Ma039 mature light chain variable domain protein sequence
155 SCT-Ma011 mature light chain variable domain protein sequence
156 SCT-Ma035 mature light chain variable domain protein sequence
157 SCT-Ma040 mature light chain variable domain protein sequence
158 SCT-Ma017 mature light chain variable domain protein sequence
158 SCT-Ma024 mature light chain variable domain protein sequence
158 SCT-Ma037 mature light chain variable domain protein sequence
158 SCT-Ma110 mature light chain variable domain protein sequence
159 SCT-Ma118 mature light chain variable domain protein sequence
160 SCT-Ma105 mature light chain variable domain protein sequence
161 SCT-Ma101 mature light chain variable domain protein sequence
162 SCT-Ma128 mature light chain variable domain protein sequence
163 SCT-Ma121 mature light chain variable domain protein sequence
164 SCT-Ma021 mature light chain variable domain protein sequence
165 SCT-Ma006 mature light chain variable domain protein sequence
165 SCT-Ma116 mature light chain variable domain protein sequence
166 SCT-Ma008 mature light chain variable domain protein sequence
167 SCT-Ma046 mature light chain variable domain protein sequence
168 SCT-Ma120 mature light chain variable domain protein sequence
169 SCT-Ma098 mature light chain variable domain protein sequence
170 SCT-Ma016 mature light chain variable domain protein sequence
171 SCT-Ma129 mature light chain variable domain protein sequence
172 SCT-Ma117 mature light chain variable domain protein sequence
173 SCT-Ma086 mature light chain variable domain protein sequence
174 SCT-Ma054 mature light chain variable domain protein sequence
175 SCT-Ma018 mature light chain variable domain protein sequence
176 SCT-Ma082 mature light chain variable domain protein sequence
177 SCT-Ma076 mature light chain variable domain protein sequence
178 SCT-Ma064 mature light chain variable domain protein sequence
178 SCT-Ma107 mature light chain variable domain protein sequence
178 SCT-Ma130 mature light chain variable domain protein sequence
179 SCT-Ma062 mature light chain variable domain protein sequence
180 SCT-Ma096 mature light chain variable domain protein sequence
181 SCT-Ma114 mature light chain variable domain protein sequence
182 SCT-Ma057 mature light chain variable domain protein sequence
183 SCT-Ma087 mature light chain variable domain protein sequence
184 SCT-Ma013 mature light chain variable domain protein sequence
184 SCT-Ma051 mature light chain variable domain protein sequence
185 SCT-Ma032 mature light chain variable domain protein sequence
186 SCT-Ma003 mature light chain variable domain protein sequence
186 SCT-Ma023 mature light chain variable domain protein sequence
186 SCT-Ma060 mature light chain variable domain protein sequence
186 SCT-Ma066 mature light chain variable domain protein sequence
186 SCT-Ma074 mature light chain variable domain protein sequence
187 SCT-Ma115 mature light chain variable domain protein sequence
188 SCT-Ma122 mature light chain variable domain protein sequence
189 SCT-Ma041 mature light chain variable domain protein sequence
190 SCT-Ma007 mature light chain variable domain protein sequence
191 SCT-Ma083 mature light chain variable domain protein sequence
192 SCT-Ma001 mature light chain variable domain protein sequence
192 SCT-Ma061 mature light chain variable domain protein sequence
193 SCT-Ma078 mature light chain variable domain protein sequence
194 SCT-Ma084 mature light chain variable domain protein sequence
195 SCT-Ma014 mature light chain variable domain protein sequence
196 SCT-Ma092 mature light chain variable domain protein sequence
197 SCT-Ma019 mature light chain variable domain protein sequence
198 SCT-Ma025 mature light chain variable domain protein sequence
199 SCT-Ma085 mature light chain variable domain protein sequence
200 SCT-Ma106 mature light chain variable domain protein sequence
201 SCT-Ma067 mature light chain variable domain protein sequence
202 SCT-Ma126 mature light chain variable domain protein sequence
203 SCT-Ma010 mature light chain variable domain protein sequence
204 SCT-Ma015 mature light chain variable domain protein sequence
204 SCT-Ma052 mature light chain variable domain protein sequence
204 SCT-Ma113 mature light chain variable domain protein sequence
204 SCT-Ma125 mature light chain variable domain protein sequence
205 SCT-Ma029 mature light chain variable domain protein sequence
206 SCT-Ma048 mature light chain variable domain protein sequence
207 SCT-Ma075 mature light chain variable domain protein sequence
208 SCT-Ma026 mature light chain variable domain protein sequence
209 SCT-Ma038 mature light chain variable domain protein sequence
209 SCT-Ma071 mature light chain variable domain protein sequence
209 SCT-Ma090 mature light chain variable domain protein sequence
210 SCT-Ma005 mature light chain variable domain protein sequence
210 SCT-Ma022 mature light chain variable domain protein sequence
210 SCT-Ma059 mature light chain variable domain protein sequence
210 SCT-Ma070 mature light chain variable domain protein sequence
211 SCT-Ma043 mature light chain variable domain protein sequence
211 SCT-Ma049 mature light chain variable domain protein sequence
212 SCT-Ma108 mature light chain variable domain protein sequence
213 SCT-Ma073 mature light chain variable domain protein sequence
214 SCT-Ma094 mature light chain variable domain protein sequence
215 SCT-Ma034 mature light chain variable domain protein sequence
216 SCT-Ma045 mature light chain variable domain protein sequence
217 SCT-Ma123 mature light chain variable domain protein sequence
218 SCT-Ma100 mature light chain variable domain protein sequence
219 SCT-Ma111 mature light chain variable domain protein sequence
220 SCT-Ma133 mature light chain variable domain protein sequence
221 SCT-Ma063 mature light chain variable domain protein sequence
222 SCT-Ma079 mature light chain variable domain protein sequence
223 SCT-Ma036 mature light chain variable domain protein sequence
224 SCT-Ma095 mature light chain variable domain protein sequence
225 SCT-Ma047 mature light chain variable domain protein sequence
226 SCT-Ma069 mature light chain variable domain protein sequence
227 SCT-Ma093 mature light chain variable domain protein sequence
228 SCT-Ma119 mature light chain variable domain protein sequence
229 SCT-Ma112 mature light chain variable domain protein sequence
230 SCT-Ma020 mature light chain variable domain protein sequence
231 SCT-Ma102 mature light chain variable domain protein sequence
542 SCT-Ma134 mature heavy chain variable domain protein sequence
543 SCT-Ma134 mature light chain variable domain protein sequence
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1. shows a map of epitope bins for a select subset of the anti-SARS-CoV-2 antibodies. Antibodies within a circle have either an identical epitope or epitopes that overlap to a substantial degree. For example, SCT-Ma009 and SCT-Ma058 may have identical or largely overlapping epitope whereas SCT-Ma087 definitely has an epitope distinct from that of SCT-Ma009.
