WO2022026775A1

WO2022026775A1 - Compositions and methods for targeting coronavirus

Info

Publication number: WO2022026775A1
Application number: PCT/US2021/043799
Authority: WO
Inventors: Erin STEPHENS; Melanie P. MATHEU
Original assignee: Prellis Biologics, Inc
Priority date: 2020-07-30
Filing date: 2021-07-29
Publication date: 2022-02-03

Abstract

The present disclosure provides compositions (e.g., antibodies and formulations) and methods for targeting a coronavirus (e.g., SARS-CoV-2). Such antibodies may be incorporated into formulations and/or pharmaceutical compositions, for example for the treatment for or protection against diseases that may be caused by a coronavirus, such as COVID-19.

Description

COMPOSITIONS AND METHODS FOR TARGETING CORONA VIRUS

CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Patent Application No.

63/058,097 filed on July 30, 2020 which is entirely incorporated herein by reference.

BACKGROUND

[0002] Viruses are small infectious agents that can enter a living cell of an organism, and can cause disease in the organism and spread between organisms. The mechanism by which a virus can cause disease can vary between viruses, and can include cell lysis and/or cell death. [0003] Coronaviruses are a group of related viruses that can cause disease, for example in mammals and birds. Coronaviruses can cause respiratory tract infections, such as those causing pneumonia-like diseases, that can range from mild to lethal.

[0004] SARS-CoV-2 is a coronavirus responsible for a pandemic of a respiratory disease,

COVID-19. Since the outbreak of this virus in Wuhan, Hubei, China, and a pandemic recognized by the World Health Organization on March 11, 2020, the COVID-19 pandemic is still not eradicated even with the roll out of various vaccination programs worldwide. The range of the severity of COVID-19 is large, and ranges from asymptomatic to death among unvaccinated population. With vaccinated population, it remains unclear how effective current vaccines are against various COVID-19 variants. Many fully vaccinated people have been reported to be infected with the Delta variant (also known as B.1.617.2.1 or AY.1). Therefore, effective treatment, such as antibody treatment against COVID-19 is needed.

SUMMARY

[0005] In an aspect, provided herein are formulations for treatment of an infectious disease comprising a therapeutically effective amount of an antibody comprising a peptide or a polypeptide that is at least about 70% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935. In some embodiments, the peptide or the polypeptide is at least about 80% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935. In some embodiments, the peptide or the polypeptide is at least about 85% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935. In some embodiments, the peptide or the polypeptide is at least about 90% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935. In some embodiments, the peptide or the polypeptide is at least about 95% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935.

[0006] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467. In some embodiments, the peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467. In some embodiments, the peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467. In some embodiments, the peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467. In some embodiments, peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467. [0007] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990. In some embodiments, the peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990. In some embodiments, the peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990. In some embodiments, the peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990. In some embodiments, the peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.

1468 - 1990.

[0008] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702. In some embodiments, the peptide or the polypeptide is at least about 80% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702. In some embodiments, the peptide or the polypeptide is at least about 85% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702. In some embodiments, the peptide or the polypeptide is at least about 90% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702. In some embodiments, the peptide or the polypeptide is at least about 95% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702. [0009] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962. In some embodiments, the peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962. In some embodiments, the peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962. In some embodiments, the peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962. In some embodiments, the peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962.

[0010] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of sequences SEQ ID NOS. 2963 - 3221, for a treatment of an infectious disease. In some embodiments, the peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2963 - 3221. In some embodiments, the peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2963 - 3221. In some embodiments, the peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2963 -

3221. In some embodiments, the peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2963 - 3221.

[0011] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of sequences SEQ ID NOS. 3222 - 6329, for a treatment of an infectious disease. In some embodiments, the peptide or the polypeptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 3222 - 6329. In some embodiments, the peptide or the polypeptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 3222 - 6329. In some embodiments, the peptide or the polypeptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 3222 - 6329. In some embodiments, the peptide or the polypeptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 3222 - 6329.

[0012] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876. In some embodiments, the peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876. In some embodiments, the peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876. In some embodiments, the peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876. In some embodiments, the peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.

6330 - 6876.

[0013] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of sequences SEQ ID NOS. 6877 - 7418, for a treatment of an infectious disease. In some embodiments, the peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6877 - 7418. In some embodiments, the peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6877 - 7418. In some embodiments, the peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6877 - 7418. In some embodiments, the peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6877 - 7418.

[0014] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a first peptide or a first polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990 and a second peptide or a second polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418. In some embodiments, the first peptide or the first polypeptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990. In some embodiments, the first peptide or the first polypeptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990. In some embodiments, the first peptide or the first polypeptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990. In some embodiments, the first peptide or the first polypeptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990. In some embodiments, the second peptide or the second polypeptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418. In some embodiments, the second peptide or the second polypeptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS.

1991 - 7418. In some embodiments, the second peptide or the second polypeptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991

- 7418. In some embodiments, the second peptide or the second polypeptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418. [0015] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843. In some embodiments, the antibody comprises a variable domain of a heavy chain and a variable domain of a light chain kappa (IGK) or a light chain lambda (IGL). In some embodiments, the antibody is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843. In some embodiments, the antibody is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419

- 7843. In some embodiments, the antibody is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843. In some embodiments, the antibody is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843.

[0016] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950. In some embodiments, the antibody comprises a variable domain of a heavy chain and a variable domain of a light chain kappa (IGK) or a light chain lambda (IGL). In some embodiments, the antibody is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950. In some embodiments, the antibody is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950. In some embodiments, the antibody is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950. In some embodiments, the antibody is at least about 95% homologous to a sequence selected from the group consisting of

SEQ ID NOS. 7844 - 7950.

[0017] In another aspect, provided herein are formulations for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046. In some embodiments, the antibody comprises a variable domain of a heavy chain and a variable domain of a light chain kappa (IGK) or a light chain lambda (IGL). In some embodiments, the antibody is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046. In some embodiments, the antibody is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046. In some embodiments, the antibody is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046. In some embodiments, the antibody is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046. In some embodiments, the antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 7958, SEQ ID NO: 7960, SEQ ID NO: 7990, SEQ ID NO: 8013, SEQ ID NO: 8022, SEQ ID NO: 8023, SEQ ID NO: 8026, or SEQ ID NO: 8041. In some embodiments, the antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 7958. In some embodiments, the antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 8022. In some embodiments, the antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 8023. In some embodiments, the antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 8041. In some embodiments, the antibody comprises a peptide or a polypeptide that is homologous to SEQ ID NO: 7958. In some embodiments, the antibody comprises a peptide or a polypeptide that is homologous to SEQ ID

NO: 8022. In some embodiments, the antibody comprises a peptide or a polypeptide that is homologous to SEQ ID NO: 8023. In some embodiments, the antibody comprises a peptide or a polypeptide that is homologous to SEQ ID NO: 8041.

[0018] In another aspect, provided herein are formulations for treatment of an infectious disease comprising an antibody that specifically binds to SI domain of SARS-CoV-2 spike protein with a dissociation constant (KD) value of less than about 100 nM. In some embodiments, the antibody is multivalent. In some embodiments, the antibody is bivalent, trivalent, or tetravalent. In some embodiments, the antibody is specific to SARS-Cov-2 spike protein. In some embodiments, the antibody specifically binds to a SI domain of the SARS-Cov- 2 spike protein. In some embodiments, the antibody specifically binds to a receptor-binding domain (RBD) of the SI domain. In some embodiments, the antibody specifically binds to a S2 domain of the SARS-Cov-2 spike protein. In some embodiments, the antibody neutralizes the infectivity of severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). In some embodiments, the antibody blocks binding of the RBD of the R1 domain to a human ACE2 receptor (hACE2) by at least 50% when measured using a binding assay. In some embodiments, the binding assay is blocking ELISA assay. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is a human antibody. In some embodiments, the antibody is derived from a naive B-cell. In some embodiments, the antibody is derived from a memory B-cell. In some embodiments, the infectious disease is a coronavirus disease 2019 (COVID-19). In some embodiments, the antibody comprises a full-length antibody, a functional fragment thereof, a Fv fragment, a Fab fragment, a Fab’ fragment, a Fab2 fragment, a scFv fragment, a diabody, a minibody, a nanobody (sdAb), or a camelid single-domain antibody (VHH). [0019] In another aspect, provided herein are nucleic acid molecules encoding an antibody disclosed herein. Also provided herein are vectors comprising the nucleic acid molecules provided herein.

[0020] In another aspect, provided herein are pharmaceutical compositions comprising an antibody provided herein. In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, an excipient, or any combination thereof.

[0021] In another aspect, provided herein are methods for treating a subject having

COVID-19, comprising administering to the subject an effective amount of the pharmaceutical composition disclosed herein. In some embodiments, the method further comprises administering a pain reliever, an antiviral compound, an antibiotic compound, or a steroid. In some embodiments, the pain reliever is ibuprofen or acetaminophen. In some embodiments, the antiviral compound is remdesivir. In some embodiments, the antibiotic compound is azithromycin. In some embodiments, the steroid is dexamethasone.

[0022] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

INCORPORATION BY REFERENCE

[0023] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and/or take precedence over any such contradictory material.

BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0025] FIGS. 1A-1C show affinity of a plurality of scFvs disclosed herein against SARS-

CoV-2 SI trimer protein via indirect ELISA;

[0026] FIG. 2 shows sequences disclosed in Table 13 expressed as human IgGl were screened using an endpoint serial dilution sandwich ELISA against purified recombinant SARS- CoV-2 wt WA1 SI sFc-tagged protein;

[0027] FIG. 3 shows serial 2-fold dilution of antibodies against SI antigens were incubated with SARS-CoV-2 spike pseudovirus for neutralization assay; and [0028] FIGS. 4A and 4B show phylogenetic trees of about 457 VH sequence and about

413 VL sequences.

DETAILED DESCRIPTION

[0029] While various embodiments of the invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed.

[0030] The present disclosure provides compositions (antibodies, formulations comprising antibodies, pharmaceutical compositions, etc.) and methods for treating or protecting a subject against a coronavirus (e.g., SARS-CoV-2) and diseases that may be caused by such virus. Provided herein are formulations for treatment of an infectious disease. In some embodiments, the infectious disease can be coronavirus disease 2019 (COVID-19). COVID-19 can be an infectious disease caused by infection of an organism (e.g., a human) by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A formulation herein may comprise a therapeutically effective amount of an antibody. An antibody in a formulation herein may comprise a peptide or a polypeptide of a sequence listing provided herein or an antibody having homology to an antibody of a sequence listing provided herein.

[0031] SEQ ID NOS.: 1-935 disclosed herein comprise heavy chain sequences for antibodies. SEQ ID NOS. 1-935 include sequences for CDR1, CDR2, and CDR3 sequences for the heavy chains. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1-935. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1-935. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1-935. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1-935. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about

95% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ

ID NOS.: 1-935. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 65%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1-935, or a range between any two foregoing values. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 65%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous a sequence selected from the group consisting of SEQ ID NOS.: 1-935, or a range between any two foregoing values. Table 2 attached herein lists SEQ ID NOS.: 1-935.

[0032] A sequence that is N percent (%) homologous, as used herein, generally refers to the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity without considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity may be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as

EMBOSS MATCHER, EMBOSS WATER, EMBOSS STRETCHER, EMBOSS NEEDLE,

EMBOSS LALIGN, BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.

[0033] SEQ ID NOS.: 936-1467 comprise CDR3 sequences for heavy chains of antibodies provided herein. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 936-1467. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 936-1467. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 936-1467. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 936-1467. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 936-1467. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 60%, about 65%, about 70%, about 75%, about 80%, about

85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 936-1467, or a range between any two foregoing values. Table 3 attached herein lists SEQ ID NOS.: 936-1467.

[0034] SEQ ID NOS.: 1468-1990 comprise core CDR3 sequences for heavy chains for antibodies provided herein. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1468-1990. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1468-1990. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to of a sequence selected from the group consisting of SEQ ID NOS.: 1468-1990. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NSO.: 1468-1990. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1468-1990. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1468-1990, or a range between any two foregoing values. Table 4 attached herein lists SEQ ID NOS.: 1468-1990. [0035] SEQ ID NOS.: 1991-2702 comprise CDR1, CDR2, and CDR3 sequences for antibody light chain lambda sequences herein. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1991-2702. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1991-2702. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID

NOS.: 1991-2702. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1991-2702. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1991-2702. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 95% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID

NOS.: 1991-2702. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about

95%, or about 100% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS.: 1991-2702, or a range between any two foregoing values. Table 5 attached herein lists SEQ ID NOS.: 1991-2702.

