Jagged-1 binding agents and uses thereof

Abstract

The present disclosure provides Jagged-1 binding agents, including agents that bind to human Jagged-1. Such agents include antibodies that bind to Jagged-1, including antibodies that bind to human Jagged-1. Such binding agents are useful, including in compositions and in methods of treating, preventing, or alleviating a Jagged-1 related disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition.

Description

Attorney Docket No. 13366-015-228JAGGED-1 BINDING AGENTS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 695,239 filed September 16, 2024, the content of which is incorporated by reference in its entirety.SEQUENCE LISTING

[0002] This application contains an electronic Sequence Listing which has been submitted in XML file format with this application, the entire content of which is incorporated by reference herein in its entirety. The Sequence Listing XML file submitted with this application is entitled “13366-015- 228_SEQLISTING.xml”, was created on July 1, 2025, and is 280,805 bytes in size.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0003] This invention was made with government support under award 1R01 AR077152 awarded by the NIH. The government has certain rights in this invention.FIELD

[0004] Provided herein are Jagged- 1 binding agents, including agents that bind to human Jagged- 1. Such agents include antibodies that bind to Jagged- 1, including antibodies that bind to human Jagged- 1. Such binding agents are useful, including in compositions and in methods of treating, preventing, or alleviating a Jagged- 1 related disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition.BACKGROUND

[0005] The canonical Notch signaling pathway plays a key role in many aspects of tissue development and self-renewal and has also been implicated in tumor development and metastasis. Mammals express four Notch receptors, Notch- 1 through Notch-4, and five Notch ligands, Jagged- 1, Jagged-2, Delta-like ligand (DLL)-l, DLL-3 and DLL-4 that are all single pass type 1 membrane proteins (Kopan and Hagan, Cell 137: 216-233. (2009); Cordle et al., Nat Struct Biol. 15:849-857 (2008)). Jagged- 1, Jagged-2 DLL-1 and DLL-4 are Notch agonists but DLL-3 acts as an antagonist of DLL-1 (D’Sousa et al., 2008; Katoh and Katoh, 2020, Inti J Mol. Med. 45:279-297). All five ligands have a similar structure comprised of a DSL (Delta / Serrate / Lag) domain that is essential for binding to the Notch receptor followed by tandem repeats of epidermal growth factor (EGF) domains. (Cordle et al., 2008 Nat Struct Biol. 15:849-857). Notch activation occurs in ajuxtacrine manner through cellcell contact, whereby ligand binding triggers a disintegrin cleavage of the Notch extracellular domain followed by Y-secretase cleavage that releases the Notch receptor intracellular domain, which then traffics to the nucleus and triggers target gene activation.Page 1 of 320NAI-5001326827v1

[0006] The extracellular domain (approximately 113.5 kDa) of Jagged- 1 is comprised of a Delta- Serrate-Lagl (DSL) domain and 15 EGF domains which encompasses residues 34 to 1218. The interaction between Jagged- 1 and Notch 1 has been mapped within a DSL-EGF1-3 region that spans residues 185 to 335 with the residues that interact directly with Notch residing within the DSL domain from residues 199 to 207 (Cordle et al., Nat Struct Biol. 15:849-857 (2008); Chillakuri et al., Sem. Cell Devel. Biol. 23:421-428 (2012)). This region is conserved between all five Notch ligands while the flanking regions necessary for binding of the isolated domain to Notch receptors exhibits lower, albeit significant homology. This homology presents a challenge in isolating highly specific antagonist antibody clones against Jagged- 1 with minimal cross-reactivity to other antagonist Notch ligands to minimize untoward side effects.

[0007] Human Jagged- 1, also known as CD339, has been implicated in hematopoietic and cardiovascular development as well as tumor growth and metastasis (Sethi et al., Cancer Cell 19: 192- 205 (2011); Kode et al., Nature 206:240-244 (2014); Li et al., Front Oncol 4:254 (2014); Masiero et al., Mol Cancer Ther. Nov; 18:2030-2042 (2019)). In addition to being upregulated on tumor and smooth muscle cells of tumor vasculature, Jagged- 1 upregulation within the tumor microenvironment has also been shown to play a role in oncogenesis, proliferation of cancer stem cells or metastases (Shafat et al., Blood Rev. 31:277-286 (2017; Kode et al., Nature 506: 240-244 (2014); Witkowski et al., Exp Med. 217(2):e20190589 (2020)).

[0008] Constitutive upregulation of [3-catenin in osteoblasts results in mice bom with myelodysplastic syndrome (MDS) that rapidly develops into acute myeloid leukemia (AML) by 10 days of birth. Further studies indicated that this is due to upregulation of Jagged- 1 by osteoblasts interacting with Notch-1 on hematopoietic stem cells (HSCs) (Kode et al., Nature 506: 240-244 (2014); US Patent No. 10,350,216). Ablating one of the Jagged-1 alleles in these [3-cat(ex3)osb transgenic mice reverses AML and prevents the ensuing mortality typically observed by 6 weeks in the mutant [3-cat(ex3)osb mice. Subsequent studies with bone marrow biopsies of MDS and AML patients have indicated that up to 40 percent of patients present with activated, nuclear [3-catenin and surface expression of Jagged- 1 on their osteoblasts, and evidence of elevated Notch- 1 signalling on their MDS / AML blast cells.

[0009] Currently the treatment for advanced stages of MDS remains chemotherapy, either hypomethylating agents or an azacytidine plus anthracycline regimen, with patients often requiring blood transfusions to counter severe anemia. The current standard of care for AML patients remains high dose induction chemotherapy for medically fit patients (usually < 65 years of age), followed by consolidation therapy, often including hematopoietic stem cell (HSC) or bone marrow transplants. Despite some advances in targeted therapy for patients with AML cells expressing FLT3 or IDH, these agents remain associated with serious side effects and 5 -year survival rates remain around 29.5% overall, and for patients > 60 years of age 5-year survival rates drop to 7.4%. Because the rate of relapse is high in AML patients due to the hypermutability of the leukemic cells and rapidPage 2 of 320NAI-5001326827v1emergence of resistant clones, there is an urgent medical need for new therapies, including, for example, those that more effectively target the supportive bone marrow tumor-microenvironment giving rise to, and supporting proliferation, of leukemic stem cells and leukemic blasts.

[0010] Many studies are ongoing to understand more about Jagged- 1, including its effects on the tumor microenvironment, and there is an urgent need for agents that can be used in methods for treating, preventing, or ameliorating a Jagged- 1 related disease, disorder, or condition.SUMMARY

[0011] The present disclosure provides Jagged- 1 binding agents, including agents that bind to a human Jagged- 1. Such agents include antibodies that bind to Jagged- 1, including antibodies that bind to human Jagged- 1. Such antibodies (e.g. , monospecific or multispecific, including bispecific) may bind to human Jagged-1, the extracellular domain of Jagged-1, a DSL-EGF1-3 region of the extracellular domain of human Jagged- 1, and / or a receptor binding domain of human Jagged- 1.

[0012] The present disclosure also provides compositions comprising a Jagged- 1 binding agent, including an agent that binds to human Jagged- 1. Such compositions comprise agents that include antibodies that bind to Jagged- 1, including antibodies that bind to human Jagged- 1.

[0013] The present disclosure also provides methods of treating, preventing, or alleviating a Jagged- 1 related disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition with a Jagged- 1 binding agent or a composition comprising the Jagged- 1 binding agent, including an agent that binds to human Jagged- 1 or composition comprising such an agent. Such compositions comprise agents that include antibodies that bind to Jagged- 1, including antibodies that bind to human Jagged- 1.

[0014] In one aspect, provided herein is an antibody or fragment thereof that binds to Jagged- 1, wherein the antibody comprises: (a) a heavy chain variable (VH) region comprising a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in Tables 1-18; or (b) a light chain variable (VL) region comprising a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in Tables 1-18.

[0015] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in Tables 1- 18; and (b) a light chain variable (VL) region comprising a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in Tables 1-18.

[0016] In certain embodiments, the antibody comprises a heavy chain variable (VH) region comprising a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in Tables 1- 18.

[0017] In certain embodiments, the antibody comprises a light chain variable (VL) region comprising a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in Tables 1-18.Page 3 of 320NAI-5001326827v1

[0018] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 7, 12, 13, and 18; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:2, 8, 14, 19 and 24; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:3, 9, 15 and 20; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:4, 10, 16 and 21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:5, 11, and 22; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:6, 17, and 23.

[0019] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:27, 32, 36, 37, and 41; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:28, 33, 38, 42, and 46; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:29, 34, 39, and 43; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:4, 10, 16, and 21; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:31, 40, and 45.

[0020] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:49, 55, 60, 61, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 59, and 69; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:54, 65, and 70.

[0021] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:74, 78, 81, 82, and 86; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:75, 79, 83, 87, and 90; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:76, 80, 84, and 88; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 59, and 69; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:77, 85, and 89.Page 4 of 320NAI-5001326827v1

[0022] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:93, 97, 101, 102, and 105; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:94, 98, 103, 106, and 109; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:39, 95, 99, and 107; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:96, 100, 104, and 108; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 59, and 69; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 6, 17, and 23.

[0023] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:27, 32, 36, 37, and 41; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 112, 116, 118, 121, and 125; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 113, 117, 119, and 122; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 11, 114, and 123; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 115, 120, and 124.

[0024] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 128, 133, 137, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 129, 134, 138, 141, and 143; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 130, and 135; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:68, 131, 136, and 139; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 132, 140, and 142.

[0025] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68; (2) a VL CDR2 having an amino acidPage 5 of 320NAI-5001326827v1sequence selected from the group consisting of SEQ ID NOS: 147, 150, and 166; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 148, 152, and 153.

[0026] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 156, 158, 160, 161, and 162; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 157, and 159; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:54, 65, and 70.

[0027] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

[0028] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and (3)a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 171, 172, 173, and 174; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

[0029] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68; (2) a VL CDR2 having an amino acidPage 6 of 320NAI-5001326827v1sequence selected from the group consisting of SEQ ID NOS: 176, 177, and 178; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

[0030] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:68, 180, 181, and 182; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

[0031] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 184, 186, 187, and 189; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 59, and 69; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 185, 188, and 190.

[0032] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:68, 192, 193, and 194; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

[0033] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 156, 158, 160, 161, and 162; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 157, and 159; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VLPage 7 of 320NAI-5001326827v1CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 196, 197, and 198.

[0034] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 156, 158, 160, 161, and 162; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 157, and 159; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:200, 202, 203, and 205; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:201, 204, and 206.

[0035] In certain embodiments, the antibody comprises: (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165; (2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 156, 158, 160, 161, and 162; and (3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 157, and 159; and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:68, 208, 209, and 210; (2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:201, 204, and 206.

[0036] In various embodiments, the VH region or VL region further comprises human framework sequences. In specific embodiments, the VH region and VL region further comprises human framework sequences.

[0037] In various embodiments, the VH region or VL region further comprises a framework 1 (FR1), a framework 2 (FR2), a framework 3 (FR3) and / or a framework 4 (FR4) sequence. In specific embodiments, the VH region and VL region further comprises a framework 1 (FR1), a framework 2 (FR2), a framework 3 (FR3) and a framework 4 (FR4) sequence.

[0038] In various embodiments, the antibody is a monoclonal antibody. In specific embodiments, the monoclonal antibody is a humanized, human or chimeric antibody.

[0039] In various embodiments, the antibody or fragment thereof is a Fab, Fab’, F(ab’)2, Fv, scFv, (SCFV)2, single chain antibody molecule, dual variable region antibody, single variable region antibody, linear antibody, V region, or a multispecific antibody formed from antibody fragments.

[0040] In various embodiments, the antibody or fragment thereof is conjugated or recombinantly fused to a diagnostic agent, detectable agent, effector agent, or therapeutic agent. In specific embodiments, the therapeutic agent is a chemotherapeutic agent, cytotoxin, or drug.Page 8 of 320NAI-5001326827v1

[0041] In one aspect, provided herein is a binding agent that binds to essentially the same epitope as an antibody or fragment thereof described herein.

[0042] In certain embodiments, the binding agent is an antibody or fragment thereof. In specific embodiments, the binding agent comprises a non-antibody protein scaffold. In a specific embodiment, the non-antibody protein scaffold comprises a fibronectin scaffold, an anticalin, an adnectin, an affibody, a DARPin, a fynomer, an affitin, an affilin, an avimer, a cysteine-rich knottin peptide, or an engineered Kunitz-type inhibitor.

[0043] In one aspect, provided herein is a binding agent that competes for binding to human Jagged- 1 with an antibody or fragment thereof described herein.

[0044] In certain embodiments, the binding agent is an antibody or fragment thereof.

[0045] In one aspect, provided herein is one or more vectors comprising one or more polynucleotides encoding an antibody or fragment thereof described herein.

[0046] In one aspect, provided herein is a pharmaceutical composition that comprises an antibody or fragment thereof described herein, and a pharmaceutically acceptable carrier.

[0047] In one aspect, provided herein is a method for treating abnormal hematopoiesis, a blood disorder, cancer or a tumor in a subject comprising administering to the subject an antibody or fragment thereof described herein or a pharmaceutical composition described herein.

[0048] In one aspect, provided herein is a method for alleviating one or more symptoms associated with abnormal hematopoiesis, a blood disorder, cancer or a tumor in a subject comprising administering to the subject an antibody or fragment thereof described herein or a pharmaceutical composition described herein.

[0049] In one aspect, provided herein is a method for treating or preventing acute myeloid leukemia (AML) and / or myelodysplastic syndrome (MDS) in a subject comprising administering to the subject an antibody or fragment thereof described herein or a pharmaceutical composition described herein.

[0050] In one aspect, provided herein is a method for treating or preventing abnormal hematopoiesis in a subject comprising administering to the subject an antibody or fragment thereof described herein or a pharmaceutical composition described herein.

[0051] In one aspect, provided herein is a method for treating a Jagged- 1 -related disease, disorder or condition in a subject comprising administering to the subject an antibody or fragment thereof described herein or a pharmaceutical composition described herein. In certain embodiments, the Jagged- 1 -related disease, disorder or condition is AML, MDS, or abnormal hematopoiesis.

[0052] In various embodiments of a method described herein, the subject is administered one or more therapeutic agents in combination with the antibody or fragment thereof or with the pharmaceutical composition.

[0053] In another aspect, the application provides surprising results showing that the antibody or fragment thereof provided herein is particularly effective in treating patients with elevated expression levels of Jagged- 1 in their bone marrow osteoblasts.Page 9 of 320NAI-5001326827v1

[0054] In one aspect, provided herein is a method for selectively treating a subject, comprising administering to the subject a Jagged-1 binding agent, wherein the subject has been determined to have an elevated expression level of Jagged-1 in the subject’s bone marrow osteoblasts, and wherein the Jagged- 1 binding agent is the antibody or fragment thereof provided herein.

[0055] In one aspect, provided herein is a method for selecting or identifying a subject for a treatment with a Jagged- 1 binding agent, comprising: (1) determining the expression level of Jagged- 1 in the subject; (2) selecting the subject that has an elevated expression level of Jagged- 1 in the subject’s bone marrow osteoblasts, wherein the Jagged-1 binding agent is the antibody or fragment thereof provided herein. In some embodiments, the method further comprises administering the Jagged- 1 binding agent to the subject selected based on step (2) of the method provided herein.BRIEF DESCRIPTION OF THE DRAWINGS

[0056] FIG. 1 illustrates the binding properties of exemplary anti -Jagged- 1 antibody clones. Binding of monomeric biotinylated, His-tagged Jagged- 1 -extracellular domain at different concentrations to immobilized anti-Jagged-1 antibodies or control IgG4 coated on wells of Immobilon plates.

