Anti-trop2 antibodies, compositions comprising Anti-trop2 antibodies and methods of making and using Anti-trop2 antibodies

Abstract

The present disclosure relates to antibodies and antibody conjugates that selectively bind to TROP2 and its isoforms and homologs, and compositions comprising the antibodies and antibody conjugates. Also provided are methods of using the antibodies and compositions, such as therapeutic and diagnostic methods.

Description

Attorney Docket No.108843.00551 SU-0450WO ANTI-TROP2 ANTIBODIES, COMPOSITIONS COMPRISING ANTI-TROP2 ANTIBODIES AND METHODS OF MAKING AND USING ANTI-TROP2 ANTIBODIES CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of, and priority to, U.S. Provisional Application No.63 / 653,440, filed May 30, 2024. The entire contents of the above-identified applications are hereby fully incorporated herein by reference. FIELD OF THE INVENTION

[0002] The present disclosure generally relates to antibodies and antibody conjugates with binding specificity for Trophoblast cell surface antigen 2 (TROP2) and compositions comprising the antibodies or antibody conjugates, including pharmaceutical compositions, diagnostic compositions, and kits. Also provided are methods of making anti-TROP2 antibodies and antibody conjugates, and methods of using anti-TROP2 antibodies and antibody conjugates, for example, for therapeutic purposes, diagnostic purposes, and research purposes. BACKGROUND

[0003] TROP2, also known as tumor-associated calcium signal transducer 2 (TACSTD2), is a cell surface protein that is a regulator of calcium signal transduction, and also plays an important role in tumor cell proliferation, apoptosis, and invasion, thereby impacting the prognosis and treatment of cancer patients. An exemplary TROP protein may include hydrophobic precursor peptide, an extracellular domain, a transmembrane domain, and a cytoplasmic tail. TROP2 is expressed in many normal tissues and also overexpressed in various types of tumors. A number of candidate therapeutics that target TROP2 are under development, and at least one (e.g., sacituzumab govitecan) is approved for treatment in the US and EU. Thus, TROP2 is a promising target in cancer treatment and diagnosis.

[0004] There is a need for improved therapeutics and methods of targeting and / or modulating the activity of TROP2 in treating and diagnosing diseases such as cancers. SUMMARY

[0005] Provided herein are antibodies that selectively bind TROP2. In some embodiments, the antibodies bind human TROP2. In some embodiments, the antibodies also bind homologs of human TROP2. In some embodiments, the antibodies bind cynomolgus monkey TROP2. In some embodiments, the antibodies also bind homologs of cynomolgus monkey TROP2. In some 1 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO embodiments, the antibodies bind murine TROP2. In some embodiments, the antibodies also bind homologs of murine TROP2.

[0006] In some embodiments, the antibodies comprise, consist essentially of, or consist of, an illustrative CDR, framework, VH, or VL, or combination thereof, sequence provided in this disclosure, or a variant thereof. In some aspects, the variant is a variant with one or more conservative amino acid substitutions. In some aspects, the variant has sequence identity to the illustrative sequence or sequences. In some embodiments, provided herein are conjugates of the antibodies.

[0007] Also provided are compositions and kits comprising the antibodies or antibody conjugates described herein. In some embodiments, the compositions are pharmaceutical compositions. Any suitable pharmaceutical composition may be used. In some embodiments, the pharmaceutical composition is a composition for parenteral administration.

[0008] This disclosure also provides methods of using the anti-TROP2 antibodies or antibody conjugates provided herein. In some embodiments, the methods are methods of treatment. In some embodiments, the methods are diagnostic methods. In some embodiments, the methods are analytical methods. In some embodiments, the methods are methods of purifying and / or quantifying TROP2.

[0009] In some embodiments, the antibodies or antibody conjugates are used to treat a disease or condition. In some aspects, the disease or condition is selected from a cancer, autoimmune disease, and infection.

[0010] These and other embodiments along with many of its features are described in more detail in conjunction with the text below and attached figures. BRIEF DESCRIPTION OF THE FIGURES

[0011] FIG.1 provides a comparison of the Kabat and Chothia numbering systems for CDR- H1. Adapted from Martin A.C.R. (2010). Protein Sequence and Structure Analysis of Antibody Variable Domains. In R. Kontermann & S. Dübel (Eds.), Antibody Engineering vol.2 (pp.33- 51). Springer-Verlag, Berlin Heidelberg.

[0012] FIG.2 provides alignments of the VH sequences of SRP1748 (SEQ ID NOs: 3789- 3870) for the antibodies provided herein. CDRs according to Chothia are boxed, and CDRs according to Kabat are shaded.

[0013] FIG. 3 provides alignments of the VH sequences of SRP2292-2293 (SEQ ID NOs: 3871-4046) for the antibodies provided herein. CDRs according to Chothia are boxed, and CDRs according to Kabat are shaded. 2 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0014] FIG.4 provides alignments of the VHsequences of SRP2316 (SEQ ID NOs: 4382- 4396) for the antibodies provided herein. CDRs according to Chothia are boxed, and CDRs according to Kabat are shaded.

[0015] FIG.5 provides alignments of the VHsequences of SRP3454 (SEQ ID NOs: 4397- 4402) for the antibodies provided herein. CDRs according to Chothia are boxed, and CDRs according to Kabat are shaded.

[0016] FIG.6 provides alignments of the VHsequences of SRP2333 (SEQ ID NOs: 4403- 4435) for the antibodies provided herein. CDRs according to Chothia are boxed, and CDRs according to Kabat are shaded.

[0017] FIG.7 provides alignments of the VHsequences of SRP1925 (SEQ ID NOs: 4436- 4462) for the antibodies provided herein. CDRs according to Chothia are boxed, and CDRs according to Kabat are shaded.

[0018] FIG.8 provides alignments of the VH sequences of SRP1966 (SEQ ID NOs: 4463- 4491) for the antibodies provided herein. CDRs according to Chothia are boxed, and CDRs according to Kabat are shaded.

[0019] FIG.9 provides alignments of the VL sequences of SRP2333 (SEQ ID NOs: 4635- 4667) for the antibodies provided herein. CDRs are boxed.

[0020] FIG.10 provides alignments of the VLsequences of SRP1925 (SEQ ID NOs: 4668- 4694) for the antibodies provided herein. CDRs are boxed.

[0021] FIG.11 provides alignments of the VLsequences of SRP1966 (SEQ ID NOs: 4695- 4723) for the antibodies provided herein. CDRs are boxed. DETAILED DESCRIPTION OF THE EMBODIMENTS 1. Definitions

[0022] Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a difference over what is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodologies by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. As appropriate, procedures involving the use of 3 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO commercially available kits and reagents are generally carried out in accordance with manufacturer-defined protocols and conditions unless otherwise noted.

[0023] As used herein, the singular forms “a,” “an,” and “the” include the plural referents unless the context clearly indicates otherwise.

[0024] The term “about” indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ± 10%, ± 5%, or ± 1%. In certain embodiments, the term “about” indicates the designated value ± one standard deviation of that value.

[0025] The term “combinations thereof” includes every possible combination of elements to which the term refers to. For example, a sentence stating that “if α2is A, then α3is not D; α5is not S; or α6is not S; or combinations thereof” includes the following combinations when α2is A: (1) α3 is not D; (2) α5 is not S; (3) α6 is not S; (4) α3 is not D; α5 is not S; and α6 is not S; (5) α3 is not D and α5 is not S; (6) α3 is not D and α6 is not S; and (7) α5 is not S and α6 is not S. In another example, if a set of antibody heavy chains comprise {A, B, and C} and a set of antibody light chains comprise {D, E, and F} then the potential combinations of heavy and light chains comprise the set of {AD, AE, AF, BD, BE, BF, CD, CE, and CF}.

[0026] The term “TROP2” refers to, unless specified otherwise, any variants, isoforms and species homologs of human Trophoblast cell surface antigen 2 (TROP2) that are naturally expressed by cells, or that are expressed by cells transfected with a TROP2 or TROP2 gene. TROP2 proteins include, for example, human TROP2 (SEQ ID NO: 1). In some embodiments, TROP2 proteins include cynomolgus monkey TROP2 (SEQ ID NO: 2). In some embodiments, TROP2 proteins include murine TROP2 (SEQ ID NO: 3).

[0027] The term “immunoglobulin” refers to a class of structurally related proteins generally comprising two pairs of polypeptide chains: one pair of light (L) chains and one pair of heavy (H) chains. In an “intact immunoglobulin,” all four of these chains are interconnected by disulfide bonds. The structure of immunoglobulins has been well characterized. See, e.g., Paul, Fundamental Immunology 7th ed., Ch. 5 (2013) Lippincott Williams & Wilkins, Philadelphia, PA. Briefly, each heavy chain typically comprises a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region typically comprises three domains, abbreviated CH1, CH2, and CH3. Each light chain typically comprises a light chain variable region (VL) and a light chain constant region. The light chain constant region typically comprises one domain, abbreviated CL.

[0028] The term “antibody” describes a type of immunoglobulin molecule and is used herein in its broadest sense. An antibody specifically includes intact antibodies (e.g., intact 4 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO immunoglobulins), and antibody fragments. Antibodies comprise at least one antigen-binding domain. One example of an antigen-binding domain is an antigen binding domain formed by a VH-VL dimer. A “TROP2 antibody,” “anti-TROP2 antibody,” “TROP2 Ab,” “TROP2-specific antibody,” “anti-TROP2 Ab,” “TROP2 antibody,” “anti-TROP2 antibody,” “TROP2 Ab,” “TROP2-specific antibody,” or “anti-TROP2 Ab” is an antibody, as described herein, which binds specifically to TROP2. In some embodiments, the antibody binds the extracellular domain of TROP2. As used herein, unless otherwise specified, an antibody may also comprise an “antibody fragment” as defined herein.

[0029] The VH and VL regions may be further subdivided into regions of hypervariability (“hypervariable regions (HVRs)” also called “complementarity determining regions” (CDRs)) interspersed with regions that are more conserved. The more conserved regions are called framework regions (FRs). Each VH and VL generally comprises three CDRs and four FRs, arranged in the following order (from N-terminus to C-terminus): FR1 - CDR1 - FR2 - CDR2 - FR3 - CDR3 - FR4. The CDRs are involved in antigen binding, and influence antigen specificity and binding affinity of the antibody. See Kabat et al., Sequences of Proteins of Immunological Interest 5th ed. (1991) Public Health Service, National Institutes of Health, Bethesda, MD, incorporated by reference in its entirety.

[0030] The light chain from any vertebrate species can be assigned to one of two types, called kappa and lambda, based on the sequence of the constant domain.

[0031] The heavy chain from any vertebrate species can be assigned to one of five different classes (or isotypes): IgA, IgD, IgE, IgG, and IgM. These classes are also designated α, δ, ε, γ, and µ, respectively. The IgG and IgA classes are further divided into subclasses on the basis of differences in sequence and function. Humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.

[0032] The amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol.262:732-745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Plückthun, J. Mol. Biol., 2001, 309:657-70 (“AHo” numbering scheme), each of which is incorporated by reference in its entirety.

[0033] Table 1A provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is provided using both the Kabat and Chothia numbering schemes. Table 1B provides the 5 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO positions of LFR1, CDR-L1, LFR2, CDR-L2, LFR3, CDR-L3, LFR4, HFR1, CDR-H1, HFR2, CDR-H2, HFR3, CDR-H3, and HFR4 as identified by the Kabat and Chothia schemes. Table 1A. Residues in CDRs according to Kabat and Chothia numbering schemes. CDR Kabat Chothia * The C-terminus of- , g g convention, varies between H32 and H34, depending on the length of the CDR, as illustrated in FIG.1. Table 1B. Residues in CDRs according to Kabat and Chothia numbering schemes.03- 3 03- 3 * The C-terminus of CDR-H1, when numbered using the Kabat numbering convention, varies between H32 and H34, depending on the length of the CDR, as illustrated in FIG.1.

[0034] Unless otherwise specified, the numbering scheme used for identification of a particular CDR herein is the Kabat / Chothia numbering scheme. Where the residues encompassed by these two numbering schemes diverge (e.g., CDR-H1 and / or CDR-H2), the numbering scheme is specified as either Kabat or Chothia. For convenience, CDR-H3 is sometimes referred to herein as either Kabat or Chothia. However, this is not intended to imply 6 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO differences in sequence where they do not exist, and one of skill in the art can readily confirm whether the sequences are the same or different by examining the sequences.

[0035] CDRs may be assigned, for example, using antibody numbering software, such as Abnum, available atwww.bioinf.org.uk / abs / abnum, and described in Abhinandan and Martin, Immunology, 2008, 45:3832-3839, incorporated by reference in its entirety.

[0036] The “framework region” refers to a subdivision of the variable region acting as a scaffold for the CDRs. Unless specified otherwise, there are four framework regions for each heavy chain and light chain, wherein each CDRs is flanked by one framework region. Unless stated otherwise, the numbering of the framework region is based on using either the Kabat or Chothia numbering scheme. Table 1B provides the positions of framework positions LFR1, LFR2, LFR3, LFR4, HFR1, HFR2, HFR3, and HFR4 as identified by the Kabat and Chothia schemes.

[0037] The “EU numbering scheme” is generally used when referring to a residue in an antibody heavy chain constant region (e.g., as reported in Kabat et al., supra). Unless stated otherwise, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein.

[0038] An “antibody fragment” comprises a portion of an intact antibody, such as the antigen binding or variable region of an intact antibody. Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab’)2 fragments, Fab’ fragments, scFv (sFv) fragments, and scFv- Fc fragments.

[0039] “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain.

[0040] “Fab” fragments comprise, in addition to the heavy and light chain variable domains, the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab fragments may be generated, for example, by recombinant methods or by papain digestion of a full-length antibody.

[0041] “F(ab’)2” fragments contain two Fab’ fragments joined, near the hinge region, by disulfide bonds. F(ab’)2fragments may be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody. The F(ab’) fragments can be dissociated, for example, by treatment with β-mercaptoethanol.

[0042] “Single-chain Fv” or “sFv” or “scFv” antibody fragments comprise a VHdomain and a VL domain in a single polypeptide chain. The VH and VL are generally linked by a peptide linker. See Plückthun A. (1994). Antibodies from Escherichia coli. In Rosenberg M. & Moore G.P. (Eds.), The Pharmacology of Monoclonal Antibodies vol. 113 (pp. 269-315). Springer- 7 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Verlag, New York, incorporated by reference in its entirety. In some embodiments, the linker is SEQ ID NO: 5221. In some embodiments, the linker is SEQ ID NO: 5222. In some embodiments, the linker is SEQ ID NO: 5223.

[0043] “scFv-Fc” fragments comprise an scFv attached to an Fc domain. For example, an Fc domain may be attached to the C-terminus of the scFv. The Fc domain may follow the VH or VL, depending on the orientation of the variable domains in the scFv (i.e., VH-VL or VL-VH). Any suitable Fc domain known in the art or described herein may be used. In some cases, the Fc domain comprises an IgG1 Fc domain. In some embodiments, the IgG1 Fc domain comprises SEQ ID NO: 5225, or a portion thereof. SEQ ID NO: 5225 provides the sequence of CH1, CH2, and CH3of the human IgG1 constant region.

[0044] “Single chain Fab” refers to a polypeptide comprising a light chain variable domain, a light chain constant domain, and a heavy chain variable domain. In some embodiments, a single chain Fab comprises or is a “VLCL-VH” fragment comprising comprise VL, CL, and VH domains in a single polypeptide chain. The CLand VHdomains are generally linked by a peptide linker. In some embodiments, the linker is SEQ ID NO: 5224.

[0045] The term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies. A population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts. A monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies. For example, the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further altered, for example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and / or to reduce its immunogenicity in a subject.

[0046] The term “chimeric antibody” refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0047] “Humanized” forms of non-human antibodies are chimeric antibodies that contain minimal sequence derived from the non-human antibody. A humanized antibody is generally a human immunoglobulin (recipient antibody) in which residues from one or more CDRs are replaced by residues from one or more CDRs of a non-human antibody (donor antibody). The donor antibody can be any suitable non-human antibody, such as a mouse, rat, rabbit, chicken, 8 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO or non-human primate antibody having a desired specificity, affinity, or biological effect. In some instances, selected framework region residues of the recipient antibody are replaced by the corresponding framework region residues from the donor antibody. Humanized antibodies may also comprise residues that are not found in either the recipient antibody or the donor antibody. Such modifications may be made to further refine antibody function. For further details, see Jones et al., Nature, 1986, 321:522-525; Riechmann et al., Nature, 1988, 332:323-329; and Presta, Curr. Op. Struct. Biol., 1992, 2:593-596, each of which is incorporated by reference in its entirety.

[0048] A “human antibody” is one which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies.

[0049] An “isolated antibody” is one that has been separated and / or recovered from a component of its natural environment. Components of the natural environment may include enzymes, hormones, and other proteinaceous or nonproteinaceous materials. In some embodiments, an isolated antibody is purified to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence, for example by use of a spinning cup sequenator. In some embodiments, an isolated antibody is purified to homogeneity by gel electrophoresis (e.g., SDS-PAGE) under reducing or nonreducing conditions, with detection by Coomassie blue or silver stain. An isolated antibody includes an antibody in situ within recombinant cells, since at least one component of the antibody’s natural environment is not present. In some aspects, an isolated antibody is prepared by at least one purification step.

[0050] In some embodiments, an isolated antibody is purified to at least 80%, 85%, 90%, 95%, or 99% by weight. In some embodiments, an isolated antibody is purified to at least 80%, 85%, 90%, 95%, or 99% by volume. In some embodiments, an isolated antibody is provided as a solution comprising at least 85%, 90%, 95%, 98%, 99% to 100% by weight. In some embodiments, an isolated antibody is provided as a solution comprising at least 85%, 90%, 95%, 98%, 99% to 100% by volume.

[0051] “Affinity” refers to the strength of the sum total of non-covalent 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 affinity, which 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 be represented by the dissociation constant 9 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO (KD). Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) technology, such as a Biacore®instrument. In some embodiments, the affinity is determined at 25°C.

[0052] With regard to the binding of an antibody to a target molecule, the terms “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule. Specific binding can also be determined by competition with a control molecule that mimics the antibody binding site on the target. In that case, specific binding is indicated if the binding of the antibody to the target is competitively inhibited by the control molecule.

[0053] The term “kd” (sec-1), as used herein, refers to the dissociation rate constant of a particular antibody-antigen interaction. This value is also referred to as the koff value.

[0054] The term “ka” (M-1×sec-1), as used herein, refers to the association rate constant of a particular antibody-antigen interaction. This value is also referred to as the konvalue.

[0055] The term “KD” (M), as used herein, refers to the dissociation equilibrium constant of a particular antibody-antigen interaction. KD = kd / ka.

[0056] The term “KA” (M-1), as used herein, refers to the association equilibrium constant of a particular antibody-antigen interaction. KA= ka / kd.

[0057] An “affinity matured” antibody is one with one or more alterations in one or more CDRs or FRs that result in an improvement in the affinity of the antibody for its antigen, compared to a parent antibody which does not possess the alteration(s). In one embodiment, an affinity matured antibody has nanomolar or picomolar affinity for the target antigen. Affinity matured antibodies may be produced using a variety of methods known in the art. For example, Marks et al. (Bio / Technology, 1992, 10:779-783, incorporated by reference in its entirety) describes affinity maturation by VHand VLdomain shuffling. Random mutagenesis of CDR and / or framework residues is described by, for example, Barbas et al. (Proc. Nat. Acad. Sci. U.S.A., 1994, 91:3809-3813); Schier et al., Gene, 1995, 169:147-155; Yelton et al., J. Immunol., 1995, 155:1994-2004; Jackson et al., J. Immunol., 1995, 154:3310-33199; and Hawkins et al, J. Mol. Biol., 1992, 226:889-896, each of which is incorporated by reference in its entirety.

[0058] When used herein in the context of two or more antibodies, the term “competes with” or “cross-competes with” indicates that the two or more antibodies compete for binding to an 10 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO antigen (e.g., TROP2). In one exemplary assay, TROP2 is coated on a plate and allowed to bind a first antibody, after which a second, labeled antibody is added. If the presence of the first antibody reduces binding of the second antibody, then the antibodies compete. In another exemplary assay, a first antibody is coated on a plate and allowed to bind the antigen, and then the second antibody is added. The term “competes with” also includes combinations of antibodies where one antibody reduces binding of another antibody, but where no competition is observed when the antibodies are added in the reverse order. However, in some embodiments, the first and second antibodies inhibit binding of each other, regardless of the order in which they are added. In some embodiments, one antibody reduces binding of another antibody to its antigen by at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%.

[0059] The term “epitope” means a portion of an antigen capable of specific binding to an antibody. Epitopes frequently consist of surface-accessible amino acid residues and / or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents. An epitope may comprise amino acid residues that are directly involved in the binding, and other amino acid residues, which are not directly involved in the binding. The epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to variants of TROP2 with different point-mutations.

[0060] Percent “identity” between a polypeptide sequence and a reference sequence, is defined as the percentage of amino acid residues in the polypeptide sequence that are identical to the amino acid residues in the reference sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.

[0061] A “conservative substitution” or a “conservative amino acid substitution,” refers to the substitution an amino acid with a chemically or functionally similar amino acid. Conservative substitution tables providing similar amino acids are well known in the art. Polypeptide sequences having such substitutions are known as “conservatively modified variants.” By way 11 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO of example, the groups of amino acids provided in Tables 2-4 are, in some embodiments, considered conservative substitutions for one another. Table 2. Selected groups of amino acids that are considered conservative substitutions for one another, in certain embodiments. Acidic Residues D and E B H Al N Ar Al Al C H N P P S Ve Re FlTable 3. Additional selected groups of amino acids that are considered conservative substitutions for one another, in certain embodiments. G G G G G Group 6 , , and W Table 4. Further selected groups of amino acids that are considered conservative substitutions for one another in certain embodiments G G G G G G GGroup H C and M 12 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0062] Additional conservative substitutions may be found, for example, in Creighton, Proteins: Structures and Molecular Properties 2nd ed. (1993) W. H. Freeman & Co., New York, NY. An antibody generated by making one or more conservative substitutions of amino acid residues in a parent antibody is referred to as a “conservatively modified variant.”

[0063] The term “amino acid” refers to the twenty common naturally occurring amino acids. Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V).

[0064] “Treating” or “treatment” of any disease or disorder refers, in certain embodiments, to ameliorating a disease or disorder that exists in a subject. In another embodiment, “treating” or “treatment” includes ameliorating at least one physical parameter, which may be indiscernible by the subject. In yet another embodiment, “treating” or “treatment” includes modulating the disease or disorder, either physically (e.g., stabilization of a discernible symptom) or physiologically (e.g., stabilization of a physical parameter) or both. In yet another embodiment, “treating” or “treatment” includes delaying or preventing the onset of the disease or disorder.

[0065] As used herein, the term “therapeutically effective amount” or “effective amount” refers to an amount of an antibody or composition that when administered to a subject is effective to treat a disease or disorder.

[0066] As used herein, the term “subject” means a mammalian subject. Exemplary subjects include, but are not limited to humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, avians, goats, and sheep. In certain embodiments, the subject is a human. In some embodiments, the subject has a disease that can be treated or diagnosed with an antibody provided herein. In some embodiments, the disease is gastric carcinoma, colorectal carcinoma, renal cell carcinoma, cervical carcinoma, non-small cell lung carcinoma, ovarian cancer, prostate cancer, and / or a cancer of epithelial origin. 2. Antibodies

[0067] Provided herein are antibodies that selectively bind TROP2. In some aspects, the antibodies selectively bind to human TROP2. In some aspects, the antibodies selectively bind to the extracellular domain of human TROP2.

[0068] In some embodiments, the antibody comprises three heavy chain CDRs from a VH sequence selected from SEQ ID NOs: 3802, 3984, 4396, and 4459, or variants thereof, and three light chain CDRs from a VLsequence selected from SEQ ID NOs: 4634 and 4691, or variants 13 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO thereof. In some embodiments, the antibody comprises three heavy chain CDRs from a VHsequence selected from SEQ ID NOs: 3789-3801, 3803-3983, 3985-4046, 4382-4395, 4397- 4458, and 4460-4491, or variants thereof, and three light chain CDRs from a VL sequence selected from SEQ ID NOs: 4634-4690, and 4692-4723, or variants thereof.

[0069] In some embodiments, the antibody binds to a homolog of human TROP2. In some aspects, the antibody binds to a homolog of human TROP2 from a species selected from monkeys, mice, dogs, cats, rats, cows, horses, goats, and sheep. In some aspects, the homolog is a cynomolgus monkey homolog. In some aspects, the homolog is a mouse or murine analog.

[0070] In some embodiments, the antibody comprises a light chain. In some aspects, the light chain is a kappa light chain. In some aspects, the light chain is a lambda light chain.

[0071] In some embodiments, the antibody comprises a heavy chain. In some aspects, the heavy chain is an IgA. In some aspects, the heavy chain is an IgD. In some aspects, the heavy chain is an IgE. In some aspects, the heavy chain is an IgG. In some aspects, the heavy chain is an IgM. In some aspects, the heavy chain is an IgG1. In some aspects, the heavy chain is an IgG2. In some aspects, the heavy chain is an IgG3. In some aspects, the heavy chain is an IgG4. In some aspects, the heavy chain is an IgA1. In some aspects, the heavy chain is an IgA2.

[0072] In some embodiments, the antibody is an antibody fragment. In some aspects, the antibody fragment is an Fv fragment. In some aspects, the antibody fragment is a Fab fragment. In some aspects, the antibody fragment is a F(ab’)2 fragment. In some aspects, the antibody fragment is a Fab’ fragment. In some aspects, the antibody fragment is an scFv (sFv) fragment. In some aspects, the antibody fragment is an scFv-Fc fragment. In some aspects, the antibody fragment is a single chain Fab (e.g., comprising VLCL-VH) fragment.

[0073] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a polyclonal antibody.

[0074] In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is a human antibody.

[0075] In some embodiments, the antibody is an affinity matured antibody. In some aspects, the antibody is an affinity matured antibody derived from an illustrative sequence provided in this disclosure.

[0076] The antibodies provided herein may be useful for the treatment of a variety of diseases and conditions including cancers. In some embodiments, the antibodies provided herein may be useful for the treatment of cancers of solid tumors. For example, the antibodies provided herein can be useful for the treatment of colorectal cancer. 2.1. Kabat CDR-H1 + Kabat CDR-H2 + Kabat CDR-H3 14 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0077] In some embodiments, the antibody comprises a VHsequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 707-964 and 1300-1409, a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 2113-2370 and 2706- 2815, and a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 2816-3073 and 3409-3518. In some aspects, the Kabat CDR-H1 sequence, Kabat CDR-H2 sequence, and Kabat CDR-H3 sequence are all from a single illustrative VH sequence provided in this disclosure. For example, in some aspects, the Kabat CDR-H1, Kabat CDR-H2, and Kabat CDR-H3 are all from a single illustrative VH sequence selected from SEQ ID NOs: 3789-4046 and 4382-4491.

[0078] In some embodiments, the antibody comprises three Kabat HC CDRs selected from the group consisting of SEQ ID NOs: 707 / 2113 / 2816; 708 / 2114 / 2817; 709 / 2115 / 2818; 710 / 2116 / 2819; 711 / 2117 / 2820; 712 / 2118 / 2821; 713 / 2119 / 2822; 714 / 2120 / 2823; 715 / 2121 / 2824; 716 / 2122 / 2825; 717 / 2123 / 2826; 718 / 2124 / 2827; 719 / 2125 / 2828; 720 / 2126 / 2829; 721 / 2127 / 2830; 722 / 2128 / 2831; 723 / 2129 / 2832; 724 / 2130 / 2833; 725 / 2131 / 2834; 726 / 2132 / 2835; 727 / 2133 / 2836; 728 / 2134 / 2837; 729 / 2135 / 2838; 730 / 2136 / 2839; 731 / 2137 / 2840; 732 / 2138 / 2841; 733 / 2139 / 2842; 734 / 2140 / 2843; 735 / 2141 / 2844; 736 / 2142 / 2845; 737 / 2143 / 2846; 738 / 2144 / 2847; 739 / 2145 / 2848; 740 / 2146 / 2849; 741 / 2147 / 2850; 742 / 2148 / 2851; 743 / 2149 / 2852; 744 / 2150 / 2853; 745 / 2151 / 2854; 746 / 2152 / 2855; 747 / 2153 / 2856; 748 / 2154 / 2857; 749 / 2155 / 2858; 750 / 2156 / 2859; 751 / 2157 / 2860; 752 / 2158 / 2861; 753 / 2159 / 2862; 754 / 2160 / 2863; 755 / 2161 / 2864; 756 / 2162 / 2865; 757 / 2163 / 2866; 758 / 2164 / 2867; 759 / 2165 / 2868; 760 / 2166 / 2869; 761 / 2167 / 2870; 762 / 2168 / 2871; 763 / 2169 / 2872; 764 / 2170 / 2873; 765 / 2171 / 2874; 766 / 2172 / 2875; 767 / 2173 / 2876; 768 / 2174 / 2877; 769 / 2175 / 2878; 770 / 2176 / 2879; 771 / 2177 / 2880; 772 / 2178 / 2881; 773 / 2179 / 2882; 774 / 2180 / 2883; 775 / 2181 / 2884; 776 / 2182 / 2885; 777 / 2183 / 2886; 778 / 2184 / 2887; 779 / 2185 / 2888; 780 / 2186 / 2889; 781 / 2187 / 2890; 782 / 2188 / 2891; 783 / 2189 / 2892; 784 / 2190 / 2893; 785 / 2191 / 2894; 786 / 2192 / 2895; 787 / 2193 / 2896; 788 / 2194 / 2897; 789 / 2195 / 2898; 790 / 2196 / 2899; 791 / 2197 / 2900; 792 / 2198 / 2901; 793 / 2199 / 2902; 794 / 2200 / 2903; 795 / 2201 / 2904; 796 / 2202 / 2905; 797 / 2203 / 2906; 798 / 2204 / 2907; 799 / 2205 / 2908; 800 / 2206 / 2909; 801 / 2207 / 2910; 802 / 2208 / 2911; 803 / 2209 / 2912; 804 / 2210 / 2913; 805 / 2211 / 2914; 806 / 2212 / 2915; 807 / 2213 / 2916; 808 / 2214 / 2917; 809 / 2215 / 2918; 810 / 2216 / 2919; 811 / 2217 / 2920; 812 / 2218 / 2921; 813 / 2219 / 2922; 814 / 2220 / 2923; 815 / 2221 / 2924; 816 / 2222 / 2925; 817 / 2223 / 2926; 818 / 2224 / 2927; 819 / 2225 / 2928; 15 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 820 / 2226 / 2929; 821 / 2227 / 2930; 822 / 2228 / 2931; 823 / 2229 / 2932; 824 / 2230 / 2933; 825 / 2231 / 2934; 826 / 2232 / 2935; 827 / 2233 / 2936; 828 / 2234 / 2937; 829 / 2235 / 2938; 830 / 2236 / 2939; 831 / 2237 / 2940; 832 / 2238 / 2941; 833 / 2239 / 2942; 834 / 2240 / 2943; 835 / 2241 / 2944; 836 / 2242 / 2945; 837 / 2243 / 2946; 838 / 2244 / 2947; 839 / 2245 / 2948; 840 / 2246 / 2949; 841 / 2247 / 2950; 842 / 2248 / 2951; 843 / 2249 / 2952; 844 / 2250 / 2953; 845 / 2251 / 2954; 846 / 2252 / 2955; 847 / 2253 / 2956; 848 / 2254 / 2957; 849 / 2255 / 2958; 850 / 2256 / 2959; 851 / 2257 / 2960; 852 / 2258 / 2961; 853 / 2259 / 2962; 854 / 2260 / 2963; 855 / 2261 / 2964; 856 / 2262 / 2965; 857 / 2263 / 2966; 858 / 2264 / 2967; 859 / 2265 / 2968; 860 / 2266 / 2969; 861 / 2267 / 2970; 862 / 2268 / 2971; 863 / 2269 / 2972; 864 / 2270 / 2973; 865 / 2271 / 2974; 866 / 2272 / 2975; 867 / 2273 / 2976; 868 / 2274 / 2977; 869 / 2275 / 2978; 870 / 2276 / 2979; 871 / 2277 / 2980; 872 / 2278 / 2981; 873 / 2279 / 2982; 874 / 2280 / 2983; 875 / 2281 / 2984; 876 / 2282 / 2985; 877 / 2283 / 2986; 878 / 2284 / 2987; 879 / 2285 / 2988; 880 / 2286 / 2989; 881 / 2287 / 2990; 882 / 2288 / 2991; 883 / 2289 / 2992; 884 / 2290 / 2993; 885 / 2291 / 2994; 886 / 2292 / 2995; 887 / 2293 / 2996; 888 / 2294 / 2997; 889 / 2295 / 2998; 890 / 2296 / 2999; 891 / 2297 / 3000; 892 / 2298 / 3001; 893 / 2299 / 3002; 894 / 2300 / 3003; 895 / 2301 / 3004; 896 / 2302 / 3005; 897 / 2303 / 3006; 898 / 2304 / 3007; 899 / 2305 / 3008; 900 / 2306 / 3009; 901 / 2307 / 3010; 902 / 2308 / 3011; 903 / 2309 / 3012; 904 / 2310 / 3013; 905 / 2311 / 3014; 906 / 2312 / 3015; 907 / 2313 / 3016; 908 / 2314 / 3017; 909 / 2315 / 3018; 910 / 2316 / 3019; 911 / 2317 / 3020; 912 / 2318 / 3021; 913 / 2319 / 3022; 914 / 2320 / 3023; 915 / 2321 / 3024; 916 / 2322 / 3025; 917 / 2323 / 3026; 918 / 2324 / 3027; 919 / 2325 / 3028; 920 / 2326 / 3029; 921 / 2327 / 3030; 922 / 2328 / 3031; 923 / 2329 / 3032; 924 / 2330 / 3033; 925 / 2331 / 3034; 926 / 2332 / 3035; 927 / 2333 / 3036; 928 / 2334 / 3037; 929 / 2335 / 3038; 930 / 2336 / 3039; 931 / 2337 / 3040; 932 / 2338 / 3041; 933 / 2339 / 3042; 934 / 2340 / 3043; 935 / 2341 / 3044; 936 / 2342 / 3045; 937 / 2343 / 3046; 938 / 2344 / 3047; 939 / 2345 / 3048; 940 / 2346 / 3049; 941 / 2347 / 3050; 942 / 2348 / 3051; 943 / 2349 / 3052; 944 / 2350 / 3053; 945 / 2351 / 3054; 946 / 2352 / 3055; 947 / 2353 / 3056; 948 / 2354 / 3057; 949 / 2355 / 3058; 950 / 2356 / 3059; 951 / 2357 / 3060; 952 / 2358 / 3061; 953 / 2359 / 3062; 954 / 2360 / 3063; 955 / 2361 / 3064; 956 / 2362 / 3065; 957 / 2363 / 3066; 958 / 2364 / 3067; 959 / 2365 / 3068; 960 / 2366 / 3069; 961 / 2367 / 3070; 962 / 2368 / 3071; 963 / 2369 / 3072; 964 / 2370 / 3073; 1300 / 2706 / 3409; 1301 / 2707 / 3410; 1302 / 2708 / 3411; 1303 / 2709 / 3412; 1304 / 2710 / 3413; 1305 / 2711 / 3414; 1306 / 2712 / 3415; 1307 / 2713 / 3416; 1308 / 2714 / 3417; 1309 / 2715 / 3418; 1310 / 2716 / 3419; 1311 / 2717 / 3420; 1312 / 2718 / 3421; 1313 / 2719 / 3422; 1314 / 2720 / 3423; 1315 / 2721 / 3424; 1316 / 2722 / 3425; 1317 / 2723 / 3426; 1318 / 2724 / 3427; 1319 / 2725 / 3428; 1320 / 2726 / 3429; 1321 / 2727 / 3430; 1322 / 2728 / 3431; 1323 / 2729 / 3432; 1324 / 2730 / 3433; 16 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 1325 / 2731 / 3434; 1326 / 2732 / 3435; 1327 / 2733 / 3436; 1328 / 2734 / 3437; 1329 / 2735 / 3438; 1330 / 2736 / 3439; 1331 / 2737 / 3440; 1332 / 2738 / 3441; 1333 / 2739 / 3442; 1334 / 2740 / 3443; 1335 / 2741 / 3444; 1336 / 2742 / 3445; 1337 / 2743 / 3446; 1338 / 2744 / 3447; 1339 / 2745 / 3448; 1340 / 2746 / 3449; 1341 / 2747 / 3450; 1342 / 2748 / 3451; 1343 / 2749 / 3452; 1344 / 2750 / 3453; 1345 / 2751 / 3454; 1346 / 2752 / 3455; 1347 / 2753 / 3456; 1348 / 2754 / 3457; 1349 / 2755 / 3458; 1350 / 2756 / 3459; 1351 / 2757 / 3460; 1352 / 2758 / 3461; 1353 / 2759 / 3462; 1354 / 2760 / 3463; 1355 / 2761 / 3464; 1356 / 2762 / 3465; 1357 / 2763 / 3466; 1358 / 2764 / 3467; 1359 / 2765 / 3468; 1360 / 2766 / 3469; 1361 / 2767 / 3470; 1362 / 2768 / 3471; 1363 / 2769 / 3472; 1364 / 2770 / 3473; 1365 / 2771 / 3474; 1366 / 2772 / 3475; 1367 / 2773 / 3476; 1368 / 2774 / 3477; 1369 / 2775 / 3478; 1370 / 2776 / 3479; 1371 / 2777 / 3480; 1372 / 2778 / 3481; 1373 / 2779 / 3482; 1374 / 2780 / 3483; 1375 / 2781 / 3484; 1376 / 2782 / 3485; 1377 / 2783 / 3486; 1378 / 2784 / 3487; 1379 / 2785 / 3488; 1380 / 2786 / 3489; 1381 / 2787 / 3490; 1382 / 2788 / 3491; 1383 / 2789 / 3492; 1384 / 2790 / 3493; 1385 / 2791 / 3494; 1386 / 2792 / 3495; 1387 / 2793 / 3496; 1388 / 2794 / 3497; 1389 / 2795 / 3498; 1390 / 2796 / 3499; 1391 / 2797 / 3500; 1392 / 2798 / 3501; 1393 / 2799 / 3502; 1394 / 2800 / 3503; 1395 / 2801 / 3504; 1396 / 2802 / 3505; 1397 / 2803 / 3506; 1398 / 2804 / 3507; 1399 / 2805 / 3508; 1400 / 2806 / 3509; 1401 / 2807 / 3510; 1402 / 2808 / 3511; 1403 / 2809 / 3512; 1404 / 2810 / 3513; 1405 / 2811 / 3514; 1406 / 2812 / 3515; 1407 / 2813 / 3516; 1408 / 2814 / 3517; and 1409 / 2815 / 3518. 2.2. Variants of VHSequences Comprising Illustrative Kabat CDRs

[0079] In some embodiments, the VH sequences provided herein comprise a variant of an illustrative Kabat CDR-H3, CDR-H2, and / or CDR-H1 sequence provided in this disclosure.

[0080] In some aspects, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H3 sequence provided in this disclosure. In some aspects, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative Kabat CDR-H3 sequences provided in this disclosure. In some aspects, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0081] In some aspects, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H2 sequence provided in this disclosure. In some aspects, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative Kabat CDR-H2 sequences provided in this disclosure. In some 17 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO aspects, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0082] In some aspects, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H1 sequence provided in this disclosure. In some aspects, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative Kabat CDR-H1 sequences provided in this disclosure. In some aspects, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 2.3. Chothia CDR-H1 + Chothia CDR-H2 + Chothia CDR-H3

[0083] In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 4-261 and 597-706, a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 1410-1667 and 2003-2112, and a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 2816-3073 and 3409-3518. In some aspects, the Chothia CDR-H1 sequence, Chothia CDR-H2 sequence, and Chothia CDR-H3 sequence are all from a single illustrative VH sequence provided in this disclosure. For example, in some aspects, the Chothia CDR-H1, Chothia CDR-H2, and Chothia CDR-H3 are all from a single illustrative VH sequence selected from SEQ ID NOs: 3789-4046 and 4382-4491.

[0084] In some embodiments, the isolated antibody comprises three Chothia HC CDRs selected from the group consisting of SEQ ID NOs: 4 / 1410 / 2816; 5 / 1411 / 2817; 6 / 1412 / 2818; 7 / 1413 / 2819; 8 / 1414 / 2820; 9 / 1415 / 2821; 10 / 1416 / 2822; 11 / 1417 / 2823; 12 / 1418 / 2824; 13 / 1419 / 2825; 14 / 1420 / 2826; 15 / 1421 / 2827; 16 / 1422 / 2828; 17 / 1423 / 2829; 18 / 1424 / 2830; 19 / 1425 / 2831; 20 / 1426 / 2832; 21 / 1427 / 2833; 22 / 1428 / 2834; 23 / 1429 / 2835; 24 / 1430 / 2836; 25 / 1431 / 2837; 26 / 1432 / 2838; 27 / 1433 / 2839; 28 / 1434 / 2840; 29 / 1435 / 2841; 30 / 1436 / 2842; 31 / 1437 / 2843; 32 / 1438 / 2844; 33 / 1439 / 2845; 34 / 1440 / 2846; 35 / 1441 / 2847; 36 / 1442 / 2848; 37 / 1443 / 2849; 38 / 1444 / 2850; 39 / 1445 / 2851; 40 / 1446 / 2852; 41 / 1447 / 2853; 42 / 1448 / 2854; 43 / 1449 / 2855; 44 / 1450 / 2856; 45 / 1451 / 2857; 46 / 1452 / 2858; 47 / 1453 / 2859; 48 / 1454 / 2860; 49 / 1455 / 2861; 50 / 1456 / 2862; 51 / 1457 / 2863; 52 / 1458 / 2864; 53 / 1459 / 2865; 54 / 1460 / 2866; 18 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 55 / 1461 / 2867; 56 / 1462 / 2868; 57 / 1463 / 2869; 58 / 1464 / 2870; 59 / 1465 / 2871; 60 / 1466 / 2872; 61 / 1467 / 2873; 62 / 1468 / 2874; 63 / 1469 / 2875; 64 / 1470 / 2876; 65 / 1471 / 2877; 66 / 1472 / 2878; 67 / 1473 / 2879; 68 / 1474 / 2880; 69 / 1475 / 2881; 70 / 1476 / 2882; 71 / 1477 / 2883; 72 / 1478 / 2884; 73 / 1479 / 2885; 74 / 1480 / 2886; 75 / 1481 / 2887; 76 / 1482 / 2888; 77 / 1483 / 2889; 78 / 1484 / 2890; 79 / 1485 / 2891; 80 / 1486 / 2892; 81 / 1487 / 2893; 82 / 1488 / 2894; 83 / 1489 / 2895; 84 / 1490 / 2896; 85 / 1491 / 2897; 86 / 1492 / 2898; 87 / 1493 / 2899; 88 / 1494 / 2900; 89 / 1495 / 2901; 90 / 1496 / 2902; 91 / 1497 / 2903; 92 / 1498 / 2904; 93 / 1499 / 2905; 94 / 1500 / 2906; 95 / 1501 / 2907; 96 / 1502 / 2908; 97 / 1503 / 2909; 98 / 1504 / 2910; 99 / 1505 / 2911; 100 / 1506 / 2912; 101 / 1507 / 2913; 102 / 1508 / 2914; 103 / 1509 / 2915; 104 / 1510 / 2916; 105 / 1511 / 2917; 106 / 1512 / 2918; 107 / 1513 / 2919; 108 / 1514 / 2920; 109 / 1515 / 2921; 110 / 1516 / 2922; 111 / 1517 / 2923; 112 / 1518 / 2924; 113 / 1519 / 2925; 114 / 1520 / 2926; 115 / 1521 / 2927; 116 / 1522 / 2928; 117 / 1523 / 2929; 118 / 1524 / 2930; 119 / 1525 / 2931; 120 / 1526 / 2932; 121 / 1527 / 2933; 122 / 1528 / 2934; 123 / 1529 / 2935; 124 / 1530 / 2936; 125 / 1531 / 2937; 126 / 1532 / 2938; 127 / 1533 / 2939; 128 / 1534 / 2940; 129 / 1535 / 2941; 130 / 1536 / 2942; 131 / 1537 / 2943; 132 / 1538 / 2944; 133 / 1539 / 2945; 134 / 1540 / 2946; 135 / 1541 / 2947; 136 / 1542 / 2948; 137 / 1543 / 2949; 138 / 1544 / 2950; 139 / 1545 / 2951; 140 / 1546 / 2952; 141 / 1547 / 2953; 142 / 1548 / 2954; 143 / 1549 / 2955; 144 / 1550 / 2956; 145 / 1551 / 2957; 146 / 1552 / 2958; 147 / 1553 / 2959; 148 / 1554 / 2960; 149 / 1555 / 2961; 150 / 1556 / 2962; 151 / 1557 / 2963; 152 / 1558 / 2964; 153 / 1559 / 2965; 154 / 1560 / 2966; 155 / 1561 / 2967; 156 / 1562 / 2968; 157 / 1563 / 2969; 158 / 1564 / 2970; 159 / 1565 / 2971; 160 / 1566 / 2972; 161 / 1567 / 2973; 162 / 1568 / 2974; 163 / 1569 / 2975; 164 / 1570 / 2976; 165 / 1571 / 2977; 166 / 1572 / 2978; 167 / 1573 / 2979; 168 / 1574 / 2980; 169 / 1575 / 2981; 170 / 1576 / 2982; 171 / 1577 / 2983; 172 / 1578 / 2984; 173 / 1579 / 2985; 174 / 1580 / 2986; 175 / 1581 / 2987; 176 / 1582 / 2988; 177 / 1583 / 2989; 178 / 1584 / 2990; 179 / 1585 / 2991; 180 / 1586 / 2992; 181 / 1587 / 2993; 182 / 1588 / 2994; 183 / 1589 / 2995; 184 / 1590 / 2996; 185 / 1591 / 2997; 186 / 1592 / 2998; 187 / 1593 / 2999; 188 / 1594 / 3000; 189 / 1595 / 3001; 190 / 1596 / 3002; 191 / 1597 / 3003; 192 / 1598 / 3004; 193 / 1599 / 3005; 194 / 1600 / 3006; 195 / 1601 / 3007; 196 / 1602 / 3008; 197 / 1603 / 3009; 198 / 1604 / 3010; 199 / 1605 / 3011; 200 / 1606 / 3012; 201 / 1607 / 3013; 202 / 1608 / 3014; 203 / 1609 / 3015; 204 / 1610 / 3016; 205 / 1611 / 3017; 206 / 1612 / 3018; 207 / 1613 / 3019; 208 / 1614 / 3020; 209 / 1615 / 3021; 210 / 1616 / 3022; 211 / 1617 / 3023; 212 / 1618 / 3024; 213 / 1619 / 3025; 214 / 1620 / 3026; 215 / 1621 / 3027; 216 / 1622 / 3028; 217 / 1623 / 3029; 218 / 1624 / 3030; 219 / 1625 / 3031; 220 / 1626 / 3032; 221 / 1627 / 3033; 222 / 1628 / 3034; 223 / 1629 / 3035; 224 / 1630 / 3036; 225 / 1631 / 3037; 226 / 1632 / 3038; 227 / 1633 / 3039; 228 / 1634 / 3040; 229 / 1635 / 3041; 230 / 1636 / 3042; 231 / 1637 / 3043; 232 / 1638 / 3044; 19 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 233 / 1639 / 3045; 234 / 1640 / 3046; 235 / 1641 / 3047; 236 / 1642 / 3048; 237 / 1643 / 3049; 238 / 1644 / 3050; 239 / 1645 / 3051; 240 / 1646 / 3052; 241 / 1647 / 3053; 242 / 1648 / 3054; 243 / 1649 / 3055; 244 / 1650 / 3056; 245 / 1651 / 3057; 246 / 1652 / 3058; 247 / 1653 / 3059; 248 / 1654 / 3060; 249 / 1655 / 3061; 250 / 1656 / 3062; 251 / 1657 / 3063; 252 / 1658 / 3064; 253 / 1659 / 3065; 254 / 1660 / 3066; 255 / 1661 / 3067; 256 / 1662 / 3068; 257 / 1663 / 3069; 258 / 1664 / 3070; 259 / 1665 / 3071; 260 / 1666 / 3072; 261 / 1667 / 3073; 597 / 2003 / 3409; 598 / 2004 / 3410; 599 / 2005 / 3411; 600 / 2006 / 3412; 601 / 2007 / 3413; 602 / 2008 / 3414; 603 / 2009 / 3415; 604 / 2010 / 3416; 605 / 2011 / 3417; 606 / 2012 / 3418; 607 / 2013 / 3419; 608 / 2014 / 3420; 609 / 2015 / 3421; 610 / 2016 / 3422; 611 / 2017 / 3423; 612 / 2018 / 3424; 613 / 2019 / 3425; 614 / 2020 / 3426; 615 / 2021 / 3427; 616 / 2022 / 3428; 617 / 2023 / 3429; 618 / 2024 / 3430; 619 / 2025 / 3431; 620 / 2026 / 3432; 621 / 2027 / 3433; 622 / 2028 / 3434; 623 / 2029 / 3435; 624 / 2030 / 3436; 625 / 2031 / 3437; 626 / 2032 / 3438; 627 / 2033 / 3439; 628 / 2034 / 3440; 629 / 2035 / 3441; 630 / 2036 / 3442; 631 / 2037 / 3443; 632 / 2038 / 3444; 633 / 2039 / 3445; 634 / 2040 / 3446; 635 / 2041 / 3447; 636 / 2042 / 3448; 637 / 2043 / 3449; 638 / 2044 / 3450; 639 / 2045 / 3451; 640 / 2046 / 3452; 641 / 2047 / 3453; 642 / 2048 / 3454; 643 / 2049 / 3455; 644 / 2050 / 3456; 645 / 2051 / 3457; 646 / 2052 / 3458; 647 / 2053 / 3459; 648 / 2054 / 3460; 649 / 2055 / 3461; 650 / 2056 / 3462; 651 / 2057 / 3463; 652 / 2058 / 3464; 653 / 2059 / 3465; 654 / 2060 / 3466; 655 / 2061 / 3467; 656 / 2062 / 3468; 657 / 2063 / 3469; 658 / 2064 / 3470; 659 / 2065 / 3471; 660 / 2066 / 3472; 661 / 2067 / 3473; 662 / 2068 / 3474; 663 / 2069 / 3475; 664 / 2070 / 3476; 665 / 2071 / 3477; 666 / 2072 / 3478; 667 / 2073 / 3479; 668 / 2074 / 3480; 669 / 2075 / 3481; 670 / 2076 / 3482; 671 / 2077 / 3483; 672 / 2078 / 3484; 673 / 2079 / 3485; 674 / 2080 / 3486; 675 / 2081 / 3487; 676 / 2082 / 3488; 677 / 2083 / 3489; 678 / 2084 / 3490; 679 / 2085 / 3491; 680 / 2086 / 3492; 681 / 2087 / 3493; 682 / 2088 / 3494; 683 / 2089 / 3495; 684 / 2090 / 3496; 685 / 2091 / 3497; 686 / 2092 / 3498; 687 / 2093 / 3499; 688 / 2094 / 3500; 689 / 2095 / 3501; 690 / 2096 / 3502; 691 / 2097 / 3503; 692 / 2098 / 3504; 693 / 2099 / 3505; 694 / 2100 / 3506; 695 / 2101 / 3507; 696 / 2102 / 3508; 697 / 2103 / 3509; 698 / 2104 / 3510; 699 / 2105 / 3511; 700 / 2106 / 3512; 701 / 2107 / 3513; 702 / 2108 / 3514; 703 / 2109 / 3515; 704 / 2110 / 3516; 705 / 2111 / 3517; and 706 / 2112 / 3518. 2.4. Variants of VH Sequences Comprising Illustrative Chothia CDRs

[0085] In some embodiments, the VH sequences provided herein comprise a variant of an illustrative Chothia CDR-H3, CDR-H2, and / or CDR-H1 sequence provided in this disclosure.

