Compositions and methods for modulating CDCP1 mediated signal transduction

Abstract

The invention provides CDCP1 immunomodulatory and targeted killing (Toxin payload delivery) agents which modulate CDCP1 expression, ligand binding, crosslinking, CDCP1 mediated signaling, and / or survival of cells expressing CDCP1 or a combination thereof. The CDCP1 immunomodulatory agents include soluble CDCP1 polypeptide or fusion proteins, anti-CDCP1 antibodies, and antibody-drug conjugates. Such agents can be used to modulate an immune response, effect survival of malignant cells expressing CDCP1 or both in a subject in need thereof.

Description

COMPOSITIONS AND METHODS FOR MODULATING CDCP1 MEDIATED SIGNAL TRANSDUCTION CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This invention claims the benefit of priority to United States Provisional Application No.63 / 613,225, filed on December 21, 2023, and to United States Provisional Application No.63 / 680,401, filed on August 7, 2024, each of which is incorporated herein by reference in their entirety. FIELD

[0002] This relates generally to the field of immunomodulation, and more particularly to compositions and methods for modulating immune responses in a subject BACKGROUND

[0003] Immunotherapies have made significant advances in the treatment of diseases such as cancer (Iwai, Y., et al., Journal of Biomedical Science, 24:26 (2017). Early immunotherapies accelerated T-cell activity. Current immune-checkpoint inhibitors take the brakes off the anti-tumor immune responses. Successful clinical trials with programmed cell death protein 1 (PD-1) monoclonal antibodies and other immune-checkpoint inhibitors have opened new avenues in cancer immunology. The failure of a large subset of cancer patients to respond to these new immunotherapies has led to intensified research to find new therapies.

[0004] Therefore, it is an object of the invention to provide compositions that increase CUB domain-containing protein 1 (CDCP1) mediated signal transduction thereby promoting a suppressive immunological response. Such compositions are useful for the treatment of inflammatory diseases and disorders and autoimmune diseases.

[0005] It is also an object of the invention to provide compositions that inhibit CDCP1 mediated signal transduction to thereby enhance or promote an activating immunological response. Such compositions are useful for the treatment of cancer and infectious diseases. SUMMARY

[0006] Compositions and methods of their use for modulating CDCP1 mediated signal transduction are provided. One embodiment provides compositions and 1064467-020PCTmethods that induce, promote, or enhance CDCP1 mediated signal transduction. For example, immunomodulatory agents are provided that induce, promote, or enhance CDCP1 expression, ligand binding, crosslinking, signal transduction, or a combination thereof.

[0007] Another embodiment provides compositions and methods for inhibiting, reducing, or blocking CDCP1 mediated signal transduction. For example, immunomodulatory agents are provided that inhibit, reduce, or block CDCP1 expression, ligand binding, crosslinking, signal transduction, or a combination thereof.

[0008] Immunostimulatory agents (also referred to as binding moieties) specifically bind to CDCP1 and modulate CDCP1 mediated signal transduction, for example CDCP1 signal transduction in immune cells.

[0009] In one embodiment the disclosed immunomodulatory agents can be used to modulate an immune response in a subject in need thereof by inducing, promoting, or enhancing CDCP1 mediated signaling. An immune response can be, for example, inducing, promoting, or enhancing Tregs activation or proliferation.

[0010] In another embodiment the disclosed immunomodulatory agents can be used to modulate an immune response in a subject in need thereof by inhibiting CDCP1 mediated signaling. An immune response can be, for example, inhibiting, reducing, or blocking migration of immunosuppressive regulatory T cells (Tregs) and / or tumor-associated macrophages (TAMs) to the tumor microenvironment, depletion of tumor-resident Tregs, depletion of tumor-resident TAMs, depletion of tumor cells expressing CDCP1, or inhibiting, reducing, or blocking trafficking of Tregs, TAMs, or tumor cells.

[0011] In one embodiment the disclosed immunomodulatory agents can be used to modulate an immune response in a subject in need thereof by inhibiting CDCP1 mediated signaling to inhibit, reduce, or block tumor metastasis.

[0012] One embodiment provides an antibody or antigen binding fragment thereof that immunospecifically binds to CDCP1 (any one of SEQ ID NO:1-5) and induces, promotes, or enhances CDCP1 mediated signal transduction. Another embodiment provides and anti-CDCP1 antibody or antigen binding fragment thereof that induces, promotes, or enhances the interaction between CDCP1 and its ligands.

[0013] Another embodiment provides an antibody or antigen binding fragment thereof that immunospecifically binds to CDCP1 (any one of SEQ ID NO:1-5) and 2064467-020PCTinhibits, reduces, or blocks CDCP1 mediated signal transduction. Another embodiment provides and anti-CDCP1 antibody or antigen binding fragment thereof that inhibits, interferes, or blocks the interaction between CDCP1 and its ligands.

[0014] In another embodiment the agent is a CDCP1 fusion protein, for example a fusion protein that includes one or more extracellular domains of CDCP1 or functional variant thereof linked to an immunoglobulin domain. An exemplary fusion protein includes the amino acid sequence having at least 80%, 90%, 95%, or 100% sequence identity to SEQ ID NO:1-5 or a fragment thereof.

[0015] In other embodiments the immunomodulatory agent is a CDCP1 protein (any one of SEQ ID NO:1-5) or a functional fragment or variant thereof. For example, the CDCP1 protein or functional fragment or variant thereof can have at least 80%, 90%, 95%, or 100% sequence identity to any one of SEQ ID NO:1-5.

[0016] In other embodiments the immunomodulatory agent is a soluble CDCP1 protein or a functional fragment or variant thereof. For example, the soluble CDCP1 protein can consist of one or more extracellular domains of CDCP1or a functional fragment or variant thereof.

[0017] One embodiment provides an immunomodulatory agent that specifically binds any one of SEQ ID NO:1-5 and modulates CDCP1 mediated signal transduction.

[0018] Another embodiment provides a fusion protein or an antigen binding fragment thereof comprising a CDCP1 protein having at least 99% sequence identity to SEQ ID NO: 1, 2, 3, 4, 5, or a functional variant thereof and linked to an immunoglobulin domain. Other embodiments provide a fusion protein or an antigen binding fragment thereof having 80%, 85%, 90%, 95%, 99%, or 100% to any one of SEQ ID NO:6-17, wherein the fusion protein inhibits, reduces, or blocks CDCP1 mediated signal transduction.

[0019] Methods of promoting a suppressive immune response in a subject typically include administering to a subject in need thereof an effective amount of an immunomodulatory agent that induces, promotes, or enhances CDCP1 expression, ligand binding, crosslinking, signal transduction, or a combination thereof. The subject can have, for example, inflammatory disease including, but not limited to autoimmune disease and transplant rejection disease.

[0020] Methods of increasing an immune response in a subject typically include administering to a subject in need thereof an effective amount of an 3064467-020PCTimmunomodulatory agent that inhibits, reduces, or blocks CDCP1 expression, ligand binding, crosslinking, signal transduction, or a combination thereof. The subject can have, for example, a hyperproliferative disease, cancer or an infectious disease.

[0021] In some embodiments, the subject, the cancer, or the disease is characterized by increased expression of CDCP1, increased expression of a CDCP1 ligand, or a combination thereof. In particular embodiments, the cancer is any of a variety of cancers or abnormal proliferative growths as listed within this application. The agent can be administered contemporaneously, in alternation, or in combination formulated as a unit dose, optionally with a one or more additional therapeutic agents including but not limited to a vaccine or a component thereof.

[0022] One embodiment provides an anti-CDCP1 antibody produced by a hybridoma.

[0023] Another embodiment provides an anti-CDCP1 antibody having at least one light chain or at least one heavy chain of the antibody produced by one or more of hybridomas.

[0024] Another embodiment provides an antibody or antigen binding fragment thereof that immunospecifically binds to SEQ ID NO:1, 2, 3, 4, 5, or an ECD thereof.

[0025] Other embodiments the antibody or antigen binding fragment thereof comprises a variable light chain having at least 99% sequence identity to SEQ ID NO: 27, 31, 32, 42, 46, 47, 57, 61, 62, 72, 75, 76, 86, 90, 91, 100, 104, 105, 115, 119, 120, 130, 133, 134, 144, 148, 149, 159, 163, 164, 174, 178, 179, 284, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 399, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, or 427; and a variable heavy chain having an amino acid sequence according to SEQ ID NO: 18, 22, 23, 24, 25, 26, 33, 37, 38, 39, 40, 41, 48, 49, 52, 53, 55, 56, 63, 67, 68, 69, 70, 71, 77, 81, 82, 83, 84, 85, 92, 95, 96, 97, 98, 99, 106, 110, 111, 112, 113, 114, 121, 125, 126, 127, 128, 129, 135, 139, 140, 141, 142, 143, 150, 154, 155, 156, 157, 158, 165, 169, 170, 171, 172, 173, 180,184, 185, 186, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 216, 217, 217, 219, 220, 221, 222, 223, 224, 225, 226, 207, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238; 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 260, 261, 262, 263, 264, 265, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, or 283; or combinations thereof. 4064467-020PCT

[0026] Additional embodiments provide the antibody or antigen binding fragment thereof comprising complementarity-determining regions (CDRs) selected from the group of CDRs consisting of at least 99% sequence identity to SEQ ID NOs: 19-21, 28-30, 34-36, 43-45, 49-51, 58-60, 64-66, 73, 74, 78-80, 87-89, 93, 94, 102- 103, 107-109, 116-118, 122-124, 131, 132, 136-138, 145-147, 151-153, 160-162, 166-168, 175-177, 182-183, 190, 258, 259, 266, 285, 310-311, 355-357, 400-401, 428, 429-431, 433, or 434.

[0027] Other embodiments provide a humanized antibody or antigen binding fragment thereof comprising: a heavy chain variable domain of SEQ ID NO:180 and a light chain variable domain of SEQ ID NO:288; a heavy chain variable domain of SEQ ID NO:220 and a light chain variable domain of SEQ ID NO:291; a heavy chain variable domain of SEQ ID NO:180 and a light chain variable domain of SEQ ID NO: 288; a heavy chain variable domain of SEQ ID NO:220 and a light chain variable domain of SEQ ID NO:291); a heavy chain variable domain of SEQ ID NO:189 and a light chain variable domain of SEQ ID NO:288; a heavy chain variable domain of SEQ ID NO:196 and a light chain variable domain of SEQ ID NO:284; a heavy chain variable domain of SEQ ID NO:202 and a light chain variable domain of SEQ ID NO:288; a heavy chain variable domain of SEQ ID NO:208 and a light chain variable domain of SEQ ID NO:297; a heavy chain variable domain of SEQ ID NO:214 and a light chain variable domain of SEQ ID NO:300; a heavy chain variable domain of SEQ ID NO:226 and a light chain variable domain of SEQ ID NO:294; a heavy chain variable domain of SEQ ID NO:232 and a light chain variable domain of SEQ ID NO:303; a heavy chain variable domain of SEQ ID NO:238 and a light chain variable domain of SEQ ID NO:294; a heavy chain variable domain of SEQ ID NO:245 and a light chain variable domain of SEQ ID NO:306; a heavy chain variable domain of SEQ ID NO:251 and a light chain variable domain of SEQ ID NO:294; a heavy chain variable domain of SEQ ID NO: 257 and a light chain variable domain of SEQ ID NO:288; a heavy chain variable domain of SEQ ID NO:265 and a light chain variable domain of SEQ ID NO:288; a heavy chain variable domain of SEQ ID NO:272 and a light chain variable domain of SEQ ID NO:284; or a heavy chain variable domain of SEQ ID NO:278 and a light chain variable domain of SEQ ID NO:288.

[0028] Other embodiments provide a humanized antibody or antigen binding fragment thereof comprising: a heavy chain variable domain of SEQ ID NO:309 and a light chain variable domain of SEQ ID NO:407; a heavy chain variable domain of 5064467-020PCTSEQ ID NO:363 and a light chain variable domain of SEQ ID NO:416; a heavy chain variable domain of SEQ ID NO:369 and a light chain variable domain of SEQ ID NO:413; a heavy chain variable domain of SEQ ID NO:375 and a light chain variable domain of SEQ ID NO:413; a heavy chain variable domain of SEQ ID NO:317 and a light chain variable domain of SEQ ID NO:399; a heavy chain variable domain of SEQ ID NO::324 and a light chain variable domain of SEQ ID NO:404; a heavy chain variable domain of SEQ ID NO:330 and a light chain variable domain of SEQ ID NO:404; a heavy chain variable domain of SEQ ID NO:342 and a light chain variable domain of SEQ ID NO:422; a heavy chain variable domain of SEQ ID NO:348 and a light chain variable domain of SEQ ID NO:413; a heavy chain variable domain of SEQ ID NO:381 and a light chain variable domain of SEQ ID NO:416; a heavy chain variable domain of SEQ ID NO:387 and a light chain variable domain of SEQ ID NO:413; a heavy chain variable domain of SEQ ID NO:354 and a light chain variable domain of SEQ ID NO:419; a heavy chain variable domain of SEQ ID NO:363 and a light chain variable domain of SEQ ID NO:425; a heavy chain variable domain of SEQ ID NO:393 and a light chain variable domain of SEQ ID NO:410; a heavy chain variable domain of SEQ ID NO:336 and a light chain variable domain of SEQ ID NO:425; or a heavy chain variable domain of SEQ ID NO:393 and a light chain variable domain of SEQ ID NO:425

[0029] Another embodiment provides an antibody-drug conjugate having an antibody or antigen binding fragment thereof comprising a variable light chain having at least 99% sequence identity to SEQ ID NO: 27, 31, 32, 42, 46, 47, 57, 61, 62, 72, 75, 76, 86, 90, 91, 100, 104, 105, 115, 119, 120, 130, 133, 134, 144, 148, 149, 159, 163, 164, 174, 178, 179, 284, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 399, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, or 427; and a variable heavy chain having an amino acid sequence according to SEQ ID NO: 18, 22, 23, 24, 25, 26, 33, 37, 38, 39, 40, 41, 48, 49, 52, 53, 55, 56, 63, 67, 68, 69, 70, 71, 77, 81, 82, 83, 84, 85, 92, 95, 96, 97, 98, 99, 106, 110, 111, 112, 113, 114, 121, 125, 126, 127, 128, 129, 135, 139, 140, 141, 142, 143, 150, 154, 155, 156, 157, 158, 165, 169, 170, 171, 172, 173, 180,184, 185, 186, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 216, 217, 217, 219, 220, 221, 222, 223, 224, 225, 226, 207, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238; 240, 241, 242, 6064467-020PCT243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 260, 261, 262, 263, 264, 265, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, or 283 or combinations thereof; and a cytotoxic payload.

[0030] In some embodiments, the cytotoxic payload is selected from a group of therapeutics consisting of auristatins, maytansinoids, DNA alkylating agents, mitotic inhibitors, antitumor antibiotics, immunomodulating agents, gene therapy vectors, alkylating agents, antiangiogenic agents, antimetabolites, boron-containing agents, chemoprotective agents, hormone agents, glucocorticoids, photoactive therapeutic agents, oligonucleotides, radioactive isotopes, radiosensitizers, topoisomerase inhibitors, tyrosine kinase inhibitors, or combinations thereof.

[0031] Other embodiments provide a pharmaceutical composition comprising an effective amount of the CDCP1 immunomodulatory agent provided herein to modulate CDCP1 expression, ligand binding, crosslinking, CDCP1 mediated signaling, or a combination thereof.

[0032] In some embodiments, the composition further comprises one or more additional therapeutic agents selected from cytokines, chemotherapeutic agents, radionuclides, other immunotherapeutics, enzymes, antibiotics, antivirals, anti- parasitics, growth factors, growth inhibitors, hormones, hormone antagonists, antibodies and bioactive fragments thereof, antigen and vaccine formulations, peptide drugs, anti-inflammatories, ligands that bind to Toll-Like Receptors to activate the innate immune system, molecules that mobilize and optimize the adaptive immune system, other molecules that activate or up-regulate the action of cytotoxic T lymphocytes, natural killer cells and helper T-cells, other molecules that deactivate or down-regulate suppressor or regulatory T-cells, or combinations thereof.

[0033] In other embodiment, the composition is administered with other immunomodulatory agents selected from PD-1 antagonists, CTLA4 antagonists, potentiating agents or other CDCP1 antagonists.

[0034] In some embodiments, the subject or the disease or condition is characterized by increased expression of CDCP1 relative to express of CDCP1 in subjects without the disease or condition.

[0035] One embodiment provides a method for treating cancer or an infection in a subject in need thereof by administering to the subject an effective amount of a pharmaceutical composition including a CDCP1 monoclonal antibody, soluble 7064467-020PCTCDCP1 polypeptide, CDCP1 fusion protein, or combinations thereof in an amount effective to inhibit, reduce, or block CDCP1 signal transduction in immune cells.

[0036] One embodiment the CDCP1 immunomodulatory agents can be used to treat inflammation and or autoimmune disorders, including but not limited CDCP1 fusion proteins.

[0037] In one embodiment anti-CDCP1 antibodies that bind to ligands of CDCP1 can be used to treat cancer.

[0038] One embodiment provides a method for assessing or predicting the efficacy of a treatment using an anti-CDCP1 binding moiety by assaying the cells of a subject in need of treatment to determine whether the cells express CDCP1, binding partners of CDCP1, or both. In one embodiment, a treatment is effective if it inhibits, reduces, or blocks CDCP1 expression, ligand binding, crosslinking, signal transduction, or a combination thereof. Exemplary cells to be assayed include, but are not limited to, cancer cells obtained from the subjected.

[0039] Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. BRIEF DESCRIPTIONS OF THE DRAWINGS

[0040] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate (one) several embodiment(s) of the invention and together with the description, serve to explain the principles of the invention.

[0041] Figure 1 shows anti-CDCP1 antibody binding to HCT116 cells.

[0042] Figure 2 shows cell internalization of the anti-CDCP1 antibodies.

[0043] Figures 3A-3H show that antibodies derived from the 1E12 and 5B4 hybridomas are internalized into HCT116 and 293T-CDCP1 cells.

[0044] Figures 4A-4C show cytotoxicity of the 5B4 antibody drug conjugated with exatecan.

[0045] Figures 5A-5B show Carterra kinetic profiling for binding studies for the variants binding to human and cynomolgus monkey CDCP1 (Carterra, SPR LSA Platform). 8064467-020PCT

[0046] Figures 6A-6EE show binding studies for the variants binding to human and cynomolgus monkey CDCP1 using Octet kinetic analysis. DETAILED DESCRIPTION

[0047] The present invention may be understood more readily by reference to the following detailed description of preferred embodiments of the invention and the Examples included therein and to the Figures and their previous and following description. I. Definitions

[0048] To facilitate an understanding of the principles and features of the various embodiments of the disclosure, various illustrative embodiments are explained herein. Although exemplary embodiments of the disclosure are explained in detail, it is to be understood that other embodiments are contemplated. Accordingly, it is not intended that the disclosure is limited in its scope to the details of construction and arrangement of components set forth in the description or examples. The disclosure is capable of other embodiments and of being practiced or carried out in various ways.

[0049] In describing the exemplary embodiments, specific terminology will be resorted to for the sake of clarity. As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. For example, reference to a component is intended also to include composition of a plurality of components. References to a composition containing “a” constituent is intended to include other constituents in addition to the one named.

[0050] Ranges may be expressed herein as from “about” or “approximately” or “substantially” one particular value and / or to “about” or “approximately” or “substantially” another particular value. When such a range is expressed, other exemplary embodiments include from the one particular value and / or to the other particular value.

[0051] As used herein, the terms “immunomodulatory agent” and “binding moiety” are used interchangeably.

[0052] As used herein, the term “CDCP1 immunomodulatory agent” refers to CUB domain-containing protein 1 (CDCP1) binding moieties including, but not limited to antibodies and antigen binding fragments thereof, and CDCP1 fusion proteins and binding fragments thereof. 9064467-020PCT

[0053] As used herein, a molecule is said to be able to “immunospecifically bind” a second molecule if such binding exhibits the specificity and affinity of an antibody to its cognate antigen. Antibodies are said to be capable of immunospecifically binding to a target region or conformation (“epitope”) of an antigen if such binding involves the antigen recognition site of the immunoglobulin molecule. An antibody that immunospecifically binds to a particular antigen may bind to other antigens with lower affinity if the other antigen has some sequence or conformational similarity that is recognized by the antigen recognition site as determined by, e.g., immunoassays, BIACORE® assays, or other assays known in the art, but would not bind to a totally unrelated antigen. In some embodiments, however, antibodies (and their antigen binding fragments) will not cross-react with other antigens. Antibodies may also bind to other molecules in a way that is not immunospecific, such as to FcR receptors, by virtue of binding domains in other regions / domains of the molecule that do not involve the antigen recognition site, such as the Fc region.

[0054] As used herein, a molecule is said to “bind” a second molecule if such binding exhibits the specificity and affinity of a receptor to its cognate binding ligand. A molecule can be capable of binding to more than one other molecule.

[0055] As used herein, the term “antibody” is intended to denote an immunoglobulin molecule that possesses a “variable region” antigen recognition site. The term “variable region” is intended to distinguish such domain of the immunoglobulin from domains that are broadly shared by antibodies (such as an antibody Fc domain). The variable region includes a “hypervariable region” whose residues are responsible for antigen binding. The hypervariable region includes amino acid residues from a “Complementarity Determining Region” or “CDR” (i.e., typically at approximately residues 24-34 (L1), 50-56 (L2) and 89-97 (L3) in the light chain variable domain and at approximately residues 27-35 (H1), 50-65 (H2) and 95- 102 (H3) in the heavy chain variable domain; Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)) and / or those residues from a “hypervariable loop” (i.e., residues 26-32 (L1), 50-52 (L2) and 91-96 (L3) in the light chain variable domain and 26-32 (H1), 53-55 (H2) and 96-101 (H3) in the heavy chain variable domain; Chothia and Lesk, 1987, J. Mol. Biol.196:901-917). “Framework Region” or “FR” residues are those variable domain residues other than the hypervariable region residues as 10064467-020PCTherein defined. The term antibody includes monoclonal antibodies, multi-specific antibodies, human antibodies, humanized antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies (See e.g., Muyldermans et al., 2001, Trends Biochem. Sci.26:230; Nuttall et al., 2000, Cur. Pharm. Biotech.1:253; Reichmann and Muyldermans, 1999, J. Immunol. Meth.231:25; International Publication Nos. WO 94 / 04678 and WO 94 / 25591; U.S. Patent No.6,005,079), single-chain Fvs (scFv) (see, e.g., see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol.113, Rosenburg and Moore eds. Springer-Verlag, New York, pp.269-315 (1994)), single chain antibodies, disulfide-linked Fvs (sdFv), intrabodies, and anti-idiotypic (anti-Id) antibodies (including, e.g., anti-Id and anti-anti-Id antibodies to antibodies). In particular, such antibodies include immunoglobulin molecules of any type (e.g., IgG, IgE, IgM, IgD, IgA and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass.

[0056] As used herein, the term “antigen binding fragment” of an antibody refers to one or more portions of an antibody that contain the antibody’s Complementarity Determining Regions (“CDRs”) and optionally the framework residues that include the antibody’s “variable region” antigen recognition site and exhibit an ability to immunospecifically bind antigen. Such fragments include Fab', F(ab')2, Fv, single chain (ScFv), and mutants thereof, naturally occurring variants, and fusion proteins including the antibody’s “variable region” antigen recognition site and a heterologous protein (e.g., a toxin, an antigen recognition site for a different antigen, an enzyme, a receptor or receptor ligand, etc.).

[0057] As used herein, the term “fragment” refers to a peptide or polypeptide including an amino acid sequence of at least 5 contiguous amino acid residues, at least 10 contiguous amino acid residues, at least 15 contiguous amino acid residues, at least 20 contiguous amino acid residues, at least 25 contiguous amino acid residues, at least 40 contiguous amino acid residues, at least 50 contiguous amino acid residues, at least 60 contiguous amino residues, at least 70 contiguous amino acid residues, at least 80 contiguous amino acid residues, at least 90 contiguous amino acid residues, at least 100 contiguous amino acid residues, at least 125 contiguous amino acid residues, at least 150 contiguous amino acid residues, at least 175 contiguous amino acid residues, at least 200 contiguous amino acid residues, or at least 250 contiguous amino acid residues. 11064467-020PCT

[0058] As used herein the term “modulate” relates to a capacity to alter an effect, result, or activity (e.g., signal transduction). Such modulation can be agonistic or antagonistic. Antagonistic modulation can be partial (i.e., attenuating, but not abolishing) or it can completely abolish such activity (e.g., neutralizing). Modulation can include internalization of a receptor following binding of an antibody or a reduction in expression of a receptor on the target cell. Agonistic modulation can enhance or otherwise increase or enhance an activity (e.g., signal transduction). In a still further embodiment, such modulation can alter the nature of the interaction between a ligand and its cognate receptor so as to alter the nature of the elicited signal transduction. For example, the molecules can, by binding to the ligand or receptor, alter the ability of such molecules to bind to other ligands or receptors and thereby alter their overall activity. In some embodiments, such modulation will provide at least a 10% change in a measurable immune system activity, at least a 50% change in such activity, or at least a 2-fold, 5-fold, 10-fold, or at least a 100-fold change in such activity.

