Antibodies having pan-antiviral activity and methods thereof

Abstract

Described herein are antibodies having pan-antiviral activity. The antibodies recognize glycosylation patterns, such as those found on viral proteins, or, in some instances, those found on host proteins. Also described herein are methods of preventing, treating and / or ameliorating viral infections using the antibodies of the disclosure. The present disclosure also describes tetramer and hexamer assemblies of the antibodies described herein.

Description

[0001] Attorney Docket No. 047162-7515WO1(02827)

[0002] ANTIBODIES HAVING PAN-ANTIVIRAL ACTIVITY AND METHODS THEREOF

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U. S. Provisional Patent Application No.

[0004] 63 / 756,581, filed February 10, 2025, which is hereby incorporated herein by reference in its entirety.

[0005] REFERENCE TO SEQUENCE LISTING

[0006] This application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML copy, created on January 15, 2026. is named “047162-7515WO1 sequence listing. xml” and is 160,724 bytes in size.

[0007] BACKGROUND

[0008] Antibody therapies have been used as a treatment for viral infections since the early 20thcentury, when serum from infected subjects who had recovered from the same infection was used as a therapeutic agent. Since then, antibodies purified from sera, monoclonal antibodies generated using the hybridoma method, and engineered antibodies (such as humanized antibodies) against viruses have also been used to treat viral infections.

[0009] Conventional antibodies recognize specific protein sequences or structural features found in viral surface proteins. Sequences and structures of the viral proteins, such as viral surface proteins vary' considerably across viral families, species, or strains of the same species. As such, most antiviral antibodies have limited adaptability', as they are specific for limited species, sometimes even strains, of viruses. Accordingly, health care facilities need to store large numbers of different antibodies, some of which with stringent storage requirements, putting further pressure on the facilities.

[0010] Therefore, there is a need for broad-spectrum antibodies that recognize viruses across multiple viral families. The present invention addresses this need.

[0011] BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The foregoing and other features and advantages of the present invention will be more fully understood from the following detailed description of illustrative embodiments taken in conjunction with the accompanying drawings.

[0013] FIG. 1A-FIG. IB present graphical representations of binding of anti-viral mAbs to 1

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[0015] SARS-CoV-2 spike (FIG. 1 A) and to HIV gp120 (FIG. 1B).

[0016] FIG. 2 presents heat map visualization of anti-viral antibodies 1F6, 2C8, 3D3, 5H8, and 7C6 binding to a wide variety of viral glycoproteins.

[0017] FIG. 3A-FIG. 3E present images of an HSV-1GFPneutralization assay. FIG. 3 A presents an image of the neutralization assay. FIG. 3B presents a close-up image of complement enhanced antibody 1F6. FIG. 3C presents a close-up image of complement enhanced antibody 2C8. FIG. 3D presents a close-up image of complement enhanced antibody 3D3. FIG. 3E presents a close-up image of complement enhanced antibody 5H8.

[0018] FIG. 4 presents a graphical representation of the results of the HSV-1GFPneutralization assay.

[0019] FIG. 5A-FIG. 5E present images of an HSV-2WTneutralization assay. FIG. 5 A presents an image of the neutralization assay. FIG. 5B presents a close-up image of complement enhanced antibody 1F6. FIG. 5C presents a close-up image of complement enhanced antibody 2C8. FIG. 5D presents a close-up image of complement enhanced antibody 5H8. FIG. 5E presents a close-up image of complement enhanced antibody 7C6.

[0020] FIG. 6 presents a graphical representation of the results of the HSV-2WTneutralization assay.

[0021] FIG. 7A-FIG. 7B present images of SDS-PAGE gels of purified antibodies under nonreducing and reducing conditions. FIG. 7A presents an image of a gel representing the first batch production of the antibodies. FIG. 7B presents an image of a gel representing the second batch production of the antibodies.

[0022] FIG. 8A-FIG. 8B present schematic representations and data related to glycan binding analysis of antibodies 2C8, 1F6, 5H8, 3D3, and 7C6. FIG. 8A presents schematic representations of glycan structures. FIG. 8B presents graphical representation of the glycan binding analysis.

[0023] FIG. 9 presents a schematic representation of a single chain diabody Fc fusion.

[0024] FIG. 10 presents an image of reducing and non-reducing gel-based analysis of the purity of each single chain diabody Fc fusion.

[0025] FIG. 11A-FIG. 11E present data and results related to gel filtration based analysis of the single chain diabody Fc (scDbFc) fusions. The following single chain diabody Fc fusions were analyzed: 2C8 (FIG. 11 A), 1F6 (FIG. 11B), 3D3 (FIG. 11C), 5H8 (FIG. 11D), and 7C6 (FIG. 11E).

[0026] FIG. 12 A-FIG. 12B present graphical representations of binding curves of the antiviral scDbFc fusions 1F6, 2C8, 3D3, 5H8, and 7C6 to SARS-CoV-2 spike (FIG. 12A)

[0027] 2

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[0029] and HIV gpl20 (FIG. 12B).

[0030] FIG. 13 presents an image of reducing and non-reducing gel-based analysis of hexamer assemblies of 2C8, 1F6, 3D3, 5H8, and 7C6.

[0031] FIG. 14A-FIG. 14C present images of reducing and non-reducing gel-based analysis of the hexamer assemblies of 2C8 and 1F6 (FIG. 14A); 3D3 and 5H8 (FIG. 14B); and 7C6 (FIG. 14C).

[0032] FIG. 15A-FIG. I5E present data and results related to gel filtration based analysis of the hexamer assemblies. Hexamer assemblies of the following antibodies were analyzed: 2C8 (FIG. 15A), 1F6 (FIG. 15B), 3D3 (FIG. 15C), 5H8 (FIG. 15D), and 7C6 (FIG. 15E).

[0033] FIG. 16A-FIG. 16E present surface plasmon resonance sensorgrams of the binding of the anti-viral antibodies 1F6 (FIG. 16A), 2C8 (FIG. 16B), 3D3 (FIG. 16C). 5H8 (FIG. 16D). and 7C6 (FIG. 16E) to HIV gp120, EBOV GP, and CMV gB.

[0034] FIG. 17A-FIG. 17E present graphical representations of the glycan binding analysis of antibodies 7C6 (FIG. 17A), 2C8 (FIG. 17B), 1F6 (FIG. 17C), 3D3 (FIG. 17D), and 5H8 (FIG. 17E) at 10 pg / rnL.

[0035] FIG. 18A-FIG. 18B present a schematic, data, and results related to the hexamer complement activation ELISA assay. FIG. 18A presents a schematic representation of the hexamer complement activation ELISA assay. FIG. 18B presents a graphical representation of the results of the assay.

[0036] FIG. 19 presents a graphical representation of data and results related to PanV (complement-enhanced 2C8)-based reduction of clinical disease severity following wild-type HSV-2 challenge in Depo-Provera-treated mice (n=10 per group).

[0037] FIG. 20 presents graphical representations of data and results related to immunofluorescence-based analysis of antibody binding to tissue sections.

[0038] FIG. 21A-FIG. 21D present representative images of immunofluorescence-based analysis of human peripheral tissues. FIG. 21 A presents representative images of adrenal gland tissue, breast tissue, cervix tissue, and endometrium tissue. FIG. 21B presents representative images of liver tissue, gall bladder tissue, heart muscle tissue, kidney tissue, ovary tissue, and pancreas tissue. FIG. 21C presents representative images of parathyroid tissue, prostate tissue, placenta tissue, rectum tissue, retina tissue, and small intestine tissue. FIG. 21D presents representative images of stomach tissue, testis tissue, thyroid tissue, and urinary bladder tissue.

[0039] FIG. 22A-FIG. 22G present data and results related to comparative HuProt protein microarray profiling of antibodies. FIG. 22A presents the total number of proteins exceeding 3

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[0041] the F635 positivity threshold (> 1000) for each antibody, thereby providing a global measure of antibody polyreactivity or breadth of protein recognition. FIG. 22B-FIG. 22G present, for each antibody, the mean fluorescence intensity (F635) for individual proteins plotted as log₂ fold-change relative to the negative control antibody (9H2). FIG. 22B presents positive control antibody 5F5 versus negative control. FIG. 22C presents antibody 7C6 versus negative control. FIG. 22D presents antibody 1F6 versus negative control. FIG. 22E presents antibody 5H8 versus negative control. FIG. 22F presents antibody 2C8 versus negative control. FIG. 22G presents antibody 3D3 versus negative control.

[0042] DETAILED DESCRIPTION

[0043] As described herein, antibodies with pan antiviral activity were produced according to the present disclosure. In some aspects, such antibodies are able to recognize viral proteins across several virus families. In some aspects, the antibodies recognize glycosylation patterns specific to viral proteins (e.g., the N-acetylglucosamine (GlcNAc) residues on the nonreducing end of oligosaccharides), rather than specific peptide sequences, which vary significantly among viral families. These glycosylation features are conserved glycan epitopes enriched in a broad range of viral antigens. The specificities against such conserved glycan modification ensure the recognition of various viral antigens despite the broad diversity of the peptide sequences of the viral proteins.

[0044] Indeed, the pan antiviral antibodies described herein are able to recognize surface proteins of HIV, influenza, encephalitis, Hantaan virus, coronavirus, RSV, vesicular stomatitis virus (VSV), herpesvirus, Zika virus, Dengue virus, rabies, Ebola, and / or cytomegalovirus (CMV). The surface proteins of these viruses share little similarities, except that they all have certain glycosylation features recognized by the present antibodies.

[0045] Furthermore, in some aspects, since certain antibodies of the disclosure recognize terminal GlcNAc moieties but not GlcNAc in the core structure of oligosaccharide, in some aspects these antibodies pose minimal risk of autoreactivity because glycan chains on host proteins are capped with sialic acid. Moreover, in some aspects, certain antibodies of the disclosure recognize glycans that do not end in terminal GlcNAc.

[0046] DEFINITIONS

[0047] Unless otherwise defined, scientific and technical terms used herein have the meanings that are commonly understood by those of ordinary skill in the art. In the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or 4

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[0049] extrinsic definition. Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The use of “or” means “and / or” unless stated otherwise. The use of the term “including,” as well as other forms, such as “includes” and “included,” is not limiting.

[0050] Generally, nomenclature used in connection with cell and tissue culture, molecular biology, immunology’, microbiology, genetics, protein and nucleic acid chemistry’, and nucleic acid hybridization described herein is well-known and commonly used in the art. The methods and techniques provided herein are generally performed according to conventional methods well know n in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherw ise indicated. Enzy matic reactions and purification techniques are performed according to manufacturer’s specifications, as commonly accomplished in the art or as described herein. The nomenclatures used in connection with, and the laboratory procedures and techniques of, analy tical chemistry, synthetic organic chemistry’, and medicinal and pharmaceutical chemistry’ described herein are those well-known and commonly used in the art. Standard techniques are used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients.

[0051] Furthermore, the experiments described herein, unless otherwise indicated, use conventional molecular and cellular biological and immunological techniques within the skill of the art. Such techniques are well known to the skilled worker, and are explained fully in the literature. See, e.g., Ausubel, et al., ed.. Current Protocols in Molecular Biology, John Wiley & Sons, Inc., NY, N. Y. (1987-2008), including all supplements, Molecular Cloning: A Laboratory Manual (Fourth Edition) by MR Green and J. Sambrook and Harlow et al., Antibodies: A Laboratory Manual, Chapter 14, Cold Spring Harbor Laboratory, Cold Spring Harbor (2013, 2nd edition).

[0052] In the disclosure, where an element or component is said to be included in and / or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components and can be selected from a group consisting of two or more of the recited elements or components.

[0053] In the methods described herein, the acts can be carried out in any order, except when a temporal or operational sequence is explicitly recited. Furthermore, specified acts can be carried out concurrently unless explicit claim language recites that they be carried out separately. For example, a claimed act of doing X and a claimed act of doing Y can be conducted simultaneously within a single operation, and the resulting process will fall within 5

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[0055] the literal scope of the claimed process.

[0056] That the disclosure may be more readily understood, select terms are defined below. Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 and so forth, as well as individual numbers within that range, for example. 1, 2, 2.7, 3. 4, 5, 5.3. and 6. This applies regardless of the breadth of the range.

[0057] As used herein, the terms "a," "an," or "the" are used to include one or more than one unless the context clearly dictates otherwise. By way of example, “an element” means one element or more than one element. The term "or" is used to refer to a nonexclusive "or" unless otherwise indicated. The statement "at least one of A and B" or "at least one of A or B" has the same meaning as " A, B, or A and B."

[0058] “About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20% or ±10%, more preferably ±5%, even more preferably ±1%, and still more preferably ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

[0059] As used herein, to “alleviate” a disease means reducing the severity of one or more symptoms of the disease.

[0060] An “amino acid” as used herein is meant to include both natural and synthetic amino acids, and both D and L amino acids. “Standard amino acid” means any of the twenty L-amino acids commonly found in naturally occurring peptides. “Nonstandard amino acid residues” means any amino acid, other than the standard amino acids, regardless of whether it is prepared synthetically or derived from a natural source. As used herein, “synthetic amino acid” also encompasses chemically modified amino acids, including but not limited to salts, amino acid derivatives (such as amides), and substitutions. Amino acids contained within the peptides, and particularly at the carboxy- or amino-terminus, can be modified by methylation, amidation, acetylation or substitution with other chemical groups which can change a peptide's circulating half-life without adversely affecting activity of the peptide. Additionally, a disulfide linkage may be present or absent in the peptides.

[0061] The term “antibody” or “Ab” or “immunoglobulin” are terms of art and can be used 6

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[0063] interchangeably and refer to a protein, or polypeptide sequence which is or is derived from an immunoglobulin molecule having at least one antigen binding site which specifically binds to a specific epitope on an antigen (See. e.g, Harlow et al., 1998, Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, NY; Harlow et al., 1989, Antibodies: A Laboratory7Manual, Cold Spring Harbor, New York; Houston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Bird et al.. 1988, Science 242:423-426).

[0064] Antibodies can be intact immunoglobulins derived from natural sources or from recombinant sources and can be immunoreactive portions of intact immunoglobulins. The antibodies useful in the present invention may exist in a variety of forms including, for example, polyclonal antibodies, monoclonal antibodies, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, synthetic antibodies, tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, an antibody heavy chain monomer, an antibody light chain dimer, an antibody¬ heavy7chain dimer, an antibody light chain-antibody heavy chain pair, intrabodies, heteroconjugate antibodies, single domain antibodies, monovalent antibodies, single chain antibodies or single chain Fv (scFv), nanobodies, intracellular antibodies, intrabodies, camelized antibodies, camelid antibodies, IgNAR antibodies, affybodies, Fab fragments, F(ab') fragments. F(ab)2, disulfide-linked Fvs (sdFv), anti-idiotypic (anti-Id) antibodies (including, e.g., anti-anti-Id antibodies), and antigen-binding fragments of any of the above. Antibodies can be of any type (e.g., IgG, IgE, IgM, IgD, IgA or TgY), any class, (e.g., IgGl, IgG2, IgG3, IgG4, IgAl or IgA2), or any subclass (e.g., IgG2a or IgG2b) of immunoglobulin molecule. In some aspects, antibodies described herein are IgG antibodies, or a class (e.g., human IgGl or IgG4) or subclass thereof. Full-length antibodies are sometimes tetramers comprising two heavy chain and two light chain immunoglobulin molecules.

[0065] The terms "antibody fragment,” ’‘antigen-binding fragment,” and “antigen-binding domain” of an antibody and similar terms are used interchangeably and refer to at least one portion of an intact antibody, or recombinant variants thereof, and comprising or consisting of the antigen-binding domain, e.g.. an antigenic determining variable region of an intact antibody, that is sufficient to confer recognition and specific binding of the antibody fragment to a target, such as an antigen. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments, scFv antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL or VH). VHH domains, and multi-specific (e.g., bispecific) antibodies formed from antibody fragments. The term “scFv” refers to a fusion 7

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[0067] protein comprising at least one antibody fragment comprising a variable region of a light chain and at least one antibody fragment comprising a variable region of a heavy chain, wherein the light and heavy chain variable regions are contiguously linked via a short flexible polypeptide linker, and capable of being expressed as a single chain polypeptide, and wherein the scFv retains the specificity of the intact antibody from which it is derived. Unless specified, as used herein an scFv may have the VL and VH variable regions in either order, e.g., with respect to the N-terminal and C-terminal ends of the polypeptide, the scFv may comprise VL-linker-VH or may comprise VH-linker-VL.

[0068] An “antibody heavy chain,” as used herein, refers to the larger of the tw o types of polypeptide chains present in antibody molecules in their naturally occurring conformations, and which normally determines the class to which the antibody belongs.

[0069] An “antibody light chain,” as used herein, refers to the smaller of the two types of polypeptide chains present in antibody molecules in their naturally occurring conformations. Kappa (K) and lambda ( ) light chains refer to the two major antibody light chain isotypes.

[0070] The term “antigen” or “Ag” as used herein is defined as a molecule that provokes an immune response. This immune response may involve either antibody production, or the activation of specific immunologically-competent cells, or both. The skilled artisan will understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. Furthermore, antigens can be derived from recombinant or genomic DNA. A skilled artisan will understand that any DNA, which comprises a nucleotide sequence or a partial nucleotide sequence encoding a protein that elicits an immune response therefore encodes an “antigen” as that term is used herein. Furthermore, one skilled in the art will understand that an antigen need not be encoded solely by a full-length nucleotide sequence of a gene. It is readily apparent that the present invention includes, but is not limited to. the use of partial nucleotide sequences of more than one gene and that these nucleotide sequences are arranged in various combinations to elicit the desired immune response. Moreover, a skilled artisan will understand that an antigen need not be encoded by a “gene” at all. It is readily apparent that an antigen can be generated or synthesized, or can be derived from a biological sample. Such a biological sample can include, but is not limited to a tissue sample, a tumor sample, a cell or a biological fluid.

[0071] The term “avidity” as used herein refers to the total binding strength of an antibody for an antigen at every binding site in a single non-covalent interaction, which affects the functional affinity.

[0072] “Binding affinity” generally refers to the strength of the sum total of non-covalent 8

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[0074] interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity’" refers to intrinsic binding affinity7which reflects a 1: 1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by the equilibrium dissociation constant (KD). Affinity7can be measured and / or expressed in a number of ways known in the art, including, but not limited to, equilibrium dissociation constant (KD), equilibrium association constant (KA), and IC50. The KD is calculated from the quotient of koff / kon, whereas KA is calculated from the quotient of kon / koff, where konrefers to the association rate constant of, e.g., an antibody to an antigen, and koff refers to the dissociation rate constant of, e.g., an antibody to an antigen.

[0075] The term “biological” or “biological sample” refers to a sample obtained from an organism or from components (e.g., cells) of an organism. The sample may be of any biological tissue or fluid. Frequently the sample will be a “clinical sample” which is a sample derived from a patient. Such samples include, but are not limited to, bone marrow, cardiac tissue, sputum, blood, lymphatic fluid, blood cells (e.g.. white cells), tissue or fine needle biopsy samples, urine, peritoneal fluid, and pleural fluid, or cells therefrom. Biological samples may also include sections of tissues such as frozen sections taken for histological purposes.

[0076] A “coding region” of a gene consists of the nucleotide residues of the coding strand of the gene and the nucleotides of the non-coding strand of the gene that are homologous with or complementary7to, respectively, the coding region of an mRNA molecule produced by transcription of the gene.

[0077] A “coding region” of an mRNA molecule also consists of the nucleotide residues of the mRNA molecule that are matched with an anti-codon region of a transfer RNA molecule during translation of the mRNA molecule or that encode a stop codon. The coding region may thus include nucleotide residues corresponding to amino acid residues not present in the mature protein encoded by the mRNA molecule (e.g., amino acid residues in a protein export signal sequence).

[0078] “Complementary” as used herein to refer to a nucleic acid, refers to the broad concept of sequence complementarity between regions of two nucleic acid strands or between two regions of the same nucleic acid strand. It is known that an adenine residue of a first nucleic acid region is capable of forming specific hydrogen bonds (“base pairing”) with a residue of a second nucleic acid region which is antiparallel to the first region if the residue is thymine or uracil. Similarly, it is known that a cytosine residue of a first nucleic acid strand is capable of 9

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[0080] base pairing with a residue of a second nucleic acid strand which is antiparallel to the first strand if the residue is guanine. A first region of a nucleic acid is complementary to a second region of the same or a different nucleic acid if, when the two regions are arranged in an antiparallel fashion, at least one nucleotide residue of the first region is capable of base pairing with a residue of the second region. Preferably, the first region comprises a first portion and the second region comprises a second portion, whereby, when the first and second portions are arranged in an antiparallel fashion, at least about 50%, and preferably at least about 75%, at least about 90%, or at least about 95% of the nucleotide residues of the first portion are capable of base pairing with nucleotide residues in the second portion. More preferably, all nucleotide residues of the first portion are capable of base pairing with nucleotide residues in the second portion.

[0081] In this disclosure, “comprises,” “comprising,” “containing” and “having” and the like can have the meaning ascribed to them in U. S. patent law and can mean “includes,” “including,” and the like; “consisting essentially of’ or “consists essentially” likewise has the meaning ascribed in U. S. patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not changed by the presence of more than that which is recited, but excludes prior art embodiments.

[0082] As used herein, the terms "conservative variation" or "conservative substitution" generally refers to the replacement of an amino acid residue by another, biologically similar residue. Conservative variations or substitutions are not likely to change the shape of the peptide chain. Examples of conservative variations, or substitutions, include the replacement of one hydrophobic residue such as isoleucine, valine, leucine or methionine for another, or the substitution of one polar residue for another, such as the substitution of arginine for lysine, glutamic for aspartic acid, or glutamine for asparagine.

[0083] As used herein, the term “constant region” or “constant domain” refers to an antibody portion, e.g., a carboxy l terminal portion of a light and / or heavy chain which is not directly involved in binding of an antibody to antigen but which can exhibit various effector functions, such as interaction with the Fc receptor. The terms refer to a portion of an immunoglobulin molecule having a generally more conserved amino acid sequence relative to an immunoglobulin variable domain.

[0084] A “constitutive” promoter is a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell under most or all physiological conditions of the cell.

[0085] 10

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[0087] The term “delivery vehicle” is used herein as a generic reference to any delivery vehicle capable of delivering a compound to a subject, including, but not limited to, dermal delivery vehicles and transdermal delivery vehicles.

[0088] “Effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein, effective to achieve a particular biological result. Such results may include, but are not limited to, treatment of a disease or condition as determined by any means suitable in the art.

[0089] “Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.

[0090] As used herein, an “epitope” is a term in the art and refers to a localized region of an antigen to which an antibody can specifically bind. An epitope can be, for example, contiguous amino acids of a polypeptide (linear or contiguous epitope), or an epitope can, for example, come together from two or more non-contiguous regions of a polypeptide or polypeptides (conformational, non-linear, discontinuous, or non-contiguous epitope), or an epitope can be. for example, glycan and lipid groups from post-translational modification, such as on the amino acids of a polypeptide. In some aspects, the epitope can be determined by structural methods, e.g., X-ray diffraction crystallography, nuclear magnetic resonance (NMR), or electron microscopy (e.g., negative stain or cryo-EM), ELISA assays, hydrogen / deuterium exchange coupled with mass spectrometry (e.g., MALDI mass spectrometry), array-based oligo-peptide scanning assays, and / or mutagenesis mapping (e.g., site-directed mutagenesis mapping). In some aspects, the epitope of an antibody or antigenbinding fragment can be determined using cryo-EM studies.

[0091] As used herein, the term “expression” as used herein is defined as the transcription and / or translation of a particular nucleotide sequence driven by its promoter.

[0092] As used herein, the term “expression vector” refers to a vector comprising a

[0093] 11

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[0095] recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, such as cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., Sendai viruses, lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinant polynucleotide.

[0096] As used herein, the term '‘fragment,’’ as applied to a protein or peptide, refers to a subsequence of a larger protein or peptide. A “fragment” of a protein or peptide can be at least about 20 amino acids in length; for example, at least about 50 amino acids in length; at least about 100 amino acids in length, at least about 200 amino acids in length, at least about 300 amino acids in length, and at least about 400 amino acids in length (and any integer value in between). As used herein, an antibody fragment refers to active fragments thereof, i.e., fragments having the same or similar characteristics that are used for the definition of an antibody according to the invention, in some aspects affinity for viral glycosylation features. For convenience when the term antibody is used, fragments thereof exhibiting the same characteristic are also being considered.

[0097] As used herein, the term “fragment,” as applied to a nucleic acid, refers to a subsequence of a larger nucleic acid. A “fragment” of a nucleic acid can be at least about 15 nucleotides in length; for example, at least about 50 nucleotides to about 100 nucleotides; at least about 100 to about 500 nucleotides, at least about 500 to about 1000 nucleotides, at least about 1000 nucleotides to about 1500 nucleotides; or about 1500 nucleotides to about 2500 nucleotides; or about 2500 nucleotides (and any integer value in between).

[0098] As used herein, the term “host cell” includes an individual cell or cell culture that can 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 in vivo with a polynucleotide(s) of this invention.

[0099] “Humanized” forms of non-human (e g., murine) antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) which 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- 12

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[0101] determining region (CDR) of the recipient are replaced by residues from a CDR of a nonhuman species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity, and capacity. In some instances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies can comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. These modifications are made to further refine and optimize antibody performance. In general, the humanized antibody will 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 sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature, 321: 522-525, 1986; Reichmann et al., Nature, 332: 323-329, 1988; Presta, Curr. Op. Struct. Biol., 2: 593-596, 1992.

[0102] As used herein, the term “identity"’ refers to the subunit sequence identity between two polymeric molecules particularly between two amino acid molecules, such as, between two polypeptide molecules. When two amino acid sequences have the same residues at the same positions; e.g., if aposition in each of two polypeptide molecules is occupied by an arginine, then they are identical at that position. The identity or extent to which two amino acid sequences have the same residues at the same positions in an alignment is often expressed as a percentage. The identity between two amino acid sequences is a direct function of the number of matching or identical positions; e.g., if half (e.g., five positions in a polymer ten amino acids in length) of the positions in two sequences are identical, the two sequences are 50% identical; if 90% of the positions (e.g., 9 of 10), are matched or identical, the two amino acids sequences are 90% identical.

[0103] An “inducible” promoter is a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell substantially only when an inducer which corresponds to the promoter is present in the cell.

[0104] “Instructional material,” as that term is used herein, includes a publication, a recording, a diagram, or any other medium of expression which can be used to communicate the usefulness of the composition and / or compound of the invention in a kit. The instructional material of the kit may, for example, be affixed to a container that contains the compound and / or composition of the invention or be shipped together with a container which contains 13

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[0106] the compound and / or composition. Alternatively, the instructional material may be shipped separately from the container with the intention that the recipient uses the instructional material and the compound cooperatively. Delivery of the instructional material may be, for example, by physical delivery of the publication or other medium of expression communicating the usefulness of the kit, or may alternatively be achieved by electronic transmission, for example by means of a computer, such as by electronic mail, or download from a website.

[0107] As used herein, the term '‘isolated” means altered or removed from the natural state. For example, a nucleic acid or a polypeptide naturally present in a living animal is not “isolated,” but the same nucleic acid or polypeptide partially or completely separated from the coexisting materials of its natural state is "isolated.” An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell. Isolated nucleic acids, proteins, and antibodies include recombinant nucleic acids, proteins, and antibodies, respectively.

[0108] An "isolated nucleic acid" refers to a nucleic acid segment or fragment which has been separated from sequences which flank it in a naturally occurring state, z.e., a DNA fragment which has been removed from the sequences that are normally adjacent to the fragment, i.e., the sequences adjacent to the fragment in a genome in which it naturally occurs. The term also applies to nucleic acids that have been substantially purified from other components which naturally accompany the nucleic acid, i.e.. RNA or DNA or proteins, which naturally accompany it in the cell. The term therefore includes, for example, a recombinant DNA that is incorporated into a vector, into an autonomously replicating plasmid or virus, or into the genomic DNA of a prokaryote or eukaryote, or which exists as a separate molecule (i.e., as a cDNA or a genomic or cDNA fragment produced by PCR or restriction enzy me digestion) independent of other sequences. It also includes a recombinant DNA that is part of a hybrid gene encoding additional polypeptide sequence.

[0109] By the term “modified” as used herein, is meant a changed state or structure of a molecule or cell of the invention. Molecules may be modified in many ways, including chemically, structurally, and functionally. Cells may be modified through the introduction of nucleic acids.

[0110] As used herein, the term “monoclonal antibody” refers to an antibody obtained from a population of homogenous or substantially homogeneous antibodies. The term “monoclonal” is not limited to any particular method for making the antibody. Generally, a population of monoclonal antibodies can be generated by cells, a population of cells, or a cell line. In some 14

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[0112] aspects, a “monoclonal antibody,’' as used herein, is an antibody encoded by identical nucleic acid sequence, originating from a single clone of cells or cell line, wherein the antibody binds to a glycosylation feature specific to viral proteins as determined, e.g., by ELISA or other antigen-binding or competitive binding assay known in the art. In some aspects, a monoclonal antibody can be a chimeric antibody, a human antibody, or a humanized antibody. Methods for generating a humanized antibody are known in the art. In some aspects, a monoclonal antibody is a monovalent antibody or multivalent (e.g., bivalent) antibody. In some aspects, a monoclonal antibody is a monospecific or multi-specific antibody (e.g., bispecific antibody). Monoclonal antibodies described herein can, for example, can be made by the hybridoma method as described in Kohler et al.; Nature, 256:495 (1975) or can be isolated from phage libraries, for example. Other methods for the preparation of clonal cell lines and of monoclonal antibodies expressed thereby are well known in the art (see, for example, Chapter 11 in: Short Protocols in Molecular Biology, (2002) 5th Ed., Ausubel et al., eds., John Wiley and Sons, New York). Monoclonal antibodies may be identified by high-throughput direct sequencing of fully recombined VDJ sequences of B cell receptor (BCR) repertoires from single cells of animals immunized with an antigen for which the desired monoclonal antibody will specifically bind as described herein. See, e.g., Goldstein et al., Communications Biology (2019)2:304; Homs et al., Cell Reports (2020) 30:905-913). The identified monoclonal antibodies are then produced recombinantly.

[0113] As used herein, a “neutralizing” antibody or antigen-binding fragment is an antibody that defends a cell from a pathogen or infectious particle such as a virus by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might otherwise infect and destroy. Neutralizing antibodies can inhibit the infectivity of the pathogen by binding to the pathogen and blocking the molecules needed for cell entry. This can be due to the antibodies sterically interfering with the pathogens or toxins attaching to host cell receptors. In case of a virus infection, neutralizing antibodies can bind, e.g., to glycoproteins of enveloped viruses or capsid proteins of non-enveloped viruses. Furthermore, neutralizing antibodies can act by preventing particles from undergoing structural changes often needed for successful cell entry. For example, neutralizing antibodies can prevent conformational changes of viral proteins that mediate the membrane fusion needed for entry into the host cell. In some cases, the virus is unable to infect even after the antibody dissociates. The pathogen-antibody complex is eventually taken up and degraded by host 15

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[0115] macrophages.

[0116] By “nucleic acid” is meant any nucleic acid, whether composed of deoxyribonucleosides or ribonucleosides, and whether composed of phosphodiester linkages or modified linkages such as phosphotriester, phosphoramidate, siloxane, carbonate, carboxymethylester, acetamidate, carbamate, thioether, bridged phosphoramidate, bridged methylene phosphonate, phosphorothioate, methylphosphonate, phosphorodithioate, bridged phosphorothioate or sulfone linkages, and combinations of such linkages. The term nucleic acid also specifically includes nucleic acids composed of bases other than the five biologically occurring bases (adenine, guanine, thymine, cytosine and uracil).

[0117] Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s).

[0118] As used herein, "operably linked" sequences include both expression control sequences that are contiguous with the gene of interest and expression control sequences that act in trans or at a distance to control the gene of interest. Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and poly adenylation (poly A) signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (i.e., Kozak consensus sequence); sequences that enhance protein stability; and when desired, sequences that enhance secretion of the encoded product. There are numerous expression control sequences, including promoters which are native, constitutive, inducible and / or tissue-specific, are known in the art that may be used in the compositions of the invention. “Operably linked” should be construed to include RNA expression and control sequences in addition to DNA expression and control sequences.

[0119] As used herein, the term “oligonucleotide” typically refers to short polynucleotides. It will be understood that when a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), this also includes an RNA sequence (i.e.. A, U. C, G) in which “U” replaces “T.” “Parenteral” administration of an immunogenic composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrastemal injection, or infusion techniques.

[0120] The terms “patient”, “subject”, and “individual” are used interchangeably and are intended to include living organisms that may be subjected to treatment for a given disease.

[0121] 16

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[0123] e.g., mammals. A “subject”, “patient”, or “individual”, as used herein, can be a human or non-human mammal. Non-human mammals include, for example, livestock and pets, such as ovine, bovine, porcine, canine, feline, and murine mammals, as well as simian and non-human primate mammals. Preferably, the subject is human.

[0124] As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein’s or peptide’s sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof.

[0125] As used herein, the term “pharmaceutical composition” refers to a mixture of at least one compound useful within the invention with other chemical components, such as carriers, stabilizers, diluents, adjuvants, dispersing agents, suspending agents, thickening agents, and / or excipients. The pharmaceutical composition facilitates administration of the compound to an organism. Multiple techniques of administering a compound exist in the art including, but not limited to: intravenous, oral, aerosol, parenteral, ophthalmic, pulmonary and topical administration.

[0126] The language “pharmaceutically acceptable carrier” includes a pharmaceutically acceptable salt, pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a compound(s) of the present invention within or to the subject such that it may perform its intended function. Typically, such compounds are carried or transported from one organ, or portion of the body, to another organ, or portion of the body. Each salt or carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation, and not injurious to the subject. Some examples of materials that may serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as com starch and potato starch; cellulose, and its derivatives, such as sodium 17

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[0128] carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin: talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil. cottonseed oil, safflower oil, sesame oil, olive oil, com oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide: alginic acid; pyrogen-free water; isotonic saline;

[0129] Ringer’s solution; ethyl alcohol; phosphate buffer solutions; diluent; granulating agent; lubricant; binder; disintegrating agent; wetting agent; emulsifier; coloring agent; release agent; coating agent; sweetening agent; flavoring agent; perfuming agent; preservative; antioxidant; plasticizer; gelling agent; thickener; hardener; setting agent; suspending agent; surfactant; humectant; carrier; stabilizer; and other non-toxic compatible substances employed in pharmaceutical formulations, or any combination thereof. As used herein, “pharmaceutically acceptable carrier” also includes any and all coatings, antibacterial and antifungal agents, and absorption delaying agents, and the like that are compatible with the activity of the compound, and are physiologically acceptable to the subject. Supplementary active compounds may also be incorporated into the compositions.