[0086] In some aspects, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia CDR-H3 sequence provided in this disclosure. In some aspects, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially 20 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative Chothia CDR-H3 sequences provided in this disclosure. In some aspects, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0087] In some aspects, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia CDR-H2 sequence provided in this disclosure. In some aspects, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative Chothia CDR-H2 sequences provided in this disclosure. In some aspects, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0088] In some aspects, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia CDR-H1 sequence provided in this disclosure. In some aspects, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative Chothia CDR-H1 sequences provided in this disclosure. In some aspects, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 2.5. VHSequences

[0089] In some embodiments, the antibody comprises, consists of, or consists essentially of a VHsequence provided in SEQ ID NOs: 3789-4046 and 4382-4491. In some embodiments, the antibody comprises, consists of, or consists essentially of a VHsequence provided in SEQ ID NOs: 4492-4633.

[0090] In some embodiments, the antibody comprises a CDR-H3, a CDR-H2, and a CDR- H1, each consisting of a CDR sequence of a VHhaving the sequence set forth in one of SEQ ID NOS: 3789-4491. In some embodiments, the antibody comprises a CDR-H3, a CDR-H2, a CDR- H1, and framework regions, each consisting of a CDR sequence or framework sequence of a VH having the sequence set forth in one of SEQ ID NOS: 3789-4046 and 4382-4491. In some 21 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO embodiments, the antibody comprises a VHsequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 3789-4046 and 4382-4491.

[0091] In some embodiments, the antibody comprises a VH sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 4492-4633. 2.6. Variants of VH Sequences

[0092] In some embodiments, the VH sequences provided herein comprise, consist of, or consist essentially of a variant of an illustrative VHsequence provided in this disclosure.

[0093] In some aspects, the VH sequence comprises, consists of, or consists essentially of a variant of an illustrative VH sequence provided in this disclosure. In some aspects, the VH sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identity with any of the illustrative VHsequences provided in this disclosure.

[0094] In some embodiments, the VH sequence comprises, consists of, or consists essentially of any of the illustrative VHsequences provided in this disclosure having 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 2.7. CDR-L1 + CDR-L2 + CDR-L3

[0095] In some embodiments, the antibody comprises a VLsequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 3519-3608, a CDR-L2 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 3609-3698, and a CDR-L3 sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 3699-3788. In some aspects, the CDR-L1 sequence, CDR-L2 sequence, and CDR-L3 sequence are all from a single illustrative VL sequence provided in this disclosure. For example, in some aspects, the CDR-L1, CDR-L2, and CDR-L3 are all from a single illustrative VLsequence selected from SEQ ID NOs: 4634-4723.

[0096] In some embodiments, the antibody comprises three LC CDRs selected from the group consisting of SEQ ID NOs: 3519 / 3609 / 3699; 3520 / 3610 / 3700; 3521 / 3611 / 3701; 3522 / 3612 / 3702; 3523 / 3613 / 3703; 3524 / 3614 / 3704; 3525 / 3615 / 3705; 3526 / 3616 / 3706; 3527 / 3617 / 3707; 3528 / 3618 / 3708; 3529 / 3619 / 3709; 3530 / 3620 / 3710; 3531 / 3621 / 3711; 3532 / 3622 / 3712; 3533 / 3623 / 3713; 3534 / 3624 / 3714; 3535 / 3625 / 3715; 3536 / 3626 / 3716; 3537 / 3627 / 3717; 3538 / 3628 / 3718; 3539 / 3629 / 3719; 3540 / 3630 / 3720; 3541 / 3631 / 3721; 22 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 3542 / 3632 / 3722; 3543 / 3633 / 3723; 3544 / 3634 / 3724; 3545 / 3635 / 3725; 3546 / 3636 / 3726; 3547 / 3637 / 3727; 3548 / 3638 / 3728; 3549 / 3639 / 3729; 3550 / 3640 / 3730; 3551 / 3641 / 3731; 3552 / 3642 / 3732; 3553 / 3643 / 3733; 3554 / 3644 / 3734; 3555 / 3645 / 3735; 3556 / 3646 / 3736; 3557 / 3647 / 3737; 3558 / 3648 / 3738; 3559 / 3649 / 3739; 3560 / 3650 / 3740; 3561 / 3651 / 3741; 3562 / 3652 / 3742; 3563 / 3653 / 3743; 3564 / 3654 / 3744; 3565 / 3655 / 3745; 3566 / 3656 / 3746; 3567 / 3657 / 3747; 3568 / 3658 / 3748; 3569 / 3659 / 3749; 3570 / 3660 / 3750; 3571 / 3661 / 3751; 3572 / 3662 / 3752; 3573 / 3663 / 3753; 3574 / 3664 / 3754; 3575 / 3665 / 3755; 3576 / 3666 / 3756; 3577 / 3667 / 3757; 3578 / 3668 / 3758; 3579 / 3669 / 3759; 3580 / 3670 / 3760; 3581 / 3671 / 3761; 3582 / 3672 / 3762; 3583 / 3673 / 3763; 3584 / 3674 / 3764; 3585 / 3675 / 3765; 3586 / 3676 / 3766; 3587 / 3677 / 3767; 3588 / 3678 / 3768; 3589 / 3679 / 3769; 3590 / 3680 / 3770; 3591 / 3681 / 3771; 3592 / 3682 / 3772; 3593 / 3683 / 3773; 3594 / 3684 / 3774; 3595 / 3685 / 3775; 3596 / 3686 / 3776; 3597 / 3687 / 3777; 3598 / 3688 / 3778; 3599 / 3689 / 3779; 3600 / 3690 / 3780; 3601 / 3691 / 3781; 3602 / 3692 / 3782; 3603 / 3693 / 3783; 3604 / 3694 / 3784; 3605 / 3695 / 3785; 3606 / 3696 / 3786; 3607 / 3697 / 3787; and 3608 / 3698 / 3788. 2.8. Variants of VL Sequences Comprising Illustrative CDR-Ls

[0097] In some embodiments, the VL sequences provided herein comprise a variant of an illustrative CDR-L3, CDR-L2, and / or CDR-L1 sequence provided in this disclosure.

[0098] In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L3 sequence provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative CDR-L3 sequences provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0099] In some aspects, the CDR-L2 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L2 sequence provided in this disclosure. In some aspects, the CDR-L2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative CDR-L2 sequences provided in this disclosure. In some aspects, the CDR-L2 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 23 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0100] In some aspects, the CDR-L1 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L1 sequence provided in this disclosure. In some aspects, the CDR-L1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative CDR-L1 sequences provided in this disclosure. In some aspects, the CDR-L1 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 2.9. VL Sequences

[0101] In some embodiments, the antibody comprises, consists of, or consists essentially of a VLsequence provided in SEQ ID NOs: 4634-4723. In some embodiments, the antibody comprises, consists of, or consists essentially of a VL sequence provided in SEQ ID NOs: 4724- 4865.

[0102] In some embodiments, the antibody comprises a CDR-L3, a CDR-L2, and a CDR- L1, each consisting of a CDR sequence of a VL having the sequence set forth in one of SEQ ID NOS: 4634-4723. In some embodiments, the antibody comprises a CDR-L3, a CDR-L2, a CDR- L1, and framework regions, each consisting of a CDR sequence or framework sequence of a VLhaving the sequence set forth in one of SEQ ID NOS: 4634-4723. In some embodiments, the antibody comprises a VL sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 4634-4723.

[0103] In some embodiments, the antibody comprises a VLsequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 4724-4865. 2.10. Variants of VL Sequences

[0104] In some embodiments, the VLsequences provided herein comprise, consist of, or consist essentially of a variant of an illustrative VLsequence provided in this disclosure.

[0105] In some aspects, the VL sequence comprises, consists of, or consists essentially of a variant of an illustrative VLsequence provided in this disclosure. In some aspects, the VLsequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identity with any of the illustrative VL sequences provided in this disclosure.

[0106] In some embodiments, the VLsequence comprises, consists of, or consists essentially of any of the illustrative VL sequences provided in this disclosure having 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 24 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 2.11. VH – VL Pairs

[0107] In some embodiments, the antibody comprises a VHsequence and a VLsequence. In some aspects, the VH sequence is a VH sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3789-4046 or 4382-4491, and the VL sequence is a VL sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4634- 4723.

[0108] In some aspects, the VH - VL pairs are selected from SEQ ID NOs: 3789 and 4634; 3790 and 4634; 3791 and 4634; 3792 and 4634; 3793 and 4634; 3794 and 4634; 3795 and 4634; 3796 and 4634; 3797 and 4634; 3798 and 4634; 3799 and 4634; 3800 and 4634; 3801 and 4634; 3802 and 4634; 3803 and 4634; 3804 and 4634; 3805 and 4634; 3806 and 4634; 3807 and 4634; 3808 and 4634; 3809 and 4634; 3810 and 4634; 3811 and 4634; 3812 and 4634; 3813 and 4634; 3814 and 4634; 3815 and 4634; 3816 and 4634; 3817 and 4634; 3818 and 4634; 3819 and 4634; 3820 and 4634; 3821 and 4634; 3822 and 4634; 3823 and 4634; 3824 and 4634; 3825 and 4634; 3826 and 4634; 3827 and 4634; 3828 and 4634; 3829 and 4634; 3830 and 4634; 3831 and 4634; 3832 and 4634; 3833 and 4634; 3834 and 4634; 3835 and 4634; 3836 and 4634; 3837 and 4634; 3838 and 4634; 3839 and 4634; 3840 and 4634; 3841 and 4634; 3842 and 4634; 3843 and 4634; 3844 and 4634; 3845 and 4634; 3846 and 4634; 3847 and 4634; 3848 and 4634; 3849 and 4634; 3850 and 4634; 3851 and 4634; 3852 and 4634; 3853 and 4634; 3854 and 4634; 3855 and 4634; 3856 and 4634; 3857 and 4634; 3858 and 4634; 3859 and 4634; 3860 and 4634; 3861 and 4634; 3862 and 4634; 3863 and 4634; 3864 and 4634; 3865 and 4634; 3866 and 4634; 3867 and 4634; 3868 and 4634; 3869 and 4634; 3870 and 4634; 3871 and 4634; 3872 and 4634; 3873 and 4634; 3874 and 4634; 3875 and 4634; 3876 and 4634; 3877 and 4634; 3878 and 4634; 3879 and 4634; 3880 and 4634; 3881 and 4634; 3882 and 4634; 3883 and 4634; 3884 and 4634; 3885 and 4634; 3886 and 4634; 3887 and 4634; 3888 and 4634; 3889 and 4634; 3890 and 4634; 3891 and 4634; 3892 and 4634; 3893 and 4634; 3894 and 4634; 3895 and 4634; 3896 and 4634; 3897 and 4634; 3898 and 4634; 3899 and 4634; 3900 and 4634; 3901 and 4634; 3902 and 4634; 3903 and 4634; 3904 and 4634; 3905 and 4634; 3906 and 4634; 3907 and 4634; 3908 and 4634; 3909 and 4634; 3910 and 4634; 3911 and 4634; 3912 and 4634; 3913 and 4634; 3914 and 4634; 3915 and 4634; 3916 and 4634; 3917 and 4634; 3918 and 4634; 3919 and 4634; 3920 and 4634; 3921 and 4634; 3922 and 4634; 3923 and 4634; 3924 and 4634; 3925 and 4634; 3926 and 4634; 3927 and 4634; 3928 and 4634; 3929 and 4634; 3930 and 4634; 3931 and 4634; 3932 and 4634; 3933 and 4634; 3934 and 4634; 3935 and 4634; 3936 and 4634; 3937 and 4634; 3938 and 4634; 3939 and 4634; 25 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 3940 and 4634; 3941 and 4634; 3942 and 4634; 3943 and 4634; 3944 and 4634; 3945 and 4634; 3946 and 4634; 3947 and 4634; 3948 and 4634; 3949 and 4634; 3950 and 4634; 3951 and 4634; 3952 and 4634; 3953 and 4634; 3954 and 4634; 3955 and 4634; 3956 and 4634; 3957 and 4634; 3958 and 4634; 3959 and 4634; 3960 and 4634; 3961 and 4634; 3962 and 4634; 3963 and 4634; 3964 and 4634; 3965 and 4634; 3966 and 4634; 3967 and 4634; 3968 and 4634; 3969 and 4634; 3970 and 4634; 3971 and 4634; 3972 and 4634; 3973 and 4634; 3974 and 4634; 3975 and 4634; 3976 and 4634; 3977 and 4634; 3978 and 4634; 3979 and 4634; 3980 and 4634; 3981 and 4634; 3982 and 4634; 3983 and 4634; 3984 and 4634; 3985 and 4634; 3986 and 4634; 3987 and 4634; 3988 and 4634; 3989 and 4634; 3990 and 4634; 3991 and 4634; 3992 and 4634; 3993 and 4634; 3994 and 4634; 3995 and 4634; 3996 and 4634; 3997 and 4634; 3998 and 4634; 3999 and 4634; 4000 and 4634; 4001 and 4634; 4002 and 4634; 4003 and 4634; 4004 and 4634; 4005 and 4634; 4006 and 4634; 4007 and 4634; 4008 and 4634; 4009 and 4634; 4010 and 4634; 4011 and 4634; 4012 and 4634; 4013 and 4634; 4014 and 4634; 4015 and 4634; 4016 and 4634; 4017 and 4634; 4018 and 4634; 4019 and 4634; 4020 and 4634; 4021 and 4634; 4022 and 4634; 4023 and 4634; 4024 and 4634; 4025 and 4634; 4026 and 4634; 4027 and 4634; 4028 and 4634; 4029 and 4634; 4030 and 4634; 4031 and 4634; 4032 and 4634; 4033 and 4634; 4034 and 4634; 4035 and 4634; 4036 and 4634; 4037 and 4634; 4038 and 4634; 4039 and 4634; 4040 and 4634; 4041 and 4634; 4042 and 4634; 4043 and 4634; 4044 and 4634; 4045 and 4634; 4046 and 4634; 4382 and 4634; 4383 and 4634; 4384 and 4634; 4385 and 4634; 4386 and 4634; 4387 and 4634; 4388 and 4634; 4389 and 4634; 4390 and 4634; 4391 and 4634; 4392 and 4634; 4393 and 4634; 4394 and 4634; 4395 and 4634; 4396 and 4634; 4397 and 4634; 4398 and 4634; 4399 and 4634; 4400 and 4634; 4401 and 4634; 4402 and 4634; 4403 and 4635; 4404 and 4636; 4405 and 4637; 4406 and 4638; 4407 and 4639; 4408 and 4640; 4409 and 4641; 4410 and 4642; 4411 and 4643; 4412 and 4644; 4413 and 4645; 4414 and 4646; 4415 and 4647; 4416 and 4648; 4417 and 4649; 4418 and 4650; 4419 and 4651; 4420 and 4652; 4421 and 4653; 4422 and 4654; 4423 and 4655; 4424 and 4656; 4425 and 4657; 4426 and 4658; 4427 and 4659; 4428 and 4660; 4429 and 4661; 4430 and 4662; 4431 and 4663; 4432 and 4664; 4433 and 4665; 4434 and 4666; 4435 and 4667; 4436 and 4668; 4437 and 4669; 4438 and 4670; 4439 and 4671; 4440 and 4672; 4441 and 4673; 4442 and 4674; 4443 and 4675; 4444 and 4676; 4445 and 4677; 4446 and 4678; 4447 and 4679; 4448 and 4680; 4449 and 4681; 4450 and 4682; 4451 and 4683; 4452 and 4684; 4453 and 4685; 4454 and 4686; 4455 and 4687; 4456 and 4688; 4457 and 4689; 4458 and 4690; 4459 and 4691; 4460 and 4692; 4461 and 4693; 4462 and 4694; 4463 and 4695; 4464 and 4696; 4465 and 4697; 4466 and 4698; 4467 and 4699; 4468 and 4700; 4469 and 4701; 4470 and 4702; 4471 and 4703; 4472 and 4704; 4473 and 4705; 4474 and 4706; 4475 and 4707; 4476 and 4708; 4477 and 4709; 4478 and 4710; 26 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 4479 and 4711; 4480 and 4712; 4481 and 4713; 4482 and 4714; 4483 and 4715; 4484 and 4716; 4485 and 4717; 4486 and 4718; 4487 and 4719; 4488 and 4720; 4489 and 4721; 4490 and 4722; and 4491 and 4723.

[0109] In some aspects, the VHsequence is a VHsequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4492-4633, and the VL sequence is a VL sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4724- 4865.

[0110] In some aspects, the VH - VL pairs are selected from SEQ ID NOs: 4492 and 4724; 4493 and 4725; 4494 and 4726; 4495 and 4727; 4496 and 4728; 4497 and 4729; 4498 and 4730; 4499 and 4731; 4500 and 4732; 4501 and 4733; 4502 and 4734; 4503 and 4735; 4504 and 4736; 4505 and 4737; 4506 and 4738; 4507 and 4739; 4508 and 4740; 4509 and 4741; 4510 and 4742; 4511 and 4743; 4512 and 4744; 4513 and 4745; 4514 and 4746; 4515 and 4747; 4516 and 4748; 4517 and 4749; 4518 and 4750; 4519 and 4751; 4520 and 4752; 4521 and 4753; 4522 and 4754; 4523 and 4755; 4524 and 4756; 4525 and 4757; 4526 and 4758; 4527 and 4759; 4528 and 4760; 4529 and 4761; 4530 and 4762; 4531 and 4763; 4532 and 4764; 4533 and 4765; 4534 and 4766; 4535 and 4767; 4536 and 4768; 4537 and 4769; 4538 and 4770; 4539 and 4771; 4540 and 4772; 4541 and 4773; 4542 and 4774; 4543 and 4775; 4544 and 4776; 4545 and 4777; 4546 and 4778; 4547 and 4779; 4548 and 4780; 4549 and 4781; 4550 and 4782; 4551 and 4783; 4552 and 4784; 4553 and 4785; 4554 and 4786; 4555 and 4787; 4556 and 4788; 4557 and 4789; 4558 and 4790; 4559 and 4791; 4560 and 4792; 4561 and 4793; 4562 and 4794; 4563 and 4795; 4564 and 4796; 4565 and 4797; 4566 and 4798; 4567 and 4799; 4568 and 4800; 4569 and 4801; 4570 and 4802; 4571 and 4803; 4572 and 4804; 4573 and 4805; 4574 and 4806; 4575 and 4807; 4576 and 4808; 4577 and 4809; 4578 and 4810; 4579 and 4811; 4580 and 4812; 4581 and 4813; 4582 and 4814; 4583 and 4815; 4584 and 4816; 4585 and 4817; 4586 and 4818; 4587 and 4819; 4588 and 4820; 4589 and 4821; 4590 and 4822; 4591 and 4823; 4592 and 4824; 4593 and 4825; 4594 and 4826; 4595 and 4827; 4596 and 4828; 4597 and 4829; 4598 and 4830; 4599 and 4831; 4600 and 4832; 4601 and 4833; 4602 and 4834; 4603 and 4835; 4604 and 4836; 4605 and 4837; 4606 and 4838; 4607 and 4839; 4608 and 4840; 4609 and 4841; 4610 and 4842; 4611 and 4843; 4612 and 4844; 4613 and 4845; 4614 and 4846; 4615 and 4847; 4616 and 4848; 4617 and 4849; 4618 and 4850; 4619 and 4851; 4620 and 4852; 4621 and 4853; 4622 and 4854; 4623 and 4855; 4624 and 4856; 4625 and 4857; 4626 and 4858; 4627 and 4859; 4628 and 4860; 4629 and 4861; 4630 and 4862; 4631 and 4863; 4632 and 4864; and 4633 and 4865. 2.12. Variants of VH – VL Pairs 27 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0111] In some embodiments, the VH– VLpairs provided herein comprise a variant of an illustrative VH and / or VL sequence provided in this disclosure.

[0112] In some embodiments, the antibody comprises a VH –VL pair, or a variant thereof, selected from the group consisting of SEQ ID NOS: 3789 and 4634; 3790 and 4634; 3791 and 4634; 3792 and 4634; 3793 and 4634; 3794 and 4634; 3795 and 4634; 3796 and 4634; 3797 and 4634; 3798 and 4634; 3799 and 4634; 3800 and 4634; 3801 and 4634; 3802 and 4634; 3803 and 4634; 3804 and 4634; 3805 and 4634; 3806 and 4634; 3807 and 4634; 3808 and 4634; 3809 and 4634; 3810 and 4634; 3811 and 4634; 3812 and 4634; 3813 and 4634; 3814 and 4634; 3815 and 4634; 3816 and 4634; 3817 and 4634; 3818 and 4634; 3819 and 4634; 3820 and 4634; 3821 and 4634; 3822 and 4634; 3823 and 4634; 3824 and 4634; 3825 and 4634; 3826 and 4634; 3827 and 4634; 3828 and 4634; 3829 and 4634; 3830 and 4634; 3831 and 4634; 3832 and 4634; 3833 and 4634; 3834 and 4634; 3835 and 4634; 3836 and 4634; 3837 and 4634; 3838 and 4634; 3839 and 4634; 3840 and 4634; 3841 and 4634; 3842 and 4634; 3843 and 4634; 3844 and 4634; 3845 and 4634; 3846 and 4634; 3847 and 4634; 3848 and 4634; 3849 and 4634; 3850 and 4634; 3851 and 4634; 3852 and 4634; 3853 and 4634; 3854 and 4634; 3855 and 4634; 3856 and 4634; 3857 and 4634; 3858 and 4634; 3859 and 4634; 3860 and 4634; 3861 and 4634; 3862 and 4634; 3863 and 4634; 3864 and 4634; 3865 and 4634; 3866 and 4634; 3867 and 4634; 3868 and 4634; 3869 and 4634; 3870 and 4634; 3871 and 4634; 3872 and 4634; 3873 and 4634; 3874 and 4634; 3875 and 4634; 3876 and 4634; 3877 and 4634; 3878 and 4634; 3879 and 4634; 3880 and 4634; 3881 and 4634; 3882 and 4634; 3883 and 4634; 3884 and 4634; 3885 and 4634; 3886 and 4634; 3887 and 4634; 3888 and 4634; 3889 and 4634; 3890 and 4634; 3891 and 4634; 3892 and 4634; 3893 and 4634; 3894 and 4634; 3895 and 4634; 3896 and 4634; 3897 and 4634; 3898 and 4634; 3899 and 4634; 3900 and 4634; 3901 and 4634; 3902 and 4634; 3903 and 4634; 3904 and 4634; 3905 and 4634; 3906 and 4634; 3907 and 4634; 3908 and 4634; 3909 and 4634; 3910 and 4634; 3911 and 4634; 3912 and 4634; 3913 and 4634; 3914 and 4634; 3915 and 4634; 3916 and 4634; 3917 and 4634; 3918 and 4634; 3919 and 4634; 3920 and 4634; 3921 and 4634; 3922 and 4634; 3923 and 4634; 3924 and 4634; 3925 and 4634; 3926 and 4634; 3927 and 4634; 3928 and 4634; 3929 and 4634; 3930 and 4634; 3931 and 4634; 3932 and 4634; 3933 and 4634; 3934 and 4634; 3935 and 4634; 3936 and 4634; 3937 and 4634; 3938 and 4634; 3939 and 4634; 3940 and 4634; 3941 and 4634; 3942 and 4634; 3943 and 4634; 3944 and 4634; 3945 and 4634; 3946 and 4634; 3947 and 4634; 3948 and 4634; 3949 and 4634; 3950 and 4634; 3951 and 4634; 3952 and 4634; 3953 and 4634; 3954 and 4634; 3955 and 4634; 3956 and 4634; 3957 and 4634; 3958 and 4634; 3959 and 4634; 3960 and 4634; 3961 and 4634; 3962 and 4634; 3963 and 4634; 3964 and 4634; 3965 and 4634; 3966 and 4634; 3967 and 4634; 3968 and 4634; 3969 and 4634; 3970 and 4634; 3971 28 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO and 4634; 3972 and 4634; 3973 and 4634; 3974 and 4634; 3975 and 4634; 3976 and 4634; 3977 and 4634; 3978 and 4634; 3979 and 4634; 3980 and 4634; 3981 and 4634; 3982 and 4634; 3983 and 4634; 3984 and 4634; 3985 and 4634; 3986 and 4634; 3987 and 4634; 3988 and 4634; 3989 and 4634; 3990 and 4634; 3991 and 4634; 3992 and 4634; 3993 and 4634; 3994 and 4634; 3995 and 4634; 3996 and 4634; 3997 and 4634; 3998 and 4634; 3999 and 4634; 4000 and 4634; 4001 and 4634; 4002 and 4634; 4003 and 4634; 4004 and 4634; 4005 and 4634; 4006 and 4634; 4007 and 4634; 4008 and 4634; 4009 and 4634; 4010 and 4634; 4011 and 4634; 4012 and 4634; 4013 and 4634; 4014 and 4634; 4015 and 4634; 4016 and 4634; 4017 and 4634; 4018 and 4634; 4019 and 4634; 4020 and 4634; 4021 and 4634; 4022 and 4634; 4023 and 4634; 4024 and 4634; 4025 and 4634; 4026 and 4634; 4027 and 4634; 4028 and 4634; 4029 and 4634; 4030 and 4634; 4031 and 4634; 4032 and 4634; 4033 and 4634; 4034 and 4634; 4035 and 4634; 4036 and 4634; 4037 and 4634; 4038 and 4634; 4039 and 4634; 4040 and 4634; 4041 and 4634; 4042 and 4634; 4043 and 4634; 4044 and 4634; 4045 and 4634; 4046 and 4634; 4382 and 4634; 4383 and 4634; 4384 and 4634; 4385 and 4634; 4386 and 4634; 4387 and 4634; 4388 and 4634; 4389 and 4634; 4390 and 4634; 4391 and 4634; 4392 and 4634; 4393 and 4634; 4394 and 4634; 4395 and 4634; 4396 and 4634; 4397 and 4634; 4398 and 4634; 4399 and 4634; 4400 and 4634; 4401 and 4634; 4402 and 4634; 4403 and 4635; 4404 and 4636; 4405 and 4637; 4406 and 4638; 4407 and 4639; 4408 and 4640; 4409 and 4641; 4410 and 4642; 4411 and 4643; 4412 and 4644; 4413 and 4645; 4414 and 4646; 4415 and 4647; 4416 and 4648; 4417 and 4649; 4418 and 4650; 4419 and 4651; 4420 and 4652; 4421 and 4653; 4422 and 4654; 4423 and 4655; 4424 and 4656; 4425 and 4657; 4426 and 4658; 4427 and 4659; 4428 and 4660; 4429 and 4661; 4430 and 4662; 4431 and 4663; 4432 and 4664; 4433 and 4665; 4434 and 4666; 4435 and 4667; 4436 and 4668; 4437 and 4669; 4438 and 4670; 4439 and 4671; 4440 and 4672; 4441 and 4673; 4442 and 4674; 4443 and 4675; 4444 and 4676; 4445 and 4677; 4446 and 4678; 4447 and 4679; 4448 and 4680; 4449 and 4681; 4450 and 4682; 4451 and 4683; 4452 and 4684; 4453 and 4685; 4454 and 4686; 4455 and 4687; 4456 and 4688; 4457 and 4689; 4458 and 4690; 4459 and 4691; 4460 and 4692; 4461 and 4693; 4462 and 4694; 4463 and 4695; 4464 and 4696; 4465 and 4697; 4466 and 4698; 4467 and 4699; 4468 and 4700; 4469 and 4701; 4470 and 4702; 4471 and 4703; 4472 and 4704; 4473 and 4705; 4474 and 4706; 4475 and 4707; 4476 and 4708; 4477 and 4709; 4478 and 4710; 4479 and 4711; 4480 and 4712; 4481 and 4713; 4482 and 4714; 4483 and 4715; 4484 and 4716; 4485 and 4717; 4486 and 4718; 4487 and 4719; 4488 and 4720; 4489 and 4721; 4490 and 4722; and 4491 and 4723.

[0113] In some embodiments, the antibody comprises a VH –VL pair, or a variant thereof, selected from the group consisting of SEQ ID NOS: 4492 and 4724; 4493 and 4725; 4494 and 4726; 4495 and 4727; 4496 and 4728; 4497 and 4729; 4498 and 4730; 4499 and 4731; 4500 and 29 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 4732; 4501 and 4733; 4502 and 4734; 4503 and 4735; 4504 and 4736; 4505 and 4737; 4506 and 4738; 4507 and 4739; 4508 and 4740; 4509 and 4741; 4510 and 4742; 4511 and 4743; 4512 and 4744; 4513 and 4745; 4514 and 4746; 4515 and 4747; 4516 and 4748; 4517 and 4749; 4518 and 4750; 4519 and 4751; 4520 and 4752; 4521 and 4753; 4522 and 4754; 4523 and 4755; 4524 and 4756; 4525 and 4757; 4526 and 4758; 4527 and 4759; 4528 and 4760; 4529 and 4761; 4530 and 4762; 4531 and 4763; 4532 and 4764; 4533 and 4765; 4534 and 4766; 4535 and 4767; 4536 and 4768; 4537 and 4769; 4538 and 4770; 4539 and 4771; 4540 and 4772; 4541 and 4773; 4542 and 4774; 4543 and 4775; 4544 and 4776; 4545 and 4777; 4546 and 4778; 4547 and 4779; 4548 and 4780; 4549 and 4781; 4550 and 4782; 4551 and 4783; 4552 and 4784; 4553 and 4785; 4554 and 4786; 4555 and 4787; 4556 and 4788; 4557 and 4789; 4558 and 4790; 4559 and 4791; 4560 and 4792; 4561 and 4793; 4562 and 4794; 4563 and 4795; 4564 and 4796; 4565 and 4797; 4566 and 4798; 4567 and 4799; 4568 and 4800; 4569 and 4801; 4570 and 4802; 4571 and 4803; 4572 and 4804; 4573 and 4805; 4574 and 4806; 4575 and 4807; 4576 and 4808; 4577 and 4809; 4578 and 4810; 4579 and 4811; 4580 and 4812; 4581 and 4813; 4582 and 4814; 4583 and 4815; 4584 and 4816; 4585 and 4817; 4586 and 4818; 4587 and 4819; 4588 and 4820; 4589 and 4821; 4590 and 4822; 4591 and 4823; 4592 and 4824; 4593 and 4825; 4594 and 4826; 4595 and 4827; 4596 and 4828; 4597 and 4829; 4598 and 4830; 4599 and 4831; 4600 and 4832; 4601 and 4833; 4602 and 4834; 4603 and 4835; 4604 and 4836; 4605 and 4837; 4606 and 4838; 4607 and 4839; 4608 and 4840; 4609 and 4841; 4610 and 4842; 4611 and 4843; 4612 and 4844; 4613 and 4845; 4614 and 4846; 4615 and 4847; 4616 and 4848; 4617 and 4849; 4618 and 4850; 4619 and 4851; 4620 and 4852; 4621 and 4853; 4622 and 4854; 4623 and 4855; 4624 and 4856; 4625 and 4857; 4626 and 4858; 4627 and 4859; 4628 and 4860; 4629 and 4861; 4630 and 4862; 4631 and 4863; 4632 and 4864; and 4633 and 4865.

[0114] In some aspects, the VHsequence comprises, consists of, or consists essentially of a variant of an illustrative VHsequence provided in this disclosure. In some aspects, the VHsequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.1% identity with any of the illustrative VHsequences provided in this disclosure.

[0115] In some embodiments, the VH sequence comprises, consists of, or consists essentially of any of the illustrative VH sequences provided in this disclosure having 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 30 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0116] In some aspects, the VLsequence comprises, consists of, or consists essentially of a variant of an illustrative VL sequence provided in this disclosure. In some aspects, the VL sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identity with any of the illustrative VLsequences provided in this disclosure.

[0117] In some embodiments, the VL sequence comprises, consists of, or consists essentially of any of the illustrative VLsequences provided in this disclosure having 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 2.13. Heavy Chain – Light Chain Pairs

[0118] In some embodiments, the antibody comprises a heavy chain sequence of an antibody disclosed herein and a light chain sequence of a suitable antibody. In some embodiments, the antibody comprises a heavy chain sequence of an antibody disclosed herein and a light chain sequence of an antibody disclosed herein.

[0119] In some embodiments, the heavy chain comprises a VHsequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3789-4046 and 4382-4491, and the light chain comprises a light chain sequence of any suitable antibody. In some embodiments, the heavy chain comprises a VHsequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4492-4633, and the light chain comprises a light chain sequence of any suitable antibody. In some embodiments, the light chain comprises a VL sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4634- 4723, and the heavy chain comprises a heavy chain sequence of any suitable antibody. In some embodiments, the light chain comprises a VLsequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4724-4865, and the heavy chain comprises a heavy chain sequence of any suitable antibody. Techniques for determining whether a particular light chain will pair with a heavy chain as described herein are well known to those of skill in the art. For example, a cell-free protein synthesis reaction comprising a nucleic acid encoding the heavy chain of interest and a nucleic acid encoding the light chain to be assessed may be performed as described.

[0120] In some embodiments, the heavy chain comprises a VH sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3789-4046 and 4382-4491, 31 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO and the light chain comprises a VLsequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4634-4723.

[0121] In some embodiments, the heavy chain comprises a VH sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4492-4633, and the light chain comprises a VL sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4724-4865. 2.14. Antibodies Comprising All Six CDRs

[0122] In some embodiments, the antibody comprises a CDR-H1 sequence, a CDR-H2 sequence, a CDR-H3 sequence, a CDR-L1 sequence, and a CDR-L3 sequence. In some aspects, the CDR sequences are part of a VH(for CDR-H) or VL(for CDR-L).

[0123] In some embodiments, the antibody comprises a CDR-H3, a CDR-H2, CDR-H1, a CDR-L3, a CDR-L2, and a CDR-L1 of a VH - VL pair selected from the group consisting of SEQ ID NOS: 3789 and 4634; 3790 and 4634; 3791 and 4634; 3792 and 4634; 3793 and 4634; 3794 and 4634; 3795 and 4634; 3796 and 4634; 3797 and 4634; 3798 and 4634; 3799 and 4634; 3800 and 4634; 3801 and 4634; 3802 and 4634; 3803 and 4634; 3804 and 4634; 3805 and 4634; 3806 and 4634; 3807 and 4634; 3808 and 4634; 3809 and 4634; 3810 and 4634; 3811 and 4634; 3812 and 4634; 3813 and 4634; 3814 and 4634; 3815 and 4634; 3816 and 4634; 3817 and 4634; 3818 and 4634; 3819 and 4634; 3820 and 4634; 3821 and 4634; 3822 and 4634; 3823 and 4634; 3824 and 4634; 3825 and 4634; 3826 and 4634; 3827 and 4634; 3828 and 4634; 3829 and 4634; 3830 and 4634; 3831 and 4634; 3832 and 4634; 3833 and 4634; 3834 and 4634; 3835 and 4634; 3836 and 4634; 3837 and 4634; 3838 and 4634; 3839 and 4634; 3840 and 4634; 3841 and 4634; 3842 and 4634; 3843 and 4634; 3844 and 4634; 3845 and 4634; 3846 and 4634; 3847 and 4634; 3848 and 4634; 3849 and 4634; 3850 and 4634; 3851 and 4634; 3852 and 4634; 3853 and 4634; 3854 and 4634; 3855 and 4634; 3856 and 4634; 3857 and 4634; 3858 and 4634; 3859 and 4634; 3860 and 4634; 3861 and 4634; 3862 and 4634; 3863 and 4634; 3864 and 4634; 3865 and 4634; 3866 and 4634; 3867 and 4634; 3868 and 4634; 3869 and 4634; 3870 and 4634; 3871 and 4634; 3872 and 4634; 3873 and 4634; 3874 and 4634; 3875 and 4634; 3876 and 4634; 3877 and 4634; 3878 and 4634; 3879 and 4634; 3880 and 4634; 3881 and 4634; 3882 and 4634; 3883 and 4634; 3884 and 4634; 3885 and 4634; 3886 and 4634; 3887 and 4634; 3888 and 4634; 3889 and 4634; 3890 and 4634; 3891 and 4634; 3892 and 4634; 3893 and 4634; 3894 and 4634; 3895 and 4634; 3896 and 4634; 3897 and 4634; 3898 and 4634; 3899 and 4634; 3900 and 4634; 3901 and 4634; 3902 and 4634; 3903 and 4634; 3904 and 4634; 3905 and 4634; 3906 and 4634; 3907 and 4634; 3908 and 4634; 3909 and 4634; 3910 and 4634; 3911 and 4634; 3912 and 4634; 3913 and 4634; 3914 and 4634; 3915 and 4634; 3916 and 4634; 3917 and 4634; 3918 and 4634; 3919 and 4634; 3920 32 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO and 4634; 3921 and 4634; 3922 and 4634; 3923 and 4634; 3924 and 4634; 3925 and 4634; 3926 and 4634; 3927 and 4634; 3928 and 4634; 3929 and 4634; 3930 and 4634; 3931 and 4634; 3932 and 4634; 3933 and 4634; 3934 and 4634; 3935 and 4634; 3936 and 4634; 3937 and 4634; 3938 and 4634; 3939 and 4634; 3940 and 4634; 3941 and 4634; 3942 and 4634; 3943 and 4634; 3944 and 4634; 3945 and 4634; 3946 and 4634; 3947 and 4634; 3948 and 4634; 3949 and 4634; 3950 and 4634; 3951 and 4634; 3952 and 4634; 3953 and 4634; 3954 and 4634; 3955 and 4634; 3956 and 4634; 3957 and 4634; 3958 and 4634; 3959 and 4634; 3960 and 4634; 3961 and 4634; 3962 and 4634; 3963 and 4634; 3964 and 4634; 3965 and 4634; 3966 and 4634; 3967 and 4634; 3968 and 4634; 3969 and 4634; 3970 and 4634; 3971 and 4634; 3972 and 4634; 3973 and 4634; 3974 and 4634; 3975 and 4634; 3976 and 4634; 3977 and 4634; 3978 and 4634; 3979 and 4634; 3980 and 4634; 3981 and 4634; 3982 and 4634; 3983 and 4634; 3984 and 4634; 3985 and 4634; 3986 and 4634; 3987 and 4634; 3988 and 4634; 3989 and 4634; 3990 and 4634; 3991 and 4634; 3992 and 4634; 3993 and 4634; 3994 and 4634; 3995 and 4634; 3996 and 4634; 3997 and 4634; 3998 and 4634; 3999 and 4634; 4000 and 4634; 4001 and 4634; 4002 and 4634; 4003 and 4634; 4004 and 4634; 4005 and 4634; 4006 and 4634; 4007 and 4634; 4008 and 4634; 4009 and 4634; 4010 and 4634; 4011 and 4634; 4012 and 4634; 4013 and 4634; 4014 and 4634; 4015 and 4634; 4016 and 4634; 4017 and 4634; 4018 and 4634; 4019 and 4634; 4020 and 4634; 4021 and 4634; 4022 and 4634; 4023 and 4634; 4024 and 4634; 4025 and 4634; 4026 and 4634; 4027 and 4634; 4028 and 4634; 4029 and 4634; 4030 and 4634; 4031 and 4634; 4032 and 4634; 4033 and 4634; 4034 and 4634; 4035 and 4634; 4036 and 4634; 4037 and 4634; 4038 and 4634; 4039 and 4634; 4040 and 4634; 4041 and 4634; 4042 and 4634; 4043 and 4634; 4044 and 4634; 4045 and 4634; 4046 and 4634; 4382 and 4634; 4383 and 4634; 4384 and 4634; 4385 and 4634; 4386 and 4634; 4387 and 4634; 4388 and 4634; 4389 and 4634; 4390 and 4634; 4391 and 4634; 4392 and 4634; 4393 and 4634; 4394 and 4634; 4395 and 4634; 4396 and 4634; 4397 and 4634; 4398 and 4634; 4399 and 4634; 4400 and 4634; 4401 and 4634; 4402 and 4634; 4403 and 4635; 4404 and 4636; 4405 and 4637; 4406 and 4638; 4407 and 4639; 4408 and 4640; 4409 and 4641; 4410 and 4642; 4411 and 4643; 4412 and 4644; 4413 and 4645; 4414 and 4646; 4415 and 4647; 4416 and 4648; 4417 and 4649; 4418 and 4650; 4419 and 4651; 4420 and 4652; 4421 and 4653; 4422 and 4654; 4423 and 4655; 4424 and 4656; 4425 and 4657; 4426 and 4658; 4427 and 4659; 4428 and 4660; 4429 and 4661; 4430 and 4662; 4431 and 4663; 4432 and 4664; 4433 and 4665; 4434 and 4666; 4435 and 4667; 4436 and 4668; 4437 and 4669; 4438 and 4670; 4439 and 4671; 4440 and 4672; 4441 and 4673; 4442 and 4674; 4443 and 4675; 4444 and 4676; 4445 and 4677; 4446 and 4678; 4447 and 4679; 4448 and 4680; 4449 and 4681; 4450 and 4682; 4451 and 4683; 4452 and 4684; 4453 and 4685; 4454 and 4686; 4455 and 4687; 4456 and 4688; 4457 and 4689; 4458 and 4690; 4459 33 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO and 4691; 4460 and 4692; 4461 and 4693; 4462 and 4694; 4463 and 4695; 4464 and 4696; 4465 and 4697; 4466 and 4698; 4467 and 4699; 4468 and 4700; 4469 and 4701; 4470 and 4702; 4471 and 4703; 4472 and 4704; 4473 and 4705; 4474 and 4706; 4475 and 4707; 4476 and 4708; 4477 and 4709; 4478 and 4710; 4479 and 4711; 4480 and 4712; 4481 and 4713; 4482 and 4714; 4483 and 4715; 4484 and 4716; 4485 and 4717; 4486 and 4718; 4487 and 4719; 4488 and 4720; 4489 and 4721; 4490 and 4722; and 4491 and 4723.

[0124] In some aspects, the CDR-H1 sequence is a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 4-261 and 597-706; the CDR- H2 sequence is a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 1410-1667 and 2003-2112; the CDR-H3 sequence is a CDR-H3 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 2816- 3073 and 3409-3518; the CDR-L1 sequence is a CDR-L1 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3519-3608; the CDR-L2 sequence is a CDR-L2 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3609-3698; and the CDR-L3 sequence is a CDR-L3 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3699-3788.

[0125] In some aspects, the CDR-H1 sequence is a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 707-964 and 1300-1409; the CDR-H2 sequence is a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 2113-2370 and 2706-2815; the CDR-H3 sequence is a CDR-H3 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 2816-3073 and 3409-3518; the CDR-L1 sequence is a CDR-L1 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3519-3608; the CDR-L2 sequence is a CDR-L2 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3609-3698; and the CDR-L3 sequence is a CDR-L3 sequence comprising, consisting of, or consisting essentially of, any one of SEQ ID NOs: 3699-3788.