[0036] SEQ ID NOS.: 2703-2962 comprise CDR3 sequences for antibody light chain lambda sequences herein. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2703-2962. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2703-2962. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to of a sequence selected from the group consisting of SEQ ID NOS.: 2703-2962. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2703-2962. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2703-2962. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 60%, about

65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2703-2962, or a range between any two foregoing values. Table 6 attached herein lists SEQ ID NOS.: 2703-2962.

[0037] SEQ ID NOS.: 2963-3221 comprise core CDR3 sequences for antibody light chain lambda sequences herein. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2963-3221. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2963-3221. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to of a sequence selected from the group consisting of SEQ ID NOS.: 2963-3221. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2963-3221. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2963-3221. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 60%, about

65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100 homologous to a sequence selected from the group consisting of SEQ ID NOS.: 2963-3221, or a range between any two foregoing values. Table 7 attached herein lists SEQ ID NOS.: 2963-3221.

[0038] SEQ ID NOS.: 3222-6329 comprise CDR1, CDR2, and CDR3 sequences for antibody light chain kappa sequences herein. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 3222-6329. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 3222-6329. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to of a sequence selected from the group consisting of SEQ ID NOS.: 3222-6329. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 3222-6329. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 3222-6329. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 60%, about

65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 3222-6329, or a range between any two foregoing values. Table 8 attached herein lists SEQ ID NOS.: 3222-6329.

[0039] SEQ ID NOS.: 6330-6876 comprise CDR3 sequences for antibody light chain kappa sequences herein. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6330-6876. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6330-6876. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to of a sequence selected from the group consisting of SEQ ID NOS.: 6330-6876. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6330-6876. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6330-6876. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 60%, about

65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6330-6876, or a range between any two foregoing values. Table 9 attached herein lists SEQ ID NOS.: 6330-6876. [0040] SEQ ID NOS.: 6877-7418 comprise core CDR3 sequences for antibody light chain kappa sequences herein. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6877-7418. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6877-7418. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 85% homologous to of a sequence selected from the group consisting of SEQ ID NOS.: 6877-7418. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6877-7418. In some embodiments, the antibody may comprise a peptide or polypeptide that is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6877-7418. In some embodiments, the antibody may comprise a peptide or polypeptide that is about 60%, about

65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 6877-7418, or a range between any two foregoing values. Table 10 attached herein lists SEQ ID NOS.: 6877-

7418.

[0041] In some embodiments, a formulation for treatment of an infectious disease herein may comprise an antibody that may comprise two peptides of sequences provided herein or homologous sequences thereof (i.e., a first peptide or polypeptide and a second peptide or polypeptide). In some embodiments, such an antibody may comprise a first peptide or a first polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990 and a second peptide or a second polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418. In some embodiments, the first peptide or polypeptide may be at least 80% homologous to a sequence selected from the group consisting of SE ID NOS.: 1-1990. In some embodiments, the first peptide or polypeptide may be at least 85% homologous to a sequence selected from the group consisting of SE ID NOS.: 1-1990. In some embodiments, the first peptide or polypeptide may be at least 90% homologous to a sequence selected from the group consisting of SE ID

NOS.: 1-1990. In some embodiments, the first peptide or polypeptide may be at least 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1-1990. In some embodiments, the first peptide or polypeptide may be about 60%, about 65%, about 70%, about

75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1-1990, or a range between any two foregoing values. In some embodiments, the second peptide or polypeptide may be at least about

70% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1991-7418.

In some embodiments, the second peptide or polypeptide may be at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1991-7418. In some embodiments, the second peptide or polypeptide may be at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1991-7418. In some embodiments, the second peptide or polypeptide may be at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1991-7418. In some embodiments, the second peptide or polypeptide may be at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1991-7418. In some embodiments, the second peptide or polypeptide may be about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 1991-7418, or a range between any two foregoing values.

[0042] SEQ ID NOS.: 7419-7483 comprise immunoglobulin heavy (IGH), immunoglobulin light kappa (IGK), and immunoglobulin light lambda (IGL) sequences for antibody light chain kappa sequences herein. In some embodiments, an antibody, for example of a formulation for treatment of an infectious disease, may comprise a peptide or polypeptide that may be at least about 70% homologous to a sequence selected from the group consisting of SEQ

ID NOS.: 7419-7483. In some embodiments, such an antibody may comprise a peptide or polypeptide that may be at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7419-7483. In some embodiments, such an antibody may comprise a peptide or polypeptide that may be at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7419-7483. In some embodiments, such an antibody may comprise a peptide or polypeptide that may be at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7419-7483. In some embodiments, such an antibody may comprise a peptide or polypeptide that may be at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7419-7483. In some embodiments, such an antibody may comprise a peptide or polypeptide that may be about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about

100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7419-

7483, or a range between any two foregoing values. Table 11 attached herein lists SEQ ID NOS.:

7419-7483.

[0043] In some embodiments, an antibody, such as one in a formulation provided herein, may comprise a variable domain of a heavy chain and a variable domain of either a light chain kappa (IGK) or a light chain lambda (IGL). In some embodiments, a light chain kappa may be a peptide that may be encoded by an immunoglobulin kappa locus, for example on human chromosome 2, or a homologue thereof. In some embodiments, a light chain lambda may be a peptide that may be encoded by the immunoglobulin lambda locus on human chromosome 22, or a homologue thereof. Such an antibody may be, for example, an antibody comprising a peptide or polypeptide having homology to a sequence selected from the group consisting of SEQ ID NOS.: 7844-7950, such as those antibodies provided herein. Table 12 attached herein lists SEQ ID

NOS.: 7844-7950. [0044] In some embodiments, the antibody may comprise a peptide at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7844-7950. In some embodiments, the antibody may be at least 80% homologous to SEQ ID.: 7844-7950. In some embodiments, the antibody may comprise a peptide at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7844-7950. In some embodiments, the antibody may be at least 85% homologous to SEQ ID NOS.: 7844-7950. In some embodiments, the antibody may comprise a peptide at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7844-7950. In some embodiments, the antibody may be at least 90% homologous to SEQ ID NOS.: 7844-7950. In some embodiments, the antibody may comprise a peptide at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7844-7950. In some embodiments, the antibody may be at least 95% homologous to SEQ ID NOS.: 7844-7950. In some embodiments, the antibody may comprise a peptide about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to a sequence selected from the group consisting of SEQ ID NOS.: 7844-7950, or a range between any two foregoing values. In some embodiments, the antibody may be about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% homologous to SEQ ID NOS.: 7844-7950, or a range between any two foregoing values.

[0045] In some embodiments, an amino acid in a peptide or polypeptide of a sequence provided herein may comprise a conservative substitution. A conservative substitution may comprise a substitution of one amino acid with a different amino acid with similar biochemical properties (e.g. charge, hydrophobicity, and size). Examples of conservative substitutions, as well as substitutions that may be, but are not necessarily, preferred, are provided in TABLE 1. TABLE 1 — Exemplary Conservative Substitutions

[0046] Also provided herein are nucleic acid molecules encoding antibodies, fragments thereof, peptides, and polypeptides provided herein, and homologues thereof provided herein. Also contemplated herein are vectors that encode the one or more antibodies, fragments thereof, peptides, and polypeptides described herein. As used herein, “vector” generally refer to a construct, which can be capable of delivering, and possibly expressing, one or more gene(s) or sequence(s) of interest in a host cell. Examples of vectors include, but are not limited to, viral vectors; naked DNA or RNA expression vectors; plasmid, nanoplasmid, cosmid, minicircles or phage vectors; DNA or RNA expression vectors associated with cationic condensing agents; DNA or RNA expression vectors encapsulated in liposomes; and certain eukaryotic cells, such as producer cells.

[0047] Also provided herein are pharmaceutical compositions, wherein a pharmaceutical composition may comprise an antibody provided herein or a fragment thereof. In some embodiments, a pharmaceutical composition may comprise a vector provided herein, such as a vector comprising a sequence encoding for an antibody provided herein, or a fragment thereof. In some embodiments, a pharmaceutical composition may further comprise a pharmaceutically acceptable carrier, an excipient, or any combination thereof. A “pharmaceutically acceptable carrier or excipient” may comprise one or more molecular entities that do not materially affect the composition or change the active agent(s) contained therein, are physiologically tolerable, and do not typically produce an allergic reaction, or similar untoward reaction, when administered to a subject.

[0048] The pharmaceutical compositions or medicaments, which may be used for in vivo administration as described herein may, in some instances, be sterilized. This may be accomplished by, for example, filtration through sterile filtration membranes, or any other suitable method for sterilization. Other methods for sterilization and filtration are within the scope of the present disclosure.

[0049] Also provided herein are methods for treating a subject, such as a subject having or suspected of having COVID-19, using a formulation or pharmaceutical composition provided herein. Also provided herein are methods for prophylactic treatment of a subject, such as a subject at risk for contracting COVID-19, using a formulation or pharmaceutical composition provided herein. Pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable excipients that facilitate processing of the active compounds, i.e., antibodies or functional fragments thereof, into preparations that may be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. A summary of pharmaceutical compositions described herein may be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins 1999), herein incorporated by reference for such disclosure.

[0050] Such methods may comprise administering to a subject an effective amount of the pharmaceutical composition or formulation. An effective amount may be determined, for example, based on the KD of an antibody within the formulation or pharmaceutical composition, the bioavailability of an antibody within the formulation or pharmaceutical composition, the route of administration of the formulation or pharmaceutical composition, other factors, or a combination thereof.

[0051] In some embodiments, a formulation or pharmaceutical composition may further comprise a second therapeutic. For example, a formulation or pharmaceutical composition may further comprise a pain reliever (e.g., ibuprofen or acetaminophen), an antiviral compound (e.g., remdesivir), an antibiotic compound (e.g., asithromycin) or a steroid (e.g., dexamethasone).

[0052] In some embodiments, a method may further comprise administering a pain reliever (e.g., ibuprofen or acetaminophen), an antiviral compound (e.g., remdesivir), an antibiotic compound (e.g., asithromycin) or a steroid (e.g., dexamethasone). In some cases, the second therapeutic compositions may be administered prior to the administration of the antibodies or the functional fragments thereof disclosed therein. In some cases, the second therapeutic compositions may be administered subsequent to the administration of the antibodies or the functional fragments thereof disclosed therein. In some cases, the second therapeutic compositions may be administered at the same time to the administration of the antibodies or the functional fragments thereof disclosed therein.

[0053] The term “antibody”, as used herein, generally refers to an immunoglobulin (Ig), polypeptide, or a protein having a binding domain which is, or is homologous to, an antigen binding domain. The term further includes “antigen-binding fragments” and other interchangeable terms for similar binding fragments as described below. Native antibodies and native immunoglobulins (Igs) may be generally heterotetrameric glycoproteins of about 150,000 Daltons, composed of two identical light chains and two identical heavy chains. Each light chain may be typically linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain may also comprise regularly spaced intrachain disulfide bridges. Each heavy chain may have at one end a variable domain (“VH”) followed by a number of constant domains (“CH”). Each light chain may have a variable domain at one end (“VL”) and a constant domain (“CL”) at its other end; the constant domain of the light chain may be aligned with the first constant domain of the heavy chain, and the light-chain variable domain is aligned with the variable domain of the heavy chain. Particular amino acid residues may form an interface between the light- and heavy-chain variable domains. [0054] In some instances, an antibody or an antigen-binding fragment thereof may comprise an isolated antibody or antigen-binding fragment thereof, a purified antibody or antigen-binding fragment thereof, a recombinant antibody or antigen-binding fragment thereof, a modified antibody or antigen-binding fragment thereof, or a synthetic antibody or antigen binding fragment thereof.

[0055] Antibodies and antigen-binding fragments herein may be partly or wholly synthetically produced. An antibody or antigen-binding fragment may be a polypeptide or protein having a binding domain which may be, or may be homologous to, an antigen binding domain. In one instance, an antibody or an antigen-binding fragment thereof may be produced in an appropriate in vivo animal model and then isolated and/or purified.

