Anti-CD122 antibodies and uses thereof

Abstract

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

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 377,847, filed September 30, 2022, which is incorporated herein by reference in its entirety. [Background technology]

[0002] Interleukin receptors are involved in mediating many cellular responses, including T cell immune responses. Interleukin 2 receptors exist in three forms based on their ability to bind interleukin 2 (IL2). The low-affinity form of the receptor is a monomer of the α receptor subunit (IL2RA, also known as CD25) and does not participate in signal transduction. The intermediate-affinity receptor form is composed of an α / β subunit heterodimer, while the high-affinity receptor form is composed of an α / β / γ subunit heterotrimer. Both the intermediate-affinity and high-affinity forms of the receptor participate in receptor-mediated endocytosis and the IL2 transduction pathway. The IL2RB gene encodes the β subunit of the interleukin 2 receptor. The protein encoded by the IL2RB gene (IL2RB) is a type I transmembrane protein whose amino (N)-terminal domain is extracellular relative to the cell membrane in its mature form. IL2RB is also known as IL15RB or CD122. The CD122 protein is primarily expressed in the hematopoietic system. The gamma subunit of the IL2 receptor is IL2RG (also known as CD132).

[0003] In addition to its function as a β receptor subunit in IL2-mediated signal transduction, CD122 also transduces signals from the cytokine interleukin-15 (IL15). Unlike the α subunit of the IL2 receptor, the α subunit of the IL15 receptor (IL15RA or IL15Rα) can bind to its ligand (IL15) with high affinity, independently of other receptor subunits. IL15RA can form an α / β subunit heterodimer with CD122 for signal transduction. IL15RA can also form an α / β / γ subunit heterotrimer with CD122 and CD132 for signal transduction. Through these various interleukin receptor complexes, CD122 is involved in the transduction of signals from the cytokines IL2 and IL15.

[0004] Therefore, anti-CD122 antibodies can be used for diagnostic and therapeutic purposes for diseases or conditions associated with abundant CD122 expression. Therefore, there is a need to develop improved anti-CD122 antibodies. Summary of the Invention

[0005] In certain aspects, disclosed herein are anti-CD122 antibodies and pharmaceutical compositions comprising anti-CD122 antibodies. In some embodiments, anti-CD122 antibodies and pharmaceutical compositions comprising anti-CD122 antibodies can be used to target CD122-expressing tissues and cells.

[0006] Described herein in some embodiments is an anti-CD122 antibody comprising: 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 an HCDR1 sequence comprising SEQ ID NO: 1, an HCDR2 sequence comprising SEQ ID NO: 12, an HCDR3 sequence comprising SEQ ID NO: 24, 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 an HCDR1 sequence comprising SEQ ID NO:2, an HCDR2 sequence comprising SEQ ID NO:13, an HCDR3 sequence comprising SEQ ID NO:25, 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 an HCDR1 sequence comprising SEQ ID NO:3, an HCDR2 sequence comprising SEQ ID NO:14, an HCDR3 sequence comprising SEQ ID NO:26, 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 an HCDR1 sequence comprising SEQ ID NO:4, an HCDR2 sequence comprising SEQ ID NO:15, an HCDR3 sequence comprising SEQ ID NO:27, an LCDR1 sequence comprising SEQ ID NO:40, an LCDR2 sequence comprising SEQ ID NO:51, and an LCDR3 comprising SEQ ID NO:59. In some embodiments, the anti-CD122 antibody comprises an HCDR1 sequence comprising SEQ ID NO: 5, an HCDR2 sequence comprising SEQ ID NO: 16, an HCDR3 sequence comprising SEQ ID NO: 28, 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 an HCDR1 sequence comprising SEQ ID NO: 6, an HCDR2 sequence comprising SEQ ID NO: 17, an HCDR3 sequence comprising SEQ ID NO: 29, 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 an HCDR1 sequence comprising SEQ ID NO: 7, an HCDR2 sequence comprising SEQ ID NO: 18, an HCDR3 sequence comprising SEQ ID NO: 30, 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 an HCDR1 sequence comprising SEQ ID NO: 8, an HCDR2 sequence comprising SEQ ID NO: 19, an HCDR3 sequence comprising SEQ ID NO: 31, 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 an HCDR1 sequence comprising SEQ ID NO:9, an HCDR2 sequence comprising SEQ ID NO:20, an HCDR3 sequence comprising SEQ ID NO:32, 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 anti-CD122 antibody comprises an HCDR1 sequence comprising SEQ ID NO:1, an HCDR2 sequence comprising SEQ ID NO:21, an HCDR3 sequence comprising SEQ ID NO:33, 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 an HCDR1 sequence comprising SEQ ID NO:1, an HCDR2 sequence comprising SEQ ID NO:21, an HCDR3 sequence comprising SEQ ID NO:34, 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 an HCDR1 sequence comprising SEQ ID NO: 10, an HCDR2 sequence comprising SEQ ID NO: 22, an HCDR3 sequence comprising SEQ ID NO: 35, 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 an HCDR1 sequence comprising SEQ ID NO: 11, an HCDR2 sequence comprising SEQ ID NO: 23, an HCDR3 sequence comprising SEQ ID NO: 36, 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. In some embodiments, the anti-CD122 antibody comprises a VH domain comprising 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 comprising 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 comprising 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 comprising 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 comprising 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 comprising 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 comprising 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 comprising 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 a heavy chain comprising a leader sequence at the N-terminus of the heavy chain polypeptide. In some embodiments, the anti-CD122 antibody comprises a 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 a light chain comprising a leader sequence at the N-terminus of the light chain polypeptide. In some embodiments, the anti-CD122 antibody comprises a 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 antigen-binding fragment thereof. In some embodiments, the anti-CD122 antibody is a chimeric antibody or antigen-binding fragment thereof. In some embodiments, the anti-CD122 antibody comprises an IgG-scFv, a nanobody, a miniantibody, a minibody, an scFv-CH3 KIH, a Fab-scFv-Fc KIH, a Fab-scFv, a scFv-CH-CL-scFv, a Fab', a F(ab')2, a F(ab')3, a F(ab')2-scFv2, a scFv, a scFv-KIH, a Fab-scFv-Fc, or an intrabody. 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, and the light chain is a κ chain. In some embodiments, the anti-CD122 antibody has a binding affinity for human CD122 of about 100 pM to about 3 nM. In some embodiments, the pharmaceutical compositions described herein comprise an anti-CD122 antibody described herein and a pharmaceutically acceptable excipient.

[0007] Incorporation by Reference All publications, patents, and patent applications mentioned herein are herein incorporated 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. In the event that the publications and patents or patent applications incorporated by reference conflict with the disclosure contained herein, the present specification is intended to supersede and / or supersede any such conflicting material. [Brief explanation of the drawings]

[0008] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings. [Figure 1] FIG. 1 shows sensorgram plots of anti-CD122 antibodies G1 (top) and G2 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 2] FIG. 2 shows sensorgram plots of anti-CD122 antibodies G3 (top) and G4 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 3] FIG. 3 shows sensorgram plots of anti-CD122 antibodies G5 (top) and G6 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 4] FIG. 4 shows sensorgram plots of anti-CD122 antibodies G7 (top) and G8 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 5] FIG. 5 shows sensorgram plots of anti-CD122 antibodies G9 (second batch) (top) and G10 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 6]FIG. 6 shows sensorgram plots of anti-CD122 antibodies G11 (top) and G12 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 7] FIG. 7 shows sensorgram plots of anti-CD122 antibodies G13 (top) and G14 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 8] FIG. 8 shows sensorgram plots of anti-CD122 antibodies G15 (top) and G16 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 9] FIG. 9 shows sensorgram plots of anti-CD122 antibodies G17 (top) and G18 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 10] FIG. 10 shows sensorgram plots of anti-CD122 antibodies G19 (top) and G20 (bottom) to measure the binding and dissociation properties to different concentrations of huCD122. [Figure 11] Figure 11 shows graphs and IC50 calculations for anti-CD122 antibody inhibition of IL2 (top graph) and IL15 (bottom graph) signaling in cell lines expressing intermediate affinity IL-βγ receptors using luciferase-expressing reporter assays under IL2 or IL15 stimulation. Results are shown for Antibody 1, Antibody 2, and a commercially available anti-CD122 antibody. [Figure 12] FIG. 12 shows a graph of anti-CD122 antibody (Antibody 1 and Antibody 2) inhibition of IL2 signaling in cell lines expressing high affinity IL-αβγ receptors using a reporter assay. [Figure 13] FIG. 13 shows a summary of the IL2RB epitope mapping results from the analysis of the humanized anti-CD122 Mabs described herein, as detailed in the epitope mapping experiments in Example 5. [Figure 14]Figure 14 shows a heat map of modification changes in bound humanized anti-CD122 Mab versus unbound IL2RB, as detailed in the epitope mapping experiment in Example 5. Significant changes (p<0.05) are indicated by the shaded boxes in the t-test column. [Figure 15] Figure 15 shows a representation of the crystal structure of interleukin-2 receptor subunit β (IL2RB) and IL2 with candidate epitope regions. Amino acid residues with significant changes in solvent accessibility are indicated by a star (epitope region) and by arrows pointing to residues with conformational changes. DETAILED DESCRIPTION OF THE INVENTION

[0009] Immune cell responses can be context-dependent and influenced by signals from their environment via various receptor-ligand interactions. For example, these signals can amplify and modify T cell receptor (TCR) signals received upon antigen stimulation in resting naive or memory T cells, regulate T cell proliferation and differentiation in recently activated T cells, or control effector function in specific somatic environments. IL2 and IL15 share similar and contrasting roles in regulating T cell function. As a non-limiting example, both IL2 and IL15 are involved in T cell differentiation. IL2 can promote the differentiation of immature T cells into regulatory T cells, thereby suppressing other T cells that may attack normal, healthy cells in the body. IL2 signaling is involved in peripheral immune tolerance through the elimination of autoreactive T cells via the activation-induced cell death (AICD) pathway. IL2 can also promote the differentiation of immature T cells into either effector or memory T cells when early T cells are stimulated by antigen. IL2 has also been demonstrated to enhance the activity of both 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 inducing anti-apoptotic effects. IL15 can stimulate the persistence of memory CD8+ T cells involved in the elimination of invading pathogens, thereby protecting subjects from infection.

[0010] IL2 and IL15 have distinct means for initiating signal transduction through various IL receptors. IL2 is secreted and can bind to heterodimeric and heterotrimeric receptor complexes, both of which contain CD122 on the surface of activated cells. IL15 is primarily membrane-bound and induces signal transduction in the context of cell-cell contact at the immunological synapse. IL15RA transfects membrane-bound IL15 to adjacent CD8+ T cells and NK cells. Despite these differences in the mechanisms of initiation of ligand-mediated signal transduction, once activated, the IL2 and IL15 receptor complexes activate shared molecular pathways, including the JAK1 / JAK3 / STAT5, PI3K, and MAPK signaling pathways. Activation of these pathways can regulate gene transcription and modulate immune cell apoptosis, proliferation, or differentiation. CD122, which contains both the IL2 and IL15 receptors, plays an important role in all of these functions.

[0011] In certain aspects, disclosed herein are anti-CD122 antibodies and pharmaceutical compositions comprising anti-CD122 antibodies. Also disclosed herein, in some embodiments, are methods used to target CD122-expressing tissues and cells using the anti-CD122 antibodies described herein.

[0012] Anti-CD122 antibody Antibodies that bind to CD122 are provided herein. In some examples, the antibodies that bind to CD122 are monoclonal antibodies, and in particular embodiments, anti-CD122 antibodies are disclosed herein. In some examples, the anti-CD122 antibodies specifically bind to mammalian CD122. In some examples, the anti-CD122 antibodies specifically bind to human CD122. In some examples, the anti-CD122 antibodies specifically bind to the extracellular portion of CD122. In some examples, the anti-CD122 antibodies specifically bind to the extracellular portion of human CD122. In some examples, the anti-CD122 antibodies are made with chimeric amino acid sequences, some of which are mouse-derived and some of which are human-derived. In some examples, the anti-CD122 antibodies are made with complementarity-determining regions (CDRs) incorporated into an antibody scaffold. In some examples, the anti-CD122 antibodies are made with complementarity-determining regions (CDRs) incorporated into a human antibody variable region framework. In some examples, the human antibody variable region framework is sequence-optimized to retain CD122 affinity with the grafted murine CDR sequences. In some examples, the anti-CD122 antibody is a humanized antibody. In some examples, the anti-CD122 antibody is a human antibody.

[0013] 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.

[0014] In some embodiments, the VH region of the anti-CD122 antibody comprises HCDR1, HCDR2, and HCDR3 sequences selected from Table 1.

[0015] [Table 1]

[0016] 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.

[0017] In some embodiments, the VL region of the anti-CD122 antibody comprises LCDR1, LCDR2, and LCDR3 sequences selected from Table 2.

[0018] [Table 2]

[0019] 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.

[0020] 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 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 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 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 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 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 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 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 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 ID NO:20, and an HCDR3 sequence comprising SEQ ID NO:32, and 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 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 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 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 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 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.

[0021] In some embodiments, an 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 for each anti-CD122 antibody described herein is listed in Table 3. The series of CDR sequences are designated E1-E13.

[0022] [Table 3]

[0023] In some embodiments, the anti-CD122 antibody comprises a framework for grafting CDRs from another animal species. In some embodiments, CDRs from a mammalian antibody are grafted onto human framework sequences. In some embodiments, CDRs from a mouse antibody are grafted onto human framework sequences. In some embodiments, the human framework sequences form part of the VH region of the antibody. In some embodiments, sequences from HCDR1, HCDR2, and HCDR3 are grafted onto human framework sequences.

[0024] 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 examples, 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 framework to form the heavy chain sequence. In some embodiments, the IgG framework is an IgG1 framework, an IgG2 framework, an IgG3 framework, or an IgG4 framework. In some embodiments, the IgG framework comprises a human IgG heavy chain framework sequence. In some embodiments, a human IgG heavy chain framework sequence has anti-CD122 HCDR sequences grafted onto it. In some embodiments, the human IgG heavy chain framework sequence onto which the anti-CD122 HCDR sequences have been grafted is analyzed and modeled relative to the monoclonal antibody 3D structure to identify critical amino acid positions that support CDR loop structure. In some embodiments, critical amino acid positions are identified in the human IgG heavy chain framework sequence that, when grafted back onto the murine framework sequence from the murine anti-CD122 antibody, restores affinity for human CD122 in the context of a humanized antibody using the human IgG heavy chain framework sequence onto which the murine anti-CD122 CDR sequences have been grafted. In some embodiments, those critical amino acid positions are mutated in the human IgG heavy chain framework sequence back to the murine sequence, referred to as backmutations.In some embodiments, human IgG heavy chain framework sequences into which murine anti-CD122 CDR sequences have been grafted and back mutations incorporated into the framework sequences are used in a human IgG scaffold to generate a humanized IgG heavy chain sequence. In some embodiments, a humanized IgG heavy chain sequence is used to generate an anti-CD122 antibody. Table 4 lists the human IgG heavy chain framework sequences used herein to graft anti-CD122 HCDR sequences. Table 4 also lists the human IgG heavy chain framework sequences used herein to graft anti-CD122 HCDR sequences with back mutations incorporated into the framework to potentially restore lost affinity for the human CD122 ligand. Table 4 also lists the murine parent heavy chain variable framework sequences used to graft murine anti-CD122 heavy chain variable regions into a human IgG scaffold to generate an anti-CD122 chimeric heavy chain. In the disclosed sequences in Table 4, the X residue is the CDR insertion site. In the disclosed sequences in Table 4, (X). n=1-25refers to the CDR1, CDR2, or CDR3 sequence, X refers to the CDR amino acid sequence, and n is equal to the number of amino acid residues in the CDR sequence. In Table 4, the CDR1, CDR2, or CDR3 sequence is an HCDR sequence. The framework sequences disclosed in Table 4 are designated F1 through F7. In some embodiments, F1 is a human IgG heavy chain framework sequence used herein to graft anti-CD122 HCDR sequences. In some embodiments, F2 is a human IgG heavy chain framework sequence used herein to graft anti-CD122 HCDR sequences. In some embodiments, F3 is a human IgG heavy chain framework sequence used herein to graft anti-CD122 HCDR sequences. In some embodiments, F4 is a human IgG heavy chain framework sequence used herein to graft anti-CD122 HCDR sequences with back mutations incorporated into the framework to potentially restore lost affinity for the human CD122 ligand. In some embodiments, F5 is a human IgG heavy chain framework sequence used herein to graft anti-CD122 HCDR sequences with back mutations incorporated into the framework to potentially restore lost affinity for human CD122 ligand. In some embodiments, F6 is a human IgG heavy chain framework sequence used herein to graft anti-CD122 HCDR sequences with back mutations incorporated into the framework to potentially restore lost affinity for human CD122 ligand. In some embodiments, F7 is a murine parent heavy chain variable framework sequence used to create an anti-CD122 chimeric heavy chain by incorporating a murine anti-CD122 heavy chain variable region into a human IgG scaffold to potentially restore lost affinity for human CD122 ligand. In some embodiments, an HCDR sequence from one of series E1-E13 is grafted into F1 to create a heavy chain variable domain sequence. In some embodiments, an HCDR sequence from one of series E1-E13 is grafted into F2 to create a heavy chain variable domain sequence.In some embodiments, an HCDR sequence from one of series E1-E13 is grafted into F3 to create a heavy chain variable domain sequence. In some embodiments, an HCDR sequence from one of series E1-E13 is grafted into F4 to create a heavy chain variable domain sequence. In some embodiments, an HCDR sequence from one of series E1-E13 is grafted into F5 to create a heavy chain variable domain sequence. In some embodiments, an HCDR sequence from one of series E1-E13 is grafted into F6 to create a heavy chain variable domain sequence. In some embodiments, an HCDR sequence from one of series E1-E13 is grafted into F7 to create a heavy chain variable domain sequence.

