Anti-CD122 antibodies and uses thereof

Abstract

In certain aspects, provided herein are anti-CD122 antibodies and pharmaceutical compositions comprising the anti-CD122 antibodies. In some embodiments, the anti-CD122 antibodies and pharmaceutical compositions comprising the anti-CD122 antibodies are useful for targeting tissues and cells expressing CD122.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 377,847, filed on September 30, 2022; the entire content of which is hereby incorporated by reference. Background of the Invention

[0003] Interleukin receptors are involved in mediating a variety of cellular responses, including T cell immune responses. The interleukin-2 receptor exists in three forms based on its ability to bind interleukin-2 (IL-2). The low-affinity form of the receptor is a monomer of the α receptor subunit (IL-2RA; also known as CD25) and does not participate in signal transduction. The intermediate-affinity receptor form consists of an α / β subunit heterodimer, while the high-affinity receptor form consists of an α / β / γ subunit heterotrimer. Both the intermediate-affinity and high-affinity forms of the receptor are involved in receptor-mediated IL-2 endocytosis and transduction pathways. The IL-2RB gene encodes the β subunit of the interleukin-2 receptor. The protein encoded by the IL-2RB gene (IL-2RB) is a type I transmembrane protein, and its amino (N)-terminal domain is extracellular relative to the plasma membrane in its mature form. IL-2RB is also known as IL-15RB or CD122. The CD122 protein is mainly expressed in the hematopoietic system. The γ subunit of the interleukin-2 receptor is IL-2RG (also known as CD132).

[0004] In addition to acting as a β receptor subunit in IL-2-mediated signal transduction, CD122 also transmits signals from the cytokine interleukin-15 (IL-15). Different from the α subunit of the IL-2 receptor, the α subunit of the IL-15 receptor (IL-15RA or IL-15Rα) can bind to its ligand (IL-15) with high affinity independently of other receptor subunits. IL-15RA can form an α / β subunit heterodimer with CD122 for signal transduction. IL-15RA can also form an α / β / γ subunit heterotrimer with CD122 and CD132 for signal transduction. CD122 is involved in transmitting signals from the cytokines IL-2 and IL-15 through these different interleukin receptor complexes.

[0005] Therefore, anti-CD122 antibodies can be used for diagnostic purposes and for the treatment of diseases or conditions associated with high expression of CD122. Accordingly, there is a need to develop improved anti-CD122 antibodies. Summary of the Invention

[0006] In certain aspects, anti-CD122 antibodies and pharmaceutical compositions comprising the anti-CD122 antibodies are disclosed herein. In some embodiments, the anti-CD122 antibodies and the pharmaceutical compositions comprising the anti-CD122 antibodies can be used to target tissues and cells expressing CD122.

[0007] In some embodiments, anti-CD122 antibodies are described herein that comprise i) a heavy chain comprising a variable heavy (VH) domain and ii) a light chain comprising a variable light (VL) domain, wherein the VH domain comprises: an HCDR1 sequence comprising a sequence selected from SEQ ID NOs: 1-11, an HCDR2 sequence comprising a sequence selected from SEQ ID NOs: 12-23, and an HCDR3 sequence comprising a sequence selected from SEQ ID NOs: 24-36, and the VL domain comprises: an LCDR1 sequence comprising a sequence selected from SEQ ID NOs: 37-47, an LCDR2 sequence comprising a sequence selected from SEQ ID NOs: 48-55, and an LCDR3 sequence comprising a sequence selected from SEQ ID NOs: 56-67. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence of SEQ ID NO: 1, the HCDR2 sequence of SEQ ID NO: 12, the HCDR3 sequence of SEQ ID NO: 24, the LCDR1 sequence of SEQ ID NO: 37, the LCDR2 sequence of SEQ ID NO: 48, and the LCDR3 sequence of SEQ ID NO: 56. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence of SEQ ID NO: 2, the HCDR2 sequence of SEQ ID NO: 13, the HCDR3 sequence of SEQ ID NO: 25, the LCDR1 sequence of SEQ ID NO: 38, the LCDR2 sequence of SEQ ID NO: 49, and the LCDR3 sequence of SEQ ID NO: 57. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence of SEQ ID NO: 3, the HCDR2 sequence of SEQ ID NO: 14, the HCDR3 sequence of SEQ ID NO: 26, the LCDR1 sequence of SEQ ID NO: 39, the LCDR2 sequence of SEQ ID NO: 50, and the LCDR3 sequence of SEQ ID NO: 58. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence of SEQ ID NO: 4, the HCDR2 sequence of SEQ ID NO: 15, the HCDR3 sequence of SEQ ID NO: 27, the LCDR1 sequence of SEQ ID NO: 40, the LCDR2 sequence of SEQ ID NO: 51, and the LCDR3 of SEQ ID NO: 59.In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:5, the HCDR2 sequence comprising SEQ ID NO:16, the HCDR3 sequence comprising SEQ ID NO:28, the LCDR1 sequence comprising SEQ ID NO:41, the LCDR2 sequence comprising SEQ ID NO:50, and the LCDR3 sequence comprising SEQ ID NO:60. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:6, the HCDR2 sequence comprising SEQ ID NO:17, the HCDR3 sequence comprising SEQ ID NO:29, the LCDR1 sequence comprising SEQ ID NO:42, the LCDR2 sequence comprising SEQ ID NO:52, and the LCDR3 sequence comprising SEQ ID NO:61. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:7, the HCDR2 sequence comprising SEQ ID NO:18, the HCDR3 sequence comprising SEQ ID NO:30, the LCDR1 sequence comprising SEQ ID NO:43, the LCDR2 sequence comprising SEQ ID NO:50, and the LCDR3 sequence comprising SEQ ID NO:62. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:8, the HCDR2 sequence comprising SEQ ID NO:19, the HCDR3 sequence comprising SEQ ID NO:31, the LCDR1 sequence comprising SEQ ID NO:44, the LCDR2 sequence comprising SEQ ID NO:50, and the LCDR3 sequence comprising SEQ ID NO:63. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:9, the HCDR2 sequence comprising SEQ ID NO:20, the HCDR3 sequence comprising SEQ ID NO:32, the LCDR1 sequence comprising SEQ ID NO:45, the LCDR2 sequence comprising SEQ ID NO:53, and the LCDR3 sequence comprising SEQ ID NO:64.In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:1, the HCDR2 sequence comprising SEQ ID NO:21, the HCDR3 sequence comprising SEQ ID NO:33, the LCDR1 sequence comprising SEQ ID NO:37, the LCDR2 sequence comprising SEQ ID NO:48, and the LCDR3 sequence comprising SEQ ID NO:65. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:1, the HCDR2 sequence comprising SEQ ID NO:21, the HCDR3 sequence comprising SEQ ID NO:34, the LCDR1 sequence comprising SEQ ID NO:37, the LCDR2 sequence comprising SEQ ID NO:48, and the LCDR3 sequence comprising SEQ ID NO:65. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:10, the HCDR2 sequence comprising SEQ ID NO:22, the HCDR3 sequence comprising SEQ ID NO:35, the LCDR1 sequence comprising SEQ ID NO:46, the LCDR2 sequence comprising SEQ ID NO:54, and the LCDR3 sequence comprising SEQ ID NO:66. In some embodiments, the anti-CD122 antibody comprises: the HCDR1 sequence comprising SEQ ID NO:11, the HCDR2 sequence comprising SEQ ID NO:23, the HCDR3 sequence comprising SEQ ID NO:36, the LCDR1 sequence comprising SEQ ID NO:47, the LCDR2 sequence comprising SEQ ID NO:55, and the LCDR3 sequence comprising SEQ ID NO:67. In some embodiments, the anti-CD122 antibody comprises a VH domain having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 82-94. In some embodiments, the anti-CD122 antibody comprises a VL domain having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 95-107. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 108-120.In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 121-133. In some embodiments, the anti-CD122 antibody comprises a heavy chain having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibody comprises a light chain having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 142-145. In some embodiments, the anti-CD122 antibody comprises a heavy chain encoded by a nucleic acid having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 146-153. In some embodiments, the anti-CD122 antibody comprises a light chain encoded by a nucleic acid having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 154-157. In some embodiments, the anti-CD122 antibody comprises the heavy chain, wherein the heavy chain polypeptide comprises a leader sequence at the N-terminus. In some embodiments, the anti-CD122 antibody comprises the heavy chain, wherein the leader sequence comprises SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, or SEQ ID NO: 161. In some embodiments, the anti-CD122 antibody comprises the light chain, wherein the light chain polypeptide comprises a leader sequence at the N-terminus. In some embodiments, the anti-CD122 antibody comprises the light chain, wherein the leader sequence comprises SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, or SEQ ID NO: 161. In some embodiments, the anti-CD122 antibody is a humanized antibody or an antigen-binding fragment thereof. In some embodiments, the anti-CD122 antibody is a chimeric antibody or an antigen-binding fragment thereof. In some embodiments, the anti-CD122 antibody comprises IgG-scFv, nanobody, mini-antibody, minibody, scFv-CH3 KIH, Fab-scFv-Fc KIH, Fab-scFv, scFv-CH-CL-scFv, Fab’, F(ab’)2, F(ab’)3, F(ab’)2-scFv2, scFv, scFv-KIH, Fab-scFv-Fc, or an intracellular antibody. In some embodiments, the anti-CD122 antibody is an IgG1 antibody. In some embodiments, the anti-CD122 antibody is an IgG2 antibody.In some embodiments, the anti-CD122 antibody is an IgG4 antibody. In some embodiments, the anti-CD122 antibody comprises a light chain, wherein the light chain is a κ chain. In some embodiments, the anti-CD122 antibody has a binding affinity for human CD122 of from about 100 pM to about 3 nM. In some embodiments, the pharmaceutical compositions described herein comprise the anti-CD122 antibody described herein and a pharmaceutically acceptable excipient.

[0008] Incorporation by reference

[0009] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. If the publications and patents or patent applications incorporated by reference conflict with the disclosure contained in this specification, this specification is intended to supersede and / or take precedence over any such conflicting material. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The novel features of the invention are set forth with particularity in the appended claims. The features and advantages of the invention will be better understood from the following detailed description when considered in conjunction with the accompanying drawings, which illustrate exemplary embodiments of the principles of the invention, wherein:

[0011] Figure 1 Sensorgrams of anti-CD122 antibodies G1 (top) and G2 (bottom) are shown for measuring their binding and dissociation characteristics with different concentrations of huCD122.

[0012] Figure 2 Sensorgrams of anti-CD122 antibodies G3 (top) and G4 (bottom) are shown for measuring their binding and dissociation characteristics with different concentrations of huCD122.

[0013] Figure 3 Sensorgrams of anti-CD122 antibodies G5 (top) and G6 (bottom) are shown for measuring their binding and dissociation characteristics with different concentrations of huCD122.

[0014] Figure 4 Sensorgrams of anti-CD122 antibodies G7 (top) and G8 (bottom) are shown for measuring their binding and dissociation characteristics with different concentrations of huCD122.

[0015] Figure 5 Sensorgrams of anti-CD122 antibody G9 (second batch) (top) and G10 (bottom) are shown for measuring their binding and dissociation characteristics with different concentrations of huCD122.

[0016] Figure 6Shows the sensorgrams of anti-CD122 antibodies G11 (top) and G12 (bottom) for measuring their binding and dissociation characteristics with different concentrations of huCD122.

[0017] Figure 7 Shows the sensorgrams of anti-CD122 antibodies G13 (top) and G14 (bottom) for measuring the binding and dissociation characteristics with different concentrations of huCD122.

[0018] Figure 8 Shows the sensorgrams of anti-CD122 antibodies G15 (top) and G16 (bottom) for measuring the binding and dissociation characteristics with different concentrations of huCD122.

[0019] Figure 9 Shows the sensorgrams of anti-CD122 antibodies G17 (top) and G18 (bottom) for measuring the binding and dissociation characteristics with different concentrations of huCD122.

[0020] Figure 10 Shows the sensorgrams of anti-CD122 antibodies G19 (top) and G20 (bottom) for measuring the binding and dissociation characteristics with different concentrations of huCD122.

[0021] Figure 11 Shows the graphs and calculated IC50 values of the inhibition of IL2 (top graph) and IL15 (bottom graph) signaling by anti-CD122 antibodies in cell lines expressing medium-affinity IL-βγ receptors using a reporter gene assay detecting luciferase expression upon IL2 or IL15 stimulation. Results are for antibody 1, antibody 2, and a commercially available anti-CD122 antibody, respectively.

[0022] Figure 12 Shows the graphs of the inhibition of IL2 signaling by anti-CD122 antibodies (antibody 1 and antibody 2) in cell lines expressing high-affinity IL-αβγ receptors using a reporter gene assay.

[0023] Figure 13 Shows a summary of the results of the IL2RB epitope mapping obtained by analyzing the humanized anti-CD122 Mab described herein, as detailed in the epitope mapping experiment in Example 5.

[0024] Figure 14 Shows a heatmap of the modified changes of the humanized anti-CD122 Mab with and without bound IL2RB, as detailed in the epitope mapping experiment in Example 5. The shaded boxes in the t-test column indicate significant changes (p < 0.05).

[0025] Figure 15Figure showing the crystal structures of interleukin-2 receptor subunit beta (IL2RB), IL2, and the candidate epitope regions. Amino acid residues with significant changes in solvent accessibility are indicated by asterisks (epitope regions), and arrows point to residues with conformational changes. Detailed implementation

[0026] Immune cell responses can be environment-dependent and can be influenced by signals from their environment through various receptor-ligand interactions. For example, these signals can amplify and modify the T cell receptor (TCR) signals received through antigen stimulation in naive or memory T cells at rest, regulate the proliferation and differentiation of recently activated T cells, or control effector functions in specific somatic environments. IL2 and IL15 have similar and opposing roles in regulating T cell function. As a non-limiting example, both IL2 and IL15 are involved in T cell differentiation. IL2 promotes the differentiation of immature T cells into regulatory T cells, which can then inhibit other T cells that may attack normal healthy cells in the body. IL2 signaling is involved in peripheral tolerance by eliminating autoreactive T cells using the activation-induced cell death (AICD) pathway. When naive T cells are stimulated by antigens, IL2 can also promote the differentiation of immature T cells into effector T cells or memory T cells. IL2 has also been shown to enhance the activity of cytotoxic T cells and natural killer (NK) cells. IL15 can regulate the activation and proliferation of T cells and NK cells. In contrast to IL2 signaling, IL15 signaling can inhibit IL2-mediated AICD by triggering anti-apoptotic effects. IL15 can stimulate the persistence of memory phenotype CD8+ T cells involved in clearing invading pathogens, thereby protecting the subject from infection.

[0027] IL2 and IL15 initiate signal transduction through various IL receptors in different ways. IL2 is secreted and can bind to heterodimeric and heterotrimeric receptor complexes on the surface of activated cells, both of which contain CD122. IL15 is mainly membrane-bound and induces signal transduction at the immunological synapse, in the context of cell-cell contact. IL15RA trans-presents membrane-bound IL15 to neighboring CD8+ T cells and NK cells. Despite these differences in the mechanisms of ligand-mediated signal transduction initiation, once activated, the IL2 receptor complex and the IL15 receptor complex activate common molecular pathways, including the JAK1 / JAK3 / STAT5, PI3K, and MAPK signal transduction pathways. Activation of these pathways can regulate gene transcription, thereby controlling apoptosis, proliferation, or differentiation of immune cells. Since CD122 is part of both the IL2 receptor and the IL15 receptor, it plays a key role in all of these functions.

[0028] In some aspects, the present disclosure provides anti-CD122 antibodies and pharmaceutical compositions comprising these anti-CD122 antibodies. In some embodiments, the present disclosure also provides methods of targeting tissues and cells expressing CD122 with the anti-CD122 antibodies described herein.

[0029] Anti-CD122 antibody

[0030] The present disclosure provides antibodies that bind to CD122. In some cases, the antibody that binds to CD122 is a monoclonal antibody. In some aspects, the present disclosure provides anti-CD122 antibodies. In some cases, the anti-CD122 antibody specifically binds to mammalian CD122. In some cases, the anti-CD122 antibody specifically binds to human CD122. In some cases, the anti-CD122 antibody specifically binds to the extracellular portion of CD122. In some cases, the anti-CD122 antibody specifically binds to the extracellular portion of human CD122. In some cases, the anti-CD122 antibody consists of chimeric amino acid sequences, some of which are derived from mice and some from humans. In some cases, the anti-CD122 antibody is formed by complementarity-determining regions (CDRs) incorporated into an antibody scaffold. In some cases, the anti-CD122 antibody is formed by complementarity-determining regions (CDRs) incorporated into the framework of a human antibody variable region. In some cases, the human antibody variable region framework is sequence-optimized to retain CD122 affinity for the implanted murine CDR sequences. In some cases, the anti-CD122 antibody is a humanized antibody. In some cases, the anti-CD122 antibody is a human antibody.

[0031] In some embodiments, the anti-CD122 antibody comprises i) a heavy chain comprising a variable heavy (VH) domain and ii) a light chain comprising a variable light (VL) domain. In some embodiments, the VH domain comprises: a heavy chain CDR1 (HCDR1) sequence comprising a sequence selected from SEQ ID NOs: 1-11; a heavy chain CDR2 (HCDR2) sequence comprising a sequence selected from SEQ ID NOs: 12-23; and a heavy chain CDR3 (HCDR3) sequence comprising a sequence selected from SEQ ID NOs: 24-36. In some embodiments, the VL domain comprises: a light chain CDR1 (LCDR1) sequence comprising a sequence selected from SEQ ID NOs: 37-47; a light chain CDR2 (LCDR2) sequence comprising a sequence selected from SEQ ID NOs: 48-55; and a light chain CDR3 (LCDR3) sequence comprising a sequence selected from SEQ ID NOs: 56-67.

[0032] In some embodiments, the VH region of the anti-CD122 antibody comprises HCDR1, HCDR2, and HCDR3 sequences selected from Table 1.

[0033] Table 1: HCDR sequences

[0034] SEQ ID NO: HCDR1 sequence 1 GFSLTSYG 2 GYTFTSYW 3 GSTFNRYW 4 GFTFTDYN 5 GYSFTAYT 6 GFNIKDDY 7 GYTFTSHW 8 GFTFSTFA 9 GFTFTDHT 10 GFSLTSYD 11 GYTFTAYW SEQ ID NO: HCDR2 sequence 12 MWGGGST 13 IYPGRGST 14 ILPGSGNT 15 INPNNGRS 16 INPYNGYA 17 IDPENGDT 18 IYPGSGNT 19 ITGDGGTYT 20 IYPRDGYT 21 IWGGGGST 22 IWTGGGT 23 IDPNSGYT SEQ ID NO: HCDR3 sequence 24 ARRTYSDSYYYEMDY 25 ARELGGFAY 26 ARLDYYGSRYYFDY 27 AREDWEGFYAMDY 28 ARVGYYFDY 29 TGYFDY 30 ARERGGFDY 31 ARHSVSSWFAY 32 ARPTSLLRFPY 33 ARHNYDGYYYSLDY 34 ARHNYDNYYYTLDY 35 VRDLFPYAMDY 36 ARGHFGYDDS

[0035] In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:1; an HCDR2 sequence comprising SEQ ID NO:12; and an HCDR3 sequence comprising SEQ ID NO:24. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:2; an HCDR2 sequence comprising SEQ ID NO:13; and an HCDR3 sequence comprising SEQ ID NO:25. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:3; an HCDR2 sequence comprising SEQ ID NO:14; and an HCDR3 sequence comprising SEQ ID NO:26. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:4; an HCDR2 sequence comprising SEQ ID NO:15; and an HCDR3 sequence comprising SEQ ID NO:27. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:5; an HCDR2 sequence comprising SEQ ID NO:16; and an HCDR3 sequence comprising SEQ ID NO:28. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:6; an HCDR2 sequence comprising SEQ ID NO:17; and an HCDR3 sequence comprising SEQ ID NO:29. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:7; an HCDR2 sequence comprising SEQ ID NO:18; and an HCDR3 sequence comprising SEQ ID NO:30. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:8; an HCDR2 sequence comprising SEQ ID NO:19; and an HCDR3 sequence comprising SEQ ID NO:31. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:9; an HCDR2 sequence comprising SEQ ID NO:20; and an HCDR3 sequence comprising SEQ ID NO:32. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:1; an HCDR2 sequence comprising SEQ ID NO:21; and an HCDR3 sequence comprising SEQ ID NO:33. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:1; an HCDR2 sequence comprising SEQ ID NO:21; and an HCDR3 sequence comprising SEQ ID NO:34.In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:10; an HCDR2 sequence comprising SEQ ID NO:22; and an HCDR3 sequence comprising SEQ ID NO:35. In some embodiments, the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:11; an HCDR2 sequence comprising SEQ ID NO:23; and an HCDR3 sequence comprising SEQ ID NO:36.

[0036] In some embodiments, the VL region of the anti-CD122 antibody comprises LCDR1, LCDR2, and LCDR3 sequences selected from Table 2.

[0037] Table 2: LCDR Sequences

[0038]

[0039] In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:37; an LCDR2 sequence comprising SEQ ID NO:48; and an LCDR3 sequence comprising SEQ ID NO:56. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:38; an LCDR2 sequence comprising SEQ ID NO:49; and an LCDR3 sequence comprising SEQ ID NO:57. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:39; an LCDR2 sequence comprising SEQ ID NO:50; and an LCDR3 sequence comprising SEQ ID NO:58. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:40; an LCDR2 sequence comprising SEQ ID NO:51; and an LCDR3 sequence comprising SEQ ID NO:59. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:41; an LCDR2 sequence comprising SEQ ID NO:50; and an LCDR3 sequence comprising SEQ ID NO:60. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:42; an LCDR2 sequence comprising SEQ ID NO:52; and an LCDR3 sequence comprising SEQ ID NO:61. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:43; an LCDR2 sequence comprising SEQ ID NO:50; and an LCDR3 sequence comprising SEQ ID NO:62. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:44; an LCDR2 sequence comprising SEQ ID NO:50; and an LCDR3 sequence comprising SEQ ID NO:63. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:45; an LCDR2 sequence comprising SEQ ID NO:53; and an LCDR3 sequence comprising SEQ ID NO:64. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:37; an LCDR2 sequence comprising SEQ ID NO:48; and an LCDR3 sequence comprising SEQ ID NO:65. In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:46; an LCDR2 sequence comprising SEQ ID NO:54; and an LCDR3 sequence comprising SEQ ID NO:66.In some embodiments, the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:47; an LCDR2 sequence comprising SEQ ID NO:55; and an LCDR3 sequence comprising SEQ ID NO:67.

