Anti-CD94 antibody and method of use thereof

Abstract

To provide anti- CD94 antibodies and methods of using the same.SOLUTION: Antibodies that bind to human CD94 and methods, uses, polynucleotides, vectors, host cells, and pharmaceutical compositions related thereto. In some embodiments, the antibodies are human or humanized antibodies that bind to human CD94 and do not block binding between CD94 and HLA-E. In some embodiments, the antibodies cross-react with cynomolgus CD94. In some embodiments, the antibodies do not promote intemalization of surface-expressed CD94 as well as pre-existing antibodies. In some embodiments, the antibodies promote ADCC targeting cells that express human CD94, e.g., on the surface of the cells.SELECTED DRAWING: None

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Application No. 63 / 085,932, filed on 30 September 2020, and U.S. Provisional Application No. 63 / 088,926, filed on 7 October 2020, the disclosures of each of those documents being incorporated herein by reference in their entirety.

[0002] Submission of sequence listings in ASCII text files. The contents of the following ASCII text file submission are incorporated herein by reference in their entirety: Sequence listing in computer-readable format (CRF) (filename: 186542000340SEQLIST.TXT, date: September 28, 2021, size: 52,165 bytes).

[0003] This disclosure relates to a CD94-binding antibody and its use for treating diseases and disorders associated with NK cells and / or T cells. [Background technology]

[0004] Natural killer (NK) / T-cell lymphoma and leukemia are characterized by clonal proliferation of NK cells and / or CD8+ and CD4+ T cells. NK / T-cell lymphoma accounts for a small proportion of non-Hodgkin lymphoma (NHL), with a 5-year survival rate of less than 50% (Kwong, 2012). Approximately 4,000–7,000 new cases are reported annually in the United States alone, with a higher prevalence in the Asian population (Bajaj, A. (2019) Int. J. Hemat.. Ther 5:1-7). NK / T-cell lymphoma can occur at any age, but more than half of NHL patients are over 65 years old (Bajaj, 2019). There are also NK and T-cell-based leukemias, such as LGL leukemia and invasive NK leukemia. Other examples of diseases and disorders in which NK cells play a role include LGL leukemia (e.g., T-cell LGL leukemia), chronic NK cell lymphoproliferative disorder (CLPD-NK, formerly known as NK-LGL), rheumatoid arthritis, Felty syndrome, invasive NK leukemia (e.g., invasive natural killer leukemia (ANKL) and extranodal NKL nasal type (ENKL)), IBM, and IBD.

[0005] There are 13 distinct diseases involving NK / T-cell lymphoma: extranodal NK / T-cell lymphoma, hepatosplenic T-cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL (unspecified type), angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic enteric TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, and subcutaneous panniculitis TCL (Bajaj, 2019). Mostly driven by cytotoxic cells (NK / CD8+ T cells), the major subtypes of NK / T-cell lymphoma include extranodal NK / T-cell lymphoma, hepatosplenic TCL, enteropathy-associated TCL, monomorphic epitheliotropic enteric TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, and subcutaneous panniculitis TCL. NK / T-cell lymphoma affects various organs, including the skin, gastrointestinal (GI) tract, liver, spleen, and bone marrow. Symptoms include cervical lymphadenopathy. Most NK / T-cell lymphoma subtypes are driven by Epstein-Barr virus infection.

[0006] Current treatments include chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by stem cell transplantation, but progression-free survival rates remain at only 40-50%. Current treatments under investigation include alemtuzumab, carfilzomib (proteasome inhibitor), romidepsin (HDAC inhibitor), bevacizumab, brentuximab vedotin (antibody-drug conjugate), bortezomib (proteasome inhibitor), belinostat (HDAC inhibitor), pralatrexate, vorinostat (HDAC inhibitor), and avelumab. Despite the diversity of drugs under investigation, many are used off-label, resulting in mixed outcomes.

[0007] Currently, there are no effective therapies for NK / T-cell lymphoma, and no therapies selectively targeting NK / T-cell lymphoma have been developed. Current therapies for NK / T-cell lymphoma may have off-target effects and are not entirely effective. The high mortality rate of the disease, coupled with the lack of effective treatments, highlights the need for advancements in the treatment of NK / T-cell lymphoma.

[0008] Therefore, in this field, there is a need to develop safe and effective therapies to treat diseases mediated by CD94-expressing NK cells and / or T cells, such as NK / T cell lymphoma. [Overview of the Initiative] [Means for solving the problem]

[0009] To meet these and other needs, the Disclosure provides, among other things, antibodies that specifically bind to CD94 (e.g., human CD94), methods for treating diseases or injuries associated with CD94-expressing NK cells and / or T cells, e.g., NK / T-cell lymphoma and leukemia (e.g., LGL leukemia), and methods for depleting or reducing the number of CD94-expressing NK cells and / or T cells in a subject upon administration of an antibody that specifically binds to CD94. These antibodies of the Disclosure may have one or more of the following properties: high affinity binding to human CD94 (e.g., cells expressing human CD94 on their surface), cross-reactivity with cynomolgus monkey CD94 (useful for preclinical studies), ability to bind to human CD94 without blocking the interaction between human CD94 and HLA-E, minimal internalization following binding to CD94, and / or induction of ADCC in CD94-expressing cells such as leukemia cells. These properties are considered advantageous for testing, development, and use in treating NK / T cell-based diseases such as lymphoma and leukemia. For example, although we do not wish to be constrained by theory, it is thought that targeting CD94 on NK cells with ADCC could induce cancer cells (e.g., LGL leukemia or lymphoma cells) to kill other cancer cells.

[0010] In some embodiments, human antibodies or humanized antibodies that bind to human CD94 are provided herein, and the binding of such antibodies to human CD94 does not block the binding between human CD94 and human HLA-E. In some embodiments, the antibodies bind to human CD94 expressed on the surface of cells (e.g., human natural killer (NK) cells). In some embodiments, the antibodies bind to the extracellular domain of human CD94. In some embodiments, the antibodies bind to cynomolgus monkey CD94 expressed on the surface of cells. In some embodiments, the binding of such antibodies to cells expressing human CD94 blocks less than 20% of the HLA-E binding to human CD94. In other embodiments, human antibodies or humanized antibodies that bind to both human CD94 and cynomolgus monkey CD94 (e.g., they can bind to human CD94 and cynomolgus monkey CD94 separately) are provided herein. In some embodiments, the antibodies bind to human CD94 expressed on the surface of cells (e.g., human natural killer (NK) cells). In some embodiments, the antibody binds to cynomolgus monkey CD94 expressed on the surface of cells (e.g., cynomolgus monkey NK cells, or human cells overexpressing cynomolgus monkey CD94). In some embodiments, the binding of the antibody to human CD94 does not block the binding between human CD94 and human HLA-E. In some embodiments, the reduction in surface antibody staining due to internalization, resulting from incubation of the antibody with cells expressing human CD94 on their surface at 37°C for 24 hours, is less than 50%.

[0011] In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 1, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 2, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 4, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 5, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 1, CDR-H2 containing the amino acid sequence of SEQ ID NO: 2, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 4, CDR-L2 containing the amino acid sequence of SEQ ID NO: 5, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 6. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain comprises an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain includes an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 19, and the VL domain includes an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain includes an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 19, and the VL domain includes,The antibody contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 19, and the VL domain contains the amino acid sequence of SEQ ID NO: 20. In some embodiments, the antibody contains a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 7, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 8, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 9, and the VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 10, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 11, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 7, CDR-H2 containing the amino acid sequence of SEQ ID NO: 8, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 10, CDR-L2 containing the amino acid sequence of SEQ ID NO: 11, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 21, and the VL domain comprises an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 22. In some embodiments, the VH domain comprises an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 21, and the VL domain comprises an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 22. In some embodiments, the VH domain includes an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 21, and the VL domain includes,The amino acid sequence contains at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 22. In some embodiments, the VH domain contains an amino acid sequence containing at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 21, and the VL domain contains an amino acid sequence containing at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 22. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 21, and the VL domain contains the amino acid sequence of SEQ ID NO: 22. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 13, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 14, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 16, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 17, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 13, CDR-H2 containing the amino acid sequence of SEQ ID NO: 14, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 16, CDR-L2 containing the amino acid sequence of SEQ ID NO: 17, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 18. In some embodiments, the VH domain comprises an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 23, and the VL domain comprises an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain comprises an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 23, and the VL domain comprisesThe amino acid sequence includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain includes an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 23, and the VL domain includes an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain includes an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 23, and the VL domain includes an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain includes the amino acid sequence of SEQ ID NO: 23, and the VL domain includes the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, (a) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 30, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 31, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and SEQ ID NO: (b) The VH domain comprises CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 37, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 33, and CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34.(c) The VH domain includes CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 35, (d) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 39, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 40, and the VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 35, (d) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 41, and at least 8 (e) The VH domain comprises CDR-H2 containing an amino acid sequence having 0% sequence identity, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 43, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 44, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 46, or (e) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 49,(f) The VH domain comprises a CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 51, and a CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 52, or (f) the VH domain comprises a CDR-H containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 53. 1. The VL domain comprises CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 54, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 55, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 57, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 58, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 59, wherein the VL domain comprises at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 60 (h) The VH domain comprises CDR-L1 containing an amino acid sequence having the same sequence identity, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 61, or (h) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 83, and CDR- H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 84. (i) The VH domain comprises CDR-H3 containing an amino acid sequence having at least 80% sequence identity with H2 and the amino acid sequence of SEQ ID NO: 85, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 86, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 61, or (i) the VH domain comprisesThe CDR-H1 contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 47, the CDR-H2 contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 48, and the CDR-H3 contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 62. The VL domain contains the CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 63, the CDR-L2 contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34, and the CDR-L3 contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, (a) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 88, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91, and SEQ ID NO: (b) The VH domain comprises CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of 35, or (b) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 90, and CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 91.(c) The VH domain includes CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 35, (c) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 94, and the VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 35, (d) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 95, and at least 80% with respect to the amino acid sequence of SEQ ID NO: 96 CDR-H2 contains an amino acid sequence having sequence identity, and CDR-H3 contains an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 97, wherein the VL domain contains CDR-L1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 98, CDR-L2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 99, and CDR containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 100. -Includes L3, or (e) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 114, and the VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 115,(f) The VH domain includes CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 52, or (f) the VH domain contains CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 116, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 117, and the amino acid sequence of SEQ ID NO: 118 (g) The VH domain comprises a CDR-H3 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 115, a CDR-L2 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 99, and a CDR-L3 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain comprises at least 80% of the amino acid sequence of SEQ ID NO: 101 The VL domain comprises CDR-H1 containing an amino acid sequence having % sequence identity, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 102, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 103, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 104, and CD containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 91. (h) The VH domain includes CDR-L3 containing an amino acid sequence having at least 80% sequence identity with R-L2 and the amino acid sequence of SEQ ID NO: 61, or (h) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 105, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 106, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 107, and the VL domain is(i) The VH domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 108, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 61, or (i) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 109, and at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 110 The CDR-H2 contains an amino acid sequence having % sequence identity, and the CDR-H3 contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 111, wherein the VL domain contains a CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 112, a CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 113, and a CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, where (a) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 30, CDR-H2 containing the amino acid sequence of SEQ ID NO: 31, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (b) the VH domain comprises the amino acid sequence of SEQ ID NO: 36 (c) The VL domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 37, CDR-H2 containing the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (c) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing the amino acid sequence of SEQ ID NO: 39, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises(d) The VH domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (d) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 41, CDR-H2 containing the amino acid sequence of SEQ ID NO: 42, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 44, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR containing the amino acid sequence of SEQ ID NO: 46, -Includes L3, or (e) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 49, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 51, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 52, or (f) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 53, sequence (a) The VL domain comprises CDR-H2 containing the amino acid sequence of number 54, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 55, wherein the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 57, CDR-H2 containing the amino acid sequence of SEQ ID NO: 58, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 59 (h) The VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 60, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or (h) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 83, CDR-H2 containing the amino acid sequence of SEQ ID NO: 84, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 86, and the amino acid sequence of SEQ ID NO: 34 The antibody comprises a CDR-L2 containing an amino acid sequence and a CDR-L3 containing the amino acid sequence of SEQ ID NO. 61, or (i) the VH domain comprises a CDR-H1 containing the amino acid sequence of SEQ ID NO. 47, a CDR-H2 containing the amino acid sequence of SEQ ID NO. 48, and a CDR-H3 containing the amino acid sequence of SEQ ID NO. 62, and the VL domain comprises a CDR-L1 containing the amino acid sequence of SEQ ID NO. 63, a CDR-L2 containing the amino acid sequence of SEQ ID NO. 34, and a CDR-L3 containing the amino acid sequence of SEQ ID NO. 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, (a) the VH domain comprises a CDR-H1 containing the amino acid sequence of SEQ ID NO. 87, a CDR-H2 containing the amino acid sequence of SEQ ID NO. 88, and a CDR-H3 containing the amino acid sequence of SEQ ID NO. 89, and the VL domain,(b) The VH domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (c) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 350, or (c) (d) The VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 94, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (d) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 95, CDR-H2 containing the amino acid sequence of SEQ ID NO: 96, and CDR-H (e) The VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 98, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 100, or (e) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 114, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 115, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and the amino acid sequence of SEQ ID NO: 52 (f) The VH domain includes CDR-L3 containing the sequence of SEQ ID NO: 116, CDR-H2 containing the amino acid sequence of SEQ ID NO: 117, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 118, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 115, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 56, (g) The VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 101, CDR-H2 containing the amino acid sequence of SEQ ID NO: 102,(h) The VH domain comprises CDR-H3 containing the amino acid sequence of SEQ ID NO: 103, wherein the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 104, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or (h) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 105, CDR-H2 containing the amino acid sequence of SEQ ID NO: 106, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 107, wherein the VL domain comprises CDR-H3 containing the amino acid sequence of SEQ ID NO: 108 - The VH domain comprises CDR-L1, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or (i) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 111, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 112, CDR-L2 containing the amino acid sequence of SEQ ID NO: 113, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 66, or (b) the VH domain comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 68 (c) The VH domain contains an amino acid sequence having a unique sequence identity, or (d) the VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 69, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 70, or (e) the VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 71, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 72,(f) The VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 73, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 74, or (g) The VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 75, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 76, or (g) The VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 77, and the VL domain (h) the VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 78, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 79, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 80, or (i) the VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 81, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 70; (d) the VH domain comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain comprises(e) The VH domain contains an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 72, and the VL domain contains an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 73, and the VL domain contains an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 74, (f) The VH domain contains an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 75, and the VL domain contains an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 76, (g) The VH domain contains at least (h) The VL domain contains an amino acid sequence having 90% sequence identity, wherein the VL domain contains an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 78; (h) The VH domain contains an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 79, wherein the VL domain contains an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 80; or (i) The VH domain contains an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 81, wherein the VL domain contains an amino acid sequence having at least 90% sequence identity with respect to the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, where (a) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 70; (d) the VH domain(e) The VL domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 71, and the VL domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 72, or (e) the VH domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 73, (f) The VL domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 74, or (g) the VH domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 75, and the VL domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 76, or (g) the VH domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 77, and the VL domain has at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 78. (i) The VH domain contains an amino acid sequence having 95% sequence identity with the amino acid sequence of SEQ ID NO: 79, and the VL domain contains an amino acid sequence having 95% sequence identity with the amino acid sequence of SEQ ID NO: 80, or (i) the VH domain contains an amino acid sequence having 95% sequence identity with the amino acid sequence of SEQ ID NO: 81, and the VL domain contains an amino acid sequence having 95% sequence identity with the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein (a) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 66, or (b) the VH domain comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain comprises at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 68. (c) The VH domain contains an amino acid sequence having 9% sequence identity, or (d) the VH domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 70, or (c) the VH domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 72.(e) The VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 73, and the VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 74, or (f) The VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 75, and the VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 76, or (g) The VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 77, (h) The VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 78, or (i) the VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 79, and the VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 80, or (i) the VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 81, and the VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, where (a) the VH domain comprises the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises the amino acid sequence of SEQ ID NO: 66, (b) the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68, (c) the VH domain comprises the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises the amino acid sequence of SEQ ID NO: 70, (d) the V (e) The H domain contains the amino acid sequence of SEQ ID NO: 71 and the VL domain contains the amino acid sequence of SEQ ID NO: 72; (f) The VH domain contains the amino acid sequence of SEQ ID NO: 73 and the VL domain contains the amino acid sequence of SEQ ID NO: 74; (g) The VH domain contains the amino acid sequence of SEQ ID NO: 75 and the VL domain contains the amino acid sequence of SEQ ID NO: 76; (g) The VH domain contains the amino acid sequence of SEQ ID NO: 77 and the VL domain contains the amino acid sequence of SEQ ID NO: 78.(h) The VH domain contains the amino acid sequence of SEQ ID NO: 79 and the VL domain contains the amino acid sequence of SEQ ID NO: 80, or (i) the VH domain contains the amino acid sequence of SEQ ID NO: 81 and the VL domain contains the amino acid sequence of SEQ ID NO: 82.