[0025] [Table 4]

[0026] In some embodiments, the anti-CD122 antibody comprises a framework for grafting CDRs from another animal species. In some embodiments, CDRs from a mammalian antibody are grafted onto human framework sequences. In some embodiments, CDRs from a mouse antibody are grafted onto human framework sequences. In some embodiments, the human framework sequences form part of the VL region of the antibody. In some embodiments, sequences from LCDR1, LCDR2, and LCDR3 are grafted onto human framework sequences.

[0027] In some embodiments, the anti-CD122 antibodies described herein comprise a lambda or kappa framework. In some examples, the anti-CD122 antibodies comprise a kappa framework onto which LCDR1, LCDR2, and LCDR3 sequences have been grafted. In some examples, the anti-CD122 antibodies comprise a kappa framework onto which LCDR1, LCDR2, and LCDR3 sequences have been grafted. In some embodiments, the kappa framework forms part of a light chain. In some embodiments, the kappa framework forming part of a light chain is paired with a heavy chain described herein. In some embodiments, the kappa framework is a human kappa light chain framework. In some embodiments, the human kappa light chain framework comprises a human kappa light chain framework sequence. In some embodiments, the human kappa light chain framework sequence has an anti-CD122 LCDR sequence grafted onto it. In some embodiments, the human kappa light chain framework sequence onto which the anti-CD122 LCDR sequence has been grafted is analyzed and modeled relative to the monoclonal antibody 3D structure to identify important amino acid positions that support the CDR loop structure. In some embodiments, key amino acid positions are identified in the human κ light chain framework sequence that, when reverted from a mouse anti-CD122 antibody to the mouse framework sequence, restores affinity for human CD122 in the context of a humanized antibody using a human κ light chain framework sequence grafted with mouse anti-CD122 CDR sequences. In some embodiments, these key amino acid positions are mutated back to the mouse sequence in the human κ light chain framework sequence, referred to as back mutations. In some embodiments, the human κ light chain framework sequence grafted with mouse anti-CD122 CDR sequences and the back mutations incorporated into the framework sequence are used in a human light chain framework to create a humanized light chain sequence. In some embodiments, the humanized κ light chain sequence is used to create an anti-CD122 antibody. Table 5 lists the human κ light chain framework sequences used herein to graft anti-CD122 LCDR sequences.Table 5 also lists the human kappa light chain framework sequences used herein to graft anti-CD122 LCDR sequences with back mutations incorporated into the framework to potentially restore lost affinity for the human CD122 ligand. Table 5 also lists the murine parent light chain variable framework sequences used to incorporate the murine anti-CD122 light chain variable region into a human light chain framework to create an anti-CD122 chimeric light chain. In the disclosed sequences of Table 5, the X residue is the CDR insertion site. In the disclosed sequences of Table 5, (X). n=1-25refers to the CDR1, CDR2, or CDR3 sequence, X refers to the CDR amino acid sequence, and n is equal to 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 designated F8 through F14. In some embodiments, F8 is a human kappa light chain framework sequence used herein to graft an anti-CD122 LCDR sequence. In some embodiments, F9 is a human kappa light chain framework sequence used herein to graft an anti-CD122 LCDR sequence. In some embodiments, F10 is a human kappa light chain framework sequence used herein to graft an anti-CD122 LCDR sequence. In some embodiments, F11 is a human kappa light chain framework sequence used herein to graft an anti-CD122 LCDR sequence with back mutations incorporated into the framework to potentially restore lost affinity for the human CD122 ligand. In some embodiments, F12 is a human kappa light chain framework sequence used herein to graft an anti-CD122 LCDR sequence with back mutations incorporated into the framework to potentially restore lost affinity for human CD122 ligand. In some embodiments, F13 is a human IgG heavy chain framework sequence used herein to graft an anti-CD122 LCDR sequence with back mutations incorporated into the framework to potentially restore lost affinity for human CD122 ligand. In some embodiments, F14 is a murine parent light chain variable framework sequence used to incorporate a murine anti-CD122 light chain variable region into a human light chain scaffold to create an anti-CD122 chimeric light chain into the framework to potentially restore lost affinity for human CD122 ligand. In some embodiments, an LCDR sequence from one of series E1-E13 is grafted into F8 to create a light chain variable domain sequence. In some embodiments, an LCDR sequence from one of series E1-E13 is grafted into F9 to create a light chain variable domain sequence.In some embodiments, an LCDR sequence from one of lineages E1-E13 is grafted into F10 to create a light chain variable domain sequence. In some embodiments, an LCDR sequence from one of lineages E1-E13 is grafted into F11 to create a light chain variable domain sequence. In some embodiments, an LCDR sequence from one of lineages E1-E13 is grafted into F12 to create a light chain variable domain sequence. In some embodiments, an LCDR sequence from one of lineages E1-E13 is grafted into F13 to create a light chain variable domain sequence. In some embodiments, an LCDR sequence from one of lineages E1-E13 is grafted into F14 to create a light chain variable domain sequence.

[0028] [Table 5]

[0029] In some embodiments, the anti-CD122 antibody comprises a VH region and a VL region, wherein the sequence of the VH region comprises about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NOs: 82-94, and the sequence of the VL region comprises about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NOs: 95-107. In some embodiments, the anti-CD122 antibody comprises a VH domain comprising at least 80% sequence identity to a sequence selected from SEQ ID NOs: 82-94. In some embodiments, the anti-CD122 antibody comprises a VH domain comprising at least 85% sequence identity to a sequence selected from SEQ ID NOs: 82-94. In some embodiments, the anti-CD122 antibody comprises a VH domain comprising at least 90% sequence identity to a sequence selected from SEQ ID NOs: 82-94. In some embodiments, an anti-CD122 antibody comprises a VH domain comprising at least 95% sequence identity to a sequence selected from SEQ ID NOs: 82-94. In some embodiments, an anti-CD122 antibody comprises a VL domain comprising at least 80% sequence identity to a sequence selected from SEQ ID NOs: 95-107. In some embodiments, an anti-CD122 antibody comprises a VL domain comprising at least 85% sequence identity to a sequence selected from SEQ ID NOs: 95-107. In some embodiments, an anti-CD122 antibody comprises a VL domain comprising at least 90% sequence identity to a sequence selected from SEQ ID NOs: 95-107. In some embodiments, an anti-CD122 antibody comprises a VL domain comprising at least 95% sequence identity to 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). 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.

[0030] [Table 6]

[0031] [Table 7]

[0032] In some embodiments, an anti-CD122 antibody comprises a VH region having an HCDR sequence from a CDR series incorporated into a heavy chain framework sequence. In some embodiments, an anti-CD122 antibody comprises a VH region comprising an HCDR sequence from series E7 incorporated into framework sequence F1. In some embodiments, an anti-CD122 antibody comprises a VH region comprising an HCDR sequence from series E7 incorporated into framework sequence F2. In some embodiments, an anti-CD122 antibody comprises a VH region comprising an HCDR sequence from series E7 incorporated into framework sequence F3. In some embodiments, an anti-CD122 antibody comprises a VH region comprising an HCDR sequence from series E7 incorporated into framework sequence F4. In some embodiments, an anti-CD122 antibody comprises a VH region comprising an HCDR sequence from series E7 incorporated into framework sequence F5. In some embodiments, an anti-CD122 antibody comprises a VH region comprising an HCDR sequence from series E7 incorporated into framework sequence F6. In some embodiments, the anti-CD122 antibody comprises a VH region comprising HCDR sequences from series E7 integrated into framework sequence F7.

[0033] In some embodiments, an anti-CD122 antibody comprises a VL region having an LCDR sequence from a CDR series incorporated into a light chain framework sequence. In some embodiments, an anti-CD122 antibody comprises a VL region comprising an LCDR sequence from lineage E7 incorporated into framework sequence F8. In some embodiments, an anti-CD122 antibody comprises a VL region comprising an LCDR sequence from lineage E7 incorporated into framework sequence F9. In some embodiments, an anti-CD122 antibody comprises a VL region comprising an LCDR sequence from lineage E7 incorporated into framework sequence F10. In some embodiments, an anti-CD122 antibody comprises a VL region comprising an LCDR sequence from lineage E7 incorporated into framework sequence F11. In some embodiments, an anti-CD122 antibody comprises a VL region comprising an LCDR sequence from lineage E7 incorporated into framework sequence F12. In some embodiments, an anti-CD122 antibody comprises a VL region comprising an LCDR sequence from lineage E7 incorporated into framework sequence F13. In some embodiments, the anti-CD122 antibody comprises a VL region comprising an LCDR sequence from lineage E7 integrated into framework sequence F14.

[0034] 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.

[0035] In some embodiments, an anti-CD122 antibody comprises a VH domain encoded by a nucleic acid having at least 80% sequence identity to a sequence selected from SEQ ID NOs: 108-120. In some embodiments, an anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising at least 85% sequence identity to a sequence selected from SEQ ID NOs: 108-120. In some embodiments, an anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising at least 90% sequence identity to a sequence selected from SEQ ID NOs: 108-120. In some embodiments, an anti-CD122 antibody comprises a VH domain encoded by a nucleic acid comprising at least 95% sequence identity to a sequence selected from SEQ ID NOs: 108-120. In some embodiments, an anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising at least 80% sequence identity to a sequence selected from SEQ ID NOs: 121-133. In some embodiments, an anti-CD122 antibody comprises a VL domain encoded by a nucleic acid comprising at least 85% sequence identity to 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 comprising at least 90% sequence identity to 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 comprising at least 95% sequence identity to a sequence selected from SEQ ID NOs: 121-133.

[0036] 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, 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.

[0037] [Table 8-1]

[0038] [Table 8-2]

[0039] [Table 8-3]

[0040] In some embodiments, the anti-CD122 antibody described herein is a full-length antibody. 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 antigen-binding fragment thereof, a chimeric antibody or antigen-binding fragment thereof, or a monoclonal antibody or 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), Ig NAR, camelid antibody or antigen-binding fragment thereof, or a chemically modified derivative thereof.

[0041] In some cases, the anti-CD122 antibody comprises one or more mutations in a framework region, such as the CH1 domain, CH2 domain, CH3 domain, hinge region, or a combination thereof. In some examples, the one or more mutations are for stabilizing the antibody. In some examples, the one or more mutations are for increasing half-life. In some examples, the one or more mutations are for modulating Fc receptor interaction. In some examples, the one or more mutations are for reducing or eliminating an Fc effector function, such as FcyR, antibody-dependent cell-mediated cytotoxicity (ADCC), or complement-dependent cytotoxicity (CDC). In a further example, the one or more mutations are for modulating glycosylation.

[0042] In some embodiments, the one or more mutations are located in the Fc region.

[0043] In some embodiments, the human IgG constant region is selected from the group consisting of, for example, 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 Modified to alter antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) using amino acid modifications described in Immunol. Nov 25;12:724361; Zhou et al., 2020 MAbs. Jan-Dec;12(1):1814583; Reviewed in Kaneko and Niwa, 2011 Biodrugs,25(1):1-11.

[0044] In some embodiments, the anti-CD122 antibodies described herein are full-length antibodies comprising a heavy chain (HC) and a light chain (LC). In some embodiments, the HC comprises about 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibodies comprise a heavy chain comprising at least 80% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibodies comprise a heavy chain comprising at least 85% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibodies comprise a heavy chain comprising at least 90% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibodies comprise a heavy chain comprising at least 90% sequence identity to SEQ ID NO: 134. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 90% sequence identity to SEQ ID NO: 135. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 90% sequence identity to SEQ ID NO: 136. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 90% sequence identity to SEQ ID NO: 137. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 90% sequence identity to SEQ ID NO: 138. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 90% sequence identity to SEQ ID NO: 139. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 90% sequence identity to SEQ ID NO: 140. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 90% sequence identity to SEQ ID NO: 141. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 95% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 96% sequence identity to a sequence selected from SEQ ID NOs: 134-141.In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 97% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 98% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising at least 99% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the anti-CD122 antibody comprises a heavy chain comprising 100% sequence identity to a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the VH domain of the anti-CD122 antibody comprises 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 to the VH domain found in a sequence selected from SEQ ID NOs: 134-141. In some embodiments, the VH domain of an anti-CD122 antibody comprises at least 90% sequence identity to the VH domain found in SEQ ID NO: 134. In some embodiments, the VH domain of an anti-CD122 antibody comprises at least 90% sequence identity to the VH domain found in SEQ ID NO: 135. In some embodiments, the VH domain of an anti-CD122 antibody comprises at least 90% sequence identity to the VH domain found in SEQ ID NO: 136. In some embodiments, the VH domain of an anti-CD122 antibody comprises at least 90% sequence identity to the VH domain found in SEQ ID NO: 137. In some embodiments, the VH domain of an anti-CD122 antibody comprises at least 90% sequence identity to the VH domain found in SEQ ID NO: 138. In some embodiments, the VH domain of an anti-CD122 antibody comprises at least 90% sequence identity to the VH domain found in SEQ ID NO: 139. In some embodiments, the VH domain of the anti-CD122 antibody comprises at least 90% sequence identity to the VH domain found in SEQ ID NO:140.In some embodiments, the VH domain of an anti-CD122 antibody comprises at least 90% sequence identity to the VH domain found in SEQ ID NO: 141. In some embodiments, the VH domain of an anti-CD122 antibody comprises 100% sequence identity to the VH domain found in SEQ ID NO: 134. In some embodiments, the VH domain of an anti-CD122 antibody comprises 100% sequence identity to the VH domain found in SEQ ID NO: 135. In some embodiments, the VH domain of an anti-CD122 antibody comprises at least 100% sequence identity to the VH domain found in SEQ ID NO: 136. In some embodiments, the VH domain of an anti-CD122 antibody comprises 100% sequence identity to the VH domain found in SEQ ID NO: 137. In some embodiments, the VH domain of an anti-CD122 antibody comprises 100% sequence identity to the VH domain found in SEQ ID NO: 138. In some embodiments, the VH domain of an anti-CD122 antibody comprises 100% sequence identity to the VH domain found in SEQ ID NO: 139. In some embodiments, the VH domain of an anti-CD122 antibody comprises 100% sequence identity to the VH domain found in SEQ ID NO: 140. In some embodiments, the VH domain of an anti-CD122 antibody comprises 100% sequence identity to the VH domain found 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.

