Anti-IL18 binding protein antibody and method of use thereof

Abstract

The present disclosure is generally directed to compositions comprising monovalent antibodies, such as monoclonal monovalent antibodies, that specifically bind an IL18BP polypeptide (e.g., a mammalian IL18BP polypeptide or a human IL18BP polypeptide), and to the use of such compositions in the treatment of individuals in need thereof.

Description

[Technical Field]

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application Nos. 63 / 615,158, filed December 27, 2023, 63 / 515,493, filed July 25, 2023, and 63 / 478,793, filed January 6, 2023, the contents of each of which are hereby incorporated by reference in their entirety for all purposes.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. The XML manuscript, created on December 18, 2023, is named 2023-12-18_01209-0015-62US_SL.xml and is 254,583 bytes in size.

[0003] The present disclosure relates to anti-IL18BP antibodies and uses of such antibodies (eg, therapeutic applications). [Background technology]

[0004] Interleukin-18 (IL-18), originally described as an interferon-γ (IFNγ) inducer, is an early signal in the development of T lymphocyte helper type 1 (Th1) responses. Interleukin-18 binding protein (IL18BP) binds and neutralizes IL-18 activity, thereby acting as a natural inhibitor of IL-18-induced interferon-γ (IFNγ) and suppressing Th1 responses (Novick et al., 1999, Immunity, 10:127-136). IL18BP is constitutively secreted and has an exceptionally high affinity for IL-18 (approximately 400 pM). It is present in healthy human serum at a 20-fold molar excess over IL-18, thereby competing with IL-18 for its cell surface receptor and acting as a natural anti-inflammatory and immunosuppressive molecule.

[0005] The human IL18BP gene encodes at least four different isoforms derived from mRNA splice variants, and two isoforms of mouse IL18BP have been identified: IL18BPa, b, c, and d (Kim et al., 2000, PNAS, 97:1190-1195). IL18BPa is the most widely expressed isoform and binds mature IL-18 (but not pro-IL-18) with significantly higher affinity than IL-18 receptor a.

[0006] IL-18 and IL18BP are abundant in the tumor microenvironment (TME). IL18BP is upregulated in various tumors, limiting the antitumor activity of IL-18 (Zhou et al., 2020, Nature, 583:609). In tumor mouse models, administration of mIL-18 did not affect tumor growth in wild-type animals, whereas administration of IL18BP significantly reduced tumor growth in wild-type animals. - / - It significantly inhibited tumor growth in mice, suggesting that IL-18BP expression is common in cancer and may function as a soluble immune checkpoint.

[0007] Anti-IL18BP antibodies have been described so far, for example in WO2002 / 092008, WO2015 / 032932, WO2016 / 139297, WO2019 / 213686, and WO2023 / 178192.

[0008] There is a need for novel therapeutic anti-IL18BP antibodies that are effective in treating a variety of diseases, disorders and conditions, including cancer.

[0009] All references cited herein, including patent applications and publications, are hereby incorporated by reference in their entirety. Summary of the Invention

[0010] The present disclosure is generally directed to anti-IL18BP antibodies and methods of using such antibodies. The present disclosure includes multiple embodiments, including but not limited to the following embodiments:

[0011] Embodiment 1 is an isolated anti-interleukin-18 binding protein (IL18BP) antibody that blocks IL-18 from binding to IL18BP.

[0012] Embodiment 2 is the anti-IL18BP antibody of Embodiment 1, wherein the anti-IL18BP antibody increases the expression level of interferon-gamma (IFNγ) in peripheral blood mononuclear cells.

[0013] Embodiment 3 is the anti-IL18BP antibody of Embodiment 1 or 2, wherein the anti-IL18BP antibody increases IFNγ expression in natural killer cells.

[0014] Embodiment 4 is an anti-IL18BP antibody according to any one of Embodiments 1 to 3, wherein the anti-IL18BP antibody increases the level of inflammatory cytokines in serum.

[0015] Embodiment 5 is an anti-IL18BP antibody according to any one of Embodiments 1 to 4, wherein the anti-IL18BP antibody increases serum IFNγ levels.

[0016] Embodiment 6 is an anti-IL18BP antibody according to any one of Embodiments 1 to 5, wherein the anti-IL18BP antibody increases serum IL-10 levels.

[0017] Embodiment 7 is an anti-IL18BP antibody according to any one of Embodiments 1 to 6, wherein the anti-IL18BP antibody increases serum IL-6 levels.

[0018] Embodiment 8 is an anti-IL18BP antibody according to any one of Embodiments 1 to 7, wherein the anti-IL18BP antibody increases serum tumor necrosis factor alpha (TNFα) levels.

[0019] Embodiment 9 is an anti-IL18BP antibody according to any one of embodiments 1 to 8, wherein the anti-IL18BP antibody reduces the percentage of CD3+ T cells in vivo.

[0020] Embodiment 10 is an anti-IL18BP antibody according to any one of embodiments 1 to 9, wherein the anti-IL18BP antibody reduces the percentage of CD19+ B cells in vivo.

[0021] Embodiment 11 is an anti-IL18BP antibody according to any one of Embodiments 1 to 10, wherein the anti-IL18BP antibody reduces the percentage of CD11b+ cells in vivo.

[0022] Embodiment 12 is an anti-IL18BP antibody according to any one of Embodiments 1 to 11, wherein the anti-IL18BP antibody increases the percentage of macrophages in vivo.

[0023] Embodiment 13 includes BP-10, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-04.01, BP-04. 02, BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04.14, BP-04.15, 13. An anti-IL18BP antibody according to any one of embodiments 1 to 12, which competes for binding to IL18BP with one or more antibodies selected from BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31 and BP-04.32, and any combination thereof.

[0024] Embodiment 14 is a method for treating IL18BP comprising administering to a patient a medicament for the treatment of an IL18BP infection, the method ... 14. The anti-IL18BP antibody of any one of embodiments 1 to 13, comprising at least one, at least two, at least three, at least four, at least five, or six HVRs selected from HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3 of an antibody selected from BP-04.1, BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31, and BP-04.32.

[0025] Embodiment 15 is a. HVR-H1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 167, 168, and 169; b. HVR-H2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 170, 171, 172, 173, 174, 175, 176, 177, and 178; c. HVR-H3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188; d. HVR-L1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, and 247; e. HVR-L2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, and 248; and / or f. HVR-L3 is the anti-IL18BP antibody of embodiment 14, comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, and 249.

[0026] Embodiment 16 is a. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 60, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 71, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 87, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 112, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 122, or b. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 72, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 102, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 123, or c. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 73, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 103, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 123, or d. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 62, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 74, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 89, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 104, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 114, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 124, or e. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 75, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 90, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 105, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 123, or f. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 63, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 76, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 91, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 106, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 115, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 125, or g. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 77, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 103, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 123, or h. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 64, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 78, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 92, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 107, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 126, or i. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 65, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 79, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 93, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 127, or j. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 66, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 80, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 94, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 108, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 117, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 128, or k. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 66, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 81, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 95, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 109, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 118, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 129, or l. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 67, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 82, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 96, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 130, or m. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 68, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 83, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 97, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 119, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 131, or n. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 69, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 84, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 98, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 110, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 120, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 132, or o. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 70, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 85, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 99, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 111, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 121, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 133, or p. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 70, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 86, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 100, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 111, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 121, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 133, or q. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 167, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 170, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 179, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or r. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 168, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 180, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or s. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 181, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or t. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 182, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or u. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or v. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or w. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or x. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 1704, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or y. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or z. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or aa. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or bb. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 176, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or cc. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 187, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or dd. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 188, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or ee. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 182, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or ff. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or gg. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or hh. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or ii. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or jj. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or kk. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or ll. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or mm. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or nn. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or oo. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or pp. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or qq. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or rr. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or ss. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or tt. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or uu. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or vv. An anti-IL18BP antibody described in embodiment 14 or 15, wherein HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249.

[0027] Embodiment 17 is an isolated anti-IL18BP antibody, wherein the anti-IL18BP antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region (VH) comprises: a. HVR-H1 comprising an amino acid sequence selected from any one of SEQ ID NOs: 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 167, 168, and 169; b. HVR-H2 comprising an amino acid sequence selected from any one of SEQ ID NOs: 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 170, 171, 172, 173, 174, 175, 176, 177, and 178; and c. An anti-IL18BP antibody comprising HVR-H3 comprising an amino acid sequence selected from any one of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 179, 180, 181, 182, 183, 184, 185, 186, 187 and 188.

[0028] Embodiment 18 is an embodiment of the present invention, wherein the light chain variable region comprises: a. HVR-L1 comprising an amino acid sequence selected from any one of SEQ ID NOs: 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, and 247; b. HVR-L2 comprising an amino acid sequence selected from any one of SEQ ID NOs: 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, and 248; and c. An antibody described in embodiment 17, comprising an HVR-L3 comprising an amino acid sequence selected from any one of SEQ ID NOs: 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133 and 249.

[0029] Embodiment 19 is the antibody of embodiment 17 or 18, comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to an amino acid sequence selected from any one of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, and 165.

[0030] Embodiment 20 is an antibody according to any one of embodiments 17 to 19, comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to an amino acid sequence selected from any one of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, and 166.

[0031] Embodiment 21 is the antibody of any one of embodiments 17 to 20, wherein the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions, insertions and / or deletions compared to an amino acid sequence selected from any one of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 and 165.

[0032] Embodiment 22 is an antibody according to any one of embodiments 17 to 21, wherein the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions, insertions and / or deletions compared to an amino acid sequence selected from any one of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 and 166.

[0033] Embodiment 23 is an antibody according to any one of embodiments 17 to 22, comprising a VH comprising an amino acid sequence selected from any one of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, and 165.

[0034] Embodiment 24 is the antibody of any one of embodiments 17 to 23, comprising a VL comprising an amino acid sequence selected from any one of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, and 166.

[0035] Embodiment 25 is an isolated anti-IL18BP antibody, comprising: a. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 60, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 87, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 112, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122; b. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 72, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 102, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123; c. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 73, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 103, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123; d. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 62, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 74, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 89, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 104, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 114, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 124; e. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 75, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 90, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 105, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123; f. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 63, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 76, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 91, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 106, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 115, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125; g. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 77, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 103, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123; h. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 64, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 78, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 92, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 107, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 126; i. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 65, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 79, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 93, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 127; j. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 66, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 80, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 94, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 108, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 117, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 128; k. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 66, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 81, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 95, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 109, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 118, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 129; l. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 67, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 82, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 96, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 130; m. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 68, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 83, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 97, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 119, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 131; n. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 69, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 84, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 98, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 110, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 120, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 132; o. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 70, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 85, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 99, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 111, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 121, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 133; p. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 70, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 86, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 100, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 111, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 121, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 133; q. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 167, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 170, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 179, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; r. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 168, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 180, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; s. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 181, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; t. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 182, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; u. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; v. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; w. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; x. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 1704, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; y. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; z. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; aa. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; bb. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 176, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; cc. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 187, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; dd. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 188, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ee. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 182, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ff. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; gg. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; hh. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ii. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; jj. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; kk. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ll. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; mm. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; nn. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; oo. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; pp. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249. qq. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; rr. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ss. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; tt. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; uu. HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or vv. An anti-IL18BP antibody in which HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249.