[0056] Depending on the amino acid sequence of the constant domain of its heavy chains, immunoglobulins (Igs) may be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGl, IgG2, IgG3, IgG4, IgAl and IgA2. An Ig or portion thereof may, in some cases, be a human Ig. In some instances, a CH3 domain may be from an immunoglobulin. In some cases, a chain or a part of an antibody or antigen binding fragment thereof, a modified antibody or antigen-binding fragment thereof, or a binding agent may be from an Ig. In such cases, an Ig may be IgG, an IgA, an IgD, an IgE, or an IgM. In cases where the Ig is an IgG, it may be a subtype of IgG, wherein subtypes of IgG may include IgGl, an IgG2a, an IgG2b, an IgG3, and an IgG4. In some cases, a CH3 domain may be from an immunoglobulin selected from the group consisting of an IgG, an IgA, an IgD, an IgE, and an IgM.

[0057] The “light chains” of antibodies (immunoglobulins) from any vertebrate species may be assigned to one of two clearly distinct types, called kappa (“K” or “K”) or lambda (“l”), based on the amino acid sequences of their constant domains.

[0058] A “variable region” of an antibody may refer to the variable region of the antibody light chain or the variable region of the antibody heavy chain, either alone or in combination. The variable regions of the heavy and light chain may each comprise four framework regions (FR) connected by three complementarity determining regions (CDRs) also referred to as hypervariable regions. The CDRs in each chain are held together in close proximity by the FRs and, with the CDRs from the other chain, contribute to the formation of the antigen-binding site of antibodies. There are at least two techniques for determining CDRs: (1) an approach based on cross-species sequence variability (i.e., Rabat et al., Sequences of Proteins of Immunological

Interest, (5th ed., 1991, National Institutes of Health, Bethesda Md.)); and (2) an approach based on crystallographic studies of antigen-antibody complexes (Al-Iazikani et al. (1997) J. Molec.

Biol. 273:927-948)). As used herein, a CDR may refer to CDRs defined by either approach or by a combination of both approaches.

[0059] With respect to antibodies, the term “variable domain” may refer to the variable domains of antibodies that are used in the binding and specificity of each particular antibody for its particular antigen. However, the variability is not evenly distributed throughout the variable domains of antibodies. Rather, it is concentrated in three segments called hypervariable regions (also referred to as CDRs) in both the light chain and the heavy chain variable domains. More highly conserved portions of variable domains are called the “framework regions” or “FRs.” The variable domains of unmodified heavy and light chains each contain four FRs (FR1, FR2, FR3, and FR4), largely adopting a b-sheet configuration interspersed with three CDRs which form loops connecting and, in some cases, part of the b-sheet structure. The CDRs in each chain are held together in close proximity by the FRs and, with the CDRs from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Rabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991), pages 647-669).

[0060] The terms “hypervariable region” and “CDR” when used herein, may refer to the amino acid residues of an antibody which are responsible for antigen-binding. The CDRs comprise amino acid residues from three sequence regions which may bind in a complementary manner to an antigen and are referred to as CDR1, CDR2, and CDR3 for each of the VH and VL chains. In the light chain variable domain, the CDRs may typically correspond to approximately residues 24-34 (CDRLl), 50-56 (CDRL2), and 89-97 (CDRL3), and in the heavy chain variable domain the CDRs may typically correspond to approximately residues 31-35 (CDRH1), 50-65

(CDRH2), and 95-102 (CDRH3) according to Rabat et al., Id. The CDRs of different antibodies may contain insertions, thus the amino acid numbering may differ. The Rabat numbering system accounts for such insertions with a numbering scheme that utilizes letters attached to specific residues (e.g., 27A, 27B, 27C, 27D, 27E, and 27F of CDRLl in the light chain) to reflect any insertions in the numberings between different antibodies. Alternatively, in the light chain variable domain, the CDRs typically correspond to approximately residues 26-32 (CDRLl), 50-

52 (CDRL2), and 91-96 (CDRL3), and in the heavy chain variable domain, the CDRs typically correspond to approximately residues 26-32 (CDRH1), 53-55 (CDRH2), and 96-101 (CDRH3) according to Chothia and Lesk, J. Mol. Biol., 196: 901-917 (1987)).

[0061] “Framework region” or “FR”, as used herein, may refer to framework amino acid residues that form a part of the antigen binding pocket or groove. In some embodiments, the framework residues form a loop that is a part of the antigen binding pocket or groove and the amino acids residues in the loop may or may not contact the antigen. Framework regions generally comprise the regions between the CDRs. In the light chain variable domain, the FRs typically correspond to approximately residues 0-23 (FRLl), 35-49 (FRL2), 57-88 (FRL3), and 98-109 and in the heavy chain variable domain the FRs typically correspond to approximately residues 0-30 (FRH1), 36-49 (FRH2), 66-94 (FRH3), and 103-133 according to Rabat et al., Id. As discussed above with the Rabat numbering for the light chain, the heavy chain too accounts for insertions in a similar manner (e.g., 35 A, 35B of CDRH1 in the heavy chain). Alternatively, in the light chain variable domain, the FRs typically correspond to approximately residues 0-25 (FRLl), 33-49 (FRL2) 53-90 (FRL3), and 97-109 (FRL4), and in the heavy chain variable domain, the FRs typically correspond to approximately residues 0-25 (FRH1), 33-52 (FRH2), 56- 95 (FRH3), and 102-113 (FRH4) according to Chothia and Lesk, Id. The loop amino acids of a

FR may be assessed and determined by inspection of the three-dimensional structure of an antibody heavy chain and/or antibody light chain. The three-dimensional structure may be analyzed for solvent accessible amino acid positions as such positions are likely to form a loop and/or provide antigen contact in an antibody variable domain. Some of the solvent accessible positions may tolerate amino acid sequence diversity and others (e.g., structural positions) are, generally, less diversified. The three dimensional structure of the antibody variable domain may be derived from a crystal structure or protein modeling.

[0062] In the present disclosure, the following abbreviations (in the parentheses) are used in accordance with the customs, as necessary: heavy chain (H chain), light chain (L chain), heavy chain variable region (VH), light chain variable region (VL), complementarity determining region (CDR), first complementarity determining region (CDR1), second complementarity determining region (CDR2), third complementarity determining region (CDR3), heavy chain first complementarity determining region (VH CDR1), heavy chain second complementarity determining region (VH CDR2), heavy chain third complementarity determining region (VH CDR3), light chain first complementarity determining region (VL CDR1), light chain second complementarity determining region (VL CDR2), and light chain third complementarity determining region (VL CDR3).

[0063] The term “Fc region” is used to define a C-terminal region of an immunoglobulin heavy chain. The “Fc region” may be a native sequence Fc region or a variant Fc region. Although the boundaries of the Fc region of an immunoglobulin heavy chain may vary, the human IgG heavy chain Fc region is generally defined to stretch from an amino acid residue at position Cys226, or from Pro230, to the carboxyl-terminus thereof. The numbering of the residues in the Fc region is that of the EU index as in Rabat et ak, (Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991). The Fc region of an immunoglobulin generally comprises two constant domains,

CH2 and CH3.

[0064] In some embodiments, an antibody or antigen binding fragment, such as an antibody or antigen binding fragment against SARS-CoV-2, may comprise variable regions. A variable region may be the variable region of the antibody light chain or the variable region of the antibody heavy chain, either alone or in combination. The variable regions of the heavy and light chain may each include four framework regions (FR) connected by three complementarity determining regions (CDRs), also referred to as hypervariable regions. The CDRs in each chain are held together in close proximity by the FRs and, with the CDRs from the other chain, contribute to the formation of the antigen-binding site of antibodies.

[0065] In some instances, an antibody or antigen binding fragment, such as an antibody or antigen binding fragment against SARS-CoV-2, may comprise light chain regions, heavy chain regions, or light chain and heavy chain regions that confer specific binding of the molecule to SARS-CoV-2. In some instances, an antibody or antigen binding fragment, such as an antibody or antigen binding fragment against SARS-CoV-2, may comprise constant regions. A constant region may include the constant region of the antibody light chain either alone or in combination with the constant region of the antibody heavy chain.

[0066] “Antibodies” useful in the present disclosure encompass, but are not limited to, monoclonal antibodies, polyclonal antibodies, chimeric antibodies, bispecific antibodies, multispecific antibodies, heteroconjugate antibodies, humanized antibodies, human antibodies, deimmunized antibodies, mutants thereof, fusions thereof, immunoconjugates thereof, antigen binding fragments thereof, and/or any other modified configuration of the immunoglobulin molecule that comprises an antigen recognition site of the required specificity, including glycosylation variants of antibodies, amino acid sequence variants of antibodies, and covalently modified antibodies. [0067] “Epitope” may refer to that portion of an antigen or other macromolecule capable of forming a binding interaction with the variable region binding pocket of an antibody. Such binding interactions may be manifested as an intermolecular contact with one or more amino acid residues of one or more CDRs. Antigen binding may involve, for example, a CDR3, a CDR3 pair or, in some cases, interactions of up to all six CDRs of the VH and VL chains. An epitope may be a linear peptide sequence (i.e., “continuous”) or may be composed of noncontiguous amino acid sequences (i.e., “conformational” or “discontinuous”). An antibody may recognize one or more amino acid sequence; therefore, an epitope may define more than one distinct amino acid sequence. Epitopes recognized by antibodies may be determined by peptide mapping and sequence analysis techniques. Binding interactions are manifested as intermolecular contacts between an epitope on an antigen and one or more amino acid residues of a CDR. Epitopes recognized by antibodies may be determined, for example, by peptide mapping or sequence analysis techniques. Binding interactions may manifest as intermolecular contacts between an epitope on an antigen and one or more amino acid residues of a complementarity determining region (CDR).

[0068] An epitope that “preferentially binds” or “selectively binds” (used interchangeably herein) to an antibody or a polypeptide is a term well understood in the art, and methods to determine such specific or preferential binding are also well known in the art. An antibody selectively binds or preferentially binds to a target if it binds with greater affinity, avidity, more readily, and/or with greater duration than it binds to other substances. For example, an antibody that specifically or preferentially binds to an epitope on SARS-CoV-2 may represent an antibody that may bind this epitope with greater affinity, avidity, more readily, and/or with greater duration than it binds to other SARS-CoV-2 epitopes or non-SARS-CoV-2 epitopes. An antibody (or moiety or epitope) that specifically or preferentially binds to a first target may or may not specifically or preferentially bind to a second target. As such, “specific binding” or “preferential binding” does not necessarily require (although it can include) exclusive binding. Generally, reference to specific binding means preferential binding where the affinity of the antibody, or antigen-binding fragment thereof, is at least at least 2-fold greater, at least 3 -fold greater, at least

4-fold greater, at least 5-fold greater, at least 6-fold greater, at least 7-fold greater, at least 8-fold greater, at least 9-fold greater, at least 10-fold greater, at least 20-fold greater, at least 30-fold greater, at least 40-fold greater, at least 50-fold greater, at least 60-fold greater, at least 70-fold greater, at least 80-fold greater, at least 90-fold greater, at least 100-fold greater, or at least 1000- fold greater than the affinity of the antibody for unrelated amino acid sequences.

[0069] In some instances, an antibody or antigen binding fragment, such as an antibody or antigen binding fragment against SARS-CoV-2, can be a monoclonal antibody. A

“monoclonal antibody”, as used herein, generally refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population can identical except for possible naturally-occurring mutations that may be present in minor amounts. In contrast to polyclonal antibody preparations, which can typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen (epitope). The modifier “monoclonal” can indicate the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present disclosure may be made by the hybridoma method first described by Kohler and Milstein,

1975, Nature, 256:495, or may be made by recombinant DNA methods such as described in U.S.

Pat. No. 4,816,567. The monoclonal antibodies may also be isolated from phage libraries generated using the techniques described in McCafferty et al., 1990, Nature, 348:552-554, for example. Other suitable methods are also within the scope of the present disclosure.

[0070] In some instances, an antibody or antigen binding fragment, such as an antibody or antigen binding fragment against SARS-CoV-2, may be a humanized antibody. “Humanized” antibodies, as used herein, generally refer to forms of non-human (e.g., murine) antibodies that are specific chimeric immunoglobulins, immunoglobulin chains, or fragments thereof that contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementarity determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and biological activity. In some instances, Fv framework region (FR) residues of the human immunoglobulin can be replaced by corresponding non-human residues.