[0130] The term “polynucleotide” as used herein is defined as a chain of nucleotides.

[0131] Furthermore, nucleic acids are polymers of nucleotides. Thus, “nucleic acid” and “polynucleotide” as used herein are interchangeable. One skilled in the art has the general knowledge that nucleic acids are polynucleotides, which can be hydrolyzed into the monomeric “nucleotides” and which comprise one or more “nucleotide sequence(s)”. The monomeric nucleotides can be hydrolyzed into nucleosides. As used herein polynucleotides include, but are not limited to, all nucleic acid sequences (z.e., “nucleotide sequences”) which are obtained by any means available in the art, including, without limitation, recombinant means, i.e., the cloning of nucleic acid sequences from a recombinant library or a cell genome, using ordinary cloning technology and PCR, and the like, and by synthetic means.

[0132] The term “promoter” as used herein is defined as a DNA sequence recognized by the synthetic machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence.

[0133] As used herein, the term “promoter / regulatory sequence” means a nucleic acid sequence, which is required for expression of a gene product operably linked to the promoter / regulatory sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements, which are required for expression of the gene product. The 18

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[0135] promoter / regulatory sequence may, for example, be one which expresses the gene product in a tissue specific manner.

[0136] By the term “recombinant antibody” as used herein, is meant an antibody which is generated using recombinant DNA technology, such as, for example, an antibody expressed by a bacteriophage, insect, or yeast expression system or by a human cell line expression system. The term should also be construed to mean an antibody which has been generated by the synthesis of a DNA molecule encoding the antibody and which DNA molecule expresses an antibody protein, or an amino acid sequence specifying the antibody, wherein the DNA or amino acid sequence has been obtained using recombinant DNA or amino acid sequence technology which is available and well known in the art.

[0137] The term "recombinant DNA" as used herein is defined as DNA produced by joining pieces of DNA from different sources.

[0138] The term "recombinant polypeptide" as used herein is defined as a polypeptide produced by using recombinant DNA methods.

[0139] The term “substantially” as used herein refers to a majority of, or mostly, as in at least about 50%. 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%. or at least about 99.999% or more, or 100%. The term “substantially free of’ as used herein can mean having none or having a trivial amount of, such that the amount of material present does not affect the material properties of the composition including the material, such that the composition is about 0 wt% to about 5 wt% of the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less. The term “substantially free of’ can mean having a trivial amount of, such that a composition is about 0 wt% to about 5 wt% of the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less, or about 0 wt%.

[0140] The term “therapeutic” as used herein means a treatment and / or prophylaxis. A therapeutic effect is obtained by any degree of suppression, remission, or eradication of a disease state.

[0141] To “treat” a disease as the term is used herein, means to reduce the frequency or severity of at least one sign or symptom of a disease, disorder, or condition experienced by a subject. Treating a disease, disorder or condition may or may not include complete eradication or elimination of the symptom.

[0142] As used herein, the terms “variable region” or “variable domain” refer to a portion of 19

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[0144] an antibody, generally, a portion of a light or heavy chain, ty pically about the amino-terminal 110 to 120 amino acids in the mature heavy chain and about 90 to 100 amino acids in the mature light chain, which differ extensively in sequence among antibodies and are used in the binding and specificity of a particular antibody for its particular antigen. The variability in sequence is concentrated in those regions called complementarity determining regions (CDRs) while the more highly conserved regions in the variable domain are called framework regions (FR). Without wishing to be bound by any particular mechanism or theory, it is believed that the CDRs of the light and heavy chains are primarily responsible for the interaction and specificity of the antibody with antigen. In some aspects, the variable region is a human variable region. In some aspects, the variable region comprises rodent or murine CDRs and human framework regions (FRs). In some aspects. CDRs can be defined by any of the five conventions: Chothia, AbM, Katab, Contact, and IMGT. See, for instance, Zhu, Z., et al., 50 years of antibody numbering schemes: a statistical and structural evaluation reveals key differences and limitations, bioRxiv (2024): 2024-07, which is hereby incorporated by reference in its entirety herein.

[0145] " Variant" as the term is used herein, is a nucleic acid sequence or a peptide sequence that differs in sequence from a reference nucleic acid sequence or peptide sequence respectively, but retains essential properties of the reference molecule. Changes in the sequence of a nucleic acid variant may not alter the amino acid sequence of a peptide encoded by the reference nucleic acid, or may result in amino acid substitutions, additions, deletions, fusions and truncations. Changes in the sequence of peptide variants are typically limited or conservative, so that the sequences of the reference peptide and the variant are closely similar overall and, in many regions, identical. A variant and reference peptide may differ in amino acid sequence by one or more substitutions, additions, or deletions in any combination. A variant of a nucleic acid or peptide may be a naturally occurring such as an allelic variant, or may be a variant that is not known to occur naturally. Non-naturally occurring variants of nucleic acids and peptides may be made by mutagenesis techniques or by direct synthesis.

[0146] A ’'v ector ' is a composition of matter which comprises an isolated nucleic acid and which can be used to deliver the isolated nucleic acid to the interior of a cell. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. Thus, the term "vector" includes an autonomously replicating plasmid or a virus. The term should also be construed to include non-plasmid and non-viral compounds which facilitate 20

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[0148] transfer of nucleic acid into cells, such as, for example, polylysine compounds, liposomes, and the like. Examples of viral vectors include, but are not limited to. Sendai viral vectors, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, lentiviral vectors, and the like.

[0149] The following abbreviations are used herein: CDR, complementarity-determining region; VH, heavy chain variable region; VL, light chain variable region.

[0150] ANTIBODIES AND ANTIGEN BINDING FRAGMENTS THEREOF, AND COMPOSITIONS AND METHODS COMPRISING SUCH ANTIBODIES AND ANTIGEN BINDING FRAGMENTS THEREOF

[0151] In one aspect, the disclosure generally relates to an isolated and / or recombinant antibody or antigen binding fragment thereof.

[0152] In one aspect, the present disclosure generally relates to a composition comprising an isolated and / or recombinant antibody or antigen binding fragment thereof as described herein.

[0153] In one aspect, the present disclosure relates to a method of treating, ameliorating, and / or preventing a viral infection, where the method comprises treatment of the subject with an isolated and / or recombinant antibody or antigen binding fragment as described herein.

[0154] In one aspect, the disclosure generally relates to an isolated nucleic acid comprising a polynucleotide sequence encoding an isolated and / or recombinant antibody or antigen binding fragment thereof as described herein.

[0155] In one aspect, the disclosure generally relates to a method of detecting a virus, wherein the method comprises use of an isolated and / or recombinant antibody or antigen binding fragment as described herein.

[0156] In one aspect, the disclosure generally relates to a method of neutralizing a virus, wherein the method comprises use of an isolated and / or recombinant antibody or antigen binding fragment as described herein.

[0157] Antibodies and Antigen Binding Fragments Thereof

[0158] In one aspect, the disclosure relates to an isolated and / or recombinant antibody or antigen binding fragment thereof. In some aspects, the present disclosure is directed to a pan antiviral antibody or antigen binding fragment thereof, or an antibody or antigen binding fragment thereof that recognizes viruses from multiple (i.e., more than one) viral families. In some aspects, the antibody, or antigen binding fragment thereof, recognizes a glycosylation feature specific to a viral protein, such as a viral surface protein, which is not present on a 21

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[0160] host protein.

[0161] In one aspect, the present disclosure relates to an isolated and / or recombinant antibody or antigen binding fragment thereof comprising a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein:

[0162] the VH comprises:

[0163] (a) a complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 1; a CDR2 comprising the amino acid sequence of SEQ ID NO: 2; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 3;

[0164] (b) a CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 6;

[0165] (c) a CDR1 comprising the amino acid sequence of SEQ ID NO: 7; a CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 9;

[0166] (d) a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12;

[0167] (e) a CDR1 comprising the amino acid sequence of SEQ ID NO: 13; a CDR2 comprising the amino acid sequence of SEQ ID NO: 14; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

[0168] (f) a CDR1 comprising the amino acid sequence of SEQ ID NO: 32; a CDR2 comprising the amino acid sequence of SEQ ID NO: 33; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 34;

[0169] (g) CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 37;

[0170] (h) CDR1 comprising the amino acid sequence of SEQ ID NO: 38; a CDR2 comprising the amino acid sequence of SEQ ID NO: 39; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 40;

[0171] (i) CDR1 comprising the amino acid sequence of SEQ ID NO: 41; a CDR2 comprising the amino acid sequence of SEQ ID NO: 42; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 43;

[0172] (j) CDR1 comprising the amino acid sequence of SEQ ID NO: 44; a CDR2 comprising the amino acid sequence of SEQ ID NO: 45; and a CDR3 comprising the amino acid 22

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[0174] sequence of SEQ ID NO: 46;

[0175] (k) a CDR1 comprising the amino acid sequence of SEQ ID NO: 63; a CDR2 comprising the amino acid sequence of SEQ ID NO: 64; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 65;

[0176] (l) a CDR1 comprising the amino acid sequence of SEQ ID NO: 66; a CDR2 comprising the amino acid sequence of SEQ ID NO: 67; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 68;

[0177] (m) a CDR1 comprising the amino acid sequence of SEQ ID NO: 69; a CDR2 comprising the amino acid sequence of SEQ ID NO: 70; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 71;

[0178] (n) a CDR1 comprising the amino acid sequence of SEQ ID NO: 72; a CDR2 comprising the amino acid sequence of SEQ ID NO: 73; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 74;

[0179] (o) a CDR1 comprising the amino acid sequence of SEQ ID NO: 75; a CDR2 comprising the amino acid sequence of SEQ ID NO: 76; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 77;

[0180] (p) a CDR1 comprising the amino acid sequence of SEQ ID NO: 94; a CDR2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 96;

[0181] (q) a CDR1 comprising the amino acid sequence of SEQ ID NO: 97; a CDR2 comprising the amino acid sequence of SEQ ID NO: 98; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 99;

[0182] (r) a CDR1 comprising the amino acid sequence of SEQ ID NO: 100; a CDR2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 102;

[0183] (s) a CDR1 comprising the amino acid sequence of SEQ ID NO: 103; a CDR2 comprising the amino acid sequence of SEQ ID NO: 104; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 105;

[0184] (t) a CDR1 comprising the amino acid sequence of SEQ ID NO: 106; a CDR2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 108;

[0185] (u) a CDR1 comprising the amino acid sequence of SEQ ID NO: 125; a CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 127;

[0186] 23

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[0188] (v) a CDR1 comprising the amino acid sequence of SEQ ID NO: 128; a CDR2 comprising the amino acid sequence of SEQ ID NO: 129; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 130;

[0189] (w) a CDR1 comprising the amino acid sequence of SEQ ID NO: 131; a CDR2 comprising the amino acid sequence of SEQ ID NO: 132; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 133;

[0190] (x) a CDR1 comprising the amino acid sequence of SEQ ID NO: 134; a CDR2 comprising the amino acid sequence of SEQ ID NO: 135; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 136; or

[0191] (y) a CDR1 comprising the amino acid sequence of SEQ ID NO: 137; a CDR2 comprising the amino acid sequence of SEQ ID NO: 138; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 139;

[0192] and / or the VL comprises:

[0193] (z) a CDR1 comprising the amino acid sequence of SEQ ID NO: 17; a CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 19;

[0194] (aa) a CDR1 comprising the amino acid sequence of SEQ ID NO: 20; a CDR2 comprising the amino acid sequence of SEQ ID NO: 21; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 22;

[0195] (bb) a CDR1 comprising the amino acid sequence of SEQ ID NO: 23; a CDR2 comprising the amino acid sequence of SEQ ID NO: 24; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 25;

[0196] (cc) a CDR1 comprising the amino acid sequence of SEQ ID NO: 26; a CDR2 comprising the amino acid sequence of SEQ ID NO: 27; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 28;

[0197] (dd) a CDR1 comprising the amino acid sequence of SEQ ID NO: 29; a CDR2 comprising the amino acid sequence of NN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 30;

[0198] (ee) a CDR1 comprising the amino acid sequence of SEQ ID NO: 48; a CDR2 comprising the amino acid sequence of SEQ ID NO: 49; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 50;

[0199] (ff) a CDR1 comprising the amino acid sequence of SEQ ID NO: 51; a CDR2 comprising the amino acid sequence of SEQ ID NO: 52; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 53;

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[0202] (gg) a CDR1 comprising the amino acid sequence of SEQ ID NO: 54; a CDR2 comprising the amino acid sequence of SEQ ID NO: 55; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 56;

[0203] (hh) a CDR1 comprising the amino acid sequence of SEQ ID NO: 57; a CDR2 comprising the amino acid sequence of SEQ ID NO: 58; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 59;

[0204] (ii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 60; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 61;

[0205] (jj) a CDR1 comprising the amino acid sequence of SEQ ID NO: 79; a CDR2 comprising the amino acid sequence of SEQ ID NO: 80; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 81;

[0206] (kk) a CDR1 comprising the amino acid sequence of SEQ ID NO: 82; a CDR2 comprising the amino acid sequence of SEQ ID NO: 83; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 84;

[0207] (11) a CDR1 comprising the amino acid sequence of SEQ ID NO: 85; a CDR2 comprising the amino acid sequence of SEQ ID NO: 86; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 87;

[0208] (mm) a CDR1 comprising the amino acid sequence of SEQ ID NO: 88; a CDR2 comprising the amino acid sequence of SEQ ID NO: 89; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 90;

[0209] (nn) a CDR1 comprising the amino acid sequence of SEQ ID NO: 91; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 92;

[0210] (oo) a CDR1 comprising the amino acid sequence of SEQ ID NO: 110; a CDR2 comprising the amino acid sequence of SEQ ID NO: 111; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 112;

[0211] (pp) a CDR1 comprising the amino acid sequence of SEQ ID NO: 113; a CDR2 comprising the amino acid sequence of SEQ ID NO: 114; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 115;

[0212] (qq) a CDR1 comprising the amino acid sequence of SEQ ID NO: 116; a CDR2 comprising the amino acid sequence of SEQ ID NO: 117; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 118;

[0213] (rr) a CDR1 comprising the amino acid sequence of SEQ ID NO: 119; a CDR2

[0214] 25

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[0216] comprising the amino acid sequence of SEQ ID NO: 120; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 121;

[0217] (ss) a CDR1 comprising the amino acid sequence of SEQ ID NO: 122; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 123;

[0218] (tt) a CDR1 comprising the amino acid sequence of SEQ ID NO: 141; a CDR2 comprising the amino acid sequence of SEQ ID NO: 142; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 143

[0219] (uu) a CDR1 comprising the amino acid sequence of SEQ ID NO: 144; a CDR2 comprising the amino acid sequence of SEQ ID NO: 145; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 146;

[0220] (vv) a CDR1 comprising the amino acid sequence of SEQ ID NO: 147; a CDR2 comprising the amino acid sequence of SEQ ID NO: 148; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 149;

[0221] (ww) a CDR1 comprising the amino acid sequence of SEQ ID NO: 150; a CDR2 comprising the amino acid sequence of SEQ ID NO: 151; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 152;

[0222] (xx) a CDR1 comprising the amino acid sequence of SEQ ID NO: 153; a CDR2 comprising the amino acid sequence of NN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 154.

[0223] In some aspects, the antibody or antigen binding fragment thereof comprises a VH and a VL.

[0224] In some aspects, the antibody or antigen binding fragment thereof comprises:

[0225] (a) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 1; the CDR2 comprising the amino acid sequence of SEQ ID NO: 2; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 3; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 17; the CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 19;

[0226] (b) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 4; the CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 20; the CDR2 comprising the amino acid sequence of SEQ ID NO: 21; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 22;

[0227] (c) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 7;

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[0230] the CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 9; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 23; the CDR2 comprising the amino acid sequence of SEQ ID NO: 24; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 25;

[0231] (d) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 10; the CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 26; the CDR2 comprising the amino acid sequence of SEQ ID NO: 27; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 28;

[0232] (e) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 13; the CDR2 comprising the amino acid sequence of SEQ ID NO: 14; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 15; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 29; the CDR2 comprising the amino acid sequence of NN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 30;

[0233] (f) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 32; the CDR2 comprising the amino acid sequence of SEQ ID NO: 33; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 48; the CDR2 comprising the amino acid sequence of SEQ ID NO: 49; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 50;

[0234] (g) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 35; the CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 51; the CDR2 comprising the amino acid sequence of SEQ ID NO: 52; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 53;

[0235] (h) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 38; the CDR2 comprising the amino acid sequence of SEQ ID NO: 39; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 40; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 54; the CDR2 comprising the amino acid sequence of SEQ ID NO: 55; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 56:

[0236] (i) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 41; the CDR2 comprising the amino acid sequence of SEQ ID NO: 42; and the CDR3 comprising 27

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[0238] the amino acid sequence of SEQ ID NO: 43; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 57; the CDR2 comprising the amino acid sequence of SEQ ID NO: 58; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 59;

[0239] (j) VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 44; the CDR2 comprising the amino acid sequence of SEQ ID NO: 45; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 46; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 60; the CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 61;

[0240] (k) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 63; the CDR2 comprising the amino acid sequence of SEQ ID NO: 64; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 65; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 79; the CDR2 comprising the amino acid sequence of SEQ ID NO: 80; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 81;

[0241] (l) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 66; the CDR2 comprising the amino acid sequence of SEQ ID NO: 67; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 68; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 82; the CDR2 comprising the amino acid sequence of SEQ ID NO: 83; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 84;

[0242] (m) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 69; the CDR2 comprising the amino acid sequence of SEQ ID NO: 70; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 71; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 85; the CDR2 comprising the amino acid sequence of SEQ ID NO: 86; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 87;

[0243] (n) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 72; the CDR2 comprising the amino acid sequence of SEQ ID NO: 73; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 74; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 88; the CDR2 comprising the amino acid sequence of SEQ ID NO: 89; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 90;

[0244] (o) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 75; the CDR2 comprising the amino acid sequence of SEQ ID NO: 76; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 77; and the VL comprising the CDR1

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[0247] comprising the amino acid sequence of SEQ ID NO: 91; the CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 92;

[0248] (p) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 94; the CDR2 comprising the amino acid sequence of SEQ ID NO: 95; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 96; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 110; the CDR2 comprising the amino acid sequence of SEQ ID NO: 111; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 112;

[0249] (q) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 97; the CDR2 comprising the amino acid sequence of SEQ ID NO: 98; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 99; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 113; the CDR2 comprising the amino acid sequence of SEQ ID NO: 114; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 115;

[0250] (r) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 100; the CDR2 comprising the amino acid sequence of SEQ ID NO: 101; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 102; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 116; the CDR2 comprising the amino acid sequence of SEQ ID NO: 117; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 118;

[0251] (s) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 103; the CDR2 comprising the amino acid sequence of SEQ ID NO: 104; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 105; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 119; the CDR2 comprising the amino acid sequence of SEQ ID NO: 120; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 121;

[0252] (t) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 106; the CDR2 comprising the amino acid sequence of SEQ ID NO: 107; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 108; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 122; the CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 123;

[0253] (u) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 125; the CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and the CDR3

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[0255] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0256] comprising the amino acid sequence of SEQ ID NO: 127; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 141; the CDR2 comprising the amino acid sequence of SEQ ID NO: 142; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 143;

[0257] (v) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 128; the CDR2 comprising the amino acid sequence of SEQ ID NO: 129; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 130; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 144; the CDR2 comprising the amino acid sequence of SEQ ID NO: 145; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 146;

[0258] (w) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 131; the CDR2 comprising the amino acid sequence of SEQ ID NO: 132; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 133; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 147; the CDR2 comprising the amino acid sequence of SEQ ID NO: 148; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 149;

[0259] (x) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 134; the CDR2 comprising the amino acid sequence of SEQ ID NO: 135; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 136; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 150; the CDR2 comprising the amino acid sequence of SEQ ID NO: 151; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 152;

[0260] (y) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 137; the CDR2 comprising the amino acid sequence of SEQ ID NO: 138; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 139; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 153; the CDR2 comprising the amino acid sequence of NN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 154.

[0261] In some aspects,

[0262] a) the VH comprises an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 47, SEQ ID NO: 78, SEQ ID NO: 109, and SEQ ID NO: 140; and / or

[0263] b) the VL comprises an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID 30

[0264] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0265] NO: 93, SEQ ID NO: 124, and SEQ ID NO: 155.

[0266] In some aspects,

[0267] a) the VH comprises an amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 47, SEQ ID NO: 78, SEQ ID NO: 109, and SEQ ID NO: 140; and / or

[0268] b) the VL comprises an amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 93, SEQ ID NO: 124, and SEQ ID NO: 155

[0269] In some aspects,

[0270] a) the VH comprises an amino acid sequence at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 47, SEQ ID NO: 78, SEQ ID NO: 109, and SEQ ID NO: 140; and / or

[0271] b) the VL comprises an amino acid sequence at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 93, SEQ ID NO: 124, and SEQ ID NO: 155.

[0272] In some aspects,

[0273] a) the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 47, SEQ ID NO: 78, SEQ ID NO: 109, and SEQ ID NO: 140; and / or

[0274] b) the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 93, SEQ ID NO: 124, and SEQ ID NO: 155.

[0275] In some aspects,

[0276] a) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 16, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 31;

[0277] b) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 47, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 62;

[0278] c) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 78, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 93;

[0279] d) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 109. and the VL polypeptide comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 124; or

[0280] 31

[0281] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0282] e) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 140. and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 155.

[0283] In some aspects,

[0284] a) the VH comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 16, and the VL comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 31;

[0285] b) the VH comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 47, and the VL comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 62;

[0286] c) the VH comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 78, and the VL comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 93;

[0287] d) the VH comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 109, and the VL polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 124; or

[0288] e) the VH comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 140, and the VL comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 155.

[0289] In some aspects,

[0290] a) the VH comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 16, and the VL comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 31;

[0291] b) the VH comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 47, and the VL comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 62;

[0292] c) the VH comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 78, and the VL comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 93;

[0293] d) the VH comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 109, and the VL polypeptide comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 124; or

[0294] e) the VH comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 140, and the VL comprises an amino acid sequence at least 99%

[0295] 32

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[0297] identical to the amino acid sequence of SEQ ID NO: 155.

[0298] In some aspects,

[0299] a) the VH comprises the amino acid sequence of SEQ ID NO: 16, and the VL comprises the amino acid sequence of SEQ ID NO: 31;

[0300] b) the VH comprises the amino acid sequence of SEQ ID NO: 47, and the VL comprises the amino acid sequence of SEQ ID NO: 62;

[0301] c) the VH comprises the amino acid sequence of SEQ ID NO: 78. and the VL comprises the amino acid sequence of SEQ ID NO: 93;

[0302] d) the VH comprises the amino acid sequence of SEQ ID NO: 109, and the VL comprises the amino acid sequence of SEQ ID NO: 124; or

[0303] e) the VH comprises the amino acid sequence of SEQ ID NO: 140, and the VL comprises the amino acid sequence of SEQ ID NO: 155.

[0304] In some aspects, the antibody or antigen binding fragment thereof comprises an IgGl, IgG2, IgG3 or IgG4 constant region or fragment thereof. In some aspects, the antibody or antigen binding fragment thereof comprises an IgGl constant region or fragment thereof. In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain constant region comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 156 and SEQ ID NO: 158; and / or further comprises a light chain constant region comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 157 and SEQ ID NO: 159.

[0305] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain constant region comprising an amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 156 and SEQ ID NO: 158; and / or further comprises a light chain constant region comprising an amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 157 and SEQ ID NO: 159.

[0306] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain constant region comprising an amino acid sequence at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 156 and SEQ ID NO: 158; and / or further comprises a light chain constant region comprising an amino acid sequence at least 99% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 157 and SEQ ID NO: 159.

[0307] In some aspects, the antibody or antigen binding fragment thereof of comprises a 33

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[0309] heavy chain constant region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 156 and SEQ ID NO: 158; and / or further comprises a light chain constant region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 157 and SEQ ID NO: 159.

[0310] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy¬ chain comprising an amino acid sequence at least 90% identical to an amino acid sequence selected of SEQ ID NO: 161; and / or further comprises a light chain comprising an amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO: 162.

[0311] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 95% identical to an amino acid sequence selected of SEQ ID NO: 161; and / or further comprises a light chain comprising an amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 162.

[0312] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 99% identical to an amino acid sequence selected of SEQ ID NO: 161; and / or further comprises a light chain comprising an amino acid sequence at least 99% identical to an amino acid sequence of SEQ ID NO: 162.

[0313] In some aspects, the antibody or antigen binding fragment thereof of comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 161; and / or further comprises a light chain comprising the amino acid sequence of SEQ ID NO: 162.

[0314] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 90% identical to an amino acid sequence selected of SEQ ID NO: 163; and / or further comprises a light chain comprising an amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO: 164.

[0315] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 95% identical to an amino acid sequence selected of SEQ ID NO: 163; and / or further comprises a light chain comprising an amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 164.

[0316] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 99% identical to an amino acid sequence selected of SEQ ID NO: 163; and / or further comprises a light chain comprising an amino acid sequence at least 99% identical to an amino acid sequence of SEQ ID NO: 164.

[0317] In some aspects, the antibody or antigen binding fragment thereof of comprises a heavy- chain comprising the amino acid sequence of SEQ ID NO: 163; and / or further comprises a light chain comprising the amino acid sequence of SEQ ID NO: 164.

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[0320] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 90% identical to an amino acid sequence selected of SEQ ID NO: 165; and / or further comprises a light chain comprising an amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO: 166.

[0321] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy¬ chain comprising an amino acid sequence at least 95% identical to an amino acid sequence selected of SEQ ID NO: 165; and / or further comprises a light chain comprising an amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 166.

[0322] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 99% identical to an amino acid sequence selected of SEQ ID NO: 165; and / or further comprises a light chain comprising an amino acid sequence at least 99% identical to an amino acid sequence of SEQ ID NO: 166.

[0323] In some aspects, the antibody or antigen binding fragment thereof of comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 165; and / or further comprises a light chain comprising the amino acid sequence of SEQ ID NO: 166.

[0324] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 90% identical to an amino acid sequence selected of SEQ ID NO: 167; and / or further comprises a light chain comprising an amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO: 168.

[0325] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 95% identical to an amino acid sequence selected of SEQ ID NO: 167; and / or further comprises a light chain comprising an amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 168.

[0326] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 99% identical to an amino acid sequence selected of SEQ ID NO: 167; and / or further comprises a light chain comprising an amino acid sequence at least 99% identical to an amino acid sequence of SEQ ID NO: 168.

[0327] In some aspects, the antibody or antigen binding fragment thereof of comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 167; and / or further comprises a light chain comprising the amino acid sequence of SEQ ID NO: 168.

[0328] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy¬ chain comprising an amino acid sequence at least 90% identical to an amino acid sequence selected of SEQ ID NO: 169; and / or further comprises a light chain comprising an amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO: 170.

[0329] 35

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[0331] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy chain comprising an amino acid sequence at least 95% identical to an amino acid sequence selected of SEQ ID NO: 169; and / or further comprises a light chain comprising an amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO: 170.

[0332] In some aspects, the antibody or antigen binding fragment thereof comprises a heavy¬ chain comprising an amino acid sequence at least 99% identical to an amino acid sequence selected of SEQ ID NO: 169; and / or further comprises a light chain comprising an amino acid sequence at least 99% identical to an amino acid sequence of SEQ ID NO: 170.

[0333] In some aspects, the antibody or antigen binding fragment thereof of comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 169; and / or further comprises a light chain comprising the amino acid sequence of SEQ ID NO: 170.

[0334] In some aspects, the antibody or antigen binding fragment thereof comprises at least one selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a variable fragment (Fv), an antigen-binding fragment (Fab or F(ab)2), a single chain antibody (scFv), a camelid antibody and a humanized antibody.

[0335] In some aspects, the antibody or antigen binding fragment thereof is directly or indirectly attached to a detectable label or a therapeutic agent.

[0336] In some aspects, the antibody or antigen binding fragment thereof binds to viral proteins of two or more viruses from different viral families. In some aspects, the viral families include one or more of Rhabdoviridae, Filvoviridae, Flaviviridae, Bunyaviridae, Paramyxoviridae, Retroviridae Orthomyxoviridae, Coronaviridae, and Herpesviridae. In some aspects, the antibody or antigen binding fragment thereof binds to at least one viral protein from a virus selected from the group consisting of HIV, influenza, encephalitis, Hantaan virus, coronavirus, RSV, vesicular stomatitis virus (VSV). herpesvirus, Zika virus, Dengue virus, rabies, Ebola, cytomegalovirus (CMV), and combinations thereof. In some aspects, the coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), HCov 229e, HCoV HKU1, HCoV NL63, or HCoV OC43. In some aspects, the herpesvirus is HSV-1 or HSV-2. In some aspects, the influenza is H1N1. In some aspects, the antibody or antigen binding fragment thereof binds to a glycosylation feature specific to a viral protein which is not found in a protein of a host of the virus. In some aspects, the glycosylation feature comprises one or more glycans. In some aspects, the glycosylation feature comprises an N-acetylglucosamine (GlcNAc) residue on a non-reducing end of an oligosaccharide. In some aspects, the antibody or antigen binding fragment thereof binds to SARS-CoV-2 spike. In some aspects, the antibody or antigen binding fragment thereof binds to HIV gp120. In 36

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[0338] some aspects, the antibody or antigen binding fragment thereof binds to ebolavirus glycoprotein (EBOV GP). In some aspects, the antibody or antigen binding fragment thereof binds to cytomegalovirus glycoprotein B (CMV gB).

[0339] In some aspects, the antibody or antigen binding fragment thereof comprises a tetramer assembly, such as a tetramer assembly of one or more of the antibodies or antigen binding fragments thereof described herein. In some aspects, the tetramer assemblies are constructed using Fc mutations. In some aspects, the tetramer assembly comprises a divalent single-chain diabody Fc (scDbFc) fusion molecule, which molecule can dimerize via Fc domain to form the tetraval ent molecule. See, for instance, Example 6 which describes examples of such scDbFc tetramer assemblies. In some aspects, the tetramer assemblies are formed as generally described in Alt, M et al.. FEBS letters vol. 454,1-2 (1999): 90-4, which is incorporated by reference herein in its entirety. In some aspects, the tetramer assembly comprises the amino acid sequence of any one of SEQ ID NOs: 171-175. In some aspects, the tetramer assembly comprises the amino acid sequence of SEQ ID NO: 171. In some aspects, the tetramer assembly comprises the amino acid sequence of SEQ ID NO: 172. In some aspects, the tetramer assembly comprises the amino acid sequence of SEQ ID NO: 173. In some aspects, the tetramer assembly comprises the amino acid sequence of SEQ ID NO: 174. In some aspects, the tetramer assembly comprises the amino acid sequence of SEQ ID NO: 175. In some aspects, the tetramer assembly binds to SARS-CoV-2 spike protein. In some aspects, the tetramer assembly binds to HIV gpl20.

[0340] In some aspects, the antibody or antigen binding fragment thereof comprises a hexamer assembly, such as a hexamer assembly of one or more of the antibodies or antigen binding fragments thereof described herein. In some aspects, the hexamer assemblies are constructed using Fc mutations. In some aspects, the hexamer assemblies comprise mutations in the Fc heavy chain to promote hexamer formation. In some aspects, the hexamer assemblies comprise E345R and E430G mutations in the Fc heavy chain, wherein the numbering is according to the EU index. In some aspects, the hexamer assemblies comprise an E345R mutation in the Fc heavy chain, wherein the numbering is according to the EU index. In some aspects, the hexamer assemblies comprise an E430G mutation in the Fc heavy chain, wherein the numbering is according to the EU index. In some aspects, the Fc heavy chain is an IgGl Fc heavy chain. In some aspects, the Fc heavy chain is an IgGl Fc heavy chain comprising E345R and E430G mutations, wherein the numbering is according to the EU index. In some aspects, the hexamer assemblies are formed as generally described in de Jong, Rob N et al., PLoS biology / vol. 14,1 el002344. 6 Jan. 2016. In some aspects, hexamer 37

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[0342] assemblies are formed as generally described in Example 6. In some aspects, the hexamer assemblies comprise E345R and / or E430G mutations in the Fc region, wherein the numbering is according to the numbering of the EU index.

[0343] Nucleic Acids, Polynucleotides, and Vectors

[0344] In one aspect, the present disclosure relates to an isolated nucleic acid comprising a nucleotide sequence encoding an antibody or antigen binding fragment thereof as described herein. Moreover, in one aspect, the present disclosure relates to a vector comprising a nucleic acid encoding an antibody or antigen binding fragment thereof as described herein.

[0345] In some aspects, an antibody or antigen binding fragment thereof as described herein is encoded by a polynucleotide. In some aspects, the polynucleotide comprises recombinant or isolated or synthetic DNA. In some aspects, the polynucleotide comprises recombinant or isolated or synthetic RNA. In some aspects, the polynucleotide encodes a recombinant or synthetic polypeptide comprising the antibody or antigen binding fragment thereof. In some aspects, a vector encodes the antibody or antigen binding fragment thereof. In some aspects, the vector is an expression vector.

[0346] In some aspects, the polynucleotide encoding the antibody or antigen binding fragment thereof is operably linked to a transcriptional control element, e.g., a promoter, and enhancer, and so forth. Suitable promoter and enhancer elements are known to those of skill in the art. In some aspects, the polynucleotide encoding the antibody or antigen binding fragment thereof is operably linked to a promoter. For expression in a bacterial cell, suitable promoters include, but are not limited to, lacl, lacZ, T3, T7, gpt, lambda P and trc. For expression in a eukaryotic cell, suitable promoters include, but are not limited to, light and / or heavy chain immunoglobulin gene promoter and enhancer elements; cytomegalovirus immediate early promoter; herpes simplex virus thymidine kinase promoter; early and late SV40 promoters; promoter present in long terminal repeats from a retrovirus; mouse metallothionein-I promoter; and various art-known tissue specific promoters. Suitable reversible promoters, including reversible inducible promoters are known in the art. Such reversible promoters may be isolated and derived from many organisms, e.g., eukaryotes and prokaryotes. Modification of reversible promoters derived from a first organism for use in a second organism, e.g., a first prokaryote and a second a eukaryote, a first eukaryote and a second a prokaryote, and so forth, is well known in the art. Such reversible promoters, and systems based on such reversible promoters but also comprising additional control proteins, include, but are not limited to, alcohol regulated promoters (e.g., alcohol dehydrogenase I 38

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[0348] (alcA) gene promoter, promoters responsive to alcohol transactivator proteins (AlcR), and so forth), tetracycline regulated promoters, (e.g., promoter systems including Tet Activators, TetON, TetOFF, and so forth), steroid regulated promoters (e.g., rat glucocorticoid receptor promoter systems, human estrogen receptor promoter systems, retinoid promoter systems, thyroid promoter systems, ecdysone promoter systems, mifepristone promoter systems, and so forth), metal regulated promoters (e.g., metallothionein promoter systems, and so forth), pathogenesis-related regulated promoters (e.g., salicylic acid regulated promoters, ethylene regulated promoters, benzothiadiazole regulated promoters, and so forth), temperature regulated promoters (e.g., heat shock inducible promoters (e.g., HSP-70, HSP-90, soybean heat shock promoter, and so forth), light regulated promoters, synthetic inducible promoters, and the like.