[0036] Embodiment 26 is a. As described in embodiment 25a, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 29; b. As described in embodiment 25b, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 30; c. As described in embodiment c of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 31; d. As described in embodiment 25(d), further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 32; e. As described in embodiment e of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 33; f. As described in f of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 34; g. As described in embodiment 25g, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 35; h. As described in embodiment h of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 36; i. As described in i of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 37; j. As described in embodiment j of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 38; k. As described in embodiment k of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 39; l. As described in l of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 40; m. As described in embodiment m of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 41; n. As described in embodiment n of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 42; o. As described in embodiment 25, o, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 43; p. As described in p of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 44; q. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 134; r. As described in r of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 135; s. As described in s of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 136; t. As described in t of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 137; u. As described in u of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 138; v. As described in v of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 139; w. As described in w of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 140; x. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 141; y. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 142; z. As described in embodiment z of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 143; aa. As set forth in aa of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 144; bb. As described in embodiment 25, bb, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 145; cc. As described in cc of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 146; dd. As described in embodiment 25, dd, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 147; ee. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 148; ff. As described in ff of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 149; gg. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 150; hh. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 151; ii. As described in ii of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 152; jj. As described in embodiment jj of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 153; kk. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 154; ll. As described in embodiment ll of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 155; mm. As described in embodiment mm of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 156; nn. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 157; oo. As described in embodiment 25, oo, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 158; pp. 25-27, in addition to the description on pp. 25-27, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 159; qq. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 160; rr. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 161; ss. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; tt. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 163; uu. As described in embodiment 25, uu, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; vv. An antibody described in embodiment 25, further comprising, in addition to the description of vv of embodiment 25, an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 165.

[0037] Embodiment 27 is a. As described in embodiment 25a, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 45; b. As described in embodiment 25b, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 46; c. As described in embodiment c of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 47; d. As described in embodiment 25(d), further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 48; e. As described in embodiment e of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 49; f. As described in f of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 50; g. As described in embodiment 25g, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 51; h. As described in embodiment h of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 52; i. As described in i of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 53; j. As described in embodiment j of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 54; k. As described in embodiment k of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 55; l. As described in l of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 56; m. As described in embodiment m of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 57; n. As described in embodiment n of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 58; o. As described in embodiment 25, o, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 59; p. As described in p of embodiment 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 59; q. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 134; r. As described in r of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 135; s. As described in s of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 136; t. As described in t of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 137; u. As described in u of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 138; v. As described in v of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 139; w. As described in w of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 140; x. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 141; y. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 142; z. As described in embodiment z of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 143; aa. As set forth in aa of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 144; bb. As described in embodiment 25, bb, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 145; cc. As described in cc of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 146; dd. As described in embodiment 25, dd, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 147; ee. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 148; ff. As described in ff of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 149; gg. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 150; hh. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 151; ii. As described in ii of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 152; jj. As described in embodiment jj of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 153; kk. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 154; ll. As described in embodiment ll of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 155; mm. As described in embodiment mm of embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 156; nn. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 157; oo. As described in embodiment 25, oo, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 158; pp. 25-27, in addition to the description on pp. 25-27, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 159; qq. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 160; rr. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 161; ss. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; tt. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 163; uu. As set forth in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; or vv. An antibody described in embodiment 25 or 26, further comprising, in addition to the description of vv of embodiment 25, an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 165.

[0038] Embodiment 28 is a. In addition to the description of a of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 29; b. As described in embodiment 25b, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 30; c. As described in embodiment 25c, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 31; d. As described in embodiment 25, d, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 32; e. As described in embodiment e of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 33; f. In addition to the description of f of embodiment 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 34; g. In addition to the description of embodiment 25g, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 35; h. As described in embodiment 25(h), further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 36; i. In addition to the description of i of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 37; j. As described in embodiment j of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 38; k. As described in embodiment k of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 39; l. In addition to the description of l of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 40; m. As described in embodiment m of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 41; n. In addition to the description of n of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 42; o. In addition to the description of o of embodiment 25, a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 43; p. In addition to the description of p of embodiment 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 44; q. In addition to the description of q in embodiment 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 134; r. In addition to the description of r of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 135; s. As described in s of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 136; t. As described in t of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 137; u. In addition to the description of u in embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 138; v. In addition to the description of v of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 139; w. In addition to the description of w of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 140; x. In addition to the description of x in embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 141; y. As described in embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 142; z. As described in embodiment z of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 143; aa. In addition to the aa described in embodiment 25, a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 144; bb. As described in embodiment 25, bb, further comprising: a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 145; cc. In addition to the description of cc of embodiment 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 146; dd. In addition to the description of dd in embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 147; ee. As described in embodiment 25, further comprising: a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 148; ff. In addition to the description of ff of embodiment 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 149; gg. In addition to the description of gg in embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 150; hh. In addition to the description of hh of embodiment 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 151; ii. In addition to the description of ii of embodiment 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 152; jj. In addition to the description of jj of embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 153; kk. As described in embodiment 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to a VH comprising the amino acid sequence of SEQ ID NO: 154; ll. As described in ll of embodiment 25, further comprising: a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 155; mm. In addition to the description of mm of embodiment 25, further comprising: a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 156; nn. In addition to the description of embodiment 25, nn, further comprising: a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 157; oo. In addition to the description of oo in embodiment 25, further comprising: a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 158; pp. 25-27, in addition to the description on pp. 25-27, further comprising: an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 159; qq. In addition to the description of qq of embodiment 25, further comprising: a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 160; rr. In addition to the description of rr in embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 161; ss. As described in embodiment 25, further comprising a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 162; tt. In addition to the description of tt in embodiment 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 163; uu. In addition to the description of uu in embodiment 25, a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 164; or vv. The antibody of any one of embodiments 25 to 27, further comprising, in addition to the description of vv of embodiment 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 165.

[0039] Embodiment 29 is a. As described in embodiment 25a, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 45; b. As described in embodiment 25b, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 46; c. As described in embodiment 25c, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 47; d. As described in embodiment 25, d, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 48; e. As described in embodiment e of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 49; f. As described in f of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 50; g. In addition to the description of embodiment 25g, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 51; h. As described in embodiment 25(h), further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 52; i. As described in i of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 53; j. As described in embodiment j of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 54; k. As described in embodiment k of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 55; l. In addition to the description of l of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 56; m. As described in embodiment m of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 57; n. In addition to the description of n of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 58; o. As described in embodiment 25, o, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 59; or p. In addition to the description of p of embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 59; q. In addition to the description of q in embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; r. In addition to the description of r of embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; s. As described in s of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; t. As described in t of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; u. As described in u of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; v. As described in v of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; w. As described in w of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; x. In addition to the description of x in embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; y. As described in embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; z. As described in embodiment z of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; aa. In addition to the aa described in embodiment 25, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; bb. As described in embodiment 25, bb, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; cc. In addition to the description of cc. of embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; dd. As described in embodiment 25, dd, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; ee. As described in embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; ff. In addition to the description of ff of embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; gg. In addition to the description of gg of embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; hh. In addition to the description of hh of embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; ii. As described in ii of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; jj. As described in jj of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; kk. In addition to the description of kk of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; ll. As described in embodiment ll of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; mm. In addition to the description of mm of embodiment 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; nn. In addition to the description of embodiment 25, nn, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; oo. As described in embodiment 25, oo, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; pp. 25-27, in addition to the description on pp. 25-27, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; qq. In addition to the description of embodiment 25qq, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; rr. In addition to the description of rr in embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; ss. As described in embodiment 25, further comprising a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; tt. As described in embodiment 25, further comprising a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; uu. As described in embodiment 25, uu, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; or vv. The antibody of any one of embodiments 25 to 28, further comprising, in addition to the description of vv of embodiment 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166.