[0126] In some embodiments, the antibody comprises six CDRs selected from the group consisting of SEQ ID NOs: 4 / 1410 / 2816 / 3519 / 3609 / 3699; 5 / 1411 / 2817 / 3519 / 3609 / 3699; 6 / 1412 / 2818 / 3519 / 3609 / 3699; 7 / 1413 / 2819 / 3519 / 3609 / 3699; 8 / 1414 / 2820 / 3519 / 3609 / 3699; 9 / 1415 / 2821 / 3519 / 3609 / 3699; 10 / 1416 / 2822 / 3519 / 3609 / 3699; 11 / 1417 / 2823 / 3519 / 3609 / 3699; 12 / 1418 / 2824 / 3519 / 3609 / 3699; 13 / 1419 / 2825 / 3519 / 3609 / 3699; 14 / 1420 / 2826 / 3519 / 3609 / 3699; 15 / 1421 / 2827 / 3519 / 3609 / 3699; 16 / 1422 / 2828 / 3519 / 3609 / 3699; 17 / 1423 / 2829 / 3519 / 3609 / 3699; 18 / 1424 / 2830 / 3519 / 3609 / 3699; 19 / 1425 / 2831 / 3519 / 3609 / 3699; 34 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 20 / 1426 / 2832 / 3519 / 3609 / 3699; 21 / 1427 / 2833 / 3519 / 3609 / 3699; 22 / 1428 / 2834 / 3519 / 3609 / 3699; 23 / 1429 / 2835 / 3519 / 3609 / 3699; 24 / 1430 / 2836 / 3519 / 3609 / 3699; 25 / 1431 / 2837 / 3519 / 3609 / 3699; 26 / 1432 / 2838 / 3519 / 3609 / 3699; 27 / 1433 / 2839 / 3519 / 3609 / 3699; 28 / 1434 / 2840 / 3519 / 3609 / 3699; 29 / 1435 / 2841 / 3519 / 3609 / 3699; 30 / 1436 / 2842 / 3519 / 3609 / 3699; 31 / 1437 / 2843 / 3519 / 3609 / 3699; 32 / 1438 / 2844 / 3519 / 3609 / 3699; 33 / 1439 / 2845 / 3519 / 3609 / 3699; 34 / 1440 / 2846 / 3519 / 3609 / 3699; 35 / 1441 / 2847 / 3519 / 3609 / 3699; 36 / 1442 / 2848 / 3519 / 3609 / 3699; 37 / 1443 / 2849 / 3519 / 3609 / 3699; 38 / 1444 / 2850 / 3519 / 3609 / 3699; 39 / 1445 / 2851 / 3519 / 3609 / 3699; 40 / 1446 / 2852 / 3519 / 3609 / 3699; 41 / 1447 / 2853 / 3519 / 3609 / 3699; 42 / 1448 / 2854 / 3519 / 3609 / 3699; 43 / 1449 / 2855 / 3519 / 3609 / 3699; 44 / 1450 / 2856 / 3519 / 3609 / 3699; 45 / 1451 / 2857 / 3519 / 3609 / 3699; 46 / 1452 / 2858 / 3519 / 3609 / 3699; 47 / 1453 / 2859 / 3519 / 3609 / 3699; 48 / 1454 / 2860 / 3519 / 3609 / 3699; 49 / 1455 / 2861 / 3519 / 3609 / 3699; 50 / 1456 / 2862 / 3519 / 3609 / 3699; 51 / 1457 / 2863 / 3519 / 3609 / 3699; 52 / 1458 / 2864 / 3519 / 3609 / 3699; 53 / 1459 / 2865 / 3519 / 3609 / 3699; 54 / 1460 / 2866 / 3519 / 3609 / 3699; 55 / 1461 / 2867 / 3519 / 3609 / 3699; 56 / 1462 / 2868 / 3519 / 3609 / 3699; 57 / 1463 / 2869 / 3519 / 3609 / 3699; 58 / 1464 / 2870 / 3519 / 3609 / 3699; 59 / 1465 / 2871 / 3519 / 3609 / 3699; 60 / 1466 / 2872 / 3519 / 3609 / 3699; 61 / 1467 / 2873 / 3519 / 3609 / 3699; 62 / 1468 / 2874 / 3519 / 3609 / 3699; 63 / 1469 / 2875 / 3519 / 3609 / 3699; 64 / 1470 / 2876 / 3519 / 3609 / 3699; 65 / 1471 / 2877 / 3519 / 3609 / 3699; 66 / 1472 / 2878 / 3519 / 3609 / 3699; 67 / 1473 / 2879 / 3519 / 3609 / 3699; 68 / 1474 / 2880 / 3519 / 3609 / 3699; 69 / 1475 / 2881 / 3519 / 3609 / 3699; 70 / 1476 / 2882 / 3519 / 3609 / 3699; 71 / 1477 / 2883 / 3519 / 3609 / 3699; 72 / 1478 / 2884 / 3519 / 3609 / 3699; 73 / 1479 / 2885 / 3519 / 3609 / 3699; 74 / 1480 / 2886 / 3519 / 3609 / 3699; 75 / 1481 / 2887 / 3519 / 3609 / 3699; 76 / 1482 / 2888 / 3519 / 3609 / 3699; 77 / 1483 / 2889 / 3519 / 3609 / 3699; 78 / 1484 / 2890 / 3519 / 3609 / 3699; 79 / 1485 / 2891 / 3519 / 3609 / 3699; 80 / 1486 / 2892 / 3519 / 3609 / 3699; 81 / 1487 / 2893 / 3519 / 3609 / 3699; 82 / 1488 / 2894 / 3519 / 3609 / 3699; 83 / 1489 / 2895 / 3519 / 3609 / 3699; 84 / 1490 / 2896 / 3519 / 3609 / 3699; 85 / 1491 / 2897 / 3519 / 3609 / 3699; 86 / 1492 / 2898 / 3519 / 3609 / 3699; 87 / 1493 / 2899 / 3519 / 3609 / 3699; 35 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 88 / 1494 / 2900 / 3519 / 3609 / 3699; 89 / 1495 / 2901 / 3519 / 3609 / 3699; 90 / 1496 / 2902 / 3519 / 3609 / 3699; 91 / 1497 / 2903 / 3519 / 3609 / 3699; 92 / 1498 / 2904 / 3519 / 3609 / 3699; 93 / 1499 / 2905 / 3519 / 3609 / 3699; 94 / 1500 / 2906 / 3519 / 3609 / 3699; 95 / 1501 / 2907 / 3519 / 3609 / 3699; 96 / 1502 / 2908 / 3519 / 3609 / 3699; 97 / 1503 / 2909 / 3519 / 3609 / 3699; 98 / 1504 / 2910 / 3519 / 3609 / 3699; 99 / 1505 / 2911 / 3519 / 3609 / 3699; 100 / 1506 / 2912 / 3519 / 3609 / 3699; 101 / 1507 / 2913 / 3519 / 3609 / 3699; 102 / 1508 / 2914 / 3519 / 3609 / 3699; 103 / 1509 / 2915 / 3519 / 3609 / 3699; 104 / 1510 / 2916 / 3519 / 3609 / 3699; 105 / 1511 / 2917 / 3519 / 3609 / 3699; 106 / 1512 / 2918 / 3519 / 3609 / 3699; 107 / 1513 / 2919 / 3519 / 3609 / 3699; 108 / 1514 / 2920 / 3519 / 3609 / 3699; 109 / 1515 / 2921 / 3519 / 3609 / 3699; 110 / 1516 / 2922 / 3519 / 3609 / 3699; 111 / 1517 / 2923 / 3519 / 3609 / 3699; 112 / 1518 / 2924 / 3519 / 3609 / 3699; 113 / 1519 / 2925 / 3519 / 3609 / 3699; 114 / 1520 / 2926 / 3519 / 3609 / 3699; 115 / 1521 / 2927 / 3519 / 3609 / 3699; 116 / 1522 / 2928 / 3519 / 3609 / 3699; 117 / 1523 / 2929 / 3519 / 3609 / 3699; 118 / 1524 / 2930 / 3519 / 3609 / 3699; 119 / 1525 / 2931 / 3519 / 3609 / 3699; 120 / 1526 / 2932 / 3519 / 3609 / 3699; 121 / 1527 / 2933 / 3519 / 3609 / 3699; 122 / 1528 / 2934 / 3519 / 3609 / 3699; 123 / 1529 / 2935 / 3519 / 3609 / 3699; 124 / 1530 / 2936 / 3519 / 3609 / 3699; 125 / 1531 / 2937 / 3519 / 3609 / 3699; 126 / 1532 / 2938 / 3519 / 3609 / 3699; 127 / 1533 / 2939 / 3519 / 3609 / 3699; 128 / 1534 / 2940 / 3519 / 3609 / 3699; 129 / 1535 / 2941 / 3519 / 3609 / 3699; 130 / 1536 / 2942 / 3519 / 3609 / 3699; 131 / 1537 / 2943 / 3519 / 3609 / 3699; 132 / 1538 / 2944 / 3519 / 3609 / 3699; 133 / 1539 / 2945 / 3519 / 3609 / 3699; 134 / 1540 / 2946 / 3519 / 3609 / 3699; 135 / 1541 / 2947 / 3519 / 3609 / 3699; 136 / 1542 / 2948 / 3519 / 3609 / 3699; 137 / 1543 / 2949 / 3519 / 3609 / 3699; 138 / 1544 / 2950 / 3519 / 3609 / 3699; 139 / 1545 / 2951 / 3519 / 3609 / 3699; 140 / 1546 / 2952 / 3519 / 3609 / 3699; 141 / 1547 / 2953 / 3519 / 3609 / 3699; 142 / 1548 / 2954 / 3519 / 3609 / 3699; 143 / 1549 / 2955 / 3519 / 3609 / 3699; 144 / 1550 / 2956 / 3519 / 3609 / 3699; 145 / 1551 / 2957 / 3519 / 3609 / 3699; 146 / 1552 / 2958 / 3519 / 3609 / 3699; 147 / 1553 / 2959 / 3519 / 3609 / 3699; 148 / 1554 / 2960 / 3519 / 3609 / 3699; 149 / 1555 / 2961 / 3519 / 3609 / 3699; 150 / 1556 / 2962 / 3519 / 3609 / 3699; 151 / 1557 / 2963 / 3519 / 3609 / 3699; 152 / 1558 / 2964 / 3519 / 3609 / 3699; 153 / 1559 / 2965 / 3519 / 3609 / 3699; 154 / 1560 / 2966 / 3519 / 3609 / 3699; 155 / 1561 / 2967 / 3519 / 3609 / 3699; 36 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 156 / 1562 / 2968 / 3519 / 3609 / 3699; 157 / 1563 / 2969 / 3519 / 3609 / 3699; 158 / 1564 / 2970 / 3519 / 3609 / 3699; 159 / 1565 / 2971 / 3519 / 3609 / 3699; 160 / 1566 / 2972 / 3519 / 3609 / 3699; 161 / 1567 / 2973 / 3519 / 3609 / 3699; 162 / 1568 / 2974 / 3519 / 3609 / 3699; 163 / 1569 / 2975 / 3519 / 3609 / 3699; 164 / 1570 / 2976 / 3519 / 3609 / 3699; 165 / 1571 / 2977 / 3519 / 3609 / 3699; 166 / 1572 / 2978 / 3519 / 3609 / 3699; 167 / 1573 / 2979 / 3519 / 3609 / 3699; 168 / 1574 / 2980 / 3519 / 3609 / 3699; 169 / 1575 / 2981 / 3519 / 3609 / 3699; 170 / 1576 / 2982 / 3519 / 3609 / 3699; 171 / 1577 / 2983 / 3519 / 3609 / 3699; 172 / 1578 / 2984 / 3519 / 3609 / 3699; 173 / 1579 / 2985 / 3519 / 3609 / 3699; 174 / 1580 / 2986 / 3519 / 3609 / 3699; 175 / 1581 / 2987 / 3519 / 3609 / 3699; 176 / 1582 / 2988 / 3519 / 3609 / 3699; 177 / 1583 / 2989 / 3519 / 3609 / 3699; 178 / 1584 / 2990 / 3519 / 3609 / 3699; 179 / 1585 / 2991 / 3519 / 3609 / 3699; 180 / 1586 / 2992 / 3519 / 3609 / 3699; 181 / 1587 / 2993 / 3519 / 3609 / 3699; 182 / 1588 / 2994 / 3519 / 3609 / 3699; 183 / 1589 / 2995 / 3519 / 3609 / 3699; 184 / 1590 / 2996 / 3519 / 3609 / 3699; 185 / 1591 / 2997 / 3519 / 3609 / 3699; 186 / 1592 / 2998 / 3519 / 3609 / 3699; 187 / 1593 / 2999 / 3519 / 3609 / 3699; 188 / 1594 / 3000 / 3519 / 3609 / 3699; 189 / 1595 / 3001 / 3519 / 3609 / 3699; 190 / 1596 / 3002 / 3519 / 3609 / 3699; 191 / 1597 / 3003 / 3519 / 3609 / 3699; 192 / 1598 / 3004 / 3519 / 3609 / 3699; 193 / 1599 / 3005 / 3519 / 3609 / 3699; 194 / 1600 / 3006 / 3519 / 3609 / 3699; 195 / 1601 / 3007 / 3519 / 3609 / 3699; 196 / 1602 / 3008 / 3519 / 3609 / 3699; 197 / 1603 / 3009 / 3519 / 3609 / 3699; 198 / 1604 / 3010 / 3519 / 3609 / 3699; 199 / 1605 / 3011 / 3519 / 3609 / 3699; 200 / 1606 / 3012 / 3519 / 3609 / 3699; 201 / 1607 / 3013 / 3519 / 3609 / 3699; 202 / 1608 / 3014 / 3519 / 3609 / 3699; 203 / 1609 / 3015 / 3519 / 3609 / 3699; 204 / 1610 / 3016 / 3519 / 3609 / 3699; 205 / 1611 / 3017 / 3519 / 3609 / 3699; 206 / 1612 / 3018 / 3519 / 3609 / 3699; 207 / 1613 / 3019 / 3519 / 3609 / 3699; 208 / 1614 / 3020 / 3519 / 3609 / 3699; 209 / 1615 / 3021 / 3519 / 3609 / 3699; 210 / 1616 / 3022 / 3519 / 3609 / 3699; 211 / 1617 / 3023 / 3519 / 3609 / 3699; 212 / 1618 / 3024 / 3519 / 3609 / 3699; 213 / 1619 / 3025 / 3519 / 3609 / 3699; 214 / 1620 / 3026 / 3519 / 3609 / 3699; 215 / 1621 / 3027 / 3519 / 3609 / 3699; 216 / 1622 / 3028 / 3519 / 3609 / 3699; 217 / 1623 / 3029 / 3519 / 3609 / 3699; 218 / 1624 / 3030 / 3519 / 3609 / 3699; 219 / 1625 / 3031 / 3519 / 3609 / 3699; 220 / 1626 / 3032 / 3519 / 3609 / 3699; 221 / 1627 / 3033 / 3519 / 3609 / 3699; 222 / 1628 / 3034 / 3519 / 3609 / 3699; 223 / 1629 / 3035 / 3519 / 3609 / 3699; 37 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 224 / 1630 / 3036 / 3519 / 3609 / 3699; 225 / 1631 / 3037 / 3519 / 3609 / 3699; 226 / 1632 / 3038 / 3519 / 3609 / 3699; 227 / 1633 / 3039 / 3519 / 3609 / 3699; 228 / 1634 / 3040 / 3519 / 3609 / 3699; 229 / 1635 / 3041 / 3519 / 3609 / 3699; 230 / 1636 / 3042 / 3519 / 3609 / 3699; 231 / 1637 / 3043 / 3519 / 3609 / 3699; 232 / 1638 / 3044 / 3519 / 3609 / 3699; 233 / 1639 / 3045 / 3519 / 3609 / 3699; 234 / 1640 / 3046 / 3519 / 3609 / 3699; 235 / 1641 / 3047 / 3519 / 3609 / 3699; 236 / 1642 / 3048 / 3519 / 3609 / 3699; 237 / 1643 / 3049 / 3519 / 3609 / 3699; 238 / 1644 / 3050 / 3519 / 3609 / 3699; 239 / 1645 / 3051 / 3519 / 3609 / 3699; 240 / 1646 / 3052 / 3519 / 3609 / 3699; 241 / 1647 / 3053 / 3519 / 3609 / 3699; 242 / 1648 / 3054 / 3519 / 3609 / 3699; 243 / 1649 / 3055 / 3519 / 3609 / 3699; 244 / 1650 / 3056 / 3519 / 3609 / 3699; 245 / 1651 / 3057 / 3519 / 3609 / 3699; 246 / 1652 / 3058 / 3519 / 3609 / 3699; 247 / 1653 / 3059 / 3519 / 3609 / 3699; 248 / 1654 / 3060 / 3519 / 3609 / 3699; 249 / 1655 / 3061 / 3519 / 3609 / 3699; 250 / 1656 / 3062 / 3519 / 3609 / 3699; 251 / 1657 / 3063 / 3519 / 3609 / 3699; 252 / 1658 / 3064 / 3519 / 3609 / 3699; 253 / 1659 / 3065 / 3519 / 3609 / 3699; 254 / 1660 / 3066 / 3519 / 3609 / 3699; 255 / 1661 / 3067 / 3519 / 3609 / 3699; 256 / 1662 / 3068 / 3519 / 3609 / 3699; 257 / 1663 / 3069 / 3519 / 3609 / 3699; 258 / 1664 / 3070 / 3519 / 3609 / 3699; 259 / 1665 / 3071 / 3519 / 3609 / 3699; 260 / 1666 / 3072 / 3519 / 3609 / 3699; 261 / 1667 / 3073 / 3519 / 3609 / 3699; 597 / 2003 / 3409 / 3519 / 3609 / 3699; 598 / 2004 / 3410 / 3519 / 3609 / 3699; 599 / 2005 / 3411 / 3519 / 3609 / 3699; 600 / 2006 / 3412 / 3519 / 3609 / 3699; 601 / 2007 / 3413 / 3519 / 3609 / 3699; 602 / 2008 / 3414 / 3519 / 3609 / 3699; 603 / 2009 / 3415 / 3519 / 3609 / 3699; 604 / 2010 / 3416 / 3519 / 3609 / 3699; 605 / 2011 / 3417 / 3519 / 3609 / 3699; 606 / 2012 / 3418 / 3519 / 3609 / 3699; 607 / 2013 / 3419 / 3519 / 3609 / 3699; 608 / 2014 / 3420 / 3519 / 3609 / 3699; 609 / 2015 / 3421 / 3519 / 3609 / 3699; 610 / 2016 / 3422 / 3519 / 3609 / 3699; 611 / 2017 / 3423 / 3519 / 3609 / 3699; 612 / 2018 / 3424 / 3519 / 3609 / 3699; 613 / 2019 / 3425 / 3519 / 3609 / 3699; 614 / 2020 / 3426 / 3519 / 3609 / 3699; 615 / 2021 / 3427 / 3519 / 3609 / 3699; 616 / 2022 / 3428 / 3519 / 3609 / 3699; 617 / 2023 / 3429 / 3519 / 3609 / 3699; 618 / 2024 / 3430 / 3520 / 3610 / 3700; 619 / 2025 / 3431 / 3521 / 3611 / 3701; 620 / 2026 / 3432 / 3522 / 3612 / 3702; 621 / 2027 / 3433 / 3523 / 3613 / 3703; 622 / 2028 / 3434 / 3524 / 3614 / 3704; 623 / 2029 / 3435 / 3525 / 3615 / 3705; 624 / 2030 / 3436 / 3526 / 3616 / 3706; 625 / 2031 / 3437 / 3527 / 3617 / 3707; 626 / 2032 / 3438 / 3528 / 3618 / 3708; 38 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 627 / 2033 / 3439 / 3529 / 3619 / 3709; 628 / 2034 / 3440 / 3530 / 3620 / 3710; 629 / 2035 / 3441 / 3531 / 3621 / 3711; 630 / 2036 / 3442 / 3532 / 3622 / 3712; 631 / 2037 / 3443 / 3533 / 3623 / 3713; 632 / 2038 / 3444 / 3534 / 3624 / 3714; 633 / 2039 / 3445 / 3535 / 3625 / 3715; 634 / 2040 / 3446 / 3536 / 3626 / 3716; 635 / 2041 / 3447 / 3537 / 3627 / 3717; 636 / 2042 / 3448 / 3538 / 3628 / 3718; 637 / 2043 / 3449 / 3539 / 3629 / 3719; 638 / 2044 / 3450 / 3540 / 3630 / 3720; 639 / 2045 / 3451 / 3541 / 3631 / 3721; 640 / 2046 / 3452 / 3542 / 3632 / 3722; 641 / 2047 / 3453 / 3543 / 3633 / 3723; 642 / 2048 / 3454 / 3544 / 3634 / 3724; 643 / 2049 / 3455 / 3545 / 3635 / 3725; 644 / 2050 / 3456 / 3546 / 3636 / 3726; 645 / 2051 / 3457 / 3547 / 3637 / 3727; 646 / 2052 / 3458 / 3548 / 3638 / 3728; 647 / 2053 / 3459 / 3549 / 3639 / 3729; 648 / 2054 / 3460 / 3550 / 3640 / 3730; 649 / 2055 / 3461 / 3551 / 3641 / 3731; 650 / 2056 / 3462 / 3552 / 3642 / 3732; 651 / 2057 / 3463 / 3553 / 3643 / 3733; 652 / 2058 / 3464 / 3554 / 3644 / 3734; 653 / 2059 / 3465 / 3555 / 3645 / 3735; 654 / 2060 / 3466 / 3556 / 3646 / 3736; 655 / 2061 / 3467 / 3557 / 3647 / 3737; 656 / 2062 / 3468 / 3558 / 3648 / 3738; 657 / 2063 / 3469 / 3559 / 3649 / 3739; 658 / 2064 / 3470 / 3560 / 3650 / 3740; 659 / 2065 / 3471 / 3561 / 3651 / 3741; 660 / 2066 / 3472 / 3562 / 3652 / 3742; 661 / 2067 / 3473 / 3563 / 3653 / 3743; 662 / 2068 / 3474 / 3564 / 3654 / 3744; 663 / 2069 / 3475 / 3565 / 3655 / 3745; 664 / 2070 / 3476 / 3566 / 3656 / 3746; 665 / 2071 / 3477 / 3567 / 3657 / 3747; 666 / 2072 / 3478 / 3568 / 3658 / 3748; 667 / 2073 / 3479 / 3569 / 3659 / 3749; 668 / 2074 / 3480 / 3570 / 3660 / 3750; 669 / 2075 / 3481 / 3571 / 3661 / 3751; 670 / 2076 / 3482 / 3572 / 3662 / 3752; 671 / 2077 / 3483 / 3573 / 3663 / 3753; 672 / 2078 / 3484 / 3574 / 3664 / 3754; 673 / 2079 / 3485 / 3575 / 3665 / 3755; 674 / 2080 / 3486 / 3576 / 3666 / 3756; 675 / 2081 / 3487 / 3577 / 3667 / 3757; 676 / 2082 / 3488 / 3578 / 3668 / 3758; 677 / 2083 / 3489 / 3579 / 3669 / 3759; 678 / 2084 / 3490 / 3580 / 3670 / 3760; 679 / 2085 / 3491 / 3581 / 3671 / 3761; 680 / 2086 / 3492 / 3582 / 3672 / 3762; 681 / 2087 / 3493 / 3583 / 3673 / 3763; 682 / 2088 / 3494 / 3584 / 3674 / 3764; 683 / 2089 / 3495 / 3585 / 3675 / 3765; 684 / 2090 / 3496 / 3586 / 3676 / 3766; 685 / 2091 / 3497 / 3587 / 3677 / 3767; 686 / 2092 / 3498 / 3588 / 3678 / 3768; 687 / 2093 / 3499 / 3589 / 3679 / 3769; 688 / 2094 / 3500 / 3590 / 3680 / 3770; 689 / 2095 / 3501 / 3591 / 3681 / 3771; 690 / 2096 / 3502 / 3592 / 3682 / 3772; 691 / 2097 / 3503 / 3593 / 3683 / 3773; 692 / 2098 / 3504 / 3594 / 3684 / 3774; 693 / 2099 / 3505 / 3595 / 3685 / 3775; 694 / 2100 / 3506 / 3596 / 3686 / 3776; 39 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 695 / 2101 / 3507 / 3597 / 3687 / 3777; 696 / 2102 / 3508 / 3598 / 3688 / 3778; 697 / 2103 / 3509 / 3599 / 3689 / 3779; 698 / 2104 / 3510 / 3600 / 3690 / 3780; 699 / 2105 / 3511 / 3601 / 3691 / 3781; 700 / 2106 / 3512 / 3602 / 3692 / 3782; 701 / 2107 / 3513 / 3603 / 3693 / 3783; 702 / 2108 / 3514 / 3604 / 3694 / 3784; 703 / 2109 / 3515 / 3605 / 3695 / 3785; 704 / 2110 / 3516 / 3606 / 3696 / 3786; 705 / 2111 / 3517 / 3607 / 3697 / 3787; and 706 / 2112 / 3518 / 3608 / 3698 / 3788

[0127] In some embodiments, the antibody comprises six CDRs selected from the group consisting of SEQ ID NOs: 707 / 2113 / 2816 / 3519 / 3609 / 3699; 708 / 2114 / 2817 / 3519 / 3609 / 3699; 709 / 2115 / 2818 / 3519 / 3609 / 3699; 710 / 2116 / 2819 / 3519 / 3609 / 3699; 711 / 2117 / 2820 / 3519 / 3609 / 3699; 712 / 2118 / 2821 / 3519 / 3609 / 3699; 713 / 2119 / 2822 / 3519 / 3609 / 3699; 714 / 2120 / 2823 / 3519 / 3609 / 3699; 715 / 2121 / 2824 / 3519 / 3609 / 3699; 716 / 2122 / 2825 / 3519 / 3609 / 3699; 717 / 2123 / 2826 / 3519 / 3609 / 3699; 718 / 2124 / 2827 / 3519 / 3609 / 3699; 719 / 2125 / 2828 / 3519 / 3609 / 3699; 720 / 2126 / 2829 / 3519 / 3609 / 3699; 721 / 2127 / 2830 / 3519 / 3609 / 3699; 722 / 2128 / 2831 / 3519 / 3609 / 3699; 723 / 2129 / 2832 / 3519 / 3609 / 3699; 724 / 2130 / 2833 / 3519 / 3609 / 3699; 725 / 2131 / 2834 / 3519 / 3609 / 3699; 726 / 2132 / 2835 / 3519 / 3609 / 3699; 727 / 2133 / 2836 / 3519 / 3609 / 3699; 728 / 2134 / 2837 / 3519 / 3609 / 3699; 729 / 2135 / 2838 / 3519 / 3609 / 3699; 730 / 2136 / 2839 / 3519 / 3609 / 3699; 731 / 2137 / 2840 / 3519 / 3609 / 3699; 732 / 2138 / 2841 / 3519 / 3609 / 3699; 733 / 2139 / 2842 / 3519 / 3609 / 3699; 734 / 2140 / 2843 / 3519 / 3609 / 3699; 735 / 2141 / 2844 / 3519 / 3609 / 3699; 736 / 2142 / 2845 / 3519 / 3609 / 3699; 737 / 2143 / 2846 / 3519 / 3609 / 3699; 738 / 2144 / 2847 / 3519 / 3609 / 3699; 739 / 2145 / 2848 / 3519 / 3609 / 3699; 740 / 2146 / 2849 / 3519 / 3609 / 3699; 741 / 2147 / 2850 / 3519 / 3609 / 3699; 742 / 2148 / 2851 / 3519 / 3609 / 3699; 743 / 2149 / 2852 / 3519 / 3609 / 3699; 744 / 2150 / 2853 / 3519 / 3609 / 3699; 745 / 2151 / 2854 / 3519 / 3609 / 3699; 746 / 2152 / 2855 / 3519 / 3609 / 3699; 747 / 2153 / 2856 / 3519 / 3609 / 3699; 748 / 2154 / 2857 / 3519 / 3609 / 3699; 749 / 2155 / 2858 / 3519 / 3609 / 3699; 750 / 2156 / 2859 / 3519 / 3609 / 3699; 751 / 2157 / 2860 / 3519 / 3609 / 3699; 752 / 2158 / 2861 / 3519 / 3609 / 3699; 753 / 2159 / 2862 / 3519 / 3609 / 3699; 754 / 2160 / 2863 / 3519 / 3609 / 3699; 755 / 2161 / 2864 / 3519 / 3609 / 3699; 756 / 2162 / 2865 / 3519 / 3609 / 3699; 757 / 2163 / 2866 / 3519 / 3609 / 3699; 758 / 2164 / 2867 / 3519 / 3609 / 3699; 759 / 2165 / 2868 / 3519 / 3609 / 3699; 760 / 2166 / 2869 / 3519 / 3609 / 3699; 40 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 761 / 2167 / 2870 / 3519 / 3609 / 3699; 762 / 2168 / 2871 / 3519 / 3609 / 3699; 763 / 2169 / 2872 / 3519 / 3609 / 3699; 764 / 2170 / 2873 / 3519 / 3609 / 3699; 765 / 2171 / 2874 / 3519 / 3609 / 3699; 766 / 2172 / 2875 / 3519 / 3609 / 3699; 767 / 2173 / 2876 / 3519 / 3609 / 3699; 768 / 2174 / 2877 / 3519 / 3609 / 3699; 769 / 2175 / 2878 / 3519 / 3609 / 3699; 770 / 2176 / 2879 / 3519 / 3609 / 3699; 771 / 2177 / 2880 / 3519 / 3609 / 3699; 772 / 2178 / 2881 / 3519 / 3609 / 3699; 773 / 2179 / 2882 / 3519 / 3609 / 3699; 774 / 2180 / 2883 / 3519 / 3609 / 3699; 775 / 2181 / 2884 / 3519 / 3609 / 3699; 776 / 2182 / 2885 / 3519 / 3609 / 3699; 777 / 2183 / 2886 / 3519 / 3609 / 3699; 778 / 2184 / 2887 / 3519 / 3609 / 3699; 779 / 2185 / 2888 / 3519 / 3609 / 3699; 780 / 2186 / 2889 / 3519 / 3609 / 3699; 781 / 2187 / 2890 / 3519 / 3609 / 3699; 782 / 2188 / 2891 / 3519 / 3609 / 3699; 783 / 2189 / 2892 / 3519 / 3609 / 3699; 784 / 2190 / 2893 / 3519 / 3609 / 3699; 785 / 2191 / 2894 / 3519 / 3609 / 3699; 786 / 2192 / 2895 / 3519 / 3609 / 3699; 787 / 2193 / 2896 / 3519 / 3609 / 3699; 788 / 2194 / 2897 / 3519 / 3609 / 3699; 789 / 2195 / 2898 / 3519 / 3609 / 3699; 790 / 2196 / 2899 / 3519 / 3609 / 3699; 791 / 2197 / 2900 / 3519 / 3609 / 3699; 792 / 2198 / 2901 / 3519 / 3609 / 3699; 793 / 2199 / 2902 / 3519 / 3609 / 3699; 794 / 2200 / 2903 / 3519 / 3609 / 3699; 795 / 2201 / 2904 / 3519 / 3609 / 3699; 796 / 2202 / 2905 / 3519 / 3609 / 3699; 797 / 2203 / 2906 / 3519 / 3609 / 3699; 798 / 2204 / 2907 / 3519 / 3609 / 3699; 799 / 2205 / 2908 / 3519 / 3609 / 3699; 800 / 2206 / 2909 / 3519 / 3609 / 3699; 801 / 2207 / 2910 / 3519 / 3609 / 3699; 802 / 2208 / 2911 / 3519 / 3609 / 3699; 803 / 2209 / 2912 / 3519 / 3609 / 3699; 804 / 2210 / 2913 / 3519 / 3609 / 3699; 805 / 2211 / 2914 / 3519 / 3609 / 3699; 806 / 2212 / 2915 / 3519 / 3609 / 3699; 807 / 2213 / 2916 / 3519 / 3609 / 3699; 808 / 2214 / 2917 / 3519 / 3609 / 3699; 809 / 2215 / 2918 / 3519 / 3609 / 3699; 810 / 2216 / 2919 / 3519 / 3609 / 3699; 811 / 2217 / 2920 / 3519 / 3609 / 3699; 812 / 2218 / 2921 / 3519 / 3609 / 3699; 813 / 2219 / 2922 / 3519 / 3609 / 3699; 814 / 2220 / 2923 / 3519 / 3609 / 3699; 815 / 2221 / 2924 / 3519 / 3609 / 3699; 816 / 2222 / 2925 / 3519 / 3609 / 3699; 817 / 2223 / 2926 / 3519 / 3609 / 3699; 818 / 2224 / 2927 / 3519 / 3609 / 3699; 819 / 2225 / 2928 / 3519 / 3609 / 3699; 820 / 2226 / 2929 / 3519 / 3609 / 3699; 821 / 2227 / 2930 / 3519 / 3609 / 3699; 822 / 2228 / 2931 / 3519 / 3609 / 3699; 823 / 2229 / 2932 / 3519 / 3609 / 3699; 824 / 2230 / 2933 / 3519 / 3609 / 3699; 825 / 2231 / 2934 / 3519 / 3609 / 3699; 826 / 2232 / 2935 / 3519 / 3609 / 3699; 827 / 2233 / 2936 / 3519 / 3609 / 3699; 828 / 2234 / 2937 / 3519 / 3609 / 3699; 41 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 829 / 2235 / 2938 / 3519 / 3609 / 3699; 830 / 2236 / 2939 / 3519 / 3609 / 3699; 831 / 2237 / 2940 / 3519 / 3609 / 3699; 832 / 2238 / 2941 / 3519 / 3609 / 3699; 833 / 2239 / 2942 / 3519 / 3609 / 3699; 834 / 2240 / 2943 / 3519 / 3609 / 3699; 835 / 2241 / 2944 / 3519 / 3609 / 3699; 836 / 2242 / 2945 / 3519 / 3609 / 3699; 837 / 2243 / 2946 / 3519 / 3609 / 3699; 838 / 2244 / 2947 / 3519 / 3609 / 3699; 839 / 2245 / 2948 / 3519 / 3609 / 3699; 840 / 2246 / 2949 / 3519 / 3609 / 3699; 841 / 2247 / 2950 / 3519 / 3609 / 3699; 842 / 2248 / 2951 / 3519 / 3609 / 3699; 843 / 2249 / 2952 / 3519 / 3609 / 3699; 844 / 2250 / 2953 / 3519 / 3609 / 3699; 845 / 2251 / 2954 / 3519 / 3609 / 3699; 846 / 2252 / 2955 / 3519 / 3609 / 3699; 847 / 2253 / 2956 / 3519 / 3609 / 3699; 848 / 2254 / 2957 / 3519 / 3609 / 3699; 849 / 2255 / 2958 / 3519 / 3609 / 3699; 850 / 2256 / 2959 / 3519 / 3609 / 3699; 851 / 2257 / 2960 / 3519 / 3609 / 3699; 852 / 2258 / 2961 / 3519 / 3609 / 3699; 853 / 2259 / 2962 / 3519 / 3609 / 3699; 854 / 2260 / 2963 / 3519 / 3609 / 3699; 855 / 2261 / 2964 / 3519 / 3609 / 3699; 856 / 2262 / 2965 / 3519 / 3609 / 3699; 857 / 2263 / 2966 / 3519 / 3609 / 3699; 858 / 2264 / 2967 / 3519 / 3609 / 3699; 859 / 2265 / 2968 / 3519 / 3609 / 3699; 860 / 2266 / 2969 / 3519 / 3609 / 3699; 861 / 2267 / 2970 / 3519 / 3609 / 3699; 862 / 2268 / 2971 / 3519 / 3609 / 3699; 863 / 2269 / 2972 / 3519 / 3609 / 3699; 864 / 2270 / 2973 / 3519 / 3609 / 3699; 865 / 2271 / 2974 / 3519 / 3609 / 3699; 866 / 2272 / 2975 / 3519 / 3609 / 3699; 867 / 2273 / 2976 / 3519 / 3609 / 3699; 868 / 2274 / 2977 / 3519 / 3609 / 3699; 869 / 2275 / 2978 / 3519 / 3609 / 3699; 870 / 2276 / 2979 / 3519 / 3609 / 3699; 871 / 2277 / 2980 / 3519 / 3609 / 3699; 872 / 2278 / 2981 / 3519 / 3609 / 3699; 873 / 2279 / 2982 / 3519 / 3609 / 3699; 874 / 2280 / 2983 / 3519 / 3609 / 3699; 875 / 2281 / 2984 / 3519 / 3609 / 3699; 876 / 2282 / 2985 / 3519 / 3609 / 3699; 877 / 2283 / 2986 / 3519 / 3609 / 3699; 878 / 2284 / 2987 / 3519 / 3609 / 3699; 879 / 2285 / 2988 / 3519 / 3609 / 3699; 880 / 2286 / 2989 / 3519 / 3609 / 3699; 881 / 2287 / 2990 / 3519 / 3609 / 3699; 882 / 2288 / 2991 / 3519 / 3609 / 3699; 883 / 2289 / 2992 / 3519 / 3609 / 3699; 884 / 2290 / 2993 / 3519 / 3609 / 3699; 885 / 2291 / 2994 / 3519 / 3609 / 3699; 886 / 2292 / 2995 / 3519 / 3609 / 3699; 887 / 2293 / 2996 / 3519 / 3609 / 3699; 888 / 2294 / 2997 / 3519 / 3609 / 3699; 889 / 2295 / 2998 / 3519 / 3609 / 3699; 890 / 2296 / 2999 / 3519 / 3609 / 3699; 891 / 2297 / 3000 / 3519 / 3609 / 3699; 892 / 2298 / 3001 / 3519 / 3609 / 3699; 893 / 2299 / 3002 / 3519 / 3609 / 3699; 894 / 2300 / 3003 / 3519 / 3609 / 3699; 895 / 2301 / 3004 / 3519 / 3609 / 3699; 896 / 2302 / 3005 / 3519 / 3609 / 3699; 42 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 897 / 2303 / 3006 / 3519 / 3609 / 3699; 898 / 2304 / 3007 / 3519 / 3609 / 3699; 899 / 2305 / 3008 / 3519 / 3609 / 3699; 900 / 2306 / 3009 / 3519 / 3609 / 3699; 901 / 2307 / 3010 / 3519 / 3609 / 3699; 902 / 2308 / 3011 / 3519 / 3609 / 3699; 903 / 2309 / 3012 / 3519 / 3609 / 3699; 904 / 2310 / 3013 / 3519 / 3609 / 3699; 905 / 2311 / 3014 / 3519 / 3609 / 3699; 906 / 2312 / 3015 / 3519 / 3609 / 3699; 907 / 2313 / 3016 / 3519 / 3609 / 3699; 908 / 2314 / 3017 / 3519 / 3609 / 3699; 909 / 2315 / 3018 / 3519 / 3609 / 3699; 910 / 2316 / 3019 / 3519 / 3609 / 3699; 911 / 2317 / 3020 / 3519 / 3609 / 3699; 912 / 2318 / 3021 / 3519 / 3609 / 3699; 913 / 2319 / 3022 / 3519 / 3609 / 3699; 914 / 2320 / 3023 / 3519 / 3609 / 3699; 915 / 2321 / 3024 / 3519 / 3609 / 3699; 916 / 2322 / 3025 / 3519 / 3609 / 3699; 917 / 2323 / 3026 / 3519 / 3609 / 3699; 918 / 2324 / 3027 / 3519 / 3609 / 3699; 919 / 2325 / 3028 / 3519 / 3609 / 3699; 920 / 2326 / 3029 / 3519 / 3609 / 3699; 921 / 2327 / 3030 / 3519 / 3609 / 3699; 922 / 2328 / 3031 / 3519 / 3609 / 3699; 923 / 2329 / 3032 / 3519 / 3609 / 3699; 924 / 2330 / 3033 / 3519 / 3609 / 3699; 925 / 2331 / 3034 / 3519 / 3609 / 3699; 926 / 2332 / 3035 / 3519 / 3609 / 3699; 927 / 2333 / 3036 / 3519 / 3609 / 3699; 928 / 2334 / 3037 / 3519 / 3609 / 3699; 929 / 2335 / 3038 / 3519 / 3609 / 3699; 930 / 2336 / 3039 / 3519 / 3609 / 3699; 931 / 2337 / 3040 / 3519 / 3609 / 3699; 932 / 2338 / 3041 / 3519 / 3609 / 3699; 933 / 2339 / 3042 / 3519 / 3609 / 3699; 934 / 2340 / 3043 / 3519 / 3609 / 3699; 935 / 2341 / 3044 / 3519 / 3609 / 3699; 936 / 2342 / 3045 / 3519 / 3609 / 3699; 937 / 2343 / 3046 / 3519 / 3609 / 3699; 938 / 2344 / 3047 / 3519 / 3609 / 3699; 939 / 2345 / 3048 / 3519 / 3609 / 3699; 940 / 2346 / 3049 / 3519 / 3609 / 3699; 941 / 2347 / 3050 / 3519 / 3609 / 3699; 942 / 2348 / 3051 / 3519 / 3609 / 3699; 943 / 2349 / 3052 / 3519 / 3609 / 3699; 944 / 2350 / 3053 / 3519 / 3609 / 3699; 945 / 2351 / 3054 / 3519 / 3609 / 3699; 946 / 2352 / 3055 / 3519 / 3609 / 3699; 947 / 2353 / 3056 / 3519 / 3609 / 3699; 948 / 2354 / 3057 / 3519 / 3609 / 3699; 949 / 2355 / 3058 / 3519 / 3609 / 3699; 950 / 2356 / 3059 / 3519 / 3609 / 3699; 951 / 2357 / 3060 / 3519 / 3609 / 3699; 952 / 2358 / 3061 / 3519 / 3609 / 3699; 953 / 2359 / 3062 / 3519 / 3609 / 3699; 954 / 2360 / 3063 / 3519 / 3609 / 3699; 955 / 2361 / 3064 / 3519 / 3609 / 3699; 956 / 2362 / 3065 / 3519 / 3609 / 3699; 957 / 2363 / 3066 / 3519 / 3609 / 3699; 958 / 2364 / 3067 / 3519 / 3609 / 3699; 959 / 2365 / 3068 / 3519 / 3609 / 3699; 960 / 2366 / 3069 / 3519 / 3609 / 3699; 961 / 2367 / 3070 / 3519 / 3609 / 3699; 962 / 2368 / 3071 / 3519 / 3609 / 3699; 963 / 2369 / 3072 / 3519 / 3609 / 3699; 964 / 2370 / 3073 / 3519 / 3609 / 3699; 43 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 1300 / 2706 / 3409 / 3519 / 3609 / 3699; 1301 / 2707 / 3410 / 3519 / 3609 / 3699; 1302 / 2708 / 3411 / 3519 / 3609 / 3699; 1303 / 2709 / 3412 / 3519 / 3609 / 3699; 1304 / 2710 / 3413 / 3519 / 3609 / 3699; 1305 / 2711 / 3414 / 3519 / 3609 / 3699; 1306 / 2712 / 3415 / 3519 / 3609 / 3699; 1307 / 2713 / 3416 / 3519 / 3609 / 3699; 1308 / 2714 / 3417 / 3519 / 3609 / 3699; 1309 / 2715 / 3418 / 3519 / 3609 / 3699; 1310 / 2716 / 3419 / 3519 / 3609 / 3699; 1311 / 2717 / 3420 / 3519 / 3609 / 3699; 1312 / 2718 / 3421 / 3519 / 3609 / 3699; 1313 / 2719 / 3422 / 3519 / 3609 / 3699; 1314 / 2720 / 3423 / 3519 / 3609 / 3699; 1315 / 2721 / 3424 / 3519 / 3609 / 3699; 1316 / 2722 / 3425 / 3519 / 3609 / 3699; 1317 / 2723 / 3426 / 3519 / 3609 / 3699; 1318 / 2724 / 3427 / 3519 / 3609 / 3699; 1319 / 2725 / 3428 / 3519 / 3609 / 3699; 1320 / 2726 / 3429 / 3519 / 3609 / 3699; 1321 / 2727 / 3430 / 3520 / 3610 / 3700; 1322 / 2728 / 3431 / 3521 / 3611 / 3701; 1323 / 2729 / 3432 / 3522 / 3612 / 3702; 1324 / 2730 / 3433 / 3523 / 3613 / 3703; 1325 / 2731 / 3434 / 3524 / 3614 / 3704; 1326 / 2732 / 3435 / 3525 / 3615 / 3705; 1327 / 2733 / 3436 / 3526 / 3616 / 3706; 1328 / 2734 / 3437 / 3527 / 3617 / 3707; 1329 / 2735 / 3438 / 3528 / 3618 / 3708; 1330 / 2736 / 3439 / 3529 / 3619 / 3709; 1331 / 2737 / 3440 / 3530 / 3620 / 3710; 1332 / 2738 / 3441 / 3531 / 3621 / 3711; 1333 / 2739 / 3442 / 3532 / 3622 / 3712; 1334 / 2740 / 3443 / 3533 / 3623 / 3713; 1335 / 2741 / 3444 / 3534 / 3624 / 3714; 1336 / 2742 / 3445 / 3535 / 3625 / 3715; 1337 / 2743 / 3446 / 3536 / 3626 / 3716; 1338 / 2744 / 3447 / 3537 / 3627 / 3717; 1339 / 2745 / 3448 / 3538 / 3628 / 3718; 1340 / 2746 / 3449 / 3539 / 3629 / 3719; 1341 / 2747 / 3450 / 3540 / 3630 / 3720; 1342 / 2748 / 3451 / 3541 / 3631 / 3721; 1343 / 2749 / 3452 / 3542 / 3632 / 3722; 1344 / 2750 / 3453 / 3543 / 3633 / 3723; 1345 / 2751 / 3454 / 3544 / 3634 / 3724; 1346 / 2752 / 3455 / 3545 / 3635 / 3725; 1347 / 2753 / 3456 / 3546 / 3636 / 3726; 1348 / 2754 / 3457 / 3547 / 3637 / 3727; 1349 / 2755 / 3458 / 3548 / 3638 / 3728; 1350 / 2756 / 3459 / 3549 / 3639 / 3729; 1351 / 2757 / 3460 / 3550 / 3640 / 3730; 1352 / 2758 / 3461 / 3551 / 3641 / 3731; 1353 / 2759 / 3462 / 3552 / 3642 / 3732; 1354 / 2760 / 3463 / 3553 / 3643 / 3733; 1355 / 2761 / 3464 / 3554 / 3644 / 3734; 1356 / 2762 / 3465 / 3555 / 3645 / 3735; 1357 / 2763 / 3466 / 3556 / 3646 / 3736; 1358 / 2764 / 3467 / 3557 / 3647 / 3737; 1359 / 2765 / 3468 / 3558 / 3648 / 3738; 1360 / 2766 / 3469 / 3559 / 3649 / 3739; 1361 / 2767 / 3470 / 3560 / 3650 / 3740; 1362 / 2768 / 3471 / 3561 / 3651 / 3741; 1363 / 2769 / 3472 / 3562 / 3652 / 3742; 1364 / 2770 / 3473 / 3563 / 3653 / 3743; 1365 / 2771 / 3474 / 3564 / 3654 / 3744; 1366 / 2772 / 3475 / 3565 / 3655 / 3745; 1367 / 2773 / 3476 / 3566 / 3656 / 3746; 44 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 1368 / 2774 / 3477 / 3567 / 3657 / 3747; 1369 / 2775 / 3478 / 3568 / 3658 / 3748; 1370 / 2776 / 3479 / 3569 / 3659 / 3749; 1371 / 2777 / 3480 / 3570 / 3660 / 3750; 1372 / 2778 / 3481 / 3571 / 3661 / 3751; 1373 / 2779 / 3482 / 3572 / 3662 / 3752; 1374 / 2780 / 3483 / 3573 / 3663 / 3753; 1375 / 2781 / 3484 / 3574 / 3664 / 3754; 1376 / 2782 / 3485 / 3575 / 3665 / 3755; 1377 / 2783 / 3486 / 3576 / 3666 / 3756; 1378 / 2784 / 3487 / 3577 / 3667 / 3757; 1379 / 2785 / 3488 / 3578 / 3668 / 3758; 1380 / 2786 / 3489 / 3579 / 3669 / 3759; 1381 / 2787 / 3490 / 3580 / 3670 / 3760; 1382 / 2788 / 3491 / 3581 / 3671 / 3761; 1383 / 2789 / 3492 / 3582 / 3672 / 3762; 1384 / 2790 / 3493 / 3583 / 3673 / 3763; 1385 / 2791 / 3494 / 3584 / 3674 / 3764; 1386 / 2792 / 3495 / 3585 / 3675 / 3765; 1387 / 2793 / 3496 / 3586 / 3676 / 3766; 1388 / 2794 / 3497 / 3587 / 3677 / 3767; 1389 / 2795 / 3498 / 3588 / 3678 / 3768; 1390 / 2796 / 3499 / 3589 / 3679 / 3769; 1391 / 2797 / 3500 / 3590 / 3680 / 3770; 1392 / 2798 / 3501 / 3591 / 3681 / 3771; 1393 / 2799 / 3502 / 3592 / 3682 / 3772; 1394 / 2800 / 3503 / 3593 / 3683 / 3773; 1395 / 2801 / 3504 / 3594 / 3684 / 3774; 1396 / 2802 / 3505 / 3595 / 3685 / 3775; 1397 / 2803 / 3506 / 3596 / 3686 / 3776; 1398 / 2804 / 3507 / 3597 / 3687 / 3777; 1399 / 2805 / 3508 / 3598 / 3688 / 3778; 1400 / 2806 / 3509 / 3599 / 3689 / 3779; 1401 / 2807 / 3510 / 3600 / 3690 / 3780; 1402 / 2808 / 3511 / 3601 / 3691 / 3781; 1403 / 2809 / 3512 / 3602 / 3692 / 3782; 1404 / 2810 / 3513 / 3603 / 3693 / 3783; 1405 / 2811 / 3514 / 3604 / 3694 / 3784; 1406 / 2812 / 3515 / 3605 / 3695 / 3785; 1407 / 2813 / 3516 / 3606 / 3696 / 3786; 1408 / 2814 / 3517 / 3607 / 3697 / 3787; and 1409 / 2815 / 3518 / 3608 / 3698 / 3788. 2.15. Variants of Antibodies Comprising All Six CDRs

[0128] In some embodiments, the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 provided herein comprise a variant of an illustrative CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and / or CDR-L3 sequence provided in this disclosure.

[0129] In some aspects, the CDR-H1 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia or Kabat CDR-H1 sequence provided in this disclosure. In some aspects, the CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative Chothia or Kabat CDR-H1 sequences provided in this disclosure. In some aspects, the CDR-H1 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia or Kabat CDR-H1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 45 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0130] In some aspects, the CDR-H2 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia or Kabat CDR-H2 sequence provided in this disclosure. In some aspects, the CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative Chothia or Kabat CDR-H2 sequences provided in this disclosure. In some aspects, the CDR-H2 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia or Kabat CDR-H2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0131] In some aspects, the CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-H3 sequence provided in this disclosure. In some aspects, the CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative CDR-H3 sequences provided in this disclosure. In some aspects, the CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0132] In some aspects, the CDR-L1 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L1 sequence provided in this disclosure. In some aspects, the CDR-L1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative CDR-L1 sequences provided in this disclosure. In some aspects, the CDR-L1 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions.

[0133] In some aspects, the CDR-L2 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L2 sequence provided in this disclosure. In some aspects, the CDR-L2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative CDR-L2 sequences provided in this disclosure. In some aspects, the CDR-L2 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 46 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0134] In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L3 sequence provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative CDR-L3 sequences provided in this disclosure. In some aspects, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 2.16. Consensus Sequences

[0135] In some embodiments, provided herein are anti-TROP2 antibodies comprising one or more sequences defined by consensus sequences. Each consensus sequence is based, at least in part, on one or more alignments of two or more useful anti-TROP2 CDR sequences provided in this disclosure. Based on such alignments, a person of skill in the art would recognize that different amino acid residues may be useful in certain positions of the CDRs. Accordingly, each consensus sequence encompasses two or more useful anti-TROP2 CDR sequences.

[0136] In some embodiments, the antibodies comprise one to six of the consensus CDR sequences provided herein. In some embodiments, the antibodies comprise two to six of the consensus CDR sequences provided herein. In some embodiments, the antibodies comprise three to six of the consensus CDR sequences provided herein. In some embodiments, the antibodies comprise four to six of the consensus CDR sequences provided herein. In some embodiments, the antibodies comprise five to six of the consensus CDR sequences provided herein. In some embodiments, the antibodies comprise six of the consensus CDR sequences provided herein. In some embodiments, the antibodies comprise a VL comprising the CDR-L consensus sequence(s). In some embodiments, the antibodies comprise a VHcomprising the CDR-H consensus sequence(s). In some embodiments, the antibodies comprise a VHcomprising the CDR-H consensus sequence(s) and a VL comprising the CDR-L consensus sequence(s). 2.16.1. CDR-H3 Consensus Sequences

[0137] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence α1-α2-α3-α4-α5-α6-α7-α8-α9-α10-α11-α12-α13-α14-α15, where α1 is absent, D, E, Q, S, or V; α2is absent, A, D, E, F, G, K, L, N Q, S, or Y; α3is absent, D, E, F, G, I, L, M, Q, R, S, T, V, W, or Y; α4 is absent, G, H, N, R, S, V, W, or Y; α5 is absent, D, F, I, L, N, P, R, S, T, V, W, or Y; α6 is absent, C, D, F, G, H, I, L, N, P, Q, R, S, T, V, W, or Y; α7 is C, E, F, G, I, L, M, N, P, Q, R, S, V, W, or Y; α8 is absent, D, G, K, N, P, R, S, W, or Y; α9 is absent, A, C, D, G, I, N, P, Q, S, V, W, or Y; α10 is absent, A, D, F, G, H, I, N, S, W, or Y; α11 is absent, F, L, 47 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO S, or Y; α12 is absent, D, E, F, H, I, L, P, S, V, W, or Y; α13 is absent, F, L, M, Q, or Y; α14 is absent, C, D, E, N, or Y; α15 is F, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 2816-2897, or a variant thereof having three, two, or one amino acid substitution(s).

[0138] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence α1-α2-α3-α4-α5-α6-W-α8-α9-α10-α11-α12, where α1 is absent, or E; α2 is A, E, G, P, S, or T; α3 is A, F, M, P, S, T, or Y; α4 is A, E, H, K, M, N, Q, R, S, T, V, or Y; α5 is A, F, H, S, W, or Y; α6 is F, I, M, P, S, V, or Y; α8 is F, or Y; α9 is F, I, L, V, or Y; α10 is F, I, L, M, or Y; α11 is D, E, or N; α12 is H, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 2898-3073, or a variant thereof having three, two, or one amino acid substitution(s).

[0139] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence α1-α2-α3-α4-α5-α6-α7-α8-α9-α10-α11-α12-α13-α14-α15, where α1 is A, D, E, G, S, or Y; α2 is absent, A, D, G, I, S, or Y; α3 is absent, E, F, G, N, P, S, or Y; α4 is I, L, P, R, S, T, V, or Y; α5 is absent, A, G, S, W, or Y; α6 is absent, A, D, N, P, Q, S, T, V, W, or Y; α7 is absent, A, E, F, G, N, P, S, or Y; α8 is absent, F, G, I, L, S, W, or Y; α9 is absent, D, E, N, P, Q, W, or Y; α10 is absent, F, S, W, or Y; α11 is absent, D, L, P, S, V, W, or Y; α12 is D, F, G, L, P, V, or Y; α13 is F, L, or M,; α14 is D; α15 is Y. In some embodiments, the sequence is selected from SEQ ID NOs: 3409-3423, or a variant thereof having three, two, or one amino acid substitution(s).

[0140] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence α1-α2-α3-α4-α5-α6-α7-α8-α9-α10-α11-α12-D-Y, where α1 is absent, D, or E; α2 is absent, D, N, S, or Y; α3 is D, G, N, V, or Y; α4 is absent, G, I, Q, or T; α5 is absent, D, P, S, or W; α6 is I, L, P, Y; α7 is D, G, P, S, or Y; α8 is F, R, W, or Y; α9 is absent, A, T, W, or Y; α10 is G, or Y; α11 is A, G, L, M, or N; α12 is F, or L. In some embodiments, the sequence is selected from SEQ ID NOs: 3424-3429, or a variant thereof having three, two, or one amino acid substitution(s).

[0141] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence α1-α2-α3-α4-α5-α6-α7-α8-α9-α10-α11-α12-α13-α14-α15-α16-α17-α18-α19-α20, where α1 is absent, A, D, G, Q, S, or Y; α2 is absent, A, D, E, F, G, l, P, Q, R, S, or Y; α3 is absent, D, F, I, W, or Y; α4is absent, G, S, or W; α5is absent, D, E, F, L, N, P, S, or V; α6is absent, D, E, I, M, P, R, S, V, or Y; α7 is absent, A D, F, I, L, N, Q, R, T, V, W, or Y; α8 is absent, A, D, G, I, K, or S; α9 is absent, D, G, K, L, P, Q, S, T, or Y; α10 is absent, A, D, G, P, S, W, or Y; α11 is absent, F, L, R, S, T, V, W, or Y; α12 is absent, A, D, E, G, I, P, Q, R, S, T, V, W, or Y; α13 is absent, F, G, H, L, S, W, or Y; α14 is absent, A, G, P, R, S, W, or Y; α15 is absent, 48 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO D, E, G, I, P, Q, T, W, or Y; α16 is absent, D, F, G, I, N, P, S, W, or Y; α17 is absent, D, I, L, M, N, Q, S, V, or Y; α18 is absent, or F; α19 is absent, or D; α20 is absent, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 3430-3462, or a variant thereof having three, two, or one amino acid substitution(s).