[0057] FIG. 2 illustrates exemplary cell death responses of human 0CI-AML3 cells when cocultured with U2OS cells or stably transfected U2OS cells expressing Jagged 1. 0CI-AML3 cells were overlayed onto the U2OS monolayers at a density of 1 x 106 cells / ml in the presence of 20 nM test antibody. Apoptosis was measured 24 hours later by staining with AnnexinV-Pacific blue / Sytox AADvanced for apoptotic / dead cells (Invitrogen A35136), according to manufacturer’s protocol and with CD45-PE for exclusion of any contaminating U2OS cells and gating for AnnexinV-positive cells in the CD45-positive population.

[0058] FIG. 3 illustrates exemplary cell death responses of patient MDS cells co-cultured with their own osteoblasts exhibiting nuclear (activated) [3-catenin localization, determined using co-staining of bone marrow cells with an antibody that recognizes activated (non-phosphorylated) [3-catenin (Cell Signaling 13537BC) and the CD34-Lin- / Osteocalcin+ / Runx2+ cocktail (Becton-Dickenson) that recognizes the osteoblast lineage. MDS cells were overlaid onto the osteoblast feeder layer and the test antibodies were added at a concentration of 1 pg / mL diluted in PBS. After 24 hours of coculture, cells were stained with AnnexinV-Pacific blue / Sytox AADvanced and the number of apoptotic MDS cells were analyzed by flow cytometry.

[0059] FIG. 4 shows exemplary results of testing the binding of recombinant biotinylated Jagl-His and biotinylated Jag2-Fc compared to a biotinylated control Fc-fusion protein to individual Fab- displaying yeast clones. Replica plates of individual clones harvested in the final round of FACS of the affinity optimization campaign were incubated in the presence of 20 nM of recombinant biotinylated Jagl-His (right panel), biotinylated Jag2-Fc (middle panel) or biotinylated control Fc- fusion (left panel) for 30 minutes at 4°C. Bound biotinylated protein was detected with APC-labeled streptavidin.Page 10 of 320NAI-5001326827v1

[0060] FIG. 5 shows exemplary relative binding curves of antibody clones selected from an affinity optimization campaign for wells coated with Jagged- 1 (Jag 1 -His) or Jagged-2 (Jag2-Fc).

[0061] FIGS. 6A-6C illustrates binding activity of exemplary variant antibody clones compared to parental antibody clone for binding to 293 cell expressing full-length human Jagged- 1, Jagged-2, DLL-1 or DLL-4. FIG. 6A. The data for the test 96-well plate shown as the geomean fluorescence intensity. Columns 1 to 11 represent the dilution series (3-fold) of the AvGn(Jagl)-C, column 12 represents staining with the FITC secondary goat anti- human IgG alone. The concentration series for Jagged- 1 started at 100 nM whereas for the cells expressing the other Notch ligands, the starting concentration was 500 nM (Column 1). FIG. 6B. The corresponding cytogram of the well where Jagged- 1 expressing cells were stained in the presence of 100 nM AvGn-Jagl-Dl detected with FITC- labeled secondary goat anti-human IgG alone (left panel) and for the well stained with FITC-labeled secondary goat anti-human IgG only. FIG. 6C. Binding curves derived from the mean 650 nm fluorescence data from a 3-fold dilution series ranging from 100 down to 0.0017 nM for Jagged-1 or 500 to 0.0085 nM for Jagged-2, DLL-1 and DLL-4 for two exemplary clones. Curve fitting was performed using Prism software (Graphpad. San Diego, CA).

[0062] FIG. 7 illustrates the ability of an exemplary antibody clone produced as a human VH / VL. murine IgGl Fc chimera to antagonize Jagged- 1 induced activation of Notch- 1 in a Notch- 1 reporter cell assay. Reporter cells were added to U2OS cells or Jagged- 1 U2OS cells stably transfected with human Jagged- 1 in the absence or presence of different concentrations of the exemplary anti -Jagged- 1 antibody.

[0063] FIG. 8 illustrates a study design for testing an exemplary anti- Jagged- 1 antibody clone compared to standard or high dose cytarabine+anthracycline standard of care chemotherapy regimen for AML patients in the [3-cat(ex3)osb mice and wild type C57BL mice.

[0064] FIGS. 9A- 9C illustrate effects of an exemplary anti- Jagged- 1 antibody clone administered weekly from Day 10 to Day 60 on body weight (FIG. 9A), overall survival (FIG. 9B) or survival from leukemia (FIG. 9C) of [3-cat(ex3)osb and wild type C57BL mice.

[0065] FIGS. 10A and 10B illustrate effects of low (l x DA) and high dose (2x DA) standard of care chemotherapy administered between Day 10 and Day 15 on body weight (FIG. 10A) and survival (FIG. 10B) of [3-cat(ex3)osb and wild type (WT) C57BL mice.

[0066] FIGS. HA and 11B illustrate effects of an exemplary anti -Jagged- 1 antibody clone or control murine IgGl on the presence of blasts and hypersegmented neutrophils in the circulation of [3- cat(ex3)osb and wild type C57BL mice. FIG. 11A. blood smears of WT mice treated with control IgGl (left panel) compared to [3-cat(ex3)osb mice treated with control murine IgGl (middle panel) or the exemplary anti-Jagged-1 antibody (right panel). FIG. 11B. Comparison of blasts count as %white blood cells (left panel) or hypersegmented neutrophils as percent neutrophils (right panel) in WT mice treated with control IgGl compared to [3-cat(ex3)osb mice treated with control murine IgGl or the exemplary anti-Jagged-1 antibody.Page 11 of 320NAI-5001326827v1

[0067] FIGS. 12A- 12C illustrate how treatment with an exemplary anti -Jagged- 1 antibody is associated with (FIG. 12A) reversal of anemia shown as both platelet count (left bar graph) and hematocrit (right bar graph), (FIG. 12B) reversal of thrombocytopenia shown as both platelet count and CD14+ / CD45- megakaryocyte precursors, and (FIG. 12C) restoration of normal wbc (left panel), lymphocyte (middle panel) and neutrophil (right panel) counts.

[0068] FIG. 13 illustrates effects of chemotherapy compared to vehicle alone on blood cells in blood smears of WT mice and the effect of chemotherapy on the presence of blasts and blood cells in the circulation of [3-cat(ex3)osb mice.

[0069] FIG. 14 illustrates the correlation between % osteoblasts with activated [3-catenin and % with upregulated expression of Jagged- 1 determined by flow cytometry.

[0070] FIGS. 15A and 15B show the effect of AvGn(Jagl)-C on proliferation (FIG. 15A) and survival (FIG. 15B) of co-cultures of osteoblasts with bone marrow mononuclear blasts from healthy subjects (H), MDS or AML patients with low osteoblast activated [3-catenin (black bars on the left in each panel) or high osteoblast activated [3-catenin (red bars on the right in each panel) relative to the effect of control IgG.

[0071] FIGS. 16A-16E show a breakdown of responders (R) compared to non-responders (NR) by risk category in the proliferation assay (left bar graph in each panel) or apoptosis assay (right bar graph in each panel). FIG. 16A. MDS samples stratified by IPSS-R status of very low to low risk or high to very high risk. ND = not determined. FIG. 16B. AML samples stratified by ELN risk categories of favorable, intermediate or adverse outcomes and ND (not determined). FIG. 16C. AML samples stratified by whether they were from patients with de novo or secondary disease. ND= not determined. FIG. 16D. MDS samples stratified by their karyotype status of normal, 1-2 lesions, > 3 lesions or ND. FIG. 16E. AML samples stratified by their karyotype status of normal, 1-2 lesions, > 3 lesions or ND.

[0072] FIGS. 17A and 17B illustrate the effect of AvGn(Jagl)-C on restoration of myeloid cell levels using CD15 and CD1 lb staining (FIG. 17A) and erythrocyte count using Band 3 and glycophorin A (GPA) staining (FIG. 17B) in AML patients with low osteoblast activated [3-catenin levels (black bars on the left in each panel) or high osteoblast activated [3-catenin levels (red bars on the right in each panel).

[0073] FIG. 18 illustrates mutational status of responders versus non-responders to AvGn(Jagl)-C among the 22 [Beat111811AML patients. P: cell proliferation. D: cell death. Each column represents one patient sample. Blue cells (marked cells) indicate presence of mutant gene.

[0074] FIGS. 19A and 19B show a sequence alignment of heavy chain variable regions and light chain variable regions, respectively, of exemplary antibody clones AvGn(Jagl)-A, AvGn(Jagl)-B, AvGn(Jagl)-C, AvGn(Jagl)-D, AvGn(Jagl)-E, and AvGn(Jagl)-F, including sequences for VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. Boundaries of CDRs are indicated by Kabat, AbM, Chothia, Contact, IMGT, and AHon numbering.Page 12 of 320NAI-5001326827v1

[0075] FIGS. 20A and 20B show a sequence alignment of heavy chain variable regions and light chain variable regions, respectively, of exemplary antibody clones AvGn(Jagl)-Cl, AvGn(Jagl)-C2, AvGn(Jagl)-C3, AvGn(Jagl)-C2(#2), AvGn(Jagl)-C2(#5), AvGn(Jagl)-C2(#8), AvGn(Jagl)- C2(#9), AvGn(Jagl)-C2(#14), AvGn(Jagl)-C3(#4), and AvGn(Jagl)-C3(#10), including sequences for VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. Boundaries of CDRs are indicated by Kabat, AbM, Chothia, Contact, IMGT, and AHon numbering.DETAILED DESCRIPTION

[0076] The present disclosure provides Jagged- 1 binding agents, including agents that bind to human Jagged- 1. Such agents include antibodies that bind to Jagged- 1, including antibodies that bind to human Jagged- 1. Such antibodies (e.g., monospecific or multispecific, including bispecific) may bind to human Jagged-1, the extracellular domain of Jagged-1, a DSL-EGF1-3 region of the extracellular domain of human Jagged- 1, and / or a receptor binding domain of human Jagged- 1. Such binding agents (e.g., antibodies) are useful in compositions and in methods of treating, preventing, or alleviating a Jagged- 1 -mediated disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition.

[0077] The present disclosure provides Jagged- 1 binding agents such as agents the bind to human Jagged- 1, including agents that are antibodies or antibody fragments, and methods of using Jagged- 1 binding agents such as agents that bind to human Jagged- 1, in methods of treating, preventing, or alleviating a Jagged- 1 related disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition. For example, Jagged- 1 binding agents such as agents, including antibodies, that bind to human Jagged- 1 (e.g., monospecific or multispecific antibodies, including bispecific antibodies) are useful in such methods of treatment, prevention, or alleviation.

[0078] Provided herein are binding agents (e.g., antibodies) which bind to Jagged- 1, including agents (e.g., antibodies) that bind to human Jagged-1 (e.g., with an amino acid sequence of SEQ ID NO:225). A Jagged- 1 binding agent (e.g., antibody) may bind to human Jagged- 1 or portion thereof such as the extracellular domain of Jagged- 1, a DSL-EGF1-3 region of the extracellular domain or a receptor binding domain. An exemplary amino acid sequence of human Jagged- 1 is provided by UniProtKB accession number P78504 (see, e.g., amino acids Gln34-Serl046). An exemplary amino acid sequence of the extracellular domain is provided by UniProtKB accession number P78502 (see e.g., amino acids Gln34- Serl067 (as defined in UniProtKB,), a DSL-EGF1-3 region of the extracellular domain of human Jagged-1 is provided by UniProtKB accession number P78504 (see, e.g., amino acids Vall85-Ile335). An exemplary amino acid sequence of a receptor binding domain (RBD) of human Jagged-1 is provided by UniProtKB accession number P78502 (see. e.g., amino acids Phel99- Phe207).

[0079] The term “antibody,” “immunoglobulin,” or “Ig” is used interchangeably herein, and is used in the broadest sense and specifically covers, for example polyclonal antibodies, monoclonalPage 13 of 320NAI-5001326827v1antibodies (including agonist, antagonist, neutralizing antibodies, full length or intact monoclonal antibodies), antibody compositions with polyepitopic or monoepitopic specificity, recombinantly produced antibodies, monospecific antibodies, multispecific antibodies (including bispecific antibodies), synthetic antibodies, chimeric antibodies, humanized antibodies, or human versions of antibodies having full length heavy and / or light chains. Antibodies and fragments thereof as disclosed herein include antibodies and fragments thereof that bind to Jagged- 1, including, for example, human Jagged-1, an extracellular domain of Jagged-1, a DSL-EGF1-3 region of the extracellular domain of human Jagged- 1, and / or a receptor binding domain of human Jagged- 1. Antibodies may be neutralizing antibodies. The present disclosure includes antibody fragments (and / or polypeptides that comprise antibody fragments) that retain Jagged- 1 binding characteristics. Non-limiting examples of antibody fragments include antigen-binding regions and / or effector regions of the antibody, e.g., F(ab)2, F(ab')2, Fab, Fab', Fd, Fc, and Fv fragments (e.g., fragments consisting of the variable regions of the heavy and light chains that are non-covalently coupled), disulfide-linked Fvs (dsFv), or singledomain antibodies (e.g., nanobodies). In general terms, a variable (V) region domain may be any suitable arrangement of immunoglobulin heavy (VH) and / or light (VL) chain variable domains. For example, the present disclosure also includes tetrameric antibodies comprising two heavy chain and two light chain molecules, an antibody light chain monomer, and an antibody heavy chain monomer. Thus, for example, the V region domain may be dimeric and contain VH-VH, VH-VL, or VL-VL dimers that bind Jagged- 1, including human Jagged- 1 or portion thereof (e.g. , an extracellular domain of Jagged-1, a DSL-EGF1-3 region of the extracellular domain or a receptor binding domain). If desired, the VH and VL chains may be covalently coupled either directly or through a linker to form a single chain Fv (scFv). For ease of reference, scFv proteins are referred to herein as included in the category “antibody fragments.” Antibody fragments (e.g., single-chain antibodies or other binding domains) can exist alone or in combination with one or more of the following: hinge region, CHI, CH2, CH3, or CH4 domains, J chain, or secretory component. Another form of an antibody fragment is a peptide comprising one or more complementarity determining regions (CDRs) of an antibody. CDRs (also termed "minimal recognition units" or "hypervariable region") can be obtained by constructing polynucleotides that encode the CDR of interest. Such polynucleotides are prepared, for example, by using the polymerase chain reaction to synthesize the variable region using mRNA of antibody-producing cells as a template (see, for example, Larrick et al., Methods: A Companion to Methods in Enzymology, 2: 106 (1991); Courtenay-Luck, "Genetic Manipulation of Monoclonal Antibodies," in Monoclonal Antibodies Production, Engineering and Clinical Application, Ritter et al. (eds.), page 166, Cambridge University Press (1995); and Ward et al., "Genetic Manipulation and Expression of Antibodies," in Monoclonal Antibodies: Principles and Applications, Birch et al., (eds.), page 137, Wiley-Liss, Inc. (1995)). Antibody fragments may be incorporated into single domain antibodies, maxibodies, minibodies, intrabodies, diabodies, triabodies, tetrabodies, variable domains of new antigen receptors (v-NAR), and bis-single chain Fv regions (see, e.g., Hollinger andPage 14 of 320NAI-5001326827v1Hudson, Nature Biotechnology, 23(9): 1126-1136, 2005). The binding agent, in some embodiments, contains a light chain and / or a heavy chain constant region, such as one or more constant regions, including one or more IgGl, IgG2, IgG3 and / or IgG4 constant regions. In some embodiments, antibodies can include epitope-binding fragments of any of the above. The antibodies provided herein can be of any class (e.g., IgG, IgE, IgM, IgD, and IgA) or any subclass (e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2) of immunoglobulin molecule. Antibodies may be neutralizing antibodies.