[0040] Embodiment 30 is a. a VH comprising the amino acid sequence of SEQ ID NO: 29, and a VL comprising the amino acid sequence of SEQ ID NO: 45; b. a VH comprising the amino acid sequence of SEQ ID NO: 30, and a VL comprising the amino acid sequence of SEQ ID NO: 46; c. a VH comprising the amino acid sequence of SEQ ID NO: 31, and a VL comprising the amino acid sequence of SEQ ID NO: 47; d. a VH comprising the amino acid sequence of SEQ ID NO: 32, and a VL comprising the amino acid sequence of SEQ ID NO: 48; e. a VH comprising the amino acid sequence of SEQ ID NO: 33, and a VL comprising the amino acid sequence of SEQ ID NO: 49; f. a VH comprising the amino acid sequence of SEQ ID NO: 34, and a VL comprising the amino acid sequence of SEQ ID NO: 50; g. a VH comprising the amino acid sequence of SEQ ID NO: 35, and a VL comprising the amino acid sequence of SEQ ID NO: 51; h. a VH comprising the amino acid sequence of SEQ ID NO: 36, and a VL comprising the amino acid sequence of SEQ ID NO: 52; i. a VH comprising the amino acid sequence of SEQ ID NO: 37, and a VL comprising the amino acid sequence of SEQ ID NO: 53; j. a VH comprising the amino acid sequence of SEQ ID NO: 38, and a VL comprising the amino acid sequence of SEQ ID NO: 54; k. a VH comprising the amino acid sequence of SEQ ID NO: 39, and a VL comprising the amino acid sequence of SEQ ID NO: 55; l. VH comprising the amino acid sequence of SEQ ID NO: 40, and VL comprising the amino acid sequence of SEQ ID NO: 56; m. a VH comprising the amino acid sequence of SEQ ID NO: 41, and a VL comprising the amino acid sequence of SEQ ID NO: 57; n. VH comprising the amino acid sequence of SEQ ID NO: 42, and VL comprising the amino acid sequence of SEQ ID NO: 58; o. a VH comprising the amino acid sequence of SEQ ID NO: 43, and a VL comprising the amino acid sequence of SEQ ID NO: 59; p. a VH comprising the amino acid sequence of SEQ ID NO: 44, and a VL comprising the amino acid sequence of SEQ ID NO: 59; q. a VH comprising the amino acid sequence of SEQ ID NO: 134, and a VL comprising the amino acid sequence of SEQ ID NO: 166; r. VH comprising the amino acid sequence of SEQ ID NO: 135, and VL comprising the amino acid sequence of SEQ ID NO: 166; s. VH comprising the amino acid sequence of SEQ ID NO: 136, and VL comprising the amino acid sequence of SEQ ID NO: 166; t. a VH comprising the amino acid sequence of SEQ ID NO: 137, and a VL comprising the amino acid sequence of SEQ ID NO: 166; u. a VH comprising the amino acid sequence of SEQ ID NO: 138, and a VL comprising the amino acid sequence of SEQ ID NO: 166; v. a VH comprising the amino acid sequence of SEQ ID NO: 139, and a VL comprising the amino acid sequence of SEQ ID NO: 166; w. a VH comprising the amino acid sequence of SEQ ID NO: 140, and a VL comprising the amino acid sequence of SEQ ID NO: 166; x. a VH comprising the amino acid sequence of SEQ ID NO: 141, and a VL comprising the amino acid sequence of SEQ ID NO: 166; y. a VH comprising the amino acid sequence of SEQ ID NO: 142, and a VL comprising the amino acid sequence of SEQ ID NO: 166; z. a VH comprising the amino acid sequence of SEQ ID NO: 143, and a VL comprising the amino acid sequence of SEQ ID NO: 166; aa. VH comprising the amino acid sequence of SEQ ID NO: 144, and VL comprising the amino acid sequence of SEQ ID NO: 166; bb. VH comprising the amino acid sequence of SEQ ID NO: 145 and VL comprising the amino acid sequence of SEQ ID NO: 166; cc. VH comprising the amino acid sequence of SEQ ID NO: 146, and VL comprising the amino acid sequence of SEQ ID NO: 166; dd. VH comprising the amino acid sequence of SEQ ID NO: 147 and VL comprising the amino acid sequence of SEQ ID NO: 166; ee. VH comprising the amino acid sequence of SEQ ID NO: 148, and VL comprising the amino acid sequence of SEQ ID NO: 166; ff. VH comprising the amino acid sequence of SEQ ID NO: 149 and VL comprising the amino acid sequence of SEQ ID NO: 166; gg. VH comprising the amino acid sequence of SEQ ID NO: 150, and VL comprising the amino acid sequence of SEQ ID NO: 166; hh. VH comprising the amino acid sequence of SEQ ID NO: 151, and VL comprising the amino acid sequence of SEQ ID NO: 166; ii. a VH comprising the amino acid sequence of SEQ ID NO: 152, and a VL comprising the amino acid sequence of SEQ ID NO: 166; jj. VH comprising the amino acid sequence of SEQ ID NO: 153, and VL comprising the amino acid sequence of SEQ ID NO: 166; kk. VH comprising the amino acid sequence of SEQ ID NO: 154, and VL comprising the amino acid sequence of SEQ ID NO: 166; ll. VH comprising the amino acid sequence of SEQ ID NO: 155, and VL comprising the amino acid sequence of SEQ ID NO: 166; mm. VH comprising the amino acid sequence of SEQ ID NO: 156, and VL comprising the amino acid sequence of SEQ ID NO: 166; nn. VH comprising the amino acid sequence of SEQ ID NO: 157, and VL comprising the amino acid sequence of SEQ ID NO: 166; oo. VH comprising the amino acid sequence of SEQ ID NO: 158, and VL comprising the amino acid sequence of SEQ ID NO: 166; pp. VH comprising the amino acid sequence of SEQ ID NO: 159, and VL comprising the amino acid sequence of SEQ ID NO: 166; qq. VH comprising the amino acid sequence of SEQ ID NO: 160, and VL comprising the amino acid sequence of SEQ ID NO: 166; rr. VH comprising the amino acid sequence of SEQ ID NO: 161, and VL comprising the amino acid sequence of SEQ ID NO: 166; ss. VH comprising the amino acid sequence of SEQ ID NO: 162, and VL comprising the amino acid sequence of SEQ ID NO: 166; tt. VH comprising the amino acid sequence of SEQ ID NO: 163, and VL comprising the amino acid sequence of SEQ ID NO: 166; a VH comprising the amino acid sequence of SEQ ID NO: 164 and a VL comprising the amino acid sequence of SEQ ID NO: 166; or vv. An antibody described in embodiment 25, comprising a VH comprising the amino acid sequence of SEQ ID NO: 165 and a VL comprising the amino acid sequence of SEQ ID NO: 166.

[0041] Embodiment 31 is a. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 190; b. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 191; c. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 192; d. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 193; e. As described in embodiment 25, s, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 194; f. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 195; g. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 196; h. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 197; i. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 198; j. As described in embodiment 25, s, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 199; k. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 200; l. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 201; m. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 202; n. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 203; o. As described in s of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 204; p. As set forth in embodiment 25, u, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 205; q. As described in u of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 206; r. As set forth in embodiment 25, u, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 207; s. As described in u of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 208; t. As described in u of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 209; u. As described in embodiment 25, u, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 210; v. As described in u of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 211; w. As described in u of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 212; x. As described in u of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 213; y. As described in u of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 214; z. As described in u of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 215; aa. As set forth in embodiment 25, u, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 216; bb. As set forth in embodiment 25, u, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 217; cc. As set forth in embodiment 25, u, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 218; dd. As set forth in embodiment 25, u, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 219; ee. As described in embodiment w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 220; ff. As described in embodiment w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 221; gg. As described in w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 222; hh. As described in w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 223; ii. As described in embodiment 25-w, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 224; jj. As set forth in embodiment w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 225; kk. As described in w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 226; ll. As described in embodiment 25(w), further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 227; mm. As described in embodiment w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 228; nn. As described in embodiment w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 229; oo. As described in w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 230; pp. 25. In addition to the description of w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 231; qq. As described in w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 232; rr. As described in embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 233; or ss. The antibody of embodiment 25, as described in w of embodiment 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 234.

[0042] Embodiment 32 is a. As described in s of embodiment 25, further comprising an HVR comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; b. As set forth in embodiment 25, u, further comprising an HVR comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; or c. An antibody described in embodiment 25 or embodiment 31, further comprising an HVR comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189, in addition to the description of w in embodiment 25.

[0043] Embodiment 33 is a. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 190, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; b. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 191, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; c. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 192, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; d. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 193, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; e. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 194, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; f. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 195, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; g. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 196, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; h. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 197, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; i. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 198, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; j. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 199, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; k. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 200, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; l. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 201, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; m. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 202, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; n. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 203, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; o. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 204, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; p. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 205, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; q. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 206, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; r. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 207, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; s. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 208, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; t. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 209, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; u. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 210, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; v. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 211, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; w. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 212, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; x. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 213, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; y. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 214, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; z. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 215, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; aa. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 216, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; bb. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 217, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; cc. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 218, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; dd. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 219, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; ee. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 220, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; ff. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 221, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; gg. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 222, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; hh. a heavy chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 223, and a light chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; ii. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 224, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; jj. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 225, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; kk. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 226, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; ll. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 227, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; mm. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 228, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; nn. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 229, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; oo. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 230, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; pp. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 231, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; qq. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 232, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; rr. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 233, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189, or ss. The antibody of embodiment 25, comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 234, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189.

[0044] Embodiment 34 is an isolated anti-IL18BP antibody, comprising: a. a heavy chain comprising the amino acid sequence of SEQ ID NO: 190, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; b. a heavy chain comprising the amino acid sequence of SEQ ID NO: 191, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; c. a heavy chain comprising the amino acid sequence of SEQ ID NO: 192 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; d. a heavy chain comprising the amino acid sequence of SEQ ID NO: 193, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; e. a heavy chain comprising the amino acid sequence of SEQ ID NO: 194 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; f. a heavy chain comprising the amino acid sequence of SEQ ID NO: 195, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; g. a heavy chain comprising the amino acid sequence of SEQ ID NO: 196 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; h. a heavy chain comprising the amino acid sequence of SEQ ID NO: 197, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; i. a heavy chain comprising the amino acid sequence of SEQ ID NO: 198, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; j. a heavy chain comprising the amino acid sequence of SEQ ID NO: 199 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; k. a heavy chain comprising the amino acid sequence of SEQ ID NO: 200, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; l. a heavy chain comprising the amino acid sequence of SEQ ID NO: 201, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; m. a heavy chain comprising the amino acid sequence of SEQ ID NO: 202, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; n. a heavy chain comprising the amino acid sequence of SEQ ID NO: 203, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; o. a heavy chain comprising the amino acid sequence of SEQ ID NO: 204 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; p. a heavy chain comprising the amino acid sequence of SEQ ID NO: 205, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; q. a heavy chain comprising the amino acid sequence of SEQ ID NO: 206, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; r. a heavy chain comprising the amino acid sequence of SEQ ID NO: 207, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; s. a heavy chain comprising the amino acid sequence of SEQ ID NO: 208, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; t. a heavy chain comprising the amino acid sequence of SEQ ID NO: 209, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; u. a heavy chain comprising the amino acid sequence of SEQ ID NO: 210, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; v. a heavy chain comprising the amino acid sequence of SEQ ID NO: 211, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; w. a heavy chain comprising the amino acid sequence of SEQ ID NO: 212 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; x. a heavy chain comprising the amino acid sequence of SEQ ID NO: 213, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; y. a heavy chain comprising the amino acid sequence of SEQ ID NO: 214, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; z. a heavy chain comprising the amino acid sequence of SEQ ID NO: 215, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; aa. a heavy chain comprising the amino acid sequence of SEQ ID NO: 216, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; bb. a heavy chain comprising the amino acid sequence of SEQ ID NO: 217 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; cc. a heavy chain comprising the amino acid sequence of SEQ ID NO: 218, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; dd. a heavy chain comprising the amino acid sequence of SEQ ID NO: 219, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; ee. a heavy chain comprising the amino acid sequence of SEQ ID NO: 220, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; ff. a heavy chain comprising the amino acid sequence of SEQ ID NO: 221 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; gg. a heavy chain comprising the amino acid sequence of SEQ ID NO: 222 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; hh. a heavy chain comprising the amino acid sequence of SEQ ID NO: 223 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; ii. a heavy chain comprising the amino acid sequence of SEQ ID NO: 224 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; jj. a heavy chain comprising the amino acid sequence of SEQ ID NO: 225 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; kk. A heavy chain comprising the amino acid sequence of SEQ ID NO: 226 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; ll. a heavy chain comprising the amino acid sequence of SEQ ID NO: 227 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; mm. a heavy chain comprising the amino acid sequence of SEQ ID NO: 228 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; nn. a heavy chain comprising the amino acid sequence of SEQ ID NO: 229, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; oo. a heavy chain comprising the amino acid sequence of SEQ ID NO: 230 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; pp. A heavy chain comprising the amino acid sequence of SEQ ID NO: 321, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; qq. A heavy chain comprising the amino acid sequence of SEQ ID NO: 232 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; rr. a heavy chain comprising the amino acid sequence of SEQ ID NO: 233 and a light chain comprising the amino acid sequence of SEQ ID NO: 189, or ss. An anti-IL18BP antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 234 and a light chain comprising the amino acid sequence of SEQ ID NO: 189.