FIG. 2. shows a titration plot of a select subset of antibodies with regards to their ability to inhibit the reporter virus particles (RVPs) to infect an appropriate host cell. Antibodies with their data points showing a significant level of inhibition at lower concentrations are more potent. The antibodies each with an IC50 that can be reasonably calculated from the data points are shown.
FIG. 3. shows a titration plot of a single antibody (SCT-Ma134) with regards to their ability to inhibit the RVPs representative of the South African SARS-CoV-2 variant (Benslimane et al., 2021) to infect an appropriate host cell. Antibodies with their data points showing a significant level of inhibition at lower concentrations are more potency. The antibodies each with an IC50 that can be reasonably calculated from the data points are shown. SCT-Ma134 is compared to Casirivimab, a potent monoclonal antibody developed by Regeneron Pharmaceuticals, Inc. (US Patent No. 10,975,139) . It shows that the potency of SCT-Ma134 was not affected by the South African SARS-CoV-2 variant mutations whereas Casirivimab’s potency was reduced.
DETAILED DESCRIPTION
The disclosure provides antibodies that bind to SARS-CoV-2 S protein. In one embodiment, the disclosure provides an isolated antibody that binds to SEQ ID NO: 1.
Antibodies
The disclosure provides antibodies that bind specifically to SEQ ID NO: 1. The term “antibody” as used herein, includes both full-length immunoglobulins and antibody fragments that bind to the same antigen. The antibodies can be, e.g., a monoclonal, polyclonal, chimeric, humanized, or single chain antibody. As used herein, the terms “antigen binding fragment, ” “fragment, ” and “antibody fragment” are used interchangeably to refer to any fragment that comprises a portion of a full-length antibody, generally at least the antigen binding portion or the variable region  thereof. Examples of antibody fragments include, but are not limited to, diabodies, single-chain antibody molecules, multi-specific antibodies, Fab, Fab’, F (ab') 2, Fv or scFv.
As used herein, the term “excipient” refers to a natural or synthetic substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations, or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility.
The phrase “therapeutically effective” is intended to qualify the amount of active ingredients used in the treatment of a disease or disorder or on the effecting of a clinical endpoint.
The term “therapeutically acceptable” refers to those compounds (or salts, prodrugs, tautomers, zwitterionic forms, etc. ) which are suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit/risk ratio, and are effective for their intended use.
The terms “treating, ” “treatment, ” and the like, as used herein, mean ameliorating a disease, so as to reduce, ameliorate, or eliminate its cause, its progression, its severity, or one or more of its symptoms, or otherwise beneficially alter the disease in a subject. Reference to “treating, ” or “treatment” of a patient is intended to include prophylaxis. Treatment may also be preemptive in nature, i.e., it may include prevention of disease in a subject exposed to or at risk for the disease. Prevention of a disease may involve complete protection from disease, for example as in the case of prevention of infection with a pathogen, or may involve prevention of disease progression. For example, prevention of a disease may not mean complete foreclosure of any effect related to the diseases at any level, but instead may mean prevention of the symptoms of a disease to a clinically significant or detectable level. Prevention of diseases may also mean prevention of progression of a disease to a later stage of the disease.
The terms “subject” and “patient” are used interchangeably herein to mean all mammals including humans. Examples of subjects include, but are not limited to, humans, monkeys, dogs, cats, horses, cows, goats, sheep, pigs, and rabbits. In one embodiment, the subject or patient is a human.
As used herein, “moderate severity COVID-19” refers to individuals who have evidence of lower respiratory disease by clinical assessment or imaging and a saturation of  oxygen (SpO 2) ≥94%on room air at sea level. While the diagnosis can be made on clinical grounds; chest imaging (radiograph, CT scan, ultrasound) may assist in diagnosis and identify or exclude pulmonary complications.
As used herein, “standard of care” or “SOC” refers to the diagnostic and treatment process that a clinician should follow for a certain type of patient, illness, or clinical circumstance. SOC may include administration of drugs that are being used in clinical practice for the treatment of COVID-19 (e.g. lopinavir/ritonavir; darunavir/cobicistat; hydroxy/chloroquine, tocilizumab, etc. ) , other than those used as part of another clinical trial.
As used herein, “acute respiratory distress syndrome” or “ARDS” is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath, rapid breathing, and bluish skin coloration.
In certain embodiments, provided antibodies disclosed herein can be used for identifying SARS-CoV-2 infected patients by specifically detecting the virus via its S protein. Such a test is necessary to help protect frontline healthcare workers to isolate those who are infected by the virus and treat them before their illness worsen. Epidemiologists can reliably identify infected subjects in hot spots to better measure the extent of the outbreaks, and government officials can use those results to help decide when and how to return residents to daily life. Most importantly, it is key to economic recovery because the infected population can be identified and quarantined to allow the rest of the society to function and operate.
In one aspect, the present disclosure provides a composition or kit comprising the antibody or antigen-binding fragment discussed above or herein in association with a further therapeutic agent.
In one aspect, the present disclosure provides a pharmaceutical composition comprising the antigen-binding protein, antibody or antigen-binding fragment discussed above or herein and a pharmaceutically acceptable carrier and, optionally, a further therapeutic agent. In some embodiments, the further therapeutic agent is an anti-viral drug or a vaccine. In some embodiments, the further therapeutic agent is selected from the group consisting of an anti-inflammatory agent, and an antimalarial agent. In some cases, the antimalarial agent is chloroquine or hydroxychloroquine. In some cases, the anti-inflammatory agent is an antibody, such as sarilumab, tocilizumab, or gimsilumab. In some embodiments, the further therapeutic  agent is a second antibody or antigen-binding fragment comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences of Table 3.