[0045] In some embodiments, the anti-CD122 antibodies described herein are full-length antibodies comprising a heavy chain (HC) and a light chain (LC). In some embodiments, the LC comprises 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 antibodies comprise a light chain comprising 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 antibodies comprise a light chain comprising at least 80% sequence identity to a sequence selected from SEQ ID NOs: 142-145. In some embodiments, the anti-CD122 antibodies comprise a light chain comprising 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 comprising 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 comprising at least 90% sequence identity to SEQ ID NO: 142. In some embodiments, the anti-CD122 antibody comprises a light chain comprising at least 90% sequence identity to SEQ ID NO: 143. In some embodiments, the anti-CD122 antibody comprises a light chain comprising at least 90% sequence identity to SEQ ID NO: 144. In some embodiments, the anti-CD122 antibody comprises a light chain comprising at least 90% sequence identity to SEQ ID NO: 145. In some embodiments, the anti-CD122 antibody comprises a light chain comprising 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 comprising 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 comprising 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 comprising 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 comprising 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 comprises 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 to a VL domain found in a sequence selected from SEQ ID NOs: 142-145. In some embodiments, the VL domain of the anti-CD122 antibody comprises at least 90% sequence identity to the VL domain found in SEQ ID NO: 142. In some embodiments, the VL domain of the anti-CD122 antibody comprises at least 90% sequence identity to the VL domain found in SEQ ID NO: 143. In some embodiments, the VL domain of the anti-CD122 antibody comprises at least 90% sequence identity to the VL domain found in SEQ ID NO: 144. In some embodiments, the VL domain of an anti-CD122 antibody comprises at least 90% sequence identity to the VL domain found in SEQ ID NO: 145. In some embodiments, the VL domain of an anti-CD122 antibody comprises 100% sequence identity to the VL domain found in SEQ ID NO: 142. In some embodiments, the VL domain of an anti-CD122 antibody comprises 100% sequence identity to the VL domain found in SEQ ID NO: 143. In some embodiments, the VL domain of an anti-CD122 antibody comprises 100% sequence identity to the VL domain found in SEQ ID NO: 144. In some embodiments, the VL domain of an anti-CD122 antibody comprises 100% sequence identity to the VL domain found 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.

[0046] In some cases of the anti-CD122 antibodies described herein, the heavy chain (HC) comprises a sequence selected from Table 9. In some cases of 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 murine HC variable framework sequences and HCDR sequences is in an IgG1 scaffold and is listed as SEQ ID NO: 134. In some embodiments, the HC having a VH domain with murine HC variable framework sequences and HCDR sequences is in an IgG4 scaffold and is listed as SEQ ID NO: 138. In some embodiments, the LC having a VL domain with murine light chain variable framework sequences and LCDR sequences is in a kappa light chain scaffold and is listed as SEQ ID NO: 142.

[0047] [Table 9-1]

[0048] [Table 9-2]

[0049] [Table 10]

[0050] In some embodiments, the anti-CD122 antibodies described herein are full-length antibodies comprising a heavy chain (HC) and a light chain (LC). In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 134 and a LC comprising SEQ ID NO: 142. In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 135 and a LC comprising SEQ ID NO: 143. In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 135 and a LC comprising SEQ ID NO: 144. In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 135 and a LC comprising SEQ ID NO: 145. In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 136 and a LC comprising SEQ ID NO: 143. In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 136 and a LC comprising SEQ ID NO: 144. In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 136 and a LC comprising SEQ ID NO: 145. In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 137 and a LC comprising SEQ ID NO: 143. In some embodiments, the full-length antibody comprises a HC comprising SEQ ID NO: 137 and a LC comprising SEQ ID NO: 144. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 137 and a LC comprising SEQ ID NO: 145. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 138 and a LC comprising SEQ ID NO: 142. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 139 and a LC comprising SEQ ID NO: 143. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 139 and a LC comprising SEQ ID NO: 144. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 139 and a LC comprising SEQ ID NO: 145. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 140 and a LC comprising SEQ ID NO: 143. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 140 and a LC comprising SEQ ID NO: 144. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 140 and a LC comprising SEQ ID NO: 145. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 141 and a LC comprising SEQ ID NO: 143. In some embodiments, the full length antibody comprises a HC comprising SEQ ID NO: 141 and a 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.

[0051] In some embodiments, an anti-CD122 antibody comprises a full-length antibody chain polypeptide encoded by a nucleic acid comprising 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, an anti-CD122 antibody comprises a heavy chain encoded by a nucleic acid comprising at least 80% sequence identity to a sequence selected from SEQ ID NOs: 146-153. In some embodiments, an anti-CD122 antibody comprises a heavy chain encoded by a nucleic acid comprising at least 85% sequence identity to a sequence selected from SEQ ID NOs: 146-153. In some embodiments, an anti-CD122 antibody comprises a heavy chain encoded by a nucleic acid comprising 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 comprising 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 comprising 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 comprising 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 comprising 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 comprising at least 95% sequence identity to a sequence selected from SEQ ID NOs: 154-157. In some embodiments, the full-length antibody chain encoded by a nucleic acid is selected from Table 11.

[0052] [Table 11-1]

[0053]

Table 11-2

[0054]

Table 11-3

[0055]

Table 11-4

[0056] In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain polypeptide 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 a full length antibody chain 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 a full length antibody chain 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 a full length antibody chain 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 a full length antibody chain 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 a full length antibody chain 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 a full length antibody chain 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 a full length antibody chain 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 a full-length antibody chain 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 a full-length antibody chain encoded by an HC nucleic acid sequence comprising SEQ ID NO: 153 and an LC nucleic acid sequence comprising SEQ ID NO: 157.

[0057] In some embodiments, the anti-CD122 antibody heavy chain and the anti-CD122 antibody light chain have a leader sequence near the amino-terminal region of each polypeptide. In some embodiments, the leader sequence is at the N-terminus of the anti-CD122 antibody heavy chain sequence. In some embodiments, the leader sequence is at the N-terminus of the anti-CD122 antibody heavy chain sequence provided in Table 9. In some embodiments, the leader sequence is at the N-terminus of the anti-CD122 antibody light chain sequence. In some embodiments, the leader sequence is at the N-terminus of the anti-CD122 antibody light chain sequence provided in Table 10. In some embodiments, the leader sequence is at the N-terminus of the anti-CD122 antibody light chain sequence provided in Table 10. n=14-40 is used to represent the amino acid of the leader sequence at the amino terminus of the anti-CD122 antibody heavy chain sequence. In some embodiments, (X) n=14-40is used to represent the amino acid of the leader sequence at the amino terminus of the anti-CD122 antibody light chain sequence. In some embodiments, the leader sequence is 14 to 40 amino acids in length. In some embodiments, the leader sequence is 15 to 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 paired to form the 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 paired to form the anti-CD122 antibody are not identical to each other. In some embodiments, the leader sequence comprises an amino acid sequence listed in Table 12. In some embodiments, the anti-CD122 antibody heavy chain contains an additional amino acid sequence N-terminal to the leader sequence. In some embodiments, the anti-CD122 antibody heavy chain contains an additional amino acid sequence immediately following the leader sequence. In some embodiments, the additional amino acid sequence immediately following the leader sequence is before the start of the heavy chain variable domain. In some embodiments, the anti-CD122 antibody light chain contains an additional amino acid sequence N-terminal to the leader sequence. In some embodiments, the anti-CD122 antibody light chain contains an additional amino acid sequence immediately following the leader sequence. In some embodiments, the additional amino acid sequence immediately following the leader sequence is before the start 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 a leader sequence comprising SEQ ID NO: 158. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody heavy chain sequence comprises a leader sequence comprising SEQ ID NO: 159. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody heavy chain sequence comprises a leader sequence comprising SEQ ID NO: 160. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody heavy chain sequence comprises a leader sequence comprising SEQ ID NO: 161.

[0058] In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody light chain sequence comprises a leader sequence comprising SEQ ID NO: 158. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody light chain sequence comprises a leader sequence comprising SEQ ID NO: 159. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody light chain sequence comprises a leader sequence comprising SEQ ID NO: 160. In some embodiments, the leader sequence used at the N-terminus of the anti-CD122 antibody light chain sequence comprises a leader sequence comprising SEQ ID NO: 161.

[0059] In some embodiments, the anti-CD122 antibody comprises a full-length antibody chain polypeptide encoded by an HC nucleic acid sequence and an LC nucleic acid sequence, each having a nucleic acid sequence encoding a leader sequence 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 at the 5' end of the anti-CD122 antibody heavy chain-encoding nucleic acid sequence. In some embodiments, anti-CD122 antibody heavy chain-encoding nucleic acid sequences with nucleic acid sequences encoding a leader sequence are provided in Table 11. In some embodiments, the nucleic acid sequence encoding a leader sequence is at the 5' end of the anti-CD122 antibody light chain-encoding nucleic acid sequence. In some embodiments, anti-CD122 antibody light chain-encoding nucleic acid sequences with nucleic acid sequences encoding a leader sequence are provided in Table 11. In some embodiments, (X) n=42-120 is used to represent the nucleotide of the leader sequence at the 5' end of the anti-CD122 antibody heavy chain-encoding nucleic acid sequence. In some embodiments, (X) n=42-120is used to represent the nucleotides of the leader sequence at the 5' end of the anti-CD122 antibody light chain-encoding nucleic acid sequence. In some embodiments, the leader sequence is 42 to 120 nucleotides in length. In some embodiments, the leader sequence is 45 to 105 nucleotides in length. In some embodiments, the leader sequence of the anti-CD122 antibody heavy chain coding sequence and the leader sequence of the anti-CD122 antibody light chain coding sequence are identical to one another. In some embodiments, the leader sequence of the anti-CD122 antibody heavy chain coding sequence and the leader sequence of the anti-CD122 antibody light chain coding sequence are not identical to one another. In some embodiments, the leader sequence encodes an amino acid sequence listed in Table 12. In some embodiments, the anti-CD122 antibody heavy chain coding sequence contains an additional nucleotide sequence at the 5' end of the leader sequence. In some embodiments, the sequence encoding the anti-CD122 antibody heavy chain contains an additional nucleotide sequence directly at the 3' end of the leader sequence. In some embodiments, the anti-CD122 antibody light chain coding sequence contains an additional nucleotide sequence at the 5' end of the leader sequence. In some embodiments, the anti-CD122 antibody light chain encoding sequence contains an additional nucleotide sequence immediately at the 3' end of the leader sequence. In some embodiments, the leader sequence at the 5' end of the anti-CD122 antibody heavy chain coding sequence encodes the amino acid leader sequence of SEQ ID NO: 158. In some embodiments, the leader sequence at the 5' end of the anti-CD122 antibody heavy chain coding sequence encodes the amino acid leader sequence of SEQ ID NO: 159. In some embodiments, the leader sequence at the 5' end of the anti-CD122 antibody heavy chain coding sequence encodes the amino acid leader sequence of SEQ ID NO: 160. In some embodiments, the leader sequence at the 5' end of the anti-CD122 antibody heavy chain coding sequence encodes the amino acid leader sequence of SEQ ID NO: 161. In some embodiments, the leader sequence at the 5' end of the anti-CD122 antibody light chain coding sequence encodes the amino acid leader sequence of SEQ ID NO: 158. In some embodiments, the leader sequence at the 5' end of the anti-CD122 antibody light chain coding sequence encodes the amino acid leader sequence of SEQ ID NO: 159.In some embodiments, the leader sequence at the 5' end of the anti-CD122 antibody light chain coding sequence encodes the amino acid leader sequence of SEQ ID NO: 160. In some embodiments, the leader sequence at the 5' end of the anti-CD122 antibody light chain coding sequence encodes the amino acid leader sequence of SEQ ID NO: 161.

[0060] [Table 12]

[0061] In some embodiments, an HC polypeptide and an LC polypeptide are paired to form an anti-CD122 antibody or anti-CD122 antibody fragment. In some embodiments, the two heavy chains are linked to each other by a disulfide bond, and each heavy chain is linked to a light chain by a disulfide bond. In some embodiments, the specific HC polypeptide and the specific LC polypeptide paired to form the anti-CD122 antibody are designated G1-G20 according to Table 13. In some embodiments, G1 is a chimeric anti-CD122 antibody with murine parent variable domain sequences in a human IgG1 backbone. In some embodiments, G2-10 are humanized anti-CD122 antibodies with murine-derived CDRs incorporated into human variable domain framework sequences that have been optimized to retain affinity for CD122 in a human IgG1 backbone. In some embodiments, G11 is a chimeric anti-CD122 antibody with murine parent variable domain sequences in a human IgG4 backbone. In some embodiments, G12-20 is a humanized anti-CD122 antibody with murine-derived CDRs incorporated into human variable domain framework sequences that have been optimized to retain affinity for CD122 in a human IgG4 backbone.

[0062] [Table 13]

[0063] In some embodiments, anti-CD122 antibody CDR sequences can be defined by an antibody numbering scheme. In embodiments, the antibody numbering scheme is Kabat. In embodiments, the antibody numbering scheme is IMGT. In embodiments, the antibody numbering scheme is AbM. In embodiments, the antibody numbering scheme is Chothia. In embodiments, the antibody numbering scheme is Contact. Table 14 lists CDR sequences of anti-CD122 antibodies and antigen-binding fragments thereof according to various antibody numbering schemes. In Table 14, the HCDR1, HCDR2, and HCDR3 sequences defined according to a particular antibody numbering scheme are found in the VH region of the heavy chain, and representative heavy chain sequences with SEQ ID NOs are listed in Table 9. In Table 14, the LCDR1, LCDR2, and LCDR3 sequences defined according to a particular antibody numbering scheme are found in the VL region of the light chain, and representative light chain sequences with SEQ ID NOs are listed in Table 10.

[0064] [Table 14]

[0065] In some aspects, the anti-CD122 antibody or antigen-binding fragment thereof comprises a CDR sequence listed in Table 14. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain comprising an HCDR sequence listed in Table 14. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VL domain comprising an LCDR sequence listed in Table 14. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain comprising an HCDR sequence listed in Table 14, and a VL domain comprising an LCDR sequence listed in Table 14. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain comprising the HCDR1, HCDR2, and HCDR3 sequences 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 comprising the HCDR1, HCDR2, and HCDR3 sequences 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 comprising the HCDR1, HCDR2, and HCDR3 sequences 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 comprising the HCDR1, HCDR2, and HCDR3 sequences 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 comprising the HCDR1, HCDR2, and HCDR3 sequences 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 comprising the LCDR1, LCDR2, and LCDR3 sequences 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 comprising the LCDR1, LCDR2, and LCDR3 sequences 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 comprising the LCDR1, LCDR2, and LCDR3 sequences 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 comprising the LCDR1, LCDR2, and LCDR3 sequences 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 comprising the LCDR1, LCDR2, and LCDR3 sequences 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 comprising the HCDR1, HCDR2, and HCDR3 sequences listed in Table 14 according to the Kabat numbering scheme, and a VL domain comprising the LCDR1, LCDR2, and LCDR3 sequences listed in Table 14 according to the Kabat numbering scheme. In some embodiments, an anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain comprising the HCDR1, HCDR2, and HCDR3 sequences listed in Table 14 according to the IMGT numbering scheme, and a VL domain comprising the LCDR1, LCDR2, and LCDR3 sequences listed in Table 14 according to the IMGT numbering scheme. In some embodiments, an anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain comprising the HCDR1, HCDR2, and HCDR3 sequences listed in Table 14 according to the AbM numbering scheme, and a VL domain comprising the LCDR1, LCDR2, and LCDR3 sequences 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 comprising the HCDR1, HCDR2, and HCDR3 sequences listed in Table 14 according to the Chothia numbering scheme, and a VL domain comprising the LCDR1, LCDR2, and LCDR3 sequences 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 comprising the HCDR1, HCDR2, and HCDR3 sequences listed in Table 14 according to the Contact numbering scheme, and a VL domain comprising the LCDR1, LCDR2, and LCDR3 sequences listed in Table 14 according to the Contact numbering scheme.

[0066] In some aspects, an anti-CD122 antibody or antigen-binding fragment thereof comprises a VH domain comprising an HCDR sequence listed according to the antibody numbering scheme of Table 14 as identified by a SEQ ID NO: and a VL domain comprising an LCDR sequence listed according to the antibody numbering scheme of Table 14 as identified by a SEQ ID NO:. In some embodiments, an anti-CD122 antibody comprises a VH domain comprising an HCDR sequence listed according to the antibody numbering scheme of Table 14 as identified by a SEQ ID NO: and a VL domain comprising an LCDR sequence listed according to the antibody numbering scheme of Table 14 as identified by a SEQ ID NO:. In some embodiments, an anti-CD122 antigen-binding fragment thereof comprises a VH domain comprising an HCDR sequence listed according to the antibody numbering scheme of Table 14 as identified by a SEQ ID NO: and a VL domain comprising an LCDR sequence listed according to the antibody numbering scheme of Table 14 as identified by a SEQ ID NO:. In some embodiments, the anti-CD122 antibody or 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 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 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.