[0349] For expression in a yeast cell, a suitable promoter is a constitutive promoter such as an ADH1 promoter, a PGK1 promoter, an ENO promoter, a PYK1 promoter and the like; or a regulatable promoter such as a GALI promoter, a GAL 10 promoter, an ADH2 promoter, a PHOS promoter, a CUP1 promoter, a GALT promoter, a MET25 promoter, a MET3 promoter, a CYC1 promoter, a HIS3 promoter, an ADH1 promoter, a PGK promoter, a GAPDH promoter, an ADC1 promoter, a TRP1 promoter, a URA3 promoter, a LEU2 promoter, an ENO promoter, a TP1 promoter, and A0X1 (e.g., for use in Pichia). Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art. Suitable promoters for use in prokaryotic host cells include, but are not limited to, a bacteriophage T7 RNA polymerase promoter; atrp promoter; a lac operon promoter; a hybrid promoter, e.g., a lac / tac hybrid promoter, a tac / trc hybrid promoter, a trp / lac promoter, a T7 / lac promoter; a trc promoter; a tac promoter, and the like; an araBAD promoter; in vivo regulated promoters, such as an ssaG promoter or a related promoter (see, e.g., U. S. Patent Publication No. 20040131637), a pagC promoter (Pulkkinen and Miller, J. Bacteriol. (1991) 173(1): 86-93; Alpuche-Aranda et al., Proc. Natl. Acad. Sci. USA (1992) 89(21): 10079-83), anirB promoter (Harbome et al. Mol. Micro. (1992) 6:2805-2813), and the like (see, e.g., Dunstan et al., Infect. Immun. (1999) 67:5133-5141; McKelvie et al.. Vaccine (2004) 22:3243-3255; and Chatfield et al., Biotechnol. (1992) 10:888-892); a sigma70 promoter, e.g., a consensus sigma70 promoter (see, e.g., GenBank Accession Nos. AX798980, AX798961, and AX798183); a stationary phase promoter, e.g., a dps promoter, an spv promoter, and the like; a promoter derived from the pathogenicity island SPI-2 (see, e.g.. WO96 / 17951); an actA promoter (see, e.g., Shetron-Rama et al., Infect. Immun. (2002) 70: 1087-1096); an rpsM promoter (see, e.g., Valdivia and Falkow Mol. Microbiol. (1996).

[0350] 39

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[0352] 22:367); a tet promoter (see, e.g., Hillen, W. and Wissmann, A. (1989) In Saenger, W. and Heinemann, U. (eds), Topics in Molecular and Structural Biology, Protein--Nucleic Acid Interaction. Macmillan, London, UK, Vol. 10, pp. 143-162); an SP6 promoter (see, e.g., Melton et al., Nucl. Acids Res. (1984) 12:7035); and the like. Suitable strong promoters for use in prokary otes such as Escherichia coli include, but are not limited to Trc, Tac, T5, T7, and PLambda. Non-limiting examples of operators for use in bacterial host cells include a lactose promoter operator (LacI repressor protein changes conformation when contacted with lactose, thereby preventing the Lad repressor protein from binding to the operator), a tr ptophan promoter operator (when complexed with tryptophan. TrpR repressor protein has a conformation that binds the operator; in the absence of tryptophan, the TrpR repressor protein has a conformation that does not bind to the operator), and a tac promoter operator (see, e.g., deBoer et al.. Proc. Natl. Acad. Sci. U. S. A. (1983) 80:21-25).

[0353] Other examples of suitable promoters include the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto. Other constitutive promoter sequences may also be used, including, but not limited to a simian virus 40 (SV40) early promoter, a mouse mammary tumor virus (MMTV) or human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, a MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter, the EF-1 alpha promoter, as well as human gene promoters such as, but not limited to, an actin promoter, a myosin promoter, a hemoglobin promoter, and a creatine kinase promoter. Further, the invention should not be limited to the use of constitutive promoters. Inducible promoters are also contemplated as part of the invention. The use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. Examples of inducible promoters include, but are not limited to a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter.

[0354] In some aspects, the polynucleotide or vector containing the suitable promoter is irreversibly switched through the induction of an inducible system. Suitable systems for induction of an irreversible switch are well known in the art, e.g., induction of an irreversible switch may make use of a Cre-lox-mediated recombination (see, e.g., Fuhrmann-Benzakein, et al.. Proc. Natl. Acad. Sci. USA (2000) 28:e99, the disclosure of which is incorporated herein by reference). Any suitable combination of recombinase, endonuclease, ligase.

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[0357] recombination sites, and so forth known to the art may be used in generating an irreversibly switchable promoter. Methods, mechanisms, and requirements for performing site-specific recombination, described elsewhere herein, find use in generating irreversibly switched promoters and are well known in the art, see, e.g., Grindley et al. Annual Review of Biochemistry (2006) 567-605; and Tropp, Molecular Biology (2012) (Jones & Bartlett Publishers, Sudbury, Mass.), the disclosures of which are incorporated herein by reference.

[0358] A polynucleotide encoding the antibody or antigen binding fragment thereof of the present disclosure can be present within an expression vector and / or a cloning vector. An expression vector can include a selectable marker, an origin of replication, and other features that provide for replication and / or maintenance of the vector. Suitable expression vectors include, e.., plasmids, viral vectors, and the like. Large numbers of suitable vectors and promoters are known to those of skill in the art; many are commercially available for generating a subject recombinant construct. The following vectors are provided by way of example and should not be construed in anyway as limiting: Bacterial: pBs, phagescript, PsiX174. pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene, La Jolla, Calif., USA); pTrc99A, pKK223-3, pKK233-3. pDR540. and pRIT5 (Pharmacia, Uppsala. Sweden). Eukaryotic: pWLneo, pSV2cat, pOG44, PXR1, pST-Ki, pST-KiT, pSG (Stratagene) pSVK3, pBPV, pMSG and pSVL (Pharmacia).

[0359] Expression vectors generally have convenient restriction sites located near the promoter sequence to provide for the insertion of nucleic acid sequences encoding heterologous proteins. A selectable marker operative in the expression host may be present. Suitable expression vectors include, but are not limited to, viral vectors (e.g. viral vectors based on vaccinia virus; poliovirus; adenovirus (see, e.g., Li et al., Invest. Opthalmol. Vis. Sci. (1994) 35: 2543-2549; Borras et al., Gene Then (1999) 6: 515-524; Li and Davidson, Proc. Natl. Acad. Sci. USA (1995) 92: 7700-7704; Sakamoto et al., H. Gene Ther. (1999) 5: 1088-1097; WO 94 / 12649, WO 93 / 03769; WO 93 / 19191; WO 94 / 28938; WO 95 / 11984 and WO 95 / 00655); adeno-associated virus (see, e.g., Ali et al., Hum. Gene Ther. (1998) 9: 81-86, Flannery et al., Proc. Natl. Acad. Sci. USA (1997) 94: 6916-6921; Bennett et al., Invest. Opthalmol. Vis. Sci. (1997) 38: 2857-2863; Jomary et al., Gene Ther. (1997) 4:683 690, Rolling et al.. Hum. Gene Ther. (1999) 10: 641-648; Ali et al., Hum. Mol. Genet. (1996) 5: 591-594; Srivastava in WO 93 / 09239, Samulski et al., J. Vir. (1989) 63: 3822-3828;

[0360] Mendelson et al., Virol. (1988) 166: 154-165; and Flotte et al., Proc. Natl. Acad. Sci. USA (1993) 90: 10613-10617); SV40; herpes simplex virus; human immunodeficiency virus (see, e.g., Miyoshi et al., Proc. Natl. Acad. Sci. USA (1997) 94: 10319-23; Takahashi et al., J.

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[0363] Virol. (1999) 73: 7812-7816); a retroviral vector (e.g., Murine Leukemia Virus, spleen necrosis virus, and vectors derived from retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, human immunodeficiency virus, myeloproliferative sarcoma virus, and mammary tumor virus); and the like.

[0364] Additional expression vectors suitable for use are, e.g., without limitation, a lentivirus vector, a gamma retrovirus vector, a foamy virus vector, an adeno-associated virus vector, an adenovirus vector, a pox virus vector, a herpes virus vector, an engineered hybrid virus vector, a transposon mediated vector, and the like. Viral vector technology is well known in the art and is described, for example, in Sambrook et al., 2012, Molecular Cloning: A Laboratory Manual, volumes 1 -4, Cold Spring Harbor Press, NY), and in other virology and molecular biology manuals. Viruses, which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno- associated viruses, herpes viruses, and lentiviruses.

[0365] In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers, (e.g., WO 01 / 96584; WO 01 / 29058; and U.S. Patent No. 6,326,193).

[0366] In some aspects, an expression vector can be used to introduce the antibody or antigen binding fragment thereof into a cell. Accordingly, an expression vector (e.g., a lentiviral vector) of the present invention may comprise a nucleic acid encoding for the antibody or antigen binding fragment thereof. In some aspects, the expression vector will comprise additional elements that will aid in the functional expression of the antibody or antigen binding fragment thereof encoded therein. In some aspects, an expression vector comprising a nucleic acid encoding for the antibody or antigen binding fragment thereof further comprises a mammalian promoter. In one aspect, the vector further comprises an elongation-factor-1-alpha promoter (EF-1α promoter). Use of an EF-1α promoter may increase the efficiency in expression of downstream transgenes. Physiologic promoters (e.g., an EF-1α promoter) may be less likely to induce integration mediated genotoxicity, and may abrogate the ability of the retroviral vector to transform stem cells. Other physiological promoters suitable for use in a vector are known to those of skill in the art and may be incorporated into a vector of the present invention. In some aspects, the vector further comprises a non-requisite cis acting sequence that may improve titers and gene expression. One non-limiting example of a nonrequisite cis acting sequence is the central polypurine tract and central termination sequence (cPPT / CTS) which is important for efficient reverse transcription and nuclear import. Other non-requisite cis acting sequences are known to those of skill in the art and may be incorporated into a vector (e.g., lentiviral vector) of the present invention. In some aspects,

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[0369] the vector further comprises a posttranscriptional regulatory element. Posttranscriptional regulatory elements may improve RNA translation, improve transgene expression and stabilize RNA transcripts. One example of a posttranscriptional regulatory element is the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Accordingly, in some aspects a vector for the present invention further comprises a WPRE sequence. Various posttranscriptional regulator elements are known to those of skill in the art and may be incorporated into a vector of the present invention. A vector of the present invention may further comprise additional elements such as a rev response element (RRE) for RNA transport, packaging sequences, and 5’ and 3’ long terminal repeats (LTRs). The term “long terminal repeat” or “LTR” refers to domains of base pairs located at the ends of retroviral DNAs which comprise U3, R and U5 regions. LTRs generally provide functions required for the expression of retroviral genes (e.g., promotion, initiation and polyadenylation of gene transcripts) and to viral replication. In one aspect, a vector of the present invention includes a 3’ U3 deleted LTR. Accordingly, a vector of the present invention may comprise any combination of the elements described herein to enhance the efficiency of functional expression of transgenes.

[0370] In some aspects, a polynucleotide encoding the antibody or antigen binding fragment thereof can be RNA, e.g., in vitro synthesized RNA. Methods for in vitro synthesis of RNA are known to those of skill in the art; any known method can be used to synthesize RNA comprising a sequence encoding the antibody or antigen binding fragment thereof of the present disclosure. Methods for introducing RNA into a host cell are known in the art. See, e.g., Zhao et al. Cancer Res. (2010) 15: 9053. Introducing RNA comprising a nucleotide sequence encoding the antibody or antigen binding fragment thereof of the present disclosure into a host cell can be carried out in vitro, ex vivo or in vivo. For example, a host cell can be electroporated in vitro or ex vivo with RNA comprising a nucleotide sequence encoding an antibody or antigen binding fragment thereof of the present disclosure.

[0371] In order to assess the expression of a polypeptide or portions thereof, the expression vector to be introduced into a cell may also contain either a selectable marker gene or a reporter gene, or both, to facilitate identification and selection of expressing cells from the population of cells sought to be transfected or infected through viral vectors. In some aspects, the selectable marker may be carried on a separate piece of DNA and used in a cotransfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells. Useful selectable markers include, without limitation, antibiotic-resistance genes.

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[0374] Reporter genes are used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences. In general, a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assessed at a suitable time after the DNA has been introduced into the recipient cells. Suitable reporter genes may include, without limitation, genes encoding luciferase, beta-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tei et al., 2000 FEBS Letters 479: 79-82).

[0375] In one aspect, the present disclosure generally relates to an isolated polynucleotide comprising a nucleotide sequence encoding an antibody or antigen binding fragment thereof as described herein. In one aspect, the present disclosure generally relates to a vector comprising a polynucleotide as described herein. In one aspect, the present disclosure generally relates to an isolated host cell that recombinantly produces an antibody or antigen binding fragment thereof as described herein.

[0376] Compositions

[0377] Also provided herein are compositions comprising an antibody or antigen binding fragment thereof as described herein, such as compositions comprising a polynucleotide encoding the antibody or antigen binding fragment thereof and / or compositions comprising the isolated or recombinant antibody or antigen binding fragment thereof. Among the compositions are pharmaceutical compositions and formulations for administration, such as for treating viral infection(s). Also provided are therapeutic methods for administering the antibody or antigen binding fragment thereof and compositions to subjects, e.g., patients. In one aspect, the present disclosure is directed to a composition comprising an antibody or antigen binding fragment thereof as described herein. In some aspects, the composition further comprises an additional therapeutic agent. In one aspect, the present disclosure generally relates to a pharmaceutical composition comprising an antibody or antigen binding fragment as described herein and at least one pharmaceutically acceptable carrier.

[0378] Also provided are compositions for administration, including pharmaceutical compositions and formulations, such as unit dose form compositions including the amount of the antibody or antigen binding fragment thereof for administration in a given dose or fraction thereof. The pharmaceutical compositions and formulations generally include one or more optional pharmaceutically acceptable carrier or excipient. In some aspects, the

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[0381] composition includes at least one additional therapeutic agent.

[0382] The term “pharmaceutical formulation” or “pharmaceutical composition” refers to a preparation which is in such form as to permit the biological activity of an active ingredient contained therein to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. A “pharmaceutically acceptable carrier” refers to an ingredient in a pharmaceutical formulation, other than an active ingredient, which is nontoxic to a subject. A pharmaceutically acceptable carrier includes, but is not limited to, a buffer, excipient, stabilizer, or preservative. In some aspects, the choice of carrier is determined in part by the particular cell and / or by the method of administration. Accordingly, there are a variety of suitable formulations. For example, the pharmaceutical composition can contain preservatives. Suitable preservatives may include, for example, methylparaben, propylparaben, sodium benzoate, and benzalkonium chloride. In some aspects, a mixture of two or more preservatives is used. The preservative or mixtures thereof are typically present in an amount of about 0.0001% to about 2% by weight of the total composition. Carriers are described, e.g., by Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980). Pharmaceutically acceptable carriers are generally nontoxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride: hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g. Zn-protein complexes); and / or non-ionic surfactants such as polyethylene glycol (PEG).

[0383] Buffering agents in some aspects are included in the compositions. Suitable buffering agents include, for example, citric acid, sodium citrate, phosphoric acid, potassium phosphate, and various other acids and salts. In some aspects, a mixture of two or more buffering agents is used. The buffering agent or mixtures thereof are typically present in an amount of about 0.001% to about 4% by weight of the total composition. Methods for 45

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[0385] preparing administrable pharmaceutical compositions are known. Exemplary methods are described in more detail in, for example, Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins; 21st ed. (May 1, 2005).

[0386] The formulations can include aqueous solutions. The formulation or composition may also contain more than one active ingredient useful for the particular indication, disease, or condition being treated, where the respective activities do not adversely affect one another. Such active ingredients are suitably present in combination in amounts that are effective for the purpose intended. Thus, in some aspects, the pharmaceutical composition further includes other pharmaceutically active agents or drugs. The pharmaceutical composition in some aspects contains the antibody or antigen binding fragment thereof in amounts effective to treat or prevent the disease or condition, such as a therapeutically effective or prophylactically effective amount. Therapeutic or prophylactic efficacy in some aspects is monitored by periodic assessment of treated subjects. The desired dosage can be delivered by a single administration of the antibody or antigen binding fragment thereof, by multiple administrations of the antibody or antigen binding fragment thereof, or by continuous administration of the antibody or antigen binding fragment thereof.

[0387] Formulations include those for oral, intravenous, intraperitoneal, subcutaneous, pulmonary, transdermal, intramuscular, intranasal, buccal, sublingual, or suppository administration. In some aspects, the antibody or antigen binding fragment thereof is administered parenterally. The term “parenteral / ’ as used herein, includes intravenous, intramuscular, subcutaneous, rectal, vaginal, and intraperitoneal administration. In some aspects, the cells are administered to the subject using peripheral systemic delivery by intravenous, intraperitoneal, or subcutaneous injection. Compositions in some aspects are provided as sterile liquid preparations, e.g., isotonic aqueous solutions, suspensions, emulsions, dispersions, or viscous compositions, which may in some aspects be buffered to a selected pH. Liquid preparations are normally7easier to prepare than gels, other viscous compositions, and solid compositions. Additionally, liquid compositions are somewhat more convenient to administer, especially by injection. Viscous compositions, on the other hand, can be formulated within the appropriate viscosity range to provide longer contact periods with specific tissues. Liquid or viscous compositions can comprise carriers, which can be a solvent or dispersing medium containing, for example, water, saline, phosphate buffered saline, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol) and suitable mixtures thereof.

[0388] Sterile injectable solutions can be prepared by incorporating the cells in a solvent.

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[0391] such as in admixture with a suitable carrier, diluent, or excipient such as sterile water, physiological saline, glucose, dextrose, or the like. The compositions can contain auxiliary substances such as wetting, dispersing, or emulsifying agents (e.g., methylcellulose), pH buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, and / or colors, depending upon the route of administration and the preparation desired.

[0392] Standard texts may in some aspects be consulted to prepare suitable preparations.

[0393] Various additives which enhance the stability and sterility of the compositions, including antimicrobial preservatives, antioxidants, chelating agents, and buffers, can be added. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, and sorbic acid.

[0394] Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.

[0395] The formulations to be used for in vivo administration are generally sterile. Sterility may be readily accomplished, e.g., by filtration through sterile filtration membranes.

[0396] In some aspects, the composition includes an antibody and at least one pharmaceutically acceptable carrier. In some aspects, the antibody is an antibody that recognizes a virus. In some aspects, the virus is a virus having a protein glycosylation, such as a surface protein glycosylation. In some aspects, the glycosylation of the viral protein, such as the viral surface protein, includes a glycan and / or an N-acetylglucosamine (GlcNAc) residue on a non-reducing end of oligosaccharides. In some aspects, the antibody recognizes the glycan and / or the GlcNAc residue on the non-reducing end of the oligosaccharides. In some aspects, the antibody is the same as or similar to those as described elsewhere herein. In some aspects, the composition further includes a second compound for treating, preventing and / or ameliorating the viral infection, such as influenza infection, SARS-CoV-2 infection, HIV infection, encephalitis infection, Hantaan virus infection, coronavirus infection, RSV infection, vesicular stomatitis virus (VSV) infection, herpesvirus infection, Zika virus infection, Dengue virus infection, rabies infection, and / or Ebola infection, cytomegalovirus (CMV) infection. Examples of the second compound is described elsewhere herein.

[0397] Methods

[0398] Methods of Detecting Virus

[0399] In some aspects, the present specification is directed to a method of detecting a virus. In some aspects, the method includes contacting a sample suspected to include the virus with 47

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[0401] an antibody that recognizes the virus, and visualizing the antibody. In some aspects, a presence of a signal of the antibody indicates a presence of the virus, and / or an absence of the signal of the antibody indicates an absence of the virus. In some aspects, the antibody and / or the viruses that the antibody recognize are the same as or similar to those as described elsewhere herein.

[0402] In some aspects, visualizing the antibody includes visualizing the antibody using an immunostaining technique. Non-limiting examples of immunostaining techniques includes an immunohistochemistry staining, flow cytometry, western blotting, an enzyme-linked immunosorbent assay (ELISA), and immuno-electron microscopy.

[0403] Methods of Neutralizing Virus

[0404] In some aspects, the present specification is directed to a method of neutralizing a virus. In some aspects, the method includes contacting the virus with an antibody. In some aspects, the antibody and / or the viruses that the antibody recognize are the same as or similar to those as described elsewhere herein. In some aspects, the virus is further contacted with one or more complement proteins.

[0405] In some aspects, the virus is in a cell, such as an isolated cell, a cultured cell, and / or a cell in a subject.

[0406] In some aspects, the virus is in a subject. In some aspects, the subject is infected with the virus. In some aspects, the subject is a mammal, such as a human.

[0407] Methods of Preventing, Treating, and / or Ameliorating Viral Infection

[0408] In one aspect, the present disclosure is generally related to a method of preventing, treating, and / or ameliorating a viral infection in a subject in need thereof. In some aspects, the method includes administering to the subject an effective amount of an antibody or antigen binding fragment thereof, such as any of the antibodies or antigen binding fragments thereof as described herein.

[0409] In some aspects, a protein of the virus has a glycosylation feature is not found in a protein of a host of the virus, and wherein the antibody specifically recognizes the glycosylation feature. In some aspects, the glycosylation feature comprises an N-acetylglucos amine (GlcNAc) residue on a non-reducing end of an oligosaccharide. In some aspects, the virus is an Orthomyxoviridae, a Coronaviridae, and / or a Herpesviridae family virus. In some aspects, the virus is HIV. influenza, encephalitis, Hantaan virus, coronavirus, RSV, vesicular stomatitis virus (VSV), herpesvirus, Zika virus, Dengue virus, rabies, Ebola,

[0410] 48

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[0412] cytomegalovirus (CMV), or any combination thereof. In some aspects, the coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). HCov 229e, HCoV HKU1, HCoV NL63, or HCoV OC43. In some aspects, the herpesvirus is HSV-1 or HSV-2. In some aspects, the influenza is H INI.

[0413] In some aspects, the subject is further administered a second compound suitable for treating, preventing and / or ameliorating infection by the virus. In some aspects, the subject is a mammal. In some aspects, the subject is a human.

[0414] Methods of Targeting Glycans

[0415] Glycan epitopes, such as terminal GlcNAc epitopes, exist in bacteria and viruses. Furthermore, such glycan epitopes have been identified on malignant cells and in autoimmune disease. As such, targeting glycan epitopes by antigen binding proteins that recognize these epitopes can be used to detect and / or neutralize bacteria, viruses, malignant cells and / or cells involved in autoimmune diseases that express such epitopes.

[0416] Accordingly, in some aspects, the present invention is directed to a method of targeting a glycan epitope, such as, for instance, a terminal GlcNAc epitope, wherein the method comprises use of one or more of the antibodies described herein. In some aspects, the method is a method of detecting a bacterium, a virus, a malignant cell and / or a cell involved in autoimmune diseases that express a glycan epitope. In some aspects, the method is a method of neutralizing a bacterium, a virus, a malignant cell and / or a cell involved in autoimmune diseases that express a glycan epitope. In some aspects, the method is a method of treating a disease, disorder and / or condition that is caused by a bacterium, a virus and / or a cell that express a glycan epitope.

[0417] In some aspects, the method includes contacting the bacterium, the virus, the malignant cell and / or the cell involved in the autoimmune disease an antibody recognizing a glycan epitope. In some aspects, the antibody is the same as or similar to those as described elsewhere herein.

[0418] In some aspects, the bacterium, the virus, the malignant cell and / or the cell involved in the autoimmune disease is further contacted with one or more complement proteins.

[0419] Moreover, in some aspects, the present disclosure generally relates to a method of targeting a glycan comprising a glycan epitope, wherein the glycan comprises one or more of the glycans listed in Table 1. In some aspects, the glycan does not comprise a terminal GlcNAc epitope. In some aspects, the glycan comprises a terminal GlcNAc epitope. In some aspects, the glycan comprises one or more of Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glc,

[0420] 49

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[0422] Neu5Acα2-3(GalNAcβ1-4)Galβ1-4Glc, Neu5Acα2–3Galβ1–3GalNAcβ1–4(Neu5Acα2–3)Galβ1–4Glc, Neu5Acα2–3Galβ1–4Glc, Neu5Acα2-3Galβ, Neu5Acα2–8Neu5Acα2–3Galβ1–3GalNAcβ1–4(Neu5Acα2–3)Galβ1–4Glc, Neu5Acα2-3Galβ1-4GlcNAc, Neu5Acα2-3Galβ1-4GlcNAcβ1-2Manα1-6(Neu5Acα2-3Galβ1-4GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, Manα1-6(Manα1-3)Manα1-6(Neu5Acα2-3Galβ1-4GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, Manα1-6(Manα1-3)Manα1-6(Neu5Acα2-6Galβ1-4GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-2Manα1-6(GlcNAcβ1-4)(Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc, Neu5Acα2-6Galβ1-4GlcNAc, Neu5Acα2-3Galβ1-3(Neu5Acα2-6)GlcNAcβ1-3Galβ1-4Glc, Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-2Manα1-6(Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, Manα1-6(Manα1-3)Manα1-6(Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, Neu5Acα2-3Galβ1-4GlcNAcβ1-2Manα1-6(GlcNAcβ1-4)(Neu5Acα2-3Galβ1-4GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, and / or Neu5Acα2-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-2Manα1-6(Neu5Acα2-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc. In some aspects, the glycan comprises glycans of one or more glycan types, such as GSL, HMO, oligosaccharides, complex N-glycan. hybrid N-glycan, bisecting N-glycan, blood group and Lewis antigens, and LacNAc-extended N-glycan. In some aspects, the glycan is GM1, GM2, GDI a, 3’-Sialyllactose, 3’-Sialylgalactose (GM4), GTla, 3’-a-Sialyl-N-acetyllactosamine, 3’-Sialyl Lewis X, 6’-a-Sialyl-N-acetyllactosamine, or Disialyllacto-N-tetraose (DSLNT).

[0423] Combination Therapies

[0424] In some aspects, a compound comprises one or more of the isolated and / or recombinant antibodies or antigen binding fragments as described herein. In some aspects, compounds useful within the methods described herein can be used in combination with one or more additional therapeutic agents useful for preventing, treating and / or ameliorating viral infection. These additional therapeutic agents may comprise compounds that are commercially available or synthetically accessible to those skilled in the art. These additional therapeutic agents are known to treat, prevent, and / or reduce the symptoms, of the viral infection. These additional therapeutic agents are administered before, at the same time with, or after the administration of any of the antibodies or antigen binding fragments thereof as described herein. In some aspects, the combination therapy comprises use of at least two or 50

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[0426] more of the antibodies or antigen binding fragments as described herein in combination with one another.

[0427] In some aspects, the compounds described herein, e.g., compounds comprising one or more of the isolated and / or recombinant antibodies or antigen binding fragments described herein, can be used in combination with second compound for treating, preventing and / or ameliorating the viral infection, such as infection with HIV, influenza, encephalitis, Hantaan virus, coronavirus, RSV, vesicular stomatitis virus (VSV), herpesvirus, Zika virus. Dengue virus, rabies, Ebola, and / or cytomegalovirus (CMV).

[0428] For example, in the case of an infection by an influenza virus, the second compound includes a compound suitable for treating, preventing and / or ameliorating an influenza virus infection. In some aspects, the compound includes an influenza vaccine that immunizes the subject against influenza infection; a decongestant that relieves nasal congestion, swelling, and runny nose; a cough medication that blocks the cough reflex, thin and loosen mucus; a nonsteroidal anti-inflammatory dmg (NSAID) that relieves pain, decreases inflammation, and reduces fever; an analgesic that relieves pain; and / or an antiviral dmg against influenza virus, such as oseltamivir, zanamivir, peramivir, baloxavir marboxil, and derivatives thereof.

[0429] For example, in the case of an infection by SARS-CoV-2, the second compound includes a compound suitable for treating, preventing and / or ameliorating COVID-19. In some aspects, the compound comprises an COVID-19 vaccine that immunizes the subject against SARS-CoV-2; a cough medication that blocks the cough reflex, thin and loosen mucus; a nonsteroidal anti-inflammatory dmg (NSAID) that relieves pain, decreases inflammation, and reduces fever; an analgesic that relieves pain; an antibody (other than the present antibody) that neutralizing SARS-CoV-2 virus; an immunomodulator such as a corticosteroid (e.g., dexamethasone), an interleukin (IL-6) inhibitor (e.g.. tocilizumab or sarilumab), a Janus kinase (JAK) inhibitor (baricitinib or tofacitinib); and / or an antiviral drug against SARS-CoV-2, such as remdesivir. The compounds suitable for treating SARS-CoV-2 infections are also detailed in the ‘‘Coronavirus Disease 2019 (COVID-19) Treatment Guidelines'’ by the National Institutes of Health (NIH), the entirety of which is hereby incorporated herein by reference.

[0430] In some aspects, a synergistic effect is observed when a compound as described herein is administered with one or more additional therapeutic agents or compounds. A synergistic effect may be calculated, for example, using suitable methods such as, for example, the Sigmoid-Emaxequation (Holford & Scheiner, 1981, Clin. Pharmacokinet. 6:429-453), the equation of Loewe additivity (Loewe & Muischnek, 1926, Arch. Exp. Pathol 51

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[0432] Pharmacol. 114:313-326) and the median-effect equation (Chou & Talalay, 1984, Adv.

[0433] Enzyme Regul. 22:27-55). Each equation referred to above may be applied to experimental data to generate a corresponding graph to aid in assessing the effects of the drug combination. The corresponding graphs associated with the equations referred to above are the concentration-effect curve, isobologram curve and combination index curve, respectively.

[0434] Administration / Dosage / Formulations

[0435] The regimen of administration may affect what constitutes an effective amount. The therapeutic formulations may be administered to the subject either prior to or after the onset of a disease or disorder contemplated herein (in a non-limiting aspect, a viral infection). Further, several divided dosages, as well as staggered dosages may be administered daily or sequentially, or the dose may be continuously infused, or may be a bolus injection. Further, the dosages of the therapeutic formulations may be proportionally increased or decreased as indicated by the exigencies of the therapeutic or prophylactic situation.

[0436] Administration of the compositions described herein to a patient, preferably a mammal, more preferably a human, may be carried out using known procedures, at dosages and for periods of time effective to treat, prevent and / or ameliorate a viral infection in the patient. An effective amount of the therapeutic compound necessary to achieve a therapeutic effect may vary according to factors such as the state of the disease or disorder in the patient; the age, sex, and weight of the patient; and the ability of the therapeutic compound to treat, prevent and / or ameliorate a viral infection in the patient. Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. A non-limiting example of an effective dose range for a therapeutic compound described herein is from about 1 and 5,000 mg / kg of body weight / per day. One of ordinary ■ skill in the art would be able to study the relevant factors and make the determination regarding the effective amount of the therapeutic compound without undue experimentation.

[0437] Actual dosage levels of the active ingredients in the pharmaceutical compositions described herein may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.

[0438] In particular, the selected dosage level depends upon a variety of factors including the activity of the particular compound employed, the time of administration, the rate of

[0439] 52

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[0441] excretion of the compound, the duration of the treatment, other drugs, compounds or materials used in combination with the compound, the age, sex. weight, condition, general health and prior medical history of the patient being treated, and like factors well, known in the medical arts.

[0442] A medical doctor, e.g., physician or veterinarian, having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the compounds described herein employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.

[0443] In some aspects, it is especially advantageous to formulate the compound in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the patients to be treated; each unit containing a predetermined quantity of therapeutic compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical vehicle. The dosage unit forms of the compound(s) described herein are dictated by and directly dependent on (a) the unique characteristics of the therapeutic compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding / formulating such a therapeutic compound.

[0444] In some aspects, the compositions described herein are formulated using one or more pharmaceutically acceptable excipients or carriers. In some aspects, the pharmaceutical compositions described herein comprise a therapeutically effective amount of a compound described herein and a pharmaceutically acceptable carrier.

[0445] The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity may be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms may be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it is preferable to include isotonic agents, for example, sugars, sodium chloride, or poly alcohols such as mannitol and sorbitol, in the composition. Prolonged absorption of the injectable compositions may be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate or gelatin.

[0446] 53

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[0448] In some aspects, the compositions described herein are administered to the patient in dosages that range from one to five times per day or more. In some aspects, the compositions described herein are administered to the patient in range of dosages that include, but are not limited to, once every day, every two, days, every three days to once a week, and once every two weeks. It is readily apparent to one skilled in the art that the frequency of administration of the various combination compositions described herein varies from individual to individual depending on many factors including, but not limited to, age, disease or disorder to be treated, gender, overall health, and other factors. Thus, administration of the compounds and compositions described herein should not be construed to be limited to any particular dosage regime and the precise dosage and composition to be administered to any patient is determined by the attending physician taking all other factors about the patient into account.

[0449] The compound(s) described herein for administration may be in the range of from about 1 pg to about 10,000 mg, about 20 pg to about 9,500 mg, about 40 pg to about 9,000 mg, about 75 pg to about 8,500 mg, about 150 pg to about 7,500 mg, about 200 pg to about 7,000 mg, about 350 pg to about 6,000 mg, about 500 pg to about 5,000 mg, about 750 pg to about 4,000 mg, about 1 mg to about 3,000 mg, about 10 mg to about 2,500 mg, about 20 mg to about 2,000 mg, about 25 mg to about 1,500 mg, about 30 mg to about 1,000 mg, about 40 mg to about 900 mg, about 50 mg to about 800 mg, about 60 mg to about 750 mg, about 70 mg to about 600 mg, about 80 mg to about 500 mg, and any and all whole or partial increments therebetween.

[0450] In some aspects, the dose of a compound described herein is from about 1 mg and about 2,500 mg. In some aspects, a dose of a compound described herein used in compositions described herein is less than about 10,000 mg, or less than about 8,000 mg, or less than about 6,000 mg, or less than about 5.000 mg, or less than about 3.000 mg, or less than about 2,000 mg, or less than about 1,000 mg, or less than about 500 mg, or less than about 200 mg, or less than about 50 mg. Similarly, in some aspects, a dose of a second compound as described herein is less than about 1,000 mg, or less than about 800 mg, or less than about 600 mg, or less than about 500 mg, or less than about 400 mg. or less than about 300 mg, or less than about 200 mg, or less than about 100 mg, or less than about 50 mg, or less than about 40 mg, or less than about 30 mg, or less than about 25 mg, or less than about 20 mg, or less than about 15 mg, or less than about 10 mg, or less than about 5 mg, or less than about 2 mg, or less than about 1 mg, or less than about 0.5 mg, and any and all whole or partial increments thereof.