In one aspect, the present disclosure provides a pharmaceutical composition comprising an isolated antibody as discussed above or herein, and a pharmaceutically acceptable carrier or diluent. In some embodiments, the pharmaceutical composition comprises one or more excipients.
In some embodiments, the pharmaceutical composition further comprises a second therapeutic agent. In some cases, the second therapeutic agent is selected from the group consisting of: a second antibody, or an antigen-binding fragment thereof, that binds a SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 1, an anti-inflammatory agent, and an antimalarial agent.
The disclosure provides antibodies that bind specifically to SEQ ID NO: 1. The term “antibody” as used herein, includes both full-length immunoglobulins and antibody fragments that bind to the same antigens. The antibodies can be, e.g., a monoclonal, polyclonal, chimeric, humanized, or single chain antibody.
The provided antibodies may be used to diagnose, treat, or monitor infection by SARS-CoV-2 virus. In some embodiments, the antibodies or fragments thereof described herein may be used for various in vitro molecular biology applications such as, enzyme-linked immunosorbent assays (ELISA) , Western blots, immunohistochemistry, immunocytochemistry, flow cytometry and fluorescence-activated cell sorting (FACS) , immunoprecipitation, and/or enzyme-linked immunospot assays. In some embodiments, the antibodies or fragments thereof may be packaged in kits with or without additional reagents known to those of skill in the art for practicing any of the molecular biology techniques disclosed above.
In another aspect, the present disclosure provides a method of preventing or treating SARS-CoV-2 infection in a subject in need thereof, comprising administering to the subject a therapeutically or prophylactically effective amount of a pharmaceutical composition comprising one or more of the antibodies described herein. Such a method can comprise administration of any dose of the antibodies described herein effective for ameliorating or treating symptoms of SARS-CoV-2 infection.
In some embodiments, administration of a pharmaceutical composition comprising one or more of the antibodies described herein can be made to a subject exposed to  SARS-CoV-2. In some embodiments, the pharmaceutical compositions described herein can be administered alone or in combination with other therapies deemed appropriate by a clinician or practitioner. In some embodiments, the pharmaceutical compositions described herein may reduce the number of days of COVID-19 symptoms by one or more days, such as reducing symptoms by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 days.
In another aspect, the present disclosure provides a method of reducing, retarding, or otherwise inhibiting growth and/or replication of SARS-CoV-2 in an individual confirmed to have COVID-19 comprising administering a pharmaceutical composition comprising one or more of the antibodies described herein.
In some embodiments, the COVID-19 is of moderate severity. In some embodiments, administration of a prophylactic or therapeutic dose of one or more of the antibodies described herein is initiated within the earlier of 24 to 72 hours of illness onset or confirmation of the individual having COVID-19. In some embodiments, administration is initiated within the earlier of 24 hours of illness onset or confirmation of the individual having COVID-19.
In some embodiments, the individual is at an elevated risk of exposure to SARS-CoV-2. In some embodiments, the individual is a health care worker. In some embodiments, the individual is located in an area where ongoing community spread of SARS-CoV-2 has been reported. In some embodiments, the individual has been in close contacts with one or more persons with COVID-19.
In some embodiments, the individual is at an elevated risk of severe illness. In some embodiments, the individual is 60 years of age or older. In some embodiments, the individual has a serious chronic medical condition. In some embodiments, the chronic medical condition is chosen from pulmonary disease, diabetes mellitus (type 2) , requiring oral medication or insulin for treatment, hypertension, cardiovascular disease.
In some embodiments, the individual has a baseline blood pressure under 110 mmHg systolic at rest. In some embodiments, the individual has a body mass index ≥30.
In some embodiments, the method further comprises testing the individual for SARS-CoV-2 infection. In some embodiments, testing comprises testing nasopharyngeal and oropharyngeal swabs by real-time reverse-transcriptase–polymerase-chain-reaction (rRT-PCR) assay. A description of this assay and sequence information for the rRT-PCR panel primers and  probes are available on the CDC Laboratory Information website for 2019-nCoV (https: //www. cdc. gov/coronavirus/2019-nCoV/lab/index. html) , which is incorporated herein by reference in its entirety.
In some embodiments, the antibodies disclosed herein can be genetically engineered to enhance binding to a major component, mucin, of the mucosal membrane to enable a prophylactic application. This is accomplished by coating the upper airways of a subject with a single anti-SARS-CoV-2 neutralizing antibody or a panel of anti-SARS-CoV-2 antibodies disclosed herein to prevent the virus from reaching its target or directly neutralize infectious virus.
The disclosure provides the antibodies SCT-Ma001, SCT-Ma002, SCT-Ma003, SCT-Ma004, SCT-Ma005, SCT-Ma006, SCT-Ma007, SCT-Ma008, SCT-Ma009, SCT-Ma010, SCT-Ma011, SCT-Ma012, SCT-Ma013, SCT-Ma014, SCT-Ma015, SCT-Ma016, SCT-Ma017, SCT-Ma018, SCT-Ma019, SCT-Ma020, SCT-Ma021, SCT-Ma022, SCT-Ma023, SCT-Ma024, SCT-Ma025, SCT-Ma026, SCT-Ma027, SCT-Ma028, SCT-Ma029, SCT-Ma030, SCT-Ma031, SCT-Ma032, SCT-Ma033, SCT-Ma034, SCT-Ma035, SCT-Ma036, SCT-Ma037, SCT-Ma038, SCT-Ma039, SCT-Ma040, SCT-Ma041, SCT-Ma042, SCT-Ma043, SCT-Ma044, SCT-Ma045, SCT-Ma046, SCT-Ma047, SCT-Ma048, SCT-Ma049, SCT-Ma050, SCT-Ma051, SCT-Ma052, SCT-Ma053, SCT-Ma054, SCT-Ma055, SCT-Ma056, SCT-Ma057, SCT-Ma058, SCT-Ma059, SCT-Ma060, SCT-Ma061, SCT-Ma062, SCT-Ma063, SCT-Ma064, SCT-Ma065, SCT-Ma066, SCT-Ma067, SCT-Ma068, SCT-Ma069, SCT-Ma070, SCT-Ma071, SCT-Ma072, SCT-Ma073, SCT-Ma074, SCT-Ma075, SCT-Ma076, SCT-Ma077, SCT-Ma078, SCT-Ma079, SCT-Ma080, SCT-Ma081, SCT-Ma082, SCT-Ma083, SCT-Ma084, SCT-Ma085, SCT-Ma086, SCT-Ma087, SCT-Ma088, SCT-Ma089, SCT-Ma090, SCT-Ma091, SCT-Ma092, SCT-Ma093, SCT-Ma094, SCT-Ma095, SCT-Ma096, SCT-Ma097, SCT-Ma098, SCT-Ma099, SCT-Ma100, SCT-Ma101, SCT-Ma102, SCT-Ma103, SCT-Ma104, SCT-Ma105, SCT-Ma106, SCT-Ma107, SCT-Ma108, SCT-Ma109, SCT-Ma110, SCT-Ma111, SCT-Ma112, SCT-Ma113, SCT-Ma114, SCT-Ma115, SCT-Ma116, SCT-Ma117, SCT-Ma118, SCT-Ma119, SCT-Ma120, SCT-Ma121, SCT-Ma122, SCT-Ma123, SCT-Ma124, SCT-Ma125, SCT-Ma126, SCT-Ma127, SCT-Ma128, SCT-Ma129, SCT-Ma130, SCT-Ma131, SCT-Ma132, and SCT-Ma133. Each of these is a murine monoclonal antibody. In addition, SCT-Ma134 is a humanized version of SCT-Ma009.