[0040] In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:1; an HCDR2 sequence comprising SEQ ID NO:12; and an HCDR3 sequence comprising SEQ ID NO:24, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:37; an LCDR2 sequence comprising SEQ ID NO:48; and an LCDR3 sequence comprising SEQ ID NO:56. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:2; an HCDR2 sequence comprising SEQ ID NO:13; and an HCDR3 sequence comprising SEQ ID NO:25, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:38; an LCDR2 sequence comprising SEQ ID NO:49; and an LCDR3 sequence comprising SEQ ID NO:57. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:3; an HCDR2 sequence comprising SEQ ID NO:14; and an HCDR3 sequence comprising SEQ ID NO:26, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:39; an LCDR2 sequence comprising SEQ ID NO:50; and an LCDR3 sequence comprising SEQ ID NO:58. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:4; an HCDR2 sequence comprising SEQ ID NO:15; and an HCDR3 sequence comprising SEQ ID NO:27, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:40; an LCDR2 sequence comprising SEQ ID NO:51; and an LCDR3 sequence comprising SEQ ID NO:59. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:5; an HCDR2 sequence comprising SEQ ID NO:16; and an HCDR3 sequence comprising SEQ ID NO:28, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:41; an LCDR2 sequence comprising SEQ ID NO:50; and an LCDR3 sequence comprising SEQ ID NO:60.In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:6; an HCDR2 sequence comprising SEQ ID NO:17; and an HCDR3 sequence comprising SEQ ID NO:29, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:42; an LCDR2 sequence comprising SEQ ID NO:52; and an LCDR3 sequence comprising SEQ ID NO:61. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:7; an HCDR2 sequence comprising SEQ ID NO:18; and an HCDR3 sequence comprising SEQ ID NO:30, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:43; an LCDR2 sequence comprising SEQ ID NO:50; and an LCDR3 sequence comprising SEQ ID NO:62. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:8; an HCDR2 sequence comprising SEQ ID NO:19; and an HCDR3 sequence comprising SEQ ID NO:31, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:44; an LCDR2 sequence comprising SEQ ID NO:50; and an LCDR3 sequence comprising SEQ ID NO:63. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:9; an HCDR2 sequence comprising SEQ IDNO:20; and an HCDR3 sequence comprising SEQ ID NO:32, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ IDNO:45; an LCDR2 sequence comprising SEQ ID NO:53; and an LCDR3 sequence comprising SEQ ID NO:64. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:1; an HCDR2 sequence comprising SEQ ID NO:21; and an HCDR3 sequence comprising SEQ ID NO:33, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:37; an LCDR2 sequence comprising SEQ ID NO:48; and an LCDR3 sequence comprising SEQ ID NO:65.In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:1; an HCDR2 sequence comprising SEQ ID NO:21; and an HCDR3 sequence comprising SEQ ID NO:34, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:37; an LCDR2 sequence comprising SEQ ID NO:48; and an LCDR3 sequence comprising SEQ ID NO:65. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:10; an HCDR2 sequence comprising SEQ ID NO:22; and an HCDR3 sequence comprising SEQ ID NO:35, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:46; an LCDR2 sequence comprising SEQ ID NO:54; and an LCDR3 sequence comprising SEQ ID NO:66. In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the VH region comprises: an HCDR1 sequence comprising SEQ ID NO:11; an HCDR2 sequence comprising SEQ ID NO:23; and an HCDR3 sequence comprising SEQ ID NO:36, and wherein the VL region comprises: an LCDR1 sequence comprising SEQ ID NO:47; an LCDR2 sequence comprising SEQ ID NO:55; and an LCDR3 sequence comprising SEQ ID NO:67.

[0041] In some embodiments, the anti-CD122 antibody comprises a series of CDR sequences. In some embodiments, the series of CDR sequences comprises an HCDR1 sequence, an HCDR2 sequence, an HCDR3 sequence, an LCDR1 sequence, an LCDR2 sequence, and an LCDR3 sequence. The series of CDR sequences of each anti-CD122 antibody described herein is listed in Table 3. The name of the series of CDR sequences is E1-E13.

[0042] Table 3: Series of CDR Sequences of Anti-CD122 Antibodies

[0043]

[0044] In some embodiments, the anti-CD122 antibody comprises a framework for grafting CDRs from other animal species. In some embodiments, CDRs from mammalian antibodies are grafted onto a human framework sequence. In some embodiments, CDRs from murine antibodies are grafted onto a human framework sequence. In some embodiments, the human framework sequence forms part of the VH region of the antibody. In some embodiments, the sequences from HCDR1, HCDR2, and HCDR3 are grafted into the human framework sequence.

[0045] In some embodiments, the anti-CD122 antibodies described herein comprise an IgG framework, an IgA framework, an IgE framework, or an IgM framework. In some cases, the anti-CD122 antibody comprises an IgG framework (e.g., IgG1, IgG2, IgG3, or IgG4). In some cases, the anti-CD122 antibody comprises an IgG1 framework. In some cases, the anti-CD122 antibody comprises an IgG2 (e.g., IgG2a or IgG2b) framework. In some cases, the anti-CD122 antibody comprises an IgG2a framework. In some cases, the anti-CD122 antibody comprises an IgG2b framework. In some cases, the anti-CD122 antibody comprises an IgG3 framework. In some cases, the anti-CD122 antibody comprises an IgG4 framework. In some embodiments, a human framework sequence is inserted into the IgG backbone to form a heavy chain sequence. In some embodiments, the IgG backbone is an IgG1 backbone, an IgG2 backbone, an IgG3 backbone, or an IgG4 backbone. In some embodiments, the IgG framework comprises a human IgG heavy chain framework sequence. In some embodiments, the anti-CD122 HCDR sequences are grafted into the human IgG heavy chain framework sequence. In some embodiments, the human IgG heavy chain framework sequence grafted with the anti-CD122 HCDR sequences is analyzed and monoclonal antibody 3D structure modeling is performed to identify key amino acid positions that support the CDR loop structure. In some embodiments, the key amino acid positions in the human IgG heavy chain framework sequence are identified, which, if the human IgG heavy chain framework sequence is reverted to the murine framework sequence from a murine anti-CD122 antibody, would restore affinity for human CD122 in the context of a humanized antibody using the human IgG heavy chain framework sequence grafted with the murine anti-CD122 CDR sequences. In some embodiments, the key amino acid positions in the human IgG heavy chain framework sequence are mutated back to the murine sequence, which is referred to as back mutation. In some embodiments, the human IgG heavy chain framework sequence grafted with the murine anti-CD122 CDR sequences and having the back mutations integrated into the framework sequence is used in the human IgG backbone to construct a humanized IgG heavy chain sequence. In some embodiments, the humanized IgG heavy chain sequence is used to construct an anti-CD122 antibody. Table 4 lists the human IgG heavy chain framework sequences used herein for grafting the anti-CD122 HCDR sequences. Table 4 also lists the human IgG heavy chain framework sequences used herein for grafting the anti-CD122 HCDR sequences, which have integrated back mutations into the framework to potentially restore the lost affinity for the human CD122 ligand. Table 4 also lists the murine parental heavy chain variable framework sequences used for integrating the murine anti-CD122 heavy chain variable region into the human IgG backbone to construct an anti-CD122 chimeric heavy chain. In the sequences of Table 4 disclosed, the X residue is the CDR insertion site. In the sequences of Table 4 disclosed, (X) n＝1-25Refers to the CDR1, CDR2 or CDR3 sequence, where X refers to the CDR amino acid sequence and n equals the number of amino acid residues in the CDR sequence. In Table 4, the CDR1, CDR2 or CDR3 sequence is the HCDR sequence. The framework sequences disclosed in Table 4 are named F1 - F7. In some embodiments, F1 is the human IgG heavy chain framework sequence used herein for grafting the anti - CD122 HCDR sequence. In some embodiments, F2 is the human IgG heavy chain framework sequence used herein for grafting the anti - CD122 HCDR sequence. In some embodiments, F3 is the human IgG heavy chain framework sequence used herein for grafting the anti - CD122 HCDR sequence. In some embodiments, F4 is the human IgG heavy chain framework sequence used herein for grafting the anti - CD122 HCDR sequence, which has incorporated back - mutations into the framework to potentially restore the lost affinity for the human CD122 ligand. In some embodiments, F5 is the human IgG heavy chain framework sequence used herein for grafting the anti - CD122 HCDR sequence, which has incorporated back - mutations into the framework to potentially restore the lost affinity for the human CD122 ligand. In some embodiments, F6 is the human IgG heavy chain framework sequence used herein for grafting the anti - CD122 HCDR sequence, which has incorporated back - mutations into the framework to potentially restore the lost affinity for the human CD122 ligand. In some embodiments, F7 is the murine parental heavy chain variable framework sequence, which is used to integrate the murine anti - CD122 heavy chain variable region into the human IgG backbone to construct an anti - CD122 chimeric heavy chain in the framework, thereby potentially restoring the lost affinity for the human CD122 ligand. In some embodiments, the HCDR sequence from one of the E1 - E13 series is grafted into F1 to construct the heavy chain variable domain sequence. In some embodiments, the HCDR sequence from one of the E1 - E13 series is grafted into F2 to construct the heavy chain variable domain sequence. In some embodiments, the HCDR sequence from one of the E1 - E13 series is grafted into F3 to construct the heavy chain variable domain sequence. In some embodiments, the HCDR sequence from one of the E1 - E13 series is grafted into F4 to construct the heavy chain variable domain sequence. In some embodiments, the HCDR sequence from one of the E1 - E13 series is grafted into F5 to construct the heavy chain variable domain sequence. In some embodiments, the HCDR sequence from one of the E1 - E13 series is grafted into F6 to construct the heavy chain variable domain sequence. In some embodiments, the HCDR sequence from one of the E1 - E13 series is grafted into F7 to construct the heavy chain variable domain sequence.

[0046] Table 4: Human IgG Heavy Chain Framework Sequences and Parental Murine IgG Heavy Chain Framework Sequences

[0047]

[0048] (X) n＝1-25 is a CDR1, CDR2, or CDR3 sequence.

[0049] In some embodiments, the anti-CD122 antibody comprises a framework for grafting CDRs from other animal species. In some embodiments, CDRs from mammalian antibodies are grafted onto a human framework sequence. In some embodiments, CDRs from murine antibodies are grafted onto a human framework sequence. In some embodiments, the human framework sequence forms part of the VL region of the antibody. In some embodiments, sequences from LCDR1, LCDR2, and LCDR3 are grafted into a human framework sequence.

[0050] In some embodiments, the anti-CD122 antibodies described herein comprise a λ or κ framework. In some cases, the anti-CD122 antibody comprises a κ framework grafted with LCDR1, LCDR2, and LCDR3 sequences. In some cases, the anti-CD122 antibody comprises a κ framework grafted with LCDR1, LCDR2, and LCDR3 sequences. In some embodiments, the κ framework forms part of the light chain. In some embodiments, the κ framework that forms part of the light chain pairs with the heavy chain described herein. In some embodiments, the κ framework is a human κ light chain framework. In some embodiments, the human κ light chain framework comprises a human κ light chain framework sequence. In some embodiments, the human κ light chain framework sequence is grafted with anti-CD122 LCDR sequences. In some embodiments, the human κ light chain framework sequence grafted with anti-CD122 LCDR sequences is analyzed and 3D monoclonal antibody structure modeling is performed to identify key amino acid positions that support the CDR loop structure. In some embodiments, key amino acid positions in the human κ light chain framework sequence are identified such that if the human κ light chain framework sequence is reverted to the mouse framework sequence from a murine anti-CD122 antibody, these positions would restore affinity for human CD122 in the context of a humanized antibody using the human κ light chain framework sequence grafted with murine anti-CD122 CDR sequences. In some embodiments, the key amino acid positions in the human κ light chain framework sequence are mutated back to the mouse sequence, which is referred to as back mutation. In some embodiments, the human κ light chain framework sequence grafted with murine anti-CD122 CDR sequences and having back mutations integrated into the framework sequence is used in the human light chain scaffold to construct a humanized light chain sequence. In some embodiments, the humanized κ light chain sequence is used to construct an anti-CD122 antibody. Table 5 lists the human κ light chain framework sequences used herein for grafting anti-CD122 LCDR sequences. Table 5 also lists the human κ light chain framework sequences used herein for grafting anti-CD122 LCDR sequences that have integrated back mutations into the framework to potentially restore affinity lost for the human CD122 ligand. Table 5 also lists the murine parental light chain variable framework sequences used to integrate the murine anti-CD122 light chain variable region into the human light chain scaffold to construct an anti-CD122 chimeric light chain. In the sequences disclosed in Table 5, the X residue is the CDR insertion site. In the sequences disclosed in Table 5, (X) n＝1-25Refers to the CDR1, CDR2, or CDR3 sequence, where X refers to the CDR amino acid sequence and n equals the number of amino acid residues in the CDR sequence. In Table 5, the CDR1, CDR2, or CDR3 sequence is the LCDR sequence. The framework sequences disclosed in Table 5 are named F8 - F14. In some embodiments, F8 is the human κ light chain framework sequence used herein for grafting the anti - CD122 LCDR sequence. In some embodiments, F9 is the human κ light chain framework sequence used herein for grafting the anti - CD122 LCDR sequence. In some embodiments, F10 is the human κ light chain framework sequence used herein for grafting the anti - CD122 LCDR sequence. In some embodiments, F11 is the human κ light chain framework sequence used herein for grafting the anti - CD122 LCDR sequence, and this human κ light chain framework sequence has incorporated back - mutations into the framework to potentially restore the lost affinity for the human CD122 ligand. In some embodiments, F12 is the human κ light chain framework sequence used herein for grafting the anti - CD122 LCDR sequence, and this human κ light chain framework sequence has incorporated back - mutations into the framework to potentially restore the lost affinity for the human CD122 ligand. In some embodiments, F13 is the human IgG heavy chain framework sequence used herein for grafting the anti - CD122 LCDR sequence, and this human IgG heavy chain framework sequence has incorporated back - mutations into the framework to potentially restore the lost affinity for the human CD122 ligand. In some embodiments, F14 is the mouse parental light chain variable framework sequence, which is used to integrate the mouse anti - CD122 light chain variable region into the human light chain backbone to create an anti - CD122 chimeric light chain in the framework, thereby potentially restoring the lost affinity for the human CD122 ligand. In some embodiments, the LCDR sequence from one of the E1 - E13 series is grafted into F8 to create a light chain variable domain sequence. In some embodiments, the LCDR sequence from one of the E1 - E13 series is grafted into F9 to construct a light chain variable domain sequence. In some embodiments, the LCDR sequence from one of the E1 - E13 series is grafted into F10 to construct a light chain variable domain sequence. In some embodiments, the LCDR sequence from one of the E1 - E13 series is grafted into F11 to construct a light chain variable domain sequence. In some embodiments, the LCDR sequence from one of the E1 - E13 series is grafted into F12 to construct a light chain variable domain sequence. In some embodiments, the LCDR sequence from one of the E1 - E13 series is grafted into F13 to construct a light chain variable domain sequence. In some embodiments, the LCDR sequence from one of the E1 - E13 series is grafted into F14 to construct a light chain variable domain sequence.

[0051] Table 5: Human κ Light Chain Framework Sequences and Parental Mouse Light Chain Framework Sequences

[0052]

[0053] (X) n＝1-25 is a CDR1, CDR2, or CDR3 sequence

[0054] In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the sequence of the VH region has about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with SEQ ID NOs: 82-94, and the sequence of the VL region has about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with SEQ ID NOs: 95-107. In some embodiments, the anti-CD122 antibody comprises a VH domain that has at least 80% sequence identity with a sequence selected from SEQ ID NOs: 82-94. In some embodiments, the anti-CD122 antibody comprises a VH domain that has at least 85% sequence identity with a sequence selected from SEQ ID NOs: 82-94. In some embodiments, the anti-CD122 antibody comprises a VH domain that has at least 90% sequence identity with a sequence selected from SEQ ID NOs: 82-94. In some embodiments, the anti-CD122 antibody comprises a VH domain that has at least 95% sequence identity with a sequence selected from SEQ ID NOs: 82-94. In some embodiments, the anti-CD122 antibody comprises a VL domain that has at least 80% sequence identity with a sequence selected from SEQ ID NOs: 95-107. In some embodiments, the anti-CD122 antibody comprises a VL domain that has at least 85% sequence identity with a sequence selected from SEQ ID NOs: 95-107. In some embodiments, the anti-CD122 antibody comprises a VL domain that has at least 90% sequence identity with a sequence selected from SEQ ID NOs: 95-107. In some embodiments, the anti-CD122 antibody comprises a VL domain that has at least 95% sequence identity with a sequence selected from SEQ ID NOs: 95-107. In some embodiments, the VH region comprises a sequence selected from SEQ ID NOs: 82-94 (Table 6), and the VL region comprises a sequence selected from SEQ ID NOs: 95-107 (Table 7). The VH sequences, names, and corresponding SEQ ID NOs are listed in Table 6. The VL sequences, names, and corresponding SEQ ID NOs are listed in Table 7.

[0055] Table 6: VH Sequences

[0056]

[0057] Table 7: VL sequences

[0058]

[0059]

[0060] In some embodiments, the anti-CD122 antibody comprises a VH region having a series of HCDR sequences of CDRs integrated into the heavy chain framework sequence. In some embodiments, the anti-CD122 antibody comprises a VH region comprising a series of HCDR sequences of E7 integrated into framework sequence F1. In some embodiments, the anti-CD122 antibody comprises a VH region comprising a series of HCDR sequences of E7 integrated into framework sequence F2. In some embodiments, the anti-CD122 antibody comprises a VH region comprising a series of HCDR sequences of E7 integrated into framework sequence F3. In some embodiments, the anti-CD122 antibody comprises a VH region comprising a series of HCDR sequences of E7 integrated into framework sequence F4. In some embodiments, the anti-CD122 antibody comprises a VH region comprising a series of HCDR sequences of E7 integrated into framework sequence F5. In some embodiments, the anti-CD122 antibody comprises a VH region comprising a series of HCDR sequences of E7 integrated into framework sequence F6. In some embodiments, the anti-CD122 antibody comprises a VH region comprising a series of HCDR sequences of E7 integrated into framework sequence F7.

[0061] In some embodiments, the anti-CD122 antibody comprises a VL region having a series of LCDR sequences of CDRs integrated into the light chain framework sequence. In some embodiments, the anti-CD122 antibody comprises a VL region comprising a series of LCDR sequences of E7 integrated into framework sequence F8. In some embodiments, the anti-CD122 antibody comprises a VL region comprising a series of LCDR sequences of E7 integrated into framework sequence F9. In some embodiments, the anti-CD122 antibody comprises a VL region comprising a series of LCDR sequences of E7 integrated into framework sequence F10. In some embodiments, the anti-CD122 antibody comprises a VL region comprising a series of LCDR sequences of E7 integrated into framework sequence F11. In some embodiments, the anti-CD122 antibody comprises a VL region comprising a series of LCDR sequences of E7 integrated into framework sequence F12. In some embodiments, the anti-CD122 antibody comprises a VL region comprising a series of LCDR sequences of E7 integrated into framework sequence F13. In some embodiments, the anti-CD122 antibody comprises a VL region comprising a series of LCDR sequences of E7 integrated into framework sequence F14.

[0062] In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:82 and a VL region comprising SEQ ID NO:95. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:83 and a VL region comprising SEQ ID NO:96. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:84 and a VL region comprising SEQ ID NO:97. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:85 and a VL region comprising SEQ ID NO:98. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:86 and a VL region comprising SEQ ID NO:99. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:87 and a VL region comprising SEQ ID NO:100. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:88 and a VL region comprising SEQ ID NO:101. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:89 and a VL region comprising SEQ ID NO:102. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:90 and a VL region comprising SEQ ID NO:103. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:91 and a VL region comprising SEQ ID NO:104. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:92 and a VL region comprising SEQ ID NO:105. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:93 and a VL region comprising SEQ ID NO:106. In some embodiments, the anti-CD122 antibody comprises a VH region comprising SEQ ID NO:94 and a VL region comprising SEQ ID NO:107.

[0063] In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid that has at least 80% sequence identity with a sequence selected from SEQ ID NOs: 108-120. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid that has at least 85% sequence identity with a sequence selected from SEQ ID NOs: 108-120. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid that has at least 90% sequence identity with a sequence selected from SEQ ID NOs: 108-120. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid that has at least 95% sequence identity with a sequence selected from SEQ ID NOs: 108-120. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid that has at least 80% sequence identity with a sequence selected from SEQ ID NOs: 121-133. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid that has at least 85% sequence identity with a sequence selected from SEQ ID NOs: 121-133. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid that has at least 90% sequence identity with a sequence selected from SEQ ID NOs: 121-133. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid that has at least 95% sequence identity with a sequence selected from SEQ ID NOs: 121-133.

[0064] The nucleic acid sequences encoding the VH and VL domains are listed in Table 8. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 108. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 109. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 110. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 111. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 112. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 113. In some embodiments, in some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 114. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 115. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 116. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 117. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 118. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 119. In some embodiments, the anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising SEQ ID NO: 120. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO: 121. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO: 122. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO: 123. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO: 124. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO: 125. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO: 126. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO: 127.In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO:128. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO:129. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO:130. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO:131. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO:132. In some embodiments, the anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising SEQ ID NO:133.

[0065] Table 8: Nucleic acid sequences encoding VH and VL domains

[0066]

[0067]

[0068]

[0069]

[0070] In some embodiments, the anti-CD122 antibodies described herein are full-length antibodies. In other aspects, the anti-CD122 antibody is an antigen-binding fragment thereof. In some cases, the anti-CD122 antibody is a humanized antibody or an antigen-binding fragment thereof, a chimeric antibody or an antigen-binding fragment thereof, a monoclonal antibody or an antigen-binding fragment thereof. In some cases, the anti-CD122 antibody is a monovalent Fab’, F(ab)’3 fragment, single-chain variable fragment (scFv), (scFv)2, minibody, nanobody, disulfide-stabilized Fv protein (“dsFv”), single-domain antibody (sdAb), IgNAR, camelid antibody or an antigen-binding fragment thereof, or a chemically modified derivative thereof.

[0071] In some cases, the anti-CD122 antibody comprises one or more mutations in the framework region (such as the CH1 domain, CH2 domain, CH3 domain, hinge region, or a combination thereof). In some cases, the one or more mutations are used to stabilize the antibody. In some cases, the one or more mutations are used to increase the half-life. In some cases, the one or more mutations are used to modulate Fc receptor interaction. In some cases, the one or more mutations are used to reduce or eliminate Fc effector functions (such as FcγR), antibody-dependent cell-mediated cytotoxicity (ADCC), or complement-dependent cytotoxicity (CDC). In additional cases, the one or more mutations are used to modulate glycosylation.

[0072] In some embodiments, the one or more mutations are located in the Fc region.

[0073] In some embodiments, the human IgG constant region is modified to alter antibody-dependent cell cytotoxicity (ADCC) and / or complement-dependent cytotoxicity (CDC), for example, using amino acid modifications described in the following references: Natsume et al., 2008 Cancer Res, 68(10):3863-72; Idusogie et al., 2001 J Immunol, 166(4):2571-5; Moore et al., 2010 mAbs, 2(2):181-189; Lazar et al., 2006 PNAS, 103(11):4005-4010, Shields et al., 2001 JBC, 276(9):6591-6604; Stavenhagen et al., 2007 Cancer Res, 67(18):8882-8890; Stavenhagen et al., 2008 Advan. Enzyme Regul., 48:152-164; Alegre et al., 1992 J Immunol, 148:3461-3468; Urban et al., 2021 Front Immunol. November 25; 12:724361; Zhou et al., 2020 MAbs. January - December; 12(1):1814583; Revised Kaneko and Niwa, 2011 Biodrugs, 25(1):1-11.