[0045] Embodiment 35 is an isolated anti-IL18BP antibody, comprising antibodies BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-04.01, BP-04.02, BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04. and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of any one of BP-04.14, BP-04.15, BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31, and BP-04.32.

[0046] Embodiment 36 includes antibodies BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-04.01, BP-04.02 , BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04.14, BP-04.15, BP-04 36. An isolated antibody as described in embodiment 35, comprising a VH and / or VL that is at least 90%, at least 95%, at least 97% or at least 99% identical to the VH and / or VL of any one of BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31 and BP-04.32.

[0047] Embodiment 37 includes antibodies BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-04. 01, BP-04.02, BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, B 37. An isolated antibody according to embodiment 35 or embodiment 36, comprising a VH and / or VL of any one of BP-04.1, BP-04.14, BP-04.15, BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31 and BP-04.32.

[0048] Embodiment 38 is an isolated anti-IL18BP antibody, comprising: a. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-01 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-01 (as shown in Table 2); b. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-02 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-02 (as shown in Table 2); c. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-03 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-03 (as shown in Table 2); d. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04 (as set forth in Table 2); e. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-05 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-05 (as shown in Table 2); f. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-06 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-06 (as shown in Table 2); g. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-07 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-07 (as set forth in Table 2); h. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-08 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-08 (as set forth in Table 2); i. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-09 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-09 (as set forth in Table 2); j. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-10 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-10 (as set forth in Table 2); k. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-11 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-11 (as set forth in Table 2); l. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-12 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-12 (as set forth in Table 2); m. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-13 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-13 (as set forth in Table 2); n. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-14 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-14 (as set forth in Table 2); o. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-15 (as set forth in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-15 (as set forth in Table 2); p. a VH comprising HVR-H1, HVR-H2 and HVR-H3 of antibody BP-16 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2 and HVR-L3 of antibody BP-16 (as shown in Table 2); q. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.01 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); r. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.02 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); s. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.03 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); t. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.04 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); u. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.05 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); v. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.06 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); w. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.07 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); x. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.08 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); y. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.09 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); z. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.10 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); aa. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.11 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); bb. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.12 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); cc. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.13 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); dd. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.14 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); ee. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.15 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); ff. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.16 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); gg. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.17 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); hh. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.18 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); ii. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.19 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); jj. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.20 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); kk. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.21 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); 11. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.22 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); mm. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.23 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); nn. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.24 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); oo. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.25 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); pp. A VH comprising HVR-H1, HVR-H2 and HVR-H3 of antibody BP-04.26 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2 and HVR-L3 of antibody BP-04.LC (as shown in Table 13); qq. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.27 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); rr. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.28 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); ss. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.29 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); tt. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.30 (as set forth in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.31 (as set forth in Table 12) and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as set forth in Table 13); or vv. An anti-IL18BP antibody comprising a VH comprising HVR-H1, HVR-H2 and HVR-H3 of antibody BP-04.32 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2 and HVR-L3 of antibody BP-04.LC (as shown in Table 13).

[0049] Embodiment 39 is the antibody according to any one of Embodiments 25 to 38, wherein the anti-IL18BP antibody is an antibody that blocks the binding of IL-18 to IL18BP.

[0050] Embodiment 40 is the antibody of any one of embodiments 25 to 39, having the following characteristics: a. Anti-IL18BP antibodies increase the expression level of interferon-gamma (IFNγ) in peripheral blood mononuclear cells; b. Anti-IL18BP antibody increases IFNγ expression in natural killer cells. c. Anti-IL18BP antibodies increase the levels of inflammatory cytokines in serum. d. Anti-IL18BP antibodies increase serum IFNγ levels. e. Anti-IL18BP antibodies increase serum IL-10 levels. f. Anti-IL18BP antibodies increase serum IL-6 levels. g. Anti-IL18BP antibodies increase serum tumor necrosis factor alpha (TNFα) levels. h. Anti-IL18BP antibodies reduce the percentage of CD3+ T cells in vivo; i. anti-IL18BP antibodies reduce the percentage of CD19+ B cells in vivo; j. Anti-IL18BP antibodies reduce the percentage of CD11b+ cells in vivo; and k. Anti-IL18BP antibodies increase the percentage of macrophages in vivo; l. Anti-IL18BP antibodies increase serum levels of free IL-18; m. Anti-IL18BP antibodies reduce serum levels of IL-18BP; n. Anti-IL18BP antibodies increase IFNγ levels in tumor lysates; o. Anti-IL18BP antibodies increase IL-1β levels in tumor lysates; p. Anti-IL18BP antibodies increase IL-15 levels in tumor lysates. q. Anti-IL18BP antibody increases IL-27 levels in tumor lysates. r. Anti-IL18BP antibody increases MIP-1α levels in tumor lysates, and s. The anti-IL18BP antibody is an antibody that has one or more of the following properties: reduces tumor volume.

[0051] Embodiment 41 is the antibody according to any one of embodiments 1 to 30 and 35 to 40, which is a monoclonal antibody.

[0052] Embodiment 42 is the antibody of any one of embodiments 1 to 41, which is a humanized antibody.

[0053] Embodiment 43 is the antibody of any one of embodiments 1 to 42, which is an antigen-binding fragment, such as a Fab, Fab', Fab'-SH, F(ab')2, Fv or scFv fragment.

[0054] Embodiment 44 is the antibody of any one of embodiments 1 to 43, which is a bispecific or multispecific antibody.

[0055] Embodiment 45 is an antibody according to any one of embodiments 1 to 44, which is of the IgG class, the IgM class, or the IgA class.

[0056] Embodiment 46 is the antibody of embodiment 45, which is of the IgG class and of a human IgG1, IgG2, IgG3 or IgG4 isotype, or a murine IgG1 or IgG2 isotype.

[0057] Embodiment 47 is a human or mouse IgG1 isotype antibody that is selected from the group consisting of N297A, D265A, D270A, L234A, L235A, G237A, P238D, L328E, E233D, G237D, H268D, P271G, A330R, C226S, C229S, E233P, L234V, L234F, L235E, P331S, P331G, S267E, L328F, A330L, M252Y, S254T, T256E, N297Q, P238S, P238A, A330R ...V, P238V, P238V, A330R, M252Y, S254V, T256E, N297Q, P238V, P238V, A330R, M252Y, S254V, T256E, N297Q, P238V, P238V, A330R, M 47. The antibody of any one of embodiments 1 to 46, comprising one or more amino acid substitutions in the Fc region at amino acid residues selected from the group consisting of 27Q, A327G, P329A, P329S, P329G, K322A, N325S, T394D, A330S, E430G, E430S, E430F, E430T, E345K, E345Q, E345R, E345Y, S440Y, S440W, and any combination thereof, wherein residue numbering is according to EU numbering.

[0058] Embodiment 48 is the antibody of any one of embodiments 1 to 40 or 35 to 46, having a human or murine IgG2 isotype and comprising one or more amino acid substitutions in the Fc region at amino acid residues selected from the group consisting of A330S, C127S, C214S, C219S, C220S, E345K, E345Q, E345R, E345Y, E430F, E430G, E430S, E430T, G237A, H268Q, L328F, M252Y, P331S, S254T, S267E, S440W, S440Y, T256E, V234A, V309L, and any combination thereof, where residue numbering is according to EU numbering.

[0059] Embodiment 49 is the antibody of any one of embodiments 1 to 46, having a human or murine IgG4 isotype and comprising one or more amino acid substitutions in the Fc region at amino acid residues selected from the group consisting of C127S, E318A, E345R, E430G, F234A, G237A, K322A, L235A, L235E, L236E, L243A, L328F, M252Y, P331S, S228P, S229P, S254T, S267E, S440Y, T256E, and any combination thereof, wherein residue numbering is according to EU numbering.

[0060] Embodiment 50 is the antibody of any one of embodiments 1 to 49, comprising one or more amino acid substitutions in the Fc region at residue positions selected from the group consisting of A330L, A330S, C127S, E345R, E430G, K322A, L234A, L234F, L235A, L235E, L243A, L328F, P331S, P331G, S267E, S440Y, and any combination thereof, wherein amino acid residues are numbered according to EU numbering or Kabat numbering.

[0061] Embodiment 51 is the antibody of any one of embodiments 1 to 50, wherein the IgG Fc amino acid sequence is selected from the group consisting of SEQ ID NOs: 8 to 27 and 235 to 246.

[0062] Embodiment 52 is a pharmaceutical composition comprising the anti-IL18BP antibody of any one of Embodiments 1 to 51 and a pharmaceutically acceptable carrier.

[0063] Embodiment 53 is an isolated nucleic acid comprising a nucleic acid sequence encoding the anti-IL18BP antibody of any one of Embodiments 1 to 51.

[0064] Embodiment 54 is an isolated vector comprising the nucleic acid of embodiment 53.

[0065] Embodiment 55 is an isolated host cell comprising the nucleic acid of embodiment 52 or the vector of embodiment 54.

[0066] Embodiment 56 is a method for producing an antibody, comprising culturing the cell of embodiment 55 to produce an anti-IL18BP antibody.

[0067] Embodiment 57 is the method of embodiment 56, further comprising recovering the antibody produced by the cells.

[0068] Embodiment 58 is a method of treating cancer in a subject in need thereof, comprising administering to an individual in need thereof a therapeutically effective amount of an anti-IL18BP antibody of any one of embodiments 1 to 51, thereby treating the cancer.

[0069] Embodiment 59 is the method of embodiment 58, further comprising administering one or more therapeutic agents.

[0070] Embodiment 60 is the method of embodiment 59, wherein at least one therapeutic agent is a checkpoint inhibitor.

[0071] Embodiment 61 is the method of embodiment 60, wherein the checkpoint inhibitor is selected from a PD1, PD-L1, and PD-L2 inhibitor.

[0072] Embodiment 62 is the method of embodiment 60, wherein the checkpoint inhibitor is selected from an anti-PD-L1 antibody, an anti-PD-L2 antibody, and an anti-PD-1 antibody.