[0059] The term “substantially,” as used in the context of binding or exhibited effect, is intended to denote that the observed effect is physiologically or therapeutically relevant. Thus, for example, a molecule is able to substantially block an activity of a ligand or receptor if the extent of blockage is physiologically or therapeutically relevant (for example if such extent is greater than 60% complete, greater than 70% complete, greater than 75% complete, greater than 80% complete, greater than 85% complete, greater than 90% complete, greater than 95% complete, or greater than 97% complete). Similarly, a molecule is said to have substantially the same immunospecificity and / or characteristic as another molecule, if such immunospecificities and characteristics are greater than 60% identical, greater than 70% identical, greater than 75% identical, greater than 80% identical, greater than 85% identical, greater than 90% identical, greater than 95% identical, or greater than 97% identical).

[0060] As used herein, the “activating” or “stimulatory” signals encompass signals that result in enhancing an activity or enhancing signal transduction.

[0061] As used herein, “suppressive” signals refer to signals that suppress immune activity.

[0062] The term “derivative” refers to an antibody or antigen-binding fragment thereof that immunospecifically binds to the same target of a parent or 12064467-020PCTreference antibody but which differs in amino acid sequence from the parent or reference antibody or antigen binding fragment thereof by including one, two, three, four, five or more amino acid substitutions, additions, deletions or modifications relative to the parent or reference antibody or antigen binding fragment thereof. In some embodiments, such derivatives will have substantially the same immunospecificity and / or characteristics, or the same immunospecificity and characteristics as the parent or reference antibody or antigen binding fragment thereof. The amino acid substitutions or additions of such derivatives can include naturally occurring (i.e., DNA-encoded) or non-naturally occurring amino acid residues. The term “derivative” encompasses, for example, chimeric or humanized variants, as well as variants having altered CH1, hinge, CH2, CH3 or CH4 regions, so as to form, for example antibodies, etc., having variant Fc regions that exhibit enhanced or impaired effector or binding characteristics.

[0063] As used herein, a “chimeric antibody” is a molecule in which different portions of the antibody are derived from different immunoglobulin molecules such as antibodies having a variable region derived from a non-human antibody and a human immunoglobulin constant region.

[0064] As used herein, the term “humanized antibody” refers to an immunoglobulin including a human framework region and one or more CDR’s from a non-human (usually a mouse or rat) immunoglobulin. The non-human immunoglobulin providing the CDR's is called the “donor” and the human immunoglobulin providing the framework is called the “acceptor.” Constant regions need not be present, but if they are, they should be substantially identical to human immunoglobulin constant regions, i.e., at least about 85-99%, or about 95% or more identical. Hence, all parts of a humanized immunoglobulin, except possibly the CDR’s, are substantially identical to corresponding parts of natural human immunoglobulin sequences. A humanized antibody is an antibody including a humanized light chain and a humanized heavy chain immunoglobulin. For example, a humanized antibody would not encompass a typical chimeric antibody, because, e.g., the entire variable region of a chimeric antibody is non-human.

[0065] The term “endogenous concentration” refers to the level at which a molecule is natively expressed (i.e., in the absence of expression vectors or recombinant promoters) by a cell (which cell can be a normal cell, a cancer cell or an infected cell). 13064467-020PCT

[0066] As used herein, the terms “treat,” “treating,” “treatment” and “therapeutic use” refer to the elimination, reduction or amelioration of one or more symptoms of a disease or disorder. As used herein, a “therapeutically effective amount” refers to that amount of a therapeutic agent sufficient to mediate a clinically relevant elimination, reduction or amelioration of such symptoms. An effect is clinically relevant if its magnitude is sufficient to impact the health or prognosis of a recipient subject. A therapeutically effective amount may refer to the amount of therapeutic agent sufficient to delay or minimize the onset of disease, e.g., delay or minimize the spread of cancer. A therapeutically effective amount may also refer to the amount of the therapeutic agent that provides a therapeutic benefit in the treatment or management of a disease.

[0067] As used herein, the term “prophylactic agent” refers to an agent that can be used in the prevention of a disorder or disease prior to the detection of any symptoms of such disorder or disease. A “prophylactically effective” amount is the amount of prophylactic agent sufficient to mediate such protection. A prophylactically effective amount may also refer to the amount of the prophylactic agent that provides a prophylactic benefit in the prevention of disease.

[0068] As used herein, the term “cancer” refers to a neoplasm or tumor resulting from abnormal uncontrolled growth of cells. The term “cancer” refers to a disease involving cells that have the potential to metastasize to distal sites and exhibit phenotypic traits that differ from those of non-cancer cells, for example, formation of colonies in a three-dimensional substrate such as soft agar or the formation of tubular networks or web-like matrices in a three-dimensional basement membrane or extracellular matrix preparation. Non-cancer cells do not form colonies in soft agar and form distinct sphere-like structures in three-dimensional basement membrane or extracellular matrix preparations.

[0069] Exemplary cancers that can be treated by the antibody-drug conjugates of the invention include cancers of the gastrointestinal tract (colon carcinoma, rectal carcinoma, colorectal carcinoma, colorectal cancer, colorectal adenoma, hereditary nonpolyposis type 1, hereditary nonpolyposis type 2, hereditary nonpolyposis type 3, hereditary nonpolyposis type 6; colorectal cancer, hereditary nonpolyposis type 7, small and / or large bowel carcinoma, esophageal carcinoma, tylosis with esophageal cancer, stomach carcinoma, pancreatic carcinoma, pancreatic endocrine tumors), endometrial carcinoma, dermatofibrosarcoma protuberans, gallbladder carcinoma, 14064467-020PCTbiliary tract tumors, prostate cancer, prostate adenocarcinoma, renal cancer (e.g., Wilms' tumor type 2 or type 1), liver cancer (e.g., hepatoblastoma, hepatocellular carcinoma, hepatocellular cancer), bladder cancer, embryonal rhabdomyosarcoma, germ cell tumor, trophoblastic tumor, testicular germ cells tumor, immature teratoma of ovary, uterine, epithelial ovarian, sacrococcygeal tumor, choriocarcinoma, placental site trophoblastic tumor, epithelial adult tumor, ovarian carcinoma, serous ovarian cancer, ovarian sex cord tumors, cervical carcinoma, uterine cervix cancer, small-cell and non-small cell lung cancer, nasopharyngeal, breast cancer (e.g., ductal breast cancer, invasive intraductal breast cancer; breast cancer, triple-negative breast cancer, HR+ / HER2- breast cancer, susceptibility to breast cancer, type 4 breast cancer, breast cancer-1, breast cancer-3; breast-ovarian cancer), squamous cell carcinoma (e.g., in head and neck), neurogenic tumor, astrocytoma, ganglioblastoma, neuroblastoma, gliomas, adenocarcinoma, adrenal tumor, hereditary adrenocortical carcinoma, brain malignancy (tumor), various other carcinomas (e.g., bronchogenic large cell, ductal, Ehrlich-Lettre ascites, epidermoid, large cell, Lewis lung, medullary, mucoepidermoid, oat cell, small cell, spindle cell, spinocellular, transitional cell, undifferentiated, carcinosarcoma, choriocarcinoma, cystadenocarcinoma), ependimoblastoma, epithelioma, erythroleukemia (e.g., Friend, lymphoblast), fibrosarcoma, giant cell tumor, glial tumor, glioblastoma (e.g., multiforme, astrocytoma), glioma hepatoma, heterohybridoma, heteromyeloma, histiocytoma, hybridoma (e.g., B cell), hypernephroma, insulinoma, islet tumor, keratoma, leiomyoblastoma, leiomyosarcoma, lymphosarcoma, melanoma, mammary tumor, mastocytoma, medulloblastoma, mesothelioma, metastatic tumor, monocyte tumor, multiple myeloma, myelodysplastic syndrome, myeloma, nephroblastoma, nervous tissue glial tumor, nervous tissue neuronal tumor, neurinoma, neuroblastoma, oligodendroglioma, osteochondroma, osteomyeloma, osteosarcoma (e.g., Ewing's), papilloma, transitional cell, pheochromocytoma, pituitary tumor (invasive), plasmacytoma, retinoblastoma, rhabdomyosarcoma, sarcoma (e.g., Ewing's, histiocytic cell, Jensen, osteogenic, reticulum cell), schwannoma, subcutaneous tumor, teratocarcinoma (e.g., pluripotent), teratoma, testicular tumor, thymoma and trichoepithelioma, gastric cancer, fibrosarcoma, glioblastoma multiforme; multiple glomus tumors, Li-Fraumeni syndrome, liposarcoma, lynch cancer family syndrome II, male germ cell tumor, medullary thyroid, multiple meningioma, endocrine neoplasia myxosarcoma, paraganglioma, familial nonchromaffin, pilomatricoma, 15064467-020PCTpapillary, familial and sporadic, rhabdoid predisposition syndrome, familial, rhabdoid tumors, soft tissue sarcoma, and Turcot syndrome with glioblastoma. In some embodiments, the mixture is used to treat eye cancer, e.g., uveal melanoma.

[0070] As used herein, an “immune cell” refers to any cell from the hemopoietic origin including, but not limited to, T cells, B cells, monocytes, dendritic cells, and macrophages.

[0071] As used herein, “inflammatory molecules” refer to molecules that result in inflammatory responses including, but not limited to, cytokines and metalloproteases such as including, but not limited to, IL-1β, TNF-α, TGF-beta, IFN- γ, IL-18, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs.

[0072] As used herein, “valency” refers to the number of binding sites available per molecule.

[0073] As used herein, the terms “immunologic,” “immunological” or “immune” response is the development of a beneficial humoral (antibody mediated) and / or a cellular (mediated by antigen-specific T cells or their secretion products) response directed against a peptide in a recipient patient. Such a response can be an active response induced by administration of immunogen or a passive response induced by administration of antibody or primed T-cells. A cellular immune response is elicited by the presentation of polypeptide epitopes in association with Class I or Class II MHC molecules to activate antigen-specific CD4+T helper cells and / or CD8+cytotoxic T cells. The response may also involve activation of monocytes, macrophages, NK cells, basophils, dendritic cells, astrocytes, microglia cells, eosinophils, activation or recruitment of neutrophils or other components of innate immunity. The presence of a cell-mediated immunological response can be determined by proliferation assays (CD4+T cells) or CTL (cytotoxic T lymphocyte) assays. The relative contributions of humoral and cellular responses to the protective or therapeutic effect of an immunogen can be distinguished by separately isolating antibodies and T-cells from an immunized syngeneic animal and measuring protective or therapeutic effect in a second subject.

[0074] An “immunogenic agent” or “immunogen” is capable of inducing an immunological response against itself on administration to a mammal, optionally in conjunction with an adjuvant. 16064467-020PCT

[0075] As used herein, the terms “individual,” “host,” “subject,” and “patient” are used interchangeably herein, and refer to a mammal, including, but not limited to, humans, rodents, such as mice and rats, and other laboratory animals.

[0076] As used herein, the term “polypeptide” refers to a chain of amino acids of any length, regardless of modification (e.g., phosphorylation or glycosylation). The term polypeptide includes proteins and fragments thereof. The polypeptides can be “exogenous,” meaning that they are “heterologous,” i.e., foreign to the host cell being utilized, such as human polypeptide produced by a bacterial cell. Polypeptides are disclosed herein as amino acid residue sequences. Those sequences are written left to right in the direction from the amino to the carboxy terminus. In accordance with standard nomenclature, amino acid residue sequences are denominated by either a three letter or a single letter code as indicated as follows: Alanine (Ala, A), Arginine (Arg, R), Asparagine (Asn, N), Aspartic Acid (Asp, D), Cysteine (Cys, C), Glutamine (Gln, Q), Glutamic Acid (Glu, E), 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).

[0077] As used herein, the term “variant” refers to a polypeptide or polynucleotide that differs from a reference polypeptide or polynucleotide, but retains essential properties. A typical variant of a polypeptide differs in amino acid sequence from another, reference polypeptide. Generally, differences are limited so that the sequences of the reference polypeptide and the variant are closely similar overall and, in many regions, identical. A variant and reference polypeptide may differ in amino acid sequence by one or more modifications (e.g., substitutions, additions, and / or deletions). A substituted or inserted amino acid residue may or may not be one encoded by the genetic code. A variant of a polypeptide may be naturally occurring such as an allelic variant, or it may be a variant that is not known to occur naturally.

[0078] Modifications and changes can be made in the structure of the polypeptides of the disclosure and still obtain a molecule having similar characteristics as the polypeptide (e.g., a conservative amino acid substitution). For example, certain amino acids can be substituted for other amino acids in a sequence without appreciable loss of activity. Because it is the interactive capacity and nature of a polypeptide that defines that polypeptide’s biological functional activity, certain 17064467-020PCTamino acid sequence substitutions can be made in a polypeptide sequence and nevertheless obtain a polypeptide with like properties.

[0079] In making such changes, the hydropathic index of amino acids can be considered. The importance of the hydropathic amino acid index in conferring interactive biologic function on a polypeptide is generally understood in the art. It is known that certain amino acids can be substituted for other amino acids having a similar hydropathic index or score and still result in a polypeptide with similar biological activity. Each amino acid has been assigned a hydropathic index on the basis of its hydrophobicity and charge characteristics. Those indices are: isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8); cysteine / cystine (+2.5); methionine (+1.9); alanine (+1.8); glycine (-0.4); threonine (-0.7); serine (-0.8); tryptophan (-0.9); tyrosine (-1.3); proline (-1.6); histidine (-3.2); glutamate (-3.5); glutamine (-3.5); aspartate (-3.5); asparagine (-3.5); lysine (-3.9); and arginine (-4.5).

[0080] It is believed that the relative hydropathic character of the amino acid determines the secondary structure of the resultant polypeptide, which in turn defines the interaction of the polypeptide with other molecules, such as enzymes, substrates, receptors, antibodies, antigens, and cofactors. It is known in the art that an amino acid can be substituted by another amino acid having a similar hydropathic index and still obtain a functionally equivalent polypeptide. In such changes, the substitution of amino acids whose hydropathic indices are within ± 2 is preferred, those within ± 1 are particularly preferred, and those within ± 0.5 are even more particularly preferred.

[0081] Substitution of like amino acids can also be made on the basis of hydrophilicity, particularly where the biological functional equivalent polypeptide or peptide thereby created is intended for use in immunological embodiments. The following hydrophilicity values have been assigned to amino acid residues: arginine (+3.0); lysine (+3.0); aspartate (+3.0 ± 1); glutamate (+3.0 ± 1); serine (+0.3); asparagine (+0.2); glutamine (+0.2); glycine (0); proline (-0.5 ± 1); threonine (-0.4); alanine (-0.5); histidine (-0.5); cysteine (-1.0); methionine (-1.3); valine (-1.5); leucine (-1.8); isoleucine (-1.8); tyrosine (-2.3); phenylalanine (-2.5); tryptophan (-3.4). It is understood that an amino acid can be substituted for another having a similar hydrophilicity value and still obtain a biologically equivalent, and in particular, an immunologically equivalent polypeptide. In such changes, the substitution of amino acids whose hydrophilicity values are within ± 2 is preferred, those within ± 1 are particularly preferred, and those within ± 0.5 are even more particularly preferred. 18064467-020PCT

[0082] As outlined above, amino acid substitutions are generally based on the relative similarity of the amino acid side-chain substituents, for example, their hydrophobicity, hydrophilicity, charge, size, and the like. Exemplary substitutions that take various foregoing characteristics into consideration are well known to those of skill in the art and include (original residue: exemplary substitution): (Ala: Gly, Ser), (Arg: Lys), (Asn: Gln, His), (Asp: Glu, Cys, Ser), (Gln: Asn), (Glu: Asp), (Gly: Ala), (His: Asn, Gln), (Ile: Leu, Val), (Leu: Ile, Val), (Lys: Arg), (Met: Leu, Tyr), (Ser: Thr), (Thr: Ser), (Trp: Tyr), (Tyr: Trp, Phe), and (Val: Ile, Leu). Embodiments of this disclosure thus contemplate functional or biological equivalents of a polypeptide as set forth above. In particular embodiments of the polypeptides can include variants having about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to the polypeptide of interest.

[0083] The term “percent (%) sequence identity” is defined as the percentage of nucleotides or amino acids in a candidate sequence that are identical with the nucleotides or amino acids in a reference nucleic acid sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent 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, ALIGN-2 or Megalign (DNASTAR) software. Appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full-length of the sequences being compared can be determined by known methods.

[0084] For purposes herein, the % sequence identity of a given nucleotides or amino acids sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given sequence C that has or comprises a certain % sequence identity to, with, or against a given sequence D) is calculated as follows: 100 times the fraction W / Z, where W is the number of nucleotides or amino acids scored as identical matches by the sequence alignment program in that program’s alignment of C and D, and where Z is the total number of nucleotides or amino acids in D. It will be appreciated that where the length of sequence C is not equal to the length of sequence D, the % sequence identity of C to D will not equal the % sequence identity of D to C.

[0085] As used herein, the term “pharmaceutically acceptable carrier” encompasses any of the standard pharmaceutical carriers, such as a phosphate 19064467-020PCTbuffered saline solution, water and emulsions such as an oil / water or water / oil emulsion, and various types of wetting agents. II. Compositions

[0086] One embodiment provides compositions that specifically bind to CDCP1 and modulate signal transduction through CDCP1, for example to reduce, inhibit, or block CDCP1 mediated signal transduction in immune cells. Representative immune cells include, but are not limited to, monocytes and T cells. Another embodiment provides compositions that inhibit, reduce, or block the interaction with CDCP1 with one or more ligands of CDCP1, and thereby reduce, inhibit, or block CDCP1 mediated signal transduction in immune cells. The binding moieties can bind directly to CDCP1 and inhibit, reduce or block the interaction of CDCP1 with one or more of its ligands. In still another embodiment, the binding moieties specifically bind or to a complex of CDCP1 with one or more ligands. A. CDCP1 Polypeptides

[0087] CDCP1 polypeptides are disclosed as well as binding moieties that specifically bind to CDCP1, for example bind immunospecifically to CDCP1, and inhibit, reduce or block CDCP1 mediated signal transduction in immune cells. Inhibiting, reducing, or blocking CDCP1 signal transduction in immune cells can occur as a result of the binding moiety binding directly to CDCP1. In some embodiments the CDCP1 binding moiety binds to CDCP1 and inhibits, reduces or blocks the interaction or association of CDCP1 and one or more of ligands of CDCP1. The polypeptides can include an amino acid sequence of full-length CDCP1, or a fragment or variant thereof, or a fusion protein thereof.

[0088] CDCP1 encodes a transmembrane protein which contains three extracellular CUB domains and acts as a substrate for Src family kinases. The protein plays a role in the tyrosine phosphorylation-dependent regulation of cellular events that are involved in tumor invasion and metastasis. Alternative splicing results in multiple transcript variants of this gene.

[0089] CDCP1 is strongly expressed in tumors derived from lung, colon, ovary, or kidney. Although expression and phosphorylation of CDCP1 have been investigated in many tumor cell lines, the CDCP1 features responsible for transformation have not been fully evaluated. 20064467-020PCT1. Human CDCP1

[0090] Sequences for human CDCP1 are known in the art. For example, a consensus amino acid sequence for CDCP1 is MAGLNCGVSIALLGVLLLGAARLPRGAEAFEIALPRESNITVLIKLGTPTLLAK PCYIVISKRHITMLSIKSGERIVFTFSCQSPENHFVIEIQKNIDCMSGPCPFGEVQ LQPSTSLLPTLNRTFIWDVKAHKSIGLELQFSIPRLRQIGPGESCPDGVTHSISG RIDATVVRIGTFCSNGTVSRIKMQEGVKMALHLPWFHPRNVSGFSIANRSSIK RLCIIESVFEGEGSATLMSANYPEGFPEDELMTWQFVVPAHLRASVSFLNFNL SNCERKEERVEYYIPGSTTNPEVFKLEDKQPGNMAGNFNLSLQGCDQDAQSP GILRLQFQVLVQHPQNESNKIYVVDLSNERAMSLTIEPRPVKQSRKFVPGCFV CLESRTCSSNLTLTSGSKHKISFLCDDLTRLWMNVEKTISCTDHRYCQRKSYS LQVPSDILHLPVELHDFSWKLLVPKDRLSLVLVPAQKLQQHTHEKPCNTSFSY LVASAIPSQDLYFGSFCPGGSIKQIQVKQNISVTLRTFAPSFQQEASRQGLTVSF IPYFKEEGVFTVTPDTKSKVYLRTPNWDRGLPSLTSVSWNISVPRDQVACLTF FKERSGVVCQTGRAFMIIQEQRTRAEEIFSLDEDVLPKPSFHHHSFWVNISNCS PTSGKQLDLLFSVTLTPRTVDLTVILIAAVGGGVLLLSALGLIICCVKKKKKK TNKGPAVGIYNDNINTEMPRQPKKFQKGRKDNDSHVYAVIEDTMVYGHLLQ DSSGSFLQPEVDTYRPFQGTMGVCPPSPPTICSRAPTAKLATEEPPPRSPPESES EPYTFSHPNNGDVSSKDTDIPLLNTQEPMEPAE (SEQ ID NO:1) UniProtKB - Q9H5V8 (CDCP1_HUMAN) which incorporate by reference in its entirety. In some embodiments that leading methionine is cleaved off in the mature polypeptide (i.e., a post-translationally modified polypeptide).

[0091] The underlined amino acids 1 – 29 of SEQ ID NO:1 represent the signal peptide of CDCP1. In one embodiment, the signal peptide is cleaved off of the mature protein.

[0092] The unmarked amino acids 30 – 667 of SEQ ID NO:1 represent the extracellular domain of CDCP1.

[0093] The double underlined amino acid 668-836 of SEQ ID NO:1 represent the intracellular domain sequence 21064467-020PCT

[0094] In one embodiment, the CDCP1 binding moieties specifically bind, for example immunospecifically bind to the ECD (amino acids 30 – 667 of SEQ ID NO:1) of human CDCP1 having the following sequence: F EIALPRESNI TVLIKLGTPT 60 70 80 90 100 LLAKPCYIVI SKRHITMLSI KSGERIVFTF SCQSPENHFV IEIQKNIDCM 110 120 130 140 150 SGPCPFGEVQ LQPSTSLLPT LNRTFIWDVK AHKSIGLELQ FSIPRLRQIG 160 170 180 190 200 PGESCPDGVT HSISGRIDAT VVRIGTFCSN GTVSRIKMQE GVKMALHLPW 210 220 230 240 250 FHPRNVSGFS IANRSSIKRL CIIESVFEGE GSATLMSANY PEGFPEDELM 260 270 280 290 300 TWQFVVPAHL RASVSFLNFN LSNCERKEER VEYYIPGSTT NPEVFKLEDK 310 320 330 340 350 QPGNMAGNFN LSLQGCDQDA QSPGILRLQF QVLVQHPQNE SNKIYVVDLS 360 370 380 390 400 NERAMSLTIE PRPVKQSRKF VPGCFVCLES RTCSSNLTLT SGSKHKISFL 410 420 430 440 450 CDDLTRLWMN VEKTISCTDH RYCQRKSYSL QVPSDILHLP VELHDFSWKL 460 470 480 490 500 LVPKDRLSLV LVPAQKLQQH THEKPCNTSF SYLVASAIPS QDLYFGSFCP 510 520 530 540 550 GGSIKQIQVK QNISVTLRTF APSFQQEASR QGLTVSFIPY FKEEGVFTVT 560 570 580 590 600 PDTKSKVYLR TPNWDRGLPS LTSVSWNISV PRDQVACLTF FKERSGVVCQ 610 620 630 640 650 TGRAFMIIQE QRTRAEEIFS LDEDVLPKPS FHHHSFWVNI SNCSPTSGKQ 660 670 680 690 700 LDLLFSVTLT PRTVDLT (SEQ ID NO:2).

[0095] One embodiment provides human CDCPI isoform 3 having the following sequence: MAGLNCGVSIALLGVLLLGAARLPRGAEAFEIALPRESNITVLIKLGTPTLLAK PCYIVISKRHITMLSIKSGERIVFTFSCQSPENHFVIEIQKNIDCMSGPCPFGEVQ 22064467-020PCTLQPSTSLLPTLNRTFIWDVKAHKSIGLELQFSIPRLRQIGPGESCPDGVTHSISG RIDATVVRIGTFCSNGTVSRIKMQEGVKMALHLPWFHPRNVSGFSIANRSSIK RLCIIESVFEGEGSATLMSANYPEGFPEDELMTWQFVVPAHLRASVSFLNFNL SNCERKEERVEYYIPGSTTNPEVFKLEDKQPGNMAGNFNLSLQGCDQDAQSP GILRLQFQVLVQHPQNESSE (SEQ ID NO:3) Q9H5V8-3|CDCP1_HUMAN Isoform 3.