[0012] In some embodiments, antibodies that bind to human CD94 are provided herein. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 1, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 2, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 4, CDR-L2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 5, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 1, CDR-H2 containing the amino acid sequence of SEQ ID NO: 2, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 3, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 4, CDR-L2 containing the amino acid sequence of SEQ ID NO: 5, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 6. In some embodiments, the VH domain includes an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 19, and the VL domain includes an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the VH domain includes the amino acid sequence of SEQ ID NO: 19, and the VL domain includes the amino acid sequence of SEQ ID NO: 20.In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 7, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 8, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 10, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 11, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 7, CDR-H2 containing the amino acid sequence of SEQ ID NO: 8, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 9, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 10, CDR-L2 containing the amino acid sequence of SEQ ID NO: 11, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 12. In some embodiments, the VH domain includes an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 21, and the VL domain includes an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 22. In some embodiments, the VH domain includes the amino acid sequence of SEQ ID NO: 21, and the VL domain includes the amino acid sequence of SEQ ID NO: 22.In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 13, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 14, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 16, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 17, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 13, CDR-H2 containing the amino acid sequence of SEQ ID NO: 14, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 15; the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 16, CDR-L2 containing the amino acid sequence of SEQ ID NO: 17, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 18. In some embodiments, the VH domain includes an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 23, and the VL domain includes an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VH domain includes the amino acid sequence of SEQ ID NO: 23, and the VL domain includes the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody is a human antibody.

[0013] In some embodiments, antibodies that bind to human CD94 are provided herein. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, where (a) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 30, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 31, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35, or (b) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 36, and at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 37 (c) The VH domain comprises CDR-H2 containing an amino acid sequence having uniformity, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 38, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 35, or (c) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 39, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 40, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with respect to the amino acid sequence of SEQ ID NO: 33,(d) The VH domain includes CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 35, or (d) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 41, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 42, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 43, and the VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 44, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 46, or (e) the VH domain has at least 8 (f) The VL domain comprises CDR-H1 containing an amino acid sequence having 0% sequence identity, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 49, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 51, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 52, or (f) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 53, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 54, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 55,(g) The VH domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 57, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 58, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 59, and the VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 60, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34, and having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 61. (h) The VH domain includes CDR-L3 containing an amino acid sequence, (i) the VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 83, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 84, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 85, and the VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 86, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 61,The CDR-H3 comprises an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 63, CDR-L2 having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 64. In some embodiments, (a) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 30, CDR-H2 containing the amino acid sequence of SEQ ID NO: 31, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 32, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35; (b) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing the amino acid sequence of SEQ ID NO: 37, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 38, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35; (c) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, and SEQ ID NO: 39 (d) The VH domain includes CDR-H2 containing the amino acid sequence of SEQ ID NO: 40, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (d) The VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 41, CDR-H2 containing the amino acid sequence of SEQ ID NO: 42, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 43, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 44, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 46, or (e) The VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 49, and the VL domain is(f) The VH domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 51, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 52, and the VL domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 53, CDR-H2 containing the amino acid sequence of SEQ ID NO: 54, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 55, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 56, and the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 57, CDR-H2 containing the amino acid sequence of SEQ ID NO: 58, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 59, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 60, and the amino acid sequence of SEQ ID NO: 34 (h) The VH domain includes CDR-L2 and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or (i) The VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 83, CDR-H2 containing the amino acid sequence of SEQ ID NO: 84, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 85, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 86, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or (i) The VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 62, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 63, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 64. In some embodiments, the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, (a) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 88, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 89, and the VL domain(b) The VH domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 35, or (b) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 87, and at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 92, The VL domain comprises CDR-H2 containing an identical amino acid sequence, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 35, (c) The VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 94, and the VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 90, and the amino acid sequence of SEQ ID NO: 91 (d) The VH domain comprises CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 35, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 95, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 96, and an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 97. (e) The CDR-H3 comprises a column, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 98, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 100, or (e) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 109,The VL domain comprises CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 114, wherein the VL domain contains CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 115, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 99, and less than the amino acid sequence of SEQ ID NO: 52. (f) The VH domain includes CDR-L3 containing an amino acid sequence having 80% sequence identity, or (f) the VL domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 116, CDR-H2 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 117, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 118, and the VL domain has at least 80% of the amino acid sequence of SEQ ID NO: 115 (g) The VH domain comprises CDR-L1 containing an amino acid sequence having sequence identity, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 101, and C containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 102. (h) The VL domain comprises CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 103, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 104, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 61, or (h) the VH domainThe VL domain comprises CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 105, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 106, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 107, wherein the VL domain comprises CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 108, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 61, or (i) the The VH domain includes CDR-H1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 111. The VL domain includes CDR-L1 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 112, CDR-L2 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 113, and CDR-L3 containing an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 64. In some embodiments, (a) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing the amino acid sequence of SEQ ID NO: 88, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 89, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (b) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 93, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91,(c) The VH domain includes CDR-L3 containing the amino acid sequence of SEQ ID NO: 350, (c) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 94, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (d) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 95, and the amino acid sequence of SEQ ID NO: 96 (e) The VL domain includes CDR-H2 containing the sequence, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 97, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 98, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 100, or (e) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 114, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 115, sequence (f) The VH domain contains CDR-L2 containing the amino acid sequence of number 99 and CDR-L3 containing the amino acid sequence of SEQ ID NO: 52, or (g) the VH domain contains CDR-H1 containing the amino acid sequence of SEQ ID NO: 116, CDR-H2 containing the amino acid sequence of SEQ ID NO: 117, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 118, and the VL domain contains CDR-L1 containing the amino acid sequence of SEQ ID NO: 115, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain contains the amino acid sequence of SEQ ID NO: 101 The VL domain includes CDR-H1 containing the sequence, CDR-H2 containing the amino acid sequence of SEQ ID NO: 102, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 103, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 104, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or the (h)VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 105, CDR-H2 containing the amino acid sequence of SEQ ID NO: 106, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 107, and the VL domain is(i) The VH domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 108, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or (i) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 111, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 112, CDR-L2 containing the amino acid sequence of SEQ ID NO: 113, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 64. In some embodiments, (a) the VH domain includes an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 65, and the VL domain includes an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 66; (b) the VH domain includes an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 67, and the VL domain includes an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 68; (c) the VH domain includes an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 69, and the VL domain includes an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 70; (d) the VH domain includes an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 71 (e) The VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 72, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 73, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 74, (f) The VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 75, and the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 76, (g) The VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 77, and the VL domain contains(h) The VH domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 78, or the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 79, or the VL domain contains an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 80, or (i) the VH domain has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 81. The VL domain contains an amino acid sequence that has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 82. In some embodiments, (a) the VH domain includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 65, and the VL domain includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 66; (b) the VH domain includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 67, and the VL domain includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 68; (c) the VH domain includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 69, and the VL domain includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 70; (d) the VH domain includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 71, and the VL domain includes an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 72; (e (f) The VH domain contains an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 73, and the VL domain contains an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 74, or (g) The VH domain contains an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 75, and the VL domain contains an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 76, or (h) The VH domain contains an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 77, and the VL domain contains an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 78, or (i) The VH domain contains,The VL domain contains an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 81, and the VL domain contains an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 82. In some embodiments, (a) the VH domain includes an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain includes an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain includes an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain includes an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain includes an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain includes an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 70; (d) the VH domain includes an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain includes an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 72. (e) The VH domain contains an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 73, and the VL domain contains an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 74, (f) The VH domain contains an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 75, and the VL domain contains an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 76, (g) The VH domain contains an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 77, and the VL domain contains an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 78, (h) The VH domain contains an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 79, and the VL domain contains an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 80,Alternatively, (i) the VH domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 81, and the VL domain contains an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 82. In some embodiments, (a) the VH domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 65, and the VL domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 66; (b) the VH domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 67, and the VL domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 68; (c) the VH domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 69, and the VL domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 70; (d) the VH domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 71, and the VL domain contains an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 72. (e) The VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 73, and the VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 74, (f) The VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 75, and the VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 76, (g) The VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 77, and the VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 78, (h) The VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 79, and the VL domain contains(i) The VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 80, or (i) the VH domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 81, and the VL domain contains an amino acid sequence having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 82. In some embodiments, (a) the VH domain contains the amino acid sequence of SEQ ID NO: 65, and the VL domain contains the amino acid sequence of SEQ ID NO: 66, (b) the VH domain contains the amino acid sequence of SEQ ID NO: 67, and the VL domain contains the amino acid sequence of SEQ ID NO: 68, (c) the VH domain contains the amino acid sequence of SEQ ID NO: 69, and the VL domain contains the amino acid sequence of SEQ ID NO: 70, (d) the VH domain contains the amino acid sequence of SEQ ID NO: 71, and the VL domain contains the amino acid sequence of SEQ ID NO: 72, or (e) the VH domain contains the amino acid sequence of SEQ ID NO: 73 (f) The VL domain contains the amino acid sequence of SEQ ID NO: 74, (g) The VH domain contains the amino acid sequence of SEQ ID NO: 75 and the VL domain contains the amino acid sequence of SEQ ID NO: 76, (h) The VH domain contains the amino acid sequence of SEQ ID NO: 77 and the VL domain contains the amino acid sequence of SEQ ID NO: 78, (h) The VH domain contains the amino acid sequence of SEQ ID NO: 79 and the VL domain contains the amino acid sequence of SEQ ID NO: 80, or (i) The VH domain contains the amino acid sequence of SEQ ID NO: 81 and the VL domain contains the amino acid sequence of SEQ ID NO: 82.

[0014] In further embodiments, antibodies that bind to the same epitope as the antibody of any one of the above embodiments are provided herein. In some embodiments, the antibody of the Disclosure binds to the same epitope as the reference antibody. In some embodiments, the reference antibody includes a VH domain comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a VL domain comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the reference antibody includes a VH domain comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a VL domain comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the reference antibody includes a VH domain comprising CDR-H1 containing the amino acid sequence of SEQ ID NO: 13, CDR-H2 containing the amino acid sequence of SEQ ID NO: 14, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 15, and a VL domain comprising CDR-L1 containing the amino acid sequence of SEQ ID NO: 16, CDR-L2 containing the amino acid sequence of SEQ ID NO: 17, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 18. In some embodiments, the reference antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, where (a) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 30, CDR-H2 containing the amino acid sequence of SEQ ID NO: 31, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (b) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing the amino acid sequence of SEQ ID NO: 37, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34,(c) The VH domain includes CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, (d) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing the amino acid sequence of SEQ ID NO: 39, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 40, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, (c) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 41, and the amino acid sequence of SEQ ID NO: 42 (e) The VH domain comprises CDR-H2 and CDR-H3 containing the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 44, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 46, or (e) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, and the amino acid sequence of SEQ ID NO: 51 (f) The VH domain includes CDR-L2 containing the sequence and CDR-L3 containing the amino acid sequence of SEQ ID NO: 52, or (g) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 53, CDR-H2 containing the amino acid sequence of SEQ ID NO: 54, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 55, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 57, sequence number (h) The VH domain comprises CDR-H2 containing the amino acid sequence of SEQ ID NO. 58, and CDR-H3 containing the amino acid sequence of SEQ ID NO. 59, wherein the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO. 60, CDR-L2 containing the amino acid sequence of SEQ ID NO. 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO. 61, or (h) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO. 83, CDR-H2 containing the amino acid sequence of SEQ ID NO. 84, and CDR-H3 containing the amino acid sequence of SEQ ID NO. 85, wherein the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO. 86,(i) The VH domain comprises CDR-L2 containing the amino acid sequence of SEQ ID NO: 34 and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or (i) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 63, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 64.

[0015] In further embodiments, antibodies are provided herein that compete with the antibodies of any one of the above embodiments in terms of binding to human CD94. In some embodiments, the antibodies of the Disclosure compete with a reference antibody in terms of binding to human CD94. In some embodiments, the reference antibody includes a VH domain comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a VL domain comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the reference antibody includes a VH domain comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and a VL domain comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the reference antibody includes a VH domain comprising CDR-H1 containing the amino acid sequence of SEQ ID NO: 13, CDR-H2 containing the amino acid sequence of SEQ ID NO: 14, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 15, and a VL domain comprising CDR-L1 containing the amino acid sequence of SEQ ID NO: 16, CDR-L2 containing the amino acid sequence of SEQ ID NO: 17, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 18. In some embodiments, the reference antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, where (a) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 30, CDR-H2 containing the amino acid sequence of SEQ ID NO: 31, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, or (b) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing the amino acid sequence of SEQ ID NO: 37, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34,(c) The VH domain includes CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, (d) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing the amino acid sequence of SEQ ID NO: 39, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 40, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35, (c) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 41, and the amino acid sequence of SEQ ID NO: 42 (e) The VH domain comprises CDR-H2 and CDR-H3 containing the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 44, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 46, or (e) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, and the amino acid sequence of SEQ ID NO: 51 (f) The VH domain includes CDR-L2 containing the sequence and CDR-L3 containing the amino acid sequence of SEQ ID NO: 52, or (g) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 53, CDR-H2 containing the amino acid sequence of SEQ ID NO: 54, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 55, and the VL domain includes CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 56, or (g) the VH domain includes CDR-H1 containing the amino acid sequence of SEQ ID NO: 57, sequence number (h) The VH domain comprises CDR-H2 containing the amino acid sequence of SEQ ID NO. 58, and CDR-H3 containing the amino acid sequence of SEQ ID NO. 59, wherein the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO. 60, CDR-L2 containing the amino acid sequence of SEQ ID NO. 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO. 61, or (h) the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO. 83, CDR-H2 containing the amino acid sequence of SEQ ID NO. 84, and CDR-H3 containing the amino acid sequence of SEQ ID NO. 85, wherein the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO. 86,Comprising a CDR-L2 containing the amino acid sequence of SEQ ID NO: 34 and a CDR-L3 containing the amino acid sequence of SEQ ID NO: 61, or (i) the VH domain comprises a CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, a CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and a CDR-H3 containing the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises a CDR-L1 containing the amino acid sequence of SEQ ID NO: 63, a CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and a CDR-L3 containing the amino acid sequence of SEQ ID NO: 64.

[0016] In some embodiments according to any of the embodiments described herein, the antibody is an antigen-binding antibody fragment or a single-chain antibody. In some embodiments, the antibody further comprises an Fc region, for example, a human IgG1 Fc region. In some embodiments, the antibody comprises a non-fucosylated human Fc region. In some embodiments, the antibody is produced in a cell line deficient in an alpha-1,6-fucosyltransferase gene such as FUT8 (e.g., a CHO cell line). In some embodiments, the antibody binds to human cell Fc gamma receptor IIIA to a greater extent than an antibody comprising a wild-type human IgG1 Fc region. In some embodiments, the antibody can induce antibody-dependent cell-mediated cytotoxicity (ADCC) against cells expressing human CD94 on their surface.

[0017] In a further aspect, a polynucleotide(s) encoding an antibody according to any one of the above embodiments is provided herein. Further, a vector (e.g., an expression vector) comprising a polynucleotide(s) according to any one of the above embodiments is provided herein. Further, a host cell (e.g., an isolated host cell or cell line) comprising a polynucleotide(s) or vector according to any one of the above embodiments is provided herein. Further, a method for producing an antibody is provided herein, which comprises culturing a host cell according to any one of the above embodiments under conditions suitable for the production of the antibody. In some embodiments, the method further comprises recovering the antibody from the host cell.

[0018] Furthermore, compositions (e.g., pharmaceutical compositions) comprising an antibody according to any one of the above embodiments and a pharmaceutically acceptable carrier are provided herein.