[0074] In some embodiments, the anti-CD122 antibodies described herein are full-length antibodies that comprise a heavy chain (HC) and a light chain (LC). In some embodiments, the HC has about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 80% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 85% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with SEQ ID NO: 134. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with SEQ ID NO: 135. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with SEQ ID NO: 136. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with SEQ ID NO: 137. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with SEQ ID NO: 138. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with SEQ ID NO: 139. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with SEQ ID NO: 140. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 90% sequence identity with SEQ ID NO: 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 95% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 96% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 97% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 98% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141.In some embodiments, the anti-CD122 antibody comprises a heavy chain that has at least 99% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain that has 100% sequence identity with a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the VH domain of the anti-CD122 antibody has at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with the VH domain in a sequence selected from SEQ ID NOs: 134 - 141. In some embodiments, the VH domain of the anti-CD122 antibody has at least 90% sequence identity with the VH domain in SEQ ID NO: 134. In some embodiments, the VH domain of the anti-CD122 antibody has at least 90% sequence identity with the VH domain in SEQ ID NO: 135. In some embodiments, the VH domain of the anti-CD122 antibody has at least 90% sequence identity with the VH domain in SEQ ID NO: 136. In some embodiments, the VH domain of the anti-CD122 antibody has at least 90% sequence identity with the VH domain in SEQ ID NO: 137. In some embodiments, the VH domain of the anti-CD122 antibody has at least 90% sequence identity with the VH domain in SEQ ID NO: 138. In some embodiments, the VH domain of the anti-CD122 antibody has at least 90% sequence identity with the VH domain in SEQ ID NO: 139. In some embodiments, the VH domain of the anti-CD122 antibody has at least 90% sequence identity with the VH domain in SEQ ID NO: 140. In some embodiments, the VH domain of the anti-CD122 antibody has at least 90% sequence identity with the VH domain in SEQ ID NO: 141. In some embodiments, the VH domain of the anti-CD122 antibody has 100% sequence identity with the VH domain in SEQ ID NO: 134. In some embodiments, the VH domain of the anti-CD122 antibody has 100% sequence identity with the VH domain in SEQ ID NO: 135. In some embodiments, the VH domain of the anti-CD122 antibody has at least 100% sequence identity with the VH domain in SEQ ID NO: 136. In some embodiments, the VH domain of the anti-CD122 antibody has 100% sequence identity with the VH domain in SEQ ID NO: 137. In some embodiments, the VH domain of the anti-CD122 antibody has 100% sequence identity with the VH domain in SEQ ID NO: 138.In some embodiments, the VH domain of the anti-CD122 antibody has 100% sequence identity with the VH domain in SEQ ID NO: 139. In some embodiments, the VH domain of the anti-CD122 antibody has 100% sequence identity with the VH domain in SEQ ID NO: 140. In some embodiments, the VH domain of the anti-CD122 antibody has 100% sequence identity with the VH domain in SEQ ID NO: 141. In some embodiments, the heavy chain comprises one or more conservative amino acid substitutions from the sequences described herein. In some embodiments, the VH domain comprises one or more conservative amino acid substitutions from the sequences described herein.

[0075] In some embodiments, the anti-CD122 antibodies described herein are full-length antibodies that comprise a heavy chain (HC) and a light chain (LC). In some embodiments, the LC has about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 80% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 85% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 90% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 90% sequence identity to SEQ ID NO: 142. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 90% sequence identity to SEQ ID NO: 143. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 90% sequence identity to SEQ ID NO: 144. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 90% sequence identity to SEQ ID NO: 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 95% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 96% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 97% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 98% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145. In some embodiments, the anti-CD122 antibody comprises a light chain that has at least 99% sequence identity to a sequence selected from SEQ ID NOs: 142 - 145.In some embodiments, the VL domain of the anti-CD122 antibody has at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity with the VL domain in the sequences selected from SEQ ID NOs: 142 - 145. In some embodiments, the VL domain of the anti-CD122 antibody has at least 90% sequence identity with the VL domain in SEQ ID NO: 142. In some embodiments, the VL domain of the anti-CD122 antibody has at least 90% sequence identity with the VL domain in SEQ ID NO: 143. In some embodiments, the VL domain of the anti-CD122 antibody has at least 90% sequence identity with the VL domain in SEQ ID NO: 144. In some embodiments, the VL domain of the anti-CD122 antibody has at least 90% sequence identity with the VL domain in SEQ ID NO: 145. In some embodiments, the VL domain of the anti-CD122 antibody has 100% sequence identity with the VL domain in SEQ ID NO: 142. In some embodiments, the VL domain of the anti-CD122 antibody has 100% sequence identity with the VL domain in SEQ ID NO: 143. In some embodiments, the VL domain of the anti-CD122 antibody has 100% sequence identity with the VL domain in SEQ ID NO: 144. In some embodiments, the VL domain of the anti-CD122 antibody has 100% sequence identity with the VL domain in SEQ ID NO: 145. In some embodiments, the light chain comprises one or more conservative amino acid substitutions from the sequences described herein. In some embodiments, the VL domain comprises one or more conservative amino acid substitutions from the sequences described herein.

[0076] In some cases, for the anti-CD122 antibodies described herein, the heavy chain (HC) comprises a sequence selected from Table 9. In some cases, for the anti-CD122 antibodies described herein, the light chain (LC) comprises a sequence selected from Table 10. In some embodiments, the HC having a VH domain with a murine HC variable framework sequence and HCDR sequences is within an IgG1 backbone and is listed as SEQ ID NO: 134. In some embodiments, the HC having a VH domain with a murine HC variable framework sequence and HCDR sequences is within an IgG4 backbone and is listed as SEQ ID NO: 138. In some embodiments, the LC having a VL domain with a murine light chain variable framework sequence and LCDR sequences is within a κ light chain backbone and is listed as SEQ ID NO: 142.

[0077] Table 9: Anti-CD122 Antibody Heavy Chain Sequences

[0078]

[0079]

[0080] (X) n＝14-40 is the leader sequence

[0081] Table 10: Light chain sequence of anti-CD122 antibody

[0082]

[0083] (X) n＝14-40 is the leader sequence

[0084] In some embodiments, the anti-CD122 antibodies described herein are full-length antibodies that comprise a heavy chain (HC) and a light chain (LC). In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:134 and an LC comprising SEQ ID NO:142. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:135 and an LC comprising SEQ ID NO:143. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:135 and an LC comprising SEQ ID NO:144. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:135 and an LC comprising SEQ ID NO:145. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:136 and an LC comprising SEQ ID NO:143. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:136 and an LC comprising SEQ ID NO:144. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:136 and an LC comprising SEQ ID NO:145. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:137 and an LC comprising SEQ ID NO:143. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:137 and an LC comprising SEQ ID NO:144. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:137 and an LC comprising SEQ ID NO:145. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:138 and an LC comprising SEQ ID NO:142. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:139 and an LC comprising SEQ ID NO:143. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:139 and an LC comprising SEQ ID NO:144. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:139 and an LC comprising SEQ ID NO:145. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:140 and an LC comprising SEQ ID NO:143. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:140 and an LC comprising SEQ ID NO:144. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:140 and an LC comprising SEQ ID NO:145.In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:141 and an LC comprising SEQ ID NO:143. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:141 and an LC comprising SEQ ID NO:144. In some embodiments, the full-length antibody comprises: an HC comprising SEQ ID NO:129 and an LC comprising SEQ ID NO:145.

[0085] In some embodiments, the anti-CD122 antibody comprises full-length antibody chain polypeptides encoded by nucleic acids having at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to a sequence selected from SEQ ID NOs: 146 - 157. In some embodiments, the full-length antibody chain is encoded by a heavy chain nucleic acid sequence selected from SEQ ID NOs: 146 - 153. In some embodiments, the full-length antibody chain is encoded by a light chain nucleic acid sequence selected from SEQ ID NOs: 154 - 157. In some embodiments, the anti-CD122 antibody comprises a heavy chain encoded by a nucleic acid having at least 80% sequence identity to a sequence selected from SEQ ID NOs: 146 - 153. In some embodiments, the anti-CD122 antibody comprises a heavy chain encoded by a nucleic acid having at least 85% sequence identity to a sequence selected from SEQ ID NOs: 146 - 153. In some embodiments, the anti-CD122 antibody comprises a heavy chain encoded by a nucleic acid having at least 90% sequence identity to a sequence selected from SEQ ID NOs: 146 - 153. In some embodiments, the anti-CD122 antibody comprises a heavy chain encoded by a nucleic acid having at least 95% sequence identity to a sequence selected from SEQ ID NOs: 146 - 153. In some embodiments, the anti-CD122 antibody comprises a light chain encoded by a nucleic acid having at least 80% sequence identity to a sequence selected from SEQ ID NOs: 154 - 157. In some embodiments, the anti-CD122 antibody comprises a light chain encoded by a nucleic acid having at least 85% sequence identity to a sequence selected from SEQ ID NOs: 154 - 157. In some embodiments, the anti-CD122 antibody comprises a light chain encoded by a nucleic acid having at least 90% sequence identity to a sequence selected from SEQ ID NOs: 154 - 157. In some embodiments, the anti-CD122 antibody comprises a light chain encoded by a nucleic acid having at least 95% sequence identity to a sequence selected from SEQ ID NOs: 154 - 157. In some embodiments, the full-length antibody chain is encoded by a nucleic acid selected from Table 11.

[0086] Table 11: Nucleic acid sequences encoding full-length heavy and light chains

[0087]

[0088]

[0089]

[0090]

[0091]

[0092]

[0093] (X) n＝42-120 is a leader sequence

[0094] In some embodiments, the anti-CD122 antibody comprises full-length antibody chain polypeptides encoded by an HC nucleic acid sequence and an LC nucleic acid sequence. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:146 and an LC nucleic acid sequence comprising SEQ ID NO:154. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:147 and an LC nucleic acid sequence comprising SEQ ID NO:155. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:147 and an LC nucleic acid sequence comprising SEQ ID NO:156. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:147 and an LC nucleic acid sequence comprising SEQ ID NO:157. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:148 and an LC nucleic acid sequence comprising SEQ ID NO:155. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:148 and an LC nucleic acid sequence comprising SEQ ID NO:156. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:148 and an LC nucleic acid sequence comprising SEQ ID NO:157. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:149 and an LC nucleic acid sequence comprising SEQ ID NO:155. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:149 and an LC nucleic acid sequence comprising SEQ ID NO:156. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:149 and an LC nucleic acid sequence comprising SEQ ID NO:157. In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO:150 and an LC nucleic acid sequence comprising SEQ ID NO:154.In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:151 and an LC nucleic acid sequence comprising SEQ ID NO:155. In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:151 and an LC nucleic acid sequence comprising SEQ ID NO:156. In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:151 and an LC nucleic acid sequence comprising SEQ ID NO:157. In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:152 and an LC nucleic acid sequence comprising SEQ ID NO:155. In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:152 and an LC nucleic acid sequence comprising SEQ ID NO:156. In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:152 and an LC nucleic acid sequence comprising SEQ ID NO:157. In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:153 and an LC nucleic acid sequence comprising SEQ ID NO:155. In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:153 and an LC nucleic acid sequence comprising SEQ ID NO:156. In some embodiments, the anti-CD122 antibody comprises full-length antibody chains encoded by an HC nucleic acid sequence comprising SEQ ID NO:153 and an LC nucleic acid sequence comprising SEQ ID NO:157.

[0095] In some embodiments, the anti-CD122 antibody heavy chain and the anti-CD122 antibody light chain have leader sequences near the amino-terminal region of each polypeptide. In some embodiments, the leader sequence is located at the N-terminus of the anti-CD122 antibody heavy chain sequence. In some embodiments, the leader sequence is located at the N-terminus of the anti-CD122 antibody heavy chain sequence provided in Table 9. In some embodiments, the leader sequence is located at the N-terminus of the anti-CD122 antibody light chain sequence. In some embodiments, the leader sequence is located at the N-terminus of the anti-CD122 antibody light chain sequence provided in Table 10. In some embodiments, (X) n＝14-40Amino acids of a leader sequence representing the amino terminus of an anti-CD122 antibody heavy chain sequence. In some embodiments, (X)n = 14 -40 Amino acids of a leader sequence representing the amino terminus of an anti-CD122 antibody light chain sequence. In some embodiments, the leader sequence is 14 - 40 amino acids in length. In some embodiments, the leader sequence is 15 - 35 amino acids in length. In some embodiments, the leader sequences of the anti-CD122 antibody heavy chain and the anti-CD122 antibody light chain that pair to form an anti-CD122 antibody are identical to each other. In some embodiments, the leader sequences of the anti-CD122 antibody heavy chain and the anti-CD122 antibody light chain that pair to form an anti-CD122 antibody are different from each other. In some embodiments, the leader sequence comprises the amino acid sequence listed in Table 12. In some embodiments, the anti-CD122 antibody heavy chain comprises an additional amino acid sequence at the N-terminus of the leader sequence. In some embodiments, the anti-CD122 antibody heavy chain comprises an additional amino acid sequence immediately following the leader sequence. In some embodiments, the additional amino acid sequence immediately following the leader sequence is located before the start position of the heavy chain variable domain. In some embodiments, the anti-CD122 antibody light chain comprises an additional amino acid sequence at the N-terminus of the leader sequence. In some embodiments, the anti-CD122 antibody light chain comprises an additional amino acid sequence immediately following the leader sequence. In some embodiments, the additional amino acid sequence immediately following the leader sequence is located before the start position of the light chain variable domain. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody heavy chain sequence comprises the leader sequence containing SEQ ID NO:158. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody heavy chain sequence comprises the leader sequence containing SEQ ID NO:159. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody heavy chain sequence comprises the leader sequence containing SEQ ID NO:160. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody heavy chain sequence comprises the leader sequence containing SEQ ID NO:161.

[0096] In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody light chain sequence comprises the leader sequence containing SEQ ID NO:158. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody light chain sequence comprises the leader sequence containing SEQ ID NO:159. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody light chain sequence comprises the leader sequence containing SEQ ID NO:160. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody light chain sequence comprises the leader sequence containing SEQ ID NO:161.

[0097] In some embodiments, the anti-CD122 antibody comprises full-length antibody chain polypeptides encoded by an HC nucleic acid sequence and an LC nucleic acid sequence, each of which has a nucleic acid sequence encoding a leader sequence located near the 5'-end of the nucleic acid encoding the HC or near the 5'-end of the nucleic acid encoding the LC. In some embodiments, the nucleic acid sequence encoding the leader sequence is located at the 5'-end of the nucleic acid encoding the heavy chain of the anti-CD122 antibody. In some embodiments, the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody having a nucleic acid sequence encoding a leader sequence is provided in Table 11. In some embodiments, the nucleic acid sequence encoding the leader sequence is located at the 5'-end of the nucleic acid encoding the light chain of the anti-CD122 antibody. In some embodiments, the nucleic acid sequence encoding the light chain of the anti-CD122 antibody having a nucleic acid sequence encoding a leader sequence is provided in Table 11. In some embodiments, (X) n＝42-120 Nucleotides for the leader sequence representing the 5'-end of the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody. In some embodiments, (X) n＝42-120Nucleotides of a leader sequence representing the 5' end of a nucleic acid sequence encoding the light chain of an anti-CD122 antibody. In some embodiments, the leader sequence is 42-120 nucleotides in length. In some embodiments, the leader sequence is 45-105 nucleotides in length. In some embodiments, the leader sequence of the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody and the leader sequence of the nucleic acid sequence encoding the light chain of the anti-CD122 antibody are identical to each other. In some embodiments, the leader sequence of the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody and the leader sequence of the nucleic acid sequence encoding the light chain of the anti-CD122 antibody are different from each other. In some embodiments, the leader sequence encodes the amino acid sequence listed in Table 12. In some embodiments, the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody contains an additional nucleotide sequence at the 5' end of the leader sequence. In some embodiments, the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody contains an additional nucleotide sequence immediately adjacent to the 3' end of the leader sequence. In some embodiments, the nucleic acid sequence encoding the light chain of the anti-CD122 antibody contains an additional nucleotide sequence at the 5' end of the leader sequence. In some embodiments, the nucleic acid sequence encoding the light chain of the anti-CD122 antibody contains an additional nucleotide sequence immediately adjacent to the 3' end of the leader sequence. In some embodiments, the leader sequence at the 5' end of the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody encodes the amino acid leader sequence of SEQ ID NO:158. In some embodiments, the leader sequence at the 5' end of the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody encodes the amino acid leader sequence of SEQ ID NO:159. In some embodiments, the leader sequence at the 5' end of the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody encodes the amino acid leader sequence of SEQ ID NO:160. In some embodiments, the leader sequence at the 5' end of the nucleic acid sequence encoding the heavy chain of the anti-CD122 antibody encodes the amino acid leader sequence of SEQ ID NO:161. In some embodiments, the leader sequence at the 5' end of the nucleic acid sequence encoding the light chain of the anti-CD122 antibody encodes the amino acid leader sequence of SEQ ID NO:158. In some embodiments, the leader sequence at the 5' end of the nucleic acid sequence encoding the light chain of the anti-CD122 antibody encodes the amino acid leader sequence of SEQ ID NO:159. In some embodiments, the leader sequence at the 5' end of the nucleic acid sequence encoding the light chain of the anti-CD122 antibody encodes the amino acid leader sequence of SEQ ID NO:160. In some embodiments, the leader sequence at the 5' end of the nucleic acid sequence encoding the light chain of the anti-CD122 antibody encodes the amino acid leader sequence of SEQ ID NO:161.

[0098] Table 12: Leader sequences for the heavy and light chains

[0099] SEQ ID NO: Leader sequence 158 MDPKGSLSWRILLFLSLAFELSYG 159 METDTLLLWVLLLWVPGSTG 160 MGWSLILLFLVAVATRVHS 161 MRVPAQLLGLLLLWLPGARC

[0100] In some embodiments, the HC polypeptide and the LC polypeptide pair together to form an anti-CD122 antibody or an anti-CD122 antibody fragment. In some embodiments, the two heavy chains are linked to each other by disulfide bonds, and each heavy chain is linked to the light chain by a disulfide bond. In some embodiments, the specific HC polypeptide and the specific LC polypeptide that pair together to form an anti-CD122 antibody are named G1-G20 according to Table 13. In some embodiments, G1 is a chimeric anti-CD122 antibody having mouse parental variable domain sequences in a human IgG1 backbone. In some embodiments, G2-10 are humanized anti-CD122 antibodies having mouse-derived CDRs integrated into the human variable domain framework sequences in a human IgG1 backbone, and these CDRs have been optimized to retain affinity for CD122. In some embodiments, G11 is a chimeric anti-CD122 antibody having mouse parental variable domain sequences in a human IgG4 backbone. In some embodiments, G12-20 are humanized anti-CD122 antibodies having mouse-derived CDRs integrated into the human variable domain framework sequences in a human IgG4 backbone, and these CDRs have been optimized to retain affinity for CD122.

[0101] Table 13: Antibody Name and Heavy Chain / Light Chain Sequence Combinations

[0102]

[0103] In some embodiments, the anti-CD122 antibody CDR sequences can be defined by an antibody numbering scheme. In an embodiment, the antibody numbering scheme is Kabat. In an embodiment, the antibody numbering scheme is IMGT. In an embodiment, the antibody numbering scheme is AbM. In an embodiment, the antibody numbering scheme is Chothia. In an embodiment, the antibody numbering scheme is Contact. Table 14 lists the CDR sequences of anti-CD122 antibodies and their antigen-binding fragments according to various antibody numbering schemes. In Table 14, the HCDR1, HCDR2, and HCDR3 sequences defined according to a specific antibody numbering scheme are located in the VH region of the heavy chain, where the heavy chain sequences according to the representative SEQ ID NO. are listed in Table 9. In Table 14, the LCDR1, LCDR2, and LCDR3 sequences defined according to a specific antibody numbering scheme are located in the VL region of the light chain, where the light chain sequences according to the representative SEQ ID NO. are listed in Table 10.

[0104] Table 14: CDR Sequences of the Heavy Chain Variable Domain and Light Chain Variable Domain of Anti-CD122 Antibodies Contained in the Heavy Chain or Light Chain

[0105]

[0106]

[0107] In some aspects, the anti-CD122 antibody or antigen-binding fragment thereof comprises the CDR sequences listed in Table 14. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain that comprises the HCDR sequences listed in Table 14. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VL domain that comprises the LCDR sequences listed in Table 14. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain and a VL domain, the VH domain comprising the HCDR sequences listed in Table 14 and the VL domain comprising the LCDR sequences listed in Table 14. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain that comprises the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the Kabat numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain that comprises the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the IMGT numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain that comprises the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the AbM numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain that comprises the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the Chothia numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain that comprises the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the Contact numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VL domain that comprises the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the Kabat numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VL domain that comprises the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the IMGT numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VL domain that comprises the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the AbM numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VL domain that comprises the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the Chothia numbering scheme.In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VL domain that comprises the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the Contact numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain and a VL domain, the VH domain comprising the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the Kabat numbering scheme, and the VL domain comprising the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the Kabat numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain and a VL domain, the VH domain comprising the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the IMGT numbering scheme, and the VL domain comprising the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the IMGT numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain and a VL domain, the VH domain comprising the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the AbM numbering scheme, and the VL domain comprising the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the AbM numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain and a VL domain, the VH domain comprising the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the Chothia numbering scheme, and the VL domain comprising the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the Chothia numbering scheme. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain and a VL domain, the VH domain comprising the HCDR1 sequence, HCDR2 sequence, and HCDR3 sequence listed in Table 14 according to the Contact numbering scheme, and the VL domain comprising the LCDR1 sequence, LCDR2 sequence, and LCDR3 sequence listed in Table 14 according to the Contact numbering scheme.