[0096] The underlined sequence is the signal sequence.

[0097] Another embodiment provides an antibody or antigen binding fragment thereof that immunospecifically binds to SEQ ID NO:3 or and ECD thereof. 2. Murine CDCP1

[0098] The amino acid sequence for mouse CDCP1 is: 10 20 30 40 50 MAHSACGFSV ALLGALLLGT ARLLRGTEAS EIALPQRSGV TVSIKLGNPA 60 70 80 90 100 LPVKICYIVM SRQHITELII RPGERKSFTF SCSNPEKHFV LKIEKNIDCM 110 120 130 140 150 SGPCPFGEVH LQPSTSELPI LNRTFIWDVR AHKSIGLELQ FATPRLRQIG 160 170 180 190 200 PGESCADGVT HSISGHIDAT EVRIGTFCSN GTVSRIKMQE GVKMALHLPW 210 220 230 240 250 FHRRNVSGFS IANRSSIKRL CIIESVFEGE GSATLMSANY PGGFPEDELM 260 270 280 290 300 TWQFVVPAHL RASVSFLNFN VSNCERKEER VEYYIPGSTT NPEVFRLEDK 310 320 330 340 350 QPGNMAGNFN LSLQGCDQDA QSPGILRLQF QVLVQRPQDE SNKTYMVDLS 360 370 380 390 400 RERTMSLTIE PRPVKHGRRF VPGCFVCLES RTCSTNVTLT AGSIHKISFL 410 420 430 440 450 CDDLTRLWVN VEKTLSCLDH RYCYRQSFKL QVPDYILQLP VQLHDFSWKL 460 470 480 490 500 LVPKDKLSLM LVPGQKLQQH TQERPCNTSF GYHVTSTTPG QDLYFGSFCS 510 520 530 540 550 GGSIEKIQVK QNSSVTLRAY APSFQQEVSK QGLIVSYTPY FKEEGIFTVT 560 570 580 590 600 23064467-020PCTPDTKNKVYLR SPNWDRGLPA LSSVSWNISV PSNQVACLTV LKERSGLACQ 610 620 630 640 650 SGRAFMIIQE QQSRAEEIFS LEEEVLPKPS FHHHSFWVNI SNCSPMNGKQ 660 670 680 690 700 LDLLFWVTLT PRTVDLAVVI GAAGGGALLL FALVLIICFV KKKKKVDKGP 710 720 730 740 750 AVGIYNGNVN TQMPQTQKFP KGRKDNDSHV YAVIEDTMVY GHLLQDSGGS 760 770 780 790 800 FIQPEVDTYR PFQGPMGDCP PTPPPLFSRT PTAKFTAEEL APSSPPESES 810 820 830 EPYTFSHPNK GEIGVRETDI PLLHTQGPVE TEE (SEQ ID NO:4) UniProtKB - Q5U462 (CDCP1_MOUSE) which is incorporated by reference in its entirety.

[0099] Amino acids 1-29 of SEQ ID NO:3 represent the signal peptide for mouse CDP1. In some embodiments, the signal peptide is cleaved off of the mature protein. One embodiment provides an antibody or antigen binding fragment thereof that immunospecifically binds to amino acids 30-833 of SEQ ID NO:1.

[0100] Amino acids 30 – 666 of SEQ ID NO:3 represent the ECD for mouse CDP1. In one embodiment, the CDCP1 binding moiety specifically binds, for example immunospecifically binds to the ECD for mouse. B. Ligands of CDCP1

[0101] In one embodiment, a ligand for CDCP1 is CD6. The human sequence for CD6 is 10 20 30 40 50 MWLFFGITGL LTAALSGHPS PAPPDQLNTS SAESELWEPG ERLPVRLTNG 60 70 80 90 100 SSSCSGTVEV RLEASWEPAC GALWDSRAAE AVCRALGCGG AEAASQLAPP 110 120 130 140 150 TPELPPPPAA GNTSVAANAT LAGAPALLCS GAEWRLCEVV EHACRSDGRR 160 170 180 190 200 ARVTCAENRA LRLVDGGGAC AGRVEMLEHG EWGSVCDDTW DLEDAHVVCR 210 220 230 240 250 QLGCGWAVQA LPGLHFTPGR GPIHRDQVNC SGAEAYLWDC PGLPGQHYCG 260 270 280 290 300 24064467-020PCTHKEDAGAVCS EHQSWRLTGG ADRCEGQVEV HFRGVWNTVC DSEWYPSEAK 310 320 330 340 350 VLCQSLGCGT AVERPKGLPH SLSGRMYYSC NGEELTLSNC SWRFNNSNLC 360 370 380 390 400 SQSLAARVLC SASRSLHNLS TPEVPASVQT VTIESSVTVK IENKESRELM 410 420 430 440 450 LLIPSIVLGI LLLGSLIFIA FILLRIKGKY ALPVMVNHQH LPTTIPAGSN 460 470 480 490 500 SYQPVPITIP KEVFMLPIQV QAPPPEDSDS GSDSDYEHYD FSAQPPVALT 510 520 530 540 550 TFYNSQRHRV TDEEVQQSRF QMPPLEEGLE ELHASHIPTA NPGHCITDPP 560 570 580 590 600 SLGPQYHPRS NSESSTSSGE DYCNSPKSKL PPWNPQVFSS ERSSFLEQPP 610 620 630 640 650 NLELAGTQPA FSAGPPADDS SSTSSGEWYQ NFQPPPQPPS EEQFGCPGSP 660 SPQPDSTDND DYDDISAA (SEQ ID NO:5) UniProtKB - P30203 (CD6_HUMAN)which is incorporated by reference in its entirety.

[0102] One embodiment provides an antibody or antigen binding fragment that immunospecifically binds SEQ ID NO: 5.

[0103] Amino acids 18-402 of SEQ ID NO:5 represent the ECD of human CD6. One embodiment provides an antibody or antigen binding fragment thereof that immunospecifically binds to SEQ ID NO:5.

[0104] Another embodiment provides an antibody or antigen binding fragment thereof that immunospecifically binds to the ECD of mouse CD6 (amino acids 17-398 of UniProtKB - Q61003 (CD6_MOUSE) which is incorporated by reference in its entirety. C. Immunomodulatory Agents or Binding Moieties

[0105] Immunomodulatory agents or binding moieties including agonists and antagonists of CDCP1 are provided. An agonist of CDCP1 typically induces, promotes, or enhances CDCP1 mediated signaling. An antagonist of CDCP1 typically inhibits, reduces, or blocks CDCP1 mediated signaling. The disclosed 25064467-020PCTcompositions and methods can be used to modulate CDCP1 and / or counter-receptor signaling on, for example, immune cells including but not limited to monocytes, Tregs, tumor-associated macrophages (TAMs), Myeloid Derived Suppressor Cells (MDSC), T cells, Th2 cells, myeloid cells including antigen-presenting cells (e.g., monocyte, macrophage, or dendritic cell), T cells, Natural Killer (NK) cells or a combination thereof. In some embodiments, the compositions are specifically targeted to one or more cell types. In some embodiments, the disclosed compositions can be used on tumor cells.

[0106] In some embodiments, the anti-CDCP1 agonists induce, promote, or enhance CDCP1 mediated signaling through a known ligand or unknown counter- receptor through CDCP1 interaction with said known or unknown counter-receptor. For example, in some embodiments, the CDCP1 agonist binds to, induces, promotes or creates conformation change, or otherwise promotes CDCP1 mediated signal transduction.

[0107] In some embodiments, the anti-CDCP1 antagonists inhibit, reduce, block, or otherwise disrupt signaling through a known or unknown counter-receptor through blockade of CDCP1 interaction with said known or unknown counter-receptor. For example, in some embodiments, the CDCP1 antagonist binds to, inhibits, blocks, creates conformation change, or otherwise interferes with CDCP1 mediated signal transduction. 1. Antibodies

[0108] In one embodiment the immunomodulatory agent or binding moiety is an antibody. Suitable antibodies can be prepared by one of skill in the art. Nucleic acid and polypeptide sequences for CDCP1 are known in the art and exemplary sequences are provided above. The sequences can be used, as discussed in more detail below, by one of skill in the art to prepare an antibody or antigen binding fragment thereof specific for CDCP1. The antibody or antigen binding fragments therefore, can be an agonist or antagonist of CDCP1 mediated signaling.

[0109] The activity of an antibody or antigen binding fragment thereof that is specific for CDCP1 can be determined using functional assays that are known in the art, and include the assays discussed below. Typically, the assays include determining if the antibody or antigen binding fragment thereof increases (i.e., agonist) or decreases (i.e., antagonist) signaling through CDCP1. 26064467-020PCT

[0110] In some embodiments, the disclosed antibodies and antigen binding fragments thereof immunospecifically bind to human or mouse CDCP1. In some embodiments, the antibody binds to an extracellular domain of human or mouse CDCP1.

[0111] For example, molecules are provided that can immunospecifically bind to CDCP1: (I) arrayed on the surface of a cell (especially a live cell); (II) arrayed on the surface of a cell (especially a live cell) at an endogenous concentration; (III) arrayed on the surface of a live cell, and modulates binding between CDCP1 and a ligand thereof; (IV) arrayed on the surface of a live cell, and reduces or inhibits immune response by CDCP1; (V) arrayed on the surface of a live cell, wherein the cell is a tumor cell; (VI) combinations of I-IV and V; (VII) combinations of I-III and V; and (VIII) arrayed on the surface of a live myeloid or lymphoid derived cancer cells (AML or ALL) and enhances apoptosis and differentiation resulting in reduced self-renewal of cancer stem cells.

[0112] To prepare an antibody or antigen binding fragment thereof that specifically binds to CDCP1 purified proteins, polypeptides, fragments, fusions, or epitopes to CDCP1 or polypeptides expressed from nucleic acid sequences thereof, can be used. The antibodies or antigen binding fragments thereof can be prepared using any suitable methods known in the art such as those discussed in more detail below. a. Human and Humanized Antibodies

[0113] In some embodiments, the antibodies are humanized antibodies. Many non-human antibodies (e.g., those derived from mice, rats, or rabbits) are naturally antigenic in humans, and thus can give rise to undesirable immune responses when administered to humans. Therefore, the use of human or humanized antibodies in the methods serves to lessen the chance that an antibody administered to a human will evoke an undesirable immune response.

[0114] Transgenic animals (e.g., mice) that are capable, upon immunization, of producing a full repertoire of human antibodies in the absence of endogenous 27064467-020PCTimmunoglobulin production can be employed. For example, it has been described that the homozygous deletion of the antibody heavy chain joining region (J(H)) gene in chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production. Transfer of the human germ-line immunoglobulin gene array in such germ-line mutant mice will result in the production of human antibodies upon antigen challenge.

[0115] Optionally, the antibodies are generated in other species and “humanized” for administration in humans. Humanized forms of non-human (e.g., murine) antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2, or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non- human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementarity determining region (CDR) of the recipient antibody are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also contain residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will contain substantially all of at least one, and typically two, variable domains, in which all or substantially all, of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will contain at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.

[0116] Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source that is non-human. These non-human amino acid residues are often referred to as “import” residues, which are typically taken from an “import” variable domain. Antibody humanization techniques generally involve the use of recombinant DNA technology to manipulate the DNA sequence encoding one or more polypeptide chains of an antibody molecule. Humanization can be essentially performed by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, a humanized form of a nonhuman 28064467-020PCTantibody (or a fragment thereof) is a chimeric antibody or fragment, wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.

[0117] The choice of human variable domains, both light and heavy, to be used in making the humanized antibodies is very important in order to reduce antigenicity. According to the “best-fit” method, the sequence of the variable domain of a rodent antibody is screened against the entire library of known human variable domain sequences. The human sequence which is closest to that of the rodent is then accepted as the human framework (FR) for the humanized antibody. Another method uses a particular framework derived from the consensus sequence of all human antibodies of a particular subgroup of light or heavy chains. The same framework may be used for several different humanized antibodies.

[0118] It is further important that antibodies be humanized with retention of high affinity for the antigen and other favorable biological properties. To achieve this goal, humanized antibodies can be prepared by a process of analysis of the parental sequences and various conceptual humanized products using three dimensional models of the parental and humanized sequences Three dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art. Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e., the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen. In this way, FR residues can be selected and combined from the consensus and import sequence so that the desired antibody characteristic, such as increased affinity for the target antigen(s), is achieved. In general, the CDR residues are directly and most substantially involved in influencing antigen binding.

[0119] The antibody can be bound to a substrate or labeled with a detectable moiety or both bound and labeled. The detectable moieties contemplated with the present compositions include fluorescent, enzymatic and radioactive markers. 29064467-020PCTb. Single-Chain Antibodies

[0120] In some embodiments, the antibodies are single-chain antibodies. Methods for the production of single-chain antibodies are well known to those of skill in the art. A single chain antibody is created by fusing together the variable domains of the heavy and light chains using a short peptide linker, thereby reconstituting an antigen binding site on a single molecule. Single-chain antibody variable fragments (scFvs) in which the C-terminus of one variable domain is tethered to the N-terminus of the other variable domain via a 15 to 25 amino acid peptide or linker have been developed without significantly disrupting antigen binding or specificity of the binding. The linker is chosen to permit the heavy chain and light chain to bind together in their proper conformational orientation. These Fvs lack the constant regions (Fc) present in the heavy and light chains of the native antibody. c. Monovalent Antibodies

[0121] In some embodiments, the antibodies are monovalent antibodies. In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce fragments thereof, particularly, Fab fragments, can be accomplished using routine techniques known in the art. For instance, digestion can be performed using papain. Papain digestion of antibodies typically produces two identical antigen binding fragments, called Fab fragments, each with a single antigen binding site, and a residual Fc fragment. Pepsin treatment yields a fragment, called the F(ab’)2 fragment, that has two antigen combining sites and is still capable of cross- linking antigen.

[0122] The Fab fragments produced in the antibody digestion also contain the constant domains of the light chain and the first constant domain of the heavy chain. Fab’ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain domain including one or more cysteines from the antibody hinge region. The F(ab’)2 fragment is a bivalent fragment comprising two Fab’ fragments linked by a disulfide bridge at the hinge region. Fab’-SH is the designation herein for Fab’ in which the cysteine residue(s) of the constant domains bear a free thiol group. Antibody fragments originally were produced as pairs of Fab’ fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known. 30064467-020PCTd. Hybrid Antibodies

[0123] In some embodiments, the antibodies are hybrid antibodies. In hybrid antibodies, one heavy and light chain pair is homologous to that found in an antibody raised against one epitope, while the other heavy and light chain pair is homologous to a pair found in an antibody raised against another epitope. This results in the property of multi-functional valency, i.e., ability to bind at least two different epitopes simultaneously. Such hybrids can be formed by fusion of hybridomas producing the respective component antibodies, or by recombinant techniques. Such hybrids may, of course, also be formed using chimeric chains. e. Conjugates or Fusions of Antibody Fragments

[0124] In some embodiments the immunomodulatory agents are conjugates or fusions of antibody fragments. The targeting function of the antibody can be used therapeutically by coupling the antibody or a fragment thereof with a therapeutic agent. Such coupling of the antibody or fragment (e.g., at least a portion of an immunoglobulin constant region (Fc)) with the therapeutic agent can be achieved by making an immunoconjugate or by making a fusion protein, comprising the antibody or antibody fragment and the therapeutic agent.

[0125] Such coupling of the antibody or fragment with the therapeutic agent can be achieved by making an immunoconjugate or by making a fusion protein, or by linking the antibody or fragment to a nucleic acid such as an siRNA, comprising the antibody or antibody fragment and the therapeutic agent.

[0126] In some embodiments, the antibody is modified to alter its half-life. In some embodiments, it is desirable to increase the half-life of the antibody so that it is present in the circulation or at the site of treatment for longer periods of time. For example, it may be desirable to maintain titers of the antibody in the circulation or in the location to be treated for extended periods of time. Antibodies can be engineered with Fc variants that extend half-life, e.g., using Xtend™ antibody half-life prolongation technology (Xencor, Monrovia, CA). In other embodiments, the half-life of the anti-DNA antibody is decreased to reduce potential side effects. The conjugates disclosed can be used for modifying a given biological response. The drug moiety is not to be construed as limited to classical chemical therapeutic agents. For example, the drug moiety may be a protein or polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin. 31064467-020PCT2. Antibody-Drug Conjugates

[0127] Antibody-drug conjugates (ADC) of the invention are comprised of an anti- CDCP1 antibody, a cytotoxin and a linker. Antibodies are comprised of light and heavy chains. Each chain is comprised of a variable domain and a constant domain. The constant domain of the light chain can be kappa or lamba sequences as are well known in the art. The heavy chain constant domain is comprised of a first constant domain, a hinge and an Fc domain. Antibodies come in 5 classes, as determined by their sequences. The classes are IgA, IgD, IgE, IgG and IgM. The IgG antibodies comprise 4 subclasses, including IgG1, IgG2, IgG3 and IgG4. The antibody-drug conjugates of the invention are typically of the IgG class and more typically either IgG1 or IgG4. If the IgG1 classes are utilized, the constant domain sequence can be wild type or contain specific mutations to reduce the binding to Fc gamma receptors. These mutations are well known in the art, but include mutating the glycosylation site (e.g., N297Q), mutating the Fc gamma receptor binding site (L234A and L235A or L234F, L235E and P331S). If the IgG4 class is utilized, the constant domain sequence can be wild type or contain a specific mutation (S228P) to reduce chain exchange as is well known in the art.

[0128] Antibody-drug conjugates also encompass antibody fragments thereof, including antigen biding fragments, scFv, diabodies, single domain antibodies and nanobodies directed to CDCP1 and a linker that links a payload to the antibody.

[0129] The linker can be conjugated to the antibody by means well known in the art. For example, stochastic conjugation may be used to attach the linker to cysteine residues within the antibody. Other means include site specific conjugation, where a specific sequence is added to either the heavy chain or light chain and will serve as linker location. Examples include CAAX, as described in WO 2012 / 153193 and WO 2023 / 194800, wherein C is a cysteine residue, A is an aliphatic amino acid, and X is selected from glutamine, glutamate, serine, cysteine, methionine, alanine, and leucine. An exemplary CAAX sequence is CVIM. A preferred site-specific linker sequence is CVIM, which can be attached to the C-terminus of the light chain via a short spacer comprised of a series of 4, 5, 6, 7, 8, or more glycine residues. A preferred spacer is a series of 7 glycine residues.

[0130] Anti- CDCP1antibodies, cytotoxins and linkers are well known in the art and are described below. 32064467-020PCT3. CDCP1 Antibodies

[0131] One embodiment provides antibodies or binding fragments that specifically bind to CDCP1.

[0132] One embodiment provides an anti-CDCP1 antibody produced by a hybridoma selected from the group consisting of 1E12, 1H11, 3C7, 3D7, 3H8, 4B12, 4G11, 5B4, 5B8, 5B8, and 6A3.

[0133] Another embodiment provides an anti-CDCP1 antibody having at least one light chain or at least one heavy chain of the antibody produced by one or more of the hybridomas selected from the group consisting of 1E12, 1H11, 3C7, 3D7, 3H8, 4B12, 4G11, 5B4, 5B8, 5B8, and 6A3.

[0134] Another embodiment provides an anti-CDCP1 antibody having a variable light chain having at least 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, or 100% sequence identity to a variable light chain having an amino acid sequence according to SEQ ID NO: 27, 31, 32, 42, 46, 47, 57, 61, 62, 72, 75, 76, 86, 90, 91, 100, 104, 105, 115, 119, 120, 130, 133, 134, 144, 148, 149, 159, 163, 164, 174, 178, or 179.

[0135] Another embodiment provides an anti-CDCP1 antibody having a variable heavy chain having at least 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, or 100% sequence identity to a variable heavy chain having an amino acid sequence according to SEQ ID NO: 18, 22, 23, 24, 25, 26, 33, 37, 38, 39, 40, 41, 48, 49, 52, 53, 55, 56, 63, 67, 68, 69, 70, 71, 77, 81, 82, 83, 84, 85, 92, 95, 96, 97, 98, 99, 106, 110, 111, 112, 113, 114, 121, 125, 126, 127, 128, 129, 135, 139, 140, 141, 142, 143, 150, 154, 155, 156, 157, 158, 165, 169, 170, 171, 172, or 173.

[0136] Another embodiment provides an anti-CDCP1 antibody having a variable light chain having at least 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, or 100% sequence identity to a variable light chain having an amino acid sequence according to SEQ ID NO: 27, 31, 32, 42, 46, 47, 57, 61, 62, 72, 75, 76, 86, 90, 91, 100, 104, 105, 115, 119, 120, 130, 133, 134, 144, 148, 149, 159, 163, 164, 174, 178, or 179., and a variable heavy chain having at least 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, or 100% sequence identity to an amino acid sequence according to SEQ ID NO: 18, 22, 23, 24, 25, 26, 33, 37, 38, 39, 40, 41, 48, 49, 52, 53, 55, 56, 63, 67, 68, 69, 70, 71, 77, 81, 82, 83, 84, 85, 92, 95, 96, 97, 98, 99, 106, 110, 111, 112, 113, 114, 121, 125, 126, 127, 128, 129, 135, 139, 140, 141, 142, 143, 150, 154, 155, 156, 157, 158, 165, 169, 170, 171, 172, or 173. 33064467-020PCT

[0137] Another embodiment provides an anti-CDCP1 antibody having a complementarity-determining region (CDR) selected from the group of CDRs having an amino acid sequence selected from the group consisting of SEQ ID NOs: 19-21, 28-30, 34-36, 43-45, 49-51, 58-60, 64-66, 73, 74, 78-80, 87-89, 93, 94, 102-103, 107- 109, 116-118, 122-124, 131, 132, 136-138, 145-147, 151-153, 160-162, 166-168, and 175-177.

[0138] Another embodiment provides an anti-CDCP1 antibody having a plurality of CDRs selected from the group consisting of SEQ ID NOs: 19-21, 28-30, 34-36, 43-45, 49-51, 58-60, 64-66, 73, 74, 78-80, 87-89, 93, 94, 102-103, 107-109, 116-118, 122-124, 131, 132, 136-138, 145-147, 151-153, 160-162, 166-168, and 175- 177. The plurality of CDRs can be from 2 -12. a.1E12 Sequences i.1E12 Heavy Chain aa.1E12 Murine heavy chain variable region

[0139] One embodiment provides a 1E12 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTASGFNIKDGHMHWVMQRPEQGLEWIGW IDPENGDLEYASKFQGKATLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRG YFFDYWGQGTTLTVSS (SEQ ID NO: 18), with

[0140] 1E12 CDRH1: DGHMH (SEQ ID NO: 19),

[0141] 1E12 CDRH2: WIDPENGDLEYASKFQG (SEQ ID NO: 20),

[0142] 1E12 CDRH3: SRRGYFFDY (SEQ ID NO: 21). bb.1E12 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0143] One embodiment provides a 1E12 chimeric heavy chain, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTASGFNIKDGHMHWVMQRPEQGLEWIGWI DPENGDLEYASKFQGKATLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRGY FFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV 34064467-020PCTVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 22) with

[0144] CDRH1: DGHMH (SEQ ID NO: 19),

[0145] CDRH2: WIDPENGDLEYASKFQG (SEQ ID NO: 20),

[0146] CDRH3: SRRGYFFDY (SEQ ID NO: 21).

[0147] The italicized sequence is the heavy chain constant domain (wild type). cc.1E12 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0148] One embodiment provides a 1E12 chimeric heavy chain, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTASGFNIKDGHMHWVMQRPEQGLEWIGW IDPENGDLEYASKFQGKATLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRG YFFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 23) with

[0149] CDRH1: DGHMH (SEQ ID NO: 19),

[0150] CDRH2: WIDPENGDLEYASKFQG (SEQ ID NO: 20),

[0151] CDRH3: SRRGYFFDY (SEQ ID NO: 21).

[0152] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations. dd.1E12 Chimeric Heavy Chain, human IgG1 constant domains (FES)

[0153] One embodiment provides a 1E12 chimeric heavy chain, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTASGFNIKDGHMHWVMQRPEQGLEWIGW IDPENGDLEYASKFQGKATLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRG 35064467-020PCTYFFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 24) with

[0154] CDRH1: DGHMH (SEQ ID NO: 19),

[0155] CDRH2: WIDPENGDLEYASKFQG (SEQ ID NO: 20),

[0156] CDRH3: SRRGYFFDY (SEQ ID NO: 21).

[0157] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. ee.1E12 Chimeric Heavy Chain, human IgG1 constant domains (AA)

[0158] One embodiment provides a 1E12 chimeric heavy chain, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTASGFNIKDGHMHWVMQRPEQGLEWIGW IDPENGDLEYASKFQGKATLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRG YFFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 25) with

[0159] CDRH1: DGHMH (SEQ ID NO: 19),

[0160] CDRH2: WIDPENGDLEYASKFQG (SEQ ID NO: 20),

[0161] CDRH3: SRRGYFFDY (SEQ ID NO: 21).