[0080] The term "monospecific" antibody as used herein denotes an antibody that has one or more binding sites each of which bind to the same epitope of the same antigen. The term "bispecific" means that the antibody is able to specifically bind to at least two distinct antigenic determinants, for example two binding sites each formed by a pair of an antibody heavy chain variable domain (VH) and an antibody light chain variable domain (VL) binding to different antigens or to different epitopes on the same antigen. Such a bispecific antibody may have a 1+1 format. Other bispecific antibody formats may be 2+1 formats (comprising two binding sites for a first antigen or epitope and one binding site for a second antigen or epitope) or 2+2 formats (comprising two binding sites for a first antigen or epitope and two binding sites for a second antigen or epitope). When a bispecific antibody comprises two antigen binding sites, each may bind to a different antigenic determinant. Such a bispecific antibody may bind to two different epitopes on the same antigen (e.g., epitopes on human Jagged- 1).

[0081] The terms “identical” or percent “identity” in the context of two or more nucleic acids or polypeptides, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. The percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software that can be used to obtain alignments of amino acid or nucleotide sequences are well-known in the art. These include, but are not limited to, BLAST, ALIGN, Megalign, BestLit, GCG Wisconsin Package, and variants thereof. In some embodiments, two nucleic acids or polypeptides are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. In some embodiments, identity exists over a region of the amino acid sequences that is at least about 10 residues, at least about 20 residues, at least about 40-60 residues, at least about 60-80 residues in length or any integral value there between. In some embodiments, identity exists over a longer region than 60-80 residues, such as at least about 80- 100 residues, and in some embodiments the sequences are substantially identical over the full length of the sequences being compared, such as the coding region of a target protein or an antibody. In some embodiments, identity exists over a region of the nucleotide sequences that is at least about 10Page 15 of 320NAI-5001326827v1bases, at least about 20 bases, at least about 40-60 bases, at least about 60-80 bases in length or any integral value there between. In some embodiments, identity exists over a longer region than 60-80 bases, such as at least about 80-1000 bases or more, and in some embodiments the sequences are substantially identical over the full length of the sequences being compared, such as a nucleotide sequence encoding a protein of interest.

[0082] A “conservative amino acid substitution” is one in which one amino acid residue is replaced with another amino acid residue having a side chain with similar chemical characteristics. Families of amino acid residues having similar side chains have been generally defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). For example, substitution of a phenylalanine for a tyrosine is a conservative substitution. Generally, conservative substitutions in the sequences of the polypeptides, soluble proteins, and / or antibodies of the disclosure do not abrogate the binding of the polypeptide, soluble protein, or antibody containing the amino acid sequence, to the target binding site. Methods of identifying amino acid conservative substitutions which do not eliminate binding are well-known in the art.

[0083] The terms “polypeptide” refers to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can include (e.g., be interrupted by) non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as linkage to or conjugation with (directly or indirectly) a moiety such as a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids), as well as other modifications known in the art. It is understood that, because the polypeptides of this disclosure can be based upon antibodies or other members of the immunoglobulin superfamily, in some embodiments, the polypeptides can occur as single chains.

[0084] As used herein, an “antigen” is a moiety or molecule that contains an epitope to which an antibody can bind. As such, an antigen is alsobound by an antibody. In some embodiments, the antigen, to which an antibody described herein binds is Jagged- 1 (e.g., human Jagged- 1), or a fragment thereof.

[0085] As used herein, an “epitope” is a term in the art and refers to a localized region of an antigen to which an antibody can bind. An epitope can be a linear epitope or a conformational, non-linear, or discontinuous, epitope. In the case of a polypeptide antigen, for example, an epitope can be contiguous amino acids of the polypeptide (a “linear” epitope) or an epitope can comprise amino acidsPage 16 of 320NAI-5001326827v1from two or more non-contiguous regions of the polypeptide (a “conformational,” “non-linear” or “discontinuous” epitope), e.g. , human Jagged- 1. It will be appreciated by one of skill in the art that, in general, a linear epitope may or may not be dependent on secondary, tertiary, or quaternary structure. For example, in some embodiments, an antibody binds to a group of amino acids regardless of whether they are folded in a natural three dimensional protein structure. In other embodiments, an antibody requires amino acid residues making up the epitope to exhibit a particular conformation (e.g. , bend, twist, turn or fold) in order to recognize and bind the epitope.

[0086] As used herein, the terms “specifically binds,” “specifically recognizes,” “immunospecifically binds,” “selectively binds,” “immunospecifically recognizes” and “immunospecific” are analogous terms in the context of antibodies and refer to molecules that bind to an antigen (e.g., epitope) as such binding is understood by one skilled in the art. In some embodiments, “specifically binds” means, for instance that a polypeptide or molecule interacts more frequently, more rapidly, with greater duration, with greater affinity, or with some combination of the above to the epitope, protein, or target molecule than with alternative substances, including related and unrelated proteins. For example, a molecule that specifically binds to an antigen may bind to other peptides or polypeptides, generally with lower affinity as determined by, e.g., immunoassays, europium-based Time Resolved FRET (TRF) assays (Perkin Elmer, Waltham, MA), Biacore™, KinExA 3000 instrument (Sapidyne Instruments, Boise, ID), or Bio-Layer Interferometry (BLI) assays, (BioForte or Gator™ instrument (Probe Life, Inc., Palo Alto, CA)), or other assays known in the art. In some embodiments, an antibody or antigen binding domain binds to or specifically binds to an antigen when it binds to an antigen with higher affinity than to any cross-reactive antigen as determined using experimental techniques, such as radioimmunoassays (RIA) and enzyme linked immunosorbent assays (ELIS As). Typically, a specific or selective reaction will be at least twice background signal or noise and may be more than 10 times background. See, e.g., Fundamental Immunology 332-36 (Paul ed., 2d ed. 1989) for a discussion regarding binding specificity. In some embodiments, the extent of binding of an antibody or antigen binding domain to a “non-target” protein is less than about 10% of the binding of the antibody or antigen binding domain to its particular target antigen, for example, as determined by fluorescence activated cell sorting (FACS) analysis, RIA, ELISA, BLI or TRF assays. In some embodiments, molecules that specifically bind to an antigen bind to the antigen with a Ka that is at least 2 logs, 2.5 logs, 3 logs, 4 logs or greater than the Ka when the molecules bind to another antigen. In some embodiments, molecules that specifically bind to an antigen do not cross react with other proteins. In some embodiments “specifically binds” means, for instance, that a polypeptide or molecule binds a protein or target with a KD of about 0. ImM or less, but more usually less than about 1 pM. In some embodiments, “specifically binds” means that a polypeptide or molecule binds a target with a KD of at least about 0.1 pM or less, at least about 0.0 IpM or less, or at least about InM or less. Because of the sequence identity between homologous proteins in different species, specific binding can include a polypeptide or molecule that recognizes a protein or target in more than one species. Likewise,Page 17 of 320NAI-5001326827v1because of homology within certain regions of polypeptide sequences of different proteins, specific binding can include a polypeptide or molecule that recognizes more than one protein or target. It is understood that, in some embodiments, a polypeptide or molecule that specifically binds a first target may or may not specifically bind a second target. As such, “specific binding” does not necessarily require (although it can include) exclusive binding, e.g., binding to a single target. Thus, a polypeptide or molecule can, in some embodiments, specifically bind more than one target. In some embodiments, multiple targets can be bound by the same antigen-binding site on the polypeptide or molecule. For example, an antibody can, in certain instances, comprise two identical antigen-binding sites, each of which specifically binds the same epitope on two or more proteins. In certain alternative embodiments, an antibody can be bispecific and comprise at least two antigen-binding sites with differing specificities. Generally, but not necessarily, reference to “binding” means “specific binding”.

[0087] As used herein, the term “constant region” or “constant domain” is a well-known antibody term of art and refers to an antibody portion, e.g., for example, a carboxyl terminal portion of a light and / or heavy chain which is not directly involved in binding of an antibody to antigen but which can exhibit various effector functions, such as interaction with the Fc receptor. The term refers to a portion of an immunoglobulin molecule having a generally more conserved amino acid sequence relative to an immunoglobulin variable domain.

[0088] Antibody “effector functions” refer to those biological activities attributable to the Fc region (e.g., a native sequence Fc region or amino acid sequence variant Fc region of an antibody) and vary with the antibody isotype. Examples of antibody effector functions include: Clq binding and complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor); and B cell activation. Anti-Jagged- 1 antibodies as described herein include those without such antibody effector functions (so-called “effectorless” antibodies).

[0089] The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain, including, for example, native sequence Fc regions, recombinant Fc regions, and variant Fc regions. Although the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy chain Fc region is often defined to stretch from an amino acid residue at position Cys226 (according to the EU numbering system), or from Pro230 (according to the EU numbering system), to the carboxyl-terminus thereof. The C-terminal lysine (residue 447 according to the EU numbering system) of the Fc region may be removed, for example, during production or purification of the antibody, or by recombinantly engineering the nucleic acid encoding a heavy chain of the antibody. An exemplary Fc region sequence is provided below (CH2 domain = bold text; CH3 domain = underline text):CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPage 18 of 320NAI-5001326827v1PREPQVYTLPPSRDELTKNOVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWOOGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:223).

[0090] A “functional Fc region” possesses an “effector function” of a native sequence Fc region. Exemplary “effector functions” include Clq binding; complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor; BCR), etc. Such effector functions generally require the Fc region to be combined with a binding region or binding domain (e.g., an antibody variable region or domain) and can be assessed using various assays as known in the art.

[0091] A “native sequence Fc region” comprises an amino acid sequence identical to the amino acid sequence of an Fc region found in nature, and not manipulated, modified, and / or changed (e.g., isolated, purified, selected, including or combining with other sequences such as variable region sequences) by a human. Native sequence human Fc regions include a native sequence human IgGl Fc region (non-A and A allotypes); native sequence human IgG2 Fc region; native sequence human IgG3 Fc region; and native sequence human IgG4 Fc region as well as naturally occurring variants thereof.

[0092] A “variant Fc region” comprises an amino acid sequence which differs from that of a native sequence Fc region by virtue of at least one amino acid modification, (e.g., substituting, addition, or deletion) preferably one or more amino acid substitution(s). In some embodiments, the variant Fc region has at least one amino acid substitution compared to a native sequence Fc region or to the Fc region of a parent polypeptide, for example, from about one to about ten amino acid substitutions, and preferably from about one to about five amino acid substitutions in a native sequence Fc region or in the Fc region of the parent polypeptide. The variant Fc region described herein can possess at least about 80% homology with a native sequence Fc region and / or with an Fc region of a parent polypeptide, or at least about 90% homology therewith, for example, at least about 95% homology therewith. The variant Fc region herein described herein may have a loss of effector function (e.g. , silent Fc). An exemplary variant Fc region (“silent Fc”) sequence is provided below (CH2 domain = bold text with amino acid changes underlined; CH3 domain = underline text):CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSRDELTKNOVSLTCLVKGFYPSDIAVEWESNGOPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWOOGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 224). Exemplary variant Fc sequences including the following variants (according to the EU numbering system): N297A / Q (N297A or N297Q), LALA (L234A, L235A), LALAPS (L234A, L235A, P331S), LALAPG (L234A, L235A, P329G), and TM (L234F, L235E, P331S).

[0093] A “variant Fc region” As used herein, the term “heavy chain” when used in reference to an antibody refers to a polypeptide chain of about 50-70 kDa, wherein the amino-terminal portion includes a variable region of about 120 to 130 or more amino acids, and a carboxy-terminal portionPage 19 of 320NAI-5001326827v1includes one or more constant regions. The “heavy chain” can refer to any distinct types, e.g., for example, alpha (a), delta (5), epsilon (a), gamma (y) and mu (p), based on the amino acid sequence of the constant domain, which give rise to IgA, IgD, IgE, IgG and IgM classes of antibodies, respectively, including subclasses of IgG, e.g., IgGl, IgG2, IgG3 and IgG4.

[0094] As used herein, the term “light chain” when used in reference to an antibody can refer to a polypeptide chain of about 25 kDa, wherein the amino-terminal portion includes a variable region of about 100 to about 110 or more amino acids, and a carboxy-terminal portion includes a constant region. The approximate length of a light chain is 211 to 217 amino acids. There are two distinct types, e.g., kappa (K) of lambda (X) based on the amino acid sequence of the constant domains. Light chain amino acid sequences are well known in the art. As used herein, an “isolated” or “purified” antibody or antigen binding fragment is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the antibody or antigen binding fragment is derived, or substantially free of chemical precursors or other chemicals when the antibody or antigen binding fragment is chemically synthesized.

[0095] The terms “antigen binding fragment,” “antigen binding domain,” “antigen binding region,” and similar terms refer to that portion of an antibody, which comprises the amino acid residues that interact with an antigen and confer on the binding fragment, domain, or region its specificity and affinity for the antigen (e.g., the CDRs). “Antigen binding fragment” as used herein include “antibody fragment,” which comprise a portion of an intact antibody including one or more CDRs, such as the antigen binding or variable region of the intact antibody. Examples of antibody fragments include, without limitation, Fab, Fab’, F(ab’)2, and Fv fragments; diabodies and di-diabodies (see, e.g., Holliger et al., Proc Natl Acad Sci 1993, 90:6444-48; Lu et al., J Biol Chem, 2005, 280: 19665- 72; Hudson et al., Nat Med, 2003, 9: 129-34; WO 93 / 11161; and U.S. Pat. Nos. 5,837,242 and 6,492,123); single-chain antibody molecules (see, e.g., U.S. Pat. Nos. 4,946,778; 5,260,203;5,482,858; and 5,476,786); dual variable domain antibodies (see, e.g., U.S. Pat. No. 7,612,181); single variable domain antibodies (sdAbs) (see, e.g., Woolven et al., Immunogenetics, 1999, 50: 98-101; and Streltsov et al., Proc Natl Acad Sci USA. 2004, 101: 12444-49); and multispecific antibodies formed from antibody fragments.

[0096] As used herein, the terms “antibody” and “immunoglobulin” and “Ig” are terms of art and can be used interchangeably herein and refer to a molecule with one or more antigen binding sites that bind an antigen.

[0097] In some embodiments, a Jagged- 1 binding agent such as an agent that binds to human Jagged- 1 can bind to human Jagged-1, an extracellular domain of Jagged-1, a DSL-EGF1-3 region of the extracellular domain of human Jagged- 1, and / or a receptor binding domain of human Jagged- 1.

[0098] In some embodiments, a Jagged- 1 binding agent such as an agent that binds to human Jagged- 1, an extracellular domain of Jagged- 1, a DSL-EGF1-3 region of the extracellular domain of human Jagged- 1, and / or a receptor binding domain of human Jagged- 1. Such a Jagged- 1 binding agentPage 20 of 320NAI-5001326827v1includes an antibody, antibody fragment, or other peptide-based molecule. Antibodies provided herein include, but are not limited to, synthetic antibodies, monoclonal antibodies, recombinantly produced antibodies, multispecific antibodies (e.g., including bispecific antibodies), human antibodies, humanized antibodies, chimeric antibodies, intrabodies, single-chain Fvs (scFv) (e.g., including monospecific, bispecific, etc.), camelized antibodies, Fab fragments, F(ab’) fragments, disulfide-linked Fvs (sdFv), anti-idiotypic (anti-Id) antibodies, and epitope-binding fragments of any of the above.