[0142] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence α1-α2-α3-α4-α5-α6-α7-α8-α9-α10-α11-α12-α13-α14-α15-α16, where α1 is absent, D, or H; α2 is absent, D, E, G, L, R, S, T, or V; α3 is absent A, D, G, R, S, T, or V; α4 is absent W, or Y; α5 is absent, G, or S; α6 is absent, A, G, N, S, or Y; α7 is absent, A, D, H, I, K, R, T, V, or Y; α8 is absent, D, M, N, P, S, or T; α9 is absent, A, G, or S; α10 is absent, A, F, P, V, W, or Y; α11 is absent, G, R, W, or Y; α12 is absent, A, D, S, or Y; α13 is absent, D, E, G, M, N, P, Q, R, or Y; α14 is absent, F, I, L, or M; α15 is absent, D, G, N, or S; α16 is absent, I, or P. In some embodiments, the sequence is selected from SEQ ID NOs: 3463-3489, or a variant thereof having three, two, or one amino acid substitution(s).

[0143] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence α1-α2-α3-α4-α5-α6-α7-α8-α9-α10-α11-α12-α13-α14-α15-α16, where α1 is absent, D, or H; α2 is absent, D, E, G, L, R, S, T, or V; α3 is absent, A, D, G, R, S, T, or V; α4 is absent, W, or Y; α5 is absent, G, or S; α6 is absent, A, G, N, S, or Y; α7 is absent A, D, H, I, K, R, T, V, or Y; α8 is absent, D, M, N, P, S, or T; α9 is absent, A, G, or S; α10 is absent, A, F, P, V, W, or Y; α11 is absent, G, R, W, or Y; α12 is absent, A, D, S, or Y; α13 is absent, D, E, G, M, N, P, Q, R, or Y; α14 is absent, F, I, L, or M; α15 is absent, D, G, N, or S; α16 is absent, I, or P. In some embodiments, the sequence is selected from SEQ ID NOs: 3490-3518, or a variant thereof having three, two, or one amino acid substitution(s). 2.16.2. Chothia CDR-H1 Consensus Sequences

[0144] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence ε1-F-ε3-I-ε5-ε6-ε7, where ε1 is D, or G; ε3 is K, N, or S; ε5 is K, N, S, or T; ε6 is D, G, N, or S; ε7 is N, S, T, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 4-85, or a variant thereof having two or one amino acid substitutions(s).

[0145] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-ε2-ε3-ε4-ε5-ε6-ε7, where ε2 is F, or L; ε3 is D, N; ε4 is I, T, or V; ε5 is A, D, E, G, H, I, K, N, R, S, T, or V; ε6 is A, E, F, G, H, I, K, M, N, P, Q, R, S, W, or Y; ε7 is A, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 86-261, or a variant thereof having two or one amino acid substitutions(s). 49 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0146] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-F-N-I-ε5-ε6-ε7, where ε5 is N, S, or T; ε6 is D, N, or S; ε7 is F, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 597-611, or a variant thereof having two or one amino acid substitutions(s).

[0147] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-F-ε3-I-ε5-ε6-Y-ε8, where ε3 is N, or T; ε5 is G, or S; ε6 is D, or S; ε8 is absent, E, V, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 612-617, or a variant thereof having two or one amino acid substitutions(s).

[0148] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-F-N-I-ε5-ε6-ε7, where ε5 is E, G, N, S, or T; ε6 is D, N, or S; ε7 is D, F, V, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 618-650, or a variant thereof having two or one amino acid substitutions(s).

[0149] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-F-ε3-ε4-ε5-ε6-ε7, where ε3 is D, S, or T; ε4 is F, I, or L; ε5 is D, N, or S; ε6 is D, N, S, or T; ε7 is A, N, S, W, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 651-677, or a variant thereof having two or one amino acid substitutions(s).

[0150] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-F-ε3-ε4-ε5-ε6-ε7, where ε3 is D, S, or T; ε4 is F, I, or L; ε5 is D, N, or S; ε6 is D, N, S, or T; ε7 is A, N, S, W, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 678-706, or a variant thereof having two or one amino acid substitutions(s). 2.16.3. Chothia CDR-H2 Consensus Sequences

[0151] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ζ1-P-ζ3-ζ4-G-ζ6, where ζ1 is A, D, N, S, T, or Y; ζ3 is A, D, N, S, T, or Y; ζ4 is D, G, N, or S; ζ6 is A, D, H, N, T, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 1410-1491, or a variant thereof having two or one amino acid substitutions.

[0152] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ζ1-ζ2-ζ3-ζ4-G- ζ6, where ζ1 is A, F, G, H, I, K, N, Q, R, S, T, W, or Y; ζ2is P, or T; ζ3is A, D, E, G, H, I, K, L, N, Q, R, S, T, V, or Y; ζ4is A, D, F, G, I, L, R, S, T, V, or W; ζ6 is A, D, F, G, H, I, L, N, P, R, S, T, V, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 1492-1667, or a variant thereof having two or one amino acid substitutions. 50 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0153] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ζ1-P-ζ3-ζ4-G- ζ6, where ζ1 is D, K, N, S, or Y; ζ3 is D, N, S, W, or Y; ζ4 is D, F, G, N, or S; ζ6 is D, I, R, S, T, V, or Y. In some embodiments, the sequence is selected from Q s: -2017, or a variant thereof having two or one amino acid substitutions.

[0154] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ζ1-P-ζ3-ζ4-G-ζ6, where ζ1 is D, G, I, or S; ζ3 is I, N, S, or Y; ζ4 is D, G, S, or T; ζ6 is D, E, S, V, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 2018-2023, or a variant thereof having two or one amino acid substitutions.

[0155] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ζ1-P-ζ3-ζ4-G-ζ6, where ζ1 is D, F, I, K, N, S, W, or Y; ζ3 is D, G, N,R, S W or Y ζ4 is A D F G K N S or T ζ6 is D E N P R S T V or Y In someembodiments, the sequence is selected from SEQ ID NOs: 2024-2056, or a variant thereof having two or one amino acid substitutions.

[0156] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ζ1-ζ2-ζ3-ζ4-ζ5- ζ6, where ζ1 is absent, F, I, or Y; ζ2 is D, G, S, T, or V; ζ3 is F, G, I, N, S, T, or Y; ζ4 is A, G, S, T, V, or Y; ζ5 is D or, G; ζ6 is A, G, N, S, or T. In some embodiments, the sequence is selected from SEQ ID NOs: 2057-2083, or a variant thereof having two or one amino acid substitutions.

[0157] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ζ1-ζ2-ζ3-ζ4-ζ5- ζ6, where ζ1 is absent, F, I, or Y; ζ2 is D, S, T, or V; ζ3 is, , , , , , , , , , , , , , , , . In some embodiments, the sequence is selected from SEQ ID NOs: 2084-2112, or a variant thereof having two or one amino acid substitutions. 2.16.4. Kabat CDR-H1 Consensus Sequences

[0158] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence µ1-µ2-µ3-µ4-H, where µ1 is D, G, N, or S; µ2 is N, S, T, or Y; µ3 is A, C, D, G, S, W, or Y; µ4 is I, or T. In some embodiments, the sequence is selected from SEQ ID NOs: 707-788, or a variant thereof having two or one amino acid substitutions(s).

[0159] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence µ1-µ2-µ3-µ4-H, where µ1is A, E, F, G, H, I, K, M, N, P, Q, R, S, W, or Y; µ2 is A, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, or Y; µ3 is F, or W; µ4 is I, T, or V. In some embodiments, the sequence is selected from SEQ ID NOs: 789-964, or a variant thereof having two or one amino acid substitutions(s). 51 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0160] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence µ1-µ2-µ3-I-H, where µ1 is D, N, or S; µ2 is F, or Y; µ3 is A, D, N, V, W, Y. In some embodiments, the sequence is selected from SEQ ID NOs: 1300-1314, or a variant thereof having two or one amino acid substitutions(s).

[0161] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence µ1-Y-µ3-µ4-I-H, where µ1 is D, or S; µ3 is absent, E, V, or Y; µ4 is absent, W, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 1315-1320, or a variant thereof having two or one amino acid substitutions(s).

[0162] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence µ1-µ2-µ3-I-H, where µ1 is D, N, or S; µ2 is D, F, V, or Y; µ3 is A, D, E, G, L, N, S, W, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 1321- 1353, or a variant thereof having two or one amino acid substitutions(s).

[0163] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence µ1-µ2-µ3-µ4-µ5, where µ1 is D, N, S, or T; µ2 is A, N, S, W, or Y; µ3 is D, G, H, P, or Y; µ4 is I, M, V; µ5 is I, N, S, or T. In some embodiments, the sequence is selected from SEQ ID NOs: 1354-1380, or a variant thereof having two or one amino acid substitutions(s).

[0164] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence µ1-µ2-µ3-µ4-µ5, where µ1 is D, N, S, or T; µ2 is A, N, S, W, or Y; µ3 is D, G, H, P, or Y; µ4 is I, M, or V; µ5 is I, N, S, or T. In some embodiments, the sequence is selected from SEQ ID NOs: 1381-1409, or a variant thereof having two or one amino acid substitutions(s). 2.16.5. Kabat CDR-H2 Consensus Sequences

[0165] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence θ1-θ2-θ3-P-θ5-θ6-G-θ8-θ9-θ10-Y-A-D-S-θ15-K-θ17, where θ1 is A, C, D, E, G, I, N, R, V, or W; θ2 is I, T, or V; θ3 is A, D, N, S, T, or Y; θ5 is A, D, N, S, T, or Y; θ6 is D, G, N, or S; θ8 is A, D, H, N, T, or Y; θ9 is N, or T; θ10 is D, N, R, or Y; θ15 is A, or V; θ17 is G, or S. In some embodiments, a sequence is selected from SEQ ID NOs: 2113-2194, or a variant thereof having three, two, or one amino acid substitutions(s).

[0166] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence θ1-θ2-θ3-θ4-θ5-θ6-G-θ8-T-θ10-Y-θ12-θ13-θ14-θ15-θ16-θ17, where θ1 is A, D, E, G, L, M, V, or W; θ2 is A, I, N, S, or T; θ3 is A, F, G, H, I, K, N, Q, R, S, T, W, or Y; θ4 is P, or T; θ5 is A, D, E, G, H, I, K, L, N, Q, R, S, T, V, or Y; θ6 is A, D, F, G, I, L, R, S, T, V, or W; θ8 is A, D, F, G, H, I, L, N, P, R, S, T, V, or Y; θ10 is A, D, E, K, S, or V; θ12 is A, or 52 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO T; θ13 is D, or G; θ14 is P, or S; θ15 is A, or V; θ16 is K, or R; θ17 is D, or G. In some embodiments, a sequence is selected from SEQ ID NOs: 2195-2370, or a variant thereof having three, two, or one amino acid substitutions(s).

[0167] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence θ1-I-θ3-P-θ5-θ6-G-θ8-T-θ10-Y-A-D-S-V-K-G, where θ1 is A, G, M, R, S, T, V, or Y; θ3 is D, K, N, S, or Y; θ5 is D, N, S, W, or Y; θ6 is D, F, G, N, or S; θ8 is D, I, R, S, T, V, or Y; θ10 is H, K, N, S, or Y. In some embodiments, a sequence is selected from SEQ ID NOs: 2706-2720, or a variant thereof having three, two, or one amino acid substitutions(s).

[0168] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence θ1-I-θ3-P-θ5-θ6-G-θ8-T-θ10-Y-A-D-S-V-K-G, where θ1 is A, L, R, S, or Y; θ3 is D, G, I, or S; θ5 is I, N, S, or Y; θ6 is D, G, S, or T; θ8 is D, E, S, V, or Y; θ10 is D, E, N, R, or Y. In some embodiments, a sequence is selected from SEQ ID NOs: 2721-2726, or a variant thereof having three, two, or one amino acid substitutions(s).

[0169] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence θ1-I-θ3-P-θ5-θ6-G-θ8-T-θ10-Y-A-D-S-V-K-G, where θ1 is D, E, G, H, I, L, R, S, T, V, W, or Y; θ3 is D, F, I, K, N, S, W, or Y; θ5 is D, G, N, R, S, W, or Y; θ6 is A, D, F, G, K, N, S or, T; θ8 is D, E, N, P, R, S, T, V, or Y; θ10 is D, E, I, K, N, R, or Y. In some embodiments, a sequence is selected from SEQ ID NOs: 2727-2759, or a variant thereof having three, two, or one amino acid substitutions(s).

[0170] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence θ1-θ2-θ3-θ4-θ5-θ6-θ7-θ8-θ9-θ10-θ11-A-θ13-W-θ15-θ16-θ17, where θ1 is absent, A, F, I, K, M, or Y; θ2 is F, I, V; θ3 is absent, F, I, or Y; θ4 is D, G, S, T, or V; θ5 is F, G, I, N, S, T, or Y; θ6 is A, G, S, T, V, or Y; θ7 is D, or G; θ8 is A, G, N, S, or T; θ9 is A, S, or T; θ10 is A, F, G, H, N, W, or Y; θ11 is F, or Y; θ13 is N, S, or T; θ15 is A, or V; θ16 is I, or K; θ17 is G, or S. In some embodiments, a sequence is selected from SEQ ID NOs: 2760-2786, or a variant thereof having three, two, or one amino acid substitutions(s).

[0171] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence θ1-θ2-θ3-θ4-θ5-θ6-θ7-θ8-θ9-θ10-θ11-A-θ13-W-θ15-θ16-θ17, where θ1 is absent, A, F, I, K, M, or Y; θ2 is F, I, M, or V; θ3 is absent, F, I, or Y; θ4 is D, G, S, T, or V; θ5 is F, G, I, N, S, T, or Y; θ6is A, G, S, T, V, or Y; θ7is D, or G; θ8is A, G, N, S, or T; θ9is A, S, or T; θ10 is A, F, G, H, N, W, or Y; θ11 is F, or Y; θ13 is N, S, or T; θ15 is A, or V; θ16 is I, or K; θ17 is G, or S. In some embodiments, a sequence is selected from SEQ ID NOs: 2787-2815, or a variant thereof having three, two, or one amino acid substitutions(s). 2.16.6. CDR-L3 Consensus Sequences 53 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0172] In some embodiments, the antibody comprises a CDR-L3 sequence defined by the sequence the consensus sequence Q-Q-β3-β4-β5-β6-P-P-T, where β3 is absent, A, D, G, H, N, S, W, or Y; β4 is D, G, H, I, L, N, R, S, T, or Y; β5 is D, F, G, H, L, N, Q, S, W, or Y; β6 is D, F, G, I, L, N, P, S, T, V, W, or Y. In some embodiments, the sequence is selected from SEQ ID NOs: 3700-3732, or a variant thereof having three, two, or one amino acid substitution(s).

[0173] In some embodiments, the antibody comprises a CDR-L3 sequence defined by the sequence the consensus sequence β1-β2-β3-β4-β5-β6-β7-β8-β9-β10-β11-β12, where β1is absent, A, L, or Q; β2 is C, G, Q, S, or T; β3 is A, D, G, N, S, or T; β4 is absent, H, W, or Y; β5 is absent, A, D, G, S, T, W, or Y; β6 is D, G, I, N, S, V, or Y; β7 is A, D, G, I, N, or S; β8 is A, G, H, N, R, S, or T; β9is absent, D, G, I, K, V, or W; β10is D, E, G, N, R, S, or Y; β11is F, G, I, N, S, or Y; β12is A, D, P, S, T, or V. In some embodiments, the sequence is selected from SEQ ID NOs: 3733- 3759, or a variant thereof having three, two, or one amino acid substitution(s).

[0174] In some embodiments, the antibody comprises a CDR-L3 sequence defined by the sequence the consensus sequence β1-β2-β3-β4-β5-β6-β7-β8-β9-β10-β11-β12, where β1is absent, A, E, L, or Q; β2 is A, C, E, G, Q, S, or T; β3 is A, D, G, N, S, or T; β4 is absent, H, N, T, W, or Y; β5 is absent, A, D, G, I, S, T, W, or Y; β6 is D, G, I, N, S, T, V, or Y; β7 is A, D, G, I, N, S, or T; β8is A, G, H, I, N, R, S, or T; β9is absent, D, G, I, K, M, V, or W; β10is A, D, E, G, I, N, R, S, or Y; β11is F, G, I, M, N, Q, S, or Y; β12is A, D, N, P, S, T, or V. In some embodiments, the sequence is selected from SEQ ID NOs: 3760-3788, or a variant thereof having three, two, or one amino acid substitution(s). 2.16.7. CDR-L2 Consensus Sequences

[0175] In some embodiments, the antibody comprises a CDR-L2 sequence defined by the sequence the consensus sequence S-A-S-F-L-Y-S.

[0176] In some embodiments, the antibody comprises a CDR-L2 sequence defined by the sequence the consensus sequence δ1-δ2-δ3-δ4-δ5-δ6-δ7, where δ1is D, E, G, K, Q, R, or S; δ2is A, or T; δ3 is F, or S; δ4 is D, K, N, R, T, or Y; δ5 is L, or R; δ6 is A, D, E, P, or T; δ7 is F, or S. In some embodiments, the sequence is selected from SEQ ID NOs: 3643-3669, or a variant thereof having three, two, or one amino acid substitution(s).

[0177] In some embodiments, the antibody comprises a CDR-L2 sequence defined by the sequence the consensus sequence δ1-δ2-δ3-δ4-δ5-δ6-δ7, where δ1 is D, E, G, K, Q, R, or S; δ2 is A, or T; δ3is F, or S; δ4is D, K, N, R, T, or Y; δ5is L, or R; δ6is A, D, E, P, or T; δ7is F, or S. In some embodiments, the sequence is selected from SEQ ID NOs: 3643-3669, or a variant thereof having three, two, or one amino acid substitution(s). 54 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0178] In some embodiments, the antibody comprises a CDR-L2 sequence defined by the sequence the consensus sequence δ1-δ2-δ3-δ4-δ5-δ6-δ7-δ8-δ9, where δ1 is D, E, G, K, Q, R, or S; δ2 is absent, A, D, S, or T; δ3 is absent, A, F, L, or T; δ4 is N, or S; δ5 is absent, D, K, N, P, R, or T; δ6is absent, S, or Y; δ7is A, L, or R; δ8is A, D, E, P, or T; δ9is C, F, S, or W. In some embodiments, the sequence is selected from SEQ ID NOs: 3670-3698, or a variant thereof having three, two, or one amino acid substitution(s). 2.16.8. CDR-L1 Consensus Sequences

[0179] In some embodiments, the antibody comprises a CDR-L1 sequence defined by the sequence the consensus sequence R-A-S-Q-D-V-N-T-A-V-A.

[0180] In some embodiments, the antibody comprises a CDR-L1 sequence defined by the sequence the consensus sequence Q-γ2-S-γ4-γ5-γ6-γ7-γ8-γ9-γ10-γ11-L-γ13, where γ2is A, or S; γ4is E, or Q; γ5 is D, N, or S; γ6 is I, or V; γ7 is absent, A, G, I, N, W, or Y; γ8 is absent, D, G, N, or S; γ9 is absent, K, N, S, or T; γ10 is absent, L, N, W, or Y; γ11 is absent, E, F, G, or L; γ13 is A, or S. In some embodiments, the sequence is selected from SEQ ID NOs: 3553-3579, or a variant thereof having three, two, or one amino acid substitution(s).

[0181] In some embodiments, the antibody comprises a CDR-L1 sequence defined by the sequence the consensus sequence γ1-γ2-γ3-γ4-γ5-γ6-γ7-γ8-γ9-γ10-γ11-γ12-γ13-γ14-γ15-γ16-γ17, where γ1is Q, or S; γ2is A, R, or S; γ3is N, S; γ4is E, or Q; γ5is absent, or G; γ6is absent, D, N, or S; γ7 is absent, I, L, or V; γ8 is absent, A, G, I, N, P, W, or Y; γ9 is absent, D, N, or S; γ10 is absent, I, K, N, S, or T; γ11is absent, G, N, or Y; γ12is absent, G, or S; γ13is absent, E, F, G, M, N, P, W, or Y; γ14is G, L, or M; γ15is absent, H, or L; γ16is A, P, or S; γ17is absent, I, or L. In some embodiments, the sequence is selected from SEQ ID NOs: 3580-3608, or a variant thereof having three, two, or one amino acid substitution(s). 2.17. Constant Region Sequences

[0182] In some embodiments, the antibody of any one of the preceding embodiments comprises at least one constant region domain.

[0183] In some embodiments, the antibody, of any one of the preceding embodiments, comprises a constant region comprises a sequence selected from SEQ ID Nos: 4962, 4963, and 5225-5228. 2.18. Framework Regions

[0184] In some embodiments, the antibody of any of the previous embodiments further comprises human framework regions.

[0185] In some embodiments, the antibody of any of the previous embodiments, further comprises human kappa framework regions. 55 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0186] In some embodiments, the antibody comprises one or more frameworks in of a VHsequence selected from SEQ ID NOS: 3789-4046 and 4382-4491.

[0187] In some embodiments, the antibody comprises one or more frameworks in of a VH sequence selected from SEQ ID NOS: 4492-4633.

[0188] In some embodiments, the antibody comprises one or more frameworks in of a VL sequence selected from SEQ ID NOS: 4634-4723.

[0189] In some embodiments, the antibody comprises one or more frameworks in of a VLsequence selected from SEQ ID NOS: 4724-4865. 3. scFv

[0190] In some embodiments, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, a scFv sequence provided herein. In some aspects, the scFv sequence is an scFv sequence provided in SEQ ID NOs: 4906-4932.

[0191] In some embodiments, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 4906-4932. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4906. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4907. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4908. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4909. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4910. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4911. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4912. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4913. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4914. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4915. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4916. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4917. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4918. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4919. In some 56 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4920. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4921. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4922. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4923. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4924. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4925. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4926. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4927. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4928. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4929. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4930. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4931. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4932.

[0192] In some embodiments, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, a scFv sequence provided herein. In some aspects, the scFv sequence is an scFv sequence provided in SEQ ID NOs: 4933-4961.

[0193] In some embodiments, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 4933-4961. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4933. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4934. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4935. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4936. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4937. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4938. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4939. In some 57 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4940. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4941. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4942. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4943. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4944. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4945. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4946. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4947. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4948. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4949. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4950. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4951. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4952. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4953. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4954. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4955. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4956. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4957. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4958. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4959. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4960. In some aspects, the antibody comprises an scFv sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4961.

[0194] In some aspects, the scFv sequence comprises, consists of, or consists essentially of a variant of an illustrative scFv sequence provided in this disclosure. In some aspects, the scFv 58 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with any of the illustrative scFv sequences provided in this disclosure. In some aspects, the scFv sequence comprises, consists of, or consists essentially of any of the illustrative scFv sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some aspects, the amino acid substitutions are conservative amino acid substitutions. 4.Single chain Fab

[0195] In some embodiments, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, a single chain Fab sequence provided herein. In some aspects, the single chain Fab sequence is a single chain Fab sequence provided in SEQ ID NOs: 4872-4905.

[0196] In some embodiments, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, a sequence selected from SEQ ID NOs: 4872-4905. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4872. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4873. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4874. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4875. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4876. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4877. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4878. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4879. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4880. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4881. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4882. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4883. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4884. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, 59 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO or consisting essentially of, SEQ ID NO: 4885. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4886. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4887. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4888. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4889. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4890. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4891. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4892. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4893. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4894. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4895. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4896. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4897. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4898. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4899. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4900. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4901. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4902. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4903. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4904. In some aspects, the antibody comprises a single chain Fab sequence comprising, consisting of, or consisting essentially of, SEQ ID NO: 4905. 5. Germline

[0197] One of skill in the art would recognize that the CDR sequences provided herein may also be useful when combined with variable regions encoded by other variable region germline 60 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO genes, or variants thereof. In particular, the CDR sequences provided herein may be useful when combined with variable regions encoded by variable region germline genes, or variants thereof, that are structurally similar to the variable region germline genes recited above. For example, in some embodiments, a CDR-H sequence provided herein may be combined with a variable region encoded by a variable region germline gene selected from the VH 1, VH 2, VH 3, or VH 4 families, or a variant thereof. In some embodiments, a CDR-L sequence provided herein may be combined with a variable region encoded by a variable region germline gene selected from the Vκ1, Vκ2, or Vκ3, or a variant thereof. 6. Affinity

[0198] In some embodiments, the affinity of the antibody for TROP2 as indicated by KD, is less than about 10-5M, less than about 10-6M, less than about 10-7M, less than about 10-8M, less than about 10-9M, less than about 10-10M, less than about 10-11M, less than about 10-12M. In some embodiments, the affinity of the antibody is between about 10-7M and 10-12M. In some embodiments, the affinity of the antibody is between about 10-7M and 10-11M. In some embodiments, the affinity of the antibody is between about 10-7M and 10-10M. In some embodiments, the affinity of the antibody is between about 10-7M and 10-9M. In some embodiments, the affinity of the antibody is between about 10-7M and 10-8M. In some embodiments, the affinity of the antibody is between about 10-8M and 10-12M. In some embodiments, the affinity of the antibody is between about 10-8M and 10-11M. In some embodiments, the affinity of the antibody is between about 10-8M and 10-10M. In some embodiments, the affinity of the antibody is between about 10-8M and 10-9M. In some embodiments, the affinity of the antibody is between about 10-9M and 10-12M. In some embodiments, the affinity of the antibody is between about 10-9M and 10-11M. In some embodiments, the affinity of the antibody is between about 10-9M and 10-10M. In some embodiments, the affinity of the antibody is between about 10-10M and 10-12M. In some embodiments, the affinity of the antibody is between about 10-11M and 10-12M.

[0199] In some embodiments the antibody has a kaof at least about 103M-1×sec-1. In some embodiments the antibody has a kaof at least about 104M-1×sec-1. In some embodiments the antibody has a ka of at least about 105M-1×sec-1. In some embodiments the antibody has a ka of at least about 106M-1×sec-1. In some embodiments the antibody has a ka of between about 103M-1×sec-1and about 107M-1×sec-1. In some embodiments the antibody has a kaof between about 103M-1×sec-1and about 104M-1×sec-1. In some embodiments the antibody has a ka of between about 103M-1×sec-1and about 105M-1×sec-1. In some embodiments the antibody has a ka of between about 103M-1×sec-1and about 106M-1×sec-1. In some embodiments the antibody has a 61 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO kaof between about 104M-1×sec-1and about 105M-1×sec-1. In some embodiments the antibody has a ka of between about 104M-1×sec-1and about 106M-1×sec-1. In some embodiments the antibody has a ka of between about 104M-1×sec-1and about 107M-1×sec-1. In some embodiments the antibody has a kaof between about 105M-1×sec-1and about 106M-1×sec-1. In some embodiments the antibody has a ka of between about 105M-1×sec-1and about 107M-1×sec-1. In some embodiments the antibody has a ka of between about 106M-1×sec-1and about 107M-1×sec-1.

[0200] In some embodiments the antibody has a kd of about 10-8sec-1or less. In some embodiments the antibody has a kd of about 10-7sec-1or less. In some embodiments the antibody has a kdof about 10-6sec-1or less. In some embodiments the antibody has a kdof about 10-5sec-1or less. In some embodiments the antibody has a kdof about 10-4sec-1or less. In some embodiments the antibody has a kd of about 10-3sec-1or less. In some embodiments the antibody has a kd of between about 10-2sec-1and about 10-8sec-1. In some embodiments the antibody has a kdof between about 10-2sec-1and about 10-7sec-1. In some embodiments the antibody has a kdof between about 10-2sec-1and about 10-6sec-1. In some embodiments the antibody has a kd of between about 10-2sec-1and about 10-5sec-1. In some embodiments the antibody has a kd of between about 10-2sec-1and about 10-4sec-1. In some embodiments the antibody has a kdof between about 10-2sec-1and about 10-3sec-1. In some embodiments the antibody has a kdof between about 10-3sec-1and about 10-8sec-1. In some embodiments the antibody has a kd of between about 10-3sec-1and about 10-7sec-1. In some embodiments the antibody has a kdof between about 10-3sec-1and about 10-6sec-1. In some embodiments the antibody has a kdof between about 10-3sec-1and about 10-5sec-1. In some embodiments the antibody has a kd of between about 10-3sec-1and about 10-4sec-1. In some embodiments the antibody has a kd of between about 10-4sec-1and about 10-8sec-1. In some embodiments the antibody has a kdof between about 10-4sec-1and about 10-7sec-1. In some embodiments the antibody has a kdof between about 10-4sec-1and about 10-6sec-1. In some embodiments the antibody has a kd of between about 10-4sec-1and about 10-5sec-1. In some embodiments the antibody has a kdof between about 10-5sec-1and about 10-8sec-1. In some embodiments the antibody has a kdof between about 10-5sec-1and about 107sec-1. In some embodiments the antibody has a kd of between about 10-5sec-1and about 10-6sec-1. In some embodiments the antibody has a kd of between about 10-6sec-1and about 10-8sec-1. In some embodiments the antibody has a kdof between about 10-6sec-1and about 10-7sec-1. In some embodiments the antibody has a kd of between about 10-7sec-1and about 10-8sec-1. 62 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0201] In some embodiments, the affinity of the antibody for human TROP2, human TROP2 extracellular domain, or for individual domains within human TROP2, as determined by surface plasmon resonance at 25°C, and as indicated by KD, is from about 1.34 x10-9M to about 7.31x10-8M. In some embodiments, the affinity of the antibody for human TROP2 is about any of the KD values reported for human TROP2 in the examples below.

[0202] In some embodiments the antibody has a ka when associating with human TROP2, human TROP2 extracellular domain, or for individual domains within human TROP2, as determined by surface plasmon resonance at 25°C, of from about 1.78x104M-1×sec-1to about 1.46×105M-1×sec-1. In some embodiments the antibody has a ka when associating with human TROP2 of about any of the kavalues reported for human TROP2 in the examples below.

[0203] In some embodiments the antibody has a kdwhen dissociating from human TROP2, human TROP2 extracellular domain, or for individual domains within human TROP2, as determined by surface plasmon resonance at 25°C, of from about 1.96×10-4sec-1to about 1.81×10-3sec-1. In some embodiments the antibody has a kdwhen dissociating from human TROP2 of about any of the kd values reported for human TROP2 in the examples below.

[0204] In some aspects, the KD, ka, and kd are determined at 25°C. In some embodiments, the KD,ka, and kdare determined by surface plasmon resonance. In some embodiments, the KD,ka, and kdare determined according to the methods described in the Examples provided herein. 7. Epitope Bins

[0205] In some embodiments, the antibody binds the same epitope as an antibody encompassing any of SEQ ID NOs: 3789-4046 and 4382-4865. In some embodiments, the antibody binds the same epitope as an antibody comprising any of the VH-VL pairs, above.

[0206] In some embodiments, the antibody competes for epitope binding with an antibody encompassing any of SEQ ID NOs: 3789-4046 and 4382-4865. In some embodiments, the antibody competes for epitope binding with an antibody comprising any of the VH-VLpairs, above.

[0207] In some embodiments, the antibody specifically binds to TROP2, wherein the antibody binds to the same epitope as a second antibody with a VHregion selected from any one of SEQ ID NOs: 3789-4046 and 4382-4633, and a VL region selected from any one of SEQ ID NOs: 4634-4865. 63 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 8. Glycosylation Variants

[0208] In certain embodiments, an antibody may be altered to increase, decrease or eliminate the extent to which it is glycosylated. In certain embodiments, an antibody may be altered to be aglycosylated. Glycosylation of polypeptides is typically either “N-linked” or “O-linked.”

[0209] “N-linked” glycosylation refers to the attachment of a carbohydrate moiety to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain. Thus, the presence of either of these tripeptide sequences in a polypeptide creates a potential glycosylation site.

[0210] “O-linked” glycosylation refers to the attachment of one of the sugars N- acetylgalactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.

[0211] Addition or deletion of N-linked glycosylation sites to the antibody may be accomplished by altering the amino acid sequence such that one or more of the above-described tripeptide sequences is created or removed. Addition or deletion of O-linked glycosylation sites may be accomplished by addition, deletion, or substitution of one or more serine or threonine residues in or to (as the case may be) the sequence of an antibody. 9. Fc Variants

[0212] In certain embodiments, amino acid modifications may be introduced into the Fc region of an antibody provided herein to generate an Fc region variant. In certain embodiments, the Fc region variant possesses some, but not all, effector functions. Such antibodies may be useful, for example, in applications in which the half-life of the antibody in vivo is important, yet certain effector functions are unnecessary or deleterious. Examples of effector functions include complement-dependent cytotoxicity (CDC) and antibody-directed complement- mediated cytotoxicity (ADCC). Numerous substitutions or substitutions or deletions with altered effector function are known in the art.

[0213] An alteration in CDC and / or ADCC activity can be confirmed using in vitro and / or in vivo assays. For example, Fc receptor (FcR) binding assays can be conducted to measure FcγR binding. The primary cells for mediating ADCC, NK cells, express FcγRIII only, whereas monocytes express FcγRI, FcγRII and FcγRIII. FcR expression on hematopoietic cells is summarized in Ravetch and Kinet, Ann. Rev. Immunol., 1991, 9:457-492, incorporated by reference in its entirety. 64 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0214] Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest are provided in U.S. Patent NOs 5,500,362 and 5,821,337; Hellstrom et al., Proc. Natl. Acad. Sci. U.S.A., 1986, 83:7059-7063; Hellstrom et al., Proc. Natl. Acad. Sci. U.S.A., 1985, 82:1499-1502; and Bruggemann et al., J. Exp. Med., 1987, 166:1351-1361; each of which is incorporated by reference in its entirety. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, using an animal model such as that disclosed in Clynes et al. Proc. Natl. Acad. Sci. U.S.A., 1998, 95:652-656, incorporated by reference in its entirety.

[0215] C1q binding assays may also be carried out to confirm that the antibody is unable to bind C1q and hence lacks CDC activity. Examples of C1q binding assays include those described in WO 2006 / 029879 and WO 2005 / 100402, each of which is incorporated by reference in its entirety.

[0216] Complement activation assays include those described, for example, in Gazzano- Santoro et al., J. Immunol. Methods, 1996, 202:163-171; Cragg et al., Blood, 2003, 101:1045- 1052; and Cragg and Glennie, Blood, 2004, 103:2738-2743; each of which is incorporated by reference in its entirety.

[0217] FcRn binding and in vivo clearance (half-life determination) can also be measured, for example, using the methods described in Petkova et al., Intl. Immunol., 2006, 18:1759-1769, incorporated by reference in its entirety. 10. Preparation of Antibodies 10.1. Antigen Preparation

[0218] The TROP2 protein to be used for isolation of the antibodies may be intact TROP2 or a fragment of TROP2. The intact TROP2 protein, or fragment of TROP2, may be in the form of an isolated protein or protein expressed by a cell. Other forms of TROP2 useful for generating antibodies will be apparent to those skilled in the art. 10.2. Monoclonal Antibodies

[0219] Monoclonal antibodies may be obtained, for example, using the hybridoma method first described by Kohler et al., Nature, 1975, 256:495-497 (incorporated by reference in its entirety), and / or by recombinant DNA methods (see e.g., U.S. Patent No. 4,816,567, incorporated by reference in its entirety). Monoclonal antibodies may also be obtained, for example, using phage or yeast-based libraries. See e.g., U.S. Patent NOs 8,258,082 and 8,691,730, each of which is incorporated by reference in its entirety. 65 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0220] In the hybridoma method, a mouse or other appropriate host animal is immunized to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization. Alternatively, lymphocytes may be immunized in vitro. Lymphocytes are then fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell. See Goding J.W., Monoclonal Antibodies: Principles and Practice 3rded. (1986) Academic Press, San Diego, CA, incorporated by reference in its entirety.

[0221] The hybridoma cells are seeded and grown in a suitable culture medium that contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells. For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.

[0222] Useful myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive media conditions, such as the presence or absence of HAT medium. Among these, preferred myeloma cell lines are murine myeloma lines, such as those derived from MOP-21 and MC-11 mouse tumors (available from the Salk Institute Cell Distribution Center, San Diego, CA), and SP-2 or X63-Ag8-653 cells (available from the American Type Culture Collection, Rockville, MD). Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies. See e.g., Kozbor, J. Immunol., 1984, 133:3001, incorporated by reference in its entirety.

[0223] After the identification of hybridoma cells that produce antibodies of the desired specificity, affinity, and / or biological activity, selected clones may be subcloned by limiting dilution procedures and grown by standard methods. See Goding, supra. Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal.

[0224] DNA encoding the monoclonal antibodies may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies). Thus, the hybridoma cells can serve as a useful source of DNA encoding antibodies with the desired properties. Once isolated, the DNA may be placed into expression vectors, which are then transfected into host cells such as bacteria (e.g., E. coli), yeast (e.g., Saccharomyces or Pichia 66 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO sp.), COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce antibody, to produce the monoclonal antibodies. 10.3. Humanized Antibodies

[0225] Humanized antibodies may be generated by replacing most, or all, of the structural portions of a non-human monoclonal antibody with corresponding human antibody sequences. Consequently, a hybrid molecule is generated in which only the antigen-specific variable, or CDR, is composed of non-human sequence. Methods to obtain humanized antibodies include those described in, for example, Winter and Milstein, Nature, 1991, 349:293-299; Rader et al., Proc. Nat. Acad. Sci. U.S.A., 1998, 95:8910-8915; Steinberger et al., J. Biol. Chem., 2000, 275:36073-36078; Queen et al., Proc. Natl. Acad. Sci. U.S.A., 1989, 86:10029-10033; and U.S. Patent NOs 5,585,089, 5,693,761, 5,693,762, and 6,180,370; each of which is incorporated by reference in its entirety.

[0226] In some embodiments, an isolated antibody that binds to TROP2 has been humanized.

[0227] In some embodiments, the humanized antibody comprises one or more framework regions of a VH comprising any one of SEQ ID NOS: 4492-4633. In some embodiments, the humanized antibody comprises one or more framework regions of a VLcomprising any one of SEQ ID NOS: 4724-4865. 10.4. Human Antibodies

[0228] Human antibodies can be generated by a variety of techniques known in the art, for example by using transgenic animals (e.g., humanized mice). See, e.g., Jakobovits et al., Proc. Natl. Acad. Sci. U.S.A., 1993, 90:2551; Jakobovits et al., Nature, 1993, 362:255-258; Bruggermann et al., Year in Immuno., 1993, 7:33; and U.S. Patent NOs 5,591,669, 5,589,369 and 5,545,807; each of which is incorporated by reference in its entirety. Human antibodies can also be derived from phage-display libraries (see e.g., Hoogenboom et al., J. Mol. Biol., 1991, 227:381-388; Marks et al., J. Mol. Biol., 1991, 222:581-597; and U.S. Pat. NOs 5,565,332 and 5,573,905; each of which is incorporated by reference in its entirety). Human antibodies may also be generated by in vitro activated B cells (see e.g., U.S. Patent. NOs 5,567,610 and 5,229,275, each of which is incorporated by reference in its entirety). Human antibodies may also be derived from yeast-based libraries (see e.g., U.S. Patent No.8,691,730, incorporated by reference in its entirety). 11. Antibody conjugates Antibody Drug Conjugates (ADCs) and Immune Stimulator Antibody Conjugates (ISACs) 67 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0229] In some aspects, the present disclosure provides antibody conjugates comprising an isolated anti-TROP2 antibody described herein linked to at least one payload optionally via a linker, wherein the payload is a cytotoxic agent or an immunomodulatory agent.

[0230] In some embodiments, the antibody conjugates are according to the following Formula (I): or a pharmaceutically acceptable salt, solvate,stereoisomer, regioisomer, or tautomer thereof, wherein: COMP is a residue of an anti-TROP2 antibody; PAY is a residue a payload moiety, wherein the payload moiety is a cytotoxic agent or an immunomodulatory agent; LINK is a linker; and n2 is an integer from 1 to 10, wherein COMP comprises one or more non-natural amino acids.

[0231] In some embodiments, n2 is 2. In some embodiments, n2 is 3. In some embodiments, n2 is 4. In some embodiments, n2 is 5. In some embodiments, n2 is 6. In some embodiments, n2 is 7. In some embodiments, n2 is 8. In some embodiments, n2 is 9. In some embodiments, n2 is 10. Immunomodulatory Antibody Drug Conjugates (iADCs)

[0232] In some aspects, the present disclosure provides antibody conjugates comprising an isolated an anti-TROP antibody that comprises (a) three heavy chain CDRs from a VHsequence selected from SEQ ID NOs: 3789-3801, 3803-3983, 3985-4046, 4382-4395, 4397-4458, and 4460-4491, or variants thereof, and (b) three light chain CDRs from a VL sequence selected from SEQ ID NOs: 4634-4690, and 4692-4723, or variants thereof, linked to at least one cytotoxic agent optionally via a linker and at least one immunomodulatory agent optionally via a linker.

[0233] In some embodiments, the antibody conjugates are according to the followingFormula (II): or a pharmaceutically acceptable salt,solvate, stereoisomer, regioisomer, or tautomer thereof, wherein: COMP is a residue of an anti-TROP2 antibody that comprises (a) three heavy chain CDRs from a VHsequence selected from SEQ ID NOs: 3789-3801, 3803-3983, 3985- 4046, 4382-4395, 4397-4458, and 4460-4491, or variants thereof, and (b) three light chain CDRs from a VL sequence selected from SEQ ID NOs: 4634-4690, and 4692-4723, or variants thereof; Lais a first linker; 68 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Lbis a second linker; each CY is independently a residue of a cytotoxic agent thereof; each IM is independently a residue of an immunomodulatory agent thereof; subscript n is an integer selected from 1 to 10; and subscript m is an integer selected from 1 to 10.

[0234] In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. In some embodiments, m is 7. In some embodiments, m is 8. In some embodiments, m is 9. In some embodiments, m is 10.

[0235] In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10.

[0236] In some embodiments, the payload is a cytotoxic payload. Non-limiting examples of a cytotoxic payload include a tubulin inhibitor, a DNA topoisomerase I inhibitor, and a DNA topoisomerase II inhibitor. In some embodiments, including any of the foregoing, the payload is a tubulin inhibitor. In some embodiments, including any of the foregoing, the payload is a DNA topoisomerase I inhibitor. In some embodiments, including any of the foregoing, the payload is a DNA topoisomerase I inhibitor selected from the group consisting of irinotecan, SN-38, topotecan, and exatecan. In some embodiments, including any of the foregoing, the payload is irinotecan. In some embodiments, including any of the foregoing, the payload is SN-38. In some embodiments, including any of the foregoing, the payload is topotecan. In some embodiments, including any of the foregoing, the payload is exatecan. In some embodiments, including any of the foregoing, the payload is a DNA topoisomerase II inhibitor. In some embodiments, including any of the foregoing, the payload is a DNA topoisomerase II inhibitor selected from the group consisting of etoposide, teniposide, and tafluposide. In some embodiments, including any of the foregoing, the payload is etoposide. In some embodiments, including any of the foregoing, the payload is teniposide. In some embodiments, including any of the foregoing, the payload is tafluposide. In some embodiments, including any of the foregoing, the payload is selected from the group consisting of hemiasterlins, camptothecins, and anthracyclines. Anthracyclines may include PNU-159682 and EDA PNU-159682 derivatives. In some embodiments, including any of the foregoing, the payload is an anthracycline selected from the group consisting of daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone, and valrubicin. In some embodiments, including any of the foregoing, the payload is daunorubicin. In some embodiments, including any of the foregoing, the payload is doxorubicin. In some embodiments, 69 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO including any of the foregoing, the payload is epirubicin. In some embodiments, including any of the foregoing, the payload is idarubicin. In some embodiments, including any of the foregoing, the payload is mitoxantrone. In some embodiments, including any of the foregoing, the payload is valrubicin. In some embodiments, including any of the foregoing, the payload is a hemiasterlin. In some embodiments, including any of the foregoing, the payload is a camptothecin. In some embodiments, including any of the foregoing, the payload is an anthracycline. In some embodiments, including any of the foregoing, the payload is PNU- 159682. In some embodiments, including any of the foregoing, the payload is an EDA PNU compound. In some embodiments, including any of the foregoing, the payload is an EDA PNU- 159682 derivative. In some embodiments, including any of the foregoing, the payload is hemiasterlin, exatecan, PNU-159682, or an EDA PNU-159682 derivative. In some embodiments, including any of the foregoing, the payload is hemiasterlin. In some embodiments, including any of the foregoing, the payload is exatecan. In some embodiments, including any of the foregoing, the payload is PNU-159682. In some embodiments, including any of the foregoing, the payload is EDA PNU-159682 compound or derivative.

[0237] In some embodiments, including any of the foregoing, the payload is an alkylating agent. In some embodiments, including any of the foregoing, the payload is a bifunctional alkylator. In some embodiments, including any of the foregoing, the payload is a bifunctional alkylator selected from the group consisting of cyclophosphamide, mechlorethamine, chlorambucil, and melphalan. In some embodiments, including any of the foregoing, the payload is cyclophosphamide. In some embodiments, including any of the foregoing, the payload is mechlorethamine. In some embodiments, including any of the foregoing, the payload is chlorambucil. In some embodiments, including any of the foregoing, the payload is melphalan. In some embodiments, including any of the foregoing, the payload is a monofunctional alkylator. In some embodiments, including any of the foregoing, the payload is a monofunctional alkkylator selected from the group consisting of dacabazine, nitrosourea, and temozolomide. In some embodiments, including any of the foregoing, the payload is dacabazine. In some embodiments, including any of the foregoing, the payload is nitrosourea. In some embodiments, including any of the foregoing, the payload is temozolomide. In some embodiments, including any of the foregoing, the payload is a cytoskeletal disruptor (e.g., a taxane). In some embodiments, including any of the foregoing, the payload is a cytoskeletal disruptor selected from the group consisting of paclitaxel, docetaxel, abraxane, and taxotere. In some embodiments, including any of the foregoing, the payload is paclitaxel. In some embodiments, including any of the foregoing, the payload is docetaxel. In some embodiments, including any 70 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO of the foregoing, the payload is abraxane. In some embodiments, including any of the foregoing, the payload is taxotere. In some embodiments, including any of the foregoing, the payload is an epothilone. In some embodiments, including any of the foregoing, the payload is an epothilone selected from the group consisting of epothilone A, epothilone B, epothilone C, epothilone D, and ixabepilone. In some embodiments, including any of the foregoing, the payload is epothilone A. In some embodiments, including any of the foregoing, the payload is epothilone B. In some embodiments, including any of the foregoing, PAY is epothilone C. In some embodiments, including any of the foregoing, the payload is epothilone D. In some embodiments, including any of the foregoing, the payload is ixabepilone. In some embodiments, including any of the foregoing, the payload is a histone deacetylase inhibitor. In some embodiments, including any of the foregoing, the payload is a histone deacetylase inhibitor selected from the group consisting of vorinostat and romidepsin. In some embodiments, including any of the foregoing, the payload is vorinostat. In some embodiments, including any of the foregoing, the payload is romidepsin. In some embodiments, including any of the foregoing, the payload is a kinase inhibitor. In some embodiments, including any of the foregoing, the payload is a kinase inhibitor selected from the group consisting of bortezomib, erlotinib, gefitinib, imatinib, vemurafenib, and vismodegib. In some embodiments, including any of the foregoing, the payload is bortezomib. In some embodiments, including any of the foregoing, PAY is erlotinib. In some embodiments, including any of the foregoing, the payload is gefitinib. In some embodiments, including any of the foregoing, the payload is imatinib. In some embodiments, including any of the foregoing, the payload is vemurafenib. In some embodiments, including any of the foregoing, the payload is vismodegib. In some embodiments, including any of the foregoing, the payload is a nucleotide analog and / or precursor analog. In some embodiments, including any of the foregoing, the payload is a nucleotide analog and / or precursor analog selected from the group consisting of azacitidine, azathioprine, capecitabine, cyatarabine, doxifluridine, fluorouracil, gemcitabine, hydroxyurea, mercaptopurine, methotrexate, and tioguanine (formerly thioguanine). In some embodiments, including any of the foregoing, the payload is azacitidine. In some embodiments, including any of the foregoing, the payload is azathioprine. In some embodiments, including any of the foregoing, the payload is capecitabine. In some embodiments, including any of the foregoing, the payload is cyatarabine. In some embodiments, including any of the foregoing, the payload is doxifluridine. In some embodiments, including any of the foregoing, the payload is fluorouracil. In some embodiments, including any of the foregoing, the payload is gemcitabine. In some embodiments, including any of the foregoing, the payload is hydroxyurea. In some embodiments, including any of the foregoing, the payload is mercaptopurine. In some 71 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO embodiments, including any of the foregoing, the payload is methotrexate. In some embodiments, including any of the foregoing, the payload is tioguanine (formerly thioguanine). In some embodiments, including any of the foregoing, the payload is a peptide antibiotic. In some embodiments, including any of the foregoing, the payload is a peptide antibiotic selected from the group consisting of bleomycin and actinomycin. In some embodiments, including any of the foregoing, the payload is bleomycin. In some embodiments, including any of the foregoing, the payload is actinomycin. In some embodiments, including any of the foregoing, the payload is a platinum-based agent. In some embodiments, including any of the foregoing, the payload is a platinum-based agent selected from the group consisting of carboplatin, cisplatin, and oxaliplatin. In some embodiments, including any of the foregoing, the payload is carboplatin. In some embodiments, including any of the foregoing, the payload is cisplatin. In some embodiments, including any of the foregoing, the payload is oxaliplatin. In some embodiments, including any of the foregoing, the payload is a retinoid. In some embodiments, including any of the foregoing, the payload is a retinoid selected from the group consisting of tretinoin, alitretinoin, and bexarotene. In some embodiments, including any of the foregoing, the payload is tretinoin. In some embodiments, including any of the foregoing, the payload is alitretinoin. In some embodiments, including any of the foregoing, the payload is bexarotene. In some embodiments, including any of the foregoing, the payload is a vinca alkaloid and derivatives thereof. In some embodiments, including any of the foregoing, the payload is a vinca alkaloid and derivatives thereof selected from the group consisting of vinblastine, vincristine, vindesine, vinorelbine. In some embodiments, including any of the foregoing, the payload is a residue of vinblastine. In some embodiments, including any of the foregoing, the payload is vincristine. In some embodiments, including any of the foregoing, the payload is vindesine.