Additionally, recombinant anti-SARS-CoV-2 S protein antibodies, such as chimeric and humanized monoclonal antibodies, comprising both human and non-human portions, which can be made using standard recombinant DNA techniques, are within the scope of the disclosure. Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques such as, for example, the methods described in U.S. Pat. No. 7,112,421; Better et al. (1988) Science 240: 1041-1043; or Liu et al. (1987) Proc. Natl. Acad. Sci. USA 84: 3439-3443.
Antibody Variable Domain Sequences
The antibodies of the disclosure may comprise the heavy chain variable domain sequences of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID  NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 542. The heavy chain variable domain sequences may consist essentially of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 542.
The antibodies of the disclosure may comprise the light chain variable domain sequences of ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID  NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, or SEQ ID NO: 543. The light chain variable domain sequences may consist essentially of ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID  NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, or SEQ ID NO: 543.
The disclosure also provides a variable domain sequence comprising a sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to a sequence selected from SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID  NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, or SEQ ID NO: 542. The disclosure also provides a variable domain sequence comprising a sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to a sequence selected from ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, or SEQ ID NO: 543.
The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 81 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 192. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 53 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 134. The  disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 89 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 40 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 6 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 210. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 67 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 165. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 98 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 190. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 69 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 166. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 94 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 140. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 11 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 203. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 74 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 155. The disclosure also provides antibodies  comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 49 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 134. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 99 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 184. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 111 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 195. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 29 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 204. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 61 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 170. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 127 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 158. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 51 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 175. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 60 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 197. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 18 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 230. The disclosure also provides antibodies comprising a heavy chain variable domain  sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 71 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 164. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 24 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 210. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 100 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 130 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 158. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 62 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 198. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 10 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 208. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 52 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 131. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 117 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 141. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 24 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 205. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at  least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 97 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 50 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 86 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 185. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 85 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 145. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 80 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 215. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 124 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 156. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 126 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 223. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 125 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 158. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 13 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 209. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 73 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 154. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 75 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 157. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 76 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 189. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 47 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 135. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 14 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 211. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 95 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 140. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 79 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 216. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 63 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 167. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 112 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 225. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 20 and a light  chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 206. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 15 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 211. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 41 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 132. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 102 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 184. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 30 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 204. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 46 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 143. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 27 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 174. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 118 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 142. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 45 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 143. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 107 and a light chain variable domain sequence  that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 182. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 48 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 135. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 19 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 210. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 101 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 82 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 192. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 83 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 179. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 122 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 221. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 105 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 178. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 103 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 133. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 87 and a light chain variable domain sequence that is at least 80%, at least 85%, at least  90%, or at least 95%identical to SEQ ID NO: 186. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 38 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 201. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 42 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 137. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 8 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 226. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 23 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 210. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 17 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 209. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 43 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 9 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 213. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 91 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 186. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 21 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ  ID NO: 207. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 5 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 177. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 36 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 149. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 84 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 193. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 128 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 222. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 120 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 147. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 116 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 152. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 4 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 176. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 92 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 191. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 110 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 194. The disclosure also provides antibodies  comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 119 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 199. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 59 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 173. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 109 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 183. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 96 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 113 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 151. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 12 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 209. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 54 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 138. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 49 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 196. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 22 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 227. The disclosure also provides antibodies comprising a heavy chain variable domain  sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 31 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 214. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 39 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 224. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 108 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 180. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 78 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 153. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 66 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 169. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 37 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 150. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 33 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 218. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 56 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 161. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 25 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 231. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at  least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 34 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 146. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 77 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 153. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 55 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 160. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 7 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 200. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 104 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 178. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 72 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 212. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 93 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 136. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 129 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 158. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 123 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 219. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 16 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 229. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 15 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 204. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 107 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 181. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 90 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 187. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 71 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 165. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 65 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 172. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 71 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 159. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 26 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 228. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 58 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 168. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 68 and a light  chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 163. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 88 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 188. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 35 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 217. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 121 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 148. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 28 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 204. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 32 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 202. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 44 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 139. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 70 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 162. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 64 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 171. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 106 and a light chain variable domain sequence  that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 178. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 114 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 144. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 115 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 146. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 57 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 220. The disclosure also provides antibodies comprising a heavy chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 542 and a light chain variable domain sequence that is at least 80%, at least 85%, at least 90%, or at least 95%identical to SEQ ID NO: 543.
The provided antibodies disclosed herein when appropriately humanized can be used to treat and prevent infection by SARS-CoV-2 by blocking binding of the S protein to human angiotensin converting enzyme 2 (huACE2) . It was shown that such a binding event is a part of a multi-step process for a virus to enter cells and multiply (Hoffmann et al., 2020) . The provided antibodies disclosed herein when appropriately humanized, can be used to provide passive immunity to frontline healthcare workers to prevent infection.
For discovering and developing antibody therapeutics to SARS-CoV-2 S protein generally known in the art, see U.S. Patent No. 10,975,139, which describes discovering and developing antibody therapeutics to SARS-CoV-2 and is incorporated herein in its entirety by reference.