[0067] CD122 binding affinity In some embodiments, the anti-CD122 antibodies and antigen-binding fragments thereof described herein bind to CD122 with measurable affinity. In some embodiments, the anti-CD122 antibodies or antigen-binding fragments thereof bind to mammalian CD122. In some embodiments, the anti-CD122 antibodies or antigen-binding fragments thereof bind to murine CD122. In some embodiments, the anti-CD122 antibodies or antigen-binding fragments thereof bind to human CD122. In some embodiments, the anti-CD122 antibodies or antigen-binding fragments thereof that bind to CD122 comprise an HCDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, an HCDR3 comprising the amino acid sequence of SEQ ID NO: 24, 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: 56. In some embodiments, an anti-CD122 antibody or antigen-binding fragment thereof that binds to CD122 comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 13, an HCDR3 comprising the amino acid sequence of SEQ ID NO: 25, an LCDR1 comprising the amino acid sequence of SEQ ID NO: 38, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 49, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 57. In some embodiments, an anti-CD122 antibody or antigen-binding fragment thereof that binds to CD122 comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 14, an HCDR3 comprising the amino acid sequence of SEQ ID NO: 26, an LCDR1 comprising the amino acid sequence of SEQ ID NO: 39, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 50, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, an anti-CD122 antibody or antigen-binding fragment thereof that binds to CD122 comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 4, an HCDR2 having the amino acid sequence of SEQ ID NO: 15, an HCDR3 having the amino acid sequence of SEQ ID NO: 27, an LCDR1 having the amino acid sequence of SEQ ID NO: 40, an LCDR2 having the amino acid sequence of SEQ ID NO: 51, and an LCDR3 having the amino acid sequence of SEQ ID NO: 59.In some embodiments, an anti-CD122 antibody or 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 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 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 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 antigen-binding fragment thereof that binds to CD122 comprises an HCDR1 having the amino acid sequence of SEQ ID NO: 9, an HCDR2 having the amino acid sequence of SEQ ID NO: 20, an HCDR3 having the amino acid sequence of SEQ ID NO: 32, an LCDR1 having the amino acid sequence of SEQ ID NO: 45, an LCDR2 having the amino acid sequence of SEQ ID NO: 53, and an LCDR3 having the amino acid sequence of SEQ ID NO: 64.In some embodiments, an anti-CD122 antibody or 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 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, the anti-CD122 antibody or 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, the anti-CD122 antibody or 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 to CD122 is K D The binding affinity is measured by the equilibrium dissociation constant (Eq.

[0068] In some embodiments, the anti-CD122 antibodies and antigen-binding fragments thereof described herein have a K DIn some embodiments, the anti-CD122 antibody binds to CD122 with measurable affinity as measured by . 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 antigen-binding fragment thereof specifically binds to CD122. In some embodiments, the antibody or antigen-binding fragment thereof exhibits moderate to low non-specific binding (NBS) to unintended peptides, proteins, receptors, or transporters. In some embodiments, the antibody or antigen-binding fragment thereof exhibits low non-specific binding (NBS) to unintended peptides, proteins, receptors, or transporters. In some embodiments, the antibody or antigen-binding fragment thereof specifically binds to mammalian CD122. In some embodiments, the antibody or antigen-binding fragment thereof binds to mouse CD122. In some embodiments, the antibody or antigen-binding fragment thereof binds to human CD122. In some embodiments, the antibody or antigen-binding fragment thereof binds to about 10 -6 M~10 -12 M, 10 -7 M~10 -12 M, 10 -8 M~10 -12 M, 10 -9 M~10 -12 M, 10 -6 M~10 -11 M, 10 -7 M~10 -11 M, 10 -8 M~10 -11 M, 10 -9 M~10 -11 M, 10 -10 M~10 -11 M, 10 -6 M~10 -10 M, 10 -7 M~10 -10 M, 10 -8 M~10 -10 M, 10 -9 M~10 -10 M, 10 -6 M~10 -9 M, 10 -7 M~10 -9 M, 10 -8 M~10-9 M, 10 -6 M~10 -8 M, 10 -7 M~10 -8 M, or 10 -6 M~10 -7 K of M D In some embodiments, the antibody or antigen-binding fragment thereof binds to the CD122 protein or a domain of the CD122 protein with a binding affinity measured by about 10 -6 M~10 -12 M, 10 -7 M~10 -12 M, 10 -8 M~10 -12 M, 10 -9 M~10 -12 M, 10 -6 M~10 -11 M, 10 -7 M~10 -11 M, 10 -8 M~10 -11 M, 10 -9 M~10 -11 M, 10 -10 M~10 -11 M, 10 -6 M~10 -10 M, 10 -7 M~10 -10 M, 10 -8 M~10 -10 M, 10 -9 M~10 -10 M, 10 -6 M~10 -9 M, 10 -7 M~10 -9 M, 10 -8 M~10 -9 M, 10 -6 M~10 -8 M, 10 -7 M~10 -8 M, or 10 -6 M~10 -7 K of M D In some embodiments, the antibody or antigen-binding fragment thereof binds to one or more epitopes within the extracellular domain of the CD122 protein with a binding affinity measured by about 9E. -08 M, 8E -08 M, 7E -08M, 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 K less than M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity measured by . -7 ~10 -9 K of M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity in the low nanomolar range (10 -9 K of M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity in the picomolar range (10 -10 ~10 -12 K of M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity in the high picomolar range (10 -10 K of M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity in the low nanomolar range to the high picomolar range (10 -9 ~10 -10 K of M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity within about 3E -09 K less than M DIn some embodiments, the antibody binds to human CD122 protein with a binding affinity measured by about 2E -09 K less than M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity measured by about 1E -09 K less than M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity measured by about 9E -10 K less than M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity measured by about 8E -10 K less than M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity measured by about 5E -09 ~5E -10 K of M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity measured by about 3E -09 ~7E -10 K of M D In some embodiments, the antibody binds to human CD122 protein with a binding affinity measured by about 2E -09 ~8E -10 K of M D The antibody binds to human CD122 protein with a binding affinity measured by approximately 1E -09 ~9E -10 K of M D The IgG1-binding domain binds to human CD122 protein with a binding affinity measured by

[0069] In some embodiments, the antibody or antigen-binding fragment thereof is measured for binding to mouse CD122 protein by assaying antibody binding affinity to a mouse CD122 protein sequence listed in Table 15. In some embodiments, the antibody or antigen-binding fragment thereof is measured for binding to mouse CD122 protein by assaying antibody binding affinity to a portion of the mouse CD122 protein sequence listed in Table 15. In some embodiments, the antibody or antigen-binding fragment thereof is measured for binding to mouse CD122 protein by assaying antibody binding affinity to an extracellular portion of the mouse CD122 protein sequence listed in Table 15 containing the CD122 extracellular domain (A26-E240). In some embodiments, the antibody or antigen-binding fragment thereof is measured for binding to human CD122 protein by assaying antibody binding affinity to a human CD122 protein sequence listed in Table 15. In some embodiments, the antibody or antigen-binding fragment thereof is measured for binding to human CD122 protein by assaying antibody binding affinity to a portion of the human CD122 protein sequence listed in Table 15. In some embodiments, the antibody or antigen-binding fragment thereof is measured for binding to human CD122 protein by assaying antibody binding affinity to a polypeptide sequence comprising a portion of the amino acid sequence listed in Table 15. In some embodiments, the antibody or antigen-binding fragment thereof is measured for binding to human CD122 protein by assaying antibody binding affinity to the extracellular portion of a human CD122 protein sequence listed in Table 15 containing the CD122 extracellular domain (A26-D239). In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof cross-competes for binding to CD122 with another anti-CD122 antibody or antigen-binding fragment thereof described herein. In some embodiments, the anti-CD122 antibody or antigen-binding fragment thereof cross-competes for binding to CD122 with a known anti-CD122 antibody.

[0070] [Table 15]

[0071] Comparison with known anti-CD122 antibodies The CD122 antibodies described herein can be compared to other known anti-CD122 antibodies by their properties, structure, and / or functional characteristics. In some embodiments, the humanized monoclonal antibodies described herein have one or more determined 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 contained in 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 in the extracellular portion of human CD122 that are comprised in the CD122-binding epitope of the humanized monoclonal antibody. In some embodiments, the amino acid residues in human CD122 that comprise the anti-CD122 antibody epitope differ from the amino acid residues in human CD122 that comprise the anti-CD122 antibody epitope of a known anti-CD122 antibody. In some embodiments, the humanized monoclonal anti-CD122 antibodies described herein bind to a human CD122 epitope that is different from that bound by other known anti-CD122 antibodies. In some embodiments, the human CD122 epitope bound by a 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 antibodies described herein act as more potent functional inhibitors of IL2-induced cell signaling than one or more known anti-CD122 antibodies. In some embodiments, the humanized monoclonal antibodies described herein act as more potent functional inhibitors of IL15-induced cell signaling than one or more known anti-CD122 antibodies. In some embodiments, the humanized monoclonal antibodies described herein act as more potent functional inhibitors of IL2-induced and IL-15 cell signaling than one or more known anti-CD122 antibodies.In some embodiments, the properties, structures, and / or functional characteristics of the humanized anti-CD122 antibodies described herein are compared to the properties, structures, and / or functional characteristics of known humanized anti-CD122 antibodies comprising the CDR sequences listed in Table 16. In some embodiments, the known humanized anti-CD122 antibodies used to compare CD122 epitopes or functional properties, such as the ability to act as functional inhibitors or inhibitors 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 an HCDR1 comprising the sequence of SEQ ID NO: 189, an HCDR2 comprising the sequence of SEQ ID NO: 190, and an HCDR3 comprising the sequence of SEQ ID NO: 191, and the VL domain comprises an LCDR1 comprising the sequence of SEQ ID NO: 192, an LCDR2 comprising the sequence of SEQ ID NO: 193, and an LCDR3 comprising the sequence of SEQ ID NO: 194.

[0072] [Table 16]

[0073] In some aspects, the isolated anti-CD122 antibodies described herein have one or more characterized binding epitopes on the CD122 protein. In some embodiments, the CD122 epitopes bound by the anti-CD122 antibodies described herein are functional epitopes. In some embodiments, the CD122 epitopes bound by the anti-CD122 antibodies described herein are conformational epitopes. In some embodiments, the CD122 epitopes bound by the anti-CD122 antibodies described herein are conformational rather than linear. In some embodiments, the conformational epitope comprises at least two, at least three, or at least four nonlinear 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 IL2 binding to high-affinity IL-αβγ receptors, including CD122, CD132, and CD25. In some embodiments, the isolated anti-CD122 antibodies described herein inhibit the binding of IL15, expressed in trans at IL15Rα, to intermediate affinity IL-βγ receptors, including CD122 and CD132. In some embodiments, the isolated anti-CD122 antibodies described herein inhibit the binding of IL15 to high affinity IL-αβγ receptors, including CD122, CD132, and IL15Rα. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, or all twenty-two of 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 human CD122 protein according to the amino acid numbering listed in SEQ ID NO: 187.In some embodiments, at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, or all twenty-two of 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 human CD122 protein according to the amino acid numbering listed in SEQ ID NO: 187 comprise the epitope to which an isolated anti-CD122 monoclonal antibody described herein binds. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one amino acid residue from epitope site 1) residues 39-41 (WPD) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one amino acid residue from epitope site 2) residues 76-81 (VDIVTL) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one amino acid residue from epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein bind to at least one amino acid residue from epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of human CD122 protein comprising the amino acid sequence of 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 from epitope site 1) residues 39-41 (WPD) of the extracellular domain of human CD122 protein comprising the amino acid sequence of 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 from epitope site 2) residues 76-81 (VDIVTL) of the extracellular domain of human CD122 protein comprising the amino acid sequence of 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 from epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of human CD122 protein comprising the amino acid sequence of 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 from epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187. In some embodiments, an isolated anti-CD122 monoclonal antibody described herein binds to at least one amino acid residue from epitope site 1) residues 39-41 (WPD) and i) at least one amino acid residue from epitope site 2) residues 76-81 (VDIVTL) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187, or ii) at least one amino acid residue from epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187, or iii) at least one amino acid residue from epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187.In some embodiments, an isolated anti-CD122 monoclonal antibody described herein binds to at least one amino acid residue from epitope site 2) residues 76-81 (VDIVTL) and i) at least one amino acid residue from epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of a human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187, or ii) at least one amino acid residue from epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of a human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187. In some embodiments, an isolated anti-CD122 monoclonal antibody described herein binds to at least one amino acid residue from epitope site 3) residues 99-105 (FKPFENL) and at least one amino acid residue from epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of a human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187. In some embodiments, the isolated anti-CD122 monoclonal antibodies described herein comprise epitope sequences comprising at least one, two, or three amino acid residues from epitope site 1) residues 39-41 (WPD) and at least one, two, three, four, five, or six amino acid residues from epitope site 2) residues 76-81 (VDIVTL) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187, or ii) the amino acid sequence of SEQ ID NO: 187. or iii) at least one, two, three, four, five, six, or seven amino acid residues from residues 99 to 105 (FKPFENL) of the extracellular domain of human CD122 protein, which comprises the amino acid sequence of SEQ ID NO: 187.In some embodiments, an isolated anti-CD122 monoclonal antibody described herein binds to at least one, two, three, four, five, or six amino acid residues from epitope site 2) residues 76-81 (VDIVTL) and i) at least one, two, three, four, five, six, or seven amino acid residues from epitope site 3) residues 99-105 (FKPFENL) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187, or ii) at least one, two, three, four, five, or six amino acid residues from epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of human CD122 protein comprising the amino acid sequence of 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 from epitope site 3) residues 99-105 (FKPFENL) and at least one, two, three, four, five, or six amino acid residues from epitope site 4) residues 134-139 (HYFERH) of the extracellular domain of human CD122 protein comprising the amino acid sequence of SEQ ID NO: 187.

[0074] Production and manufacturing of antibodies or antigen-binding fragments thereof In some embodiments, the polypeptides (e.g., antibodies or antigen-binding fragments thereof) described herein are produced using any method known in the art to be useful for synthesizing polypeptides (e.g., antibodies), in particular by chemical synthesis or recombinant expression, preferably by use of recombinant expression techniques.

[0075] In some examples, antibodies or antigen-binding fragments thereof are recombinantly expressed, and nucleic acids encoding the antibodies or antigen-binding fragments thereof are assembled from chemically synthesized oligonucleotides (e.g., those described in Kutmeier et al., 1994, BioTechniques 17:242), which involve synthesis of overlapping oligonucleotides containing portions of the antibody-encoding sequence, annealing and ligating those oligonucleotides, and then amplifying the ligated oligonucleotides by PCR.

[0076] Alternatively, nucleic acid molecules encoding antibodies are optionally generated from a suitable source (e.g., an antibody cDNA library or a cDNA library generated from any tissue or cell that expresses immunoglobulins) by PCR amplification using synthetic primers hybridizable to the 5' and 3' ends of the sequence, or by cloning using oligonucleotides specific for the particular nucleic acid sequence.

[0077] In some examples, the antibody or binding thereof is optionally produced by generating a monoclonal antibody, e.g., as described by Kohler and Milstein (1975, Nature 256:495-497), or 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, clones encoding at least the Fab portion of the antibody can be obtained by screening a Fab expression library for clones of Fab fragments that bind a specific antigen (e.g., as described in Huse et al., 1989, Science 246:1275-1281) 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).

[0078] 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) by splicing genes from a murine antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity are used. Chimeric antibodies are molecules in which different portions are derived from different animal species, such as those having a variable region derived from a murine monoclonal antibody and a human immunoglobulin constant region, e.g., a humanized antibody.

[0079] In some embodiments, techniques described for the production of single-chain antibodies (see U.S. Pat. No. 4,694,778; Bird, 1988, Science 242:423-42; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Ward et al., 1989, Nature 334:544-54) are adapted to produce 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, resulting in a single-chain polypeptide. Techniques for the assembly of functional Fv fragments in E. coli are also optionally used (Skerra et al., 1988, Science 242:1038-1041).

[0080] In some embodiments, a nucleic acid sequence encodes an antibody disclosed herein. In some embodiments, the polynucleotide sequence encoding the antibody is operably linked to a eukaryotic regulatory sequence. In some embodiments, a cell comprises the nucleic acid sequence. In some embodiments, the 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 E. 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 mouse myeloma cell, or a PER.C6® human cell. In some embodiments, the antibody nucleotide sequence or an expression vector comprising the antibody nucleotide sequence is transferred into a host cell by conventional techniques (e.g., electroporation, liposome transfection, and calcium phosphate precipitation), and the transfected cell is then cultured by conventional techniques to produce the antibody. In certain aspects, expression of the antibody is regulated by a constitutive, inducible, or tissue-specific promoter. Standard cell lines and methods for the production of antibodies from large-scale cell culture are known in the art. See, for example, Li et al., "Cell culture processes for monoclonal antibody production." Mabs. 2010 Sep-Oct;2(5):466-477.

[0081] In certain aspects, methods of making antibodies are described herein, including culturing cells containing an antibody-encoding nucleic acid under in vitro conditions sufficient to allow for antibody production and secretion. In some embodiments, the antibody is harvested from the cell culture medium. Harvesting may further include one or more purification steps to remove viable cells, cellular debris, non-antibody proteins or polypeptides, undesired salts, buffers, and 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.