[0019] In further embodiments, methods for treating a disease or disorder in a subject are provided herein, the methods comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments. In some embodiments, the administration of the antibody results in a reduction in the number of peripheral blood LGL cells or NK cells in the subject. In some embodiments, the disease or disorder is Felty syndrome, and the administration of the antibody to the subject results in a reduction of one or more symptoms of Felty syndrome in the subject. In some embodiments, the disease or disorder is inclusion body myositis, and the administration of the antibody to the subject results in a reduction of one or more symptoms of inclusion body myositis in the subject. In some embodiments, the disease or disorder is invasive NK leukemia, and the administration of the antibody to the subject results in a reduction of one or more symptoms of invasive NK leukemia in the subject. In some embodiments, the disease or disorder is rheumatoid arthritis, and the administration of the antibody to the subject results in a reduction of one or more symptoms of rheumatoid arthritis in the subject. In some embodiments, the disease or disorder is LGL leukemia, and administration of the antibody to the subject results in a reduction of one or more symptoms of LGL leukemia in the subject. In some embodiments, the disease or disorder is CLPD-NK, and administration of the antibody to the subject results in a reduction of one or more symptoms of CLPD-NK in the subject. In some embodiments, the disease or disorder is natural killer (NK) cell lymphoma or T-cell lymphoma, and administration of the antibody to the subject results in a reduction of one or more symptoms of lymphoma in the subject. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic enteroplastic TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, or subcutaneous panniculitis TCL. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.In some embodiments, the disease or disorder is microscopic colitis, and administration of the antibody to the subject results in a reduction of one or more symptoms of microscopic colitis in the subject.

[0020] In further embodiments, a method for reducing the number of peripheral blood LGL cells and / or NK cells in a subject is provided herein, the method comprising administering to the subject an effective amount of the antibody or composition according to any one of the above embodiments. In further embodiments, a method for inducing ADCC activity in a subject is provided herein, the method comprising administering to the subject an effective amount of the antibody or composition according to any one of the above embodiments. In further embodiments, a method for treating CLPD-NK in a human subject requiring treatment for CLPD-NK is provided herein, the method comprising administering to the subject an effective amount of the antibody or composition according to any one of the above embodiments. In some embodiments, the administration of the antibody results in improvement of one or more symptoms of CLPD-NK in the subject.

[0021] In further embodiments, methods for treating natural killer (NK) cell lymphoma or T-cell lymphoma are provided herein, the methods comprising administering an effective amount of an antibody or composition according to any one of the above embodiments to a subject in need thereof. In some embodiments, the antibody does not bind to the same epitopes on human CD94 as anti-CD94 antibody clones HP-3D9, HP-3B1, DX22, 131412, or 12K45. In some embodiments, the antibody binds to human CD94 with higher affinity than anti-CD94 antibody clones HP-3D9, HP-3B1, DX22, 131412, and 12K45. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, or adult TCL.

[0022] In further embodiments, methods for augmenting chimeric antigen receptor T cell (CAR-T) therapy in human subjects requiring augmentation of chimeric antigen receptor T cell (CAR-T) therapy are provided herein, the method comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments prior to administering CAR-T treatment to the subject. In some embodiments, the administration of the antibody or composition results in NK cell depletion in the subject prior to administering CAR-T treatment.

[0023] In a further embodiment, a method for depleting CD8+ CD94+ T cells in a human subject requiring CD8+ CD94+ T cell depletion is provided herein, the method comprising administering to the subject an effective amount of an antibody or composition according to any one of the above embodiments. In some embodiments, the administration of the antibody or composition results in CD8+ CD94+ T cell depletion in the subject.

[0024] In some embodiments of any of the embodiments described herein, the method further comprises administering an IL-2 polypeptide as the target.

[0025] In some embodiments of any of the embodiments described herein, the subject is a human.

[0026] In further embodiments, antibodies or compositions according to any one of the above embodiments are provided herein for use in treating a disease or disorder in a subject, reducing the number of peripheral blood LGL cells and / or NK cells in a subject, treating CLPD-NK in a human subject requiring CLPD-NK treatment, treating natural killer (NK) cell lymphoma or T-cell lymphoma, treating microscopic colitis in a subject, or augmenting CAR-T therapy in a subject requiring augmentation of CAR-T therapy. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic enteroplastic TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, or subcutaneous panniculitis TCL. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.

[0027] In further embodiments, the use of antibodies or compositions according to any one of the above embodiments is provided herein for the manufacture of pharmaceuticals for use in augmenting CAR-T therapy in subjects requiring treatment of disease or disorder, reducing the number of peripheral blood LGL cells and / or NK cells in subjects, treating CLPD-NK in human subjects requiring CLPD-NK treatment, treating natural killer (NK) cell lymphoma or T cell lymphoma, treating microscopic colitis in subjects, or augmenting CAR-T therapy in subjects requiring augmentation of CAR-T therapy. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, or adult TCL. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.

[0028] In further embodiments, kits or products comprising an antibody or composition according to any one of the embodiments described above are provided herein. In some embodiments, the kit further includes instructions for use of the kit for, for example, treating a disease or disorder in a subject, reducing the number of peripheral blood LGL cells and / or NK cells in a subject, treating CLPD-NK in a human subject requiring CLPD-NK treatment, treating natural killer (NK) cell lymphoma or T-cell lymphoma, treating microscopic colitis in a subject, or augmenting CAR-T therapy in a subject requiring augmentation of CAR-T therapy. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-associated TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic enteroplastic TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, or subcutaneous panniculitis TCL. In some embodiments, NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-associated TCL.

[0029] In some embodiments that may be combined with any of the prior embodiments, the antibody of this disclosure comprises six CDRs from a single antibody listed in Table 1 (e.g., antibody 18H3, 1M4, 1E4, ATX-122, ATX-123, ATX-124, ATX-125, ATX-126, ATX-127, ATX-128, ATX-129, or ATX-130). In some embodiments that may be combined with any of the prior embodiments, the antibody of this disclosure comprises VH and VL domains from a single antibody listed in Table 2 (e.g., antibody 18H3, 1M4, 1E4, ATX-122, ATX-123, ATX-124, ATX-125, ATX-126, ATX-127, ATX-128, ATX-129, or ATX-130).

[0030] All references cited herein, including patent applications and publications, are incorporated in their entirety by reference.

[0031] Novel features of the present invention are described in particular in the appended claims. A better understanding of the features and advantages of the present invention can be obtained by referring to the following detailed description, which describes exemplary embodiments in which the principles of the present invention are utilized, and to the accompanying drawings. [Brief explanation of the drawing]