Pharmaceutical Compositions
Pharmaceutical compositions comprising the antibodies or antibody fragments of the present disclosure are also contemplated and can be used in the methods disclosed herein. Pharmaceutical compositions can comprise one or more of the antibodies or antibody fragments described herein and a pharmaceutically acceptable carrier or excipient. Although the carrier or excipient may facilitate administration, it should not itself induce the production of antibodies  harmful to the subject or individual receiving the composition; nor should it be toxic. Suitable carriers may be large, slowly metabolized macromolecules such as proteins, polypeptides, liposomes, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers and inactive virus particles, and are known to one of skill in the art.
The antibodies or an antigen binding fragments described herein, or the pharmaceutical compositions disclosed herein, may be administered by any number of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intraperitoneal, intrathecal, intraventricular, transdermal, transcutaneous, topical, subcutaneous, intranasal, enteral, sublingual, intravaginal or rectal routes. Typically, the therapeutic compositions may be prepared as injectables, either as liquid solutions or suspensions. Solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection may also be prepared.
In one embodiment, the antibody, or an antigen binding fragment thereof, or pharmaceutical composition is administered intravenously. In another embodiment, the antibody, or an antigen binding fragment thereof, or pharmaceutical composition is administered by intravenous infusion.
Direct delivery of the compositions will generally be accomplished by injection, subcutaneously, intraperitoneally, intravenously or intramuscularly, or delivered to the interstitial space of a tissue. The compositions can also be administered into a lesion. Dosage treatment may be a single dose schedule or a multiple dose schedule. Known antibody-based pharmaceuticals provide guidance relating to frequency of administration e.g., whether a pharmaceutical should be delivered daily, weekly, monthly, etc. Frequency and dosage may also depend on the severity of symptoms.
It will be appreciated that the active ingredient in the composition will be an antibody molecule, an antibody fragment or variants and derivatives thereof. As such, it will be susceptible to degradation in the gastrointestinal tract. Thus, if the composition is to be administered by a route using the gastrointestinal tract, the composition will need to contain agents which protect the antibody from degradation but which release the antibody once it has been absorbed from the gastrointestinal tract.
The methods of the present disclosure can use an antibody, or an antigen binding fragment thereof, as described above, alone or in combination with other pharmaceutically active  compounds, to treat conditions such as those disclosed hereinabove. The additional pharmaceutically active compound (s) can be administered simultaneously (either in the same dosage form or in separate dosage forms) or sequentially. Accordingly, in one embodiment, the present disclosure comprises methods for treating a condition by administering to the subject a therapeutically-effective amount of an antibody, or an antigen binding fragment thereof, of the present disclosure and one or more additional pharmaceutically active compounds.
In certain aspects, provided antibodies disclosed herein can be used for identifying SARS-CoV-2 infected patients by specifically detecting the virus via its S protein. Such a test is absolutely necessary to help protect frontline healthcare workers to isolate those who are infected by the virus and treat them before their illness worsen. Epidemiologists can reliably identify infected subjects in hot spots to better measure the extent of the outbreaks, and government officials can use those results to help decide when and how to return residents to daily life. Most importantly, it is key to economic recovery because the infected population can be identified and quarantined to allow the rest of the society to function and operate.
Table 1 provides a summary of the SARS-CoV-2 S protein-specific antibodies described herein.
EXAMPLES
The following example is put forth so as to provide those of ordinary skill in the art with a complete description of how to make and use the present disclosure, and is not intended to limit the scope of what the inventors regard as their disclosure nor is it intended to represent that the experiment below is all or the only experiment that could be performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g. amounts, temperature, etc. ) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric.
Example 1: Isolation of murine anti-SARS-CoV-2 S protein antibodies
Immunization, &single cell suspension generation
Recombinant SARS-CoV-2 S protein (R683A, R685A) His tagged catalog no: SPN-C52H4 (ACROBiosystems, Beijing, China, SEQ ID NO: 2) was used to immunize young CD-1 mice each with 80 μg of the protein in Sigma Adjuvant 
Figure PCTCN2021096185-appb-000001
 (Sigma-Aldrich, St.  Louis, MO) over a period of 35 days using a rapid immunization protocol of Antibody Solutions (Santa Clara, CA) . The lymph nodes were harvested on day 35. Single cell suspension of the lymph node was generated, and the suspension was filtered through a 70 μm mesh (BD Bioscience) to remove clumps.
Plasma cell isolation, antibody capture, and antigen interrogation
The filtered lymphocyte suspension was enriched for plasma cells actively secreting IgGs using a kit based on cell surface expression of CD138 (Miltenyi, Auburn, CA) . Using a method described in U.S. Patent No. 9,328,172, freshly enriched plasma cells were deposited on a PDMS device to allow a single cell settled in the microwells on the device. Antibody secreted from each plasma cell was captured on a derivatized microscope slide. Antigen-specific antibody secreting cells were identified by interrogating the antibody capture slide with varying concentrations of fluorescently labeled full-length SARS-CoV-2 S protein tagged with His (ACROBiosystems, Beijing, China, catalog no: SPN-C52H4, SEQ ID NO: 2) and counter-screen with fluorescently labeled SARS-CoV-2 S protein RBD, His, Avitag (ACROBiosystems, Beijing, China, catalog no: SPD-C82E9, SEQ ID NO: 3) to detect recognizing and/or neutralizing antibodies. Labeling was done using a kit (AnaSpec, Fremont, CA, AS-72046, AnaTag TM HiLyte TM Fluor 555 Microscale Protein Labeling Kit *Ultra Convenient*) .
mRNA capture
After antibody capture, the medium was removed, and replaced with lysis buffer followed by prompt closure of the top of the microwells with a custom oligonucleotide microarray (Agilent, Santa Clara, CA) . This procedure was previously described in U.S. Patent No. 9,328,172. The custom oligonucleotide microarray is prepared such that each feature contains not only a unique tag specifying its coordinate but also capture probes for all subclasses (1, 2a, 2b, and 3) of murine IgG heavy chain, murine Ig kappa light chain.
cDNA synthesis, PCR amplification, and Next Generation Sequencing
Captured mRNA on the custom microarray was further processed to synthesize cDNA of each mRNA incorporating the unique tag originally on each feature. The cDNA is then amplify using a Taq polymerase (Promega, Madison, WI) and appropriate set of primers to allow amplification of the following genes: variable domain of IgG heavy chain subclasses and variable domain of Ig kappa light chain. Though now released from cells, these fragments of  each gene are now labeled with the unique tag from the custom oligonucleotide microarray manifesting their originating locations. The amplicons were further manipulated to have appropriate sequence attached at both ends to enable sequencing on an Illumina MiSeq instrument using 2 x 250 bp chemistry at SeqMatic LLC (Fremont, CA) .