Furthermore, the humanized antibody may comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance. In general, a humanized antibody can comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence.

The humanized antibody may also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Antibodies may have Fc regions modified as described in, for example, WO 99/58572. Other forms of humanized antibodies have one or more CDRs (one, two, three, four, five, or six) which are altered with respect to the original antibody, which are also termed one or more CDRs “derived from” one or more CDRs from the original antibody.

[0071] In some embodiments, an antibody or antigen binding fragment, such as an antibody or antigen binding fragment against SARS-CoV-2, may be assessed for immunogenicity and, as needed, be deimmunized (i.e., the antibody is made less immunoreactive by altering one or more T cell epitopes). A “deimmunized antibody” as used herein, generally refers to an antibody wherein one or more T cell epitopes in the antibody sequence have been modified such that a T cell response after administration of the antibody to a subject is reduced compared to an antibody that has not been deimmunized. Analysis of immunogenicity and T-cell epitopes present in the antibodies and antigen-binding fragments described herein may be carried out via the use of software and specific databases. Exemplary software and databases include iTope™ developed by Antitope of Cambridge, England. iTope™, is an in silico technology for analysis of peptide binding to human MHC class II alleles. The iTope™ software predicts peptide binding to human MHC class II alleles and thereby provides an initial screen for the location of such

“potential T cell epitopes.” iTope™ software predicts favorable interactions between amino acid side chains of a peptide and specific binding pockets within the binding grooves of 34 human

MHC class II alleles. The location of key binding residues is achieved by the in silico generation of 9mer peptides that overlap by one amino acid spanning the test antibody variable region sequence. Each 9mer peptide may be tested against each of the 34 MHC class II allotypes and scored based on their potential “fit” and interactions with the MHC class II binding groove.

Peptides that produce a high mean binding score (>0.55 in the iTope™ scoring function) against

>50% of the MHC class II alleles are considered as potential T cell epitopes. In such regions, the core 9 amino acid sequence for peptide binding within the MHC class II groove is analyzed to determine the MHC class II pocket residues (PI, P4, P6, P7, and P9) and the possible T cell receptor (TCR) contact residues (P-1, P2, P3, P5, P8). After identification of any T-cell epitopes, amino acid residue changes, substitutions, additions, and/or deletions may be introduced to remove the identified T-cell epitope. Such changes can be made so as to preserve antibody structure and function while still removing the identified epitope. Exemplary changes can include, but are not limited to, conservative amino acid changes.

[0072] In some instances, an antibody or antigen binding fragment, such as an antibody or antigen binding fragment against SARS-CoV-2, can be a human antibody, which can refer to an antibody having an amino acid sequence corresponding to that of an antibody produced by a human and/or that has been made using any suitable technique for making human antibodies. A human antibody can be an antibody comprising at least one human heavy chain polypeptide or at least one human light chain polypeptide. One such example can be an antibody comprising murine light chain and human heavy chain polypeptides. In some embodiment, the human antibody can be selected from a phage library, where that phage library expresses human antibodies (Vaughan et al., 1996, Nature Biotechnology, 14:309-314; Sheets et al., 1998, PNAS

USA, 95:6157-6162; Hoogenboom and Winter, 1991, J. Mol. Biol., 227:381; Marks et al., 1991,

J. Mol. Biol., 222:581). Human antibodies can also be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. This approach is described in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; and 5,661,016.

Alternatively, a human antibody may be prepared by immortalizing human B lymphocytes that can produce an antibody directed against a target antigen (such B lymphocytes may be recovered from an individual or may have been immunized in vitro). See, e.g., Cole et al., Monoclonal

Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boerner et al., 1991, J. Immunol.,

147 (l):86-95; and U.S. Pat. No. 5,750,373.

[0073] Any of the antibodies herein can be bispecific. Bispecific antibodies are antibodies that have binding specificities for at least two different antigens and can be prepared using the antibodies disclosed herein. Methods for making bispecific antibodies are described (see, e.g., Suresh et al., 1986, Methods in Enzymology 121:210). Traditionally, the recombinant production of bispecific antibodies was based on the coexpression of two immunoglobulin heavy chain-light chain pairs, with the two heavy chains having different specificities (Millstein and Cuello, 1983, Nature, 305, 537-539). Bispecific antibodies can comprise a hybrid immunoglobulin heavy chain with a first binding specificity in one arm, and a hybrid immunoglobulin heavy chain-light chain pair (providing a second binding specificity) in the other arm. This asymmetric structure, with an immunoglobulin light chain in only one half of the bispecific molecule, can facilitate the separation of the desired bispecific compound from unwanted immunoglobulin chain combinations. This approach is described in PCT Publication No. WO 94/04690. [0074] According to at least one approach to making bispecific antibodies, antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion can be with an immunoglobulin heavy chain constant domain, comprising at least part of the hinge, CH2 and CH3 regions. The first heavy chain constant region (CHI), containing the site necessary for light chain binding, can be present in at least one of the fusions. DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. This provides for great flexibility in adjusting the mutual proportions of the three polypeptide fragments in embodiments when unequal ratios of the three polypeptide chains used in the construction provide the optimum yields. It is, however, possible to insert the coding sequences for two or all three polypeptide chains in one expression vector when the expression of at least two polypeptide chains in equal ratios results in high yields or when the ratios are of no particular significance.

[0075] A heteroconjugate antibody, which can be antibody such as an antibody or antigen binding fragment against SARS-CoV-2, can comprise two covalently joined antibodies, and are also within the scope of the disclosure. Such antibodies can in some cases target immune system cells to unwanted cells (U.S. Pat. No. 4,676,980). Heteroconjugate antibodies may be made using any suitable cross-linking methods. Suitable cross-linking agents and techniques are described, for example, in U.S. Pat. No. 4,676,980.

[0076] In some instances, an antibody or antigen binding fragment, such as an antibody or antigen binding fragment against SARS-CoV-2, can be a chimeric antibody. “Chimeric” forms of non-human (e.g., murine) antibodies can include chimeric antibodies, which can contain minimal sequence derived from a non-human Ig. Chimeric antibodies can be murine antibodies in which at least a portion of an immunoglobulin constant region (Fc), for example that of a human immunoglobulin, is inserted in place of the murine Fc. [0077] Chimeric or hybrid antibodies also may be prepared in vitro using suitable methods of synthetic protein chemistry, including those involving cross-linking agents. For example, immunotoxins may be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this purpose can include iminothiolate and methyl-4-mercaptobutyrimidate.

[0078] Provided herein are antibodies and antigen-binding fragments thereof, modified antibodies and antigen-binding fragments thereof, and binding agents that specifically bind to one or more epitopes on one or more target antigens. In some such embodiments, the one or more target antigens can comprise SARS-CoV-2. In some embodiments, a binding agent can selectively bind to an epitope on a single antigen. In some embodiments, a binding agent can be bivalent and can either selectively bind to two distinct epitopes on a single antigen, or can bind to two distinct epitopes on two distinct antigens. In some embodiments, a binding agent can be multivalent (i.e., trivalent, quatravalent, etc.) and the binding agent can binds to three or more distinct epitopes on a single antigen, or binds to three or more distinct epitopes on two or more (multiple) antigens.

[0079] Functional fragments of any of the antibodies herein, such as antibodies against

SARS-CoV-2, are also contemplated herein. The terms “antigen-binding portion of an antibody,” “antigen-binding fragment,” “antigen-binding domain,” “antibody fragment,” or a “functional fragment of an antibody” can be used interchangeably herein to refer to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. Representative antigen binding fragments include, but are not limited to, a Fab, a Fab', a F(ab')2, a Fv, a scFv, a dsFv, a variable heavy domain, a variable light domain, a variable NAR domain, bi-specific scFv, a bi- specific Fab2, a tri-specific Fab3, an AVIMER®, a minibody, a diabody, a maxibody, a camelid, a VHH, a minibody, an intrabody, fusion proteins comprising an antibody portion (e.g., a domain antibody), and a single chain binding polypeptide. [0080] “F(ab')2” and “Fab¹” moieties can be produced by treating an Ig with a protease such as pepsin and papain, and can include antibody fragments generated by digesting immunoglobulin near the disulfide bonds existing between the hinge regions in each of the two heavy chains. For example, papain can cleave an IgG upstream of the disulfide bonds existing between the hinge regions in each of the two heavy chains to generate two homologous antibody fragments in which an light chain composed of VL and CL (light chain constant region), and a heavy chain fragment composed of VH and CFTyl (gΐ) region in the constant region of the heavy chain) are connected at their C terminal regions through a disulfide bond. Each of these two homologous antibody fragments can be referred to as Fab'. In some cases, pepsin can cleave an

IgG downstream of the disulfide bonds existing between the hinge regions in each of the two heavy chains to generate an antibody fragment slightly larger than the fragment in which the two above-mentioned Fab' are connected at the hinge region. Such an antibody fragment can be referred to as F(ab')2.

[0081] An Fab fragment also contains the constant domain of the light chain and the first constant domain (CHI) of the heavy chain. Fab' fragments differ from Fab fragments by the addition of a few residues at the carboxyl terminus of the heavy chain CHI domain including one or more cysteine(s) from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

[0082] A “Fv” as used herein generally refer to an antibody fragment which can comprise a complete antigen-recognition and antigen-binding site. This region can comprise a dimer of one heavy chain and one light chain variable domain in tight, non-covalent or covalent association (disulfide linked Fvs have been described, see, e.g., Reiter et al. (1996) Nature Biotechnology 14: 1239-1245). It is in this configuration that the three CDRs of each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, a combination of one or more of the CDRs from each of the VH and VL chains confer antigen-binding specificity to the antibody. It may be understood that, for example, the CDRH3 and CDRL3 may be sufficient to confer antigen-binding specificity to an antibody when transferred to VH and VL chains of a recipient antibody or antigen-binding fragment thereof and this combination of CDRs can be tested for binding, specificity, affinity, etc. using any of the techniques described herein.

Even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) can comprise an ability to recognize and bind antigen, although likely at a lower specificity or affinity than when combined with a second variable domain. Furthermore, although the two domains of a Fv fragment (VL and VH) are coded for by separate genes, they can be joined using recombinant methods by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (referred to as single chain Fv (scFv); Bird et al. (1988) Science 242:423-426; Huston et al. (1988) Proc. Natl.

Acad. Sci. USA 85:5879-5883; and Osbourn et al. (1998) Nat. Biotechnol. 16:778). Such scFvs can be encompassed within the term “antigen-binding portion” of an antibody. Any VH and VL sequences of specific scFv can be linked to an Fc region cDNA or genomic sequences in order to generate expression vectors encoding complete Ig (e.g., IgG) molecules or other isotypes. VH and VL can also be used in the generation of Fab, Fv, or other fragments of Igs using either protein chemistry or recombinant DNA technology.

[0083] “Single-chain Fv” or “sFv” antibody fragments can comprise the VH and VL domains of an antibody, wherein these domains can be present in a single polypeptide chain. In some embodiments, the Fv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the sFv to form the desired structure for antigen binding. For a review of sFvs, see, e.g., Pluckthun in The Pharmacology of Monoclonal Antibodies, Vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315 (1994).

[0084] The term “AVIMER®” can refer to a class of therapeutic proteins of human origin, which are unrelated to antibodies and antibody fragments, and are composed of several modular and reusable binding domains, referred to as A-domains (also referred to as class A module, complement type repeat, or LDL-receptor class A domain). They were developed from human extracellular receptor domains by in vitro exon shuffling and phage display (Silverman et al., 2005, Nat. Biotechnol. 23:1493-1494; Silverman et al., 2006, Nat. Biotechnol. 24:220). The resulting proteins can contain multiple independent binding domains that can exhibit improved affinity and/or specificity compared with single-epitope binding proteins. Each of the 217 human

A-domains comprises ~35 amino acids (~4 kDa); and these domains are separated by linkers that average five amino acids in length. Native A-domains fold quickly and efficiently to a uniform, stable structure mediated primarily by calcium binding and disulfide formation. A conserved scaffold motif of only 12 amino acids is required for this common structure. The end result can be a single protein chain containing multiple domains, each of which represents a separate function. Each domain of the proteins binds independently, and the energetic contributions of each domain are additive.