[0099] In some embodiments, antibodies provided herein include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, including molecules that contain one or more antigen binding sites that bind to a Jagged- 1 antigen.

[0100] Antibodies can be of any type (e.g. , IgG, IgE, IgM, IgD, IgA or IgY), any class, (e.g. , IgGl, IgG2, IgG3, IgG4, IgAl or IgA2), or any subclass (e.g., IgG2a or IgG2b) of immunoglobulin molecule. Antibodies may be neutralizing antibodies. In some embodiments, antibodies described herein are IgG antibodies (e.g., human IgG), or a class (e.g., human IgGl, IgG2, IgG3 or IgG4) or subclass thereof. In some embodiments, antibodies described herein are IgA antibodies (e.g., human IgA), or a class (e.g., human IgAl or IgA2) or subclass thereof. Antibody classes and subclasses, including IgGl, IgG2, IgG3, IgG4, IgAl, IgA2, are well known in the art and are known to confer functional specialization. Modified versions of each of these classes and subclasses may be prepared by those skilled in the art. In some embodiments, antibodies are hybrid antibodies with properties of more than one class or subclass of antibody. Methods for making hybrid antibodies (e.g., IgA / IgG and IgM / IgG) are known in the art. Antibodies include those of all isotypes, sub-classes and forms, including their fragments, for example, Jagged-1 binding fragments. An antibody can include a J- chain and / or a secretory component. Antibodies may be modified to include sequences from other isotypes, such as IgG to produce chimeric antibodies. An antibody encompasses anything ranging from a small binding fragment of an antibody to a full sized antibody, including a multimeric antibody, for example, an IgA antibody that includes four complete heavy chains and four complete light chains and optionally includes a J chain and / or a secretory component, or an IgM antibody that includes ten or twelve complete heavy chains and ten or twelve complete light chains and, optionally, includes a J-chain and / or a secretory component.

[0101] In some embodiments, an antibody is a 4-chain antibody unit comprising two heavy (H) chain / light (L) chain pairs, wherein the amino acid sequences of the H chains are identical and the amino acid sequences of the L chains are identical. In some embodiments, the H and L chains comprise constant regions, for example, human constant regions. In some embodiments, the L chain constant region of such antibodies is a kappa or lambda light chain constant region, for example, a human kappa or lambda light chain constant region. In some embodiments, the H chain constant region of such antibodies comprise a gamma heavy chain constant region, for example, a human gamma heavyPage 21 of 320NAI-5001326827v1chain constant region. In some embodiments, such antibodies comprise IgG constant regions, for example, human IgG constant regions (e.g., IgGl, IgG2, IgG3, and / or IgG4 constant regions).

[0102] An antibody or fragment thereof may preferentially bind to Jagged- 1 meaning that the antibody or fragment thereof binds Jagged- 1 with greater affinity than it binds to an unrelated control protein and / or binds Jagged- 1 with greater affinity than it binds to an unrelated control protein. For example, the antibody or fragment thereof may specifically recognize and bind human Jagged- 1 or a portion thereof. “Specific binding” means that the antibody or fragment thereof binds to Jagged- 1 with an affinity that is at least 5, 10, 15, 20, 25, 50, 100, 250, 500, 1000, or 10,000 times greater than the affinity for an unrelated control protein (e.g., hen egg white lysozyme). In some embodiments, the antibody or fragment thereof may bind Jagged- 1 substantially exclusively (e.g., is able to distinguish Jagged- 1 from other known polypeptides such other Notch receptor ligands, for example, by virtue of measurable differences in binding affinity). The term “hypervariable region”, “HVR”, or “HV”, when used herein refers to the regions of an antibody variable region that are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies comprise six hypervariable regions; three in the VH (Hl, H2, H3), and three in the VL (LI, L2, L3). A number of hypervariable region delineations are in use and are encompassed herein. The Kabat Complementarity Determining Regions (CDRs) are based on sequence variability and are the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Chothia refers instead to the location of the structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The end of the Chothia CDR- H1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop (this is because the Kabat numbering scheme places the insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). The AbM hypervariable regions represent a compromise between the Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular’s AbM antibody modeling software (see, e.g., Martin, in Antibody Engineering, Vol. 2, Chapter 3, Springer Verlag). The “contact” hypervariable regions are based on an analysis of the available complex crystal structures. The residues from each of these hypervariable regions or CDRs are noted below.

[0103] A universal numbering system has been developed and widely adopted, ImMunoGeneTics (IMGT) Information System® (Lefranc et al., Dev. Comp. Immunol. 27(l):55-77 (2003)). IMGT is an integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates. Herein, the CDRs are referred to in terms of both the amino acid sequence and the location within the light or heavy chain. As the “location” of the CDRs within the structure of the immunoglobulin variable domain is conserved between species and present in structures called loops, by using numbering systems that align variable domain sequences according to structural features, CDR and framework residues andPage 22 of 320NAI-5001326827v1are readily identified. This information can be used in grafting and replacement of CDR residues from immunoglobulins of one species into an acceptor framework from, typically, a human antibody. An additional numbering system (AHon) has been developed by Honegger and Pltickthun, J. Mol. Biol. 309: 657-670 (2001). Correspondence between the numbering system, including, for example, the Kabat numbering and the IMGT unique numbering system, is well known to one skilled in the art (see, e.g., Kabat, supra, Chothia and Lesk, supra, Martin, supra, Lefranc et al., supra) and is also illustrated below. An Exemplary system, shown herein, combines Kabat and Chothia.

[0104] Hypervariable regions may comprise “extended hypervariable regions” as follows: 24-36 or 24-34 (LI), 46-56 or 50-56 (L2) and 89-97 or 89-96 (L3) in the VL and 26-35 or 26-35A (Hl), 50-65 or 49-65 (H2) and 93-102, 94-102, or 95-102 (H3) in the VH. As used herein, the terms “HVR” and “CDR” are used interchangeably.

[0105] In some embodiments, a Jagged- 1 binding agent (e.g., antibody), including an agent (e.g., antibody) that binds to human Jagged- 1, comprises a VH region which comprises VH CDR1, VH CDR2, and / or VH CDR3, and a VL region which comprises VL CDR1, VL CDR2, and / or VL CDR3 of any one of the binding agents described herein (see, e.g., Tables 1-18). In some embodiments, the Jagged- 1 binding agent (e.g., antibody) provided herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Tables 1-18. In some embodiments, the Jagged- 1 binding agent (e.g., antibody) provided herein is bispecific and comprises a first binding site that comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Tables 1-18 and a second binding site that comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from another antibody, including, for example, another antibody that binds to Jagged- 1.

[0106] In some embodiments, the Jagged- 1 binding agents (e.g., antibodies) as described herein compete for the binding to Jagged- 1, such as human Jagged- 1, with a Jagged- 1 binding agent (e.g., an antibody) that comprises a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the antibodies as described herein, such as an amino acid sequence of a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 as set forth in Tables 1-18. Accordingly, in some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein competes for the binding to Jagged- 1, such as human Jagged-1, with a Jagged-1 binding agent (e.g., an antibody) that comprises one, two, and / or three VHPage 23 of 320NAI-5001326827v1CDRs and / or one, two, and / or three VL CDRs from: (a) the antibody designated AvGn(Jagl)-A; (b) the antibody designated AvGn(Jagl)-B; (c) the antibody designated AvGn(Jagl)-C; (d) the antibody designated AvGn(Jagl)-D; (e) the antibody designated AvGn(Jagl)-E; (f) the antibody designated AvGn(Jagl)-F; (g) the antibody designated AvGn(Jagl)-Cl; (h) the antibody designated AvGn(Jagl)- C2; (i) the antibody designated AvGn(Jagl)-C3; (j) the antibody designated AvGn(Jagl)-C2(#l); (k) the antibody designated AvGn(Jagl)-C2(#2); (1) the antibody designated AvGn(Jagl)-C2(#5); (m) the antibody designated AvGn(Jagl)-C2(#8); (n) the antibody designated AvGn(Jagl)-C2(#9); (o) the antibody designated AvGn(Jagl)-C2(#14); (p) the antibody designated AvGn(Jagl)-C3(#3); (q) the antibody designated AvGn(Jagl)-C3(#4); and (r) the antibody designated AvGn(Jagl)-C3(#10) as shown in Tables 1-18. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein competes for the binding to Jagged- 1, such as human Jagged- 1, with a Jagged- 1 binding agent (e.g., an antibody) that comprises one, two, and / or three VH CDRs and one, two, and / or three VL CDRs from: (a) the antibody designated AvGn(Jagl)-A; (b) the antibody designated AvGn(Jagl)-B; (c) the antibody designated AvGn(Jagl)-C; (d) the antibody designated AvGn(Jagl)- D; (e) the antibody designated AvGn(Jagl)-E; (f) the antibody designated AvGn(Jagl)-F; (g) the antibody designated AvGn(Jagl)-Cl; (h) the antibody designated AvGn(Jagl)-C2; (i) the antibody designated AvGn(Jagl)-C3; (j) the antibody designated AvGn(Jagl)-C2(#l); (k) the antibody designated AvGn(Jagl)-C2(#2); (1) the antibody designated AvGn(Jagl)-C2(#5); (m) the antibody designated AvGn(Jagl)-C2(#8); (n) the antibody designated AvGn(Jagl)-C2(#9); (o) the antibody designated AvGn(Jagl)-C2(#14); (p) the antibody designated AvGn(Jagl)-C3(#3); (q) the antibody designated AvGn(Jagl)-C3(#4); and (r) the antibody designated AvGn(Jagl)-C3(#10) as shown in Tables 1-18. In some embodiments, a Jagged-1 binding agent (e.g., an antibody) as described herein competes for the binding to Jagged- 1, such as human Jagged- 1, with a Jagged- 1 binding agent (e.g., an antibody) that comprises a VH region and VL region from: (a) the antibody designated AvGn(Jagl)-A; (b) the antibody designated AvGn(Jagl)-B; (c) the antibody designated AvGn(Jagl)- C; (d) the antibody designated AvGn(Jagl)-D; (e) the antibody designated AvGn(Jagl)-E; (f) the antibody designated AvGn(Jagl)-F; (g) the antibody designated AvGn(Jagl)-Cl; (h) the antibody designated AvGn(Jagl)-C2; (i) the antibody designated AvGn(Jagl)-C3; (j) the antibody designated AvGn(Jagl)-C2(#l); (k) the antibody designated AvGn(Jagl)-C2(#2); (1) the antibody designated AvGn(Jagl)-C2(#5); (m) the antibody designated AvGn(Jagl)-C2(#8); (n) the antibody designated AvGn(Jagl)-C2(#9); (o) the antibody designated AvGn(Jagl)-C2(#14); (p) the antibody designated AvGn(Jagl)-C3(#3); (q) the antibody designated AvGn(Jagl)-C3(#4); and (r) the antibody designated AvGn(Jagl)-C3(#10) as shown in Tables 1-18. In some embodiments, a Jagged-1 binding agent (e.g., an antibody) as described herein competes for the binding to Jagged- 1, such as human Jagged- 1, with a Jagged- 1 binding agent (e.g., an antibody) that comprises: (a) a VH region comprising the amino acid sequence of SEQ ID NO:25 and a VL region comprising the amino acid sequence of SEQ ID NO:26; (b) a VH region comprising the amino acid sequence of SEQ ID NO:47 and a VL regionPage 24 of 320NAI-5001326827v1comprising the amino acid sequence of SEQ ID NO:48; (c) a VH region comprising the amino acid sequence of SEQ ID NO:72 and a VL region comprising the amino acid sequence of SEQ ID NO:73; (d) a VH region comprising the amino acid sequence of SEQ ID NO:91 and a VL region comprising the amino acid sequence of SEQ ID NO:92; (e) a VH region comprising the amino acid sequence of SEQ ID NO: 110 and a VL region comprising the amino acid sequence of SEQ ID NO: 111; (f) a VH region comprising the amino acid sequence of SEQ ID NO: 126 and a VL region comprising the amino acid sequence of SEQ ID NO: 127; (g) a VH region comprising the amino acid sequence of SEQ ID NO: 144 and a VL region comprising the amino acid sequence of SEQ ID NO: 145; (h) a VH region comprising the amino acid sequence of SEQ ID NO: 154 and a VL region comprising the amino acid sequence of SEQ ID NO: 155; (i) a VH region comprising the amino acid sequence of SEQ ID NO: 163 and a VL region comprising the amino acid sequence of SEQ ID NO: 164; (j) a VH region comprising the amino acid sequence of SEQ ID NO: 154 and a VL region comprising the amino acid sequence of SEQ ID NO: 170; (k) a VH region comprising the amino acid sequence of SEQ ID NO: 154 and a VL region comprising the amino acid sequence of SEQ ID NO: 175; (1) a VH region comprising the amino acid sequence of SEQ ID NO: 154 and a VL region comprising the amino acid sequence of SEQ ID NO: 179; (m) a VH region comprising the amino acid sequence of SEQ ID NO: 154 and a VL region comprising the amino acid sequence of SEQ ID NO: 183; (n) a VH region comprising the amino acid sequence of SEQ ID NO: 154 and a VL region comprising the amino acid sequence of SEQ ID NO: 191; (o) a VH region comprising the amino acid sequence of SEQ ID NO: 154 and a VL region comprising the amino acid sequence of SEQ ID NO: 195; (p) a VH region comprising the amino acid sequence of SEQ ID NO: 163 and a VL region comprising the amino acid sequence of SEQ ID NO: 199; (q) a VH region comprising the amino acid sequence of SEQ ID NO: 163 and a VL region comprising the amino acid sequence of SEQ ID NO:207; and (r) a VH region comprising the amino acid sequence of SEQ ID NO: 163 and a VL region comprising the amino acid sequence of SEQ ID NO:211.

[0107] In some embodiments, the Jagged- 1 binding agents (e.g., antibodies) as described herein comprise a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the antibodies as described herein, such as an amino acid sequence of a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 as set forth in Tables 1-18. Accordingly, in some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from: (a) the antibody designated AvGn(Jagl)-A; (b) the antibody designated AvGn(Jagl)-B; (c) the antibody designated AvGn(Jagl)-C; (d) the antibody designated AvGn(Jagl)-D; (e) the antibody designated AvGn(Jagl)-E; (f) the antibody designated AvGn(Jagl)- F; (g) the antibody designated AvGn(Jagl)-Cl; (h) the antibody designated AvGn(Jagl)-C2; (i) the antibody designated AvGn(Jagl)-C3; (j) the antibody designated AvGn(Jagl)-C2(#l); (k) the antibody designated AvGn(Jagl)-C2(#2); (1) the antibody designated AvGn(Jagl)-C2(#5); (m) thePage 25 of 320NAI-5001326827v1antibody designated AvGn(Jagl)-C2(#8); (n) the antibody designated AvGn(Jagl)-C2(#9); (o) the antibody designated AvGn(Jagl)-C2(#14); (p) the antibody designated AvGn(Jagl)-C3(#3); (q) the antibody designated AvGn(Jagl)-C3(#4); and (r) the antibody designated AvGn(Jagl)-C3(#10) as shown in Tables 1-18. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and one, two, and / or three light chain CDRs from: (a) the antibody designated AvGn(Jagl)-A; (b) the antibody designated AvGn(Jagl)-B; (c) the antibody designated AvGn(Jagl)-C; (d) the antibody designated AvGn(Jagl)- D; (e) the antibody designated AvGn(Jagl)-E; (f) the antibody designated AvGn(Jagl)-F; (g) the antibody designated AvGn(Jagl)-Cl; (h) the antibody designated AvGn(Jagl)-C2; (i) the antibody designated AvGn(Jagl)-C3; (j) the antibody designated AvGn(Jagl)-C2(#l); (k) the antibody designated AvGn(Jagl)-C2(#2); (1) the antibody designated AvGn(Jagl)-C2(#5); (m) the antibody designated AvGn(Jagl)-C2(#8); (n) the antibody designated AvGn(Jagl)-C2(#9); (o) the antibody designated AvGn(Jagl)-C2(#14); (p) the antibody designated AvGn(Jagl)-C3(#3); (q) the antibody designated AvGn(Jagl)-C3(#4); and (r) the antibody designated AvGn(Jagl)-C3(#10) as shown in Tables 1-18.