[0162] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. 36064467-020PCTff.1E12 Chimeric Heavy Chain, human IgG4 constant domain (G4P)

[0163] One embodiment provides a 1E12 chimeric heavy chain, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTASGFNIKDGHMHWVMQRPEQGLEWIGW IDPENGDLEYASKFQGKATLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRG YFFDYWGQGTTLTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 26) with

[0164] CDRH1: DGHMH (SEQ ID NO: 19),

[0165] CDRH2: WIDPENGDLEYASKFQG (SEQ ID NO: 20),

[0166] CDRH3: SRRGYFFDY (SEQ ID NO: 21).

[0167] The dash underlined sequence is the IgG4 heavy chain constant domain. ii.1E12 Light Chain aa.1E12 Murine light chain variable region

[0168] One embodiment provides a 1E12 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQTTPSLSASLGDRVTISCRASQDINNYLNWYQQKPDGTVKLLIYYTS RLHSGVPSRFSGSGSGTDYSLTISNLEQEDIAAYFCQQGNTLPWTFGGGTKL EIK (SEQ ID NO: 27) with

[0169] CDRL1: RASQDINNYLN (SEQ ID NO: 28),

[0170] CDRL2: YTSRLHS (SEQ ID NO: 29),

[0171] CDRL3: QQGNTLPWT (SEQ ID NO: 30). bb.1E12 Chimeric Light Chain, human kappa wild type constant domain

[0172] One embodiment provides a 1E12 human chimeric Light Chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 37064467-020PCTDIQMTQTTPSLSASLGDRVTISCRASQDINNYLNWYQQKPDGTVKLLIYYTS RLHSGVPSRFSGSGSGTDYSLTISNLEQEDIAAYFCQQGNTLPWTFGGGTKL EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGEC (SEQ ID NO: 31) with

[0173] CDRL1: RASQDINNYLN (SEQ ID NO: 28),

[0174] CDRL2: YTSRLHS (SEQ ID NO: 29),

[0175] CDRL3: QQGNTLPWT (SEQ ID NO: 30).

[0176] The underlined sequence is the light chain constant domain (wild type, kappa). cc. Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0177] One embodiment provides a 1E12 human chimeric Light Chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQTTPSLSASLGDRVTISCRASQDINNYLNWYQQKPDGTVKLLIYYTS RLHSGVPSRFSGSGSGTDYSLTISNLEQEDIAAYFCQQGNTLPWTFGGGTKL EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECGGGGGGGCVIM (SEQ ID NO: 32) with

[0178] CDRL1: RASQDINNYLN (SEQ ID NO: 28),

[0179] CDRL2: YTSRLHS (SEQ ID NO: 29),

[0180] CDRL3: QQGNTLPWT (SEQ ID NO: 30). b.1E12 Humanized Sequences i.1E12 Humanized Heavy Chain 1 (HC-1) aa.1E12 Humanized HC-1 Variable Domain

[0181] One embodiment provides a 1E12 humanized HC-1 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGYMHWVQQAPGKGLEWMGL VDPENGDTIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRRG YFFDYWGQGTLVTVSS (SEQ ID NO:180) with

[0182] CDR-H1 GFNIKDGY (SEQ ID NO:181), 38064467-020PCT

[0183] CDR-H2 VDPENGDT (SEQ ID NO:182),

[0184] CDR-H3 ATSRRGYFFDY (SEQ ID NO:183). bb.1E12 Humanized HC-1, human wild type IgG1 constant domains

[0185] One embodiment provides a 1E12 humanized HC-1, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGYMHWVQQAPGKGLEWMGL VDPENGDTIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:184). cc.1E12 Humanized HC-1, human IgG1 constant domains (DLE)

[0186] One embodiment provides a 1E12 humanized HC-1, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGYMHWVQQAPGKGLEWMGL VDPENGDTIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:185). 39064467-020PCTdd.1E12 Humanized HC-1, human IgG1 constant domains (FES)

[0187] One embodiment provides a 1E12 humanized HC-1, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGYMHWVQQAPGKGLEWMGL VDPENGDTIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:186). ee.1E12 Humanized HC-1, human IgG1 constant domains (AA)

[0188] One embodiment provides a 1E12 humanized HC-1, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGYMHWVQQAPGKGLEWMGL VDPENGDTIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:187). ff.1E12 Humanized HC-1, human IgG4 constant domain (G4P)

[0189] One embodiment provides a 1E12 humanized HC-1, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 40064467-020PCTEVQLVQSGAEVKKPGATVKISCKVSGFNIKDGYMHWVQQAPGKGLEWMGL VDPENGDTIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:188). ii.1E12 Humanized Heavy Chain 2 (HC-2) aa.1E12 Humanized HC-2 Variable Domain

[0190] One embodiment provides a 1E12 humanized HC-2 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGYTFTDGHMHWVQQAPGKGLEWMG WIDPENGDLEYASKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRR GYFFDYWGQGTLVTVSS (SEQ ID NO:189) with

[0191] CDR-H1 GYTFTDGH (SEQ ID NO:190),

[0192] CDR-H2 IDPENGDL (SEQ ID NO:428),

[0193] CDR-H3 ATSRRGYFFDY (SEQ ID NO:183). bb.1E12 Humanized HC-2, human wild type IgG1 constant domains

[0194] One embodiment provides a 1E12 humanized HC-2, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGYTFTDGHMHWVQQAPGKGLEWMG WIDPENGDLEYASKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRR GYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:191). 41064467-020PCTcc.1E12 Humanized HC-2, human IgG1 constant domains (DLE)

[0195] One embodiment provides a 1E12 humanized HC-2, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGYTFTDGHMHWVQQAPGKGLEWMG WIDPENGDLEYASKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRR GYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:192). dd.1E12 Humanized HC-2, human IgG1 constant domains (FES)

[0196] One embodiment provides a 1E12 humanized HC-2, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGYTFTDGHMHWVQQAPGKGLEWMG WIDPENGDLEYASKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRR GYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:193). ee.1E12 Humanized HC-2, human IgG1 constant domains (AA)

[0197] One embodiment provides a 1E12 humanized HC-2, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 42064467-020PCTEVQLVQSGAEVKKPGATVKISCKVSGYTFTDGHMHWVQQAPGKGLEWMG WIDPENGDLEYASKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRR GYFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:194). ff.1E12 Humanized HC-2, human IgG4 constant domain (G4P)

[0198] One embodiment provides a 1E12 humanized HC-2, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGYTFTDGHMHWVQQAPGKGLEWMG WIDPENGDLEYASKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCATSRR GYFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKP SNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:195). iii.1E12 Humanized Heavy Chain 3 (HC-3) aa.1E12 Humanized HC-3 Variable Domain

[0199] One embodiment provides a 1E12 humanized HC-3 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWMGLI DPENGDLIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGYF FDYWGQGTLVTVSS (SEQ ID NO: 196) with

[0200] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0201] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0202] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). 43064467-020PCTbb.1E12 Humanized HC-3, human wild type IgG1 constant domains

[0203] One embodiment provides a 1E12 humanized HC-3, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWMGLI DPENGDLIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:197). cc.1E12 Humanized HC-3, human IgG1 constant domains (DLE)

[0204] One embodiment provides a 1E12 humanized HC-3, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWMGLI DPENGDLIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:198). dd.1E12 Humanized HC-3, human IgG1 constant domains (FES)

[0205] One embodiment provides a 1E12 humanized HC-3, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 44064467-020PCTEVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWMGLI DPENGDLIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:199). ee.1E12 Humanized HC-3, human IgG1 constant domains (AA)

[0206] One embodiment provides a 1E12 humanized HC-3, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWMGLI DPENGDLIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:200). ff.1E12 Humanized HC-3, human IgG4 constant domain (G4P)

[0207] One embodiment provides a 1E12 humanized HC-3, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWMGLI DPENGDLIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNT KVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN 45064467-020PCTGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:201). iv.1E12 Humanized Heavy Chain 4 (HC-4) aa.1E12 Humanized HC-4 Variable Domain

[0208] One embodiment provides a 1E12 humanized HC-4 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCTASGFNIKDGHMHWVQQAPGKGLEWMGW IDPENGDLEYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSS (SEQ ID NO: 202) with

[0209] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0210] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0211] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-4, human wild type IgG1 constant domains

[0212] One embodiment provides a 1E12 humanized HC-4, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCTASGFNIKDGHMHWVQQAPGKGLEWMGW IDPENGDLEYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:203). cc.1E12 Humanized HC-4, human IgG1 constant domains (DLE)

[0213] One embodiment provides a 1E12 humanized HC-4, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 46064467-020PCTEVQLVQSGAEVKKPGATVKISCTASGFNIKDGHMHWVQQAPGKGLEWMGW IDPENGDLEYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:204). dd.1E12 Humanized HC-4, human IgG1 constant domains (FES)

[0214] One embodiment provides a 1E12 humanized HC-4, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCTASGFNIKDGHMHWVQQAPGKGLEWMGW IDPENGDLEYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:205). ee.1E12 Humanized HC-4, human IgG1 constant domains (AA)

[0215] One embodiment provides a 1E12 humanized HC-4, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCTASGFNIKDGHMHWVQQAPGKGLEWMGW IDPENGDLEYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ 47064467-020PCTDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:206). ff.1E12 Humanized HC-4, human IgG4 constant domain (G4P)

[0216] One embodiment provides a 1E12 humanized HC-4, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCTASGFNIKDGHMHWVQQAPGKGLEWMGW IDPENGDLEYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:207). v.1E12 Humanized Heavy Chain 5 (HC-5) aa.1E12 Humanized HC-5 Variable Domain

[0217] One embodiment provides a 1E12 humanized HC-5 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWIGWI DPENGDLEYASKFQGRATLTADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSS (SEQ ID NO: 208) with

[0218] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0219] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0220] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-5, human wild type IgG1 constant domains

[0221] One embodiment provides a 1E12 humanized HC-5, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 48064467-020PCTEVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWIGWI DPENGDLEYASKFQGRATLTADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:209). cc.1E12 Humanized HC-5, human IgG1 constant domains (DLE)

[0222] One embodiment provides a 1E12 humanized HC-5, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWIGWI DPENGDLEYASKFQGRATLTADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:210). dd.1E12 Humanized HC-5, human IgG1 constant domains (FES)

[0223] One embodiment provides a 1E12 humanized HC-5, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWIGWI DPENGDLEYASKFQGRATLTADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD 49064467-020PCTWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:211). ee.1E12 Humanized HC-5, human IgG1 constant domains (AA)

[0224] One embodiment provides a 1E12 humanized HC-5, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWIGWI DPENGDLEYASKFQGRATLTADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:212). ff.1E12 Humanized HC-5, human IgG4 constant domain (G4P)

[0225] One embodiment provides a 1E12 humanized HC-5, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVQSGAEVKKPGATVKISCKVSGFNIKDGHMHWVQQAPGKGLEWIGWI DPENGDLEYASKFQGRATLTADTSTDTAYMELSSLRSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:213). 50064467-020PCTvi.1E12 Humanized Heavy Chain 6 (HC-6) aa.1E12 Humanized HC-6 Variable Domain

[0226] One embodiment provides a 1E12 humanized HC-6 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAVSGFNIKDGHMHWIRQAPGKGLEWVAWI DPENGDLEYASKFQGRITISRDDSKNTFYLQMNSLRAEDTAVYYCTTSRRGYF FDYWGQGTLVTVSS (SEQ ID NO:214) with

[0227] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0228] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0229] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-6, human wild type IgG1 constant domains

[0230] One embodiment provides a 1E12 humanized HC-6, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAVSGFNIKDGHMHWIRQAPGKGLEWVAWI DPENGDLEYASKFQGRITISRDDSKNTFYLQMNSLRAEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:215). cc.1E12 Humanized HC-6, human IgG1 constant domains (DLE)

[0231] One embodiment provides a 1E12 humanized HC-6, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAVSGFNIKDGHMHWIRQAPGKGLEWVAWI DPENGDLEYASKFQGRITISRDDSKNTFYLQMNSLRAEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT 51064467-020PCTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:216). dd.1E12 Humanized HC-6, human IgG1 constant domains (FES)

[0232] One embodiment provides a 1E12 humanized HC-6, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAVSGFNIKDGHMHWIRQAPGKGLEWVAWI DPENGDLEYASKFQGRITISRDDSKNTFYLQMNSLRAEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:217). ee.1E12 Humanized HC-6, human IgG1 constant domains (AA)

[0233] One embodiment provides a 1E12 humanized HC-6, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAVSGFNIKDGHMHWIRQAPGKGLEWVAWI DPENGDLEYASKFQGRITISRDDSKNTFYLQMNSLRAEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:218). 52064467-020PCTff.1E12 Humanized HC-6, human IgG4 constant domain (G4P)

[0234] One embodiment provides a 1E12 humanized HC-6, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLVESGGGLVQPGGSLRLSCAVSGFNIKDGHMHWIRQAPGKGLEWVAWI DPENGDLEYASKFQGRITISRDDSKNTFYLQMNSLRAEDTAVYYCTTSRRGYF FDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNT KVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:219). vii.1E12 Humanized Heavy Chain 7 (HC-7) aa.1E12 Humanized HC-7 Variable Domain

[0235] One embodiment provides a 1E12 humanized HC-7 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKRPGASVKLSCTASGFNIKDGHMHWVRQAPGQGLEWIGWI DPENGDLEYAQKFQGRVTLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSS (SEQ ID NO:220) with

[0236] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0237] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0238] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-7, human wild type IgG1 constant domains

[0239] One embodiment provides a 1E12 humanized HC-7, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKRPGASVKLSCTASGFNIKDGHMHWVRQAPGQGLEWIGWI DPENGDLEYAQKFQGRVTLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN 53064467-020PCTTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:221). cc.1E12 Humanized HC-7, human IgG1 constant domains (DLE)

[0240] One embodiment provides a 1E12 humanized HC-7, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKRPGASVKLSCTASGFNIKDGHMHWVRQAPGQGLEWIGWI DPENGDLEYAQKFQGRVTLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:222). dd.1E12 Humanized HC-7, human IgG1 constant domains (FES)

[0241] One embodiment provides a 1E12 humanized HC-7, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKRPGASVKLSCTASGFNIKDGHMHWVRQAPGQGLEWIGWI DPENGDLEYAQKFQGRVTLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:223). 54064467-020PCTee.1E12 Humanized HC-7, human IgG1 constant domains (AA)

[0242] One embodiment provides a 1E12 humanized HC-7, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKRPGASVKLSCTASGFNIKDGHMHWVRQAPGQGLEWIGWI DPENGDLEYAQKFQGRVTLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:224). ff.1E12 Humanized HC-7, human IgG4 constant domain (G4P)

[0243] One embodiment provides a 1E12 humanized HC-7, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKRPGASVKLSCTASGFNIKDGHMHWVRQAPGQGLEWIGWI DPENGDLEYAQKFQGRVTLTADTSSNTAYLQLSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:225). viii.1E12 Humanized Heavy Chain 8 (HC-8) aa.1E12 Humanized HC-8 Variable Domain

[0244] One embodiment provides a 1E12 humanized HC-8 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 55064467-020PCTQVQLVQSGAEVKKPGASVKVSCKASGYTFTDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSS (SEQ ID NO:226) with

[0245] CDR-H1 GYTFTDGH (SEQ ID NO: 190),

[0246] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0247] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-8, human wild type IgG1 constant domains

[0248] One embodiment provides a 1E12 humanized HC-8, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGYTFTDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:227). cc.1E12 Humanized HC-8, human IgG1 constant domains (DLE)

[0249] One embodiment provides a 1E12 humanized HC-8, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGYTFTDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:228). 56064467-020PCTdd.1E12 Humanized HC-8, human IgG1 constant domains (FES)

[0250] One embodiment provides a 1E12 humanized HC-8, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGYTFTDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:229). ee.1E12 Humanized HC-8, human IgG1 constant domains (AA)

[0251] One embodiment provides a 1E12 humanized HC-8, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGYTFTDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:230). ff.1E12 Humanized HC-8, human IgG4 constant domain (G4P)

[0252] One embodiment provides a 1E12 humanized HC-8, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 57064467-020PCTQVQLVQSGAEVKKPGASVKVSCKASGYTFTDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:231). ix.1E12 Humanized Heavy Chain 9 (HC-9) aa.1E12 Humanized HC-9 Variable Domain

[0253] One embodiment provides a 1E12 humanized HC-9 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRATLTADTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSS (SEQ ID NO:232) with

[0254] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0255] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0256] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-9, human wild type IgG1 constant domains

[0257] One embodiment provides a 1E12 humanized HC-9, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRATLTADTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:233). 58064467-020PCTcc.1E12 Humanized HC-9, human IgG1 constant domains (DLE)

[0258] One embodiment provides a 1E12 humanized HC-9, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRATLTADTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:234). dd.1E12 Humanized HC-9, human IgG1 constant domains (FES)

[0259] One embodiment provides a 1E12 humanized HC-9, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRATLTADTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:235). ee.1E12 Humanized HC-9, human IgG1 constant domains (AA)

[0260] One embodiment provides a 1E12 humanized HC-9, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 59064467-020PCTQVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRATLTADTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:236). ff.1E12 Humanized HC-9, human IgG4 constant domain (G4P)

[0261] One embodiment provides a 1E12 humanized HC-9, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWIGW IDPENGDLEYASKFQGRATLTADTSSNTAYLELSSLTSEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:237). x.1E12 Humanized Heavy Chain 10 (HC-10) aa.1E12 Humanized HC-10 Variable Domain

[0262] One embodiment provides a 1E12 humanized HC-10 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGYMHWVRQAPGQGLEWMG WIDPENGDTEYAQKFQGRVTLTRDTSINTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSS (SEQ ID NO:238) with

[0263] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0264] CDR-H2 IDPENGDT (SEQ ID NO: 239),

[0265] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). 60064467-020PCTbb.1E12 Humanized HC-10, human wild type IgG1 constant domains

[0266] One embodiment provides a 1E12 humanized HC-10, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGYMHWVRQAPGQGLEWMG WIDPENGDTEYAQKFQGRVTLTRDTSINTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:240). cc.1E12 Humanized HC-10, human IgG1 constant domains (DLE)

[0267] One embodiment provides a 1E12 humanized HC-10, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGYMHWVRQAPGQGLEWMG WIDPENGDTEYAQKFQGRVTLTRDTSINTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:241). dd.1E12 Humanized HC-10, human IgG1 constant domains (FES)

[0268] One embodiment provides a 1E12 humanized HC-10, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 61064467-020PCTQVQLVQSGAEVKKPGASVKVSCKASGFNIKDGYMHWVRQAPGQGLEWMG WIDPENGDTEYAQKFQGRVTLTRDTSINTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:242). ee.1E12 Humanized HC-10, human IgG1 constant domains (AA)

[0269] One embodiment provides a 1E12 humanized HC-10, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGYMHWVRQAPGQGLEWMG WIDPENGDTEYAQKFQGRVTLTRDTSINTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:243). ff.1E12 Humanized HC-10, human IgG4 constant domain (G4P)

[0270] One embodiment provides a 1E12 humanized HC-10, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGYMHWVRQAPGQGLEWMG WIDPENGDTEYAQKFQGRVTLTRDTSINTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL 62064467-020PCTNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:244). xi.1E12 Humanized Heavy Chain 11 (HC-11) aa.1E12 Humanized HC-11 Variable Domain

[0271] One embodiment provides a 1E12 humanized HC-11 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSS (SEQ ID NO:245) with

[0272] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0273] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0274] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-11, human wild type IgG1 constant domains

[0275] One embodiment provides a 1E12 humanized HC-11, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:246). cc.1E12 Humanized HC-11, human IgG1 constant domains (DLE)

[0276] One embodiment provides a 1E12 humanized HC-11, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 63064467-020PCTQVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:247). dd.1E12 Humanized HC-11, human IgG1 constant domains (FES)

[0277] One embodiment provides a 1E12 humanized HC-11, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:248). ee.1E12 Humanized HC-11, human IgG1 constant domains (AA)

[0278] One embodiment provides a 1E12 humanized HC-11, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH 64064467-020PCTQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:249). ff.1E12 Humanized HC-11, human IgG4 constant domain (G4P)

[0279] One embodiment provides a 1E12 humanized HC-11, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCKASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:250). xii.1E12 Humanized Heavy Chain 12 (HC-12) aa.1E12 Humanized HC-12 Variable Domain

[0280] One embodiment provides a 1E12 humanized HC-12 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCTASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSS (SEQ ID NO:251) with

[0281] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0282] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0283] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-12, human wild type IgG1 constant domains

[0284] One embodiment provides a 1E12 humanized HC-12, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 65064467-020PCTQVQLVQSGAEVKKPGASVKVSCTASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:252). cc.1E12 Humanized HC-12, human IgG1 constant domains (DLE)

[0285] One embodiment provides a 1E12 humanized HC-12, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCTASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:253). dd.1E12 Humanized HC-12, human IgG1 constant domains (FES)

[0286] One embodiment provides a 1E12 humanized HC-12, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCTASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ 66064467-020PCTDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:254). ee.1E12 Humanized HC-12, human IgG1 constant domains (AA)

[0287] One embodiment provides a 1E12 humanized HC-12, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCTASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:255). ff.1E12 Humanized HC-12, human IgG4 constant domain (G4P)

[0288] One embodiment provides a 1E12 humanized HC-12, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGASVKVSCTASGFNIKDGHMHWVRQAPGQGLEWMG WIDPENGDLEYAQKFQGRVTLTRDTSSNTAYLELSSLTSEDTAVYYCTTSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:256). 67064467-020PCTxiii.1E12 Humanized Heavy Chain 13 (HC-13) aa.1E12 Humanized HC-13 Variable Domain

[0289] One embodiment provides a 1E12 humanized HC-13 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGHMHWVRQAPGKGLEWVSWI DPENGDLEYASKFQGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRGY FFDYWGQGTLVTVSS (SEQ ID NO:257) with

[0290] CDR-H1 GFTFSDGH (SEQ ID NO:258),

[0291] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0292] CDR-H3 AKSRRGYFFDY (SEQ ID NO:259). bb.1E12 Humanized HC-13, human wild type IgG1 constant domains

[0293] One embodiment provides a 1E12 humanized HC-13, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGHMHWVRQAPGKGLEWVSWI DPENGDLEYASKFQGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:260). cc.1E12 Humanized HC-13, human IgG1 constant domains (DLE)

[0294] One embodiment provides a 1E12 humanized HC-13, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGHMHWVRQAPGKGLEWVSWI DPENGDLEYASKFQGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN 68064467-020PCTTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:261). dd.1E12 Humanized HC-13, human IgG1 constant domains (FES)

[0295] One embodiment provides a 1E12 humanized HC-13, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGHMHWVRQAPGKGLEWVSWI DPENGDLEYASKFQGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:262). ee.1E12 Humanized HC-13, human IgG1 constant domains (AA)

[0296] One embodiment provides a 1E12 humanized HC-13, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGHMHWVRQAPGKGLEWVSWI DPENGDLEYASKFQGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:263). 69064467-020PCTff.1E12 Humanized HC-13, human IgG4 constant domain (G4P)

[0297] One embodiment provides a 1E12 humanized HC-13, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFTFSDGHMHWVRQAPGKGLEWVSWI DPENGDLEYASKFQGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:264). xiv.1E12 Humanized Heavy Chain 14 (HC-14) aa.1E12 Humanized HC-14 Variable Domain

[0298] One embodiment provides a 1E12 humanized HC-14 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGAMSWVRQAPGKGLEWVSAI DPENGDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRG YFFDYWGQGTLVTVSS (SEQ ID NO:265) with

[0299] CDR-H1 GFNIKDGA (SEQ ID NO:266),

[0300] CDR-H2 IDPENGDT (SEQ ID NO: 239),

[0301] CDR-H3 AKSRRGYFFDY (SEQ ID NO:259). bb.1E12 Humanized HC-14, human wild type IgG1 constant domains

[0302] One embodiment provides a 1E12 humanized HC-14, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGAMSWVRQAPGKGLEWVSAI DPENGDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS 70064467-020PCTNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:267). cc.1E12 Humanized HC-14, human IgG1 constant domains (DLE)

[0303] One embodiment provides a 1E12 humanized HC-14, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGAMSWVRQAPGKGLEWVSAI DPENGDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:268). dd.1E12 Humanized HC-14, human IgG1 constant domains (FES)

[0304] One embodiment provides a 1E12 humanized HC-14, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGAMSWVRQAPGKGLEWVSAI DPENGDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:269). 71064467-020PCTee.1E12 Humanized HC-14, human IgG1 constant domains (AA)

[0305] One embodiment provides a 1E12 humanized HC-14, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGAMSWVRQAPGKGLEWVSAI DPENGDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:270). ff.1E12 Humanized HC-14, human IgG4 constant domain (G4P)