[0238] In one embodiment, the payload is a residue of a cytotoxic agent selected from the group consisting of an alkylating agent, a DNA-crosslinking agent, an anti-tumor antibiotic, an anti-metabolite, an anti-mitotic agent, a histone-deacetylase (HDAC) inhibitor, a telomerase inhibitor, an immunogenic cell death agent, a tubulin inhibitor, and a topoisomerase inhibitor, or derivative thereof. In one embodiment, the cytotoxic agent is a topoisomerase inhibitor and the topoisomerase inhibitor is a topoisomerase I inhibitor or derivative thereof. In one embodiment, the topoisomerase I inhibitor is selected from the group consisting of camptothecin, irinotecan, SN-38, topotecan, and exatecan, or a derivative thereof. In one embodiment, the topoisomerase I inhibitor is exatecan or a derivative thereof. In one embodiment, the cytotoxic agent is a tubulin inhibitor. In one embodiment, the tubulin inhibitor is a hemiasterlin, a maytansine, or derivative thereof. 72 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0239] In addition to the payloads described above, the molecular payload can be any molecular entity that one of skill in the art might desire to conjugate to the polypeptide. In certain embodiments, the payload is a therapeutic moiety. In such embodiment, the antibody conjugate can be used to target the therapeutic moiety to its molecular target. In certain embodiments, the payload is a labeling moiety. In such embodiments, the antibody conjugate can be used to detect binding of the polypeptide to its target. In certain embodiments, the payload is a cytotoxic moiety. In such embodiments, the antibody conjugate can be used target the cytotoxic moiety to a diseased cell, for example a cancer cell, to initiate destruction or elimination of the cell. Conjugates comprising other molecular payloads apparent to those of skill in the art are within the scope of the conjugates described herein.

[0240] In certain embodiments, an antibody conjugate can have a payload selected from the group consisting of a label, a dye, a polymer, a water-soluble polymer, polyethylene glycol, a derivative of polyethylene glycol, a photocrosslinker, a cytotoxic compound, a radionuclide, a drug, an affinity label, a photoaffinity label, a reactive compound, a resin, a second protein or polypeptide or polypeptide analog, an antibody or antibody fragment, a metal chelator, a cofactor, a fatty acid, a carbohydrate, a polynucleotide, a DNA, a RNA, an antisense polynucleotide, a peptide, a water-soluble dendrimer, a cyclodextrin, an inhibitory ribonucleic acid, a biomaterial, a nanoparticle, a spin label, a fluorophore, a metal-containing moiety, a radioactive moiety, a novel functional group, a group that covalently or noncovalently interacts with other molecules, a photocaged moiety, a photoisomerizable moiety, biotin, a derivative of biotin, a biotin analogue, a moiety incorporating a heavy atom, a chemically cleavable group, a photocleavable group, an elongated side chain, a carbon-linked sugar, a redox-active agent, an amino thioacid, a toxic moiety, an isotopically labeled moiety, a biophysical probe, a phosphorescent group, a chemiluminescent group, an electron dense group, a magnetic group, an intercalating group, a chromophore, an energy transfer agent, a biologically active agent, a detectable label, a small molecule, or any combination thereof. In an embodiment, the payload is a label, a dye, a polymer, a cytotoxic compound, a radionuclide, a drug, an affinity label, a resin, a protein, a polypeptide, a polypeptide analog, an antibody, antibody fragment, a metal chelator, a cofactor, a fatty acid, a carbohydrate, a polynucleotide, a DNA, a RNA, a peptide, a fluorophore, or a carbon-linked sugar. In another embodiment, the payload is a label, a dye, a polymer, a drug, an antibody, antibody fragment, a DNA, an RNA, or a peptide.

[0241] Useful drug payloads include any cytotoxic or cytostatic agent. Useful classes of cytotoxic agents include, for example, antitubulin agents, auristatins, DNA minor groove binders, DNA replication inhibitors, alkylating agents (e.g., platinum complexes such as cis- 73 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO platin, mono(platinum), bis(platinum) and tri-nuclear platinum complexes and carboplatin), anthracyclines, antibiotics, antifolates, antimetabolites, calmodulin inhibitors, chemotherapy sensitizers, duocarmycins, etoposides, fluorinated pyrimidines, ionophores, lexitropsins, maytansinoids, nitrosoureas, platinols, pore-forming compounds, purine antimetabolites, puromycins, radiation sensitizers, rapamycins, steroids, taxanes, topoisomerase inhibitors, vinca alkaloids, or the like.

[0242] Individual cytotoxic agents include, for example, an androgen, anthramycin (AMC), asparaginase, 5-azacytidine, azathioprine, bleomycin, busulfan, buthionine sulfoximine, calicheamicin, calicheamicin derivatives, camptothecin, carboplatin, carmustine (BSNU), CC- 1065, chlorambucil, cisplatin, colchicine, cyclophosphamide, cytarabine, cytidine arabinoside, cytochalasin B, dacarbazine, dactinomycin (formerly actinomycin), daunorubicin, decarbazine, DM1, DM4, docetaxel, doxorubicin, etoposide, an estrogen, 5-fluordeoxyuridine, 5-fluorouracil, gemcitabine, gramicidin D, hydroxyurea, idarubicin, ifosfamide, irinotecan, lomustine (CCNU), maytansine, mechlorethamine, melphalan, 6-mercaptopurine, methotrexate, mithramycin, mitomycin C, mitoxantrone, nitroimidazole, paclitaxel, palytoxin, plicamycin, procarbizine, rhizoxin, streptozotocin, tenoposide, 6-thioguanine, thioTEPA, topotecan, vinblastine, vincristine, vinorelbine, VP-16 and VM-26.

[0243] In some embodiments, suitable cytotoxic agents include, for example, DNA minor groove binders (e.g., enediynes and lexitropsins, a CBI compound; see also U.S. Pat. No. 6,130,237), duocarmycins, taxanes (e.g., paclitaxel and docetaxel), puromycins, vinca alkaloids, CC-1065, SN-38, topotecan, morpholino-doxorubicin, rhizoxin, cyanomorpholino-doxorubicin, echinomycin, combretastatin, netropsin, epothilone A and B, estramustine, cryptophycins, cemadotin, maytansinoids, discodermolide, eleutherobin, and mitoxantrone.

[0244] In some embodiments, the payload is an anti-tubulin agent. Examples of anti-tubulin agents include, but are not limited to, taxanes (e.g., Taxol® (paclitaxel), Taxotere® (docetaxel)), T67 (Tularik) and vinca alkyloids (e.g., vincristine, vinblastine, vindesine, and vinorelbine). Other antitubulin agents include, for example, baccatin derivatives, taxane analogs, epothilones (e.g., epothilone A and B), nocodazole, colchicine and colcimid, estramustine, cryptophycins, cemadotin, maytansinoids, combretastatins, discodermolide, and eleutherobin.

[0245] In certain embodiments, the cytotoxic agent is a maytansinoid, another group of anti- tubulin agents. For example, in specific embodiments, the maytansinoid can be maytansine or DM1 (ImmunoGen, Inc.; see also Chari et al., 1992, Cancer Res.52:127-131).

[0246] In some embodiments, the payload is an auristatin, such as auristatin E or a derivative thereof. For example, the auristatin E derivative can be an ester formed between auristatin E and 74 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO a keto acid. For example, auristatin E can be reacted with paraacetyl benzoic acid or benzoylvaleric acid to produce AEB and AEVB, respectively. Other typical auristatin derivatives include AFP (auristatin phenylalanine phenylenediamine), MMAF (monomethyl auristatin F), and MMAE (monomethyl auristatin E). The synthesis and structure of auristatin derivatives are described in U.S. Patent Application Publication Nos. 2003-0083263, 2005- 0238649 and 2005-0009751; International Patent Publication No. WO 04 / 010957, International Patent Publication No. WO 02 / 088172, and U.S. Pat. Nos. 6,323,315; 6,239,104; 6,034,065; 5,780,588; 5,665,860; 5,663,149; 5,635,483; 5,599,902; 5,554,725; 5,530,097; 5,521,284; 5,504,191; 5,410,024; 5,138,036; 5,076,973; 4,986,988; 4,978,744; 4,879,278; 4,816,444; and 4,486,414.

[0247] In some embodiments, the payload is a hemiasterlin. Hemiasterlins suitable for use in the antibody-drug conjugates described herein are described, for example, in International Patent Publication No. WO 2016 / 2016 / 123582, which is incorporated herein by reference in its entirety.

[0248] In some embodiments, the payload is not a radioisotope. In some embodiments, the payload is not radioactive.

[0249] In some embodiments, the payload is an antimetabolite. The antimetabolite can be, for example, a purine antagonist (e.g., azothioprine or mycophenolate mofetil), a dihydrofolate reductase inhibitor (e.g., methotrexate), acyclovir, gangcyclovir, zidovudine, vidarabine, ribavarin, azidothymidine, cytidine arabinoside, amantadine, dideoxyuridine, iododeoxyuridine, poscarnet, or trifluridine.

[0250] In other embodiments, the payload is tacrolimus, cyclosporine, FU506 or rapamycin. In further embodiments, the Drug is aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, amifostine, anastrozole, arsenic trioxide, bexarotene, bexarotene, calusterone, capecitabine, celecoxib, cladribine, Darbepoetin alfa, Denileukin diftitox, dexrazoxane, dromostanolone propionate, epirubicin, Epoetin alfa, estramustine, exemestane, Filgrastim, floxuridine, fludarabine, fulvestrant, gemcitabine, gemtuzumab ozogamicin (MYLOTARG), goserelin, idarubicin, ifosfamide, imatinib mesylate, Interferon alfa-2a, irinotecan, letrozole, leucovorin, levamisole, meclorethamine or nitrogen mustard, megestrol, mesna, methotrexate, methoxsalen, mitomycin C, mitotane, nandrolone phenpropionate, oprelvekin, oxaliplatin, pamidronate, pegademase, pegaspargase, pegfilgrastim, pentostatin, pipobroman, a pladienolide, plicamycin, porfimer sodium, procarbazine, quinacrine, rasburicase, Rituximab, Sargramostim, streptozocin, tamoxifen, temozolomide, teniposide, testolactone, thioguanine, 75 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO toremifene, Tositumomab, Trastuzumab (HERCEPTIN), tretinoin, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine or zoledronate.

[0251] Other useful drug payloads include chemical compounds useful in the treatment of cancer. Examples of chemotherapeutic agents include Erlotinib (TARCEVA®, Genentech / OSI Pharm.), Bortezomib (VELCADE®, Millennium Pharm.), Fulvestrant (FASLODEX®, AstraZeneca), Sutent (SU11248, Pfizer), Letrozole (FEMARA®, Novartis), Imatinib mesylate (GLEEVEC®, Novartis), PTK787 / ZK 222584 (Novartis), Oxaliplatin (Eloxatin®, Sanofi), 5- FU (5-fluorouracil), Leucovorin, Rapamycin (Sirolimus, RAPAMUNE®, Wyeth), Lapatinib (TYKERB®, GSK572016, Glaxo Smith Kline), Lonafarnib (SCH 66336), Sorafenib (BAY43- 9006, Bayer Labs), and Gefitinib (IRESSA®, AstraZeneca), AG1478, AG1571 (SU 5271; Sugen), alkylating agents such as thiotepa and CYTOXAN® cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic analog topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogs); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogs, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlomaphazine, chlorophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g., calicheamicin, especially uncialamycin, calicheamicin gammall, and calicheamicin omegall (Angew Chem. Intl. Ed. Engl. (1994) 33:183-186); dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADRIAMYCIN® (doxorubicin), morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2- pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, porfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate 76 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pladienolide B, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamniprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elformithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2''- trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids, e.g., TAXOL® (paclitaxel; Bristol-Myers Squibb Oncology, Princeton, N.J.), ABRAXANE® (Cremophor-free), albumin-engineered nanoparticle formulations of paclitaxel (American Pharmaceutical Partners, Schaumberg, Ill.), and TAXOTERE® (doxetaxel; Rhone-Poulenc Rorer, Antony, France); chloranmbucil; GEMZAR® (gemcitabine); 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE® (vinorelbine); novantrone; teniposide; edatrexate; daunomycin; aminopterin; capecitabine (XELODA®); ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; and pharmaceutically acceptable salts, acids and derivatives of any of the above.

[0252] Other useful payloads include: (i) anti-hormonal agents that act to regulate or inhibit hormone action on tumors such as anti-estrogens and selective estrogen receptor modulators (SERMs), including, for example, tamoxifen (including NOLVADEX®; tamoxifen citrate), raloxifene, droloxifene, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, and FARESTON® (toremifine citrate); (ii) aromatase inhibitors that inhibit the enzyme aromatase, which regulates estrogen production in the adrenal glands, such as, for example, 4(5)- imidazoles, aminoglutethimide, MEGASE® (megestrol acetate), AROMASIN® (exemestane; Pfizer), formestanie, fadrozole, RIVISOR® (vorozole), FEMARA® (letrozole; Novartis), and 77 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ARIMIDEX® (anastrozole; AstraZeneca); (iii) anti-androgens such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; as well as troxacitabine (a 1,3-dioxolane nucleoside cytosine analog); (iv) protein kinase inhibitors; (v) lipid kinase inhibitors; (vi) antisense oligonucleotides, particularly those which inhibit expression of genes in signaling pathways implicated in aberrant cell proliferation, such as, for example, PKC-alpha, Ralf and H-Ras; (vii) ribozymes such as VEGF expression inhibitors (e.g., ANGIOZYME®) and HER2 expression inhibitors; (viii) vaccines such as gene therapy vaccines, for example, ALLOVECTIN®, LEUVECTIN®, and VAXID®; PROLEUKIN® rIL-2; a topoisomerase 1 inhibitor such as LURTOTECAN®; ABARELIX® rmRH; (ix) anti-angiogenic agents such as bevacizumab (AVASTIN®, Genentech); (x) agents that act to regulate or inhibit activity of members of the poly(ADP-ribose) polymerase (PARP) family in tumors (e.g., Talazoparib (BMN-673), Iniparib (BSI 201), Veliparib (ABT-888), Olaparib (AZD-2281, trade name LYNPARZA™), Rucaparib (AG 014699), BGB-290, E7016, E7449, and CEP-9722); (xi) agents that act to regulate or inhibit activity of members of the histone deacetylase (HDAC) family in tumors (e.g., abexinostat, entinostat, gavinostat, 4SC-202, ACY-241, AR-42, CG200745, CHR-2845, CHR-3996, CXD101, MPT0E028, OBP-801, SHP-141, CUDC-101, KA2507, panobinostat, pracinostat, quisinostat, resminostat, ricolinostat); (xii) agents that act to regulate or inhibit activity of mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2) in tumors (e.g., enasidenib mesylate (CC-90007, AG-221 mesylate); and (xiii) pharmaceutically acceptable salts, acids and derivatives of any of the above. Other useful payloads include anti-angiogenic agents, including, e.g., MMP-2 (matrix-metalloproteinase 2) inhibitors, MMP-9 (matrix-metalloproteinase 9) inhibitors, COX-II (cyclooxygenase II) inhibitors, and VEGF receptor tyrosine kinase inhibitors. Examples of such useful matrix metalloproteinase inhibitors that can be used in combination with the present compounds / compositions are described in WO 96 / 33172, WO 96 / 27583, EP 818442, EP 1004578, WO 98 / 07697, WO 98 / 03516, WO 98 / 34918, WO 98 / 34915, WO 98 / 33768, WO 98 / 30566, EP 606,046, EP 931,788, WO 90 / 05719, WO 99 / 52910, WO 99 / 52889, WO 99 / 29667, WO 99 / 07675, EP 945864, U.S. Pat. No. 5,863,949, U.S. Pat. No. 5,861,510, and EP 780,386, all of which are incorporated herein in their entireties by reference. Examples of VEGF receptor tyrosine kinase inhibitors include 4-(4-bromo-2-fluoroanilino)-6- methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (ZD6474; Example 2 within WO 01 / 32651), 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-pyrrolidin-1- ylpropoxy)quinazoline (AZD2171; Example 240 within WO 00 / 47212), vatalanib (PTK787; WO 98 / 35985) and SU11248 (sunitinib; WO 01 / 60814), and compounds such as those disclosed in PCT Publication Nos. WO 97 / 22596, WO 97 / 30035, WO 97 / 32856, and WO 98 / 13354). 78 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0253] In some embodiments, the payload is a cytotoxic agent or an immunomodulatory agent. In some embodiments, the payload is a cytotoxic agent, e.g., a cytotoxic agent described herein. In some embodiments, the payload is an immunomodulatory agent. In some embodiments, the immunomodulatory agent is selected from the group consisting of toll-like receptor agonists, kinase inhibitors, growth factor inhibitors (e.g., EGFR, PDGF, VEGF inhibitors), Calcineurin inhibitors, CRAC inhibitors, PARPl antagonists, PPAR^ agonists, Kvl.3 antagonists, PP2A agonists, MYD88 inhibitors, BCL-2 inhibitors, Adenosine A2A receptor (A2ar) agonists, Toll-like receptor 7 / 8 (TLR7 / 8) agonists, Toll-like receptor 4 (TLR4) agonists, Toll-like receptor 9 (TLR9) agonists, calcium-activated potassium channel (Kca3.1) agonists, TGF-Rl inhibitors, TGF-R2 inhibitors, GLi 1 inhibitors, tankyrase (TNKS) antagonists, Traf2 and Nck-interacting kinase (TNIK) antagonists, imides, and vitamin D receptor (VDR) agonists. In some embodiments, the immunomodulatory agent is an agent that modulates components of the immune system such that it would enhance the anti-tumor activity of the conjugate. Examples of such agents include agonists of Toll-Like receptors (e.g., poly-ICLC (Hiltonol), GLA, MEDI9197, VTX-2337 (Motolimid), CpG (SD-101), and IMO-2125); agonists of the STING (stimulator of interferon genes) pathway (e.g., MK-1454, ADU-S100, and SB11285); activators of RIG-I-Like Receptor (RLR) signaling (e.g., RGT100); inhibitors of adenosinergic signaling (e.g., inhibitors of CD73, CD39 and A2R such as AB680, AB928, A000830, CPI-444), inhibitors of IDO-1 (indoleamine 2,3-dioxygenase 1) (e.g., GDC-0919 (navoximod), BMS-986205, and epacadostat); and small molecule blockers of the PD-1 pathway (e.g., CA- 170, BMS-8, BMS-202, and AUNP12). In some embodiments, the immunomodulatory agent is an anti-multiple myeloma agent. Examples of such immunomodulatory agents include lenalidomide, pomalidomide, and proteasome inhibitors. Examples of such proteasome inhibitors include, for example, bortezomib, carfilzomib, and ixazomib. In some embodiments, an immunomodulatory compound is an immunostimulatory compound. Additional examples of immunomodulatory agents include those described in WO2020252015, which is incorporated by reference in its entirety. In some embodiments, the payload is a STING agonist.

[0254] In any of the foregoing embodiments, the bracketed structure can be covalently bonded to one or more non-natural amino acids of the antibody, wherein the one or more non- natural amino acids are located at sites selected from the group consisting of: HC-F404, HC- Y180, HC-F241, LC-K42, and LC-E161, according to the Kabat or EU numbering scheme of Kabat. In some embodiments, the bracketed structure is covalently bonded to one or more non- natural amino acids at site HC-F404 of the antibody. In some embodiments, the bracketed structure is covalently bonded to one or more non-natural amino acids at site HC-Y180 of the 79 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO antibody. In some embodiments, the bracketed structure is covalently bonded to one or more non-natural amino acids at site HC-F241 of the antibody. In some embodiments, the bracketed structure is covalently bonded to one or more non-natural amino acids at site LC-K42 of the antibody. In some embodiments, the bracketed structure is covalently bonded to one or more non-natural amino acids at site LC-E161 of the antibody. In some embodiments, the bracketed structures are covalently bonded to non-natural amino acids at sites HC-F404 and HC-Y180 of the antibody. In some embodiments, the bracketed structures are covalently bonded to non- natural amino acids at sites HC-F404, HC-Y180, and LC-K42 of the antibody. In some embodiments, the bracketed structures are covalently bonded to non-natural amino acids at sites HC-F404, HC-Y180, LC-K42, and LC-E161 of the antibody. In some embodiments, the bracketed structures are covalently bonded to non-natural amino acids at sites HC-F404, HC- Y180, and HC-F241 of the antibody. In some embodiments, the bracketed structures are covalently bonded to non-natural amino acids at sites HC-F404, HC-Y180, HC-F241, and LC- K42 of the antibody.

[0255] In certain embodiments, the one or more non-natural amino acids is selected from the group consisting of p-acetyl-L-phenylalanine, O-methyl-L-tyrosine, an -3-(2-naphthyl)alanine, 3-methyl-phenylalanine, O-4-allyl-L-tyrosine, 4-propyl-L-tyrosine, a tri-O-acetyl-GlcNAcP- serine, L-Dopa, fluorinated phenylalanine, isopropyl-L-phenylalanine, p-azido-L- phenylalanine, p-azido-methyl-L-phenylalanine, p-acyl-L- phenylalanine, p-benzoyl-L- phenylalanine, L-phosphoserine, phosphonoserine, phosphonotyrosine, p-iodo-phenylalanine, p-bromophenylalanine, p-amino-L-phenylalanine, isopropyl-L-phenylalanine, and p- propargyloxy-phenylalanine. In certain embodiments, the non-natural amino acid residue is a residue of p-azido-methyl-L-phenylalanine or p-acetyl-L-phenylalanine. Further examples of non-natural amino acids include those described in WO2019055909, which is incorporated by reference herein in its entirety.

[0256] Useful linkers include those described herein. In certain embodiments, a linker is independently any divalent or multivalent linker known to those of skill in the art. Useful divalent linkers include alkylene, substituted alkylene, heteroalkylene, substituted heteroalkylene, arylene, substituted arylene, heteroarlyene, and substituted heteroarylene. In certain embodiments, a linker is C1-10 alkylene or C1-10 heteroalkylene. In some embodiments, the C1-10heteoalkylene is PEG.

[0257] In certain embodiments, the linker is hydrolytically stable. Hydrolytically stable linkages means that the linkages are substantially stable in water and do not react with water at useful pH values, including but not limited to, under physiological conditions for an extended 80 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO period of time, perhaps even indefinitely. In certain embodiments, a linker is hydrolytically unstable. Hydrolytically unstable or degradable linkages mean that the linkages are degradable in water or in aqueous solutions, including for example, blood. Enzymatically unstable or degradable linkages mean that the linkage can be degraded by one or more enzymes.

[0258] In some embodiments, the linker is protease cleavable linker, an enzyme cleavable linker, a pH-sensitive linker, or a non-cleavable linker.

[0259] As understood in the art, PEG and related polymers may include degradable linkages in the polymer backbone or in the linker group between the polymer backbone and one or more of the terminal functional groups of the polymer molecule. For example, ester linkages formed by the reaction of PEG carboxylic acids or activated PEG carboxylic acids with alcohol groups on a biologically active agent generally hydrolyze under physiological conditions to release the agent.

[0260] Other hydrolytically degradable linkers include, but are not limited to, carbonate linkages; imine linkages resulted from reaction of an amine and an aldehyde; phosphate ester linkages formed by reacting an alcohol with a phosphate group; hydrazone linkages which are reaction product of a hydrazide and an aldehyde; acetal linkages that are the reaction product of an aldehyde and an alcohol; orthoester linkages that are the reaction product of a formate and an alcohol; peptide linkages formed by an amine group, including but not limited to, at an end of a polymer such as PEG, and a carboxyl group of a peptide; and oligonucleotide linkages formed by a phosphoramidite group, including but not limited to, at the end of a polymer, and a 5' hydroxyl group of an oligonucleotide.

[0261] A number of different cleavable linkers are known to those of skill in the art. See U.S. Pat. Nos. 4,618,492; 4,542,225, and 4,625,014. The mechanisms for release of an agent from these linker groups include, for example, irradiation of a photolabile bond and acid- catalyzed hydrolysis. U.S. Pat. No. 4,671,958, for example, includes a description of immunoconjugates comprising linkers which are cleaved at the target site in vivo by the proteolytic enzymes of the patient's complement system. The length of the linker may be predetermined or selected depending upon a desired spatial relationship between the polypeptide and the molecule linked to it. In view of the large number of methods that have been reported for attaching a variety of radiodiagnostic compounds, radiotherapeutic compounds, drugs, toxins, and other agents to polypeptides one skilled in the art will be able to determine a suitable method for attaching a given agent to a polypeptide.

[0262] The linkers described herein may have a wide range of molecular weight or molecular length. Larger or smaller molecular weight linkers may be used to provide a desired spatial 81 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO relationship or conformation between the polypeptide and the linked entity. Linkers having longer or shorter molecular length may also be used to provide a desired space or flexibility between the polypeptide and the linked entity. Similarly, a linker having a particular shape or conformation may be utilized to impart a particular shape or conformation to the polypeptide or the linked entity, either before or after the polypeptide reaches its target. The functional groups present on each end of the linker may be selected to modulate the release of a polypeptide or a payload under desired conditions. This optimization of the spatial relationship between the polypeptide and the linked entity may provide new, modulated, or desired properties to the molecule.

[0263] In some embodiments, provided herein are water-soluble bifunctional linkers that have a dumbbell structure that includes: a) an azide, an alkyne, a hydrazine, a hydrazide, a hydroxylamine, or a carbonyl-containing moiety on at least a first end of a polymer backbone; and b) at least a second functional group on a second end of the polymer backbone. The second functional group can be the same or different as the first functional group. The second functional group, in some embodiments, is not reactive with the first functional group. In some embodiments, water-soluble compounds that comprise at least one arm of a branched molecular structure are provided. For example, the branched molecular structure can be a dendritic structure.

[0264] In some embodiments, a linker is derived from a linker precursor selected from the group consisting of: N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), N-succinimidyl 4- (2-pyridyldithio)pentanoate (SPP), N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB), N- succinimidyl-4-(2-pyridyldithio)-2-sulfo-butanoate (sulfo-SPDB), N-succinimidyl iodoacetate (SIA), N-succinimidyl(4-iodoacetyl)aminobenzoate (SIAB), maleimide PEG NHS, N- succinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (SMCC), N-sulfosuccinimidyl 4- (maleimidomethyl)cyclohexanecarboxylate (sulfo-SMCC) or 2,5-dioxopyrrolidin-1-yl 17-(2,5- dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5,8,11,14-tetraoxo-4,7,10,13-tetraazaheptadecan-1-oate (CX1-1). In a specific embodiment, the linker is derived from the linker precursor N- succinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate (SMCC).

[0265] In some embodiments, a linker is derived from a linker precursor selected from the group consisting of dipeptides, tripeptides, tetrapeptides, and pentapeptides. In such embodiments, the linker can be cleaved by a protease. Exemplary dipeptides include, but are not limited to, valine-citrulline (vc or val-cit), alanine-phenylalanine (af or ala-phe); phenylalanine- lysine (fk or phe-lys); phenylalanine-homolysine (phe-homolys); and N-methyl-valine-citrulline (Me-val-cit). Exemplary tripeptides include, but are not limited to, glycine-valine-citrulline (gly- 82 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO val-cit), glycine-glycine-glycine (gly-gly-gly), and glycine- methoxyethoxyethyl)serine-valine (gly-val-citalanine OMESerValAla).

[0266] In some embodiments, a linker described herein comprises a self-immolative spacer. In certain embodiments, the self-immolative spacer comprises p-aminobenzyl. In some embodiments, a p-aminobenzyl alcohol is attached to an amino acid unit via an amide bond, and a carbamate, methylcarbamate, or carbonate is made between the benzyl alcohol and the payload (Hamann et al. (2005) Expert Opin. Ther. Patents (2005) 15:1087-1103). In some embodiments, the linker comprises p-aminobenzyloxycarbonyl (PAB). Other examples of self-immolative spacers include, but are not limited to, aromatic compounds that are electronically similar to the PAB group, such as 2-aminoimidazol-5-methanol derivatives (U.S. Pat. No.7,375,078; Hay et al. (1999) Bioorg. Med. Chem. Lett. 9:2237) and ortho- or para-aminobenzylacetals. In some embodiments, spacers can be used that undergo cyclization upon amide bond hydrolysis, such as substituted and unsubstituted 4-aminobutyric acid amides (Rodrigues et al. (1995) Chemistry Biology 2:223), appropriately substituted bicyclo[2.2.1] and bicyclo[2.2.2] ring systems (Storm et al. (1972) J. Amer. Chem. Soc. 94:5815) and 2-aminophenylpropionic acid amides (Amsberry, et al. (1990) J. Org. Chem.55:5867). Linkage of a drug to the α-carbon of a glycine residue is another example of a self-immolative spacer that may be useful in conjugates (Kingsbury et al. (1984) J. Med. Chem.27:1447).

[0267] In certain embodiments, linker precursors can be combined to form larger linkers. For instance, in certain embodiments, linkers comprise the dipeptide valine-citrulline and p-aminobenzyloxycarbonyl. These are also referenced as citValCit--PAB linkers.

[0268] In some embodiments, one or more linkers in an antibody conjugate, e.g., LINK, La, and / or Lbis hydrolytically stable. Alternatively or additionally, one or more linkers in an antibody conjugate, e.g., LINK, La, and / or Lb, is cleavable. Alternatively or additionally, one or more linkers in an antibody conjugate, e.g., LINK, La, and / or Lb, is a protease cleavable linker, an enzyme cleavable linker, a pH-sensitive linker, or a non-cleavable linker. Preparation of Antibody Conjugates

[0269] The antibody conjugates can be prepared by standard techniques. In certain embodiments, an antibody is contacted with a payload precursor under conditions suitable for forming a bond from the antibody to the payload to form an antibody-payload conjugate. In certain embodiments, an antibody is contacted with a linker precursor under conditions suitable for forming a bond from the antibody to the linker. The resulting antibody-linker is contacted with a payload precursor under conditions suitable for forming a bond from the antibody-linker to the payload to form an antibody-linker-payload conjugate. In certain embodiments, a payload 83 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO precursor is contacted with a linker precursor under conditions suitable for forming a bond from the payload to the linker. The resulting payload-linker is contacted with an antibody under conditions suitable for forming a bond from the payload-linker to the antibody to form an antibody-linker-payload conjugate. Suitable linkers for preparing the antibody conjugates are disclosed herein, and exemplary conditions for conjugation are described in the Examples below.

[0270] The structures and synthesis of the payloads in the antibody conjugates herein, including those mentioned in the Example section below, include those described in WO2020257235, WO2020252043, WO2016123582, and WO2022103983, each of which is incorporated by reference herein in its entirety. 12. Multi-specific antibodies and other Trop-2 binding molecules

[0271] In some aspects, the present disclosure provides multi-specific antibodies (e.g., bispecific antibodies). The multispecific antibodies have binding specificities for at least two different epitopes. In some embodiments, the multi-specific antibodies bind to two different epitopes of a TROP2 protein. In some embodiments, the multi-specific antibodies comprise a TROP2-binding domain, and one or more binding domains for different protein(s). In some embodiments, the multi-specific antibodies may be used to localize cytotoxic agents to cells which express TROP2. These antibodies may possess a TROP2 binding domain and another domain that binds the cytotoxic agent. The multi-specific antibodies may be full length antibodies or antibody fragments (e.g., scFv, F(ab')2 and other antibody fragments disclosed herein). In some embodiments, a multi-specific antibody comprises two or more antigen binding domains, at least one of which comprises the CDRs and / or VH / VL sequences in the anti-TROP2 antibodies disclosed herein.

[0272] In some aspects, the present disclosure provides chimeric antigen receptors (CARs) comprising a TROP2-binding domain. In some embodiments, the TROP2-binding domain may comprise the CDRs and / or VH / VL sequences in the anti-TROP2 antibodies disclosed herein. In general, a chimeric antigen receptor (CAR) comprises at least two domains, which when expressed in a cell, provides the cell with specificity for a target antigen, or a target cell bearing a target antigen, typically a diseased cell bearing a specific disease-related antigen. In some embodiments, a CAR comprises at least an extracellular antigen binding domain (including a TROP2 binding domain), a transmembrane domain and a cytoplasmic signaling domain (also referred to herein as “an intracellular signaling domain”) comprising a functional signaling domain derived from one or more stimulatory and / or costimulatory molecules as provided below. In some examples, the intracellular signaling domain of a CAR is derived from the CD3 84 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO zeta chain that is normally found associated with the TCR complex. The CD3 zeta signaling domain may be fused with one or more functional signaling domains derived from at least one co-stimulatory molecule such as 4-1BB, CD27 and / or CD28. 13. Vectors, Host Cells, and Recombinant Methods

[0273] The invention also provides isolated nucleic acids encoding anti-TROP2 antibodies, vectors and host cells comprising the nucleic acids, and recombinant techniques for the production of the antibodies.

[0274] For recombinant production of the antibody, the nucleic acid(s) encoding it may be isolated and inserted into a replicable vector for further cloning (i.e., amplification of the DNA) or expression. In some aspects, the nucleic acid may be produced by homologous recombination, for example as described in U.S. Patent No.5,204,244, incorporated by reference in its entirety.

[0275] Many different vectors are known in the art. The vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence, for example as described in U.S. Patent No. 5,534,615, incorporated by reference in its entirety.

[0276] Illustrative examples of suitable host cells are provided below. These host cells are not meant to be limiting.

[0277] Suitable host cells include any prokaryotic (e.g., bacterial), lower eukaryotic (e.g., yeast), or higher eukaryotic (e.g., mammalian) cells. Suitable prokaryotes include eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as Escherichia (E. coli), Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella (S. typhimurium), Serratia (S. marcescans), Shigella, Bacilli (B. subtilis and B. licheniformis), Pseudomonas (P. aeruginosa), and Streptomyces. One useful E. coli cloning host is E. coli 294, although other strains such as E. coli B, E. coli X1776, and E. coli W3110 are suitable.

[0278] In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are also suitable cloning or expression hosts for anti-TROP2 antibody-encoding vectors. Saccharomyces cerevisiae, or common baker’s yeast, is a commonly used lower eukaryotic host microorganism. However, a number of other genera, species, and strains are available and useful, such as Schizosaccharomyces pombe, Kluyveromyces (K. lactis, K. fragilis, K. bulgaricus K. wickeramii, K. waltii, K. drosophilarum, K. thermotolerans, and K. marxianus), Yarrowia, Pichia pastoris, Candida (C. albicans), Trichoderma reesia, Neurospora crassa, Schwanniomyces (S. occidentalis), and filamentous fungi such as, for example Penicillium, Tolypocladium, and Aspergillus (A. nidulans and A. niger). 85 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0279] Useful mammalian host cells include COS-7 cells, HEK293 cells; baby hamster kidney (BHK) cells; Chinese hamster ovary (CHO); mouse sertoli cells; African green monkey kidney cells (VERO-76), and the like.

[0280] The host cells used to produce the anti-TROP2 antibody of this invention may be cultured in a variety of media. Commercially available media such as, for example, Ham’s F10, Minimal Essential Medium (MEM), RPMI-1640, and Dulbecco’s Modified Eagle’s Medium (DMEM) are suitable for culturing the host cells. In addition, any of the media described in Ham et al., Meth. Enz., 1979, 58:44; Barnes et al., Anal. Biochem., 1980, 102:255; and U.S. Patent NOs 4,767,704, 4,657,866, 4,927,762, 4,560,655, and 5,122,469, or WO 90 / 03430 and WO 87 / 00195 may be used. Each of the foregoing references is incorporated by reference in its entirety.

[0281] Any of these media may be supplemented as necessary with hormones and / or other growth factors (such as insulin, transferrin, or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics, trace elements (defined as inorganic compounds usually present at final concentrations in the micromolar range), and glucose or an equivalent energy source. Any other necessary supplements may also be included at appropriate concentrations that would be known to those skilled in the art.

[0282] The culture conditions, such as temperature, pH, and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.

[0283] When using recombinant techniques, the antibody can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the antibody is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration. For example, Carter et al. (Bio / Technology, 1992, 10:163-167) describes a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli. Briefly, cell paste is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonylfluoride (PMSF) over about 30 min. Cell debris can be removed by centrifugation.

[0284] In some embodiments, the antibody is produced in a cell-free system. In some aspects, the cell-free system is an in vitro transcription and translation system as described in Yin et al., mAbs, 2012, 4:217-225, incorporated by reference in its entirety. In some aspects, the cell-free system utilizes a cell-free extract from a eukaryotic cell or from a prokaryotic cell. In some aspects, the prokaryotic cell is E. coli. Cell-free expression of the antibody may be useful, 86 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO for example, where the antibody accumulates in a cell as an insoluble aggregate, or where yields from periplasmic expression are low.

[0285] Where the antibody is secreted into the medium, supernatants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon®or Millipore®Pellcon®ultrafiltration unit. A protease inhibitor such as PMSF may be included in any of the foregoing steps to inhibit proteolysis and antibiotics may be included to prevent the growth of adventitious contaminants.

[0286] The antibody composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being a particularly useful purification technique. The suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domain that is present in the antibody. Protein A can be used to purify antibodies that are based on human γ1, γ2, or γ4 heavy chains (Lindmark et al., J. Immunol. Meth., 1983, 62:1-13, incorporated by reference in its entirety). Protein G is useful for all mouse isotypes and for human γ3 (Guss et al., EMBO J., 1986, 5:1567-1575, incorporated by reference in its entirety).

[0287] The matrix to which the affinity ligand is attached is most often agarose, but other matrices are available. Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene allow for faster flow rates and shorter processing times than can be achieved with agarose. Where the antibody comprises a CH3 domain, the BakerBond ABX®resin is useful for purification.

[0288] Other techniques for protein purification, such as fractionation on an ion-exchange column, ethanol precipitation, Reverse Phase HPLC, chromatography on silica, chromatography on heparin Sepharose®, chromatofocusing, SDS-PAGE, and ammonium sulfate precipitation are also available, and can be applied by one of skill in the art.

[0289] Following any preliminary purification step(s), the mixture comprising the antibody of interest and contaminants may be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pH between about 2.5 to about 4.5, generally performed at low salt concentrations (e.g., from about 0 to about 0.25 M salt). 14. Pharmaceutical Compositions and Methods of Administration

[0290] Any of the antibodies and antibody conjugates provided herein can be provided in any appropriate pharmaceutical composition and be administered by any suitable route of administration. Suitable routes of administration include, but are not limited to, the inhalation, intraarterial, intradermal, intramuscular, intraperitoneal, intravenous, nasal, parenteral, pulmonary, and subcutaneous routes. 87 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0291] The pharmaceutical composition may comprise one or more pharmaceutical excipients. Any suitable pharmaceutical excipient may be used, and one of ordinary skill in the art is capable of selecting suitable pharmaceutical excipients. Accordingly, the pharmaceutical excipients provided below are intended to be illustrative, and not limiting. Additional pharmaceutical excipients include, for example, those described in the Handbook of Pharmaceutical Excipients, Rowe et al. (Eds.) 6th Ed. (2009), incorporated by reference in its entirety.

[0292] In some embodiments, the pharmaceutical composition comprises an anti-foaming agent. Any suitable anti-foaming agent may be used. In some aspects, the anti-foaming agent is selected from an alcohol, an ether, an oil, a wax, a silicone, a surfactant, and combinations thereof. In some aspects, the anti-foaming agent is selected from a mineral oil, a vegetable oil, ethylene bis stearamide, a paraffin wax, an ester wax, a fatty alcohol wax, a long chain fatty alcohol, a fatty acid soap, a fatty acid ester, a silicon glycol, a fluorosilicone, a polyethylene glycol-polypropylene glycol copolymer, polydimethylsiloxane-silicon dioxide, ether, octyl alcohol, capryl alcohol, sorbitan trioleate, ethyl alcohol, 2-ethyl-hexanol, dimethicone, oleyl alcohol, simethicone, and combinations thereof.

[0293] In some embodiments, the pharmaceutical composition comprises a cosolvent. Illustrative examples of cosolvents include ethanol, poly(ethylene) glycol, butylene glycol, dimethylacetamide, glycerin, and propylene glycol.

[0294] In some embodiments, the pharmaceutical composition comprises a buffer. Illustrative examples of buffers include acetate, borate, carbonate, lactate, malate, phosphate, citrate, hydroxide, diethanolamine, monoethanolamine, glycine, methionine, guar gum, and monosodium glutamate.

[0295] In some embodiments, the pharmaceutical composition comprises a carrier or filler. Illustrative examples of carriers or fillers include lactose, maltodextrin, mannitol, sorbitol, chitosan, stearic acid, xanthan gum, and guar gum.

[0296] In some embodiments, the pharmaceutical composition comprises a surfactant. Illustrative examples of surfactants include d-alpha tocopherol, benzalkonium chloride, benzethonium chloride, cetrimide, cetylpyridinium chloride, docusate sodium, glyceryl behenate, glyceryl monooleate, lauric acid, macrogol 15 hydroxystearate, myristyl alcohol, phospholipids, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, polyoxylglycerides, sodium lauryl sulfate, sorbitan esters, and vitamin E polyethylene(glycol) succinate. 88 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO

[0297] In some embodiments, the pharmaceutical composition comprises an anti-caking agent. Illustrative examples of anti-caking agents include calcium phosphate (tribasic), hydroxymethyl cellulose, hydroxypropyl cellulose, and magnesium oxide.

[0298] Other excipients that may be used with the pharmaceutical compositions include, for example, albumin, antioxidants, antibacterial agents, antifungal agents, bioabsorbable polymers, chelating agents, controlled release agents, diluents, dispersing agents, dissolution enhancers, emulsifying agents, gelling agents, ointment bases, penetration enhancers, preservatives, solubilizing agents, solvents, stabilizing agents, and sugars. Specific examples of each of these agents are described, for example, in the Handbook of Pharmaceutical Excipients, Rowe et al. (Eds.) 6th Ed. (2009), The Pharmaceutical Press, incorporated by reference in its entirety.

[0299] In some embodiments, the pharmaceutical composition comprises a solvent. In some aspects, the solvent is saline solution, such as a sterile isotonic saline solution or dextrose solution. In some aspects, the solvent is water for injection.

[0300] In some embodiments, the pharmaceutical compositions are in a particulate form, such as a microparticle or a nanoparticle. Microparticles and nanoparticles may be formed from any suitable material, such as a polymer or a lipid. In some aspects, the microparticles or nanoparticles are micelles, liposomes, or polymersomes.

[0301] Further provided herein are anhydrous pharmaceutical compositions and dosage forms comprising an antibody or antibody conjugate, since water can facilitate the degradation of some antibodies or conjugates.

[0302] Anhydrous pharmaceutical compositions and dosage forms provided herein can be prepared using anhydrous or low moisture containing ingredients and low moisture or low humidity conditions. Pharmaceutical compositions and dosage forms that comprise lactose and at least one active ingredient that comprises a primary or secondary amine can be anhydrous if substantial contact with moisture and / or humidity during manufacturing, packaging, and / or storage is expected.

[0303] An anhydrous pharmaceutical composition should be prepared and stored such that its anhydrous nature is maintained. Accordingly, anhydrous compositions can be packaged using materials known to prevent exposure to water such that they can be included in suitable formulary kits. Examples of suitable packaging include, but are not limited to, hermetically sealed foils, plastics, unit dose containers (e.g., vials), blister packs, and strip packs. 14.1. Parenteral Dosage Forms

[0304] In certain embodiments, provided are parenteral dosage forms. Parenteral dosage forms can be administered to subjects by various routes including, but not limited to, 89 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO subcutaneous, intravenous (including bolus injection), intramuscular, and intraarterial. Because their administration typically bypasses subjects’ natural defenses against contaminants, parenteral dosage forms are typically, sterile or capable of being sterilized prior to administration to a subject. Examples of parenteral dosage forms include, but are not limited to, solutions ready for injection, dry products ready to be dissolved or suspended in a pharmaceutically acceptable vehicle for injection, suspensions ready for injection, and emulsions.

[0305] Suitable vehicles that can be used to provide parenteral dosage forms are well known to those skilled in the art. Examples include, but are not limited to: Water for Injection USP; aqueous vehicles such as, but not limited to, Sodium Chloride Injection, Ringer’s Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, and Lactated Ringer’s Injection; water miscible vehicles such as, but not limited to, ethyl alcohol, polyethylene glycol, and polypropylene glycol; and non-aqueous vehicles such as, but not limited to, corn oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate.

[0306] Excipients that increase the solubility of one or more of the antibodies or antibody conjugates disclosed herein can also be incorporated into the parenteral dosage forms. 14.2. Dosage and Unit Dosage Forms

[0307] In human therapeutics, the doctor will determine the posology which he considers most appropriate according to a preventive or curative treatment and according to the age, weight, condition and other factors specific to the subject to be treated.

[0308] In certain embodiments, a composition provided herein is a pharmaceutical composition or a single unit dosage form. Pharmaceutical compositions and single unit dosage forms provided herein comprise a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic antibodies or antibody conjugates.

[0309] The amount of the antibody or antibody conjugate or composition which will be effective in the prevention or treatment of a disorder or one or more symptoms thereof will vary with the nature and severity of the disease or condition, and the route by which the antibody or antibody conjugate is administered. The frequency and dosage will also vary according to factors specific for each subject depending on the specific therapy (e.g., therapeutic or prophylactic agents) administered, the severity of the disorder, disease, or condition, the route of administration, as well as age, body, weight, response, and the past medical history of the subject. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[0310] In certain embodiments, exemplary doses of a composition include milligram or microgram amounts of the antibody or antibody conjugate per kilogram of subject or sample 90 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO weight (e.g., about 10 micrograms per kilogram to about 50 milligrams per kilogram, about 100 micrograms per kilogram to about 25 milligrams per kilogram, or about 100 microgram per kilogram to about 10 milligrams per kilogram).

[0311] The dose can be administered according to a suitable schedule, for example, once, two times, three times, or four times weekly. It may be necessary to use dosages of the antibody or antibody conjugate outside the ranges disclosed herein in some cases, as will be apparent to those of ordinary skill in the art. Furthermore, it is noted that the clinician or treating physician will know how and when to interrupt, adjust, or terminate therapy in conjunction with subject response.

[0312] Different therapeutically effective amounts may be applicable for different diseases and conditions, as will be readily known by those of ordinary skill in the art. Similarly, amounts sufficient to prevent, manage, treat or ameliorate such disorders, but insufficient to cause, or sufficient to reduce, adverse effects associated with the antibodies or antibody conjugates provided herein are also encompassed by the herein described dosage amounts and dose frequency schedules. Further, when a subject is administered multiple dosages of a composition provided herein, not all of the dosages need be the same.

[0313] In certain embodiments, treatment or prevention can be initiated with one or more loading doses of an antibody or antibody conjugate or composition provided herein followed by one or more maintenance doses.

[0314] In certain embodiments, a dose of an antibody or antibody conjugate or composition provided herein can be administered to achieve a steady-state concentration of the antibody or antibody conjugate in blood or serum of the subject. The steady-state concentration can be determined by measurement according to techniques available to those of skill or can be based on the physical characteristics of the subject such as height, weight and age.

[0315] In certain embodiments, administration of the same composition may be repeated and the administrations may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months. In other embodiments, administration of the same prophylactic or therapeutic agent may be repeated and the administration may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months. 15. Therapeutic Applications

[0316] For therapeutic applications, the antibodies and antibody conjugates provided herein are administered to a mammal, generally a human, in a pharmaceutically acceptable dosage form such as those known in the art and those discussed above. For example, the antibodies and 91 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO antibody conjugates provided herein may be administered to a human intravenously as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intra- cerebrospinal, subcutaneous, intra-articular, intrasynovial, intrathecal, or intratumoral routes. The antibodies or antibody conjugates also are suitably administered by peritumoral, intralesional, or perilesional routes, to exert local as well as systemic therapeutic effects. The intraperitoneal route may be particularly useful, for example, in the treatment of ovarian tumors.

[0317] The antibodies and antibody conjugates provided herein may be useful for the treatment of any disease or condition involving TROP2. In some embodiments, the disease or condition is a disease or condition that can be diagnosed by overexpression of TROP2. In some embodiments, the disease or condition is a disease or condition that can benefit from treatment with an anti-TROP2 antibody or antibody conjugate. In some embodiments, the disease or condition is a cancer.

[0318] Any suitable cancer may be treated with the antibodies or antibody conjugates provided herein. Illustrative suitable cancers include, for example, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), adrenocortical carcinoma, anal cancer, appendix cancer, astrocytoma, basal cell carcinoma, brain tumor, bile duct cancer, bladder cancer, bone cancer, breast cancer, bronchial tumor, carcinoma of unknown primary origin, cardiac tumor, cervical cancer, chordoma, colon cancer, colorectal cancer, craniopharyngioma, ductal carcinoma, embryonal tumor, endometrial cancer, ependymoma, esophageal cancer, esthesioneuroblastoma, fibrous histiocytoma, Ewing sarcoma, eye cancer, germ cell tumor, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, gestational trophoblastic disease, glioma, head and neck cancer, hepatocellular cancer, histiocytosis, Hodgkin lymphoma, hypopharyngeal cancer, intraocular melanoma, islet cell tumor, Kaposi sarcoma, kidney cancer, Langerhans cell histiocytosis, laryngeal cancer, lip and oral cavity cancer, liver cancer, lobular carcinoma in situ, lung cancer, macroglobulinemia, malignant fibrous histiocytoma, melanoma, Merkel cell carcinoma, mesothelioma, metastatic squamous neck cancer with occult primary, midline tract carcinoma involving NUT gene, mouth cancer, multiple endocrine neoplasia syndrome, multiple myeloma, mycosis fungoides, myelodysplastic syndrome, myelodysplastic / myeloproliferative neoplasm, nasal cavity and par nasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-small cell lung cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, papillomatosis, paraganglioma, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytomas, pituitary tumor, pleuropulmonary blastoma, primary central nervous system lymphoma, prostate cancer, rectal cancer, renal cell cancer, renal pelvis and ureter cancer, retinoblastoma, rhabdoid tumor, salivary 92 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO gland cancer, Sezary syndrome, skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, spinal cord tumor, stomach cancer, T-cell lymphoma, teratoid tumor, testicular cancer, throat cancer, thymoma and thymic carcinoma, thyroid cancer, urethral cancer, uterine cancer, vaginal cancer, vulvar cancer, and Wilms tumor.

[0319] In some embodiments, the disease to be treated with the antibodies or antibody conjugates provided herein is gastric cancer, colorectal cancer, renal cell carcinoma, cervical cancer, non-small cell lung carcinoma, ovarian cancer, uterine cancer, endometrial carcinoma, prostate cancer, breast cancer, head and neck cancer, brain carcinoma, liver cancer, pancreatic cancer, mesothelioma, and / or a cancer of epithelial origin. In particular embodiments, the disease is colorectal cancer. In some embodiments, the disease is ovarian cancer. In some embodiments, the disease is breast cancer. In some embodiments, the disease is lung cancer. In some embodiments, the disease is head and neck cancer. In some embodiments, the disease is renal cell carcinoma. In some embodiments, the disease is brain carcinoma. In some embodiments, the disease is endometrial carcinoma. 16. Diagnostic Applications

[0320] In some embodiments, the antibodies or antibody conjugates provided herein are used in diagnostic applications. For example, an anti-TROP2 antibody or antibody conjugate may be useful in assays for TROP2 protein. In some aspects, the antibody or antibody conjugate can be used to detect the expression of TROP2 in various cells and tissues. These assays may be useful, for example, in making a diagnosis and / or prognosis for a disease, such as a cancer.