[0451] In some aspects, a composition as described herein is a packaged pharmaceutical 54

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[0453] composition comprising a container holding a therapeutically effective amount of a compound described herein, alone or in combination with a second pharmaceutical agent; and instructions for using the compound to treat, ameliorate, and / or reduce one or more symptoms of viral infection in a patient.

[0454] Formulations may be employed in admixtures with conventional excipients, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for oral, parenteral, nasal, intravenous, subcutaneous, enteral, or any other suitable mode of administration, known to the art. The pharmaceutical preparations may be sterilized and if desired mixed with auxiliary' agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure buffers, coloring, flavoring and / or aromatic substances and the like. They may also be combined where desired with other active agents, e.g., other analgesic agents.

[0455] Routes of administration of any of the compositions described herein include oral, nasal, rectal, intravaginal, parenteral, buccal, sublingual or topical. The compounds for use in the compositions described herein can be formulated for administration by any suitable route, such as for oral or parenteral, for example, transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal e.g., trans- and perivaginally), (intra)nasal and (trans)rectal), intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration.

[0456] Suitable compositions and dosage forms include, for example, tablets, capsules, caplets, pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, transdermal patches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs, suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolized formulations for inhalation, compositions and formulations for intravesical administration and the like. It should be understood that the formulations and compositions described herein are not limited to the particular formulations and compositions that are described herein.

[0457] Oral Administration

[0458] For oral application, particularly suitable are tablets, dragees, liquids, drops, suppositories, or capsules, caplets and gelcaps. The compositions intended for oral use may be prepared according to any method known in the art and such compositions may contain one or more agents selected from the group consisting of inert, non-toxic pharmaceutically excipients that are suitable for the manufacture of tablets. Such excipients include, for 55

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[0460] example an inert diluent such as lactose: granulating and disintegrating agents such as cornstarch; binding agents such as starch; and lubricating agents such as magnesium stearate. The tablets may be uncoated or they may be coated by known techniques for elegance or to delay the release of the active ingredients. Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed wi th an inert diluent.

[0461] For oral administration, the compound(s) described herein can be in the form of tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g, polyvinylpyrrolidone, hydroxypropylcellulose or hydroxypropyl methylcellulose); fillers (e.g., cornstarch, lactose, microcrystalline cellulose or calcium phosphate); lubricants (e.g, magnesium stearate, talc, or silica); disintegrates (e.g., sodium starch glycollate); or wetting agents (e.g, sodium lauryl sulphate). If desired, the tablets may be coated using suitable methods and coating materials such as OPADRY™ film coating systems available from Colorcon, West Point, Pa. (e.g, OPADRY™ OY Type, OYC Type, Organic Enteric OY -P Type, Aqueous Enteric OY -A Type, OY -PM Type and OPADRY™ White, 32K18400). Liquid preparation for oral administration may be in the form of solutions, syrups or suspensions. The liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g, sorbitol syrup, methyl cellulose or hydrogenated edible fats); emulsifying agent (e.g, lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters or ethyl alcohol); and preservatives (e.g.. methyl or propyl p-hydroxy benzoates or sorbic acid).

[0462] Parenteral Administration

[0463] For parenteral administration, the compounds as described herein may be formulated for injection or infusion, for example, intravenous, intramuscular or subcutaneous injection or infusion, or for administration in a bolus dose and / or continuous infusion. Suspensions, solutions or emulsions in an oily or aqueous vehicle, optionally containing other formulatory agents such as suspending, stabilizing and / or dispersing agents may be used.

[0464] Sterile injectable forms of the compositions described herein may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in anon-toxic parenterally-acceptable diluent or solvent, for example as a solution in 1, 3-butanediol.

[0465] Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be 56

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[0467] employed including synthetic mono- or di-glycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically acceptable oils, such as olive oil or castor oil, especially in their polyoxy ethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant, such as Ph. Helv or similar alcohol.

[0468] Additional Administration Forms

[0469] Additional dosage forms suitable for use with the compound(s) and compositions described herein include dosage forms as described in U. S. Patents Nos. 6,340,475;

[0470] 6,488,962; 6,451,808; 5,972,389; 5,582,837; and 5,007,790. Additional dosage forms suitable for use with the compound(s) and compositions described herein also include dosage forms as described in U. S. Patent Applications Nos. 20030147952; 20030104062; 20030104053; 20030044466; 20030039688; and 20020051820. Additional dosage forms suitable for use with the compound(s) and compositions described herein also include dosage forms as described in PCT Applications Nos. WO 03 / 35041; WO 03 / 35040; WO 03 / 35029; WO 03 / 35177; WO 03 / 35039; WO 02 / 96404; WO 02 / 32416; WO 01 / 97783; WO 01 / 56544; WO 01 / 32217; WO 98 / 55107; WO 98 / 11879; WO 97 / 47285; WO 93 / 18755; and WO 90 / 11757.

[0471] Controlled Release Formulations and Drug Delivery Systems

[0472] In some aspects, the formulations described herein can be, but are not limited to, short-term, rapid-offset, as well as controlled, for example, sustained release, delayed release and pulsatile release formulations.

[0473] The term sustained release is used in its conventional sense to refer to a drug formulation that provides for gradual release of a drug over an extended period of time, and that may. although not necessarily, result in substantially constant blood levels of a drug over an extended time period. The period of time may be as long as a month or more and should be a release which is longer that the same amount of agent administered in bolus form.

[0474] For sustained release, the compounds may be formulated with a suitable polymer or hydrophobic material which provides sustained release properties to the compounds. As such, the compounds for use with the method(s) described herein may be administered in the form of microparticles, for example, by injection or in the form of wafers or discs by implantation.

[0475] In some cases, the dosage forms to be used can be provided as slow or controlled-release of one or more active ingredients therein using, for example, hydropropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, or microspheres or a combination thereof to provide the 57

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[0477] desired release profile in vary ing proportions. Suitable controlled-release formulations known to those of ordinary skill in the art, including those described herein, can be readily selected for use with the pharmaceutical compositions described herein. Thus, single unit dosage forms suitable for oral administration, such as tablets, capsules, gelcaps, and caplets, that are adapted for controlled-release are encompassed by the compositions and dosage forms described herein.

[0478] Most controlled-release pharmaceutical products have a common goal of improving drug therapy over that achieved by their non-controlled counterparts. Ideally, the use of an optimally designed controlled-release preparation in medical treatment is characterized by a minimum of drug substance being employed to cure or control the condition in a minimum amount of time. Advantages of controlled-release formulations include extended activity of the drug, reduced dosage frequency, and increased patient compliance. In addition, controlled-release formulations can be used to affect the time of onset of action or other characteristics, such as blood level of the drug, and thus can affect the occurrence of side effects.

[0479] Most controlled-release formulations are designed to initially release an amount of drug that promptly produces the desired therapeutic effect, and gradually and continually release of other amounts of drug to maintain this level of therapeutic effect over an extended period of time. In order to maintain this constant level of drug in the body, the drug must be released from the dosage form at a rate that will replace the amount of drug being metabolized and excreted from the body.

[0480] Controlled-release of an active ingredient can be stimulated by various inducers, for example pH, temperature, enzy mes, water, or other physiological conditions or compounds. The term “controlled-release component” is defined herein as a compound or compounds, including, but not limited to, polymers, polymer matrices, gels, permeable membranes, liposomes, or microspheres or a combination thereof that facilitates the controlled-release of the active ingredient. In some aspects, the compound(s) described herein are administered to a patient, alone or in combination with another pharmaceutical agent, using a sustained release formulation. In some aspects, the compound(s) described herein are administered to a patient, alone or in combination with another pharmaceutical agent, using a sustained release formulation.

[0481] The term delayed release is used herein in its conventional sense to refer to a drug formulation that provides for an initial release of the drug after some delay following drug administration and that mat, although not necessarily, includes a delay of from about 10

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[0484] minutes up to about 12 hours.

[0485] The term pulsatile release is used herein in its conventional sense to refer to a drug formulation that provides release of the drug in such a way as to produce pulsed plasma profiles of the drug after drug administration.

[0486] The term immediate release is used in its conventional sense to refer to a drug formulation that provides for release of the drug immediately after drug administration.

[0487] As used herein, short-term refers to any period of time up to and including about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes and any or all whole or partial increments thereof after drug administration after drug administration.

[0488] As used herein, rapid-offset refers to any period of time up to and including about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes, and any and all whole or partial increments thereof after drug administration.

[0489] Dosing

[0490] The therapeutically effective amount or dose of compounds described herein depends on the age, sex and weight of the patient, the current medical condition of the patient and the progression of a viral infection in the patient being treated. The skilled artisan is able to determine appropriate dosages depending on these and other factors.

[0491] A suitable dose of a compound described herein can be in the range of from about 0.01 mg to about 5,000 mg per day, such as from about 0.1 mg to about 1,000 mg, for example, from about 1 mg to about 500 mg, such as about 5 mg to about 250 mg per day. The dose may be administered in a single dosage or in multiple dosages, for example from 1 to 4 or more times per day. When multiple dosages are used, the amount of each dosage may be the same or different. For example, a dose of 1 mg per day may be administered as two 0.5 mg doses, with about a 12-hour interval between doses.

[0492] Another suitable dose of a compound described herein can be in the range of from about 0.01 mg / kg to about 100 mg / kg per day or about 0.1 pg / kg to about 100 pg / kg per day, wherein the amount of the compound administered depends on the weight of the patient. The dose of compounds described herein can be about 0.1 mg / kg to about 100 mg / kg, about 0.5 mg / kg to about 100 mg / kg, about 1 mg / kg to about 50 mg / kg. 0.5 mg / kg to about 25 mg / kg. In some aspects, the dose of a compound described herein can be greater than, less than, or at least about 0.01 mg / kg, 0.1 mg / kg, 0.5 mg / kg, 1 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg,

[0493] 59

[0494] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0495] 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 15 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg. 45 mg / kg, 50 mg / kg. 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, or about 100 mg / kg. The dose of compounds described herein can be about 0.1 pg / kg to about 100 pg / kg, about 0.5 pg / kg to about 100 pg / kg, about 1 pg / kg to about 50 pg / kg, 0.5 pg / kg to about 25 pg / kg. In some aspects, the dose of a compound described herein can be greater than, less than, or at least about 0.1 pg / kg, 0.5 pg / kg, 1 pg / kg. 1 pg / kg, 2 pg / kg. 3 pg / kg, 4 pg / kg, 5 pg / kg. 6 pg / kg, 7 pg / kg, 8 pg / kg, 9 pg / kg, 10 pg / kg, 15 pg / kg, 20 pg / kg, 25 pg / kg, 30 pg / kg, 35 pg / kg, 40 pg / kg, 45 pg / kg, 50 pg / kg, 55 pg / kg, 60 pg / kg, 65 pg / kg, 70 pg / kg, 75 pg / kg, 80 pg / kg, 85 pg / kg, 90 pg / kg, 95 pg / kg, or about 100 pg / kg.

[0496] It is understood that the amount of compound dosed per day may be administered, in non-limiting examples, every day, every' other day, every 2 days, every 3 days, every' 4 days, or every 5 days. For example, with every other day administration, a 5 mg per day dose may be initiated on Monday with a first subsequent 5 mg per day dose administered on Wednesday, a second subsequent 5 mg per day dose administered on Friday, and so on.

[0497] In the case wherein the patient's status does improve, upon the doctor's discretion the administration of the compound(s) described herein is optionally given continuously; alternatively, the dose of drug being administered is temporarily reduced or temporarily suspended for a certain length of time (z.e., a ‘‘drug holiday'’). The length of the drug holiday optionally varies between 2 days and 1 year, including by way of example only, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, 20 days, 28 days, 35 days, 50 days, 70 days, 100 days, 120 days, 150 days, 180 days, 200 days, 250 days, 280 days, 300 days, 320 days, 350 days, or 365 days. The dose reduction during a drug holiday includes from 10%-100%, including, by way of example only, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%.

[0498] Once improvement of the patient's conditions has occurred, a maintenance dose is administered if necessary. Subsequently, the dosage or the frequency of administration, or both, is reduced to a level at which the improved disease is retained. In some aspects, patients require intermittent treatment on a long-term basis upon any recurrence of symptoms and / or infection.

[0499] The compounds described herein can be formulated in unit dosage form. The term “unit dosage form” refers to physically discrete units suitable as unitary dosage for patients undergoing treatment, with each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, optionally in association with a suitable 60

[0500] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0501] pharmaceutical carrier. The unit dosage form may be for a single daily dose or one of multiple daily doses (e.g, about 1 to 4 or more times per day). When multiple daily doses are used, the unit dosage form may be the same or different for each dose.

[0502] Toxicity and therapeutic efficacy of such therapeutic regimens are optionally determined in cell cultures or experimental animals, including, but not limited to, the determination of the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between the toxic and therapeutic effects is the therapeutic index, which is expressed as the ratio between LD50 and ED50. The data obtained from cell culture assays and animal studies are optionally used in formulating a range of dosage for use in human. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with minimal toxicity. The dosage optionally varies within this range depending upon the dosage form employed and the route of administration utilized.

[0503] SEQUENCE TABLE SEQ ID NO Description Sequence

[0504] 2C8 VH CDR1 GYTFTSY

[0505] 1 amino acid sequence

[0506] (Chothia)

[0507] 2C8 VH CDR2 NPDSGN

[0508] 2 amino acid sequence

[0509] (Chothia)

[0510] 2C8 VH CDR3 APRRYKDGYDYFDY

[0511] 3 amino acid sequence

[0512] (Chothia)

[0513] 2C8 VH CDR1 GYTFTSYDIN

[0514] 4 amino acid sequence

[0515] (AbM)

[0516] 2C8 VH CDR2 WMNPDSGNTG

[0517] 5 amino acid sequence

[0518] (AbM)

[0519] 2C8 VH CDR3 APRRYKDGYDYFDY

[0520] 6 amino acid sequence

[0521] (AbM)

[0522] 2C8 VH CDR1 SYDIN

[0523] 7 amino acid sequence

[0524] (Kabat)

[0525] 2C8 VH CDR2 WMNPDSGNTGFAQKFQG

[0526] 8 amino acid sequence

[0527] (Kabat)

[0528] 2C8 VH CDR3 APRRYKDGYDYFDY

[0529] 9 amino acid sequence

[0530] (Kabat)

[0531] 10 2C8 VH CDR1 TSYDIN

[0532]

[0533] amino acid sequence

[0534] 61

[0535] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0536] (Contact)

[0537] 2C8 VH CDR2 WMGWMNPDSGNTG

[0538] 11 amino acid sequence

[0539] (Contact)

[0540] 2C8 VH CDR3 VRAPRRYKDGYDYFD

[0541] 12 amino acid sequence

[0542] (Contact)

[0543] 2C8 VH CDR1 GYTFTSYD

[0544] 13 amino acid sequence

[0545] (IMGT)

[0546] 2C8 VH CDR2 MNPDSGNT

[0547] 14 amino acid sequence

[0548] (IMGT)

[0549] 2C8 VH CDR3 VRAPRRYKDGYDYFDY

[0550] 15 amino acid sequence

[0551] (IMGT)

[0552] EVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYDINWVR QATEQGLEWMGWMNPDSGNTGFAQKFQGRVSMTRNT

[0553] 16 2C8 VH amino acid

[0554] sequence SISTAYMELSSLRPEDTAVYYCVRAPRRYKDGYDYFDY WGQGTLVTVSS

[0555] 2C8 VL CDR1 amino SGSISNIESNTVN

[0556] 17 acid sequence

[0557] (Chothia)

[0558] 2C8 VL CDR2 amino NNNQRPS

[0559] 18 acid sequence

[0560] (Chothia)

[0561] 2C8 VL CDR3 amino AAWDDSLNGRWV

[0562] 19 acid sequence

[0563] (Chothia)

[0564] 2C8 VL CDR1 amino SGSISNIESNTVN

[0565] 20

[0566] acid sequence (AbM)

[0567] 2C8 VL CDR2 amino NNNQRPS

[0568] 21

[0569] acid sequence (AbM)

[0570] 2C8 VL CDR3 amino AAWDDSLNGRWV

[0571] 22

[0572] acid sequence (AbM)

[0573] 2C8 VL CDR1 amino SGSISNIESNTVN

[0574] 23 acid sequence

[0575] (Kabat)

[0576] 2C8 VL CDR2 amino NNNQRPS

[0577] 24 acid sequence

[0578] (Kabat)

[0579] 2C8 VL CDR3 amino AAWDDSLNGRWV

[0580] 25 acid sequence

[0581] (Kabat)

[0582] 2C8 VL CDR1 amino IESNTVNWY

[0583] 26 acid sequence

[0584] (Contact)

[0585] 2C8 VL CDR2 amino LLIYNNNQRP

[0586] 27 acid sequence

[0587] (Contact)

[0588] 2C8 VL CDR3 amino AAWDDSLNGRW

[0589] 28 acid sequence

[0590] (Contact)

[0591]

[0592] 29 2C8 VL CDR1 amino ISNIESNT

[0593] 62

[0594] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0595] acid sequence

[0596] (IMGT)

[0597] 2C8 VL CDR2 amino NN

[0598] N / A acid sequence

[0599] (IMGT)

[0600] 2C8 VL CDR3 amino AAWDDSLNGRWV

[0601] 30 acid sequence

[0602] (IMGT)

[0603] QSVLTQPPSASGTPGQRVTISCSGSISNIESNTVNWYQQL

[0604] 2C8 VL amino acid

[0605] 31 PGTAPRLLIYNNNQRPSGVPDRFSGSRSGTSASLAISGLQ sequence SEDEADYYCAAWDDSLNGRWVFGGGTELTVL 1F6 VH CDR1 amino GYTFTSY

[0606] 32 acid sequence

[0607] (Chothia)

[0608] 1F6 VH CDR2 amino NPDSGN

[0609] 33 acid sequence

[0610] (Chothia)

[0611] 1F6 VH CDR3 amino APRRYRDGYDYFDY

[0612] 34 acid sequence

[0613] (Chothia)

[0614] 1F6 VH CDR1 amino GYTFTSYDIN

[0615] 35

[0616] acid sequence (AbM)

[0617] 1F6 VH CDR2 amino

[0618] 36 WMNPDSGNTG

[0619] acid sequence (AbM)

[0620] 1F6 VH CDR3 amino APRRYRDGYDYFDY

[0621] 37

[0622] acid sequence (AbM)

[0623] 1F6 VH CDR1 amino SYDIN

[0624] 38 acid sequence

[0625] (Rabat)

[0626] 1F6 VH CDR2 amino WMNPDSGNTGFAQRFQG

[0627] 39 acid sequence

[0628] (Rabat)

[0629] 1F6 VH CDR3 amino APRRYRDGYDYFDY

[0630] 40 acid sequence

[0631] (Rabat)

[0632] 1F6 VH CDR1 amino TSYDIN

[0633] 41 acid sequence

[0634] (Contact)

[0635] 1F6 VH CDR2 amino WMGWMNPDSGNTG

[0636] 42 acid sequence

[0637] (Contact)

[0638] 1F6 VH CDR3 amino VRAPRRYRDGYDYFD

[0639] 43 acid sequence

[0640] (Contact)

[0641] 1F6 VH CDR1 amino GYTFTSYD

[0642] 44 acid sequence

[0643] (IMGT)

[0644] 1F6 VH CDR2 amino MNPDSGNT

[0645] 45 acid sequence

[0646] (IMGT)

[0647] 1F6 VH CDR3 amino VRAPRRYRDGYDYFDY

[0648] 46 acid sequence

[0649] (IMGT)

[0650]

[0651] 47 1F6 VH amino acid EVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYDINWVR 63

[0652] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0653] sequence QATEQGLEWMGWMNPDSGNTGFAQRFQGRVSMTRNT SISTAYMELSSLRPEDTAVYYCVRAPRRYRDGYDYFDY WGQGTLVTVSS

[0654] 1F6 VL CDR1 amino SGSSSNIGSNTVN

[0655] 48 acid sequence

[0656] (Chothia)

[0657] 1F6 VL CDR2 amino SNNQRPS

[0658] 49 acid sequence

[0659] (Chothia)

[0660] 1F6 VL CDR3 amino AAWDDSLNGWV

[0661] 50 acid sequence

[0662] (Chothia)

[0663] 1F6 VL CDR1 amino SGSSSNIGSNTVN

[0664] 51

[0665] acid sequence (AbM)

[0666] 1F6 VL CDR2 amino

[0667] 52 SNNQRPS

[0668] acid sequence (AbM)

[0669] 1F6 VL CDR3 amino

[0670] 53 AAWDDSLNGWV

[0671] acid sequence (AbM)

[0672] 1F6 VL CDR1 amino SGSSSNIGSNTVN

[0673] 54 acid sequence

[0674] (Rabat)

[0675] 1F6 VL CDR2 amino SNNQRPS

[0676] 55 acid sequence

[0677] (Rabat)

[0678] 1F6 VL CDR3 amino AAWDDSLNGWV

[0679] 56 acid sequence

[0680] (Rabat)

[0681] 1F6 VL CDR1 amino IGSNTVNWY

[0682] 57 acid sequence

[0683] (Contact)

[0684] 1F6 VL CDR2 amino LLIYSNNQRP

[0685] 58 acid sequence

[0686] (Contact)

[0687] 1F6 VL CDR3 amino AAWDDSLNGW

[0688] 59 acid sequence

[0689] (Contact)

[0690] 1F6 VL CDR1 amino SSNIGSNT

[0691] 60 acid sequence

[0692] (IMGT)

[0693] 1F6 VL CDR2 amino SN

[0694] N / A acid sequence

[0695] (IMGT)

[0696] 1F6 VL CDR3 amino AAWDDSLNGWV

[0697] 61 acid sequence

[0698] (IMGT)

[0699] QAGLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQ

[0700] 1F6 VL amino acid

[0701] 62 LPGTAPRLLIYSNNQRPSGVPDRFSGSRSGTSASLAISGL sequence QSEDEADYYCAAWDDSLNGWVFGGGTQLTAL 3D3 VH CDR1 GYTLTNN

[0702] 63 amino acid sequence

[0703] (Chothia)

[0704] 3D3 VH CDR2 NPDNGN

[0705] 64 amino acid sequence

[0706]

[0707] (Chothia)

[0708] 64

[0709] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0710] 3D3 VH CDR3 AVGRPSRYYGLDV

[0711] 65 amino acid sequence

[0712] (Chothia)

[0713] 3D3 VH CDR1 GYTLTNNDIH

[0714] 66 amino acid sequence

[0715] (AbM)

[0716] 3D3 VH CDR2 WMNPDNGNTG

[0717] 67 amino acid sequence

[0718] (AbM)

[0719] 3D3 VH CDR3 AVGRPSRYYGLDV

[0720] 68 amino acid sequence

[0721] (AbM)

[0722] 3D3 VH CDR1 NNDIH

[0723] 69 amino acid sequence

[0724] (Kabat)

[0725] 3D3 VH CDR2 WMNPDNGNTGYAQTFQG

[0726] 70 amino acid sequence

[0727] (Kabat)

[0728] 3D3 VH CDR3 AVGRPSRYYGLDV

[0729] 71 amino acid sequence

[0730] (Kabat)

[0731] 3D3 VH CDR1 TNNDIH

[0732] 72 amino acid sequence

[0733] (Contact)

[0734] 3D3 VH CDR2 WMGWMNPDNGNTG

[0735] 73 amino acid sequence

[0736] (Contact)

[0737] 3D3 VH CDR3 ARAVGRPSRYYGLD

[0738] 74 amino acid sequence

[0739] (Contact)

[0740] 3D3 VH CDR1 GYTLTNND

[0741] 75 amino acid sequence

[0742] (IMGT)

[0743] 3D3 VH CDR2 MNPDNGNT

[0744] 76 amino acid sequence

[0745] (IMGT)

[0746] 3D3 VH CDR3 ARAVGRPSRYYGLDV

[0747] 77 amino acid sequence

[0748] (IMGT)

[0749] QVQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWV RQAPGQGLEWMGWMNPDNGNTGYAQTFQGRVSMTRD

[0750] 78 3D3 VH amino acid

[0751] sequence TSTSTAYMELSSLRFEDTAIYSCARAVGRPSRYYGLDVW GQGTLVTVSS

[0752] 3D3 VL CDR1 SGTISNIGNNPVS

[0753] 79 amino acid sequence

[0754] (Chothia)

[0755] 3D3 VL CDR2 SNSQRPS

[0756] 80 amino acid sequence

[0757] (Chothia)

[0758] 3D3 VL CDR3 AAWDDSLDALV

[0759] 81 amino acid sequence

[0760] (Chothia)

[0761] 3D3 VL CDR1 SGTISNIGNNPVS

[0762] 82

[0763]

[0764] amino acid sequence

[0765] 65

[0766] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0767] (AbM)

[0768] 3D3 VL CDR2 SNSQRPS

[0769] 83 amino acid sequence

[0770] (AbM)

[0771] 3D3 VL CDR3 AAWDDSLDALV

[0772] 84 amino acid sequence

[0773] (AbM)

[0774] 3D3 VL CDR1 SGTISNIGNNPVS

[0775] 85 amino acid sequence

[0776] (Rabat)

[0777] 3D3 VL CDR2 SNSQRPS

[0778] 86 amino acid sequence

[0779] (Rabat)

[0780] 3D3 VL CDR3 AAWDDSLDALV

[0781] 87 amino acid sequence

[0782] (Rabat)

[0783] 3D3 VL CDR1 IGNNPVSWY

[0784] 88 amino acid sequence

[0785] (Contact)

[0786] 3D3 VL CDR2 LLIYSNSQRP

[0787] 89 amino acid sequence

[0788] (Contact)

[0789] 3D3 VL CDR3 AAWDDSLDAL

[0790] 90 amino acid sequence

[0791] (Contact)

[0792] 3D3 VL CDR1 ISNIGNNP

[0793] 91 amino acid sequence

[0794] (IMGT)

[0795] 3D3 VL CDR2 SN

[0796] N / A amino acid sequence

[0797] (IMGT)

[0798] 3D3 VL CDR3 AAWDDSLDALV

[0799] 92 amino acid sequence

[0800] (IMGT)

[0801] QAGLTQPPSASGTPRQRVTISCSGTISNIGNNPVSWYQHL

[0802] 3D3 VL amino acid

[0803] 93 PGTAPRLLIYSNSQRPSGVPERFSGSRSGTSASLAISGLQS sequence EDEAD YYCAAWDDSLDALVFGGGTQLTAL

[0804] 5H8 VH CDR1 GYTLTNN

[0805] 94 amino acid sequence

[0806] (Chothia)

[0807] 5H8 VH CDR2 NPDNGN

[0808] 95 amino acid sequence

[0809] (Chothia)

[0810] 5H8 VH CDR3 AVGRPSRYYGLDV

[0811] 96 amino acid sequence

[0812] (Chothia)

[0813] 5H8 VH CDR1 GYTLTNNDIH

[0814] 97 amino acid sequence

[0815] (AbM)

[0816] 5H8 VH CDR2 WMNPDNGNTG

[0817] 98 amino acid sequence

[0818] (AbM)

[0819] 5H8 VH CDR3 AVGRPSRYYGLDV

[0820] 99

[0821]

[0822] ammo acid sequence

[0823] 66

[0824] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0825] (AbM)

[0826] 5H8 VH CDR1 NNDIH

[0827] 100 amino acid sequence

[0828] (Kabat)

[0829] 5H8 VH CDR2 WMNPDNGNTGYAQTFQG

[0830] 101 amino acid sequence

[0831] (Kabat)

[0832] 5H8 VH CDR3 AVGRPSRYYGLDV

[0833] 102 amino acid sequence

[0834] (Kabat)

[0835] 5H8 VH CDR1 TNNDIH

[0836] 103 amino acid sequence

[0837] (Contact)

[0838] 5H8 VH CDR2 WMGWMNPDNGNTG

[0839] 104 amino acid sequence

[0840] (Contact)

[0841] 5H8 VH CDR3 ARAVGRPSRYYGLD

[0842] 105 amino acid sequence

[0843] (Contact)

[0844] 5H8 VH CDR1 GYTLTNND

[0845] 106 amino acid sequence

[0846] (IMGT)

[0847] 5H8 VH CDR2 MNPDNGNT

[0848] 107 amino acid sequence

[0849] (IMGT)

[0850] 5H8 VH CDR3 ARAVGRPSRYYGLDV

[0851] 108 amino acid sequence

[0852] (IMGT)

[0853] QMQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWV RQAPGQGLEWMGWMNPDNGNTGYAQTFQGRVSMTRD

[0854] 109 5H8 VH amino acid

[0855] sequence TSTSTAYMELSSLRFEDTAIYSCARAVGRPSRYYGLDVW GQGTLVTVSS

[0856] 5H8 VL CDR1 SGGSSNIGTNPLT

[0857] 110 amino acid sequence

[0858] (Chothia)

[0859] 5H8 VL CDR2 SNDQRPS

[0860] 111 amino acid sequence

[0861] (Chothia)

[0862] 5H8 VL CDR3 ATWDDSVDGLV

[0863] 112 amino acid sequence

[0864] (Chothia)

[0865] 5H8 VL CDR1 SGGSSNIGTNPLT

[0866] 113 amino acid sequence

[0867] (AbM)

[0868] 5H8 VL CDR2 SNDQRPS

[0869] 114 amino acid sequence

[0870] (AbM)

[0871] 5H8 VL CDR3 ATWDDSVDGLV

[0872] 115 amino acid sequence

[0873] (AbM)

[0874] 5H8 VL CDR1 SGGSSNIGTNPLT

[0875] 116 amino acid sequence

[0876] (Kabat)

[0877]

[0878] 117 5H8 VL CDR2 SNDQRPS

[0879] 67

[0880] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0881] amino acid sequence

[0882] (Kabat)

[0883] 5H8 VL CDR3 ATWDDSVDGLV

[0884] 118 amino acid sequence

[0885] (Kabat)

[0886] 5H8 VL CDR1 IGTNPLTWY

[0887] 119 amino acid sequence

[0888] (Contact)

[0889] 5H8 VL CDR2 LLIYSNDQRP

[0890] 120 amino acid sequence

[0891] (Contact)

[0892] 5H8 VL CDR3 ATWDDSVDGL

[0893] 121 amino acid sequence

[0894] (Contact)

[0895] 5H8 VL CDR1 SSNIGTNP

[0896] 122 amino acid sequence

[0897] (IMGT)

[0898] 5H8 VL CDR2 SN

[0899] N / A amino acid sequence

[0900] (IMGT)

[0901] 5H8 VL CDR3 ATWDDSVDGLV

[0902] 123 amino acid sequence

[0903] (IMGT)

[0904] QAGLTQPPSASGTPGQRVTISCSGGSSNIGTNPLTWYQQ

[0905] 124 5H8 VL amino acid LPRTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLTISGL sequence

[0906] QSGDEADYYCATWDDSVDGLVFGGGTQLTVL

[0907] 7C6 VH CDR1 GYTFTSY

[0908] 125 amino acid sequence

[0909] (Chothia)

[0910] 7C6 VH CDR2 SAYNGN

[0911] 126 amino acid sequence

[0912] (Chothia)

[0913] 7C6 VH CDR3 DLGAVELYYYYGMDV

[0914] 127 amino acid sequence

[0915] (Chothia)

[0916] 7C6 VH CDR1 GYTFTSYGIS

[0917] 128 amino acid sequence

[0918] (AbM)

[0919] 7C6 VH CDR2 WISAYNGNTN

[0920] 129 amino acid sequence

[0921] (AbM)

[0922] 7C6 VH CDR3 DLGAVELYYYYGMDV

[0923] 130 amino acid sequence

[0924] (AbM)

[0925] 7C6 VH CDR1 SYGIS

[0926] 131 amino acid sequence

[0927] (Kabat)

[0928] 7C6 VH CDR2 WISAYNGNTNYAQKLQG

[0929] 132 amino acid sequence

[0930] (Kabat)

[0931] 7C6 VH CDR3 DLGAVELYYYYGMDV

[0932] 133 amino acid sequence

[0933] (Kabat)

[0934]

[0935] 134 7C6 VH CDR1 TSYGIS

[0936] 68

[0937] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0938] amino acid sequence

[0939] (Contact)

[0940] 7C6 VH CDR2 WMGWISAYNGNTN

[0941] 135 amino acid sequence

[0942] (Contact)

[0943] 7C6 VH CDR3 ARDLGAVELYYYYGMD

[0944] 136 amino acid sequence

[0945] (Contact)

[0946] 7C6 VH CDR1 GYTFTSYG

[0947] 137 amino acid sequence

[0948] (IMGT)

[0949] 7C6 VH CDR2 ISAYNGNT

[0950] 138 amino acid sequence

[0951] (IMGT)

[0952] 7C6 VH CDR3 ARDLGAVELYYYYGMDV

[0953] 139 amino acid sequence

[0954] (IMGT)

[0955] QVQLVQSGAEVRRPGASVRVSCRASGYTFTSYGISWVR

[0956] 7C6 VH amino acid QAPGQGLEWMGWISAYNGNTNYAQRLQGRVTMTTDT 140

[0957] sequence STSTAYMELRSLRSDDTAVYYCARDLGAVELYYYYGM DVWGQGTTVTVSS

[0958] 7C6 VL CDR1 amino SGSSSNIGSNTVD

[0959] 141 acid sequence

[0960] (Chothia)

[0961] 7C6 VL CDR2 amino NNNQRPS

[0962] 142 acid sequence

[0963] (Chothia)

[0964] 7C6 VL CDR3 amino ATWDDSLNGLV

[0965] 143 acid sequence

[0966] (Chothia)

[0967] 144 7C6 VL CDR1 amino SGSSSNIGSNTVD

[0968] acid sequence (AbM)

[0969] 7C6 VL CDR2 amino

[0970] 145 NNNQRPS

[0971] acid sequence (AbM)

[0972] 7C6 VL CDR3 amino

[0973] 146 ATWDDSLNGLV

[0974] acid sequence (AbM)

[0975] 7C6 VL CDR1 amino SGSSSNIGSNTVD

[0976] 147 acid sequence

[0977] (Rabat)

[0978] 7C6 VL CDR2 amino NNNQRPS

[0979] 148 acid sequence

[0980] (Rabat)

[0981] 7C6 VL CDR3 amino ATWDDSLNGLV

[0982] 149 acid sequence

[0983] (Rabat)