[0108] In some aspects, the anti-CD122 antibody or an antigen-binding fragment thereof comprises a VH domain and a VL domain, the VH domain comprising the HCDR sequences identified by SEQ ID NO. listed in Table 14 according to the antibody numbering scheme, and the VL domain comprising the LCDR sequences identified by SEQ ID NO. listed in Table 14 according to the antibody numbering scheme. In some embodiments, the anti-CD122 antibody comprises a VH domain and a VL domain, the VH domain comprising the HCDR sequences identified by SEQ ID NO. listed in Table 14 according to the antibody numbering scheme, and the VL domain comprising the LCDR sequences identified by SEQ ID NO. listed in Table 14 according to the antibody numbering scheme. In some embodiments, the anti-CD122 antigen-binding fragment thereof comprises a VH domain and a VL domain, the VH domain comprising the HCDR sequences identified by SEQ ID NO. listed in Table 14 according to the antibody numbering scheme, and the VL domain comprising the LCDR sequences identified by SEQ ID NO. listed in Table 14 according to the antibody numbering scheme. In some embodiments, the anti-CD122 antibody or an antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:7, an HCDR2 having the sequence of SEQ ID NO:18, an HCDR3 having the sequence of SEQ ID NO:30, an LCDR1 having the sequence of SEQ ID NO:43, an LCDR2 having the sequence of SEQ ID NO:50, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the IMGT antibody numbering scheme). In some embodiments, the anti-CD122 antibody or an antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:162, an HCDR2 having the sequence of SEQ ID NO:169, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Kabat antibody numbering scheme). In some embodiments, the anti-CD122 antibody or an antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:163, an HCDR2 having the sequence of SEQ ID NO:170, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the AbM antibody numbering scheme).In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:164, an HCDR2 having the sequence of SEQ ID NO:171, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Chothia antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:165, an HCDR2 having the sequence of SEQ ID NO:172, an HCDR3 having the sequence of SEQ ID NO:177, an LCDR1 having the sequence of SEQ ID NO:179, an LCDR2 having the sequence of SEQ ID NO:182, and an LCDR3 having the sequence of SEQ ID NO:184 (according to the Contact antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:166, an HCDR2 having the sequence of SEQ ID NO:173, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Kabat antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:167, an HCDR2 having the sequence of SEQ ID NO:170, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the AbM antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:164, an HCDR2 having the sequence of SEQ ID NO:171, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Chothia antibody numbering scheme).In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:168, an HCDR2 having the sequence of SEQ ID NO:174, an HCDR3 having the sequence of SEQ ID NO:177, an LCDR1 having the sequence of SEQ ID NO:179, an LCDR2 having the sequence of SEQ ID NO:182, and an LCDR3 having the sequence of SEQ ID NO:184 (according to the Contact antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:166, an HCDR2 having the sequence of SEQ ID NO:173, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:180, an LCDR2 having the sequence of SEQ ID NO:183, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Kabat antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:167, an HCDR2 having the sequence of SEQ ID NO:170, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:180, an LCDR2 having the sequence of SEQ ID NO:183, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the AbM antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:164, an HCDR2 having the sequence of SEQ ID NO:171, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:180, an LCDR2 having the sequence of SEQ ID NO:183, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Chothia antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:168, an HCDR2 having the sequence of SEQ ID NO:174, an HCDR3 having the sequence of SEQ ID NO:177, an LCDR1 having the sequence of SEQ ID NO:179, an LCDR2 having the sequence of SEQ ID NO:182, and an LCDR3 having the sequence of SEQ ID NO:184 (according to the Contact antibody numbering scheme).In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:162, an HCDR2 having the sequence of SEQ ID NO:175, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Kabat antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:163, an HCDR2 having the sequence of SEQ ID NO:170, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the AbM antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:164, an HCDR2 having the sequence of SEQ ID NO:171, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Chothia antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:165, an HCDR2 having the sequence of SEQ ID NO:174, an HCDR3 having the sequence of SEQ ID NO:177, an LCDR1 having the sequence of SEQ ID NO:179, an LCDR2 having the sequence of SEQ ID NO:182, and an LCDR3 having the sequence of SEQ ID NO:184 (according to the Contact antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:162, an HCDR2 having the sequence of SEQ ID NO:175, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:180, an LCDR2 having the sequence of SEQ ID NO:183, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Kabat antibody numbering scheme).In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:163, an HCDR2 having the sequence of SEQ ID NO:170, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:180, an LCDR2 having the sequence of SEQ ID NO:183, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the AbM antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:164, an HCDR2 having the sequence of SEQ ID NO:171, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:180, an LCDR2 having the sequence of SEQ ID NO:183, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Chothia antibody numbering scheme). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises an HCDR1 having the sequence of SEQ ID NO:165, an HCDR2 having the sequence of SEQ ID NO:174, an HCDR3 having the sequence of SEQ ID NO:177, an LCDR1 having the sequence of SEQ ID NO:179, an LCDR2 having the sequence of SEQ ID NO:182, and an LCDR3 having the sequence of SEQ ID NO:184 (according to the Contact antibody numbering scheme).

[0109] CD122 binding affinity

[0110] In some embodiments, the anti-CD122 antibodies and antigen-binding fragments thereof described herein bind to CD122 with a measurable affinity. In some embodiments, the anti-CD122 antibody or its antigen-binding fragment binds to mammalian CD122. In some embodiments, the anti-CD122 antibody or its antigen-binding fragment binds to murine CD122. In some embodiments, the anti-CD122 antibody or its antigen-binding fragment binds to human CD122. In some embodiments, the anti-CD122 antibody or its antigen-binding fragment that binds to CD122 comprises: HCDR1 comprising the amino acid sequence of SEQ ID NO:1; HCDR2 comprising the amino acid sequence of SEQ ID NO:12; HCDR3 comprising the amino acid sequence of SEQ ID NO:24; LCDR1 comprising the amino acid sequence of SEQ ID NO:37; LCDR2 comprising the amino acid sequence of SEQ ID NO:48; and LCDR3 comprising the amino acid sequence of SEQ ID NO:56. In some embodiments, the anti-CD122 antibody or its antigen-binding fragment that binds to CD122 comprises: HCDR1 comprising the amino acid sequence of SEQ ID NO:2; HCDR2 comprising the amino acid sequence of SEQ ID NO:13; HCDR3 comprising the amino acid sequence of SEQ ID NO:25; LCDR1 comprising the amino acid sequence of SEQ ID NO:38; LCDR2 comprising the amino acid sequence of SEQ ID NO:49; and LCDR3 comprising the amino acid sequence of SEQ ID NO:57. In some embodiments, the anti-CD122 antibody or its antigen-binding fragment that binds to CD122 comprises: HCDR1 comprising the amino acid sequence of SEQ ID NO:3; HCDR2 comprising the amino acid sequence of SEQ ID NO:14; HCDR3 comprising the amino acid sequence of SEQ ID NO:26; LCDR1 comprising the amino acid sequence of SEQ ID NO:39; LCDR2 comprising the amino acid sequence of SEQ ID NO:50; and LCDR3 comprising the amino acid sequence of SEQ ID NO:58. In some embodiments, the anti-CD122 antibody or its antigen-binding fragment that binds to CD122 comprises: HCDR1 comprising the amino acid sequence of SEQ ID NO:4; HCDR2 comprising the amino acid sequence of SEQ ID NO:15; HCDR3 comprising the amino acid sequence of SEQ ID NO:27; LCDR1 comprising the amino acid sequence of SEQ ID NO:40; LCDR2 comprising the amino acid sequence of SEQ ID NO:51; and LCDR3 comprising the amino acid sequence of SEQ ID NO:59.In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:5; an HCDR2 comprising the amino acid sequence of SEQ ID NO:16; an HCDR3 comprising the amino acid sequence of SEQ ID NO:28; an LCDR1 comprising the amino acid sequence of SEQ ID NO:41; an LCDR2 comprising the amino acid sequence of SEQ ID NO:50; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:60. In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:6; an HCDR2 comprising the amino acid sequence of SEQ ID NO:17; an HCDR3 comprising the amino acid sequence of SEQ ID NO:29; an LCDR1 comprising the amino acid sequence of SEQ ID NO:42; an LCDR2 comprising the amino acid sequence of SEQ ID NO:52; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:61. In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:7; an HCDR2 comprising the amino acid sequence of SEQ ID NO:18; an HCDR3 comprising the amino acid sequence of SEQ ID NO:30; an LCDR1 comprising the amino acid sequence of SEQ ID NO:43; an LCDR2 comprising the amino acid sequence of SEQ ID NO:50; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:62. In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:8; an HCDR2 comprising the amino acid sequence of SEQ ID NO:19; an HCDR3 comprising the amino acid sequence of SEQ ID NO:31; an LCDR1 comprising the amino acid sequence of SEQ ID NO:44; an LCDR2 comprising the amino acid sequence of SEQ ID NO:50; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:63. In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:9; an HCDR2 comprising the amino acid sequence of SEQ ID NO:20; an HCDR3 comprising the amino acid sequence of SEQ ID NO:32; an LCDR1 comprising the amino acid sequence of SEQ ID NO:45; an LCDR2 comprising the amino acid sequence of SEQ ID NO:53; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:64.In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:1; an HCDR2 comprising the amino acid sequence of SEQ ID NO:21; an HCDR3 comprising the amino acid sequence of SEQ ID NO:33; an LCDR1 comprising the amino acid sequence of SEQ ID NO:37; an LCDR2 comprising the amino acid sequence of SEQ ID NO:48; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:65. In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:1; an HCDR2 comprising the amino acid sequence of SEQ ID NO:21; an HCDR3 comprising the amino acid sequence of SEQ ID NO:34; an LCDR1 comprising the amino acid sequence of SEQ ID NO:37; an LCDR2 comprising the amino acid sequence of SEQ ID NO:48; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:65. In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:10; an HCDR2 comprising the amino acid sequence of SEQ ID NO:22; an HCDR3 comprising the amino acid sequence of SEQ ID NO:35; an LCDR1 comprising the amino acid sequence of SEQ ID NO:46; an LCDR2 comprising the amino acid sequence of SEQ ID NO:54; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:66. In some embodiments, an anti-CD122 antibody or an antigen-binding fragment thereof that binds to CD122 comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO:11; an HCDR2 comprising the amino acid sequence of SEQ ID NO:23; an HCDR3 comprising the amino acid sequence of SEQ ID NO:36; an LCDR1 comprising the amino acid sequence of SEQ ID NO:47; an LCDR2 comprising the amino acid sequence of SEQ ID NO:55; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:67. In some embodiments, the binding affinity of the antibody for CD122 is the binding affinity measured by K. D (equilibrium dissociation constant).

[0111] In some embodiments, the anti-CD122 antibodies and antigen-binding fragments thereof described herein bind to CD122 with a measurable affinity, such as by K DMeasurement. In some embodiments, the anti-CD122 antibody is a murine antibody. In some embodiments, the anti-CD122 antibody is a humanized antibody. In some embodiments, the anti-CD122 antibody is a human antibody. In some embodiments, the antibody or its antigen-binding fragment specifically binds to CD122. In some embodiments, the antibody or its antigen-binding fragment exhibits moderate to low non-specific binding (NBS) to non-target peptides, proteins, receptors, or transporters. In some embodiments, the antibody or its antigen-binding fragment exhibits low non-specific binding (NBS) to non-target peptides, proteins, receptors, or transporters. In some embodiments, the antibody or its antigen-binding fragment specifically binds to mammalian CD122. In some embodiments, the antibody or its antigen-binding fragment binds to murine CD122. In some embodiments, the antibody or its antigen-binding fragment binds to human CD122. In some embodiments, the antibody or its antigen-binding fragment binds to the CD122 protein or a domain of the CD122 protein, and its binding affinity is measured by K D measured to be about from 10 -6 M to 10 -12 M, from 10 -7 M to 10 -12 M, from 10 -8 M to 10 -12 M, from 10 -9 M to 10 -12 M, from 10 -6 M to 10 -11 M, from 10 -7 M to 10 -11 M, from 10 -8 M to 10 -11 M, from 10 -9 M to 10 -11 M, from 10 -10 M to 10 -11 M, from 10 -6 M to 10 -10 M, from 10 -7 M to 10 -10 M, from 10 -8 M to 10 -10 M, from 10 -9 M to 10 -10 M, from 10 -6 M to 10 -9 M, from 10 -7 M to 10 -9 M, from 10 -8 M to 10 -9 M, from 10 -6 M to 10 -8 M, from 10 -7 M to 10-8 M or from 10 -6 M to 10 -7 M. In some embodiments, the antibody or antigen-binding fragment thereof binds to one or more epitopes within the extracellular domain of the CD122 protein, and its binding affinity is determined by K D measured to be about from 10 -6 M to 10 -12 M, from 10 -7 M to 10 -12 M, from 10 -8 M to 10 -12 M, from 10 -9 M to 10 -12 M, from 10 -6 M to 10 -11 M, from 10 -7 M to 10 -11 M, from 10 -8 M to 10 -11 M, from 10 -9 M to 10 -11 M, from 10 -10 M to 10 -11 M, from 10 -6 M to 10 -10 M, from 10 -7 M to 10 -10 M, from 10 -8 M to 10 -10 M, from 10 -9 M to 10 -10 M, from 10 -6 M to 10 -9 M, from 10 -7 M to 10 -9 M, from 10 -8 M to 10 -9 M, from 10 -6 M to 10 -8 M, from 10 -7 M to 10 -8 M or from 10 -6 M to 10 -7 M. In some embodiments, the antibody or antigen-binding fragment thereof binds to the human CD122 protein, and its binding affinity is determined by K D measured to be less than about 9E -08 M, 8E -08 M, 7E -08 M, 6E -08 M, 5E -08 M, 4E -08 M, 3E -08 M, 2E -08 M, 1E -08 M, 9E-09 M, 8E -09 M, 7E -09 M, 6E -09 M, 5E -09 M, 4E -09 M, 3E -09 M, 2E -09 M, 1E -09 M, 9E -10 M, 8E - 10 M, 7E -10 M, 6E -10 M, 5E -10 M, 4E -10 M, 3E -10 M, 2E -10 M or 1E -10 M. In some embodiments, the antibody binds to the human CD122 protein with a binding affinity in the nanomolar range (K D value of 10 -7 to 10 -9 M). In some embodiments, the antibody binds to the human CD122 protein with a binding affinity in the low nanomolar range (K D value of 10 -9 M). In some embodiments, the antibody binds to the human CD122 protein with a binding affinity in the picomolar range (K D value of 10 -10 to 10 -12 M). In some embodiments, the antibody binds to the human CD122 protein with a binding affinity in the high picomolar range (K D value of 10 -10 M). In some embodiments, the antibody binds to the human CD122 protein with a binding affinity in the range from low nanomolar to high picomolar (K D value of 10 -9 to 10 -10 M). In some embodiments, the antibody binds to the human CD122 protein with a binding affinity (measured by K D less than approximately 3E -09 M. In some embodiments, the antibody binds to the human CD122 protein with a binding affinity (measured by K D less than approximately 2E -09 M. In some embodiments, the antibody binds to the human CD122 protein with a binding affinity (measured by K D less than approximately 1E -09 M. In some embodiments, the antibody binds to the human CD122 protein with a binding affinity (measured by K D less than approximately 9E -10M. In some embodiments, the antibody binds to human CD122 protein, and its binding affinity (measured by K D is less than about 8E -10 M. In some embodiments, the antibody binds to human CD122 protein, and its binding affinity (measured by K D is between about 5E -09 and 5E -10 M. In some embodiments, the antibody binds to human CD122 protein, and its binding affinity (measured by K D is between about 3E -09 and 7E -10 M. In some embodiments, the antibody binds to human CD122 protein, and its binding affinity (measured by K D is between about 2E -09 and 8E -10 M. The antibody binds to human CD122 protein, and its binding affinity (measured by K D is between about 1E -09 and 9E -10 M.

[0112] In some embodiments, the binding of an antibody or its antigen-binding fragment to murine CD122 protein is measured by determining the binding affinity of the antibody to the murine CD122 protein sequences listed in Table 15. In some embodiments, the binding of an antibody or its antigen-binding fragment to murine CD122 protein is measured by determining the binding affinity of the antibody to a portion of the murine CD122 protein sequences listed in Table 15. In some embodiments, the binding of an antibody or its antigen-binding fragment to murine CD122 protein is measured by determining the binding affinity of the antibody to the extracellular portion of the murine CD122 protein sequence containing the CD122 extracellular domain (A26-E240) listed in Table 15. In some embodiments, the binding of an antibody or its antigen-binding fragment to human CD122 protein is measured by determining the binding affinity of the antibody to the human CD122 protein sequences listed in Table 15. In some embodiments, the binding of an antibody or its antigen-binding fragment to human CD122 protein is measured by determining the binding affinity of the antibody to a portion of the human CD122 protein sequences listed in Table 15. In some embodiments, the binding of an antibody or its antigen-binding fragment to human CD122 protein is measured by determining the binding affinity of the antibody to a polypeptide sequence containing a portion of the amino acid sequences listed in Table 15. In some embodiments, the binding of an antibody or its antigen-binding fragment to human CD122 protein is measured by determining the binding affinity of the antibody to the extracellular portion of the human CD122 protein sequence containing the CD122 extracellular domain (A26-D239) listed in Table 15. In some embodiments, an anti-CD122 antibody or its antigen-binding fragment cross-competes with another anti-CD122 antibody or its antigen-binding fragment described herein for binding to CD122. In some embodiments, an anti-CD122 antibody or its antigen-binding fragment cross-competes with a known anti-CD122 antibody for binding to CD122.

[0113] Table 15: Murine and Human CD122 Protein Sequences

[0114]

[0115]

[0116] Comparison with Known Anti-CD122 Antibodies

[0117] The CD122 antibodies described herein can be compared to other known anti-CD122 antibodies based on their properties, structure, and / or functional characteristics. In some embodiments, the humanized monoclonal antibodies described herein have one or more defined CD122 binding epitopes. In some embodiments, the CD122 binding epitope comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 amino acid residues of CD122 that are contained within the CD122 binding epitope of the humanized monoclonal antibody. In some embodiments, the CD122 binding epitope comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 amino acid residues of the extracellular portion of human CD122 that are contained within the CD122 binding epitope of the humanized monoclonal antibody. In some embodiments, the amino acid residues of human CD122 that comprise the anti-CD122 antibody epitope are different from the amino acid residues of human CD122 that comprise the anti-CD122 antibody epitope of a known anti-CD122 antibody. In some embodiments, the human CD122 epitope bound by the humanized monoclonal anti-CD122 antibody described herein is different from the human CD122 epitope bound by other known anti-CD122 antibodies. In some embodiments, the human CD122 epitope bound by the humanized monoclonal anti-CD122 antibody described herein is compared to the human CD122 epitope bound by a known humanized monoclonal anti-CD122 antibody. In some embodiments, the humanized monoclonal antibody described herein can be a more effective functional inhibitor of IL2-induced cell signaling compared to one or more known anti-CD122 antibodies. In some embodiments, the humanized monoclonal antibody described herein can be a more effective functional inhibitor of IL15-induced cell signaling compared to one or more known anti-CD122 antibodies. In some embodiments, the humanized monoclonal antibody described herein can be a more effective functional inhibitor of both IL2-induced and IL-15-induced cell signaling compared to one or more known anti-CD122 antibodies. In some embodiments, the properties, structure, and / or functional characteristics of the humanized anti-CD122 antibody described herein are compared to the properties, structure, and / or functional characteristics of a known humanized anti-CD122 antibody comprising the CDR sequences listed in Table 16.In some embodiments, known humanized anti-CD122 antibodies for comparing CD122 epitopes or functional properties, such as the ability to act as a functional inhibitor of IL2 signaling, IL15 signaling, or IL-2 signaling and IL-15 signaling, comprise a VH domain and a VL domain, wherein the VH domain comprises: HCDR1 comprising the sequence of SEQ ID NO:189, HCDR2 comprising the sequence of SEQ ID NO:190, and HCDR3 comprising the sequence of SEQ ID NO:191; and wherein the VL domain comprises: LCDR1 comprising the sequence of SEQ ID NO:192, LCDR2 comprising the sequence of SEQ ID NO:193, and LCDR3 comprising the sequence of SEQ ID NO:194.

[0118] Table 16: CDR Sequences of Known Anti-CD122 Antibodies

[0119]

[0120] In some aspects, the isolated anti-CD122 antibodies described herein have one or more binding epitopes against the characterized CD122 protein. In some embodiments, the CD122 epitope bound by the anti-CD122 antibodies described herein is a functional epitope. In some embodiments, the CD122 epitope bound by the anti-CD122 antibodies described herein is a structural epitope. In some embodiments, the CD122 epitope bound by the anti-CD122 antibodies described herein is conformational and not linear. In some embodiments, the conformational epitope comprises at least two, at least three or at least four non-linear portions of CD122. In some embodiments, the epitope is an epitope on the native CD122 protein. In some embodiments, the isolated anti-CD122 antibodies described herein inhibit the binding of IL2 to the high-affinity IL-αβγ receptor comprising CD122, CD132 and CD25. In some embodiments, the isolated anti-CD122 antibodies described herein inhibit the binding of IL15 (presented in a manner that binds to IL15Rα in trans) to the intermediate-affinity IL-βγ receptor comprising CD122 and CD132. In some embodiments, the isolated anti-CD122 antibodies described herein inhibit the binding of IL15 to the high-affinity IL-αβγ receptor comprising CD122, CD132 and IL15Rα. In some embodiments, the isolated anti-CD122 monoclonal antibody binds to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or all 22 of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of the extracellular domain of the human CD122 protein according to the amino acid numbering set forth in SEQ ID NO:187. In some embodiments, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or all 22 of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of the extracellular domain of the human CD122 protein according to the amino acid numbering set forth in SEQ ID NO:187 constitute the epitope bound by the isolated anti-CD122 monoclonal antibody described herein.In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one amino acid residue of epitope site 1) residues 39-41 (WPD) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one amino acid residue of epitope site 2) residues 76-81 (VDIVTL) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one amino acid residue of epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one amino acid residue of epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one, two, or three amino acid residues of epitope site 1) residues 39-41 (WPD) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one, two, three, four, five, or six amino acid residues of epitope site 2) residues 76-81 (VDIVTL) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one, two, three, four, five, six, or seven amino acid residues of epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one, two, three, four, five, or six amino acid residues of epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187.In some embodiments, the isolated anti-CD122 monoclonal antibody described herein binds to at least one amino acid residue of epitope site 1) residues 39-41 (WPD) and binds to: i) at least one amino acid residue of epitope site 2) residues 76-81 (VDIVTL) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187; or ii) at least one amino acid residue of epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187; or iii) at least one amino acid residue of epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187. In some embodiments, the isolated anti-CD122 monoclonal antibody described herein binds to at least one amino acid residue of epitope site 2) residues 76-81 (VDIVTL) and binds to: i) at least one amino acid residue of epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187; or ii) at least one amino acid residue of epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187. In some embodiments, the isolated anti-CD122 monoclonal antibody described herein binds to at least one amino acid residue of epitope site 3) residues 99-105 (FKPFENL) and at least one amino acid residue of epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187. In some embodiments, the isolated anti-CD122 monoclonal antibody described herein binds to at least one, two, or three amino acid residues of epitope site 1) residues 39-41 (WPD) and binds to: i) at least one, two, three, four, five, or six amino acid residues of epitope site 2) residues 76-81 (VDIVTL) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187; or ii) at least one, two, three, four, five, six, or seven amino acid residues of epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187; or iii) at least one, two, three, four, five, or six amino acid residues of epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of the human CD122 protein comprising amino acid sequence SEQ ID NO:187.In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one, two, three, four, five, or six amino acid residues of epitope site 2) residues 76-81 (VDIVTL) and bind to: i) at least one, two, three, four, five, six, or seven amino acid residues of epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187; or ii) at least one, two, three, four, five, or six amino acid residues of epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one, two, three, four, five, six, or seven amino acid residues of epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of the human CD122 protein comprising the amino acid sequence SEQ ID NO: 187 and at least one, two, three, four, five, or six amino acid residues of epitope site 4) residues 134-139 (HYFERH).

[0121] Production and manufacture of antibodies or antigen-binding fragments thereof

[0122] In some embodiments, the polypeptides described herein (e.g., antibodies or antigen-binding fragments thereof) are produced using any method known in the art that can be used to synthesize polypeptides (e.g., antibodies), particularly by chemical synthesis or recombinant expression, and preferably by using recombinant expression techniques.