[0085] Antigen-binding polypeptides, such as those against SARS-CoV-2, can also include heavy chain dimers such as, for example, antibodies from camelids and sharks. Camelid and shark antibodies can comprise a homodimeric pair of two chains of V-like and C-like domains (neither has a light chain). Since in some embodiments the VH region of a heavy chain dimer IgG in a camelid does not require hydrophobic interactions with a light chain, the region in the heavy chain that normally contacts a light chain can be altered to comprise hydrophilic amino acid residues in a camelid. VH domains of heavy-chain dimer IgGs are called VHH domains. Shark Ig-NARs can comprise a homodimer of one variable domain (termed a V-NAR domain) and five C-like constant domains (C-NAR domains). In camelids, the diversity of antibody repertoire can be determined by the CDRs 1, 2, and 3 in the VH or VHH regions. The CDR3 in the camel VHH region can be characterized by its relatively long length, averaging 16 amino acids (Muyldermans et al., 1994, Protein Engineering 7(9): 1129). This may be in contrast to CDR3 regions of antibodies of many other species. For example, the CDR3 of mouse VH has an average of 9 amino acids. Libraries of camelid-derived antibody variable regions, which can maintain the in vivo diversity of the variable regions of a camelid, can be made by, for example, the methods disclosed in U.S. Patent Application Ser. No. 20050037421.

[0086] A “maxibody” as used herein generally refers to a bivalent scFv covalently attached to the Fc region of an immunoglobulin, see, e.g., Fredericks et al., Protein Engineering,

Design & Selection, 17:95-106 (2004) and Powers et al., Journal of Immunological Methods,

251:123-135 (2001).

[0087] A “dsFv” as used herein may be a Fv fragment that can be obtained by introducing a Cys residue into a suitable site in each of a heavy chain variable region and a light chain variable region, and then stabilizing the heavy chain variable region and the light chain variable region by a disulfide bond. The site in each chain, into which the Cys residue can be be introduced, can be determined based on a conformation predicted by molecular modeling. In the present disclosure, for example, a conformation is predicted from the amino acid sequences of the heavy chain variable region and light chain variable region of the above-described antibody, and DNA encoding each of the heavy chain variable region and the light chain variable region, into which a mutation can be or can have been introduced based on such prediction, is then constructed. The DNA construct can be incorporated then into a suitable vector and prepared from a transformant obtained by transformation with the aforementioned vector.

[0088] Single chain variable region fragments (“scFv”) of antibodies, such as those against SARS-CoV-2, are provided herein. Single chain variable region fragments may be made by linking light and/or heavy chain variable regions by using a short linking peptide. Bird et al. (1988) Science 242:423-426. The single chain variants can be produced either recombinantly or synthetically. For synthetic production of scFv, an automated synthesizer can be used. For recombinant production of scFv, a suitable plasmid containing polynucleotide that encodes the scFv can be introduced into a suitable host cell, either eukaryotic, such as yeast, plant, insect, or mammalian cells, or prokaryotic, such as E. coli. Polynucleotides encoding the scFv of interest can be made by routine manipulations such as ligation of polynucleotides. The resultant scFv can be isolated using any suitable protein purification techniques.

[0089] Diabodies can be single chain antibodies. In some embodiments, diabodies can be bivalent, bispecific antibodies in which VH and VL domains are expressed on a single polypeptide chain comprising a linker that is too short to allow for pairing between the two domains on the same chain, thereby forcing the domains to pair with complementary domains of another chain and creating two antigen binding sites (see, e.g., Holliger, P., et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993); and Poljak, R. I, et al., Structure, 2:1121-1123 (1994)). [0090] A “minibody” as used herein, generally refers to a scFv fused to CH3 via a peptide linker (hingeless) or via an IgG hinge has been described in Olafsen, et al., Protein Eng Des Sel. April 2004; 17(4):315-23.

[0091] An “intrabody” as used herein, generally refers to a single chain antibody, such as one against SARS-CoV-2, which can demonstrates intracellular expression and can manipulate intracellular protein function (Biocca, et al., EMBO J. 9:101-108, 1990; Colby et al., Proc Natl Acad. Sci. USA. 101:17616-21, 2004). Intrabodies, which comprise cell signal sequences which retain the antibody construct in intracellular regions, may be produced as described in Mhashilkar et al., (EMBO J., 14:1542-51, 1995) and Wheeler et al. (FASEB J. 17:1733-5. 2003).

Transbodies are cell-permeable antibodies in which a protein transduction domains (PTD) is fused with single chain variable fragment (scFv) antibodies Heng et al. (Med Hypotheses. 64:1105-8, 2005).

[0092] Suitable linkers may be used, for example to multimerize binding agents. Linkers have been designed and used, for example in Bird, et al. (Id.) Linkers can in turn be modified for additional functions, such as attachment of drugs or attachment to solid supports.

[0093] The term “avidity” as used herein, generally refers to the resistance of a complex of two or more agents to dissociation after dilution. Apparent affinities can be determined by methods such as an enzyme-linked immunosorbent assay (ELISA) or any other suitable technique. Avidities can be determined by methods such as a Scatchard analysis or any other suitable technique.

[0094] The term “affinity” as used herein, generally refers to the equilibrium constant for the reversible binding of two agents and is expressed as binding affinity (KD). In some cases, KD can be represented as a ratio of koff, which can refer to the rate constant for dissociation of an antibody from the antibody or antigen-binding fragment/antigen complex, to kon, which can refer to the rate constant for association of an antibody or antigen binding fragment to an antigen. Binding affinity may be determined using methods including, for example, surface plasmon resonance (SPR; Biacore), Kinexa Biosensor, scintillation proximity assays, enzyme-linked immunosorbent assay (ELISA), ORIGEN immunoassay (IGEN), fluorescence quenching, fluorescence transfer, yeast display, or any combination thereof. Binding affinity may also be screened using a suitable bioassay.

[0095] In some embodiments, an antibody provided herein can have affinity to or specifically bind to a SARS-CoV-2 virus or an epitope, feature, or protein thereof. In some embodiments, an antibody can have affinity to or specifically bind to a spike protein of a SARS- CoV-2 virus or a domain thereof. In some embodiments, an antibody can have affinity to or specifically bind to an SI domain of a SARS-CoV-2 spike protein. In some embodiments, the antibody can have affinity to a receptor binding domain (RBD) of the SI domain. In some such embodiments, an antibody can have affinity to or specifically bind to an S2 domain of a SARS- CoV-2 spike protein.

[0096] In some cases, the KD value may be an important factor regarding whether or not an antibody can successfully cross a blood-tissue barrier. In some cases, a mutation in the TfR gene of a subject can alter the KD of such an antibody in that subject. In some cases, different species may express TfR proteins which display affinity to antibodies and antigen-binding fragments differently. Thus, for different subjects or types of subjects, different antibodies or antigen-binding fragments can be used to ensure a proper affinity for successful transport and subsequent dissociation. In some embodiments, the KD of a binding agent, or an antibody or antigen-binding fragment described herein can be between about 1 nM and 5 mM. In some embodiments, an antibody or antigen-binding fragment described herein can have a KD of less than about 1 nM or more than about 5 mM.

[0097] In some embodiments, an antibody can have a KD value of less than about 10 pM, less than about 100 pM, less than about 500 pM, less than about 1 nM, less than about 10 nM, less than about 100 nM, less than about 500 nM, less than about 1 mM, less than about 10 mM, less than about 100 mM, or less than about 500 mM. In some embodiments, an antibody can have a KD value of about 10 pM, about 100 pM, about 500 pM, about 1 nM, about 10 nM, about 100 nM, about 500 nM, about 1 mM, about 10 mM, about 100 mM, or about 500 mM. In some embodiments, an antibody having affinity to a SARS-CoV-2 virus or an epitope, feature, or protein thereof can have a KD value of less than about 10 pM, less than about 100 pM, less than about 500 pM, less than about 1 nM, less than about 10 nM, less than about 100 nM, less than about 500 nM, less than about 1 mM, less than about 10 mM, less than about 100 mM, or less than about 500 mM. In some embodiments, an antibody having affinity to a SARS-CoV-2 virus or an epitope, feature, or protein thereof can have a KD value of about 10 pM, about 100 pM, about 500 pM, about 1 nM, about 10 nM, about 100 nM, about 500 nM, about 1 mM, about 10 mM, about 100 mM, or about 500 mM. In some embodiments, an antibody having affinity to a spike protein of a SARS-CoV-2 virus can have a KD value of less than about 10 pM, less than about 100 pM, less than about 500 pM, less than about 1 nM, less than about 10 nM, less than about 100 nM, less than about 1 mM, less than about 10 mM, or less than about 100 mM. In some embodiments, an antibody having affinity to a spike protein of a SARS-CoV-2 virus can have a KD value of about 10 pM, about 100 pM, about 500 pM, about 1 nM, about 10 nM, about 100 nM, about 1 mM, about 10 mM, or about 100 mM. In some embodiments, an antibody having affinity to an SI domain of a spike protein of a SARS-CoV-2 virus can have a KD value of less than about 10 pM, less than about 100 pM, less than about 500 pM, less than about 1 nM, less than about 10 nM, less than about 100 nM, less than about 500 nM, less than about 1 mM, less than about 10 mM, less than about 100 mM, or less than about 500 mM. In some embodiments, an antibody having affinity to an SI domain of a spike protein of a SARS-CoV-2 virus can have a

KD value of about 10 pM, about 100 pM, about 500 pM, about 1 nM, about 10 nM, about 100 nM, about 500 nM, about 750 nM, about 1 mM, about 1.5 mM, about 2 mM, about 2.5 mM, about

5 mM, about 10 mM, about 100 mM, about 500 mM. In some embodiments, an antibody having affinity to an RBD of an SI domain of a spike protein of a SARS-CoV-2 virus can have a KD value of less than about 10 pM, about 100 pM, about 500 pM, about 1 nM, about 10 nM, about

100 nM, about 500 nM, about 750 nM, about 1 mM, about 1.5 mM, about 2 mM, about 2.5 mM, about 5 mM, about 10 mM, about 100 mM, about 500 mM. In some embodiments, an antibody having affinity to an RBD of an SI domain of a spike protein of a SARS-CoV-2 virus can have a

5 mM, about 10 mM, about 100 mM, about 500 mM. In some embodiments, an antibody having affinity to an S2 domain of a spike protein of a SARS-CoV-2 virus can have a KD value of less than about 10 pM, about 100 pM, about 500 pM, about 1 nM, about 10 nM, about 100 nM, about

500 nM, about 750 nM, about 1 mM, about 1.5 mM, about 2 mM, about 2.5 mM, about 5 mM, about 10 mM, about 100 mM, about 500 mM. In some embodiments, an antibody having affinity to an S2 domain of a spike protein of a SARS-CoV-2 virus can have a KD value of about 10 pM, about 100 pM, about 500 pM, about 1 nM, about 10 nM, about 100 nM, about 500 nM, about

750 nM, about 1 mM, about 1.5 mM, about 2 mM, about 2.5 mM, about 5 mM, about 10 mM, about

100 mM, about 500 mM.

[0098] In some embodiments, an antibody herein or antigen binding fragment thereof can neutralize a virus or a fragment thereof. For example, an antibody can neutralize a SARS-CoV-2 virus. In some embodiments, the antibody can neutralize the infectivity of a SARS-CoV-2 virus. In some embodiments, neutralization of a virus can comprise decreasing or preventing replication of that virus (e.g., in a host). In some embodiments, an antibody can neutralize a virus such as a

SARS-CoV-2 virus by blocking attachment of the host cell, preventing penetration of the host cell membrane, or interfering with uncoating of the virus within the cell. An antibody can neutralize a virus such as a SARS-CoV-2 virus in vivo, in vitro, or both in vivo and in vitro.

[0099] A SARS CoV-2 virus can bind to ACE2 receptors in a human, which can lead to infection in the human. In some embodiments, an antibody provided herein can prevent, block, or reverse binding of a SARS-CoV-2 virus to an ACE2 receptor. In some embodiments, an antibody provided herein can, for example, block binding of a RBD of an R1 domain of a SARS-CoV-2 virus to a human ACE2 receptor. Such blocking can occur, for example, upon binding of the antibody to the SARS-CoV-2 virus (e.g., at or near the RBD of the R1 domain). Binding of the

RBD R1 domain to the human ACE2 receptor can be blocked by at least 40%, at least 50%, at least 60%, at least 70%, or at least 80% by an antibody provided herein. In some embodiments, binding of the RBD R1 domain to the human ACE2 receptor can be blocked by about 40%, about

50%, about 60%, about 70%, about 80%, or a range between any two foregoing values. For example, in some embodiments the antibody can block binding of the RBD of an R1 domain to a human ACE2 receptor by at least 50%. Such reduction in binding can be measured, for example, using a binding assay such as an ELISA assay (e.g., a blocking ELISA assay) or another type of binding assay, such as a ligand binding assay, a competition assay, a fluorescence based binding assay, a radiometric binding assay, or a colorimetric binding assay.