[0984] 7C6 VL CDR1 amino IGSNTVDWY

[0985] 150 acid sequence

[0986] (Contact)

[0987] 7C6 VL CDR2 amino LLIYNNNQRP

[0988] 151 acid sequence

[0989] (Contact)

[0990] 7C6 VL CDR3 amino ATWDDSLNGL

[0991] 152 acid sequence

[0992]

[0993] (Contact)

[0994] 69

[0995] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[0996] 7C6 VL CDR1 amino SSNIGSNT

[0997] 153 acid sequence

[0998] (IMGT)

[0999] 7C6 VL CDR2 amino NN

[1000] N / A acid sequence

[1001] (IMGT)

[1002] 7C6 VL CDR3 amino ATWDDSLNGLV

[1003] 154 acid sequence

[1004] (IMGT)

[1005] QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVDWYHQL

[1006] 155 7C6 VL amino acid PGTAPNLLIYNNNQRPSGVPDRFSGSKSGTSAFLAISGLQ sequence SEDEGDYYCATWDDSLNGLVFGGGTQLTVL ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEL LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

[1007] 156 uIgGIL-HC amino

[1008] acid sequence KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVT

[1009] 157 uIgGIL-LC amino VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE acid sequence QWKSHRSYSCQVTHEGSTVEKTVAPTECS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEL LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

[1010] 158 u!gGlLV236-HC KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH amino acid sequence QDWLNGKEYKCKVSNWALPAPISKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVT

[1011] 159 u!gGlLV236-LC VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE amino acid sequence QWKSHRSYSCQVTHEGSTVEKTVAPTECS 160 Skipped [no sequence]

[1012] EVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYDINWVR QATEQGLEWMGWMNPDSGNTGFAQKFQGRVSMTRNT SISTAYMELSSLRPEDTAVYYCVRAPRRYKDGYDYFDY WGQGTLVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV

[1013] 2C8 complement SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT 161 enhanced (heavy QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEL chain K326W and

[1014] E333S) heavy chain LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNWALPAPISKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK QSVLTQPPSASGTPGQRVTISCSGSISNIESNTVNWYQQL

[1015] 162 2C8 complement PGTAPKLLIYNNNQRPSGVPDRFSGSKSGTSASLAISGLQ enhanced light chain SEDEADYYCAAWDDSLNGRWVFGGGTELTVL

[1016]

[1017] GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVT

[1018] 70

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[1020] VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE QWKSHRSYSCQVTHEGSTVEKTVAPTECS EVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYDINWVR QATEQGLEWMGWMNPDSGNTGFAQKFQGRVSMTRNT SISTAYMELSSLRPEDTAVYYCVRAPRRYKDGYDYFDY WGQGTLVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV

[1021] 1F6 complement SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT 163 enhanced (heavy QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEL chain K326W and

[1022] E333S) heavy chain LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNWALPAPISKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSD1AVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK QAGLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQ LPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGL

[1023] 164 1F6 complement QSEDEADYYCAAWDDSLNGWVFGGGTQLTAL enhanced light chain GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVT VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE QWKSHRSYSCQVTHEGSTVEKTVAPTECS QVQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWV RQAPGQGLEWMGWMNPDNGNTGYAQTFQGRVSMTRD TSTSTAYMELSSLRFEDTAIYSCARAVGRPSRYYGLDVW GQGTLVTVSS

[1024] 3D3 complement ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

[1025] 165 enhanced (heavy QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEL chain K326W and

[1026] E333S) heavy chain LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNWALPAPISKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK QAGLTQPPSASGTPRQRVTISCSGTISNIGNNPVSWYQHL PGTAPKLLIYSNSQRPSGVPERFSGSKSGTSASLAISGLQS

[1027] 166 3D3 complement EDEAD YYCAAWDDSLDALVFGGGTQLTAL enhanced light chain GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVT VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE QWKSHRSYSCQVTHEGSTVEKTVAPTECS QMQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWV RQAPGQGLEWMGWMNPDNGNTGYAQTFQGRVSMTRD TSTSTAYMELSSLRFEDTAIYSCARAVGRPSRYYGLDVW GQGTLVTVSS

[1028] 5H8 complement ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

[1029] 167 enhanced (heavy QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEL chain K326W and

[1030] E333S) heavy chain LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNWALPAPISKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK

[1031]

[1032] 168 5H8 complement QAGLTQPPSASGTPGQRVTISCSGGSSNIGTNPLTWYQQ

[1033] 71

[1034] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1035] enhanced light chain LPRTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLTISGL QSGDEADYYCATWDDSVDGLVFGGGTQLTVL GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVT VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE QWKSHRSYSCQVTHEGSTVEKTVAPTECS QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVR QAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDT STSTAYMELRSLRSDDTAVYYCARDLGAVELYYYYGM DVWGQGTTVTVSS

[1036] 7C6 complement ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT

[1037] 169 enhanced (heavy

[1038] chain K326W and QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEL LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV E333S) heavy chain KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNWALPAPISKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK QSVLTQPPSASGTPGQRVTISCSGSSSN1GSNTVDWYHQL PGTAPNLLIYNNNQRPSGVPDRFSGSKSGTSAFLAISGLQ

[1039] 170 7C6 complement SEDEGDYYCATWDDSLNGLVFGGGTQLTVL enhanced light chain GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVT VAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE QWKSHRSYSCQVTHEGSTVEKTVAPTECS EVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYDINWVR QATEQGLEWMGWMNPDSGNTGFAQKFQGRVSMTRNT SISTAYMELSSLRPEDTAVYYCVRAPRRYKDGYDYFDY WGQGTLVTVSSGGGGSQSVLTQPPSASGTPGQRVTISCS GSISNIESNTVNWYQQLPGTAPKLLIYNNNQRPSGVPDR FSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGRW VFGGGTELTVLGGGGSGGGGSGGGGSEVQLVQSGAEV KKPGASVKVSCKGSGYTFTSYDINWVRQATEQGLEWM GWMNPDSGNTGFAQKFQGRVSMTRNTSISTAYMELSSL

[1040] 171 2C8_scDb_Fc RPEDTAVYYCVRAPRRYKDGYDYFDYWGQGTLVTVSS GGGGSQSVLTQPPSASGTPGQRVTISCSGSISNIESNTVN WYQQLPGTAPKLLIYNNNQRPSGVPDRFSGSKSGTSASL AISGLQSEDEADYYCAAWDDSLNGRWVFGGGTELTVL AAAEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAP1EKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGKHHHHHH EVQLVQSGAEVKKPGASVKVSCKGSGYTFTSYDINWVR QATEQGLEWMGWMNPDSGNTGFAQKFQGRVSMTRNT SISTAYMELSSLRPEDTAVYYCVRAPRRYKDGYDYFDY WGQGTLVTVSSGGGGSQAGLTQPPSASGTPGQRVTISCS

[1041] 172 GSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDR lF6_scDb_Fc FSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGWV FGGGTQLTALGGGGSGGGGSGGGGSEVQLVQSGAEVK KPGASVKVSCKGSGYTFTSYDINWVRQATEQGLEWMG WMNPDSGNTGFAQKFQGRVSMTRNTSISTAYMELSSLR

[1042]

[1043] PEDTAVYYCVRAPRRYKDGYDYFDYWGQGTLVTVSSG

[1044] 72

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[1046] GGGSQAGLTQPPSASGTPGQRVTISCSGSSSNIGSNTVN WYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASL AISGLQSEDEADYYCAAWDDSLNGWVFGGGTQLTALA AAEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGKHHHHHH QVQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWV RQAPGQGLEWMGWMNPDNGNTGYAQTFQGRVSMTRD TSTSTAYMELSSLRFEDTAIYSCARAVGRPSRYYGLDVW GQGTLVTVSSGSGGGGSQAGLTQPPSASGTPRQRVTISC SGTISNIGNNPVSWYQHLPGTAPKLLIYSNSQRPSGVPER FSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLDALVF GGGTQLTALGGGGSGGGGSGGGGSQVQLVQSGAEVKE PGASVKVSCKASGYTLTNNDIHWVRQAPGQGLEWMG WMNPDNGNTGYAQTFQGRVSMTRDTSTSTAYMELSSL

[1047] 173 3D3_scDb_Fc RFEDTAIYSCARAVGRPSRYYGLDVWGQGTLVTVSSGS GGGGSQAGLTQPPSASGTPRQRVTISCSGTISNIGNNPVS WYQHLPGTAPKLLIYSNSQRPSGVPERFSGSKSGTSASL AISGLQSEDEADYYCAAWDDSLDALVFGGGTQLTALAA AEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM1S RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKHHHHHH QMQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWV RQAPGQGLEWMGWMNPDNGNTGYAQTFQGRVSMTRD TSTSTAYMELSSLRFEDTAIYSCARAVGRPSRYYGLDVW GQGTLVTVSSGGGGSQAGLTQPPSASGTPGQRVTISCSG GSSN1GTNPLTWYQQLPRTAPKLLIYSNDQRPSGVPDRFS GSKSGTSASLTISGLQSGDEADYYCATWDDSVDGLVFG GGTQLTVLGGGGSGGGGSGGGGSQMQLVQSGAEVKEP GASVKVSCKASGYTLTNNDIHWVRQAPGQGLEWMGW MNPDNGNTGYAQTFQGRVSMTRDTSTSTAYMELSSLRF

[1048] 174 EDTAIYSCARAVGRPSRYYGLDVWGQGTLVTVSSGGGG 5H8_scDb_Fc SQAGLTQPPSASGTPGQRVTISCSGGSSNIGTNPLTWYQ QLPRTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLTISG LQSGDEADYYCATWDDSVDGLVFGGGTQLTVLAAAEP KSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP1 EKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK HHHHHH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVR

[1049] 175 QAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDT 7C6_scDb_Fc STSTAYMELRSLRSDDTAVYYCARDLGAVELYYYYGM

[1050]

[1051] DVWGQGTTVTVSSGGGGSQSVLTQPPSASGTPGQRVTIS

[1052] 73

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[1054] CSGSSSNIGSNTVDWYHQLPGTAPNLLIYNNNQRPSGVP DRFSGSKSGTSAFLAISGLQSEDEGDYYCATWDDSLNGL VFGGGTQLTVLGGGGSGGGGSGGGGSQVQLVQSGAEV KKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWM GWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRS LRSDDTAVYYCARDLGAVELYYYYGMDVWGQGTTVT VSSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSSNIGSN TVDWYHQLPGTAPNLLIYNNNQRPSGVPDRFSGSKSGTS AFLAISGLQSEDEGDYYCATWDDSLNGLVFGGGTQLTV LAAAEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSF FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

[1055]

[1056] SLSPGKHHHHHH

[1057] EXAMPLES

[1058] The instant specification further describes in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless so specified. Thus, the instant specification should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

[1059] Example 1: Antibody Design and Production

[1060] The present example described antibody design and production.

[1061] 2.2 Expression plasmid construction and preparation

[1062] Plasmids of the antibodies were synthesized by Genewiz: plasmids containing VH, in which the VH domain is fused with human IgGl CHI, hinge, CH2 (K326W / E333S) and CH3 segments in the heavy chain; and plasmids containing VL, in which the VL domain is fused wi th human Ig lambda CL domain in the light chain. A human IgK single peptide was fused at 5’ end of VH or VL for secretory expression.

[1063] 2.3 Antibody production

[1064] 2.3.1 Antibody expression

[1065] Day 1: Typically, 2.94xlO6 / mL Expi293F cells with more than 95% viability in 100 rnL of cell culture media were prepared for transfection. 100 ug plasmid DNA and 270 pl ExpiFectamine™ 293 Reagent were diluted in 5 mL and 4.73 rnL Opti-MEM respectively,

[1066] 74

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[1068] mixed, and added to Expi293F cell culture followed by incubated in a platform shaker set at HO rpm, 37°C, 8% CO2.

[1069] Day 2: 18-20 hrs after transfection, 0.5 mL Enhancer 1, and 5 mL Enhancer 2 were added to the culture medium to support high-density transient transfection and enhance protein production.

[1070] After six days of incubation, cells were pelleted by centrifuging at 4000 rpm (3724g, BECKMAN ALLERGA X-15 CENTRIFUGE, Cat No.: B31016), 25°C for 10 mins.

[1071] Supernatant was collected and used for purification and gel electrophoresis. SDS-PAGE samples were prepared by mixing 15 pL supernatant with 5 pL 4 x Loading buffer and boiling for 5 mins. 15 pL of the sample was loaded on NuPAGE™ 4-12% Bis-Tris Protein Gels (ThermoFisher) and run for 35 mins at 200 V constant using MES running buffer. Then the proteins on the gel was stained using Coomassie Blue. PageRuler™ Unstained Protein Ladder (ThermoFisher) was used alongside with the antibody samples to determine the molecular weight of the antibody.

[1072] 2.3.2 Antibody purification

[1073] 2.3.2.1 Protein A purification

[1074] Protein A column was pre-packed with 5 mL MabSelect Sure resin (GE Lifesciences, Cat. # 17543803). Column was equilibrated with 0.1 M Tris, pH7.0 before loading cell culture supernatant containing expressed IgG. After loading, the column was washed with 10 CV 0.1 M Tris, pH7.0 followed by elution with 0.1 M Glycine, pH3.5. The eluate was then neutralized by adding 0.1 M Tris, pH9.0 and dialyzed against IX PBS buffer (Sangon Biotech, B548117-0500).

[1075] 2.3.2.2 CEX purification

[1076] 1 mL Hi Trap SP FF column was used for the first step purification. The column was equilibrated with Buffer A (50 mM NaAc, pH 5.0) and the antibody after Protein A purification was loaded. Following loading, the column was washed with Buffer A followed by elution using gradient Buffer B (50 mM NaAc, 1 M NaCl, pH 5.0) as detailed below. SDS-PAGE was performed to analyze the fraction of each peak.

[1077] 2.3.2 Antibody characterization

[1078] The antibody concentrations were measured by absorbance at 280 nm using Nano Drop. The purities of antibodies were evaluated by SDS-PAGE and SEC-HPLC.

[1079] 75

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[1081] SDS-PAGE samples were prepared by mixing 15 pL protein sample with 5 pL 4X loading buffer followed by boiling for 5 mins. 15 pL of the mixture was loaded in NuPAGE Bis-Tris Mini Gels 4-12% gel and run for 35 mins at 200 V constant using MES running buffer. Then the proteins on the gel were stained using Coomassie Blue. For SEC-HPLC, 80 pL of the purified antibodies were loaded on TSKgel G3000SWxL column connected to HPLC system 1260 Infinity II with the running buffer of 50 rnM sodium phosphate, 150 mM NaCl, pH7.0. The running time was 20 min. Protein peaks were monitored by UV-detector at 280 nm. Peak retention times were analyzed using ChemStation software (V2.99.2.0).

[1082] 3. Results

[1083] 3.1 Antibody Production

[1084] Antibodies were produced and purified as described above. After purification, the antibodies were characterized by SDS-PAGE and SEC-HPLC (FIG. 7A-FIG. 7B) and data not shown). The antibodies migrated with the apparent molecular mass of 150 kDa on SDS-PAGE under non-reducing condition. The antibodies migrated with the apparent molecular mass of 50 and 25 kDa on SDS-PAGE under reducing condition, corresponding to the heavy¬ chains and light chains respectively.

[1085] 3.2 Antibody Sequences

[1086] The antibodies included the following:

[1087] 2C8

[1088] Description Sequence

[1089] 2C8 VH CDR1 amino GYTFTSY (SEQ ID NO: 1 )

[1090] acid sequence (Chothia)

[1091] 2C8 VH CDR2 ammo NPDSGN ( SEQ ID NO: 2 )

[1092] acid sequence (Chothia)

[1093] 2C8 VH CDR3 ammo APRRYKDGYDYFDY (SEQ ID NO: 3)

[1094] acid sequence (Chothia)

[1095] 2C8 VH CDR1 ammo GYTFTSYDIN (SEQ ID NO: 4 )

[1096] acid sequence (AbM)

[1097] 2C8 VH CDR2 amino WMNPDSGNTG (SEQ ID NO: 5)

[1098] acid sequence (AbM)

[1099] 2C8 VH CDR3 ammo APRRYKDGYDYFDY (SEQ ID NO: 6)

[1100] acid sequence (AbM)

[1101] 2C8 VH CDR1 ammo SYDIN (SEQ ID NO: 7 )

[1102] acid sequence (Kabat)

[1103] 2C8 VH CDR2 amino WMNPDSGNTGFAQKFQG (SEQ ID NO: 8 )

[1104]

[1105] acid sequence (Kabat)

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[1108] 2C8 VH CDR3 amino APRRYKDGYDYFDY (SEQ ID NO: 9)

[1109] acid sequence (Kabat)

[1110] 2C8 VH CDR1 amino TSYDIN ( SEQ ID NO: 10 )

[1111] acid sequence (Contact)

[1112] 2C8 VH CDR2 ammo WMGWMNPDSGNTG (SEQ ID NO: 11)

[1113] acid sequence (Contact)

[1114] 2C8 VH CDR3 ammo VRAPRRYKDGYDYFD ( SEQ ID NO: 12 )

[1115] acid sequence (Contact)

[1116] 2C8 VH CDR1 amino GYTFTSYD (SEQ ID NO: 13)

[1117] acid sequence (IMGT)

[1118] 2C8 VH CDR2 amino MNPDSGNT (SEQ ID NO: 14 )

[1119] acid sequence (IMGT)

[1120] 2C8 VH CDR3 amino VRAPRRYKDGYDYFDY (SEQ ID NO: 15 )

[1121] acid sequence (IMGT)

[1122] EVQL VQS G AEVKK P GAS VKVS CKGSGYTFTSYDI N WVRQAT E QG

[1123] 2C8 VH amino acid LEWMGWMNPDSGNTGFAQKFQGRVSMTRNTSISTAYMELSSLRP sequence EDTAVYYCVRAPRRYKDGYDYFDYWGQGTLVTVSS (SEQ ID NO: 16)

[1124] 2C8 VL CDR1 amino SGS I SNIESNTVN (SEQ ID NO: 17 )

[1125] acid sequence (Chothia)

[1126] 2C8 VL CDR2 amino NNNQRPS (SEQ ID NO: 18 )

[1127] acid sequence (Chothia)

[1128] 2C8 VL CDR3 amino AAWDDSLNGRWV (SEQ ID NO: 19)

[1129] acid sequence (Chothia)

[1130] 2C8 VL CDR1 amino SGS I SNIESNTVN (SEQ ID NO: 20)

[1131] acid sequence (AbM)

[1132] 2C8 VL CDR2 amino NNNQRPS (SEQ ID NO: 21 )

[1133] acid sequence (AbM)

[1134] 2C8 VL CDR3 amino AAWDDSLNGRWV (SEQ ID NO: 22 )

[1135] acid sequence (AbM)

[1136] 2C8 VL CDR1 amino SGS I SNIESNTVN (SEQ ID NO: 23)

[1137] acid sequence (Kabat)

[1138] 2C8 VL CDR2 amino NNNQRPS (SEQ ID NO: 24 )

[1139] acid sequence (Kabat)

[1140] 2C8 VL CDR3 amino AAWDDSLNGRWV (SEQ ID NO: 25 )

[1141] acid sequence (Kabat)

[1142] 2C8 VL CDR1 ammo IESNTVNWY (SEQ ID NO: 26)

[1143] acid sequence (Contact)

[1144] 2C8 VL CDR2 ammo LLIYNNNQRP (SEQ ID NO: 27 )

[1145] acid sequence (Contact)

[1146] 2C8 VL CDR3 ammo AAWDDSLNGRW ( SEQ ID NO: 28 )

[1147] acid sequence (Contact)

[1148] 2C8 VL CDR1 ammo ISNIESNT (SEQ ID NO: 29)

[1149] acid sequence (IMGT)

[1150] 2C8 VL CDR2 ammo NN

[1151] acid sequence (IMGT)

[1152] 2C8 VL CDR3 ammo AAWDDSLNGRWV (SEQ ID NO: 30 )

[1153] acid sequence (IMGT)

[1154]

[1155] 2C8 VL amino acid QSVLTQPPSASGTPGQRVTISCSGSISNIESNTVNWYQQLPGTA

[1156] 77

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[1158] sequence PKLLIYNNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYY

[1159]

[1160] CAAWDDSLNGRWVFGGGTELTVL (SEQ ID NO: 31 )

[1161] 1F6

[1162] Description Sequence

[1163] 1F6 VH CDR1 amino GYTFTSY (SEQ ID NO: 32 )

[1164] acid sequence (Chothia)

[1165] 1F6 VH CDR2 amino NPDSGN ( SEQ ID NO: 33 )

[1166] acid sequence (Chothia)

[1167] 1F6 VH CDR3 amino APRRYKDGYDYFDY (SEQ ID NO: 34 )

[1168] acid sequence (Chothia)

[1169] 1F6 VH CDR1 amino GYTFTSYDIN (SEQ ID NO: 35 )

[1170] acid sequence (AbM)

[1171] 1F6 VH CDR2 amino WMNPDSGNTG (SEQ ID NO: 36)

[1172] acid sequence (AbM)

[1173] 1F6 VH CDR3 amino APRRYKDGYDYFDY (SEQ ID NO: 37 )

[1174] acid sequence (AbM)

[1175] 1F6 VH CDR1 amino SYDIN (SEQ ID NO: 38 )

[1176] acid sequence (Kabat)

[1177] 1F6 VH CDR2 amino WMNPDSGNTGFAQKFQG (SEQ ID NO: 39)

[1178] acid sequence (Kabat)

[1179] 1F6 VH CDR3 amino APRRYKDGYDYFDY (SEQ ID NO: 40 )

[1180] acid sequence (Kabat)

[1181] 1F6 VH CDR1 amino TSYDIN ( SEQ ID NO: 41 )

[1182] acid sequence (Contact)

[1183] 1F6 VH CDR2 amino WMGWMNPDSGNTG (SEQ ID NO: 42 )

[1184] acid sequence (Contact)

[1185] 1F6 VH CDR3 ammo VRAPRRYKDGYDYFD ( SEQ ID NO: 43 )

[1186] acid sequence (Contact)

[1187] 1F6 VH CDR1 ammo GYTFTSYD (SEQ ID NO: 44 )

[1188] acid sequence (IMGT)

[1189] 1F6 VH CDR2 ammo MNPDSGNT (SEQ ID NO: 45)

[1190] acid sequence (IMGT)

[1191] 1F6 VH CDR3 ammo VRAPRRYKDGYDYFDY (SEQ ID NO: 46)

[1192] acid sequence (IMGT)

[1193] 1F6 VH amino acid EVQL VQS G AEVKK P GAS VKVS CKGSGYTFTSYDI N WVRQAT E QG sequence LEWMGWMNPDSGNTGFAQKFQGRVSMTRNTSISTAYMELSSLRP EDTAVYYCVRAPRRYKDGYDYFDYWGQGTLVTVSS (SEQ ID NO: 47 )

[1194] 1F6 VL CDR1 amino SGSSSNIGSNTVN (SEQ ID NO: 48 )

[1195] acid sequence (Chothia)

[1196] 1F6 VL CDR2 ammo SNNQRPS (SEQ ID NO: 49 )

[1197] acid sequence (Chothia)

[1198] 1F6 VL CDR3 ammo AAWDDSLNGWV ( SEQ ID NO: 50 )

[1199] acid sequence (Chothia)

[1200] 1F6 VL CDR1 ammo SGSSSNIGSNTVN (SEQ ID NO: 51)

[1201] acid sequence (AbM)

[1202]

[1203] 1F6 VL CDR2 ammo SNNQRPS (SEQ ID NO: 52 )

[1204] 78

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[1206] acid sequence (AbM)

[1207] 1F6 VL CDR3 amino AAWDDSLNGWV ( SEQ ID NO: 53 )

[1208] acid sequence (AbM)

[1209] 1F6 VL CDR1 amino SGSSSNIGSNTVN (SEQ ID NO: 54 )

[1210] acid sequence (Kabat)

[1211] 1F6 VL CDR2 amino SNNQRPS (SEQ ID NO: 55 )

[1212] acid sequence (Kabat)

[1213] 1F6 VL CDR3 amino AAWDDSLNGWV ( SEQ ID NO: 56 )

[1214] acid sequence (Kabat)

[1215] 1F6 VL CDR1 amino IGSNTVNWY (SEQ ID NO: 57 )

[1216] acid sequence (Contact)

[1217] 1F6 VL CDR2 amino LLIYSNNQRP (SEQ ID NO: 58 )

[1218] acid sequence (Contact)

[1219] 1F6 VL CDR3 amino AAWDDSLNGW (SEQ ID NO: 59)

[1220] acid sequence (Contact)

[1221] 1F6 VL CDR1 amino SSNIGSNT (SEQ ID NO: 60)

[1222] acid sequence (IMGT)

[1223] 1F6 VL CDR2 amino SN

[1224] acid sequence (IMGT)

[1225] 1F6 VL CDR3 amino AAWDDSLNGWV ( SEQ ID NO: 61 )

[1226] acid sequence (IMGT)

[1227] 1F6 VL amino acid QAGLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTA sequence PKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYY

[1228]

[1229] CAAWDDSLNGWVFGGGTQLTAL (SEQ ID NO: 62 )

[1230] 3D3

[1231] Description Sequence

[1232] 3D3 VH CDR1 amino GYTLTNN (SEQ ID NO: 63 )

[1233] acid sequence (Chothia)

[1234] 3D3 VH CDR2 amino NPDNGN ( SEQ ID NO: 64 )

[1235] acid sequence (Chothia)

[1236] 3D3 VH CDR3 amino AVGRPSRYYGLDV (SEQ ID NO: 65)

[1237] acid sequence (Chothia)

[1238] 3D3 VH CDR1 amino GYTLTNNDIH (SEQ ID NO: 66)

[1239] acid sequence (AbM)

[1240] 3D3 VH CDR2 amino WMNPDNGNTG (SEQ ID NO: 67 )

[1241] acid sequence (AbM)

[1242] 3D3 VH CDR3 amino AVGRPSRYYGLDV (SEQ ID NO: 68 )

[1243] acid sequence (AbM)

[1244] 3D3 VH CDR1 amino NNDIH (SEQ ID NO: 69)

[1245] acid sequence (Kabat)

[1246] 3D3 VH CDR2 amino WMNPDNGNTGYAQTFQG (SEQ ID NO: 70)

[1247] acid sequence (Kabat)

[1248] 3D3 VH CDR3 amino AVGRPSRYYGLDV (SEQ ID NO: 71)

[1249] acid sequence (Kabat)

[1250] 3D3 VH CDR1 amino TNNDIH ( SEQ ID NO: 72 )

[1251] acid sequence (Contact)

[1252]

[1253] 3D3 VH CDR2 amino WMGWMNPDNGNTG (SEQ ID NO: 73)

[1254] 79

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[1256] acid sequence (Contact)

[1257] 3D3 VH CDR3 amino ARAVGRPSRYYGLD (SEQ ID NO: 74 )

[1258] acid sequence (Contact)

[1259] 3D3 VH CDR1 amino GYTLTNND (SEQ ID NO: 75)

[1260] acid sequence (IMGT)

[1261] 3D3 VH CDR2 amino MNPDNGNT (SEQ ID NO: 76)

[1262] acid sequence (IMGT)

[1263] 3D3 VH CDR3 amino ARAVGRPSRYYGLDV ( SEQ ID NO: 77 )

[1264] acid sequence (IMGT)

[1265] 3D3 VH amino acid QVQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWVRQAPGQG sequence LEWMGWMNPDNGNTGYAQTFQGRVSMTRDTSTSTAYMELSSLRF EDTAIYSCARAVGRPSRYYGLDVWGQGTLVTVSS (SEQ ID NO: 78 )

[1266] 3D3 VL CDR1 ammo SGTISNIGNNPVS (SEQ ID NO: 79)

[1267] acid sequence (Chothia)

[1268] 3D3 VL CDR2 ammo SNSQRPS (SEQ ID NO: 80 )

[1269] acid sequence (Chothia)

[1270] 3D3 VL CDR3 ammo AAWDDSLDALV ( SEQ ID NO: 81 )

[1271] acid sequence (Chothia)

[1272] 3D3 VL CDR1 ammo SGTISNIGNNPVS (SEQ ID NO: 82 )

[1273] acid sequence (AbM)

[1274] 3D3 VL CDR2 amino SNSQRPS (SEQ ID NO: 83 )

[1275] acid sequence (AbM)

[1276] 3D3 VL CDR3 amino AAWDDSLDALV ( SEQ ID NO: 84 )

[1277] acid sequence (AbM)

[1278] 3D3 VL CDR1 amino SGTISNIGNNPVS (SEQ ID NO: 85)

[1279] acid sequence (Kabat)

[1280] 3D3 VL CDR2 amino SNSQRPS (SEQ ID NO: 86 )

[1281] acid sequence (Kabat)

[1282] 3D3 VL CDR3 amino AAWDDSLDALV ( SEQ ID NO: 87 )

[1283] acid sequence (Kabat)

[1284] 3D3 VL CDR1 amino IGNNPVSWY (SEQ ID NO: 88 )

[1285] acid sequence (Contact)

[1286] 3D3 VL CDR2 amino LLIYSNSQRP (SEQ ID NO: 89)

[1287] acid sequence (Contact)

[1288] 3D3 VL CDR3 amino AAWDDSLDAL (SEQ ID NO: 90 )

[1289] acid sequence (Contact)

[1290] 3D3 VL CDR1 amino ISNIGNNP (SEQ ID NO: 91)

[1291] acid sequence (IMGT)

[1292] 3D3 VL CDR2 amino SN

[1293] acid sequence (IMGT)

[1294] 3D3 VL CDR3 amino AAWDDSLDALV ( SEQ ID NO: 92 )

[1295] acid sequence (IMGT)

[1296] 3D3 VL amino acid QAGLTQPPSASGTPRQRVTISCSGTISNIGNNPVSWYQHLPGTA sequence PKLLIYSNSQRPSGVPERFSGSKSGTSASLAISGLQSEDEADYY

[1297]

[1298] CAAWDDSLDALVFGGGTQLTAL (SEQ ID NO: 93)

[1299] 5H8

[1300] 80

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[1302] Description Sequence

[1303] 5H8 VH CDR1 amino GYTLTNN (SEQ ID NO: 94 )

[1304] acid sequence (Chothia)

[1305] 5H8 VH CDR2 amino NPDNGN ( SEQ ID NO: 95 )

[1306] acid sequence (Chothia)

[1307] 5H8 VH CDR3 amino AVGRPSRYYGLDV (SEQ ID NO: 96)

[1308] acid sequence (Chothia)

[1309] 5H8 VH CDR1 amino GYTLTNNDIH (SEQ ID NO: 97 )

[1310] acid sequence (AbM)

[1311] 5H8 VH CDR2 amino WMNPDNGNTG (SEQ ID NO: 98 )

[1312] acid sequence (AbM)

[1313] 5H8 VH CDR3 amino AVGRPSRYYGLDV (SEQ ID NO: 99)

[1314] acid sequence (AbM)

[1315] 5H8 VH CDR1 amino NNDIH (SEQ ID NO: 100 )

[1316] acid sequence (Kabat)

[1317] 5H8 VH CDR2 amino WMNPDNGNTGYAQTFQG (SEQ ID NO: 101)

[1318] acid sequence (Kabat)

[1319] 5H8 VH CDR3 amino AVGRPSRYYGLDV (SEQ ID NO: 102 )

[1320] acid sequence (Kabat)

[1321] 5H8 VH CDR1 amino TNNDIH ( SEQ ID NO: 103 )

[1322] acid sequence (Contact)

[1323] 5H8 VH CDR2 amino WMGWMNPDNGNTG (SEQ ID NO: 104 )

[1324] acid sequence (Contact)

[1325] 5H8 VH CDR3 amino ARAVGRPSRYYGLD (SEQ ID NO: 105 )

[1326] acid sequence (Contact)

[1327] 5H8 VH CDR1 amino GYTLTNND (SEQ ID NO: 106)

[1328] acid sequence (IMGT)

[1329] 5H8 VH CDR2 amino MNPDNGNT (SEQ ID NO: 107 )

[1330] acid sequence (IMGT)

[1331] 5H8 VH CDR3 amino ARAVGRPSRYYGLDV ( SEQ ID NO: 108 )

[1332] acid sequence (IMGT)

[1333] 5H8 VH amino acid QMQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWVRQAPGQG sequence LEWMGWMNPDNGNTGYAQTFQGRVSMTRDTSTSTAYMELSSLRF EDTAIYSCARAVGRPSRYYGLDVWGQGTLVTVSS (SEQ ID NO: 109)

[1334] 5H8 VL CDR1 amino SGGSSNIGTNPLT (SEQ ID NO: 110 )

[1335] acid sequence (Chothia)

[1336] 5H8 VL CDR2 amino SNDQRPS (SEQ ID NO: 111)

[1337] acid sequence (Chothia)

[1338] 5H8 VL CDR3 amino ATWDDSVDGLV ( SEQ ID NO: 112 )

[1339] acid sequence (Chothia)

[1340] 5H8 VL CDR1 amino SGGSSNIGTNPLT (SEQ ID NO: 113 )

[1341] acid sequence (AbM)

[1342] 5H8 VL CDR2 amino SNDQRPS (SEQ ID NO: 114 )

[1343] acid sequence (AbM)

[1344] 5H8 VL CDR3 amino ATWDDSVDGLV ( SEQ ID NO: 115 )

[1345] acid sequence (AbM)

[1346] 5H8 VL CDR1 amino SGGSSNIGTNPLT (SEQ ID NO: 116)

[1347]

[1348] acid sequence (Kabat)

[1349] 81

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[1351] 5H8 VL CDR2 amino SNDQRPS (SEQ ID NO: 117 )

[1352] acid sequence (Kabat)

[1353] 5H8 VL CDR3 amino ATWDDSVDGLV ( SEQ ID NO: 118 )

[1354] acid sequence (Kabat)

[1355] 5H8 VL CDR1 amino IGTNPLTWY (SEQ ID NO: 119)

[1356] acid sequence (Contact)

[1357] 5H8 VL CDR2 amino LLIYSNDQRP (SEQ ID NO: 120 )

[1358] acid sequence (Contact)

[1359] 5H8 VL CDR3 amino ATWDDSVDGL (SEQ ID NO: 121 )

[1360] acid sequence (Contact)

[1361] 5H8 VL CDR1 amino SSNIGTNP (SEQ ID NO: 122 )

[1362] acid sequence (IMGT)

[1363] 5H8 VL CDR2 amino SN

[1364] acid sequence (IMGT)

[1365] 5H8 VL CDR3 amino ATWDDSVDGLV ( SEQ ID NO: 123 )

[1366] acid sequence (IMGT)