[0073] Embodiment 63 is a method according to any one of embodiments 58 to 62, wherein the cancer is bile duct carcinoma, diffuse large B-cell lymphoma, glioblastoma multiforme, head and neck squamous cell carcinoma, renal clear cell carcinoma, sarcoma, bladder cancer, breast cancer, colorectal cancer, endometrial cancer, renal cancer, pancreatic adenocarcinoma, cutaneous melanoma, gastric adenocarcinoma, lung cancer, non-small cell lung cancer, melanoma, lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, gastric cancer, thyroid cancer, uterine cancer, liver cancer, cervical cancer, testicular cancer, squamous cell carcinoma, glioma, glioblastoma, adenoma, neuroblastoma, bladder carcinoma, esophageal carcinoma, or triple-negative breast carcinoma.

[0074] Embodiment 64 is a method for detecting the presence of IL18BP in a sample or an individual in vitro, the method comprising an anti-IL18bp antibody according to any one of embodiments 1 to 51.

[0075] Embodiment 65 is the method of embodiment 64, further comprising quantification of antigen-binding anti-IL18BP antibodies.

[0076] It should be understood that one, some, or all of the features of the various embodiments described herein may be combined to form other embodiments of the present disclosure. These and other aspects of the present disclosure will be apparent to those skilled in the art. These and other aspects of the present disclosure are further explained in the detailed description below. In some aspects, provided herein are methods for detecting IL18BP in a sample. The method includes contacting the sample with any of the anti-IL18BP antibodies described herein. [Brief explanation of the drawings]

[0077] [Figure 1] 1 shows data comparing the changes in spleen weight in mice administered various anti-IL18BP antibodies of the present disclosure to that observed in isotype control-treated mice in an animal model of macrophage activation syndrome. [Figure 2A]1 presents data showing changes in the proportion of T cells from splenocytes derived from mice administered various anti-IL18BP antibodies of the present disclosure in an animal model of macrophage activation syndrome. [Figure 2B] 1 presents data showing changes in the proportion of B cells from splenocytes derived from mice administered various anti-IL18BP antibodies of the present disclosure in an animal model of macrophage activation syndrome. [Figure 2C] 10 shows data showing changes in the percentage of CD11B+ cells from splenocytes derived from mice administered various anti-IL18BP antibodies of the present disclosure in an animal model of macrophage activation syndrome. [Figure 2D] 10 shows data demonstrating changes in the proportion of macrophages from splenocytes derived from mice administered various anti-IL18BP antibodies of the present disclosure in an animal model of macrophage activation syndrome. [Figure 3A] 1 shows data showing changes in IFN-Γ in the serum of mice administered various anti-IL18BP antibodies of the present disclosure in an animal model of macrophage activation syndrome. [Figure 3B] 1 presents data showing changes in IL-10 in the serum of mice administered various anti-IL18BP antibodies of the present disclosure in an animal model of macrophage activation syndrome. [Figure 3C] 10 shows data showing changes in TNFα in the serum of mice administered various anti-IL18BP antibodies of the present disclosure in an animal model of macrophage activation syndrome. [Figure 3D] 1 presents data showing changes in IL-6 in the serum of mice administered various anti-IL18BP antibodies of the present disclosure in an animal model of macrophage activation syndrome. [Figure 4A] 1 presents data showing the effect of anti-IL18BP antibodies of the present disclosure (as monotherapy) on tumor growth in the E0771 syngeneic tumor model. [Figure 4B] 1 shows data demonstrating the effect of anti-IL18BP antibodies of the present disclosure (in combination with anti-PDL1 antibody administration) on tumor growth in the E0771 syngeneic tumor model. [Figure 5A] 1 presents data showing the effect of anti-IL18BP antibodies of the present disclosure (as monotherapy) on tumor growth in a syngeneic tumor model. [Figure 5B] 1 shows data demonstrating the effect of anti-IL18BP antibodies of the present disclosure (in combination with anti-PDL1 antibody administration) on tumor growth in the E0771 syngeneic tumor model. [Figure 6A] 1 presents data showing that anti-IL-18BP antibodies of the present disclosure increase free IL-18 levels in serum. [Figure 6B] 1 presents data showing that anti-IL-18BP antibodies of the present disclosure increase free IL-18 levels in serum. [Figure 6C] 1 presents data showing that anti-IL-18BP antibodies of the present disclosure increase free IL-18 levels in serum. [Figure 7A] 1 presents data showing that an anti-IL-18BP antibody of the present disclosure reduced tumor volume in an E0771 syngeneic tumor model, either as monotherapy or in combination with an anti-PDL1 antibody. [Figure 7B] 1 presents data showing that an anti-IL-18BP antibody of the present disclosure reduced tumor volume in an E0771 syngeneic tumor model, either as monotherapy or in combination with an anti-PDL1 antibody. [Figure 8A]

[0023] Data are presented showing that anti-IL-18BP antibodies of the present disclosure were effective (as monotherapy) or in combination with anti-0-PDL1 antibody administration in reducing serum levels of IL-18BP and increasing levels of the pro-inflammatory cytokines and chemokines IFNγ, IL-1β, IL-15, IL-27, and MIP-1α in tumor lysates in the E0771 syngeneic tumor model. [Figure 8B]

[0023] Data are presented showing that anti-IL-18BP antibodies of the present disclosure were effective (as monotherapy) or in combination with anti-0-PDL1 antibody administration in reducing serum levels of IL-18BP and increasing levels of the pro-inflammatory cytokines and chemokines IFNγ, IL-1β, IL-15, IL-27, and MIP-1α in tumor lysates in the E0771 syngeneic tumor model. [Figure 8C]

[0023] Data are presented showing that anti-IL-18BP antibodies of the present disclosure were effective (as monotherapy) or in combination with anti-0-PDL1 antibody administration in reducing serum levels of IL-18BP and increasing levels of the pro-inflammatory cytokines and chemokines IFNγ, IL-1β, IL-15, IL-27, and MIP-1α in tumor lysates in the E0771 syngeneic tumor model. [Figure 8D]

[0023] Data are presented showing that anti-IL-18BP antibodies of the present disclosure were effective (as monotherapy) or in combination with anti-0-PDL1 antibody administration in reducing serum levels of IL-18BP and increasing levels of the pro-inflammatory cytokines and chemokines IFNγ, IL-1β, IL-15, IL-27, and MIP-1α in tumor lysates in the E0771 syngeneic tumor model. [Figure 8E]

[0023] Data are presented showing that anti-IL-18BP antibodies of the present disclosure were effective (as monotherapy) or in combination with anti-0-PDL1 antibody administration in reducing serum levels of IL-18BP and increasing levels of the pro-inflammatory cytokines and chemokines IFNγ, IL-1β, IL-15, IL-27, and MIP-1α in tumor lysates in the E0771 syngeneic tumor model. [Figure 8F]

[0023] Data are presented showing that anti-IL-18BP antibodies of the present disclosure were effective (as monotherapy) or in combination with anti-0-PDL1 antibody administration in reducing serum levels of IL-18BP and increasing levels of the pro-inflammatory cytokines and chemokines IFNγ, IL-1β, IL-15, IL-27, and MIP-1α in tumor lysates in the E0771 syngeneic tumor model. [Figure 9A] 1 presents data showing that an anti-IL-18BP antibody of the present disclosure reduced tumor volume in an EMT6 animal tumor model, either as monotherapy or in combination with an anti-PDL1 antibody. [Figure 9B] 1 presents data showing that an anti-IL-18BP antibody of the present disclosure reduced tumor volume in an EMT6 animal tumor model, either as monotherapy or in combination with an anti-PDL1 antibody. DETAILED DESCRIPTION OF THE INVENTION

[0078] The present disclosure relates to anti-IL18BP antibodies (e.g., monoclonal antibodies), methods of making and using such antibodies, pharmaceutical compositions comprising such antibodies, nucleic acids encoding such antibodies, and host cells comprising nucleic acids encoding such antibodies.

[0079] The techniques and procedures described or referenced herein are generally well understood and commonly employed by those skilled in the art using conventional methodology, examples of which include, for example, widely used methodologies such as those described in Sambrook et al. Molecular Cloning: A Laboratory Manual 3rd edition (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Current Protocols in Molecular Biology (F.M. Ausubel, et al. eds., (2003); Monoclonal Antibodies: A Practical Approach (P. Shepherd and C. Dean, eds., Oxford University Press, 2000).

[0080] definition As used herein, the terms "interleukin-18 binding protein" or "IL18BP" or "IL18BP polypeptide" or "IL18BP protein" are used interchangeably and, unless otherwise indicated herein, refer to any naturally occurring IL18BP from any vertebrate source, including mammals, examples of which include primates (e.g., humans and cynomolgus monkeys (cyno)) and rodents (e.g., mice and rats). IL18BP is also known as tadekinig alpha and interferon-g inducer. In some embodiments, the term encompasses both wild-type sequences and naturally occurring variant sequences, e.g., splice variants or allelic variants. In some embodiments, the term encompasses "full-length," unprocessed IL18BP, as well as all forms of IL18BP produced by processing within cells. In some embodiments, the IL18BP is human IL18BP. As used herein, the term "human IL18BP" refers to a polypeptide having the amino acid sequence of SEQ ID NO: 1.

[0081] The terms "anti-IL18BP antibody," "antibody that binds to IL18BP," and "antibody that specifically binds IL18BP" refer to an antibody that is capable of binding IL18BP with sufficient affinity to be useful as a diagnostic and / or therapeutic agent in targeting IL18BP. In one embodiment, the extent of binding of the anti-IL18BP antibody to an unrelated, non-IL18BP polypeptide is less than about 10% of the binding of the antibody to IL18BP as measured, for example, by radioimmunoassay (RIA). In certain embodiments, an antibody that binds to IL18BP has an affinity of <1 μM, <100 nM, <10 nM, <1 nM, <0.1 nM, <0.01 nM, or <0.001 nM (e.g., 10 -8 M or less, e.g. 10 -8 M~10 -13 M, e.g., 10 -9 M~10 -13 In certain embodiments, the anti-IL18BP antibody binds to an epitope of IL18BP that is conserved among IL18BPs from different species.

[0082] With respect to the binding of an antibody to a target molecule, the terms "specific binding" or "specifically binding" or "specific for" a particular polypeptide or epitope on a particular polypeptide target refer to binding that is measurably different from non-specific interactions. Specific binding can be measured, for example, by determining the binding of a molecule compared to the binding of a control molecule. For example, specific binding can be determined by competition with a control molecule similar to the target, e.g., an excess of unlabeled target. In this case, specific binding is indicated when the binding of the labeled target to the probe is competitively inhibited by the excess of unlabeled target. As used herein, the terms "specific binding" or "specifically binding" or "specific for" a particular polypeptide or epitope on a particular polypeptide target refer to binding that is measurably different from non-specific interactions, for example, about 10 -4 M or less, 10 -5 M or less, 10 -6 M or less, 10 -7 M or less, 10 -8 M or less, 10 -9 M or less, 10 -10 M or less, 10 -11 M or less, 10 -12 KD for any target less than or equal to M, or 10 -4 M~10 -6 M or 10 -6 M~10 -10 M or 10 -7 M~10 -9 Affinity can be exhibited by a molecule having a KD in the range of M. As will be understood by those skilled in the art, affinity and KD values ​​are inversely related. High affinity for an antigen is measured by a low KD value. In one embodiment, the term "specific binding" refers to binding of a molecule to a particular polypeptide or an epitope on a particular polypeptide without substantially binding to any other polypeptides or polypeptide epitopes.

