Antibody molecules against APRIL and their use

Abstract

Providing an antibody molecule against APRIL and its use. [Solution] Antibody molecules that specifically bind to APRIL are disclosed. The antibody molecules may be used to treat, prevent and / or diagnose disorders such as IgA nephropathy. Antibody molecules that bind to APRIL, e.g., human APRIL, mouse APRIL, or both, with high affinity and specificity are disclosed herein. Advantageously, some of the antibody molecules described herein have an improved ability to reduce (e.g., inhibit, block or neutralize) one or more biological activities of APRIL.

Description

[Technical Field]

[0001] Cross-references to related applications This application claims the benefits of U.S. Provisional Application No. 62 / 259,897 filed November 25, 2015, U.S. Provisional Application No. 62 / 313,684 filed March 25, 2016, U.S. Provisional Application No. 62 / 399,087 filed September 23, 2016, and U.S. Provisional Application No. 62 / 422,848 filed November 16, 2016. The contents of the aforementioned applications are incorporated herein by reference in their entirety.

[0002] Sequence List This application includes a sequence listing, which is filed electronically in ASCII format and is incorporated herein by reference in its entirety. The ASCII copy, created on November 21, 2016, is named P2029-7004WO_SL.txt and is 259,298 bytes in size. [Background technology]

[0003] IgA nephropathy is one of the most prevalent chronic glomerular diseases worldwide. Conservative epidemiological estimates cite a global incidence of approximately 5–50 cases / million (children) and 10–40 cases / million (adults). This incidence of the disease shows regional bias, with prevalence higher in Asia and the Americas, and disease burden particularly high in Japan and several regions of China. In Japan, the number of biopsy-confirmed cases of IgA nephropathy was estimated at approximately 350,000. In the United States, this estimate is approximately 100,000. Thus, it is the most frequently diagnosed glomerular disease in adults. Although a relatively painless disease, IgA nephropathy leads to end-stage renal disease (ESRD), or renal failure, in 20–50% of patients within a 20–30 year span. These numbers are often significantly underreported due to the need to confirm the disease through kidney biopsy, a protocol performed in various clinical settings. This disease has a complex etiology, involving genetic, epidemiological, and potentially environmental components in its pathogenesis, pathology, and exacerbations. It also presents with a wide range of clinical presentations, from asymptomatic to end-stage renal disease (ESRD). IgA nephropathy is typically caused by the deposition of IgA in the form of immune complexes in the glomerular interstitium of the kidney. Currently, there are no disease-specific treatments to address primary disease or exacerbations. [Overview of the Initiative] [Problems that the invention aims to solve]

[0004] There is a need to develop new approaches to treat, prevent, and diagnose IgA nephropathy and other disorders that share similar disease mechanisms. [Means for solving the problem]

[0005] This disclosure presents antibody molecules that bind, at least in part, to APRIL, e.g., human and / or mouse APRIL, and that include one or more functional and structural properties disclosed herein. In some embodiments, the antibody molecule binds to APRIL and / or reduces (e.g., inhibits, blocks, or neutralizes) one or more activities of APRIL. In some embodiments, the antibody molecule binds to a region in APRIL that interacts with TACI (e.g., the CRD2 domain of TACI). In some embodiments, the antibody molecule binds to one or more residues within a region of human APRIL as defined in either Tables 3-4 or 7-8. While we do not wish to be constrained by theory, in some embodiments, improved or optimal inhibition of APRIL activity occurs in certain regions (multiple) on APRIL (e.g., regions (multiple) associated with the interaction between APRIL and the CDR2 domain of TACI). This can be achieved by targeting ). In some embodiments, the antibody molecule is selected from Table 1 or 5, or competes for binding to APRIL with an antibody molecule selected from Table 1 or 5. In some embodiments, the antibody molecule binds to the same or overlapping epitopes recognized by an antibody molecule selected from Table 1 or 5. In some embodiments, the antibody molecule includes one or more heavy chain variable regions and / or one or more light chain variable regions as listed in Table 1 or 5. In some embodiments, the antibody molecule includes one or more heavy chain CDRs and / or one or more light chain CDRs as listed in Table 1 or 5. In some embodiments, nucleic acid molecules encoding the antibody molecule, expression vectors, host cells, compositions (e.g., pharmaceutical compositions), kits, containers, and methods for producing the antibody molecule are also presented. The antibody molecules disclosed herein can be used (alone or in combination with other drugs or therapeutic modalities) to treat, prevent, and / or diagnose APRIL-related disorders, such as IgA nephropathy.

[0006] Therefore, in certain aspects, this disclosure has the following characteristics: a) High affinity, for example less than about 100 nM, typically about 10 nM, more typically about 10 to 0.001 nM, about 10 to 0.01 nM, about 5 to 0.01 nM, about 3 to 0.05 nM, about 1 to 0.1 nM or stronger, for example less than about 80, 70, 60, 50, 40, 30, 20, 10, 8, 6, 4, 3, 2, 1, 0.5, 0.2, 0.1, 0.05, 0.01, 0.005 or 0.001 nM of dissociation constant (K D ) binds to human APRIL, b) High affinity, for example less than about 100 nM, typically about 10 nM, more typically about 10 to 0.001 nM, about 10 to 0.01 nM, about 5 to 0.01 nM, about 3 to 0.05 nM, about 1 to 0.1 nM or stronger, for example less than about 80, 70, 60, 50, 40, 30, 20, 10, 8, 6, 4, 3, 2, 1, 0.5, 0.2, 0.1, 0.05, 0.01, 0.005 or 0.001 nM of dissociation constant (K D ) binds to mouse APRIL, c) Does not bind to mouse APRIL, or has low affinity, with a dissociation constant (K) greater than, for example, about 500 nM, or greater than about 1000 nM. D ) binds to mouse APRIL, d) One or more cytokines (e.g., 2, 3, 4, 5, 6, 7, 8 or more) derived from TNF superfamily other than APRIL (TNFSF) that do not bind or have low affinity to, for example, TNFα, CD40 (TNFSF4), FasL (TNFSF6), TRAIL (TNFSF10), RANKL (TNFSF11), Tweak (TNFSF12), BAFF (TNFSF13B), or LIGHT (TNFSF14)) with a dissociation constant (K) greater than approximately 500 nM, for example, greater than approximately 1000 nM. D ) is used to join them, e) Binding to one or more residues within the region of APRIL as defined in Table 3 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or all), or specifically binding to an epitope on APRIL, for example, an epitope containing one or more residues listed in Table 3 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or all), f) Binding to one or more residues (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10 or all) within the region of APRIL as defined in Table 4, or specifically binding to an epitope on APRIL, for example, an epitope containing one or more residues (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10 or all) listed in Table 4. g) One or more of the APRIL region as defined in Table 7 (for example) , binds to residues (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or all), or specifically binds to epitopes on APRIL, for example, epitopes containing one or more residues (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or all) as listed in Table 7. h) Binding to one or more residues within the region of APRIL as defined in Table 8 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or all), or specifically binding to an epitope on APRIL, for example, an epitope containing one or more residues listed in Table 8 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or all), i) Epitope on APRIL, e.g., monoclonal antibodies listed in Table 1 or 5, e.g., monoclonal antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419 -1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237 specifically bind to the same, similar, or overlapping epitopes as those recognized by any of these. j) Reduce the biological activity of one or more APRIL (e.g., human APRIL, mouse APRIL, or both) in vitro, ex vivo, or in vivo (e.g., inhibit, block, or neutralize), k) For example, when determined by the method described herein, the binding of human APRIL to TACI is, for example, about 50 nM or less, typically about 0.01 to 50 nM, 0.1 to 25 nM, 0.1 to 10 nM, 0.5 to 5 nM or 1 to 5 nM, for example, about 40, 30, 20, 10, 5, 1, 0.5, 0.2, 0.1, 0.05 or less IC 50 To reduce (e.g., inhibit, block, or neutralize), l) For example, when determined by the method described herein, the binding of mouse APRIL to TACI is, for example, about 100 nM or less, typically about 0.01 to 75 nM, 0.1 to 50 nM, 0.1 to 25 nM, 0.1 to 10 nM, 0.5 to 5 nM or 1 to 5 nM, for example, about 80, 60, 40, 20, 10, 5, 1, 0.5, 0.2, 0.1, 0.05 or less IC 50 To reduce (e.g., inhibit, block, or neutralize), m) For example, when determined by the method described herein, the binding of human APRIL to BMCA is, for example, about 50 nM or less, typically about 0.01 to 50 nM, 0.1 to 25 nM, 0.1 to 10 nM, 0.5 to 5 nM or 1 to 5 nM, for example, about 40, 30, 20, 10, 5, 1, 0.5, 0.2, 0.1, 0.05 or less IC 50 To reduce (e.g., inhibit, block, or neutralize), n) For example, when determined by the method described herein, the binding of mouse APRIL to BMCA is, for example, about 200 nM or less, typically about 0.01 to 200 nM, 0.1 to 150 nM, 0.1 to 100 nM, 0.1 to 50 nM, 0.1 to 25 nM, 0.1 to 10 nM, 0.5 to 5 nM, or 1 to 5 nM, for example, about 150, 100, 50, 40, 30, 20, 10, 5, 1, 0.5, 0.2, 0.1, 0.05, or less than 0.01 nM IC 50 To reduce (e.g., inhibit, block, or neutralize), o) Monoclonal antibodies listed in Table 1 or 5, for example, monoclonal antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419 -1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237 exhibit the same or similar binding affinity or specificity, or both. p) Heavy chain variable regions and / or light chain variable regions listed in Table 1 or 5, e.g., monoclonal antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1 An antibody molecule exhibiting the same or similar binding affinity or specificity, or both, to an antibody molecule containing any of the following heavy chain variable regions and / or light chain variable regions: 310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237. q) One or more (e.g., two or three) heavy chain CDRs and / or one or more (e.g., two or three) light chain CDRs listed in Table 1 or 5, e.g., monoclonal antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419 An antibody molecule exhibiting the same or similar binding affinity or specificity, or both, as an antibody molecule containing one or more (e.g., two or three) heavy chain CDRs and / or one or more (two or three) light chain CDRs from any of the following: -1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237, r) The antibody molecule containing the amino acid sequence shown in Table 1 or 5 exhibits the same or similar binding affinity or specificity, or both. s) The antibody molecule containing the amino acid sequence encoded by the nucleotide sequence shown in Table 2 exhibits the same or similar binding affinity or specificity, or both. t) Inhibit the binding of a second antibody molecule to human APRIL, mouse APRIL, or both, for example, competitively, where the second antibody molecule is an antibody molecule selected from Table 1 or 5, e.g., monoclonal antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 241 It is one of the following: 9-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237. u) Compete for binding of a second antibody molecule to human APRIL, mouse APRIL, or both, where the second antibody molecule is a monoclonal antibody selected from Table 1 or 5, e.g., monoclonal antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1 It is one of the following: 204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237. v) A monoclonal antibody selected from Table 1 or 5, e.g., monoclonal antibody 2 218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2 Having one or more of the following biological characteristics: 419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237 w) Monoclonal antibodies selected from Table 1 or 5, e.g., monoclonal antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 24 Having one or more of the following structural characteristics: 19-1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439 or 4237, or x) Monoclonal antibodies selected from Table 1 or 5, e.g., monoclonal antibodies 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2 Having one or more of the following pharmacokinetic properties: 419-1306, 2419-1310, 2419-1406, 2922, 3327, 3530, 3525, 3125, 2621, 4035, 4035-062, 3934, 3833, 3631, 3732, 4338, 4540, 4540-063, 4540-033, 4439, or 4237 The present invention provides antibody molecules having one or more of the following (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23), such as the antibody molecules described herein.

[0007] In some aspects, this disclosure is, (i) Binds to or substantially binds to human APRIL; (ii) Binding to mouse APRIL, or substantially binding to it; (iii) inhibiting or substantially inhibiting the binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to TACI (e.g., human TACI, mouse TACI, or both); and (iv) An anti-APRIL antibody molecule characterized by inhibiting or substantially inhibiting the binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to BCMA (e.g., human BCMA, mouse BCMA, or both).

[0008] In one embodiment, the antibody molecule is a synthetic antibody molecule. In another embodiment, the antibody molecule is an isolated antibody molecule.

[0009] In one embodiment, the antibody molecule, as determined by the method described herein, is 20 nM or less to human APRIL, for example, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.8 nM, less than 0.6 nM, less than 0.4 nM, less than 0.2 nM, less than 0.1 nM, less than 0.05 nM, less than 0.02 nM, less than 0.01 nM, less than 0.005 nM, less than 0.002 nM, or 0 0.001 nM or less, for example, 0.001 nM to 20 nM, for example, 0.01 nM to 20 nM, 0.1 nM to 20 nM, 0.1 nM to 10 nM, 0.5 nM to 5 nM, 1 nM to 5 nM, 0.001 nM to 0.1 nM, 0.001 nM to 0.01 nM, 0.001 nM to 0.005 nM, 0.01 nM to 0.05 nM or 0.01 nM to 0.1 nM of EC 50 binds or substantially binds with.