[0321] In some diagnostic and prognostic applications, the antibody or antibody conjugate may be labeled with a detectable moiety. Suitable detectable moieties include, but are not limited to radioisotopes, fluorescent labels, and enzyme-substrate labels. In another embodiment, the anti-TROP2 antibody or antibody conjugate need not be labeled, and the presence of the antibody or antibody conjugate can be detected using a labeled antibody which specifically binds to the anti-TROP2 antibody. 17. Affinity Purification Reagents

[0322] The antibodies or antibody conjugates provided herein may be used as affinity purification agents. In this process, the antibodies or antibody conjugates may be immobilized on a solid phase such a resin or filter paper, using methods well known in the art. The immobilized antibody or antibody conjugate is contacted with a sample containing the TROP2 protein (or fragment thereof) to be purified, and thereafter the support is washed with a suitable solvent that will remove substantially all the material in the sample except the TROP2 protein, 93 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO which is bound to the immobilized antibody or antibody conjugate. Finally, the support is washed with another suitable solvent, such as glycine buffer, pH 5.0 that will release the TROP2 protein from the antibody or antibody conjugate. 18. Kits

[0323] In some embodiments, an anti-TROP2 antibody or antibody conjugate provided herein is provided in the form of a kit, i.e., a packaged combination of reagents in predetermined amounts with instructions for performing a procedure. In some embodiments, the procedure is a diagnostic assay. In other embodiments, the procedure is a therapeutic procedure.

[0324] In some embodiments, the kit further comprises a solvent for the reconstitution of the anti-TROP2 antibody or antibody conjugate. In some embodiments, the anti-TROP2 antibody or antibody conjugate is provided in the form of a pharmaceutical composition. In some embodiments, the anti-TROP2 antibody or antibody conjugate is provided in a lyophilized form. EXAMPLES EXAMPLE 1 GENERATION AND PRIMARY SCREENING OF ANTI-TROP2 ANTIBODIES

[0325] SPR1748 antibodies were generated by ribosome display Fab HC naïve selection. SRP2292 and SRP2293 antibodies were discovered by affinity maturation by ribosome display of SRP1748-A01, - B04, and -C11. SRP2312-2316 and SRP3454 antibodies were discovered by phase display Fab HC naïve selection. SRP1748, SRP2292, 2293, 2312-2316, SRP3454 antibodies have a common light chain (trastuzumab light chain).

[0326] SRP2333 antibodies were discovered by phase displayed single chain Fab format.

[0327] SRP1966 and SRP1925 antibodies were discovered by phase displayed rabbit scFvs. SRP2268 antibodies were generated by reformatting SRP1925 antibodies onto a consensus human gene for VH / VLand converting to the IgG format. SRP2296 and SRP2295 antibodies were generated by rehumanizing SRP2268-A10 (for SRP2296) and SRP2268-A02 (for SRP2295) for additional VH / VLframework diversity. Ribosome Display Selections

[0328] Ribosome display was used to discover initial human antibodies. Ribosome display was also used to affinity mature the antibodies to generate improved derivative antibodies.

[0329] Briefly, antibody Fab libraries were constructed using a standard overlap extension PCR protocol (Kechman and Pease Nat Protoc 2007, 2, 924-932) with mutagenic primers targeting complementary determining regions (CDRs). Selections for novel antibodies were 94 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO performed using standard ribosome display protocols (Hanes and Plückthun Proc Natl Acad Sci USA 1997, 94, 4937-4942). Specifically, Fab-based (Stafford et al Protein Eng Des Sel 2014, 4, 97-109). Ribosome display selections were performed according to published protocols (Dreier and Plückthun Method Mol Biol Clifton, NJ 2011, 687, 283-306) selecting against biotinylated Trop-2-Fc. After multiple rounds of selection, the DNA from RT-PCR output was cloned into an optimized vector for cell-free expression (Yin et al mAbs 2012, 4, 217-25) using standard molecular biology techniques. All constructs were HIS- and FLAG-tagged to streamline purification and testing during screening. Phage Display Selections

[0330] Briefly, antibody Fab libraries were constructed using a trastuzumab Fab sequence codon optimized for XpressCF® in a modified, commercially available p3 phagemid vector (Antibody Design Labs). The phagemid vector was modified to express Fab heavy chains as a C-terminal p3 fusion proteins and regulatory regions (start codons, restriction enzyme sites, periplasmic leader sequences) were optimized for Fab display levels. Libraries were constructed using standard overlap expression PCR protocols (Heckman and Pease Nat Protoc 2007, 2, 924- 932) with mutagenic primers targeting heavy chain complementary determining regions (CDRs) and rescued through electroporation in M13-K07 infected SS320 E. coli cells (Rajan and Sidhu Methods Enzym 2012, 502, 3-23). Library selections were performed using standard phage display protocols (Marks and Bradbury Methods Mol Biol 2004, 248, 161-76) selecting against Trop-2-Fc protein. Following multiple selection rounds, Fab heavy chain pools were transferred into cell-free expression vectors for expression as His6 and FLAG-tagged IgG1. Hydrophobicity reducing variant construction

[0331] Select hydrophobic CDR residues were selected for mutation to Alanine or Aspartic acids, and single mutations were introduced into the parent 2293-C04 sequence by standard molecular biology methods described. Select single mutations were later combined to create 2293-C04 variants with two mutations. Variants were assayed as described. The Biacore kinetics results for 2293-C04 hydrophobicity reduced variants are shown in Table 5. Rabbit antibody phage display

[0332] The initial antibody 1925-C06 / 1915-G02 was derived from immunizing rabbits (YZ5479 and YZ5480) with Trop-2-Fc (R&D Systems cat# 650-T2) at YenZym Antibodies, LLC. Spleens were harvested and scFv antibody fragment phage libraries were constructed by standard methods (Ayyar et al Appl Micobiol Biotechnol 2015, 99, 2693-703) using a commercially available p3 phagemid vector (Antibody Design Labs). Phage libraries were selected against Trop-2-Fc protein using standard methods (Marks and Bradbury Methods Mol 95 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Biol 2004, 248, 161-76). Clonal phage ELISAs were performed against Trop-2-Fc and Fc to identify Trop-2 specific antibodies. Humanization of rabbit antibodies

[0333] A phage of immune rabbit scFvs identified by phage display as described were humanized onto consensus human frameworks, and antibodies with favorable properties were identified, SRP1925-A04 and SRP1925-C06, and were selected for humanization.

[0334] Human germline framework sequences from family IGHV3 and IGHJ4 were used for “CDR-grafting” the heavy chain variable region of the selected rabbit antibodies. Some mutations were designed in the frameworks of “CDR-grafted” heavy chain variable region sequences.

[0335] Human germline framework sequences from family IGKV1, IGKV3 and IGKJ4 were used for “CDR-grafting” the light chain variable region of the selected rabbit antibodies. Some mutations were designed in the frameworks of “CDR-grafted” light chain variable region sequences.

[0336] Humanized heavy chain variable region and light chain variable region sequences were fused to human IGHG1 and IGKC constant region sequences respectively to construct full- length humanized antibody heavy chain and light chain sequences. High throughput cell free expression and ELISA screening of selection outputs

[0337] Libraries of antibody variants generated by selection workflow were cloned into an expression vector containing c-terminal flag and 6X his tags then transformed into E. coli and grown on agar plates with antibiotic (Kanamycin). To enable in frame expression of phage displayed antibodies, sequences are cloned in a way that adds an Alanine insert between the start Methionine and first antibody framework residue. Individual colonies were grown in liquid broth (TB+antibiotic Kanamycin) and used as a template for DNA amplification via rolling circle amplification (RCA). The variants were then expressed in a cell-free protein synthesis reaction as described. See Yin et al., mAbs, 2012, 4:217-225. Briefly, cell-free extracts were treated with 50 μM iodoacetamide for 30 min at RT (20° C) and added to a premix containing cell-free components (see Cai et al., Biotechnol Prg, 2015, 3:823-831), 10% (v / v) RCA DNA template (approximately 10 μg / mL DNA) for HC variants of interest, and 2.5 μg / mL of the trastuzumab LC.60 μL cell free (CF) reactions were incubated at 30° C for 12hr on a shaker at 650 rpm in 96-well plates. 400-1500 colonies were screened, depending on the predicted diversity of different selection campaigns. Following synthesis, each reaction was diluted 1:200 and tested for binding to human or mouse Trop2 protein by ELISA. Briefly, Trop2 protein was coated to 384-well Maxisorp plates in 0.l M bicarbonate (pH 8.9) and blocked with 100 BSA in 96 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO PBST. Antibodies diluted 1:200 from CF reaction were incubated on the plates, washed, and detected with HRP-conjugated anti-flag tag antibodies (Jackson ImmunoResearch, West Grove, Pa.) and Pierce Pico Supersignal ELISA substrate (ThermoFisher Scientific). Secondary screening of antibody variants

[0338] The candidates from the initial round of screening were cultured and miniprepped via the Qiaprep 96 Turbo miniprep kit (Qiagen) according to the manufacturer’s instructions. 5 μg / mL miniprepped HC DNA and 5 μg / mL of the appropriate LC (either Trastuzumab LC or anti-CD3 SP34 LC) was added to 4 mL cell-free reactions and incubated overnight for 12 hr at 30°C, 650 rpm. Expressed variants from clarified cell-free reactions were purified via IMAC purification using a semi-automated high throughput batch purification method. Briefly, purifications were performed in a 96-well plate format where 50 μL / well of IMAC resin (Ni Sepharose High Performance, GE Healthcare) was equilibrated in IMAC binding buffer (50 mM Tris pH 8.0, 300 mM NaCl, 10 mM imidazole), incubated with 1 mL cell-free reaction for 15 minutes followed by two washes in IMAC binding buffer. His-tagged antibody variants were then eluted using 200 μL IMAC elution buffer (50 mM Tris pH 8.0, 300mM NaCl, 500 mM imidazole) and buffer exchanged into PBS using a 96-well Zeba plate (7 kD MWCO, Thermofisher). Purified antibodies were quantified via high throughput capillary electrophoresis using the Labchip GXII (Perkin Elmer) against a Herceptin standard curve, according to the manufacturer’s instructions. EXAMPLE 2 BIACORE KINETIC ANALYSIS

[0339] Anti-Fc polyclonal antibodies were immobilized onto a CM4 chip (GE Life Sciences) using amine coupling chemistry (from Amine Coupling Kit, GE Life Sciences). The immobilization steps were carried out at a flow rate of 25 µL / min in 1x HBS-EP+ buffer (GE Life Sciences; 10x Stock diluted before use). The sensor surfaces were activated for 7 min with a mixture of NHS (0.05 M) and EDC (0.2 M). The anti-Fc antibodies were injected over all 4 flow cells at a concentration of 25ug / ml in 10 mM sodium acetate, pH 4.5, for 7 min. Ethanolamine (1^M, pH 8.5) was injected for 7 min to block any remaining activated groups. An average of 2,500 response units (RU) of capture antibody was immobilized on each flow cell.

[0340] Off-rate and kinetic binding experiments were performed at 25 °C using 1x HBS- EP+ buffer. Test and control antibodies were injected over the anti-Fc surface at concentrations of 5-15 µg / mL for 12 seconds at a flow rate of 10 µL / min on flow cells 2, 3 and 4, followed by a buffer wash for 30 seconds at the same flow rate. Kinetic characterization of antibody samples was carried out with a range of antigen concentrations from 0.2-200 nM and 1 injection of 0 nM 97 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO antigen (for example, 200, 100, 25, 6.25, 1.56, 0.390625, and 0 nM). After capturing ligand (antibody) on the anti-Fc surface, the analyte (hTrop2, Acro Biosystems, Delaware) was bound for 240 seconds, followed by a 540 second dissociation phase at a flow rate of 50 µL / min. Between each ligand capture and analyte binding cycle, regeneration was carried out using 2 injections of 3M magnesium chloride for 30 seconds at 30 µL / min.

[0341] The data was fit with the Biacore T200 Evaluation software, using a 1-1 Langmuir binding model with constant RI of 0. KD (affinity, nM) was determined as a ratio of the kinetic rate constants calculated from the fits of the association and dissociation phases. The kinetics of consensus humanized rabbit IgGs (2268 constructs) are shown in Table 6. EXAMPLE 3 FLOW CYTOMETRY-BASED CELL BINDING ASSAY FOR SCREENING

[0342] CHO-K cells were purchased from ATCC (American Type Culture Collection) and DMEM / F-12 (50:50) high glucose medium (Corning) supplemented with 10% heat-inactivated fetal bovine serum (Corning), 1% Penicillin / Streptomycin (Corning) and 2 mmol / L-glutamax (Thermo Fisher). CHO-hTROP2 cells were generated by transfecting CHO cells to stably express human TROP2 on the cell surface and maintained in the same cell culture medium supplied with 30ug / mL puromycin.

[0343] Parental CHO cells were washed twice in PBS and incubated in PBS containing with 1 nM CellTraceTM Oregon Green488® (Life Technologies) at 37°C for 30 minutes. Labeled parental CHO cells were then washed 2x with Ham’s F-12 media and 2x with FACS buffer (PBS with 1% bovine serum albumin). Unlabeled CHO-hTROP2 cells were washed with PBS and mixed with labeled parental CHO at 1:1 ratio.200,000 cells in 50 µL FACS buffer were seeded in 96 well polypropylene plates and mixed with 50µl of test antibodies serially diluted in FACS buffer. After incubation on ice for 60 mins, cells were washed with FACS buffer and incubated on ice for 60 mins with 100 µL FACS buffer containing 2.5 µg / mL R-Phycoerythrin-conjugated goat anti-Human IgG (Jackson ImmunoResearch Laboratories). Cells were washed twice and fixed in 2% paraformaldehyde in PBS (Santa Cruz Biotechnology) for 10 mins on ice in the dark, and analyzed using the Attune Flow Cytometer (Thermo Fisher). Data were analyzed using FlowJo® software to determine mean fluorescence intensities. Binding constants were calculated using the statistical software, GraphPad Prism (GraphPad Software; La Jolla, CA) using the nonlinear regression equation, one site – specific binding with Hill slope. Secondary antibody alone was used as a control, in addition to measuring non-specific antibody binding to CHO parental cells. The cell binding characteristics of example antibodies are shown in Tables 7, 10, 15, 18, 22, and 24. 98 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO EXAMPLE 4 RABBIT LIBRARY PHAGE CELL BINDING

[0344] The cell binding activity of the ELISA positive phage particles was confirmed in a FACS binding assay. Phage particles were produced from scFv phage library generated from the Rabbit spleens immunized with TROP2-Fc. The cell binding activity of the phage particles was evaluated using CHO-hTROP2 and parental CHO cells described in previous examples. Parental CHO cells labeled with CellTraceTM Oregon Green488® (Life Technologies) were combined with un-labeled CHO-hTROP2 at 1:1 ratio and seeded at 50 µL per well (200,000 cells per well) in 96 well polypropylene plates. Cells were mixed with 50ul of 1:6 serially diluted phage particles in FACS buffer and incubated on ice for 60 mins. Cells were washed with FACS buffer and incubated on ice for 60 mins with 100 µL FACS buffer containing 2.5 µg / mL anti-M13 phage coat protein g8p antibody-PE (Sino Biological). Cells were washed twice with FACS buffer, fixed in 2% paraformaldehyde in PBS (Santa Cruz Biotechnology) for 10 mins on ice in the dark, and analyzed using the Attune Flow Cytometer (Thermo Fisher). Data were analyzed using FlowJo® software to determine mean fluorescence intensities. Binding constants were calculated using the statistical software, GraphPad Prism (GraphPad Software; La Jolla, CA) using the nonlinear regression equation, one site – specific binding with Hill slope. Secondary antibody alone was used as a control, in addition to measuring non-specific antibody binding to CHO parental cells. The results are shown in Tables 13, 19, and 25. EXAMPLE 5 ADC CELL KILLING ASSAY

[0345] The cytotoxicity of ADCs was measured in a cell proliferation assay. TROP2 positive MDA-MB-468, NCI-N87, NCI-H441, Colo205, A431, HCC1954, CAOV3 cells and TROP2 negative BT549 cells were obtained from ATCC (American Type Culture Collection) and maintained in DMEM / F12 (1:1), high glucose (Corning) supplemented with 10% heat- inactivated fetal bovine serum (Thermo Scientific), 2mM glutamax (Thermo Scientific), and 1x Penicillin / Streptomycin (Corning).

[0346] Cells were collected and counted by the Vi-CELL Cell Viability Analyzers (Beckman Coulter). A total of 625 cells in a volume of 25 µl were seeded in each well of a 384- well flat bottom white Polystyrene plate. Antibodies were diluted at 2x final concentration in the cell culture medium and 25µl of antibody was added into each treatment well. Assay plates were cultured at 37°C in a CO2 incubator for 120hrs. For cell viability measurement, 30μl of Cell Titer-Glo® reagent (Promega Corp. Madison, WI) was added into each well, and plates were 99 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO processed as per product instructions. Relative luminescence was measured on an ENVISION® plate reader (Perkin-Elmer; Waltham, MA). Relative luminescence readings were converted to % viability using untreated cells as controls. Data was fitted with non-linear regression analysis, using log(inhibitor) vs. response -variable slope, 4 parameter fit equation using GraphPad Prism (GraphPad v 5.00, Software; San Diego, CA). The ADC cell killing results for example antibody constructs are shown in Tables 8, 11, 16, 20, 21, 23, and 26. EXAMPLE 6 2ND ADC CELL KILLING ASSAY

[0347] The internalization ability of the candidate antibodies was evaluated by 2nd ADC cell killing assay on TROP2 positive MDA-MB-468 cells. MDA-MB-468 cells were obtained from ATCC (American Type Culture Collection) and maintained in DMEM / F12 (1:1), high glucose (Corning) supplemented with 10% heat-inactivated fetal bovine serum (Thermo Scientific), 2mM glutamax (Thermo Scientific), and 1x Penicillin / Streptomycin (Corning).

[0348] Cells were collected and counted by the Vi-CELL Cell Viability Analyzers (Beckman Coulter). A total of 625 cells in a volume of 25 µl were seeded in each well of a 384- well flat bottom white Polystyrene plate. Antibodies were diluted at 4x final concentration in the cell culture medium.12.5µl of antibody was added into each treatment well and 12.5µl of Anti- hFc-nanobody conjugated to a drug-linker (a cleavable 2-aminophenyl hemiasterlin agent-linker, CAS No. : 1977557-97-3, details of the structure and synthesis include those described in WO2016123582, which is incorporate by reference herein in its entirety) was then added into each well at a fixed concentration of 20nM. Assay plates were cultured at 37°C in a CO2incubator for 120hrs. For cell viability measurement, 30μl of Cell Titer-Glo® reagent (Promega Corp. Madison, WI) was added into each well, and plates were processed as per product instructions. Relative luminescence was measured on an ENVISION® plate reader (Perkin- Elmer; Waltham, MA). Relative luminescence readings were converted to % viability using untreated cells as controls. Data was fitted with non-linear regression analysis, using log(inhibitor) vs. response -variable slope, 4 parameter fit equation using GraphPad Prism (GraphPad v 5.00, Software; San Diego, CA). The 2ndADC cell binding characteristics of example antibody constructs are shown in Tables 9, 12, 14, and 17. EXAMPLE 7 FACS BASED CELL BINDING ASSAYS

[0349] TROP2 positive cells (CAOV3, NCI-H441) or TROP2 negative cells (BT539, CHO- K) cells were purchased from ATCC (American Type Culture Collection) and DMEM / F-12 100 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO (50:50) high glucose medium (Corning) supplemented with 10% heat-inactivated fetal bovine serum (Corning), 1% Penicillin / Streptomycin (Corning) and 2 mmol / L-glutamax (Thermo Fisher). CHO-humanTROP2, CHO-cynoTROP2, CHO-mouseTROP2 and CHO-human EpCAM cells were generated by transfecting CHO cells to stably express human TROP2 or cynomolgus monkey TROP2 or mouse TROP2 or human EpCAM on the cell surface and maintained in the same cell culture medium supplied with 30ug / mL puromycin.

[0350] 200,000 cells in 50 µL FACS buffer were seeded in 96 well polypropylene plates and mixed with 50ul of test antibodies serially diluted in FACS buffer. After incubation on ice for 60 mins, cells were washed with FACS buffer and incubated on ice for 60 mins with 100 µL FACS buffer containing 2.5 µg / mL R-Phycoerythrin-conjugated goat anti-Human IgG (Jackson ImmunoResearch Laboratories). Cells were washed twice and fixed in 2% paraformaldehyde in PBS (Santa Cruz Biotechnology) for 10 mins on ice in the dark, and analyzed using the Attune Flow Cytometer (Thermo Fisher). Data were analyzed using FlowJo® software to determine mean fluorescence intensities. Binding constants were calculated using the statistical software, GraphPad Prism (GraphPad Software; La Jolla, CA) using the nonlinear regression equation, one site – specific binding with Hill slope. Secondary antibody alone was used as a control. The results of example antibodies are shown in Table 19. EXAMPLE 8 IN VITRO CELL KILLING AND BINDING ON PRIMARY KERATINOCYTES

[0351] Primary adult human keratinocyte cells were purchased from Thermo Fisher Scientific. Keratinocytes were cultured in defined keratinocyte culture medium (EpiLife Medium, Thermo Fisher Scientific) supplemented with growth supplement S7 (S0175 from Thermo Fisher Scientific) and Penicillin / Streptomycin on plates coated with keratinocyte coating matrix (Thermo Fisher Scientific). To evaluate the cytotoxicity effects of the ADC on the adult primary keratinocytes, a total of 2,000 keratinocytes in a volume of 50ul were seeded in a 96-well flat bottom cell culture plate coated with keratinocyte coating matrix (Thermo Fisher Scientific) the day before. ADCs were formulated at 2x starting concentration in cell culture medium, serial diluted (1:3) under sterile conditions and added onto cells in triplicates. Plates were cultured at 37°C in a CO2 incubator for 120 hours. For cell viability measurement, 10ul of WST-8 reagent (VWR) were added into each well and plates were incubated at 37°C in a CO2 incubator for 4 hours. The absorbance at 450 nm was measured using a microplate reader (M5, Molecular Devices) and readings were converted to % viability using untreated cells as controls. Data was fitted with non-linear regression analysis, using log (inhibitor) vs. response, variable slope, 4-parameter fit equation using GraphPad Prism. Data was expressed as % relative cell 101 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO viability vs. dose of free linker-warhead or ADC in nanomolar with error bars indicating the Standard Deviation (SD) of the triplicates.

[0352] To evaluate antibody binding activity of the anti-TROP2 antibodies on the adult primary keratinocytes, a total of 100,000 keratinocytes per well were incubated on ice with serial dilutions of anti-TROP2 antibodies in FACS buffer (PBS buffer supplemented with 1% bovine serum albumin, and 0.05% sodium azide) for 60 minutes. Cells were washed twice with ice-cold FACS buffer and then incubated with 5 microgram / mL Alexa 647 labeled donkey anti-human Fc antibody (Jackson ImmunoResearch, West Grove, PA) on ice for another 60 minutes. Unstained cells and cells stained with secondary antibodies alone were used as controls. Samples were then washed twice using FACS buffer and analyzed using an Attune flow cytometer (Thermo Fisher). Geometric mean fluorescence intensities were fitted using non-linear regression analysis with one site specific binding equation on GraphPad Prism. The results of example antibodies are shown in Tables 16 and 23. EXAMPLE 9 ASSAYS TO MEASURE TROP2 ADCS INDUCED IMMUNOGENIC CELL DEATH

[0353] Immunogenic cell death elicited by the TROP2 ADCs and free exatecan were measured by cell surface translocate of calreticulin and release of HMGB1 in the cell culture supernatant. Briefly, TROP2 positive cell line NCI-H292 were seeded into a 96-well flat bottom plate 4 hours prior to the initialization of the assay. Free exatecan and TROP2 ADCs were formulated at a 2x starting concentration in cell culture medium, and samples were serial diluted (1:3) under sterile conditions and added onto the cells in duplicates. After incubation at 37°C in a CO2 incubator for 48 hours, the cell supernatant was collected for measuring HMGB1 released, and the adherent cells were collected for calreticulin expression on the cell surface.

[0354] HMGB1 released in the supernatant was assessed via sandwich ELISA using mouse anti-human HMGB1 clone 2F6 (Sigma-Aldrich) as the capture, polyclonal rabbit anti-human HMGB1 (Abcam) as secondary, and polyclonal goat anti-rabbit IgG HRP as the detection antibody. The HMGB1 concentrations in the cell culture medium were calculated based a standard curve built on commercially available recombinant human HMGB1 (R&D Systems).

[0355] NCI-H292 cells were detached using Accutase (Innovative Cell Technologies) and viability was accessed using a 1:500 dilution of Zombie NIR viability dye. Calreticulin induction was measured via commercial anti-calreticulin antibody conjugated to Alexa Fluor 647 (Abcam) diluted at 1:60. Surface calreticulin measures on the live cells were gathered using an Attune NXT Flow Cytometer (ThermoFisher Scientific) to obtain median fluorescence intensity values. 102 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO All data were fitted with non-linear regression analysis, using log(agonist) vs. response, variable slope, 4 parameter fit equation using GraphPad Prism. The results are shown in Table 27. Table 5. Biacore kinetics for 2293-C04 hydrophobicity reduced variants: Note Bioreg Id SP - SP - β-Glu Name (HC / LC) Biacore 2 s ( e d, d, d, d, d,c_ 7 ,W 05 _FH 103 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Note Bioreg Id SP - SP - β-Glu Name (HC / LC) BiacoreTable 6. Kinetics of consensus humanized rabbit IgGs (2268): Ligand Ligand Rmax ka kd KD Chi² Chi² / Rmax Ligand CF . L 5g Table 7. SRP1748 cell binding and 2ndADC cell killing VSRP1748-A11 1293 7.0 NK NK 104 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-468cleavable 2- VSRP1748 E11 3864 1.1 NK NK 105 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-468cleavable 2- VS 7 8 5 .5 N N NK=No Killing Table 8 Select ADCs from SRP1748 ADC cell killin1890-E09 linker-maytansinoid 440 43 82 NK=No Killing Table 9. SRP2292 and SRP22932ndADC cell killing 106 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-4682nd ADC cell )SRP1748-A01 SRP2292-D05 0.14 71 1906 107 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-4682nd ADC cell )SRP1748-B04 SRP2292-G10 0.17 87 450 108 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-4682nd ADC cell )SRP1748-B04 SRP2293-C04 0.045 79 561 109 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-4682nd ADC cell )SRP1748-C11 SRP2293-F09 NK NK 1197 110 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-468 2nd ADC cell )NK=No Killing Table 10. SRP2292 and SRP2293 cell binding ) S 4 S S 5 S 7 S S S SSRP1748-A01 SRP2292-D09 11689 0.37 13278 0.99 NB NB NB NB 111 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO CHO-human CHO-cyno CHO-mouse CHO-k ) S S S S S S 4 S S S S S S S S S S 9 S S 9 S S S S S S S S S S S S S S S 7 S S SSRP1748-B04 SRP2293-A07 22483 0.59 16060 0.75 802 6.9 NB NB NB=No Binding TaADC # Description DAR MDA-MB-468 NCI-N87 112 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO EC50 Span EC50 (nM) Spanhemiasterlin agent-linker Table 12. SRP23162ndADC cell killing 113 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-468- l r S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S SSRP2333-C06 ScFv IgG Trop2 Chilliwack 497 0.64 17 114 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO MDA-MB-468- l r S S S S S S NTable 13. SRP1966 Phage cell binding on CHO-hTROP2SRP1966-C08 phage 2826 2.16 115 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Phage binding CHO-hTROP2 V i ID F NTable 14. SMP22682ndADC cell killing MDA MB 4 - n ) S S S S S S S S S S S S SSMP2268-B02 IgG-FlagHis SMP1925 51.2 >20 52 NK=No Killing 116 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Table 15. SMP2268 cell binding CHO- CHO- CHO- CHO-human g S S NTable 16. Select ADCs from SRP2268 and SRP2296 ADC cell killing MDA-MB- te a ) 9 1 1 8 7 6 0 Tagent-linker Table 17. SRP34542ndADC cell killing 117 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 2nd ADC cell killing NK=No Killing Table 18. SRP3454 cell bindingNC=Not Calculable due to incomplete curve Table 19. Select TROP2 ADC cell binding )amnop eny emaster n agent- n er; pAcF 118 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 50 2293-C04 F241 / F404-cleavable 2- 939,024 1.3 NC >100Table 20. Select TROP2 ADC cell killing Sample NCI-H441 A431 (TROP2+) CAOV3 HCC1954 BT549 (TROP2-)Table 21.2293-C04 Single mutation ADC cell killing n Exaeca xaeca ee ug . . . Tabl 22 2293C04 Si l i ADC ll bidi ) )38 2293-C04-W103A_Y180 / F404TAG 503,752 1.0 NC >30 119 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Sample ADC# Name CAOV3 (TROP2+) BT549 (TROP2- ) )Table 23.2293-C04 double mutation ADC cell killing Sample Name CAOV3 BT549 Keratinocytes n eTable 24. 2293-C04 double mutation ADC cell binding ) 08 88 Ta )aTrop2 h1925-C06 HC2 S53T aTrop2 h1925-C06 LC8 73,716 2.9 NC >30 120 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO HC LC CAOV3 (TROP2+) BT549 (TROP2- )Table 26. h1925-C06 single mutation ADC cell killing Sm l ADC# HC LC CAOV3 TROP2+ BT549 TROP2 ) fg . . Table 27. TROP2 ADC and exatecan free drug induced immunogenic cell death ) fcleavable Exatecan Tabl 28 D i i f i 2293C04 i l d d bl f HTS ig: s (_ _ _SD-018786 aTrop2_2293-C04-Hc_W50D_FH5238 121 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Note Bioreg Id Name SEQ IDTable 29A. Description of molecules and sequences LC LC na rop _ - _ a rop _ - rastuzuma pAzMeF + LP-2 E02_Y180 / F404TAG LC SerOpt 122 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ADC #Name HC name HCLC name LC n28aTrop2_2293-C04-SD-018826 5299 SD-012816 5350 Hc_W50A_Y180 / F404TAG_V264 aTrop2_2293-C04- trastuzumab LC 123 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ADC #Name HC name HCLC name LC np z e ; trastuzuma er pt c_ _ er pt K42TAG pAcetylF AG_V264S K42TAG 124 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ADC #Name HC name HCLC name LC npAzMeF + LP-1 C04_Y180 / F404TAG LC SerOpt Table 29B Exem lar linker- a loads p# 125 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO LP-1 Bglu exatecan L L LTable 30. Humanization matrix to optimize 1925-C06: SRP2296 I 2 A 2 B 2 C 2 D 2 E 2 F 2- - a rop _ - - a rop _ - G01 014014 C06_Lc7 014016 C06_Hc1_FH 126 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ID LC LC name HC HC name LC VL HC VH 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2296- S - a rop _ 95- S - a rop _ 95- 506 77 998 50 C05 014010 C06_Lc3 014020 C06_Hc5_FH 127 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ID LC LC name HC HC name LC VL HC VH 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2296- S - a rop _ 95- S - a rop _ 95- 5090 800 506 568 G08 014014 C06_Lc7 014023 C06_Hc8_FH 128 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ID LC LC name HC HC name LC VL HC VH 2 HTable 31. Humanization matrix to optimize 1925-A04: SRP2295 ID LC LC name HC HC name LC VL HC VH ) 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 295- S - a rop _ 95- S - a rop_ 95- 578 8 5 59 G03 013998 A04_Lc7 014002 A04_Hc3_FH 129 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ID LC LC name HC HC name LC VL HC VH ) 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2295- S - a rop _ 95- S - a rop_ 95- 506 85 5 60 C07 013994 A04_Lc3 014006 A04_Hc7_FH 130 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO ID LC LC name HC HC name LC VL HC VH ) 2 D 2 E 2 F 2 G 2 H 2 A 2 B 2 C 2 D 2 E 2 F 2 G 2 HTable 31.2268 consensus humanization of immune 1925 clones SR e D SR SR SR SR SR SR SR SR SR SR SR SR SR_ _ _ _ SRP2268-B02 ATROP2_1925-D03_HIGG-LC 4737 ATROP2_1925-D03_HIGG-HC 4737 EXAMPLE 10 SEQUENCES

[0356] Table 32 provides sequences referred to herein. 131 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO Table 32. SEQ P P D Y L D I G K T F R P21 SRP1748-B08 CDR-H1 Chothia GFNISNT 132 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I67 SRP1748-F11 CDR-H1 Chothia GFNIKDT 133 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1112 SRP2292-C05 CDR-H1 Chothia GFNIAKS 134 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1158 SRP2292-G07 CDR-H1 Chothia GFNIISK 135 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2204 SRP2293-C09 CDR-H1 Chothia GFNISGK 136 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2250 SRP2293-G11 CDR-H1 Chothia GFNIKGY 137 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 5 5 5 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6_SRP3454- 138 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6655 SRP1925-A05 CDR-H1 Chothia GFSLSSY 139 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6700 SMP1966-C04 CDR-H1 Chothia GFSLSDA 140 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7745 SRP1748-D08 CDR-H1 Kabat NTSIH 141 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7790 SRP2292-A02 CDR-H1 Kabat QTWIH 142 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 7 7 7 7 7 7 7 7 7 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8836 SRP2292-E04 CDR-H1 Kabat RSWIH 143 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8882 SRP2293-A06 CDR-H1 Kabat GTWIH 144 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9928 SRP2293-E08 CDR-H1 Kabat GHWIH 145 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 1 1 1 1 1 1 1 11308 SRP2316-A09 CDR-H1 Kabat SYYIH 146 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11334 SRP2333-B03 CDR-H1 Kabat SYSIH 147 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11379 SRP1925-C11 CDR-H1 Kabat DSGVS 148 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11423 SRP1748-B04 CDR-H2 Chothia ISPNSGT 149 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11469 SRP1748-F07 CDR-H2 Chothia DPYGGT 150 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11514 SRP2292-C01 CDR-H2 Chothia IPAGGA 151 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11560 SRP2292-G03 CDR-H2 Chothia SPNSGT 152 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11606 SRP2293-C05 CDR-H2 Chothia SPASGG 153 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11652 SRP2293-G07 CDR-H2 Chothia NPTGGH 154 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2_SRP3454- 155 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22057 SRP1925-A01 CDR-H2 Chothia SSVGA 156 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22102 SMP1966-B09 CDR-H2 Chothia :SYGGT 157 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22147 SRP1748-D04 CDR-H2 Kabat NIYPDGGYTDYADSVKG 158 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22193 SRP1748-H09 CDR-H2 Kabat RIYPTNGYNRYADSVKG 159 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22238 SRP2292-D11 CDR-H2 Kabat WIQPAGGATDYADSVKG 160 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22284 SRP2293-A02 CDR-H2 Kabat WISPNSGHTDYADSVKG 161 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22330 SRP2293-E04 CDR-H2 Kabat GTNPRGGYTDYADSVKG 162 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22710 SRP2316-A05 CDR-H2 Kabat VIYPYFGYTNYADSVKG 163 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22736 SRP2333-A10 CDR-H2 Kabat WIYPDSGYTYYADSVKG 164 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22781 SRP1925-C04 CDR-H2 Kabat AV:DIYDNTGYATWAKS 165 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22825 SRP1748-A11 CDR-H3 :DSYFWCG::Y:LDY 166 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22871 SRP1748-F03 CDR-H3 :DT:YWYSQ:Y:LDY 167 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22916 SRP2292-B08 CDR-H3 ESYSAIWYYFDY 168 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 22962 SRP2292-F10 CDR-H3 ETYNYYWYVLDY 169 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 33008 SRP2293-C01 CDR-H3 ETYNYYWYVLDY 170 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33054 SRP2293-G03 CDR-H3 :ESQFPWYVLDY 171 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3_SRP3454- 172 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33459 SRP2333-C08 CDR-H3 DYYG::Y::GY:Y:::M:DY 173 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33503 SMP1966-B04 CDR-H3 ::V:GST:::WDDLNI 174 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33547 SRP2333-C06 CDR-L1 RASQDVNTAVA 175 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33591 SMP1966-B02 CDR-L1 QASQ:SIYS:::GL:A: 176 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33635 SRP2333-C04 CDR-L2 SASFLYS 177 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33679 SMP1966-A10 CDR-L2 GA:ST:LDS 178 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33723 SRP2333-C02 CDR-L3 QQWLHYPPT 179 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 33767 SMP1966-A08 CDR-L3 QSNYGGGSGNYA 180 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 S 3 G 3 3 I 3 3 V 3WYVLDYWGQGTLVTVSS 181 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 V T 3 3 W 3 P 3 I 3 F 3 3 3 V 3 3 V 3 I 3 VV GPSYFDYWGQGTLVTVSS 182 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 V 3 3 V 3 V 3 V 3 I 3 3 3 3 W 3 F 3 3VRQAPGKGLEWVGGITPYSGDTDYADSVKGR 183 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 D 3 V 3 3 3 3 V 3 Y 3 W 3 S 3 G 3F PWYVLDYWGQGTLVTVSS 184 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 F 3 3 3 Y 3 3 V S 3 3 3 3 V 3 V 3 V V 3 F 3VRQAPGKGLEWVGWIYPDGGDTDYADSVKG 185 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I C 3 3 L 3 3 3 3 S 3 3 3 3 I 3 V 3 3L YEGSFDYWGQGTLVTVSS 186 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 L 3 R 3 3 W 3 3 V 3 V 3 I 3 I 3 3 S 3 3S SIWYYFDYWGQGTLVTVSS 187 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 W 3 A 3 S 3 F 3 3 I 3 S 3 I 3 W S 3 3 S 3 I 3 I 3VRQAPGKGLEWVGVIYPAAGATDYADSVKG 188 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I I 3 I 3 S 3 3 A 3 3 S 3 A 3 S 3 I 3 W S 3 S 3 V 3V YYWYVFDYWGQGTLVTVSS 189 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 T 3 I 3 W 3 I 3 W 3 I 3 3 W 3 3 S 3 3 3W VRQAPGKGLEWVGGIHPAGGHTDYADSVK 190 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 3 3 I 3 W S 3 W S 3 A 3 W 3 3 3 A 3 I 3 3H YYWYVFDYWGQGTLVTVSS 191 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO SEQ I 3 Y 3 V Y 3 3 3 N 3 Y 3 W Y 3 N 3 V 3 K 3 S 3 N 3 3VRQAPG...

Claims

Attorney Docket No.108843.00551 SU-0450WO WHAT IS CLAIMED IS:

1. An isolated antibody that specifically binds to Trop2, wherein the antibody comprises three heavy chain CDRs from a VH sequence selected from SEQ ID NOs: 3802, 3984, 4396, and 4459, or variants thereof, and three light chain CDRs from a VLsequence selected from SEQ ID NOs: 4634 and 4691, or variants thereof.

2. The isolated antibody of claim 1, comprising six CDRs set forth in SEQ ID NOs: 674 / 2080 / 3486 / 3576 / 3666 / 3756.

3. The isolated antibody of claim 1, comprising six CDRs set forth in SEQ ID NOs: 1377 / 2783 / 3486 / 3576 / 3666 / 3756.

4. The isolated antibody of claim 1, comprising a VH / VLpair set forth in SEQ ID NO: 4459 / 4691.

5. The isolated antibody of claim 1, comprising SEQ ID NO: 4929.

6. The isolated antibody of claim 1, comprising a VH / VL pair set forth in SEQ ID NO: 5374 / 5375.

7. The isolated antibody of claim 1, comprising a heavy chain / light chain pair set forth in SEQ ID NO: 5291 / 5342.

8. The isolated antibody of claim 1 comprising a VH / VLpair set forth in SEQ ID NO: 5374 / 5376.

9. The isolated antibody of claim 1, comprising a heavy chain / light chain pair set forth in SEQ ID NOs: 5317 / 5368.

10. The isolated antibody of claim 1, comprising a VH / VLpair set forth in SEQ ID NO: 4501 / 4733.

11. The isolated antibody of claim 1, comprising six CDRs set forth in SEQ ID NOs: 17 / 1423 / 2829 / 3519 / 3609 / 3699.

12. The isolated antibody of claim 1, comprising six CDRs set forth in SEQ ID NOs: 720 / 2126 / 2829 / 3519 / 3609 / 3699. 319 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 13. The isolated antibody of claim 1 comprising a VH / VLpair set forth in SEQ ID NOs: 3802 / 4634.

14. The isolated antibody of claim 1, comprising six CDRs set forth in SEQ ID NOs: 199 / 1605 / 3011 / 3519 / 3609 / 3699.

15. The isolated antibody of claim 1, comprising six CDRs set forth in SEQ ID NOs: 902 / 2308 / 3011 / 3519 / 3609 / 3699.

16. The isolated antibody of claim 1, comprising a VH / VLpair set forth in SEQ ID NOs: 3984 / 4634.

17. The isolated antibody of claim 1, comprising a heavy chain / light chain pair set forth in SEQ ID NOs: 5304 / 5355.

18. The isolated antibody of claim 1, comprising a heavy chain / light chain pair set forth in SEQ ID NOs: 5309 / 5360.

19. The isolated antibody of claim 1, comprising a heavy chain / light chain pair set forth in SEQ ID NOs: 5275 / 5326.

20. The isolated antibody of claim 1, comprising six CDRs set forth in SEQ ID NOs: 611 / 2017 / 3423 / 3519 / 3609 / 3699.

21. The isolated antibody of claim 1, comprising six CDRs set forth in SEQ ID NOs: 1314 / 2720 / 3423 / 3519 / 3609 / 3699.

22. The isolated antibody of claim 1, comprising a VH / VL pair set forth in SEQ ID NOs: 4396 / 4634.

23. The isolated antibody of any of the preceding claims, wherein the antibody inhibits binding of a second antibody to Trop2 by at least 50%, or wherein the second antibody inhibits binding of the isolated antibody to Trop2 by at least 50%.

24. The isolated antibody of any of the preceding claims, wherein the antibody comprises at least one constant region domain. 320 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 25. The isolated antibody of claim 24, wherein the constant region comprises a sequence selected from the group consisting of SEQ ID No: 4962, 4963, 5225, 5226, 5227, and 5228.

26. The isolated antibody of any of the preceding claims, wherein the antibody is a monoclonal antibody.

27. The isolated antibody of any of the preceding claims, wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM.

28. The isolated antibody of any of the preceding claims, wherein the antibody is humanized or human.

29. The isolated antibody of any of the preceding claims, wherein the antibody is aglycosylated.

30. The isolated antibody of any of the preceding claims, wherein the antibody is an antibody fragment.

31. The isolated antibody of claim 30, wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab’)2 fragment, a Fab’ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment.

32. The isolated antibody of claim 31, wherein the antibody is an scFv fragment.

33. The isolated antibody of any of the preceding claims, wherein the antibody has a kaof about 103M-1×sec-1to about 106M-1×sec-1when associating with human Trop2 at a temperature of 25°C.

34. The isolated antibody of any of the preceding claims, wherein the antibody has a kdof about 10-4sec-1to about 10-8sec-1when dissociating from human Trop2 at a temperature of 25°C.

35. The isolated antibody of any of the preceding claims, wherein the antibody has a KDof about 10-7M to about 10-12M when bound to human Trop2 at a temperature of 25°C.

36. The isolated antibody of any of claims 1-35, further comprising human framework regions. 321 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 37. The isolated antibody of any of claims 1-35, further comprising human kappa framework regions.

38. An isolated antibody that specifically binds to Trop2, wherein the antibody comprises three heavy chain CDRs from a VHsequence selected from SEQ ID NOs: 3789-3801, 3803-3983, 3985-4046, 4382-4395, 4397-4458, and 4460-4491, or variants thereof, and three light chain CDRs from a VL sequence selected from SEQ ID NOs: 4634-4690, and 4692-4723, or variants thereof.

39. The isolated antibody of claim 38, wherein the antibody comprises a CDR-H3, a CDR- H2, CDR-H1, a CDR-L3, a CDR-L2, and a CDR-L1 of a VH - VL pair selected from the group consisting of SEQ ID NOs: 3789 / 4634; 3790 / 4634; 3791 / 4634; 3792 / 4634; 3793 / 4634; 3794 / 4634; 3795 / 4634; 3796 / 4634; 3797 / 4634; 3798 / 4634; 3799 / 4634; 3800 / 4634; 3801 / 4634; 3803 / 4634; 3804 / 4634; 3805 / 4634; 3806 / 4634; 3807 / 4634; 3808 / 4634; 3809 / 4634; 3810 / 4634; 3811 / 4634; 3812 / 4634; 3813 / 4634; 3814 / 4634; 3815 / 4634; 3816 / 4634; 3817 / 4634; 3818 / 4634; 3819 / 4634; 3820 / 4634; 3821 / 4634; 3822 / 4634; 3823 / 4634; 3824 / 4634; 3825 / 4634; 3826 / 4634; 3827 / 4634; 3828 / 4634; 3829 / 4634; 3830 / 4634; 3831 / 4634; 3832 / 4634; 3833 / 4634; 3834 / 4634; 3835 / 4634; 3836 / 4634; 3837 / 4634; 3838 / 4634; 3839 / 4634; 3840 / 4634; 3841 / 4634; 3842 / 4634; 3843 / 4634; 3844 / 4634; 3845 / 4634; 3846 / 4634; 3847 / 4634; 3848 / 4634; 3849 / 4634; 3850 / 4634; 3851 / 4634; 3852 / 4634; 3853 / 4634; 3854 / 4634; 3855 / 4634; 3856 / 4634; 3857 / 4634; 3858 / 4634; 3859 / 4634; 3860 / 4634; 3861 / 4634; 3862 / 4634; 3863 / 4634; 3864 / 4634; 3865 / 4634; 3866 / 4634; 3867 / 4634; 3868 / 4634; 3869 / 4634; 3870 / 4634; 3871 / 4634; 3872 / 4634; 3873 / 4634; 3874 / 4634; 3875 / 4634; 3876 / 4634; 3877 / 4634; 3878 / 4634; 3879 / 4634; 3880 / 4634; 3881 / 4634; 3882 / 4634; 3883 / 4634; 3884 / 4634; 3885 / 4634; 3886 / 4634; 3887 / 4634; 3888 / 4634; 3889 / 4634; 3890 / 4634; 3891 / 4634; 3892 / 4634; 3893 / 4634; 3894 / 4634; 3895 / 4634; 3896 / 4634; 3897 / 4634; 3898 / 4634; 3899 / 4634; 3900 / 4634; 3901 / 4634; 3902 / 4634; 3903 / 4634; 3904 / 4634; 3905 / 4634; 3906 / 4634; 3907 / 4634; 3908 / 4634; 3909 / 4634; 3910 / 4634; 3911 / 4634; 3912 / 4634; 3913 / 4634; 3914 / 4634; 3915 / 4634; 3916 / 4634; 3917 / 4634; 3918 / 4634; 3919 / 4634; 3920 / 4634; 3921 / 4634; 3922 / 4634; 3923 / 4634; 3924 / 4634; 3925 / 4634; 3926 / 4634; 3927 / 4634; 3928 / 4634; 3929 / 4634; 3930 / 4634; 3931 / 4634; 3932 / 4634; 3933 / 4634; 3934 / 4634; 3935 / 4634; 3936 / 4634; 3937 / 4634; 3938 / 4634; 3939 / 4634; 3940 / 4634; 3941 / 4634; 3942 / 4634; 3943 / 4634; 3944 / 4634; 3945 / 4634; 3946 / 4634; 3947 / 4634; 3948 / 4634; 3949 / 4634; 3950 / 4634; 3951 / 4634; 3952 / 4634; 3953 / 4634; 3954 / 4634; 322 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 3955 / 4634; 3956 / 4634; 3957 / 4634; 3958 / 4634; 3959 / 4634; 3960 / 4634; 3961 / 4634; 3962 / 4634; 3963 / 4634; 3964 / 4634; 3965 / 4634; 3966 / 4634; 3967 / 4634; 3968 / 4634; 3969 / 4634; 3970 / 4634; 3971 / 4634; 3972 / 4634; 3973 / 4634; 3974 / 4634; 3975 / 4634; 3976 / 4634; 3977 / 4634; 3978 / 4634; 3979 / 4634; 3980 / 4634; 3981 / 4634; 3982 / 4634; 3983 / 4634; 3985 / 4634; 3986 / 4634; 3987 / 4634; 3988 / 4634; 3989 / 4634; 3990 / 4634; 3991 / 4634; 3992 / 4634; 3993 / 4634; 3994 / 4634; 3995 / 4634; 3996 / 4634; 3997 / 4634; 3998 / 4634; 3999 / 4634; 4000 / 4634; 4001 / 4634; 4002 / 4634; 4003 / 4634; 4004 / 4634; 4005 / 4634; 4006 / 4634; 4007 / 4634; 4008 / 4634; 4009 / 4634; 4010 / 4634; 4011 / 4634; 4012 / 4634; 4013 / 4634; 4014 / 4634; 4015 / 4634; 4016 / 4634; 4017 / 4634; 4018 / 4634; 4019 / 4634; 4020 / 4634; 4021 / 4634; 4022 / 4634; 4023 / 4634; 4024 / 4634; 4025 / 4634; 4026 / 4634; 4027 / 4634; 4028 / 4634; 4029 / 4634; 4030 / 4634; 4031 / 4634; 4032 / 4634; 4033 / 4634; 4034 / 4634; 4035 / 4634; 4036 / 4634; 4037 / 4634; 4038 / 4634; 4039 / 4634; 4040 / 4634; 4041 / 4634; 4042 / 4634; 4043 / 4634; 4044 / 4634; 4045 / 4634; 4046 / 4634; 4382 / 4634; 4383 / 4634; 4384 / 4634; 4385 / 4634; 4386 / 4634; 4387 / 4634; 4388 / 4634; 4389 / 4634; 4390 / 4634; 4391 / 4634; 4392 / 4634; 4393 / 4634; 4394 / 4634; 4395 / 4634; 4397 / 4634; 4398 / 4634; 4399 / 4634; 4400 / 4634; 4401 / 4634; 4402 / 4634; 4403 / 4635; 4404 / 4636; 4405 / 4637; 4406 / 4638; 4407 / 4639; 4408 / 4640; 4409 / 4641; 4410 / 4642; 4411 / 4643; 4412 / 4644; 4413 / 4645; 4414 / 4646; 4415 / 4647; 4416 / 4648; 4417 / 4649; 4418 / 4650; 4419 / 4651; 4420 / 4652; 4421 / 4653; 4422 / 4654; 4423 / 4655; 4424 / 4656; 4425 / 4657; 4426 / 4658; 4427 / 4659; 4428 / 4660; 4429 / 4661; 4430 / 4662; 4431 / 4663; 4432 / 4664; 4433 / 4665; 4434 / 4666; 4435 / 4667; 4436 / 4668; 4437 / 4669; 4438 / 4670; 4439 / 4671; 4440 / 4672; 4441 / 4673; 4442 / 4674; 4443 / 4675; 4444 / 4676; 4445 / 4677; 4446 / 4678; 4447 / 4679; 4448 / 4680; 4449 / 4681; 4450 / 4682; 4451 / 4683; 4452 / 4684; 4453 / 4685; 4454 / 4686; 4455 / 4687; 4456 / 4688; 4457 / 4689; 4458 / 4690; 4460 / 4692; 4461 / 4693; 4462 / 4694; 4463 / 4695; 4464 / 4696; 4465 / 4697; 4466 / 4698; 4467 / 4699; 4468 / 4700; 4469 / 4701; 4470 / 4702; 4471 / 4703; 4472 / 4704; 4473 / 4705; 4474 / 4706; 4475 / 4707; 4476 / 4708; 4477 / 4709; 4478 / 4710; 4479 / 4711; 4480 / 4712; 4481 / 4713; 4482 / 4714; 4483 / 4715; 4484 / 4716; 4485 / 4717; 4486 / 4718; 4487 / 4719; 4488 / 4720; 4489 / 4721; 4490 / 4722; and 4491 / 4723.