[0032] [Figure 1] This study shows the affinity of the anti-CD94 antibody 18H3 to human primary natural killer (NK) cells, as measured by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from healthy donor HD-40 were used for antibody staining. The 18H3 antibody was titrated from 100 nM to 0.046 nM at a 1:3 dilution and incubated with PBMCs. NK cells were identified based on flow scattering light using CD3 and CD56 antibodies. The affinity of 18H3 was assessed by measuring the binding of the 18H3 antibody to CD3+ and CD56 bright NK cells. Titration curves and EC50 were generated using Graphpad Prism. 18H3 bound to CD3+ CD56 bright NK cells with an affinity of 2.6 nM. Human IgG1 isotype control (hIgG1) using secondary antibodies and goat (Fab)2 fragment anti-human Fcy-specific secondary antibody AF647 only (secondary Ab) were used as controls. [Figure 2] This shows the binding of anti-CD94 antibodies to human primary NK cells as measured by flow cytometry. Anti-CD94 hybridoma supernatant was screened in human primary NK cells by flow cytometry. HP-3D9 is a commercially available anti-CD94 antibody used as a positive control. Mouse IgG1, IgG2a, IgG2b, and IgG3 were used as negative controls. Anti-CD94 antibodies 18H3, 1M4, and 1E4 bound to CD94 expressed on human primary NK cells. [Figure 3]A and B show the cross-reactivity of anti-CD94 antibodies against cynomolgus monkey CD94. A shows the cross-reactivity of hybridoma antibodies against cynomolgus monkey CD94. Anti-CD94 hybridoma supernatant was screened for cross-reactivity against cynomolgus monkey CD94 in cynomolgus monkey CD94-expressing HEK293 cells by flow cytometry. HP-3D9 is a commercially available anti-CD94 antibody used as a negative control. Mouse IgG1, IgG2a, IgG2b, and IgG3 were used as negative controls. 18H3, 1M4, and 1E4 cross-reacted with cynomolgus monkey CD94, while 20F2 is an example of another CD94 antibody clone that reacts with human CD94 but not with cynomolgus monkey CD94. B shows the cross-reactivity of commercial antibodies against cynomolgus monkey CD94. Cynomolgus monkey cross-reactivity was tested using commercially available anti-CD94 antibodies. 18H3 was used as a positive control. The MFI of each antibody was normalized to the MFI of its respective isotype. Unlike 18H3, HP-3B1, 131412, 12K45, DX22, and HP-3D9 did not cross-react with cynomolgus monkey CD94. [Figure 4] The results of HLA-E tetramer blockade assays performed using anti-CD94 and commercially available anti-CD94 antibodies, as measured by flow cytometry, are presented. PBMCs from healthy donors were incubated with anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a cell-antibody mixture and detected using flow cytometry. 2.5 μl of HLA-E tetramer reagent was used for HP-3B1, 131412, 12K45, DX22, 1M4, and 1E4, while 5 μl was used for 18H3 and HP-3D9. Saturated concentrations of each antibody were used in this assay. Blockade percentages were calculated as 100 - ((percentage of HLA-E positive against anti-CD94 antibody) / (percentage of HLA-E positive against isotype) × 100). The 18H3 and 1E4 antibodies did not block HLA-E binding to CD94. [Figure 5A]The results of competitive assays performed to evaluate the 18H3 anti-CD94 antibody are shown. For all competitive assays, 18H3 was incubated with PBMCs at a concentration of 1.3 μg / ml. Competitive assays between 18H3 and commercially available anti-CD94 antibodies are shown. Commercially available anti-CD94 antibodies were titrated and incubated with PBMCs in parallel with 18H3. 18H3 was fluorescently tagged with AF647 and incubated with cells in parallel with 18H3-AF647. 18H3 competed only partially with HP-3D9 and not with DX22, HP-3B1, 131412, and 12K45. These results suggest that the 18H3 antibody binds to epitopes not shared with the commercially available antibody. [Figure 5B] The results of competitive assays performed to evaluate the 18H3 anti-CD94 antibody are shown. For all competitive assays, 18H3 was incubated with PBMCs at a concentration of 1.3 μg / ml. Competitive assays using 18H3 and other hybridoma anti-CD94 antibodies disclosed herein (1M4 and 1E4) are shown. To test competition between 18H3 and 1M4 / 1E4, 1M4 and 1E4 were incubated with cells at concentrations of 8.5 μg / ml and 11 μg / ml, respectively. 18H3 was fluorescently tagged with AF647 and incubated with cells in parallel with 18H3-AF647. 18H3 did not compete with 1E4 and 1M4. These results suggest that the 18H3 antibody binds to an epitope not shared with commercially available antibodies. [Figure 6A] The results of competitive assays performed to evaluate the 1M4 anti-CD94 antibody are shown. For all competitive assays, 1M4 was incubated with PBMCs at a concentration of 8.5 μg / ml. Competitive assays between 1M4 and a commercially available anti-CD94 antibody are also shown. The commercially available anti-CD94 antibody was titrated and incubated with PBMCs in parallel with 1M4. The 1M4 antibody did not compete with the commercially available antibody. [Figure 6B]The results of competitive assays performed to evaluate the 1M4 anti-CD94 antibody are shown. For all competitive assays, 1M4 was incubated with PBMCs at a concentration of 8.5 μg / ml. Competitive assays using 1M4 and 1E4 antibodies are shown. To test competition between 1M4 and 1E4, 1E4 was incubated with cells at a concentration of 11 μg / ml. 1M4 with an anti-mouse secondary antibody was incubated with cells in parallel with 1E4. The 1M4 antibody competed with 1E4. [Figure 7] The results of competitive assays performed to evaluate the 1E4 anti-CD94 antibody are shown. For all competitive assays, 1E4 was incubated with PBMCs at a concentration of 11 μg / ml. Commercial anti-CD94 antibodies were titrated and incubated with PBMCs in parallel with 1E4. The 1E4 antibody did not compete with four of the five commercial anti-CD94 antibodies tested, but partially competed with 12K45. [Figure 8A] The results of the anti-CD94 antibody internalization assay are shown. Peripheral blood mononuclear cells (PBMCs) from healthy donors were incubated with unconjugated anti-CD94 antibodies at multiple time points ranging from 30 minutes to 24 hours. Cells were maintained at either 4°C, which inhibits internalization, or 37°C, which induces internalization. The results for the commercially available antibodies HP-3D9 and DX22 are shown. The commercially available anti-CD94 antibodies internalized in a time-dependent manner. [Figure 8B] The results of the anti-CD94 antibody internalization assay are shown. Peripheral blood mononuclear cells (PBMCs) from healthy donors were incubated with unconjugated anti-CD94 antibodies at multiple time points ranging from 30 minutes to 24 hours. Cells were maintained at either 4°C, which inhibits internalization, or 37°C, which induces internalization. The results for 18H3, 1M4, and 1E4 antibodies are shown. The 18H3, 1M4, and 1E4 antibodies did not significantly internalize upon binding to CD94. [Figure 9A]The results of an antibody-dependent cell-mediated cytotoxicity (ADCC) assay using PBMCs from healthy donors with an anti-CD94 antibody are presented. 18H3 antibodies were produced in Expi-CHO cells cultured in the presence of kifunensin, a potent inhibitor of mannosidase I enzyme, and these were used to create 18H3-KIF, which mimics non-fucosylated antibodies. PBMCs were plated in 96-well plates and incubated overnight in the presence of anti-CD94 antibodies ranging from 1 × 10⁻⁶ to 10 μg / ml at a 10-fold dilution. NK cell counts were quantified by flow cytometry. NK cell counts under human IgG1 and anti-CD94 antibody treatment conditions were normalized relative to the NK cell count from human IgG1-treated wells. The results of an ADCC assay using human IgG1 18H3 antibody are also presented. Human IgG1 18H3 depleted human primary NK cells in a concentration-dependent manner. [Figure 9B] The results of an antibody-dependent cell-mediated cytotoxicity (ADCC) assay using PBMCs from healthy donors with an anti-CD94 antibody are presented. Fucosylated 1E4 antibody was used in the ADCC assay. PBMCs were plated in 96-well plates and incubated overnight in the presence of anti-CD94 antibody at a 10-fold dilution ranging from 1 × 10⁻⁶ to 10 μg / ml. NK cell counts were quantified by flow cytometry. NK cell counts under human IgG1 and anti-CD94 antibody treatment conditions were normalized relative to the NK cell count from human IgG1-treated wells. The results of the ADCC assay using fucosylated 1E4 antibody are also presented. Fucosylated 1E4 depleted human primary NK cells in a concentration-dependent manner. [Figure 10]The results of an ADCC assay of anti-CD94 antibodies using PBMCs from CLPD-NK patients are presented. 18H3 was generated in Expi-CHO cells cultured in the presence of kifunensin, a potent inhibitor of mannosidase I enzyme, to produce 18H3-KIF, which mimics non-fucosylated antibodies. PBMCs were plated in 96-well plates and incubated overnight in the presence of anti-CD94 antibodies ranging from 1 × 10⁻⁶ to 10 ug / ml at a 10-fold dilution. The number of CD3-CD16+ leukemia cells was quantified by flow cytometry. The number of leukemia cells under human IgG1 and anti-CD94 antibody treatment conditions was normalized to the number of leukemia cells from human IgG1-treated wells. Partially non-fucosylated human IgG1 18H3 depleted human CLPD-NK leukemia cells in a concentration-dependent manner. [Figure 11] A summary of the characteristics and functional evaluation of the anti-CD94 antibody compared to commercially available anti-CD94 antibodies is illustrated. [Figure 12]This study demonstrates the affinity of the anti-CD94 antibody ATX-130 against human primary natural killer (NK) cells, and the affinity of the anti-CD94 antibody ATX-130-KIF against cynomolgus monkey primary natural killer (NK) cells, chronic NK cell lymphoproliferative disorder (CLPD-NK), and T-cell large granular lymphocytic leukemia cells (T-LGLL), as measured by flow cytometry. ATX-130 antibody was produced in Expi-CHO cells cultured in the presence of kifunensin, a potent inhibitor of mannosidase I enzyme, and this was used to produce ATX-130-KIF, which mimics a non-fucosylated antibody. PBMCs from healthy donors were used for antibody staining. The ATX-130 antibody was titrated from 50 nM to 0.02 nM. Binding on CD3-CD56 bright NK cells was detected using a secondary anti-human antibody labeled with Alexa Fluor 647. ATX-130-KIF antibody conjugated with Alexa Fluor 647 titrated from 50 nM to 0.02 nM. T-LGLL cells were identified using CD3+CD16+ gating, while CLPD-NK cells were identified using a CD3-CD16+ gating strategy. Titration curves and EC50 were generated using Graphpad Prism. ATX-130 bound to CD3-CD56 bright NK cells with an affinity of 0.6 nM. ATX-130-KIF showed affinities of 1 nM on primary cynomolgus monkey NK cells, 1.4 nM on CLPD-NK cells, and 3 nM on T-LGLL cells. Fluorescently labeled human IgG1-KIF isotype-KIF antibody was used as a control. Arrows indicate data points for ATX-130 and human IgG1-KIF. [Figure 13]This study demonstrates the affinity of the anti-CD94 antibody ATX-130 for CD94 homodimers or heterodimers. BaF3 cells overexpressing CD94 homodimers (top panel), CD94 / NKG2A heterodimers (bottom left panel), and CD94 / NKG2C heterodimers (bottom right panel) were incubated with unconjugated ATX-130 antibody in dilution series from 50 nM to 0.02 nM. ATX-130 binding on cells was detected using a secondary anti-human antibody labeled with Alexa Fluor 647. ATX-130 bound to CD94 homodimer, CD94 / NKG2A, and CD94 / NKG2C heterodimer BaF3 cells with affinities of 0.3, 0.8, and 1.8 nM, respectively. [Figure 14] This figure shows IFN-gamma secretion from human NK cells in the presence of ATX-130 antibody, as assessed by ELISA. NK cells were isolated from healthy donor PBMCs and cultured in the presence of ATX-130 with mouse IgG1 inactive Fc (mATX-130), human IgG1-KIF isotype control, ATX-130 (hATX-130), and the medium alone. After 24 hours of incubation, the supernatant of the cell cultures was collected and ELISA was performed to detect secreted IFN-gamma. The concentrations of ATX-130 (10 μg / mL, 5 μg / mL, 1 μg / mL, or the medium) are shown above each bar, corresponding to the concentrations shown in the legend of the figure. [Figure 15] The results of competitive assays performed to evaluate the ATX-130 anti-CD94 antibody are shown. For all competitive assays, ATX-130 was incubated with PBMCs at a concentration of 7.5 μg / ml. Commercially available anti-CD94 antibodies (clones HP-3D9, DX22, 131412, 12K45, and HP-3B1) were titrated and incubated with PBMCs in parallel with ATX-130. Competition was assessed by plotting the MFI of the titrated commercial anti-CD94 antibodies. ATX-130 did not compete with HP-3D9, DX22, 131412, 12K45, or HP-3B1. [Figure 16]The results of an HLA-E tetramer blockade assay performed using ATX-130-KIF and isotype control antibodies, using flow cytometry, are shown. PBMCs from healthy donors were incubated with ATX-130-KIF. Then, PE-labeled HLA-E tetramers were incubated with a cell-antibody mixture and detected by flow cytometry. Saturated concentrations of ATX-130-KIF were used in this assay. The blockade percentage was calculated as 100 - ((percentage of HLA-E positive against anti-CD94 antibody) / (percentage of HLA-E positive against isotype) × 100). Arrows indicate histograms for ATX-130-KIF and isotype. ATX-130-KIF did not block HLA-E binding to CD94. [Figure 17] The results of an anti-CD94 antibody internalization assay are shown. PBMCs from healthy donors were incubated with unconjugated ATX-130 at multiple time points ranging from 30 minutes to 24 hours. Cells were maintained at either 4°C, which inhibits internalization, or 37°C, which induces internalization. ATX-130 was not significantly internalized within 24 hours. [Figure 18] This shows the binding of ATX-130-KIF to immune cell types as measured by flow cytometry. Immune cell types (monocytes, CD4 T cells, B cells, CD8 T cells, and NK cells) from PBMCs derived from normal human, cynomolgus monkey, and LGL leukemia patient samples were stained with ATX-130-KIF Alexa Fluor 647 (50 nM) and evaluated for binding. ATX-130-KIF selectively binds to NK cells (CD3-CD56+ / CD16+), a subset of normal CD8 T cells (CD3+CD8+), and all LGLL cells (CD3-CD16+). The arrows show histograms of ATX-130-KIF and isotypes. [Figure 19]The results of an ADCC assay for ATX-130-KIF using PBMCs from healthy donors are shown. PBMCs from healthy donors were plated in 96-well plates and incubated with ATX-130 (10-fold dilution and titrated) for 24 hours. Exhaustion of different immune cell types was assessed by quantifying the number of remaining cells using flow cytometry. Arrows indicate curves for ATX-130-KIF and isotype. ATX-130 depletes human NK cells at a potency of 0.8 ng / ml while not harming other immune cell types. [Figure 20] The results of an ADCC assay using cynomolgus monkey PBMCs with an anti-CD94 antibody are shown. Cynomolgus monkey PBMCs were plated in a 96-well plate and incubated with ATX-130-KIF (10-fold dilution and titrated) for 24 hours. Depletion of different immune cell types (NK cells, CD8 T cells, CD4 T cells, and B cells) was assessed by quantifying the number of remaining cells by flow cytometry. Arrows show the curves for ATX-130-KIF and isotype. ATX-130-KIF depletes cynomolgus monkey NK cells at a potency of 0.3 ng / ml while not harming other immune cell types. [Figure 21] The results of an ADCC assay using T-LGLL and CLPD-NK PBMCs with an anti-CD94 antibody are shown. T-LGLL and CLPD-NK PBMCs were plated in 96-well plates and incubated with ATX-130-KIF (10-fold dilution and titrated) for 24 hours. Exhaustion of different immune cell types was assessed by quantifying the number of remaining cells by flow cytometry. Arrows indicate curves for ATX-130-KIF and isotype. ATX-130-KIF exhausted T-LGLL and CLPD-NK cells at potencies of 0.2 and 0.6 ng / ml, respectively, while not harming other immune cell types. [Figure 22A] This study design describes a study to examine the effects of ATK-130 or an isotype control on humanized IL-15 transgenic mice transplanted with PBMCs from healthy human donors. [Figure 22B]This study demonstrates the depletion of normal human NK cells and CD8 T cells in IL-15 transgenic mice. Healthy donor PBMCs were transplanted into mice and left for 3 days. A single dose of either human IgG1 isotype control or ATX-130 (5 mg / kg) was injected into the mice (5 mice per group). NK cell (upper panel) and CD8 T cell (lower panel) depletion in the blood, spleen, and bone marrow was assessed by flow cytometry 48 hours after administration. Depletion was quantified by the number of remaining NK cells and CD8 T cells in each sample. [Figure 23] This study demonstrates the depletion of LGLL cells in the blood, spleen, bone marrow, and liver of IL-15 transgenic mice. LGLL PBMCs were transplanted into mice and left for 28 days. A single dose of either human IgG1 isotype control or ATX-130 (5 mg / kg) was injected into the mice (5 mice per group). LGLL cell depletion in the blood, spleen, bone marrow, and liver was assessed by flow cytometry 48 hours after administration. Depletion was quantified by the number of remaining CD94+ LGLL cells in each sample. [Figure 24A] This paper describes the design of an exploratory pharmacodynamic (PD) study in non-human primates to evaluate the efficacy of ATK-130 in vivo. [Figure 24B] This study demonstrates in vivo depletion of cynomolgus monkey NK cells by administration of 2 mg / kg ATX-130-KIF, as assessed by flow cytometry. Two naive cynomolgus monkeys (monkey #1 and monkey #2) were administered ATX-130-KIF (2 mg / kg) via intravenous (IV) infusion over 60 minutes. Monkey #1 received an additional 2 mg / kg of ATX-130-KIF at 8 weeks, and monkey #2 at 16 weeks. Body weight and clinical observations were recorded regularly. PBMCs were isolated from 5 mL of blood samples per animal per time point. 0.3 × 10⁶ cells per well were plated in technical triplicates and stained with an antibody panel. Cynomolgus monkey NK cells were identified using a CD3-CD8+ gating strategy. NK cells were quantified by calculating the percentage of the relevant cell population within the total number of PBMCs. Arrows indicate the time at which the dose was administered. [Figure 25A] This study assesses the depletion of CD4 T cells, CD8 T cells, and B cells in cynomolgus monkeys. PBMCs were isolated from 5 mL of blood sample per time point for each cynomolgus monkey. 0.3 × 10⁶ cells per well were plated in technical triplicates and stained with an antibody panel. CD4+ T cells, CD8+ T cells, and B cells were identified in each cynomolgus monkey using CD3+CD4+, CD3+CD8+, and CD3-CD20+ gating strategies. Cells were quantified by calculating the percentage of the relevant cell population within the total PBMCs. [Figure 25B] This study assesses the depletion of CD4 T cells, CD8 T cells, and B cells in cynomolgus monkeys. PBMCs were isolated from 5 mL of blood samples per time point from cynomolgus monkey #2. 0.3 × 10⁶ cells per well were plated in technical triplicates and stained with an antibody panel. CD4+ T cells, CD8+ T cells, and B cells were identified from cynomolgus monkey #2, respectively, using CD3+CD4+, CD3+CD8+, and CD3-CD20+ gating strategies. Cells were quantified by calculating the percentage of the relevant cell population within the total PBMCs. [Figure 26] The results of monocyte depletion assessment by flow cytometry are shown. PBMCs were isolated from 5 mL of blood samples per time point from cynomolgus monkeys #1 (left panel) and #2 (right panel). 0.3 × 10⁶ cells per well were plated in a technical triplicate and stained with an antibody panel. Monocytes were identified using a CD3-CD14+ gating strategy. Cell quantification was performed by calculating the percentage of the relevant cell population out of the total PBMCs. [Figure 27] The results of CD16 expression assessment on monocytes by flow cytometry are shown. PBMCs were isolated from 5 mL of blood samples per time point from cynomolgus monkeys #1 (left panel) and #2 (right panel). 0.3 × 10⁶ cells per well were plated using technical triplicates and stained with an antibody panel. Monocytes were identified using a CD3-CD14+ gating strategy. CD16 MFI was assessed in monocytes. [Figure 28A] This paper describes the design of a non-GLP PD study in non-human primates to evaluate the efficacy of ATK-130 in vivo. [Figure 28B] This study demonstrates in vivo depletion of cynomolgus monkey NK cells by ATX-130 administration at 5, 50, and 100 mg / kg. PBMCs were isolated from 0.5 mL of blood per animal per time point. 0.3 × 10⁶ cells per well were plated in technical triplicates and stained with an antibody panel. Cynomolgus monkey NK cells were identified using a CD3-CD16+ gating strategy. NK cells were quantified by calculating the percentage of this cell population out of the total PBMCs. [Figure 29] This figure shows in vivo depletion of cynomolgus monkey CD94+CD8+NKG2A+ cells by administration of ATX-130 at 5, 50, and 100 mg / kg. PBMCs were isolated from 0.5 mL of blood per animal per time point. 0.3 × 10⁶ cells per well were plated in technical triplicates and stained with an antibody panel. CD8+ T cells were identified using a CD3+CD8+NKG2A+ gating strategy. CD8 T cells were quantified by calculating the percentage of this cell population out of the total PBMCs. The identification symbols above each bar indicate the time point at which the PMBCs were isolated, corresponding to the time points illustrated in the figure legend. [Figure 30] This study demonstrates in vivo depletion of cynomolgus monkey NK cells and CD94+CD8+NKG2A+ T cells by dosing with ATX-130 at 5, 50, and 100 mg / kg or a vehicle control (using Dulbecco's phosphate-buffered saline (PBS)) at 0 mg / kg. Duodenum, liver, spleen, and bone marrow were collected at the study endpoint. Tissues were dissociated into single-cell suspensions, plated with 0.3 × 10⁶ cells per well using technical triplicates, and stained with an antibody panel. Cynomolgus monkey CD8+ T cells were identified using a CD3+CD8+NKG2A+ gating strategy. Cynomolgus monkey NK cells were identified using a CD45+CD3-NKG2A+ marker. Identifiers above each box plot indicate the antibodies used in the experiment. [Figure 31A]The graph shows the binding of the anti-CD94 antibody to normal human NK cells. The antibody is indicated by its ATX number. The results show that the anti-CD94 antibody with the ATX number bound to human NK cells. [Figure 31B] The figure shows the binding of the anti-CD94 antibody to HEK293 cells expressing cynomolgus monkey CD94. The antibody is indicated by its ATX number. The results show that the anti-CD94 antibody with the ATX number bound to cells expressing cynomolgus monkey CD94. [Figure 32A] The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Figure 32B] The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Figure 32C] The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Figure 32D] The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Figure 32E]The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Figure 32F] The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Figure 32G] The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Figure 32H] The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Figure 32I] The results of an HLA-E tetramer blockade assay to determine whether the anti-CD94 antibody shown blocks HLA-E binding are presented. PBMCs from healthy donors were incubated with the anti-CD94 antibody. PE-labeled HLA-E tetramers were then incubated with a mixture of cells and antibody and detected by flow cytometry. [Modes for carrying out the invention]

[0033] Several embodiments are described below with reference to illustrative uses for illustrative purposes. It should be understood that numerous specific details, relationships, and methods are described to provide a complete understanding of the features described herein. However, those skilled in the art will readily recognize that the features described herein can be implemented without using one or more of the specific details, or by other means. Since some actions can occur in different orders and / or simultaneously with other actions or events, the features described herein are not limited by the order of the exemplified actions or events. Furthermore, not all of the exemplified actions or events are required to implement a method according to the features described herein.

[0034] As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms unless explicitly indicated otherwise in the context. Furthermore, to the extent that the terms “including,” “includes,” “having,” “has,” and “with,” or their variations thereof, are used in either the detailed description and / or the claims, such terms are intended to be comprehensive in a manner similar to that of “comprising.” As used herein, “comprising” is synonymous with “including” or “contains,” and is either comprehensive or open.

[0035] Any reference to “or” in this specification is intended to include “and / or” unless otherwise specified. As used herein, “about” in reference to a number refers to that number and plus or minus 10% of that number. “About” in reference to a range refers to that range and minus 10% of its lower limit and plus 10% of its upper limit.

[0036] I. Antibodies In some embodiments, antibodies that bind to CD94, for example, human CD94 expressed on the surface of NK cells or T cells, are provided herein. Also provided herein are antibodies that bind to CD94 and have an immunoglobulin Fc moiety having modifications including reduced fucosylation, non-fucosylation, or mutations that enhance ADCC activity and / or improve the affinity of the Fc region to Fc receptors such as CD16 (e.g., CD16a). Also provided herein are antibodies that bind to CD94 and have one or more of the following properties: binding to human CD94 and cynomolgus monkey CD94, not blocking the binding of HLA-E to the CD94 / NKG2A heterodimer, having a low degree of target (e.g., CD94) internalization, having non-fucosylation or reduced fucosylation, and / or inducing or promoting ADCC activity.

[0037] A. Antibody target and affinity In some embodiments, the antibodies provided herein bind to CD94. In some embodiments, the antibodies provided herein bind to human CD94 (e.g., the extracellular domain of human CD94). In some embodiments, the antibodies provided herein bind to cynomolgus monkey CD94 (e.g., the extracellular domain of cynomolgus monkey CD94). In some embodiments, the antibodies provided herein bind to both human CD94 and cynomolgus monkey CD94. In some embodiments, the antibodies of this disclosure bind to CD94 on the surface of NK cells and / or T cells.

[0038] In some embodiments, the antibodies of this disclosure bind to human CD94 protein or a portion thereof, or to proteins having at least 80% homology (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) to human CD94 protein or a portion thereof. Representative amino acid sequences of human CD94 protein are provided as sequences of SEQ ID NOs. 25-27. [ka]

[0039] In some embodiments, the terms binding, specifically binding to, or being specific to refer to measurable and reproducible interactions, such as binding between a target and an antibody that determines the presence of the target in the presence of a heterogeneous population of molecules, including biomolecules. For example, an antibody that binds to, or specifically binds to, a target (which may be an epitope) is an antibody that binds to this target with higher affinity, binding activity, more readily, and / or for a longer duration than it would to bind to other targets. In one embodiment, the degree of antibody binding to an unrelated target is less than about 10% of the antibody binding to the target, as measured, for example, by radioimmunoassay (RIA). In certain embodiments, an antibody that specifically binds to a target has a dissociation constant (K) of <1 μM, <100 nM, <10 nM, <1 nM, or <0.1 nM. D ) has. In certain embodiments, the antibody specifically binds to an epitope on a protein that is conserved between different species of proteins. In other embodiments, specific binding may include, but is not required to include, exclusive binding.