[0082] Pharmaceutical Composition Provided herein are pharmaceutical compositions 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 an 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 formulation. In some embodiments, the pharmaceutical formulation is selected based on a preferred route of administration of the antibody or antibody fragment to a subject.

[0083] In some embodiments, pharmaceutical formulations include, but are not limited to, aqueous liquid dispersions, self-emulsifying dispersions, solid solutions, liposomal dispersions, solid dosage forms, powders, immediate release formulations, controlled release formulations, fast dissolve formulations, tablets, capsules, pills, delayed release formulations, extended release formulations, pulsed release formulations, multiparticulate formulations (e.g., nanoparticle formulations), and combined immediate and controlled release formulations.

[0084] In some examples, the pharmaceutical formulation comprises a multiparticulate formulation. In some examples, the pharmaceutical formulation comprises a nanoparticle formulation. In some examples, the nanoparticle comprises cMAP, cyclodextrin, or lipid. In some cases, the nanoparticle comprises solid lipid nanoparticles, polymeric nanoparticles, self-emulsifying nanoparticles, liposomes, microemulsions, or micellar solutions. Further exemplary nanoparticles include, but are not limited to, paramagnetic nanoparticles, superparamagnetic nanoparticles, metal nanoparticles, fullerene-like materials, inorganic nanotubes, dendrimers (such as those with covalently bound metal chelates), nanofibers, nanorods, nanoropes, and quantum dots. In some examples, 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.

[0085] In some examples, the nanoparticles comprise a core or a core and a shell, such as in a core-shell nanoparticle. In some examples, the nanoparticles comprise nanospheres or nanocapsules.

[0086] In some examples, the nanoparticles are further coated with molecules for attachment of functional elements (e.g., having one or more of the polynucleic acid molecules or binding moieties described herein). In some examples, the coating comprises chondroitin sulfate, dextran sulfate, carboxymethyldextran, alginate, pectin, carrageenan, fucoidan, agaropectin, porphyran, karaya gum, xanthan gum, hyaluronic acid, glucosamine, galactosamine, chitosan, polyglutamic acid, -chymotrypsin, polylysine, polyarginine, histones, protamine, ovalbumin, or dextrin or cyclodextrin.

[0087] In some embodiments, the pharmaceutical formulations described herein are administered to a subject by multiple 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 examples, the pharmaceutical compositions described herein are formulated for parenteral (e.g., intravenous, subcutaneous, intramuscular, intraarterial, intraperitoneal, intrathecal, intracerebral, intraventricular, or intracranial) administration. In other examples, the pharmaceutical compositions described herein are formulated for oral administration. In yet other examples, the pharmaceutical compositions described herein are formulated for intranasal administration.

[0088] 1. Pharmaceutically Acceptable Excipients, Carriers, and Diluents Compositions comprising antibodies of the present disclosure are contained in pharmaceutical compositions comprising one or more pharmaceutically acceptable excipients, carriers, and diluents. In some embodiments, antibodies of the present disclosure are administered suspended in a sterile solution. In some embodiments, antibodies of the present disclosure are administered suspended in an isotonic solution. In some examples, pharmaceutical formulations contain one or more salts in an amount necessary to bring the osmolality of the composition into an acceptable range. Such salts include those having sodium, potassium, or ammonium cations and chloride, citrate, ascorbic acid, borate, phosphate, bicarbonate, sulfate, thiosulfate, or bisulfite anions; suitable salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite, and ammonium sulfate. In certain embodiments, the solution contains about 0.9% NaCl. In certain embodiments, the solution contains about 5.0% dextrose. In certain embodiments, the solution further comprises one or more of the following: a buffer, such as acetate, citrate, histidine, succinate, phosphate, bicarbonate, and tris(hydroxymethyl)aminomethane; a surfactant, such as polysorbate 80 (Tween 80), polysorbate 20 (Tween 20); a polyol / disaccharide / polysaccharide, such as glucose, dextrose, mannose, mannitol, sorbitol, sucrose, and dextran 40; an amino acid, such as glycine or arginine; an antioxidant, such as ascorbic acid, methionine; or a chelating agent, such as EDTA or EGTA. The carbomer in the aqueous pharmaceutical composition acts as an emulsifier and viscosity adjuster. In certain embodiments, the pharmaceutically acceptable excipient comprises or consists of a carbomer. In certain embodiments, the carbomer comprises or consists of carbomer 910, carbomer 934, carbomer 934P, carbomer 940, carbomer 941, carbomer 1342, or a combination thereof. The cyclodextrin in the aqueous pharmaceutical composition serves as a solubilizer and stabilizer. In certain embodiments, the pharmaceutically acceptable excipient comprises or consists of a cyclodextrin.In certain embodiments, the cyclodextrin comprises or consists of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, or a combination thereof. The lecithin in the pharmaceutical composition can serve as a solubilizer. In certain embodiments, the solubilizer comprises or consists of lecithin. The poloxamer in the pharmaceutical composition serves as an emulsifier, solubilizer, and dispersant. In certain embodiments, the pharmaceutically acceptable excipient comprises or consists of a poloxamer. In certain embodiments, the poloxamer comprises or consists of poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, poloxamer 407, or a combination thereof. The polyoxyethylene sorbitan fatty acid ester in the pharmaceutical composition serves as an emulsifier, solubilizer, surfactant, and dispersant. In certain embodiments, the pharmaceutically acceptable excipient comprises or consists of a polyoxyethylene sorbitan fatty acid ester. In certain embodiments, the polyoxyethylene sorbitan fatty acid ester comprises or consists of polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 61, polysorbate 65, polysorbate 80, polysorbate 81, polysorbate 85, polysorbate 120, or a combination thereof. Polyoxyethylene stearate in the pharmaceutical composition functions as an emulsifier, solubilizer, surfactant, and dispersant. In certain embodiments, the pharmaceutically acceptable excipient comprises or consists of polyoxyethylene stearate.In certain embodiments, the polyoxyethylene stearate comprises or consists of polyoxyl 2 stearate, polyoxyl 4 stearate, polyoxyl 6 stearate, polyoxyl 8 stearate, polyoxyl 12 stearate, polyoxyl 20 stearate, polyoxyl 30 stearate, polyoxyl 40 stearate, polyoxyl 50 stearate, polyoxyl 100 stearate, polyoxyl 150 stearate, polyoxyl 4 distearate, polyoxyl 8 distearate, polyoxyl 12 distearate, polyoxyl 32 distearate, polyoxyl 150 distearate, or a combination thereof. The sorbitan ester in the pharmaceutical composition functions as an emulsifier, solubilizer, nonionic surfactant, and dispersant. In certain embodiments, the pharmaceutically acceptable excipient comprises or consists of a sorbitan ester. In certain embodiments, the sorbitan ester comprises or consists of sorbitan laurate, sorbitan oleate, sorbitan palmitate, sorbitan stearate, sorbitan trioleate, sorbitan sesquioleate, or combinations thereof.

[0089] In certain embodiments, antibodies of the present disclosure can be shipped and / or stored lyophilized and then reconstituted prior to administration. In certain embodiments, lyophilized antibody formulations include bulking agents such as mannitol, sorbitol, sucrose, trehalose, dextran 40, or combinations thereof. The lyophilized formulations can be contained in vials made of glass or other suitable non-reactive materials. When formulated, antibodies, whether reconstituted or not, can be buffered at a specific pH, generally below about 7.5. In certain embodiments, the pH can be 4.5-7.5, 4.5-7.0, 4.5-6.5, 4.5-6.0, or 5.5 or 5.0.

[0090] definition Unless otherwise defined, all technical terms, notations, and other technical and scientific terms or terminology 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, terms having a commonly understood meaning are defined herein for clarity and / or ease of reference, and the inclusion of such definitions herein should not necessarily be construed as representing a substantial difference from what is generally understood in the art.

[0091] Throughout this application, various embodiments may be expressed 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 an inflexible limitation on the scope of the present disclosure. Thus, the description of a range should be considered to have all possible subranges specifically disclosed, as well as individual numerical values ​​within that range. For example, the description of a range such as 1 to 6 should be considered to specifically disclose subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0092] As used in this specification and claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a sample" includes a plurality of samples, mixtures thereof.

[0093] The terms "determining," "measuring," "evaluating," "assessing," "assaying," and "analyzing" are often used interchangeably herein to refer to forms of measurement. These terms include determining whether an element is present or not (e.g., detecting). These terms can include quantitative, qualitative, or quantitative and qualitative determinations. Evaluation can be relative or absolute. "Detecting the presence of" can include determining the amount of something present in addition to determining presence or absence, depending on the context.

[0094] The terms "subject," "individual," or "patient" are often used interchangeably herein. A "subject" can be a biological entity that contains expressed genetic material. The biological entity can be, for example, a plant, animal, or microorganism, including bacteria, viruses, fungi, and protozoa. A subject can be tissues, cells, and their progeny of a biological entity obtained in vivo or cultured in vitro. A subject can be a mammal. A mammal can be a human. A subject can be diagnosed or suspected of being at high risk for a disease. In some cases, a subject is not necessarily diagnosed or suspected of being at high risk for a disease.

[0095] The term "in vivo" is used to describe events that take place inside the body of a subject.

[0096] The term "in vitro" is used to describe an event in which a material is contained in a container for holding laboratory reagents, such that the material is separated from the biological source from which it is obtained. In vitro assays can include cell-based assays in which live or dead cells are used. In vitro assays can also include cell-free assays in which intact cells are not used.

[0097] As used herein, the term "about" refers to a number plus or minus 10% of that number. The term "about" refers to a range minus 10% of the lowest value and plus 10% of the highest value.

[0098] As used herein, the terms "treatment" or "treating" are used in reference to a pharmaceutical or other intervention regimen to obtain a beneficial or desired result in a recipient. Beneficial or desired results include, but are not limited to, therapeutic benefit and / or prophylactic benefit. Therapeutic benefit can refer to the eradication or amelioration of the condition or underlying disease being treated. Therapeutic benefit can also 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 benefit includes delaying, preventing, or eliminating the appearance 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 benefit, a subject at risk of developing a particular disease or reporting one or more physiological symptoms of a disease may receive treatment even if a diagnosis of the disease has not been made.

[0099] The term "antibody" as used herein is used in the broadest sense and includes monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments thereof, 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 also encompasses genetically engineered and / or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, tandem di-scFv, tandem tri-scFv, etc. Unless otherwise specified, the term "antibody" should be understood to encompass functional antibody fragments thereof. 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. The antibody may comprise a human IgG1 constant region. The antibody may comprise a human IgG4 constant region. Antibodies include full-length and native antibodies, as well as any specific binding portion thereof, including those having any number of immunoglobulin classes and / or isotypes (e.g., IgG1, IgG2, IgG3, IgG4, IgM, IgA, IgD, IgE, and IgM), as well as fragments and portions thereof that retain their binding specificity, such as biologically relevant (antigen-binding) fragments or specific binding portions thereof, including, but not limited to, Fab, F(ab'), Fv, and scFv (single-chain or related entities) / fragments and portions thereof that retain their binding specificity. Monoclonal antibodies are generally within a substantially homogeneous antibody composition; thus, any individual antibodies comprised within a monoclonal antibody composition are identical except for possible naturally occurring mutations that may be present in minor amounts. The monoclonal antibody can comprise a human IgG1 constant region or a human IgG4 constant region.

[0100] The terms "complementarity determining region" and "CDR" are synonymous with "hypervariable region" or "HVR" and are known in the art and refer to non-contiguous sequences of amino acids in an antibody variable region that confer antigen specificity and / or binding affinity. Generally, each heavy chain variable region has three CDRs (CDR-H1, CDR-H2, CDR-H3; also referred to as HCDR1, HCDR2, and HCDR3), and each light chain variable region has three CDRs (CDR-11, CDR-12, and CDR-13; also referred to as LCDR1, LCDR2, and LCDR3). The terms "framework region" and "FR" are known in the art and refer to the non-CDR portions of the heavy and light chain variable regions. Generally, there are four FRs (FR-H1, FR-H2, FR-H3, and FR-H4) in each full-length heavy chain variable region, and four FRs (FR-L1, FR-L2, FR-L3, and FR-L4) in each full-length light chain variable region.The exact amino acid sequence boundaries of a given CDR or FR can be determined by 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. 2003 Jan;27(1):55-77 ("IMGT" numbering scheme), Honegger A and Pluckthun A, "Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool," J Mol Biol, 2001 Jun 8;309(3):657-70, ("Aho" numbering scheme), and Whitelegg NR and Rees AR, "WAM: an improved algorithm for modeling antibodies on the WEB," Protein Eng. 2000 Dec;13(12):819-24 ("AbM" numbering scheme).In certain embodiments, 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.

[0101] The boundaries of a 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. Both the Kabat and Chothia numbering schemes are based on the most common antibody region sequence lengths, with insertions accommodated by insertion letters, such as "30a," and deletions occurring in some antibodies. The two schemes place specific insertions and deletions ("indels") at different positions, resulting in differential numbering. The contact scheme is based on the analysis of complex crystal structures and is similar in many respects to the Chothia numbering scheme.

[0102] The term "variable region" or "variable domain" refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to an antigen. The variable domains of the heavy and light chains (VH and VL, respectively) of natural antibodies generally have similar structures, with each domain containing four conserved framework regions (FR) and three CDRs (see, e.g., Kindt et al., Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007)). A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind to a specific antigen can be isolated using a VH or VL domain derived from an antibody that binds to the antigen and screening a library of complementary VL or VH domains, respectively (see, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991)).

[0103] The provided antibodies include antibody fragments. An "antibody fragment" can refer to a molecule other than a complete antibody that contains a portion of the complete antibody that binds to the antigen to which the complete 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 containing a variable heavy chain region and / or a variable light chain region, such as an scFv. Antibody fragments can be produced by various techniques, including, but not limited to, proteolytic digestion of complete antibodies and production by recombinant host cells. In some embodiments, the antibody is a recombinantly produced fragment, a fragment containing a non-naturally occurring sequence, e.g., one having two or more antibody regions or chains linked by a synthetic linker, e.g., a polypeptide linker, and / or one not produced by enzymatic digestion of a naturally occurring complete antibody.

[0104] "Binding moiety" refers to a portion of a molecule, peptide, polypeptide, antibody, or antibody fragment that mediates specific binding to a recited target or antigen or epitope. By way of example, the binding portion of an antibody may comprise a heavy / light chain variable region pair or one or more complementarity determining regions (CDRs).

[0105] As referred to herein, a "target" refers to the portion of a molecule that engages the binding moiety of the molecule: a peptide, polypeptide, antibody, or antibody fragment. A target may include an amino acid sequence and / or a carbohydrate, lipid, or other chemical entity. An "antigen" is a target that includes a portion that can be bound by an adaptive immune molecule, such as an antibody or antibody fragment, a B-cell receptor, or a T-cell receptor.

[0106] As referred to herein, an "epitope" refers to one or more contact regions of an antibody. An antibody contact region consists of noncontiguous amino acids where contact residues and contiguous adjacent residues of the antibody (generally CDR residues) contact each other. For example, a contact region can consist of a contiguous stretch of the target protein of between 5 and 20 amino acids, between 5 and 15 amino acids, or between 5 and 10 amino acids. An antibody may bind to multiple contact regions separated by 10, 20, 30, 40, 50, 75, or 100 or more amino acids as a result of protein folding. Epitopes can be determined using X-ray crystallography, hydrogen-deuterium exchange mass spectrometry, alanine-spanning mutagenesis, competition with excess synthetic peptides, as determined by immunoblotting, ELISA, surface plasmon emission, flow cytometry, or any other suitable protein binding assay.

[0107] The terms "cross-compete" or "cross-competes" are used interchangeably herein and refer to the ability of an antibody or antigen-binding fragment thereof to interfere with the direct or indirect 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) via allosteric modulation. The extent to which an antibody or antigen-binding fragment thereof can interfere with the binding of another antibody or antigen-binding fragment thereof to a target, and therefore whether an antibody or antigen-binding fragment thereof can be said to cross-compete, can be determined using one or more competitive binding assays. One example of a competitive binding assay is Homogeneous Time Resolved Fluorescence (HTRF). Another example of a competitive binding assay is epitope binning analysis performed using surface plasmon resonance (SPR).