40. The isolated antibody of any one of claims 38-39, wherein the antibody comprises a CDR-H3, a CDR-H2, CDR-H1, a CDR-L3, a CDR-L2, a CDR-L1, and framework regions of a VH – VL pair selected from the group consisting of SEQ ID Nos: 3789 / 4634; 3790 / 4634; 3791 / 4634; 3792 / 4634; 3793 / 4634; 3794 / 4634; 3795 / 4634; 323 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 3796 / 4634; 3797 / 4634; 3798 / 4634; 3799 / 4634; 3800 / 4634; 3801 / 4634; 3803 / 4634; 3804 / 4634; 3805 / 4634; 3806 / 4634; 3807 / 4634; 3808 / 4634; 3809 / 4634; 3810 / 4634; 3811 / 4634; 3812 / 4634; 3813 / 4634; 3814 / 4634; 3815 / 4634; 3816 / 4634; 3817 / 4634; 3818 / 4634; 3819 / 4634; 3820 / 4634; 3821 / 4634; 3822 / 4634; 3823 / 4634; 3824 / 4634; 3825 / 4634; 3826 / 4634; 3827 / 4634; 3828 / 4634; 3829 / 4634; 3830 / 4634; 3831 / 4634; 3832 / 4634; 3833 / 4634; 3834 / 4634; 3835 / 4634; 3836 / 4634; 3837 / 4634; 3838 / 4634; 3839 / 4634; 3840 / 4634; 3841 / 4634; 3842 / 4634; 3843 / 4634; 3844 / 4634; 3845 / 4634; 3846 / 4634; 3847 / 4634; 3848 / 4634; 3849 / 4634; 3850 / 4634; 3851 / 4634; 3852 / 4634; 3853 / 4634; 3854 / 4634; 3855 / 4634; 3856 / 4634; 3857 / 4634; 3858 / 4634; 3859 / 4634; 3860 / 4634; 3861 / 4634; 3862 / 4634; 3863 / 4634; 3864 / 4634; 3865 / 4634; 3866 / 4634; 3867 / 4634; 3868 / 4634; 3869 / 4634; 3870 / 4634; 3871 / 4634; 3872 / 4634; 3873 / 4634; 3874 / 4634; 3875 / 4634; 3876 / 4634; 3877 / 4634; 3878 / 4634; 3879 / 4634; 3880 / 4634; 3881 / 4634; 3882 / 4634; 3883 / 4634; 3884 / 4634; 3885 / 4634; 3886 / 4634; 3887 / 4634; 3888 / 4634; 3889 / 4634; 3890 / 4634; 3891 / 4634; 3892 / 4634; 3893 / 4634; 3894 / 4634; 3895 / 4634; 3896 / 4634; 3897 / 4634; 3898 / 4634; 3899 / 4634; 3900 / 4634; 3901 / 4634; 3902 / 4634; 3903 / 4634; 3904 / 4634; 3905 / 4634; 3906 / 4634; 3907 / 4634; 3908 / 4634; 3909 / 4634; 3910 / 4634; 3911 / 4634; 3912 / 4634; 3913 / 4634; 3914 / 4634; 3915 / 4634; 3916 / 4634; 3917 / 4634; 3918 / 4634; 3919 / 4634; 3920 / 4634; 3921 / 4634; 3922 / 4634; 3923 / 4634; 3924 / 4634; 3925 / 4634; 3926 / 4634; 3927 / 4634; 3928 / 4634; 3929 / 4634; 3930 / 4634; 3931 / 4634; 3932 / 4634; 3933 / 4634; 3934 / 4634; 3935 / 4634; 3936 / 4634; 3937 / 4634; 3938 / 4634; 3939 / 4634; 3940 / 4634; 3941 / 4634; 3942 / 4634; 3943 / 4634; 3944 / 4634; 3945 / 4634; 3946 / 4634; 3947 / 4634; 3948 / 4634; 3949 / 4634; 3950 / 4634; 3951 / 4634; 3952 / 4634; 3953 / 4634; 3954 / 4634; 3955 / 4634; 3956 / 4634; 3957 / 4634; 3958 / 4634; 3959 / 4634; 3960 / 4634; 3961 / 4634; 3962 / 4634; 3963 / 4634; 3964 / 4634; 3965 / 4634; 3966 / 4634; 3967 / 4634; 3968 / 4634; 3969 / 4634; 3970 / 4634; 3971 / 4634; 3972 / 4634; 3973 / 4634; 3974 / 4634; 3975 / 4634; 3976 / 4634; 3977 / 4634; 3978 / 4634; 3979 / 4634; 3980 / 4634; 3981 / 4634; 3982 / 4634; 3983 / 4634; 3985 / 4634; 3986 / 4634; 3987 / 4634; 3988 / 4634; 3989 / 4634; 3990 / 4634; 3991 / 4634; 3992 / 4634; 3993 / 4634; 3994 / 4634; 3995 / 4634; 3996 / 4634; 3997 / 4634; 3998 / 4634; 3999 / 4634; 4000 / 4634; 4001 / 4634; 4002 / 4634; 4003 / 4634; 4004 / 4634; 4005 / 4634; 4006 / 4634; 4007 / 4634; 4008 / 4634; 4009 / 4634; 4010 / 4634; 4011 / 4634; 4012 / 4634; 4013 / 4634; 4014 / 4634; 4015 / 4634; 4016 / 4634; 4017 / 4634; 4018 / 4634; 4019 / 4634; 4020 / 4634; 4021 / 4634; 4022 / 4634; 4023 / 4634; 4024 / 4634; 4025 / 4634; 4026 / 4634; 4027 / 4634; 4028 / 4634; 4029 / 4634; 4030 / 4634; 4031 / 4634; 4032 / 4634; 4033 / 4634; 4034 / 4634; 4035 / 4634; 324 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 4036 / 4634; 4037 / 4634; 4038 / 4634; 4039 / 4634; 4040 / 4634; 4041 / 4634; 4042 / 4634; 4043 / 4634; 4044 / 4634; 4045 / 4634; 4046 / 4634; 4382 / 4634; 4383 / 4634; 4384 / 4634; 4385 / 4634; 4386 / 4634; 4387 / 4634; 4388 / 4634; 4389 / 4634; 4390 / 4634; 4391 / 4634; 4392 / 4634; 4393 / 4634; 4394 / 4634; 4395 / 4634; 4397 / 4634; 4398 / 4634; 4399 / 4634; 4400 / 4634; 4401 / 4634; 4402 / 4634; 4403 / 4635; 4404 / 4636; 4405 / 4637; 4406 / 4638; 4407 / 4639; 4408 / 4640; 4409 / 4641; 4410 / 4642; 4411 / 4643; 4412 / 4644; 4413 / 4645; 4414 / 4646; 4415 / 4647; 4416 / 4648; 4417 / 4649; 4418 / 4650; 4419 / 4651; 4420 / 4652; 4421 / 4653; 4422 / 4654; 4423 / 4655; 4424 / 4656; 4425 / 4657; 4426 / 4658; 4427 / 4659; 4428 / 4660; 4429 / 4661; 4430 / 4662; 4431 / 4663; 4432 / 4664; 4433 / 4665; 4434 / 4666; 4435 / 4667; 4436 / 4668; 4437 / 4669; 4438 / 4670; 4439 / 4671; 4440 / 4672; 4441 / 4673; 4442 / 4674; 4443 / 4675; 4444 / 4676; 4445 / 4677; 4446 / 4678; 4447 / 4679; 4448 / 4680; 4449 / 4681; 4450 / 4682; 4451 / 4683; 4452 / 4684; 4453 / 4685; 4454 / 4686; 4455 / 4687; 4456 / 4688; 4457 / 4689; 4458 / 4690; 4460 / 4692; 4461 / 4693; 4462 / 4694; 4463 / 4695; 4464 / 4696; 4465 / 4697; 4466 / 4698; 4467 / 4699; 4468 / 4700; 4469 / 4701; 4470 / 4702; 4471 / 4703; 4472 / 4704; 4473 / 4705; 4474 / 4706; 4475 / 4707; 4476 / 4708; 4477 / 4709; 4478 / 4710; 4479 / 4711; 4480 / 4712; 4481 / 4713; 4482 / 4714; 4483 / 4715; 4484 / 4716; 4485 / 4717; 4486 / 4718; 4487 / 4719; 4488 / 4720; 4489 / 4721; 4490 / 4722; and 4491 / 4723.

41. The isolated antibody of any one of claims 38-40, wherein the antibody comprises three Chothia HC CDRs selected from the group consisting of SEQ ID NOs: 4 / 1410 / 2816; 5 / 1411 / 2817; 6 / 1412 / 2818; 7 / 1413 / 2819; 8 / 1414 / 2820; 9 / 1415 / 2821; 10 / 1416 / 2822; 11 / 1417 / 2823; 12 / 1418 / 2824; 13 / 1419 / 2825; 14 / 1420 / 2826; 15 / 1421 / 2827; 16 / 1422 / 2828; 18 / 1424 / 2830; 19 / 1425 / 2831; 20 / 1426 / 2832; 21 / 1427 / 2833; 22 / 1428 / 2834; 23 / 1429 / 2835; 24 / 1430 / 2836; 25 / 1431 / 2837; 26 / 1432 / 2838; 27 / 1433 / 2839; 28 / 1434 / 2840; 29 / 1435 / 2841; 30 / 1436 / 2842; 31 / 1437 / 2843; 32 / 1438 / 2844; 33 / 1439 / 2845; 34 / 1440 / 2846; 35 / 1441 / 2847; 36 / 1442 / 2848; 37 / 1443 / 2849; 38 / 1444 / 2850; 39 / 1445 / 2851; 40 / 1446 / 2852; 41 / 1447 / 2853; 42 / 1448 / 2854; 43 / 1449 / 2855; 44 / 1450 / 2856; 45 / 1451 / 2857; 46 / 1452 / 2858; 47 / 1453 / 2859; 48 / 1454 / 2860; 49 / 1455 / 2861; 50 / 1456 / 2862; 51 / 1457 / 2863; 52 / 1458 / 2864; 53 / 1459 / 2865; 54 / 1460 / 2866; 55 / 1461 / 2867; 56 / 1462 / 2868; 57 / 1463 / 2869; 58 / 1464 / 2870; 59 / 1465 / 2871; 60 / 1466 / 2872; 61 / 1467 / 2873; 62 / 1468 / 2874; 63 / 1469 / 2875; 64 / 1470 / 2876; 65 / 1471 / 2877; 66 / 1472 / 2878; 67 / 1473 / 2879; 68 / 1474 / 2880; 69 / 1475 / 2881; 70 / 1476 / 2882; 71 / 1477 / 2883; 72 / 1478 / 2884; 73 / 1479 / 2885; 74 / 1480 / 2886; 75 / 1481 / 2887; 76 / 1482 / 2888; 325 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 77 / 1483 / 2889; 78 / 1484 / 2890; 79 / 1485 / 2891; 80 / 1486 / 2892; 81 / 1487 / 2893; 82 / 1488 / 2894; 83 / 1489 / 2895; 84 / 1490 / 2896; 85 / 1491 / 2897; 86 / 1492 / 2898; 87 / 1493 / 2899; 88 / 1494 / 2900; 89 / 1495 / 2901; 90 / 1496 / 2902; 91 / 1497 / 2903; 92 / 1498 / 2904; 93 / 1499 / 2905; 94 / 1500 / 2906; 95 / 1501 / 2907; 96 / 1502 / 2908; 97 / 1503 / 2909; 98 / 1504 / 2910; 99 / 1505 / 2911; 100 / 1506 / 2912; 101 / 1507 / 2913; 102 / 1508 / 2914; 103 / 1509 / 2915; 104 / 1510 / 2916; 105 / 1511 / 2917; 106 / 1512 / 2918; 107 / 1513 / 2919; 108 / 1514 / 2920; 109 / 1515 / 2921; 110 / 1516 / 2922; 111 / 1517 / 2923; 112 / 1518 / 2924; 113 / 1519 / 2925; 114 / 1520 / 2926; 115 / 1521 / 2927; 116 / 1522 / 2928; 117 / 1523 / 2929; 118 / 1524 / 2930; 119 / 1525 / 2931; 120 / 1526 / 2932; 121 / 1527 / 2933; 122 / 1528 / 2934; 123 / 1529 / 2935; 124 / 1530 / 2936; 125 / 1531 / 2937; 126 / 1532 / 2938; 127 / 1533 / 2939; 128 / 1534 / 2940; 129 / 1535 / 2941; 130 / 1536 / 2942; 131 / 1537 / 2943; 132 / 1538 / 2944; 133 / 1539 / 2945; 134 / 1540 / 2946; 135 / 1541 / 2947; 136 / 1542 / 2948; 137 / 1543 / 2949; 138 / 1544 / 2950; 139 / 1545 / 2951; 140 / 1546 / 2952; 141 / 1547 / 2953; 142 / 1548 / 2954; 143 / 1549 / 2955; 144 / 1550 / 2956; 145 / 1551 / 2957; 146 / 1552 / 2958; 147 / 1553 / 2959; 148 / 1554 / 2960; 149 / 1555 / 2961; 150 / 1556 / 2962; 151 / 1557 / 2963; 152 / 1558 / 2964; 153 / 1559 / 2965; 154 / 1560 / 2966; 155 / 1561 / 2967; 156 / 1562 / 2968; 157 / 1563 / 2969; 158 / 1564 / 2970; 159 / 1565 / 2971; 160 / 1566 / 2972; 161 / 1567 / 2973; 162 / 1568 / 2974; 163 / 1569 / 2975; 164 / 1570 / 2976; 165 / 1571 / 2977; 166 / 1572 / 2978; 167 / 1573 / 2979; 168 / 1574 / 2980; 169 / 1575 / 2981; 170 / 1576 / 2982; 171 / 1577 / 2983; 172 / 1578 / 2984; 173 / 1579 / 2985; 174 / 1580 / 2986; 175 / 1581 / 2987; 176 / 1582 / 2988; 177 / 1583 / 2989; 178 / 1584 / 2990; 179 / 1585 / 2991; 180 / 1586 / 2992; 181 / 1587 / 2993; 182 / 1588 / 2994; 183 / 1589 / 2995; 184 / 1590 / 2996; 185 / 1591 / 2997; 186 / 1592 / 2998; 187 / 1593 / 2999; 188 / 1594 / 3000; 189 / 1595 / 3001; 190 / 1596 / 3002; 191 / 1597 / 3003; 192 / 1598 / 3004; 193 / 1599 / 3005; 194 / 1600 / 3006; 195 / 1601 / 3007; 196 / 1602 / 3008; 197 / 1603 / 3009; 198 / 1604 / 3010; 200 / 1606 / 3012; 201 / 1607 / 3013; 202 / 1608 / 3014; 203 / 1609 / 3015; 204 / 1610 / 3016; 205 / 1611 / 3017; 206 / 1612 / 3018; 207 / 1613 / 3019; 208 / 1614 / 3020; 209 / 1615 / 3021; 210 / 1616 / 3022; 211 / 1617 / 3023; 212 / 1618 / 3024; 213 / 1619 / 3025; 214 / 1620 / 3026; 215 / 1621 / 3027; 216 / 1622 / 3028; 217 / 1623 / 3029; 218 / 1624 / 3030; 219 / 1625 / 3031; 220 / 1626 / 3032; 221 / 1627 / 3033; 222 / 1628 / 3034; 223 / 1629 / 3035; 224 / 1630 / 3036; 225 / 1631 / 3037; 226 / 1632 / 3038; 227 / 1633 / 3039; 228 / 1634 / 3040; 229 / 1635 / 3041; 230 / 1636 / 3042; 231 / 1637 / 3043; 232 / 1638 / 3044; 233 / 1639 / 3045; 234 / 1640 / 3046; 235 / 1641 / 3047; 236 / 1642 / 3048; 237 / 1643 / 3049; 238 / 1644 / 3050; 239 / 1645 / 3051; 240 / 1646 / 3052; 241 / 1647 / 3053; 242 / 1648 / 3054; 243 / 1649 / 3055; 244 / 1650 / 3056; 245 / 1651 / 3057; 246 / 1652 / 3058; 247 / 1653 / 3059; 326 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 248 / 1654 / 3060; 249 / 1655 / 3061; 250 / 1656 / 3062; 251 / 1657 / 3063; 252 / 1658 / 3064; 253 / 1659 / 3065; 254 / 1660 / 3066; 255 / 1661 / 3067; 256 / 1662 / 3068; 257 / 1663 / 3069; 258 / 1664 / 3070; 259 / 1665 / 3071; 260 / 1666 / 3072; 261 / 1667 / 3073; 597 / 2003 / 3409; 598 / 2004 / 3410; 599 / 2005 / 3411; 600 / 2006 / 3412; 601 / 2007 / 3413; 602 / 2008 / 3414; 603 / 2009 / 3415; 604 / 2010 / 3416; 605 / 2011 / 3417; 606 / 2012 / 3418; 607 / 2013 / 3419; 608 / 2014 / 3420; 609 / 2015 / 3421; 610 / 2016 / 3422; 612 / 2018 / 3424; 613 / 2019 / 3425; 614 / 2020 / 3426; 615 / 2021 / 3427; 616 / 2022 / 3428; 617 / 2023 / 3429; 618 / 2024 / 3430; 619 / 2025 / 3431; 620 / 2026 / 3432; 621 / 2027 / 3433; 622 / 2028 / 3434; 623 / 2029 / 3435; 624 / 2030 / 3436; 625 / 2031 / 3437; 626 / 2032 / 3438; 627 / 2033 / 3439; 628 / 2034 / 3440; 629 / 2035 / 3441; 630 / 2036 / 3442; 631 / 2037 / 3443; 632 / 2038 / 3444; 633 / 2039 / 3445; 634 / 2040 / 3446; 635 / 2041 / 3447; 636 / 2042 / 3448; 637 / 2043 / 3449; 638 / 2044 / 3450; 639 / 2045 / 3451; 640 / 2046 / 3452; 641 / 2047 / 3453; 642 / 2048 / 3454; 643 / 2049 / 3455; 644 / 2050 / 3456; 645 / 2051 / 3457; 646 / 2052 / 3458; 647 / 2053 / 3459; 648 / 2054 / 3460; 649 / 2055 / 3461; 650 / 2056 / 3462; 651 / 2057 / 3463; 652 / 2058 / 3464; 653 / 2059 / 3465; 654 / 2060 / 3466; 655 / 2061 / 3467; 656 / 2062 / 3468; 657 / 2063 / 3469; 658 / 2064 / 3470; 659 / 2065 / 3471; 660 / 2066 / 3472; 661 / 2067 / 3473; 662 / 2068 / 3474; 663 / 2069 / 3475; 664 / 2070 / 3476; 665 / 2071 / 3477; 666 / 2072 / 3478; 667 / 2073 / 3479; 668 / 2074 / 3480; 669 / 2075 / 3481; 670 / 2076 / 3482; 671 / 2077 / 3483; 672 / 2078 / 3484; 673 / 2079 / 3485; 675 / 2081 / 3487; 676 / 2082 / 3488; 677 / 2083 / 3489; 678 / 2084 / 3490; 679 / 2085 / 3491; 680 / 2086 / 3492; 681 / 2087 / 3493; 682 / 2088 / 3494; 683 / 2089 / 3495; 684 / 2090 / 3496; 685 / 2091 / 3497; 686 / 2092 / 3498; 687 / 2093 / 3499; 688 / 2094 / 3500; 689 / 2095 / 3501; 690 / 2096 / 3502; 691 / 2097 / 3503; 692 / 2098 / 3504; 693 / 2099 / 3505; 694 / 2100 / 3506; 695 / 2101 / 3507; 696 / 2102 / 3508; 697 / 2103 / 3509; 698 / 2104 / 3510; 699 / 2105 / 3511; 700 / 2106 / 3512; 701 / 2107 / 3513; 702 / 2108 / 3514; 703 / 2109 / 3515; 704 / 2110 / 3516; 705 / 2111 / 3517; and 706 / 2112 / 3518.

42. The isolated antibody of any one of claims 38-41, wherein the antibody comprises three Kabat HC CDRs according to one of the following groups of HC CDR SEQ ID NOs: 707 / 2113 / 2816; 708 / 2114 / 2817; 709 / 2115 / 2818; 710 / 2116 / 2819; 711 / 2117 / 2820; 712 / 2118 / 2821; 713 / 2119 / 2822; 714 / 2120 / 2823; 715 / 2121 / 2824; 716 / 2122 / 2825; 717 / 2123 / 2826; 718 / 2124 / 2827; 719 / 2125 / 2828; 721 / 2127 / 2830; 722 / 2128 / 2831; 723 / 2129 / 2832; 724 / 2130 / 2833; 725 / 2131 / 2834; 726 / 2132 / 2835; 727 / 2133 / 2836; 728 / 2134 / 2837; 729 / 2135 / 2838; 730 / 2136 / 2839; 731 / 2137 / 2840; 732 / 2138 / 2841; 733 / 2139 / 2842; 734 / 2140 / 2843; 735 / 2141 / 2844; 736 / 2142 / 2845; 737 / 2143 / 2846; 327 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 738 / 2144 / 2847; 739 / 2145 / 2848; 740 / 2146 / 2849; 741 / 2147 / 2850; 742 / 2148 / 2851; 743 / 2149 / 2852; 744 / 2150 / 2853; 745 / 2151 / 2854; 746 / 2152 / 2855; 747 / 2153 / 2856; 748 / 2154 / 2857; 749 / 2155 / 2858; 750 / 2156 / 2859; 751 / 2157 / 2860; 752 / 2158 / 2861; 753 / 2159 / 2862; 754 / 2160 / 2863; 755 / 2161 / 2864; 756 / 2162 / 2865; 757 / 2163 / 2866; 758 / 2164 / 2867; 759 / 2165 / 2868; 760 / 2166 / 2869; 761 / 2167 / 2870; 762 / 2168 / 2871; 763 / 2169 / 2872; 764 / 2170 / 2873; 765 / 2171 / 2874; 766 / 2172 / 2875; 767 / 2173 / 2876; 768 / 2174 / 2877; 769 / 2175 / 2878; 770 / 2176 / 2879; 771 / 2177 / 2880; 772 / 2178 / 2881; 773 / 2179 / 2882; 774 / 2180 / 2883; 775 / 2181 / 2884; 776 / 2182 / 2885; 777 / 2183 / 2886; 778 / 2184 / 2887; 779 / 2185 / 2888; 780 / 2186 / 2889; 781 / 2187 / 2890; 782 / 2188 / 2891; 783 / 2189 / 2892; 784 / 2190 / 2893; 785 / 2191 / 2894; 786 / 2192 / 2895; 787 / 2193 / 2896; 788 / 2194 / 2897; 789 / 2195 / 2898; 790 / 2196 / 2899; 791 / 2197 / 2900; 792 / 2198 / 2901; 793 / 2199 / 2902; 794 / 2200 / 2903; 795 / 2201 / 2904; 796 / 2202 / 2905; 797 / 2203 / 2906; 798 / 2204 / 2907; 799 / 2205 / 2908; 800 / 2206 / 2909; 801 / 2207 / 2910; 802 / 2208 / 2911; 803 / 2209 / 2912; 804 / 2210 / 2913; 805 / 2211 / 2914; 806 / 2212 / 2915; 807 / 2213 / 2916; 808 / 2214 / 2917; 809 / 2215 / 2918; 810 / 2216 / 2919; 811 / 2217 / 2920; 812 / 2218 / 2921; 813 / 2219 / 2922; 814 / 2220 / 2923; 815 / 2221 / 2924; 816 / 2222 / 2925; 817 / 2223 / 2926; 818 / 2224 / 2927; 819 / 2225 / 2928; 820 / 2226 / 2929; 821 / 2227 / 2930; 822 / 2228 / 2931; 823 / 2229 / 2932; 824 / 2230 / 2933; 825 / 2231 / 2934; 826 / 2232 / 2935; 827 / 2233 / 2936; 828 / 2234 / 2937; 829 / 2235 / 2938; 830 / 2236 / 2939; 831 / 2237 / 2940; 832 / 2238 / 2941; 833 / 2239 / 2942; 834 / 2240 / 2943; 835 / 2241 / 2944; 836 / 2242 / 2945; 837 / 2243 / 2946; 838 / 2244 / 2947; 839 / 2245 / 2948; 840 / 2246 / 2949; 841 / 2247 / 2950; 842 / 2248 / 2951; 843 / 2249 / 2952; 844 / 2250 / 2953; 845 / 2251 / 2954; 846 / 2252 / 2955; 847 / 2253 / 2956; 848 / 2254 / 2957; 849 / 2255 / 2958; 850 / 2256 / 2959; 851 / 2257 / 2960; 852 / 2258 / 2961; 853 / 2259 / 2962; 854 / 2260 / 2963; 855 / 2261 / 2964; 856 / 2262 / 2965; 857 / 2263 / 2966; 858 / 2264 / 2967; 859 / 2265 / 2968; 860 / 2266 / 2969; 861 / 2267 / 2970; 862 / 2268 / 2971; 863 / 2269 / 2972; 864 / 2270 / 2973; 865 / 2271 / 2974; 866 / 2272 / 2975; 867 / 2273 / 2976; 868 / 2274 / 2977; 869 / 2275 / 2978; 870 / 2276 / 2979; 871 / 2277 / 2980; 872 / 2278 / 2981; 873 / 2279 / 2982; 874 / 2280 / 2983; 875 / 2281 / 2984; 876 / 2282 / 2985; 877 / 2283 / 2986; 878 / 2284 / 2987; 879 / 2285 / 2988; 880 / 2286 / 2989; 881 / 2287 / 2990; 882 / 2288 / 2991; 883 / 2289 / 2992; 884 / 2290 / 2993; 885 / 2291 / 2994; 886 / 2292 / 2995; 887 / 2293 / 2996; 888 / 2294 / 2997; 889 / 2295 / 2998; 890 / 2296 / 2999; 891 / 2297 / 3000; 892 / 2298 / 3001; 893 / 2299 / 3002; 894 / 2300 / 3003; 895 / 2301 / 3004; 896 / 2302 / 3005; 897 / 2303 / 3006; 898 / 2304 / 3007; 899 / 2305 / 3008; 900 / 2306 / 3009; 901 / 2307 / 3010; 903 / 2309 / 3012; 904 / 2310 / 3013; 905 / 2311 / 3014; 906 / 2312 / 3015; 907 / 2313 / 3016; 908 / 2314 / 3017; 328 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 909 / 2315 / 3018; 910 / 2316 / 3019; 911 / 2317 / 3020; 912 / 2318 / 3021; 913 / 2319 / 3022; 914 / 2320 / 3023; 915 / 2321 / 3024; 916 / 2322 / 3025; 917 / 2323 / 3026; 918 / 2324 / 3027; 919 / 2325 / 3028; 920 / 2326 / 3029; 921 / 2327 / 3030; 922 / 2328 / 3031; 923 / 2329 / 3032; 924 / 2330 / 3033; 925 / 2331 / 3034; 926 / 2332 / 3035; 927 / 2333 / 3036; 928 / 2334 / 3037; 929 / 2335 / 3038; 930 / 2336 / 3039; 931 / 2337 / 3040; 932 / 2338 / 3041; 933 / 2339 / 3042; 934 / 2340 / 3043; 935 / 2341 / 3044; 936 / 2342 / 3045; 937 / 2343 / 3046; 938 / 2344 / 3047; 939 / 2345 / 3048; 940 / 2346 / 3049; 941 / 2347 / 3050; 942 / 2348 / 3051; 943 / 2349 / 3052; 944 / 2350 / 3053; 945 / 2351 / 3054; 946 / 2352 / 3055; 947 / 2353 / 3056; 948 / 2354 / 3057; 949 / 2355 / 3058; 950 / 2356 / 3059; 951 / 2357 / 3060; 952 / 2358 / 3061; 953 / 2359 / 3062; 954 / 2360 / 3063; 955 / 2361 / 3064; 956 / 2362 / 3065; 957 / 2363 / 3066; 958 / 2364 / 3067; 959 / 2365 / 3068; 960 / 2366 / 3069; 961 / 2367 / 3070; 962 / 2368 / 3071; 963 / 2369 / 3072; 964 / 2370 / 3073; 1300 / 2706 / 3409; 1301 / 2707 / 3410; 1302 / 2708 / 3411; 1303 / 2709 / 3412; 1304 / 2710 / 3413; 1305 / 2711 / 3414; 1306 / 2712 / 3415; 1307 / 2713 / 3416; 1308 / 2714 / 3417; 1309 / 2715 / 3418; 1310 / 2716 / 3419; 1311 / 2717 / 3420; 1312 / 2718 / 3421; 1313 / 2719 / 3422; 1315 / 2721 / 3424; 1316 / 2722 / 3425; 1317 / 2723 / 3426; 1318 / 2724 / 3427; 1319 / 2725 / 3428; 1320 / 2726 / 3429; 1321 / 2727 / 3430; 1322 / 2728 / 3431; 1323 / 2729 / 3432; 1324 / 2730 / 3433; 1325 / 2731 / 3434; 1326 / 2732 / 3435; 1327 / 2733 / 3436; 1328 / 2734 / 3437; 1329 / 2735 / 3438; 1330 / 2736 / 3439; 1331 / 2737 / 3440; 1332 / 2738 / 3441; 1333 / 2739 / 3442; 1334 / 2740 / 3443; 1335 / 2741 / 3444; 1336 / 2742 / 3445; 1337 / 2743 / 3446; 1338 / 2744 / 3447; 1339 / 2745 / 3448; 1340 / 2746 / 3449; 1341 / 2747 / 3450; 1342 / 2748 / 3451; 1343 / 2749 / 3452; 1344 / 2750 / 3453; 1345 / 2751 / 3454; 1346 / 2752 / 3455; 1347 / 2753 / 3456; 1348 / 2754 / 3457; 1349 / 2755 / 3458; 1350 / 2756 / 3459; 1351 / 2757 / 3460; 1352 / 2758 / 3461; 1353 / 2759 / 3462; 1354 / 2760 / 3463; 1355 / 2761 / 3464; 1356 / 2762 / 3465; 1357 / 2763 / 3466; 1358 / 2764 / 3467; 1359 / 2765 / 3468; 1360 / 2766 / 3469; 1361 / 2767 / 3470; 1362 / 2768 / 3471; 1363 / 2769 / 3472; 1364 / 2770 / 3473; 1365 / 2771 / 3474; 1366 / 2772 / 3475; 1367 / 2773 / 3476; 1368 / 2774 / 3477; 1369 / 2775 / 3478; 1370 / 2776 / 3479; 1371 / 2777 / 3480; 1372 / 2778 / 3481; 1373 / 2779 / 3482; 1374 / 2780 / 3483; 1375 / 2781 / 3484; 1376 / 2782 / 3485; 1378 / 2784 / 3487; 1379 / 2785 / 3488; 1380 / 2786 / 3489; 1381 / 2787 / 3490; 1382 / 2788 / 3491; 1383 / 2789 / 3492; 1384 / 2790 / 3493; 1385 / 2791 / 3494; 1386 / 2792 / 3495; 1387 / 2793 / 3496; 1388 / 2794 / 3497; 1389 / 2795 / 3498; 1390 / 2796 / 3499; 1391 / 2797 / 3500; 1392 / 2798 / 3501; 1393 / 2799 / 3502; 1394 / 2800 / 3503; 1395 / 2801 / 3504; 1396 / 2802 / 3505; 1397 / 2803 / 3506; 1398 / 2804 / 3507; 1399 / 2805 / 3508; 1400 / 2806 / 3509; 1401 / 2807 / 3510; 1402 / 2808 / 3511; 1403 / 2809 / 3512; 1404 / 2810 / 3513; 1405 / 2811 / 3514; 1406 / 2812 / 3515; 1407 / 2813 / 3516; 1408 / 2814 / 3517; and 1409 / 2815 / 3518. 329 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 43. The isolated antibody of any one of claims 38-42, wherein the antibody comprises six CDRs selected from the group consisting of SEQ ID NOs: 4 / 1410 / 2816 / 3519 / 3609 / 3699; 5 / 1411 / 2817 / 3519 / 3609 / 3699; 6 / 1412 / 2818 / 3519 / 3609 / 3699; 7 / 1413 / 2819 / 3519 / 3609 / 3699; 8 / 1414 / 2820 / 3519 / 3609 / 3699; 9 / 1415 / 2821 / 3519 / 3609 / 3699; 10 / 1416 / 2822 / 3519 / 3609 / 3699; 11 / 1417 / 2823 / 3519 / 3609 / 3699; 12 / 1418 / 2824 / 3519 / 3609 / 3699; 13 / 1419 / 2825 / 3519 / 3609 / 3699; 14 / 1420 / 2826 / 3519 / 3609 / 3699; 15 / 1421 / 2827 / 3519 / 3609 / 3699; 16 / 1422 / 2828 / 3519 / 3609 / 3699; 18 / 1424 / 2830 / 3519 / 3609 / 3699; 19 / 1425 / 2831 / 3519 / 3609 / 3699; 20 / 1426 / 2832 / 3519 / 3609 / 3699; 21 / 1427 / 2833 / 3519 / 3609 / 3699; 22 / 1428 / 2834 / 3519 / 3609 / 3699; 23 / 1429 / 2835 / 3519 / 3609 / 3699; 24 / 1430 / 2836 / 3519 / 3609 / 3699; 25 / 1431 / 2837 / 3519 / 3609 / 3699; 26 / 1432 / 2838 / 3519 / 3609 / 3699; 27 / 1433 / 2839 / 3519 / 3609 / 3699; 28 / 1434 / 2840 / 3519 / 3609 / 3699; 29 / 1435 / 2841 / 3519 / 3609 / 3699; 30 / 1436 / 2842 / 3519 / 3609 / 3699; 31 / 1437 / 2843 / 3519 / 3609 / 3699; 32 / 1438 / 2844 / 3519 / 3609 / 3699; 33 / 1439 / 2845 / 3519 / 3609 / 3699; 34 / 1440 / 2846 / 3519 / 3609 / 3699; 35 / 1441 / 2847 / 3519 / 3609 / 3699; 36 / 1442 / 2848 / 3519 / 3609 / 3699; 37 / 1443 / 2849 / 3519 / 3609 / 3699; 38 / 1444 / 2850 / 3519 / 3609 / 3699; 39 / 1445 / 2851 / 3519 / 3609 / 3699; 40 / 1446 / 2852 / 3519 / 3609 / 3699; 41 / 1447 / 2853 / 3519 / 3609 / 3699; 42 / 1448 / 2854 / 3519 / 3609 / 3699; 43 / 1449 / 2855 / 3519 / 3609 / 3699; 44 / 1450 / 2856 / 3519 / 3609 / 3699; 45 / 1451 / 2857 / 3519 / 3609 / 3699; 46 / 1452 / 2858 / 3519 / 3609 / 3699; 47 / 1453 / 2859 / 3519 / 3609 / 3699; 48 / 1454 / 2860 / 3519 / 3609 / 3699; 49 / 1455 / 2861 / 3519 / 3609 / 3699; 50 / 1456 / 2862 / 3519 / 3609 / 3699; 51 / 1457 / 2863 / 3519 / 3609 / 3699; 52 / 1458 / 2864 / 3519 / 3609 / 3699; 53 / 1459 / 2865 / 3519 / 3609 / 3699; 54 / 1460 / 2866 / 3519 / 3609 / 3699; 55 / 1461 / 2867 / 3519 / 3609 / 3699; 56 / 1462 / 2868 / 3519 / 3609 / 3699; 57 / 1463 / 2869 / 3519 / 3609 / 3699; 58 / 1464 / 2870 / 3519 / 3609 / 3699; 59 / 1465 / 2871 / 3519 / 3609 / 3699; 60 / 1466 / 2872 / 3519 / 3609 / 3699; 61 / 1467 / 2873 / 3519 / 3609 / 3699; 62 / 1468 / 2874 / 3519 / 3609 / 3699; 63 / 1469 / 2875 / 3519 / 3609 / 3699; 64 / 1470 / 2876 / 3519 / 3609 / 3699; 65 / 1471 / 2877 / 3519 / 3609 / 3699; 66 / 1472 / 2878 / 3519 / 3609 / 3699; 67 / 1473 / 2879 / 3519 / 3609 / 3699; 68 / 1474 / 2880 / 3519 / 3609 / 3699; 330 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 69 / 1475 / 2881 / 3519 / 3609 / 3699; 70 / 1476 / 2882 / 3519 / 3609 / 3699; 71 / 1477 / 2883 / 3519 / 3609 / 3699; 72 / 1478 / 2884 / 3519 / 3609 / 3699; 73 / 1479 / 2885 / 3519 / 3609 / 3699; 74 / 1480 / 2886 / 3519 / 3609 / 3699; 75 / 1481 / 2887 / 3519 / 3609 / 3699; 76 / 1482 / 2888 / 3519 / 3609 / 3699; 77 / 1483 / 2889 / 3519 / 3609 / 3699; 78 / 1484 / 2890 / 3519 / 3609 / 3699; 79 / 1485 / 2891 / 3519 / 3609 / 3699; 80 / 1486 / 2892 / 3519 / 3609 / 3699; 81 / 1487 / 2893 / 3519 / 3609 / 3699; 82 / 1488 / 2894 / 3519 / 3609 / 3699; 83 / 1489 / 2895 / 3519 / 3609 / 3699; 84 / 1490 / 2896 / 3519 / 3609 / 3699; 85 / 1491 / 2897 / 3519 / 3609 / 3699; 86 / 1492 / 2898 / 3519 / 3609 / 3699; 87 / 1493 / 2899 / 3519 / 3609 / 3699; 88 / 1494 / 2900 / 3519 / 3609 / 3699; 89 / 1495 / 2901 / 3519 / 3609 / 3699; 90 / 1496 / 2902 / 3519 / 3609 / 3699; 91 / 1497 / 2903 / 3519 / 3609 / 3699; 92 / 1498 / 2904 / 3519 / 3609 / 3699; 93 / 1499 / 2905 / 3519 / 3609 / 3699; 94 / 1500 / 2906 / 3519 / 3609 / 3699; 95 / 1501 / 2907 / 3519 / 3609 / 3699; 96 / 1502 / 2908 / 3519 / 3609 / 3699; 97 / 1503 / 2909 / 3519 / 3609 / 3699; 98 / 1504 / 2910 / 3519 / 3609 / 3699; 99 / 1505 / 2911 / 3519 / 3609 / 3699; 100 / 1506 / 2912 / 3519 / 3609 / 3699; 101 / 1507 / 2913 / 3519 / 3609 / 3699; 102 / 1508 / 2914 / 3519 / 3609 / 3699; 103 / 1509 / 2915 / 3519 / 3609 / 3699; 104 / 1510 / 2916 / 3519 / 3609 / 3699; 105 / 1511 / 2917 / 3519 / 3609 / 3699; 106 / 1512 / 2918 / 3519 / 3609 / 3699; 107 / 1513 / 2919 / 3519 / 3609 / 3699; 108 / 1514 / 2920 / 3519 / 3609 / 3699; 109 / 1515 / 2921 / 3519 / 3609 / 3699; 110 / 1516 / 2922 / 3519 / 3609 / 3699; 111 / 1517 / 2923 / 3519 / 3609 / 3699; 112 / 1518 / 2924 / 3519 / 3609 / 3699; 113 / 1519 / 2925 / 3519 / 3609 / 3699; 114 / 1520 / 2926 / 3519 / 3609 / 3699; 115 / 1521 / 2927 / 3519 / 3609 / 3699; 116 / 1522 / 2928 / 3519 / 3609 / 3699; 117 / 1523 / 2929 / 3519 / 3609 / 3699; 118 / 1524 / 2930 / 3519 / 3609 / 3699; 119 / 1525 / 2931 / 3519 / 3609 / 3699; 120 / 1526 / 2932 / 3519 / 3609 / 3699; 121 / 1527 / 2933 / 3519 / 3609 / 3699; 122 / 1528 / 2934 / 3519 / 3609 / 3699; 123 / 1529 / 2935 / 3519 / 3609 / 3699; 124 / 1530 / 2936 / 3519 / 3609 / 3699; 125 / 1531 / 2937 / 3519 / 3609 / 3699; 126 / 1532 / 2938 / 3519 / 3609 / 3699; 127 / 1533 / 2939 / 3519 / 3609 / 3699; 128 / 1534 / 2940 / 3519 / 3609 / 3699; 129 / 1535 / 2941 / 3519 / 3609 / 3699; 130 / 1536 / 2942 / 3519 / 3609 / 3699; 131 / 1537 / 2943 / 3519 / 3609 / 3699; 132 / 1538 / 2944 / 3519 / 3609 / 3699; 133 / 1539 / 2945 / 3519 / 3609 / 3699; 134 / 1540 / 2946 / 3519 / 3609 / 3699; 135 / 1541 / 2947 / 3519 / 3609 / 3699; 136 / 1542 / 2948 / 3519 / 3609 / 3699; 331 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 137 / 1543 / 2949 / 3519 / 3609 / 3699; 138 / 1544 / 2950 / 3519 / 3609 / 3699; 139 / 1545 / 2951 / 3519 / 3609 / 3699; 140 / 1546 / 2952 / 3519 / 3609 / 3699; 141 / 1547 / 2953 / 3519 / 3609 / 3699; 142 / 1548 / 2954 / 3519 / 3609 / 3699; 143 / 1549 / 2955 / 3519 / 3609 / 3699; 144 / 1550 / 2956 / 3519 / 3609 / 3699; 145 / 1551 / 2957 / 3519 / 3609 / 3699; 146 / 1552 / 2958 / 3519 / 3609 / 3699; 147 / 1553 / 2959 / 3519 / 3609 / 3699; 148 / 1554 / 2960 / 3519 / 3609 / 3699; 149 / 1555 / 2961 / 3519 / 3609 / 3699; 150 / 1556 / 2962 / 3519 / 3609 / 3699; 151 / 1557 / 2963 / 3519 / 3609 / 3699; 152 / 1558 / 2964 / 3519 / 3609 / 3699; 153 / 1559 / 2965 / 3519 / 3609 / 3699; 154 / 1560 / 2966 / 3519 / 3609 / 3699; 155 / 1561 / 2967 / 3519 / 3609 / 3699; 156 / 1562 / 2968 / 3519 / 3609 / 3699; 157 / 1563 / 2969 / 3519 / 3609 / 3699; 158 / 1564 / 2970 / 3519 / 3609 / 3699; 159 / 1565 / 2971 / 3519 / 3609 / 3699; 160 / 1566 / 2972 / 3519 / 3609 / 3699; 161 / 1567 / 2973 / 3519 / 3609 / 3699; 162 / 1568 / 2974 / 3519 / 3609 / 3699; 163 / 1569 / 2975 / 3519 / 3609 / 3699; 164 / 1570 / 2976 / 3519 / 3609 / 3699; 165 / 1571 / 2977 / 3519 / 3609 / 3699; 166 / 1572 / 2978 / 3519 / 3609 / 3699; 167 / 1573 / 2979 / 3519 / 3609 / 3699; 168 / 1574 / 2980 / 3519 / 3609 / 3699; 169 / 1575 / 2981 / 3519 / 3609 / 3699; 170 / 1576 / 2982 / 3519 / 3609 / 3699; 171 / 1577 / 2983 / 3519 / 3609 / 3699; 172 / 1578 / 2984 / 3519 / 3609 / 3699; 173 / 1579 / 2985 / 3519 / 3609 / 3699; 174 / 1580 / 2986 / 3519 / 3609 / 3699; 175 / 1581 / 2987 / 3519 / 3609 / 3699; 176 / 1582 / 2988 / 3519 / 3609 / 3699; 177 / 1583 / 2989 / 3519 / 3609 / 3699; 178 / 1584 / 2990 / 3519 / 3609 / 3699; 179 / 1585 / 2991 / 3519 / 3609 / 3699; 180 / 1586 / 2992 / 3519 / 3609 / 3699; 181 / 1587 / 2993 / 3519 / 3609 / 3699; 182 / 1588 / 2994 / 3519 / 3609 / 3699; 183 / 1589 / 2995 / 3519 / 3609 / 3699; 184 / 1590 / 2996 / 3519 / 3609 / 3699; 185 / 1591 / 2997 / 3519 / 3609 / 3699; 186 / 1592 / 2998 / 3519 / 3609 / 3699; 187 / 1593 / 2999 / 3519 / 3609 / 3699; 188 / 1594 / 3000 / 3519 / 3609 / 3699; 189 / 1595 / 3001 / 3519 / 3609 / 3699; 190 / 1596 / 3002 / 3519 / 3609 / 3699; 191 / 1597 / 3003 / 3519 / 3609 / 3699; 192 / 1598 / 3004 / 3519 / 3609 / 3699; 193 / 1599 / 3005 / 3519 / 3609 / 3699; 194 / 1600 / 3006 / 3519 / 3609 / 3699; 195 / 1601 / 3007 / 3519 / 3609 / 3699; 196 / 1602 / 3008 / 3519 / 3609 / 3699; 197 / 1603 / 3009 / 3519 / 3609 / 3699; 198 / 1604 / 3010 / 3519 / 3609 / 3699; 200 / 1606 / 3012 / 3519 / 3609 / 3699; 201 / 1607 / 3013 / 3519 / 3609 / 3699; 202 / 1608 / 3014 / 3519 / 3609 / 3699; 203 / 1609 / 3015 / 3519 / 3609 / 3699; 204 / 1610 / 3016 / 3519 / 3609 / 3699; 205 / 1611 / 3017 / 3519 / 3609 / 3699; 332 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 206 / 1612 / 3018 / 3519 / 3609 / 3699; 207 / 1613 / 3019 / 3519 / 3609 / 3699; 208 / 1614 / 3020 / 3519 / 3609 / 3699; 209 / 1615 / 3021 / 3519 / 3609 / 3699; 210 / 1616 / 3022 / 3519 / 3609 / 3699; 211 / 1617 / 3023 / 3519 / 3609 / 3699; 212 / 1618 / 3024 / 3519 / 3609 / 3699; 213 / 1619 / 3025 / 3519 / 3609 / 3699; 214 / 1620 / 3026 / 3519 / 3609 / 3699; 215 / 1621 / 3027 / 3519 / 3609 / 3699; 216 / 1622 / 3028 / 3519 / 3609 / 3699; 217 / 1623 / 3029 / 3519 / 3609 / 3699; 218 / 1624 / 3030 / 3519 / 3609 / 3699; 219 / 1625 / 3031 / 3519 / 3609 / 3699; 220 / 1626 / 3032 / 3519 / 3609 / 3699; 221 / 1627 / 3033 / 3519 / 3609 / 3699; 222 / 1628 / 3034 / 3519 / 3609 / 3699; 223 / 1629 / 3035 / 3519 / 3609 / 3699; 224 / 1630 / 3036 / 3519 / 3609 / 3699; 225 / 1631 / 3037 / 3519 / 3609 / 3699; 226 / 1632 / 3038 / 3519 / 3609 / 3699; 227 / 1633 / 3039 / 3519 / 3609 / 3699; 228 / 1634 / 3040 / 3519 / 3609 / 3699; 229 / 1635 / 3041 / 3519 / 3609 / 3699; 230 / 1636 / 3042 / 3519 / 3609 / 3699; 231 / 1637 / 3043 / 3519 / 3609 / 3699; 232 / 1638 / 3044 / 3519 / 3609 / 3699; 233 / 1639 / 3045 / 3519 / 3609 / 3699; 234 / 1640 / 3046 / 3519 / 3609 / 3699; 235 / 1641 / 3047 / 3519 / 3609 / 3699; 236 / 1642 / 3048 / 3519 / 3609 / 3699; 237 / 1643 / 3049 / 3519 / 3609 / 3699; 238 / 1644 / 3050 / 3519 / 3609 / 3699; 239 / 1645 / 3051 / 3519 / 3609 / 3699; 240 / 1646 / 3052 / 3519 / 3609 / 3699; 241 / 1647 / 3053 / 3519 / 3609 / 3699; 242 / 1648 / 3054 / 3519 / 3609 / 3699; 243 / 1649 / 3055 / 3519 / 3609 / 3699; 244 / 1650 / 3056 / 3519 / 3609 / 3699; 245 / 1651 / 3057 / 3519 / 3609 / 3699; 246 / 1652 / 3058 / 3519 / 3609 / 3699; 247 / 1653 / 3059 / 3519 / 3609 / 3699; 248 / 1654 / 3060 / 3519 / 3609 / 3699; 249 / 1655 / 3061 / 3519 / 3609 / 3699; 250 / 1656 / 3062 / 3519 / 3609 / 3699; 251 / 1657 / 3063 / 3519 / 3609 / 3699; 252 / 1658 / 3064 / 3519 / 3609 / 3699; 253 / 1659 / 3065 / 3519 / 3609 / 3699; 254 / 1660 / 3066 / 3519 / 3609 / 3699; 255 / 1661 / 3067 / 3519 / 3609 / 3699; 256 / 1662 / 3068 / 3519 / 3609 / 3699; 257 / 1663 / 3069 / 3519 / 3609 / 3699; 258 / 1664 / 3070 / 3519 / 3609 / 3699; 259 / 1665 / 3071 / 3519 / 3609 / 3699; 260 / 1666 / 3072 / 3519 / 3609 / 3699; 261 / 1667 / 3073 / 3519 / 3609 / 3699; 597 / 2003 / 3409 / 3519 / 3609 / 3699; 598 / 2004 / 3410 / 3519 / 3609 / 3699; 599 / 2005 / 3411 / 3519 / 3609 / 3699; 600 / 2006 / 3412 / 3519 / 3609 / 3699; 601 / 2007 / 3413 / 3519 / 3609 / 3699; 602 / 2008 / 3414 / 3519 / 3609 / 3699; 603 / 2009 / 3415 / 3519 / 3609 / 3699; 604 / 2010 / 3416 / 3519 / 3609 / 3699; 605 / 2011 / 3417 / 3519 / 3609 / 3699; 606 / 2012 / 3418 / 3519 / 3609 / 3699; 607 / 2013 / 3419 / 3519 / 3609 / 3699; 608 / 2014 / 3420 / 3519 / 3609 / 3699; 333 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 609 / 2015 / 3421 / 3519 / 3609 / 3699; 610 / 2016 / 3422 / 3519 / 3609 / 3699; 612 / 2018 / 3424 / 3519 / 3609 / 3699; 613 / 2019 / 3425 / 3519 / 3609 / 3699; 614 / 2020 / 3426 / 3519 / 3609 / 3699; 615 / 2021 / 3427 / 3519 / 3609 / 3699; 616 / 2022 / 3428 / 3519 / 3609 / 3699; 617 / 2023 / 3429 / 3519 / 3609 / 3699; 618 / 2024 / 3430 / 3520 / 3610 / 3700; 619 / 2025 / 3431 / 3521 / 3611 / 3701; 620 / 2026 / 3432 / 3522 / 3612 / 3702; 621 / 2027 / 3433 / 3523 / 3613 / 3703; 622 / 2028 / 3434 / 3524 / 3614 / 3704; 623 / 2029 / 3435 / 3525 / 3615 / 3705; 624 / 2030 / 3436 / 3526 / 3616 / 3706; 625 / 2031 / 3437 / 3527 / 3617 / 3707; 626 / 2032 / 3438 / 3528 / 3618 / 3708; 627 / 2033 / 3439 / 3529 / 3619 / 3709; 628 / 2034 / 3440 / 3530 / 3620 / 3710; 629 / 2035 / 3441 / 3531 / 3621 / 3711; 630 / 2036 / 3442 / 3532 / 3622 / 3712; 631 / 2037 / 3443 / 3533 / 3623 / 3713; 632 / 2038 / 3444 / 3534 / 3624 / 3714; 633 / 2039 / 3445 / 3535 / 3625 / 3715; 634 / 2040 / 3446 / 3536 / 3626 / 3716; 635 / 2041 / 3447 / 3537 / 3627 / 3717; 636 / 2042 / 3448 / 3538 / 3628 / 3718; 637 / 2043 / 3449 / 3539 / 3629 / 3719; 638 / 2044 / 3450 / 3540 / 3630 / 3720; 639 / 2045 / 3451 / 3541 / 3631 / 3721; 640 / 2046 / 3452 / 3542 / 3632 / 3722; 641 / 2047 / 3453 / 3543 / 3633 / 3723; 642 / 2048 / 3454 / 3544 / 3634 / 3724; 643 / 2049 / 3455 / 3545 / 3635 / 3725; 644 / 2050 / 3456 / 3546 / 3636 / 3726; 645 / 2051 / 3457 / 3547 / 3637 / 3727; 646 / 2052 / 3458 / 3548 / 3638 / 3728; 647 / 2053 / 3459 / 3549 / 3639 / 3729; 648 / 2054 / 3460 / 3550 / 3640 / 3730; 649 / 2055 / 3461 / 3551 / 3641 / 3731; 650 / 2056 / 3462 / 3552 / 3642 / 3732; 651 / 2057 / 3463 / 3553 / 3643 / 3733; 652 / 2058 / 3464 / 3554 / 3644 / 3734; 653 / 2059 / 3465 / 3555 / 3645 / 3735; 654 / 2060 / 3466 / 3556 / 3646 / 3736; 655 / 2061 / 3467 / 3557 / 3647 / 3737; 656 / 2062 / 3468 / 3558 / 3648 / 3738; 657 / 2063 / 3469 / 3559 / 3649 / 3739; 658 / 2064 / 3470 / 3560 / 3650 / 3740; 659 / 2065 / 3471 / 3561 / 3651 / 3741; 660 / 2066 / 3472 / 3562 / 3652 / 3742; 661 / 2067 / 3473 / 3563 / 3653 / 3743; 662 / 2068 / 3474 / 3564 / 3654 / 3744; 663 / 2069 / 3475 / 3565 / 3655 / 3745; 664 / 2070 / 3476 / 3566 / 3656 / 3746; 665 / 2071 / 3477 / 3567 / 3657 / 3747; 666 / 2072 / 3478 / 3568 / 3658 / 3748; 667 / 2073 / 3479 / 3569 / 3659 / 3749; 668 / 2074 / 3480 / 3570 / 3660 / 3750; 669 / 2075 / 3481 / 3571 / 3661 / 3751; 670 / 2076 / 3482 / 3572 / 3662 / 3752; 671 / 2077 / 3483 / 3573 / 3663 / 3753; 672 / 2078 / 3484 / 3574 / 3664 / 3754; 673 / 2079 / 3485 / 3575 / 3665 / 3755; 675 / 2081 / 3487 / 3577 / 3667 / 3757; 676 / 2082 / 3488 / 3578 / 3668 / 3758; 677 / 2083 / 3489 / 3579 / 3669 / 3759; 678 / 2084 / 3490 / 3580 / 3670 / 3760; 334 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 679 / 2085 / 3491 / 3581 / 3671 / 3761; 680 / 2086 / 3492 / 3582 / 3672 / 3762; 681 / 2087 / 3493 / 3583 / 3673 / 3763; 682 / 2088 / 3494 / 3584 / 3674 / 3764; 683 / 2089 / 3495 / 3585 / 3675 / 3765; 684 / 2090 / 3496 / 3586 / 3676 / 3766; 685 / 2091 / 3497 / 3587 / 3677 / 3767; 686 / 2092 / 3498 / 3588 / 3678 / 3768; 687 / 2093 / 3499 / 3589 / 3679 / 3769; 688 / 2094 / 3500 / 3590 / 3680 / 3770; 689 / 2095 / 3501 / 3591 / 3681 / 3771; 690 / 2096 / 3502 / 3592 / 3682 / 3772; 691 / 2097 / 3503 / 3593 / 3683 / 3773; 692 / 2098 / 3504 / 3594 / 3684 / 3774; 693 / 2099 / 3505 / 3595 / 3685 / 3775; 694 / 2100 / 3506 / 3596 / 3686 / 3776; 695 / 2101 / 3507 / 3597 / 3687 / 3777; 696 / 2102 / 3508 / 3598 / 3688 / 3778; 697 / 2103 / 3509 / 3599 / 3689 / 3779; 698 / 2104 / 3510 / 3600 / 3690 / 3780; 699 / 2105 / 3511 / 3601 / 3691 / 3781; 700 / 2106 / 3512 / 3602 / 3692 / 3782; 701 / 2107 / 3513 / 3603 / 3693 / 3783; 702 / 2108 / 3514 / 3604 / 3694 / 3784; 703 / 2109 / 3515 / 3605 / 3695 / 3785; 704 / 2110 / 3516 / 3606 / 3696 / 3786; 705 / 2111 / 3517 / 3607 / 3697 / 3787; and 706 / 2112 / 3518 / 3608 / 3698 / 3788.