[0083] As used herein, the term "immunoglobulin (Ig)" is used interchangeably with "antibody." The term "antibody" is used herein in the broadest sense to specifically encompass monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), including those formed from at least two intact antibodies, and antigen-binding antibody fragments so long as they exhibit the desired biological activity.

[0084] "Native antibodies" are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light chains ("L") and two identical heavy chains ("H"). Each light chain is linked to a heavy chain by one covalent disulfide bond, although the number of disulfide linkages varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain contains at one end a variable domain (V H ), followed by multiple constant domains. Each light chain has a variable domain (V L ) at its other end and a constant domain. The constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain. Particular amino acid residues are believed to form an interface between the light chain variable domain and the heavy chain variable domain.

[0085] For the structure and properties of different classes of antibodies, see, e.g., BASIC AND CLINICAL IMMUNOLOGY, 8TH ED., DANIEL P. STITES, ABBA I. TERR AND TRISTRAM G. PARSLOW (EDS.), APPLETON & LANGE, NORWALK, CT, 1994, PAGE 71 AND CHAPTER 6.

[0086] The light chains of any vertebrate species can be assigned to one of two clearly distinct types, called kappa ("κ") and lambda ("λ"), based on the amino acid sequence of their constant domains. Depending on the amino acid sequence of the constant domain (CH) of their heavy chains, immunoglobulins can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, with heavy chains designated alpha ("α"), delta ("δ"), epsilon ("ε"), gamma ("γ"), and mu ("μ"), respectively. The gamma and alpha classes are further divided into subclasses (isotypes) based on relatively minor differences in CH sequence and function; for example, humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known and generally described in, for example, Abbas et al., Cellular and Molecular Immunology, 4 th ed. (WB Saunders Co., 2000).

[0087] A "variable region" or "variable domain" of an antibody (such as an anti-IL18BP antibody of the present disclosure) refers to the amino-terminal domains of the heavy or light chain of the antibody. The variable domains of the heavy and light chains are referred to as "V" and "V" respectively. H " and "V L These domains are generally the most variable parts of an antibody (compared to other antibodies of the same class) and contain the antigen-binding sites.

[0088] The term "variable" refers to the fact that the sequences of certain segments of the variable domains vary extensively among antibodies, such as the anti-IL18BP antibodies of the present disclosure. The variable domains mediate antigen binding and define the specificity of a particular antibody for a particular antigen. However, variability is not uniformly distributed throughout the span of the variable domains. Instead, it is concentrated in three segments called hypervariable regions (HVRs) in both the light-chain and heavy-chain variable domains. The more highly conserved portions of the variable domains are called framework regions (FRs). Naturally occurring heavy- and light-chain variable domains each contain four FR regions, which primarily adopt a beta-sheet structure connected by three HVRs that form loops connecting the beta-sheet structure and, in some cases, form part of the beta-sheet structure. The HVRs of each chain are held together in close proximity by the FR regions and, together with the HVRs from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al., Sequences of Immunological Interest, Fifth Edition, National Institutes of Health, Bethesda, MD (1991)). The constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, an example of which is participation of the antibody in antibody-dependent cellular toxicity.

[0089] As used herein, the term "monoclonal antibody" refers to an antibody (such as the monoclonal anti-IL18BP antibody of the present disclosure) obtained from a substantially homogeneous population of antibodies; i.e., the individual antibodies comprising the population are identical except for naturally occurring mutations and / or post-translational modifications (e.g., isomerization, amidation, etc.), which may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, monoclonal antibodies are advantageous in that they are synthesized by hybridoma culture, uncontaminated by other immunoglobulins. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and should not be construed as requiring production of the antibody by any particular method. For example, monoclonal antibodies to be used in accordance with the present invention may be produced by a variety of techniques, including, but not limited to, one or more of the following methods: These include methods of immunization of animals (including, but not limited to, rats, mice, rabbits, guinea pigs, hamsters and / or chickens) with one or more of DNA(s), virus-like particles, polypeptide(s) and / or cell(s), hybridoma methods, B-cell cloning methods, recombinant DNA methods, and techniques for producing human or human-like antibodies in animals that contain some or all of the human immunoglobulin loci or genes encoding human immunoglobulin sequences.

[0090] The terms "full-length antibody," "intact antibody," or "whole antibody" are used interchangeably to refer to an antibody in a substantially intact form (such as an anti-IL18BP antibody), as opposed to an antibody fragment. Specifically, full-length antibodies include those having two light chains and two heavy chains, including an Fc region. The constant domains may be native-sequence constant domains (e.g., human native-sequence constant domains) or amino acid sequence variants thereof. In some cases, intact antibodies may have one or more effector functions.

[0091] The term "monovalent antibody" or "mono-arm antibody" refers to an antibody that has a single antigen-binding recognition domain specific for a target antigen (i.e., the antibody contains only one antigen-binding domain). In some embodiments, the single antigen-binding domain comprises a single variable region heavy chain polypeptide and a single variable region light chain polypeptide. An antibody that is "monovalent" with respect to a target contains only one antigen-binding domain with respect to that target.

[0092] "Antibody fragment" refers to a molecule other than an intact antibody that contains a portion of an intact antibody that binds the antigen to which the intact antibody binds. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments, diabodies, linear antibodies (see U.S. Pat. No. 5,641,870, Example 2; Zapata et al., Protein Eng. 8(10):1057-1062 (1995)), single-chain antibody molecules, and multispecific antibodies formed from antibody fragments.

[0093] As used herein, the terms "antigen-binding domain," "antigen-binding region," "antigen-binding site," and similar terms refer to the portion of an antibody molecule (e.g., the hypervariable region (HVR)) that contains the amino acid residues that confer specificity to the antibody molecule for an antigen.

[0094] Papain digestion of an antibody (such as the anti-IL18BP antibody of the present disclosure) produces two identical antigen-binding fragments called "Fab" fragments and a residual "Fc" fragment, a name reflecting its ability to crystallize readily. The Fab fragment contains the entire light chain plus the variable region domain (V H ) and the first constant domain of one heavy chain (C H1). Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody yields a single large F(ab')2 fragment that roughly corresponds to two disulfide-linked Fab fragments with different antigen-binding activities and is still capable of antigen cross-linking. The Fab' fragment contains one or more cysteines from the antibody hinge region, C H F(ab')2 antibody fragments differ from Fab fragments by having a few additional residues at the carboxy terminus of one domain. Fab'-SH is the designation used herein for Fab' in which the cysteine ​​residue(s) in the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

[0095] The Fc fragment contains the carboxy-terminal portions of both heavy chains held together by disulfides. The effector functions of an antibody are determined by sequences in the Fc region, which is also recognized by Fc receptors (FcRs) found on certain types of cells.

[0096] A "functional fragment" of an antibody (such as an anti-IL18BP antibody of the present disclosure) includes a portion of an intact antibody, generally including the antigen-binding or variable region of the intact antibody, or the Fc region of the antibody that retains or has modified FcR binding ability. Examples of antibody fragments include linear antibodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments.

[0097] The term "diabody" refers to a V-type antibody that achieves inter-chain but not intra-chain variable domain pairing, resulting in a bivalent fragment, i.e., a fragment with two antigen-binding sites. H Domains and V L This refers to small antibody fragments prepared by constructing scFv fragments with a short linker (approximately 5-10 residues) between the domains. Bispecific diabodies are small antibody fragments prepared by constructing scFv fragments with a short linker (approximately 5-10 residues) between the domains. H and V LIt is a heterodimer of two "crossover" sFv fragments in which the domains are present on different polypeptide chains.

[0098] As used herein, "chimeric antibody" refers to antibodies (immunoglobulins) such as the chimeric anti-IL18BP antibodies of the present disclosure (in which a portion of the heavy and / or light chain is identical to or homologous to corresponding sequences in antibodies from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical to or homologous to corresponding sequences in antibodies from another species or belonging to another antibody class or subclass), as well as fragments of such antibodies, so long as they exhibit the desired biological activity. Chimeric antibodies of interest herein include PRIMATIZED® antibodies, in which the antigen-binding region of the antibody is derived from, for example, an antibody produced by immunizing macaques with an antigen of interest. As used herein, "humanized antibody" is used as a subset of "chimeric antibody."

[0099] "Humanized" forms of non-human (e.g., murine) antibodies (such as humanized forms of the anti-IL18BP antibodies of the present disclosure) are chimeric antibodies comprising amino acid residues from non-human HVRs and amino acid residues from human FRs. In certain embodiments, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, with all or substantially all of its HVRs (e.g., CDRs) corresponding to those of a non-human antibody and all or substantially all of its FRs corresponding to those of a human antibody. A humanized antibody may optionally comprise at least a portion of an antibody constant region derived from a human antibody. A "humanized form" of an antibody (e.g., a non-human antibody) refers to an antibody that has undergone humanization.

[0100] A "human antibody" is an antibody having an amino acid sequence corresponding to that of an antibody produced by a human (such as the anti-IL18BP antibody of the present disclosure) and / or an antibody made using any technique for making human antibodies as disclosed herein. This definition of a human antibody specifically excludes humanized antibodies, which comprise non-human antigen-binding residues. Human antibodies can be produced using various techniques known in the art, including phage display libraries and yeast display libraries. Human antibodies can be prepared by administering antigen to transgenic animals (e.g., immunized xeno-mouse) that have been modified to produce such antibodies in response to antigen challenge but whose endogenous gene loci have been disabled, and can also be generated by human B-cell hybridoma technology.

[0101] As used herein, the terms "hypervariable region," "HVR," or "HV" refer to the regions of an antibody variable domain (such as those of the anti-IL18BP antibodies of the present disclosure) that are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies contain six HVRs, i.e., V H Three inside (H1, H2, H3) and V L HVRs contain three (L1, L2, and L3) within the HVR. In natural antibodies, H3 and L3 show the most diversity among the six HVRs, and H3 in particular is thought to play a unique role in conferring excellent specificity to antibodies. Naturally occurring camelid antibodies, which consist only of heavy chains, are functional and stable in the absence of light chains.