[0306] One embodiment provides a 1E12 humanized HC-14, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGAMSWVRQAPGKGLEWVSAI DPENGDTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSRRG YFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:271). xv.1E12 Humanized Heavy Chain 15 (HC-15) aa.1E12 Humanized HC-15 Variable Domain

[0307] One embodiment provides a 1E12 humanized HC-15 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 72064467-020PCTEVQLLESGGGLVQPGGSLRLSCAASGFNIKDGHMSWVRQAPGKGLEWVSAI DPENGDLYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSS (SEQ ID NO:272) with

[0308] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0309] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0310] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-15, human wild type IgG1 constant domains

[0311] One embodiment provides a 1E12 humanized HC-15, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGHMSWVRQAPGKGLEWVSAI DPENGDLYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:273). cc.1E12 Humanized HC-15, human IgG1 constant domains (DLE)

[0312] One embodiment provides a 1E12 humanized HC-15, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGHMSWVRQAPGKGLEWVSAI DPENGDLYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:274). 73064467-020PCTdd.1E12 Humanized HC-15, human IgG1 constant domains (FES)

[0313] One embodiment provides a 1E12 humanized HC-15, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGHMSWVRQAPGKGLEWVSAI DPENGDLYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:275). ee.1E12 Humanized HC-15, human IgG1 constant domains (AA)

[0314] One embodiment provides a 1E12 humanized HC-15, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFNIKDGHMSWVRQAPGKGLEWVSAI DPENGDLYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:276). ff.1E12 Humanized HC-15, human IgG4 constant domain (G4P)

[0315] One embodiment provides a 1E12 humanized HC-15, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 74064467-020PCTEVQLLESGGGLVQPGGSLRLSCAASGFNIKDGHMSWVRQAPGKGLEWVSAI DPENGDLYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:277). xvi.1E12 Humanized Heavy Chain 16 (HC-16) aa.1E12 Humanized HC-16 Variable Domain

[0316] One embodiment provides a 1E12 humanized HC-16 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCTASGFNIKDGHMHWVRQAPGKGLEWVSWI DPENGDLEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSS (SEQ ID NO:278) with

[0317] CDR-H1 GFNIKDGH (SEQ ID NO:429),

[0318] CDR-H2 IDPENGDL (SEQ ID NO:430),

[0319] CDR-H3 TTSRRGYFFDY (SEQ ID NO:431). bb.1E12 Humanized HC-16, human wild type IgG1 constant domains

[0320] One embodiment provides a 1E12 humanized HC-16, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCTASGFNIKDGHMHWVRQAPGKGLEWVSWI DPENGDLEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:279). 75064467-020PCTcc.1E12 Humanized HC-16, human IgG1 constant domains (DLE)

[0321] One embodiment provides a 1E12 humanized HC-16, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCTASGFNIKDGHMHWVRQAPGKGLEWVSWI DPENGDLEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:280). dd.1E12 Humanized HC-16, human IgG1 constant domains (FES)

[0322] One embodiment provides a 1E12 humanized HC-16, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCTASGFNIKDGHMHWVRQAPGKGLEWVSWI DPENGDLEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:281). ee.1E12 Humanized HC-16, human IgG1 constant domains (AA)

[0323] One embodiment provides a 1E12 humanized HC-16, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 76064467-020PCTEVQLLESGGGLVQPGGSLRLSCTASGFNIKDGHMHWVRQAPGKGLEWVSWI DPENGDLEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:282). ff.1E12 Humanized HC-16, human IgG4 constant domain (G4P)

[0324] One embodiment provides a 1E12 humanized HC-16, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCTASGFNIKDGHMHWVRQAPGKGLEWVSWI DPENGDLEYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTTSRRGY FFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:283). xvii.1E12 Humanized Light Chain 1 (LC-1) aa.1E12 Humanized LC-1 variable region

[0325] One embodiment provides a 1E12 humanized LC-1 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLAWYQQKPGKVPKLLIYYTST LQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI K (SEQ ID NO:284) with

[0326] CDR-L1 QDINNY (SEQ ID NO:434),

[0327] CDR-L2 YTS (SEQ ID NO:285),

[0328] CDR-L3 QQGNTLPWT (SEQ ID NO: 30). 77064467-020PCTbb.1E12 humanized LC-1, human kappa wild type constant domain

[0329] One embodiment provides a 1E12 humanized LC-1, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLAWYQQKPGKVPKLLIYYTST LQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GEC (SEQ ID NO:286).

[0330] The underlined sequence is the light chain constant domain (wild type, kappa). cc.1E12 Humanized LC-1, human kappa wild type constant domain (CAAX)

[0331] One embodiment provides a 1E12 humanized LC-1, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLAWYQQKPGKVPKLLIYYTST LQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GECGGGGGGGCVIM (SEQ ID NO:287). xviii.1E12 Humanized Light Chain 2 (LC-2) aa.1E12 Humanized LC-2 variable region

[0332] One embodiment provides a 1E12 humanized LC-2 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKVPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI K (SEQ ID NO:288) with

[0333] CDR-L1 QDINNY (SEQ ID NO:434),

[0334] CDR-L2 YTS (SEQ ID NO:285),

[0335] CDR-L3 QQGNTLPWT (SEQ ID NO: 30). 78064467-020PCTbb.1E12 humanized LC-2, human kappa wild type constant domain

[0336] One embodiment provides a 1E12 humanized LC-2, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKVPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GEC (SEQ ID NO:289).

[0337] The underlined sequence is the light chain constant domain (wild type, kappa). cc.1E12 Humanized LC-2, human kappa wild type constant domain (CAAX)

[0338] One embodiment provides a 1E12 humanized LC-2, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKVPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GECGGGGGGGCVIM (SEQ ID NO:290). xix.1E12 Humanized Light Chain 1 (LC-3) aa.1E12 Humanized LC-3 variable region

[0339] One embodiment provides a 1E12 humanized LC-3 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTISCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISNLQPEDIATYFCQQGNTLPWTFGQGTKVEIK (SEQ ID NO:291) with

[0340] CDR-L1 QDINNY (SEQ ID NO:434),

[0341] CDR-L2 YTS (SEQ ID NO:285),

[0342] CDR-L3 QQGNTLPWT (SEQ ID NO: 30). 79064467-020PCTbb.1E12 humanized LC-3, human kappa wild type constant domain

[0343] One embodiment provides a 1E12 humanized LC-3, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTISCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISNLQPEDIATYFCQQGNTLPWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC (SEQ ID NO:292).

[0344] The underlined sequence is the light chain constant domain (wild type, kappa). cc. Chimeric LC-3, human kappa wild type constant domain (CAAX)

[0345] One embodiment provides a 1E12 humanized LC-3, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTISCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISNLQPEDIATYFCQQGNTLPWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG ECGGGGGGGCVIM (SEQ ID NO:293). xx.1E12 Humanized Light Chain 1 (LC-4) aa.1E12 Humanized LC-4 variable region

[0346] One embodiment provides a 1E12 humanized LC-4 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK (SEQ ID NO:294) with

[0347] CDR-L1 QDINNY (SEQ ID NO:434),

[0348] CDR-L2 YTS (SEQ ID NO:285),

[0349] CDR-L3 QQGNTLPWT (SEQ ID NO: 30). 80064467-020PCTbb.1E12 humanized LC-4, human kappa wild type constant domain

[0350] One embodiment provides a 1E12 humanized LC-4, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC (SEQ ID NO:295).

[0351] The underlined sequence is the light chain constant domain (wild type, kappa). cc.1E12 Humanized LC-4, human kappa wild type constant domain (CAAX)

[0352] One embodiment provides a 1E12 humanized LC-4, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG ECGGGGGGGCVIM (SEQ ID NO:296). xxi.1E12 Humanized Light Chain 5 (LC-5) aa.1E12 Humanized LC-5 variable region

[0353] One embodiment provides a 1E12 humanized LC-5 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKVPKLLIYYTSR LHSGVPSRFSGSGSGTDYTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI K (SEQ ID NO:297) with

[0354] CDR-L1 QDINNY (SEQ ID NO: 434),

[0355] CDR-L2 YTS (SEQ ID NO:285),

[0356] CDR-L3 QQGNTLPWT (SEQ ID NO: 30). 81064467-020PCTbb.1E12 humanized LC-5, human kappa wild type constant domain

[0357] One embodiment provides a 1E12 humanized LC-5, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKVPKLLIYYTSR LHSGVPSRFSGSGSGTDYTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GEC (SEQ ID NO:298).

[0358] The underlined sequence is the light chain constant domain (wild type, kappa). cc.1E12 Humanized LC-5, human kappa wild type constant domain (CAAX)

[0359] One embodiment provides a 1E12 humanized LC-5, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKVPKLLIYYTSR LHSGVPSRFSGSGSGTDYTLTISSLQPEDVATYYCQQGNTLPWTFGQGTKVEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GECGGGGGGGCVIM (SEQ ID NO:299). xxii.1E12 Humanized Light Chain 6 (LC-6) aa.1E12 Humanized LC-6 variable region

[0360] One embodiment provides a 1E12 humanized LC-6 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQLTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK (SEQ ID NO:300) with

[0361] CDR-L1 QDINNY (SEQ ID NO: 434),

[0362] CDR-L2 YTS (SEQ ID NO:285),

[0363] CDR-L3 QQGNTLPWT (SEQ ID NO: 30). 82064467-020PCTbb.1E12 humanized LC-6, human kappa wild type constant domain

[0364] One embodiment provides a 1E12 humanized LC-6, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQLTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC (SEQ ID NO:301).

[0365] The underlined sequence is the light chain constant domain (wild type, kappa). cc.1E12 Humanized LC-6, human kappa wild type constant domain (CAAX)

[0366] One embodiment provides a 1E12 humanized LC-6, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQLTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG ECGGGGGGGCVIM (SEQ ID NO:302). xxiii.1E12 Humanized Light Chain 7 (LC-7) aa.1E12 Humanized LC-7 variable region

[0367] One embodiment provides a 1E12 humanized LC-7 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEI K (SEQ ID NO:303) with

[0368] CDR-L1 QDINNY (SEQ ID NO: 434),

[0369] CDR-L2 YTS (SEQ ID NO:285),

[0370] CDR-L3 QQGNTLPWT (SEQ ID NO: 30). 83064467-020PCTbb.1E12 humanized LC-7, human kappa wild type constant domain

[0371] One embodiment provides a 1E12 humanized LC-7, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GEC (SEQ ID NO:304).

[0372] The underlined sequence is the light chain constant domain (wild type, kappa). cc.1E12 Humanized LC-7, human kappa wild type constant domain (CAAX)

[0373] One embodiment provides a 1E12 humanized LC-7, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSR LHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GECGGGGGGGCVIM (SEQ ID NO:305). xxiv.1E12 Humanized Light Chain 8 (LC-8) aa.1E12 Humanized LC-1 variable region

[0374] One embodiment provides a 1E12 humanized LC-8 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSS LQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK (SEQ ID NO:306) with

[0375] CDR-L1 QDINNY (SEQ ID NO: 434),

[0376] CDR-L2 YTS (SEQ ID NO:285),

[0377] CDR-L3 QQGNTLPWT (SEQ ID NO: 30). 84064467-020PCTbb.1E12 humanized LC-8, human kappa wild type constant domain

[0378] One embodiment provides a 1E12 humanized LC-8, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSS LQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC (SEQ ID NO:307).

[0379] The underlined sequence is the light chain constant domain (wild type, kappa). cc.1E12 Humanized LC-8, human kappa wild type constant domain (CAAX)

[0380] One embodiment provides a 1E12 humanized LC-8, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQSPSSLSASVGDRVTITCRASQDINNYLNWYQQKPGKAPKLLIYYTSS LQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPWTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG ECGGGGGGGCVIM (SEQ ID NO:308). c.1H11 Sequences i.1H11 Heavy Chain aa.1H11 Murine heavy chain variable region

[0381] One embodiment provides a 1H11 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVRLSCKASGYTFTNYWMHWLKQRPGRGLEWIGE IDPSDNSTYYSHEFSGKATLTVDKSSSTAYMQLSSLTSDDSAVYYCARSGGD GYYEGVDYWGQGTTLTVSS (SEQ ID NO: 33) with

[0382] CDRH1: NYWMH (SEQ ID NO: 34),

[0383] CDRH2: EIDPSDNSTYYSHEFSG (SEQ ID NO: 35), 85064467-020PCT

[0384] CDRH3: SGGDGYYEGVDY (SEQ ID NO: 36). bb.1H11 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0385] One embodiment provides a 1H11 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVRLSCKASGYTFTNYWMHWLKQRPGRGLEWIGEI DPSDNSTYYSHEFSGKATLTVDKSSSTAYMQLSSLTSDDSAVYYCARSGGDG YYEGVDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 37) with

[0386] CDRH1: NYWMH (SEQ ID NO: 34),

[0387] CDRH2: EIDPSDNSTYYSHEFSG (SEQ ID NO: 35),

[0388] CDRH3: SGGDGYYEGVDY (SEQ ID NO: 36).

[0389] The bold italicized sequence is the heavy chain constant domain (wild type). cc.1H11 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0390] One embodiment provides a 1H11 chimeric heavy chain, human IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVRLSCKASGYTFTNYWMHWLKQRPGRGLEWIGE IDPSDNSTYYSHEFSGKATLTVDKSSSTAYMQLSSLTSDDSAVYYCARSGGD GYYEGVDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRT PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELT 86064467-020PCTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 38) with

[0391] CDRH1: NYWMH (SEQ ID NO: 34),

[0392] CDRH2: EIDPSDNSTYYSHEFSG (SEQ ID NO: 35),

[0393] CDRH3: SGGDGYYEGVDY (SEQ ID NO: 36).

[0394] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations. dd.1H11 Chimeric Heavy Chain, human IgG1 constant domains (FES)

[0395] One embodiment provides a 1H11 chimeric heavy chain, human IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVRLSCKASGYTFTNYWMHWLKQRPGRGLEWIGE IDPSDNSTYYSHEFSGKATLTVDKSSSTAYMQLSSLTSDDSAVYYCARSGGD GYYEGVDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTP EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 39) with

[0396] CDRH1: NYWMH (SEQ ID NO: 34),

[0397] CDRH2: EIDPSDNSTYYSHEFSG (SEQ ID NO: 35),

[0398] CDRH3: SGGDGYYEGVDY (SEQ ID NO: 36).

[0399] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. ee. Chimeric Heavy Chain, human IgG1 constant domains (AA)

[0400] One embodiment provides a 1H11 chimeric heavy chain, human IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 87064467-020PCTQVQLQQPGAELVKPGASVRLSCKASGYTFTNYWMHWLKQRPGRGLEWIGE IDPSDNSTYYSHEFSGKATLTVDKSSSTAYMQLSSLTSDDSAVYYCARSGGD GYYEGVDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVN HKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRT PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 40) with

[0401] CDRH1: NYWMH (SEQ ID NO: 34),

[0402] CDRH2: EIDPSDNSTYYSHEFSG (SEQ ID NO: 35),

[0403] CDRH3: SGGDGYYEGVDY (SEQ ID NO: 36).

[0404] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. ff.1H11 Chimeric Heavy Chain, human IgG1 constant domains (G4P)

[0405] One embodiment provides a 1H11 chimeric heavy chain, human IgG1 constant domains (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVRLSCKASGYTFTNYWMHWLKQRPGRGLEWIGE IDPSDNSTYYSHEFSGKATLTVDKSSSTAYMQLSSLTSDDSAVYYCARSGGD GYYEGVDYWGQGTTLTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVD HKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 41) with

[0406] CDRH1: NYWMH (SEQ ID NO: 34),

[0407] CDRH2: EIDPSDNSTYYSHEFSG (SEQ ID NO: 35),

[0408] CDRH3: SGGDGYYEGVDY (SEQ ID NO: 36).

[0409] The dash underlined sequence is the IgG4 heavy chain constant domain. 88064467-020PCTii.1H11 Light Chain aa.1H11 Murine light chain variable region

[0410] One embodiment provides a 1H11 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVVMTQTPLTLSVTIGQPASISCKSSQSLLYGNGETYLNWLLQRPGQSPKRLI YLVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCLQSTHFPQTFGG GTKLEIK (SEQ ID NO: 42) with

[0411] CDRL1: KSSQSLLYGNGETYLN (SEQ ID NO: 43),

[0412] CDRL2: LVSKLDS (SEQ ID NO: 44),

[0413] CDRL3: LQSTHFPQT (SEQ ID NO: 45). bb.1H11 Chimeric Light Chain, human kappa wild type constant domain

[0414] One embodiment provides a 1H11 chimeric heavy chain, human kappa wild type constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVVMTQTPLTLSVTIGQPASISCKSSQSLLYGNGETYLNWLLQRPGQSPKRLI YLVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCLQSTHFPQTFGG GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGEC (SEQ ID NO: 46) with

[0415] CDRL1: KSSQSLLYGNGETYLN (SEQ ID NO: 43),

[0416] CDRL2: LVSKLDS (SEQ ID NO: 44),

[0417] CDRL3: LQSTHFPQT (SEQ ID NO: 45).

[0418] The underlined sequence is the light chain constant domain (wild type, kappa). cc.1H11 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0419] One embodiment provides a 1H11 chimeric heavy chain, human kappa wild type constant domains (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 89064467-020PCTDVVMTQTPLTLSVTIGQPASISCKSSQSLLYGNGETYLNWLLQRPGQSPKRLI YLVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCLQSTHFPQTFGG GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGECGGGGGGGCVIM (SEQ ID NO: 47) with

[0420] CDRL1: KSSQSLLYGNGETYLN (SEQ ID NO: 43),

[0421] CDRL2: LVSKLDS (SEQ ID NO: 44),

[0422] CDRL3: LQSTHFPQT (SEQ ID NO: 45). d.3C7 Sequences i.3C7 Heavy Chain aa.3C7 Murine heavy chain variable region

[0423] One embodiment provides a 3C7 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWINWLKQRPGPGLKWIGSIS PETNITDYNEMFKTKATLTVDTSSNTAYMQLNSLTSDDSAVYYCAIFHSNSF AYWGQGTLVTVSA (SEQ ID NO: 48) with

[0424] CDRH1: NYWIN (SEQ ID NO: 49),

[0425] CDRH2: SISPETNITDYNEMFKT (SEQ ID NO: 50),

[0426] CDRH3: FHSNSFAY (SEQ ID NO: 51). bb.3C7 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0427] One embodiment provides a 3C7 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWINWLKQRPGPGLKWIGSIS PETNITDYNEMFKTKATLTVDTSSNTAYMQLNSLTSDDSAVYYCAIFHSNSFA YWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT 90064467-020PCTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 52) with

[0428] CDRH1: NYWIN (SEQ ID NO: 49),

[0429] CDRH2: SISPETNITDYNEMFKT (SEQ ID NO: 50),

[0430] CDRH3: FHSNSFAY (SEQ ID NO: 51).

[0431] The bold italicized sequence is the heavy chain constant domain (wild type). cc.3C7 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0432] One embodiment provides a 3C7 chimeric heavy chain, human IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWINWLKQRPGPGLKWIGSIS PETNITDYNEMFKTKATLTVDTSSNTAYMQLNSLTSDDSAVYYCAIFHSNSF AYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 53) with

[0433] CDRH1: NYWIN (SEQ ID NO: 49),

[0434] CDRH2: SISPETNITDYNEMFKT (SEQ ID NO: 50),

[0435] CDRH3: FHSNSFAY (SEQ ID NO: 51).

[0436] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations dd.3C7 Chimeric Heavy Chain, human IgG1 constant domains (FES)

[0437] One embodiment provides a 3C7 chimeric heavy chain, human IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 91064467-020PCTQVQLQQPGAELVKPGASVKLSCKASGYTFTNYWINWLKQRPGPGLKWIGSIS PETNITDYNEMFKTKATLTVDTSSNTAYMQLNSLTSDDSAVYYCAIFHSNSF AYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 54) with

[0438] CDRH1: NYWIN (SEQ ID NO: 49),

[0439] CDRH2: SISPETNITDYNEMFKT (SEQ ID NO: 50),

[0440] CDRH3: FHSNSFAY (SEQ ID NO: 51).

[0441] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. ee.3C7 Chimeric Heavy Chain, human IgG1 constant domains (AA)

[0442] One embodiment provides a 3C7 chimeric heavy chain, human IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWINWLKQRPGPGLKWIGSIS PETNITDYNEMFKTKATLTVDTSSNTAYMQLNSLTSDDSAVYYCAIFHSNSF AYWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 55) with

[0443] CDRH1: NYWIN (SEQ ID NO: 49),

[0444] CDRH2: SISPETNITDYNEMFKT (SEQ ID NO: 50),

[0445] CDRH3: FHSNSFAY (SEQ ID NO: 51). 92064467-020PCT

[0446] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. ff.3C7 Chimeric Heavy Chain, human IgG1 constant domains (G4P)

[0447] One embodiment provides a 3C7 chimeric heavy chain, human IgG4 constant domains (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWINWLKQRPGPGLKWIGSIS PETNITDYNEMFKTKATLTVDTSSNTAYMQLNSLTSDDSAVYYCAIFHSNSF AYWGQGTLVTVSAASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTK VDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGK EYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 56) with

[0448] CDRH1: NYWIN (SEQ ID NO: 49),

[0449] CDRH2: SISPETNITDYNEMFKT (SEQ ID NO: 50),

[0450] CDRH3: FHSNSFAY (SEQ ID NO: 51).

[0451] The dash underlined sequence is the IgG4 heavy chain constant domain. ii.3C7 Light Chain aa.3C7 Murine light chain variable region

[0452] One embodiment provides a 3C7 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQSPKSMSISVGDRVTLTCKASENVGTYVSWYQQKAEQSPKLLIYGTS NRYTGVPDRFTGSGSATDFTLTISNVQADDLADYYCGQSSSYTFGSGTKLEIK (SEQ ID NO: 57) with

[0453] CDRL1: KASENVGTYVS (SEQ ID NO: 58),

[0454] CDRL2: GTSNRYT (SEQ ID NO: 59),

[0455] CDRL3: GQSSSYT (SEQ ID NO: 60). 93064467-020PCTbb.3C7 Chimeric Light Chain, human kappa wild type constant domain

[0456] One embodiment provides a 3C7 chimeric Light chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQSPKSMSISVGDRVTLTCKASENVGTYVSWYQQKAEQSPKLLIYGTS NRYTGVPDRFTGSGSATDFTLTISNVQADDLADYYCGQSSSYTFGSGTKLEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC (SEQ ID NO: 61) with

[0457] CDRL1: KASENVGTYVS (SEQ ID NO: 58),

[0458] CDRL2: GTSNRYT (SEQ ID NO: 59),

[0459] CDRL3: GQSSSYT (SEQ ID NO: 60).

[0460] The underlined sequence is the light chain constant domain (wild type, kappa). cc.3C7 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0461] One embodiment provides a 3C7 chimeric Light chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQSPKSMSISVGDRVTLTCKASENVGTYVSWYQQKAEQSPKLLIYGTS NRYTGVPDRFTGSGSATDFTLTISNVQADDLADYYCGQSSSYTFGSGTKLEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG ECGGGGGGGCVIM (SEQ ID NO: 62) with

[0462] CDRL1: KASENVGTYVS (SEQ ID NO: 58),

[0463] CDRL2: GTSNRYT (SEQ ID NO: 59),

[0464] CDRL3: GQSSSYT (SEQ ID NO: 60).

[0465] The double underlined sequence is the light chain constant domain with CAAX Sequence. 94064467-020PCTe.3D7 Sequences i.3D7 Heavy Chain aa.3D7 Murine heavy chain variable region

[0466] One embodiment provides a 3D7 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVKVVESGGGLVQSGRSLRLSCATSGFIFSDFYMEWVRQAPGKGLEWVATS RNKDFDYETEYSASVKGRFIVSRDTSQSILYLQMNVLRVEDTAIYYCAREYR GAMDYWGQGISVTVSS (SEQ ID NO: 63) with

[0467] CDRH1: DFYME (SEQ ID NO: 64),

[0468] CDRH2: TSRNKDFDYETEYSASVKG (SEQ ID NO: 65),

[0469] CDRH3: EYRGAMDY (SEQ ID NO: 66). bb.3D7 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0470] One embodiment provides a 3D7 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVKVVESGGGLVQSGRSLRLSCATSGFIFSDFYMEWVRQAPGKGLEWVATSR NKDFDYETEYSASVKGRFIVSRDTSQSILYLQMNVLRVEDTAIYYCAREYRG AMDYWGQGISVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 67) with

[0471] CDRH1: DFYME (SEQ ID NO: 64),

[0472] CDRH2: TSRNKDFDYETEYSASVKG (SEQ ID NO: 65),

[0473] CDRH3: EYRGAMDY (SEQ ID NO: 66).