[00100] Also provided herein are affinity matured antibodies. For example, affinity matured antibodies can be produced by any suitable procedure (see, e.g., Marks et ak, 1992,

Bio/Technology, 10:779-783; Barbas et ak, 1994, Proc Nat. Acad. Sci, USA 91:3809-3813;

Schier et ak, 1995, Gene, 169:147-155; Yelton et ak, 1995, J. Immunol., 155:1994-2004; Jackson et ak, 1995, J. Immunol., 154(7):3310-9; Hawkins et al, 1992, J. Mol. Biol., 226:889-896; and

W02004/058184). The following methods may be used for adjusting the affinity of an antibody and for characterizing a CDR. One way of characterizing a CDR of an antibody and/or altering (such as improving) the binding affinity of a polypeptide, such as an antibody, is termed “library scanning mutagenesis.” Generally, library scanning mutagenesis works as follows. One or more amino acid position in the CDR is replaced with two or more (such as 3, 4, 5, 6, 7, 8, 9, 10, 11,

12, 13, 14, 15, 16, 17, 18, 19, or 20) amino acids. This can generate small libraries of clones (in some embodiments, one for every amino acid position that is analyzed), each with a complexity of two or more members (if two or more amino acids are substituted at every position).

Generally, the library also includes a clone comprising the native (unsubstituted) amino acid. A small number of clones, for example, about 20-80 clones (depending on the complexity of the library), from each library can be screened for binding specificity or affinity to the target polypeptide (or other binding target), and candidates with increased, the same, decreased, or no binding are identified. Binding affinity may be determined using Biacore surface plasmon resonance analysis, which detects differences in binding affinity of about 2-fold or greater.

[00101] In some instances, an antibody or antigen binding fragment, such as an antibody against SARS-CoV-2, may be bi-specific or multi-specific and may specifically bind to more than one antigen. In some cases, such a bi-specific or multi-specific antibody or antigen binding fragment may specifically bind to 2 or more different antigens. In some cases, a bi-specific antibody or antigen-binding fragment may be a bivalent antibody or antigen-binding fragment. In some cases, a multi specific antibody or antigen-binding fragment may be a bivalent antibody or antigen-binding fragment, a trivalent antibody or antigen-binding fragment, a tetravalent antibody or antigen-binding fragment, or a quatravalent antibody or antigen-binding fragment.

[00102] An antibody or antigen binding fragment described herein can be an isolated, purified, recombinant, or synthetic.

[00103] Methods of making and expressing antibodies

[00104] The antibodies described herein may be made by any suitable method. Antibodies can be produced in large quantities, particularly when utilizing high level expression vectors. Techniques, such as those provided and incorporated herein, can be used to modify nucleotides encoding amino acid sequences using recombinant techniques in restriction endonuclease sites.

[00105] In some embodiments, when an animal (e.g., a mouse, rat, rabbit, primate, etc.) is utilized to make an antibody, the route and schedule of immunization of the host animal with the target antigen are generally in keeping with established and conventional techniques for antibody stimulation and production, as further described herein.

[00106] In some embodiments, an antibody provided herein may be derived from (e.g., grown in, extracted from, purified from, or otherwise derived from) an animal or a cell thereof. For example, in some embodiments, an antibody provided herein may be derived from a B-cell, such as a naive B-cell or a memory B-cell.

[00107] It is contemplated that any mammalian subject including humans or antibody producing cells therefrom may be manipulated to serve as the basis for production of mammalian, including human, hybridoma cell lines. Typically, the host animal may be inoculated intraperitoneally, intramuscularly, orally, subcutaneously, intraplantar, and/or intradermally with an amount of immunogen, including as described herein.

[00108] Immunization of a host animal with a human protein, or a fragment containing a target amino acid sequence conjugated to an adjuvant that is immunogenic in the species to be immunized, e.g., keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, or soybean trypsin inhibitor using a bifunctional or derivatizing agent, for example, maleimidobenzoyl sulfosuccinimide ester (conjugation through cysteine residues), N-hydroxysuccinimide (through lysine residues), glutaradehyde, succinic anhydride, SOC12, or any other suitable adjuvant may yield a population of antibodies.

[00109] Hybridomas can be prepared from the lymphocytes of immunized animals and immortalized myeloma cells using the general somatic cell hybridization technique of Kohler, B. and Milstein, C. (1975) Nature 256:495-497 or as modified by Buck, D. W., et ah, In Vitro, 18:377-381 (1982). Available myeloma lines may be used in the hybridization. The technique may involve fusing myeloma cells and lymphoid cells using a fusogen, such as polyethylene glycol, or by an electrical approach (e.g., using an electroporation device). After the fusion, the cells are separated from the fusion medium and grown in a selective growth medium, such as hypoxanthine-aminopterin-thymidine (HAT) medium, to eliminate unhybridized parent cells.

Any of the media described herein, supplemented with or without serum, can be used for culturing hybridomas that secrete monoclonal antibodies. As another alternative to the cell fusion technique, EBV immortalized B cells may be used to produce monoclonal antibodies. The hybridomas are expanded and subcloned, if desired, and supernatants are assayed for anti immunogen activity by conventional immunoassay procedures (e.g., radioimmunoassay, enzyme immunoassay, fluorescence immunoassay, etc.). Hybridomas that may be used as source of antibodies encompass all derivatives, progeny cells of the parent hybridomas that produce monoclonal antibodies, or a portion thereof. Hybridomas that produce such antibodies may be grown in vitro or in vivo using known procedures. The monoclonal antibodies may be isolated from the culture media or body fluids by conventional immunoglobulin purification procedures such as ammonium sulfate precipitation, gel electrophoresis, dialysis, chromatography, and ultrafiltration, if desired.

[00110] Undesired activity, if present, may be removed, for example, by running the preparation over adsorbents made of the immunogen attached to a solid phase and eluting or releasing the desired antibodies off the immunogen.

[00111] Antibodies may be made recombinantly and expressed using any suitable method. Antibodies may be made recombinantly by phage display technology. For example, U phage display technology may be used to produce human antibodies and antibody fragments in vitro, from immunoglobulin variable (V) domain gene repertoires from unimmunized donors. According to this technique, antibody V domain genes are cloned in-frame into either a major or minor coat protein gene of a filamentous bacteriophage, such as Ml 3 or fd, and displayed as functional antibody fragments on the surface of the phage particle. Because the filamentous particle contains a single-stranded DNA copy of the phage genome, selections based on the functional properties of the antibody also result in selection of the gene encoding the antibody exhibiting those properties. Thus, the phage mimics some of the properties of the B cell. Several sources of V-gene segments may be used for phage display. Clackson et al., Nature 352:624-628

(1991) isolated a diverse array of anti -oxazol one antibodies from a small random combinatorial library of V genes derived from the spleens of immunized mice. A repertoire of V genes from unimmunized human donors may be constructed and antibodies to a diverse array of antigens

(including self-antigens) may be isolated essentially following the techniques described by Mark et al., J. Mol. Biol. 222:581-597 (1991), or Griffith et al., EMBO J. 12:725-734 (1993). In a natural immune response, antibody genes accumulate mutations at a high rate (somatic hypermutation). Some of the changes introduced will confer higher affinity, and B cells displaying high-affinity surface immunoglobulin are preferentially replicated and differentiated during subsequent antigen challenge. This natural process may be mimicked by employing the technique referred to as “chain shuffling.” In this method, the affinity of “primary” human antibodies obtained by phage display may be improved by sequentially replacing the heavy and light chain V region genes with repertoires of naturally-occurring variants (repertoires) of V domain genes obtained from unimmunized donors. This technique allows the production of antibodies and antibody fragments with affinities in the pM-nM range. Another strategy for making antibodies includes, for example, large phage antibody repertoires.

[00112] Gene shuffling may also be used to derive human antibodies from rodent antibodies, where the human antibody has similar affinities and specificities to the starting rodent antibody. According to this method, which is also referred to as “epitope imprinting,” the heavy or light chain V domain gene of rodent antibodies obtained by phage display technique is replaced with a repertoire of human V domain genes, creating rodent-human chimeras. Selection on antigen results in isolation of human variable regions capable of restoring a functional antigen-binding site, i.e., the epitope governs (imprints) the choice of partner. When the process is repeated in order to replace the remaining rodent V domain, a human antibody is obtained.

Unlike traditional humanization of rodent antibodies by CDR grafting, this technique may provide completely human antibodies, which have no framework or CDR residues of rodent origin.

[00113] In some embodiments, an antibody may comprise a humanized antibody. A humanized antibody may be an antibody from a non-human species whose protein sequence has been modified to increase its similarity to antibody variants produced naturally in humans. Humanization may be performed for any antibody, but may be commonly be applied to monoclonal antibodies, e.g., for administration into humans. In some embodiments, humanization may be performed when the process of developing a specific antibody involves generation in a non-human immune system (e.g., mouse, goat, or other animal). The protein sequence of an antibody produced in a non-human immune system may be at least partially distinct from homologous antibodies that may occur naturally in humans, and may be immunogenic when administered to human patients. In some embodiments, humanization of an antibody may reduce or eliminate its immunogenicity in a human subject.

[00114] General steps to humanize a monoclonal antibody may comprise one or more of: (1) determining the nucleotide and predicted amino acid sequence of the starting antibody light and heavy variable domains, (2) designing the humanized antibody, i.e., deciding which antibody framework region to use during the humanizing process, (3) the actual humanizing methodologies/techniques, and (4) the transfection and expression of the humanized antibody. See, for example, U.S. Pat. Nos. 4,816,567; 5,807,715; 5,866,692; 6,331,415; 5,530,101; 5,693,761; 5,693,762; 5,585,089; and 6,180,370. A number of “humanized” antibody molecules comprising an antigen-binding site derived from a non-human immunoglobulin have been described, including chimeric antibodies having rodent or modified rodent V regions and their associated complementarity determining regions (CDRs) fused to human constant domains. See, for example, Winter et al. Nature 349:293-299 (1991), Lobuglio et al. Proc. Nat. Acad. Sci. USA 86:4220-4224 (1989), Shaw et al. J. Immunol. 138:4534-4538 (1987), and Brown et al. Cancer

Res. 47:3577-3583 (1987).

[00115] Other references describe rodent CDRs grafted into a human supporting framework region (FR) prior to fusion with an appropriate human antibody constant domain. See, for example, Riechmann et al. Nature 332:323-327 (1988), Verhoeyen et al., Science, 239:1534- 1536 (1988), and Jones et al., Nature, 321:522-525 (1986). Another reference describes rodent CDRs supported by recombinantly veneered rodent framework regions. See, e.g., European Patent Publication No. 0519596. These “humanized” molecules are designed to minimize unwanted immunological response toward rodent anti-human antibody molecules which limits the duration and effectiveness of therapeutic applications of those moieties in human recipients. For example, the antibody constant region may be engineered such that it is immunologically inert (e.g., does not trigger complement lysis). See, e.g., PCT Publication No. WO 99/058572 and UK Patent Application No. 9809951.8.

[00116] Other methods of humanizing antibodies that may also be utilized are disclosed by Daugherty et al., Nucl. Acids Res., 19:2471-2476 (1991) and in U.S. Pat. Nos. 6,180,377; 6,054,297; 5,997,867; 5,866,692; 6,210,671; and 6,350,861; and in PCT Publication No. WO 01/27160.

[00117] In yet another alternative, fully human antibodies may be obtained by using commercially available mice that have been engineered to express specific human immunoglobulin proteins. Transgenic animals that are designed to produce a more desirable (e.g., fully human antibodies) or more robust immune response may also be used for generation of humanized or human antibodies. Examples of such technology are XENOMOUSE™ from Abgenix, Inc. (Fremont, Calif.) and HUMAB-MOUSE® and TC MOUSE™ from Medarex, Inc. (Princeton, N.J.).