[0040] In some embodiments, the antibodies provided herein bind to human CD94 (natural killer cell antigen CD94; CD94 Entrez Gene ID: 3824; KLRD1 (HGNC symbol); UniProtKB identification symbol: Q13241; HGNC: 6378; Ensembl: ENSG00000134539 OMIM: 602894; KP43).

[0041] In some embodiments, the antibodies of this disclosure bind to the cynomolgus monkey CD94 protein or a portion thereof, or to a protein having at least 80% homology (e.g., at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) to the cynomolgus monkey CD94 protein or a portion thereof. The amino acid sequence of the cynomolgus monkey CD94 protein is known in the art (e.g., UniProtKB identifier: Q68VD4).

[0042] In a particular embodiment, the affinity of an antibody for its target (e.g., CD94) is determined by the dissociation constant (K). D Affinity can be expressed by ). Affinity can be measured using assays described herein (e.g., in the Examples) by common methods known in the art, such as flow cytometry or Western blotting. In some embodiments, K D This is measured using an radiolabeled antigen-binding assay (RIA) performed with the Fab version of the antibody of this disclosure and its target (e.g., CD94). In some embodiments, K D This is measured using a surface plasmon resonance assay. A typical assay is described, for example, in Drake, A.W. and Klakamp, ​​SL (2007) J. Immunol. Methods 318:147-152.

[0043] In some embodiments, the binding of the antibodies of this disclosure to CD94, for example, human CD94 and / or cynomolgus monkey CD94, may be assessed using any method known in the art. For example, the binding of the antibodies of this disclosure to human CD94 may be assessed in an ex vivo flow cytometry-based assay using peripheral blood mononuclear cells (PMBCs) and / or NK cells, for example, as described in the Examples. Titration curves and EC50 may be generated and evaluated using methods known in the art, such as using Graphpad prism. In another example, the binding of the antibodies of this disclosure to cynomolgus monkey CD94 may be assessed in an ex vivo or in vitro flow cytometry-based assay using cynomolgus monkey CD94-expressing cells, such as cynomolgus monkey CD94-expressing HEK293 cells, for example, as described in the Examples.

[0044] In certain embodiments, the antibody of this disclosure has a binding ratio of less than approximately 10 μM to its target (e.g., human and / or cynomolgus monkey CD94). D It has. In certain embodiments, the antibody of this disclosure has a binding ratio of less than about 1 μM to its target (e.g., human and / or cynomolgus monkey CD94). D In certain embodiments, the antibodies of this disclosure have binding concentrations of less than approximately 1000 nM, less than approximately 900 nM, less than approximately 800 nM, less than approximately 700 nM, less than approximately 600 nM, less than approximately 500 nM, less than approximately 400 nM, less than approximately 300 nM, less than approximately 200 nM, less than approximately 100 nM, less than approximately 90 nM, with respect to their binding to their target (e.g., human and / or cynomolgus monkey CD94). K of any of the following types: less than approximately 80 nM, less than approximately 70 nM, less than approximately 60 nM, less than approximately 50 nM, less than approximately 40 nM, less than approximately 30 nM, less than approximately 20 nM, less than approximately 10 nM, less than approximately 9 nM, less than approximately 8 nM, less than approximately 7 nM, less than approximately 6 nM, less than approximately 5 nM, less than approximately 4 nM, less than approximately 3 nM, less than approximately 2 nM, less than approximately 1 nM, less than approximately 0.5 nM, or less than approximately 0.1 nM. Dhas. In some embodiments, the antibodies of the present disclosure have a K of less than about 100 pM, less than about 75 pM, less than about 50 pM, less than about 25 pM, less than about 10 pM, less than about 5 pM, less than about 1 pM, less than about 0.5 pM, or less than about 0.1 pM with respect to binding to its target (e.g., human and / or cynomolgus CD94). D has.

[0045] In certain embodiments, the antibodies of the present disclosure have a K of less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM with respect to binding to human CD94 on human NK cells or T cells. D has. In certain embodiments, the antibodies of the present disclosure have a K of less than about 75 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 9 nM, less than about 8 nM, less than about 7 nM, less than about 6 nM, less than about 5 nM, less than about 4 nM, less than about 3 nM, less than about 2 nM, less than about 1 nM, less than about 0.5 nM, or less than about 0.1 nM with respect to binding to human CD94 on human NK cells or T cells. D has. In certain embodiments, the antibodies of the present disclosure have a K of about 2 nM to about 80 nM with respect to binding to human CD94 on human NK cells or T cells. D [[ID=十二]]has.

[0046] In certain embodiments, the antibodies of this disclosure bind to cynomolgus monkey CD94 on cells expressing cynomolgus monkey CD94 in K levels of less than approximately 100 nM, less than approximately 90 nM, less than approximately 80 nM, less than approximately 70 nM, less than approximately 60 nM, less than approximately 50 nM, less than approximately 40 nM, less than approximately 30 nM, less than approximately 20 nM, less than approximately 10 nM, less than approximately 9 nM, less than approximately 8 nM, less than approximately 7 nM, less than approximately 6 nM, less than approximately 5 nM, less than approximately 4 nM, less than approximately 3 nM, less than approximately 2 nM, less than approximately 1 nM, less than approximately 0.5 nM, or less than approximately 0.1 nM. D In certain embodiments, the antibody of this disclosure has a K content of less than approximately 75 nM, less than approximately 80 nM, less than approximately 70 nM, less than approximately 60 nM, less than approximately 50 nM, less than approximately 40 nM, less than approximately 30 nM, less than approximately 20 nM, less than approximately 10 nM, less than approximately 9 nM, less than approximately 8 nM, less than approximately 7 nM, less than approximately 6 nM, less than approximately 5 nM, less than approximately 4 nM, less than approximately 3 nM, less than approximately 2 nM, less than approximately 1 nM, less than approximately 0.5 nM, or less than approximately 0.1 nM. D It has. In certain embodiments, the antibody of this disclosure has a binding of about 2 nM to about 80 nM to cynomolgus monkey CD94 on cells expressing cynomolgus monkey CD94. D It has.

[0047] In some embodiments, the antibodies of the Disclosure bind to their target (e.g., CD94) at an epitope that is the same as or different from that of antibodies known in the Art with respect to that target. In some embodiments, the antibodies of the Disclosure bind to an epitope different from that of antibodies known in the Art. In some embodiments, the antibodies of the Disclosure bind specifically to human CD94, and the antibodies do not bind to the same epitope as anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45 on human CD94. In some embodiments, the antibodies of the Disclosure bind specifically to human CD94, and the antibodies do not bind to the same epitope as anti-CD94 antibody clones DX22, HP-3B1, or 131412 on human CD94. In some embodiments, the antibody of the Disclosure specifically binds to human CD94, and the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, the antibody of the Disclosure specifically binds to human CD94, and the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clone HP-3D9. In some embodiments, the antibody of the Disclosure specifically binds to human CD94, and the antibody binds to the same epitope on human CD94 as anti-CD94 antibody clone 12K45.

[0048] In some embodiments, if the antibody of the Disclosure does not bind to its target (e.g., CD94) at the same epitope as another antibody against its target, such as a commercially available antibody or an antibody known in the art with respect to that target, the antibody of the Disclosure does not block, for example, more than 50% of the binding of the other antibody to the target in a competitive assay (e.g., as described in the Examples).

[0049] In some embodiments, the antibodies of the Disclosure bind to their target (e.g., CD94) with higher affinity than antibodies known in the Art with respect to that target. In some embodiments, the antibodies of the Disclosure bind to their target (e.g., CD94) with higher affinity than anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45. In some embodiments, the antibodies of the Disclosure bind to their target (e.g., CD94) with higher affinity than anti-CD94 antibody clones HP-3B1, 131412, or 12K45.

[0050] In some embodiments, the antibodies of the Disclosure bind specifically to human CD94, and the antibodies bind to human CD94 with higher affinity than anti-CD94 antibody clones HP-3D9, DX22, HP-3B1, 131412, or 12K45.

[0051] In some embodiments, the antibodies of the present disclosure bind to their target (e.g., CD94) with any affinity that is at least 1.5 times, at least 2 times, at least 2.5 times, at least 3 times, at least 3.5 times, at least 4 times, at least 4.5 times, at least 5 times, at least 5.5 times, at least 6 times, at least 6.5 times, at least 7 times, at least 7.5 times, at least 8 times, at least 8.5 times, at least 9 times, at least 9.5 times, at least 10 times, or more than any other antibody known in the art with respect to that target.

[0052] B. Representative anti-CD94 antibodies In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 1. CDR-H1, containing an amino acid sequence with at least 99% or 100% sequence identity, contains an amino acid sequence with at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 3. CDR-L1 comprising DR-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 4.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 5, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 6.

[0053] In some embodiments, the antibodies of the present disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 1; CDR-H2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 2; and CDR-H3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 3; and the VL domain includes CDR-L1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 4; CDR-L2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 5; and CDR-L3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 6.

[0054] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 1, CDR-H2 containing the amino acid sequence of SEQ ID NO: 2, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 4, CDR-L2 containing the amino acid sequence of SEQ ID NO: 5, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 6.

[0055] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 20.

[0056] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 19 and the VL domain comprises the amino acid sequence of SEQ ID NO: 20.

[0057] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less CDR-H1, containing amino acid sequences with 99% or 100% sequence identity, and the amino acid sequence of Sequence ID No. 8, both have at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having the same properties, and CD containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 9. CDR-L1 containing R-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 10.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 11, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 12.

[0058] In some embodiments, the antibodies of the present disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 7; CDR-H2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 8; and CDR-H3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 9; and the VL domain includes CDR-L1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 10; CDR-L2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 11; and CDR-L3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 12.

[0059] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 7, CDR-H2 containing the amino acid sequence of SEQ ID NO: 8, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 10, CDR-L2 containing the amino acid sequence of SEQ ID NO: 11, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 12.

[0060] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 22.

[0061] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 21 and the VL domain comprises the amino acid sequence of SEQ ID NO: 22.

[0062] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 13. CDR-H1, containing an amino acid sequence with at least 99% or 100% sequence identity, contains an amino acid sequence with at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to the amino acid sequence of Sequence ID No. 14. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 15. CDR-L1 comprising DR-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 16.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 17, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 18.

[0063] In some embodiments, the antibodies of the present disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 13; CDR-H2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 14; and CDR-H3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 15; and the VL domain includes CDR-L1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 16; CDR-L2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 17; and CDR-L3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 18.

[0064] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 13, CDR-H2 containing the amino acid sequence of SEQ ID NO: 14, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 16, CDR-L2 containing the amino acid sequence of SEQ ID NO: 17, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 18.

[0065] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 24.

[0066] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 23 and the VL domain comprises the amino acid sequence of SEQ ID NO: 24.

[0067] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 30. CDR-H1, which contains an amino acid sequence having at least 99% or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 31, contains at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 31. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 32. CDR-L1 comprising DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 33.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 35.

[0068] In some embodiments, the antibodies of this disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, CDR-H2, CDR-H3, and CDR-L1, CDR-L2, and CDR-L3, CDR-H1, CDR-L2, and CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L3, CDR-L1, CDR-L2, and CDR-L3, respectively. The VL domain includes CDR-L1, CDR-L2, and CDR-L3, CDR-L3, and CDR-L2, CDR-L3, and CDR-L3, CDR-L2, and CDR-L3, respectively.

[0069] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 30, CDR-H2 containing the amino acid sequence of SEQ ID NO: 31, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35.

[0070] In some embodiments, the antibody of the Disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 66.

[0071] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises the amino acid sequence of SEQ ID NO: 66.

[0072] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 36. CDR-H1, which contains an amino acid sequence having at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 37, has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 38. CDR-L1 comprising DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 33.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 35.

[0073] In some embodiments, the antibodies of this disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 36; CDR-H2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 37; and CDR-H3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 38; and the VL domain includes CDR-L1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 33; CDR-L2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 34; and CDR-L3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 35.

[0074] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing the amino acid sequence of SEQ ID NO: 37, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35.

[0075] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 68.

[0076] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68.

[0077] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 36. CDR-H1, containing an amino acid sequence having at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 39, has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 40. CDR-L1 comprising DR-H3, wherein the VL domain comprises an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 33.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 35.

[0078] In some embodiments, the antibodies of this disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 36; CDR-H2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 39; and CDR-H3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 40; and the VL domain includes CDR-L1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 33; CDR-L2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 34; and CDR-L3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 35.

[0079] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 36, CDR-H2 containing the amino acid sequence of SEQ ID NO: 39, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 33, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35.

[0080] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 70.

[0081] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises the amino acid sequence of SEQ ID NO: 70.

[0082] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 41. CDR-H1, which contains an amino acid sequence having at least 99% or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 42, has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 43. CDR-L1 comprising DR-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 44.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 45, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 46.

[0083] In some embodiments, the antibodies of this disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, CDR-H2, CDR-H3, and CDR-H3, CDR-L1, CDR-L2, and CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L3, CDR-L2, and CDR-L3, CDR-L2, and CDR-L3, respectively.

[0084] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 41, CDR-H2 containing the amino acid sequence of SEQ ID NO: 42, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 44, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 46.

[0085] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 72.

[0086] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises the amino acid sequence of SEQ ID NO: 72.

[0087] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 47. CDR-H1, which contains an amino acid sequence having at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 48, has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 49. CDR-L1 comprising DR-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 50.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 51, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 52.

[0088] In some embodiments, the antibodies of the present disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, CDR-H2, CDR-H3, and CDR-L1, CDR-L2, and CDR-L3, CDR-H1, CDR-L2, and CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L2, and CDR-L3, respectively.

[0089] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 51, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 52.

[0090] In some embodiments, the antibody of the Disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 74.

[0091] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises the amino acid sequence of SEQ ID NO: 74.

[0092] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 53. CDR-H1, containing an amino acid sequence having at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 54, has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 55. CDR-L1 comprising DR-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 50.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 45, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 56.

[0093] In some embodiments, the antibodies of this disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 53; CDR-H2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 54; and CDR-H3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 55; and the VL domain includes CDR-L1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 50; CDR-L2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 45; and CDR-L3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 56.

[0094] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 53, CDR-H2 containing the amino acid sequence of SEQ ID NO: 54, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 45, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 56.

[0095] In some embodiments, the antibody of the Disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 76.

[0096] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises the amino acid sequence of SEQ ID NO: 76.

[0097] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 57. CDR-H1, containing an amino acid sequence having at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 58, has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 59. CDR-L1 comprising DR-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 60.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 61.

[0098] In some embodiments, the antibodies of the present disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, CDR-H2, CDR-H3, and CDR-H3, CDR-L1, CDR-L2, and CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L3, CDR-L1, CDR-L2, and CDR-L3, CDR-L3, CDR-L2, and CDR-L3, CDR-L2, and CDR-L3, respectively.

[0099] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 57, CDR-H2 containing the amino acid sequence of SEQ ID NO: 58, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 60, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61.

[0100] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 78.

[0101] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises the amino acid sequence of SEQ ID NO: 78.

[0102] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 83. CDR-H1, which contains an amino acid sequence having at least 99% or 100% sequence identity with the amino acid sequence of Sequence ID No. 84, has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 85. CDR-L1 comprising DR-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 86.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 61.

[0103] In some embodiments, the antibodies of the present disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 83; CDR-H2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 84; and CDR-H3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 85; and the VL domain includes CDR-L1, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 86; CDR-L2, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 34; and CDR-L3, which includes an amino acid sequence comprising one, two, or three amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 61.

[0104] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 83, CDR-H2 containing the amino acid sequence of SEQ ID NO: 84, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 86, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61.

[0105] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 80.

[0106] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises the amino acid sequence of SEQ ID NO: 80.