[0123] In some cases, the antibody or antigen-binding fragment thereof is expressed recombinantly, and the nucleic acid encoding the antibody or antigen-binding fragment thereof is assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier et al., 1994, BioTechniques 17:242), which involves synthesizing overlapping oligonucleotides containing portions of the sequence encoding the antibody, annealing and ligating those oligonucleotides, and then amplifying the ligated oligonucleotides by PCR.

[0124] Alternatively, the nucleic acid molecule encoding the antibody is optionally generated from a suitable source (e.g., an antibody cDNA library, or a cDNA library generated from any tissue or cell expressing immunoglobulins), by PCR amplification using synthetic primers that hybridize to the 5′ and 3′ ends of the sequence, or by cloning using oligonucleotides specific for a particular nucleic acid sequence.

[0125] In some cases, the antibody or its binding is optionally prepared by generating monoclonal antibodies, e.g., as described by Kohler and Milstein (1975, Nature 256:495-497), or as described by Kozbor et al. (1983, Immunology Today 4:72) or Cole et al. (1985 in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Alternatively, a clone encoding at least the Fab portion of the antibody is optionally obtained by screening a Fab expression library (e.g., as described by Huse et al., 1989, Science 246:1275-1281) for clones of Fab fragments that bind a specific antigen, or by screening an antibody library (see, e.g., Clackson et al., 1991, Nature 352:624; Hane et al., 1997 Proc. Natl. Acad. Sci. USA 94:4937).

[0126] In some embodiments, techniques developed for the production of "chimeric antibodies" (Morrison et al., 1984, Proc. Natl. Acad. Sci. 81:851-855; Neuberger et al., 1984, Nature 312:604-608; Takeda et al., 1985, Nature 314:452-454) are used, which are performed by splicing the genes from mouse antibody molecules with appropriate antigen specificity to the genes from human antibody molecules with appropriate biological activity. Chimeric antibodies are molecules in which different portions are derived from different animal species, such as molecules having variable regions derived from murine monoclonal antibodies and human immunoglobulin constant regions, e.g., humanized antibodies.

[0127] In some embodiments, the techniques described for the production of single-chain antibodies (U.S. Patent No. 4,694,778; Bird, 1988, Science 242:423-42; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; and Ward et al., 1989, Nature 334:544-54) are applicable for the production of single-chain antibodies. Single-chain antibodies are formed by linking the heavy and light chain fragments of the Fv region via an amino acid bridge, thereby producing a single-chain polypeptide. Techniques for assembling functional Fv fragments in E. coli (Skerra et al., 1988, Science 242:1038-1041) may also optionally be used.

[0128] In some embodiments, a nucleic acid sequence encodes an antibody disclosed herein. In some embodiments, the polynucleotide sequence encoding the antibody is operably coupled to eukaryotic regulatory sequences. In some embodiments, a cell comprises the nucleic acid sequence. In some embodiments, a cell comprises a nucleic acid encoding an antibody disclosed herein. In some embodiments, the cell comprises a prokaryotic cell. In some embodiments, the prokaryotic cell is an Escherichia coli cell. In some embodiments, the cell comprises a eukaryotic cell. In some embodiments, the eukaryotic cell is a Chinese Hamster Ovary (CHO) cell, a HEK293 cell, a BHK cell, an NS0 murine myeloma cell, or a human cell. In some embodiments, an expression vector comprising the nucleotide sequence of the antibody or the nucleotide sequence of the antibody is transferred into a host cell by conventional techniques (e.g., electroporation, liposome transfection, and calcium phosphate precipitation), and then the transfected cell is cultured by conventional techniques to produce the antibody. In a particular aspect, the expression of the antibody is regulated by a constitutive promoter, an inducible promoter, or a tissue-specific promoter. Standard cell lines and methods for producing antibodies from large-scale cell cultures are known in the art. See, e.g., Li et al., “Cell culture processes for monoclonal antibody production.” Mabs. September–October 2010;2(5):466–477.

[0129] In certain aspects, a method of preparing an antibody is described herein, which comprises culturing a cell comprising a nucleic acid encoding an antibody under in vitro conditions sufficient to permit antibody production and secretion. In some embodiments, the antibody is harvested from the cell culture medium. The harvesting may further comprise one or more purification steps to remove live cells, cell debris, non-antibody proteins or polypeptides, unwanted salts, buffers, and culture medium components. In certain aspects, additional purification steps include centrifugation, ultracentrifugation, protein A, protein G, protein A / G, or protein L purification, and / or ion exchange chromatography.

[0130] Pharmaceutical composition

[0131] The present disclosure provides a pharmaceutical composition comprising an antibody or antibody fragment and at least one pharmaceutically acceptable carrier. In some embodiments, the antibody or antibody fragment binds to CD122. In some embodiments, the antibody or antibody fragment is an anti-CD122 antibody or anti-CD122 antibody fragment. In some embodiments, the pharmaceutical composition comprises the anti-CD122 antibody described herein. In some embodiments, the antibody or antibody fragment binds to human CD122. In some embodiments, the antibody or antibody fragment and at least one pharmaceutically acceptable carrier are formulated into a pharmaceutical preparation. In some embodiments, the pharmaceutical preparation is selected based on the preferred route of administration of the antibody or antibody fragment to a subject.

[0132] In some embodiments, the pharmaceutical preparation includes, but is not limited to, aqueous liquid dispersions, self-emulsifying dispersions, solid solutions, liposomal dispersions, solid dosage forms, powders, immediate-release preparations, controlled-release preparations, fast-dissolving preparations, tablets, capsules, pills, delayed-release preparations, extended-release preparations, pulsatile-release preparations, multiparticulate preparations (e.g., nanoparticle preparations), and mixed immediate-release and controlled-release preparations.

[0133] In some cases, the pharmaceutical preparation includes a multiparticulate preparation. In some cases, the pharmaceutical preparation includes a nanoparticle preparation. In some cases, the nanoparticles comprise cMAP, cyclodextrin, or lipids. In some cases, the nanoparticles include solid lipid nanoparticles, polymeric nanoparticles, self-emulsifying nanoparticles, liposomes, microemulsions, or micellar solutions. Additional exemplary nanoparticles include, but are not limited to, paramagnetic nanoparticles, superparamagnetic nanoparticles, metal nanoparticles, fullerene-based materials, inorganic nanotubes, dendrimers (such as those having covalently attached metal chelates), nanofibers, nanorods, nanowires, and quantum dots. In some cases, the nanoparticles are metal nanoparticles, such as nanoparticles of scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, yttrium, zirconium, niobium, molybdenum, ruthenium, rhodium, palladium, silver, cadmium, hafnium, tantalum, tungsten, rhenium, osmium, iridium, platinum, gold, gadolinium, aluminum, gallium, indium, tin, thallium, bismuth, magnesium, calcium, strontium, barium, lithium, sodium, potassium, boron, silicon, phosphorus, germanium, arsenic, antimony, and combinations, alloys, or oxides thereof.

[0134] In some cases, the nanoparticles comprise a core or a core and a shell, such as core-shell nanoparticles. In some cases, the nanoparticles comprise nanospheres or nanocapsules.

[0135] In some cases, the nanoparticles are further coated with molecules for attaching functional elements (e.g., one or more polynucleic acid molecules or binding moieties described herein). In some cases, the coating comprises chondroitin sulfate, dextran sulfate, carboxymethyl dextran, alginate, pectin, carragheenan, fucoidan, agarose, porphyran, karaya gum, xanthan gum, hyaluronic acid, glucosamine, galactosamine, chitosan, polyglutamic acid, polyaspartic acid, lysozyme, cytochrome C, trypsinogen, chymotrypsinogen, α-chymotrypsin, polylysine, polyarginine, histone, protamine, ovalbumin or dextrin or cyclodextrin.

[0136] In some embodiments, the pharmaceutical formulations described herein are administered to a subject by a variety of routes of administration, including but not limited to parenteral (e.g., intravenous, subcutaneous, intramuscular), oral, intranasal, buccal, rectal or transdermal routes of administration. In some cases, the pharmaceutical compositions described herein are formulated for parenteral (e.g., intravenous, subcutaneous, intramuscular, intraarterial, intraperitoneal, intrathecal, intracerebral, intraventricular or intracranial) administration. In other cases, the pharmaceutical compositions described herein are formulated for oral administration. In other cases, the pharmaceutical compositions described herein are formulated for intranasal administration.

[0137] 1. Pharmaceutically acceptable excipients, carriers and diluents

[0138] Compositions comprising an antibody of the disclosure are included in a pharmaceutical composition that comprises one or more pharmaceutically acceptable excipients, carriers and diluents. In some embodiments, the antibody of the disclosure is administered in the form of a suspension in a sterile solution. In some embodiments, the antibody of the disclosure is administered in the form of a suspension in an isotonic solution. In some cases, the pharmaceutical formulation comprises one or more salts in an amount sufficient to bring the weight osmolarity of the composition to an acceptable range. Such salts include salts having sodium, potassium or ammonium cations and chloride, citrate, ascorbate, borate, phosphate, bicarbonate, sulfate, thiosulfate or bisulfite anions; suitable salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite and ammonium sulfate. In certain aspects, the solution comprises about 0.9% NaCl. In certain aspects, the solution comprises about 5.0% glucose. In certain aspects, the solution further comprises one or more of the following: buffers, such as acetate, citrate, histidine, succinate, phosphate, bicarbonate and tris(hydroxymethyl)aminomethane; surfactants, such as polysorbate 80 (Tween 80), polysorbate 20 (Tween 20);

[0139] Polyols / disaccharides / polysaccharides, such as glucose, dextrose, mannose, mannitol, sorbitol, sucrose, and dextran 40; amino acids, such as glycine or arginine; antioxidants, such as ascorbic acid, methionine; or chelating agents, such as EDTA or EGTA. Carbomer is used as an emulsifier and viscosity modifier in aqueous pharmaceutical compositions. In certain aspects, the pharmaceutically acceptable excipient comprises carbomer or consists of carbomer. In certain aspects, carbomer comprises carbomer 910, carbomer 934, carbomer 934P, carbomer 940, carbomer 941, carbomer 1342, or a combination thereof or consists of them. Cyclodextrin is used as a solubilizer and stabilizer in aqueous pharmaceutical compositions. In certain aspects, the pharmaceutically acceptable excipient comprises cyclodextrin or consists of cyclodextrin. In certain aspects, cyclodextrin comprises alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, or a combination thereof or consists of them. Lecithin can be used as a solubilizer in pharmaceutical compositions. In certain aspects, the solubilizer comprises lecithin or consists of lecithin. Poloxamer is used as an emulsifier, solubilizer, and dispersant in pharmaceutical compositions. In certain aspects, the pharmaceutically acceptable excipient comprises poloxamer or consists of poloxamer. In certain aspects, poloxamer comprises poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or a combination thereof or consists of them. Polyoxyethylene sorbitan fatty acid esters are used as emulsifiers, solubilizers, surfactants, and dispersants in pharmaceutical compositions. In certain aspects, the pharmaceutically acceptable excipient comprises polyoxyethylene sorbitan fatty acid esters or consists of polyoxyethylene sorbitan fatty acid esters. In certain aspects, polyoxyethylene sorbitan fatty acid esters comprise polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, polysorbate 81, polysorbate 85, polysorbate 120, or a combination thereof or consists of them. Polyoxyethylene stearates are used as emulsifiers, solubilizers, surfactants, and dispersants in pharmaceutical compositions. In certain aspects, the pharmaceutically acceptable excipient comprises polyoxyethylene stearates or consists of polyoxyethylene stearates. In certain aspects, polyoxyethylene stearates comprise polyethylene glycol 2 stearate, polyethylene glycol 4 stearate, polyethylene glycol 6 stearate, polyethylene glycol 8 stearate, polyethylene glycol 12 stearate, polyethylene glycol 20 stearate, polyethylene glycol 30 stearate, polyethylene glycol 40 stearate, polyethylene glycol 50 stearate, polyethylene glycol 100 stearate, polyethylene glycol 150 stearate, polyethylene glycol 4 distearate, polyethylene glycol 8 distearate, polyethylene glycol 12 distearate, polyethylene glycol 32 distearate, polyethylene glycol 150 distearate, or a combination thereof or consists of them. Sorbitan esters are used as emulsifiers, solubilizers, nonionic surfactants, and dispersants in pharmaceutical compositions.In some aspects, the pharmaceutically acceptable excipient comprises or consists of sorbitan esters. In some aspects, the sorbitan esters comprise, consist of, or are a combination of sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan stearate, sorbitan trioleate, sorbitan sesquioleate, or combinations thereof.

[0140] In some aspects, the antibodies of the present disclosure are shipped and / or stored in a lyophilized state and can then be reconstituted prior to administration. In some aspects, the lyophilized antibody formulation comprises a filler such as mannitol, sorbitol, sucrose, trehalose, dextran 40, or combinations thereof. The lyophilized formulation can be contained in vials made of glass or other suitable non-reactive materials. Whether or not the antibody is reconstituted, it can be buffered at a specific pH after formulation, typically at a pH below about 7.5. In some aspects, the pH can be between 4.5 and 7.5, 4.5 and 7.0, 4.5 and 6.5, 4.5 and 6.0, or 5.5 and 5.0.

[0141] Definitions

[0142] Unless otherwise defined, all professional terms, symbols, and other technical and scientific terms used herein are intended to have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, for purposes of clarity and / or timely reference, terms with commonly understood meanings are defined herein, and such definitions included herein should not necessarily be construed as representing a substantial difference from the commonly understood meaning in the art.

[0143] Throughout this application, various embodiments may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as the individual numerical values within that range. For example, the description of a range such as 1 to 6 should be considered to have specifically disclosed sub-ranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as the individual numerical values within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the width of the range.

[0144] Unless the context clearly dictates otherwise, as used in this specification and the claims, the singular forms "a", "an", and "the" include plural referents. For example, the term "a sample" includes a plurality of samples, including mixtures thereof.

[0145] The terms "determining", "measuring", "evaluating", "assessing", "assaying", and "analyzing" are generally used interchangeably herein to refer to various forms of measurement. These terms include determining the presence of an element (e.g., detecting). These terms can include quantitative determinations, qualitative determinations, or both quantitative and qualitative determinations. Evaluations can be relative or absolute. "Detecting... the presence of" can include determining the amount of its presence in addition to determining whether a substance is present, depending on the context.

[0146] The terms "subject", "individual", or "patient" are generally used interchangeably herein. A "subject" can be a biological entity that contains genetic material that is expressed. The biological entity can be a plant, an animal, or a microorganism, such as including bacteria, viruses, fungi, and protozoa. The subject can be a tissue, a cell, and its progeny of a biological entity obtained in vivo or cultured in vitro. The subject can be a mammal. The mammal can be a human. The subject may be diagnosed with or suspected of having a high risk of a certain disease. In some cases, the subject is not necessarily diagnosed with or suspected of having a high risk of the disease.

[0147] The term "in vivo" is used to describe an event that occurs within a subject.

[0148] The term "in vitro" is used to describe an event that occurs in a container used to hold laboratory reagents, such that the event is separated from the biological source from which the material was obtained. In vitro assays can encompass cell-based assays, in which live or dead cells are used. In vitro assays can also encompass cell-free assays, in which intact cells are not used.

[0149] As used herein, the term "about" a number means that number plus or minus 10% of that number. The term "about" a range means that range minus 10% of its minimum value and plus 10% of its maximum value.

[0150] As used herein, the term "treatment" or "treating" refers to a pharmaceutical or other intervention regimen that is employed to obtain a beneficial or desired result in a recipient. Beneficial or desired results include, but are not limited to, therapeutic benefits and / or prophylactic benefits. A therapeutic benefit may refer to the eradication or amelioration of a symptom or of the underlying disorder being treated. Additionally, a therapeutic benefit may be achieved by the eradication or amelioration of one or more physiological symptoms associated with the underlying disorder, such that an improvement is observed in the subject, even though the subject may still be afflicted with the underlying disorder. Prophylactic effects include delaying, preventing or eliminating the onset of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting or reversing the progression of a disease or condition, or any combination thereof. For prophylactic benefits, a subject at risk of developing a particular disease or a subject reporting one or more physiological symptoms of a disease may be treated even if the disease has not yet been diagnosed.

[0151] The term "antibody" is used herein in the broadest sense and includes monoclonal antibodies, including intact antibodies and their functional (antigen-binding) antibody fragments, including fragment antigen-binding (Fab) fragments, F(ab’)2 fragments, Fab’ fragments, Fv fragments, recombinant IgG (rIgG) fragments, single-chain antibody fragments (including single-chain variable fragments (sFv or scFv) and single-domain antibody (e.g., sdAb, sdFv, nanobody) fragments). The term encompasses genetically engineered / otherwise modified immunoglobulins, such as intracellular antibodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, tandem bis-scFv, tandem tris-scFv. Unless otherwise specified, the term "antibody" shall be understood to encompass its functional antibody fragments. The term also encompasses intact or full-length antibodies, including antibodies of any class or subclass, including IgG and its subclasses, IgM, IgE, IgA, and IgD. An antibody may comprise a human IgG1 constant region. An antibody may comprise a human IgG4 constant region. Antibodies include, but are not limited to, full-length antibodies and native antibodies, as well as fragments and portions that retain their binding specificity, such as any of its specific binding portions, including binding portions having any number of immunoglobulin classes and / or isotypes (e.g., IgG1, IgG2, IgG3, IgG4, IgM, IgA, IgD, IgE, and IgM); and its biologically relevant (antigen-binding) fragments or specific binding portions, including, but not limited to, Fab, F(ab')2, Fv, and scFv (single-chain or related entities). A monoclonal antibody is generally one of a composition of antibodies that is substantially homogeneous; thus, any individual antibody contained in a monoclonal antibody composition is identical, except for possible naturally occurring mutations that may be present in minor amounts. A monoclonal antibody may comprise a human IgG1 constant region or a human IgG4 constant region.

[0152] The terms "complementary determining region" and "CDR" are synonymous with "hypervariable region" or "HVR", are well known in the art and refer to the discontinuous amino acid sequences within the variable regions of antibodies that confer antigen specificity and / or binding affinity. Typically, each heavy chain variable region has three CDRs (CDR-H1, CDR-H2, CDR-H3; also referred to as HCDR1, HCDR2, HCDR3), and each light chain variable region has three CDRs (CDR-L1, CDR-L2, CDR-L3; also referred to as LCDR1, LCDR2, LCDR3). "Framework region" and "FR" are well known in the art and refer to the non-CDR portions of the variable regions of the heavy and light chains. Typically, each full-length heavy chain variable region has four FRs (FR-H1, FR-H2, FR-H3 and FR-H4), and each full-length light chain variable region has four FRs (FR-L1, FR-L2, FR-L3 and FR-L4).The exact amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a variety of well-known schemes, including those described in the following: Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD (“Kabat” numbering scheme); Al-Lazikani et al., (1997) JMB 273, 927-948 (“Chothia” numbering scheme); MacCallum et al., J. Mol. Biol. 262:732-745 (1996), “Antibody-antigen interactions: Contact analysis and binding site topography,” J. Mol. Biol. 262, 732-745 (“Contact” numbering scheme); Lefranc MP et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev Comp Immunol, January 2003; 27(1):55-77 (“IMGT” numbering scheme); Honegger A and Plückthun A, “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J Mol Biol, June 8, 2001; 309(3):657-70, (“Aho” numbering scheme); and Whitelegg NR and Rees AR, “WAM: an improved algorithm for modelling antibodies on the WEB,” Protein Eng. December 2000; 13(12):819-24 (“AbM” numbering scheme). In certain aspects, the CDRs of the antibodies described herein can be defined by a method selected from Kabat, Chothia, IMGT, Aho, AbM, Contact, or a combination thereof.

[0153] The boundaries of the given CDR or FR may vary depending on the scheme used for identification. For example, the Kabat scheme is based on structural alignment, while the Chothia scheme is based on structural information. The numbering of both the Kabat and Chothia schemes is based on the length of the most common antibody region sequences, where insertions can accommodate inserted letters, such as "30a", and deletions can occur in some antibodies. These two schemes place certain insertions and deletions ("indels") in different positions, resulting in numbering differences. The Contact scheme is based on the analysis of complex crystal structures and is similar to the Chothia numbering scheme in many respects.

[0154] The term "variable region" or "variable domain" refers to the domain in an antibody heavy or light chain that is involved in binding of the antibody to an antigen. The variable domains of the heavy and light chains of a native antibody (VH and VL, respectively) generally have similar structures, each containing four conserved framework regions (FRs) and three CDRs (see, e.g., Kindt et al., Kuby Immunology, 6th ed., W.H. Freeman and Co., p. 91 (2007)). A single VH or VL domain may be sufficient to confer antigen-binding specificity. In addition, antibodies that bind to a particular antigen can be isolated and used to screen libraries of complementary VL or VH domains using the VH or VL domain from the antibody that binds to that antigen (see, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991)).

[0155] The provided antibodies include antibody fragments. An "antibody fragment" can refer to a molecule other than a full antibody that contains a portion of a full antibody that binds to an antigen to which the full antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab’, Fab’-SH, F(ab’)2; diabodies; linear antibodies; and single-chain antibody molecules (e.g., scFv or sFv). In certain aspects, the antibody is a single-chain antibody fragment that includes a variable heavy chain region and / or a variable light chain region, such as scFv. Antibody fragments can be prepared by a variety of techniques, including but not limited to proteolytic digestion of full antibodies and production by recombinant host cells. In some embodiments, the antibody is a recombinantly produced fragment, such as a fragment that includes non-naturally occurring arrangements, such as a fragment having two or more antibody regions or chains joined by a synthetic linker (e.g., a polypeptide linker), and / or a fragment that is not produced by enzymatic digestion of a naturally occurring full antibody.

[0156] "Binding moiety" refers to the portion of a molecule, peptide, polypeptide, antibody, or antibody fragment that mediates specific binding to the target or antigen or epitope. For example, the binding moiety of an antibody can comprise a heavy chain / light chain variable region pair or one or more complementarity determining regions (CDRs).

[0157] As used herein, "target" refers to the portion of a molecule that participates in the binding moiety of a molecule, peptide, polypeptide, antibody, or antibody fragment. A target can comprise an amino acid sequence and / or a carbohydrate, lipid, or other chemical entity. An "antigen" is a target that comprises a portion capable of being bound by an adaptive immune molecule such as an antibody or antibody fragment, B cell receptor, or T cell receptor.

[0158] An "epitope" as described herein refers to one or more contact regions of an antibody. The contact region of an antibody consists of a discrete number of amino acids that contact the amino acid residues of the antibody (usually CDR residues) and the residues adjacent to these contacting residues. For example, the contact region can consist of a continuous segment between 5 and 20 amino acids, 5 and 15 amino acids, or 5 and 10 amino acids of the target protein. Due to protein folding, an antibody can bind to more than one contact region that are separated by 10, 20, 30, 40, 50, 75, or 100 or more amino acids. Epitopes can be determined using: X-ray crystallography, hydrogen-deuterium exchange mass spectrometry, alanine scanning mutagenesis, competition with an over-synthesized peptide (as determined by immunoblotting, ELISA, surface plasmon radiation, flow cytometry, or any other suitable protein binding assay).