[0102] Several HVR delineations are in use and are encompassed herein. In some embodiments, HVRs may be Kabat complementarity determining regions (CDRs), which are based on sequence variation and are the most commonly used (Kabat et al., supra). In some embodiments, HVRs may be Chothia CDRs. Chothia refers instead to the location of structural loops (Chothia and Lesk J. Mol. Biol, 196:901-917 (1987)). In some embodiments, HVRs may be AbM HVRs. AbM HVRs represent a compromise between Kabat CDRs and Chothia structural loops and are used in Oxford Molecular's AbM antibody modeling software. In some embodiments, HVRs may be "contact" HVRs. "Contact" HVRs are based on analysis of available complex crystal structures. The residues of each of these HVRs are shown below. Loop Kabat AbM Chothia Contact L1 L24-L34 L24-L34 L26-L32 L30-L36 L2 L50-L56 L50-L56 L50-L52 L46-L55 L3 L89-L97 L89-L97 L91-L96 L89-L96 H1 H31-H35B H26-H35B H26-H32 H30-H35B (Kabat numbering) H1 H31-H35 H26-H35 H26-H32 H30-H35 (Chothia numbering) H2 H50-H65 H50-H58 H53-H55 H47-H58 H3 H95-H102 H95-H102 H96-H101 H93-H101

[0103] HVRs may include the following "extended HVRs": 24-36 or 24-34 (L1), 46-56 or 50-56 (L2), and 89-97 or 89-96 (L3) for VL, and 26-35 (H1), 50-65 or 49-65 (preferred embodiment) (H2), and 93-102, 94-102, or 95-102 (H3) for VH. For each of these extended HVR definitions, the variable domain residues are numbered according to Kabat et al. (see above).

[0104] "Framework" or "FR" residues are those variable domain residues other than the HVR residues as herein defined.

[0105] As used herein, an "acceptor human framework" refers to a V-framework derived from a human immunoglobulin framework or a human consensus framework. L or V H The acceptor human framework "derived" from a human immunoglobulin framework or a human consensus framework may comprise the same amino acid sequence, or may comprise pre-existing amino acid sequence changes. In some embodiments, the number of pre-existing amino acid changes is 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less. When pre-existing amino acid changes are present in the VH, preferably, those changes occur at only three, two, or one of positions 71H, 73H, and 78H; for example, the amino acid residues at those positions may be 71A, 73T, and / or 78A. In one embodiment, the sequence of the VL acceptor human framework is V L It is identical to a human immunoglobulin framework sequence or a human consensus framework sequence.

[0106] The "human consensus framework" is based on human immunoglobulin V L or V HA framework representing the most commonly occurring amino acid residues in a selection of framework sequences. Generally, human immunoglobulin V L or V H The selection of sequences is from a subgroup of variable domain sequences. Generally, the subgroup of sequences is as follows: Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991). L Examples include that the subgroup may be subgroup kappa I, kappa II, kappa III, or kappa IV as per Kabat et al., supra. H For , the subgroup may be subgroup I, subgroup II or subgroup III as in Kabat et al., supra.

[0107] An "amino acid modification" at a specifically stated position (e.g., in an anti-IL18BP antibody of the present disclosure) refers to a substitution or deletion of the specifically stated residue, or an insertion of at least one amino acid residue adjacent to the specifically stated residue. An insertion "adjacent" a specifically stated residue means an insertion within 1-2 residues thereof. The insertion may be N-terminal or C-terminal to the specified residue. Preferred amino acid modifications herein are substitutions.

[0108] An "Fv" is the minimum antibody fragment that contains a complete antigen-recognition and binding site. This fragment consists of a dimer of one heavy-chain and one light-chain variable domain in tight, non-covalent association. Extending from the folding of these two domains are six hypervariable loops (three loops each from the H and L chains), which contribute antigen-binding amino acid residues and confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three antigen-specific HVRs) has the ability to recognize and bind antigen (albeit with lower affinity than the entire binding site).

[0109] "Single-chain Fv," also abbreviated as "sFv" or "scFv," is an antibody fragment comprising the VH and VL antibody domains joined in a single polypeptide chain. H and V L Preferably, the sFv further includes a polypeptide linker between the domains which enables the sFv to form the desired structure for antigen binding.

[0110] Antibody "effector functions" refer to those biological activities attributable to the Fc region (a native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vary depending on the antibody isotype.

[0111] The term "Fc region" herein is used to define the C-terminal region of an immunoglobulin heavy chain, and includes native-sequence Fc regions and variant Fc regions. Although the boundaries of the Fc region of an immunoglobulin heavy chain can vary, the human IgG heavy chain Fc region is usually defined to stretch from the amino acid residue at position Cys226 or Pro230 to its carboxyl terminus. The C-terminal lysine of the Fc region (residue 447 (according to the EU numbering system)) can be removed, for example, during antibody production or purification, or by recombinantly engineering the nucleic acid encoding the antibody heavy chain. Thus, an intact antibody composition may include an antibody population in which all K447 residues have been removed, an antibody population in which the K447 residue has not been removed, and an antibody population having a mixture of antibodies containing and not containing the K447 residue. Suitable native-sequence Fc regions for use in the antibodies of the present disclosure include human IgG1, IgG2, IgG3, and IgG4.

[0112] A "native sequence Fc region" comprises an amino acid sequence identical to that of an Fc region found in nature. Native sequence human Fc regions include native sequence human IgG1 Fc regions (non-A and A allotypes), native sequence human IgG2 Fc regions, native sequence human IgG3 Fc regions, and native sequence human IgG4 Fc regions, as well as naturally occurring variants thereof.

[0113] A "variant Fc region" comprises an amino acid sequence that differs from that of a native-sequence Fc region by virtue of at least one amino acid modification, preferably one or more amino acid substitution(s). Preferably, the variant Fc region has at least one amino acid substitution compared to a native-sequence Fc region or the Fc region of a parent polypeptide, e.g., about 1 to about 10 amino acid substitutions, and preferably about 1 to about 5 amino acid substitutions, in the native-sequence Fc region or in the Fc region of the parent polypeptide. A variant Fc region herein preferably has at least 80% homology with a native-sequence Fc region and / or the Fc region of a parent polypeptide, most preferably at least 90% homology thereto, and more preferably at least 95% homology thereto.

[0114] "Fc receptor" or "FcR" describes a receptor that binds to the Fc region of an antibody. A preferred FcR is a native-sequence human FcR. Further, a preferred FcR is one that binds IgG antibodies (gamma receptors) and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced ​​forms of these receptors. FcγRII receptors include FcγRIIA (an "activating receptor") and FcγRIIB (an "inhibiting receptor"), which have similar amino acid sequences but differ primarily in their cytoplasmic domains. Activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif ("ITAM") in its cytoplasmic domain. Inhibiting receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif ("ITIM") in its cytoplasmic domain. Other FcRs, including those identified in the future, are encompassed by the term "FcR" herein. FcRs can also extend the serum half-life of antibodies.

[0115] As used herein, "percent (%) amino acid sequence identity" and "homology" with respect to a peptide, polypeptide, or antibody sequence refer to the percentage of amino acid residues in a candidate sequence that are identical to amino acid residues in a specific peptide or polypeptide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and without considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in a variety of ways within the skill of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALIGN™ (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms known in the art necessary to achieve maximum alignment over the entire length of the sequences being compared.

[0116] The term "competition," when used in the context of antibodies competing for the same or overlapping epitope, refers to competition between the antibodies as determined by an assay in which the antibody being tested prevents or inhibits (e.g., reduces) specific binding of a reference molecule (e.g., a ligand or reference antibody) to a common antigen (e.g., IL18BP or a fragment thereof). Many types of competitive binding assays can be used to determine whether an antibody competes with another antibody. For example, solid-phase direct or indirect radioimmunoassays (RIA), solid-phase direct or indirect enzyme immunoassays (EIA), sandwich competition assays (see, e.g., Stahli et al., 1983, Methods in Enzymology 9:242-253), solid-phase direct biotin-avidin EIA (see, e.g., Kirkland et al., 1986, J. Immunol. 137:3614-3619), solid-phase direct label assays, solid-phase direct label sandwich assays (see, e.g., Harlow and Lane, 1988, Antibodies, A Laboratory Manual, Cold Spring Harbor Press), solid-phase direct label RIA using 1-125 labels (see, e.g., Morel et al., 1988, Molec. Immunol. 25:7-15), solid-phase direct biotin-avidin EIA (see, e.g., Cheung, et al., 1990, Virology 176:546-552), and direct label RIA (Moldenhauer et al., 1990, Scand. J. Immunol. 32:77-82). Typically, such assays involve the use of purified antigen bound to a solid surface, or cells bearing either of these (unlabeled, labeled test antibody and labeled reference antibody). Competitive inhibition is measured by determining the amount of label bound to the solid surface or cells in the presence of the test antibody. Typically, the test antibody is present in excess. Antibodies identified by competitive assays (competing antibodies) include antibodies that bind to the same epitope as the reference antibody and antibodies that bind to adjacent epitopes sufficiently close to the epitope bound by the reference antibody so that steric hindrance occurs.Typically, a competing antibody, when present in excess, inhibits (e.g., reduces) specific binding of a reference antibody to a common antigen by at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97.5%, and / or nearly 100%.

[0117] As used herein, "interaction" between an IL18BP polypeptide and a second polypeptide includes, but is not limited to, protein-protein interactions, physical interactions, chemical interactions, bonds, covalent bonds, and ionic bonds. As used herein, an antibody "inhibits interaction" between two polypeptides if the antibody disrupts, reduces, or completely eliminates the interaction between the two polypeptides. An antibody of the present disclosure "suppresses interaction" between two polypeptides if the antibody binds to one of the two polypeptides. In some embodiments, the interaction can be inhibited by at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 97.5%, and / or nearly 100%.

[0118] The term "epitope" includes any determinant capable of binding to an antibody. An epitope is the region of an antigen bound by an antibody targeting that antigen, and, if the antigen is a polypeptide, includes specific amino acids that make direct contact with the antibody. In most cases, epitopes reside on polypeptides, but in some cases, they may reside on other types of molecules, such as nucleic acids. Epitopes may include chemically active surface groups of molecules, such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and may have specific three-dimensional structural characteristics and / or specific charge characteristics. Generally, antibodies specific for a particular target antigen preferentially recognize epitopes on the target antigen in a complex mixture of polypeptides and / or macromolecules.

[0119] An "isolated" antibody (such as an isolated anti-IL18BP antibody of the present disclosure) is one that has been identified, separated, and / or recovered from components of its production environment (e.g., natural or recombinant). Preferably, an isolated antibody is free from association with all other contaminating components from its production environment. Contaminating components from its production environment (such as those arising from recombinantly transfected cells) are substances that would normally interfere with research, diagnostic, or therapeutic uses of the antibody and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, the antibody is purified (1) to greater than 95%, and in some embodiments, greater than 99%, by weight of the antibody, as measured, for example, by the Lowry assay; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence using a spinning cup sequenator; or (3) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver staining. Isolated antibody includes the antibody in situ within recombinant T cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated polypeptide or antibody will be prepared by at least one purification step.