[0108] A "humanized" antibody is an antibody in which all or substantially all CDR amino acid residues are derived from non-human CDRs and all or substantially all FR amino acid residues are derived from human FRs. A humanized antibody may optionally contain at least a portion of an antibody constant region derived from a human antibody. A "humanized form" of a non-human antibody refers to a variant of a non-human antibody that has undergone humanization, typically to reduce immunogenicity to humans, while retaining the specificity and affinity of the parent non-human antibody. In some embodiments, some FR residues in a humanized antibody are substituted with corresponding residues from a non-human antibody (e.g., the antibody from which the CDR residues are derived), e.g., to restore or improve antibody specificity or affinity.

[0109] Among the antibodies provided are human antibodies. A "human antibody" is an antibody having an amino acid sequence corresponding to that of an antibody produced by a human or human cell, or a non-human source, utilizing a human antibody repertoire or other human antibody-encoding sequences, including a human antibody library. The term excludes humanized forms of non-human antibodies, including those in which all or substantially all CDRs are non-human, containing non-human antigen-binding regions. Human antibodies can be prepared by administering an immunogen to transgenic animals that have been modified to produce intact human antibodies or intact antibodies with human variable regions in response to antigen challenge. Such animals typically contain all or part of human immunoglobulin loci that replace endogenous immunoglobulin loci or that are present extrachromosomally or randomly integrated into the animal's chromosomes. In such transgenic animals, the endogenous immunoglobulin loci are generally inactivated. Human antibodies can also be derived from human antibody libraries, including phage display and cell-free libraries, containing antibody-encoding sequences derived from the human repertoire.

[0110] As used herein, "ADCC" or "antibody-dependent cell-mediated cytotoxicity" refers to a cell-mediated reaction in which nonspecific cytotoxic cells expressing FcγR recognize bound antibodies on target cells, subsequently causing lysis of the target cells. ADCC can be correlated with binding to FcγRIIIa, where increased binding to FcγRIIIa results in increased ADCC activity. "ADCP" or antibody-dependent cell-mediated phagocytosis, as used herein, can refer to a cell-mediated reaction in which nonspecific cytotoxic cells expressing FcγR recognize bound antibodies on target cells, subsequently causing phagocytosis of the target cells.

[0111] The terms "polypeptide" and "protein" are used interchangeably and refer to a polymer of amino acid residues and are not limited to a minimum length. Polypeptides, including the provided antibodies and antibody chains and other peptides, e.g., linkers and connecting peptides, can contain amino acid residues, including natural and / or unnatural amino acid residues. The term also includes post-expression modifications of the polypeptide, e.g., glycosylation, sialylation, acetylation, phosphorylation, etc. In some embodiments, a polypeptide can contain modifications relative to its native or native sequence, so long as the protein maintains the desired activity. These modifications can be deliberate, such as by site-directed mutagenesis, or can be accidental, such as by mutations of the host producing the protein or by errors in PCR amplification.

[0112] The percent sequence identity (%) to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical to those in the reference polypeptide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity; any conservative substitutions are not considered as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in a variety of known ways, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Appropriate parameters for aligning sequences, including the algorithm required to achieve maximum alignment over the entire length of the sequences being compared, can be determined. However, for purposes of this specification, percent amino acid sequence identity values ​​are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was created by Genentech, Inc., and the source code has been submitted, along with user documentation, to the U.S. Copyright Office, Washington, DC 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, Calif., or can be compiled from source code. The ALIGN-2 program should be compiled for use on UNIX operating systems, including Digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.In situations where ALIGN-2 is utilized for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (alternatively, it can be expressed as a given amino acid sequence A having or containing a particular % amino acid sequence identity to, with, or 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 by the sequence alignment program ALIGN-2 as identical matches in that program's alignment of A and B, and Y is the total number of amino acid residues in B. It will be understood that if the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. Unless otherwise specified, all % amino acid sequence identity values ​​used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0113] Amino acid sequence variants of the antibodies provided herein are contemplated and may be devised. Variants typically differ from the polypeptides specifically disclosed herein in one or more substitutions, deletions, additions, and / or insertions. Such variants may be naturally occurring or may be synthetically produced, for example, by modifying one or more of the above polypeptide sequences of the present invention and evaluating one or more biological activities of the polypeptides described herein, and / or using any of several known techniques. For example, it may be desirable to improve the binding affinity and / or other biological properties of antibody amino acid sequence variants of the antibody, which may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, deletions from, and / or insertions into, and / or substitutions of residues within the amino acid sequence of the antibody. Any combination of deletions, insertions, and substitutions may be made to arrive at the final construct, provided that the final construct possesses the desired characteristics, e.g., antigen binding. Antibody variants with one or more amino acid substitutions may be provided. Target sites for substitutional mutagenesis include CDRs and FRs. Amino acid substitutions can be introduced into the antibody of interest and the products screened for a desired activity, e.g., retained / improved antigen binding, reduced immunogenicity, or improved ADCC or CDC.

[0114] Conservative amino acid substitutions are those in which an amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues with similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., arginine, lysine, and histidine), acidic side chains (e.g., aspartic acid and glutamic acid), uncharged polar side chains (e.g., asparagine, cysteine, glutamine, glycine, serine, threonine, tyrosine, and tryptophan), nonpolar side chains (e.g., alanine, isoleucine, leucine, methionine, phenylalanine, proline, and valine), beta-branched side chains (e.g., isoleucine, threonine, and valine), and aromatic side chains (e.g., histidine, phenylalanine, tryptophan, and tyrosine) and aromatic side chains (e.g., histidine, phenylalanine, tryptophan, and tyrosine). Exemplary conservative amino acid substitutions are listed in Table 17.

[0115] [Table 17]

[0116] The antibodies described herein can be encoded by nucleic acids. A nucleic acid is a type of polynucleotide containing two or more nucleotide bases. In certain embodiments, a 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 linked nucleic acid. One type of vector is a genomic integration vector or "integration vector," which can be integrated into the chromosomal DNA of a host cell. Another type of vector is an "episomal" vector, e.g., a nucleic acid capable of extrachromosomal replication. Vectors capable of directing the expression of an operably linked gene are referred to herein as "expression vectors." Suitable vectors include plasmids, bacterial artificial chromosomes, yeast artificial chromosomes, viral vectors, and the like. In expression vectors, regulatory elements such as promoters, enhancers, and polyadenylation signals used to control transcription can be derived from mammalian, microbial, viral, or insect genes. The ability to replicate in a host is usually conferred by an origin of replication, and a selection gene can be further incorporated to facilitate recognition of transformed cells. For example, vectors derived from viruses such as lentivirus, retrovirus, adenovirus, and adeno-associated virus may be utilized. Plasmid vectors may be linearized for integration into chromosomal locations. Vectors may contain sequences that direct site-specific integration (e.g., AttP-AttB recombination) into a defined location or a limited set of sites in the genome. Additionally, vectors may contain sequences derived from transposable elements.

[0117] The nucleic acids encoding the antibodies described herein can be used to infect, transfect, transform, or otherwise transgenic suitable cells, thereby enabling the production of antibodies for commercial or therapeutic use. Standard cell lines and methods for producing antibodies from large-scale cell culture are known in the art. See, for example, Li et al., "Cell culture processes for monoclonal antibody production." Mabs. 2010 Sep-Oct; 2(5): 466-47. In certain embodiments, the cells are eukaryotic cells. In certain embodiments, the eukaryotic cells are mammalian cells. In certain embodiments, the mammalian cells are cell lines useful for producing antibodies, such as Chinese hamster ovary (CHO) cells, NS0 mouse myeloma cells, or PER.C6® cells. In certain embodiments, the nucleic acids encoding the antibodies are integrated into the genomic loci of cells useful for producing antibodies. In certain embodiments, methods of making an antibody are described herein that include culturing a cell containing nucleic acid encoding the antibody under in vitro conditions sufficient to allow the production and secretion of the antibody.

[0118] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. [Example]

[0119] The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention.

[0120] Example 1: Humanization of a murine anti-CD122 antibody To facilitate the identification of anti-CD122 antibodies that can be used in human subjects, mouse monoclonal anti-CD122 antibodies are used as the starting point for antibody sequence analysis and homology modeling of antibody three-dimensional (3D) structure.This process is used to design humanized forms of anti-CD122 antibodies, produce designed antibodies, and then test the functional properties of the antibodies.This process of designing and constructing humanized VH and VL genes is described in (Tsurishita et al.2005;Methods 36:69-83).

[0121] The VH and VL regions of a mouse monoclonal anti-CD122 antibody were substituted into both human IgG1 and human IgG4 scaffolds to generate parent chimeric sequences. Sequence analysis and homology modeling of the 3D antibody structure were performed to identify key positions supporting the CDR loop structure and the VH-VL interface. These results were used to determine specific amino acid substitutions for selection in the design of humanized variants of the VH and VL regions. Three VH variants and three VL variants were selected based on the modeling results and further tested in both IgG1 and IgG4 scaffolds. Each HC-LC pairing was reformatted in two ways: using human IgG1 (G1M17 allotype) and human IgG4 (S228P isotype) scaffolds. Various regions of the parent mouse were similarly reformatted as hIgG1 or hIgG4 chimeras. Gene sequences encoding each designed VH and VL region were constructed for subsequent cloning into mammalian expression vectors.

[0122] The humanity of each pairing of one VH variant with one VL variant in both the IgG1 and IgG4 backbones was assessed using the T20 humanity score (Gao et al. 2013, BMC Biotechnol. 13:55). A sufficiently high T20 score indicates the potential to eliminate immunogenicity issues to the same extent as using fully human antibodies in human subjects.

[0123] The humanity scores for parental and humanized antibodies are shown in Table 18 (heavy chain) and Table 19 (kappa light chain). Based on this method, a score of 84 or higher indicates a human-like heavy chain framework, and a score of 90 or higher indicates humanity of the kappa light chain framework. For full-length variable regions, a cutoff of 79 for VH and 86 for VL is recommended. In some embodiments, the variable light chain region is referred to as the VK region.

[0124] [Table 18]

[0125] [Table 19]

[0126] result: The T20 Analyzer humanity scores ranged from 81 to 88 for the humanized full-length variable regions (VH and VK) and from 90 to 99 for the humanized variable region frameworks, exceeding the humanity threshold. The Hu5-LC1 full-length sequence fell below the recommended cutoff score of 86.

[0127] A tendency of the VK sequence to undergo isomerization was identified. Asp in DGTLK (parent sequence) has the potential to undergo isomerization in the framework region. This tendency was eliminated in the humanized variant.

[0128] Production:

[0129] Two parental chimeric Fab variants and 18 humanized Fab variants were transiently produced using 0.01 L in CHO cells (an extended 14-day process with TunaCHO™) and purified by affinity-based purification of protein A. Endotoxin levels were assayed, and seven of the 18 humanized Fab variants were also produced in a second production batch. Because production yield can be important for the use of these antibodies, a second production batch was performed on a portion of the antibodies to compare yields.

[0130] Binding Affinities of Chimeric and Humanized Antibodies: Nineteen antibodies were assayed for binding to human CD122 (huCD122). Their affinity (KD) values ​​are reported in the summary table below and on the subsequent slides, along with the sensorgrams. Humanized variants from both batches showed less than a three-fold change in KD values ​​compared to the parent chimera.

[0131] Based on Bio-Layer Interferometry (BLI), the Octet® BLI system is a fluidics-free instrument platform that enables real-time, label-free analysis for determining kinetics, affinity, and antibody / protein quantification. Binding experiments were performed at 25°C on an Octet HTX. The analyte used was huCD122-HIS (ARCO Bio|Cat. No. CD2-H5221) with a molecular weight of 25.4 kDa. The antibody was loaded onto an anti-human Fc capture (AHC) sensor. The loaded sensor was immersed in serial dilutions of huCD122-His (starting at 20 nM, 1:3 dilutions, 4 points). A reference sample well (buffer) was used for data analysis. Rate 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 anti-CD122 antibody binding and dissociation characteristics: 0.0 nM, 2.2 nM, 6.7 nM, and 20 nM. Sensorgram plots showing the antibody binding characteristics were generated. The mouse parent chimeric constructs (M5 IgG1 parent and M5 IgG4 parent) in both IgG1 and IgG4 backbones, as well as each combination of the humanized 3HC and 3LC variants in either the IgG1 or IgG4 backbone, were tested. Sensorgram plots for each variant are shown in Figures 1-10.

[0132] The binding affinities of the antibodies tested are listed in Table 20.

[0133] [Table 20]

[0134] result: Comparing the binding affinities for various HC and LC paired antibodies (G1-G20), many of the humanized versions exhibited 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 7.27 E -10 The KD value of the humanized IgG1 variants (G2 to G10) was 1.78E -09 ~7.54E -10 The measured KD value of the parental IgG4 chimera in G11 mice was 7.95E -10 and 8.66E -10 (2nd batch). The KD value of the humanized IgG4 variants (G12 to G20) was 2.57E -09 ~6.98E -10 Robust production yields of all antibody variants were also achieved. These features, along with the high T20 humanity scores attributed to each variant VH or VL domain, indicated high-affinity humanized versions of anti-CD122 antibodies with low potential for immunogenic complications when used in human subjects.

[0135] Example 2: Inhibition of IL2-mediated proliferation in vitro by humanized anti-CD122 antibodies The ability of humanized anti-CD122 antibodies to inhibit proliferation was tested in vitro. TF-1 (ATCC, Manassas, VA), a human cell line originally established from bone marrow cells of a subject with erythroleukemia, 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 for proliferation. TF-1 expresses the common γ-chain IL receptor (CD132) but not the β-chain IL2 / IL15 receptor (CD122). Expression of the CD122 expression gene in TF-1 allows for the expression of intermediate- and high-affinity IL2 and IL15 receptors. TF-1-CD122 cells were generated by transfecting TF-1 with a mammalian expression vector carrying a gene encoding human CD122 and a puromycin resistance gene.

[0136] The ability of anti-CD122 monoclonal antibody variants to inhibit IL2-mediated cell proliferation is examined using TF-CD122 cells. Prior to the experiment, TF-CD122 cells are cultured in RPMI 1640 (ThermoFisher Scientific, Cat. No. 11875093) supplemented with 10% heat-inactivated FBS, 50 IU / mL IL2, 2 mM l-glutamine, 50 U / mL penicillin, and 50 μg / mL streptomycin. Cells are maintained at 37°C in a humidified 5% CO2 atmosphere. In a typical experiment, TF-1-CD122 cells are first deprived of IL2 for 2 days. Approximately 10 cells per well are then cultured. 4Cells were incubated with serial dilutions of anti-CD122 monoclonal antibody variants (G1-G20) at concentrations between 0.1 and 10.0 μg / mL. Control wells contained three control conditions: 1) no antibody + 50 IU / mL IL2, 2) InVivoMAb human IgG1 isotype control (BioXCell, NH, catalog no. BE0297) at a concentration compatible with the serial dilutions, or 3) human IgG4κ (S228P) isotype control - CrownVivo™ antibody (MBL International Corp, MA, catalog no. C0045) at a concentration compatible with the serial dilutions. Treatment with anti-CD122 monoclonal antibody variants G1-G20 (or control conditions) was maintained at 37°C for 10 minutes, after which 50 IU / mL IL2 was added to the medium. Cells were then cultured for 48 hours. Next, 20 μL of alamarBlue™ cell viability reagent (ThermoFisher Scientific, Catalog No. DAL1025) is added per well and the plate is incubated for 6 hours. After washing the wells, the plate is read at 540 nm and 620 nm using a spectrophotometer microplate reader. Growth curves are obtained following the manufacturer's recommendations.

[0137] Example 3: Inhibition of IL15-mediated proliferation in vitro by humanized anti-CD122 antibodies The ability of humanized anti-CD122 antibodies to inhibit proliferation was tested in vitro. 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 simulate in-trans presentation of IL15, a soluble complex of human IL15 bound to a portion of the extracellular domain of human IL15Ra (scIL15 / IL15Ra) was constructed as described below (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 could support the proliferation of TF-CD122 cells. Cells are maintained at 37°C in a humidified 5% CO2 atmosphere. In a typical experiment, TF-1-CD122 cells are first deprived of scIL15 / IL15Ra for 2 days. Approximately 10 cells per well are then cultured. 4Cells were incubated with serial dilutions of anti-CD122 monoclonal antibody variants (G1-G20) at concentrations between 0.1 μg / mL and 10.0 μg / mL. Control wells contained three control conditions: 1) no antibody + 10 nM scIL15 / IL15Ra, 2) InVivoMAb human IgG1 isotype control (BioXCell, NH, catalog no. BE0297) at a concentration compatible with the serial dilutions, or 3) human IgG4κ (S228P) isotype control - CrownVivo™ antibody (MBL International Corp, MA, catalog no. C0045) at a concentration compatible with the serial dilutions. Treatment with anti-CD122 monoclonal antibody variants G1-G20 (or control condition) was maintained at 37°C for 10 minutes, followed by the addition of 10 nM scIL15 / IL15Ra IL2 to the medium. Cells were then cultured for 48 hours. Next, 20 μL of alamarBlue™ cell viability reagent (ThermoFisher Scientific, Catalog No. DAL1025) is added per well and the plate is incubated for 6 hours. After washing the wells, the plate is read at 540 nm and 620 nm using a spectrophotometer microplate reader. Growth curves are obtained following the manufacturer's recommendations.