[0474] The bold italicized sequence is the heavy chain constant domain (wild type). 95064467-020PCTcc.3D7 Chimeric Heavy Chain, human wild type IgG1 constant domains (DLE)

[0475] One embodiment provides a 3D7 chimeric heavy chain, human wild type IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVKVVESGGGLVQSGRSLRLSCATSGFIFSDFYMEWVRQAPGKGLEWVATS RNKDFDYETEYSASVKGRFIVSRDTSQSILYLQMNVLRVEDTAIYYCAREYR GAMDYWGQGISVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 68) with

[0476] CDRH1: DFYME (SEQ ID NO: 64),

[0477] CDRH2: TSRNKDFDYETEYSASVKG (SEQ ID NO: 65),

[0478] CDRH3: EYRGAMDY (SEQ ID NO: 66).

[0479] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations dd.3D7 Chimeric Heavy Chain, human wild type IgG1 constant domains (FES)

[0480] One embodiment provides a 3D7 chimeric heavy chain, human wild type IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVKVVESGGGLVQSGRSLRLSCATSGFIFSDFYMEWVRQAPGKGLEWVATS RNKDFDYETEYSASVKGRFIVSRDTSQSILYLQMNVLRVEDTAIYYCAREYR GAMDYWGQGISVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 96064467-020PCT(SEQ ID NO: 69) with

[0481] CDRH1: DFYME (SEQ ID NO: 64),

[0482] CDRH2: TSRNKDFDYETEYSASVKG (SEQ ID NO: 65),

[0483] CDRH3: EYRGAMDY (SEQ ID NO: 66).

[0484] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. dd.3D7 Chimeric Heavy Chain, human wild type IgG1 constant domains (AA)

[0485] One embodiment provides a 3D7 chimeric heavy chain, human wild type IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence:

[0486] EVKVVESGGGLVQSGRSLRLSCATSGFIFSDFYMEWVRQAPGKG LEWVATSRNKDFDYETEYSASVKGRFIVSRDTSQSILYLQMNVLRVEDTAIY YCAREYRGAMDYWGQGISVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMI SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 70) with

[0487] CDRH1: DFYME (SEQ ID NO: 64),

[0488] CDRH2: TSRNKDFDYETEYSASVKG (SEQ ID NO: 65),

[0489] CDRH3: EYRGAMDY (SEQ ID NO: 66).

[0490] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. ee.3D7 Chimeric Heavy Chain, human wild type IgG4 constant domains (G4P)

[0491] One embodiment provides a 3D7 chimeric heavy chain, human wild type IgG4 constant domains (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVKVVESGGGLVQSGRSLRLSCATSGFIFSDFYMEWVRQAPGKGLEWVATS RNKDFDYETEYSASVKGRFIVSRDTSQSILYLQMNVLRVEDTAIYYCAREYR GAMDYWGQGISVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV 97064467-020PCTTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 71) with

[0492] CDRH1: DFYME (SEQ ID NO: 64),

[0493] CDRH2: TSRNKDFDYETEYSASVKG (SEQ ID NO: 65),

[0494] CDRH3: EYRGAMDY (SEQ ID NO: 66).

[0495] The dash underlined sequence is the IgG4 heavy chain constant domain. ii.3D7 Light Chain aa.3D7 Murine light chain variable region

[0496] One embodiment provides a 3D7 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQTTPSLSASLGDRVTISCRASQDINNYLNWYQQKPAGTVKLLIFYTSK LHSGVPSRFSGSGSGTDYSLTINTLEPEDIATYYCQQYRDYPFTFGTGTNLEIK (SEQ ID NO: 72) with

[0497] CDRL1: CDRL1: RASQDINNYLN (SEQ ID NO: 28),

[0498] CDRL2: YTSKLHS (SEQ ID NO: 73),

[0499] CDRL3: QQYRDYPFT (SEQ ID NO: 74). bb.3D7 Chimeric Light Chain, human kappa wild type constant domain

[0500] One embodiment provides a 3D7 chimeric light chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQTTPSLSASLGDRVTISCRASQDINNYLNWYQQKPAGTVKLLIFYTSK LHSGVPSRFSGSGSGTDYSLTINTLEPEDIATYYCQQYRDYPFTFGTGTNLEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG EC (SEQ ID NO: 75) with

[0501] CDRL1: CDRL1: RASQDINNYLN (SEQ ID NO: 28), 98064467-020PCT

[0502] CDRL2: YTSKLHS (SEQ ID NO: 73),

[0503] CDRL3: QQYRDYPFT (SEQ ID NO: 74).

[0504] The underlined sequence is the light chain constant domain (wild type, kappa). cc.3D7 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0505] One embodiment provides a 3D7 chimeric light chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQTTPSLSASLGDRVTISCRASQDINNYLNWYQQKPAGTVKLLIFYTSK LHSGVPSRFSGSGSGTDYSLTINTLEPEDIATYYCQQYRDYPFTFGTGTNLEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG ECGGGGGGGCVIM (SEQ ID NO: 76) with

[0506] CDRL1: CDRL1: RASQDINNYLN (SEQ ID NO: 28),

[0507] CDRL2: YTSKLHS (SEQ ID NO: 73),

[0508] CDRL3: QQYRDYPFT (SEQ ID NO: 74).

[0509] The double underlined sequence is the light chain constant domain with CAAX Sequence. f.3H8 Sequences i.3H8 Heavy Chain aa.3H8 Murine heavy chain variable region

[0510] One embodiment provides a 3H8 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVQLQESGPGLVKPSQSLSLTCSVSGYSITSGYYWNWIRQFPGNELEWMGY MSYDGTNNYNPSLKNRISITRDTSKNQFFLNLNSVTTEDTATYYCARGPYYS NNPWFHFWGQGTLVTVSA (SEQ ID NO: 77) with

[0511] CDRH1: SGYYWN (SEQ ID NO: 78),

[0512] CDRH2: YMSYDGTNNYNPSLKN (SEQ ID NO: 79),

[0513] CDRH3: GPYYSNNPWFHF (SEQ ID NO: 80). 99064467-020PCTbb.3H8 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0514] One embodiment provides a 3H8 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVQLQESGPGLVKPSQSLSLTCSVSGYSITSGYYWNWIRQFPGNELEWMGYM SYDGTNNYNPSLKNRISITRDTSKNQFFLNLNSVTTEDTATYYCARGPYYSNN PWFHFWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 81) with

[0515] CDRH1: SGYYWN (SEQ ID NO: 78),

[0516] CDRH2: YMSYDGTNNYNPSLKN (SEQ ID NO: 79),

[0517] CDRH3: GPYYSNNPWFHF (SEQ ID NO: 80).

[0518] The bold italicized sequence is the heavy chain constant domain (wild type). cc.3H8 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0519] One embodiment provides a 3H8 chimeric heavy chain, human wild type IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVQLQESGPGLVKPSQSLSLTCSVSGYSITSGYYWNWIRQFPGNELEWMGY MSYDGTNNYNPSLKNRISITRDTSKNQFFLNLNSVTTEDTATYYCARGPYYS NNPWFHFWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 100064467-020PCT(SEQ ID NO: 82) with

[0520] CDRH1: SGYYWN (SEQ ID NO: 78),

[0521] CDRH2: YMSYDGTNNYNPSLKN (SEQ ID NO: 79),

[0522] CDRH3: GPYYSNNPWFHF (SEQ ID NO: 80).

[0523] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations cc.3H8 Chimeric Heavy Chain, human wild type IgG1 constant domains (FES)

[0524] One embodiment provides a 3H8 chimeric heavy chain, human IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVQLQESGPGLVKPSQSLSLTCSVSGYSITSGYYWNWIRQFPGNELEWMGY MSYDGTNNYNPSLKNRISITRDTSKNQFFLNLNSVTTEDTATYYCARGPYYS NNPWFHFWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 83) with

[0525] CDRH1: SGYYWN (SEQ ID NO: 78),

[0526] CDRH2: YMSYDGTNNYNPSLKN (SEQ ID NO: 79),

[0527] CDRH3: GPYYSNNPWFHF (SEQ ID NO: 80).

[0528] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. dd.3H8 Chimeric Heavy Chain, human wild type IgG1 constant domains (AA)

[0529] One embodiment provides a 3H8 chimeric heavy chain, human IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVQLQESGPGLVKPSQSLSLTCSVSGYSITSGYYWNWIRQFPGNELEWMGY MSYDGTNNYNPSLKNRISITRDTSKNQFFLNLNSVTTEDTATYYCARGPYYS NNPWFHFWGQGTLVTVSAASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP 101064467-020PCTEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 84) with

[0530] CDRH1: SGYYWN (SEQ ID NO: 78),

[0531] CDRH2: YMSYDGTNNYNPSLKN (SEQ ID NO: 79),

[0532] CDRH3: GPYYSNNPWFHF (SEQ ID NO: 80).

[0533] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. ee.3H8 Chimeric Heavy Chain, human IgG4 constant domain (G4P)

[0534] One embodiment provides a 3H8 chimeric heavy chain, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVQLQESGPGLVKPSQSLSLTCSVSGYSITSGYYWNWIRQFPGNELEWMGY MSYDGTNNYNPSLKNRISITRDTSKNQFFLNLNSVTTEDTATYYCARGPYYS NNPWFHFWGQGTLVTVSAASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDH KPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSR WQEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 85) with

[0535] CDRH1: SGYYWN (SEQ ID NO: 78),

[0536] CDRH2: YMSYDGTNNYNPSLKN (SEQ ID NO: 79),

[0537] CDRH3: GPYYSNNPWFHF (SEQ ID NO: 80).

[0538] The dash underlined sequence is the IgG4 heavy chain constant domain. 102064467-020PCTii.3H8 Light Chain aa.3H8 Murine light chain variable region

[0539] One embodiment provides a 3H8 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQSQRFLSTSVGDRVSISCKASQNVGNVIAWYQQKPGQSPKVLIYLAS YRFSGVPDRFTGGGSGTVFTLTISNVQSEDLAAYFCQQYHSSPLTFGAGTKL ELK (SEQ ID NO: 86) with

[0540] CDRL1: KASQNVGNVIA (SEQ ID NO: 87),

[0541] CDRL2: LASYRFS (SEQ ID NO: 88),

[0542] CDRL3: QQYHSSPLT (SEQ ID NO: 89). bb.3H8 Chimeric Light Chain, human kappa wild type constant domain

[0543] One embodiment provides a 3H8 chimeric light chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQSQRFLSTSVGDRVSISCKASQNVGNVIAWYQQKPGQSPKVLIYLAS YRFSGVPDRFTGGGSGTVFTLTISNVQSEDLAAYFCQQYHSSPLTFGAGTKL ELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF NRGEC (SEQ ID NO: 90) with

[0544] CDRL1: KASQNVGNVIA (SEQ ID NO: 87),

[0545] CDRL2: LASYRFS (SEQ ID NO: 88),

[0546] CDRL3: QQYHSSPLT (SEQ ID NO: 89).

[0547] The underlined sequence is the light chain constant domain (wild type, kappa). cc.3H8 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0548] One embodiment provides a 3H8 chimeric light chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 103064467-020PCTDIVMTQSQRFLSTSVGDRVSISCKASQNVGNVIAWYQQKPGQSPKVLIYLAS YRFSGVPDRFTGGGSGTVFTLTISNVQSEDLAAYFCQQYHSSPLTFGAGTKL ELKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSF NRGECGGGGGGGCVIM (SEQ ID NO: 91) with

[0549] CDRL1: KASQNVGNVIA (SEQ ID NO: 87),

[0550] CDRL2: LASYRFS (SEQ ID NO: 88),

[0551] CDRL3: QQYHSSPLT (SEQ ID NO: 89).

[0552] The double underlined sequence is the light chain constant domain with CAAX Sequence. g.4B12 Sequences i.4B12 Heavy Chain aa.4B12 Murine heavy chain variable region

[0553] One embodiment provides a 4B12 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQLQESGPGLVKPSQSLSLTCSVTGFSITSGYYWNWIRQFPGNKLEWMAYIS YDGRNNYNPSLKNRISITRDTSKNQFFLRLNSVTTEDTATYYCARAGIRRGG YYWGRGTTLTVSS (SEQ ID NO: 92) with

[0554] CDRH1: SGYYWN (SEQ ID NO: 78),

[0555] CDRH2: YISYDGRNNYNPSLKN (SEQ ID NO: 93),

[0556] CDRH3: AGIRRGGYY (SEQ ID NO: 94). bb.4B12 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0557] One embodiment provides a 4B12 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQLQESGPGLVKPSQSLSLTCSVTGFSITSGYYWNWIRQFPGNKLEWMAYIS YDGRNNYNPSLKNRISITRDTSKNQFFLRLNSVTTEDTATYYCARAGIRRGGY YWGRGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKV DKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV 104064467-020PCTDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ GNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 95) with

[0558] CDRH1: SGYYWN (SEQ ID NO: 78),

[0559] CDRH2: YISYDGRNNYNPSLKN (SEQ ID NO: 93),

[0560] CDRH3: AGIRRGGYY (SEQ ID NO: 94).The bold italicized sequence is the heavy chain constant domain (wild type). cc.4B12 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0561] One embodiment provides a 4B12 chimeric heavy chain, human IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQLQESGPGLVKPSQSLSLTCSVTGFSITSGYYWNWIRQFPGNKLEWMAYIS YDGRNNYNPSLKNRISITRDTSKNQFFLRLNSVTTEDTATYYCARAGIRRGG YYWGRGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 96) with

[0562] CDRH1: SGYYWN (SEQ ID NO: 78),

[0563] CDRH2: YISYDGRNNYNPSLKN (SEQ ID NO: 93),

[0564] CDRH3: AGIRRGGYY (SEQ ID NO: 94).The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations dd.4B12 Chimeric Heavy Chain, human IgG1 constant domains (FES)

[0565] One embodiment provides a 4B12 chimeric heavy chain, human IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 105064467-020PCTDIQLQESGPGLVKPSQSLSLTCSVTGFSITSGYYWNWIRQFPGNKLEWMAYIS YDGRNNYNPSLKNRISITRDTSKNQFFLRLNSVTTEDTATYYCARAGIRRGG YYWGRGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 97) with

[0566] CDRH1: SGYYWN (SEQ ID NO: 78),

[0567] CDRH2: YISYDGRNNYNPSLKN (SEQ ID NO: 93),

[0568] CDRH3: AGIRRGGYY (SEQ ID NO: 94).The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. ee.4B12 Chimeric Heavy Chain, human IgG1 constant domains (AA)

[0569] One embodiment provides a 4B12 chimeric heavy chain, human IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQLQESGPGLVKPSQSLSLTCSVTGFSITSGYYWNWIRQFPGNKLEWMAYIS YDGRNNYNPSLKNRISITRDTSKNQFFLRLNSVTTEDTATYYCARAGIRRGG YYWGRGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 98) with

[0570] CDRH1: SGYYWN (SEQ ID NO: 78),

[0571] CDRH2: YISYDGRNNYNPSLKN (SEQ ID NO: 93),

[0572] CDRH3: AGIRRGGYY (SEQ ID NO: 94).The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. 106064467-020PCTff.4B12 Chimeric Heavy Chain, human IgG4 constant domain (G4P)

[0573] One embodiment provides a 4B12 chimeric heavy chain, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQLQESGPGLVKPSQSLSLTCSVTGFSITSGYYWNWIRQFPGNKLEWMAYIS YDGRNNYNPSLKNRISITRDTSKNQFFLRLNSVTTEDTATYYCARAGIRRGG YYWGRGTTLTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTK VDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS QEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGK EYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV FSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 99) with

[0574] CDRH1: SGYYWN (SEQ ID NO: 78),

[0575] CDRH2: YISYDGRNNYNPSLKN (SEQ ID NO: 93),

[0576] CDRH3: AGIRRGGYY (SEQ ID NO: 94).The dash underlined sequence is the IgG4 heavy chain constant domain. ii.4B12 Light Chain aa.4B12 Murine light chain variable region

[0577] One embodiment provides a 4B12 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: IVLTQSPVSLAVSLGQRATISCRASESVDNYGNSYVYWYQQKPGQPPKLLIYL SSYLESGVPARFSGSGSRTDFTLTIDPVETDDAATYYCQQNNEDPHSFGGGT KLEIK (SEQ ID NO: 100) with

[0578] CDRL1: RASESVDNYGNSYVY (SEQ ID NO: 101),

[0579] CDRL2: LSSYLES (SEQ ID NO: 102),

[0580] CDRL3: QQNNEDPHS (SEQ ID NO: 103). 107064467-020PCTbb.4B12 Chimeric Light Chain, human kappa wild type constant domain

[0581] One embodiment provides a 4B12 chimeric light chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: IVLTQSPVSLAVSLGQRATISCRASESVDNYGNSYVYWYQQKPGQPPKLLIYL SSYLESGVPARFSGSGSRTDFTLTIDPVETDDAATYYCQQNNEDPHSFGGGT KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS FNRGEC (SEQ ID NO: 104) with

[0582] CDRL1: RASESVDNYGNSYVY (SEQ ID NO: 101),

[0583] CDRL2: LSSYLES (SEQ ID NO: 102),

[0584] CDRL3: QQNNEDPHS (SEQ ID NO: 103).

[0585] The underlined sequence is the light chain constant domain (wild type, kappa). cc.4B12 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0586] One embodiment provides a 4B12 chimeric light chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: IVLTQSPVSLAVSLGQRATISCRASESVDNYGNSYVYWYQQKPGQPPKLLIYL SSYLESGVPARFSGSGSRTDFTLTIDPVETDDAATYYCQQNNEDPHSFGGGT KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS FNRGECGGGGGGGCVIM (SEQ ID NO: 105) with

[0587] CDRL1: RASESVDNYGNSYVY (SEQ ID NO: 101),

[0588] CDRL2: LSSYLES (SEQ ID NO: 102),

[0589] CDRL3: QQNNEDPHS (SEQ ID NO: 103).

[0590] The double underlined sequence is the light chain constant domain with CAAX Sequence. 108064467-020PCTh.4G11 Sequences i.4G11 Heavy Chain aa.4G11 Murine heavy chain variable region

[0591] One embodiment provides a 4G11 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTTSGFNIKDSLMHWVKQRPEQGLEWIGWI DPEDGEGKYVPKFQDKATITSDTSSNTVYLQLSSLTSEDSAIYYCVREWDGY SFDYWGQGTTLTVSS (SEQ ID NO: 106) with

[0592] CDRH1: DSLMH (SEQ ID NO: 107),

[0593] CDRH2: WIDPEDGEGKYVPKFQD (SEQ ID NO: 108),

[0594] CDRH3: EWDGYSFDY (SEQ ID NO: 109). bb.4G11 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0595] One embodiment provides a 4G11 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTTSGFNIKDSLMHWVKQRPEQGLEWIGWID PEDGEGKYVPKFQDKATITSDTSSNTVYLQLSSLTSEDSAIYYCVREWDGYSF DYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 110) with

[0596] CDRH1: DSLMH (SEQ ID NO: 107),

[0597] CDRH2: WIDPEDGEGKYVPKFQD (SEQ ID NO: 108),

[0598] CDRH3: EWDGYSFDY (SEQ ID NO: 109).

[0599] The bold italicized sequence is the heavy chain constant domain (wild type). 109064467-020PCTcc.4G11 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0600] One embodiment provides a 4G11 chimeric heavy chain, human IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTTSGFNIKDSLMHWVKQRPEQGLEWIGWI DPEDGEGKYVPKFQDKATITSDTSSNTVYLQLSSLTSEDSAIYYCVREWDGY SFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 111) with

[0601] CDRH1: DSLMH (SEQ ID NO: 107),

[0602] CDRH2: WIDPEDGEGKYVPKFQD (SEQ ID NO: 108),

[0603] CDRH3: EWDGYSFDY (SEQ ID NO: 109).

[0604] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations dd.4G11 Chimeric Heavy Chain, human IgG1 constant domains (FES)

[0605] One embodiment provides a 4G11 chimeric heavy chain, human IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTTSGFNIKDSLMHWVKQRPEQGLEWIGWI DPEDGEGKYVPKFQDKATITSDTSSNTVYLQLSSLTSEDSAIYYCVREWDGY SFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 110064467-020PCT(SEQ ID NO: 112) with

[0606] CDRH1: DSLMH (SEQ ID NO: 107),

[0607] CDRH2: WIDPEDGEGKYVPKFQD (SEQ ID NO: 108),

[0608] CDRH3: EWDGYSFDY (SEQ ID NO: 109).

[0609] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. ee.4G11 Chimeric Heavy Chain, human IgG1 constant domains (AA)

[0610] One embodiment provides a 4G11 chimeric heavy chain, human IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTTSGFNIKDSLMHWVKQRPEQGLEWIGWI DPEDGEGKYVPKFQDKATITSDTSSNTVYLQLSSLTSEDSAIYYCVREWDGY SFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 113) with

[0611] CDRH1: DSLMH (SEQ ID NO: 107),

[0612] CDRH2: WIDPEDGEGKYVPKFQD (SEQ ID NO: 108),

[0613] CDRH3: EWDGYSFDY (SEQ ID NO: 109).

[0614] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. ff.4G11 Chimeric Heavy Chain, human IgG4 constant domain (G4P)

[0615] One embodiment provides a 4G11 chimeric heavy chain, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLQQSGAELVRPGASVKLSCTTSGFNIKDSLMHWVKQRPEQGLEWIGWI DPEDGEGKYVPKFQDKATITSDTSSNTVYLQLSSLTSEDSAIYYCVREWDGY SFDYWGQGTTLTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT 111064467-020PCTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 114) with

[0616] CDRH1: DSLMH (SEQ ID NO: 107),

[0617] CDRH2: WIDPEDGEGKYVPKFQD (SEQ ID NO: 108),

[0618] CDRH3: EWDGYSFDY (SEQ ID NO: 109).

[0619] The dash underlined sequence is the IgG4 heavy chain constant domain. ii.4G11 Light Chain aa.4G11 Murine light chain variable region

[0620] One embodiment provides a 4G11 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVLMTQTPRSLPVSLGDQASISCRSSQSIVHSHGNTYLEWYLQKPGQSPKLLI YKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGG GTKLEIK (SEQ ID NO: 115) with

[0621] CDRL1: RSSQSIVHSHGNTYLE (SEQ ID NO: 116),

[0622] CDRL2: KVSNRFS (SEQ ID NO: 117),

[0623] CDRL3: FQGSHVPWT (SEQ ID NO: 118). bb.4G11 Chimeric Light Chain, human kappa wild type constant domain

[0624] One embodiment provides a 4G11 chimeric light chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVLMTQTPRSLPVSLGDQASISCRSSQSIVHSHGNTYLEWYLQKPGQSPKLLI YKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGG GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGEC (SEQ ID NO: 119) with 112064467-020PCT

[0625] CDRL1: RSSQSIVHSHGNTYLE (SEQ ID NO: 116),

[0626] CDRL2: KVSNRFS (SEQ ID NO: 117),

[0627] CDRL3: FQGSHVPWT (SEQ ID NO: 118).

[0628] The underlined sequence is the light chain constant domain (wild type, kappa). cc.4G11 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0629] One embodiment provides a 4G11 chimeric light chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVLMTQTPRSLPVSLGDQASISCRSSQSIVHSHGNTYLEWYLQKPGQSPKLLI YKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGG GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGECGGGGGGGCVIM (SEQ ID NO: 120) with

[0630] CDRL1: RSSQSIVHSHGNTYLE (SEQ ID NO: 116),

[0631] CDRL2: KVSNRFS (SEQ ID NO: 117),

[0632] CDRL3: FQGSHVPWT (SEQ ID NO: 118).

[0633] The double underlined sequence is the light chain constant domain with CAAX Sequence. i.5B4 Sequences i.5B4 Heavy Chain aa.5B4 Murine heavy chain variable region

[0634] One embodiment provides a5B4 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQSGPGLVRPGTSMKLSCKASGYTFTDYGITWVKQRPGQGLEWIGWI YPKDDSSTYNERFKGKATLTVDTSSSTAYMALHRLTSEDSAVYFCARGNWE TPFDYWGHGTTLTVSS (SEQ ID NO: 121) with

[0635] CDRH1: DYGIT (SEQ ID NO: 122),

[0636] CDRH2: WIYPKDDSSTYNERFKG (SEQ ID NO: 123),

[0637] CDRH3: GNWETPFDY (SEQ ID NO: 124). 113064467-020PCTbb.5B4 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0638] One embodiment provides a 5B4 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQSGPGLVRPGTSMKLSCKASGYTFTDYGITWVKQRPGQGLEWIGWI YPKDDSSTYNERFKGKATLTVDTSSSTAYMALHRLTSEDSAVYFCARGNWET PFDYWGHGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 125) with

[0639] CDRH1: DYGIT (SEQ ID NO: 122),

[0640] CDRH2: WIYPKDDSSTYNERFKG (SEQ ID NO: 123),

[0641] CDRH3: GNWETPFDY (SEQ ID NO: 124).