[0108] In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) comprises a VH region, which comprises VH CDR1, VH CDR2, and / or VH CDR3, and a VL region, which comprises VL CDR1, VL CDR2, and / or VL CDR3, of any one of the binding agents as described herein (see, e.g. , any one of Tables 1-18). Accordingly, In some embodiments, a Jagged-1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 1. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 2. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 3. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 4. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 5. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 6. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 7. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 8. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 9. In some embodiments, a Jagged- 1 binding agent (e.g.,Page 26 of 320NAI-5001326827v1an antibody) as described herein comprises one, two, and / or three heavy chain CD Rs and / or one, two, and / or three light chain CDRs from Table 10. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 11. In some embodiments, a Jagged- 1 binding agent (e.g. , an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 12. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 13. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 14. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 15. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 16. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 17. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from Table 18. In some embodiments, a Jagged- 1 binding agent (e.g., an antibody) as described herein is bispecific and comprises a first binding domain that comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from any one of Tables 1-18 and a second binding domain that comprises one, two, and / or three heavy chain CDRs and / or one, two, and / or three light chain CDRs from a binding agent that binds to a second target antigen that is not Jagged- 1.

[0109] The antibody designated AvGn(Jagl)-A comprises a VH sequence that is SEQ ID NO:25 and a VL sequence that is SEQ ID NO:26.

[0110] The antibody designated AvGn(Jagl)-B comprises a VH sequence that is SEQ ID NO:47 and a VL sequence that is SEQ ID NO:48.

[0111] The antibody designated AvGn(Jagl)-C comprises a VH sequence that is SEQ ID NO:72 and a VL sequence that is SEQ ID NO:73.

[0112] The antibody designated AvGn(Jagl)-D comprises a VH sequence that is SEQ ID NO:91 and a VL sequence that is SEQ ID NO:92.

[0113] The antibody designated AvGn(Jagl)-E comprises a VH sequence that is SEQ ID NO: 110 and a VL sequence that is SEQ ID NO: 111.

[0114] The antibody designated AvGn(Jagl)-F comprises a VH sequence that is SEQ ID NO: 126 and a VL sequence that is SEQ ID NO: 127.

[0115] The antibody designated AvGn(Jagl)-Cl comprises a VH sequence that is SEQ ID NO: 144 and a VL sequence that is SEQ ID NO: 145.Page 27 of 320NAI-5001326827v1

[0116] The antibody designated AvGn(Jagl)-C2 comprises a VH sequence that is SEQ ID NO: 154 and a VL sequence that is SEQ ID NO: 155.

[0117] The antibody designated AvGn(Jagl)-C3 comprises a VH sequence that is SEQ ID NO: 163 and a VL sequence that is SEQ ID NO: 164.

[0118] The antibody designated AvGn(Jagl)-C2(#l) comprises a VH sequence that is SEQ ID NO: 154 and a VL sequence that is SEQ ID NO: 170.

[0119] The antibody designated AvGn(Jagl)-C2(#2) comprises a VH sequence that is SEQ ID NO: 154 and a VL sequence that is SEQ ID NO: 175.

[0120] The antibody designated AvGn(Jagl)-C2(#5) comprises a VH sequence that is SEQ ID NO: 154 and a VL sequence that is SEQ ID NO: 179.

[0121] The antibody designated AvGn(Jagl)-C2(#8) comprises a VH sequence that is SEQ ID NO: 154 and a VL sequence that is SEQ ID NO: 183.

[0122] The antibody designated AvGn(Jagl)-C2(#9) comprises a VH sequence that is SEQ ID NO: 154 and a VL sequence that is SEQ ID NO: 191.

[0123] The antibody designated AvGn(Jagl)-C2(#14) comprises a VH sequence that is SEQ ID NO: 154 and a VL sequence that is SEQ ID NO: 195.

[0124] The antibody designated AvGn(Jagl)-C3(#3) comprises a VH sequence that is SEQ ID NO: 163 and a VL sequence that is SEQ ID NO: 199.

[0125] The antibody designated AvGn(Jagl)-C3(#4) comprises a VH sequence that is SEQ ID NO: 163 and a VL sequence that is SEQ ID NO:207.

[0126] The antibody designated AvGn(Jagl)-C3(#10) comprises a VH sequence that is SEQ ID NO: 163 and a VL sequence that is SEQ ID NO:211.Page 28 of 320NAI-5001326827v1Table 1: Antibody Clone AvGn(Jagl)-APage 29 of 320NAI-5001326827v1Table 2: Antibody Clone AvGn(Jagl)-BPage 30 of 320NAI-5001326827v1Table 3: Antibody Clone AvGn(Jagl)-CPage 31 of 320NAI-5001326827v1Table 4: Antibody Clone AvGn(Jagl)-DPage 32 of 320NAI-5001326827v1Table 5: Antibody Clone AvGn(Jagl)-EPage 33 of 320NAI-5001326827v1Table 6: Antibody Clone AvGn(Jagl)-FPage 34 of 320NAI-5001326827v1Table 7: Antibody Clone AvGn(Jagl)-ClPage 35 of 320NAI-5001326827v1Table 8: Antibody Clone AvGn(Jagl)-C2Page 36 of 320NAI-5001326827v1Table 9: Antibody Clone AvGn(Jagl)-C3Page 37 of 320NAI-5001326827v1Table 10: Antibody Clone AvGn(Jagl)-C2(#l)Page 38 of 320NAI-5001326827v1Table 11: Antibody Clone AvGn(Jagl)-C2(#2)Page 39 of 320NAI-5001326827v1Table 12: Antibody Clone AvGn(Jagl)-C2(#5)Page 40 of 320NAI-5001326827v1Table 13: Antibody Clone AvGn(Jagl)-C2(#8)Page 41 of 320NAI-5001326827v1Table 14: Antibody Clone AvGn(Jagl)-C2(#9)Page 42 of 320NAI-5001326827v1Table 15: Antibody Clone AvGn(Jagl)-C2(#14)Page 43 of 320NAI-5001326827v1Table 16: Antibody Clone AvGn(Jagl)-C3(#3)Page 44 of 320NAI-5001326827v1Table 17: Antibody Clone AvGn(Jagl)-C3(#4)Page 45 of 320NAI-5001326827v1Table 18: Antibody Clone AvGn(Jagl)-C3(#10)Page 46 of 320NAI-5001326827v1

[0127] In some embodiments, Jagged- 1 binding agents (e.g., antibodies), including agents that bind to human Jagged- 1, provided herein comprise a VH region or VH domain. In other embodiments, Jagged- 1 binding agents (e.g., antibodies), including agents that bind to human Jagged- 1, provided herein comprise a VL region or VL chain. In some embodiments, Jagged- 1 binding agents (e.g., antibodies), including agents that bind to human Jagged- 1, provided herein have a combination of (i) a VH domain or VH region and (ii) a VL domain or VL region.

[0128] In some embodiments, the CDRs disclosed herein include consensus sequences derived from groups of related antibodies (see, e.g., Tables 1-18). As described herein, a “consensus sequence” refers to amino acid sequences having conserved amino acids common among a number of sequences and / or variable amino acids that vary within a given amino acid sequence. The CDR consensus sequences provided include CDRs corresponding to VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and / or VL CDR3.

[0129] Consensus sequences of CDRs of Jagged- 1 binding agents, including an agent that binds to human Jagged-1, are shown in FIGS. 19A and 19B.. In some embodiments, a Jagged-1 binding agent (e.g., antibody) described herein comprises (a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having the amino acid sequence of GFX1FX2X3YX4 (SEQ ID NO:212) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid; and / or (2) a VH CDR2 having the amino acid sequence of ISX1X2GX3X4K (SEQ ID NO:213) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid; and / or (3) a VH CDR3 having the amino acid sequence of ARX1X2GX3X4X5DX6 (SEQ ID NO:214) wherein Xi, X2, X3, X4, X5, and X6are each independently a naturally occurring amino acid, and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of QSVX1X2X3 (SEQ ID NO:215) wherein Xi, X2, and X3 are each independently a naturally occurring amino acid; and / or (2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:216) wherein Xi is a naturally occurring amino acid; and / or (3) a VL CDR3 having the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:217) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid. In some embodiments, a Jagged-1 binding agent (e.g., antibody) described herein comprises a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFX1FX2X3YX4 (SEQ ID NO:212) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid; (2) a VH CDR2 having the amino acid sequence of ISX1X2GX3X4K (SEQ ID NO:213) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid; and (3) a VH CDR3 having the amino acid sequence of ARX1X2GX3X4X5DX6 (SEQ ID NO:214) wherein Xi, X2, X3, X4, X5, and Xe are each independently a naturally occurring amino acid. In some embodiments, a Jagged- 1 binding agent (e.g., antibody) described herein comprises a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of QSVXIX2X3(SEQ ID NO:215) wherein Xi, X2, and X3are each independently a naturally occurring amino acid;(2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:216) wherein Xi is a naturallyPage 47 of 320NAI-5001326827v1occurring amino acid; and (3) a VL CDR3 having the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:217) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid. In some embodiments, a Jagged-1 binding agent (e.g., antibody) described herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFX1FX2X3YX4 (SEQ ID NO:212) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid; (2) a VH CDR2 having the amino acid sequence of ISX1X2GX3X4K (SEQ ID NO:213) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid; and (3) a VH CDR3 having the amino acid sequence of ARX1X2GX3X4X5DX6 (SEQ ID NO:214) wherein Xi, X2, X3, X4, X5, and Xe are each independently a naturally occurring amino acid, and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of QSVX1X2X3 (SEQ ID NO:215) wherein Xi, X2, and X3 are each independently a naturally occurring amino acid; (2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:216) wherein Xi is a naturally occurring amino acid; and (3) a VL CDR3 having the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:217) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid. In some embodiments, the VH CDR1 of a Jagged- 1 binding agent described herein has the amino acid sequence of GFX1FX2X3YX4 (SEQ ID NO:212) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid. In some embodiments, the VH CDR2 of a Jagged- 1 binding agent described herein has the amino acid sequence of a VH CDR2 having the amino acid sequence of ISX1X2GX3X4K (SEQ ID NO:213) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid. In some embodiments, the VH CDR3 of a Jagged- 1 binding agent described herein has the amino acid sequence of ARX1X2GX3X4X5DX6 (SEQ ID NO:214) wherein Xi, X2, X3, X4, X5, and Xe are each independently a naturally occurring amino acid. In some embodiments, the VL CDR1 of a Jagged- 1 binding agent described herein has the amino acid sequence of QSVX1X2X3 (SEQ ID NO:215) wherein Xi, X2, and X3 are each independently a naturally occurring amino acid. In some embodiments, the VL CDR2 of a Jagged- 1 binding agent described herein has the amino acid sequence of XiAS (SEQ ID NO:216) wherein Xi is a naturally occurring amino acid. In some embodiments, the VL CDR3 of Jagged- 1 binding agent described herein has the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:217) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid. In some embodiments, a Jagged- 1 binding agent (e.g., antibody) described herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFX1FX2X3YX4 (SEQ ID NO:218) wherein Xi is S or T, X2is G, S, or R, X3 is G, N, D, or S, and X4is D or G; and / or (2) a VH CDR2 having the amino acid sequence of ISX1X2GX3X4K (SEQ ID NO:219) wherein Xi is Y or H, X2is A, G, E, or S, X3 is R, S, or N, and X4is N, Q, I, or Y; and / or (3) a VH CDR3 having the amino acid sequence of ARXIX2GX3X4X5DX6(SEQ ID NO:235) wherein Xi is G, A, or D, X2is W or Y, X3is G or absence, X4is Y, H, or V, X5is S, I, F, or P, and X6is V, Y, or H, and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of QSVX1X2X3 (SEQ IDPage 48 of 320NAI-5001326827v1NO:220) wherein Xi is S, Y, or R, X2is N or S, and X3is K or N; and / or (2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:221) wherein Xi is D, A, or G; and / or (3) a VL CDR3 having the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:222) wherein Xi is Y or N, X2is I, D, T, or N, X3is W, A, or L, and X4 is L or V. In some embodiments, a Jagged- 1 binding agent (e.g. , antibody) described herein comprises a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFXIFX2X3YX4 (SEQ ID NO:218) wherein Xi is S or T, X2is G, S, or R, X3 is G, N, D, or S, and X4 is D or G; (2) a VH CDR2 having the amino acid sequence of ISXIX2GX3X4K (SEQ ID NO:219) wherein Xi is Y or H, X2is A, G, E, or S, X3 is R, S, or N, and X4 is N, Q, I, or Y; and (3) a VH CDR3 having the amino acid sequence of ARXIX2GX3X4X5DX6 (SEQ ID NO:235) wherein Xi is G, A, or D, X2is W or Y, X3is G or absence, X4 is Y, H, or V, X5 is S, I, F, or P, and Xe is V, Y, or H. In some embodiments, a Jagged- 1 binding agent (e.g., antibody) described herein comprises a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of QSVXIX2XS (SEQ ID NO:220) wherein Xi is S, Y, or R, X2is N or S, and X3 is K or N; (2) a VL CDR2 having the amino acid sequence of Xi AS (SEQ ID NO:221) wherein Xi is D, A, or G; and (3) a VL CDR3 having the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:222) wherein Xi is Y or N, X2is I, D, T, or N, X3is W, A, or L, and X4is L or V. In some embodiments, a Jagged-1 binding agent (e.g., antibody) described herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFXIFX2X3YX4(SEQ ID NO:218) wherein Xi is S or T, X2is G, S, or R, X3is G, N, D, or S, and X4is D or G; (2) a VH CDR2 having the amino acid sequence of ISXIX2GX3X4K (SEQ ID NO:219) wherein Xi is Y or H, X2is A, G, E, or S, X3is R, S, or N, and X4is N, Q, I, or Y; and (3) a VH CDR3 having the amino acid sequence of ARXiX2GX3X4X5DXe (SEQ ID NO:235) wherein Xi is G, A, or D, X2is W or Y, X3 is G or absence, X4 is Y, H, or V, X5 is S, I, F, or P, and Xe is V, Y, or H, and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of QSVXIX2XS (SEQ ID NO:220) wherein Xi is S, Y, or R, X2is N or S, and X3 is K or N;(2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:221) wherein Xi is D, A, or G; and (3) a VL CDR3 having the amino acid sequence of QQYXIX2XSPX4T (SEQ ID NO:222) wherein Xi is Y or N, X2is I, D, T, or N, X3 is W, A, or L, and X4 is L or V. In some embodiments, the VH CDR1 of a Jagged- 1 binding agent described herein has the amino acid sequence of GFXIFX2X3YX4 (SEQ ID NO:218) wherein Xi is S or T, X2is G, S, or R, X3 is G, N, D, or S, and X4 is D or G. In some embodiments, the VH CDR2 of a Jagged- 1 binding agent described herein has the amino acid sequence of a VH CDR2 having the amino acid sequence of ISXIX2GX3X4K (SEQ ID NO:219) wherein Xi is Y or H, X2is A, G, E, or S, X3 is R, S, or N, and X4 is N, Q, I, or Y. In some embodiments, the VH CDR3 of a Jagged- 1 binding agent described herein has the amino acid sequence of ARXIX2GX3X4X5DX6(SEQ ID NO:235) wherein Xi is G, A, or D, X2is W or Y, X3is G or absence, X4is Y, H, or V, X5is S, I, F, or P, and X6is V, Y, or H. In some embodiments, the VL CDR1 of a Jagged- 1 binding agent described herein has the amino acid sequence of QSVXIX2X3Page 49 of 320NAI-5001326827v1(SEQ ID NO:220) wherein Xi is S, Y, or R, X2is N or S, and X3is K or N. In some embodiments, the VL CDR2 of a Jagged- 1 binding agent described herein has the amino acid sequence of XiAS (SEQ ID NO:221) wherein Xi is D, A, or G. In some embodiments, the VL CDR3 of Jagged- 1 binding agent described herein has the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:222) wherein Xi is Xi is Y or N, X2is I, D, T, or N, X3is W, A, or L, and X4 is L or V.