[0010] In certain embodiments, the antibody molecule binds or substantially binds to mouse APRIL at 100 nM or less, for example, 80 nM or less, 60 nM or less, 40 nM or less, 20 nM or less, 10 nM or less, 9 nM or less, 8 nM or less, 7 nM or less, 6 nM or less, 5 nM or less, 4 nM or less, 3 nM or less, 2 nM or less, 1 nM or less, 0.8 nM or less, 0.6 nM or less, 0.4 nM or less, 0.2 nM or less, 0.1 nM or less, 0.05 nM or less, 0.02 nM or less, 0.01 nM or less, 0.005 nM or less, 0.002 nM or less, or 0.001 nM or less, for example, 0.001 nM to 100 nM, for example, 0.001 nM to 50 nM, 0.01 nM to 20 nM, 0.1 nM to 10 nM, 0.5 nM to 5 nM or 1 nM to 5 nM, 0.001 nM to 0.1 nM, 0.001 nM to 0.01 nM, 0.001 nM to 0.005 nM, 0.01 nM to 0.05 nM or 0.01 nM to 0.1 nM of EC 50 binds or substantially binds with.

[0011] In one embodiment, the antibody molecule, as determined by the method described herein, has a TACI (e.g., human TACI, mouse TACI, or both) binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to 50 nM or less, for example, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, less than 5 nM, less than 4 nM, less than 3 nM, or This includes ICs with a molecular weight of less than 2nM, less than 1nM, less than 0.8nM, less than 0.6nM, less than 0.4nM, less than 0.2nM, less than 0.1nM, less than 0.05nM, less than 0.02nM, or less than 0.01nM, for example, 0.01nM to 50nM, 0.1nM to 50nM, 0.1nM to 25nM, 0.1nM to 10nM, 0.1nM to 5nM, 0.1nM to 1nM, 0.1nM to 0.5nM, 0.5nM to 5nM, or 1nM to 5nM. 50 It inhibits or substantially inhibits.

[0012] In one embodiment, the antibody molecule, as determined by the method described herein, has a binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to BCMA (e.g., human BCMA, mouse BCMA, or both) at concentrations such as less than 200 nM, less than 150 nM, less than 100 nM, less than 50 nM, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, or less than 5 nM. or less than that, 4nM or less, 3nM or less, 2nM or less, 1nM or less, 0.8nM or less, 0.6nM or less, 0.4nM or less, 0.2nM or less, 0.1nM or less, 0.05nM or less, 0.02nM or less, 0.01nM or less, for example, ICs with a molecular weight of 0.01nM to 50nM, 0.1nM to 50nM, 0.1nM to 25nM, 0.1nM to 10nM, 0.1nM to 5nM, 0.1nM to 1nM, 0.1nM to 0.5nM, 0.5nM to 5nM or 1nM to 5nM 50 It inhibits or substantially inhibits.

[0013] In one embodiment, the antibody molecule is selected from an IgG antibody molecule, e.g., IgG, e.g., IgG1, IgG2 (e.g., IgG2a), IgG3, or IgG4, and includes, for example, a heavy chain constant region of IgG2 or IgG4. In another embodiment, the antibody molecule is an IgG1 antibody molecule, e.g., having the IgG1 constant region described herein. In yet another embodiment, the antibody molecule is an IgG2 antibody molecule, e.g., having the IgG2 constant region described herein. In one embodiment, the antibody molecule includes a light chain constant region of kappa or lambda light chains.

[0014] In some embodiments, the antibody molecule includes an Fc region. In some embodiments, the Fc region includes one or more mutations located at the interface between the CH2 and CH3 domains (e.g., such as those that increase binding affinity to the neonatal receptor FcRn and / or the half-life of the antibody molecule). In some embodiments, the Fc region includes one or more mutations, e.g., one or more (e.g., 2, 3, 4, 5, 6 or all) selected from T250Q, M252Y, S254T, T256E, M428L, H433K, N434F or any combination of these of IgG1. In some embodiments, the Fc region includes one or more mutations at positions 233-236 or 322 of human IgG1 or IgG2, or one or more substitutions at positions 327, 330 or 331 of human IgG4 (e.g., those that reduce complement-dependent cytotoxicity (CDC)). In one embodiment, the Fc region contains one or more (e.g., 2, 3, 4, 5, 6, 7, or all) mutations selected from E233P, L234V, L235A, G236, K322A, A327G, A330S, P331S or any combination thereof.

[0015] In some embodiments, the antibody molecule includes one or more framework regions derived from a humanized antibody molecule, such as a human framework germline sequence. In some embodiments, the antibody molecule includes heavy chain variable regions (VH) as described in Table 1 or 5. In some embodiments, the antibody molecule includes light chain variable regions (VL) as described in Table 1 or 5. In some embodiments, the antibody molecule includes heavy chain variable regions (VH) and light chain variable regions (VL) as described in Table 1 or 5. In some embodiments, the antibody molecule includes one, two or three CDRs of the heavy chain variable regions (VH) as described in Table 1 or 5. In some embodiments, the antibody molecule includes one, two or three CDRs of the light chain variable regions (VL) as described in Table 1 or 5. In some embodiments, the antibody molecule includes one, two or three CDRs of the heavy chain variable regions (VH) as described in Table 1 or 5, as well as one, two or three CDRs of the light chain variable regions (VL) as described in Table 1 or 5. In one embodiment, the antibody molecule includes two heavy chain variable regions and two light chain variable regions. In another embodiment, the antibody molecule is Fab, F(ab')2, Fv, Fd, or a single-chain Fv fragment (scFv).

[0016] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which is different from the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 61) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3530 (ii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 62) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (ii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3530 (e.g., SEQ ID NO: 63) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0017] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3530 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3530's LCDR3 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0018] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 61) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 62) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0019] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 61); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 62); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 45); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 46).

[0020] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region is determined by: (i) the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 64) differing by only one, two, or three or fewer amino acid residues, or by at least (ii) HCDR1 containing an amino acid sequence having 85, 90, 95, 99, or 100% homology; (ii) HCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 65), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) HCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0021] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3530 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3530's LCDR3 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0022] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 64) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 65) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0023] In one embodiment, the antibody molecule includes (i) VH containing the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 64); HCDR2 containing the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 65); and HCDR3 containing the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63); and (ii) LCDR1 containing the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67); monoclonal antibody 3530 (e.g., The antibody comprises LCDR2 containing the amino acid sequence of LCDR2 (SEQ ID NO: 45), and VL containing LCDR3 containing the amino acid sequence of LCDR3 (e.g., SEQ ID NO: 46) of monoclonal antibody 3530.

[0024] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3530 (e.g., SEQ ID NO: 66) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3530 (e.g., SEQ ID NO: 70) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0025] In one embodiment, the antibody molecule comprises (i) VH, which differs from the amino acid sequence of VH of monoclonal antibody 3530 (e.g., SEQ ID NO: 66) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which differs from the amino acid sequence of VL of monoclonal antibody 3530 (e.g., SEQ ID NO: 70) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3530 (e.g., SEQ ID NO: 66); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3530 (e.g., SEQ ID NO: 70).

[0026] In one embodiment, the antibody molecule is a monoclonal antibody 3530. In another embodiment, the antibody molecule is a humanized monoclonal antibody 3530.

[0027] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 61) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3525 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 62) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3525 (e.g., SEQ ID NO: 63) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0028] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1 containing an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) LCDR2 containing an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto 2; or (iii) comprising one, two, or all of the LCDR3s that differ by only one, two, or three or fewer amino acid residues from the amino acid sequence of the LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46), or have at least 85, 90, 95, 99, or 100% homology thereto.

[0029] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 61) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 62) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0030] In one embodiment, the antibody molecule is a VH comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable regions are: HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 61); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 62); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63), and (i i) A light chain variable region (VL) comprising three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises LCDR1, which contains the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44); LCDR2, which contains the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45); and LCDR3, which contains the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46).

[0031] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), which includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), where the heavy chain variable region comprises: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 64) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) HCDR2, which contains an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 65) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) HCDR3, which contains an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63) by only one, two, or three or fewer amino acid residues thereto It contains one, two, or all of the HCDR3 amino acid sequences having at least 85, 90, 95, 99, or 100% homology.

[0032] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3525 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3525's LCDR3 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0033] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 64) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 65) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0034] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 64); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 65); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46).

[0035] In one embodiment, the antibody molecule is derived from the amino acid sequence of the VH of monoclonal antibody 3525 (e.g., SEQ ID NO: 66) as follows: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, The VH comprises an amino acid sequence that differs by only 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises a VL comprising an amino acid sequence that differs by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues from the amino acid sequence of the VL of the monoclonal antibody 3525 (e.g., SEQ ID NO: 50), or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0036] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 3525 (e.g., SEQ ID NO: 66) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 3525 (e.g., SEQ ID NO: 50) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3525 (e.g., SEQ ID NO: 66); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3525 (e.g., SEQ ID NO: 50).

[0037] In one embodiment, the antibody molecule is monoclonal antibody 3525. In another embodiment, the antibody molecule is humanized monoclonal antibody 3525.

[0038] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 113) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3833 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 114) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3833 (e.g., SEQ ID NO: 115) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0039] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3833 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 117) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3833's LCDR3 (e.g., SEQ ID NO: 118) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0040] In one embodiment, the antibody molecule is (i) The following: VH containing one, two, or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 113) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 114) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 118), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0041] In one embodiment, the antibody molecule is a VH comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable regions are: HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 113); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 114); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115), and (i i) A light chain variable region (VL) comprising three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises LCDR1, which contains the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116); LCDR2, which contains the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117); and LCDR3, which contains the amino acid sequence of LCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 118).

[0042] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 119) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3833 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 120) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3833 (e.g., SEQ ID NO: 115) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0043] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region is as follows: (i) the amino acid sequence of LCDR1 of monoclonal antibody 3833 (for example, (ii) LCDR1 comprising an amino acid sequence that differs from sequence number 116) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the following LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 118) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0044] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs by only one, two or three or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 119), or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 120), or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115), or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 118), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0045] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 119); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 120); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 118).

[0046] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3833 (e.g., SEQ ID NO: 121) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VL of monoclonal antibody 3833 (e.g., SEQ ID NO: 122) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. Contains VL, which includes the amino acid sequence.

[0047] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 3833 (e.g., SEQ ID NO: 121) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 3833 (e.g., SEQ ID NO: 122) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3833 (e.g., SEQ ID NO: 121); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3833 (e.g., SEQ ID NO: 122).

[0048] In one embodiment, the antibody molecule is a monoclonal antibody 3833. In another embodiment, the monoclonal antibody 3833 is a humanized monoclonal antibody 3833. In another embodiment, the antibody molecule comprises VH containing any amino acid sequence of SEQ ID NOs. 246-250, VL containing any amino acid sequence of SEQ ID NOs. 251-253, or both.

[0049] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 123) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3631 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 124) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3631 (e.g., SEQ ID NO: 125) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0050] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3631. (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 127) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3631's LCDR3 (e.g., SEQ ID NO: 128) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0051] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 123) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; the amino acid sequence of HCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 123) 4) HCDR2 containing an amino acid sequence that differs from or has at least 85, 90, 95, 99, or 100% homology to it; or VH containing one, two, or all of the following: HCDR2 containing an amino acid sequence that differs from or has at least 85, 90, 95, 99, or 100% homology to the amino acid sequence of monoclonal antibody 3631 (e.g., SEQ ID NO: 125) by at least 1, 2, or 3 amino acid sequences; or HCDR3 containing an amino acid sequence that differs from or has at least 85, 90, 95, 99, or 100% homology to it; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 127), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0052] In one embodiment, the antibody molecule is a VH comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable regions are: HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 123); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 124); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 125), and (i i) A light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises LCDR1, which contains the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126); LCDR2, which contains the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 127); and LCDR3, which contains the amino acid sequence of LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128).

[0053] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: HCDR1, which differs from the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 129) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; and the amino acid sequence of HCDR2 of monoclonal antibody 3631. HCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from (e.g., SEQ ID NO: 130), or has at least 85, 90, 95, 99, or 100% homology thereto; or containing one, two, or all of the HCDR3s containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of monoclonal antibody 3631 (e.g., SEQ ID NO: 125), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0054] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: LCDR1, which differs from the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and LCDR2, which differs from the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 127) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 9 LCDR2 containing an amino acid sequence having 0, 95, 99, or 100% homology; or containing one, two, or all of LCDR3s that differ by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128), or that have at least 85, 90, 95, 99, or 100% homology to it.

[0055] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 129) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 130) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 125) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 127), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0056] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 129); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 130); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 125); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 127); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128).

[0057] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3631 (e.g., SEQ ID NO: 131) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3631 (e.g., SEQ ID NO: 132) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0058] In one embodiment, the antibody molecule is (i) the amino acid sequence of the VH of monoclonal antibody 3631 (e.g., SEQ ID NO: 131) is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 (i) VH comprising an amino acid sequence that differs by only 12, 13, 14 or 15 or fewer amino acid residues from the VL of monoclonal antibody 3631 (e.g., SEQ ID NO: 132), or has at least 85, 90, 95, 96, 97, 98, 99 or 100% homology thereto; and (ii) VL comprising an amino acid sequence that differs by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 or fewer amino acid residues from the VL of monoclonal antibody 3631 (e.g., SEQ ID NO: 132), or has at least 85, 90, 95, 96, 97, 98, 99 or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH comprising the amino acid sequence of VH of monoclonal antibody 3631 (e.g., SEQ ID NO: 131); and (ii) VL comprising the amino acid sequence of VL of monoclonal antibody 3631 (e.g., SEQ ID NO: 132).

[0059] In one embodiment, the antibody molecule is a monoclonal antibody 3631. In another embodiment, the antibody molecule is a humanized monoclonal antibody 3631.