[0107] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and less than 90% of the amino acid sequence of SEQ ID NO: 47. CDR-H1, which contains an amino acid sequence having at least 99% or 100% sequence identity with the amino acid sequence of SEQ ID NO: 48, has at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. CDR-H2 containing an amino acid sequence having a unique sequence identity, and C containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of SEQ ID NO: 62. CDR-L1 comprising DR-H3, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 63.CDR-L2 containing an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 34, and CDR-L3 contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with the amino acid sequence of SEQ ID NO: 64.

[0108] In some embodiments, the antibodies of the present disclosure include a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain includes CDR-H1, CDR-H2, CDR-H3, CDR-H1, CDR-H2, CDR-H3, CDR-H1, CDR-H2, CDR-H3, CDR-H3, CDR-H1, CDR-L2, CDR-L3, CDR-L3, CDR-L1, CDR-L2, CDR-L3, CDR-L3, CDR-L3, CDR-L1, CDR-L2, CDR-L3, CDR-L3, CDR-L3, CDR-L22, CDR-L3, CDR-L3, CDR-L2, CDR-L3, CDR-L2, CDR-L3, CDR-L2, CDR-L3, CDR-L2, CDR-L3, CDR-L2, CDR-L3,

[0109] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 63, CDR-L2 containing the amino acid sequence of SEQ ID NO: 34, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 64.

[0110] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or The VL domain contains an amino acid sequence having 100% sequence identity, wherein the VL domain contains an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity with respect to the amino acid sequence of Sequence ID No. 82.

[0111] In some embodiments, the antibody of this disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises the amino acid sequence of SEQ ID NO: 82.

[0112] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing the amino acid sequence of SEQ ID NO: 88, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 89, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35.

[0113] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 93, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35.

[0114] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 87, CDR-H2 containing the amino acid sequence of SEQ ID NO: 92, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 94, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 90, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 35.

[0115] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 95, CDR-H2 containing the amino acid sequence of SEQ ID NO: 96, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 97, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 98, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 100.

[0116] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 114, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 115, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 52.

[0117] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 116, CDR-H2 containing the amino acid sequence of SEQ ID NO: 117, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 118, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 115, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 56.

[0118] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 101, CDR-H2 containing the amino acid sequence of SEQ ID NO: 102, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 103, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 104, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61.

[0119] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 105, CDR-H2 containing the amino acid sequence of SEQ ID NO: 106, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 107, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 108, CDR-L2 containing the amino acid sequence of SEQ ID NO: 91, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 61.

[0120] In some embodiments, the antibody of the present disclosure comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 111, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 112, CDR-L2 containing the amino acid sequence of SEQ ID NO: 113, and CDR-L3 containing the amino acid sequence of SEQ ID NO: 64.

[0121] In some embodiments, the antibodies of this disclosure include a VH domain containing one, two, or three CDRs from a single antibody listed in Table 1, and / or a VL domain containing one, two, or three CDRs from a single antibody listed in Table 1. In some embodiments, the antibodies of this disclosure include VH and / or VL domains from a single antibody listed in Table 2. [Table 1-1] [Table 1-2] [Table 1-3] [Table 2-1] [Table 2-2]

[0122] Many definitions of CDR sequences for the variable domains of antibodies are known in the art and, for example, can be used to describe the antibodies of this disclosure by their CDR sequences. In some embodiments, the antibody CDR sequence is defined as found in Kabat (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991). In some embodiments, the antibody CDR sequence is defined as found in Chothia (see, e.g., Chothia and Lesk J. Mol. Biol. 196:901-917 (1987)). In some embodiments, the antibody CDR sequence is defined as found in IMGT (see, e.g., Lefranc, MP (1999) The Immunologist 7:132-136). In some embodiments, the CDR sequence of a single antibody is defined by mixing two or more definitions, e.g., Kabat, Chothia, and / or IMGT. In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 65, and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the VH domain sequence of ATX-122 described herein (see, for example, Table 2), and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the VL domain sequence of ATX-122 described herein (see, for example, Table 2). In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 67, and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 68.In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the VH domain sequence of ATX-123 described herein (see, for example, Table 2), and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the VL domain sequence of ATX-123 described herein (see, for example, Table 2). In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 69, and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 70. In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the VH domain sequence of ATX-124 described herein (see, for example, Table 2), and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the VL domain sequence of ATX-124 described herein (see, for example, Table 2). In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 71, and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the VH domain sequence of ATX-125 described herein (see, for example, Table 2), and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the VL domain sequence of ATX-125 described herein (see, for example, Table 2). In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 73, and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 74.In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the VH domain sequence of ATX-126 described herein (see, for example, Table 2), and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the VL domain sequence of ATX-126 described herein (see, for example, Table 2). In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 75, and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 76. In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the VH domain sequence of ATX-127 described herein (see, for example, Table 2), and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the VL domain sequence of ATX-127 described herein (see, for example, Table 2). In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 77, and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 78. In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the VH domain sequence of ATX-128 described herein (see, for example, Table 2), and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the VL domain sequence of ATX-128 described herein (see, for example, Table 2). In some embodiments, the antibody of this disclosure comprises a VH domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 79, and / or a VL domain containing one, two, or all three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 80.In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the VH domain sequence of ATX-129 described herein (see, for example, Table 2), and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the VL domain sequence of ATX-129 described herein (see, for example, Table 2). In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 81, and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the amino acid sequence of SEQ ID NO: 82. In some embodiments, the antibody of this disclosure comprises a VH domain containing all one, two, or three CDR or HVR sequences present in the VH domain sequence of ATX-130 described herein (see, for example, Table 2), and / or a VL domain containing all one, two, or three CDR or HVR sequences present in the VL domain sequence of ATX-130 described herein (see, for example, Table 2).

[0123] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0124] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain binds to an epitope on human or cynomolgus monkey CD94 which is the same as the CD94 epitope to which the anti-CD94 antibody binds, the VH domain comprising the amino acid sequence of SEQ ID NO: 19 and the VL domain comprising the amino acid sequence of SEQ ID NO: 20.

[0125] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0126] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain binds to an epitope on human or cynomolgus monkey CD94 which is the same as the CD94 epitope to which the anti-CD94 antibody binds, the VH domain comprising the amino acid sequence of SEQ ID NO: 21 and the VL domain comprising the amino acid sequence of SEQ ID NO: 22.

[0127] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0128] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain binds to an epitope on human or cynomolgus monkey CD94 which is the same as the CD94 epitope to which the anti-CD94 antibody binds, the VH domain comprising the amino acid sequence of SEQ ID NO: 23 and the VL domain comprising the amino acid sequence of SEQ ID NO: 24.

[0129] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0130] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain binds to an epitope on human or cynomolgus monkey CD94 which is the same as the CD94 epitope to which the anti-CD94 antibody binds, the VH domain comprising the amino acid sequence of SEQ ID NO: 65 and the VL domain comprising the amino acid sequence of SEQ ID NO: 66.

[0131] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0132] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68, and the same CD94 epitope to which the anti-CD94 antibody binds is the same.

[0133] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0134] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain binds to an epitope on human or cynomolgus monkey CD94 which is the same as the CD94 epitope to which the anti-CD94 antibody binds, the VH domain comprising the amino acid sequence of SEQ ID NO: 69 and the VL domain comprising the amino acid sequence of SEQ ID NO: 70.

[0135] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0136] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises the amino acid sequence of SEQ ID NO: 72, and the same epitope on human or cynomolgus monkey CD94 is conjugated by the anti-CD94 antibody.

[0137] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 51, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 52, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0138] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises the amino acid sequence of SEQ ID NO: 74, and the same CD94 epitope to which the anti-CD94 antibody binds is the same.

[0139] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0140] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain binds to an epitope on human or cynomolgus monkey CD94 which is the same as the CD94 epitope to which the anti-CD94 antibody binds, the VH domain comprising the amino acid sequence of SEQ ID NO: 75 and the VL domain comprising the amino acid sequence of SEQ ID NO: 76.

[0141] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0142] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises the amino acid sequence of SEQ ID NO: 78, and the same epitope on human or cynomolgus monkey CD94 to which the anti-CD94 antibody binds.

[0143] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0144] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises the amino acid sequence of SEQ ID NO: 80, and the same epitope on human or cynomolgus monkey CD94 to which the anti-CD94 antibody binds.

[0145] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64, and binds to an epitope on human or cynomolgus monkey CD94 that is the same as the CD94 epitope to which the anti-CD94 antibody binds.

[0146] In some embodiments, the antibody of the present disclosure is an anti-CD94 antibody comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain binds to an epitope on human or cynomolgus monkey CD94 which is the same as the CD94 epitope to which the anti-CD94 antibody binds, the VH domain comprising the amino acid sequence of SEQ ID NO: 81 and the VL domain comprising the amino acid sequence of SEQ ID NO: 82.

[0147] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0148] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 19 and the VL domain comprises the amino acid sequence of SEQ ID NO: 20.

[0149] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 7, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 8, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 9, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 12.

[0150] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 21 and the VL domain comprises the amino acid sequence of SEQ ID NO: 22.

[0151] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 18.

[0152] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 23 and the VL domain comprises the amino acid sequence of SEQ ID NO: 24.

[0153] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 31, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 32, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0154] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 65 and the VL domain comprises the amino acid sequence of SEQ ID NO: 66.

[0155] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 37, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 38, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0156] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 67 and the VL domain comprises the amino acid sequence of SEQ ID NO: 68.

[0157] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 36, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 40, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 33, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 35.

[0158] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 69 and the VL domain comprises the amino acid sequence of SEQ ID NO: 70.

[0159] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 41, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 42, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 43, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 44, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 46.

[0160] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 71 and the VL domain comprises the amino acid sequence of SEQ ID NO: 72.

[0161] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 51, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 52.

[0162] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises the amino acid sequence of SEQ ID NO: 74.

[0163] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 53, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 54, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 55, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 50, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 56.

[0164] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 75 and the VL domain comprises the amino acid sequence of SEQ ID NO: 76.

[0165] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 57, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 58, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 59, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 60, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0166] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 77 and the VL domain comprises the amino acid sequence of SEQ ID NO: 78.

[0167] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 83, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 84, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 85, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 86, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 61.

[0168] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 79 and the VL domain comprises the amino acid sequence of SEQ ID NO: 80.

[0169] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises CDR-H1 comprising the amino acid sequence of SEQ ID NO: 47, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 48, and CDR-H3 comprising the amino acid sequence of SEQ ID NO: 62, and the VL domain comprises CDR-L1 comprising the amino acid sequence of SEQ ID NO: 63, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 64.

[0170] In some embodiments, the antibodies of the present disclosure compete with anti-CD94 antibodies comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain for binding to human or cynomolgus monkey CD94, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 81 and the VL domain comprises the amino acid sequence of SEQ ID NO: 82.

[0171] In some embodiments, the antibody of this disclosure includes an Fc region. In some embodiments, the Fc region is a human IgG1 Fc region. In some embodiments, the antibody includes an unfucosylated human Fc region. In some embodiments, the antibody binds to human cell Fc gamma receptor IIIA to a higher degree than an antibody containing a wild-type human IgG1 Fc region. In some embodiments, the antibody can induce antibody-dependent cytotoxicity (ADCC) against cells expressing human CD94 on their surface.

[0172] In some embodiments, the term antibody is used in its broadest sense to encompass a variety of antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, as long as they exhibit the desired antigen-binding activity. In some embodiments, the antibodies of this disclosure are isolated antibodies. An “isolated” antibody is one that has been identified, separated, and / or recovered from components of its natural environment. Contaminating components of its natural environment are materials that would interfere with the research, diagnostic, and / or therapeutic use of the antibody and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In some embodiments, the antibody is purified to (1) to more than 95% by weight of antibody, and in some embodiments to more than 99% by weight, as determined, for example by the Lowry method; (2) to a degree sufficient to obtain at least 15 residues of the N-terminal or internal amino acid sequence, for example by using a spinning cup sequencer; or (3) to homogenize by SDS-PAGE under reducing or non-reducing conditions, for example, using Coomassie blue or silver staining. Isolated antibodies contain antibodies from the in situ of recombinant cells because they lack at least one component of the antibody's natural environment. However, isolated antibodies are typically prepared through at least one purification step.

[0173] In some embodiments, monoclonal antibodies are antibodies obtained from a substantially homogeneous population of antibodies, i.e., the individual antibodies constituting the population are identical and / or bind to the same epitope, with the exception of possible variant antibodies, such as those containing naturally occurring mutations or arising during the preparation of the monoclonal antibody preparation, which are generally present in small amounts. In contrast to polyclonal antibody preparations, which typically contain different antibodies pointing to different determinants (epitopes), each monoclonal antibody in a monoclonal antibody preparation points to a single determinant on an antigen. Thus, in some embodiments, monoclonal antibodies are obtained from a substantially homogeneous population of antibodies. Monoclonal antibodies may be prepared using any method known in the art. For example, monoclonal antibodies used in accordance with this disclosure may be prepared by a variety of techniques, including but not limited to hybridoma methods, recombinant DNA methods, phage display methods, and methods utilizing transgenic animals containing all or part of a human immunoglobulin locus.

[0174] Blocking of C.HLA-E binding Major histocompatibility complex class I, E (HLA-E) is a ligand for the CD94 / NKG2A heterodimer and plays an essential role in inhibiting NK cell and CD8+ T cell activity when bound to the CD94 / NKG2A heterodimer. Therefore, although we do not wish to be bound by theory, blocking the interaction between HLA-E and CD94 / NKG2A may result in the activation and proliferation of target cells, such as those expressing CD94. Thus, for example, in a subject with NK / T cell lymphoma treated with an anti-CD94 antibody, it may be beneficial that the anti-CD94 antibody does not block the interaction of HLA-E with the CD94 / NKG2A heterodimer. In some embodiments, HLA-E refers to human HLA-E, also known as QA1 and HLA-6.2. For representative HLA-E genes, please refer to, for example, NCBI gene ID number 3133, and for representative HLA-E polypeptides, please refer to, for example, NP_005507.3.

[0175] In some embodiments, blocking the binding of HLA-E to the CD94 / NKG2A heterodimer refers to blocking the binding of HLA-E to the CD94 / NKG2A heterodimer, blocking the binding of HLA-E to CD94, and / or blocking the binding of HLA-E to NKG2A.

[0176] The blocking of HLA-E binding to the CD94 / NKG2A heterodimer by the antibodies of this disclosure may be assessed using any method known in the art. For example, the blocking of HLA-E binding to the CD94 / NKG2A heterodimer by the antibodies of this disclosure may be assessed using an ex vivo assay using PBMCs and / or NK cells, for example, as described in the examples. In a typical assay, for example, PBMCs obtained from a healthy donor are incubated with human Fc block (Biolegend, San Diego, CA) and cell viability dye (Thermo Fisher, Carlsbad, CA) on ice for 30 minutes, protected from light. The cells are then washed once with FACS buffer (PBS containing 2% low IgG FBS). A saturated concentration of anti-CD94 antibody or isotype control antibody is incubated with the cells on ice for 30 minutes, protected from light. Next, the cells are washed and incubated with HLA-E tetramer PE (Creative Biolabs, Shirley, NY), CD3 Pacific Blue antibody, and CD56 FITC antibody (Biolegend, San Diego, CA) on ice for 30 minutes under protection from light. Then, the cells are subjected to a final wash in FACS buffer and quantified by flow cytometry. Data acquisition and fluorescence correction may be performed using methods known in the art, such as using a CytoFlex flow cytometer (Beckman Coulter, Chaska, MN). Data analysis may be performed using any method known in the art, such as using FlowJo software. NK cells are identified by gating lymphocytes based on forward and lateral scattered light, followed by exclusion of doublets and dead cells, and then gating the CD3-CD56+ population. HLA-E is then quantified in the CD3-CD56+ NK cell population. The percentage of HLA-E binding to the CD94 / NKG2A heterodimer blocked by an anti-CD94 antibody compared to a control antibody, such as an isotype control antibody, is calculated as 100 - ((percentage of HLA-E positive against anti-CD94 antibody) / (percentage of HLA-E positive against isotype) × 100).

[0177] In some embodiments, an antibody blocks the binding of HLA-E to the CD94 / NKG2A heterodimer if it blocks more than about 20% of HLA-E binding to the CD94 / NKG2A heterodimer compared to, for example, an isotype control antibody. In some embodiments, an antibody blocks the binding of HLA-E to the CD94 / NKG2A heterodimer if it blocks about 21%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99%, or 100% of HLA-E binding to the CD94 / NKG2A heterodimer compared to, for example, a control antibody, for example, an isotype control antibody.