[0159] The terms "cross-compete" or "cross-competes" are used interchangeably herein and refer to the ability of an antibody or an antigen-binding fragment thereof to interfere, directly or indirectly through allosteric regulation, with the binding of an anti-CD122 antibody of the present disclosure to a target CD122 (e.g., human CD122, the extracellular domain of human CD122, mouse CD122, or the extracellular domain of mouse CD122). The extent to which an antibody or an antigen-binding fragment thereof can interfere with the binding of another antibody to a target, and thus whether it can be said to cross-compete, can be determined using one or more competitive binding assays. An example of a competitive binding assay is homogeneous time-resolved fluorescence (HTRF). Another example of a competitive binding assay is epitope binning analysis using surface plasmon resonance (SPR).

[0160] A "humanized" antibody is an antibody in which all or nearly all of the CDR amino acid residues are derived from non-human CDRs and all or nearly all of the FR amino acid residues are derived from human FRs. A humanized antibody optionally may include at least a portion of the antibody constant region derived from a human antibody. A "humanized form" of a non-human antibody refers to a variant of the non-human antibody that has been humanized, typically to reduce its immunogenicity in humans while retaining the specificity and affinity of the parental non-human antibody. In some embodiments, some FR residues in the humanized antibody are replaced with the corresponding residues of the non-human antibody (e.g., the antibody from which the CDR residues are derived), e.g., to restore or enhance the specificity or affinity of the antibody.

[0161] The antibodies provided include human antibodies. A "human antibody" is an antibody whose amino acid sequence corresponds to that of an antibody produced by a human or human cell or a non-human source (using a human antibody library or other human antibody-encoding sequences, including human antibody libraries). The term does not include humanized forms of non-human antibodies that contain non-human antigen-binding regions, such as antibodies in which all or nearly all of the CDRs are non-human CDRs. Human antibodies can be prepared by administering an immunogen to a transgenic animal that has been modified to produce intact human antibodies or intact antibodies with human variable regions in response to antigen stimulation. Such animals typically contain all or part of the human immunoglobulin locus, which replaces the endogenous immunoglobulin locus or is present extrachromosomally or randomly integrated into the chromosomes of the animal. In such transgenic animals, the endogenous immunoglobulin locus is typically inactivated. Human antibodies also can be derived from human antibody libraries that contain antibody-encoding sequences from a human repertoire, including phage display libraries and cell-free libraries.

[0162] As used herein, "ADCC" or "antibody-dependent cell-mediated cytotoxicity" refers to a cell-mediated reaction in which non-specific cytotoxic cells expressing FcγR recognize an antibody bound to a target cell, subsequently resulting in lysis of the target cell. ADCC may be associated with binding to FcγRIIIa, and an increase in binding to FcγRIIIa may result in an increase in ADCC activity. As used herein, "ADCP" or antibody-dependent cell-mediated phagocytosis may refer to a cell-mediated reaction in which non-specific cytotoxic cells expressing FcγR recognize an antibody bound to a target cell, subsequently resulting in phagocytosis of the target cell.

[0163] The terms "polypeptide" and "protein" are used interchangeably and refer to polymers of amino acid residues, without limitation as to their minimum length. Polypeptides (including the provided antibodies and antibody chains, as well as other peptides such as linkers and binding peptides) can contain amino acid residues that include natural and / or non-natural amino acid residues. These terms also include post-expression modifications of polypeptides, such as glycosylation, sialylation, acetylation, phosphorylation, and the like. In some embodiments, a polypeptide can contain modifications relative to a native / natural sequence, so long as the protein retains the desired activity. These modifications can be intentional, such as by site-directed mutagenesis, or accidental, such as by mutations in the host that produces the protein or errors due to PCR amplification.

[0164] The percent sequence identity relative to a reference polypeptide sequence (%) is the percentage of amino acid residues in the candidate sequence that are identical to the amino acid residues in the reference polypeptide sequence after aligning the sequences and introducing gaps as needed to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. The alignment for determining the percent amino acid sequence identity can be achieved in a variety of known ways, such as using publicly available computer software, such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Appropriate parameters for aligning the sequences can be determined, including the algorithm required to achieve the maximum alignment over the full length of the sequences being compared. However, for the purposes of this document, the percent amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was developed by Genentech, Inc., and its source code has been submitted to the U.S. Copyright Office (Washington D.C., 20559) along with user documentation and is registered with the U.S. Copyright Office, U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc. (South San Francisco, Calif.) and can also be compiled from the source code. The ALIGN-2 program should be compiled for use on the UNIX operating system (including Digital UNIX V4.0D). All sequence comparison parameters are set by the ALIGN-2 program and are not changed. In the case of using ALIGN-2 for amino acid sequence comparison, the percent amino acid sequence identity of a given amino acid sequence A to (to / with / against) a given amino acid sequence B (alternatively stated as a given amino acid sequence A has or contains a certain percent amino acid sequence identity to (to / with / against) a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in the program alignment of A and B, and Y is the total number of amino acid residues in B. It should be understood that in the case where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the percent amino acid sequence identity of A to B will not be equal to the percent amino acid sequence identity of B to A. Unless otherwise expressly stated, all percent amino acid sequence identity values used in this document are obtained using the ALIGN-2 computer program as described in the previous paragraph.

[0165] Amino acid sequence variants of the antibodies provided herein can be contemplated and envisioned. Variants generally differ from the polypeptides specifically disclosed herein by one or more substitutions, deletions, additions, and / or insertions. Such variants can be naturally occurring or synthetically generated, for example, by modifying one or more of the above-described polypeptide sequences of the invention and evaluating one or more biological activities of the polypeptides described herein and / or using any of a variety of known techniques. For example, it may be desirable to improve the binding affinity and / or other biological properties of an antibody, and amino acid sequence variants of the antibody can be prepared by introducing appropriate modifications in the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, deletions and / or insertions and / or substitutions of residues in the amino acid sequence of the antibody. Any combination of deletions, insertions, and substitutions can be made to obtain the final construct, provided that the final construct has the desired properties, such as antigen binding. Antibody variants having one or more amino acid substitutions can be provided. Target sites for mutagenesis by substitution include the CDRs and FRs. Amino acid substitutions can be introduced into the target antibody, and the products screened to obtain the desired activity, such as retained / improved antigen binding, reduced immunogenicity, or improved ADCC or CDC.

[0166] Conservative amino acid substitutions are substitutions in which an amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids having basic side chains (e.g., arginine, lysine, and histidine), amino acids having acidic side chains (e.g., aspartic acid and glutamic acid), amino acids having uncharged polar side chains (e.g., asparagine, cysteine, glutamine, glycine, serine, threonine, tyrosine, and tryptophan), amino acids having nonpolar side chains (e.g., alanine, isoleucine, leucine, methionine, phenylalanine, proline, and valine), amino acids having β-branched side chains (e.g., isoleucine, threonine, and valine), and amino acids having aromatic side chains (e.g., histidine, phenylalanine, tryptophan, and tyrosine). Exemplary conservative amino acid substitutions are listed in Table 17.

[0167] Table 17: Exemplary Amino Acid Modifications

[0168] Side chain Member Hydrophobicity Met, Ala, Val, Leu, Ile Neutral hydrophilicity Cys, Ser, Thr Acidic Asp, Glu Basic Asn, Gln, His, Lys, Arg Residues affecting chain orientation Gly, Pro Aromatic Trp, Tyr, Phe

[0169] The antibodies described herein can be encoded by nucleic acids. A nucleic acid is a polynucleotide that comprises two or more nucleotide bases. In certain aspects, the nucleic acid is a component of a vector that can be used to transfer a polynucleotide encoding a polypeptide into a cell. As used herein, the term "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid to which it is linked. One type of vector is a genomic integration vector, or "integrating vector," which can integrate into the chromosomal DNA of a host cell. Another type of vector is an "episomal" vector, such as a nucleic acid capable of extrachromosomal replication. A vector capable of directing the expression of a gene to which it is operably linked is herein referred to as an "expression vector." Suitable vectors include plasmids, bacterial artificial chromosomes, yeast artificial chromosomes, viral vectors, and the like. In an expression vector, regulatory elements (such as promoters, enhancers, polyadenylation signals for controlling transcription) can be derived from mammalian, microbial, viral, or insect genes. The ability to replicate in a host, usually conferred by an origin of replication, and a selectable gene that facilitates the identification of transformants can also be additionally incorporated. Vectors derived from viruses such as lentiviruses, retroviruses, adenoviruses, adeno-associated viruses, etc. can be used. Plasmid vectors can be linearized for integration into chromosomal locations. The vector can contain sequences that direct site-specific integration into a defined location in the genome or a set of restriction sites (e.g., AttP-AttB recombination). Additionally, the vector can contain sequences derived from transposable elements.

[0170] The nucleic acid encoding the antibodies described herein can be used to infect, transfect, transform suitable cells, or otherwise render suitable cells transgenic for the nucleic acid, such that the antibodies can be produced for commercial or therapeutic use. Standard cell lines and methods for producing antibodies from large-scale cell cultures are known in the art. See, e.g., Li et al., "Cell culture processes for monoclonal antibody production." Mabs. September - October 2010; 2(5):466 - 477. In certain aspects, the cells are eukaryotic cells. In certain aspects the eukaryotic cells are mammalian cells. In certain aspects, the mammalian cells are cell lines that can be used for antibody production, such as Chinese hamster ovary cells (CHO), NS0 murine myeloma cells, or cells. In certain aspects, the nucleic acid encoding the antibody is integrated into a genomic locus of a cell that can be used for antibody production. In certain aspects, a method for preparing an antibody is described herein that comprises culturing a cell comprising a nucleic acid encoding the antibody under in vitro conditions sufficient to permit production and secretion of the antibody.

[0171] The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0172] Examples

[0173] The following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0174] Example 1: Humanization of a Mouse Anti-CD122 Antibody

[0175] To facilitate the identification of anti-CD122 antibodies that can be used in human subjects, a mouse monoclonal anti-CD122 antibody was used as a starting point for antibody sequence analysis and homology modeling of the three-dimensional (3D) structure of the antibody. This method was used to design a humanized form of the anti-CD122 antibody, produce the designed antibody, and then test the functional properties of the antibody. This method of designing and constructing humanized VH and VL genes is described in (Tsurishita et al., 2005; Methods 36:69-83).

[0176] The VH and VL regions of the mouse monoclonal anti-CD122 antibody were replaced into human IgG1 and human IgG4 backbones to construct parental chimeric sequences. Sequence analysis and homology modeling of the 3D antibody structure were performed to identify key positions that support the CDR loop structure and the VH-VL interface. These results were used to determine specific amino acid substitutions for the design of humanized variants of the VH and VL regions. Based on the modeling results, three VH variants and three VL variants were selected and further tested on IgG1 and IgG4 backbones. Each HC-LC pair was reformatted in two ways: using human IgG1 (G1M17 isotype) and human IgG4 (S228P isotype) backbones, respectively. The individual regions of the parental mouse were reformatted as hIgG1 or hIgG4 chimeras in a similar manner. Gene sequences encoding each designed VH and VL region were constructed for subsequent cloning into a mammalian expression vector.

[0177] The humanization of each pair of one VH variant and one VL variant in IgG1 and IgG4 backbones was evaluated using the T20 humanization score (Gao et al., 2013, BMC Biotechnol. 13:55). A sufficiently high T20 score indicates that, in human subjects, the likelihood of eliminating immunogenicity issues is the same as that of using a fully human antibody.

[0178] The humanization scores of the parental and humanized antibodies are shown in Table 18 (heavy chain) and Table 19 (κ light chain). According to this method, a score of 84 or higher indicates that the heavy chain framework is similar to that of humans, and a score of 90 or higher indicates that the κ light chain framework is humanized. For the full-length variable region, a cut-off value of 79 is recommended for VH, and a cut-off value of 86 is recommended for VL. In some embodiments, the variable light chain region is referred to as the VK region.

[0179] Table 18: Evaluation of the Humanization of Selected VH Domain Sequences

[0180]

[0181] Table 19: Humanization assessment of selected VL domain sequences

[0182]

[0183] Results:

[0184] The humanization scores of the T20 analyzer ranged as follows: the scores for humanized full-length variable regions (VH and VK) were 81 - 88, and the scores for humanized variable region framework regions were 90 - 99, exceeding the humanization threshold. The score of the Hu5-LC1 full-length sequence was lower than the recommended cut-off score of 86.

[0185] Defects in the VK sequence were identified. The Asp in DGTLK (parent sequence) has the potential to isomerize in the framework region. This defect has been eliminated in the humanized variants.

[0186] Production:

[0187] Two parental chimeric variants and 18 humanized Fab variants were transiently produced using 0.01 L of CHO cells (TunaCHOTM extended 14-day process) and purified by protein A affinity-based purification techniques. Endotoxin levels were measured, and 7 out of the 18 humanized Fab variants were also produced in the second batch. Since yield may be important for the application of these antibodies, a second batch was produced for some antibodies to compare yields. Binding affinities of chimeric and humanized antibodies:

[0188] The binding of 19 antibodies to human CD122 (huCD122) was measured. Their affinity (KD) values are reported in the following summary table and the subsequent slides, along with the sensorgrams. The KD values of the two batches of humanized variants changed less than 3-fold compared to the parental chimeras.

[0189] The BLI system is based on Bio-Layer Interferometry (BLI), a fluid-free instrument platform that enables real-time, label-free analysis for determining kinetics, affinity, and antibody / protein quantification. Binding experiments were performed on an Octet HTX at 25 °C. The analyte used was huCD122-HIS (ARCO Bio | catalog number CD2-H5221), with a molecular weight of 25.4 kDa. Antibodies were loaded onto anti-human Fc capture (AHC) sensors. The loaded sensors were immersed in serial dilutions of huCD122-His (starting concentration 20 nM, diluted 1:3, 4 points). A reference sample well (buffer) was used for data analysis. Kinetic constants were calculated using a monovalent (1:1) binding model. The assay buffer used was PBS (pH 7.2) containing 0.1% BSA and 0.02% Tween-20. The regeneration buffer used was 10 mM glycine buffer (pH 1.7). Four concentrations of huCD122-His were used to determine the binding and dissociation characteristics of the anti-CD122 antibodies: 0.0 nM, 2.2 nM, 6.7 nM, and 20 nM. Sensorgrams showing the antibody binding characteristics were generated. Mouse parental chimeric configurations on IgG1 and IgG4 backbones (M5 IgG1 parental and M5 IgG4 parental), as well as each combination of humanized 3HC and 3LC variants on IgG1 or IgG4 backbones, were tested. The sensorgrams for each variant are as shown in Figures 1 - 10 shown.

[0190] The binding affinities of the tested antibodies are listed in Table 20.

[0191] Table 20: Binding Affinities

[0192]

[0193] Results:

[0194] By comparing the binding affinities of various HC and LC paired antibodies (G1-G20), many humanized forms showed binding affinities close to those of the parental chimeric forms. For example, the equilibrium dissociation constant (KD) of the G1 mouse parental IgG1 chimera was measured to be 7.27E -10 . The KD values of the humanized IgG1 variants (G2-G10) ranged from 1.78E -09 to 7.54E -10 . The measured KD values of the G11 mouse parental IgG4 chimera were 7.95E -10 and 8.66E -10 (second batch). The KD values of the humanized IgG4 variants (G12-G20) ranged from 2.57E -09 to 6.98E -10。All antibody variants achieved stable yields. These features, together with the higher T20 humanization scores attributed to each variant's VH or VL domain, indicate that the humanized form of the anti-CD122 antibody has high affinity and a low likelihood of immunogenic complications when used in human subjects.

[0195] Example 2: Inhibition of IL-2-mediated proliferation by the humanized anti-CD122 antibodyThe ability of the humanized anti-CD122 antibody to inhibit proliferation in vitro was tested. The human cell line TF-1 (ATCC, Manassas, VA) was originally established from bone marrow cells of a subject with erythroleukemia and its growth depends on the addition of exogenous cytokines such as erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin 3 (IL3) to the culture medium. TF-1 expresses the common gamma chain IL receptor (CD132) but does not express the IL2 / IL15 receptor beta chain (CD122). Expression of the CD122 gene in TF-1 enables it to express medium- and high-affinity IL2 and IL15 receptors. TF-1-CD122 cells were generated by transfecting TF-1 with a mammalian expression vector carrying the gene encoding human CD122 and a puromycin resistance gene.

[0196] The ability of anti-CD122 monoclonal antibody variants to inhibit IL2-mediated cell proliferation was detected using TF-CD122 cells. Prior to the experiment, TF-CD122 cells were cultured in RPMI 1640 medium (ThermoFisher Scientific, catalog number 11875093) supplemented with 10% heat-inactivated FBS, 50 IU / mL IL2, 2 mM L-glutamine, 50 U / ml penicillin and 50 μg / ml streptomycin. The cells were maintained at 37 °C in a humidified 5% CO2 atmosphere. In a typical experiment, TF-1-CD122 cells were first deprived of IL2 for 2 days. Thereafter, approximately 10 4Cells per well were incubated with serial dilutions of anti-CD122 monoclonal antibody variants (G1 - G20) at concentrations between 0.1 - 10.0 μg / mL. Control wells included three control conditions: 1) no antibody plus 50 IU / mL IL2; 2) InVivoMAb human IgG1 isotype control (BioXCell, NH; catalog number BE0297), whose concentration matched the serial dilutions; or 3) human IgG4κ (S228P) isotype control - CrownVivoTM antibody (MBL International Corp, MA; catalog number C0045), whose concentration matched the serial dilutions. The treatment with anti-CD122 monoclonal antibody variants G1 - G20 (or control conditions) was maintained at 37 °C for 10 minutes, then 50 IU / mL IL2 was added to the medium. The cells were then cultured for 48 hours. Next, 20 μL of alamarBlueTM cell viability reagent (ThermoFisher Scientific; catalog number DAL1025) was added to each well, and the plate was incubated for 6 hours. After washing the wells, the plate was read at 540 and 620 nm using a spectrophotometer microplate reader. Proliferation curves were obtained as per the manufacturer's recommendations.

[0197] Example 3: Inhibition of IL15-mediated proliferation in vitro by humanized anti-CD122 antibody

[0198] The ability of the humanized anti-CD122 antibody to inhibit proliferation in vitro was tested. TF-CD122 cells were cultured in RPMI 1640 (ThermoFisher Scientific, catalog number 11875093) supplemented with 10% heat-inactivated FBS, 2 mM L-glutamine, 50 U / ml penicillin, and 50 μg / ml streptomycin. To mimic IL15 trans-presentation, a soluble complex (scIL15 / IL15Ra) of human IL15 bound to a portion of the extracellular region of human IL15Ra was constructed as described in (Mortier et al., 2006; J. Biol. Chem., 281:1612 - 1619) and added to the cell culture medium at a concentration of 10 nM. Cell proliferation was assayed to determine whether 10 nM scIL15 / IL15Ra was able to support the growth of TF-CD122 cells. The cells were maintained at 37 °C in a humidified 5% CO2 atmosphere. In a typical experiment, TF-1-CD122 cells were first depleted of scIL15 / IL15Ra and maintained for 2 days. Thereafter, approximately 10 4Cells per well were incubated with serial dilutions of anti-CD122 monoclonal antibody variants (G1-G20) at concentrations between 0.1 - 10.0 μg / mL. Control wells included three control conditions: 1) no antibody plus 10 nM scIL15 / IL15Ra; 2) InVivoMAb human IgG1 isotype control (BioXCell, NH; catalog number BE0297), whose concentration matched the serial dilutions; or 3) human IgG4κ (S228P) isotype control - CrownVivoTM antibody (MBL International Corp, MA; catalog number C0045), whose concentration matched the serial dilutions. Treatments with anti-CD122 monoclonal antibody variants G1 - G20 (or control conditions) were maintained at 37 °C for 10 minutes, then 10 nM scIL15 / IL15Ra was added to the medium. The cells were then cultured for 48 hours. Next, 20 μL of alamarBlueTM cell viability reagent (ThermoFisher Scientific; catalog number DAL1025) was added to each well, and the plate was incubated for 6 hours. After washing the wells, the plate was read at 540 and 620 nm using a spectrophotometer microplate reader. Proliferation curves were obtained according to the manufacturer's recommendations.

[0199] Example 4: Inhibition of IL2 and IL15 Signaling by Anti-CD122 Antibodies

[0200] The ability of several anti-CD122 antibodies described herein to inhibit IL2 and / or IL15 signaling was tested using in vitro assays. The ability of anti-CD122 antibodies to inhibit IL2 and / or IL15 signaling was tested using a reporter cell line that expresses the βγ receptor for IL2 and IL15 (CD122 / CD132, which has moderate affinity for both IL2 and IL15) and luciferase regulated by the binding of IL2 and IL15 to their receptors. In Figure 11 the ability of three anti-CD122 antibodies to inhibit IL2 and / or IL15 signaling was determined. The reporter cells were treated with IL2 (12.5 ng / mL) or IL15 (6 ng / mL) and with anti-CD122 antibodies at ten different antibody concentrations (ranging from 10 μg / mL to 0.5 ng / mL). A commercially available anti-CD122 antibody designated as such was used as a positive control for the experiment and was anti-human CD122 antibody clone TU27, which was obtained from Catalog number 339015. Antibody 1 and Antibody 2 are humanized anti-human CD122 antibodies. Antibody 1 is the humanized monoclonal antibody described herein, which comprises the CDR sequences of CDR set E7 listed in Table 3. Antibody 2 is a known humanized monoclonal anti-CD122 antibody, which comprises a VH domain and a VL domain, wherein the VH domain comprises: HCDR1 comprising the sequence of SEQ ID NO:189, HCDR2 comprising the sequence of SEQ ID NO:190, and HCDR3 comprising the sequence of SEQ ID NO:191; and wherein the VL domain comprises: LCDR1 comprising the sequence of SEQ IDNO:192, LCDR2 comprising the sequence of SEQ ID NO:193, and LCDR3 comprising the sequence of SEQ ID NO:194.

[0201] The results of the negative controls for these experiments are shown in Figure 11 , in which cells were treated with IL2 only (upper panel) or IL15 only (lower panel), without any co-treatment with anti-CD122 antibody, and the luminescence signals of the cell-based reporter assay were plotted as relative light unit (RLU) values. The results of another negative control for these experiments are shown in the figure in Figure 11 , in which cells were not treated with IL2 or IL15 and were not treated with anti-CD122 antibody either. The measured values of IL2 / IL15 signal transduction after co-treatment with IL2 or IL15 (12.5 and 6 ng / mL respectively) and anti-CD122 antibody (a dilution series calculated using a dose-response curve, where the tested doses ranged from 10 μg / mL to 1.5 ng / mL) were plotted as a function of the anti-CD122 antibody concentration (μg / mL, logarithmic scale). The half-maximal effective dose (EC50) of the IL2 and / or IL15 antagonist (anti-CD122 antibody) used to reduce IL2 and / or IL15 signal transduction in response to IL2 or IL15 treatment was calculated to determine the efficacy of the tested anti-CD122 antibodies. Figure 11 The results in

[0202] show that Antibody 1 is a more effective inhibitor of IL2 signal transduction and IL15 signal transduction than the commercially available antibody or Antibody 2. In this assay, Antibody 1 was able to inhibit IL2 signal transduction and IL15 signal transduction more effectively than Antibody 2 (3- to 5-fold more potent). These results also indicate that the tested anti-CD122 antibodies can inhibit the βγ receptor (CD122 / CD132), and Antibody 1 is the most effective inhibitor. Figure 12In this case, cells were treated with IL2 at a dose of 10 ng / mL and with anti-CD122 antibody at six different antibody concentrations ranging from 30 μg / mL to 30 ng / mL. The results were plotted as the percentage of cell proliferation inhibition as a function of anti-CD122 antibody concentration compared to the case without antibody treatment. The plotted data indicate that neither antibody 2 nor antibody 1 is an effective inhibitor of the αβγ receptor.