[0060] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 133) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3732 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 134) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3732 (e.g., SEQ ID NO: 135) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0061] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3732 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 127) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3732's LCDR3 (e.g., SEQ ID NO: 137) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0062] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 133) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 134) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 127), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 137), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0063] In one embodiment, the antibody molecule is a VH comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the heavy chain variable regions are: HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 133); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 134); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135), and (i i) A light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the light chain variable region comprises LCDR1, which contains the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136); LCDR2, which contains the amino acid sequence of LCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 127); and LCDR3, which contains the amino acid sequence of LCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 137).

[0064] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 138) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3732 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 139) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3732 (e.g., SEQ ID NO: 135) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0065] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3732 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 127) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3732's LCDR3 (e.g., SEQ ID NO: 137) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0066] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 138) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 139) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 127), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 137), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0067] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 138); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 139); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 127); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 137).

[0068] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3732 (e.g., SEQ ID NO: 140) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3732 (e.g., SEQ ID NO: 141) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0069] In one embodiment, the antibody molecule includes (i) a VH containing an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody 3732 (e.g., SEQ ID NO: 140) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) an amino acid sequence containing an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody 3732 (e.g., SEQ ID NO: 141) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. It includes VL. In one embodiment, the antibody molecule includes (i) VH, which comprises the amino acid sequence of VH of monoclonal antibody 3732 (e.g., SEQ ID NO: 140); and (ii) VL, which comprises the amino acid sequence of VL of monoclonal antibody 3732 (e.g., SEQ ID NO: 141).

[0070] In one embodiment, the antibody molecule is monoclonal antibody 3732. In another embodiment, monoclonal antibody 3732 is humanized monoclonal antibody 3732.

[0071] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 154), or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) H (iii) an HCDR2 comprising an amino acid sequence that differs from the amino acid sequence of CDR2 (e.g., SEQ ID NO: 155) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) a monoclonal antibody 4540, 4540-063, or 4540-033 comprising one, two, or all of the following HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of HCDR3 (e.g., SEQ ID NO: 156) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0072] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) an LCDR1 that differs from the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (iii) an LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of (e.g., SEQ ID NO: 275) or 4540-033 (e.g., SEQ ID NO: 275), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0073] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 154), or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 155). VH containing one, two, or all of the following: HCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156), or HCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR3 containing at least 85, 90, 95, 99, or 100% homology to it. Bini (ii) The following: LCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275). The VL includes one, two, or all of the following: an LCDR2 containing an amino acid sequence that differs from the amino acid sequence of by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or an LCDR3 containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0074] In one embodiment, the antibody molecule is a VH comprising (i) three heavy chain complementarity-determining regions (HCDR1, HCDR2, and HCDR3), where the heavy chain variable regions are: HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 154); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 155); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156); and (ii) a light chain variable region (VL), where the light chain variable regions are three The light chain variable region includes a light chain complementarity determining region (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: LCDR1, which contains the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274); LCDR2, which contains the amino acid sequence of LCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275); and LCDR3, which contains the amino acid sequence of LCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158).

[0075] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region containing: (i) HCDR1 which differs from the amino acid sequence of monoclonal antibody 4540 (e.g., SEQ ID NO: 159), 4540-063 (e.g., SEQ ID NO: 276), or 4540-033 (e.g., SEQ ID NO: 159) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) monoclonal antibody 4540 (e.g., SEQ ID NO: 160), 4540-063 (iii) an HCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 (e.g., SEQ ID NO: 277) or 4540-033 (e.g., SEQ ID NO: 278), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0076] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region The following are included: (i) LCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274), or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) LC of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275). (iii) an LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of DR2 by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s of monoclonal antibodies 4540, 4540-063, or 4540-033 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 (e.g., SEQ ID NO: 158) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0077] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 159), 4540-063 (e.g., SEQ ID NO: 276), or 4540-033 (e.g., SEQ ID NO: 159), or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 160), 4540-063 (e.g., SEQ ID NO: 277), or 4540-033 (e.g., SEQ ID NO: 278). VH containing one, two, or all of the following: HCDR2 containing an amino acid sequence that differs from the amino acid sequence of by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156), or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following: LCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275). The VL includes one, two, or all of the following: an LCDR2 containing an amino acid sequence that differs from the amino acid sequence of by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or an LCDR3 containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0078] In one embodiment, the antibody molecule is a VH containing one, two or all of the following: (i) HCDR1 containing the amino acid sequence of HCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 159), 4540-063 (e.g., SEQ ID NO: 276), or 4540-033 (e.g., SEQ ID NO: 159); HCDR2 containing the amino acid sequence of HCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 160), 4540-063 (e.g., SEQ ID NO: 277), or 4540-033 (e.g., SEQ ID NO: 278); or HCDR3 containing the amino acid sequence of HCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156); and (ii) HCDR1 containing monoclonal antibody The VL contains one, two, or all of the following: LCDR1 containing the amino acid sequence of LCDR1 of 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274); LCDR2 containing the amino acid sequence of LCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275); or LCDR3 containing the amino acid sequence of LCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158).

[0079] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 4540 (e.g., SEQ ID NO: 161), 4540-063 (e.g., SEQ ID NO: 258), or 4540-033 (e.g., SEQ ID NO: 256) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 4540 (e.g., SEQ ID NO: 162), 4540-063 (e.g., SEQ ID NO: 261), or 4540-033 (e.g., SEQ ID NO: 261) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0080] In one embodiment, the antibody molecule includes (i) an amino acid sequence that differs from the VH amino acid sequence of monoclonal antibody 4540 (e.g., SEQ ID NO: 161), 4540-063 (e.g., SEQ ID NO: 258), or 4540-033 (e.g., SEQ ID NO: 256) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. (ii) a VH; and a VL comprising an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody 4540 (e.g., SEQ ID NO: 162), 4540-063 (e.g., SEQ ID NO: 261), or 4540-033 (e.g., SEQ ID NO: 261) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or having at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH containing the amino acid sequence of the VH of monoclonal antibody 4540 (e.g., SEQ ID NO: 161), 4540-063 (e.g., SEQ ID NO: 258), or 4540-033 (e.g., SEQ ID NO: 256); and (ii) VL containing the amino acid sequence of the VL of monoclonal antibody 4540 (e.g., SEQ ID NO: 162), 4540-063 (e.g., SEQ ID NO: 261), or 4540-033 (e.g., SEQ ID NO: 261).

[0081] In some embodiments, the antibody molecule is a monoclonal antibody 4540, 4540-063, or 4540-033. In some embodiments, monoclonal antibody 4540 is a humanized monoclonal antibody 4540 (e.g., antibody 4540-063 or 4540-033). In some embodiments, the antibody molecule includes VH containing any amino acid sequence of SEQ ID NOs. 254-258, VL containing any amino acid sequence of SEQ ID NOs. 259-261, or both.

[0082] In one embodiment, the antibody molecule binds to or substantially binds to one or more residues within the human APRIL region as defined in either Table 3-4 or 7-8, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more.

[0083] In one embodiment, an antibody molecule within the human APRIL region as defined in Table 3 binds to or substantially binds to one or more residues, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more. In one embodiment, the antibody molecule binds to or substantially binds to an epitope containing or consisting of one or more human APRIL residues from Table 3, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or all of them. In one embodiment, the antibody molecule binds to or substantially binds to an epitope that overlaps with an epitope containing or consisting of all of the human APRIL residues from Table 3. In another embodiment, the antibody molecule binds to or substantially binds to an epitope containing one or more APRIL residues from two monomers, for example, from monomer A and monomer B as shown in Table 3.

[0084] In some embodiments, an antibody molecule within the human APRIL region as defined in Table 4 binds to or substantially binds to one or more residues, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more. In some embodiments, an antibody molecule binds to or substantially binds to an epitope containing or consisting of one or more human APRIL residues from Table 4, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of them. In some embodiments, an antibody molecule binds to or substantially binds to an epitope that overlaps with an epitope containing or consisting of all of the human APRIL residues from Table 4. In some embodiments, an antibody molecule binds to or substantially binds to an epitope containing one or more APRIL residues from the CD loop (e.g., the loop connecting β-sheets C and D), the GH loop (e.g., the loop connecting β-sheets G and H), or both.

[0085] In one embodiment, the antibody molecule binds to or substantially binds to one or more of the human APRIL regions as defined in Table 7, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all of them. In another embodiment, the antibody molecule binds to or substantially binds to an epitope containing or comprising one or more of the human APRIL residues from Table 7, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all of them. In yet another embodiment, the antibody molecule binds to or substantially binds to an epitope that overlaps with an epitope containing or comprising all of the human APRIL residues from Table 7.

[0086] In one embodiment, the antibody molecule binds to or substantially binds to one or more of the human APRIL region as defined in Table 8, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them. In one embodiment, the antibody molecule binds to or substantially binds to an epitope containing or consisting of one or more of the human APRIL residues from Table 8, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them. In one embodiment, the antibody molecule binds to an epitope that overlaps with an epitope that contains or consists of all of the human APRIL residues from Table 8, or substantially binds to such an epitope.

[0087] In one embodiment, the antibody molecule contains one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9 or all) residues of human APRIL derived from positions 105-114 and / or one or more of mouse APRIL derived from positions 96-105. Binds to or substantially binds to residues (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or all of them). In some embodiments, the antibody molecule does not bind to or substantially binds to one, two, or all of Asp129, Arg233, or His203 of human APRIL. In some embodiments, the epitope is a structural epitope.

[0088] In one embodiment, the binding of an antibody molecule to APRIL (e.g., human APRIL) inhibits or substantially inhibits the binding of the CRD2 domain of TACI (e.g., human TACI) to APRIL (e.g., human APRIL). In another embodiment, the binding of an antibody molecule to human APRIL inhibits or substantially inhibits the binding of human TACI to one or more APRIL residues from Table 3, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them. In yet another embodiment, the binding of an antibody molecule to human APRIL inhibits or substantially inhibits the binding of human TACI to one or more human APRIL residues from Table 4, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of them. In yet another embodiment, the binding of the antibody molecule to human APRIL inhibits or substantially inhibits the binding of human TACI to one or more human APRIL residues from Table 7, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all of them. In yet another embodiment, the binding of the antibody molecule to human APRIL inhibits or substantially inhibits the binding of human TACI to one or more human APRIL residues from Table 8, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them. In another embodiment, the binding of the antibody molecule to human APRIL inhibits or substantially inhibits the binding of human BCMA to one or more human APRIL residues from Table 8, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them.

[0089] In some embodiments, the present disclosure features an antibody molecule that binds to or substantially binds to one or more residues within the human APRIL region as defined in either Table 3-4 or 7-8, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more.

[0090] In one embodiment, the anti-APRIL antibody molecule binds to or substantially binds to an epitope containing or comprising one or more human APRIL residues from either Table 3-4 or 7-8, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more. In one embodiment, the antibody molecule binds to or substantially binds to a structural epitope.

[0091] In one embodiment, the antibody molecule binds to or substantially binds to one or more residues within the human APRIL region as defined in Table 3, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more. In one embodiment, the anti-APRIL antibody molecule binds to or substantially binds to an epitope containing or consisting of one or more human APRIL residues from Table 3 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or all of them). In one embodiment, the antibody molecule binds to an epitope containing one or more APRIL residues from two monomers, for example, from monomer A and monomer B as shown in Table 3. Or, to be substantially combined.

[0092] In some embodiments, the antibody molecule binds to or substantially binds to one or more human APRIL residues within the region specified in Table 4, e.g., residues 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of them. In some embodiments, the epitope contains or consists of one or more APRIL residues from Table 4, e.g., residues 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of them. In some embodiments, the epitope contains or consists of one or more APRIL residues derived from the CD loop (e.g., the loop connecting β-sheets C and D), the GH loop (e.g., the loop connecting β-sheets G and H), or both.

[0093] In one embodiment, the antibody molecule binds to or substantially binds to one or more of the human APRIL regions as defined in Table 7, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all of them. In another embodiment, the antibody molecule binds to or substantially binds to an epitope containing or comprising one or more of the human APRIL residues from Table 7, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all of them. In yet another embodiment, the antibody molecule binds to or substantially binds to an epitope that overlaps with an epitope containing or comprising all of the human APRIL residues from Table 7.

[0094] In one embodiment, the antibody molecule binds to or substantially binds to one or more of the human APRIL region as defined in Table 8, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them. In one embodiment, the antibody molecule binds to or substantially binds to an epitope containing or consisting of one or more of the human APRIL residues from Table 8, for example, residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them. In one embodiment, the antibody molecule binds to an epitope that overlaps with an epitope that contains or consists of all of the human APRIL residues from Table 8, or substantially binds to such an epitope.

[0095] In one embodiment, the antibody molecule binds to or substantially binds to one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or all) residues of human APRIL originating from positions 105–114 and / or to one or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or all) residues of mouse APRIL originating from positions 96–105. In another embodiment, the antibody molecule does not bind to or substantially binds to one, two, or all of Asp129, Arg233, or His203 of human APRIL.

[0096] In one embodiment, an antibody molecule binds to or substantially binds to an epitope containing or consisting of one or more human APRIL residues from Table 6 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or all of them).