Bioinformatic analysis of images and DNA sequences
Sequencing reads from MiSeq were processed and the embedded tag in each read was identified and converted into coordinates. The coordinates were plotted to yield a synthetic map of the mRNA recovered. Most of the coordinates form clusters that designate the location of the originating cell for the recovered mRNA sequences. Next, CDR3 motif present in each read with the coordinates was identified and collated according to the clusters that matched the location of an antibody spot visualized by an appropriate fluorescently labeled secondary antibody. Identical or nearly identical CDR3s for a given antibody spot were organized and form consistent pair of V H and V L sequences. The remaining part of V H or V L sequence containing the identified CDR3s was identified and the associated sequencing reads were assembled into full-length cDNA sequences for V H and V L. The pair of full-length cDNA was correlated with the affinity measurements associated with each of the antigen-specific antibody spot.
Example 2: Molecular reconstruction and recombinant expression of anti-SARS-CoV-2 S antibodies
The paired V H and V L anti-SARS-CoV-2 S antibody sequences were used to synthesize corresponding gene fragments by a service provider according to the known art. The resulting gene fragments were cloned into an appropriate plasmid vector and transfected into an appropriate mammalian host, such as HEK293, for recombinant expression to produce an antibody preparation in full-IgG format. The antibody preparations were characterized by measurements at OD280 to assess the amount produced and by gel electrophoresis on PAGE to assess the size of the antibody chains produced.
Example 3: Characterization of recombinant anti-SARS-CoV-2 S antibodies
A select subset of anti-SARS-CoV-2 S antibodies were recombinantly expressed and used to assess affinity of the antibodies on a biolayer interferometry (BLI) instrument, such as an Octet RED96e, against recombinant SARS-CoV-2 S protein RBD His-tagged (catalog no:  SPD-S52H6, ACROBiosystems, Beijing, China, SEQ ID NO: 3) by a method known in the art. The affinity measurements against the 2 proteins described above are shown in table 2.
A subset of the recombinantly expressed anti-SARS-CoV-2 S antibodies were further characterized by epitope binning by BLI assay using a method known in the art. A map of the epitope bins is shown in FIG. 1.
A subset of the recombinantly expressed anti-SARS-CoV-2 S antibodies were further characterized by assessing their neutralization activity using a preparation of SARS-CoV-2 reporter virus particles (RVPs, Integral Molecular, Philadelphia, PA, USA) representative of the D614G variant. The RVPs are replication-incompetent pseudotyped virus particles that enable safe viral infectivity and neutralization assays. These RVPs carry luciferase that acts as a reporter gene where infection of an appropriate host cell (a stable 293 cells stably transfected with a human ACE2 gene construct) will display bioluminescence. Antibodies capable of blocking RVPs from entering the host cells showed no signals. The results of such neutralization assays are shown in FIG. 2.
Example 4: Prophylactic application of anti-SARS-CoV-2 antibodies
A subset of the antibodies from the present disclosure will be modified to enhance binding to mucin glycoproteins produced by mucus-producing cells in the epithelium or submucosal glands. One of the modifications is to remove terminal galactose from the antibodies by enzymatic digestion with beta1, 4-galactosidase (Gunn et al., 2016) . After such a modification of the glycan structure on the antibodies, we will be able to demonstrate enhanced binding to MUC16 (Cat. No. 5609-MU-050, R&D Systems, Minneapolis, MN, USA) compared to the undigested antibodies.
To test whether antibodies introduced intranasally will be able to provide protection in vivo, a mouse model (transgenic mouse line: K18-hACE2) that supports SARS-CoV-2 infection will be used (Jackson Laboratory) . Antibodies from the present disclosure will be administered to K18-hACE2 mice intranasally (20 μL per nostril) . Ten (10) hours after antibody administration, SARS-CoV-2 spike pseudotyped lentivirus harboring a reporter luciferase gene mRNA (Cat. No. RVP-706, Integral Molecular, Philadelphia, PA, USA) representing the UK variant will be administered to the said treated mice intranasally (20 μL per nostril) . Seven (7) days after intranasal administration of the pseudotyped lentivirus carrying the  luciferase gene mRNA, bioluminescent imaging will be performed for each of the treated mouse. After bioluminescence measurement, the lungs will be dissected and also imaged. A separate cohort of transgenic mice will be similarly treated with only saline solution followed by intranasal administration of the pseudotyped lentivirus carrying the luciferase gene mRNA. The expected outcome will be that the group of mice treated with the enzyme digested antibodies will show no bioluminescence whereas the saline treated mice will show bioluminescence.
Antibodies recovered from the antibody campaign described above are listed herein. The CDR sequences and the V H and V L sequences for the anti-SARS-CoV-2 S antibodies described herein are depicted in Tables 3 and 4, respectively.
TABLE 2.
Figure PCTCN2021096185-appb-000002
TABLE 3.
Figure PCTCN2021096185-appb-000003
Figure PCTCN2021096185-appb-000004
Figure PCTCN2021096185-appb-000005
Figure PCTCN2021096185-appb-000006
Figure PCTCN2021096185-appb-000007
TABLE 4.
Figure PCTCN2021096185-appb-000008
Figure PCTCN2021096185-appb-000009
Figure PCTCN2021096185-appb-000010
Figure PCTCN2021096185-appb-000011
Figure PCTCN2021096185-appb-000012
Figure PCTCN2021096185-appb-000013
Figure PCTCN2021096185-appb-000014
Figure PCTCN2021096185-appb-000015
Figure PCTCN2021096185-appb-000016
The preceding merely illustrates the principles of the disclosure. It will be appreciated that those skilled in the art will be able to devise various arrangements which, although not explicitly described or shown herein, embody the principles of the disclosure and are included within its spirit and scope. Furthermore, all examples and conditional language recited herein are principally intended to aid the reader in understanding the principles of the disclosure and the concepts contributed by the inventors to furthering the art and are to be construed as being without limitation to such specifically recited examples and conditions. Moreover, all statements herein reciting principles, aspects, and embodiments of the disclosure as well as specific examples thereof, are intended to encompass both structural and functional equivalents thereof. Additionally, it is intended that such equivalents include both currently known equivalents and equivalents developed in the future, i.e., any elements developed that perform the same function, regardless of structure. The scope of the present disclosure, therefore, is not intended to be limited to the exemplary embodiments shown and described herein. Rather, the scope and spirit of present disclosure is embodied by the appended claims.