[00118] It will be apparent that although the above discussion pertains to humanized antibodies, the general principles discussed are applicable to customizing antibodies for use, for example, in dogs, cats, primates, equines, and bovines. It is further apparent that one or more aspects of humanizing an antibody described herein may be combined, e.g., CDR grafting, framework mutation, and CDR mutation.

[00119] If desired, an antibody of interest may be sequenced using any known method and the polynucleotide sequence may then be cloned into a vector for expression or propagation. [00120] The sequence encoding the antibody of interest may be maintained in vector in a host cell and the host cell may then be expanded and frozen for future use. In an alternative, the polynucleotide sequence may be used for genetic manipulation to “humanize” the antibody or to improve the specificity, affinity, or other characteristics of the antibody. For example, the constant region may be engineered to more resemble human constant regions to avoid immune response if the antibody is used in clinical trials and treatments in humans.

[00121] Also provided herein are methods of making any of these antibodies or polypeptides. The polypeptides may be produced by proteolytic or other degradation of the antibodies, by recombinant methods (i.e., single or fusion polypeptides) as described above, or by chemical synthesis. Polypeptides of the antibodies, especially shorter polypeptides up to about 50 amino acids, may be made by chemical synthesis. Methods of chemical synthesis are commercially available. For example, an antibody may be produced by an automated polypeptide synthesizer employing a solid phase method.

[00122] Antibodies may be made recombinantly by first isolating the antibodies and antibody producing cells from host animals, obtaining the gene sequence, and using the gene sequence to express the antibody recombinantly in host cells (e.g., CHO cells). Another method which may be employed is to express the antibody sequence in plants (e.g., tobacco) or transgenic milk. Methods for expressing antibodies recombinantly in plants or milk have been disclosed. Methods for making derivatives of antibodies, e.g., single chain, etc. are also within the scope of the present disclosure. [00123] “Host cell” includes an individual cell or cell culture that may be or has been a recipient for vector(s) for incorporation of polynucleotide inserts. Host cells include progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or in genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. A host cell includes cells transfected with a polynucleotide(s) of this disclosure.

[00124] DNA encoding an antibody may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies).

Hybridoma cells may serve as a source of such DNA. Once isolated, the DNA may be placed into one or more expression vectors (such as expression vectors disclosed in PCT Publication No.

WO 87/04462), which are then transfected into host cells such as E. coli cells, simian COS cells,

Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also may be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences, or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. In that manner, “chimeric” or “hybrid” antibodies are prepared that have the binding specificity of an antibody described herein.

[00125] Contemplated herein are vectors that encode the one or more antibodies or antigen-binding fragments described herein.

[00126] The term “vector,” as used herein, generally refers to a construct that is capable of delivering and in some cases expressing one or more gene(s) or sequence(s) (e.g., a gene or sequence of interest) in a host cell. Examples of vectors include, but are not limited to, viral vectors; naked DNA or RNA expression vectors; plasmid, cosmid, or phage vectors; DNA or RNA expression vectors associated with cationic condensing agents; DNA or RNA expression vectors encapsulated in liposomes; and certain eukaryotic cells, such as producer cells. [00127] The term “expression control sequence,” as used herein, generally refers to a nucleic acid sequence that directs transcription of a nucleic acid. An expression control sequence may be a promoter, such as a constitutive or an inducible promoter, or an enhancer. The expression control sequence is operably linked to the nucleic acid sequence to be transcribed.

[00128] An expression vector may be used to direct expression of an antibody. Expression vectors may be administered to obtain expression of an exogenous protein in vivo. See, e.g., U.S.

Pat. Nos. 6,436,908; 6,413,942; and 6,376,471, each of which is entirely incorporated herein by reference.

[00129] For high level production, a widely used mammalian expression system is one which utilizes Lonza’s GS Gene Expression System™. This system uses a viral promoter and selection via glutamine metabolism to provide development of high-yielding and stable mammalian cell lines.

[00130] For alternative high-level production, a widely used mammalian expression system is one which utilizes gene amplification by dehydrofolate reductase deficient (“dhfr-”) Chinese hamster ovary cells. The system is based upon the dehydrofolate reductase “dhfr” gene, which encodes the DHFR enzyme, which catalyzes conversion of dehydrofolate to tetrahydrofolate. In order to achieve high production, dhfr- CHO cells are transfected with an expression vector containing a functional DHFR gene, together with a gene that encodes a desired protein. In this case, the desired protein is recombinant antibody heavy chain and/or light chain.

[00131] By increasing the amount of the competitive DHFR inhibitor methotrexate (MTX), the recombinant cells develop resistance by amplifying the dhfr gene. In standard cases, the amplification unit employed is much larger than the size of the dhfr gene, and as a result the antibody heavy chain is co-amplified.

[00132] When large scale production of the protein, such as the antibody chain, is desired, both the expression level and the stability of the cells being employed are taken into account. [00133] The present application provides an isolated polynucleotide (nucleic acid) encoding an antibody or portion thereof as described herein, vectors containing such polynucleotides, and host cells and expression systems for transcribing and translating such polynucleotides into polypeptides.

[00134] The present application also provides constructs in the form of plasmids, vectors, transcription or expression cassettes which comprise at least one polynucleotide as above.

[00135] The present application also provides a recombinant host cell which comprises one or more constructs as above. A nucleic acid encoding any antibody described herein forms an aspect of the present application, as does a method of production of the antibody, which method comprises expression from encoding nucleic acid therefrom. Expression may be achieved by culturing under appropriate conditions recombinant host cells containing the nucleic acid. Following production by expression, an antibody or a portion thereof may be isolated and/or purified using any suitable technique, then used as appropriate.

[00136] Systems for cloning and expression of a polypeptide in a variety of different host cells are contemplated for use herein.

[00137] A further aspect provides a host cell containing nucleic acid as disclosed herein using any suitable method. A still further aspect provides a method comprising introducing such nucleic acid into a host cell. The introduction may be followed by causing or allowing expression from the nucleic acid, e.g., by culturing host cells under conditions for expression of the gene. [00138] A polynucleotide encoding an antibody or a portion thereof may be prepared recombinantly/synthetically in addition to, or rather than, cloned. In a further embodiment, the full DNA sequence of the recombinant DNA molecule or cloned gene of an antibody or portion thereof described herein may be operatively linked to an expression control sequence which may be introduced into an appropriate host using any suitable method.

[00139] DNA sequences may be expressed by operatively linking them to an expression control sequence in an appropriate expression vector and employing that expression vector to transform an appropriate host cell. Any of a wide variety of expression control sequences - sequences that control the expression of a DNA sequence operatively linked to it - may be used in these vectors to express the DNA sequences.

[00140] A wide variety of host/expression vector combinations may be employed in expressing the DNA sequences of this disclosure. It will be understood that not all vectors, expression control sequences, and hosts will function equally well to express the DNA sequences. Neither will all hosts function equally well with the same expression system. In some embodiments, in selecting a vector, the host is considered such that the vector may function in it. The vector’s copy number, the ability to control that copy number, and the expression of any other proteins encoded by the vector, such as antibiotic markers, may also be considered. In certain embodiments, in selecting a vector, the host is considered such that the vector functions in it. The vector’s copy number, the ability to control that copy number, and the expression of any other proteins encoded by the vector, such as antibiotic markers, may also be considered.

[00141] The present application also provides a method which comprises using a construct as stated above in an expression system in order to express the antibodies (or portions thereof) as above. Considering these and other factors, a variety of vector/expression control sequence/host combinations may be constructed that may express the DNA sequences on fermentation or in large scale animal culture.

[00142] Simultaneous incorporation of the antibody (or portion thereof)-encoding nucleic acids and the selected amino acid position changes may be accomplished by a variety of suitable methods including, for example, recombinant and chemical synthesis.

[00143] Isolation, Purification, and Detection

[00144] Specific nucleic acid molecules and vectors that encode binding agents described herein may be isolated and/or purified from their natural environment in substantially pure or homogeneous form. Methods of purifying proteins and nucleic acids are contemplated for use herein. “Isolated” (used interchangeably with “substantially pure”) when applied to polypeptides means a polypeptide or a portion thereof which, by virtue of its origin or manipulation: (i) is present in a host cell as the expression product of a portion of an expression vector; (ii) is linked to a protein or other chemical moiety other than that to which it is linked in nature; or (iii) does not occur in nature, for example, a protein that is chemically manipulated by appending, or adding at least one hydrophobic moiety to the protein so that the protein is in a form not found in nature. By “isolated” it may be further meant a protein that is: (i) synthesized chemically or (ii) expressed in a host cell and purified away from associated and contaminating proteins. The term generally means a polypeptide that has been separated from other proteins and nucleic acids with which it naturally occurs. The polypeptide may also be separated from substances such as antibodies or gel matrices (polyacrylamide) which are used to purify it.

[00145] Polypeptides may be isolated and purified from culture supernatant or ascites by saturated ammonium sulfate precipitation, an euglobulin precipitation method, a caproic acid method, a caprylic acid method, ion exchange chromatography (DEAE or DE52), or affinity chromatography using anti-Ig column or a protein A, protein G, or protein L column such as described in more detail below. In one aspect, reference to a binding agent, an antibody or an antigen-binding fragment thereof also refers to an “isolated binding agent,” an “isolated antibody,” or an “isolated antigen-binding fragment.” In another aspect, reference to a binding agent, an antibody, or an antigen-binding fragment thereof also refers to a “purified binding agent,” a “purified antibody,” or a “purified antigen-binding fragment.”

[00146] In addition to the therapeutic methods described herein, binding agents, antibodies, or antigen-binding fragments thereof that specifically bind to SARS-CoV-2 may also be used for purification and/or to detect SARS-CoV-2 levels in a sample or subject. Compositions of antibodies and antigen-binding fragments described herein may be used as non- therapeutic agents (e.g., as affinity purification agents). Generally, in one such embodiment, a protein or protein containing sample of interest may be immobilized on a solid phase such a Sephadex resin or filter paper. The immobilized protein or protein containing sample may be contacted with a sample containing the target of interest (or fragment thereof) to be purified, and thereafter the support may be washed with a suitable solvent that will remove substantially all the material in the sample except the target protein, which is bound to the immobilized antibody.

Finally, the support may be washed with another suitable solvent, such as glycine buffer, pH 5.0, which will release the target protein.

[00147] A sample may be obtained from a subject and optionally treated for use in a particular assay. The sample may be contacted with a binding agent, antibody, or antigen-binding fragment thereof that specifically bind to SARS-CoV-2, and the presence of SARS-CoV-2 in the sample may be identified when detection of the binding agent, antibody, or antigen-binding fragment thereof is observed. The term sample is used in its broadest sense. A “biological sample” as used herein, includes, but is not limited to, any quantity of a substance from a living thing or formerly living thing such as, for example, humans, mice, rats, monkeys, dogs, rabbits, and other animals. Such samples include, but are not limited to, blood, serum, mucus, saliva, urine, synovial fluid, cells, organs, tissues, bone marrow, lymph nodes, and neurons. In one instance, the binding agent, antibody, or antigen-binding fragment thereof, that specifically bind to SARS-CoV-2, may be labeled with, for example, biotin, such that addition of a secondary agent such as, for example, streptavidin alkaline phosphatase (AP), may enhance signal detection in an assay.

[00148] Assays that may be utilized in detection methods include, but are not limited to, ELISA, ELISPOT, western Blot, FACS, flow cytometry, immunohistochemistry, etc.

[00149] Whenever the term “at least,” “greater than,” or “greater than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “at least,” “greater than” or “greater than or equal to” applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3. [00150] Whenever the term “no more than,” “less than,” or “less than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “no more than,” “less than,” or “less than or equal to” applies to each of the numerical values in that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

EXAMPLES

[00151] Phylogenetic studies of antibody sequences

[00152] In the current disclosure, at least about 457 VH sequences and at least about 413 of LH sequences are aligned using a constraint-based multiple alignment tool. As a result, FIGS. 4A and 4B show phylogenetic trees that were generated using a fast-minimum evolution and evolutionary distance measured using the Grishin protein model with a max sequence difference of 0.85. Scale is measured in expected fraction of amino acid substitutions per site. Multiple sequence alignments of protein sequences is the alignment of three or more biological sequences, such as the amino acid sequences of the CDR regions of immunoglobulins. When visualized as phylogenetic trees, multiple sequence alignments can be used to infer the homology between the sequences and the evolutionary relationships between the sequences studied. For the sequences identified against SARS-Cov-2 SI, it is expected that members of homologous families of CDR3s will bind similar epitopes of the SI antigen.