[0097] In one embodiment, the antibody molecule binds to or substantially binds to one or more (e.g., 2, 3, 4, 5, or all) amino acid residues of human APRIL selected from V174, F176, Q190, R195, R206, or Y208. In another embodiment, the antibody molecule is selected from V181, S226, I228, or N237. In some embodiments, the antibody molecule does not bind to, or substantially binds to, one or more (e.g., two, three, or all) of the amino acid residues of human APRIL selected from F176, V181, Q190, or I228, or substantially binds to, one or more (e.g., two, three, or all) of the amino acid residues of human APRIL selected from Y208 or N237, or substantially binds to, one or both of the amino acid residues of human APRIL selected from Y208 or N237, or substantially binds to, one or more (e.g., two, three, or all) of the amino acid residues of human APRIL selected from V174, R206, or Y208, or substantially binds to, one or more (e.g., two, three, or all) of the amino acid residues of human APRIL selected from F176, V181, Q190, or N237, or substantially binds to, one or more (e.g., two, three, or all) of the amino acid residues of human APRIL selected from F176, V181, Q190, or N237, or substantially binds to, one or more.

[0098] In some embodiments, the antibody molecule binds to or substantially binds to human April. In some embodiments, the antibody molecule binds to or substantially binds to both human April and mouse April. In some embodiments, the antibody molecule binds to or substantially binds to human April but does not bind to mouse April, or binds to mouse April with low affinity.

[0099] In one embodiment, the antibody molecule is determined, for example, by the method described herein, to have a concentration of 20 nM or less against human APRIL, for example, less than 10 nM, less than 9 nM or less, less than 8 nM or less, less than 7 nM or less, less than 6 nM or less, less than 5 nM or less, less than 4 nM or less, less than 3 nM or less, less than 2 nM or less, less than 1 nM or less, less than 0.8 nM or less, less than 0.6 nM or less, less than 0.4 nM or less, less than 0.2 nM or less, less than 0.1 nM or less EC less than, 0.05nM or less, 0.02nM or less, 0.01nM or less, 0.005nM or less, 0.002nM or less, or 0.001nM or less, for example, 0.001nM to 20nM, for example, 0.01nM to 20nM, 0.1nM to 20nM, for example, 0.1nM to 10nM, 0.5nM to 5nM, 1nM to 5nM, 0.001nM to 0.1nM, 0.001nM to 0.01nM, 0.001nM to 0.005nM, 0.01nM to 0.05nM, or 0.01nM to 0.1nM 50 They are joined by or effectively joined.

[0100] In one embodiment, the antibody molecule is determined, for example, by the method described herein, to mouse APRIL with a concentration of 100 nM or less, for example, less than 80 nM, less than 60 nM, less than 40 nM, less than 20 nM, for example, less than 10 nM, for example, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.8 nM, less than 0.6 nM, less than 0.4 nM, EC of 0.2nM or less, 0.1nM or less, 0.05nM or less, 0.02nM or less, 0.01nM or less, 0.005nM or less, 0.002nM or less, or 0.001nM or less, for example, 0.001nM to 100nM, for example, 0.001nM to 50nM, 0.01nM to 20nM, 0.1nM to 20nM, for example, 0.1nM to 10nM, 0.5nM to 5nM, 1nM to 5nM, 0.001nM to 0.1nM, 0.001nM to 0.01nM, 0.001nM to 0.005nM, 0.01nM to 0.05nM, or 0.01nM to 0.1nM 50 They are joined by or effectively joined.

[0101] In one embodiment, for example, when determined by the method described herein, the antibody molecule It does not bind to mouse APRIL, or has low affinity, for example, 1000 nM or greater, for example, 2000 nM or greater EC 50 It binds to mouse APRIL.

[0102] In some embodiments, the antibody molecule inhibits or substantially inhibits the binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to TACI (e.g., human TACI, mouse TACI, or both). In some embodiments, the antibody molecule inhibits the binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to TACI (e.g., human TACI, mouse TACI, or both) to 50 nM or less, for example, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, less than 5 nM, less than 4 nM, less than 3 nM, or This includes ICs with a molecular weight of less than 2nM, less than 1nM, less than 0.8nM, less than 0.6nM, less than 0.4nM, less than 0.2nM, less than 0.1nM, less than 0.05nM, less than 0.02nM, or less than 0.01nM, for example, 0.01nM to 50nM, 0.1nM to 50nM, 0.1nM to 25nM, 0.1nM to 10nM, 0.1nM to 5nM, 0.1nM to 1nM, 0.1nM to 0.5nM, 0.5nM to 5nM, or 1nM to 5nM. 50 It inhibits or substantially inhibits.

[0103] In some embodiments, the binding of an antibody molecule to APRIL (e.g., human APRIL) inhibits or substantially inhibits the binding of the CRD2 domain of TACI (e.g., human TACI) to APRIL (e.g., human APRIL). In some embodiments, the binding of an antibody molecule to human APRIL inhibits or substantially inhibits the binding of human TACI to one or more human APRIL residues from Table 3, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them. In some embodiments, the binding of an antibody molecule to human APRIL inhibits or substantially inhibits the binding of human TACI to one or more human APRIL residues from Table 4, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or all of them. In one embodiment, the binding of the antibody molecule to human APRIL inhibits or substantially inhibits the binding of human TACI to one or more human APRIL residues from Table 7, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all of them. In another embodiment, the binding of the antibody molecule to human APRIL inhibits or substantially inhibits the binding of human TACI to one or more human APRIL residues from Table 8, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them. In another embodiment, the binding of the antibody molecule to human APRIL inhibits or substantially inhibits the binding of human BCMA to one or more human APRIL residues from Table 8, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or all of them.

[0104] In some embodiments, the antibody molecule inhibits or substantially inhibits the BCMA (e.g., human BCMA, mouse BCMA, or both) of APRIL (e.g., human APRIL, mouse APRIL, or both). In some embodiments, the antibody molecule inhibits the binding of BCMA (e.g., human BCMA, mouse BCMA, or both) of APRIL (e.g., human BCMA, mouse BCMA, or both), as determined by the method described herein, for example, at concentrations of less than 200 nM, less than 150 nM, less than 100 nM, less than 50 nM, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, less than 5 nM, ICs with a molecular weight of 4nM or less, 3nM or less, 2nM or less, 1nM or less, 0.8nM or less, 0.6nM or less, 0.4nM or less, 0.2nM or less, 0.1nM or less, 0.05nM or less, 0.02nM or less, 0.01nM or less, for example, 0.01nM to 50nM, 0.1nM to 50nM, 0.1nM to 25nM, 0.1nM to 10nM, 0.1nM to 5nM, 0.1nM to 1nM, 0.1nM to 0.5nM, 0.5nM to 5nM, or 1nM to 5nM. 50 It inhibits or substantially inhibits.

[0105] In some embodiments, the antibody molecule is a synthetic antibody molecule. In some embodiments, the antibody molecule is an isolated antibody molecule. In some embodiments, the antibody molecule is an IgG antibody molecule, for example, selected from IgG, for example, IgG1, IgG2 (e.g., IgG2a), IgG3, or IgG4, and includes, for example, a heavy chain constant region of IgG2 or IgG4. In some embodiments, the antibody molecule is an IgG1 antibody molecule. In some embodiments, the antibody molecule is an IgG2 antibody molecule. In some embodiments, the antibody molecule includes a light chain constant region of a kappa or lambda light chain.

[0106] In some embodiments, the antibody molecule includes an Fc region. In some embodiments, the Fc region includes one or more mutations located at the interface between the CH2 and CH3 domains (e.g., such as those that increase binding affinity to the neonatal receptor FcRn and / or the half-life of the antibody molecule). In some embodiments, the Fc region includes one or more mutations, e.g., one or more (e.g., 2, 3, 4, 6 or all) selected from T250Q, M252Y, S254T, T256E, M428L, H433K, N434F or any combination of these of IgG1. In some embodiments, the Fc region includes one or more mutations at positions 233-236 or 322 of human IgG1 or IgG2, or one or more substitutions at positions 327, 330 or 331 of human IgG4 (e.g., those that reduce complement-dependent cytotoxicity (CDC)). In one embodiment, the Fc region contains one or more (e.g., 2, 3, 4, 6, 7, or all) mutations selected from E233P, L234V, L235A, G236, K322A, A327G, A330S, P331S or any combination thereof.

[0107] In one embodiment, the antibody molecule is a humanized antibody molecule, for example, as described in Table 1 or 5, which includes one or more framework regions derived from a human framework germline sequence.

[0108] In one embodiment, the antibody molecule includes two heavy chain variable regions and two light chain variable regions. In another embodiment, the antibody molecule is Fab, F(ab')2, Fv, Fd, or a single-chain Fv fragment (scFv).

[0109] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1 which differs from the amino acid sequence of HCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 1) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) H (iii) HCDR2 containing an amino acid sequence that differs from the amino acid sequence of CDR2 (e.g., SEQ ID NO: 2) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 3) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto. This includes one, two, or all of the following.

[0110] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 4) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 2218 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 5) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 2218's LCDR3 (e.g., SEQ ID NO: 6) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0111] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 1) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 2) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 3) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 4), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 5), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 6), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0112] In one embodiment, the antibody molecule comprises (i) HCDR1, which includes an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 1) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2, which includes an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 2) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and monoclonal antibody 2 VH containing HCDR3 which differs from the amino acid sequence of HCDR3 of 218 (e.g., SEQ ID NO: 3) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto, and (ii) LCDR1 containing an amino acid sequence which differs from the amino acid sequence of LCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 4) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; the amino acid sequence of LCDR2 of monoclonal antibody 2218 (e.g. The VL includes an LCDR2 containing an amino acid sequence that differs from the sequence number 5) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and an LCDR3 containing an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 2218's LCDR3 (e.g., sequence number 6) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0113] In one embodiment, the antibody molecule includes a VH comprising one, two, or all of the following: (i) HCDR1 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 7), or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) HCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 8), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) HCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 3), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0114] In one embodiment, the antibody molecule includes a VL comprising one, two, or all of the following: (i) LCDR1 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 4), or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 5), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 6), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0115] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 7) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 8) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 3) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 4), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 5), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 6), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0116] In one embodiment, the antibody molecule comprises: (i) HCDR1, which includes an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 7) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2, which includes an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 8) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and HCDR3, which includes an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 3) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto. VH, and VL comprising (ii) LCDR1 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 2218 (e.g., SEQ ID NO: 4), or has at least 85, 90, 95, 99, or 100% homogeneity with it; LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2218 (e.g., SEQ ID NO: 5), or has at least 85, 90, 95, 99, or 100% homology with it; and LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2218 (e.g., SEQ ID NO: 6), or has at least 85, 90, 95, 99, or 100% homology with it.

[0117] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 2218 (e.g., SEQ ID NO: 9) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or includes an amino acid sequence having at least 85, 90, 95, 96, 97, 98, 99, or 100% homogeneity with it. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 2218 (e.g., SEQ ID NO: 10) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or includes an amino acid sequence having at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with it.

[0118] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 2218 (e.g., SEQ ID NO: 9) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 2218 (e.g., SEQ ID NO: 10) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 2218 (e.g., SEQ ID NO: 9); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 2218 (e.g., SEQ ID NO: 10).

[0119] In one embodiment, the antibody molecule is a monoclonal antibody 2218. In another embodiment, the monoclonal antibody 2218 is a humanized monoclonal antibody 2218. In another embodiment, the antibody molecule comprises VH containing any amino acid sequence of SEQ ID NOs. 190-201, VL containing any amino acid sequence of SEQ ID NOs. 202-208, or both.

[0120] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region , comprising one, two or all of the following: (i) HCDR1 containing an amino acid sequence of monoclonal antibody 2419 (e.g., SEQ ID NO: 11) or an amino acid sequence that differs by only one, two or three or fewer amino acid residues from the 2419-related antibody, or has at least 85, 90, 95, 99 or 100% homology thereto; (ii) HCDR2 containing an amino acid sequence of monoclonal antibody 2419 (e.g., SEQ ID NO: 12) or an amino acid sequence that differs by only one, two or three or fewer amino acid residues from the 2419-related antibody, or has at least 85, 90, 95, 99 or 100% homology thereto; or (iii) HCDR3 containing an amino acid sequence of monoclonal antibody 2419 (e.g., SEQ ID NO: 13) or an amino acid sequence that differs by only one, two or three or fewer amino acid residues from the 2419-related antibody, or has at least 85, 90, 95, 99 or 100% homology thereto.

[0121] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1 which differs from the amino acid sequence of LCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 14) or 2419-associated antibody by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) monoclonal antibody 2419 (e.g., SEQ ID NO: 15) or 24 (iii) comprising one, two, or all of the following LCDR2s: (iii) an LCDR2 that differs from the amino acid sequence of the LCDR2 of the 19-related antibody by only one, two, or three or fewer amino acid residues, or an amino acid sequence having at least 85, 90, 95, 99, or 100% homology thereto; or (iii) an LCDR3 that differs from the amino acid sequence of the LCDR3 of the monoclonal antibody 2419 (e.g., SEQ ID NO: 16) or the 2419-related antibody by only one, two, or three or fewer amino acid residues, or an amino acid sequence having at least 85, 90, 95, 99, or 100% homology thereto.