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Claims (23)

  1. An antibody that binds SARS-CoV-2 S protein (SEQ ID NO: 1) comprising:
    a) a HCDR1 having the amino acid sequence of SEQ ID NO: 251, a HCDR2 having the amino acid sequence of SEQ ID NO: 252, a HCDR3 having the amino acid sequence of SEQ ID NO: 253, a LCDR1 having the amino acid sequence of SEQ ID NO: 453, a LCDR2 having the amino acid sequence of SEQ ID NO: 441, and a LCDR3 having the amino acid sequence of SEQ ID NO: 445; or
    b) a HCDR1 having the amino acid sequence of SEQ ID NO: 235, a HCDR2 having the amino acid sequence of SEQ ID NO: 322, a HCDR3 having the amino acid sequence of SEQ ID NO: 241, a LCDR1 having the amino acid sequence of SEQ ID NO: 440, a LCDR2 having the amino acid sequence of SEQ ID NO: 441, and a LCDR3 having the amino acid sequence of SEQ ID NO: 489; or
    c) a HCDR1 having the amino acid sequence of SEQ ID NO: 434, a HCDR2 having the amino acid sequence of SEQ ID NO: 435, a HCDR3 having the amino acid sequence of SEQ ID NO: 436, a LCDR1 having the amino acid sequence of SEQ ID NO: 484, a LCDR2 having the amino acid sequence of SEQ ID NO: 454, and a LCDR3 having the amino acid sequence of SEQ ID NO: 541; or
    d) a HCDR1 having the amino acid sequence of SEQ ID NO: 251, a HCDR2 having the amino acid sequence of SEQ ID NO: 252, a HCDR3 having the amino acid sequence of SEQ ID NO: 253, a LCDR1 having the amino acid sequence of SEQ ID NO: 453, a LCDR2 having the amino acid sequence of SEQ ID NO: 441, and a LCDR3 having the amino acid sequence of SEQ ID NO: 445.
  2. The antibody of claim 1, wherein the HCDR1 has the amino acid sequence of SEQ ID NO: 251, the HCDR2 has the amino acid sequence of SEQ ID NO: 252, the HCDR3 has the amino acid sequence of SEQ ID NO: 253, the LCDR1 has the amino acid sequence of SEQ ID NO: 453, the LCDR2 has the amino acid sequence of SEQ ID NO: 441, and the LCDR3 has the amino acid sequence of SEQ ID NO: 445.
  3. The antibody of claim 1, wherein the HCDR1 has the amino acid sequence of SEQ ID  NO: 235, the HCDR2 has the amino acid sequence of SEQ ID NO: 322, the HCDR3 has the amino acid sequence of SEQ ID NO: 241, the LCDR1 has the amino acid sequence of SEQ ID NO: 440, the LCDR2 has the amino acid sequence of SEQ ID NO: 441, and the LCDR3 has the amino acid sequence of SEQ ID NO: 489.
  4. The antibody of claim 1, wherein the HCDR1 has the amino acid sequence of SEQ ID NO: 434, the HCDR2 has the amino acid sequence of SEQ ID NO: 435, the HCDR3 has the amino acid sequence of SEQ ID NO: 436, the LCDR1 has the amino acid sequence of SEQ ID NO: 484, the LCDR2 has the amino acid sequence of SEQ ID NO: 454, and the LCDR3 has the amino acid sequence of SEQ ID NO: 541.
  5. The antibody of claim 1, wherein the HCDR1 has the amino acid sequence of SEQ ID NO: 251, the HCDR2 has the amino acid sequence of SEQ ID NO: 252, the HCDR3 has the amino acid sequence of SEQ ID NO: 253, the LCDR1 has the amino acid sequence of SEQ ID NO: 453, the LCDR2 has the amino acid sequence of SEQ ID NO: 441, and the LCDR3 has the amino acid sequence of SEQ ID NO: 445.
  6. An antibody that binds human Spike (SEQ ID NO: 1) comprising:
    a) a VH having the amino acid sequence of SEQ ID NO: 94, and a VL having the amino acid sequence of SEQ ID NO: 140; or
    b) a VH having the amino acid sequence of SEQ ID NO: 48, and a VL having the amino acid sequence of SEQ ID NO: 135; or
    c) a VH having the amino acid sequence of SEQ ID NO: 57, and a VL having the amino acid sequence of SEQ ID NO: 220; or
    d) a VH having the amino acid sequence of SEQ ID NO: 542, and a VL having the amino acid sequence of SEQ ID NO: 543.
  7. The antibody of claim 6, wherein the VH has the amino acid sequence of SEQ ID NO: 94, and the VL has the amino acid sequence of SEQ ID NO: 140.
  8. The antibody of claim 6, wherein the VH has the amino acid sequence of SEQ ID NO: 48, and the VL has the amino acid sequence of SEQ ID NO: 135.
  9. The antibody of claim 6, wherein the VH has the amino acid sequence of SEQ ID NO: 57, and the VL has the amino acid sequence of SEQ ID NO: 220.
  10. The antibody of claim 6, wherein the VH has the amino acid sequence of SEQ ID NO: 542, and the VL has the amino acid sequence of SEQ ID NO: 543.
  11. An antibody that binds human Spike (SEQ ID NO: 1) comprising:
    a) a heavy-chain comprising the amino acid sequence of SEQ ID NO: 94 and a light-chain comprising the amino acid sequence of SEQ ID NO: 140; or
    b) a heavy-chain comprising the amino acid sequence of SEQ ID NO: 48 and a light-chain comprising the amino acid sequence of SEQ ID NO: 135; or
    c) a heavy-chain comprising the amino acid sequence of SEQ ID NO: 57 and a light-chain comprising the amino acid sequence of SEQ ID NO: 220; or
    d) a heavy-chain comprising the amino acid sequence of SEQ ID NO: 542 and a light-chain comprising the amino acid sequence of SEQ ID NO: 543.