[0138] Example 4: Inhibition of IL2 and IL15 signaling by anti-CD122 antibodies Several anti-CD122 antibodies described herein were tested for their ability to inhibit IL2 and / or IL15 signaling using an in vitro assay. A reporter cell line expressing the βγ receptor (CD122 / CD132) for IL2 and IL15, which has intermediate affinity for IL2 and IL15, respectively, and luciferase mediated by IL2 and IL15 binding to the receptor was used to test the ability of anti-CD122 antibodies to inhibit IL2 and / or IL15 signaling. In Figure 11, three anti-CD122 antibodies were assayed for their ability to inhibit IL2 and / or IL15 signaling. Reporter cells were treated with either IL2 (12.5 ng / mL) or IL15 (6 ng / mL) and then treated with anti-CD122 antibodies at 10 different antibody concentrations ranging from 10 μg / mL to 0.5 ng / mL. The anti-CD122 antibody designated as Commercial, used as a positive control in this experiment, is anti-human CD122 antibody clone TU27 obtained from BioLegend®, catalog number 339015. Antibody 1 and Antibody 2 are humanized anti-human CD122 antibodies. Antibody 1 is a humanized monoclonal antibody described herein that contains the CDR sequences of CDR series E7 listed in Table 3. Antibody 2 is a known anti-CD122 humanized monoclonal antibody that contains a VH domain and a VL domain, wherein the VH domain contains an HCDR1 comprising the sequence of SEQ ID NO: 189, an HCDR2 comprising the sequence of SEQ ID NO: 190, and an HCDR3 comprising the sequence of SEQ ID NO: 191, and the VL domain contains an LCDR1 comprising the sequence of SEQ ID NO: 192, an LCDR2 comprising the sequence of SEQ ID NO: 193, and an LCDR3 comprising the sequence of SEQ ID NO: 194.

[0139] Results from a negative control for these experiments are shown in the graph in Figure 11 , where cells were treated with either IL2 alone (top graph) or IL15 alone (bottom graph) without any anti-CD122 antibody co-treatment, and the luminescence signal of the cell-based reporter assay was plotted as relative luminescence units (RLU) values. Results from another negative control for these experiments are shown in the graph in Figure 11 , where cells were not treated with IL2 or IL15, nor with anti-CD122 antibody. Measurements of IL2 / IL15 signaling (calculated using a dose-response curve with test doses ranging from 10 μg / mL to 1.5 ng / mL in a dilution series) following co-treatment with anti-CD122 antibody (12.5 and 6 ng / mL, respectively) were plotted in RLU as a function of anti-CD122 antibody concentration (μg / mL, log scale). Median effective dose (EC) of IL2 and / or IL15 antagonists (anti-CD122 antibodies) to reduce IL2 and / or IL15 signaling in response to IL2 or IL15 treatment 50 ) was calculated to determine the effects of the tested anti-CD122 antibodies. The results in Figure 11 demonstrate that antibody 1 is a more potent inhibitor of IL2 signaling and IL15 signaling than the commercially available antibody or antibody 2. Antibody 1 was able to inhibit both IL2 signaling and IL15 signaling 3-5 times more efficiently than antibody 2 in this assay. These results also demonstrate the inhibition of βγ receptors (CD122 / CD132) using the tested anti-CD122 antibodies, with antibody 1 being the most efficient inhibitor.

[0140] In another in vitro assay, the ability of anti-CD122 antibody to inhibit IL2-mediated cell proliferation was tested using the TF-1αβ cell line, which expresses the αβγ receptor for IL2 (IL2Rα / IL2Rβ / IL2Rγ complex), which has high affinity for IL2. In Figure 12, cells were treated with IL2 at a dose of 10 ng / mL and also with anti-CD122 antibody at six different antibody concentrations, ranging from 30 μg / mL to 30 ng / mL. Results are plotted as the percentage of inhibition of cell proliferation compared to no antibody treatment at each concentration of anti-CD122 antibody. The plotted data indicate that neither Antibody 2 nor Antibody 1 are efficient inhibitors of the αβγ receptor.

[0141] Example 5: IL2 Interleukin Receptor β Epitope Mapping Using Humanized Anti-CD122 Antibody In this example, the objective was to map the epitope interactions of the humanized monoclonal antibodies (Mabs) described herein with human IL2 interleukin receptor β (IL2RB) using plasma-induced biomolecule modification (PLIMB) technology.

[0142] Experimental design and methods:

[0143] Optimization of PLIMB and MS: The level of antigen modification in response to several PLIMB-induced hydroxyl radical exposure doses was monitored, followed by epitope mapping. Samples were prepared and exposed to PLIMB for 20 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.

[0144] Epitope mapping of IL2RB: Differences in solvent accessibility were measured for the antigen (IL2RB) using trifluoromethyl radicals (CF3) generated via PLIMB exposure. First, two solutions were prepared for epitope mapping of IL2RB. The first solution contained IL2RB from NIST and a non-binding standard IgG control antibody. The second solution contained a humanized anti-CD122 mAb added at a 1:1 antibody / antigen molar ratio. The IL2RB sample with the NIST antibody is referred to as "unbound," while the sample with the humanized anti-CD122 mAb is referred to as "bound" or "complex." Residue-level analysis of peptides within candidate epitope regions was used to determine which individually labeled amino acids showed the greatest change in solvent accessibility upon binding. Individual residues within the epitope region that showed changes in solvent accessibility upon binding represent "hot spots," which can be used to further identify regions involved in antigen / antibody epitope interactions.

[0145] result:

[0146] IL2RB labeling and coverage

[0147] The study described in this example focuses on the beta subunit (IL2RB) of the interleukin-2 receptor (IL2R). IL2RB in this example contains the extracellular domain (A26-D239). Analysis of PLIMB-exposed samples showed sufficient labeling of all regions of IL2RB across the entire protein sequence at both 20 and 40 seconds.

[0148] IL2RB epitope determination

[0149] Residue-level analysis was performed across the entire length of the IL2RB primary sequence of PLIMB-treated samples prepared in the unbound state with a control antibody (NIST) and in the bound state with a humanized anti-CD122 MAb to detect differences in solvent accessibility (modification level) upon complex formation (Figure 13). Figure 13 shows the annotation / numbering based on the extracellular IL2RB form of the protein used in this example, which corresponds to [A26-D239] in the standard sequence (UniProt ID: P14784). The amino acid residues labeled for epitope mapping in this example are labeled according to their amino acid positions within 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). Bolded residues show significant changes in solvent accessibility (unlabeled residues between significantly altered residues are included to indicate the epitope region). Underlined residues indicate the epitope region. Residues within the frame (contained within the frame) exhibit conformational changes.

[0150] Changes in solvent accessibility were mapped onto the IL2RB crystal structure and displayed as fold changes with statistical significance (Figures 15 and 14). Protection or reduction of labeling in the experimental antibody compared to the control indicates epitope interaction. Figure 14 shows a heat map of modification changes for bound humanized anti-CD122 MAb versus unbound IL2RB. Log 2 fold changes are for humanized anti-CD122 MAb (bound) versus NIST control antibody (unbound) incubated with IL2RB at 20 and 40 seconds PLIMB time points. Green indicates a decrease, and red indicates an increase. Significant changes (p<0.05) are indicated by a shaded box in the t-test column.

[0151] High-resolution footprinting analysis using PLIMB-induced CF3 radical labeling revealed multiple residue "hot spots" on IL2RB under antibody "bound" conditions. These "hot spots" 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 mapping the 3D crystal structure, 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). All of these regions map to the IL2-binding interface within the 3D crystal structure (Figure 15). Furthermore, these regions showed relatively consistent changes over both 20 and 40 seconds of PLIMB exposure, representing a more stable interaction, indicative of the epitope / antibody binding region.

[0152] Additional "hot spots" were mapped to regions outside the IL2-binding interface. These "hot spots" correspond to distal conformational changes and do not correspond to epitope regions. This determination was based on the relative extent of the hot spots' changes, which are generally smaller than those involved in direct antibody binding, and their relative isolation from other "hot spot" clusters. The locations mapped as sites of conformational changes include: 1) residues 89-91 (VRW), 2) residue 153 (W), and 3) residue 192 (F).

[0153] In conclusion, distinct residues involved in the binding of humanized anti-CD122 antibodies to IL2RB, located primarily in the IL2-binding face of IL2RB, have been identified.

[0154] Summary of method:

[0155] Sample preparation, PLIMB treatment, and LC-MS / MS analysis: Humanized anti-CD122 MAb and NIST antibody were incubated with IL2RB at room temperature for 1 hour to promote binding. For trifluoromethylation labeling (CF3), samples were exposed to PLIMB treatment for 20 and 40 seconds in the presence of 50 mM sodium triflate and 10 mM hydrogen peroxide (three to five replicates per condition). After labeling, samples were quenched with 5 μL of a 250 mM methionine solution in PBS (pH 7.4).

[0156] After PLIMB exposure, samples were proteolytically digested into peptides with sequential trypsin and elastase digestions. 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 on an Orbitrap Exploris 240 mass spectrometer.

[0157] Data Analysis:

[0158] The ".raw" data files were searched against the IL2RB sequence using the database search engine MetaMorpheus. A list of standard expected modifications and expected PLIMB modifications was utilized for the database search. Peptides were identified using MS and MS / MS spectra with a 1% false discovery rate (FDR) cutoff. Changes in solvent accessibility for both trypsin-digested and trypsin-elastase-digested samples were determined by comparing the sum of normalized TMT channel intensities for the control antibody versus the humanized anti-CD122-targeted Mab. The reported changes in solvent accessibility were derived from the trypsin-elastase-digested samples. These changes were confirmed by examination of the trypsin-digested samples.

[0159] Statistical analysis:

[0160] Fold changes were calculated for IL2RB peptides in the humanized anti-CD122 MAb-bound and unbound states, and Student's t-test was performed for each peptide. p<0.05 was considered a significant change.

[0161] Summary of experimental conditions: Antigen sample: human IL2RB (A26-D239), His tag (Acro Biosystems) ·Antigen concentration: 0.1mg / mL (2.7μM) Control antibody (NIST) concentration: 0.42 mg / mL (2.7 μM) Experimental antibody concentration: 0.42 mg / mL (2.7 μM) ·Antibody / antigen ratio: 1:1 Experimental sample volume: 50 μL Sample buffer: 100mM PBS, pH 7.4 Proteases used: platinum trypsin (Promega) and elastase (Promega) ·Equipment: Thermo Orbitrap Exploris 240 Data processing software: MetaMorpheus

[0162] Detailed method:

[0163] Sample preparation and digestion:

[0164] After PLIMB treatment, samples were denatured and reduced with 8 M guanidine HCl (GnHCl) containing 5 mM TCEP. The samples were heated to 90 °C for 15 min and then cooled. The samples were alkylated with 15 mM IAA for 30 min at room temperature in the dark. The samples were diluted in 1.5 M GnHCl and subjected to trypsin (Promega) digestion overnight at 37 °C at a 1:10 total protease / protein mass ratio. The reaction was quenched by the addition of 2% trifluoroacetic acid, followed by desalting and cleanup using Empore C18 StageTips (CDS Analytical) using standard protocols. Half of the eluted peptides were dried in a vacuum concentrator and resuspended in 0.1% formic acid for LC-MS / MS analysis. The remaining sample was resuspended in 100 mM Tris-HCl and subjected to secondary digestion with elastase (Promega) at a 1:20 ratio for 4 h at 37 °C. After quenching, peptides were desalted, dried, and resuspended in 50 mM HEPES buffer at pH 8.5. Samples were labeled with tandem mass tags (6-plex TMT, ThermoFisher) according to the manufacturer's protocol.

[0165] LC-MS / MS acquisition

[0166] A 60-minute chromatographic gradient from 2–40% acetonitrile containing 0.1% formic acid was used for separation on a 2 μM, 15 cm Easy-Spray PepMap C18 column from ThermoFisher Scientific. MS1 parameters in the Orbitrap were 60K resolution, a scan range of 350–1200 m / z, a normalized AGC target of 300%, and charge states 1–6 selected. 2 Data-dependent acquisition of the top 10 was performed with the following parameters: quadrupole isolation window of 2 Da, HCD step collision energy of 28%, 36%, and 42%, normalized AGC value of 50%, and an automatic scan range starting at m / z 110. Dynamic exclusion of 6 seconds was used after one ion confirmation.

[0167] Data Analysis:

[0168] The following modifications were used in our MetaMorpheus searches:

[0169] Standard modifications: Carbamidomethyl / +57.021464 PLIMB modification in C (fixed): Oxidation in C, F, H, I, L, M, W, Y / +15.994915 ·C, F, M, W, Y dioxide / +31.989829 Cis-oxidation at C / +15.994915-57.021464 Cis-dioxide in C / +31.989829-57.021464 ·Cis-trioxide / +47.984745-57.021464 Nitro in W, Y / +44.985078 Trifluoromethylation of A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y / +67.9874 Di-trifluoromethylation in A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, Y / +135.9748 Cis-trifluoromethylation in C / +67.9874-57.021464

[0170] Summary of results:

[0171] The epitope of human interleukin-2 receptor β (IL2RB) with a humanized anti-CD122 MAb was mapped using PLIMB-generated hydroxyl (OH) and trifluoromethyl (CF3) labels. The resulting epitope is conformational rather than linear. The mapped epitopes are contained within the following regions: W39-D41, V76-L81, F99-L105, and H134-H139. These cluster on distinct interfaces of the IL2RB protein. The mapped conformational epitopes cover a region that significantly overlaps with the IL2 / IL2RB binding interface, suggesting that the antibody is an effective IL2RB antagonist.

[0172] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be utilized in practicing the invention. The following claims define the scope of the invention, and it is intended that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0173] Aspects Embodiment 1: An antibody that binds to CD122, wherein the antibody 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.

[0174] Embodiment 2: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the antibody or 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.

[0175] Embodiment 3: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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: 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.

[0176] Embodiment 4: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0177] Embodiment 5: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0178] Embodiment 6: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0179] Embodiment 7: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0180] Embodiment 8: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0181] Embodiment 9: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0182] Embodiment 10: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0183] Embodiment 11: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0184] Embodiment 12: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0185] Embodiment 13: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0186] Embodiment 14: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0187] Embodiment 15: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0188] Embodiment 16: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0189] Embodiment 17: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0190] Embodiment 18: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0191] Embodiment 19: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0192] Embodiment 20: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0193] Embodiment 21: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0194] Embodiment 22: An antibody or antigen-binding fragment thereof that binds to CD122, wherein the 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.

[0195] Embodiment 23: The antibody according to any one of embodiments 1 to 22, wherein the antibody is a monoclonal antibody.

[0196] Embodiment 24: The antibody according to any one of embodiments 1 to 23, wherein the antibody is a humanized monoclonal antibody.

[0197] Embodiment 25: The antibody according to any one of embodiments 1 to 23, wherein the antibody is a human antibody.

[0198] Embodiment 26: The antibody or antigen-binding fragment thereof according to any one of embodiments 1 to 25, wherein the CD122 is mammalian CD122.

[0199] Embodiment 27: The antibody or antigen-binding fragment thereof according to any one of embodiments 1 to 26, wherein CD122 is murine CD122.

[0200] Embodiment 28: The antibody or antigen-binding fragment thereof according to any one of embodiments 1 to 26, wherein CD122 is human CD122.

[0201] Aspect 29: Nanomolar range (10 -7 ~10 -9 K of M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity of

[0202] Aspect 30: Binding affinity in the low nanomolar range (10 -9 K of M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with an IgG value (IgG1 / IgG2).

[0203] Aspect 31: Picomolar range (10 -10 ~10 -12 K of M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity of

[0204] Aspect 32: High picomolar range (10 -10 K of M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity of

[0205] Aspect 33: Low nanomolar range to high picomolar range (10 -9 ~10 -10 K of M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity within the range of

[0206] Aspect 34: Approximately 3E -09 K less than M D29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0207] Aspect 35: Approximately 2E -09 K less than M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0208] Aspect 36: Approximately 1E -09 K less than M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0209] Aspect 37: Approximately 9E -10 K less than M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0210] Aspect 38: Approximately 8E -10 K less than M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0211] Aspect 39: Approximately 5E -09 ~5E -10 K between M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0212] Aspect 40: Approximately 3E -09 ~7E -10 K between M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0213] Aspect 41: Approximately 2E -09 ~8E -10 K between M D29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0214] Aspect 42: Approximately 1E -09 ~9E -10 K between M D 29. The antibody of any one of aspects 1 to 28, which binds to human CD122 protein with a binding affinity measured by:

[0215] Embodiment 43: An antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 134 and a light chain comprising the sequence of SEQ ID NO: 142.