[0203] Example 5: Epitope Mapping of the IL2 Interleukin Receptor β Using a Humanized Anti-CD122 Antibody

[0204] In this example, the goal was to map the epitope interaction of the humanized monoclonal antibody (Mab) described herein with the human IL2 interleukin receptor β (IL2RB) using the plasma-induced biomolecular modification (PLIMB) technique.

[0205] Experimental Design and Methods:

[0206] PLIMB and MS Optimization: Prior to epitope mapping, the level of antigen modification in response to several doses of PLIMB-induced hydroxyl group exposure was monitored. Samples were prepared and exposed to PLIMB for 20 seconds and 40 seconds. Samples were prepared as described below and LC-MS / MS was used to optimize labeling and digestion coverage for subsequent quantitative analysis.

[0207] IL2RB Epitope Mapping: The solvent accessibility differences of the antigen (IL2RB) were measured using the trifluoromethyl group (CF3) generated by PLIMB exposure. First, two solutions were prepared for IL2RB epitope mapping. The first solution contained IL2RB and a non-binding standard IgG control antibody from NIST. The second solution contained the humanized anti-CD122 Mab added at a 1:1 antibody / antigen molar ratio. Samples of IL2RB with the NIST antibody were designated "unbound", while samples with the added humanized anti-CD122 Mab were designated "bound" or "complex". Residue-level analysis was used on peptides in the candidate epitope region to determine which individually labeled amino acids exhibited the greatest solvent accessibility changes due to binding. Individual residues in the epitope region exhibit solvent accessibility changes after binding, which represent "hot spots" that can be used to further precisely define the region involved in antigen / antibody epitope interaction.

[0208] Results:

[0209] IL2RB Labeling and Coverage

[0210] The work described in this example focuses on the beta subunit (IL2RB) of the interleukin-2 receptor (IL2R). The IL2RB in this example contains an extracellular domain (A26 - D239). After analyzing samples exposed to PLIMB, all regions of IL2RB showed sufficient labeling across the entire protein sequence at 20 seconds and 40 seconds.

[0211] IL2RB Epitope Determination

[0212] Residue-level analysis of the full-length IL2RB primary sequence was performed on PLIMB-treated samples with a control antibody (NIST) prepared in the unbound state and PLIMB-treated samples with a humanized anti-CD122 Mab added in the bound state to detect differences in solvent accessibility (modification level) after complexation ( Figure 13 ). Figure 13 Shown is the annotation / numbering of the extracellular IL2RB form based on the protein used in this example, which corresponds to [A26 - D239] of the canonical sequence (UniProt ID: P14784). The labeling of the amino acid residues used for epitope mapping in this example was based on the amino acid positions in the human CD122 polypeptide sequence of SEQ ID NO: 187 (e.g., W39 corresponds to position 39 in SEQ ID NO: 187 and also to position 64 in SEQ ID NO: 186). Bold residues indicate significant changes in solvent accessibility (including unlabeled residues between residues with significant changes to indicate the epitope region). Underlined residues indicate the epitope region. Boxed residues (contained within the box) indicate conformational changes.

[0213] Changes in solvent accessibility were mapped onto the IL2RB crystal structure and shown as fold changes with statistical significance ( Figure 15 and Figure 14 ). A decrease in protection or labeling by the experimental antibody compared to the control indicates epitope interaction. Figure 14 A heatmap showing the modification changes of humanized anti-CD122 Mab in bound and unbound IL2RB is shown. The log2 fold change is the log2 fold change of the humanized anti-CD122 Mab (bound) and the NIST control antibody (unbound) incubated with IL2RB at 20 seconds and 40 seconds PLIMB time points. Green indicates a decrease and red indicates an increase. The shaded boxes in the t-test column indicate significant changes (p < 0.05).

[0214] High-resolution footprint analysis via PLIMB-induced CF3 group labeling revealed multiple residue "hotspots" on IL2RB under the antibody "bound" condition. These "hotspots" were mapped onto the 3D crystal structure of IL2RB (Figure 15 )。Conformational epitope regions are expected to cluster together in specific regions of the protein. From the 3D crystal structure map, four specific regions were identified as epitope sites: 1) residues 39 - 41 (WPD), 2) residues 76 - 81 (VDIVTL), 3) residues 99 - 105 (FKPFENL), and 4) residues 134 - 139 (HYFERH). These regions are all mapped to the IL2 binding interface in the 3D crystal structure ( Figure 15 ). Additionally, these regions showed relatively consistent changes at both 20 - second and 40 - second PLIMB exposure times, indicating the presence of more stable interactions that suggest the existence of epitope / antibody binding regions.

[0215] Additional "hot spots" were mapped to regions outside the IL2 binding interface. These "hot spots" are consistent with distal conformational changes rather than epitope regions. This determination is based on their relative degree of change (usually less than that of sites directly involved in antibody binding) and their relative separation from other "hot spot" clusters. Positions identified as conformational change sites include: 1) residues 89 - 91 (VRW), 2) residue 153 (W), and 3) residue 192 (F).

[0216] In summary, different residues involved in the binding of the humanized anti - CD122 antibody to IL2RB have been identified, and these residues are mainly located on the IL2 binding surface of IL2RB.

[0217] Overview of the method:

[0218] Sample preparation, PLIMB treatment, and LC - MS / MS analysis: The humanized anti - CD122 Mab and NIST antibody were incubated with IL2RB at room temperature for one hour to promote binding. For trifluoromethylation labeling (CF3), the samples were exposed to PLIMB treatment in the presence of 50 mM sodium triflinate and 10 mM hydrogen peroxide for 20 seconds and 40 seconds (repeated 3 - 5 times for each condition). After labeling, the samples were quenched with a 5 μL solution of 250 mM methionine in PBS (pH 7.4).

[0219] After PLIMB exposure, the samples were proteolytically digested into peptides with trypsin and elastase in sequence. The samples were subjected to solid - phase extraction using C18 StageTips, labeled with 6 - plex tandem mass tags (Thermo Scientific TMT 6 - plex), and then analyzed using data - dependent acquisition with an Orbitrap Exploris 240 mass spectrometer.

[0220] Data analysis:

[0221] Using the database search engine MetaMorpheus, search for ".raw" data files for the IL2RB sequence. Use a list of standard expected modifications and expected PLIMB modifications in the database search. Identify peptides using MS and MS / MS spectra, setting the false discovery rate (FDR) cutoff to 1%. Determine the solvent accessibility changes in samples digested with trypsin and trypsin-elastase by comparing the sum of the normalized TMT channel intensities of the control antibody and the humanized anti-CD122 target Mab. The reported solvent accessibility changes are from samples digested with trypsin-elastase. Verify these changes by examining samples digested with trypsin.

[0222] Statistical analysis:

[0223] Calculate the fold change of IL2RB peptides in the bound and unbound states of the humanized anti-CD122 Mab, and perform a student t-test for each peptide. A p < 0.05 is considered a significant change.

[0224] Overview of experimental conditions:

[0225] · Antigen sample: Human IL2RB (A26-D239), His-tag (Acro Biosystems)

[0226] · Antigen concentration: 0.1 mg / mL (2.7 μM)

[0227] · Control antibody (NIST) concentration: 0.42 mg / mL (2.7 μM)

[0228] · Experimental antibody concentration: 0.42 mg / mL (2.7 μM)

[0229] · Antibody / antigen ratio: 1:1

[0230] · Experimental sample volume: 50 μL

[0231] · Sample buffer: 100 mM PBS, pH 7.4

[0232] · Proteases used: Trypsin Platinum (Promega) and elastase (Promega)

[0233] · Instrument: Thermo Orbitrap Exploris 240

[0234] · Data processing software: MetaMorpheus

[0235] Detailed methods:

[0236] Sample preparation and digestion:

[0237] After PLIMB treatment, the samples were denatured and reduced with 8 M guanidine hydrochloride (GnHCl) containing 5 mM TCEP. The samples were heated to 90 °C for 15 minutes and then cooled. The samples were alkylated with 15 mM IAA for 30 minutes at room temperature in the dark. The samples were diluted to 1.5 M GnHCl and digested overnight with trypsin (Promega) at a total protease / protein mass ratio of 1:10 at 37 °C. The reaction was quenched by adding 2% trifluoroacetic acid before desalting and purified using Empore C18 StageTips (CDS Analytical) using the standard protocol. Half of the eluted peptides were dried using a vacuum concentrator and resuspended in 0.1% formic acid for LC-MS / MS analysis. The remaining samples were resuspended in 100 mM Tris-HCl and subjected to secondary digestion with elastase (Promega) at a ratio of 1:20 for 4 hours at 37 °C. After quenching, the peptides were desalted, dried, and resuspended in 50 mM HEPES buffer at pH 8.5. The samples were labeled with tandem mass tags (6-plex TMT, ThermoFisher) according to the manufacturer's protocol.

[0238] LC-MS / MS Acquisition

[0239] Separation was performed on a 2 μM, 15 cm Easy-Spray PepMap C18 column from ThermoFisher Scientific using a 60-minute chromatographic gradient of 2% to 40% acetonitrile in 0.1% formic acid. Top-10 data-dependent acquisition was performed, where the MS1 parameters were: 60K resolution on the Orbitrap, a scan range of 350 - 1200 m / z, and a normalized AGC target value of 300%; the MS 2 parameters were: charge state selection was 1 - 6, the quadrupole isolation window was 2 Da, the HCD stepped collision energy was 28%, 36%, 42%, the normalized AGC value was 50%, and the automatic scan range started from 110 m / z. After detecting a primary ion, 6-second dynamic exclusion was used.

[0240] Data Analysis:

[0241] The following modifications were used in our MetaMorpheus search:

[0242] Standard Modifications:

[0243] · Ureidomethylation / +57.021464@C (fixed)

[0244] PLIMB modification:

[0245] · Oxidation / +15.994915 @ C, F, H, I, L, M, W, Y

[0246] · Dioxidation / +31.989829 @ C, F, M, W, Y

[0247] · Cys oxidation / +15.994915 - 57.021464 @ C

[0248] · Cys dioxidation / +31.989829 - 57.021464 @ C

[0249] · Cys trioxidation / +47.984745 - 57.021464 @ C

[0250] · Nitration / +44.985078 @ W, Y

[0251] · Trifluoromethylation / +67.9874 @ A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y

[0252] · Bis(trifluoromethylation) / +135.9748 @ A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y

[0253] · Cys trifluoromethylation / +67.9874 - 57.021464 @ C

[0254] Summary of results:

[0255] Using the hydroxyl (OH) and trifluoromethyl (CF3) labels generated by PLIMB, the epitopes of human interleukin 2 receptor β (IL2RB) that bind to humanized anti-CD122 Mab were mapped. The resulting epitopes are conformational epitopes, not linear epitopes. The mapped epitopes are contained in the following regions: W39 - D41, V76 - L81, F99 - L105, and H134 - H139. These regions cluster at a unique interface of the IL2RB protein. The region covered by the mapped conformational epitope significantly overlaps with the IL2 / IL2RB binding interface, indicating that this antibody would be an effective IL2RB antagonist.

[0256] While the preferred aspects of the present invention have been shown and described herein, it will be apparent to those skilled in the art that these aspects are provided by way of example only. Many variations, changes, and substitutions will now occur to those skilled in the art without departing from the present invention. It should be understood that various alternatives to the aspects of the present invention described herein may be employed in practicing the present invention. The following claims are intended to define the scope of the present invention and cover the methods and structures within the scope of these claims and their equivalents.

[0257] Aspect

[0258] Aspect 1: An antibody that binds to CD122, comprising:

[0259] An HCDR1 comprising the amino acid sequence of SEQ ID NO:7; an HCDR2 comprising the amino acid sequence of SEQ ID NO:18; an HCDR3 comprising the amino acid sequence of SEQ ID NO:30; an LCDR1 comprising the amino acid sequence of SEQ ID NO:43; an LCDR2 comprising the amino acid sequence of SEQ ID NO:50; and an LCDR3 comprising the amino acid sequence of SEQ ID NO:62.

[0260] Aspect 2: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: an HCDR1 having the sequence of SEQ ID NO:7, an HCDR2 having the sequence of SEQ ID NO:18, an HCDR3 having the sequence of SEQ ID NO:30, an LCDR1 having the sequence of SEQ ID NO:43, an LCDR2 having the sequence of SEQ ID NO:50, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the IMGT antibody numbering scheme).

[0261] Aspect 3: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: an HCDR1 having the sequence of SEQ ID NO:162, an HCDR2 having the sequence of SEQ ID NO:169, an HCDR3 having the sequence of SEQ ID NO:176, an LCDR1 having the sequence of SEQ ID NO:178, an LCDR2 having the sequence of SEQ ID NO:181, and an LCDR3 having the sequence of SEQ ID NO:62 (according to the Kabat antibody numbering scheme).

[0262] Aspect 4: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 163, HCDR2 having the sequence of SEQ ID NO: 170, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 178, LCDR2 having the sequence of SEQ ID NO: 181, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the AbM antibody numbering scheme).

[0263] Aspect 5: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 164, HCDR2 having the sequence of SEQ ID NO: 171, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 178, LCDR2 having the sequence of SEQ ID NO: 181, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Chothia antibody numbering scheme).

[0264] Aspect 6: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 165, HCDR2 having the sequence of SEQ ID NO: 172, HCDR3 having the sequence of SEQ ID NO: 177, LCDR1 having the sequence of SEQ ID NO: 179, LCDR2 having the sequence of SEQ ID NO: 182, and LCDR3 having the sequence of SEQ ID NO: 184 (according to the Contact antibody numbering scheme).

[0265] Aspect 7: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 166, HCDR2 having the sequence of SEQ ID NO: 173, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 178, LCDR2 having the sequence of SEQ ID NO: 181, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Kabat antibody numbering scheme).

[0266] Aspect 8: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 167, HCDR2 having the sequence of SEQ ID NO: 170, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 178, LCDR2 having the sequence of SEQ ID NO: 181, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the AbM antibody numbering scheme).

[0267] Aspect 9: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 164, HCDR2 having the sequence of SEQ ID NO: 171, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 178, LCDR2 having the sequence of SEQ ID NO: 181, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Chothia antibody numbering scheme).

[0268] Aspect 10: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 168, HCDR2 having the sequence of SEQ ID NO: 174, HCDR3 having the sequence of SEQ ID NO: 177, LCDR1 having the sequence of SEQ ID NO: 179, LCDR2 having the sequence of SEQ ID NO: 182, and LCDR3 having the sequence of SEQ ID NO: 184 (according to the Contact antibody numbering scheme).

[0269] Aspect 11: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 166, HCDR2 having the sequence of SEQ ID NO: 173, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 180, LCDR2 having the sequence of SEQ ID NO: 183, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Kabat antibody numbering scheme).

[0270] Aspect 12: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 167, HCDR2 having the sequence of SEQ ID NO: 170, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 180, LCDR2 having the sequence of SEQ ID NO: 183, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the AbM antibody numbering scheme).

[0271] Aspect 13: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 164, HCDR2 having the sequence of SEQ ID NO: 171, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 180, LCDR2 having the sequence of SEQ ID NO: 183, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Chothia antibody numbering scheme).

[0272] Aspect 14: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 168, HCDR2 having the sequence of SEQ ID NO: 174, HCDR3 having the sequence of SEQ ID NO: 177, LCDR1 having the sequence of SEQ ID NO: 179, LCDR2 having the sequence of SEQ ID NO: 182, and LCDR3 having the sequence of SEQ ID NO: 184 (according to the Contact antibody numbering scheme).

[0273] Aspect 15: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 162, HCDR2 having the sequence of SEQ ID NO: 175, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 178, LCDR2 having the sequence of SEQ ID NO: 181, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Kabat antibody numbering scheme).

[0274] Aspect 16: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 163, HCDR2 having the sequence of SEQ ID NO: 170, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 178, LCDR2 having the sequence of SEQ ID NO: 181, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the AbM antibody numbering scheme).

[0275] Aspect 17: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 164, HCDR2 having the sequence of SEQ ID NO: 171, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 178, LCDR2 having the sequence of SEQ ID NO: 181, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Chothia antibody numbering scheme).

[0276] Aspect 18: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 165, HCDR2 having the sequence of SEQ ID NO: 174, HCDR3 having the sequence of SEQ ID NO: 177, LCDR1 having the sequence of SEQ ID NO: 179, LCDR2 having the sequence of SEQ ID NO: 182, and LCDR3 having the sequence of SEQ ID NO: 184 (according to the Contact antibody numbering scheme).

[0277] Aspect 19: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 162, HCDR2 having the sequence of SEQ ID NO: 175, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 180, LCDR2 having the sequence of SEQ ID NO: 183, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Kabat antibody numbering scheme).

[0278] Aspect 20: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 163, HCDR2 having the sequence of SEQ ID NO: 170, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 180, LCDR2 having the sequence of SEQ ID NO: 183, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the AbM antibody numbering scheme).

[0279] Aspect 21: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 164, HCDR2 having the sequence of SEQ ID NO: 171, HCDR3 having the sequence of SEQ ID NO: 176, LCDR1 having the sequence of SEQ ID NO: 180, LCDR2 having the sequence of SEQ ID NO: 183, and LCDR3 having the sequence of SEQ ID NO: 62 (according to the Chothia antibody numbering scheme).

[0280] Aspect 22: An antibody or antigen-binding fragment thereof that binds to CD122, comprising: HCDR1 having the sequence of SEQ ID NO: 165, HCDR2 having the sequence of SEQ ID NO: 174, HCDR3 having the sequence of SEQ ID NO: 177, LCDR1 having the sequence of SEQ ID NO: 179, LCDR2 having the sequence of SEQ ID NO: 182, and LCDR3 having the sequence of SEQ ID NO: 184 (according to the Contact antibody numbering scheme).

[0281] Aspect 23: The antibody according to any one of aspects 1-22, wherein the antibody is a monoclonal antibody.

[0282] Aspect 24: The antibody according to any one of aspects 1-23, wherein the antibody is a humanized monoclonal antibody.

[0283] Aspect 25: The antibody according to any one of aspects 1-23, wherein the antibody is a human antibody.

[0284] Aspect 26: The antibody or antigen-binding fragment thereof according to any one of aspects 1-25, wherein the CD122 is mammalian CD122.

[0285] Aspect 27: The antibody or antigen-binding fragment thereof according to any one of aspects 1-26, wherein the CD122 is murine CD122.

[0286] Aspect 28: The antibody or antigen-binding fragment thereof according to any one of aspects 1-26, wherein the CD122 is human CD122.

[0287] Aspect 29: The antibody according to any one of aspects 1-28, wherein the antibody binds to the human CD122 protein with a binding affinity (K D value) in the nanomolar range of 10 -7 to 10 -9 M.

[0288] Aspect 30: The antibody according to any one of aspects 1-28, wherein the antibody binds to the human CD122 protein with a binding affinity (K D value) in the low nanomolar range of 10 -9 M.

[0289] Aspect 31: The antibody according to any one of aspects 1-28, wherein the antibody binds to the human CD122 protein with a binding affinity (K D value) in the picomolar range of 10 -10 to 10 -12 M.

[0290] Aspect 32: The antibody according to any one of aspects 1-28, wherein the antibody binds to the human CD122 protein with a binding affinity (K D value) in the high picomolar range of 10 -10 M.

[0291] Aspect 33: The antibody according to any one of aspects 1-28, wherein the antibody binds to the human CD122 protein with a binding affinity (K D value) in the range from low nanomolar to high picomolar of 10 -9 to 10 -10 M.

[0292] Aspect 34: The antibody according to any one of aspects 1-28, wherein the antibody binds to the human CD122 protein with a binding affinity measured by a K -09 less than approximately 3E D M.

[0293] Aspect 35: The antibody according to any one of aspects 1-28, wherein the antibody binds to the human CD122 protein with a binding affinity measured by a K -09 less than approximately 2E D M.

[0294] Aspect 36: The antibody according to any one of aspects 1-28, wherein the antibody binds to the human CD122 protein with a binding affinity measured by a K -09 less than approximately 1E DThe measured binding affinity binds to human CD122 protein.

[0295] Aspect 37: The antibody according to any one of aspects 1 - 28, wherein the antibody binds to human CD122 protein with a binding affinity measured by less than about 9E -10 M of K D The measured binding affinity binds to human CD122 protein.

[0296] Aspect 38: The antibody according to any one of aspects 1 - 28, wherein the antibody binds to human CD122 protein with a binding affinity measured by less than about 8E -10 M of K D The measured binding affinity binds to human CD122 protein.

[0297] Aspect 39: The antibody according to any one of aspects 1 - 28, wherein the antibody binds to human CD122 protein with a binding affinity measured by a K between about 5E -09 and 5E -10 M D The measured binding affinity binds to human CD122 protein.

[0298] Aspect 40: The antibody according to any one of aspects 1 - 28, wherein the antibody binds to human CD122 protein with a binding affinity measured by a K between about 3E -09 and 7E -10 M D The measured binding affinity binds to human CD122 protein.

[0299] Aspect 41: The antibody according to any one of aspects 1 - 28, wherein the antibody binds to human CD122 protein with a binding affinity measured by a K between about 2E -09 and 8E -10 M D The measured binding affinity binds to human CD122 protein.

[0300] Aspect 42: The antibody according to any one of aspects 1 - 28, wherein the antibody binds to human CD122 protein with a binding affinity measured by a K between about 1E -09 and 9E -10 M D The measured binding affinity binds to human CD122 protein.

[0301] Aspect 43: The antibody according to any one of aspects 1 - 42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO:134 and a light chain containing the sequence of SEQ ID NO:142.

[0302] Aspect 44: The antibody according to any one of aspects 1 - 42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO:135 and a light chain containing the sequence of SEQ ID NO:143.

[0303] Aspect 45: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 135 and a light chain containing the sequence of SEQ ID NO: 144.

[0304] Aspect 46: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 135 and a light chain containing the sequence of SEQ ID NO: 145.

[0305] Aspect 47: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 136 and a light chain containing the sequence of SEQ ID NO: 143.

[0306] Aspect 48: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 136 and a light chain containing the sequence of SEQ ID NO: 144.

[0307] Aspect 49: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 136 and a light chain containing the sequence of SEQ ID NO: 145.

[0308] Aspect 50: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 137 and a light chain containing the sequence of SEQ ID NO: 143.

[0309] Aspect 51: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 137 and a light chain containing the sequence of SEQ ID NO: 144.

[0310] Aspect 52: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 137 and a light chain containing the sequence of SEQ ID NO: 145.

[0311] Aspect 53: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 138 and a light chain containing the sequence of SEQ ID NO: 142.

[0312] Aspect 54: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 139 and a light chain containing the sequence of SEQ ID NO: 143.

[0313] Aspect 55: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 139 and a light chain containing the sequence of SEQ ID NO: 144.