[00153] Screening ELISAs

[00154] Referring to FIGS. 1 A-1C, certain disclosed sequences as listed in Table 13 were expressed as scFvs with various concentrations in solutions. The sequences were screened for affinity to SARS-CoV-2 SI trimer protein via indirect ELISA in FIGS. 1A (with a concentration of 6pg/ml of the antibody solutions) and IB (with a concentration of 4pg/ml of the antibody solutions). Negative control was aHER23xFLAG-scFv. In FIG. 1C (with a concentration of 50pg/ml of the antibody solutions), the sequences were screened for binding affinity against purified recombinant SARS-CoV-2 wt WA1 SI sFc-tagged protein via sandwich ELISA.

Negative control was a non-specific IgGl .

[00155] Table 13. Peptide sequences of paired heavy chain (VH) and light chain (LH) of selected antibodies

[00156] Kinetic ELISA

[00157] As shown in FIG. 2, sequences expressed as human IgGl were screened using an endpoint serial dilution sandwich ELISA against purified recombinant SARS-CoV-2 wt WA1 SI sFc-tagged protein. Data was normalized and the Kd was determined by linear regression analysis. [00158] In addition, the Kd values of different antibodies respectively are listed below in

Table 14:

[00159] Pseudovirus Neutralization Assay and Live SARS-CoV-2 Neutralization Assay [00160] As shown in FIG. 3, serial 2-fold dilution of antibodies against SI antigens were incubated with SARS-CoV-2 spike pseudovirus for 1 hour at 37°C, then transferred onto HEK- 293T-hACE2 cells. After 72 hours, cells were analyzed using Bright-Glo Luciferase Assay System. Serial dilutions for Prellis-VhVl-029, -035, and -120 are a serial 2-fold dilution began at concentrations of 426 ug/mL, 442 ug/mL, and 174 ug/mL respectively (left to right). The remaining antibodies shown here are serial 2-fold dilutions beginning at a concentration of 100 ug/mL (left to right). Data was normalized by setting cells treated with virus and no antibody to 100% infectivity.

[00161] Further, sequences expressed as IgGl were screened for in vitro neutralization of live SARS-CoV-2 virus. A pilot dose ranging study was performed to determine the appropriate starting concentration(s) of mAbs for neutralizing candidates. The mAbs were then further evaluated in additional neutralization assays to determine an approximate IC50 value for each mAh as shown in Table 15 below:

[00162] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the invention be limited by the specific examples provided within the specification. While the invention has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it shall be understood that all aspects of the invention are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is therefore contemplated that the invention shall also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

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Claims

CLAIMS WHAT IS CLAIMED IS:

1. A formulation for treatment of an infectious disease in a subject in need thereof, comprising a therapeutically effective amount of an antibody or an active fragment thereof comprising a peptide or a polypeptide that is at least about 70% homologous to amino acids 1- 100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935.

2. The formulation of claim 1, wherein said peptide or said polypeptide is at least about 80% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935.

3. The formulation of claim 1, wherein said peptide or said polypeptide is at least about 85% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935.

4. The formulation of claim 1, wherein said peptide or said polypeptide is at least about 90% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935.

5. The formulation of claim 1, wherein said peptide or said polypeptide is at least about 95% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1 - 935.

6. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467.

7. The formulation of claim 6, wherein said peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467.

8. The formulation of claim 6, wherein said peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467.

9. The formulation of claim 6, wherein said peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467.

10. The formulation of claim 6, wherein said peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 936 - 1467.

11. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990.

12. The formulation of claim 11, wherein said peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990.

13. The formulation of claim 11, wherein said peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990.

14. The formulation of claim 11, wherein said peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990.

15. The formulation of claim 11, wherein said peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1468 - 1990.

16. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702.

17. The formulation of claim 16, wherein said peptide or said polypeptide is at least about 80% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702.

18. The formulation of claim 16, wherein said peptide or said polypeptide is at least about 85% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702.

19. The formulation of claim 16, wherein said peptide or said polypeptide is at least about 90% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702.

20. The formulation of claim 16, wherein said peptide or said polypeptide is at least about 95% homologous to amino acids 1-100 of a sequence selected from the group consisting of SEQ ID NOS. 1991 - 2702.

21. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962.

22. The formulation of claim 21, wherein said peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962.

23. The formulation of claim 21, wherein said peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962.

24. The formulation of claim 21, wherein said peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962.

25. The formulation of claim 21, wherein said peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2703 - 2962.

26. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of sequences SEQ ID NOS. 2963 - 3221, for a treatment of an infectious disease.

27. The formulation of claim 26, wherein said peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2963 - 3221.

28. The formulation of claim 26, wherein said peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2963 - 3221.

29. The formulation of claim 26, wherein said peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2963 - 3221.

30. The formulation of claim 26, wherein said peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 2963 - 3221.

31. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of sequences SEQ ID NOS. 3222 - 6329, for a treatment of an infectious disease.

32. The formulation of claim 31, wherein said peptide or said polypeptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 3222 - 6329.

33. The formulation of claim 31, wherein said peptide or said polypeptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 3222 - 6329.

34. The formulation of claim 31, wherein said peptide or said polypeptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 3222 - 6329.

35. The formulation of claim 31, wherein said peptide or said polypeptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 3222 - 6329.

36. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876.

37. The formulation of claim 36, wherein said peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876.

38. The formulation of claim 36, wherein said peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876.

39. The formulation of claim 36, wherein said peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876.

40. The formulation of claim 36, wherein said peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6330 - 6876.

41. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide that is at least about 70% homologous to a sequence selected from the group consisting of sequences SEQ ID NOS. 6877 - 7418, for a treatment of an infectious disease.

42. The formulation of claim 41, wherein said peptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6877 - 7418.

43. The formulation of claim 41, wherein said peptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6877 - 7418.

44. The formulation of claim 41, wherein said peptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6877 - 7418.

45. The formulation of claim 41, wherein said peptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 6877 - 7418.

46. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a first peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990 and a second peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418.

47. The formulation of claim 46, wherein said first peptide or said first polypeptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990.

48. The formulation of claim 46, wherein said first peptide or said first polypeptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990.

49. The formulation of claim 46, wherein said first peptide or said first polypeptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990.

50. The formulation of claim 46, wherein said first peptide or said first polypeptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1 - 1990.

51. The formulation of claim 46, wherein said second peptide or said second polypeptide is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418.

52. The formulation of claim 46, wherein said second peptide or said second polypeptide is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418.

53. The formulation of claim 46, wherein said second peptide or said second polypeptide is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418.

54. The formulation of claim 46, wherein said second peptide or said second polypeptide is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 1991 - 7418.

55. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843.

56. The formulation of claim 55, wherein said antibody comprises a variable domain of a heavy chain and a variable domain of a light chain kappa (IGK) or a light chain lambda (IGL).

57. The formulation of claim 55, wherein said antibody is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843.

58. The formulation of claim 55, wherein said antibody is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843.

59. The formulation of claim 55, wherein said antibody is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843.

60. The formulation of claim 55, wherein said antibody is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7419 - 7843.

61. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950.

62. The antibody of claim 61, wherein said antibody comprises a variable domain of a heavy chain and a variable domain of a light chain kappa (IGK) or a light chain lambda (IGL).

63. The formulation of claim 61, wherein said antibody is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950.

64. The formulation of claim 61, wherein said antibody is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950.

65. The formulation of claim 61, wherein said antibody is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950.

66. The formulation of claim 61, wherein said antibody is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7844 - 7950.

67. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that comprises a peptide or a polypeptide that is at least about 70% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046.

68. The antibody of claim 61, wherein said antibody comprises a variable domain of a heavy chain and a variable domain of a light chain kappa (IGK) or a light chain lambda (IGL).

69. The formulation of claim 61, wherein said antibody is at least about 80% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046.

70. The formulation of claim 61, wherein said antibody is at least about 85% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046.

71. The formulation of claim 61, wherein said antibody is at least about 90% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046.

72. The formulation of claim 61, wherein said antibody is at least about 95% homologous to a sequence selected from the group consisting of SEQ ID NOS. 7951 - 8046.

73. The formulation of claim 61, wherein said antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 7958, SEQ ID NO: 7960, SEQ ID NO: 7990, SEQ ID NO: 8013, SEQ ID NO: 8022, SEQ ID NO: 8023, SEQ ID NO: 8026, or SEQ ID NO: 8041.

74. The formulation of claim 73, wherein said antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 7958.

75. The formulation of claim 73, wherein said antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 8022.

76. The formulation of claim 73, wherein said antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 8023.

77. The formulation of claim 73, wherein said antibody comprises a peptide or a polypeptide that is at least about 95% homologous to SEQ ID NO: 8041.

78. The formulation of claim 73, wherein said antibody comprises a peptide or a polypeptide that is homologous to SEQ ID NO: 7958.

79. The formulation of claim 73, wherein said antibody comprises a peptide or a polypeptide that is homologous to SEQ ID NO: 8022.

80. The formulation of claim 73, wherein said antibody comprises a peptide or a polypeptide that is homologous to SEQ ID NO: 8023.

81. The formulation of claim 73, wherein said antibody comprises a peptide or a polypeptide that is homologous to SEQ ID NO: 8041.

82. A formulation for treatment of an infectious disease in a subject in need thereof, comprising an antibody or an active fragment thereof that specifically binds to an S 1 domain of SARS-CoV-2 spike protein with a dissociation constant (KD) value of less than about 1500 nM.

83. The formulation of any of the claims 1-82, wherein said antibody is multivalent.

84. The formulation of any of the claims 1-82, wherein said antibody is bivalent, trivalent, or tetravalent.

85. The formulation of any of the claims 1-82, wherein said antibody is specific to SARS- Cov-2 spike protein.

86. The formulation of claim 85, wherein said antibody specifically binds to a SI domain of said SARS-Cov-2 spike protein.

87. The formulation of claim 86, wherein said antibody specifically binds to a receptor binding domain (RBD) of said S 1 domain.

88. The formulation of claim 87, wherein said antibody specifically binds to a S2 domain of said SARS-Cov-2 spike protein.

89. The formulation of any of claims 1-88, wherein said antibody neutralizes the infectivity of severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2).

90. The formulation of any of claims 1-88, wherein said antibody blocks binding of said RBD of said R1 domain to a human ACE2 receptor (hACE2) by at least 50% when measured using a binding assay.

91. The formulation of claim 90, wherein said binding assay is blocking ELISA assay.

92. The formulation of any of claims 1-91, wherein said antibody is a humanized antibody.

93. The formulation of any of claims 1-91, wherein said antibody is a human antibody.

94. The formulation of any of claims 1-92, wherein said antibody is derived from a naive B- cell.

95. The formulation of any of claims 1-92, wherein said antibody is derived from a memory B-cell.

96. The formulation of any of claims 1-95, wherein said infectious disease is a coronavirus disease 2019 (COVID-19).

97. The formulation of any of claims 1-96, wherein said antibody comprises a full-length antibody, a functional fragment thereof, a Fv fragment, a Fab fragment, a Fab’ fragment, a Fab² fragment, a scFv fragment, a diabody, a minibody, a nanobody (sdAb), or a camelid single domain antibody (VHH).

98. A nucleic acid molecule encoding an antibody of any of claims 1-97.

99. A vector comprising said nucleic acid of claim 98.

100. A pharmaceutical composition comprising an antibody of any of claims 1-97.

101. The pharmaceutical composition of claim 99, further comprising a pharmaceutically acceptable carrier, an excipient, or any combination thereof.

102. A method for treating a subject having or suspected of having a coronavirus disease, comprising administering to said subject an effective amount of said pharmaceutical composition of claim 93.

103. The method of claim 102, further comprising administering a pain reliever, an antiviral compound, an antibiotic compound, or a steroid.

104. The method of claim 103, wherein said pain reliever is ibuprofen or acetaminophen.

105. The method of claim 103, wherein said antiviral compound is remdesivir.

106. The method of claim 103, wherein said antibiotic compound is azithromycin.

107. The method of claim 103, wherein said steroid is dexamethasone.

108. The method of claim 102, wherein said coronavirus disease is COVID-19.