44. The isolated antibody of any one of claims 38-43, wherein the antibody comprises six CDRs according to one of the following groups of CDR SEQ ID NOs: 707 / 2113 / 2816 / 3519 / 3609 / 3699; 708 / 2114 / 2817 / 3519 / 3609 / 3699; 709 / 2115 / 2818 / 3519 / 3609 / 3699; 710 / 2116 / 2819 / 3519 / 3609 / 3699; 711 / 2117 / 2820 / 3519 / 3609 / 3699; 712 / 2118 / 2821 / 3519 / 3609 / 3699; 713 / 2119 / 2822 / 3519 / 3609 / 3699; 714 / 2120 / 2823 / 3519 / 3609 / 3699; 715 / 2121 / 2824 / 3519 / 3609 / 3699; 716 / 2122 / 2825 / 3519 / 3609 / 3699; 717 / 2123 / 2826 / 3519 / 3609 / 3699; 718 / 2124 / 2827 / 3519 / 3609 / 3699; 719 / 2125 / 2828 / 3519 / 3609 / 3699; 721 / 2127 / 2830 / 3519 / 3609 / 3699; 722 / 2128 / 2831 / 3519 / 3609 / 3699; 723 / 2129 / 2832 / 3519 / 3609 / 3699; 724 / 2130 / 2833 / 3519 / 3609 / 3699; 725 / 2131 / 2834 / 3519 / 3609 / 3699; 726 / 2132 / 2835 / 3519 / 3609 / 3699; 727 / 2133 / 2836 / 3519 / 3609 / 3699; 728 / 2134 / 2837 / 3519 / 3609 / 3699; 729 / 2135 / 2838 / 3519 / 3609 / 3699; 730 / 2136 / 2839 / 3519 / 3609 / 3699; 731 / 2137 / 2840 / 3519 / 3609 / 3699; 732 / 2138 / 2841 / 3519 / 3609 / 3699; 733 / 2139 / 2842 / 3519 / 3609 / 3699; 734 / 2140 / 2843 / 3519 / 3609 / 3699; 735 / 2141 / 2844 / 3519 / 3609 / 3699; 736 / 2142 / 2845 / 3519 / 3609 / 3699; 737 / 2143 / 2846 / 3519 / 3609 / 3699; 738 / 2144 / 2847 / 3519 / 3609 / 3699; 739 / 2145 / 2848 / 3519 / 3609 / 3699; 740 / 2146 / 2849 / 3519 / 3609 / 3699; 741 / 2147 / 2850 / 3519 / 3609 / 3699; 335 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 742 / 2148 / 2851 / 3519 / 3609 / 3699; 743 / 2149 / 2852 / 3519 / 3609 / 3699; 744 / 2150 / 2853 / 3519 / 3609 / 3699; 745 / 2151 / 2854 / 3519 / 3609 / 3699; 746 / 2152 / 2855 / 3519 / 3609 / 3699; 747 / 2153 / 2856 / 3519 / 3609 / 3699; 748 / 2154 / 2857 / 3519 / 3609 / 3699; 749 / 2155 / 2858 / 3519 / 3609 / 3699; 750 / 2156 / 2859 / 3519 / 3609 / 3699; 751 / 2157 / 2860 / 3519 / 3609 / 3699; 752 / 2158 / 2861 / 3519 / 3609 / 3699; 753 / 2159 / 2862 / 3519 / 3609 / 3699; 754 / 2160 / 2863 / 3519 / 3609 / 3699; 755 / 2161 / 2864 / 3519 / 3609 / 3699; 756 / 2162 / 2865 / 3519 / 3609 / 3699; 757 / 2163 / 2866 / 3519 / 3609 / 3699; 758 / 2164 / 2867 / 3519 / 3609 / 3699; 759 / 2165 / 2868 / 3519 / 3609 / 3699; 760 / 2166 / 2869 / 3519 / 3609 / 3699; 761 / 2167 / 2870 / 3519 / 3609 / 3699; 762 / 2168 / 2871 / 3519 / 3609 / 3699; 763 / 2169 / 2872 / 3519 / 3609 / 3699; 764 / 2170 / 2873 / 3519 / 3609 / 3699; 765 / 2171 / 2874 / 3519 / 3609 / 3699; 766 / 2172 / 2875 / 3519 / 3609 / 3699; 767 / 2173 / 2876 / 3519 / 3609 / 3699; 768 / 2174 / 2877 / 3519 / 3609 / 3699; 769 / 2175 / 2878 / 3519 / 3609 / 3699; 770 / 2176 / 2879 / 3519 / 3609 / 3699; 771 / 2177 / 2880 / 3519 / 3609 / 3699; 772 / 2178 / 2881 / 3519 / 3609 / 3699; 773 / 2179 / 2882 / 3519 / 3609 / 3699; 774 / 2180 / 2883 / 3519 / 3609 / 3699; 775 / 2181 / 2884 / 3519 / 3609 / 3699; 776 / 2182 / 2885 / 3519 / 3609 / 3699; 777 / 2183 / 2886 / 3519 / 3609 / 3699; 778 / 2184 / 2887 / 3519 / 3609 / 3699; 779 / 2185 / 2888 / 3519 / 3609 / 3699; 780 / 2186 / 2889 / 3519 / 3609 / 3699; 781 / 2187 / 2890 / 3519 / 3609 / 3699; 782 / 2188 / 2891 / 3519 / 3609 / 3699; 783 / 2189 / 2892 / 3519 / 3609 / 3699; 784 / 2190 / 2893 / 3519 / 3609 / 3699; 785 / 2191 / 2894 / 3519 / 3609 / 3699; 786 / 2192 / 2895 / 3519 / 3609 / 3699; 787 / 2193 / 2896 / 3519 / 3609 / 3699; 788 / 2194 / 2897 / 3519 / 3609 / 3699; 789 / 2195 / 2898 / 3519 / 3609 / 3699; 790 / 2196 / 2899 / 3519 / 3609 / 3699; 791 / 2197 / 2900 / 3519 / 3609 / 3699; 792 / 2198 / 2901 / 3519 / 3609 / 3699; 793 / 2199 / 2902 / 3519 / 3609 / 3699; 794 / 2200 / 2903 / 3519 / 3609 / 3699; 795 / 2201 / 2904 / 3519 / 3609 / 3699; 796 / 2202 / 2905 / 3519 / 3609 / 3699; 797 / 2203 / 2906 / 3519 / 3609 / 3699; 798 / 2204 / 2907 / 3519 / 3609 / 3699; 799 / 2205 / 2908 / 3519 / 3609 / 3699; 800 / 2206 / 2909 / 3519 / 3609 / 3699; 801 / 2207 / 2910 / 3519 / 3609 / 3699; 802 / 2208 / 2911 / 3519 / 3609 / 3699; 803 / 2209 / 2912 / 3519 / 3609 / 3699; 804 / 2210 / 2913 / 3519 / 3609 / 3699; 805 / 2211 / 2914 / 3519 / 3609 / 3699; 806 / 2212 / 2915 / 3519 / 3609 / 3699; 807 / 2213 / 2916 / 3519 / 3609 / 3699; 808 / 2214 / 2917 / 3519 / 3609 / 3699; 809 / 2215 / 2918 / 3519 / 3609 / 3699; 336 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 810 / 2216 / 2919 / 3519 / 3609 / 3699; 811 / 2217 / 2920 / 3519 / 3609 / 3699; 812 / 2218 / 2921 / 3519 / 3609 / 3699; 813 / 2219 / 2922 / 3519 / 3609 / 3699; 814 / 2220 / 2923 / 3519 / 3609 / 3699; 815 / 2221 / 2924 / 3519 / 3609 / 3699; 816 / 2222 / 2925 / 3519 / 3609 / 3699; 817 / 2223 / 2926 / 3519 / 3609 / 3699; 818 / 2224 / 2927 / 3519 / 3609 / 3699; 819 / 2225 / 2928 / 3519 / 3609 / 3699; 820 / 2226 / 2929 / 3519 / 3609 / 3699; 821 / 2227 / 2930 / 3519 / 3609 / 3699; 822 / 2228 / 2931 / 3519 / 3609 / 3699; 823 / 2229 / 2932 / 3519 / 3609 / 3699; 824 / 2230 / 2933 / 3519 / 3609 / 3699; 825 / 2231 / 2934 / 3519 / 3609 / 3699; 826 / 2232 / 2935 / 3519 / 3609 / 3699; 827 / 2233 / 2936 / 3519 / 3609 / 3699; 828 / 2234 / 2937 / 3519 / 3609 / 3699; 829 / 2235 / 2938 / 3519 / 3609 / 3699; 830 / 2236 / 2939 / 3519 / 3609 / 3699; 831 / 2237 / 2940 / 3519 / 3609 / 3699; 832 / 2238 / 2941 / 3519 / 3609 / 3699; 833 / 2239 / 2942 / 3519 / 3609 / 3699; 834 / 2240 / 2943 / 3519 / 3609 / 3699; 835 / 2241 / 2944 / 3519 / 3609 / 3699; 836 / 2242 / 2945 / 3519 / 3609 / 3699; 837 / 2243 / 2946 / 3519 / 3609 / 3699; 838 / 2244 / 2947 / 3519 / 3609 / 3699; 839 / 2245 / 2948 / 3519 / 3609 / 3699; 840 / 2246 / 2949 / 3519 / 3609 / 3699; 841 / 2247 / 2950 / 3519 / 3609 / 3699; 842 / 2248 / 2951 / 3519 / 3609 / 3699; 843 / 2249 / 2952 / 3519 / 3609 / 3699; 844 / 2250 / 2953 / 3519 / 3609 / 3699; 845 / 2251 / 2954 / 3519 / 3609 / 3699; 846 / 2252 / 2955 / 3519 / 3609 / 3699; 847 / 2253 / 2956 / 3519 / 3609 / 3699; 848 / 2254 / 2957 / 3519 / 3609 / 3699; 849 / 2255 / 2958 / 3519 / 3609 / 3699; 850 / 2256 / 2959 / 3519 / 3609 / 3699; 851 / 2257 / 2960 / 3519 / 3609 / 3699; 852 / 2258 / 2961 / 3519 / 3609 / 3699; 853 / 2259 / 2962 / 3519 / 3609 / 3699; 854 / 2260 / 2963 / 3519 / 3609 / 3699; 855 / 2261 / 2964 / 3519 / 3609 / 3699; 856 / 2262 / 2965 / 3519 / 3609 / 3699; 857 / 2263 / 2966 / 3519 / 3609 / 3699; 858 / 2264 / 2967 / 3519 / 3609 / 3699; 859 / 2265 / 2968 / 3519 / 3609 / 3699; 860 / 2266 / 2969 / 3519 / 3609 / 3699; 861 / 2267 / 2970 / 3519 / 3609 / 3699; 862 / 2268 / 2971 / 3519 / 3609 / 3699; 863 / 2269 / 2972 / 3519 / 3609 / 3699; 864 / 2270 / 2973 / 3519 / 3609 / 3699; 865 / 2271 / 2974 / 3519 / 3609 / 3699; 866 / 2272 / 2975 / 3519 / 3609 / 3699; 867 / 2273 / 2976 / 3519 / 3609 / 3699; 868 / 2274 / 2977 / 3519 / 3609 / 3699; 869 / 2275 / 2978 / 3519 / 3609 / 3699; 870 / 2276 / 2979 / 3519 / 3609 / 3699; 871 / 2277 / 2980 / 3519 / 3609 / 3699; 872 / 2278 / 2981 / 3519 / 3609 / 3699; 873 / 2279 / 2982 / 3519 / 3609 / 3699; 874 / 2280 / 2983 / 3519 / 3609 / 3699; 875 / 2281 / 2984 / 3519 / 3609 / 3699; 876 / 2282 / 2985 / 3519 / 3609 / 3699; 877 / 2283 / 2986 / 3519 / 3609 / 3699; 337 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 878 / 2284 / 2987 / 3519 / 3609 / 3699; 879 / 2285 / 2988 / 3519 / 3609 / 3699; 880 / 2286 / 2989 / 3519 / 3609 / 3699; 881 / 2287 / 2990 / 3519 / 3609 / 3699; 882 / 2288 / 2991 / 3519 / 3609 / 3699; 883 / 2289 / 2992 / 3519 / 3609 / 3699; 884 / 2290 / 2993 / 3519 / 3609 / 3699; 885 / 2291 / 2994 / 3519 / 3609 / 3699; 886 / 2292 / 2995 / 3519 / 3609 / 3699; 887 / 2293 / 2996 / 3519 / 3609 / 3699; 888 / 2294 / 2997 / 3519 / 3609 / 3699; 889 / 2295 / 2998 / 3519 / 3609 / 3699; 890 / 2296 / 2999 / 3519 / 3609 / 3699; 891 / 2297 / 3000 / 3519 / 3609 / 3699; 892 / 2298 / 3001 / 3519 / 3609 / 3699; 893 / 2299 / 3002 / 3519 / 3609 / 3699; 894 / 2300 / 3003 / 3519 / 3609 / 3699; 895 / 2301 / 3004 / 3519 / 3609 / 3699; 896 / 2302 / 3005 / 3519 / 3609 / 3699; 897 / 2303 / 3006 / 3519 / 3609 / 3699; 898 / 2304 / 3007 / 3519 / 3609 / 3699; 899 / 2305 / 3008 / 3519 / 3609 / 3699; 900 / 2306 / 3009 / 3519 / 3609 / 3699; 901 / 2307 / 3010 / 3519 / 3609 / 3699; 903 / 2309 / 3012 / 3519 / 3609 / 3699; 904 / 2310 / 3013 / 3519 / 3609 / 3699; 905 / 2311 / 3014 / 3519 / 3609 / 3699; 906 / 2312 / 3015 / 3519 / 3609 / 3699; 907 / 2313 / 3016 / 3519 / 3609 / 3699; 908 / 2314 / 3017 / 3519 / 3609 / 3699; 909 / 2315 / 3018 / 3519 / 3609 / 3699; 910 / 2316 / 3019 / 3519 / 3609 / 3699; 911 / 2317 / 3020 / 3519 / 3609 / 3699; 912 / 2318 / 3021 / 3519 / 3609 / 3699; 913 / 2319 / 3022 / 3519 / 3609 / 3699; 914 / 2320 / 3023 / 3519 / 3609 / 3699; 915 / 2321 / 3024 / 3519 / 3609 / 3699; 916 / 2322 / 3025 / 3519 / 3609 / 3699; 917 / 2323 / 3026 / 3519 / 3609 / 3699; 918 / 2324 / 3027 / 3519 / 3609 / 3699; 919 / 2325 / 3028 / 3519 / 3609 / 3699; 920 / 2326 / 3029 / 3519 / 3609 / 3699; 921 / 2327 / 3030 / 3519 / 3609 / 3699; 922 / 2328 / 3031 / 3519 / 3609 / 3699; 923 / 2329 / 3032 / 3519 / 3609 / 3699; 924 / 2330 / 3033 / 3519 / 3609 / 3699; 925 / 2331 / 3034 / 3519 / 3609 / 3699; 926 / 2332 / 3035 / 3519 / 3609 / 3699; 927 / 2333 / 3036 / 3519 / 3609 / 3699; 928 / 2334 / 3037 / 3519 / 3609 / 3699; 929 / 2335 / 3038 / 3519 / 3609 / 3699; 930 / 2336 / 3039 / 3519 / 3609 / 3699; 931 / 2337 / 3040 / 3519 / 3609 / 3699; 932 / 2338 / 3041 / 3519 / 3609 / 3699; 933 / 2339 / 3042 / 3519 / 3609 / 3699; 934 / 2340 / 3043 / 3519 / 3609 / 3699; 935 / 2341 / 3044 / 3519 / 3609 / 3699; 936 / 2342 / 3045 / 3519 / 3609 / 3699; 937 / 2343 / 3046 / 3519 / 3609 / 3699; 938 / 2344 / 3047 / 3519 / 3609 / 3699; 939 / 2345 / 3048 / 3519 / 3609 / 3699; 940 / 2346 / 3049 / 3519 / 3609 / 3699; 941 / 2347 / 3050 / 3519 / 3609 / 3699; 942 / 2348 / 3051 / 3519 / 3609 / 3699; 943 / 2349 / 3052 / 3519 / 3609 / 3699; 944 / 2350 / 3053 / 3519 / 3609 / 3699; 945 / 2351 / 3054 / 3519 / 3609 / 3699; 946 / 2352 / 3055 / 3519 / 3609 / 3699; 338 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 947 / 2353 / 3056 / 3519 / 3609 / 3699; 948 / 2354 / 3057 / 3519 / 3609 / 3699; 949 / 2355 / 3058 / 3519 / 3609 / 3699; 950 / 2356 / 3059 / 3519 / 3609 / 3699; 951 / 2357 / 3060 / 3519 / 3609 / 3699; 952 / 2358 / 3061 / 3519 / 3609 / 3699; 953 / 2359 / 3062 / 3519 / 3609 / 3699; 954 / 2360 / 3063 / 3519 / 3609 / 3699; 955 / 2361 / 3064 / 3519 / 3609 / 3699; 956 / 2362 / 3065 / 3519 / 3609 / 3699; 957 / 2363 / 3066 / 3519 / 3609 / 3699; 958 / 2364 / 3067 / 3519 / 3609 / 3699; 959 / 2365 / 3068 / 3519 / 3609 / 3699; 960 / 2366 / 3069 / 3519 / 3609 / 3699; 961 / 2367 / 3070 / 3519 / 3609 / 3699; 962 / 2368 / 3071 / 3519 / 3609 / 3699; 963 / 2369 / 3072 / 3519 / 3609 / 3699; 964 / 2370 / 3073 / 3519 / 3609 / 3699; 1300 / 2706 / 3409 / 3519 / 3609 / 3699; 1301 / 2707 / 3410 / 3519 / 3609 / 3699; 1302 / 2708 / 3411 / 3519 / 3609 / 3699; 1303 / 2709 / 3412 / 3519 / 3609 / 3699; 1304 / 2710 / 3413 / 3519 / 3609 / 3699; 1305 / 2711 / 3414 / 3519 / 3609 / 3699; 1306 / 2712 / 3415 / 3519 / 3609 / 3699; 1307 / 2713 / 3416 / 3519 / 3609 / 3699; 1308 / 2714 / 3417 / 3519 / 3609 / 3699; 1309 / 2715 / 3418 / 3519 / 3609 / 3699; 1310 / 2716 / 3419 / 3519 / 3609 / 3699; 1311 / 2717 / 3420 / 3519 / 3609 / 3699; 1312 / 2718 / 3421 / 3519 / 3609 / 3699; 1313 / 2719 / 3422 / 3519 / 3609 / 3699; 1315 / 2721 / 3424 / 3519 / 3609 / 3699; 1316 / 2722 / 3425 / 3519 / 3609 / 3699; 1317 / 2723 / 3426 / 3519 / 3609 / 3699; 1318 / 2724 / 3427 / 3519 / 3609 / 3699; 1319 / 2725 / 3428 / 3519 / 3609 / 3699; 1320 / 2726 / 3429 / 3519 / 3609 / 3699; 1321 / 2727 / 3430 / 3520 / 3610 / 3700; 1322 / 2728 / 3431 / 3521 / 3611 / 3701; 1323 / 2729 / 3432 / 3522 / 3612 / 3702; 1324 / 2730 / 3433 / 3523 / 3613 / 3703; 1325 / 2731 / 3434 / 3524 / 3614 / 3704; 1326 / 2732 / 3435 / 3525 / 3615 / 3705; 1327 / 2733 / 3436 / 3526 / 3616 / 3706; 1328 / 2734 / 3437 / 3527 / 3617 / 3707; 1329 / 2735 / 3438 / 3528 / 3618 / 3708; 1330 / 2736 / 3439 / 3529 / 3619 / 3709; 1331 / 2737 / 3440 / 3530 / 3620 / 3710; 1332 / 2738 / 3441 / 3531 / 3621 / 3711; 1333 / 2739 / 3442 / 3532 / 3622 / 3712; 1334 / 2740 / 3443 / 3533 / 3623 / 3713; 1335 / 2741 / 3444 / 3534 / 3624 / 3714; 1336 / 2742 / 3445 / 3535 / 3625 / 3715; 1337 / 2743 / 3446 / 3536 / 3626 / 3716; 1338 / 2744 / 3447 / 3537 / 3627 / 3717; 1339 / 2745 / 3448 / 3538 / 3628 / 3718; 1340 / 2746 / 3449 / 3539 / 3629 / 3719; 1341 / 2747 / 3450 / 3540 / 3630 / 3720; 1342 / 2748 / 3451 / 3541 / 3631 / 3721; 1343 / 2749 / 3452 / 3542 / 3632 / 3722; 1344 / 2750 / 3453 / 3543 / 3633 / 3723; 1345 / 2751 / 3454 / 3544 / 3634 / 3724; 1346 / 2752 / 3455 / 3545 / 3635 / 3725; 1347 / 2753 / 3456 / 3546 / 3636 / 3726; 1348 / 2754 / 3457 / 3547 / 3637 / 3727; 1349 / 2755 / 3458 / 3548 / 3638 / 3728; 1350 / 2756 / 3459 / 3549 / 3639 / 3729; 339 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 1351 / 2757 / 3460 / 3550 / 3640 / 3730; 1352 / 2758 / 3461 / 3551 / 3641 / 3731; 1353 / 2759 / 3462 / 3552 / 3642 / 3732; 1354 / 2760 / 3463 / 3553 / 3643 / 3733; 1355 / 2761 / 3464 / 3554 / 3644 / 3734; 1356 / 2762 / 3465 / 3555 / 3645 / 3735; 1357 / 2763 / 3466 / 3556 / 3646 / 3736; 1358 / 2764 / 3467 / 3557 / 3647 / 3737; 1359 / 2765 / 3468 / 3558 / 3648 / 3738; 1360 / 2766 / 3469 / 3559 / 3649 / 3739; 1361 / 2767 / 3470 / 3560 / 3650 / 3740; 1362 / 2768 / 3471 / 3561 / 3651 / 3741; 1363 / 2769 / 3472 / 3562 / 3652 / 3742; 1364 / 2770 / 3473 / 3563 / 3653 / 3743; 1365 / 2771 / 3474 / 3564 / 3654 / 3744; 1366 / 2772 / 3475 / 3565 / 3655 / 3745; 1367 / 2773 / 3476 / 3566 / 3656 / 3746; 1368 / 2774 / 3477 / 3567 / 3657 / 3747; 1369 / 2775 / 3478 / 3568 / 3658 / 3748; 1370 / 2776 / 3479 / 3569 / 3659 / 3749; 1371 / 2777 / 3480 / 3570 / 3660 / 3750; 1372 / 2778 / 3481 / 3571 / 3661 / 3751; 1373 / 2779 / 3482 / 3572 / 3662 / 3752; 1374 / 2780 / 3483 / 3573 / 3663 / 3753; 1375 / 2781 / 3484 / 3574 / 3664 / 3754; 1376 / 2782 / 3485 / 3575 / 3665 / 3755; 1378 / 2784 / 3487 / 3577 / 3667 / 3757; 1379 / 2785 / 3488 / 3578 / 3668 / 3758; 1380 / 2786 / 3489 / 3579 / 3669 / 3759; 1381 / 2787 / 3490 / 3580 / 3670 / 3760; 1382 / 2788 / 3491 / 3581 / 3671 / 3761; 1383 / 2789 / 3492 / 3582 / 3672 / 3762; 1384 / 2790 / 3493 / 3583 / 3673 / 3763; 1385 / 2791 / 3494 / 3584 / 3674 / 3764; 1386 / 2792 / 3495 / 3585 / 3675 / 3765; 1387 / 2793 / 3496 / 3586 / 3676 / 3766; 1388 / 2794 / 3497 / 3587 / 3677 / 3767; 1389 / 2795 / 3498 / 3588 / 3678 / 3768; 1390 / 2796 / 3499 / 3589 / 3679 / 3769; 1391 / 2797 / 3500 / 3590 / 3680 / 3770; 1392 / 2798 / 3501 / 3591 / 3681 / 3771; 1393 / 2799 / 3502 / 3592 / 3682 / 3772; 1394 / 2800 / 3503 / 3593 / 3683 / 3773; 1395 / 2801 / 3504 / 3594 / 3684 / 3774; 1396 / 2802 / 3505 / 3595 / 3685 / 3775; 1397 / 2803 / 3506 / 3596 / 3686 / 3776; 1398 / 2804 / 3507 / 3597 / 3687 / 3777; 1399 / 2805 / 3508 / 3598 / 3688 / 3778; 1400 / 2806 / 3509 / 3599 / 3689 / 3779; 1401 / 2807 / 3510 / 3600 / 3690 / 3780; 1402 / 2808 / 3511 / 3601 / 3691 / 3781; 1403 / 2809 / 3512 / 3602 / 3692 / 3782; 1404 / 2810 / 3513 / 3603 / 3693 / 3783; 1405 / 2811 / 3514 / 3604 / 3694 / 3784; 1406 / 2812 / 3515 / 3605 / 3695 / 3785; 1407 / 2813 / 3516 / 3606 / 3696 / 3786; 1408 / 2814 / 3517 / 3607 / 3697 / 3787; and 1409 / 2815 / 3518 / 3608 / 3698 / 3788.

45. The isolated antibody of any one of claims 38-44, wherein the antibody comprises a VH / VLpair, or a variant thereof, selected from the group consisting of SEQ ID NOS: 3789 / 4634; 3790 / 4634; 3791 / 4634; 3792 / 4634; 3793 / 4634; 3794 / 4634; 3795 / 4634; 3796 / 4634; 3797 / 4634; 3798 / 4634; 3799 / 4634; 3800 / 4634; 3801 / 4634; 3803 / 4634; 340 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 3804 / 4634; 3805 / 4634; 3806 / 4634; 3807 / 4634; 3808 / 4634; 3809 / 4634; 3810 / 4634; 3811 / 4634; 3812 / 4634; 3813 / 4634; 3814 / 4634; 3815 / 4634; 3816 / 4634; 3817 / 4634; 3818 / 4634; 3819 / 4634; 3820 / 4634; 3821 / 4634; 3822 / 4634; 3823 / 4634; 3824 / 4634; 3825 / 4634; 3826 / 4634; 3827 / 4634; 3828 / 4634; 3829 / 4634; 3830 / 4634; 3831 / 4634; 3832 / 4634; 3833 / 4634; 3834 / 4634; 3835 / 4634; 3836 / 4634; 3837 / 4634; 3838 / 4634; 3839 / 4634; 3840 / 4634; 3841 / 4634; 3842 / 4634; 3843 / 4634; 3844 / 4634; 3845 / 4634; 3846 / 4634; 3847 / 4634; 3848 / 4634; 3849 / 4634; 3850 / 4634; 3851 / 4634; 3852 / 4634; 3853 / 4634; 3854 / 4634; 3855 / 4634; 3856 / 4634; 3857 / 4634; 3858 / 4634; 3859 / 4634; 3860 / 4634; 3861 / 4634; 3862 / 4634; 3863 / 4634; 3864 / 4634; 3865 / 4634; 3866 / 4634; 3867 / 4634; 3868 / 4634; 3869 / 4634; 3870 / 4634; 3871 / 4634; 3872 / 4634; 3873 / 4634; 3874 / 4634; 3875 / 4634; 3876 / 4634; 3877 / 4634; 3878 / 4634; 3879 / 4634; 3880 / 4634; 3881 / 4634; 3882 / 4634; 3883 / 4634; 3884 / 4634; 3885 / 4634; 3886 / 4634; 3887 / 4634; 3888 / 4634; 3889 / 4634; 3890 / 4634; 3891 / 4634; 3892 / 4634; 3893 / 4634; 3894 / 4634; 3895 / 4634; 3896 / 4634; 3897 / 4634; 3898 / 4634; 3899 / 4634; 3900 / 4634; 3901 / 4634; 3902 / 4634; 3903 / 4634; 3904 / 4634; 3905 / 4634; 3906 / 4634; 3907 / 4634; 3908 / 4634; 3909 / 4634; 3910 / 4634; 3911 / 4634; 3912 / 4634; 3913 / 4634; 3914 / 4634; 3915 / 4634; 3916 / 4634; 3917 / 4634; 3918 / 4634; 3919 / 4634; 3920 / 4634; 3921 / 4634; 3922 / 4634; 3923 / 4634; 3924 / 4634; 3925 / 4634; 3926 / 4634; 3927 / 4634; 3928 / 4634; 3929 / 4634; 3930 / 4634; 3931 / 4634; 3932 / 4634; 3933 / 4634; 3934 / 4634; 3935 / 4634; 3936 / 4634; 3937 / 4634; 3938 / 4634; 3939 / 4634; 3940 / 4634; 3941 / 4634; 3942 / 4634; 3943 / 4634; 3944 / 4634; 3945 / 4634; 3946 / 4634; 3947 / 4634; 3948 / 4634; 3949 / 4634; 3950 / 4634; 3951 / 4634; 3952 / 4634; 3953 / 4634; 3954 / 4634; 3955 / 4634; 3956 / 4634; 3957 / 4634; 3958 / 4634; 3959 / 4634; 3960 / 4634; 3961 / 4634; 3962 / 4634; 3963 / 4634; 3964 / 4634; 3965 / 4634; 3966 / 4634; 3967 / 4634; 3968 / 4634; 3969 / 4634; 3970 / 4634; 3971 / 4634; 3972 / 4634; 3973 / 4634; 3974 / 4634; 3975 / 4634; 3976 / 4634; 3977 / 4634; 3978 / 4634; 3979 / 4634; 3980 / 4634; 3981 / 4634; 3982 / 4634; 3983 / 4634; 3985 / 4634; 3986 / 4634; 3987 / 4634; 3988 / 4634; 3989 / 4634; 3990 / 4634; 3991 / 4634; 3992 / 4634; 3993 / 4634; 3994 / 4634; 3995 / 4634; 3996 / 4634; 3997 / 4634; 3998 / 4634; 3999 / 4634; 4000 / 4634; 4001 / 4634; 4002 / 4634; 4003 / 4634; 4004 / 4634; 4005 / 4634; 4006 / 4634; 4007 / 4634; 4008 / 4634; 4009 / 4634; 4010 / 4634; 4011 / 4634; 4012 / 4634; 4013 / 4634; 4014 / 4634; 4015 / 4634; 4016 / 4634; 4017 / 4634; 4018 / 4634; 4019 / 4634; 4020 / 4634; 4021 / 4634; 4022 / 4634; 4023 / 4634; 4024 / 4634; 4025 / 4634; 4026 / 4634; 4027 / 4634; 4028 / 4634; 4029 / 4634; 4030 / 4634; 4031 / 4634; 4032 / 4634; 4033 / 4634; 4034 / 4634; 4035 / 4634; 4036 / 4634; 4037 / 4634; 4038 / 4634; 4039 / 4634; 4040 / 4634; 4041 / 4634; 4042 / 4634; 341 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 4043 / 4634; 4044 / 4634; 4045 / 4634; 4046 / 4634; 4382 / 4634; 4383 / 4634; 4384 / 4634; 4385 / 4634; 4386 / 4634; 4387 / 4634; 4388 / 4634; 4389 / 4634; 4390 / 4634; 4391 / 4634; 4392 / 4634; 4393 / 4634; 4394 / 4634; 4395 / 4634; 4397 / 4634; 4398 / 4634; 4399 / 4634; 4400 / 4634; 4401 / 4634; 4402 / 4634; 4403 / 4635; 4404 / 4636; 4405 / 4637; 4406 / 4638; 4407 / 4639; 4408 / 4640; 4409 / 4641; 4410 / 4642; 4411 / 4643; 4412 / 4644; 4413 / 4645; 4414 / 4646; 4415 / 4647; 4416 / 4648; 4417 / 4649; 4418 / 4650; 4419 / 4651; 4420 / 4652; 4421 / 4653; 4422 / 4654; 4423 / 4655; 4424 / 4656; 4425 / 4657; 4426 / 4658; 4427 / 4659; 4428 / 4660; 4429 / 4661; 4430 / 4662; 4431 / 4663; 4432 / 4664; 4433 / 4665; 4434 / 4666; 4435 / 4667; 4436 / 4668; 4437 / 4669; 4438 / 4670; 4439 / 4671; 4440 / 4672; 4441 / 4673; 4442 / 4674; 4443 / 4675; 4444 / 4676; 4445 / 4677; 4446 / 4678; 4447 / 4679; 4448 / 4680; 4449 / 4681; 4450 / 4682; 4451 / 4683; 4452 / 4684; 4453 / 4685; 4454 / 4686; 4455 / 4687; 4456 / 4688; 4457 / 4689; 4458 / 4690; 4460 / 4692; 4461 / 4693; 4462 / 4694; 4463 / 4695; 4464 / 4696; 4465 / 4697; 4466 / 4698; 4467 / 4699; 4468 / 4700; 4469 / 4701; 4470 / 4702; 4471 / 4703; 4472 / 4704; 4473 / 4705; 4474 / 4706; 4475 / 4707; 4476 / 4708; 4477 / 4709; 4478 / 4710; 4479 / 4711; 4480 / 4712; 4481 / 4713; 4482 / 4714; 4483 / 4715; 4484 / 4716; 4485 / 4717; 4486 / 4718; 4487 / 4719; 4488 / 4720; 4489 / 4721; 4490 / 4722; and 4491 / 4723.

46. The isolated antibody of any one of claims 38-45, wherein the antibody comprises a VH / VLpair, or a variant thereof, selected from the group consisting of SEQ ID NOS: 4492 / 4724; 4493 / 4725; 4494 / 4726; 4495 / 4727; 4496 / 4728; 4497 / 4729; 4498 / 4730; 4499 / 4731; 4500 / 4732; 4502 / 4734; 4503 / 4735; 4504 / 4736; 4505 / 4737; 4506 / 4738; 4507 / 4739; 4508 / 4740; 4509 / 4741; 4510 / 4742; 4511 / 4743; 4512 / 4744; 4513 / 4745; 4514 / 4746; 4515 / 4747; 4516 / 4748; 4517 / 4749; 4518 / 4750; 4519 / 4751; 4520 / 4752; 4521 / 4753; 4522 / 4754; 4523 / 4755; 4524 / 4756; 4525 / 4757; 4526 / 4758; 4527 / 4759; 4528 / 4760; 4529 / 4761; 4530 / 4762; 4531 / 4763; 4532 / 4764; 4533 / 4765; 4534 / 4766; 4535 / 4767; 4536 / 4768; 4537 / 4769; 4538 / 4770; 4539 / 4771; 4540 / 4772; 4541 / 4773; 4542 / 4774; 4543 / 4775; 4544 / 4776; 4545 / 4777; 4546 / 4778; 4547 / 4779; 4548 / 4780; 4549 / 4781; 4550 / 4782; 4551 / 4783; 4552 / 4784; 4553 / 4785; 4554 / 4786; 4555 / 4787; 4556 / 4788; 4557 / 4789; 4558 / 4790; 4559 / 4791; 4560 / 4792; 4561 / 4793; 4562 / 4794; 4563 / 4795; 4564 / 4796; 4565 / 4797; 4566 / 4798; 4567 / 4799; 4568 / 4800; 4569 / 4801; 4570 / 4802; 4571 / 4803; 4572 / 4804; 4573 / 4805; 4574 / 4806; 4575 / 4807; 4576 / 4808; 4577 / 4809; 4578 / 4810; 4579 / 4811; 4580 / 4812; 4581 / 4813; 4582 / 4814; 4583 / 4815; 4584 / 4816; 4585 / 4817; 4586 / 4818; 4587 / 4819; 4588 / 4820; 4589 / 4821; 4590 / 4822; 4591 / 4823; 4592 / 4824; 4593 / 4825; 4594 / 4826; 4595 / 4827; 4596 / 4828; 4597 / 4829; 342 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 4598 / 4830; 4599 / 4831; 4600 / 4832; 4601 / 4833; 4602 / 4834; 4603 / 4835; 4604 / 4836; 4605 / 4837; 4606 / 4838; 4607 / 4839; 4608 / 4840; 4609 / 4841; 4610 / 4842; 4611 / 4843; 4612 / 4844; 4613 / 4845; 4614 / 4846; 4615 / 4847; 4616 / 4848; 4617 / 4849; 4618 / 4850; 4619 / 4851; 4620 / 4852; 4621 / 4853; 4622 / 4854; 4623 / 4855; 4624 / 4856; 4625 / 4857; 4626 / 4858; 4627 / 4859; 4628 / 4860; 4629 / 4861; 4630 / 4862; 4631 / 4863; 4632 / 4864; and 4633 / 4865.

47. The isolated antibody of any one of claims 38-46, wherein the antibody comprises a VHselected from SEQ ID NOs: 3789-3801, 3803-3983, 3985-4046, 4382-4395, 4397- 4458, and 4460-4491.

48. The isolated antibody of any one of claims 38-47, wherein the antibody comprises a VHregion selected from SEQ ID NOs: 3789-3801, 3803-3983, 3985-4046, 4382-4395, 4397-4458, and 4460-4491, or a variant thereof having 20 or fewer amino acid substitutions.

49. The isolated antibody of any one of claims 38-48, wherein the antibody comprises a VHselected from SEQ ID NOs: 4492-4633.

50. The isolated antibody of any one of claims 38-49, wherein the antibody comprises a VH region selected from SEQ ID NOs: 4492-4633, or a variant thereof having 20 or fewer amino acid substitutions.

51. The isolated antibody of any one of claims 38-50, wherein the antibody comprises a VL sequence selected from SEQ ID NOs: 4634-4723.

52. The isolated antibody of any one of claims 38-51, wherein the antibody comprises a VLregion selected from SEQ ID NOs: 4634-4723, or a variant thereof having 20 or fewer amino acid substitutions.

53. The isolated antibody of any one of claims 38-52, wherein the antibody comprises a VLsequence selected from SEQ ID NOs: 4724-4865. 343 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 54. The isolated antibody of any one of claims 38-53, wherein the antibody comprises a VLregion selected from SEQ ID NOs: 4724-4865, or a variant thereof having 20 or fewer amino acid substitutions.

55. The isolated antibody of any one of claims 38-54, wherein the antibody comprises a VHregion selected from SEQ ID NOs: 3789-3801, 3803-3983, 3985-4046, 4382-4395, 4397-4458, and 4460-4491, or a variant thereof having 20 or fewer amino acid substitutions, and a VLregion selected from SEQ ID NOs: 4634-4690, and 4692-4723, or a variant thereof having 20 or fewer amino acid substitutions.

56. The isolated antibody of any one of claims 38-55, wherein the antibody comprises a VH region selected from SEQ ID NOs: 4492-4633, or a variant thereof having 20 or fewer amino acid substitutions, and a VLregion selected from SEQ ID NOs: 4724-4865, or a variant thereof having 20 or fewer amino acid substitutions.

57. The isolated antibody of any one of claims 38-56, wherein the amino acid substitution is a conservative amino acid substitution.

58. The isolated antibody of any one of claims 38-57, wherein the antibody binds to the same epitope as a second antibody with a VH region selected from SEQ ID NOs: 3789- 3801, 3803-3983, 3985-4046, 4382-4395, 4397-4458, and 4460-4491, and a VLregion selected from SEQ ID NOs: 4634-4690, and 4692-4723.

59. The isolated antibody of any one of claims 38-58, wherein the antibody inhibits binding of a second antibody to Trop2 by at least 50%, or wherein the second antibody inhibits binding of the isolated antibody to Trop2 by at least 50%.

60. The isolated antibody of any one of claims 38-59, wherein the antibody comprises at least one constant region domain.

61. The isolated antibody of claim 60, wherein the constant region comprises a sequence selected from the group consisting of SEQ ID No: 4962, 4963, 5225, 5226, 5227, and 5228. 344 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 62. The isolated antibody of any one of claims 38-61, wherein the antibody is a monoclonal antibody.

63. The isolated antibody of any one of claims 38-62, wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM.

64. The isolated antibody of any one of claims 38-63, wherein the antibody is humanized or human.

65. The isolated antibody of any one of claims 38-64, wherein the antibody is aglycosylated.

66. The isolated antibody of any one of claims 38-65, wherein the antibody is an antibody fragment.

67. The isolated antibody of claim 66, wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab’)2 fragment, a Fab’ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment.

68. The isolated antibody of claim 67, wherein the antibody is an scFv fragment.

69. The isolated antibody of any one of claims 38-68, wherein the antibody has a ka of about 103M-1×sec-1to about 106M-1×sec-1when associating with human Trop2 at a temperature of 25°C.

70. The isolated antibody of any one of claims 38-69, wherein the antibody has a kdof about 10-4sec-1to about 10-8sec-1when dissociating from human Trop2 at a temperature of 25°C.

71. The isolated antibody of any one of claims 38-70, wherein the antibody has a KDof about 10-7M to about 10-12M when bound to human Trop2 at a temperature of 25°C.

72. The isolated antibody of any one of claims 38-71, further comprising human framework regions. 345 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 73. The isolated antibody of any one of claims 38-71, further comprising human kappa framework regions.

74. A kit comprising an isolated antibody of any one of the preceding claims, and instructions for use of the antibody.

75. The kit of claim 74, wherein the antibody is lyophilized.

76. The kit of claim 75, further comprising a fluid for reconstitution of the lyophilized antibody.

77. A polynucleotide encoding an antibody of any of claims 1 to 73.

78. A vector comprising the polynucleotide of claim 77.

79. A recombinant host cell comprising the vector of claim 78.

80. The recombinant host cell of claim 79, wherein the host cell is selected from a bacterial cell, a fungal cell, and a mammalian cell.

81. The recombinant host cell of claim 80, wherein the host cell is selected from an E. coli cell, a Saccharomyces cerevisiae cell, and a CHO cell.

82. A cell-free expression reaction comprising the vector of claim 78.

83. An antibody conjugate comprising an isolated antibody of any one of claims 1-73 linked to at least one payload optionally via a linker, wherein the payload is a cytotoxic agent or an immunomodulatory agent.

84. An antibody conjugate comprising an isolated antibody of any one of claims 38-73, linked to at least one cytotoxic agent optionally via a linker and at least one immunomodulatory agent optionally via a linker.

85. The antibody conjugate of claim 83 or 84, wherein the cytotoxic agent is selected from the group consisting of an alkylating agent, a DNA-crosslinking agent, an anti-tumor antibiotic, an anti-metabolite, an anti-mitotic agent, a histone-deacetylase (HDAC) 346 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO inhibitor, a telomerase inhibitor, an immunogenic cell death agent, a tubulin inhibitor, and a topoisomerase inhibitor.

86. The antibody conjugate of claim 85, wherein the cytotoxic agent is a topoisomerase I inhibitor and the topoisomerase I inhibitor is selected from the group consisting of camptothecin, irinotecan, SN-38, topotecan, and exatecan.

87. The antibody conjugate of claim 86, wherein the topoisomerase I inhibitor is exatecan.

88. The antibody conjugate of claim 85, wherein the cytotoxic agent is a hemiasterlin.

89. The antibody conjugate of any one of claims 83-88, wherein the linker is hydrolytically stable.

90. The antibody conjugate of any one of claims 83-88, wherein the linker is cleavable.

91. The antibody conjugate of any one of claims 83-88, wherein the linker is a protease cleavable linker, an enzyme cleavable linker, a pH-sensitive linker, or a non-cleavable linker.

92. A pharmaceutical composition comprising the antibody of any one of claims 1 to 73, or the antibody conjugate of any one of claims 83-91, and a pharmaceutically acceptable carrier.

93. A method of treating or preventing a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of an antibody of any one of claims 1 to 73, the antibody conjugate of any one of claims 83-91, or a pharmaceutical composition of claim 92.

94. A method of reducing or inhibiting cell proliferation associated with a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of an antibody of any one of claims 1 to 73, the antibody conjugate of any one of claims 83-91, or a pharmaceutical composition of claim 92.

95. A method of diagnosing a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of an antibody of any one of claims 1 to 73, the antibody conjugate of any one of claims 83-91, or a pharmaceutical composition of claim 92. 347 1104512371\1\AMERICASAttorney Docket No.108843.00551 SU-0450WO 96. A composition for use in the treatment or prevention of a disease or condition, wherein the composition comprises an antibody of any one of claims 1 to 73, the antibody conjugate of any one of claims 83-91, or a pharmaceutical composition of claim 92.

97. A composition for use in the reduction or inhibition of cell proliferation associated with a disease or condition, wherein the composition comprises an antibody of any one of claims 1 to 73, the antibody conjugate of any one of claims 83-91, or a pharmaceutical composition of claim 92.

98. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is a cancer.

99. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is colorectal cancer.

100. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is breast cancer.

101. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is ovarian cancer.

102. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is cervical cancer.

103. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is lung cancer.

104. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is head and neck cancer.

105. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is renal cell carcinoma.

106. The method of any one of claims 93-95, or the composition for use of claim 96 or 97, wherein the disease or condition is endometrial carcinoma. 348 1104512371\1\AMERICAS

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