[0314] Aspect 56: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 139 and a light chain containing the sequence of SEQ ID NO: 145.

[0315] Aspect 57: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 140 and a light chain containing the sequence of SEQ ID NO: 143.

[0316] Aspect 58: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 140 and a light chain containing the sequence of SEQ ID NO: 144.

[0317] Aspect 59: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 140 and a light chain containing the sequence of SEQ ID NO: 145.

[0318] Aspect 60: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 141 and a light chain containing the sequence of SEQ ID NO: 143.

[0319] Aspect 61: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 141 and a light chain containing the sequence of SEQ ID NO: 144.

[0320] Aspect 62: The antibody according to any one of aspects 1-42, wherein the antibody comprises a heavy chain containing the sequence of SEQ ID NO: 141 and a light chain containing the sequence of SEQ ID NO: 145.

[0321] Aspect 63: An isolated monoclonal antibody, which, when binding to CD122, binds to at least one of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0322] Aspect 64: The isolated monoclonal antibody according to aspect 63, wherein when binding to CD122, the monoclonal antibody binds to at least two of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0323] Aspect 65: The isolated monoclonal antibody according to aspect 63 or 64, wherein when binding to CD122, the monoclonal antibody binds to at least three of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0324] Aspect 66: The isolated monoclonal antibody according to any one of aspects 63 - 65, wherein when binding to CD122, the monoclonal antibody binds to at least four of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0325] Aspect 67: The isolated monoclonal antibody according to any one of aspects 63 - 66, wherein when binding to CD122, the monoclonal antibody binds to at least five of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0326] Aspect 68: The isolated monoclonal antibody according to any one of aspects 63 - 67, wherein when binding to CD122, the monoclonal antibody binds to at least six of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0327] Aspect 69: The isolated monoclonal antibody according to any one of aspects 63-68, wherein when binding to CD122, the monoclonal antibody binds to at least seven of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0328] Aspect 70: The isolated monoclonal antibody according to any one of aspects 63-69, wherein when binding to CD122, the monoclonal antibody binds to at least eight of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0329] Aspect 71: The isolated monoclonal antibody according to any one of aspects 63-70, wherein when binding to CD122, the monoclonal antibody binds to at least nine of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0330] Aspect 72: The isolated monoclonal antibody according to any one of aspects 63-71, wherein when binding to CD122, the monoclonal antibody binds to at least ten of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0331] Aspect 73: The isolated monoclonal antibody according to any one of aspects 63-72, wherein when binding to CD122, the monoclonal antibody binds to at least eleven of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0332] Aspect 74: The isolated monoclonal antibody according to any one of aspects 63-73, wherein when binding to CD122, the monoclonal antibody binds to at least twelve of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0333] Aspect 75: The isolated monoclonal antibody according to any one of aspects 63-74, wherein when binding to CD122, the monoclonal antibody binds to at least thirteen of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0334] Aspect 76: The isolated monoclonal antibody according to any one of aspects 63-75, wherein when binding to CD122, the monoclonal antibody binds to at least fourteen of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0335] Aspect 77: The isolated monoclonal antibody according to any one of aspects 63 - 76, wherein when binding to CD122, the monoclonal antibody binds to at least fifteen of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0336] Aspect 78: The isolated monoclonal antibody according to any one of aspects 63 - 77, wherein when binding to CD122, the monoclonal antibody binds to at least sixteen of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0337] Aspect 79: The isolated monoclonal antibody according to any one of aspects 63 - 78, wherein when binding to CD122, the monoclonal antibody binds to at least seventeen of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0338] Aspect 80: The isolated monoclonal antibody according to any one of aspects 63 - 79, wherein when binding to CD122, the monoclonal antibody binds to at least eighteen of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0339] Aspect 81: The isolated monoclonal antibody according to any one of aspects 63 - 80, wherein when binding to CD122, the monoclonal antibody binds to at least nineteen of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0340] Aspect 82: The isolated monoclonal antibody according to any one of aspects 63 - 81, wherein when binding to CD122, the monoclonal antibody binds to at least twenty of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0341] Aspect 83: The isolated monoclonal antibody according to any one of aspects 63 - 82, wherein when binding to CD122, the monoclonal antibody binds to at least twenty - one of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187.

[0342] Aspect 84: The isolated monoclonal antibody according to any one of aspects 63 - 83, wherein when binding to CD122, the monoclonal antibody binds to at least all twenty - two of the following residues: W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 and H139 of SEQ ID NO:187.

[0343] Aspect 85: The isolated monoclonal antibody according to any one of aspects 63 - 84, wherein the monoclonal antibody binds to at least W39.

[0344] Aspect 86: The isolated monoclonal antibody according to any one of aspects 63 - 85, wherein the monoclonal antibody binds to at least P40.

[0345] Aspect 87: The isolated monoclonal antibody according to any one of aspects 63 - 86, wherein the monoclonal antibody binds to at least D41.

[0346] Aspect 88: The isolated monoclonal antibody according to any one of aspects 63 - 87, wherein the monoclonal antibody binds to at least V76.

[0347] Aspect 89: The isolated monoclonal antibody according to any one of aspects 63 - 88, wherein the monoclonal antibody binds to at least D77.

[0348] Aspect 90: The isolated monoclonal antibody according to any one of aspects 63 - 89, wherein the monoclonal antibody binds to at least I78.

[0349] Aspect 91: The isolated monoclonal antibody according to any one of aspects 63 - 90, wherein the monoclonal antibody binds to at least V79.

[0350] Aspect 92: The isolated monoclonal antibody according to any one of aspects 63 - 91, wherein the monoclonal antibody binds to at least T80.

[0351] Aspect 93: The isolated monoclonal antibody according to any one of aspects 63 - 92, wherein the monoclonal antibody binds to at least L81.

[0352] Aspect 94: The isolated monoclonal antibody according to any one of aspects 63 - 93, wherein the monoclonal antibody binds to at least F99.

[0353] Aspect 95: The isolated monoclonal antibody according to any one of aspects 63 - 94, wherein the monoclonal antibody binds to at least K100.

[0354] Aspect 96: The isolated monoclonal antibody according to any one of aspects 63 - 95, wherein the monoclonal antibody binds to at least P101.

[0355] Aspect 97: The isolated monoclonal antibody according to any one of aspects 63 - 96, wherein the monoclonal antibody binds to at least F102.

[0356] Aspect 98: The isolated monoclonal antibody according to any one of aspects 63 - 97, wherein the monoclonal antibody binds to at least E103.

[0357] Aspect 99: The isolated monoclonal antibody according to any one of aspects 63 - 98, wherein the monoclonal antibody binds to at least N104.

[0358] Aspect 100: The isolated monoclonal antibody according to any one of aspects 63 - 99, wherein the monoclonal antibody binds to at least L105.

[0359] Aspect 101: The isolated monoclonal antibody according to any one of aspects 63 - 100, wherein the monoclonal antibody binds to at least H134.

[0360] Aspect 102: The isolated monoclonal antibody according to any one of aspects 63 - 101, wherein the monoclonal antibody binds to at least Y135.

[0361] Aspect 103: The isolated monoclonal antibody according to any one of aspects 63 - 102, wherein the monoclonal antibody binds to at least F136.

[0362] Aspect 104: The isolated monoclonal antibody according to any one of aspects 63 - 103, wherein the monoclonal antibody binds to at least E137.

[0363] Aspect 105: The isolated monoclonal antibody according to any one of aspects 63 - 104, wherein the monoclonal antibody binds to at least R138.

[0364] Aspect 106: The isolated monoclonal antibody according to any one of aspects 63 - 105, wherein the monoclonal antibody binds to at least H139.

[0365] Aspect 107: The isolated monoclonal antibody according to any one of aspects 63 - 106, wherein the monoclonal antibody blocks the binding of IL2 to CD122.

[0366] Aspect 108: The isolated monoclonal antibody according to any one of aspects 63 - 107, wherein the monoclonal antibody blocks the binding of IL15 to CD122.

[0367] Aspect 109: The isolated monoclonal antibody according to any one of aspects 63 - 108, wherein the monoclonal antibody blocks the binding of IL2 and IL15 to CD122.

[0368] Aspect 110: The isolated monoclonal antibody according to any one of aspects 63 - 109, wherein the monoclonal antibody blocks the binding of IL2 to the intermediate - affinity IL - βγ receptor complex.

[0369] Aspect 111: The isolated monoclonal antibody according to any one of aspects 63 - 110, wherein the monoclonal antibody blocks the binding of the IL15 / IL15Rα complex to the intermediate - affinity IL - βγ receptor complex.

[0370] Aspect 112: The isolated monoclonal antibody according to any one of aspects 63 - 111, wherein the monoclonal antibody blocks the binding of IL2 and the IL15 / IL15Rα complex to the intermediate affinity IL-βγ receptor complex.

[0371] Aspect 113: The isolated monoclonal antibody according to any one of aspects 63 - 112, wherein the monoclonal antibody is a human antibody.

[0372] Aspect 114: The isolated monoclonal antibody according to any one of aspects 63 - 113, wherein the monoclonal antibody is a humanized antibody.

[0373] Aspect 115: The isolated monoclonal antibody according to any one of aspects 63 - 114, wherein the isolated monoclonal antibody binds to CD122 with a K of less than or equal to about 2E -09 M. D

[0374] Aspect 116: The isolated monoclonal antibody according to any one of aspects 63 - 115, wherein the isolated monoclonal antibody binds to CD122 with a K of less than or equal to about 1.5xE -09 M. D

[0375] Aspect 117: The isolated monoclonal antibody according to any one of aspects 63 - 116, wherein the isolated monoclonal antibody binds to CD122 with a K of less than or equal to about 1xE -09 M. D

[0376] Aspect 118: The isolated monoclonal antibody according to any one of aspects 63 - 117, wherein the isolated monoclonal antibody binds to CD122 with a K of less than or equal to about 9.5xE -10 M. D

[0377] Aspect 119: The isolated monoclonal antibody according to any one of aspects 63 - 118, wherein the isolated monoclonal antibody binds to CD122 with a K of less than or equal to about 9xE -10 M. D

[0378] Aspect 120: The isolated monoclonal antibody according to any one of aspects 63 - 119, wherein the isolated monoclonal antibody binds to CD122 with a K of less than or equal to about 8xE -10 M. D

[0379] Aspect 121: The isolated monoclonal antibody according to any one of aspects 63 - 120, wherein the isolated monoclonal antibody binds to CD122 with a K -10 dissociation constant of less than or equal to about 7xE D M.

[0380] Aspect 122: The isolated monoclonal antibody according to any one of aspects 63 - 121, wherein at least one of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 forms an epitope on the extracellular domain of CD122.

[0381] Aspect 123: The isolated monoclonal antibody according to any one of aspects 63 - 122, wherein at least two of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0382] Aspect 124: The isolated monoclonal antibody according to any one of aspects 63 - 123, wherein at least three of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0383] Aspect 125: The isolated monoclonal antibody according to any one of aspects 63 - 124, wherein at least four of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0384] Aspect 126: The isolated monoclonal antibody according to any one of aspects 63 - 125, wherein at least five of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0385] Aspect 127: The isolated monoclonal antibody according to any one of aspects 63 - 126, wherein at least six of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0386] Aspect 128: The isolated monoclonal antibody according to any one of aspects 63 - 127, wherein at least seven of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0387] Aspect 129: The isolated monoclonal antibody according to any one of aspects 63 - 128, wherein at least eight of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0388] Aspect 130: The isolated monoclonal antibody according to any one of aspects 63 - 129, wherein at least nine of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0389] Aspect 131: The isolated monoclonal antibody according to any one of Aspects 63 - 130, wherein at least ten of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0390] Aspect 132: The isolated monoclonal antibody according to any one of Aspects 63 - 131, wherein at least eleven of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0391] Aspect 133: The isolated monoclonal antibody according to any one of Aspects 63 - 132, wherein at least twelve of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0392] Aspect 134: The isolated monoclonal antibody according to any one of Aspects 63 - 133, wherein at least thirteen of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0393] Aspect 135: The isolated monoclonal antibody according to any one of Aspects 63 - 134, wherein at least fourteen of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 form an epitope on the extracellular domain of CD122.

[0394] Aspect 136: The isolated monoclonal antibody according to any one of aspects 63 - 135, wherein at least fifteen of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 form an epitope on the extracellular domain of CD122.

[0395] Aspect 137: The isolated monoclonal antibody according to any one of aspects 63 - 136, wherein at least sixteen of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 form an epitope on the extracellular domain of CD122.

[0396] Aspect 138: The isolated monoclonal antibody according to any one of aspects 63 - 137, wherein at least seventeen of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 form an epitope on the extracellular domain of CD122.

[0397] Aspect 139: The isolated monoclonal antibody according to any one of aspects 63 - 138, wherein at least eighteen of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 form an epitope on the extracellular domain of CD122.

[0398] Aspect 140: The isolated monoclonal antibody according to any one of aspects 63 - 139, wherein at least nineteen of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 form an epitope on the extracellular domain of CD122.

[0399] Aspect 141: The isolated monoclonal antibody according to any one of aspects 63 - 140, wherein at least twenty of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 constitute an epitope on the extracellular domain of CD122.

[0400] Aspect 142: The isolated monoclonal antibody according to any one of aspects 63 - 141, wherein at least twenty - one of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO:187 constitute an epitope on the extracellular domain of CD122.

[0401] Aspect 143: The isolated monoclonal antibody according to any one of aspects 63 - 142, wherein at least all twenty - two of the residues W39, P40, D41, V76, D77, I78, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 and H139 of SEQ ID NO:187 constitute an epitope on the extracellular domain of CD122.

[0402] Aspect 144: The isolated monoclonal antibody according to any one of aspects 122 - 143, wherein the epitope is a functional epitope.

[0403] Aspect 145: The isolated monoclonal antibody according to any one of aspects 122 - 143, wherein the epitope is a structural epitope.

[0404] Aspect 146: The isolated monoclonal antibody according to any one of aspects 122 - 145, wherein the epitope is an epitope on the native CD122 protein.

[0405] Aspect 147: The isolated monoclonal antibody according to any one of aspects 63 - 145, wherein the isolated monoclonal antibody inhibits:

[0406] i) The binding of IL2 to the high - affinity IL - αβγ receptor comprising CD122, CD132 and CD25; or

[0407] ii) the binding of IL15 (presented in a manner that binds to IL15Rα in trans) to the intermediate affinity IL-βγ receptor comprising CD122 and CD132; or

[0408] iii) the binding of IL15 to the high affinity IL-αβγ receptor comprising CD122, CD132 and IL15Rα.

Claims

1. An anti-CD122 antibody comprising i) a heavy chain comprising a variable heavy chain (VH) domain and ii) a light chain comprising a variable light chain (VL) domain, wherein the VH domain comprises: an HCDR1 sequence comprising a sequence selected from SEQ ID NOs: 1-11, an HCDR2 sequence comprising a sequence selected from SEQ ID NOs: 12-23, and an HCDR3 sequence comprising a sequence selected from SEQ ID NOs: 24-36, and the VL domain comprises: an LCDR1 sequence comprising a sequence selected from SEQ ID NOs: 37-47, an LCDR2 sequence comprising a sequence selected from SEQ ID NOs: 48-55, and an LCDR3 sequence comprising a sequence selected from SEQ ID NOs: 56-67.

2. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO: 1, the HCDR2 sequence comprises SEQ ID NO: 12, the HCDR3 sequence comprises SEQ ID NO: 24, the LCDR1 sequence comprises SEQ ID NO: 37, the LCDR2 sequence comprises SEQ ID NO: 48, and the LCDR3 sequence comprises SEQ ID NO:

56.

3. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO: 2, the HCDR2 sequence comprises SEQ ID NO: 13, the HCDR3 sequence comprises SEQ ID NO: 25, the LCDR1 sequence comprises SEQ ID NO: 38, the LCDR2 sequence comprises SEQ ID NO: 49, and the LCDR3 sequence comprises SEQ ID NO:

57.

4. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO: 3, the HCDR2 sequence comprises SEQ ID NO: 14, the HCDR3 sequence comprises SEQ ID NO: 26, the LCDR1 sequence comprises SEQ ID NO: 39, the LCDR2 sequence comprises SEQ ID NO: 50, and the LCDR3 sequence comprises SEQ ID NO:

58.

5. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO: 4, the HCDR2 sequence comprises SEQ ID NO: 15, the HCDR3 sequence comprises SEQ ID NO: 27, the LCDR1 sequence comprises SEQ ID NO: 40, the LCDR2 sequence comprises SEQ ID NO: 51, and the LCDR3 sequence comprises SEQ ID NO:

59.

6. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:5, the HCDR2 sequence comprises SEQ ID NO:16, the HCDR3 sequence comprises SEQ ID NO:28, the LCDR1 sequence comprises SEQ ID NO:41, the LCDR2 sequence comprises SEQ ID NO:50, and the LCDR3 sequence comprises SEQ ID NO:

60.

7. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:6, the HCDR2 sequence comprises SEQ ID NO:17, the HCDR3 sequence comprises SEQ ID NO:29, the LCDR1 sequence comprises SEQ ID NO:42, the LCDR2 sequence comprises SEQ ID NO:52, and the LCDR3 sequence comprises SEQ ID NO:

61.

8. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:7, the HCDR2 sequence comprises SEQ ID NO:18, the HCDR3 sequence comprises SEQ ID NO:30, the LCDR1 sequence comprises SEQ ID NO:43, the LCDR2 sequence comprises SEQ ID NO:50, and the LCDR3 sequence comprises SEQ ID NO:

62.

9. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:8, the HCDR2 sequence comprises SEQ ID NO:19, the HCDR3 sequence comprises SEQ ID NO:31, the LCDR1 sequence comprises SEQ ID NO:44, the LCDR2 sequence comprises SEQ ID NO:50, and the LCDR3 sequence comprises SEQ ID NO:

63.

10. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:9, the HCDR2 sequence comprises SEQ ID NO:20, the HCDR3 sequence comprises SEQ ID NO:32, the LCDR1 sequence comprises SEQ ID NO:45, the LCDR2 sequence comprises SEQ ID NO:53, and the LCDR3 sequence comprises SEQ ID NO:

64.

11. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:1, the HCDR2 sequence comprises SEQ ID NO:21, the HCDR3 sequence comprises SEQ ID NO:33, the LCDR1 sequence comprises SEQ ID NO:37, the LCDR2 sequence comprises SEQ ID NO:48, and the LCDR3 sequence comprises SEQ ID NO:

65.

12. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:1, the HCDR2 sequence comprises SEQ ID NO:21, the HCDR3 sequence comprises SEQ ID NO:34, the LCDR1 sequence comprises SEQ ID NO:37, the LCDR2 sequence comprises SEQ ID NO:48, and the LCDR3 sequence comprises SEQ ID NO:

65.

13. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:10, the HCDR2 sequence comprises SEQ ID NO:22, the HCDR3 sequence comprises SEQ ID NO:35, the LCDR1 sequence comprises SEQ ID NO:46, the LCDR2 sequence comprises SEQ ID NO:54, and the LCDR3 sequence comprises SEQ ID NO:

66.

14. The anti-CD122 antibody according to claim 1, wherein the HCDR1 sequence comprises SEQ ID NO:11, the HCDR2 sequence comprises SEQ ID NO:23, the HCDR3 sequence comprises SEQ ID NO:36, the LCDR1 sequence comprises SEQ ID NO:47, the LCDR2 sequence comprises SEQ ID NO:55, and the LCDR3 sequence comprises SEQ ID NO:

67.

15. The anti-CD122 antibody according to claim 1, wherein the VH domain has at least 80%, at least 85%, at least 90% or at least 95% sequence identity with a sequence selected from SEQ ID NOs: 82-94.

16. The anti-CD122 antibody according to claim 1, wherein the VL domain has at least 80%, at least 85%, at least 90% or at least 95% sequence identity with a sequence selected from SEQ ID NOs: 95-107.

17. The anti-CD122 antibody according to claim 1, wherein the VH domain is encoded by a nucleic acid having at least 80%, at least 85%, at least 90% or at least 95% sequence identity with a sequence selected from SEQ ID NOs: 108-120.

18. The anti-CD122 antibody according to claim 1, wherein the VL domain is encoded by a nucleic acid having at least 80%, at least 85%, at least 90% or at least 95% sequence identity with a sequence selected from SEQ ID NOs: 121-133.

19. The anti-CD122 antibody according to claim 1, wherein the heavy chain has at least 80%, at least 85%, at least 90% or at least 95% sequence identity with a sequence selected from SEQ ID NOs: 134-141.

20. The anti-CD122 antibody according to claim 1, wherein the light chain has at least 80%, at least 85%, at least 90% or at least 95% sequence identity with a sequence selected from SEQ ID NOs: 142-145.

21. The anti-CD122 antibody according to claim 1, wherein the heavy chain is encoded by a nucleic acid having at least 80%, at least 85%, at least 90% or at least 95% sequence identity with a sequence selected from SEQ ID NOs: 146-153.

22. The anti-CD122 antibody according to claim 1, wherein the light chain is encoded by a nucleic acid having at least 80%, at least 85%, at least 90% or at least 95% sequence identity with a sequence selected from SEQ ID NOs: 154-157.

23. The anti-CD122 antibody according to claim 1, wherein the heavy chain comprises a leader sequence at the N-terminus of the heavy chain polypeptide.

24. The anti-CD122 antibody according to claim 23, wherein the leader sequence comprises SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160 or SEQ ID NO:

161.

25. The anti-CD122 antibody according to claim 1, wherein the light chain comprises a leader sequence at the N-terminus of the light chain polypeptide.

26. The anti-CD122 antibody according to claim 25, wherein the leader sequence comprises SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160 or SEQ ID NO:

161.

27. The anti-CD122 antibody according to any one of claims 1-26, wherein the anti-CD122 antibody is a humanized antibody or an antigen-binding fragment thereof.

28. The anti-CD122 antibody according to any one of claims 1-27, wherein the anti-CD122 antibody is a chimeric antibody or an antigen-binding fragment thereof.

29. The anti-CD122 antibody according to any one of claims 1-28, wherein the anti-CD122 antibody comprises IgG-scFv, nanobody, mini-antibody, minibody, scFv-CH3 KIH, Fab-scFv-Fc KIH, Fab-scFv, scFv-CH-CL-scFv, Fab’, F(ab’)2, F(ab’)3, F(ab’)2-scFv2, scFv, scFv-KIH, Fab-scFv-Fc or intracellular antibody.

30. The anti-CD122 antibody according to any one of claims 1-29, wherein the anti-CD122 antibody is an IgG1 antibody.

31. The anti-CD122 antibody according to any one of claims 1-30, wherein the anti-CD122 antibody is an IgG2 antibody.

32. The anti-CD122 antibody according to any one of claims 1-31, wherein the anti-CD122 antibody is an IgG4 antibody.

33. The anti-CD122 antibody according to any one of claims 1-32, wherein the light chain is a κ chain.

34. The anti-CD122 antibody according to any one of claims 1-33, wherein the binding affinity of the anti-CD122 antibody for human CD122 is from about 100 pM to about 3 nM.

35. A pharmaceutical composition comprising the anti-CD122 antibody according to any one of claims 1-34 and a pharmaceutically acceptable excipient.

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