  12. The antibody of claim 11, wherein the heavy-chain comprises the amino acid sequence of SEQ ID NO: 94 and the light-chain comprises the amino acid sequence of SEQ ID NO: 140.
  13. The antibody of claim 11, wherein the heavy-chain comprises the amino acid sequence of SEQ ID NO: 48 and the light-chain comprises the amino acid sequence of SEQ ID NO: 135.
  14. The antibody of claim 11, wherein the heavy-chain comprises the amino acid sequence of SEQ ID NO: 57 and the light-chain comprises the amino acid sequence of SEQ ID NO: 220.
  15. The antibody of claim 11, wherein the heavy-chain comprises the amino acid sequence of SEQ ID NO: 542 and the light-chain comprises the amino acid sequence of SEQ ID NO: 543.
  16. A pharmaceutical composition comprising the antibody of any of claims 1-15.
  17. A kit comprising the antibody of any of claims 1-15.
  18. A method of preventing or treating SARS-CoV-2 infection in a subject exposed to SARS-CoV-2 comprising administering the pharmaceutical composition of claim 16.
  19. The method of claim 15, wherein the pharmaceutical composition is administered via subcutaneous, intravenous, parenteral, or intramuscular routes.
  20. The method of claim 19, wherein the pharmaceutical composition is administered via subcutaneous injection or intravenous infusion.
  21. A method of reducing, retarding, or otherwise inhibiting growth and/or replication of SARS-CoV-2 in an individual confirmed to have COVID-19 comprising administering the pharmaceutical composition of claim 16.
  22. A method of treating an infection by SARS-CoV-2 virus, comprising administering to a subject in need thereof an antibody molecule capable of binding to SARS-CoV-2 S protein in an amount effective to treat COVID-19, wherein the antibody molecule comprises:
    a) a heavy chain variable region (VH) comprising a HCDR1 amino acid sequence of SEQ ID NO: 251; a HCDR2 amino acid sequence of SEQ ID NO: 252; and a HCDR3 amino acid sequence of SEQ ID NO: 253; and a light chain variable region (VL) comprising a LCDR1 amino acid sequence of SEQ ID NO: 453, a LCDR2 amino acid sequence of SEQ ID NO: 441, and a LCDR3 amino acid sequence of SEQ ID NO: 445;
    b) a heavy chain variable region (VH) comprising a HCDR1 amino acid sequence of SEQ ID NO: 235; a HCDR2 amino acid sequence of SEQ ID NO: 322; and a HCDR3 amino acid sequence of SEQ ID NO: 241; and a light chain variable  region (VL) comprising a LCDR1 amino acid sequence of SEQ ID NO: 440, a LCDR2 amino acid sequence of SEQ ID NO: 441, and a LCDR3 amino acid sequence of SEQ ID NO: 489; and
    c) a heavy chain variable region (VH) comprising a HCDR1 amino acid sequence of SEQ ID NO: 434; a HCDR2 amino acid sequence of SEQ ID NO: 435; and a HCDR3 amino acid sequence of SEQ ID NO: 436; and a light chain variable region (VL) comprising a LCDR1 amino acid sequence of SEQ ID NO: 484, a LCDR2 amino acid sequence of SEQ ID NO: 454, and a LCDR3 amino acid sequence of SEQ ID NO: 541.
  23. A method of preventing an infection by SARS-CoV-2 virus, comprising administering intranasally to a subject thereof an antibody molecule or a panel of antibody molecules capable of binding to SARS-CoV-2 S protein in an amount effective to block infection through the upper airways, wherein the antibody molecule comprises:
    a) a heavy chain variable region (VH) comprising a HCDR1 amino acid sequence of SEQ ID NO: 251; a HCDR2 amino acid sequence of SEQ ID NO: 252; and a HCDR3 amino acid sequence of SEQ ID NO: 253; and a light chain variable region (VL) comprising a LCDR1 amino acid sequence of SEQ ID NO: 453, a LCDR2 amino acid sequence of SEQ ID NO: 441, and a LCDR3 amino acid sequence of SEQ ID NO: 445;
    b) a heavy chain variable region (VH) comprising a HCDR1 amino acid sequence of SEQ ID NO: 235; a HCDR2 amino acid sequence of SEQ ID NO: 322; and a HCDR3 amino acid sequence of SEQ ID NO: 241; and a light chain variable region (VL) comprising a LCDR1 amino acid sequence of SEQ ID NO: 440, a LCDR2 amino acid sequence of SEQ ID NO: 441, and a LCDR3 amino acid sequence of SEQ ID NO: 489;
    c) a heavy chain variable region (VH) comprising a HCDR1 amino acid sequence of SEQ ID NO: 434; a HCDR2 amino acid sequence of SEQ ID NO: 435; and a HCDR3 amino acid sequence of SEQ ID NO: 436; and a light chain variable region (VL) comprising a LCDR1 amino acid sequence of SEQ ID NO: 484, a  LCDR2 amino acid sequence of SEQ ID NO: 454, and a LCDR3 amino acid sequence of SEQ ID NO: 541.
PCT/CN2021/096185 2020-05-26 2021-05-26 Anti-sars coronavirus-2 spike protein antibodies WO2021239014A1 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023042235A1 (en) * 2021-09-16 2023-03-23 Takis S.R.L. Antibodies against sars-cov-2 and uses thereof in the medical field
WO2023122786A3 (en) * 2021-12-23 2023-09-14 Novavax, Inc. ANTI-SARS-CoV-2 SPIKE (S) ANTIBODIES AND THEIR USE IN TREATING COVID-19

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BOORLA VEDA SHEERSH, CHOWDHURY RATUL, MARANAS COSTAS D.: "De novo design of high-affinity antibody variable regions (Fv) against the SARS-CoV-2 spike protein", BIORXIV, 11 April 2020 (2020-04-11), pages 1 - 13, XP055861231, DOI: 10.1101/2020.04.09.034868 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023042235A1 (en) * 2021-09-16 2023-03-23 Takis S.R.L. Antibodies against sars-cov-2 and uses thereof in the medical field
WO2023122786A3 (en) * 2021-12-23 2023-09-14 Novavax, Inc. ANTI-SARS-CoV-2 SPIKE (S) ANTIBODIES AND THEIR USE IN TREATING COVID-19

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