[0130] Consensus sequences of CDRs of Jagged- 1 binding agents, including an agent that binds to human Jagged- 1, are shown in FIGS. 20A and 20B. In some embodiments, a Jagged- 1 binding agent (e.g., antibody) described herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFXiFRDYG (SEQ ID NO:236) wherein Xi is a naturally occurring amino acid; and / or (2) a VH CDR2 having the amino acid sequence of ISXIEX2SIK (SEQ ID NO:237) wherein Xi and X2are each independently a naturally occurring amino acid; and / or (3) a VH CDR3 having the amino acid sequence of ARDWGYFDXi (SEQ ID NO:238) wherein Xi is a naturally occurring amino acid, and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of XISVRX2X3(SEQ ID NO:239) wherein Xi, X2, and X3are each independently a naturally occurring amino acid; and / or (2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:240) wherein Xi is a naturally occurring amino acid; and / or (3) a VL CDR3 having the amino acid sequence of QQYXIX2X3PX4T (SEQ ID NO:241) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid. In some embodiments, a Jagged-1 binding agent (e.g., antibody) described herein comprises a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFXiFRDYG (SEQ ID NO:236) wherein Xi is a naturally occurring amino acid; (2) a VH CDR2 having the amino acid sequence of ISXIEX2SIK (SEQ ID NO:237) wherein Xi and X2are each independently a naturally occurring amino acid; and (3) a VH CDR3 having the amino acid sequence of ARDWGYFDXi (SEQ ID NO:238) wherein Xi is a naturally occurring amino acid. In some embodiments, a Jagged- 1 binding agent (e.g., antibody) described herein comprises a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of XISVRX2X3(SEQ ID NO:239) wherein Xi, X2, and X3are each independently a naturally occurring amino acid; (2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:240) wherein Xi is a naturally occurring amino acid; and (3) a VL CDR3 having the amino acid sequence of QQYXIX2X3PX4T (SEQ ID NO:241) wherein Xi, X2, X3, and X4 are each independently a naturally occurring amino acid. In some embodiments, a Jagged-1 binding agent (e.g., antibody) described herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFXiFRDYG (SEQ ID NO:236) wherein Xi is a naturally occurring amino acid; (2) a VH CDR2 having the amino acid sequence of ISXIEX2SIK (SEQ ID NO:237) wherein Xi and X2are each independently a naturally occurring amino acid; and (3) a VH CDR3 having the amino acid sequence of ARDWGYFDXi (SEQ ID NO:238) wherein Xi is a naturally occurring amino acid, and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence ofPage 50 of 320NAI-5001326827v1X1SVRX2X3 (SEQ ID NO:239) wherein Xi, X2, and X3are each independently a naturally occurring amino acid; (2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:240) wherein Xi is a naturally occurring amino acid; and (3) a VL CDR3 having the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:241) wherein Xi, X2, X3, and X4 are each independently a naturally occurring amino acid. In some embodiments, the VH CDR1 of a Jagged- 1 binding agent described herein has the amino acid sequence of GFXiFRDYG (SEQ ID NO:236) wherein Xi is a naturally occurring amino acid. In some embodiments, the VH CDR2 of a Jagged- 1 binding agent described herein has the amino acid sequence of a VH CDR2 having the amino acid sequence of ISX1EX2SIK (SEQ ID NO:237) wherein Xi and X2are each independently a naturally occurring amino acid. In some embodiments, the VH CDR3 of a Jagged- 1 binding agent described herein has the amino acid sequence of ARDWGYFDXi (SEQ ID NO:238) wherein Xi is a naturally occurring amino acid. In some embodiments, the VL CDR1 of a Jagged- 1 binding agent described herein has the amino acid sequence of X1SVRX2X3 (SEQ ID NO:239) wherein Xi, X2, and X3 are each independently a naturally occurring amino acid. In some embodiments, the VL CDR2 of a Jagged- 1 binding agent described herein has the amino acid sequence of XiAS (SEQ ID NO:240) wherein Xi is a naturally occurring amino acid. In some embodiments, the VL CDR3 of Jagged- 1 binding agent described herein has the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:241) wherein Xi, X2, X3, and X4are each independently a naturally occurring amino acid. In some embodiments, a Jagged- 1 binding agent (e.g., antibody) described herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFXiFRDYG (SEQ ID NO:242) wherein Xi is T, S, or I; and / or (2) a VH CDR2 having the amino acid sequence of ISX1EX2SIK (SEQ ID NO:243) wherein Xi is H or Y and X2is G or E; and / or (3) a VH CDR3 having the amino acid sequence of ARDWGYFDXi (SEQ ID NO:244) wherein Xi is F, H, or Y, and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of X1SVRX2X3 (SEQ ID NO:245) wherein Xi is Q, L, I, H, or E, X2is N, S, or R, and X3 is N or K; and / or (2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:246) wherein Xi is G, S, D, or R; and / or (3) a VL CDR3 having the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:247) wherein Xi is D or N, X2is D, N, or E, X3 is W, L, or A, and X4 is I, L, or V. In some embodiments, a Jagged- 1 binding agent (e.g., antibody) described herein comprises a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFXiFRDYG (SEQ ID NO:242) wherein Xi is T, S, or I; (2) a VH CDR2 having the amino acid sequence of ISX1EX2SIK (SEQ ID NO:243) wherein Xi is H or Y and X2is G or E; and (3) a VH CDR3 having the amino acid sequence of ARDWGYFDXi (SEQ ID NO:244) wherein Xi is F, H, or Y. In some embodiments, a Jagged- 1 binding agent (e.g., antibody) described herein comprises a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of XISVRX2X3(SEQ ID NO:245) wherein Xi is Q, L, I, H, or E, X2is N, S, or R, and X3is N or K; (2) a VL CDR2 having the amino acid sequence of XiAS (SEQ ID NO:246) wherein Xi is G, S, D, or R; and (3) a VL CDR3 having thePage 51 of 320NAI-5001326827v1amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:247) wherein Xi is D or N, X2is D, N, or E, X3is W, L, or A, and X4is I, L, or V. In some embodiments, a Jagged-1 binding agent (e.g., antibody) described herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of GFXiFRDYG (SEQ ID NO:242) wherein Xi is T, S, or I; (2) a VH CDR2 having the amino acid sequence of ISX1EX2SIK (SEQ ID NO:243) wherein Xi is H or Y and X2is G or E; and (3) a VH CDR3 having the amino acid sequence of ARDWGYFDXi (SEQ ID NO:244) wherein Xi is F, H, or Y, and (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of X1SVRX2X3 (SEQ ID NO:245) wherein Xi is Q, L, I, H, or E, X2is N, S, or R, and X3 is N or K; (2) a VL CDR2 having the amino acid sequence of Xi AS (SEQ ID NO:246) wherein Xi is G, S, D, or R; and (3) a VL CDR3 having the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:247) wherein Xi is D or N, X2is D, N, or E, X3is W, L, or A, and X4is I, L, or V. In some embodiments, the VH CDR1 of a Jagged- 1 binding agent described herein has the amino acid sequence of GFXiFRDYG (SEQ ID NO:242) wherein Xi is T, S, or I. In some embodiments, the VH CDR2 of a Jagged- 1 binding agent described herein has the amino acid sequence of a VH CDR2 having the amino acid sequence of ISX1EX2SIK (SEQ ID NO:243) wherein Xi is H or Y and X2is G or E. In some embodiments, the VH CDR3 of a Jagged- 1 binding agent described herein has the amino acid sequence of ARDWGYFDXi (SEQ ID NO:244) wherein Xi is F, H, or Y. In some embodiments, the VL CDR1 of a Jagged- 1 binding agent described herein has the amino acid sequence of XISVRX2X3(SEQ ID NO:245) wherein Xi is Q, L, I, H, or E, X2is N, S, or R, and X3is N or K. In some embodiments, the VL CDR2 of a Jagged- 1 binding agent described herein has the amino acid sequence of XiAS (SEQ ID NO:246) wherein Xi is G, S, D, or R. In some embodiments, the VL CDR3 of Jagged- 1 binding agent described herein has the amino acid sequence of QQYX1X2X3PX4T (SEQ ID NO:247) wherein Xi is D or N, X2is D, N, or E, X3is W, L, or A, and X4is I, L, or V.

[0131] In some embodiments, Jagged- 1 binding agents (e.g., antibodies, including bispecific antibodies), including agents that bind to human Jagged- 1, provided herein comprise one or more CDRs, including six CDRs, for example, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 identified in Tables 1-18.

[0132] In some embodiments, Jagged- 1 binding agents (e.g., antibodies, including bispecific antibodies), including agents that bind to human Jagged- 1, provided herein comprise one or more CDRs, including six VH CDRs listed in Tables 1-18. In other embodiments, Jagged- 1 binding agents (e.g., antibodies, including bispecific antibodies), including agents that bind to human Jagged- 1, provided herein comprise one or more CDRs, including six CDRs, VL CDRs listed in Tables 1-18. In yet other embodiments, Jagged-1 binding agents (e.g., antibodies, including bispecific antibodies), including agents that bind to human Jagged- 1, provided herein comprise one or more CDRs, including six VH CDRs listed in Tables 1-18 and one or more CDRs, including six VL CDRs listed in Tables 1- 18.Page 52 of 320NAI-5001326827v1

[0133] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises one or more complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 1-24, 27-46, 49-71, 74-90, 93-109, 112-125, 128-143, 146-153, 156-162, 165-169, 171-174, 176-178, 180-182, 184-190, 192-194, 196-198, 200-206, and 208-210. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises two or more complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 1-24, 27-46, 49-71, 74-90, 93-109, 112-125, 128-143, 146-153, 156-162, 165-169, 171-174, 176-178, 180-182, 184-190, 192-194, 196-198, 200-206, and 208-210. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises three or more complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 1-24, 27-46, 49-71, 74-90, 93- 109, 112-125, 128-143, 146-153, 156-162, 165-169, 171-174, 176-178, 180-182, 184-190, 192-194, 196-198, 200-206, and 208-210. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises four or more complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 1-24, 27-46, 49-71, 74-90, 93-109, 112-125, 128-143, 146-153, 156-162, 165-169, 171-174, 176-178, 180-182, 184-190, 192-194, 196-198, 200-206, and 208-210. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises five or more complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 1-24, 27-46, 49-71, 74-90, 93-109, 112-125, 128- 143, 146-153, 156-162, 165-169, 171-174, 176-178, 180-182, 184-190, 192-194, 196-198, 200-206, and 208-210. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises six or more complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 1-24, 27-46, 49-71, 74-90, 93-109, 112-125, 128-143, 146-153, 156-162, 165-169, 171-174, 176-178, ISO- 182, 184-190, 192-194, 196-198, 200-206, and 208-210.

[0134] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 1, 2, 3, 7, 8, 9, 12, 13, 14, 15, 18, 19, 20, and 24. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:4, 5, 6, 10, 11, 16, 17, 21, 22, and 23. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs)Page 53 of 320NAI-5001326827v1comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 1, 2, 3, 7, 8, 9,12, 13, 14, 15, 18, 19, 20, and 24 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:4, 5, 6, 10, 11, 16, 17, 21, 22, and 23.

[0135] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 1, 7, 12, 13, and 18. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:2, 8, 14, 19, and 24. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 3, 9, 15, and 20.

[0136] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO :4, 10, 16, and 21. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:5, 11, and 22. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:6, 17, and 23.

[0137] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 1, 7, 12,13, and 18; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:2, 8, 14, 19, and 24; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:3, 9, 15, and 20; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NON, 10, 16, and 21; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:5, 11, and 22; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:6, 17, and 23.

[0138] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:2; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:3; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the aminoPage 54 of 320NAI-5001326827v1acid sequence of SEQ ID NO:4; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0139] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:7; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 8; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NOV; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 10; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 11; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:6.

[0140] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 12; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:2; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:3; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NON; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:5; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:6.

[0141] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 13; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 14; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 15; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 16; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 11; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 17.

[0142] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 18; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 19; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:20; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:21; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:22; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:23.

[0143] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1 ; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:24; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NON; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NON; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NON; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NON.Page 55 of 320NAI-5001326827v1

[0144] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 1, 7, 12, 13, and 18; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:2, 8, 14, 19, and 24; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:3, 9, 15, and 20; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NON, 10, 16, and 21; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:5, 11, and 22; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:6, 17, and 23.

[0145] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 1; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:2; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NON; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NON; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NON. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 1; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NON; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NON; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NON; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NON.

[0146] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NON; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:9; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 10; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 11; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NON. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NON; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:9; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ IDPage 56 of 320NAI-5001326827v1NO: 10; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 11; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6.

[0147] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 12; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:2; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:3; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:5; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 12; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:2; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:3; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NON; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NON.

[0148] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 13; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 14; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 15; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 16; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 11; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 17. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 13; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 14; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 15; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 16; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 11; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 17.

[0149] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 18; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 19; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:20; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:21; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:22; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:23. In somePage 57 of 320NAI-5001326827v1embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 18; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 19; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:20; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:21; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:22; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:23.

[0150] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 1; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:24; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:3; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:5; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 1; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:24; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NON; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NON; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NON.

[0151] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO:25 and / or a VL comprising an amino acid sequence of SEQ ID NO:26. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO:25 and a VL comprising an amino acid sequence of SEQ ID NO:26.

[0152] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:27, 28, 29, 32, 33, 34, 36, 37, 38, 39, 41, 42, 43, and 46. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:4, 10, 16, 21, 30, 31, 35, 40, 44, and 45. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs)Page 58 of 320NAI-5001326827v1comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:27, 28, 29, 32, 33, 34, 36, 37, 38, 39, 41, 42, 43, and 46 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:4, 10, 16, 21, 30, 31, 35, 40, 44, and 45.

[0153] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:27, 32, 36, 37, and 41. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:28, 33, 38, 42, and 46. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:29, 34, 39, and 43.

[0154] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO :4, 10, 16, and 21. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:31, 40, and 45.

[0155] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:27, 32, 36, 37, and 41; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:28, 33, 38, 42, and 46; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:29, 34, 39, and 43; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NON, 10, 16, and 21; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:31, 40, and 45.