[0122] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs by only one, two or three or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 11) or 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 2419 (e.g., SEQ ID NO: 12) or 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR3 of monoclonal antibody 2419 (e.g., SEQ ID NO: 13) or 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following VLs include: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 14) or a 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2419 (e.g., SEQ ID NO: 15) or a 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2419 (e.g., SEQ ID NO: 16) or a 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0123] In one embodiment, the antibody molecule comprises VH, which includes (i) HCDR1, which includes the amino acid sequence of HCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 11) or a 2419-related antibody; HCDR2, which includes the amino acid sequence of HCDR2 of monoclonal antibody 2419 (e.g., SEQ ID NO: 12) or a 2419-related antibody; or HCDR3, which includes the amino acid sequence of HCDR3 of monoclonal antibody 2419 (e.g., SEQ ID NO: 13) or a 2419-related antibody; and (ii) LCDR1, which includes the amino acid sequence of LCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 14) or a 2419-related antibody; LCDR2, which includes the amino acid sequence of LCDR2 of monoclonal antibody 2419 (e.g., SEQ ID NO: 15) or a 2419-related antibody; and LCDR3, which includes the amino acid sequence of LCDR3 of monoclonal antibody 2419 (e.g., SEQ ID NO: 16) or a 2419-related antibody.

[0124] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1 which differs from the amino acid sequence of monoclonal antibody 2419 (e.g., SEQ ID NO: 17) or 2419-associated antibody by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) monoclonal antibody 2419 (e.g., SEQ ID NO: 18) or 24 (iii) comprising one, two, or all of the following: (iii) an HCDR2 having an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the HCDR2 of the 19-related antibody, or having at least 85, 90, 95, 99, or 100% homology thereto; or (iii) a monoclonal antibody 2419 (e.g., SEQ ID NO: 13) or an HCDR3 having an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the HCDR3 of the 2419-related antibody, or having at least 85, 90, 95, 99, or 100% homology thereto.

[0125] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1 which differs from the amino acid sequence of LCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 14) or 2419-associated antibody by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) monoclonal antibody 2419 (e.g., SEQ ID NO: 15) or 24 (iii) comprising one, two, or all of the following LCDR2s: (iii) an LCDR2 that differs from the amino acid sequence of the LCDR2 of the 19-related antibody by only one, two, or three or fewer amino acid residues, or an amino acid sequence having at least 85, 90, 95, 99, or 100% homology thereto; or (iii) an LCDR3 that differs from the amino acid sequence of the LCDR3 of the monoclonal antibody 2419 (e.g., SEQ ID NO: 16) or the 2419-related antibody by only one, two, or three or fewer amino acid residues, or an amino acid sequence having at least 85, 90, 95, 99, or 100% homology thereto.

[0126] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 17) or 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 2419 (e.g., SEQ ID NO: 18) or 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR3 of monoclonal antibody 2419 (e.g., SEQ ID NO: 13) or 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; one or two of these or VH including all, and (ii) The following VLs include: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 14) or a 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2419 (e.g., SEQ ID NO: 15) or a 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2419 (e.g., SEQ ID NO: 16) or a 2419-related antibody, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0127] In one embodiment, the antibody molecule comprises VH, which includes (i) HCDR1, which includes the amino acid sequence of HCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 17) or 2419-related antibody; HCDR2, which includes the amino acid sequence of HCDR2 of monoclonal antibody 2419 (e.g., SEQ ID NO: 18) or 2419-related antibody; or HCDR3, which includes the amino acid sequence of HCDR3 of monoclonal antibody 2419 (e.g., SEQ ID NO: 13) or 2419-related antibody; and (ii) LCDR1, which includes the amino acid sequence of LCDR1 of monoclonal antibody 2419 (e.g., SEQ ID NO: 14) or 2419-related antibody; LCDR2, which includes the amino acid sequence of LCDR2 of monoclonal antibody 2419 (e.g., SEQ ID NO: 15) or 2419-related antibody; and LCDR3, which includes the amino acid sequence of LCDR3 of monoclonal antibody 2419 (e.g., SEQ ID NO: 16) or 2419-related antibody.

[0128] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of the monoclonal antibody 2419 (e.g., SEQ ID NO: 19) or a 2419-related antibody by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of the monoclonal antibody 2419 (e.g., SEQ ID NO: 20) or a 2419-related antibody by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0129] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of the VH of the monoclonal antibody 2419 (e.g., SEQ ID NO: 19) or a 2419-related antibody by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homogeneity with the VH; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of the VL of the monoclonal antibody 2419 (e.g., SEQ ID NO: 20) or a 2419-related antibody by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology with the VL.

[0130] In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 2419 (e.g., SEQ ID NO: 19) or a 2419-related antibody; and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 2419 (e.g., SEQ ID NO: 20) or a 2419-related antibody.

[0131] In one embodiment, the antibody molecule is monoclonal antibody 2419. In some embodiments, the monoclonal antibody 2419 is a humanized monoclonal antibody 2419. In one embodiment, the antibody molecule comprises VH containing any of the amino acid sequences of SEQ ID NOs. 209-214, 283, 288, 289, 291, 292, 294, 296, or 317, VL containing any of the amino acid sequences of SEQ ID NOs. 215-219, 284, 286, 295, or 316, or both.

[0132] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 21) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 2922 (iii) an HCDR2 containing an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 32) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 2922 (e.g., SEQ ID NO: 33) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0133] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 34) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 2922 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 35) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 2922's LCDR3 (e.g., SEQ ID NO: 36) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0134] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 21) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 2922 (e.g., SEQ ID NO: 32) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 2922 (e.g., SEQ ID NO: 33) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: The amino acid sequence of LCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 34) differs by only 1, 2, or 3 or fewer amino acid residues, or by fewer than that. The VL includes one, two, or all of the following: LCDR1 containing an amino acid sequence having 85, 90, 95, 99, or 100% homology; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2922 (e.g., SEQ ID NO: 35), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2922 (e.g., SEQ ID NO: 36), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0135] In one embodiment, the antibody molecule comprises VH, which includes (i) HCDR1, which includes the amino acid sequence of HCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 21); HCDR2, which includes the amino acid sequence of HCDR2 of monoclonal antibody 2922 (e.g., SEQ ID NO: 32); and HCDR3, which includes the amino acid sequence of HCDR3 of monoclonal antibody 2922 (e.g., SEQ ID NO: 33); and VL, which includes LCDR1, which includes the amino acid sequence of LCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 34); LCDR2, which includes the amino acid sequence of LCDR2 of monoclonal antibody 2922 (e.g., SEQ ID NO: 35); and LCDR3, which includes the amino acid sequence of LCDR3 of monoclonal antibody 2922 (e.g., SEQ ID NO: 36).

[0136] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 37) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 2922 (iii) an HCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the sequence (e.g., SEQ ID NO: 38) or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 2922's HCDR3 (e.g., SEQ ID NO: 33) or has at least 85, 90, 95, 99, or 100% homology thereto.

[0137] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 34) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 2922 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 35) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 2922's LCDR3 (e.g., SEQ ID NO: 36) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0138] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 37) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; the amino acid sequence of HCDR2 of monoclonal antibody 2922 (e.g., SEQ ID NO: 38). VH containing one, two, or all of the following: HCDR2 containing an amino acid sequence that differs from by only one, two, or three or fewer amino acid residues from the amino acid sequence of monoclonal antibody 2922 (e.g., SEQ ID NO: 33), or HCDR3 the amino acid sequence of monoclonal antibody 2922 (e.g., SEQ ID NO: 33), or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 2922 (e.g., SEQ ID NO: 33), and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 34), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2922 (e.g., SEQ ID NO: 35), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2922 (e.g., SEQ ID NO: 36), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0139] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 37); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 2922 (e.g., SEQ ID NO: 38); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 2922 (e.g., SEQ ID NO: 33); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 2922 (e.g., SEQ ID NO: 34); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 2922 (e.g., SEQ ID NO: 35); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 2922 (e.g., SEQ ID NO: 36).

[0140] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 2922 (e.g., SEQ ID NO: 39) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 2922 (e.g., SEQ ID NO: 40) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0141] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 2922 (e.g., SEQ ID NO: 39) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 2922 (e.g., SEQ ID NO: 40) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 2922 (e.g., SEQ ID NO: 39); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 2922 (e.g., SEQ ID NO: 40).

[0142] In one embodiment, the antibody molecule is a monoclonal antibody 2922. The antibody molecule is the humanized monoclonal antibody 2922.

[0143] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 51) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3327 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 52) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3327 (e.g., SEQ ID NO: 53) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0144] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 54) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3327 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 55) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3327's LCDR3 (e.g., SEQ ID NO: 56) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0145] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 51) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3327 (e.g., SEQ ID NO: 52) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3327 (e.g., SEQ ID NO: 53) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 54), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3327 (e.g., SEQ ID NO: 55), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3327 (e.g., SEQ ID NO: 56), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0146] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 51); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3327 (e.g., SEQ ID NO: 52); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3327 (e.g., SEQ ID NO: 53); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 54); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3327 (e.g., SEQ ID NO: 55); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3327 (e.g., SEQ ID NO: 56).

[0147] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 57) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3327 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 58) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3327 (e.g., SEQ ID NO: 53) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0148] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 54) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3327 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 55) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3327's LCDR3 (e.g., SEQ ID NO: 56) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0149] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 57) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3327 (e.g., SEQ ID NO: 58) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3327 (e.g., SEQ ID NO: 53) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: LCDs that differ by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 54), or that have at least 85, 90, 95, 99, or 100% homology thereto. R1; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3327 (e.g., SEQ ID NO: 55), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing one, two, or all of the following: an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3327 (e.g., SEQ ID NO: 56), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0150] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 57); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3327 (e.g., SEQ ID NO: 58); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3327 (e.g., SEQ ID NO: 53); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3327 (e.g., SEQ ID NO: 54); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3327 (e.g., SEQ ID NO: 55); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3327 (e.g., SEQ ID NO: 56).

[0151] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3327 (e.g., SEQ ID NO: 59) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3327 (e.g., SEQ ID NO: 60) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0152] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 3327 (e.g., SEQ ID NO: 59) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 3327 (e.g., SEQ ID NO: 60) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3327 (e.g., SEQ ID NO: 59); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3327 (e.g., SEQ ID NO: 60).

[0153] In one embodiment, the antibody molecule is a monoclonal antibody 3327. In another embodiment, the antibody molecule is a humanized monoclonal antibody 3327.

[0154] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which differs from the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 61) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) HCDR2, which differs from the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 62) by only 1, 2, or 3 or fewer amino acid residues thereto, or at least (iii) an HCDR2 containing an amino acid sequence having 85, 90, 95, 99, or 100% homology; or (iii) one, two, or all of the HCDR3s containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63), or that has at least 85, 90, 95, 99, or 100% homology thereto.

[0155] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3530 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3530's LCDR3 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0156] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 61) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 62) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0157] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 61); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 62); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 45); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 46).

[0158] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 64) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3530 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 65) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3530 (e.g., SEQ ID NO: 63) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0159] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3530 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3530's LCDR3 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0160] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 64) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 65) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0161] In one embodiment, the antibody molecule is (i) a monoclonal antibody 3530 (e.g., sequence number VH comprises (ii) HCDR1 containing the amino acid sequence of HCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 64); HCDR2 containing the amino acid sequence of HCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 65); and HCDR3 containing the amino acid sequence of HCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 63); and VL comprising LCDR1 containing the amino acid sequence of LCDR1 of monoclonal antibody 3530 (e.g., SEQ ID NO: 67); LCDR2 containing the amino acid sequence of LCDR2 of monoclonal antibody 3530 (e.g., SEQ ID NO: 45); and LCDR3 containing the amino acid sequence of LCDR3 of monoclonal antibody 3530 (e.g., SEQ ID NO: 46).

[0162] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3530 (e.g., SEQ ID NO: 66) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3530 (e.g., SEQ ID NO: 70) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0163] In one embodiment, the antibody molecule comprises (i) VH, which differs from the amino acid sequence of VH of monoclonal antibody 3530 (e.g., SEQ ID NO: 66) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which differs from the amino acid sequence of VL of monoclonal antibody 3530 (e.g., SEQ ID NO: 70) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3530 (e.g., SEQ ID NO: 66); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3530 (e.g., SEQ ID NO: 70).

[0164] In one embodiment, the antibody molecule is a monoclonal antibody 3530. In another embodiment, the antibody molecule is a humanized monoclonal antibody 3530.

[0165] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 61) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3525 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 62) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3525 (e.g., SEQ ID NO: 63) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0166] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region is determined as follows: (i) the amino acid sequence of LCDR1 of monoclonal antibody 3525 (for example, (ii) LCDR1 comprising an amino acid sequence that differs from sequence number 44) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the following LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0167] In one embodiment, the antibody molecule is (i) VH containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3525 HCDR1 (e.g., SEQ ID NO: 61) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3525 HCDR2 (e.g., SEQ ID NO: 62) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or VH containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3525 HCDR3 (e.g., SEQ ID NO: 63) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto, and (ii) A VL comprising an LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44), or has at least 85, 90, 95, 99, or 100% homology thereto; an LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45), or has at least 85, 90, 95, 99, or 100% homology thereto; or an LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0168] In certain embodiments, the antibody molecule comprises (i) a VH comprising an HCDR1 comprising the amino acid sequence of the HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 61); an HCDR2 comprising the amino acid sequence of the HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 62); and an HCDR3 comprising the amino acid sequence of the HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63), and (ii) a VL comprising an LCDR1 comprising the amino acid sequence of the LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44); an LCDR2 comprising the amino acid sequence of the LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45); and an LCDR3 comprising the amino acid sequence of the LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46).

[0169] In certain embodiments, the antibody molecule comprises a variable heavy chain region (VH), the variable heavy chain region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3), and the variable heavy chain region comprises the following: (i) an HCDR1 comprising an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 64) by 1, 2 or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; (ii) an HCDR2 comprising an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 65) by 1, 2 or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto ; or (iii) one, two or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63) by 1, 2 or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto.