[0178] In some embodiments, an antibody does not block the binding of HLA-E to the CD94 / NKG2A heterodimer if it blocks approximately 20% or less of the binding of HLA-E to the CD94 / NKG2A heterodimer compared to, for example, an isotype control antibody. In some embodiments, an antibody does not block the binding of HLA-E to the CD94 / NKG2A heterodimer if it blocks approximately 20%, approximately 18%, approximately 16%, approximately 14%, approximately 12%, approximately 10%, approximately 8%, approximately 6%, approximately 4%, approximately 2%, approximately 1%, approximately 0.5%, or 0% of the binding of HLA-E to the CD94 / NKG2A heterodimer compared to, for example, a control antibody, for example, an isotype control antibody.

[0179] In some embodiments, the antibodies provided herein do not block the binding of HLA-E to the CD94 / NKG2A heterodimer. In some embodiments, the antibodies provided herein block approximately 20% or less, approximately 19% or less, approximately 18% or less, approximately 17% or less, approximately 16% or less, approximately 15% or less, approximately 14% or less, approximately 13% or less, approximately 12% or less, approximately 11% or less, approximately 10% or less, approximately 9% or less, approximately 8% or less, approximately 6% or less, approximately 5% or less, approximately 4% or less, approximately 3% or less, approximately 2% or less, approximately 1% or less, approximately 0.5% or less, or 0% of the binding of HLA-E to the CD94 / NKG2A heterodimer compared to a control antibody, for example, an isotype control antibody.

[0180] D. Enhanced ADCC activity In some embodiments, antibody-dependent cell-mediated cytotoxicity, antibody-directed cytotoxicity, or ADCC refers to a cell-mediated response in which nonspecific cytotoxic cells that produce Fc receptors, such as natural killer (NK) cells, neutrophils, and macrophages, recognize antibodies bound to target cells, and subsequently cause lysis of the target cells. The primary mediator cells are natural killer (NK) cells. NK cells express FcγRIII (Ravetch). et al. (1991) Annu. Rev. Immunol., 9:457-92). In some embodiments, ADCC activity refers to the ability of an antibody or Fc fusion protein to induce an ADCC reaction.

[0181] In some embodiments, the antibodies provided herein have enhanced antibody-dependent cytotoxicity (ADCC) activity. In some embodiments, enhanced ADCC activity means that the antibody or the Fc region of the antibody more efficiently and / or effectively mediates or induces ADCC in vitro or in vivo in the presence of effector cells than the natural or wild-type antibody and / or the natural or wild-type Fc region of the antibody, which can be determined, for example, by using ADCC assays described herein or known in the art. In some embodiments, the effector cells are leukocytes that produce one or more Fc receptors and perform effector function. In some embodiments, such cells produce at least FcγRIII and perform ADCC effector function. Examples of human leukocytes that mediate ADCC include peripheral blood mononuclear cells (PBMCs), natural killer cells (NK), monocytes, cytotoxic T cells, and neutrophils.

[0182] In some embodiments, ADCC activity was measured using peripheral blood mononuclear cells (PBMCs) and / or NK effector cells. 51ADCC activity can be directly assessed using an in vitro assay, e.g., a Cr release assay (see, e.g., Shields et al. (2001) J. Biol. Chem., 276:6591-6604) or another preferred method. ADCC activity may be expressed as the number of cells remaining after the ADCC assay, or as the concentration of the antibody or Fc fusion protein (e.g., EC50 or IC50) at which half of the target cells are lysed. In some embodiments, ADCC activity is determined using an ex vivo assay using PBMCs, LGL cells, and / or NK cells, e.g., as described in the Examples, and the ADCC activity of the antibody of this disclosure is described as the percentage of target cells remaining after the ADCC assay and / or as the IC50 or EC50 of the antibody (i.e., the concentration of the antibody of this disclosure at which half of the maximum target cell depletion or cytolysis is achieved). The IC50 or EC50 of the antibody may be determined using any method known in the art, e.g., using dose-response curves and GraphPad Prism.

[0183] In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 of approximately 1 ng / ml to approximately 100 ng / ml (e.g., any of approximately 1 ng / ml, 2 ng / ml, 3 ng / ml, 4 ng / ml, 5 ng / ml, 10 ng / ml, 15 ng / ml, 20 ng / ml, 25 ng / ml, 30 ng / ml, 35 ng / ml, 40 ng / ml, 45 ng / ml, 50 ng / ml, 55 ng / ml, 60 ng / ml, 65 ng / ml, 70 ng / ml, 75 ng / ml, 80 ng / ml, 85 ng / ml, 90 ng / ml, 95 ng / ml, or 100 ng / ml) as measured using an ex vivo assay. In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 of approximately 20 ng / ml or less, as measured using an ex vivo assay. In some embodiments, the antibodies provided herein induce ADCC activity with an IC50 or EC50 of approximately 60 ng / ml or less, as measured using an ex vivo assay. In some embodiments, the antibodies of the Disclosure exhibit an IC50 or EC50 that is at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% lower than the IC50 or EC50 of a control antibody (e.g., a wild-type control antibody, or an antibody known or commercially available in the art against the same target).

[0184] In some embodiments, IC50 or EC50 refers to the concentration of a compound (e.g., an antibody) that induces an intermediate response between baseline and maximum after a specified exposure time. For example, IC50 or EC50 may be used to measure the potency of an antibody with respect to effector function, e.g., mediating and / or inducing ADCC activity. In some embodiments, the IC50 or EC50 of the dose-response curve represents the concentration of a compound (e.g., an antibody) at which 50% of its maximum effect is observed.

[0185] In some embodiments, the antibodies of the Disclosure have a higher maximum target cell lysis compared to a control antibody (e.g., a wild-type control antibody, or an antibody known or commercially available in the Art against the same target). For example, the antibodies of the Disclosure may exhibit a maximum target cell lysis that is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% higher than the maximum target cell lysis of a control antibody (e.g., a wild-type control antibody, or an antibody known or commercially available in the Art against the same target).

[0186] (i) Enhanced binding to Fc receptors In some embodiments, the antibodies provided herein contain a human immunoglobulin Fc region having enhanced ADCC activity compared to the wild-type Fc region. In some embodiments, the antibodies provided herein bind to human cell Fc receptors to a higher degree than antibodies containing the wild-type Fc region. In some embodiments, the Fc receptor (FcR) is a receptor that can bind to the Fc region of an antibody. Certain Fc receptors can bind to IgG (i.e., γ-receptors), and such receptors include the subclasses FcyRI, FcyRII, and FcyRIII, as well as their allele variants and alternative splicing events. For an overview of Fc receptors, see Ravetch and China: Annu. Port. Immunol. 9, 457 (1991), Capel et al. Immunomethods, 4, 25 (1994), and de Haas et al., J. Leg. Clin. Med. 126, 330 (1995).

[0187] In some embodiments, the antibodies provided herein bind to human cell Fc gamma receptor IIIA to a higher degree than antibodies containing the wild-type Fc region. In some embodiments, human cell Fc gamma receptor IIIA contains a valine or phenylalanine residue at amino acid position 158. See, for example, UniProt commission P08637 or VAR_003960. In some embodiments, human cell Fc gamma receptor IIIA contains the sequence of SEQ ID NO: 28 or 29. Human cell Fc gamma receptor IIIA 158F [ka] Human cell Fc gamma receptor IIIA 158V [ka]

[0188] In some embodiments, the antibodies provided herein are IgG (e.g., IgG1, IgG2, IgG3, or IgG4), IgA (IgA1 or IgA2), IgD, IgM, or IgE isotypes. In some embodiments, the antibodies provided herein are IgG isotypes. In some embodiments, the antibodies provided herein are IgG1 isotypes. In some embodiments, the antibodies provided herein bind to human cell Fc gamma receptor IIIA (FcγRIIIA) to a higher degree than antibodies containing the wild-type human IgG1 Fc region. In some embodiments, human cell Fc gamma receptor IIIA contains a valine or phenylalanine residue at amino acid position 158. Representative assays for determining the binding of human cells to the Fc gamma receptor IIIA are known in the art; see, for example, Lazar, GA et al. (2006) Proc. Natl. Acad. Sci. 103:4005-1010 and Ferrara, C. et al. (2011) Proc. Natl. Acad. Sci. 108:12669-12674.

[0189] In some embodiments, the Fc region is the C-terminal region of an immunoglobulin heavy chain containing at least a portion of the constant region. In some embodiments, the Fc region includes a native Fc region or a variant Fc region. In one embodiment, the human IgG heavy chain Fc region extends from Cys226 or Pro230 to the carboxyl terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. In some embodiments, the numbering of amino acid residues in the Fc region or constant region follows the EU numbering system, also known as the EU Index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991. In some embodiments, the wild-type Fc region or native Fc region is an Fc region containing an amino acid sequence identical to the amino acid sequence of an Fc region found in nature. In some embodiments, the variant Fc region is an Fc region in which at least one amino acid is in a sequence different from the natural or wild-type sequence of the Fc region. In some embodiments, the variant Fc region has at least one amino acid substitution, e.g., approximately 1 to 10 or 1 to 5 amino acid substitutions. In some embodiments, the Fc region variant is at least approximately 80% (e.g., at least about 90%, or at least about 95%) homologous to the natural or wild-type sequence of the Fc region and / or the Fc region of the original polypeptide. In some embodiments, at least one amino acid substitution in the variant Fc region enhances the effector function of the variant Fc region compared to the natural or wild-type Fc region. In some embodiments, effector function is a biological activity that can be attributed to the Fc region of the antibody, which varies depending on 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), antibody-dependent cell-mediated phagocytosis (ADCP), downregulation of cell surface receptors (e.g., B cell receptors), and B cell activation.

[0190] The binding affinity of an antibody to the Fc receptor may be assessed using any method known in the art, such as using surface plasmon resonance and / or ELISA, as described, for example, in Shields et al. (2001) J. Biol. Chem., 276:6591-6604. In some embodiments, the affinity of the antibody of this disclosure to FcγRIIIA may be at least about 1.5 times, at least about 2 times, at least about 3 times, at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times, at least about 10 times, at least about 20 times, at least about 30 times, at least about 40 times, at least about 50 times, or more than that of the wild-type control.

[0191] In some embodiments, affinity refers to the sum of the strengths of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen or target). For example, the affinity of molecule X for its partner Y is generally expressed by the dissociation constant (K). D Affinity can be expressed by ( ). Affinity can be measured by common methods known in the art, including the methods described herein.

[0192] In some embodiments, a statement that one molecule (e.g., an antibody and / or Fc region) binds to another molecule (e.g., an antibody and / or Fc region) to a greater degree than another molecule (e.g., an antibody and / or Fc region), or any other grammatical equivalent, means that one molecule (e.g., an antibody and / or Fc region) binds more tightly to a target (e.g., an Fc receptor, a cell surface protein) than another molecule (e.g., an antibody and / or Fc region) under substantially the same conditions in a binding assay (e.g., described herein and / or known in the art) (e.g., it has a lower dissociation constant). For example, a statement that antibody "X" binds to the Fc receptor to a greater degree than antibody "Y" means that antibody "X" binds more tightly to the Fc receptor than antibody "Y" under substantially the same conditions in a binding assay (e.g., described herein and / or known in the art) (e.g., it has a lower dissociation constant). In another example, a statement that antibody "X" binds to a target (e.g., a cell surface protein such as CD94) with higher affinity than antibody "Y" indicates that antibody "X" binds more tightly to the target (e.g., a cell surface protein such as CD94) than antibody "Y" under substantially the same conditions (e.g., has a lower dissociation constant).

[0193] (ii) Reduced fucosylation In some embodiments, the antibodies of this disclosure are non-fucosylated or fucose-deficient, glycosylated antibody variants that include an Fc region having reduced fucose in the carbohydrate structure bound to the Fc region, or an Fc region lacking fucose. In some embodiments, antibodies having reduced fucose or lacking fucose have improved ADCC function. Non-fucosylated or fucose-deficient antibodies have reduced fucose compared to the amount of fucose on the same antibody produced in a cell line. In some embodiments, the non-fucosylated or fucose-deficient antibody compositions of this disclosure are compositions in which less than about 50% of the N-linked glycans bound to the Fc region of the antibody in the composition are fucose.

[0194] In some embodiments, fucosylation or fucosylated refers to a fucose residue in an oligosaccharide bound to the peptide backbone of the antibody of this disclosure. Specifically, a fucosylated antibody contains α(1,6)-bound fucose at the innermost N-acetylglucosamine (GlcNAc) residue in one or both of the N-linked oligosaccharides bound to the antibody Fc region at Asn297 (EU numbering of the Fc region residue) of the human IgG1 Fc domain. Asn297 may also be located approximately +3 amino acids upstream or downstream from 297, i.e., between 294 and 300, due to slight sequence variability in immunoglobulins.

[0195] In some embodiments, the degree of fucosylation is the percentage of fucosylated oligosaccharides relative to all oligosaccharides, as determined by methods known in the art, such as in antibody compositions treated with N-glycosidase F, assessed by matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF MS). In compositions of fully fucosylated antibodies, at least 90% or essentially all oligosaccharides contain fucose residues, i.e., are fucosylated. Therefore, individual antibodies in such compositions typically contain fucose residues in each of the two N-linked oligosaccharides in the Fc region. In some embodiments, in compositions of fully non-fucosylated antibodies, less than about 10% of the oligosaccharides are fucosylated or none of the oligosaccharides are essentially fucosylated, and individual antibodies in such compositions do not contain fucose residues in either of the two N-linked oligosaccharides in the Fc region. In compositions of partially fucosylated antibodies, only a portion of the oligosaccharides contain fucose. The individual antibodies in such a composition may either not contain a fucose residue in either of the N-linked oligosaccharides in the Fc region, or may contain a fucose residue in one or both of the N-linked oligosaccharides in the Fc region, unless essentially all of the individual antibodies in the composition lack a fucose residue in the N-linked oligosaccharide in the Fc region, or essentially all of the individual antibodies contain a fucose residue in both of the N-linked oligosaccharides in the Fc region. In one embodiment, the composition of partially fucosylated antibodies has a degree of fucosylation of about 10% to about 80% (e.g., about 50% to about 80%, about 60% to about 80%, or about 70% to about 80%).

[0196] In some embodiments, the glycosylated antibody variant includes an Fc region in which the carbohydrate structure bound to the Fc region lacks fucose. Such variants have improved ADCC function. Examples of defucosylated or fucose-deficient antibodies include US2003 / 0157108, WO2000 / 61739, WO2001 / 29246, US2003 / 0115614, US2002 / 0164328, US2004 / 0093621, US2004 / 0132140, US2004 / 0110704, US2004 / 0110282, US2004 / 0109865, WO2003 / 085119, WO2003 / 084570, WO2005 / 035586, WO2005 / 035778, WO2005 / 053742, Okazaki et al. This is described in al.J.Mol.Biol.336:1239-1249(2004) and Yamane-Ohnuki et al.Biotech.Bioeng.87:614(2004).

[0197] Antibodies having reduced fucosylation, or antibodies that are not fucosylated, may be prepared using any method known in the art. In some embodiments of the antibodies of this disclosure, at least one or two of the antibody's heavy chain may be fucosylated. For example, antibodies of this disclosure having reduced fucosylation, or antibodies that are not fucosylated, may be prepared in cell lines that have alpha-1,6-fucosyltransferase (Fut8) knockout and / or overexpress β1,4-N-acetylglucosaminyltransferase III (GnT-III) and / or overexpress Golgi μ-mannosidase II (ManII). Antibodies with reduced fucosylation, or non-fucosylated antibodies, may also be produced using cell lines lacking "FUT8," i.e., alpha-1,6 fucosyltransferase, which catalyzes fucose transfer; for example, using FUT8-deficient Chinese hamster ovary (CHO) cells (Yamane-Ohnuki et al., 2004); or using small interfering RNA (siRNA) to block the expression of the FUT8 gene (Mori et al., 2004). Other cell lines that can be used to produce non-fucosylated or defucosylated antibodies or antibodies with reduced fucosylation are known in the art, for example, Lec13 cells lacking protein fucosylation. This includes CHO cells (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986), US Patent Application No. US2003 / 0157108A1 (Presta, L), and WO2004 / 056312A1 (Adams et al., particularly in Example 11)), knockout cell lines such as alpha-1,6-fucosyltransferase gene (FUT8) knockout CHO cells (Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004)), and cells overexpressing β1,4-N-acetylglucosaminyltransferase III (GnT-III) and Golgi μ-mannosidase II (ManII).