[0156] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and / or (3) a VH CDR3 having the amino acid sequence of SEQ IDPage 59 of 320NAI-5001326827v1NO:29; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:4; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:31.

[0157] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:32; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:33; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:34; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 10; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:31.

[0158] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:36; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:28; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NON; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NON 1.

[0159] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:37; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:38; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:39; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 16; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:40.

[0160] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:41; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:42; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:43; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:21; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:44; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:45.

[0161] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:46; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:29; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the aminoPage 60 of 320NAI-5001326827v1acid sequence of SEQ ID NO:4; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:31.

[0162] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:27, 32, 36, 37, and 41; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:28, 33, 38, 42, and 46; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:29, 34, 39, and 43; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:4, 10, 16, and 21; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:31, 40, and 45.

[0163] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:27; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:28; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:29; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:4; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:31. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:27; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:28; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:29; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:4; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:31.

[0164] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:32; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:33; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:34; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 10; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:31. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:32; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:33; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:34; and (b) aPage 61 of 320NAI-5001326827v1light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 10; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:31.

[0165] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:36; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:28; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:29; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NON 1. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:36; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:28; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:29; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NON; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NON 1.

[0166] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:37; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:38; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:39; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 16; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:40. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:37; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:38; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:39; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 16; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:40.

[0167] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:41; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:42; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:43; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:21; (ii) a VL CDR2 comprising an amino acid sequence of SEQPage 62 of 320NAI-5001326827v1ID NO:44; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:45. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:41; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:42; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:43; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:21; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:44; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:45.

[0168] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:27; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:46; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:29; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:4; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:31. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:27; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:46; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:29; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:4; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:31.

[0169] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO:47 and / or a VL comprising an amino acid sequence of SEQ ID NO:48. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO:47 and a VL comprising an amino acid sequence of SEQ ID NO: 48.

[0170] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:49, 50, 51, 55, 56, 57, 60, 61, 62, 63, 66, 67, 71, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:52, 53, 54, 58, 59, 64, 65, 68, 69, and 70. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chainPage 63 of 320NAI-5001326827v1variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:49, 50, 51, 55, 56, 57, 60, 61, 62, 63, 66, 67, 71, and 165 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:52, 53, 54, 58, 59, 64, 65, 68, 69, and 70.

[0171] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:49, 55, 60, 61, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and67.

[0172] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and68. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:54, 65, and 70.

[0173] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:49, 55, 60, 61, and 165; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and 67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:54, 65, and 70.

[0174] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:49; and / or (2) a VH CDR2 having the aminoPage 64 of 320NAI-5001326827v1acid sequence of SEQ ID NO:50; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:54.

[0175] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:55; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:56; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:57; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:58; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:54.

[0176] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:60; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:50; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:54.

[0177] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:61; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:62; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:64; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:65.

[0178] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 165; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:66; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:70.

[0179] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:49; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:71; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the aminoPage 65 of 320NAI-5001326827v1acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:54.

[0180] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:49, 55, 60, 61, and 165; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and 67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:54, 65, and 70.

[0181] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:49; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:49; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54.

[0182] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:55; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:56; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:57; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:55; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:56; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:57; and (b) aPage 66 of 320NAI-5001326827v1light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54.

[0183] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54.

[0184] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:61; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:62; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:65. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:61; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:62; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:65.

[0185] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:66; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQPage 67 of 320NAI-5001326827v1ID NO:69; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:70. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:66; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:69; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:70.

[0186] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:49; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:49; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54.

[0187] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO:72 and / or a VL comprising an amino acid sequence of SEQ ID NO:73. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO:72 and a VL comprising an amino acid sequence of SEQ ID NO: 73.

[0188] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:74, 75, 76, 78, 79, 80, 81, 82, 83, 84, 86, 87, 88, and 90. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:52, 53, 58, 59, 64, 68, 69, 77, 85, and 89. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chainPage 68 of 320NAI-5001326827v1variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:74, 75, 76, 78, 79, 80, 81, 82, 83, 84, 86, 87, 88, and 90 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:52, 53, 58, 59, 64, 68, 69, 77, 85, and 89.

[0189] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:74, 78, 81, 82, and 86. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:75, 79, 83, 87, and 90. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:76, 80, 84, and 88.

[0190] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:77, 85, and 89.

[0191] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:74, 78, 81, 82, and 86; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:75, 79, 83, 87, and 90; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:76, 80, 84, and 88; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:77, 85, and 89.

[0192] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including abispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:74; and / or (2) a VH CDR2 having the aminoPage 69 of 320NAI-5001326827v1acid sequence of SEQ ID NO:75; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:76; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:77.

[0193] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:78; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:79; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:80; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:58; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:77.

[0194] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:81; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:75; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:76; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:77.

[0195] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 82; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:83; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:84; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:64; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:85.

[0196] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 86; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:87; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:88; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:89.

[0197] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:74; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NOVO; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:76; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the aminoPage 70 of 320NAI-5001326827v1acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:77.

[0198] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:74, 78, 81, 82, and 86; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:75, 79, 83, 87, and 90; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:76, 80, 84, and 88; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:77, 85, and 89.

[0199] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:74; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:75; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:76; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:77. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:74; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:75; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:76; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:77.

[0200] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:78; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:79; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 80; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:77. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:78; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:79; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:80; and (b) aPage 71 of 320NAI-5001326827v1light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:77.

[0201] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:81; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:75; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:76; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:77. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:81; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:75; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:76; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:77.

[0202] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 82; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 83; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 84; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:85. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 82; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:83; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:84; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 85.

[0203] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 86; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 87; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 88; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQPage 72 of 320NAI-5001326827v1ID NO:69; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:89. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 86; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:87; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:88; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:69; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 89.

[0204] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:74; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NOVO; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:76; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:77. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:74; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NOVO; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:76; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:77.

[0205] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO:91 and / or a VL comprising an amino acid sequence of SEQ ID NO:92. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO:91 and a VL comprising an amino acid sequence of SEQ ID NO: 92.

[0206] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:39, 93, 94, 95, 97, 98, 99, 101, 102, 103, 105, 106, 107, and 109. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:6, 17, 23, 53, 59, 69, 96, 100, 104, and 108. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided hereinPage 73 of 320NAI-5001326827v1comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:39, 93, 94, 95, 97, 98, 99, 101, 102, 103, 105, 106, 107, and 109 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:6, 17, 23, 53, 59, 69, 96, 100, 104, and 108.

[0207] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 93, 97, 101, 102, and 105. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:94, 98, 103, 106, and 109. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:39, 95, 99, and107.

[0208] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:96, 100, 104, and108. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:6, 17, and 23.

[0209] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:93, 97, 101, 102, and 105; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:94, 98, 103, 106, and 109; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:39, 95, 99, and 107; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:96, 100, 104, and 108; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:6, 17, and 23.Page 74 of 320NAI-5001326827v1

[0210] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:93; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:94; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:95; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:96; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:6.

[0211] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:97; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:98; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:99; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 100; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:6.

[0212] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 101; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:94; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:95; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:96; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:6.

[0213] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 102; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 103; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:39; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 104; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:59; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 17.

[0214] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 105; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 106; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 107; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 108; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:69; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:23.

[0215] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VHPage 75 of 320NAI-5001326827v1CDR1 having the amino acid sequence of SEQ ID NO:93; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 109; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:95; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:96; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:53; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:6.

[0216] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:93, 97, 101, 102, and 105; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:94, 98, 103, 106, and 109; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:39, 95, 99, and 107; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:96, 100, 104, and 108; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:53, 59, and 69; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:6, 17, and 23.

[0217] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:93; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:94; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:95; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:96; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:93; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:94; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:95; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:96; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6.

[0218] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:97; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:98; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:99; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 100; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) providedPage 76 of 320NAI-5001326827v1herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:97; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:98; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:99; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 100; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 6.

[0219] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 101; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:94; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:95; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:96; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 101; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:94; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:95; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:96; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6.

[0220] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 102; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 103; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:39; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 104; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 17. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 102; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 103; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:39; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 104; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:59; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 17.

[0221] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 105; (ii) a VH CDR2 comprising an aminoPage 77 of 320NAI-5001326827v1acid sequence of SEQ ID NO: 106; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 107; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 108; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:69; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:23. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 105; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 106; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 107; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 108; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:69; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 23.

[0222] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:93; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 109; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:95; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:96; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:93; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 109; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:95; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:96; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:53; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:6.

[0223] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 110 and / or a VL comprising an amino acid sequence of SEQ ID NO: 111. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 110 and a VL comprising an amino acid sequence of SEQ ID NO: 111.

[0224] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:27, 32, 36, 37, 41, 112, 113, 116, 117, 118, 119, 121, 122, and 125. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VLPage 78 of 320NAI-5001326827v1complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 11, 52, 58, 64, 68, 114, 115, 120, 123, and 124. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:27, 32, 36, 37, 41, 112, 113, 116, 117, 118, 119, 121, 122, and 125 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS: 11, 52, 58, 64, 68, 114, 115, 120, 123, and 124.

[0225] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:27, 32, 36, 37, and 41. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 112, 116, 118, 121, and 125. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 113, 117, 119, and 122.

[0226] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 11, 114, and 123. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 115, 120, and 124.

[0227] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:27, 32, 36, 37, and 41; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 112, 116, 118, 121, and 125; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 113, 117, 119, and 122; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 11, 114, and 123;Page 79 of 320NAI-5001326827v1and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 115, 120, and 124.

[0228] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 112; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 113; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 114; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 115.

[0229] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:32; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 116; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 117; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:58; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 11; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 115.

[0230] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:36; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 112; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 113; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 114; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 115.

[0231] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:37; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 118; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 119; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:64; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 11; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 120.

[0232] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:41; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 121; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 122; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 123; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 124.Page 80 of 320NAI-5001326827v1

[0233] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:27; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 125; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 113; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 114; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 115.

[0234] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:27, 32, 36, 37, and 41; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 112, 116, 118, 121, and 125; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 113, 117, 119, and 122; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 11, 114, and 123; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 115, 120, and 124.

[0235] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:27; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 112; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 113; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 114; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:27; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 112; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 113; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 114; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 115.

[0236] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:32; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 116; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 117; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising anPage 81 of 320NAI-5001326827v1amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 11; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:32; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 116; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 117; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 11; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 115.

[0237] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:36; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 112; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 113; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 114; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:36; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 112; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 113; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 114; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 115.

[0238] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:37; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 118; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 119; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 11; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 120. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:37; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 118; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 119; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 11; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 120.Page 82 of 320NAI-5001326827v1

[0239] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:41; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 121; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 122; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 123; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 124. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:41; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 121; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 122; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 123; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 124.

[0240] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:27; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 125; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 113; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 114; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 115. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:27; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 125; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 113; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 114; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 115.

[0241] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 126 and / or a VL comprising an amino acid sequence of SEQ ID NO: 127. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 126 and a VL comprising an amino acid sequence of SEQ ID NO: 127.

[0242] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from aPage 83 of 320NAI-5001326827v1group consisting of SEQ ID NOS:60, 63, 67, 128, 129, 130, 133, 134, 135, 137, 138, 141, 143, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:30, 35, 44, 68, 131, 132, 136, 139, 140, and 142. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:60, 63, 67, 128, 129, 130, 133, 134, 135, 137, 138, 141, 143, and 165 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:30, 35, 44, 68, 131, 132, 136, 139, 140, and 142.

[0243] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 128, 133,137, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 129, 134,138, 141, and 143. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:63, 67, 130, and 135.

[0244] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:68, 131, 136, and139, In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 132, 140, and 142.

[0245] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 128, 133, 137, and 165; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 129, 134, 138, 141, and 143; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:63, 67, 130, and 135; and / or (b) a lightPage 84 of 320NAI-5001326827v1chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:68, 131, 136, and 139; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 132, 140, and 142.

[0246] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 128; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 129; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 130; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 131; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 132.

[0247] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 133; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 134; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 135; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 136; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 132.

[0248] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:60; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 129; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 130; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 131; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 132.

[0249] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 137; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 138; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 139; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 140.

[0250] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 165; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 141; and / or (3) a VH CDR3 having the amino acid sequence of SEQ IDPage 85 of 320NAI-5001326827v1NO:67; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:44; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 142.

[0251] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 128; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 143; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 130; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 131; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 132.

[0252] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 128, 133, 137, and 165; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 129, 134, 138, 141, and 143; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:63, 67, 130, and 135; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:68, 131, 136, and 139; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 132, 140, and 142.

[0253] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 128; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 129; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 130; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 131; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 132. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 128; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 129; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 130; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 131; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 132.

[0254] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VHPage 86 of 320NAI-5001326827v1CDR1 comprising an amino acid sequence of SEQ ID NO: 133; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 134; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 135; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 136; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 132. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 133; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 134; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 135; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 136; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 132.

[0255] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 129; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 130; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 131; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 132. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 129; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 130; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 131; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 132.

[0256] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 137; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 138; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 139; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 140. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 137; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 138; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and (b) aPage 87 of 320NAI-5001326827v1light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 139; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 140.

[0257] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 141; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:44; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 142. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 141; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:44; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 142.

[0258] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 128; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 143; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 130; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 131; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 132. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 128; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 143; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 130; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 131; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 132.

[0259] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 144 and / or a VL comprising an amino acid sequence of SEQ ID NO: 145. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 144 and a VL comprising an amino acid sequence of SEQ ID NO: 145.Page 88 of 320NAI-5001326827v1

[0260] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:50, 51, 56, 57, 60, 62, 63, 66, 67, 71, 146, 149, 151, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:52, 58, 64, 68, 147, 148, 150, 152, 153, and 166. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:50, 51, 56, 57, 60, 62, 63, 66, 67, 71, 146, 149, 151, and 165 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:52, 58, 64, 68, 147, 148, 150,152, 153, and 166.

[0261] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 60, 146, 149, 151, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56,62, 66, and 71. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57,63, and 67.

[0262] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 147, 150, and 166. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 148, 152, and153.

[0263] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VHPage 89 of 320NAI-5001326827v1CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 146, 149, 151, and 165; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and 67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 147, 150, and 166; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 148, 152, and 153.

[0264] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 146; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:50; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 147; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 148.

[0265] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 149; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:56; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:57; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:58; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 150; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 148.

[0266] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:60; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:50; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 147; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 148.

[0267] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 151; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:62; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:64; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 150; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 152.Page 90 of 320NAI-5001326827v1

[0268] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 165; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:66; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 166; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 153.

[0269] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 146; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:71; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO: 147; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 148.

[0270] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 146, 149, 151, and 165; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and 67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 147, 150, and 166; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 148, 152, and 153.

[0271] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 147; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 148. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence ofPage 91 of 320NAI-5001326827v1SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 147; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 148.

[0272] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 149; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:56; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:57; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 150; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 148. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 149; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:56; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:57; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 150; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 148.

[0273] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 147; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 148. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 147; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 148.

[0274] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 151; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:62; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 150; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 152. In somePage 92 of 320NAI-5001326827v1embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 151; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:62; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 150; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 152.

[0275] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:66; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 166; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 153. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:66; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 166; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 153.

[0276] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 147; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 148. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO: 147; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 148.

[0277] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 154Page 93 of 320NAI-5001326827v1and / or a VL comprising an amino acid sequence of SEQ ID NO: 155. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 154 and a VL comprising an amino acid sequence of SEQ ID NO: 155.