[0642] The bold italicized sequence is the heavy chain constant domain (wild type). cc.5B4 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0643] One embodiment provides a 5B4 chimeric heavy chain, human IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQSGPGLVRPGTSMKLSCKASGYTFTDYGITWVKQRPGQGLEWIGWI YPKDDSSTYNERFKGKATLTVDTSSSTAYMALHRLTSEDSAVYFCARGNWE TPFDYWGHGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 114064467-020PCT(SEQ ID NO: 126) with

[0644] CDRH1: DYGIT (SEQ ID NO: 122),

[0645] CDRH2: WIYPKDDSSTYNERFKG (SEQ ID NO: 123),

[0646] CDRH3: GNWETPFDY (SEQ ID NO: 124).

[0647] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations dd.5B4 Chimeric Heavy Chain, human IgG1 constant domains (FES)

[0648] One embodiment provides a 5B4 chimeric heavy chain, human IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQSGPGLVRPGTSMKLSCKASGYTFTDYGITWVKQRPGQGLEWIGWI YPKDDSSTYNERFKGKATLTVDTSSSTAYMALHRLTSEDSAVYFCARGNWE TPFDYWGHGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 127) with

[0649] CDRH1: DYGIT (SEQ ID NO: 122),

[0650] CDRH2: WIYPKDDSSTYNERFKG (SEQ ID NO: 123),

[0651] CDRH3: GNWETPFDY (SEQ ID NO: 124).

[0652] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. ee.5B4 Chimeric Heavy Chain, human IgG1 constant domains (AA)

[0653] One embodiment provides a 5B4 chimeric heavy chain, human IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQSGPGLVRPGTSMKLSCKASGYTFTDYGITWVKQRPGQGLEWIGWI YPKDDSSTYNERFKGKATLTVDTSSSTAYMALHRLTSEDSAVYFCARGNWE TPFDYWGHGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV 115064467-020PCTTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 128) with

[0654] CDRH1: DYGIT (SEQ ID NO: 122),

[0655] CDRH2: WIYPKDDSSTYNERFKG (SEQ ID NO: 123),

[0656] CDRH3: GNWETPFDY (SEQ ID NO: 124).

[0657] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. ff.5B4 Chimeric Heavy Chain, human IgG4 constant domain (G4P)

[0658] The chimeric heavy chain, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLQQSGPGLVRPGTSMKLSCKASGYTFTDYGITWVKQRPGQGLEWIGWI YPKDDSSTYNERFKGKATLTVDTSSSTAYMALHRLTSEDSAVYFCARGNWE TPFDYWGHGTTLTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 129) with

[0659] CDRH1: DYGIT (SEQ ID NO: 122),

[0660] CDRH2: WIYPKDDSSTYNERFKG (SEQ ID NO: 123),

[0661] CDRH3: GNWETPFDY (SEQ ID NO: 124).

[0662] The dash underlined sequence is the IgG4 heavy chain constant domain. 116064467-020PCTii.5B4 Light Chain aa.5B4 Murine light chain variable region

[0663] One embodiment provides a 5B4 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVLLTQTPLSLPVSLGDQASISCKSSQSIVHSNGNTYLEWYLQKPGQSPRFLI YEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGG GTKLEIK (SEQ ID NO: 130) with

[0664] CDRL1: KSSQSIVHSNGNTYLE (SEQ ID NO: 131),

[0665] CDRL2: EVSNRFS (SEQ ID NO: 132),

[0666] CDRL3: FQGSHVPWT (SEQ ID NO: 118). bb.5B4 Chimeric Light Chain, human kappa wild type constant domain

[0667] One embodiment provides a 5B4 chimeric light chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVLLTQTPLSLPVSLGDQASISCKSSQSIVHSNGNTYLEWYLQKPGQSPRFLI YEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGG GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGEC (SEQ ID NO: 133) with

[0668] CDRL1: KSSQSIVHSNGNTYLE (SEQ ID NO: 131),

[0669] CDRL2: EVSNRFS (SEQ ID NO: 132),

[0670] CDRL3: FQGSHVPWT (SEQ ID NO: 118).

[0671] The underlined sequence is the light chain constant domain (wild type, kappa). cc.5B4 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0672] One embodiment provides a5B4 chimeric light chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 117064467-020PCTDVLLTQTPLSLPVSLGDQASISCKSSQSIVHSNGNTYLEWYLQKPGQSPRFLI YEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGG GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNA LQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGECGGGGGGGCVIM (SEQ ID NO: 134) with

[0673] CDRL1: KSSQSIVHSNGNTYLE (SEQ ID NO: 131),

[0674] CDRL2: EVSNRFS (SEQ ID NO: 132),

[0675] CDRL3: FQGSHVPWT (SEQ ID NO: 118).

[0676] The double underlined sequence is the light chain constant domain with CAAX Sequence. j.5B8 Sequences i.5B8 Heavy Chain aa.5B8 Murine heavy chain variable region

[0677] One embodiment provides a 5B8 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QAYLQQSGTELVSPGASVKMSCKASGYTFSNYNLHWVRQTPRQGLEWIGSI YPGNGDASFNQNFKGKATLTVDISSSTAYLQFSSLTSEDSAVYFCARSGDYD YFDYWGQGTTLTVSS (SEQ ID NO: 135) with

[0678] CDRH1: NYNLH (SEQ ID NO: 136),

[0679] CDRH2: SIYPGNGDASFNQNFKG (SEQ ID NO: 137),

[0680] CDRH3: SGDYDYFDY (SEQ ID NO: 138). bb.5B8 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0681] One embodiment provides a 5B8 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QAYLQQSGTELVSPGASVKMSCKASGYTFSNYNLHWVRQTPRQGLEWIGSIY PGNGDASFNQNFKGKATLTVDISSSTAYLQFSSLTSEDSAVYFCARSGDYDYF DYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV 118064467-020PCTVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 139) with

[0682] CDRH1: NYNLH (SEQ ID NO: 136),

[0683] CDRH2: SIYPGNGDASFNQNFKG (SEQ ID NO: 137),

[0684] CDRH3: SGDYDYFDY (SEQ ID NO: 138).

[0685] The bold italicized sequence is the heavy chain constant domain (wild type). cc.5B8 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0686] One embodiment provides a 5B8 chimeric heavy chain, human IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QAYLQQSGTELVSPGASVKMSCKASGYTFSNYNLHWVRQTPRQGLEWIGSI YPGNGDASFNQNFKGKATLTVDISSSTAYLQFSSLTSEDSAVYFCARSGDYD YFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 140) with

[0687] CDRH1: NYNLH (SEQ ID NO: 136),

[0688] CDRH2: SIYPGNGDASFNQNFKG (SEQ ID NO: 137),

[0689] CDRH3: SGDYDYFDY (SEQ ID NO: 138).

[0690] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations 119064467-020PCTdd.5B8 Chimeric Heavy Chain, human IgG1 constant domains (FES)

[0691] One embodiment provides a 5B8 chimeric heavy chain, human IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QAYLQQSGTELVSPGASVKMSCKASGYTFSNYNLHWVRQTPRQGLEWIGSI YPGNGDASFNQNFKGKATLTVDISSSTAYLQFSSLTSEDSAVYFCARSGDYD YFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 141) with

[0692] CDRH1: NYNLH (SEQ ID NO: 136),

[0693] CDRH2: SIYPGNGDASFNQNFKG (SEQ ID NO: 137),

[0694] CDRH3: SGDYDYFDY (SEQ ID NO: 138).

[0695] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. ee.5B8 Chimeric Heavy Chain, human IgG1 constant domains (AA)

[0696] One embodiment provides a 5B8 chimeric heavy chain, human IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QAYLQQSGTELVSPGASVKMSCKASGYTFSNYNLHWVRQTPRQGLEWIGSI YPGNGDASFNQNFKGKATLTVDISSSTAYLQFSSLTSEDSAVYFCARSGDYD YFDYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 120064467-020PCT(SEQ ID NO: 142) with

[0697] CDRH1: NYNLH (SEQ ID NO: 136),

[0698] CDRH2: SIYPGNGDASFNQNFKG (SEQ ID NO: 137),

[0699] CDRH3: SGDYDYFDY (SEQ ID NO: 138).

[0700] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. ff.5B8 Chimeric Heavy Chain, human IgG4 constant domain (G4P)

[0701] One embodiment provides a 5B8 chimeric heavy chain, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QAYLQQSGTELVSPGASVKMSCKASGYTFSNYNLHWVRQTPRQGLEWIGSI YPGNGDASFNQNFKGKATLTVDISSSTAYLQFSSLTSEDSAVYFCARSGDYD YFDYWGQGTTLTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 143) with

[0702] CDRH1: NYNLH (SEQ ID NO: 136),

[0703] CDRH2: SIYPGNGDASFNQNFKG (SEQ ID NO: 137),

[0704] CDRH3: SGDYDYFDY (SEQ ID NO: 138).

[0705] The dash underlined sequence is the IgG4 heavy chain constant domain. ii.5B8 Light Chain aa.5B8 Murine light chain variable region

[0706] One embodiment provides a 5B8 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQTTSSLSASLGDRVTISCRASQGINNYLNWYQQKPDGTVKLLIYYTS KLHSGVPSRFSGSGSTTDYSLTISNLEQEDIATYFCQQIDTFPPTFGGGTKLEI K (SEQ ID NO: 144) with 121064467-020PCT

[0707] CDRL1: RASQGINNYLN (SEQ ID NO: 145),

[0708] CDRL2: YTSKLHS (SEQ ID NO: 146),

[0709] CDRL3: QQIDTFPPT (SEQ ID NO: 147). bb.5B8 Chimeric Light Chain, human kappa wild type constant domain

[0710] One embodiment provides a 5B8 chimeric light chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQTTSSLSASLGDRVTISCRASQGINNYLNWYQQKPDGTVKLLIYYTS KLHSGVPSRFSGSGSTTDYSLTISNLEQEDIATYFCQQIDTFPPTFGGGTKLEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GEC (SEQ ID NO: 148) with

[0711] CDRL1: RASQGINNYLN (SEQ ID NO: 145),

[0712] CDRL2: YTSKLHS (SEQ ID NO: 146),

[0713] CDRL3: QQIDTFPPT (SEQ ID NO: 147).

[0714] The underlined sequence is the light chain constant domain (wild type, kappa). cc.5B8 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0715] One embodiment provides a 5B8 chimeric light chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIQMTQTTSSLSASLGDRVTISCRASQGINNYLNWYQQKPDGTVKLLIYYTS KLHSGVPSRFSGSGSTTDYSLTISNLEQEDIATYFCQQIDTFPPTFGGGTKLEI KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GECGGGGGGGCVIM (SEQ ID NO: 149) with

[0716] CDRL1: RASQGINNYLN (SEQ ID NO: 145),

[0717] CDRL2: YTSKLHS (SEQ ID NO: 146),

[0718] CDRL3: QQIDTFPPT (SEQ ID NO: 147). 122064467-020PCT

[0719] The double underlined sequence is the light chain constant domain with CAAX Sequence. k.5H4 Sequences i.5H4 Heavy Chain aa.5H4 Murine heavy chain variable region

[0720] One embodiment provides a 5H4 murine heavy chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPGILQPSQTLSLTCSFSGFSLSTFGVGVGWFRQSSGKGLEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLKIANVDTADTATHYCARIDSTV VAYAYWGQGTTLTVSS (SEQ ID NO: 150) with

[0721] CDRH1: TFGVGVG (SEQ ID NO: 151),

[0722] CDRH2: HIWWDDEKYSNPALKT (SEQ ID NO: 152),

[0723] CDRH3: IDSTVVAYAY (SEQ ID NO: 153). bb.5H4 Chimeric Heavy Chain, human wild type IgG1 constant domains

[0724] One embodiment provides a 5H4 chimeric heavy chain, human wild type IgG1 constant domains having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPGILQPSQTLSLTCSFSGFSLSTFGVGVGWFRQSSGKGLEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLKIANVDTADTATHYCARIDSTVV AYAYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 154) with

[0725] CDRH1: TFGVGVG (SEQ ID NO: 151),

[0726] CDRH2: HIWWDDEKYSNPALKT (SEQ ID NO: 152),

[0727] CDRH3: IDSTVVAYAY (SEQ ID NO: 153). 123064467-020PCT

[0728] The bold italicized sequence is the heavy chain constant domain (wild type). cc.5H4 Chimeric Heavy Chain, human IgG1 constant domains (DLE)

[0729] One embodiment provides a 5H4 chimeric heavy chain, human IgG1 constant domains (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPGILQPSQTLSLTCSFSGFSLSTFGVGVGWFRQSSGKGLEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLKIANVDTADTATHYCARIDSTV VAYAYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 155) with

[0730] CDRH1: TFGVGVG (SEQ ID NO: 151),

[0731] CDRH2: HIWWDDEKYSNPALKT (SEQ ID NO: 152),

[0732] CDRH3: IDSTVVAYAY (SEQ ID NO: 153).

[0733] The italicized sequence is the heavy chain constant domain with aspartic acid (D), leucine (L), and glutamic acid (E) mutations dd.5H4 Chimeric Heavy Chain, human IgG1 constant domains (FES)

[0734] One embodiment provides a 5H4 chimeric heavy chain, human IgG1 constant domains (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPGILQPSQTLSLTCSFSGFSLSTFGVGVGWFRQSSGKGLEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLKIANVDTADTATHYCARIDSTV VAYAYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ 124064467-020PCTVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 156) with

[0735] CDRH1: TFGVGVG (SEQ ID NO: 151),

[0736] CDRH2: HIWWDDEKYSNPALKT (SEQ ID NO: 152),

[0737] CDRH3: IDSTVVAYAY (SEQ ID NO: 153).

[0738] The underlined and italicized sequence is the heavy chain constant domain with phenylalanine (F), glutamic acid (E), and serine (S) and mutations. ee.5H4 Chimeric Heavy Chain, human IgG1 constant domains (AA)

[0739] One embodiment provides a 5H4 chimeric heavy chain, human IgG1 constant domains (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPGILQPSQTLSLTCSFSGFSLSTFGVGVGWFRQSSGKGLEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLKIANVDTADTATHYCARIDSTV VAYAYWGQGTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 157) with

[0740] CDRH1: TFGVGVG (SEQ ID NO: 151),

[0741] CDRH2: HIWWDDEKYSNPALKT (SEQ ID NO: 152),

[0742] CDRH3: IDSTVVAYAY (SEQ ID NO: 153).

[0743] The dot underlined sequence is the heavy chain constant domain with alanine-alanine (AA) mutations. ff.5H4 Chimeric Heavy Chain, human IgG4 constant domain (G4P)

[0744] One embodiment provides a 5H4 chimeric heavy chain, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 125064467-020PCTQVTLKESGPGILQPSQTLSLTCSFSGFSLSTFGVGVGWFRQSSGKGLEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLKIANVDTADTATHYCARIDSTV VAYAYWGQGTTLTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO: 158) with

[0745] CDRH1: TFGVGVG (SEQ ID NO: 151),

[0746] CDRH2: HIWWDDEKYSNPALKT (SEQ ID NO: 152),

[0747] CDRH3: IDSTVVAYAY (SEQ ID NO: 153).

[0748] The dash underlined sequence is the IgG4 heavy chain constant domain. ii.5H4 Light Chain aa.5H4 Murine light chain variable region

[0749] One embodiment provides a5H4 murine light chain variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVLMTQTPLSLPVSLGDQASISCRSSQTILHSDGNTYLEWYLQKPGQSPKLLI YKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPYTFGG GTKLE (SEQ ID NO: 159) with

[0750] CDRL1: RSSQTILHSDGNTYLE (SEQ ID NO: 160),

[0751] CDRL2: KVSNRFS (SEQ ID NO: 161),

[0752] CDRL3: FQGSHVPYT (SEQ ID NO: 162). bb.5H4 Chimeric Light Chain, human kappa wild type constant domain

[0753] One embodiment provides a5H4 chimeric light chain, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVLMTQTPLSLPVSLGDQASISCRSSQTILHSDGNTYLEWYLQKPGQSPKLLI YKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPYTFGG GTKLERTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL 126064467-020PCTQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGEC (SEQ ID NO: 163) with

[0754] CDRL1: RSSQTILHSDGNTYLE (SEQ ID NO: 160),

[0755] CDRL2: KVSNRFS (SEQ ID NO: 161),

[0756] CDRL3: FQGSHVPYT (SEQ ID NO: 162).

[0757] The underlined sequence is the light chain constant domain (wild type, kappa). cc.5H4 Chimeric Light Chain, human kappa wild type constant domain (CAAX)

[0758] One embodiment provides a 5H4 chimeric light chain, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DVLMTQTPLSLPVSLGDQASISCRSSQTILHSDGNTYLEWYLQKPGQSPKLLI YKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPYTFGG GTKLERTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGECGGGGGGGCVIM (SEQ ID NO: 164) with

[0759] CDRL1: RSSQTILHSDGNTYLE (SEQ ID NO: 160),

[0760] CDRL2: KVSNRFS (SEQ ID NO: 161),

[0761] CDRL3: FQGSHVPYT (SEQ ID NO: 162).

[0762] The double underlined sequence is the light chain constant domain with CAAX Sequence. l.5H4 Humanized Sequences i.5H4 Humanized Heavy Chain 1 (HC-1) aa.5H4 Humanized HC-1 variable region

[0763] One embodiment provides a 5H4 humanized HC-1 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSS (SEQ ID NO:309) with

[0764] CDR-H1 GFSLSTFGVG (SEQ ID NO:432), 127064467-020PCT

[0765] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0766] CDR-H3 AHIDSTVVAYAY (SEQ ID NO:311). bb.5H4 Humanized HC-1, human wild type IgG1 constant domains

[0767] One embodiment provides a 5H4 humanized HC-1, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:312). cc.5H4 humanized HC-1, human IgG1 constant domains (DLE)

[0768] One embodiment provides a 5H4 humanized HC-1, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:313). 128064467-020PCTdd.5H4 humanized HC-1, human IgG1 constant domains (FES)

[0769] One embodiment provides a 5H4 humanized HC-1, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:314). ee.5H4 humanized HC-1, human IgG1 constant domains (AA)

[0770] One embodiment provides a 5H4 humanized HC-1, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:315). ff.5H4 humanized HC-1, human IgG4 constant domain (G4P)

[0771] One embodiment provides a 5H4 humanized HC-1, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 129064467-020PCTQVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKP SNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:316). ii.5H4 Humanized Heavy Chain 2 (HC-2) aa.5H4 Humanized HC-2 variable region

[0772] One embodiment provides a 5H4 humanized HC-2 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSS (SEQ ID NO:317) with

[0773] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0774] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0775] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-2, human wild type IgG1 constant domains

[0776] One embodiment provides a 5H4 humanized HC-2, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:318). 130064467-020PCTcc.5H4 humanized HC-2, human IgG1 constant domains (DLE)

[0777] One embodiment provides a 5H4 humanized HC-2, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:319). dd.5H4 humanized HC-2, human IgG1 constant domains (FES)

[0778] One embodiment provides a 5H4 humanized HC-2, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:320). ee.5H4 humanized HC-2, human IgG1 constant domains (AA)

[0779] One embodiment provides a 5H4 humanized HC-2, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 131064467-020PCTQVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:321). ff.5H4 humanized HC-2, human IgG4 constant domain (G4P)

[0780] One embodiment provides a 5H4 humanized HC-2, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALI WWDDEKRYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKP SNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:322). iii.5H4 Humanized Heavy Chain 3 (HC-3) aa.5H4 Humanized HC-3 variable region

[0781] One embodiment provides a 5H4 humanized HC-3 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSS (SEQ ID NO:324) with

[0782] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0783] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0784] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). 132064467-020PCTbb.5H4 Humanized HC-3, human wild type IgG1 constant domains

[0785] One embodiment provides a 5H4 humanized HC-3, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:325). cc.5H4 humanized HC-3, human IgG1 constant domains (DLE)

[0786] One embodiment provides a 5H4 humanized HC-3, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:326). dd.5H4 humanized HC-3, human IgG1 constant domains (FES)

[0787] One embodiment provides a 5H4 humanized HC-3, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 133064467-020PCTQVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:327). ee.5H4 humanized HC-3, human IgG1 constant domains (AA)

[0788] One embodiment provides a 5H4 humanized HC-3, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:328). ff.5H4 humanized HC-3, human IgG4 constant domain (G4P)

[0789] One embodiment provides a 5H4 humanized HC-3, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYGPSLKSRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKP SNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDW 134064467-020PCTLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:329). iv.5H4 Humanized Heavy Chain 4 (HC-4) aa.5H4 Humanized HC-4 variable region

[0790] One embodiment provides a 5H4 humanized HC-4 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSS (SEQ ID NO:330) with

[0791] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0792] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0793] CDR-H3 AHIDSTVVAYAY (SEQ ID NO:311). bb.5H4 Humanized HC-4, human wild type IgG1 constant domains

[0794] One embodiment provides a 5H4 humanized HC-4, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:331). cc.5H4 humanized HC-4, human IgG1 constant domains (DLE)

[0795] One embodiment provides a 5H4 humanized HC-4, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 135064467-020PCTQVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:332). dd.5H4 humanized HC-4, human IgG1 constant domains (FES)

[0796] One embodiment provides a 5H4 humanized HC-4, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:333). ee.5H4 humanized HC-4, human IgG1 constant domains (AA)

[0797] One embodiment provides a 5H4 humanized HC-4, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL 136064467-020PCTHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:334). ff.5H4 humanized HC-4, human IgG4 constant domain (G4P)

[0798] One embodiment provides a 5H4 humanized HC-4, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCAHIDSTV VAYAYWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKP SNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVV VDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:335). vi.5H4 Humanized Heavy Chain 6 (HC-6) aa.5H4 Humanized HC-6 variable region

[0799] One embodiment provides a 5H4 humanized HC-6 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSS (SEQ ID NO:336) with

[0800] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0801] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0802] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-6, human wild type IgG1 constant domains

[0803] One embodiment provides a 5H4 humanized HC-6, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 137064467-020PCTQVTLRESGPALVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:337). cc.5H4 humanized HC-6, human IgG1 constant domains (DLE)

[0804] One embodiment provides a 5H4 humanized HC-6, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:338). dd.5H4 humanized HC-6, human IgG1 constant domains (FES)

[0805] One embodiment provides a 5H4 humanized HC-6, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH 138064467-020PCTQDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:339). ee.5H4 humanized HC-6, human IgG1 constant domains (AA)

[0806] One embodiment provides a 5H4 humanized HC-6, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:340). ff.5H4 humanized HC-6, human IgG4 constant domain (G4P)

[0807] One embodiment provides a 5H4 humanized HC-6, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:341). 139064467-020PCTvii.5H4 Humanized Heavy Chain 7 (HC-7) aa.5H4 Humanized HC-7 variable region

[0808] One embodiment provides a 5H4 humanized HC-7 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTVSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSS (SEQ ID NO:342) with

[0809] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0810] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0811] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-7, human wild type IgG1 constant domains

[0812] One embodiment provides a 5H4 humanized HC-7, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTVSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:343). cc.5H4 humanized HC-7, human IgG1 constant domains (DLE)

[0813] One embodiment provides a 5H4 humanized HC-7, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTVSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP 140064467-020PCTSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:344). dd.5H4 humanized HC-7, human IgG1 constant domains (FES)

[0814] One embodiment provides a 5H4 humanized HC-7, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTVSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:345). ee.5H4 humanized HC-7, human IgG1 constant domains (AA)

[0815] One embodiment provides a 5H4 humanized HC-7, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTVSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:346). 141064467-020PCTff.5H4 humanized HC-7, human IgG4 constant domain (G4P)

[0816] One embodiment provides a 5H4 humanized HC-7, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLRESGPALVKPTQTLTLTCTVSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARIDSTV VAYAYWGQGSLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:347). viii.5H4 Humanized Heavy Chain 8 (HC-8) aa.5H4 Humanized HC-8 variable region

[0817] One embodiment provides a 5H4 humanized HC-8 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSS (SEQ ID NO:348) with

[0818] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0819] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0820] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-8, human wild type IgG1 constant domains

[0821] One embodiment provides a 5H4 humanized HC-8, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP 142064467-020PCTSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:349). cc.5H4 humanized HC-8, human IgG1 constant domains (DLE)

[0822] One embodiment provides a 5H4 humanized HC-8, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:350). dd.5H4 humanized HC-8, human IgG1 constant domains (FES)

[0823] One embodiment provides a 5H4 humanized HC-8, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:351). 143064467-020PCTee.5H4 humanized HC-8, human IgG1 constant domains (AA)

[0824] One embodiment provides a 5H4 humanized HC-8, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:352). ff.5H4 humanized HC-8, human IgG4 constant domain (G4P)

[0825] One embodiment provides a 5H4 humanized HC-8, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYSNPALKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:353). ix.5H4 Humanized Heavy Chain 9 (HC-9) aa.5H4 Humanized HC-9 variable region