[1367] 5H8 VL amino acid QAGLTQPPSASGTPGQRVTISCSGGSSNIGTNPLTWYQQLPRTA sequence PKLLIYSNDQRPSGVPDRFSGSKSGTSASLTISGLQSGDEADYY

[1368]

[1369] CATWDDSVDGLVFGGGTQLTVL (SEQ ID NO: 124 )

[1370] 7C6

[1371] Description Sequence

[1372] 7C6 VH CDR1 amino GYTFTSY (SEQ ID NO: 125)

[1373] acid sequence (Chothia)

[1374] 7C6 VH CDR2 amino SAYNGN ( SEQ ID NO: 126 )

[1375] acid sequence (Chothia)

[1376] 7C6 VH CDR3 amino DLGAVELYYYYGMDV ( SEQ ID NO: 127 )

[1377] acid sequence (Chothia)

[1378] 7C6 VH CDR1 amino GYTFTSYGIS (SEQ ID NO: 128 )

[1379] acid sequence (AbM)

[1380] 7C6 VH CDR2 amino WISAYNGNTN (SEQ ID NO: 129 )

[1381] acid sequence (AbM)

[1382] 7C6 VH CDR3 amino DLGAVELYYYYGMDV ( SEQ ID NO: 130 )

[1383] acid sequence (AbM)

[1384] 7C6 VH CDR1 amino SYGIS (SEQ ID NO: 131 )

[1385] acid sequence (Kabat)

[1386] 7C6 VH CDR2 amino WISAYNGNTNYAQKLQG (SEQ ID NO: 132 )

[1387] acid sequence (Kabat)

[1388] 7C6 VH CDR3 amino DLGAVELYYYYGMDV ( SEQ ID NO: 133 )

[1389] acid sequence (Kabat)

[1390] 7C6 VH CDR1 amino TSYGIS ( SEQ ID NO: 134 )

[1391] acid sequence (Contact)

[1392] 7C6 VH CDR2 amino WMGWISAYNGNTN (SEQ ID NO: 135 )

[1393] acid sequence (Contact)

[1394] 7C6 VH CDR3 amino ARDLGAVELYYYYGMD (SEQ ID NO: 136)

[1395] acid sequence (Contact)

[1396] 7C6 VH CDR1 amino GYTFTSYG (SEQ ID NO: 137 )

[1397]

[1398] acid sequence (IMGT)

[1399] 82

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[1401] 7C6 VH CDR2 amino ISAYNGNT (SEQ ID NO: 138 )

[1402] acid sequence (IMGT)

[1403] 7C6 VH CDR3 amino ARDLGAVELYYYYGMDV (SEQ ID NO: 139)

[1404] acid sequence (IMGT)

[1405] 7C6 VH amino acid QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQG sequence LEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRS DDTAVYYCARDLGAVELYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 140 )

[1406] 7C6 VL CDR1 amino SGSSSNIGSNTVD (SEQ ID NO: 141 )

[1407] acid sequence (Chothia)

[1408] 7C6 VL CDR2 amino NNNQRPS (SEQ ID NO: 142 )

[1409] acid sequence (Chothia)

[1410] 7C6 VL CDR3 amino ATWDDSLNGLV ( SEQ ID NO: 143 )

[1411] acid sequence (Chothia)

[1412] 7C6 VL CDR1 amino SGSSSNIGSNTVD (SEQ ID NO: 144 )

[1413] acid sequence (AbM)

[1414] 7C6 VL CDR2 amino NNNQRPS (SEQ ID NO: 145)

[1415] acid sequence (AbM)

[1416] 7C6 VL CDR3 amino ATWDDSLNGLV ( SEQ ID NO: 146)

[1417] acid sequence (AbM)

[1418] 7C6 VL CDR1 amino SGSSSNIGSNTVD (SEQ ID NO: 147 )

[1419] acid sequence (Kabat)

[1420] 7C6 VL CDR2 amino NNNQRPS (SEQ ID NO: 148 )

[1421] acid sequence (Kabat)

[1422] 7C6 VL CDR3 amino ATWDDSLNGLV ( SEQ ID NO: 149)

[1423] acid sequence (Kabat)

[1424] 7C6 VL CDR1 amino IGSNTVDWY (SEQ ID NO: 150 )

[1425] acid sequence (Contact)

[1426] 7C6 VL CDR2 amino LLIYNNNQRP (SEQ ID NO: 151 )

[1427] acid sequence (Contact)

[1428] 7C6 VL CDR3 amino ATWDDSLNGL (SEQ ID NO: 152 )

[1429] acid sequence (Contact)

[1430] 7C6 VL CDR1 amino SSNIGSNT (SEQ ID NO: 153)

[1431] acid sequence (IMGT)

[1432] 7C6 VL CDR2 amino NN

[1433] acid sequence (IMGT)

[1434] 7C6 VL CDR3 amino ATWDDSLNGLV ( SEQ ID NO: 154 )

[1435] acid sequence (IMGT)

[1436] 7C6 VL amino acid QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVDWYHQLPGTA sequence PNLLIYNNNQRPSGVPDRFSGSKSGTSAFLAISGLQSEDEGDYY

[1437]

[1438] CATWDDSLNGLVFGGGTQLTVL (SEQ ID NO: 155 )

[1439] Example 2: Binding of Anti-Viral mAbs

[1440] The present example describes the binding of anti-viral mAbs to SARS-CoV-2 spike and to HIV gpl20. To measure the binding, 2D ELISA was performed as follows.

[1441] Viral glycoproteins were immobilized onto Maxisorp microtiter plates in a 3-fold dilution. Anti-glycan antibodies were applied on a 2-fold dilutions and allowed to bind for 2 h 83

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[1443] at room temperature. Bound antibodies were detected using a pAb anti-human IgG HRP-conjugate (Dako P021402-2). Anti-SARS-CoV-2 spike (BioLegend 938602) and anti-HIV gp120 (Bei Resources ARP-12138), both 1 μg / ml, were used as positive controls. The antibodies included 2C8, 3D3, 7C6, 1F6, and 5H8.

[1444] Referring now to FIG. 1A-FIG. IB, FIG. 1A-FIG. IB present graphical representations of binding of anti-viral mAbs to SARS-CoV-2 spike (FIG. 1A) and to HIV gp120 (FIG. IB). The ELISA data demonstrated that the anti-viral antibodies bound to SARS-CoV-2 spike protein and HIV gp120 in a dose-dependent manner. FIG. 1A presents 5H8 and 7C6 binding to SARS CoV-2. FIG. IB demonstrates that all of the anti-viral antibodies bound to HIV gp120, with 3D3 and 5H8 being the top binders.

[1445] Example 3: Ligand Screening

[1446] The present example describes binding screening of anti-viral mAbs to viral glycoproteins. Binding measurements were performed as follows. Microtiter well plates (Maxisorp, Thermo Fisher Scientific) were coated with viral glycoproteins, or BSA as negative control, at 4, 2, and 0 ug / ml (no viral glycoprotein) in PBS overnight at 4 °C. Antiviral antibodies 1F6, 2C8, 3D3, 5H8, and 7C6 were added at 2 ug / ml to the coated plates and incubated for 2 hours at room temperature. Purified IgG from human serum (Sigma 14506) was used as control. Bound immunoglobulins were detected with Rabbit Anti-Human IgG HRP conjugate (Agilent. Dako P021402-2). Data are presented as the area under the curve (AUC) calculated from the viral glycoproteins dilutions (0, 2 and 4 ug / ml) from three independent replicates.

[1447] Referring now to FIG. 2, 1F6, 2C8, 3D3, 5H8, 7C6 reacted against a broad range of viral glycoproteins. 3D3 and 5H8 reacted with the most intensity.

[1448] Example 4: Neutralization Assays

[1449] The present example describes neutralization assays. The antibodies analyzed were each complement enhanced and included 2C8, 5H8. 1F6, 3D3, and 7C6. The complement enhanced antibodies were produced as generally described in Example 1. Each complement enhanced antibody (2C8, 5H8, 1F6, 3D3, and 7C6) comprised a uIgG! LV236-HC amino acid sequence (SEQ ID NO: 158). The neutralization assays included an HSV-1GFPneutralization assay, which used the complement enhanced antibodies at 40 ug / mL and 2 percent IgG depleted human serum, and an HSV-2WTneutralization assay, which used the complement enhanced antibodies at 40 ug / mL and 2 percent IgG depleted human serum. The

[1450] 84

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[1452] neutralization assays were performed as follows. Briefly, diluted HSV-1 (AI GFP) or HSV-2 (AI WT) strains were incubated with PanV monoclonal antibodies (mAbs) at a concentration of 40 pg / mL in DMEM containing 2 percent IgG-depleted human serum for 1 hour at 37°C. HSV titers were determined via plaque assay and diluted such that each well of a 24-well plate contained 20 to 100 plaque-forming units, depending on the strain. Confluent BHK-21 cells (>95 percent well coverage) were washed once with room temperature PBS to remove excess FBS -containing culture media. The virus-mAb inoculum was added dropwise to the BHK-21 cells in triplicate and incubated for 1 hour, shaking at 60 rpm at 37°C. After incubation, the inoculum was aspirated, and 1 mL of 1.2 percent MCC overlay was added to each well. The cells were incubated for 72 hours at 37°C without rotation. Following incubation, the overlay was aspirated, and the cells were fixed with 4 percent paraformaldehyde for 10 minutes before being aspirated. The cells were then washed twice with room temperature PBS and stained with a 0.5 percent crystal violet solution for 15 minutes. Plates were decanted and washed with deionized water. Clearly defined plaques were marked with a black non-permanent marker and subsequently counted. Viral reduction significance was determined using unpaired T-tests compared to negative control wells without mAbs.

[1453] Referring now to FIG. 3A-FIG. 3E, FIG. 3A-FIG. 3E present images of an HSV-1GFPneutralization assay. FIG. 3A presents an image of the neutralization assay. FIG. 3B presents a close-up image of complement enhanced antibody 1F6. FIG. 3C presents a closeup image of complement enhanced antibody 2C8. FIG. 3D presents a close-up image of complement enhanced antibody 3D3. The results of FIG. 3A-FIG. 3E demonstrated a significant reduction in the number of HSV-1 viral plaques, which served as a proxy for neutralization. FIG. 4 presents a summary of plaque reduction assay results for the 1F6, 2C8, 3D3, 5H8, 7C6, and PanV1.0. The results showed that 1F6, 2C8, 3D3, and 5H8 significantly reduced the number of HSV-1 viral plaques as compared to control (Neg., 2 percent human serum only).

[1454] Referring now to FIG. 5A-FIG. 5E, FIG. 5A-FIG. 5E present images of an HSV-2WTneutralization assay. FIG. 5A presents an image of the neutralization assay. FIG. 5B presents a close-up image of complement enhanced antibody 1F6. FIG. 5C presents a close-up image of complement enhanced antibody 2C8. FIG. 5D presents a close-up image of complement enhanced antibody 5H8. FIG. 5E presents a close-up image of complement enhanced antibody 7C6. The results of FIG. 5A-FIG. 5E demonstrated a significant reduction in the number of HSV-2 viral plaques, which served as a proxy for neutralization. FIG. 6 presents a 85

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[1456] summary of plaque reduction assay results for the 1F6, 2C8, 3D3, 5H8, 7C6, and PanV1.0. The results showed that 1F6, 2C8, 5H8, and 7C6 significantly reduced the number of HSV-2 viral plaques as compared to control (Neg., 2 percent human serum only).

[1457] Example 5: Cross-Reactivity Analysis

[1458] The present example describes cross-reactivity analysis of anti-viral mAbs. In particular, the cross-reactivity of antibodies 7C6, 5H8, 3D3, 2C8, and 1F6 to human proteins was measured using the HuProt™ human proteome array. The array includes greater than 21,000 unique human proteins and isoforms covering over 16,794 unique genes, expressed as GST fusions in yeast. Briefly, the cross-reactivity analysis was performed as follows. The human antibodies were diluted into CDI Array Buffer at 0.1 ug / mL and 1.0 ug / mL. Each blocked and diluted sample was then probed onto a HuProt™ microarray at room temperature for 1 hour with gentle shaking. Following the probing step, the arrays underwent three 10-minute washes with TBST (IxTBS / 0.1% Tween 20). Subsequently, they were probed with Alexa 647-anti-human IgG Fc specific at room temperature for 1 hour within a light-proof box, with gentle shaking. This was followed by three washes with TBST, each lasting 10 minutes, and three rinses with ddH2O. The arrays were then dried with an air duster, and scanned using a GenePix® 4000B scanner for data collection.

[1459] The data demonstrated that antibodies 7C6, 5H8, 3D3, 2C8, and 1F6 had minimal cross reactivity to the human proteome (F635 of 1552, 4384, 776, 918, and 421.5 at 1.0 ug / mL; F635 of 718.5, 674, 490.5, 576, and 521 at 0.1 ug / mL). It is noted that a positive control (5F%) has a fluorescence intensity (F635) value of greater than or equal to 1000 (1745 at 1.0 ug / mL; 475 at 0.1 ug / mL). A negative control (9H2) had F635 of 520 at 1.0 ug / mL and of 664 at 0.1 ug / mL).

[1460] Example 6: Glycan Binding Analysis

[1461] The present example describes binding analysis for 2C8, 1F6, 3D3, 5H8 and 7C6 on a glycan microarray comprised of 166 glycans representing a diverse collection of carbohydrate structures. Representations of the glycans are presented in FIG. 8A.

[1462] The glycan binding abilities of the antibodies, 2C8, 1F6, 3D3, 5H8, and 7C6 were tested using a Z Biotech Catch-All glycan microarray. Briefly, the glycan binding analysis was performed as follows. The gly can binding analysis was carried out first by applying glycan array blocking buffer (GABB) to the array for thirty minutes at room temperature. Next, the five samples were diluted to 10 pg / mL and subsequently, 1 pg / mL in glycan array 86

[1463] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1464] assay buffer (GAAB). After thirty minutes of blocking, the array was washed, and the samples were added to the array and incubated for one hour at room temperature. After one hour, the microarray was washed again and the anti-human IgG (Fc) Cy3 antibody was added to the array, diluted in GAAB to 10 ug / mL concentration. The array was incubated for a further one hour and then washed for a final time before scanning. After the assay, the microarray slides were scanned at 532 nm using high-intensity settings (3 PMT).

[1465] Subsequently, the array scan was analyzed using Mapix (Carbonne, France) microarray analysis software. The software subtracted background signals and those from negative control spots to determine the binding signals.

[1466] Referring now to FIG. 8B, FIG. 8B presents a graphical representation of the glycan binding analysis of antibodies 2C8, 1F6, 5H8, 3D3, and 7C6. Table 1 below provides a tabular representation of the glycan binding analysis. An RFU value of 5000 or more was considered to be a value associated with a binding hit. At 10 ug / ml, 2C8, 1F6, and 5H8 had binding hits over 5000 RFU (FIG. 8B; FIG. 17A-FIG. 17E). Antibody 2C8 bound to CA23, CA25, CA26, CA44. and CA98. Antibody 1F6 bound to CA23, CA25, CA26, CA30, CA44. CA46, CA98, CAI 19. CA125, CA126, CA139. Antibody 5H8 bound to CA12, CA26. CA44, CA26, CA47, CA55, CA98, CAI 19, CA122, CA125, CA128, CA136, CA139, and CA145. Antibodies 2C8, 1F6, and 5H8 each bound to glycans CA26, CA44, and CA98. 7C6 and 3D3 did not bind to any of the gly cans in the array at 10 ug / ml (FIG. 8B; FIG. 17A-FIG. 17E). At 1 ug / ml, none of the antibodies bound to any glycans with an RFU value over 5000.

[1467] In summary, sample 7C6 did not show any binding on the array. Binding by sample 3D3 was generally weak, that is, not above 5000 RFU. Samples 2C8 and IF6 showed similar binding patterns, mainly binding to GM1 (CA23) and GM2 (CA25). Both samples also bound to a2,3 sialyl-galactose oligosaccharides and a2,3 Neu5Ac terminated N-glycans. IF6 bound more strongly to these glycans, whereas 2C8 was more specific to GM1 and GM2. Sample 5H8 bound most strongly to N-glycans terminated in a2,3 Neu5Ac or a sialyl-Lewis X epitope. 5H8 also bound to both a2,3 and a2,6 sialyl-galactose oligosaccharides, sialyl-Lewis type glycans (CAI 1 and CAI 2), and GDla (CA26).

[1468] TABLE 1 - Glycan Binding Analysis

[1469] Antibody Array ID Structure Name Glycan RFU Type

[1470] 2C8 CA23 Gaipi-3GalNAcpi- GM1 GSL 47291.37

[1471]

[1472] 87

[1473] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1474] 4(Neu5Aca2-3)Gaipi- 4Glc

[1475] 2C8 CA25 Neu5Aca2- GM2 GSL 40426.62

[1476] 3(GalNAcpi-4)Gaipi- 4Glc

[1477] 2C8 CA26 Neu5Aca2-3Gaipi- GDla GSL 6021.75

[1478] 3GalNAcpi- 4(Neu5Aca2-3)Gaipi- 4Glc

[1479] 2C8 CA44 Neu5Aca2-3Gaipi- 3'-Sialyllactose HMO 8425.12

[1480] 4Glc

[1481] 2C8 CA98 Neu5Aca2-3Gaip 3'-Sialylgalactose Oligosaccha 7672.12

[1482] (GM4) rides

[1483] 1F6 CA23 Gaipi-3GalNAcpi- GM1 GSL 34025.75

[1484] 4(Neu5Aca2-3)Gaipi- 4Glc

[1485] 1F6 CA25 Neu5Aca2- GM2 GSL 30589.88

[1486] 3(GalNAcβ1-4)Galβ1-4Glc

[1487] 1F6 CA26 Neu5Aca2-3Gaipi- GDla GSL 19546

[1488] 3GalNAcpi- 4(Neu5Aca2-3)Gaipi- 4Glc

[1489] 1F6 CA30 Neu5Aca2- GT la GSL 6714.38

[1490] 8Neu5Aca2-3Galpl- 3GalNAcpl- 4(Neu5Aca2-3)Gaipi- 4Glc

[1491] 1F6 CA44 Neu5Aca2-3Gaipi- 3'-Sialyllactose HMO 18769

[1492] 4Glc

[1493] 1F6 CA46 Neu5Aca2-3Gaipt- 3'-a-Sialyl-N- HMO 6669.13

[1494] 4GlcNAc acetyllactosamine

[1495] 1F6 CA98 Neu5Aca2-3Galβ 3'-Sialylgalactose Oligosaccha 17566.88

[1496] (GM4) rides

[1497] 1F6 CAI 19 Neu5 Ac a2 -3 Gaip 1 - Complex N- 6764.5

[1498] 4GlcNAcP 1 -2Manal - glycan

[1499]

[1500] 88

[1501] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1502] 6(Neu5Aca2-3Gaipi- 4GlcNAcpi-2Manal- 3)Man01-4GlcNAcpi- 4GlcNAc- 1F6 CA125 Manat -6(Manal - hybrid N- 8199.63

[1503] 3)Manal-6(Neu5Aca2- glycan

[1504] 3Gaipi-4GlcNAcpi- 2Manal-3)Manpi- 4GlcNAcpi-4GlcNAc- 1F6 CA126 Manal-6(Manal- hybrid N- 11826.63

[1505] 3)Manal-6(Neu5Aca2- glycan

[1506] 6Gaipi-4GlcNAcpi- 2Manal-3)Manpi- 4GlcNAcpi-4GlcNAc- 1F6 CA139 Neu5 Ac a2 -3 Gaip 1 - Bisecting 9389.38

[1507] 4(Fucal-3)GlcNAcpi- N-glycan 2Manal-6(GlcNAcpi- 4)(Neu5Aca2-3Gaipi- 4(Fucal-3)GlcNAcpi- 2Manal-3)Manpi- 4GlcNAcpi-4GlcNAc- 5H8 CA12 Neu5Aca2-3Gaipi- 3 '-Sialyl Lewis X Blood 9692.38

[1508] 4(Fucal-3)GlcNAc Group and Lewis

[1509] Antigens

[1510] 5H8 CA26 Neu5Aca2-3Gaipi- GDla GSL 6961.38

[1511] 3GalNAcpi- 4(Neu5Aca2-3)Gaipi- 4Glc

[1512] 5H8 CA44 Neu5Aca2-3Gaipi- 3'-Sialyllactose HMO 22628.88

[1513] 4Glc

[1514] 5H8 CA46 Neu5Aca2-3Gatpt- 3'-a-Sialyl-N- HMO 15045.25

[1515] 4GlcNAc acetyllactosamine

[1516] 5H8 CA47 Neu5Aca2-6Gaipt- 6'-a-Sialyl-N- HMO 9154.5

[1517] 4GlcNAc acetyllactosamine

[1518] 5H8 CA55 Neu5Aca2-3Galβ1- Disialyllacto-N- HMO 5775

[1519]

[1520] 89

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[1522] 3(Neu5Aca2- tetraose

[1523] 6)GlcNAcpi-3Gaipt- (DSLNT)

[1524] 4Glc

[1525] 5H8 CA98 Neu5Aca2-3Gaip 3'-Sialylgalactose Oligosaccha 5463.13

[1526] (GM4) rides

[1527] 5H8 CA119 Neu5Aca2-3Gaipt- Complex N- 19958.63

[1528] 4GlcNAcpi-2Manal- glycan 6(Neu5Aca2-3Gaipi- 4GlcNAcPl-2Manal- 3)Manpi-4GlcNAcPl- 4GlcNAc- 5H8 CA122 Neu5Aca2-3Gaipt- Complex N- 8771.88

[1529] 4(Fucal-3)GlcNAcpi- glycan

[1530] 2Manal-6(Neu5Aca2- 3Gaipi-4(Fucal- 3)GlcNAcpi-2Manal- 3)Manpi-4GlcNAcpi- 4GlcNAc- 5H8 CA125 Manat -6(Manal - hybrid N- 19778.88

[1531] 3)Manal-6(Neu5Aca2- glycan

[1532] 3Gaipi-4GlcNAcpi- 2Manal-3)Manpi- 4GlcNAcpi-4GlcNAc- 5H8 CA128 Manat -6(Manal- hybrid N- 11163

[1533] 3)Manal-6(Neu5Aca2- glycan

[1534] 3Gaipt-4(Fucal- 3)GlcNAcpt-2Manai- 3)Manpt-4GlcNAcpt- 4GlcNAc- 5H8 CA136 Neu5Aca2-3Gatpt- Bisecting 36556

[1535] 4GlcNAcPl-2Manal- N-glycan 6(GlcNAcpi- 4)(Neu5Aca2-3Gatpt- 4GlcNAcpt-2Manal- 3)Manpt-4GlcNAcpt- 4GlcNAc-

[1536]

[1537] 90

[1538] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1539] 5H8 CA139 Neu5 Aca2-3 Gaip 1 - Bisecting 24131.25

[1540] 4(Fucal-3)GlcNAcpi- N-glycan

[1541] 2Manal-6(GlcNAcpi- 4)(Neu5Aca2-3Gaipi- 4(Fucal-3)GlcNAcpi- 2Manal-3)Manpi- 4GlcNAcpi-4GlcNAc- 5H8 CA145 Neu5Aca2-3Gaipi- LacNAc- 12222.13

[1542] 4GlcNAcpi-3Gaipi- extended N- 4GlcNAcPl-2Manal- glycan

[1543] 6(Neu5Aca2-3Gaipi- 4GlcNAcpl-3Gaipi- 4GlcNAcPl-2Manal- 3)Manpi-4GlcNAcpi- 4GlcNAc

[1544]

[1545] Example 7: Antibody Assemblies

[1546] The present example describes tetramer and hexamer assemblies of the antibodies described herein, such as, for instance, 2C8, 1F6, 5H8, 3D3, and 7C6.

[1547] Tetramer Assemblies

[1548] Tetramer assemblies were made as single chain diabody Fc fusions. See, for instance, FIG. 9. In general, by restricting linker lengths, the variable heavy chain of the first scFv is sterically forced to pair with the variable light chain of the second scFv. The Fc pairing then results in a tetravalent disulfide linked dimer. In some instances, C-term 6x His is included to avoid Protein A acid elution. Sequences of tetramer assemblies used in the present example are described in Table 2.

[1549] TABLE 2

[1550] SEQID DESCRIPTION SEQUENCE NO E VQ L VQ S G AE VKK P G AS VKVS CKGSGYTFTSYDI N WVRQ ATEQGLEWMGWMNPDSGNTGFAQKFQGRVSMTRNTSIST AYMELSSLRPEDTAVYYCVRAPRRYKDGYDYFDYWGQGT

[1551] 171 2C8_scDb_Fc LVTVSSGGGGSQSVLTQPPSASGTPGQRVTISCSGSISN IESNTVNWYQQLPGTAPKLLI YNNNQRPSGVPDRFSGSK

[1552]

[1553] SGTSASLAISGLQSEDEADYYCAAWDDSLNGRWVFGGGT

[1554] 91

[1555] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1556] ELTVLGGGGSGGGGSGGGGSEVQLVQSGAEVKKPGASVK VSCKGSGYTFTS YDINWVRQATEQGLEWMGWMNPDSGNT GFAQKFQGRVSMTRNTS ISTAYMELSSLRPEDTAVYYCV RAPRRYKDGYDYFDYWGQGTLVTVSSGGGGSQSVLTQPP SASGTPGQRVTISCSGSISNIESNTVNWYQQLPGTAPKL LI YNNNQRPSGVPDRFSGSKSGTSASLAISGLQS EDEAD YYCAAWDDSLNGRWVFGGGTELTVLAAAEPKSCDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWD VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTT PPVLDSDGS FFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGKHHHHHH E VQ L VQ S G AE VKK P G AS VKVS CKGSGYTFTSYDI N WVRQ ATEQGLEWMGWMNPDSGNTGFAQKFQGRVSMTRNTSIST AYMELSSLRPEDTAVYYCVRAPRRYKDGYDYFDYWGQGT LVTVSSGGGGSQAGLTQPPSASGTPGQRVTISCSGSSSN IGSNTVNWYQQLPGTAPKLLI YSNNQRPSGVPDRFSGSK SGTSASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGTQ LTALGGGGSGGGGSGGGGSEVQLVQSGAEVKKPGASVKV SCKGSGYT FTS YDINWVRQATEQGLEWMGWMNPDSGNTG FAQKFQGRVSMTRNTS I STAYMELS SLRPEDTAVYYCVR

[1557] 172 1F6 scDb Fc APRRYKDGYDYFDYWGQGTLVTVSSGGGGSQAGLTQPPS ASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLL IYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADY YCAAWDDSLNGWVFGGGTQLTALAAAEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLS PGKHHHHHH QVQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWVRQ APGQGLEWMGWMNPDNGNTGYAQTFQGRVSMTRDTSTST AYMELSSLRFEDTAIYSCARAVGRPSRYYGLDVWGQGTL VTVSSGSGGGGSQAGLTQPPSASGTPRQRVTISCSGTIS NIGNNPVSWYQHLPGTAPKLLIYSNSQRPSGVPERFSGS KSGTSASLAISGLQSEDEADYYCAAWDDSLDALVFGGGT QLTALGGGGSGGGGSGGGGSQVQLVQSGAEVKEPGASVK VSCKASGYTLTNNDIHWVRQAPGQGLEWMGWMNPDNGNT GYAQT FQGRVSMTRDT S T STAYMEL S SLRFEDTAI YS CA

[1558] 173 3D3_scDb_Fc RAVGRPSRYYGLDVWGQGTLVTVSSGSGGGGSQAGLTQP PSASGTPRQRVTISCSGTISNIGNNPVSWYQHLPGTAPK LLIYSNSQRPSGVPERFSGSKSGTSASLAISGLQSEDEA DYYCAAWDDSLDALVFGGGTQLTALAAAEPKSCDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWD VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTT PPVLDSDGS FFLYSKLTVDKSRWQQGN

[1559]

[1560] VFSCSVMHEALHNHYTQKSLSLS PGKHHHHHH

[1561] 92

[1562] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1563] QMQLVQSGAEVKEPGASVKVSCKASGYTLTNNDIHWVRQ APGQGLEWMGWMNPDNGNTGYAQTFQGRVSMTRDTSTST AYMELSSLRFEDTAIYSCARAVGRPSRYYGLDVWGQGTL VTVSSGGGGSQAGLTQPPSASGTPGQRVTISCSGGSSNI GTNPLTWYQQLPRTAPKLLIYSNDQRPSGVPDRFSGSKS GTSASLTISGLQSGDEADYYCATWDDSVDGLVFGGGTQL TVLGGGGSGGGGSGGGGSQMQLVQSGAEVKEPGASVKVS CKASGYTLTNNDIHWVRQAPGQGLEWMGWMNPDNGNTGY AQTFQGRVSMTRDTSTSTAYMELSSLRFEDTAIYSCARA

[1564] 174 5H8_scDb_Fc VGRPSRYYGLDVWGQGTLVTVSSGGGGSQAGLTQPPSAS GTPGQRVTISCSGGSSNIGTNPLTWYQQLPRTAPKLLIY SNDQRPSGVPDRFSGSKSGTSASLTISGLQSGDEADYYC ATWDDSVDGLVFGGGTQLTVLAAAEPKSCDKTHTCPPCP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHE DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ PENNYKTT PPVLDSDGS FFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGKHHHHHH QVQLVQS GAEVKKPGAS VKVS CKAS GYTFTSYGI S WVRQ APGQGLEWMGWI SAYNGNTNYAQKLQGRVTMTTDTSTST AYMELRSLRSDDTAVYYCARDLGAVELYYYYGMDVWGQG TTVTVSSGGGGSQSVLTQPPSASGTPGQRVTISCSGSSS NIGSNTVDWYHQLPGTAPNLLIYNNNQRPSGVPDRFSGS KSGTSAFLAISGLQSEDEGDYYCATWDDSLNGLVFGGGT QLTVLGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVK VSCKASGYTFTS YGISWVRQAPGQGLEWMGWISAYNGNT NYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCA

[1565] 175 7C6_scDb_Fc RDLGAVELYYYYGMDVWGQGTTVTVSSGGGGSQSVLTQP PSASGTPGQRVTISCSGSSSNIGSNTVDWYHQLPGTAPN LLIYNNNQRPSGVPDRFSGSKSGTSAFLAISGLQSEDEG DYYCATWDDSLNGLVFGGGTQLTVLAAAEPKSCDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWD VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTT PPVLDSDGS FFLYSKLTVDKSRWQQGN

[1566]

[1567] VFSCSVMHEALHNHYTQKSLSLSPGKHHHHHH

[1568] Tetramer assemblies were produced as follows. Single chain diabody Fc fusion proteins were produced in Expi293 using Expifectamine Transfection Kit according to manufacturer’s instructions (Thermo Fisher). Supernatant was harvested by centrifugation (500xg, 10 minutes, RT) approximately 90 hours post-transfection. His-Pur Ni-NTA agarose (Thermo) was added to the supernatant and allowed to bind via end-over-end rotation for 4 hours at RT. After incubation, the Ni-NTA was collected from the supernatant put into a gravity column. The Ni-NTA was washed with 200 ml high salt HBS containing a small concentration of imidazole (200 ml 10 mM HEPES pH 7.4, 500 mM NaCl, 20 mM Imidazole 93

[1569] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1570] pH 8). The single chain diabody Fc protein was eluted from the Ni-NTA in 1 ml fractions using the same high salt HBS, but containing 300 mM imidazole pH 8. Fractions containing protein, as measured by A280, were pooled.

[1571] Analytical SEC (running buffer 10 mM HEPES pH 7.4, 300 mM NaC, 100 mM arginine monohydrochloride) using 100 ul of pooled fractions was run to check purity and monodispersity.

[1572] 2C8, 1F6, 3D3, and 5H8 single chain diabody Fc fusions were expressed in Expi293 and purified as secreted, disulfide linked dimers. Reducing and non-reducing gel-based analysis was performed to evaluate the purity of each of the single chain diabody Fc fusions (FIG. 10).

[1573] Referring now to FIG. 11A-FIG. 11E, 2C8 (FIG. 11A), 1F6 (FIG. 11B), 3D3 (FIG.

[1574] 11C), and 5H8 (FIG. 11D) were not able to be resolved by gel filtration, potentially due interaction / adsorption to the column. 7C6 (FIG. 11E) was resolved well by gel filtration and ran mainly as a monodispersed protein at 12.62 ml.

[1575] The single chain diabody Fc fusions were also analyzed by ELISA as follows.

[1576] Maxisorb microtiter well plates were coated with SARS-CoV-2 spike (R& D systems 11058-CV-100) or HIV gpl20 (Sino Biological 11233-V08H-100) in a 3-fold dilutions starting at 5 pg / ml (which corresponds to 10 nM spike or 13.89 nM gpl20) in PBS overnight at 4 °C. Plates were blocked for 1 h in PBS + 0.05% tween-20 (PBS-T). A total of 1 pg / ml of scDb Fc fusion or control antibody anti-SARS-CoV-2 SI (clone AM006415, BioLegend 938602) were incubated in PBS-T 2 h shaking. Bound antibodies were detected using a rabbit AntiHuman IgG HRP conjugate (Dako P021402-2) for 1 h shaking. The plates were developed using TMB (Thermo Fisher Scientific 34029) and the reaction was stopped with 0.5 M H2SO4. Data was recorded as optical density (OD) at 450 nm with 630 nm correction using a BioTek 800 TS absorbance reader (Agilent). Binding affinities were calculated from the background (buffer only) corrected ODs using the specific binding with Hill slope equation in Graphpad Prism 10.4 software.

[1577] Referring now to FIG. 12 A-FIG. 12B, binding curves of the antiviral scDbFc fusions 1F6, 2C8, 3D3, 5H8. and 7C6 to SARS-CoV-2 spike (FIG. 12A) and HIV gp120 (FIG. 12B) are presented. An anti-SARS-CoV-2 RBD antibody (BioLegend 938602) was used as positive control. 7C6 displayed strong binding towards both antigens, followed by 2C8. 1F6 bound to HIV gpl20 with a more moderate affinity, but the binding to SARS-CoV-2 spike could not be determined. 3D3 and 5H8 bound too weakly to both antigens to determine a KD under these experimental conditions. ND, not determined.

[1578] 94

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[1580] Hexamer Forming, Assemblies

[1581] Examples of IgGl hexamer antibodies and methods of assembly can be found, for instance, in C. Diebolder et al, 2014, the disclosure of which is hereby incorporated by reference in its entirety herein. Further examples of hexamer assemblies using IgGl Fc mutations to induce hexamerization are described in de Jong, Rob N et al., PLoS biology vol.

[1582] 14,1 el002344. 6 Jan. 2016, the disclosure of which is hereby incorporated by reference in its entirety herein.