[0170] In certain embodiments, the antibody molecule comprises a light chain variable region (VL), the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region is as follows: (i) an LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto; (ii) an LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto; or (iii) an LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto, and includes one, two, or all of them.

[0171] In certain embodiments, the antibody molecule is (i) as follows: a VH comprising one, two, or all of: an HCDR1 comprising an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 64) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto; an HCDR2 comprising an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 65) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto; or an HCDR3 comprising an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto, and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0172] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 64); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 65); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 63); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3525 (e.g., SEQ ID NO: 44); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3525 (e.g., SEQ ID NO: 45); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3525 (e.g., SEQ ID NO: 46).

[0173] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3525 (e.g., SEQ ID NO: 66) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3525 (e.g., SEQ ID NO: 50) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0174] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 3525 (e.g., SEQ ID NO: 66) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 3525 (e.g., SEQ ID NO: 50) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3525 (e.g., SEQ ID NO: 66); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3525 (e.g., SEQ ID NO: 50).

[0175] In one embodiment, the antibody molecule is monoclonal antibody 3525. In another embodiment, the antibody molecule is humanized monoclonal antibody 3525.

[0176] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 21) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 2621 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 22) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 2621 (e.g., SEQ ID NO: 23) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0177] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 24) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 2621 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 25) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 2621's LCDR3 (e.g., SEQ ID NO: 26) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0178] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 21) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 22) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 23) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 24) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 25) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 26) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0179] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 21); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 22); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 23); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 24); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 25); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 26).

[0180] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 27) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 2621 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 28) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 2621 (e.g., SEQ ID NO: 23) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0181] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region is determined by: (i) the amino acid sequence of LCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 24) differing by only one, two, or three or fewer amino acid residues, or by fewer than that. (ii) LCDR1 containing an amino acid sequence having 85, 90, 95, 99, or 100% homology; (ii) LCDR2 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 25), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) containing one, two, or all of the following LCDR3s containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 26), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0182] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 27) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 28) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 23) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 24) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 25) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 26) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0183] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 27); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 28); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 23); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 2621 (e.g., SEQ ID NO: 24); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 2621 (e.g., SEQ ID NO: 25); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 2621 (e.g., SEQ ID NO: 26).

[0184] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 2621 (e.g., SEQ ID NO: 29) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 2621 (e.g., SEQ ID NO: 30) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0185] In one embodiment, the antibody molecule includes (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 2621 (e.g., SEQ ID NO: 29) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 2621 (e.g., SEQ ID NO: 30) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 2621 (e.g., SEQ ID NO: 29); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 2621 (e.g., SEQ ID NO: 30).

[0186] In one embodiment, the antibody molecule is a monoclonal antibody 2621. In another embodiment, the antibody molecule is a humanized monoclonal antibody 2621.

[0187] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 11) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3125 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 42) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3125 (e.g., SEQ ID NO: 43) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0188] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 44) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3125 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3125's LCDR3 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0189] In one embodiment, the antibody molecule is (i) as follows: an HCDR1 comprising an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 11) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto; an HCDR2 comprising an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody 3125 (e.g., SEQ ID NO: 42) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto; or an HCDR3 comprising an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody 3125 (e.g., SEQ ID NO: 43) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto, wherein the VH comprises one, two, or all of the foregoing, and (ii) as follows: an LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 44) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto; an LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody 3125 (e.g., SEQ ID NO: 45) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto; or an LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody 3125 (e.g., SEQ ID NO: 46) by 1, 2, or 3 or fewer amino acid residues, or has at least 85%, 90%, 95%, 99%, or 100% homology thereto, wherein the VL comprises one, two, or all of the foregoing.

[0190] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 11); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3125 (e.g., SEQ ID NO: 42); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3125 (e.g., SEQ ID NO: 43); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 44); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3125 (e.g., SEQ ID NO: 45); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3125 (e.g., SEQ ID NO: 46).

[0191] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 47) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3125 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 48) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3125 (e.g., SEQ ID NO: 43) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0192] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 44) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3125 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3125's LCDR3 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0193] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 47) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3125 (e.g., SEQ ID NO: 48) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3125 (e.g., SEQ ID NO: 43) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 44) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3125 (e.g., SEQ ID NO: 45) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody 3125 (e.g., SEQ ID NO: 46) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0194] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 47); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3125 (e.g., SEQ ID NO: 48); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3125 (e.g., SEQ ID NO: 43); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3125 (e.g., SEQ ID NO: 44); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3125 (e.g., SEQ ID NO: 45); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3125 (e.g., SEQ ID NO: 46).

[0195] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3125 (e.g., SEQ ID NO: 49) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or an amino acid sequence having at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3125 (e.g., SEQ ID NO: 50) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or an amino acid sequence having at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0196] In one embodiment, the antibody molecule includes (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 3125 (e.g., SEQ ID NO: 49) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 3125 (e.g., SEQ ID NO: 50) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. It includes L. In one embodiment, the antibody molecule includes (i) VH, which comprises the amino acid sequence of VH of monoclonal antibody 3125 (e.g., SEQ ID NO: 49); and (ii) VL, which comprises the amino acid sequence of VL of monoclonal antibody 3125 (e.g., SEQ ID NO: 50).

[0197] In one embodiment, the antibody molecule is a monoclonal antibody 3125. In another embodiment, the antibody molecule is a humanized monoclonal antibody 3125.

[0198] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which is an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 93) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) HCDR2 of monoclonal antibody 4035 or 4035-062 (iii) an HCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of (e.g., SEQ ID NO: 94), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 95), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0199] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1 having an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 96), or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) LCDR2 of monoclonal antibody 4035 or 4035-062 (iii) an LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of (e.g., SEQ ID NO: 97), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 98), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0200] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 93), or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 94). VH containing one, two or all of the following: HCDR2 containing an amino acid sequence having at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 95), or having at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following: Monoclonal antibodies 4035 or 4035-062 whose LCDR1 amino acid sequence (e.g., SEQ ID NO: 96) differs by only 1, 2, or 3 or fewer amino acid residues, or which have at least 85, 90, 95, 99, or 100% homology to it. The VL comprises one, two, or all of the following: LCDR1 containing a mino acid sequence; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 97), or having at least 85, 90, 95, 99, or 100% homogeneity with it; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 98), or having at least 85, 90, 95, 99, or 100% homology with it.

[0201] In one embodiment, the antibody molecule comprises VH, which includes (i) HCDR1, which includes the amino acid sequence of HCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 93); HCDR2, which includes the amino acid sequence of HCDR2 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 94); and HCDR3, which includes the amino acid sequence of HCDR3 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 95); and VL, which includes LCDR1, which includes the amino acid sequence of LCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 96); LCDR2, which includes the amino acid sequence of LCDR2 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 97); and LCDR3, which includes the amino acid sequence of LCDR3 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 98).

[0202] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1 which differs from the amino acid sequence of HCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 99) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) monoclonal antibody 4035 (e.g., SEQ ID NO: 100) or 4035-062 (iii) an HCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 (e.g., SEQ ID NO: 273), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 95), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0203] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1 having an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 96), or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) LCDR2 of monoclonal antibody 4035 or 4035-062 (iii) an LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of (e.g., SEQ ID NO: 97), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 98), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0204] In one embodiment, the antibody molecule is (i) Below: Monoclonal antibody 4035 or 4035-062 for HCDR1 VH containing one, two, or all of the following: HCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the no-acid sequence (e.g., SEQ ID NO: 99), or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 4035 (e.g., SEQ ID NO: 100) or 4035-062 (e.g., SEQ ID NO: 273), or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence (e.g., SEQ ID NO: 95) of monoclonal antibody 4035 or 4035-062, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following: LCDR1 of monoclonal antibody 4035 or 4035-062 that differs by only 1, 2, or 3 or fewer amino acid residues from the LCDR1 amino acid sequence (e.g., SEQ ID NO: 96), or that contains an amino acid sequence having at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 of monoclonal antibody 4035 or 4035-062 that differs by only 1, 2, or 3 or fewer amino acid residues from the LCDR2 amino acid sequence (e.g., SEQ ID NO: 97) The VL comprises one, two, or all of the following: an LCDR2 containing an amino acid sequence having at least 85, 90, 95, 99, or 100% homogeneity with the same; or an LCDR3 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 98), or an amino acid sequence having at least 85, 90, 95, 99, or 100% homology with the same.

[0205] In one embodiment, the antibody molecule comprises (i) HCDR1, which includes the amino acid sequence of HCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 99); HCDR2, which includes the amino acid sequence of HCDR2 of monoclonal antibody 4035 (e.g., SEQ ID NO: 100) or 4035-062 (e.g., SEQ ID NO: 273); and HCDR3, which includes the amino acid sequence of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 95). VH containing HCDR3, and (ii) LCDR1 containing the amino acid sequence of LCDR1 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 96); LCDR2 containing the amino acid sequence of LCDR2 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 97); and VL containing LCDR3 containing the amino acid sequence of LCDR3 of monoclonal antibody 4035 or 4035-062 (e.g., SEQ ID NO: 98).

[0206] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 4035 (e.g., SEQ ID NO: 101) or 4035-062 (e.g., SEQ ID NO: 225) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 4035 (e.g., SEQ ID NO: 102) or 4035-062 (e.g., SEQ ID NO: 229) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0207] In one embodiment, the antibody molecule is (i) a VH of monoclonal antibody 4035 (e.g., SEQ ID NO: 101) or 4035-062 (e.g., SEQ ID NO: 225) that differs from the VH by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99 or 100% homology thereto; and (ii) The antibody molecule comprises a VL containing an amino acid sequence that differs from the VL of a monoclonal antibody 4035 (e.g., SEQ ID NO: 102) or 4035-062 (e.g., SEQ ID NO: 229) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) a VH containing the amino acid sequence of a monoclonal antibody 4035 (e.g., SEQ ID NO: 101) or 4035-062 (e.g., SEQ ID NO: 225); and (ii) a VL containing the amino acid sequence of a monoclonal antibody 4035 (e.g., SEQ ID NO: 102) or 4035-062 (e.g., SEQ ID NO: 229).

[0208] In one embodiment, the antibody molecule is monoclonal antibody 4035. In another embodiment, monoclonal antibody 4035 is humanized monoclonal antibody 4035 (e.g., antibody 4035-062). In yet another embodiment, the antibody molecule is antibody 4035-062. In one embodiment, the antibody molecule comprises VH containing the amino acid sequence of either SEQ ID NOs. 220-227 or 262-265, VL containing the amino acid sequence of either SEQ ID NOs. 228-234, or both.

[0209] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 103) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3934 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 104) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3934 (e.g., SEQ ID NO: 105) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0210] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 106) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3934 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 107) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3934's LCDR3 (e.g., SEQ ID NO: 108) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0211] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 103) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3934 (e.g., SEQ ID NO: 104) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; VH containing one, two, or all of the following HCDR3s: or HCDR3s that differ by only one, two, or three or fewer amino acid residues from the amino acid sequence of monoclonal antibody 3934 (e.g., SEQ ID NO: 105), or HCDR3s that have at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 106), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3934 (e.g., SEQ ID NO: 107), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3934 (e.g., SEQ ID NO: 108), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0212] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 103); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3934 (e.g., SEQ ID NO: 104); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3934 (e.g., SEQ ID NO: 105); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 106); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3934 (e.g., SEQ ID NO: 107); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3934 (e.g., SEQ ID NO: 108).

[0213] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 109) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3934 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 110) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3934 (e.g., SEQ ID NO: 105) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0214] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 106) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3934 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 107) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3934's LCDR3 (e.g., SEQ ID NO: 108) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0215] In one embodiment, the antibody molecule is (i) The following: VH containing one, two, or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 109) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3934 (e.g., SEQ ID NO: 110) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3934 (e.g., SEQ ID NO: 105) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 106), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3934 (e.g., SEQ ID NO: 107), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3934 (e.g., SEQ ID NO: 108), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0216] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 109); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3934 (e.g., SEQ ID NO: 110); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3934 (e.g., SEQ ID NO: 105); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3934 (e.g., SEQ ID NO: 106); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3934 (e.g., SEQ ID NO: 107); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3934 (e.g., SEQ ID NO: 108).

[0217] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3934 (e.g., SEQ ID NO: 111) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3934 (e.g., SEQ ID NO: 112) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0218] In one embodiment, the antibody molecule comprises (i) a VH containing an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody 3934 (e.g., SEQ ID NO: 111) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99 or 100% homology thereto; and (ii) a VL containing an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody 3934 (e.g., SEQ ID NO: 112) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 or fewer amino acid residues thereto, or has at least 85, The VL comprises an amino acid sequence having 90, 95, 96, 97, 98, 99, or 100% homology. In one embodiment, the antibody molecule comprises (i) a VH containing the amino acid sequence of the VH of monoclonal antibody 3934 (e.g., SEQ ID NO: 111); and (ii) a VL containing the amino acid sequence of the VL of monoclonal antibody 3934 (e.g., SEQ ID NO: 112).

[0219] In one embodiment, the antibody molecule is a monoclonal antibody 3934. In another embodiment, the antibody molecule is a humanized monoclonal antibody 3934.