[0826] One embodiment provides a 5H4 humanized HC-9 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 144064467-020PCTEVQLLESGGGLVQPGGSLRLSCAASGFSLSTFGVSWVRQAPGKGLEWVSAIW WDDETYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIDSTVV AYAYWGQGTLVTVSS (SEQ ID NO:354) with

[0827] CDR-H1 GFSLSTFG (SEQ ID NO:355),

[0828] CDR-H2 IWWDDET (SEQ ID NO:356),

[0829] CDR-H3 AKIDSTVVAYAY (SEQ ID NO:357), bb.5H4 Humanized HC-9, human wild type IgG1 constant domains

[0830] One embodiment provides a 5H4 humanized HC-9, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFSLSTFGVSWVRQAPGKGLEWVSAIW WDDETYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:358). cc.5H4 humanized HC-9, human IgG1 constant domains (DLE)

[0831] One embodiment provides a 5H4 humanized HC-9, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFSLSTFGVSWVRQAPGKGLEWVSAIW WDDETYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:359). 145064467-020PCTdd.5H4 humanized HC-9, human IgG1 constant domains (FES)

[0832] One embodiment provides a 5H4 humanized HC-9, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFSLSTFGVSWVRQAPGKGLEWVSAIW WDDETYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:360). ee.5H4 humanized HC-9, human IgG1 constant domains (AA)

[0833] One embodiment provides a 5H4 humanized HC-9, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: EVQLLESGGGLVQPGGSLRLSCAASGFSLSTFGVSWVRQAPGKGLEWVSAIW WDDETYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:361). ff.5H4 humanized HC-9, human IgG4 constant domain (G4P)

[0834] One embodiment provides a 5H4 humanized HC-9, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 146064467-020PCTEVQLLESGGGLVQPGGSLRLSCAASGFSLSTFGVSWVRQAPGKGLEWVSAIW WDDETYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:362). x.5H4 Humanized Heavy Chain 10 (HC-10) aa.5H4 Humanized HC-10 variable region

[0835] One embodiment provides a 5H4 humanized HC-10 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLALI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSS (SEQ ID NO:363) with

[0836] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0837] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0838] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-10, human wild type IgG1 constant domains

[0839] One embodiment provides a 5H4 humanized HC-10, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLALI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:364). 147064467-020PCTcc.5H4 humanized HC-10, human IgG1 constant domains (DLE)

[0840] One embodiment provides a 5H4 humanized HC-10, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLALI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:365). dd.5H4 humanized HC-10, human IgG1 constant domains (FES)

[0841] One embodiment provides a 5H4 humanized HC-10, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLALI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:366). ee.5H4 humanized HC-10, human IgG1 constant domains (AA)

[0842] One embodiment provides a 5H4 humanized HC-10, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 148064467-020PCTQVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLALI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:367). ff.5H4 humanized HC-10, human IgG4 constant domain (G4P)

[0843] One embodiment provides a 5H4 humanized HC-10, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLALI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:368). xii.5H4 Humanized Heavy Chain 12 (HC-12) aa.5H4 Humanized HC-12 variable region

[0844] One embodiment provides a 5H4 humanized HC-12 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSS (SEQ ID NO:369) with

[0845] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0846] CDR-H2 IWWDDEK (SEQ ID NO:310), 149064467-020PCT

[0847] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-12, human wild type IgG1 constant domains

[0848] One embodiment provides a 5H4 humanized HC-12, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:370). cc.5H4 humanized HC-12, human IgG1 constant domains (DLE)

[0849] One embodiment provides a 5H4 humanized HC-12, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:371). dd.5H4 humanized HC-12, human IgG1 constant domains (FES)

[0850] One embodiment provides a 5H4 humanized HC-12, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 150064467-020PCTQVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:372). ee.5H4 humanized HC-12, human IgG1 constant domains (AA)

[0851] One embodiment provides a 5H4 humanized HC-12, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:373). ff.5H4 humanized HC-12, human IgG4 constant domain (G4P)

[0852] One embodiment provides a 5H4 humanized HC-12, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYYNPSLKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL 151064467-020PCTNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:374). xiii.5H4 Humanized Heavy Chain 13 (HC-13) aa.5H4 Humanized HC-13 variable region

[0853] One embodiment provides a 5H4 humanized HC-13 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSS (SEQ ID NO:375) with

[0854] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0855] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0856] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-13, human wild type IgG1 constant domains

[0857] One embodiment provides a 5H4 humanized HC-13, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:376). cc.5H4 humanized HC-13, human IgG1 constant domains (DLE)

[0858] One embodiment provides a 5H4 humanized HC-13, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 152064467-020PCTQVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:377). dd.5H4 humanized HC-13, human IgG1 constant domains (FES)

[0859] One embodiment provides a 5H4 humanized HC-13, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:378). ee.5H4 humanized HC-13, human IgG1 constant domains (AA)

[0860] One embodiment provides a 5H4 humanized HC-13, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL 153064467-020PCTHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:379). ff.5H4 humanized HC-13, human IgG4 constant domain (G4P)

[0861] One embodiment provides a 5H4 humanized HC-13, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQSPGKALEWLAHI WWDDEKYSNPALKTRLSISKDTSKNQVFLTMTNVDPADTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:380). xiv.5H4 Humanized Heavy Chain 14 (HC-14) aa.5H4 Humanized HC-14 variable region

[0862] One embodiment provides a 5H4 humanized HC-14 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QITLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALIW WDDEKRYNPSLKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTVV AYAYWGQGTLVTVSS (SEQ ID NO:381) with

[0863] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0864] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0865] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-14, human wild type IgG1 constant domains

[0866] One embodiment provides a 5H4 humanized HC-14, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 154064467-020PCTQITLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALIW WDDEKRYNPSLKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:382). cc.5H4 humanized HC-14, human IgG1 constant domains (DLE)

[0867] One embodiment provides a 5H4 humanized HC-14, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QITLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALIW WDDEKRYNPSLKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:383). dd.5H4 humanized HC-14, human IgG1 constant domains (FES)

[0868] One embodiment provides a 5H4 humanized HC-14, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QITLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALIW WDDEKRYNPSLKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQ 155064467-020PCTDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:384). ee.5H4 humanized HC-14, human IgG1 constant domains (AA)

[0869] One embodiment provides a 5H4 humanized HC-14, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QITLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALIW WDDEKRYNPSLKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS NTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:385). ff.5H4 humanized HC-14, human IgG4 constant domain (G4P)

[0870] One embodiment provides a 5H4 humanized HC-14, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QITLKESGPTLVKPTQTLTLTCTFSGFSLSTFGVGVGWIRQPPGKALEWLALIW WDDEKRYNPSLKTRLTITKDTSKNQVVLTMTNMDPVDTATYYCARIDSTVV AYAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSN TKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEG NVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:386). 156064467-020PCTxv.5H4 Humanized Heavy Chain 15 (HC-15) aa.5H4 Humanized HC-15 variable region

[0871] One embodiment provides a 5H4 humanized HC-15 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYNPSLKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSS (SEQ ID NO:387) with

[0872] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0873] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0874] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-15, human wild type IgG1 constant domains

[0875] One embodiment provides a 5H4 humanized HC-15, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYNPSLKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:388). cc.5H4 humanized HC-15, human IgG1 constant domains (DLE)

[0876] One embodiment provides a 5H4 humanized HC-15, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYNPSLKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP 157064467-020PCTSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:389). dd.5H4 humanized HC-15, human IgG1 constant domains (FES)

[0877] One embodiment provides a 5H4 humanized HC-15, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYNPSLKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVT CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:390). ee.5H4 humanized HC-15, human IgG1 constant domains (AA)

[0878] One embodiment provides a 5H4 humanized HC-15, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYNPSLKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:391). 158064467-020PCTff.5H4 humanized HC-15, human IgG4 constant domain (G4P)

[0879] One embodiment provides a 5H4 humanized HC-15, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVTLKESGPTLVKPTQTLTLTCSFSGFSLSTFGVGVGWIRQPPGKALEWLAHI WWDDEKYYNPSLKTRLTISKDTSKNQVVLTMTNVDPVDTATYYCARIDSTV VAYAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPS NTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:392). xvii.5H4 Humanized Heavy Chain 17 (HC-17) aa.5H4 Humanized HC-17 variable region

[0880] One embodiment provides a 5H4 humanized HC-17 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGSSVKVSCSFSGFSLSTFGVGVGWVRQAPGQGLEWMG HIWWDDEKYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARIDST VVAYAYWGQGTMVTVSS (SEQ ID NO:393) with

[0881] CDR-H1 GFSLSTFGVG (SEQ ID NO:432),

[0882] CDR-H2 IWWDDEK (SEQ ID NO:310),

[0883] CDR-H3 ARIDSTVVAYAY (SEQ ID NO: 433). bb.5H4 Humanized HC-17, human wild type IgG1 constant domains

[0884] One embodiment provides a 5H4 humanized HC-17, human wild type IgG1 constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGSSVKVSCSFSGFSLSTFGVGVGWVRQAPGQGLEWMG HIWWDDEKYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARIDST VVAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE 159064467-020PCTPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:394). cc.5H4 humanized HC-17, human IgG1 constant domains (DLE)

[0885] One embodiment provides a 5H4 humanized HC-17, human IgG1 constant domain (DLE) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGSSVKVSCSFSGFSLSTFGVGVGWVRQAPGQGLEWMG HIWWDDEKYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARIDST VVAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPLPEEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:395). dd.5H4 humanized HC-17, human IgG1 constant domains (FES)

[0886] One embodiment provides a 5H4 humanized HC-17, human IgG1 constant domain (FES) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGSSVKVSCSFSGFSLSTFGVGVGWVRQAPGQGLEWMG HIWWDDEKYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARIDST VVAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSCDKTHTCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPSEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:396). 160064467-020PCTee.5H4 humanized HC-17, human IgG1 constant domains (AA)

[0887] One embodiment provides a 5H4 humanized HC-17, human IgG1 constant domain (AA) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGSSVKVSCSFSGFSLSTFGVGVGWVRQAPGQGLEWMG HIWWDDEKYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARIDST VVAYAYWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHK PSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:397). ff.5H4 humanized HC-17, human IgG4 constant domain (G4P)

[0888] One embodiment provides a 5H4 humanized HC-17, human IgG4 constant domain (G4P) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: QVQLVQSGAEVKKPGSSVKVSCSFSGFSLSTFGVGVGWVRQAPGQGLEWMG HIWWDDEKYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARIDST VVAYAYWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHK PSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSLG (SEQ ID NO:398). xviii.5H4 Humanized Light Chain 1 (LC-1) aa.5H4 Humanized LC-1 variable region

[0889] One embodiment provides a 5H4 humanized LC-1 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 161064467-020PCTDIVMTQTPLSLSVTPGQPASISCKSSQTILHSDGNTYLYWYLQKPGQSPQLLIY KVSSRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGT KLEIK (SEQ ID NO:399) with

[0890] CDR-L1 QTILHSDGNTY (SEQ ID NO:400),

[0891] CDR-L2 KVS (SEQ ID NO:401),

[0892] CDR-L3 FQGSHVPYT (SEQ ID NO: 162). bb.5H4 Humanized LC-1, human kappa wild type constant domain

[0893] One embodiment provides a 5H4 humanized LC-1, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQTPLSLSVTPGQPASISCKSSQTILHSDGNTYLYWYLQKPGQSPQLLIY KVSSRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGT KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS FNRGEC (SEQ ID NO:402).

[0894] The underlined sequence is the light chain constant domain (wild type, kappa). cc.5H4 Humanized LC-1, human kappa wild type constant domain (CAAX)

[0895] One embodiment provides a 5H4 humanized LC-1, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQTPLSLSVTPGQPASISCKSSQTILHSDGNTYLYWYLQKPGQSPQLLIY KVSSRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGT KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS FNRGECGGGGGGGCVIM (SEQ ID NO:403). xix.5H4 Humanized Light Chain 2 (LC-2) aa.5H4 Humanized LC-2 variable region

[0896] One embodiment provides a 5H4 humanized LC-2 variable region having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: 162064467-020PCTDIVMTQTPLSLSVTPGQPASISCRSSQTILHSDGNTYLEWYLQKPGQSPQLLIY KVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGT KLEIK (SEQ ID NO:404) with

[0897] CDR-L1 QTILHSDGNTY (SEQ ID NO:400),

[0898] CDR-L2 KVS (SEQ ID NO:401),

[0899] CDR-L3 FQGSHVPYT (SEQ ID NO: 162). bb.5H4 Humanized LC-2, human kappa wild type constant domain

[0900] One embodiment provides a 5H4 humanized LC-2, human kappa wild type constant domain having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQTPLSLSVTPGQPASISCRSSQTILHSDGNTYLEWYLQKPGQSPQLLIY KVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGT KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS FNRGEC (SEQ ID NO:405).

[0901] The underlined sequence is the light chain constant domain (wild type, kappa). cc.5H4 Humanized LC-2, human kappa wild type constant domain (CAAX)

[0902] One embodiment provides a 5H4 humanized LC-2, human kappa wild type constant domain (CAAX) having at least 50%, 60%, 70%, 80%, 85%, 90%, 95%, 99%, or 100% sequence identity with the following amino acid sequence: DIVMTQTPLSLSVTPGQPASISCRSSQTILHSDGNTYLEWYLQKPGQSPQLLIY KVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPYTFGQGT KLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV...

Claims

What is claimed is:

1. An immunomodulatory agent that modulates CUB domain-containing protein 1 (CDCP1) expression, ligand binding, crosslinking, CDCP1 mediated signaling, or a combination thereof, comprising: (i) an anti-CDCP1 antibody or an antigen binding fragments thereof, (ii) a CDCP1 fusion protein or an antigen binding fragment, or (iii) combinations thereof, wherein the immunomodulatory agent immunospecifically binds to CDCP1 having at least 99% sequence identity to SEQ ID NO: 1, 2, 3, 4, or 5.

2. The CDCP1 immunomodulatory agent of claim 1, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 27, 31, 32, 42, 46, 47, 57, 61, 62, 72, 75, 76, 86, 90, 91, 100, 104, 105, 115, 119, 120, 130, 133, 134, 144, 148, 149, 159, 163, 164, 174, 178, 179, 284, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 399, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, or 427; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 18, 22, 23, 24, 25, 26, 33, 37, 38, 39, 40, 41, 48, 49, 52, 53, 55, 56, 63, 67, 68, 69, 70, 71, 77, 81, 82, 83, 84, 85, 92, 95, 96, 97, 98, 99, 106, 110, 111, 112, 113, 114, 121, 125, 126, 127, 128, 129, 135, 139, 140, 141, 142, 143, 150, 154, 155, 156, 157, 158, 165, 169, 170, 171, 172, 173, 180,184, 185, 186, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 216, 217, 217, 219, 220, 221, 222, 223, 224, 225, 226, 207, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238; 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 260, 261, 262, 263, 264, 265, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, or 283; or combinations thereof. 263064467-020PCT3. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises complementarity-determining regions (CDRs) selected from the group of CDRs consisting of at least 99% sequence identity to SEQ ID NOs: 19-21, 28-30, 34-36, 43-45, 49-51, 58-60, 64-66, 73, 74, 78-80, 87-89, 93, 94, 102- 103, 107-109, 116-118, 122-124, 131, 132, 136-138, 145-147, 151-153, 160-162, 166- 168, 175-177, 182-183, 190, 258, 259, 266, 285, 310-311, 355-357, 400-401, 428, 429- 431, 433, or 434.

4. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof is a humanized antibody comprising: a) a variable heavy chain of SEQ ID NO:180 and a variable light chain of SEQ ID NO:288; b) a variable heavy chain of SEQ ID NO:220 and a variable light chain of SEQ ID NO:291; c) a variable heavy chain of SEQ ID NO:180 and a variable light chain of SEQ ID NO: 288; d) a variable heavy chain of SEQ ID NO:220 and a variable light chain of SEQ ID NO:291); e) a variable heavy chain of SEQ ID NO:189 and a variable light chain of SEQ ID NO:288; f) a variable heavy chain of SEQ ID NO:196 and a variable light chain of SEQ ID NO:284; g) a variable heavy chain of SEQ ID NO:202 and a variable light chain of SEQ ID NO:288; h) a variable heavy chain of SEQ ID NO:208 and a variable light chain of SEQ ID NO:297; i) a variable heavy chain of SEQ ID NO:214 and a variable light chain of SEQ ID NO:300; j) a variable heavy chain of SEQ ID NO:226 and a variable light chain of SEQ ID NO:294; k) a variable heavy chain of SEQ ID NO:232 and a variable light chain of SEQ ID NO:303; l) a variable heavy chain of SEQ ID NO:238 and a variable light chain of SEQ ID NO:294; 264064467-020PCTm) a variable heavy chain of SEQ ID NO:245 and a variable light chain of SEQ ID NO:306; n) a variable heavy chain of SEQ ID NO:251 and a variable light chain of SEQ ID NO:294; o) a variable heavy chain of SEQ ID NO: 257 and a variable light chain of SEQ ID NO:288; p) a variable heavy chain of SEQ ID NO:265 and a variable light chain of SEQ ID NO:288; q) a variable heavy chain of SEQ ID NO:272 and a variable light chain of SEQ ID NO:284; or r) a variable heavy chain of SEQ ID NO:278 and a variable light chain of SEQ ID NO:

288.

5. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof is a humanized antibody comprising: a) a variable heavy chain of SEQ ID NO:309 and a variable light chain of SEQ ID NO:407; b) a variable heavy chain of SEQ ID NO:363 and a variable light chain of SEQ ID NO:416; c) a variable heavy chain of SEQ ID NO:369 and a variable light chain of SEQ ID NO:413; d) a variable heavy chain of SEQ ID NO:375 and a variable light chain of SEQ ID NO:413; e) a variable heavy chain of SEQ ID NO:317 and a variable light chain of SEQ ID NO:399; f) a variable heavy chain of SEQ ID NO::324 and a variable light chain of SEQ ID NO:404; g) a variable heavy chain of SEQ ID NO:330 and a variable light chain of SEQ ID NO:404; h) a variable heavy chain of SEQ ID NO:342 and a variable light chain of SEQ ID NO:422; i) a variable heavy chain of SEQ ID NO:348 and a variable light chain of SEQ ID NO:413; 265064467-020PCTj) a variable heavy chain of SEQ ID NO:381 and a variable light chain of SEQ ID NO:416; k) a variable heavy chain of SEQ ID NO:387 and a variable light chain of SEQ ID NO:413; l) a variable heavy chain of SEQ ID NO:354 and a variable light chain of SEQ ID NO:419; m) a variable heavy chain of SEQ ID NO:363 and a variable light chain of SEQ ID NO:425; n) a variable heavy chain of SEQ ID NO:393 and a variable light chain of SEQ ID NO:410; o) a variable heavy chain of SEQ ID NO:336 and a variable light chain of SEQ ID NO:425; or p) a variable heavy chain of SEQ ID NO:393 and a variable light chain of SEQ ID NO:

425.

6. The CDCP1 immunomodulatory agent of claim 1, wherein the fusion protein or an antigen binding fragment thereof comprises at least 99% sequence identity to SEQ ID NO: 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16.

7. The CDCP1 immunomodulatory agent of claim 6, wherein the fusion protein inhibits, reduces, or blocks CDCP1 mediated signal transduction.

8. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 27, 31, or 32; b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 18, 22, 23, 24, 25, or 26; wherein the light chain variable region (LCVR) CDRs have at least 99% sequence identity to SEQ ID NOs: 28-30 , and the heavy chain variable region (HCVR) CDRs have at least 99% sequence identity to SEQ ID NOs: 19-21. 266064467-020PCT9. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 42, 46, or 47; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 33, 37, 38, 39, 40, or 41; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs:43- 45, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 34-36.

10. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 57, 61, or 62; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 48, 49, 52, 53, 55, or 56; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 58-60, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs:.49-51.

11. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 72, 75, or 76; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 63, 67, 68, 69, 70, or 71; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 28, 73-74, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 64- 66.

12. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 86, 90, or 91; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 77, 81, 82, 83, 84, or 85; 267064467-020PCTwherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 87-89, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 78-80.

13. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 100, 104, or 105; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 92, 95, 96, 97, 98, or 99; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 101-103, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs:78, 93-94.

14. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 115, 119, or 120; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 106, 110, 111, 112, 113, or 114; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 116-118, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 107- 109.

15. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: a. a variable light chain having at least 99% sequence identity to SEQ ID NO: 130, 133, or 134; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 121, 125, 126, 127, 128, or 129; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 131-132, 118, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 122-124. 268064467-020PCT16. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: c. a variable light chain having at least 99% sequence identity to SEQ ID NO: 144, 148, or 149; and d. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 135, 139, 140, 141, 142, or 143; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 145-147, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 136- 138.

17. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: c. a variable light chain having at least 99% sequence identity to SEQ ID NO: 159, 163, or 164; and d. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 150, 154, 155, 156, 157, or 158; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 160-162, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 151- 153.

18. The CDCP1 immunomodulatory agent of claim 2, wherein the antibody or antigen binding fragment thereof comprises: e. a variable light chain having at least 99% sequence identity to SEQ ID NO: 174, 178, or 179; and f. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 165, 169, 170, 171, 172, or 173; wherein the LCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 175-177, and the HCVR CDRs have at least 99% sequence identity to SEQ ID NOs: 166- 168.

19. The CDCP1 immunomodulatory agent of claims 2 or 6, wherein the immunomodulatory agent further comprises a linker and a cytotoxic agent to provide an antibody-drug conjugate. 269064467-020PCT20. The CDCP1 immunomodulatory agent of claim 19, wherein the antibody drug conjugate comprises an antibody or antigen binding fragment thereof having a. an antibody or antigen binding fragment thereof having:a variable light chain having at least 99% sequence identity to SEQ ID NO: 27, 31, 32, 42, 46, 47, 57, 61, 62, 72, 75, 76, 86, 90, 91, 100, 104, 105, 115, 119, 120, 130, 133, 134, 144, 148, 149, 159, 163, 164, 174, 178, 179, 284, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 399, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, or 427; and b. a variable heavy chain having an amino acid sequence according to SEQ ID NO: 18, 22, 23, 24, 25, 26, 33, 37, 38, 39, 40, 41, 48, 49, 52, 53, 55, 56, 63, 67, 68, 69, 70, 71, 77, 81, 82, 83, 84, 85, 92, 95, 96, 97, 98, 99, 106, 110, 111, 112, 113, 114, 121, 125, 126, 127, 128, 129, 135, 139, 140, 141, 142, 143, 150, 154, 155, 156, 157, 158, 165, 169, 170, 171, 172, 173, 180,184, 185, 186, 187, 188, 189, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 216, 217, 217, 219, 220, 221, 222, 223, 224, 225, 226, 207, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238; 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 260, 261, 262, 263, 264, 265, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283; or combinations thereof; and wherein the antibody drug conjugate further comprises a linker and a cytotoxic payload.

21. The CDCP1 immunomodulatory agent of claim 20, wherein the cytotoxic payload is selected from a group of therapeutics consisting of auristatins, maytansinoids, DNA alkylating agents, mitotic inhibitors, antitumor antibiotics, immunomodulating agents, gene therapy vectors, alkylating agents, antiangiogenic agents, antimetabolites, boron- containing agents, chemoprotective agents, hormone agents, glucocorticoids, photoactive therapeutic agents, oligonucleotides, radioactive isotopes, radiosensitizers, topoisomerase inhibitors, tyrosine kinase inhibitors, or combinations thereof. 270064467-020PCT22. A pharmaceutical composition comprising an effective amount of the CDCP1 immunomodulatory agent of claim 1 to modulate CDCP1 expression, ligand binding, crosslinking, CDCP1 mediated signaling, or a combination thereof.

23. The pharmaceutical composition of claim 22, wherein the composition further comprises one or more additional therapeutic agents selected from cytokines, chemotherapeutic agents, radionuclides, other immunotherapeutics, enzymes, antibiotics, antivirals, anti-parasitics, growth factors, growth inhibitors, hormones, hormone antagonists, antibodies and bioactive fragments thereof, antigen and vaccine formulations, peptide drugs, anti-inflammatories, ligands that bind to Toll-Like Receptors to activate the innate immune system, molecules that mobilize and optimize the adaptive immune system, other molecules that activate or up-regulate the action of cytotoxic T lymphocytes, natural killer cells and helper T-cells, other molecules that deactivate or down-regulate suppressor or regulatory T-cells, or combinations thereof.

24. The pharmaceutical composition of claim 22, wherein the composition is administered with other immunomodulatory agents selected from PD-1 antagonists, CTLA4 antagonists, potentiating agents or other CDCP1 antagonists.

25. A method for enhancing or inducing an immune response in a subject in need thereof comprising administering an effective amount of the CDCP1 immunomodulatory agent according to claim 1 to enhance or induce an immune response in the subject.

26. A method for promoting an immune suppressive response in a subject in need thereof comprising administering an effective amount of the CDCP1 immunomodulatory agent according to claim 1 to induce, promote, or enhance CDCP1 mediated signal transduction. 271064467-020PCT

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