[0278] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:60, 63, 67, 146, 149, 151, 156, 157, 158, 159, 160, 161, 162, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:30, 35, 44, 52, 54, 58, 64, 65, 68, and 70. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:60, 63, 67, 146, 149, 151, 156, 157, 158, 159, 160, 161, 162, and 165 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:30, 35, 44, 52, 54, 58, 64, 65, 68, and 70.

[0279] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 60, 146, 149, 151, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 156, 158, 160, 161, and 162. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:63, 67, 157, and 159.

[0280] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody)Page 94 of 320NAI-5001326827v1provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:54, 65, and 70.

[0281] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 146, 149, 151, and 165; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 156, 158, 160, 161, and 162; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:63, 67, 157, and 159; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:54, 65, and 70.

[0282] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 146; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 156; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 157; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:54.

[0283] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 149; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 158; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 159; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:58; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:54.

[0284] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:60; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 156; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 157; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:54.

[0285] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 151; and / or (2) a VH CDR2 having the aminoPage 95 of 320NAI-5001326827v1acid sequence of SEQ ID NO: 160; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:64; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:65.

[0286] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 165; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 161; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:44; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:70.

[0287] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 146; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO: 162; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO: 157; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO:54.

[0288] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 146, 149, 151, and 165; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 156, 158, 160, 161, and 162; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:63, 67, 157, and 159; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:54, 65, and 70.

[0289] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 156; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 157; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising anPage 96 of 320NAI-5001326827v1amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 156; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 157; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54.

[0290] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 149; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 158; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 159; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 149; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 158; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 159; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54.

[0291] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 156; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 157; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 156; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 157; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54.

[0292] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 151; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 160; and (iii) a VH CDR3 comprising an amino acid sequence of SEQPage 97 of 320NAI-5001326827v1ID NO:63; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:65. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 151; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 160; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:65.

[0293] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 161; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:44; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:70. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 161; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:44; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:70.

[0294] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 162; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 157; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO: 162; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO: 157; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence ofPage 98 of 320NAI-5001326827v1SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:54.

[0295] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 163 and / or a VL comprising an amino acid sequence of SEQ ID NO: 164. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 163 and a VL comprising an amino acid sequence of SEQ ID NO: 164.

[0296] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:50, 51, 56, 57, 60, 62, 63, 66, 67, 71, 146, 149, 151, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:30, 35, 44, 52, 58, 64, 68, 167, 168, and 169. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:50, 51, 56, 57, 60, 62, 63, 66, 67, 71, 146, 149, 151, and 165 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:30, 35, 44, 52, 58, 64, 68, 167, 168, and 169.

[0297] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 60, 146, 149, 151, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56,62, 66, and 71. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57,63, and 67.

[0298] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68. In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecificPage 99 of 320NAI-5001326827v1antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 167, 168, and 169.

[0299] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 146, 149, 151, and 165; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and 67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 167, 168, and 169.

[0300] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 146; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:50; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 167.

[0301] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 149; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:56; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:57; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:58; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 167.

[0302] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:60; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:50; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 167.Page 100 of 320NAI-5001326827v1

[0303] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 151; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:62; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:64; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 168.

[0304] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 165; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:66; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:68; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:44; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 169.

[0305] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 146; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:71; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO:52; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 167.

[0306] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 146, 149, 151, and 165; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and 67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:52, 58, 64, and 68; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 167, 168, and 169.

[0307] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising anPage 101 of 320NAI-5001326827v1amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167.

[0308] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 149; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:56; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:57; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 149; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:56; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:57; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:58; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167.

[0309] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167.Page 102 of 320NAI-5001326827v1

[0310] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 151; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:62; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 168. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 151; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:62; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:63; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:64; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 168.

[0311] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:66; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:44; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 169. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 165; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:66; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:67; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:68; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:44; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 169.

[0312] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising anPage 103 of 320NAI-5001326827v1amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:71; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:52; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167.

[0313] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 154 and / or a VL comprising an amino acid sequence of SEQ ID NO: 170. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH comprising an amino acid sequence of SEQ ID NO: 154 and a VL comprising an amino acid sequence of SEQ ID NO: 170.

[0314] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:50, 51, 56, 57, 60, 62, 63, 66, 67, 71, 146, 149, 151, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:30, 35, 44, 167, 168, 169, 171, 172, 173, and 174. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a heavy chain variable (VH) region comprising one or more VH complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:50, 51, 56, 57, 60, 62, 63, 66, 67, 71, 146, 149, 151, and 165 and a light chain variable (VL) region comprising one or more VL complementarity determining regions (CDRs) comprising an amino acid sequence selected from a group consisting of SEQ ID NOS:30, 35, 44, 167, 168, 169, 171, 172, 173, and 174.

[0315] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 1 (VH CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 60, 146, 149, 151, and 165. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 2 (VH CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56,62, 66, and 71. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VH complementarity determining region 3 (VH CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57,63, and 67.Page 104 of 320NAI-5001326827v1

[0316] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 1 (VL CDR1) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 171, 172, 173, and 174. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 2 (VL CDR2) comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises a VL complementarity determining region 3 (VL CDR3) comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 167, 168, and 169.

[0317] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 146, 149, 151, and 165; and / or (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71; and / or (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and 67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 171, 172, 173, and 174; and / or (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and / or (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 167, 168, and 169.

[0318] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 146; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:50; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 171; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 167.

[0319] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 149; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:56; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:57; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 172; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 167.

[0320] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO:60; and / or (2) a VH CDR2 having the aminoPage 105 of 320NAI-5001326827v1acid sequence of SEQ ID NO:50; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 171; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 167.

[0321] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 151; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:62; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:63; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 173; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:35; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 168.

[0322] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 165; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:66; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:67; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 174; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:44; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 169.

[0323] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 146; and / or (2) a VH CDR2 having the amino acid sequence of SEQ ID NO:71; and / or (3) a VH CDR3 having the amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 171; and / or (2) a VL CDR2 having the amino acid sequence of SEQ ID NO:30; and / or (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 167.

[0324] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:60, 146, 149, 151, and 165; (ii) a VH CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:50, 56, 62, 66, and 71; and (iii) a VH CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:51, 57, 63, and 67; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 171, 172, 173, and 174; (ii) a VL CDR2 comprising an amino acid sequence selected from a group consisting of SEQ ID NO:30, 35, and 44; and (iii) a VL CDR3 comprising an amino acid sequence selected from a group consisting of SEQ ID NO: 167, 168, and 169.Page 106 of 320NAI-5001326827v1

[0325] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 171; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 146; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 171; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167.

[0326] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 149; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:56; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:57; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 172; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO: 149; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:56; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:57; and (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 172; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:35; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167.

[0327] In some embodiments, the Jagged-1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:60; (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:50; and (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:51; and / or (b) a light chain variable (VL) region comprising (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO: 171; (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:30; and (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO: 167. In some embodiments, the Jagged- 1 binding agent (e.g., an antibody, including a bispecific antibody) provided herein comprises (a) a heavy chain variable (VH) region comprising (i) a VH CDR1 comprising anPage 107 of 320NAI-5001326827v1amino acid sequence of ...

Claims

WHAT IS CLAIMED IS:

1. An antibody or fragment thereof that binds to Jagged- 1 , wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in Tables 1-18; or(b) a light chain variable (VL) region comprising a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in Tables 1-18.

2. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in Tables 1-18; and(b) a light chain variable (VL) region comprising a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in Tables 1-18.

3. The antibody or fragment thereof of claim 1, wherein the antibody comprises a heavy chain variable (VH) region comprising a VH CDR1, a VH CDR2, and a VH CDR3 amino acid sequence as set forth in Tables 1-18.

4. The antibody or fragment thereof of claim 1, wherein the antibody comprises a light chain variable (VL) region comprising a VL CDR1, a VL CDR2, and a VL CDR3 amino acid sequence as set forth in Tables 1-18.

5. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 7, 12, 13, and 18;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:2, 8, 14, 19 and 24; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:3, 9, 15 and 20; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:4, 10, 16 and 21;Page 308 of 320NAI-5001326827v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 5, 11, and 22; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 6, 17, and 23.

6. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:27, 32, 36, 37, and 41;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:28, 33, 38, 42, and 46; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:29, 34, 39, and 43; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:4, 10, 16, and 21;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:31, 40, and 45.

7. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:49, 55, 60, 61, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 59, and 69; andPage 309 of 320NAI-5001326827v1(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:54, 65, and 70.

8. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:74, 78, 81, 82, and 86;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:75, 79, 83, 87, and 90; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:76, 80, 84, and 88; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 59, and 69; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:77, 85, and 89.

9. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:93, 97, 101, 102, and 105;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:94, 98, 103, 106, and 109; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:39, 95, 99, and 107; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:96, 100, 104, and 108;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 59, and 69; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 6, 17, and 23.Page 310 of 320NAI-5001326827v110. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:27, 32, 36, 37, and 41;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 112, 116, 118, 121, and 125; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 113, 117, 119, and 122; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 11, 114, and 123; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 115, 120, and 124.

11. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 128, 133, 137, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 129, 134, 138, 141, and 143; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 130, and 135; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:68, 131, 136, and 139;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 132, 140, and 142.

12. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:Page 311 of 320NAI-5001326827v1(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 147, 150, and 166; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 148, 152, and 153.

13. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 156, 158, 160, 161, and 162; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 157, and 159; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:54, 65, and 70.

14. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;Page 312 of 320NAI-5001326827v1(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

15. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 171, 172, 173, and 174;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

16. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; andPage 313 of 320NAI-5001326827v1(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 176, 177, and 178; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

17. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:68, 180, 181, and 182;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

18. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; andPage 314 of 320NAI-5001326827v1(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 184, 186, 187, and 189;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 59, and 69; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 185, 188, and 190.

19. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:50, 56, 62, 66, and 71; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51, 57, 63, and 67; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:68, 192, 193, and 194;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 167, 168, and 169.

20. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 156, 158, 160, 161, and 162; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 157, and 159; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 58, 64, and 68;Page 315 of 320NAI-5001326827v1(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 196, 197, and 198.

21. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 156, 158, 160, 161, and 162; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 157, and 159; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:200, 202, 203, and 205;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; and(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:201, 204, and 206.

22. The antibody or fragment thereof of claim 1, wherein the antibody comprises:(a) a heavy chain variable (VH) region comprising:(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:60, 146, 149, 151, and 165;(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 156, 158, 160, 161, and 162; and(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:63, 67, 157, and 159; and(b) a light chain variable (VL) region comprising:(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:68, 208, 209, and 210;(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:30, 35, and 44; andPage 316 of 320NAI-5001326827v1(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:201, 204, and 206.

23. The antibody or fragment thereof of any one of claims 5-22, wherein the VH region or VL region further comprises human framework sequences.

24. The antibody or fragment thereof of claim 23, wherein the VH region and VL region further comprises human framework sequences.

25. The antibody or fragment thereof of any one of claims 5-22, wherein the VH region or VL region further comprises a framework 1 (LR1), a framework 2 (LR2), a framework 3 (LR3) and / or a framework 4 (LR4) sequence.

26. The antibody or fragment thereof of claim 25, wherein the VH region and VL region further comprises a framework 1 (LR1), a framework 2 (LR2), a framework 3 (LR3) and a framework 4 (LR4) sequence.

27. The antibody or fragment thereof of any one of claims 1-26, wherein the antibody is a monoclonal antibody.

28. The antibody or fragment thereof of claim 27, wherein the monoclonal antibody is a humanized, human or chimeric antibody.

29. The antibody or fragment thereof of any one of claims 1-28, which is a Lab, Lab’, P(ab’)2, Fv, scFv, (scFv)2, single chain antibody molecule, dual variable region antibody, single variable region antibody, linear antibody, V region, or a multispecific antibody formed from antibody fragments.

30. The antibody or fragment thereof of any one of claims 1-29, which is conjugated or recombinantly fused to a diagnostic agent, detectable agent, effector agent, or therapeutic agent.

31. The antibody or fragment thereof of claim 30, wherein the therapeutic agent is a chemotherapeutic agent, cytotoxin, or drug.

32. A binding agent that binds to essentially the same epitope as an antibody or fragment thereof of any one of claims 1-31.Page 317 of 320NAI-5001326827v133. The binding agent of claim 32, which is an antibody or fragment thereof.

34. The binding agent of claim 33, which comprises a non-antibody protein scaffold.

35. The binding agent of claim 34, wherein the non-antibody protein scaffold comprises a fibronectin scaffold, an anticalin, an adnectin, an affibody, a DARPin, a fynomer, an affitin, an affilin, an avimer, a cysteine-rich knottin peptide, or an engineered Kunitz-type inhibitor.

36. A binding agent that competes for binding to human Jagged- 1 with an antibody or fragment thereof of any one of claims 1-31.

37. The binding agent of claim 36, wherein the binding agent is an antibody or fragment thereof.

38. One or more vectors comprising one or more polynucleotides encoding the antibody or fragment thereof of any one of claims 1-29.

39. A pharmaceutical composition that comprises the antibody or fragment thereof of any one of claims 1-31, and a pharmaceutically acceptable carrier.

40. A method for treating abnormal hematopoiesis, a blood disorder, cancer or a tumor in a subject comprising administering to the subject the antibody or fragment thereof of any one of claims 1-31 or the pharmaceutical composition of claim 39.

41. A method for alleviating one or more symptoms associated with abnormal hematopoiesis, a blood disorder, cancer or a tumor in a subject comprising administering to the subject the antibody or fragment thereof of any one of claims 1-31 or the pharmaceutical composition of claim 39.

42. A method for treating or preventing acute myeloid leukemia (AML) and / or myelodysplastic syndrome (MDS) in a subject comprising administering to the subject the antibody or fragment thereof of any one of claims 1-31 or the pharmaceutical composition of claim 39.

43. A method for treating or preventing abnormal hematopoiesis in a subject comprising administering to the subject the antibody or fragment thereof of any one of claims 1-31 or the pharmaceutical composition of claim 39.Page 318 of 320NAI-5001326827v144. A method for treating a Jagged- 1 -related disease, disorder or condition in a subject comprising administering to the subject the antibody or fragment thereof of any one of claims 1-31 or the pharmaceutical composition of claim 39.

45. The method of claim 44, wherein the Jagged- 1 -related disease, disorder or condition is AML, MDS, or abnormal hematopoiesis.

46. The method of any one of claims 40-45, wherein the subject is administered one or more therapeutic agents in combination with the antibody or fragment thereof or with the pharmaceutical composition.

47. The method of any one of claims 40-46, wherein Jagged- 1 is overexpressed by osteoblasts in said subject.

48. The method of any one of claims 40-46, wherein the subject has an elevated expression level of osteoblast Jagged- 1.

49. The method of claim 48, wherein the subject has an elevated expression level of osteoblast Jagged-1 as compared to the expression level of osteoblast Jagged-1 in a healthy subject.

50. A method for selectively treating a subject, comprising administering to the subject a Jagged- 1 binding agent, wherein the subject has been determined to have an elevated expression level of osteoblast Jagged- 1, and wherein the Jagged- 1 binding agent is the antibody or fragment thereof of any one of claims 1-31.

51. A method for selecting or identifying a subject for a treatment with a Jagged- 1 binding agent, comprising:(1) determining the expression level of Jagged-1 on osteoblasts in the subject;(2) selecting the subject that has an elevated expression level of Jagged-1.

52. The method of claim 51, wherein the method further comprises administering the Jagged-1 binding agent to the subject selected based on step (2) of claim 51.

53. The method of claim 51 or 52, wherein the Jagged-1 binding agent is the antibody or fragment thereof of any one of claims 1-31.Page 319 of 320NAI-5001326827v1

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