[1583] Hexamer forming assemblies were produced as follows. The hexamer forming assemblies of the present example contained E345R and / or E430G mutations in the Fc region, wherein the numbering is according to the numbering of the EU index. It is noted that the hexamer forming assemblies are not produced and purified in hexameric form. Rather they form hexamers upon antigen binding. See, for instance, de Jong, Rob N et al., PLoS biology vol. 14,1 el002344. 6 Jan. 2016. Hexamer-forming antibodies were produced in ExpiCHO using Expifectamine CHO Transfection according to manufacturer’s " Max Titer” protocol (Thermo Fisher). Supernatant was harvested by centrifugation (500xg, 10 minutes, RT) approximately 192 hours post-transfection. Protein G Sepharose Fastflow (Cytiva) was added to the supernatant and allowed to bind via end-over-end rotation for 4 hours at RT. After incubation, the Protein G sepharose was collected from the supernatant put into a gravity column. The Protein G was washed with 200 ml IX PBS (standard formula). The antibodies were eluted from the Protein A in fractions using 800 ul of 10 mM glycine pH 3 at a time, and collecting into waiting tubes containing 200 ul Tris pH 8.5 to

[1584] neutralize. Fractions containing protein, as measured by A280, were pooled. Pooled fractions containing antibodies were dialyzed in 10 MWCO dialysis cassettes into dialysis buffer containing 20 mM histidine, 70 mM trehalose, 0.01% Tween 80 and 0.2 M Arginine pH 5.5.

[1585] Gel-based analysis was performed to check the hexamer forming assemblies of 2C8, 1F6, 3D3, 5H8, and 7C6 (FIG. 13) for expression and purity.

[1586] Analytical SEC (running buffer 20 mM histidine, 70 mM trehalose, 0.01% Tween 80 and 0.2 M Arginine pH 5.5.) was run to check that the antibodies were pure and monodispersed (FIG. 15A-FIG. 15E). Referring to FIG. 15A-FIG. 15E, hexamer forming antibodies were monodispersed, with the exception of 3D3, and eluted on gel filtration according to the expected size of a 150kDa antibody.

[1587] Further gel-based analysis was performed to analyze the hexamer assemblies of 2C8.

[1588] 1F6, 3D3, 5H8, and 7C6 (FIG. 14A-FIG. 14C). It is noted that the gels present peak SEC 95

[1589] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1590] fractions from FIG. 15A-FIG. 15C.

[1591] Additionally, a hexamer assembly complement activation ELISA was performed as follows. Nunc 96 well Maxisorp (Thermo 439454) plate was coated with 5 ug / mL HIV gpl20 (Sino Biological 11233-V08H-100) in PBS overnight at 4 °C. Plate was washed 3X with 200 ul per well PBS containing 0.05% Tween-20 (PBST). 3-Fold dilutions starting at 10 ug / ml of panviral antibodies and control antibodies in PBST were added and allowed to incubate with shaking at room temperature (RT) for 1 hour. Plate was washed 3X with 200 ul per well HBSS (with Ca2+ and Mg2+) containing 0.05% Tween-20 (HBSST). 2% antibody-depleted normal human serum was added and allowed to incubate 45 minutes at 37°C. Plate was washed 3X and then 2ug / ml anti -human TCC (Terminal Complement Complex) aEll antibody in HBSST was added and allowed to incubate shaking for 1.5 hr at RT. Plate was washed 3X with HBSST and then rabbit anti-mouse HRP (1:5000) was added and allowed to incubate for 1 hr shaking at RT. Plate was washed 5X with HBSST, and then 1-Step Ultra TMB (Thermo 34029) was added and allowed to develop for 15 minutes. Reaction was stopped with 0.3 M sulfuric acid. Plate was read at 450 nm with 630 nm subtraction.

[1592] Referring to FIG. 18A-FIG. 18B present a schematic, data, and results related to the hexamer complement activation ELISA assay. FIG. 18A presents a schematic representation of the hexamer complement activation ELISA assay. FIG. 18B presents a graphical representation of the results of the assay. The results demonstrate that the hexamer forming assemblies effectively potentiated complement activation. Moreover, the hexamer forming E345R / E430G antibody format performed better than a K326W / E333S “complement enhanced” antibody format in complement activation potential in the presence of HIV gpl20. It was noted that the K326W / E333S versions of these antibodies did not activate complement at all. K326W / E333S number is according to EU index; of the of the K326W / E333S was the same as the “HEX” version except for the difference in Fc mutations, K326W / E333S as opposed to E345R and / or E430G.

[1593] Example 8: SPR Analysis

[1594] The present example describes surface plasmon resonance (SPR)-based analysis of the binding of the anti-viral antibodies 1F6, 2C8,3D3, 5H8, and 7C6 to HIV gpl20, EBOV GP, and CMV gB immobilized on NTA chips. The analysis proceeded as follows.

[1595] Surface plasmon resonance was performed using Biacore T200 Biosensor (GE Healthcare). His-tagged HIV gpl20. EBOV GP, and CMV gB were captured on NTA chip (Cytiva, cat. #28994951) to densities of 23-100 response units (RU). Binding was measured 96

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[1597] in single-cycle kinetics experiments REF (Karlsson. Katsamba et al. 2006) with 180 sec association and 300 sec dissociation; the antibodies were injected in a 2-fold dilution starting at 5 mM. Two blank injections were performed before and after the analyte injection and were averaged to account for system instability. The data were doubly referenced, i.e., the signal generated on cell 1 (reference cell) and the data collected for the blank injection (buffer) were subtracted from the results collected on active cells (cells that contained immobilized antigens). PBS was used as running buffer. The chip was regenerated using 0.35 M EDTA. Results were fitted into a 1: 1 binding model using Biacore T200 Evaluation software (ver. 3.1). See, for instance, Karlsson, R., P. S. Katsamba, H. Nordin, E. Pol and D. G. Myszka (2006). " Analyzing akinetic titration series using affinity biosensors." Anal Biochem 349(1): 136-147).

[1598] Surface plasmon resonance sensorgrams of the binding of the anti-viral antibodies 1F6, 2C8,3D3, 5H8, and 7C6 to HIV gpl20, EBOV GP, and CMV gB immobilized on NTA chips are presented in FIG. 16A-FIG. 16E. All antibodies showed moderate binding affinities (low micromolar range) towards all three viral antigens.

[1599] Example 9: In vivo evaluation of Pan V by ex vivo pre-incubation of wild-type HSV 2 (strain 186) with antibody prior to challenge in Depo Provera-treated mice

[1600] The present example describes in vivo analysis of PanV by ex vivo pre-incubation of wild-type HSV 2 (strain 186) with antibody prior to challenge in Depo Provera-treated mice. The analysis proceeded as follows.

[1601] Study Design and Experimental Groups

[1602] Mice were assigned to experimental groups as follows:

[1603] Group 1 (Control antibody + WT HSV-2 challenge): Wild-type HSV-2 was pre-incubated with a control antibody consisting of human IgG against SARS-CoV-2 Spike RBD, followed by HSV-2 challenge;

[1604] Group 2 (PanV + WT HSV-2 challenge): Wild-type HSV-2 was pre-incubated with complement-enhanced 2C8 (PanV) and then used for HSV-2 challenge;

[1605] Group 3 (WT HSV-2 challenge): Wild-type HSV-2 challenge without experimental antibody (vehicle / saline control). Wild-type HSV-2 incubated in saline and then used 97

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[1607] for challenge; and

[1608] Group 4 (DL6 + WT HSV-2 challenge): Wild-type HSV-2 was pre-incubated with DL6 (gD monoclonal antibody) and then used for HSV-2 challenge.

[1609] Antibodies and Preparation of Working Solutions

[1610] PanV (complement enhanced 2C8): The PanV antibody was a 2C8 monomer bearing complement-enhancing mutations with a recorded stock concentration of 3.127 mg / mL. A working dilution was prepared to achieve a required concentration of 40 pg / mL.

[1611] Control antibody (SARS-CoV-2 Spike RBD): The control antibody stock was recorded as 1 mg / mL. A working dilution stock was prepared to achieve a required concentration of 40 pg / mL.

[1612] DL6 (HSV gD monoclonal antibody): DL6 was used at the required concentration of 40 pg / mL.

[1613] Virus-Antibody Pre-Incubation Procedure

[1614] For antibody pre-incubation, wild-type HSV-2 (strain 186) was combined with the relevant antibody preparation and pre-incubated for 6 hours at room temperature prior to challenge administration.

[1615] Clinical Scoring and Readouts

[1616] Following HSV-2 challenge, mice were monitored for clinical score. Clinical scores were plotted as a function of time (days) on a 0-5 clinical score axis, as shown in the provided figure.

[1617] Results

[1618] Referring now to FIG. 19, FIG. 19 presents data and results related to PanV (complement-enhanced 2C8)-based reduction of clinical disease severity following wild-type HSV-2 challenge in Depo-Provera-treated mice (n=10 per group). Briefly, wild-type HSV-2 was combined with (i) saline control (“Saline”; black), (ii) an irrelevant isotype / control human IgG specific for SARS-CoV-2 Spike receptor-binding domain (“Spike RBD”; blue), (iii) the PanV antibody (“PanV”; pink; complement-enhanced 2C8 monomer bearing complement-enhancing mutations), or (iv) an HSV positive-control monoclonal antibody directed to glycoprotein D (“DL6 (HSV gD)”; purple), and the virus / antibody (or

[1619] 98

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[1621] virus / vehicle) mixtures were pre-incubated for 6 hours at room temperature prior to administration to mice that had received Depo-Provera (2 mg) 5 days earlier. Clinical disease was monitored longitudinally by assigning daily clinical scores on a 0-5 scale (higher scores indicating increased disease severity) over a 15-day post-challenge observation period.

[1622] Further referring to FIG. 19, the saline and Spike RBD control antibody groups exhibited progressive disease culminating in high clinical scores necessitating euthanasia, whereas pre-incubation with PanV reduced overall clinical severity, and pre-incubation with DL6 markedly limited clinical signs across the monitoring interval. Data are presented as group means with error bars indicating inter-animal variability (as plotted).

[1623] Example 9: Immunofluorescence Analysis of Antibody Binding to Tissue Sections Immunofluorescence was used to visualize and quantify antibody binding to tissue sections.

[1624] Materials and Methods

[1625] The antibodies were conjugated with Alexa Fluor 488 using Alexa Fluor™ 488 Protein Labeling Kit (Thermo Scientific, A10235) following the manufacture’s instructions.

[1626] Peripheral tissue microarray was customized with healthy human peripheral tissues from the tissue bank of the Yale Cancer Center / Pathology Tissue Microarray Facility and the Department of Pathology (mSOP44). All tissue samples were embedded in paraffin and fixed in formalin (Formalin-Fixed Paraffin-Embedded, FFPE).

[1627] The slides were subjected to deparaffinization following three sequential xylene baths for 10 min each. And then rehydrated through a grade of ethanol 100% 2 times 10 min each, 95% for 5 min. 70% for 5 min, 50% for 5 min, and rinsed in distillated water for 5 min. The antigen retrieval was performed by incubating the tissue sections in 0.1% trypsin solution in PBS at 37°C for 15 min. After enzymatic antigen retrieval, slides were washed in PBS for 5 min.

[1628] FFPE tissues samples were outlined using a hydrophobic PAP pen. Slides were blocked with a solution of 1% bovine serum albumin (BSA) and glycine (22 mg / mL) in a humidified chamber for 1 h. A 0.3% Sudan Black B / 70% ethyl alcohol (EtOH) solution was added to each sample and incubated before being washed thoroughly with PBS. Samples were incubated with 0.039 mg / ml of antibodies overnight. Slides were once again washed in PBS and immersed in distilled water. Washed slides were mounted with a solution of DAPI Prolong® Gold antifade reagent (Invitrogen, Thermo Fisher Scientific, P36930) with 17.5

[1629] 99

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[1631] pg / ml of DAPI and covered with a coverslip. Slides were stored in the dark at 4°C. Images were acquired by the Stellaris Confocal microscope at ×20 magnification and LAS X software (both from Leica Microsystems, Wetzlar, Germany). The mean of fluorescence was calculated using ImageJ software.

[1632] Results

[1633] Referring now to FIG. 20, FIG. 20 presents data and results related to immunofluorescence-based analysis of antibody binding to tissue sections. In FIG. 20, each dot represents the fluorescence intensity obtained from an independent duplicate measurement for a given antibody. Statistical significance between groups was assessed using one-way analysis of variance (ANOVA) followed by Tukey’s multiple comparisons test, which accounts for multiple pairwise comparisons across antibodies. Exact p-values are indicated directly on the figure.

[1634] Further referring to FIG. 20, the results demonstrated that the antibodies 2C8, 1F6, 3D3, 5H8 and 7C6 did not bind to the tissues evaluated.

[1635] Example 11: Immunofluorescence-based Analysis of Human Peripheral Tissues The present example describes immunofluorescence-based analysis of human peripheral tissues and presents representative images thereof.

[1636] Materials and Methods

[1637] The antibodies were conjugated with Alexa Fluor 488 using Alexa Fluor™ 488 Protein Labeling Kit (Thermo Scientific, Al 0235) following the manufacture’s instruction.

[1638] Peripheral tissue microarray was customized with healthy human peripheral tissues from the tissue bank of the Yale Cancer Center / Pathology Tissue Microarray Facility’ and the Department of Pathology (mSOP44). All tissue samples were embedded in paraffin and fixed in formalin (Formalin-Fixed Paraffin-Embedded, FFPE).

[1639] The slides were subjected to deparaffinization following three sequential xylene baths for 10 min each. And then rehydrated through a grade of ethanol 100% 2 times 10 min each, 95% for 5 min, 70% for 5 min, 50% for 5 min, and rinsed in distillated water for 5 min. The antigen retrieval was performed by incubating the tissue sections in 0.1% trypsin solution in PBS at 37°C for 15 min. After enzymatic antigen retrieval, slides were washed in PBS for 5 min.

[1640] FFPE tissues samples were outlined using a hydrophobic PAP pen. Slides were 100

[1641] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1642] blocked with a solution of 1% bovine serum albumin (BSA) and glycine (22 mg / mL) in a humidified chamber for 1 h. A 0.3% Sudan Black B / 70% ethyl alcohol (EtOH) solution was added to each sample and incubated before being washed thoroughly with PBS. Samples were incubated with 0.039 mg / ml of antibodies overnight. Slides were once again washed in PBS and immersed in distilled water. Washed slides were mounted with a solution of DAPI Prolong® Gold antifade reagent (Invitrogen, Thermo Fisher Scientific, P36930) with 17.5 pg / ml of DAPI and covered with a coverslip. Slides were stored in the dark at 4°C. Images were acquired by the Stellaris Confocal microscope at ×20 magnification and LAS X software (both from Leica Microsystems, Wetzlar, Germany). The mean of fluorescence was calculated using ImageJ software.

[1643] Results

[1644] Referring now to FIG. 21A-FIG. 21D, FIG. 21A-FIG. 21D present representative images of immunofluorescence-based analysis of human peripheral tissues. Confocal microscopy showing human tissues immunostained with anti-Epcam (positive control), 2C8.

[1645] 1F6, 3D3, 5H8, 7C6 and a negative control antibody as indicated, and nuclear DNA stain (DAPI, blue).

[1646] Further referring to FIG. 21 A-FIG. 21D, the results demonstrated that the antibodies 2C8, 1F6, 3D3, 5H8. and 7C6 did not bind to the tissues analy zed.

[1647] Example 12: Comparative HuProt Protein Microarray Profiling of Antibodies

[1648] The present example describes comparative HuProt protein microarray profiling of antibodies.

[1649] HuProt protein microarrays were used to assess the binding specificity of antibodies across thousands of human proteins simultaneously. In this platform, purified human proteins were immobilized on a microarray surface, and antibody binding was detected by fluorescence intensity measured in the 635 nm channel (F635), which reflects the strength of antibody-protein interaction. The F635 positivity threshold (> 1000) was defined as a cutoff to distinguish true antibody binding from background signal.

[1650] Referring now to FIG. 22A-FIG. 22G, FIG. 22A-FIG. 22G present data and results related to comparative HuProt protein microarray profiling of antibodies. FIG. 22A presents the total number of proteins exceeding the F635 positivity threshold (> 1000) for each antibody, thereby providing a global measure of antibody polyreactivity or breadth of protein recognition. FIG. 22B-FIG. 22G present, for each antibody, the mean fluorescence intensity 101

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[1652] (F635) for individual proteins plotted as log₂ fold-change relative to the negative control antibody (9H2). Each dot represents a single human protein on the array. Proteins with a foldchange > 3 relative to the negative control are highlighted in orange, indicating enrichment compared to background binding. Proteins that exceed both the fold-change threshold (> 3) and the F635 positivity threshold (> 1000) are shown in red, representing high-confidence antibody targets. Dashed lines indicate the applied thresholds.

[1653] The analysis and results demonstrated that 7C6 binds to FAM151A and IL1RL1, and 5H8 binds to ITGA4B7. 1F6, 2C8, and 3D3 did not bind to any of the proteins analyzed.

[1654] Enumerated Embodiments

[1655] In some aspects, the present invention is directed to the following non-limiting embodiments:

[1656] Embodiment 1: An isolated and / or recombinant antibody or antigen binding fragment thereof comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein: the VH comprises: (a) a complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 1; a CDR2 comprising the amino acid sequence of SEQ ID NO: 2; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 3; (b) a CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 6; (c) a CDR1 comprising the amino acid sequence of SEQ ID NO: 7; a CDR2 comprising the amino acid sequence of SEQ ID NO: 8 and a CDR3 comprising the amino acid sequence of SEQ ID NO: 9; (d) a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12; (e) a CDR1 comprising the amino acid sequence of SEQ ID NO: 13; a CDR2 comprising the amino acid sequence of SEQ ID NO: 14; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 15; (f) a CDR1 comprising the amino acid sequence of SEQ ID NO: 32; a CDR2 comprising the amino acid sequence of SEQ ID NO: 33; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 34; (g) CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 37; (h) CDR1 comprising the amino acid sequence of SEQ ID NO: 38; a CDR2 comprising the amino acid sequence of SEQ ID NO: 39; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 40; (i) CDR1 comprising the amino acid sequence of SEQ ID NO: 41; a CDR2 comprising the amino acid 102

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[1658] sequence of SEQ ID NO: 42; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 43; (j) CDR1 comprising the amino acid sequence of SEQ ID NO: 44; a CDR2 comprising the amino acid sequence of SEQ ID NO: 45; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 46; (k) a CDR1 comprising the amino acid sequence of SEQ ID NO: 63; a CDR2 comprising the amino acid sequence of SEQ ID NO: 64; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 65; (1) a CDR1 comprising the amino acid sequence of SEQ ID NO: 66; a CDR2 comprising the amino acid sequence of SEQ ID NO: 67; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 68; (m) a CDR1 comprising the amino acid sequence of SEQ ID NO: 69; a CDR2 comprising the amino acid sequence of SEQ ID NO: 70; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 71; (n) a CDR1 comprising the amino acid sequence of SEQ ID NO: 72; a CDR2 comprising the amino acid sequence of SEQ ID NO: 73; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 74; (o) a CDR1 comprising the amino acid sequence of SEQ ID NO: 75; a CDR2 comprising the amino acid sequence of SEQ ID NO: 76; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 77; (p) a CDR1 comprising the amino acid sequence of SEQ ID NO: 94; a CDR2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 96; (q) a CDR1 comprising the amino acid sequence of SEQ ID NO: 97; a CDR2 comprising the amino acid sequence of SEQ ID NO: 98; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 99; (r) a CDR1 comprising the amino acid sequence of SEQ ID NO: 100; a CDR2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 102; (s) a CDR1 comprising the amino acid sequence of SEQ ID NO: 103; a CDR2 comprising the amino acid sequence of SEQ ID NO: 104; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 105; (t) a CDR1 comprising the amino acid sequence of SEQ ID NO: 106; a CDR2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 108; (u) a CDR1 comprising the amino acid sequence of SEQ ID NO: 125; a CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 127; (v) a CDR1 comprising the amino acid sequence of SEQ ID NO: 128; a CDR2 comprising the amino acid sequence of SEQ ID NO: 129; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 130; (w) a CDR1 comprising the amino acid sequence of SEQ ID NO: 131; a CDR2 comprising the amino acid sequence of SEQ ID NO: 132; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 133; (x) a CDR1 comprising the amino acid sequence of SEQ ID NO: 134; a CDR2 comprising the amino acid sequence of SEQ ID 103

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[1660] NO: 135; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 136; or (y) a CDR1 comprising the amino acid sequence of SEQ ID NO: 137; a CDR2 comprising the amino acid sequence of SEQ ID NO: 138; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 139; and / or the VL comprises: (z) a CDR1 comprising the amino acid sequence of SEQ ID NO: 17; a CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 19; (aa) a CDR1 comprising the amino acid sequence of SEQ ID NO: 20; a CDR2 comprising the amino acid sequence of SEQ ID NO: 21; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 22; (bb) a CDR1 comprising the amino acid sequence of SEQ ID NO: 23; a CDR2 comprising the amino acid sequence of SEQ ID NO: 24; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 25; (cc) a CDR1 comprising the amino acid sequence of SEQ ID NO: 26; a CDR2 comprising the amino acid sequence of SEQ ID NO: 27; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 28; (dd) a CDR1 comprising the amino acid sequence of SEQ ID NO: 29; a CDR2 comprising the amino acid sequence of NN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 30; (ee) a CDR1 comprising the amino acid sequence of SEQ ID NO: 48; a CDR2 comprising the amino acid sequence of SEQ ID NO: 49; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 50; (ff) a CDR1 comprising the amino acid sequence of SEQ ID NO: 51; a CDR2 comprising the amino acid sequence of SEQ ID NO: 52; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 53; (gg) a CDR1 comprising the amino acid sequence of SEQ ID NO: 54; a CDR2 comprising the amino acid sequence of SEQ ID NO: 55; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 56; (hh) a CDR1 comprising the amino acid sequence of SEQ ID NO: 57; a CDR2 comprising the amino acid sequence of SEQ ID NO: 58; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 59; (ii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 60; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 61; (jj) a CDR1 comprising the amino acid sequence of SEQ ID NO: 79; a CDR2 comprising the amino acid sequence of SEQ ID NO: 80; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 81; (kk) a CDR1 comprising the amino acid sequence of SEQ ID NO: 82; a CDR2 comprising the amino acid sequence of SEQ ID NO: 83; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 84; (11) a CDR1 comprising the amino acid sequence of SEQ ID NO: 85; a CDR2 comprising the amino acid sequence of SEQ ID NO: 86; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 87; (mm) a CDR1 comprising the amino acid sequence of SEQ ID NO: 88; a CDR2 comprising the amino acid sequence of SEQ ID NO: 89; and a 104

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[1662] CDR3 comprising the amino acid sequence of SEQ ID NO: 90; (nn) a CDR1 comprising the amino acid sequence of SEQ ID NO: 91; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 92; (oo) a CDR1 comprising the amino acid sequence of SEQ ID NO: 110; a CDR2 comprising the amino acid sequence of SEQ ID NO: 111; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 112; (pp) a CDR1 comprising the amino acid sequence of SEQ ID NO: 113; a CDR2 comprising the amino acid sequence of SEQ ID NO: 114; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 115; (qq) a CDR1 comprising the amino acid sequence of SEQ ID NO: 116; a CDR2 comprising the amino acid sequence of SEQ ID NO: 117; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 118; (rr) a CDR1 comprising the amino acid sequence of SEQ ID NO: 119; a CDR2 comprising the amino acid sequence of SEQ ID NO: 120; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 121; (ss) a CDR1 comprising the amino acid sequence of SEQ ID NO: 122; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 123; (tt) a CDR1 comprising the amino acid sequence of SEQ ID NO: 141; a CDR2 comprising the amino acid sequence of SEQ ID NO: 142; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 143 (uu) a CDR1 comprising the amino acid sequence of SEQ ID NO: 144; a CDR2 comprising the amino acid sequence of SEQ ID NO: 145; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 146; (vv) a CDR1 comprising the amino acid sequence of SEQ ID NO: 147; a CDR2 comprising the amino acid sequence of SEQ ID NO: 148; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 149; (ww) a CDR1 comprising the amino acid sequence of SEQ ID NO: 150; a CDR2 comprising the amino acid sequence of SEQ ID NO: 151; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 152; (xx) a CDR1 comprising the amino acid sequence of SEQ ID NO: 153; a CDR2 comprising the amino acid sequence of NN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 154.

[1663] Embodiment 2: The antibody or antigen binding fragment thereof of embodiment 1, wherein the antibody or antigen binding fragment thereof comprises: (a) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 1; the CDR2 comprising the amino acid sequence of SEQ ID NO: 2; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 3; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 17; the CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 19; (b) the VH comprising the

[1664] 105

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[1666] CDR1 comprising the amino acid sequence of SEQ ID NO: 4; the CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 20; the CDR2 comprising the amino acid sequence of SEQ ID NO: 21; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 22; (c) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 7; the CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 9; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 23; the CDR2 comprising the amino acid sequence of SEQ ID NO: 24; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 25; (d) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 10; the CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 26; the CDR2 comprising the amino acid sequence of SEQ ID NO: 27; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 28; (e) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 13; the CDR2 comprising the amino acid sequence of SEQ ID NO: 14; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 15; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 29; the CDR2 comprising the amino acid sequence of NN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 30; (f) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 32; the CDR2 comprising the amino acid sequence of SEQ ID NO: 33; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 34: and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 48; the CDR2 comprising the amino acid sequence of SEQ ID NO: 49; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 50; (g) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 35; the CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 51; the CDR2 comprising the amino acid sequence of SEQ ID NO: 52; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 53; (h) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 38; the CDR2 comprising the amino acid sequence of SEQ ID NO: 39; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 40: and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 54; the CDR2 comprising the amino acid sequence of SEQ ID NO: 55; and the CDR3

[1667] 106

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[1669] comprising the amino acid sequence of SEQ ID NO: 56; (i) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 41; the CDR2 comprising the amino acid sequence of SEQ ID NO: 42; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 43; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 57; the CDR2 comprising the amino acid sequence of SEQ ID NO: 58; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 59; (j) VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 44; the CDR2 comprising the amino acid sequence of SEQ ID NO: 45; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 46; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 60; the CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 61; (k) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 63; the CDR2 comprising the amino acid sequence of SEQ ID NO: 64; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 65; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 79; the CDR2 comprising the amino acid sequence of SEQ ID NO: 80; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 81; (1) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 66; the CDR2 comprising the amino acid sequence of SEQ ID NO: 67; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 68; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 82; the CDR2 comprising the amino acid sequence of SEQ ID NO: 83; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 84; (m) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 69; the CDR2 comprising the amino acid sequence of SEQ ID NO: 70; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 71; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 85; the CDR2 comprising the amino acid sequence of SEQ ID NO: 86; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 87; (n) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 72; the CDR2 comprising the amino acid sequence of SEQ ID NO: 73; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 74; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 88; the CDR2 comprising the amino acid sequence of SEQ ID NO: 89; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 90; (o) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 75; the CDR2 comprising the amino acid sequence of SEQ ID NO: 76; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 77; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 91; the 107

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[1671] CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 92; (p) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 94; the CDR2 comprising the amino acid sequence of SEQ ID NO: 95; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 96; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 110; the CDR2 comprising the amino acid sequence of SEQ ID NO: 111; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 112; (q) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 97; the CDR2 comprising the amino acid sequence of SEQ ID NO: 98; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 99; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 113; the CDR2 comprising the amino acid sequence of SEQ ID NO: 114; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 115; (r) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 100; the CDR2 comprising the amino acid sequence of SEQ ID NO: 101; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 102; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 116; the CDR2 comprising the amino acid sequence of SEQ ID NO: 117; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 118; (s) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 103; the CDR2 comprising the amino acid sequence of SEQ ID NO: 104; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 105; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 119; the CDR2 comprising the amino acid sequence of SEQ ID NO: 120; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 121; (t) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 106; the CDR2 comprising the amino acid sequence of SEQ ID NO: 107; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 108; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 122; the CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 123; (u) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 125; the CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 127; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 141; the CDR2 comprising the amino acid sequence of SEQ ID NO: 142; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 143; (v) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 128; the CDR2 comprising the amino acid sequence of SEQ ID NO: 129; and the CDR3 comprising 108

[1672] 57068077.4Attorney Docket No. 047162-7515WO1(02827)

[1673] the amino acid sequence of SEQ ID NO: 130; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 144; the CDR2 comprising the amino acid sequence of SEQ ID NO: 145; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 146; (w) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 131; the CDR2 comprising the amino acid sequence of SEQ ID NO: 132; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 133; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 147; the CDR2 comprising the amino acid sequence of SEQ ID NO: 148; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 149; (x) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 134; the CDR2 comprising the amino acid sequence of SEQ ID NO: 135; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 136; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 150; the CDR2 comprising the amino acid sequence of SEQ ID NO: 151; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 152; (y) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 137; the CDR2 comprising the amino acid sequence of SEQ ID NO: 138; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 139; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 153; the CDR2 comprising the amino acid sequence of NN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 154.

[1674] Embodiment 3: The antibody or antigen binding fragment thereof of embodiment 1 or embodiment 2, wherein: (a) the VH comprises an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 47, SEQ ID NO: 78, SEQ ID NO: 109, and SEQ ID NO: 140; and (b) the VL comprises an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 93, SEQ ID NO: 124, and SEQ ID NO: 155.

[1675] Embodiment 4: The antibody or antigen binding fragment thereof of any one of embodiments 1-3, wherein: (a) the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 16. SEQ ID NO: 47. SEQ ID NO: 78. SEQ ID NO: 109, and SEQ ID NO: 140; and (b) the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 93, SEQ ID NO: 124, and SEQ ID NO: 155.

[1676] Embodiment 5: The antibody or antigen binding fragment thereof of any one of embodiments 1-4, wherein: (a) the VH comprises an amino acid sequence at least 90%

[1677] 109

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[1679] identical to the amino acid sequence of SEQ ID NO: 16, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 31; (b) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 47, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 62; (c) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 78, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 93; (d) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 109, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 124; (e) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 140, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 155.

[1680] Embodiment 6: The antibody or antigen binding fragment thereof of any one of embodiments 1-5, wherein: (a) the VH comprises the amino acid sequence of SEQ ID NO: 16, and the VL comprises the amino acid sequence of SEQ ID NO: 31; (b) the VH the amino acid sequence of SEQ ID NO: 47, and the VL comprises the amino acid sequence of SEQ ID NO: 62; (c) the VH comprises the amino acid sequence of SEQ ID NO: 78, and the VL comprises the amino acid sequence of SEQ ID NO: 93; (d) the VH comprises the amino acid sequence of SEQ ID NO: 109, and the VL comprises the amino acid sequence of SEQ ID NO: 124; (e) the VH comprises the amino acid sequence of SEQ ID NO: 140, and the VL comprises the amino acid sequence of SEQ ID NO: 155.

[1681] Embodiment 7: The antibody or antigen binding fragment thereof of any one of embodiments 1-6, wherein the antibody or antigen binding fragment thereof comprises an IgGl, IgG2, IgG3 or IgG4 constant region or fragment thereof.

[1682] Embodiment 8: The antibody or antigen binding fragment thereof of any one of embodiments 1-7, wherein the antibody or antigen binding fragment thereof comprises an IgGl constant region or fragment thereof.

[1683] Embodiment 9: The antibody or antigen binding fragment thereof of any one of embodiments 1-8, wherein the antibody or antigen binding fragment thereof comprises a heavy chain constant region comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 156 and SEQ ID NO: 158; and further comprises a light chain constant region comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 157 and SEQ ID NO: 159.

[1684] 110

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[1686] Embodiment 10: The antibody or antigen binding fragment of any one of embodiments 1-9, wherein the antibody or antigen binding fragment thereof of comprises a heavy chain constant region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 156 and SEQ ID NO: 158; and further comprises a light chain constant region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 157 and SEQ ID NO: 159.

[1687] Embodiment 11: The antibody or antigen binding fragment thereof of any one of embodiments 1-10, wherein the antibody or antigen binding fragment thereof comprises at least one selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a variable fragment (Fv), an antigen-binding fragment (Fab or F(ab)2), a single chain antibody (scFv), a camelid antibody and a humanized antibody.

[1688] Embodiment 12: The antibody or antigen binding fragment thereof of any one of embodiments 1-11, wherein the antibody or antigen binding fragment thereof is directly or indirectly attached to a detectable label or a therapeutic agent.

[1689] Embodiment 13: The antibody or antigen binding fragment thereof of any one of embodiments 1-12, wherein the antibody or antigen binding fragment thereof binds to viral proteins of two or more viruses from different viral families.

[1690] Embodiment 14: The antibody or antigen binding fragment thereof of embodiment 13, wherein the viral families include one or more of Rhabdoviridae, Filvoviridae, Flaviviridae, Bunyaviridae, Paramyxoviridae. Retroviridae. Orthomyxoviridae, Coronaviridae, and Herpesviridae.

[1691] Embodiment 15: The antibody or antigen binding fragment thereof of any one of embodiments 1-14, wherein the antibody or antigen binding fragment thereof binds to at least one viral protein from a virus selected from the group consisting of HIV, influenza, encephalitis, Hantaan virus, coronavirus, RSV, vesicular stomatitis virus (VSV), herpesvirus, Zika virus, Dengue virus, rabies, Ebola, cytomegalovirus (CMV), and combinations thereof.

[1692] Embodiment 16: The antibody or antigen binding fragment thereof of embodiment 15, wherein the coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), HCov 229E, HCoV HKU1, HCoV NL63. or HCoV OC43.

[1693] Embodiment 17: The antibody or antigen binding fragment thereof of embodiment 15, wherein the herpesvirus is HSV-1 or HSV-2.

[1694] Embodiment 18: The antibody or antigen binding fragment thereof of embodiment 15, wherein the influenza is H1N1.

[1695] Embodiment 19: The antibody or antigen binding fragment thereof of any one of 111

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[1697] embodiments 1-18, wherein the antibody or antigen binding fragment thereof binds to a glycosylation feature specific to a viral protein which is not found in a protein of a host of the virus.

[1698] Embodiment 20: The antibody or antigen binding fragment thereof of embodiment 19, wherein the glycosylation feature comprises an N-acetylglucosamine (GlcNAc) residue on a non-reducing end of an oligosaccharide.

[1699] Embodiment 21: A tetramer assembly of antibodies or antigen binding fragments thereof, wherein the tetramer assembly comprises one or more of the antibodies or antigen binding fragments thereof of any one of embodiments 1 -20.

[1700] Embodiment 22: The tetramer assembly of embodiment 21, wherein the tetramer assembly comprises a single chain diabody Fc (scDbFc) fusion molecule.

[1701] Embodiment 23: The tetramer assembly of embodiment 21 or embodiment 22, wherein the tetramer assembly is capable of binding to SARS-CoV-2 and / or to HIV gpl20.