[0198] In some embodiments, the antibodies of this disclosure have reduced fucose compared to the amount of fucose on the same antibody produced in wild-type CHO cells. For example, an antibody may have a lower amount of fucose than it would otherwise have if produced by natural CHO cells (e.g., CHO cells that produce a natural glycosylation pattern, such as CHO cells containing the natural FUT8 gene). In some embodiments, the antibodies provided herein are antibodies in which about 50%, 40%, 30%, 20%, 10%, 5%, or less than 1% of the N-linked glycans on which they contain fucose. In certain embodiments, the antibodies provided herein are antibodies in which none of the N-linked glycans on which they contain fucose, i.e., the antibody contains no fucose at all, has no fucose, is not fucosylated, or is defucosylated. The amount of fucose can be determined by those skilled in the art by calculating the average amount of fucose in the glycan at Asn297 relative to the total amount of all sugar structures (e.g., complex, hybrid, and high-mannose structures) bound to Asn297, measured by MALDI-TOF mass spectrometry, for example, as described in WO2008 / 077546. Asn297 refers to the asparagine residue located at approximately position 297 (Eu numbering of Fc region residues) in the Fc region, although Asn297 may also be located approximately ±3 amino acids upstream or downstream of position 297, i.e., between positions 294 and 300, due to slight sequence variability in the antibody. In some embodiments, at least one or two of the antibody's heavy chains are not fucosylated.

[0199] Antibodies lacking 1,6-fucose in heavy chain glycosylation may have enhanced binding affinity to the FcγRIII receptor and increased ADCC activity (see, e.g., Shields et al., 2002, Shinkawa et al., 2002, Okazaki, 2004, and Dall'Ozzo, 2004). In some embodiments, the antibodies provided herein include an Fc region having modifications including reduced fucosylation, non-fucosylation, and / or mutations that enhance ADCC activity and / or improve the affinity of the Fc region to Fc receptors such as FcγRIII and CD16 (e.g., CD16a). In some embodiments, the molecule (e.g., the antibodies provided herein) induces antibody-directed cytotoxicity (ADCC) to a higher degree than fucosylated or wild-type antibodies, and depletes or reduces the number of CD94-expressing NK cells and / or T cells.

[0200] In some embodiments, the antibodies of the Disclosure are engineered to improve ADCC activity by reducing fucosylation. In some embodiments, molecules provided herein (e.g., antibodies provided herein) can induce antibody-directed cytotoxicity (ADCC) to a greater extent than fucosylated or wild-type antibodies, and can deplete or reduce the number of CD94-expressing NK cells and / or T cells. In some embodiments, at least one or two heavy chains of the antibodies of the Disclosure are not fucosylated. In some embodiments, the antibodies of the Disclosure are modified so that the carbohydrates of the antibody are not fucosylated. In some embodiments, the antibodies of the Disclosure are modified so that less than about 90% of the carbohydrates of the antibody contain fucose, for example, less than about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, about 10%, about 5%, or about 1%. In some embodiments, the antibodies of this disclosure are modified so that less than 40% of the antibody's carbohydrate content is fucose. In some embodiments, the antibodies provided herein are not fucosylated.

[0201] In some embodiments, the molecules provided herein (e.g., antibodies) induce antibody-directed cytotoxicity (ADCC) to a greater extent than fucosylated or wild-type antibodies, and deplete or reduce the number of CD94-expressing NK cells and / or T cells.

[0202] (iii) Mutations that enhance ADCC activity The antibodies of this disclosure may include a variant Fc region. In some embodiments, the variant Fc region includes at least one amino acid substitution in the Fc region that improves ADCC activity. For example, the antibodies of this disclosure include one or more Fc mutations selected from S239D, A330L, I332E, F243L, and G236A, and variant IgG1 It may have an Fc region. In another example, the antibodies of this disclosure may have a human IgG1 Fc variant region containing one or more Fc mutations selected from S239D, A330L, I332E, F243L, and G236A. See, for example, Lazar et al., PNAS 103, 4005-4010 (2006), Shields et al., J. Biol. Chem. 276, 6591-6604 (2001), Stewart Other amino acid substitutions known to enhance ADCC activity may be used, such as those described in Protein Engineering, Design and Selection 24, 671-678 (2011) and Richards et al., Mol Cancer Ther 7, 2517-2527 (2008).

[0203] (iv) Reduced internalization In some embodiments, the antibodies of this disclosure have a lower degree of internalization, e.g., receptor-inducible internalization or target internalization (i.e., internalization of surface-expressed CD94), compared to, for example, a wild-type control antibody or an antibody known or commercially available in the art against the same target. Antibodies with lower internalization have a higher receptor (e.g., CD94) occupancy rate on the cell surface and a higher level of receptor-antibody complexes on the cell surface, which may enhance ADCC activity. The antibodies of this disclosure may be tested in vitro for their internalization ability. The antibodies of this disclosure may be tested for their internalization ability in ex vivo assays, e.g., using PBMCs and / or NK cells, as described in the Examples. Internalization of the target (e.g., CD94) may be expressed as a percentage decrease in mean fluorescence intensity (MFI) over a period of time, e.g., using a flow cytometry-based assay, as described in the Examples. For example, target internalization (i.e., the internalization ability of the antibody of this disclosure) may be expressed as a percentage decrease in MFI, calculated by, for example, calculating the difference in MFI over a 24-hour period (e.g., between 0.5 hours and 24 hours) in cells incubated with the antibody at 37°C, as described in the examples, and multiplying by 100.

[0204] In some embodiments, the antibody has a high degree of internalization if the decrease in MFI induced by the antibody is greater than 50%, calculated by calculating the difference in MFI over a 24-hour period (e.g., between 0.5 hours and 24 hours) in cells incubated with the antibody at 37°C for 24 hours, and multiplying by 100, as measured by an ex vivo assay using PBMCs and / or NK cells, as described in the Examples. In some embodiments, the antibody has a high degree of internalization if the decrease in surface antibody staining due to internalization induced by incubation of the antibody with cells expressing human CD94 on the surface at 37°C for 24 hours is greater than 50%, as measured using methods known in the art and / or as assessed above.

[0205] In some embodiments, the antibody has a low degree of internalization if the decrease in MFI induced by the antibody is less than 50% (e.g., any of approximately 50% or less, 45% or less, 40% or less, 35% or less, 30% or less, 25% or less, 20% or less, 15% or less, 10% or less, 5% or less, 1% or less, or 0%), calculated by calculating the difference in MFI over a 24-hour period (e.g., between 0.5 hours and 24 hours) in cells incubated with the antibody at 37°C and multiplying by 100, as measured by an ex vivo assay using PBMCs and / or NK cells, as described in the Examples. In some embodiments, the antibodies of the Disclosure have a degree of low internalization, and the resulting reduction in MFI, calculated as described above, is about 50% or less, about 40% or less, about 35% or less, about 30% or less, about 25% or less, about 20% or less, about 15% or less, about 10% or less, about 5% or less, about 2.5% or less, about 1% or less, or about 0%. In some embodiments, the antibodies have a degree of low internalization if, using methods known in the art and / or as assessed as described above, the reduction in surface antibody staining due to internalization, resulting from incubation of the antibody with cells expressing human CD94 on the surface at 37°C for 24 hours, is less than 50%.

[0206] In some embodiments, the antibodies of the Disclosure have or result in internalization activity that is at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 99%, or about 100% lower than the internalization activity of a control antibody, e.g., a commercial or wild-type control antibody, or an isotype control antibody, where internalization is assessed using any preferred method known in the art as described above.

[0207] Antibody candidates that lack or have low internalization activity may be further tested for binding to cynomolgus monkey and / or human targets (e.g., cynomolgus monkey and / or human CD94). Antibodies that bind to cynomolgus monkey and / or human targets may be used in in vitro and in vivo cell-killing assays (e.g., ADCC assays). The cell-killing activity (e.g., ADCC activity) of the selected antibodies may be compared to commercially available antibodies or antibodies known in the art.

[0208] E. Antibody production The antibodies of this disclosure may be produced using any techniques and / or methods known in the art. Techniques for preparing antibodies, such as monoclonal antibodies (mAbs), against virtually any target antigen are well known in the art. See, for example, Kohler and Milstein, Nature 256:495 (1975), and Coligan et al. (eds.), CURRENT PROTOCOLS IN IMMUNOLOGY, VOL.1, pages 2.5.1-2.6.7 (John Wiley & Sons 1991). Briefly, monoclonal antibodies can be obtained by injecting a mouse with a composition containing an antigen (e.g., CD94, or a part thereof), removing the spleen to obtain B lymphocytes, fusing the B lymphocytes with myeloma cells to produce hybridomas, cloning the hybridomas, selecting positive clones that produce antibodies against the antigen, culturing the clones that produce antibodies against the antigen, and isolating the antibodies from the hybridoma culture. Those skilled in the art will recognize that when an antibody is administered to a human subject, that antibody will bind to a human antigen (e.g., human CD94, or a part thereof).

[0209] MAb can be isolated and purified from hybridoma cultures using a variety of established techniques. These isolation techniques include affinity chromatography using protein-A or protein-G Sepharose, size exclusion chromatography, and ion exchange chromatography. See, for example, Coligan at pages 2.7.1–2.7.12 and pages 2.9.1–2.9.3. Also see Baines et al., “Purification of Immunoglobulin G (IgG),” in METHODS IN MOLECULAR BIOLOGY, VOL.10, pages 79–104 (The Humana Press, Inc. 1992).

[0210] Antibodies can be initially produced against an immunogen (e.g., CD94, or a part thereof), followed by sequencing of the antibodies, and then prepared using recombinant techniques. Humanization and chimerization of mouse antibodies and antibody fragments are well known to those skilled in the art, as discussed below.

[0211] In the typical antibody production method described herein, a recombinant target (e.g., CD94) may be used for mouse immunization. For example, antibodies produced following mouse immunization as described above may be analyzed for specific or selective binding to their target (e.g., CD94) by ELISA and flow cytometry. Antibodies may be selected based on their ability to bind to their target (e.g., CD94).

[0212] In some embodiments, non-human primate antibodies may be generated. General techniques for producing therapeutically useful antibodies in baboons can be found, for example, in Goldenberg et al., WO91 / 11465 (1991) and Losman et al., Int. J. Cancer 46:310 (1990).

[0213] In some embodiments, the antibody may be a human antibody. In some embodiments, the antibody may be a monoclonal human antibody. In some embodiments, the human antibody has an amino acid sequence corresponding to the amino acid sequence of an antibody produced by a human or human cell, or an antibody derived from the human antibody repertoire or a non-human source utilizing other human antibody coding sequences. Such antibodies may be obtained from transgenic mice engineered to produce a specific human antibody in response to an antigen stimulus, e.g., CD94 or a part thereof. Methods for producing fully human antibodies using either combinatorial techniques or transgenic animals transformed at human immunoglobulin loci are known in the art (e.g., Mancini et al., 2004, New Microbiol. 27:315-28; Conrad and Scheller, 2005, Comb. Chem. High Throughput Screen. 8:117-26; Brekke and Loset, 2003, Curr. Opin. Phamacol. 3:544-50). In certain embodiments, the claimed method and procedure may utilize human antibodies produced by such technique. Other methods for producing fully human antibodies include, for example, phage display as described in Dantas-Barbosa et al., 2005, Genet. Mol. Res. 4:126-40, the production of antibodies in normal humans or from humans exhibiting specific medical conditions as described in Dantas-Barbosa et al., 2005, or Green et al. This includes the use of genetically engineered transgenic animals (e.g., mice) to produce human antibodies using the standard immunization protocols discussed above, as described in al., 1999, J.Immunol.Methods 231:11-23, Green et al., Nature Genet. 7:13 (1994), Lonberg et al., Nature 368:856 (1994), and Taylor et al., Int.Immun. 6:579 (1994).

[0214] (i) In vitro cell killing assay...

Claims

1. An antibody that binds to human CD94, wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, An antibody in which the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 47, CDR-H2 containing the amino acid sequence of SEQ ID NO: 48, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 49, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 50, CDR-L2 containing the amino acid sequence of SEQ ID NO: 51, and CDR-L3 containing the amino acid sequence of SEQ ID NO:

52.

2. An antibody that binds to human CD94, wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, An antibody in which the VH domain comprises CDR-H1 containing the amino acid sequence of SEQ ID NO: 109, CDR-H2 containing the amino acid sequence of SEQ ID NO: 110, and CDR-H3 containing the amino acid sequence of SEQ ID NO: 114, and the VL domain comprises CDR-L1 containing the amino acid sequence of SEQ ID NO: 115, CDR-L2 containing the amino acid sequence of SEQ ID NO: 99, and CDR-L3 containing the amino acid sequence of SEQ ID NO:

52.

3. The antibody according to claim 1 or claim 2, wherein the VH domain comprises an amino acid sequence having at least 90% or at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 73, and the VL domain comprises an amino acid sequence having at least 90% or at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO:

74.

4. The antibody according to claim 3, wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 73 and the VL domain comprises the amino acid sequence of SEQ ID NO:

74.

5. The antibody according to any one of claims 1 to 4, wherein the antibody is a human antibody.

6. The antibody according to any one of claims 1 to 5, wherein the antibody is an antigen-binding antibody fragment or a single-chain antibody.

7. The antibody according to any one of claims 1 to 5, further comprising an Fc region.

8. The antibody according to claim 7, wherein the Fc region is a human IgG1 Fc region.

9. The antibody according to claim 7 or claim 8, wherein the antibody comprises a human Fc region that has not been fucosylated.

10. The antibody according to any one of claims 7 to 9, wherein the antibody binds to human cell Fc gamma receptor IIIIA to a higher degree than an antibody containing the wild-type human IgG1 Fc region.

11. The antibody according to any one of claims 7 to 10, wherein the antibody can induce antibody-dependent cell-mediated cytotoxicity (ADCC) against cells expressing human CD94 on their surface.

12. A polynucleotide encoding the antibody according to any one of claims 1 to 11.

13. A vector comprising the polynucleotide described in Claim 12, wherein the vector is an expression vector if necessary.

14. An isolated host cell comprising the polynucleotide described in claim 12 or the vector described in claim 13.

15. A method for producing an antibody, comprising culturing the host cells described in Claim 14 under conditions suitable for producing the antibody, and further comprising, if necessary, recovering the antibody from the host cells.

16. A pharmaceutical composition comprising the antibody according to any one of claims 1 to 11 and a pharmaceutically acceptable carrier.

17. A pharmaceutical for use in a method for (a) treating a disease or disorder in a subject, (b) reducing the number of peripheral blood LGL cells and / or NK cells in a subject, (c) inducing ADCC activity in a subject, (d) treating CLPD-NK in a subject requiring CLPD-NK treatment, (e) treating natural killer (NK) cell lymphoma or T cell lymphoma in a subject, (f) enhancing chimeric antigen receptor T cell (CAR-T) therapy in a subject, (g) depleting CD8+ CD94+ T cells in a subject, or (h) depleting NK cells in a subject, A pharmaceutical product comprising the antibody described in any one of claims 1 to 11.

18. The pharmacopoeia according to claim 17, wherein the pharmacopoeia is for use in a method for treating a disease or disorder in a subject, the disease or disorder being Felty syndrome, inclusion body myositis, invasive NK leukemia, rheumatoid arthritis, LGL leukemia, CLPD-NK, NK cell lymphoma, T cell lymphoma, or microscopic colitis.

19. The pharmacopoeia according to claim 17, wherein the pharmacopoeia is for use in a method for treating NK cell lymphoma or T cell lymphoma in a subject, and the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic T cell lymphoma (TCL), enteropathy-related TCL, cutaneous TCL, anaplastic large cell lymphoma (ALK+), anaplastic large cell lymphoma (ALK-), peripheral TCL, angioimmunoblastic TCL, adult TCL, monomorphic epitheliotropic enteroplastic TCL, epidermotropic CD8+ cutaneous TCL, primary cutaneous gamma / delta TCL, or subcutaneous panniculitis TCL, and optionally the NK cell lymphoma or T cell lymphoma is extranodal NK / T cell lymphoma, hepatosplenic TCL, or enteropathy-related TCL.

20. The pharmaceutical product according to any one of claims 17 to 19, wherein the pharmaceutical product further comprises an IL-2 polypeptide.

21. The pharmaceutical product according to any one of claims 17 to 20, wherein the subject is a human.

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