[0220] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 112) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3833 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 113) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3833 (e.g., SEQ ID NO: 114) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0221] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3833 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 116) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3833's LCDR3 (e.g., SEQ ID NO: 117) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0222] In one embodiment, the antibody molecule is (i) The following: VH containing one, two, or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 113) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 114) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115) by only one, two, or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following: LCDR1 containing an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117) by only 1, 2, or 3 or fewer amino acid residues thereto, or has at least 8 The VL includes one, two, or all of the following: an LCDR2 containing an amino acid sequence having 5, 90, 95, 99, or 100% homology; or an LCDR3 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 3833's LCDR3 (e.g., SEQ ID NO: 118), or an amino acid sequence having at least 85, 90, 95, 99, or 100% homology thereto.

[0223] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 113); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 114); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 118).

[0224] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 119) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3833 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 120) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3833 (e.g., SEQ ID NO: 115) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0225] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3833 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 117) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3833's LCDR3 (e.g., SEQ ID NO: 118) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0226] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 119) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 120) by only 1, 2, or 3 or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or the amino acid sequence of HCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115 ) containing one, two or all of the HCDR3s, which contain amino acid sequences that differ from ) by only one, two or three or fewer amino acid residues, or which have at least 85, 90, 95, 99, or 100% homology thereto, as well as VH containing one, two, or all of them, (ii) The following: A VL comprising one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 118), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0227] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 119); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 120); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 115); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3833 (e.g., SEQ ID NO: 116); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3833 (e.g., SEQ ID NO: 117); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3833 (e.g., SEQ ID NO: 118).

[0228] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3833 (e.g., SEQ ID NO: 121) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3833 (e.g., SEQ ID NO: 122) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0229] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 3833 (e.g., SEQ ID NO: 121) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 3833 (e.g., SEQ ID NO: 122) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3833 (e.g., SEQ ID NO: 121); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3833 (e.g., SEQ ID NO: 122).

[0230] In one embodiment, the antibody molecule is a monoclonal antibody 3833. In another embodiment, the monoclonal antibody 3833 is a humanized monoclonal antibody 3833. In another embodiment, the antibody molecule comprises VH containing any amino acid sequence of SEQ ID NOs. 246-250, VL containing any amino acid sequence of SEQ ID NOs. 251-253, or both.

[0231] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 123) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3631 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 124) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3631 (e.g., SEQ ID NO: 125) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0232] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3631. (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 127) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3631's LCDR3 (e.g., SEQ ID NO: 128) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0233] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 123) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 124) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 125) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 127), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0234] In one embodiment, the antibody molecule is (i) monoclonal antibody 3631 (e.g., sequence number VH comprises (ii) HCDR1 containing the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 124); HCDR2 containing the amino acid sequence of HCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 124); and VL comprising (ii) LCDR1 containing the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126); LCDR2 containing the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 127); and LCDR3 containing the amino acid sequence of LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128).

[0235] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 129) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; the amino acid sequence of HCDR2 of monoclonal antibody 3631 ( (iii) an HCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the HCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 125), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the HCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 125), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0236] In one embodiment, the antibody molecule includes a light chain variable region (VL), which includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), where the light chain variable region comprises: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3631. (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 127) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3631's LCDR3 (e.g., SEQ ID NO: 128) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0237] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 129) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 130) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 125) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: LCDR1 containing an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 4 5) comprising an LCDR2 containing an amino acid sequence that differs from or has at least 1, 2, or 3 amino acid residues from the LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128) by at least 1, 2, or 3 amino acid residues, or an LCDR3 containing an amino acid sequence that has at least 85, 90, 95, 99, or 100% homology to the LCDR3 of monoclonal antibody 3631, comprising one, two, or all of the above.

[0238] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 129); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 130); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 125); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3631 (e.g., SEQ ID NO: 126); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3631 (e.g., SEQ ID NO: 127); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3631 (e.g., SEQ ID NO: 128).

[0239] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3631 (e.g., SEQ ID NO: 131) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3631 (e.g., SEQ ID NO: 132) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0240] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 3631 (e.g., SEQ ID NO: 131) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 3631 (e.g., SEQ ID NO: 132) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3631 (e.g., SEQ ID NO: 131); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3631 (e.g., SEQ ID NO: 132).

[0241] In one embodiment, the antibody molecule is a monoclonal antibody 3631. In another embodiment, the antibody molecule is a humanized monoclonal antibody 3631.

[0242] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), which includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), where the heavy chain variable region comprises: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 133) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) HCD, which contains an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 134) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto. R2; or (iii) comprising one, two, or all of the HCDR3s that differ by only one, two, or three or fewer amino acid residues from the amino acid sequence of the HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135), or have at least 85, 90, 95, 99, or 100% homology thereto.

[0243] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3732 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 127) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3732's LCDR3 (e.g., SEQ ID NO: 137) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0244] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 133) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 134) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 127), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 137), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0245] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 133); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 134); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 127); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 137).

[0246] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 138) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 3732 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 139) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) comprising one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 3732 (e.g., SEQ ID NO: 135) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0247] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 3732 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 127) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 3732's LCDR3 (e.g., SEQ ID NO: 137) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0248] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 138) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 139) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following: A VL comprising one, two, or all of the following: LCDR1 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 127), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 137), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0249] In one embodiment, the antibody molecule (i) contains the amino acid sequence of HCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 138); monoclonal antibody 3732 VH comprises (ii) an HCDR2 containing the amino acid sequence of HCDR2 (e.g., SEQ ID NO: 139); and an HCDR3 containing the amino acid sequence of HCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 135); and VL comprising (ii) an LCDR1 containing the amino acid sequence of LCDR1 of monoclonal antibody 3732 (e.g., SEQ ID NO: 136); an LCDR2 containing the amino acid sequence of LCDR2 of monoclonal antibody 3732 (e.g., SEQ ID NO: 127); and an LCDR3 containing the amino acid sequence of LCDR3 of monoclonal antibody 3732 (e.g., SEQ ID NO: 137).

[0250] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 3732 (e.g., SEQ ID NO: 140) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 3732 (e.g., SEQ ID NO: 141) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0251] In one embodiment, the antibody molecule comprises (i) VH, which contains an amino acid sequence that differs from the amino acid sequence of VH of monoclonal antibody 3732 (e.g., SEQ ID NO: 140) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which contains an amino acid sequence that differs from the amino acid sequence of VL of monoclonal antibody 3732 (e.g., SEQ ID NO: 141) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 3732 (e.g., SEQ ID NO: 140); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 3732 (e.g., SEQ ID NO: 141).

[0252] In one embodiment, the antibody molecule is a monoclonal antibody 3732. In another embodiment, the antibody molecule is a humanized monoclonal antibody 3732.

[0253] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which is different from the amino acid sequence of HCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 11) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 4338 (iii) an HCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from (e.g., SEQ ID NO: 142) or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 4338 (e.g., SEQ ID NO: 143) or has at least 85, 90, 95, 99, or 100% homology thereto.

[0254] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region is determined by: (i) the amino acid sequence of LCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 144 or 146) differing by only 1, 2, or 3 or fewer amino acid residues, or (ii) an LCDR1 containing an amino acid sequence having at least 85, 90, 95, 99, or 100% homology to this; (ii) an LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 4338's LCDR2 (e.g., SEQ ID NO: 107 or 147), or has at least 85, 90, 95, 99, or 100% homology to this; or (iii) one, two, or all of the following LCDR3s containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 4338's LCDR3 (e.g., SEQ ID NO: 145 or 148), or has at least 85, 90, 95, 99, or 100% homology to this.

[0255] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 11) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 142) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 4338 (e.g., SEQ ID NO: 143) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 144 or 146), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 107 or 147), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 4338 (e.g., SEQ ID NO: 145 or 148), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0256] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 11); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 142); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 4338 (e.g., SEQ ID NO: 143); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 144 or 146); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 107 or 147); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 4338 (e.g., SEQ ID NO: 145 or 148).

[0257] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which differs from the amino acid sequence of HCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 149) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) HCDR2, which differs from the amino acid sequence of HCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 150) by only one, two, or three or fewer amino acid residues thereto, or has at least (iii) an HCDR2 having an amino acid sequence having 85, 90, 95, 99, or 100% homology; or (iii) one, two, or all of the HCDR3s having an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the monoclonal antibody 4338's HCDR3 (e.g., SEQ ID NO: 143), or having at least 85, 90, 95, 99, or 100% homology thereto.

[0258] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which differs from the amino acid sequence of LCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 144 or 146) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 4338 (e.g., (iii) an LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the LCDR3 of monoclonal antibody 4338 (e.g., LCDR3 of sequence 145 or 148), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the LCDR3 of monoclonal antibody 4338 (e.g., LCDR3 of sequence 145 or 148), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0259] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs by only one, two or three or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 149), or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 150), or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR3 of monoclonal antibody 4338 (e.g., SEQ ID NO: 143), or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 144 or 146), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 107 or 147), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 4338 (e.g., SEQ ID NO: 145 or 148), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0260] In one embodiment, the antibody molecule includes (i) VH containing the amino acid sequence of HCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 149); HCDR2 containing the amino acid sequence of HCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 150); and HCDR3 containing the amino acid sequence of HCDR3 of monoclonal antibody 4338 (e.g., SEQ ID NO: 143); and (ii) LCDR1 containing the amino acid sequence of LCDR1 of monoclonal antibody 4338 (e.g., SEQ ID NO: 144 or 146); and the amino acid sequence of LCDR2 of monoclonal antibody 4338 (e.g., SEQ ID NO: 107 or 147). The VL contains LCDR2 and LCDR3, which includes the amino acid sequence of LCDR3 in monoclonal antibody 4338 (e.g., SEQ ID NO: 145 or 148).

[0261] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 4338 (e.g., SEQ ID NO: 151) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or includes an amino acid sequence having at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 4338 (e.g., SEQ ID NO: 152 or 153) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or includes an amino acid sequence having at least 85, 90, 95, 96, 97, 98, 99, or 100% homogeneity thereto.

[0262] In one embodiment, the antibody molecule comprises (i) VH, which differs from the amino acid sequence of VH of monoclonal antibody 4338 (e.g., SEQ ID NO: 151) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) VL, which differs from the amino acid sequence of VL of monoclonal antibody 4338 (e.g., SEQ ID NO: 152 or 153) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) VH, which includes the amino acid sequence of VH of monoclonal antibody 4338 (e.g., SEQ ID NO: 150); and (ii) VL, which includes the amino acid sequence of VL of monoclonal antibody 4338 (e.g., SEQ ID NO: 152 or 153).

[0263] In one embodiment, the antibody molecule is a monoclonal antibody 4338. In another embodiment, the antibody molecule is a humanized monoclonal antibody 4338.

[0264] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 154), or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) H (iii) an HCDR2 comprising an amino acid sequence that differs from the amino acid sequence of CDR2 (e.g., SEQ ID NO: 155) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) a monoclonal antibody 4540, 4540-063, or 4540-033 comprising one, two, or all of the following HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of HCDR3 (e.g., SEQ ID NO: 156) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0265] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region having the following: (i) an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto. (ii) an LCDR1 containing a column; an LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the LCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the following LCDR3s containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of the LCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0266] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 154), or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR2 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 155). VH containing one, two, or all of the following: HCDR2 containing an amino acid sequence that is different or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156), or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following: LCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275). The VL includes one, two, or all of the following: an LCDR2 containing an amino acid sequence that differs from the amino acid sequence of by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or an LCDR3 containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0267] In one embodiment, the antibody molecule is a VH comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), where the heavy chain variable regions are: HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 154); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 155); and HCD of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156). (ii) a VH comprising HCDR3 containing the amino acid sequence of R3, and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3), wherein the light chain variable region comprises LCDR1 containing the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274) or 4540-033 (e.g., SEQ ID NO: 274); monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275) or 4540-033 (e.g., SEQ ID NO: The light chain variable region includes LCDR2 containing the amino acid sequence of LCDR2 of 275) and LCDR3 containing the amino acid sequence of LCDR3 of monoclonal antibody 4540, 4540-063 or 4540-033 (e.g., SEQ ID NO: 158).

[0268] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region containing: (i) HCDR1 which differs from the amino acid sequence of monoclonal antibody 4540 (e.g., SEQ ID NO: 159), 4540-063 (e.g., SEQ ID NO: 276), or 4540-033 (e.g., SEQ ID NO: 159) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) monoclonal antibody 4540 (e.g., SEQ ID NO: 160), 4540-063 (iii) an HCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of HCDR2 (e.g., SEQ ID NO: 277) or 4540-033 (e.g., SEQ ID NO: 278), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0269] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) an LCDR1 that differs from the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (iii) an LCDR2 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of (e.g., SEQ ID NO: 275) or 4540-033 (e.g., SEQ ID NO: 275), or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3 comprising an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0270] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of HCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 159), 4540-063 (e.g., SEQ ID NO: 276), or 4540-033 (e.g., SEQ ID NO: 159), or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 160), 4540-063 (e.g., SEQ ID NO: 277), or 4540-033 (e.g., SEQ ID NO: 278). VH containing one, two, or all of the following: HCDR2 containing an amino acid sequence that differs from the amino acid sequence of by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156), or has at least 85, 90, 95, 99, or 100% homology thereto; and (ii) The following: LCDR1 containing an amino acid sequence that differs by only 1, 2, or 3 or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275). The VL includes one, two, or all of the following: an LCDR2 containing an amino acid sequence that differs from the amino acid sequence of by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or an LCDR3 containing an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0271] In one embodiment, the antibody molecule includes (i) HCDR1 containing the amino acid sequence of HCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 159), 4540-063 (e.g., SEQ ID NO: 276), or 4540-033 (e.g., SEQ ID NO: 159); HCDR2 containing the amino acid sequence of HCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 160), 4540-063 (e.g., SEQ ID NO: 277), or 4540-033 (e.g., SEQ ID NO: 278); or HCDR3 containing the amino acid sequence of HCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 156), one, two, or all of the following: VL includes (ii) below: LCDR1 containing the amino acid sequence of LCDR1 of monoclonal antibody 4540 (e.g., SEQ ID NO: 116), 4540-063 (e.g., SEQ ID NO: 274), or 4540-033 (e.g., SEQ ID NO: 274); LCDR2 containing the amino acid sequence of LCDR2 of monoclonal antibody 4540 (e.g., SEQ ID NO: 157), 4540-063 (e.g., SEQ ID NO: 275), or 4540-033 (e.g., SEQ ID NO: 275); or VL containing one, two, or all of LCDR3 containing the amino acid sequence of LCDR3 of monoclonal antibody 4540, 4540-063, or 4540-033 (e.g., SEQ ID NO: 158).