[1702] Embodiment 24: The tetramer assembly of any one of embodiments 21-23, wherein the tetramer assembly comprises the amino acid sequence of: (a) SEQ ID NO: 171; (b) SEQ ID NO: 172; (c) SEQ ID NO: 173; (d) SEQ ID NO: 174; or (e) SEQ ID NO: 175.

[1703] Embodiment 25: A hexamer assembly of antibodies or antigen binding fragments thereof, wherein the hexamer assembly comprises one or more of the antibodies or antigen binding fragments thereof of any one of embodiments 1-20.

[1704] Embodiment 26: The hexamer assembly of embodiment 25. wherein the hexamer assembly comprises mutations in the Fc heavy chain to promote hexamer formation.

[1705] Embodiment 27: The hexamer assembly of embodiment 25 or embodiment 26, wherein the hexamer assemblies comprise E345R and / or E430G mutations in the Fc heavy chain.

[1706] Embodiment 28: The hexamer assembly of any one of embodiments 25-27, wherein the hexamer assemblies comprise an E345R mutation in the Fc heavy chain.

[1707] Embodiment 29: The hexamer assembly of any one of embodiments 25-28, wherein the hexamer assemblies comprise an E430G mutation in the Fc heavy chain.

[1708] Embodiment 30: The hexamer assembly of any one of embodiments 25-29, wherein the Fc heavy chain is an IgGl Fc heavy chain.

[1709] Embodiment 31: A composition comprising the antibody or antigen binding fragment thereof of any one of embodiments 1 -20, the tetramer assembly of any one of embodiments embodiment 21-24, or the hexamer assembly of any one of embodiments 25-30, and at least one pharmaceutically acceptable carrier.

[1710] 112

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[1712] Embodiment 32: The composition of embodiment 31, wherein the composition further comprises an additional therapeutic agent.

[1713] Embodiment 33: An isolated nucleic acid comprising a nucleotide sequence encoding the antibody or antigen binding fragment thereof of any one of embodiments 1 -20, the tetramer assembly of any one of embodiments embodiment 21-24, or the hexamer assembly of any one of embodiments 25-30.

[1714] Embodiment 34: A vector comprising the nucleic acid of embodiment 33.

[1715] Embodiment 35: An isolated host cell that recombinantly produces the antibody or antigen binding fragment thereof of any one of embodiments 1 -20, the tetramer assembly of any one of embodiments embodiment 21-24, or the hexamer assembly of any one of embodiments 25-30.

[1716] Embodiment 36: A method of preventing, treating and / or ameliorating an infection by a virus in a subject in need thereof, the method comprising administering to the subject an effective amount of the antibody or antigen binding fragment thereof of any one of embodiments 1-20, the tetramer assembly of any one of embodiments embodiment 21-24, or the hexamer assembly of any one of embodiments 25-30, or the composition of embodiment 31 or embodiment 32.

[1717] Embodiment 37: The method of embodiment 36, wherein a protein of the virus has a glycosylation feature is not found in a protein of a host of the virus, and wherein the antibody specifically recognizes the glycosylation feature.

[1718] Embodiment 38: The method of embodiment 37, wherein the glycosylation feature comprises one or more of the following glycans: Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glc, Neu5Aca2-3(GalNAcpi-4)Gaipi-4Glc, Neu5Aca2-3Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glc, Neu5Aca2-3Gaipi-4Glc, Neu5Aca2-3Gaip. Neu5Aca2-8Neu5Aca2-3Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glc, Neu5Aca2-3Gaipi-4GlcNAc, Neu5Aca2-3Gaipi-4GlcNAcpi-2Manal-6(Neu5Aca2-3Gaipi-4GlcNAcpi-2Manal -3)ManP 1 -4GlcNAcP 1 -4GlcNAc-, Manal -6(Manal -3)Manal -6(Neu5 Aca2-3Gaip 1 -4GlcNAcP 1 -2Manal -3)ManP 1 -4GlcNAcP 1 -4GlcN Ac-, Manal -6(Mana 1 -3)Manal -6(Neu5 Aca2-6Gaip 1 -4GlcN AcP 1 -2Mana 1 -3)ManP 1 -4GlcN AcP 1 -4GlcNAc-, Neu5 Aca2-3 Gaip 1 -4(Fucal -3)GlcN AcP 1 -2Mana 1 -6(GlcNAcp 1 -4)(Neu5 Aca2-3Gaip 1 -4(Fuc l-3)GlcNAcpi-2Manal-3)Manpi-4GlcNAcpi-4GlcNAc-, Neu5Aca2-3Gaipi-4(Fucal-3)GlcNAc, Neu5Aca2-6Gaipi-4GlcNAc, Neu5Aca2-3Gaipi-3(Neu5Aca2-6)GlcNAcpi-3Gaip 1 -4Glc, Neu5 Aca2-3Gaip 1 -4(Fucal -3)GlcNAcP 1 -2Manal -6(Neu5 Aca2-3Gaip 1 -4(Fuc l -3)GlcNAcP 1 -2Manal -3)ManP 1 -4GlcNAcP 1 -4GlcNAc-, Manal -6(Manal - 113

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[1720] 3)Manα1-6(Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, Neu5Acα2-3Galβ1-4GlcNAcβ1-2Manα1-6(GlcNAcβ1-4)(Neu5Acα2-3Galβ1-4GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc-, and / or Neu5Acα2-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-2Manα1-6(Neu5Acα2-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-2Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc. In some aspects, the glycan comprises one or more glycan types, such as GSL, HMO, oligosaccharides, complex N-glycan, hybrid N-glycan, bisecting N-glycan, blood group and Lewis antigens, and LacNAc-extended N-glycan. In some aspects, the glycan comprises one or more of GM1, GM2, GDla, 3’-Sialyllactose, 3’-Sialylgalactose (GM4), GTla, 3’-a-Sialyl-N-acetyllactosamine, 3 ’ -Sialyl Lewis X, 6’-a-Sialyl-N-acetyllactosamine, and Disialyllacto-N-tetraose (DSLNT).

[1721] Embodiment 39: The method of embodiment 37 or embodiment 38, wherein the glycosylation feature comprises Neu5Aca2-3Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glc, Neu5Aca2-3Gaipi-4Glc, and / or Neu5Aca2-3Gaip.

[1722] Embodiment 40: The method of embodiment 39, wherein the glycosylation feature comprises an N-acetylglucosamine (GlcNAc) residue on a non-reducing end of an oligosaccharide.

[1723] Embodiment 41: The method of any one of embodiments 36-40, wherein the virus is an Rhabdoviridae, Filvoviridae, Flaviviridae, Bunyaviridae, Paramyxoviridae, Retroviridae, Orthomyxoviridae. a Coronaviridae, and / or a Herpesviridae family virus.

[1724] Embodiment 42: The method of any one of embodiments 36-41, wherein the virus is HIV, influenza, encephalitis, Hantaan virus, coronavirus, RSV, vesicular stomatitis virus (VSV), herpesvirus, Zika virus, Dengue virus, rabies, Ebola, cytomegalovirus (CMV), or any combination thereof.

[1725] Embodiment 43: The method of embodiment 42, wherein the coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), HCov 229E, HCoV HKU1, HCoV NL63, orHCoV OC43.

[1726] Embodiment 44: The method of embodiment 42, wherein the herpesvirus is HSV-1 or HSV-2.

[1727] Embodiment 45: The method of embodiment 42, wherein the influenza is H INI. Embodiment 46: The method of any one of embodiments 36-45, wherein the subject is further administered a second compound suitable for treating, preventing and / or ameliorating infection by the virus.

[1728] Embodiment 47: The method of any one of embodiments 36-46, wherein the subject is a mammal.

[1729] 114

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[1731] Embodiment 48: The method of any one of embodiments 36-47, wherein the subject is a human.

[1732] The foregoing outlines features of several embodiments so that those skilled in the art may better understand the aspects of the present disclosure. Those skilled in the art should appreciate that they may readily use the present disclosure as a basis for designing or modifying other processes and structures for carrying out the same purposes and / or achieving the same advantages of the embodiments introduced herein. Those skilled in the art should also realize that such equivalent constructions do not depart from the spirit and scope of the present disclosure, and that they may make various changes, substitutions, and alterations herein without departing from the spirit and scope of the present disclosure.

[1733] The contents of the articles, patents, and patent applications, and all other documents and electronically available information mentioned or cited herein, are hereby incorporated by reference in their entirety to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. Applicants reserve the right to physically incorporate into this application any and all materials and information from any such articles, patents, patent applications, or other physical and electronic documents.

[1734] In sum, while this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

[1735] 115

[1736] 57068077.4

Claims

Attorney Docket No. 047162-7515WO1(02827)CLAIMSWhat is claimed:

1. An isolated and / or recombinant antibody or antigen binding fragment thereof comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein:the VH comprises:(a) a complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 1; a CDR2 comprising the amino acid sequence of SEQ ID NO: 2; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 3;(b) a CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 6;(c) a CDR1 comprising the amino acid sequence of SEQ ID NO: 7; a CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 9;(d) a CDR1 comprising the amino acid sequence of SEQ ID NO: 10; a CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 12;(e) a CDR1 comprising the amino acid sequence of SEQ ID NO: 13; a CDR2 comprising the amino acid sequence of SEQ ID NO: 14; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 15;(f) a CDR1 comprising the amino acid sequence of SEQ ID NO: 32; a CDR2 comprising the amino acid sequence of SEQ ID NO: 33; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 34;(g) CDR1 comprising the amino acid sequence of SEQ ID NO: 35; a CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 37;(h) CDR1 comprising the amino acid sequence of SEQ ID NO: 38; a CDR2 comprising the amino acid sequence of SEQ ID NO: 39; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 40;(i) CDR1 comprising the amino acid sequence of SEQ ID NO: 41; a CDR2 comprising the amino acid sequence of SEQ ID NO: 42; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 43;11657068077.4Attorney Docket No. 047162-7515WO1(02827)(j) CDR1 comprising the amino acid sequence of SEQ ID NO: 44; a CDR2 comprising the amino acid sequence of SEQ ID NO: 45; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 46;(k) a CDR1 comprising the amino acid sequence of SEQ ID NO: 63; a CDR2 comprising the amino acid sequence of SEQ ID NO: 64; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 65;(l) a CDR1 comprising the amino acid sequence of SEQ ID NO: 66; a CDR2 comprising the amino acid sequence of SEQ ID NO: 67; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 68;(m) a CDR1 comprising the amino acid sequence of SEQ ID NO: 69; a CDR2 comprising the amino acid sequence of SEQ ID NO: 70; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 71;(n) a CDR1 comprising the amino acid sequence of SEQ ID NO: 72; a CDR2 comprising the amino acid sequence of SEQ ID NO: 73; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 74;(o) a CDR1 comprising the amino acid sequence of SEQ ID NO: 75; a CDR2 comprising the amino acid sequence of SEQ ID NO: 76; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 77;(p) a CDR1 comprising the amino acid sequence of SEQ ID NO: 94; a CDR2 comprising the amino acid sequence of SEQ ID NO: 95; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 96;(q) a CDR1 comprising the amino acid sequence of SEQ ID NO: 97; a CDR2 comprising the amino acid sequence of SEQ ID NO: 98; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 99;(r) a CDR1 comprising the amino acid sequence of SEQ ID NO: 100; a CDR2 comprising the amino acid sequence of SEQ ID NO: 101; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 102;(s) a CDR1 comprising the amino acid sequence of SEQ ID NO: 103; a CDR2 comprising the amino acid sequence of SEQ ID NO: 104; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 105;(t) a CDR1 comprising the amino acid sequence of SEQ ID NO: 106; a CDR2 comprising the amino acid sequence of SEQ ID NO: 107; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 108;(u) a CDR1 comprising the amino acid sequence of SEQ ID NO: 125; a CDR2 comprising 11757068077.4Attorney Docket No. 047162-7515WO1(02827)the amino acid sequence of SEQ ID NO: 126; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 127;(v) a CDR1 comprising the amino acid sequence of SEQ ID NO: 128; a CDR2 comprising the amino acid sequence of SEQ ID NO: 129; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 130;(w) a CDR1 comprising the amino acid sequence of SEQ ID NO: 131; a CDR2 comprising the amino acid sequence of SEQ ID NO: 132; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 133;(x) a CDR1 comprising the amino acid sequence of SEQ ID NO: 134; a CDR2 comprising the amino acid sequence of SEQ ID NO: 135; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 136; or(y) a CDR1 comprising the amino acid sequence of SEQ ID NO: 137; a CDR2 comprising the amino acid sequence of SEQ ID NO: 138; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 139;the VL comprises:(z) a CDR1 comprising the amino acid sequence of SEQ ID NO: 17; a CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 19;(aa) a CDR1 comprising the amino acid sequence of SEQ ID NO: 20; a CDR2 comprising the amino acid sequence of SEQ ID NO: 21; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 22;(bb) a CDR1 comprising the amino acid sequence of SEQ ID NO: 23; a CDR2 comprising the amino acid sequence of SEQ ID NO: 24; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 25;(cc) a CDR1 comprising the amino acid sequence of SEQ ID NO: 26; a CDR2 comprising the amino acid sequence of SEQ ID NO: 27; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 28;(dd) a CDR1 comprising the amino acid sequence of SEQ ID NO: 29; a CDR2 comprising the amino acid sequence of NN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 30;(ee) a CDR1 comprising the amino acid sequence of SEQ ID NO: 48; a CDR2 comprising the amino acid sequence of SEQ ID NO: 49; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 50;(ff) a CDR1 comprising the amino acid sequence of SEQ ID NO: 51; a CDR2 comprising 11857068077.4Attorney Docket No. 047162-7515WO1(02827)the amino acid sequence of SEQ ID NO: 52; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 53;(gg) a CDR1 comprising the amino acid sequence of SEQ ID NO: 54; a CDR2 comprising the amino acid sequence of SEQ ID NO: 55; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 56;(hh) a CDR1 comprising the amino acid sequence of SEQ ID NO: 57; a CDR2 comprising the amino acid sequence of SEQ ID NO: 58; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 59;(ii) a CDR1 comprising the amino acid sequence of SEQ ID NO: 60; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 61;(jj) a CDR1 comprising the amino acid sequence of SEQ ID NO: 79; a CDR2 comprising the amino acid sequence of SEQ ID NO: 80; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 81;(kk) a CDR1 comprising the amino acid sequence of SEQ ID NO: 82; a CDR2 comprising the amino acid sequence of SEQ ID NO: 83; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 84;(11) a CDR1 comprising the amino acid sequence of SEQ ID NO: 85; a CDR2 comprising the amino acid sequence of SEQ ID NO: 86; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 87;(mm)a CDR1 comprising the amino acid sequence of SEQ ID NO: 88; a CDR2 comprising the amino acid sequence of SEQ ID NO: 89; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 90;(nn) a CDR1 comprising the amino acid sequence of SEQ ID NO: 91; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 92;(oo) a CDR1 comprising the amino acid sequence of SEQ ID NO: 110; a CDR2 comprising the amino acid sequence of SEQ ID NO: 111; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 112;(pp) a CDR1 comprising the amino acid sequence of SEQ ID NO: 113; a CDR2 comprising the amino acid sequence of SEQ ID NO: 114; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 115;(qq) a CDR1 comprising the amino acid sequence of SEQ ID NO: 116; a CDR2 comprising the amino acid sequence of SEQ ID NO: 117; and a CDR3 comprising the amino acid 11957068077.4Attorney Docket No. 047162-7515WO1(02827)sequence of SEQ ID NO: 118;(rr) a CDR1 comprising the amino acid sequence of SEQ ID NO: 119; a CDR2 comprising the amino acid sequence of SEQ ID NO: 120; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 121;(ss) a CDR1 comprising the amino acid sequence of SEQ ID NO: 122; a CDR2 comprising the amino acid sequence of SN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 123;(tt) a CDR1 comprising the amino acid sequence of SEQ ID NO: 141; a CDR2 comprising the amino acid sequence of SEQ ID NO: 142; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 143(uu) a CDR1 comprising the amino acid sequence of SEQ ID NO: 144; a CDR2 comprising the amino acid sequence of SEQ ID NO: 145; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 146;(vv) a CDR1 comprising the amino acid sequence of SEQ ID NO: 147; a CDR2 comprising the amino acid sequence of SEQ ID NO: 148; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 149;(ww)a CDR1 comprising the amino acid sequence of SEQ ID NO: 150; a CDR2 comprising the amino acid sequence of SEQ ID NO: 151; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 152;(xx) a CDR1 comprising the amino acid sequence of SEQ ID NO: 153; a CDR2 comprising the amino acid sequence of NN; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 154.

2. The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises:(a) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 1;the CDR2 comprising the amino acid sequence of SEQ ID NO: 2; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 3; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 17; the CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 19;(b) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 4;12057068077.4Attorney Docket No. 047162-7515WO1(02827)the CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 20; the CDR2 comprising the amino acid sequence of SEQ ID NO: 21; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 22;(c) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 7;the CDR2 comprising the amino acid sequence of SEQ ID NO: 8; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 9; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 23; the CDR2 comprising the amino acid sequence of SEQ ID NO: 24; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 25;(d) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 10;the CDR2 comprising the amino acid sequence of SEQ ID NO: 11; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 26; the CDR2 comprising the amino acid sequence of SEQ ID NO: 27; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 28;(e) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 13;the CDR2 comprising the amino acid sequence of SEQ ID NO: 14; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 15; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 29; the CDR2 comprising the amino acid sequence of NN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 30;(f) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 32;the CDR2 comprising the amino acid sequence of SEQ ID NO: 33; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 48; the CDR2 comprising the amino acid sequence of SEQ ID NO: 49; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 50;(g) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 35;the CDR2 comprising the amino acid sequence of SEQ ID NO: 36; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 51; the CDR2 comprising the amino acid sequence of SEQ ID NO: 52; and the CDR3 comprising the amino acid 12157068077.4Attorney Docket No. 047162-7515WO1(02827)sequence of SEQ ID NO: 53;(h) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 38;the CDR2 comprising the amino acid sequence of SEQ ID NO: 39; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 40; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 54; the CDR2 comprising the amino acid sequence of SEQ ID NO: 55; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 56;(i) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 41;the CDR2 comprising the amino acid sequence of SEQ ID NO: 42; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 43; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 57; the CDR2 comprising the amino acid sequence of SEQ ID NO: 58; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 59;(j) VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 44; the CDR2 comprising the amino acid sequence of SEQ ID NO: 45; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 46; and the VL comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 60; the CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 61;(k) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 63;the CDR2 comprising the amino acid sequence of SEQ ID NO: 64; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 65; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 79; the CDR2 comprising the amino acid sequence of SEQ ID NO: 80; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 81;(l) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 66;the CDR2 comprising the amino acid sequence of SEQ ID NO: 67; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 68; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 82; the CDR2 comprising the amino acid sequence of SEQ ID NO: 83; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 84;(m) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 69;the CDR2 comprising the amino acid sequence of SEQ ID NO: 70; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 71; and the VL comprising the 12257068077.4Attorney Docket No. 047162-7515WO1(02827)CDR1 comprising the amino acid sequence of SEQ ID NO: 85; the CDR2 comprising the amino acid sequence of SEQ ID NO: 86; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 87;(n) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 72;the CDR2 comprising the amino acid sequence of SEQ ID NO: 73; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 74; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 88; the CDR2 comprising the amino acid sequence of SEQ ID NO: 89; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 90;(o) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 75;the CDR2 comprising the amino acid sequence of SEQ ID NO: 76; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 77; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 91; the CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 92;(p) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 94;the CDR2 comprising the amino acid sequence of SEQ ID NO: 95; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 96; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 110; the CDR2 comprising the amino acid sequence of SEQ ID NO: 111; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 112;(q) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 97;the CDR2 comprising the amino acid sequence of SEQ ID NO: 98; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 99; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 113; the CDR2 comprising the amino acid sequence of SEQ ID NO: 114; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 115;(r) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 100;the CDR2 comprising the amino acid sequence of SEQ ID NO: 101; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 102; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 116; the CDR2 comprising the amino acid sequence of SEQ ID NO: 117; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 118;(s) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 103;12357068077.4Attorney Docket No. 047162-7515WO1(02827)the CDR2 comprising the amino acid sequence of SEQ ID NO: 104; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 105; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 119; the CDR2 comprising the amino acid sequence of SEQ ID NO: 120; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 121;(t) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 106;the CDR2 comprising the amino acid sequence of SEQ ID NO: 107; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 108; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 122; the CDR2 comprising the amino acid sequence of SN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 123;(u) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 125;the CDR2 comprising the amino acid sequence of SEQ ID NO: 126; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 127; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 141; the CDR2 comprising the amino acid sequence of SEQ ID NO: 142; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 143;(v) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 128;the CDR2 comprising the amino acid sequence of SEQ ID NO: 129; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 130; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 144; the CDR2 comprising the amino acid sequence of SEQ ID NO: 145; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 146;(w) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 131;the CDR2 comprising the amino acid sequence of SEQ ID NO: 132; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 133; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 147; the CDR2 comprising the amino acid sequence of SEQ ID NO: 148; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 149;(x) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 134;the CDR2 comprising the amino acid sequence of SEQ ID NO: 135; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 136; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 150; the CDR2 comprising the amino acid sequence of SEQ ID NO: 151; and the CDR3 comprising the amino acid 12457068077.4Attorney Docket No. 047162-7515WO1(02827)sequence of SEQ ID NO: 152;(y) the VH comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 137;the CDR2 comprising the amino acid sequence of SEQ ID NO: 138; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 139; and the VL comprising the CDR1 comprising the amino acid sequence of SEQ ID NO: 153; the CDR2 comprising the amino acid sequence of NN; and the CDR3 comprising the amino acid sequence of SEQ ID NO: 154.

3. The antibody or antigen binding fragment thereof of claim 1 or claim 2, wherein: (a) the VH comprises an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 47, SEQ ID NO:

78. SEQ ID NO: 109, and SEQ ID NO: 140; and(b) the VL comprises an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 93, SEQ ID NO: 124, and SEQ ID NO: 155.

4. The antibody or antigen binding fragment thereof of any one of claims 1-3. wherein: (a) the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 47, SEQ ID NO: 78, SEQ ID NO: 109, and SEQ ID NO: 140; and(b) the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 93, SEQ ID NO: 124, and SEQ ID NO: 155.

5. The antibody or antigen binding fragment thereof of any one of claims 1-4, wherein: (a) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 16, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 31;(b) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 47, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 62;(c) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 78, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 93;(d) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 109, and the VL comprises an amino acid sequence at least12557068077.4Attorney Docket No. 047162-7515WO1(02827)90% identical to the amino acid sequence of SEQ ID NO: 124;(e) the VH comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 140, and the VL comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 155.

6. The antibody or antigen binding fragment thereof of any one of claims 1-5, wherein: (a) the VH comprises the amino acid sequence of SEQ ID NO: 16, and the VL comprises the amino acid sequence of SEQ ID NO: 31;(b) the VH the amino acid sequence of SEQ ID NO: 47, and the VL comprises the amino acid sequence of SEQ ID NO: 62;(c) the VH comprises the amino acid sequence of SEQ ID NO: 78, and the VL comprises the amino acid sequence of SEQ ID NO: 93;(d) the VH comprises the amino acid sequence of SEQ ID NO: 109, and the VL comprises the amino acid sequence of SEQ ID NO: 124;(e) the VH comprises the amino acid sequence of SEQ ID NO: 140, and the VL comprises the amino acid sequence of SEQ ID NO: 155.

7. The antibody or antigen binding fragment thereof of any one of claims 1 -6, wherein the antibody or antigen binding fragment thereof comprises an IgGl, IgG2, IgG3 or IgG4 constant region or fragment thereof.

8. The antibody or antigen binding fragment thereof of any one of claims 1-7. wherein the antibody or antigen binding fragment thereof comprises an IgGl constant region or fragment thereof.

9. The antibody or antigen binding fragment thereof of any one of claims 1-8, wherein the antibody or antigen binding fragment thereof comprises a heavy chain constant region comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 156 and SEQ ID NO: 158; and further comprises a light chain constant region comprising an amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 157 and SEQ ID NO: 159.

10. The antibody or antigen binding fragment of any one of claims 1-9, wherein the antibody or antigen binding fragment thereof of comprises a heavy chain constant region comprising an amino acid sequence selected from the group consisting of SEQ12657068077.4Attorney Docket No. 047162-7515WO1(02827)ID NO: 156 and SEQ ID NO: 158; and further comprises a light chain constant region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 157 and SEQ ID NO: 159.

11. The antibody or antigen binding fragment thereof of any one of claims 1-10, wherein the antibody or antigen binding fragment thereof comprises at least one selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a variable fragment (Fv), an antigen-binding fragment (Fab or F(ab)2), a single chain antibody (scFv), a camelid antibody and a humanized antibody.

12. The antibody or antigen binding fragment thereof of any one of claims 1-11, wherein the antibody or antigen binding fragment thereof is directly or indirectly attached to a detectable label or a therapeutic agent.

13. The antibody or antigen binding fragment thereof of any one of claims 1-12, wherein the antibody or antigen binding fragment thereof binds to viral proteins of two or more viruses from different viral families.

14. The antibody or antigen binding fragment thereof of claim 13, wherein the viral families include one or more of Rhabdoviridae, Filvoviridae, Flaviviridae, Bunyaviridae, Paramyxoviridae, Retroviridae, Orthomyxoviridae, Coronaviridae, and Herpesviridae.

15. The antibody or antigen binding fragment thereof of any one of claims 1-14, wherein the antibody or antigen binding fragment thereof binds to at least one viral protein from a virus selected from the group consisting of HIV, influenza, encephalitis, Hantaan virus, coronavirus, RSV, vesicular stomatitis virus (VSV), herpesvirus, Zika virus. Dengue virus, rabies, Ebola, cytomegalovirus (CMV), and combinations thereof.

16. The antibody or antigen binding fragment thereof of claim 15, wherein the coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), HCov 229E, HCoV HKU1, HCoV NL63, or HCoV OC43.

17. The antibody or antigen binding fragment thereof of claim 15, wherein the herpesvirus is HSV-1 or HSV-2.

18. The antibody or antigen binding fragment thereof of claim 15, wherein the influenza 12757068077.4Attorney Docket No. 047162-7515WO1(02827)is H1N1.

19. The antibody or antigen binding fragment thereof of any one of claims 1-18, wherein the antibody or antigen binding fragment thereof binds to a glycosylation feature specific to a viral protein which is not found in a protein of a host of the virus.

20. The antibody or antigen binding fragment thereof of claim 19, wherein the glycosylation feature comprises an N-acetylglucosamine (GlcNAc) residue on a nonreducing end of an oligosaccharide.

21. A tetramer assembly of antibodies or antigen binding fragments thereof, wherein the tetramer assembly comprises one or more of the antibodies or antigen binding fragments thereof of any one of claims 1-20.

22. The tetramer assembly of claim 21, wherein the tetramer assembly comprises a single chain diabody Fc (scDbFc) fusion molecule.

23. The tetramer assembly of claim 21 or claim 22, wherein the tetramer assembly is capable of binding to SARS-CoV-2 and / or to HIV gpl20.

24. The tetramer assembly of any one of claims 21-23, wherein the tetramer assembly comprises the amino acid sequence of:(a) SEQ ID NO: 171;(b) SEQ ID NO: 172;(c) SEQ ID NO: 173;(d) SEQ ID NO: 174; or(e) SEQ ID NO: 175.

25. A hexamer assembly of antibodies or antigen binding fragments thereof, wherein the hexamer assembly comprises one or more of the antibodies or antigen binding fragments thereof of any one of claims 1-20.

26. The hexamer assembly of claim 25, wherein the hexamer assembly comprises mutations in the Fc heavy chain to promote hexamer formation.

27. The hexamer assembly of claim 25 or claim 26, wherein the hexamer assemblies 12857068077.4Attorney Docket No. 047162-7515WO1(02827)comprise E345R and / or E430G mutations in the Fc heavy chain.

28. The hexamer assembly of any one of claims 25-27, wherein the hexamer assemblies comprise an E345R mutation in the Fc heavy chain.

29. The hexamer assembly of any one of claims 25-28, wherein the hexamer assemblies comprise an E430G mutation in the Fc heavy chain.

30. The hexamer assembly of any one of claims 25-29, wherein the Fc heavy chain is an IgGl Fc heavy chain.

31. A composition comprising the antibody or antigen binding fragment thereof of any one of claims 1-20. the tetramer assembly of any one of claims claim 21-24, or the hexamer assembly of any one of claims 25-30, and at least one pharmaceutically acceptable carrier.

32. The composition of claim 31, wherein the composition further comprises an additional therapeutic agent.

33. An isolated nucleic acid comprising a nucleotide sequence encoding the antibody or antigen binding fragment thereof of any one of claims 1-20, the tetramer assembly of any one of claims claim 21-24, or the hexamer assembly of any one of claims 25-30.

34. A vector comprising the nucleic acid of claim 33.

35. An isolated host cell that recombinantly produces the antibody or antigen binding fragment thereof of any one of claims 1-20, the tetramer assembly of any one of claims claim 21-24, or the hexamer assembly of any one of claims 25-30.

36. A method of preventing, treating and / or ameliorating an infection by a virus in a subject in need thereof, the method comprising administering to the subject an effective amount of the antibody or antigen binding fragment thereof of any one of claims 1-20, the tetramer assembly of any one of claims claim 21-24, or the hexamer assembly of any one of claims 25-30, or the composition of claim 31 or claim 32.

37. The method of claim 36, wherein a protein of the virus has a glycosylation feature is not found in a protein of a host of the virus, and wherein the antibody specifically recognizes the glycosylation feature.12957068077.4Attorney Docket No. 047162-7515WO1(02827)38. The method of claim 37, wherein the glycosylation feature comprises one or more of the following glycans: Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glc, Neu5Aca2- 3(GalNAcpl-4)Galpl-4Glc, Neu5Aca2-3Gaipi-3GalNAcpi-4(Neu5Aca2- 3)Gaipi-4Glc, Neu5Aca2-3Galpl-4Glc, Neu5Aca2-3Gaip, Neu5Aca2- 8Neu5Aca2-3Galβ1-3GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glc, Neu5Aca2-3Gaipi- 4GlcNAc, Neu5Aca2-3Gaipi-4GlcNAcpi-2Manal-6(Neu5Aca2-3Gaipi- 4GlcNAcP 1 -2Manal -3 )ManP 1 -4GlcN AcP 1 -4GlcN Ac-. Manal -6(Mana 1 -3 )Manal - 6(Neu5 Aca2-3 Gaip 1 -4GlcN Acp 1 -2Mana 1 -3)ManP 1 -4GlcNAcP 1 -4GlcNAc-, Manal -6(Manal-3)Manal -6(Neu5 Aca2-6Gaipi -4GlcNAcP 1 -2Manal -3)ManP 1 - 4GlcNAcpi-4GlcNAc-, Neu5Aca2-3Gaipi-4(Fucal-3)GlcNAcpi-2Manal- 6(GlcNAcP 1 -4)(Neu5 Aca2-3Gaip 1 -4(Fucal -3)GlcNAcP 1 -2Manal -3)ManP 1 - 4GlcNAcpi-4GlcNAc-, Neu5Aca2-3Gaipi-4(Fucal-3)GlcNAc, Neu5Aca2-6Galpl- 4GlcNAc, Neu5Aca2-3Gaipi-3(Neu5Aca2-6)GlcNAcpl-3Gaipi-4Glc, Neu5Aca2- 3Gaip 1 -4(Fucal -3)GlcNAcP 1 -2Manal -6(Neu5 Aca2-3Gaipi -4(Fucal -3)GlcNAcP 1 - 2Manal -3)Manp 1 -4GlcNAcP 1 -4GlcNAc-, Manal -6(Manal -3)Manal -6(Neu5 Aca2- 3Gaip 1 -4(Fuca 1 -3)GlcN AcP 1 -2Mana 1 -3)ManP 1 -4GlcNAcP 1 -4GlcN Ac-, Neu5 Aca2-3 Gaip 1 -4GlcNAcP 1 -2Manal -6(GlcNAcP 1 -4)(Neu5 Aca2-3 Gaip 1 - 4GlcNAcP 1 -2Manal -3)ManP 1 -4GlcNAcP 1 -4GlcNAc-, and / or Neu5 Aca2-3 Gaip 1 - 4GlcNAcP 1 -3 Gaip 1 -4GlcNAcP 1 -2Manal -6(Neu5 Aca2-3 Gaip 1 -4GlcNAcP 1 -3Gaip 1 - 4GlcNAcpi-2Manal-3)Manpi-4GlcNAcpi-4GlcNAc. In some aspects, the glycan comprises one or more glycan types, such as GSL, HMO, oligosaccharides, complex N-glycan, hybrid N-glycan, bisecting N-glycan, blood group and Lewis antigens, and LacNAc-extended N-glycan. In some aspects, the glycan comprises one or more of GM1, GM2, GDla, 3'-Sialyllactose. 3'-Sialylgalactose (GM4), GTla, 3’-a-Sialyl-N- acetyllactosamine, 3 ’-Sialyl Lewis X, 6’-a-Sialyl-N-acetyllactosamine, and Disialyllacto-N-tetraose (DSLNT).

39. The method of claim 37 or claim 38, wherein the glycosylation feature comprises Neu5Aca2-3Gaip!-3GalNAcpi-4(Neu5Aca2-3)Gaip 1-4G1C, Neu5Aca2-3Gaip 1- 4Glc, and / or Neu5Aca2-3Gaip.

40. The method of claim 39, wherein the glycosylation feature comprises an N- acetylglucosamine (GlcNAc) residue on a non-reducing end of an oligosaccharide.

41. The method of any one of claims 36-40, wherein the virus is an Rhabdoviridae.13057068077.4Attorney Docket No. 047162-7515WO1(02827)Filvoviridae, Flaviviridae, Bunyaviridae, Paramyxoviridae, Retroviridae, Orthomyxoviridae. a Coronaviridae, and / or a Herpesviridae family virus.

42. The method of any one of claims 36-41, wherein the virus is HIV, influenza, encephalitis, Hantaan virus, coronavirus, RSV, vesicular stomatitis virus (VSV), herpesvirus, Zika virus, Dengue virus, rabies, Ebola, cytomegalovirus (CMV), or any combination thereof.

43. The method of claim 42, wherein the coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), HCov 229E, HCoV HKU1, HCoV NL63, or HCoV OC43.

44. The method of claim 42, wherein the herpesvirus is HSV-1 or HSV-2.

45. The method of claim 42, wherein the influenza is H1N1.

46. The method of any one of claims 36-45, wherein the subject is further administered a second compound suitable for treating, preventing and / or ameliorating infection by the virus.

47. The method of any one of claims 36-46, wherein the subject is a mammal.

48. The method of any one of claims 36-47, wherein the subject is a human.13157068077.4

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