[0216] Embodiment 44: An antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 135 and a light chain comprising the sequence of SEQ ID NO: 143.

[0217] Embodiment 45: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 135 and a light chain comprising the sequence of SEQ ID NO: 144.

[0218] Embodiment 46: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 135 and a light chain comprising the sequence of SEQ ID NO: 145.

[0219] Embodiment 47: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 136 and a light chain comprising the sequence of SEQ ID NO: 143.

[0220] Embodiment 48: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 136 and a light chain comprising the sequence of SEQ ID NO: 144.

[0221] Embodiment 49: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 136 and a light chain comprising the sequence of SEQ ID NO: 145.

[0222] Embodiment 50: An antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 137 and a light chain comprising the sequence of SEQ ID NO: 143.

[0223] Embodiment 51: An antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 137 and a light chain comprising the sequence of SEQ ID NO: 144.

[0224] Embodiment 52: An antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 137 and a light chain comprising the sequence of SEQ ID NO: 145.

[0225] Embodiment 53: An antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 138 and a light chain comprising the sequence of SEQ ID NO: 142.

[0226] Embodiment 54: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 139 and a light chain comprising the sequence of SEQ ID NO: 143.

[0227] Embodiment 55: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 139 and a light chain comprising the sequence of SEQ ID NO: 144.

[0228] Embodiment 56: An antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 139 and a light chain comprising the sequence of SEQ ID NO: 145.

[0229] Embodiment 57: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 140 and a light chain comprising the sequence of SEQ ID NO: 143.

[0230] Embodiment 58: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 140 and a light chain comprising the sequence of SEQ ID NO: 144.

[0231] Embodiment 59: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 140 and a light chain comprising the sequence of SEQ ID NO: 145.

[0232] Embodiment 60: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 141 and a light chain comprising the sequence of SEQ ID NO: 143.

[0233] Embodiment 61: An antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 141 and a light chain comprising the sequence of SEQ ID NO: 144.

[0234] Embodiment 62: The antibody according to any one of embodiments 1 to 42, wherein the antibody comprises a heavy chain comprising the sequence of SEQ ID NO: 141 and a light chain comprising the sequence of SEQ ID NO: 145.

[0235] Embodiment 63: An isolated monoclonal antibody, which, when bound to CD122, binds to at least one of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0236] Embodiment 64: An isolated monoclonal antibody according to embodiment 63, which, when bound to CD122, binds to at least two of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0237] Embodiment 65: An isolated monoclonal antibody according to embodiment 63 or 64, which, when bound to CD122, binds to at least three of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0238] Embodiment 66: An isolated monoclonal antibody according to any one of embodiments 63 to 65, wherein, when bound to CD122, the antibody binds to at least four of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0239] Embodiment 67: An isolated monoclonal antibody according to any one of embodiments 63 to 66, wherein when bound to CD122, the antibody binds to at least five of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0240] Embodiment 68: An isolated monoclonal antibody according to any one of embodiments 63 to 67, wherein, when bound to CD122, the antibody binds to at least six of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0241] Embodiment 69: An isolated monoclonal antibody according to any one of embodiments 63 to 68, which, when bound to CD122, binds to at least seven of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0242] Embodiment 70: An isolated monoclonal antibody according to any one of embodiments 63 to 69, wherein, when bound to CD122, the antibody binds to at least eight of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0243] Embodiment 71: An isolated monoclonal antibody according to any one of embodiments 63 to 70, which, when bound to CD122, binds to at least nine of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0244] Embodiment 72: An isolated monoclonal antibody according to any one of embodiments 63 to 71, wherein, when bound to CD122, the antibody binds to at least 10 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0245] Embodiment 73: An isolated monoclonal antibody according to any one of embodiments 63 to 72, wherein when bound to CD122, the antibody binds to at least eleven of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0246] Embodiment 74: An isolated monoclonal antibody according to any one of embodiments 63 to 73, wherein when bound to CD122, the antibody binds to at least 12 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0247] Embodiment 75: An isolated monoclonal antibody according to any one of embodiments 63 to 74, wherein, when bound to CD122, the antibody binds to at least 13 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0248] Embodiment 76: An isolated monoclonal antibody according to any one of embodiments 63 to 75, wherein, when bound to CD122, the antibody binds to at least 14 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0249] Embodiment 77: An isolated monoclonal antibody according to any one of embodiments 63 to 76, which, when bound to CD122, binds to at least 15 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0250] Embodiment 78: An isolated monoclonal antibody according to any one of embodiments 63 to 77, which, when bound to CD122, binds to at least 16 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0251] Embodiment 79: An isolated monoclonal antibody according to any one of embodiments 63 to 78, which, when bound to CD122, binds to at least 17 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0252] Embodiment 80: An isolated monoclonal antibody according to any one of embodiments 63 to 79, which, when bound to CD122, binds to at least 18 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0253] Embodiment 81: An isolated monoclonal antibody according to any one of embodiments 63 to 80, which, when bound to CD122, binds to at least 19 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0254] Embodiment 82: An isolated monoclonal antibody according to any one of embodiments 63 to 81, wherein, when bound to CD122, the monoclonal antibody binds to at least 20 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0255] Embodiment 83: An isolated monoclonal antibody according to any one of embodiments 63 to 82, which, when bound to CD122, binds to at least 21 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187.

[0256] Embodiment 84: An isolated monoclonal antibody according to any one of embodiments 63 to 83, which, when bound to CD122, binds to at least all 22 of the following residues: W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 and H139 of SEQ ID NO: 187.

[0257] Embodiment 85: An isolated monoclonal antibody according to any one of embodiments 63 to 84, which antibody binds to at least W39.

[0258] Embodiment 86: An isolated monoclonal antibody according to any one of embodiments 63 to 85, which antibody binds to at least P40.

[0259] Embodiment 87: An isolated monoclonal antibody according to any one of embodiments 63 to 86, which antibody binds to at least D41.

[0260] Embodiment 88: An isolated monoclonal antibody according to any one of embodiments 63 to 87, which antibody binds to at least V76.

[0261] Embodiment 89: An isolated monoclonal antibody according to any one of embodiments 63 to 88, which antibody binds to at least D77.

[0262] Embodiment 90: An isolated monoclonal antibody according to any one of embodiments 63 to 89, which antibody binds to at least I78.

[0263] Embodiment 91: An isolated monoclonal antibody according to any one of embodiments 63 to 90, which antibody binds to at least V79.

[0264] Embodiment 92: An isolated monoclonal antibody according to any one of embodiments 63 to 91, which antibody binds to at least T80.

[0265] Embodiment 93: An isolated monoclonal antibody according to any one of embodiments 63 to 92, which antibody binds to at least L81.

[0266] Embodiment 94: An isolated monoclonal antibody according to any one of embodiments 63 to 93, which antibody binds to at least F99.

[0267] Embodiment 95: An isolated monoclonal antibody according to any one of embodiments 63 to 94, which antibody binds to at least K100.

[0268] Embodiment 96: An isolated monoclonal antibody according to any one of embodiments 63 to 95, which antibody binds to at least P101.

[0269] Embodiment 97: An isolated monoclonal antibody according to any one of embodiments 63 to 96, which antibody binds to at least F102.

[0270] Embodiment 98: An isolated monoclonal antibody according to any one of embodiments 63 to 97, which antibody binds to at least E103.

[0271] Embodiment 99: An isolated monoclonal antibody according to any one of embodiments 63 to 98, which antibody binds to at least N104.

[0272] Embodiment 100: An isolated monoclonal antibody according to any one of embodiments 63 to 99, which antibody binds to at least L105.

[0273] Embodiment 101: An isolated monoclonal antibody according to any one of embodiments 63 to 100, which antibody binds to at least H134.

[0274] Embodiment 102: An isolated monoclonal antibody according to any one of embodiments 63 to 101, which antibody binds to at least Y135.

[0275] Embodiment 103: An isolated monoclonal antibody according to any one of embodiments 63 to 102, which antibody binds to at least F136.

[0276] Embodiment 104: An isolated monoclonal antibody according to any one of embodiments 63 to 103, which antibody binds to at least E137.

[0277] Embodiment 105: An isolated monoclonal antibody according to any one of embodiments 63 to 104, which antibody binds to at least R138.

[0278] Embodiment 106: An isolated monoclonal antibody according to any one of embodiments 63 to 105, which antibody binds to at least H139.

[0279] Embodiment 107: An isolated monoclonal antibody according to any one of embodiments 63 to 106, which blocks the binding of IL2 to CD122.

[0280] Embodiment 108: An isolated monoclonal antibody according to any one of embodiments 63 to 107, which antibody blocks the binding of IL15 to CD122.

[0281] Embodiment 109: An isolated monoclonal antibody according to any one of embodiments 63 to 108, which antibody blocks the binding of IL2 and IL15 to CD122.

[0282] Embodiment 110: An isolated monoclonal antibody according to any one of embodiments 63 to 109, which blocks the binding of IL2 to the intermediate affinity IL-βγ receptor complex.

[0283] Embodiment 111: An isolated monoclonal antibody according to any one of embodiments 63 to 110, which antibody blocks binding of the IL15 / IL15Rα complex to the intermediate affinity IL-βγ receptor complex.

[0284] Embodiment 112: An isolated monoclonal antibody according to any one of embodiments 63 to 111, which blocks the binding of IL2 and the IL15 / IL15Rα complex to the intermediate affinity IL-βγ receptor complex.

[0285] Embodiment 113: An isolated monoclonal antibody according to any one of embodiments 63 to 112, which is a human antibody.

[0286] Embodiment 114: An isolated monoclonal antibody according to any one of embodiments 63 to 113, which is a humanized antibody.

[0287] Aspect 115: Approximately 2E -09 K below M D 115. The isolated monoclonal antibody of any one of embodiments 63 to 114, wherein the antibody binds to CD122 at

[0288] Aspect 116: Approximately 1.5xE -09 K below M D 116. The isolated monoclonal antibody of any one of embodiments 63 to 115, wherein the antibody binds to CD122 at

[0289] Aspect 117: Approx. 1xE -09 K below M D 117. The isolated monoclonal antibody of any one of embodiments 63 to 116, wherein the antibody binds to CD122 at

[0290] Aspect 118: Approximately 9.5xE -10 K below M D 118. The isolated monoclonal antibody of any one of embodiments 63 to 117, wherein the antibody binds to CD122 at

[0291] Aspect 119: Approx. 9xE -10 K below M D 119. The isolated monoclonal antibody of any one of embodiments 63 to 118, wherein the antibody binds to CD122 at

[0292] Aspect 120: Approx. 8xE -10 K below M D 120. The isolated monoclonal antibody of any one of embodiments 63 to 119, wherein the antibody binds to CD122 at

[0293] Aspect 121: Approx. 7xE -10 K below M D 121. The isolated monoclonal antibody of any one of embodiments 63 to 120, which binds to CD122 at

[0294] Embodiment 122: An isolated monoclonal antibody according to any one of embodiments 63 to 121, wherein at least one of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprises an epitope on the extracellular domain of CD122.

[0295] Embodiment 123: An isolated monoclonal antibody according to any one of embodiments 63 to 122, wherein at least two of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0296] Embodiment 124: An isolated monoclonal antibody according to any one of embodiments 63 to 123, wherein at least three of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0297] Embodiment 125: An isolated monoclonal antibody according to any one of embodiments 63 to 124, wherein at least four of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0298] Embodiment 126: An isolated monoclonal antibody according to any one of embodiments 63 to 125, wherein at least five of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0299] Embodiment 127: An isolated monoclonal antibody according to any one of embodiments 63 to 126, wherein at least six of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0300] Embodiment 128: An isolated monoclonal antibody according to any one of embodiments 63 to 127, wherein at least seven of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0301] Embodiment 129: An isolated monoclonal antibody according to any one of embodiments 63 to 128, wherein at least eight of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0302] Embodiment 130: An isolated monoclonal antibody according to any one of embodiments 63 to 129, wherein at least nine of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0303] Embodiment 131: An isolated monoclonal antibody according to any one of embodiments 63 to 130, wherein at least ten of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0304] Embodiment 132: An isolated monoclonal antibody according to any one of embodiments 63 to 131, wherein at least eleven of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0305] Embodiment 133: An isolated monoclonal antibody according to any one of embodiments 63 to 132, wherein at least twelve of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0306] Embodiment 134: An isolated monoclonal antibody according to any one of embodiments 63 to 133, wherein at least thirteen of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0307] Embodiment 135: An isolated monoclonal antibody according to any one of embodiments 63 to 134, wherein at least fourteen of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0308] Embodiment 136: An isolated monoclonal antibody according to any one of embodiments 63 to 135, wherein at least fifteen of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0309] Embodiment 137: An isolated monoclonal antibody according to any one of embodiments 63 to 136, wherein at least sixteen of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0310] Embodiment 138: An isolated monoclonal antibody according to any one of embodiments 63 to 137, wherein at least seventeen of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0311] Embodiment 139: An isolated monoclonal antibody according to any one of embodiments 63 to 138, wherein at least eighteen of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0312] Embodiment 140: An isolated monoclonal antibody according to any one of embodiments 63 to 139, wherein at least 19 of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0313] Embodiment 141: An isolated monoclonal antibody according to any one of embodiments 63 to 140, wherein at least twenty of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0314] Embodiment 142: An isolated monoclonal antibody according to any one of embodiments 63 to 141, wherein at least twenty-one of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 comprise an epitope on the extracellular domain of CD122.

[0315] Embodiment 143: An isolated monoclonal antibody according to any one of embodiments 63 to 141, wherein at least twenty-two of residues W39, P40, D41, V76, D77, 178, V79, T80, L81, F99, K100, P101, F102, E103, N104, L105, H134, Y135, F136, E137, R138 or H139 of SEQ ID NO: 187 all comprise an epitope on the extracellular domain of CD122.

[0316] Embodiment 144: An isolated monoclonal antibody according to any one of embodiments 122 to 143, wherein the epitope is a functional epitope.

[0317] Embodiment 145: An isolated monoclonal antibody according to any one of embodiments 122 to 143, wherein the epitope is a conformational epitope.

[0318] Embodiment 146: An isolated monoclonal antibody according to any one of embodiments 122 to 145, wherein the epitope is an epitope on the native CD122 protein.

[0319] Embodiment 147: An isolated monoclonal antibody according to any one of embodiments 63 to 145, which inhibits i) the binding of IL2 to a high affinity IL-αβγ receptor comprising CD122, CD132, and CD25, or ii) the binding of IL15 to an intermediate affinity IL-βγ receptor comprising CD122 and CD132, expressed in trans as bound to IL15Rα, or iii) the binding of IL15 to a high affinity IL-αβγ receptor comprising CD122, CD132, and IL15Rα.

Claims

1. 1. An anti-CD122 antibody comprising: 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.

2. The anti-CD122 antibody of 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 of 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 of 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 of 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 of 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 of 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 of 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 of 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 of 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 of 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 of 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 of 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 of 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. 2. The anti-CD122 antibody of claim 1, wherein the VH domain comprises 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.

16. 2. The anti-CD122 antibody of claim 1, wherein the VL domain comprises 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.

17. 2. The anti-CD122 antibody of claim 1, wherein the VH domain is encoded by a nucleic acid comprising 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.

18. The anti-CD122 antibody of claim 1, wherein the VL domain is encoded by a nucleic acid comprising 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.

19. 2. The anti-CD122 antibody of claim 1, wherein the heavy chain comprises 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.

20. 2. The anti-CD122 antibody of claim 1, wherein the light chain comprises 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.

21. 2. The anti-CD122 antibody of claim 1, wherein the heavy chain is encoded by a nucleic acid comprising 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.

22. 2. The anti-CD122 antibody of claim 1, wherein the light chain is encoded by a nucleic acid comprising 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.

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

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

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

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

29. 29. The anti-CD122 antibody of any one of claims 1 to 28, comprising an IgG-scFv, a nanobody, a miniantibody, a 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 intrabody.

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

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

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

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

34. An anti-CD122 antibody according to any one of claims 1 to 33, having a binding affinity to human CD122 of about 100 pM to about 3 nM.

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

Images