[0272] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 4540 (e.g., SEQ ID NO: 161), 4540-063 (e.g., SEQ ID NO: 258), or 4540-033 (e.g., SEQ ID NO: 256) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In one embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 4540 (e.g., SEQ ID NO: 162), 4540-063 (e.g., SEQ ID NO: 261), or 4540-033 (e.g., SEQ ID NO: 261) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0273] In one embodiment, the antibody molecule includes (i) a VH containing an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody 4540 (e.g., SEQ ID NO: 161), 4540-063 (e.g., SEQ ID NO: 258), or 4540-033 (e.g., SEQ ID NO: 256) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) a VL containing an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody 4540 (e.g., SEQ ID NO: 162), 4540-063 (e.g., SEQ ID NO: 261), by 1, 2, 3, 4, 5, 6, 7, 8 , comprising a VL containing an amino acid sequence that differs by only 9, 10, 11, 12, 13, 14 or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99 or 100% homology thereto. In one embodiment, the antibody molecule comprises (i) a VH containing the amino acid sequence of the VH of a monoclonal antibody 4540 (e.g., SEQ ID NO: 161), 4540-063 (e.g., SEQ ID NO: 258), or 4540-033 (e.g., SEQ ID NO: 256); and (ii) a VL containing the amino acid sequence of the VL of a monoclonal antibody 4540 (e.g., SEQ ID NO: 162), 4540-063 (e.g., SEQ ID NO: 261), or 4540-033 (e.g., SEQ ID NO: 261).

[0274] In some embodiments, the antibody molecule is a monoclonal antibody 4540, 4540-063, or 4540-033. In some embodiments, monoclonal antibody 4540 is a humanized monoclonal antibody 4540 (e.g., antibody 4540-063 or 4540-033). In some embodiments, the antibody molecule includes VH containing any amino acid sequence of SEQ ID NOs. 254-258, VL containing any amino acid sequence of SEQ ID NOs. 259-261, or both.

[0275] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which is different from the amino acid sequence of HCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 163) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 4237 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 164) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 4237 (e.g., SEQ ID NO: 165) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0276] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 166) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 4237 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 167) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 4237's LCDR3 (e.g., SEQ ID NO: 168) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0277] In one embodiment, the antibody molecule is (i) The following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 163) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 4237 (e.g., SEQ ID NO: 164) by only 1, 2, or 3 or fewer amino acid residues thereto, or has at least 85, 90, 95, 99, or 100% homology thereto; or the amino acid sequence of HCDR3 of monoclonal antibody 4237 (e.g., SEQ ID NO: 165 ) containing one, two or all of the HCDR3s, which contain amino acid sequences that differ from ) by only one, two or three or fewer amino acid residues, or which have at least 85, 90, 95, 99, or 100% homology thereto, as well as VH containing one, two, or all of them, (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 166), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 4237 (e.g., SEQ ID NO: 167), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 4237 (e.g., SEQ ID NO: 168), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0278] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 163); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 4237 (e.g., SEQ ID NO: 164); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 4237 (e.g., SEQ ID NO: 165); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 166); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 4237 (e.g., SEQ ID NO: 167); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 4237 (e.g., SEQ ID NO: 168).

[0279] In one embodiment, the antibody molecule includes a heavy chain variable region (VH), the heavy chain variable region includes three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), the heavy chain variable region comprising: (i) HCDR1, which is different from the amino acid sequence of HCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 169) by only 1, 2, or 3 or fewer amino acid residues, or which has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of HCDR2 of monoclonal antibody 4237 (iii) an HCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 170) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the HCDR3s comprising an amino acid sequence that differs from the amino acid sequence of monoclonal antibody 4237 (e.g., SEQ ID NO: 165) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0280] In one embodiment, the antibody molecule includes a light chain variable region (VL), the light chain variable region includes three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), the light chain variable region comprising: (i) LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 166) by only 1, 2, or 3 or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; (ii) the amino acid sequence of LCDR2 of monoclonal antibody 4237 (iii) an LCDR2 comprising an amino acid sequence that differs from the sequence (e.g., SEQ ID NO: 167) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto; or (iii) one, two, or all of the LCDR3s comprising an amino acid sequence that differs from the amino acid sequence of the monoclonal antibody 4237's LCDR3 (e.g., SEQ ID NO: 168) by only one, two, or three or fewer amino acid residues, or has at least 85, 90, 95, 99, or 100% homology thereto.

[0281] In one embodiment, the antibody molecule is (i) The following: VH containing one, two or all of the following: HCDR1 containing an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 169) by only one, two or three or fewer amino acid residues, or has at least 85, 90, 95, 99 or 100% homology thereto; HCDR2 containing an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody 4237 (e.g., SEQ ID NO: 170) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; or HCDR3 containing an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody 4237 (e.g., SEQ ID NO: 165) by only one, two or three or fewer amino acid residues thereto, or has at least 85, 90, 95, 99 or 100% homology thereto; and (ii) The following VLs include one, two, or all of the following: LCDR1 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 166), or has at least 85, 90, 95, 99, or 100% homology thereto; LCDR2 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR2 of monoclonal antibody 4237 (e.g., SEQ ID NO: 167), or has at least 85, 90, 95, 99, or 100% homology thereto; or LCDR3 containing an amino acid sequence that differs by only one, two, or three or fewer amino acid residues from the amino acid sequence of LCDR3 of monoclonal antibody 4237 (e.g., SEQ ID NO: 168), or has at least 85, 90, 95, 99, or 100% homology thereto.

[0282] In one embodiment, the antibody molecule comprises (i) VH comprising HCDR1 comprising the amino acid sequence of HCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 169); HCDR2 comprising the amino acid sequence of HCDR2 of monoclonal antibody 4237 (e.g., SEQ ID NO: 170); and HCDR3 comprising the amino acid sequence of HCDR3 of monoclonal antibody 4237 (e.g., SEQ ID NO: 165); and (ii) VL comprising LCDR1 comprising the amino acid sequence of LCDR1 of monoclonal antibody 4237 (e.g., SEQ ID NO: 166); LCDR2 comprising the amino acid sequence of LCDR2 of monoclonal antibody 4237 (e.g., SEQ ID NO: 167); and LCDR3 comprising the amino acid sequence of LCDR3 of monoclonal antibody 4237 (e.g., SEQ ID NO: 168).

[0283] In one embodiment, the antibody molecule includes a VH that differs from the amino acid sequence of the VH of monoclonal antibody 4237 (e.g., SEQ ID NO: 171) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. In another embodiment, the antibody molecule includes a VL that differs from the amino acid sequence of the VL of monoclonal antibody 4237 (e.g., SEQ ID NO: 172) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto.

[0284] In one embodiment, the antibody molecule includes (i) a VH containing an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody 4237 (e.g., SEQ ID NO: 171) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto; and (ii) an amino acid sequence containing an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody 4237 (e.g., SEQ ID NO: 172) by only 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or fewer amino acid residues, or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology thereto. It includes VL. In one embodiment, the antibody molecule includes (i) VH, which comprises the amino acid sequence of VH of monoclonal antibody 4237 (e.g., SEQ ID NO: 171); and (ii) VL, which comprises the amino acid sequence of VL of monoclonal antibody 4237 (e.g., SEQ ID NO: 172).

[0285] In one embodiment, the antibody molecule is a monoclonal antibody 4237. In another embodiment, the monoclonal antibody 4237 is a humanized monoclonal antibody 4237. In another embodiment, the antibody molecule comprises VH containing any amino acid sequence of SEQ ID NOs. 235-240, VL containing any amino acid sequence of SEQ ID NOs. 241-245, or both.

[0286] In another aspect, this disclosure is: (i) Binds to or substantially binds to human APRIL; (ii) Inhibit or substantially inhibit the binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to TACI (e.g., human TACI, mouse TACI, or both); (iii) inhibiting or substantially inhibiting the binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to BCMA (e.g., human BCMA, mouse BCMA, or both); and (iv) Binding to or substantially binding to one or more residues within the human APRIL region as defined in either Table 3-4 or 7-8, e.g., residues 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more It is characterized by an anti-APRIL antibody molecule.

[0287] In one embodiment, the antibody molecule, as determined by the method described herein, is 20 nM or less to human APRIL, for example, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.8 nM, less than 0.6 nM, less than 0.4 nM, less than 0.2 nM, less than 0.1 nM. EC of 0.05nM or less, 0.02nM or less, 0.01nM or less, 0.005nM or less, 0.002nM or less, or 0.001nM or less, for example, 0.001nM to 20nM, for example, 0.01nM to 20nM, 0.1nM to 20nM, 0.1nM to 10nM, 0.5nM to 5nM, 1nM to 5nM, 0.001nM to 0.1nM, 0.001nM to 0.01nM, 0.001nM to 0.005nM, 0.01nM to 0.05nM, or 0.01nM to 0.1nM 50 They are joined by or effectively joined.

[0288] In some embodiments, for example, as determined by the method described herein, the antibody molecule does not bind to mouse APRIL or has low affinity, for example, 1000 nM or greater, for example, 2000 nM or greater EC 50 It binds to mouse APRIL.

[0289] In one embodiment, the antibody molecule, as determined by the method described herein, has a TACI (e.g., human TACI, mouse TACI, or both) binding to APRIL (e.g., human APRIL, mouse APRIL, or both) of 50 nM or less, for example, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.8 nM, less than 0.6 nM, less than 0.4 nM, less than 0.2 nM or less ICs with a molecular weight less than 0.01nM, less than 0.05nM, less than 0.02nM, or less than 0.01nM, for example, 0.01nM to 50nM, 0.1nM to 50nM, 0.1nM to 25nM, 0.1nM to 10nM, 0.1nM to 5nM, 0.1nM to 1nM, 0.1nM to 0.5nM, 0.5nM to 5nM, or 1nM to 5nM. 50 It inhibits or substantially inhibits.

[0290] In one embodiment, the antibody molecule, as determined by the method described herein, has a binding of APRIL (e.g., human APRIL, mouse APRIL, or both) to BCMA (e.g., human BCMA, mouse BCMA, or both) at concentrations such as less than 200 nM, less than 150 nM, less than 100 nM, less than 50 nM, less than 40 nM, less than 30 nM, less than 20 nM, less than 10 nM, less than 9 nM, less than 8 nM, less than 7 nM, less than 6 nM, or less than 5 nM. or less than that, 4nM or less, 3nM or less, 2nM or less, 1nM or less, 0.8nM or less, 0.6nM or less, 0.4nM or less, 0.2nM or less, 0.1nM or less, 0.05nM or less, 0.02nM or less, 0.01nM or less, for example, ICs with a molecular weight of 0.01nM to 50nM, 0.1nM to 50nM, 0.1nM to 25nM, 0.1nM to 10nM, 0.1nM to 5nM, 0.1nM to 1nM, 0.1nM to 0.5nM, 0.5nM to 5nM or 1nM to 5nM 50 It inhibits or substantially inhibits.

[0291] In some embodiments, the antibody molecule binds or substantially binds to an epitope containing one or more APRIL residues from two monomers, e.g., monomer A and monomer B as shown in Table 3. In some embodiments, the antibody molecule binds or substantially binds to one or more APRIL residues from the CD loop (e.g., the loop connecting β-sheets C and D), the GH loop (e.g., the loop connecting β-sheets G and H), or both. In some embodiments, the antibody molecule binds or substantially binds to one or more human APRIL residues (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or all) from positions 105–114 and / or one or more mouse APRIL residues (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or all) from positions 96–105. In one embodiment, the antibody molecule either does not bind to one, two, or all of the human APRIL Asp129, Arg233, or His203, or binds with low affinity.

[0292] In one embodiment, the antibody molecule is (i) The following: Antibodies selected from 2218, 2419, 2419-0105, 2419-0205, 2419-0206, 2419-0406, 2419-0605, 2419-0805, 2419-0806, 2419-1204, 2419-1205, 2419-1210, 2419-1305, 2419-1306, 2419-1310, 2419-1406, 2922, 3327, 3125, 2621, 4035, 4035-062, 3934, 4338, 4439, or 4237, whose HCDR1 amino acid sequence differs by only 1, 2, or 3 or fewer amino acid residues, or by at least 8 amino acid residues. Heavy chain variable region (VH) containing one, two, or all of the following: HCDR1 containing an amino acid sequence with 5, 90, 95, 99, or 100% homology; HCDR2 containing an amino acid sequence that differs by only 1, 2, ...

Claims

[Claim 1] The invention described in the present specification and drawings.

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