[0120] An "isolated" nucleic acid molecule encoding an antibody (such as an anti-IL18BP antibody of the present disclosure) is a nucleic acid molecule that is identified and separated from at least one contaminant nucleic acid molecule with which it is ordinarily associated in the environment in which it is produced. Preferably, an isolated nucleic acid is free from association with all components associated with the production environment. Isolated nucleic acid molecules encoding the polypeptides and antibodies herein are other than in the form or environment in which they are found in nature. Thus, isolated nucleic acid molecules are distinguished from nucleic acids encoding the polypeptides and antibodies herein that naturally occur in cells.

[0121] As used herein, the term "vector" is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid," which refers to a circular double-stranded DNA into which additional DNA segments may be ligated. Another type of vector is a phage vector. Another type of vector is a viral vector, into which additional DNA segments may be ligated. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) can be integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operably linked. Such vectors are referred to herein as "recombinant expression vectors" or simply, "expression vectors." In general, expression vectors useful in recombinant DNA techniques are often in the form of plasmids. As the plasmid is the most commonly used form of vector, "plasmid" and "vector" may be used interchangeably herein.

[0122] "Polynucleotide" or "nucleic acid," used interchangeably herein, refer to a polymer of nucleotides of any length, and include DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or a synthetic reaction.

[0123] A "host cell" includes an individual cell or cell culture that can be or has been the recipient of a vector(s) for incorporating a polynucleotide insert. A host cell includes the progeny of a single host cell, although the progeny may not necessarily be completely identical (in morphology or genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. A host cell includes cells transfected in vivo with a polynucleotide(s) of the invention.

[0124] As used herein, a "carrier" includes a pharmaceutically acceptable carrier, excipient, or stabilizer that is non-toxic to cells or mammals exposed thereto at the dosages and concentrations employed.

[0125] As used herein, the term "treatment" refers to a clinical intervention designed to alter the natural course of a clinical condition in an individual receiving treatment. Desirable effects of treatment include slowing the rate of progression, improving or alleviating the pathological condition, and remission or improved prognosis of a particular disease, disorder, or condition. For example, an individual is successfully "treated" if one or more symptoms associated with a particular disease, disorder, or condition are reduced or eliminated.

[0126] An "effective amount" refers to at least an amount effective, at dosages and for periods of time necessary, to achieve a desired therapeutic result. An effective amount may be provided in one or more administrations. An effective amount is also an amount in which any toxic or detrimental effects of the treatment are outweighed by the therapeutically beneficial effects. For therapeutic applications, beneficial or desired results include clinical results, such as a reduction in one or more symptoms attributable to the disease, an improvement in the quality of life of those affected by the disease, a reduction in the dosage of other drugs required to treat the disease, e.g., augmentation of other drug therapies by targeting, a delay in disease progression, and / or an extension of survival. An effective amount of a drug, compound, or pharmaceutical composition is an amount sufficient to achieve therapeutic treatment directly or indirectly. As understood in a clinical context, an effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with another drug, compound, or pharmaceutical composition. Thus, an "effective amount" may be considered in the context of administering one or more therapeutic agents, or may be considered to provide an effective amount of a single agent where a desired result may or is achieved in combination with one or more other agents.

[0127] For purposes of treatment, an "individual" refers to any animal classified as a mammal, including humans, domestic and farm animals, zoo, sport, or pet animals, examples of which include dogs, horses, rabbits, cows, pigs, hamsters, gerbils, mice, ferrets, rats, cats, etc. In some embodiments, the individual is a human.

[0128] As used herein, "in conjunction" or "in combination" administration with another compound or composition includes simultaneous administration and / or administration at different times. In conjunction or combination administration also encompasses administration as a co-formulation, or administration as separate compositions, using the same or different routes of administration, including different dosing frequencies or intervals. In some embodiments, combined administration is administration as part of the same treatment regimen.

[0129] The term "about" as used herein refers to a normal error range for the respective value, which would be readily understood by one of ordinary skill in the art. Reference herein to "about" a value or parameter includes (and describes) embodiments that are directed to the value or parameter itself.

[0130] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. For example, a reference to an "antibody" is a reference to one to many antibodies, such as molar amounts, and includes equivalents thereof known to those skilled in the art, and so forth.

[0131] Aspects and embodiments of the present disclosure described herein are understood to "comprise," "consist," and "consist essentially of" aspects and embodiments.

[0132] Anti-IL18BP antibody Anti-IL18BP antibodies are provided herein. The antibodies provided herein are useful, for example, in the treatment of various diseases, disorders, and conditions, such as cancer.

[0133] In one aspect, the present disclosure provides an isolated (e.g., monoclonal) antibody that binds to an epitope within an IL18BP protein or polypeptide of the present disclosure. IL18BP proteins or polypeptides of the present disclosure include, but are not limited to, mammalian IL18BP proteins or polypeptides, human IL18BP proteins or polypeptides, mouse (murine) IL18BP proteins or polypeptides, and cynomolgus monkey IL18BP proteins or polypeptides. IL18BP proteins and polypeptides of the present disclosure include naturally occurring variants of IL18BP. In some embodiments, the IL18BP proteins and polypeptides of the present disclosure are soluble. In some embodiments, the IL18BP proteins and polypeptides of the present disclosure are present in the extracellular space. In some embodiments, IL18BP is expressed by mononuclear cells.

[0134] IL18BP protein The human IL18BP gene encodes at least four different isoforms derived from mRNA splice variants (IL18BPa, b, c, and d), and two isoforms of mouse IL18BP have been identified (Kim et al., 2000, PNAS, 97:1190-1195). IL18BPa is the most widely expressed isoform and binds mature IL-18 with an affinity significantly higher than that of IL-18 receptor a.

[0135] Macrophage activation syndrome Macrophage activation syndrome (MAS) is a term used by rheumatologists to describe potentially life-threatening complications of systemic inflammatory disorders. Animal models of MAS provide a useful model of inflammation (McCain et al., 2018, Blood, 131:1303-1394). In the MAS model described by McCain et al., repeated stimulation of TLR9 by repeated injections of cytosine guanine 1826 oligonucleotide (CpG) results in a MAS-like disease in rodents, leading to macrophage activation, cytopenias, splenomegaly, and elevated serum cytokine levels (including elevated IL-18, IFNγ, and IFNγ-related gene expression) independent of lymphocyte dysfunction. When MAS was induced in IL-18BP-deficient mice, significant increases in IL-18, IFNγ, and CXCL9 levels were observed, which were resolved by IL-18 or IFNγ blockade. Thus, in this MAS model, increased IL-18 levels play a significant role in driving MAS, in part through increased IFNγ levels.

[0136] As described below, the effect of IL-18BP blockade by anti-IL18BP antibodies of the present disclosure on inflammation was examined using a MAS model. As shown herein, in a rodent MAS model, anti-IL18BP antibodies of the present disclosure decreased the percentage of CD3+ T cells, decreased the percentage of CD19+ B cells, decreased the percentage of CD11b+ cells, and increased the percentage of macrophages.

[0137] Furthermore, administration of the anti-IL18BP antibodies of the present disclosure to mice in the MAS model increased the levels of inflammatory cytokines in the serum, including IFNγ, IL-10, TNFα, and IL-6.

[0138] IL-18, IL18BP, and cancer IL18BP is elevated in a variety of human cancers, including cholangiocarcinoma, diffuse large B-cell lymphoma, glioblastoma multiforme, head and neck squamous cell carcinoma, renal clear cell carcinoma, pancreatic adenocarcinoma, cutaneous melanoma, and gastric adenocarcinoma. IL18BP has been described as a secreted immune checkpoint that fundamentally alters the biological effects of IL-18 within the tumor microenvironment (TME). Both IL-18BP transcripts and protein are highly expressed in the TME and are further increased by treatment with IL-18 in an IFNγ-dependent manner (Zhou et al., 2020, Nature, 583:609; Dixon and Kuchroo, 2020, Cell Research, 30:831-832).

[0139] Zhou et al. showed that an IL-18 variant that retains the ability to bind IL-18 receptor alpha and retains full receptor signaling ability but is unable to bind IL-18BP (and therefore is not inhibited by IL-18BP) can enhance the activity of IL-18 when administered to mice. Specifically, DR-18 inhibited tumor growth, increased survival, and (in some mice) completely regressed tumors. In this study, the authors suggested that the antitumor efficacy of DR-18 is due to its independence from IL18BP, highlighting the potential of the IL-18 pathway to enhance antitumor immunity (Zhou et al., 2020, Nature, 583:609).

[0140] Without being bound by theory, the anti-IL18BP antibodies of the present disclosure block the binding of IL-18 to IL18BP, thereby increasing the availability of IL-18, enhancing IL-18 activity, and enhancing anti-tumor activity. Anti-IL18BP antibody-mediated blockade of IL-18BP then renders unbound IL-18 in the tumor microenvironment (TME) available to induce inflammation and bind its receptors on T cells and NK cells to promote anti-tumor immunity.

[0141] In some embodiments, the anti-IL-18BP antibodies of the present disclosure increase free IL-18 serum levels. In some embodiments, the anti-IL18BP antibodies of the present disclosure decrease IL-18BP serum levels.

[0142] In some embodiments, anti-IL-18BP antibodies of the present disclosure increase the levels of pro-inflammatory cytokines and chemokines in vivo. In some embodiments, anti-IL-18BP antibodies of the present disclosure increase the levels of pro-inflammatory cytokines and chemokines in tumor lysates (e.g., in the tumor microenvironment). In some embodiments, anti-IL-18BP antibodies of the present disclosure increase the levels of INFγ, IL-1β, IL-15, IL-27, and / or MIP-1α in vivo. In other embodiments, anti-IL-18BP antibodies of the present disclosure increase the levels of INFγ, IL-1β, IL-15, IL-27, and / or MIP-1α in tumor lysates (e.g., in the tumor microenvironment).

[0143] The present disclosure demonstrates that reduction of IL18BP activity or expression with anti-IL18BP antibodies reduces tumor growth in mouse tumor models.

[0144] Exemplary Anti-IL18BP Antibodies and Other Specific Antibody Embodiments In some embodiments, provided herein are anti-IL18BP antibodies comprising at least one, two, three, four, five, or six HVRs selected from the following: The options are: (a) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 167, 168, and 169; (b) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 170, 171, 172, 173, 174, 175, 176, 177, and 178; and (c) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229 (d) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, and 247; (e) HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, and 248; and (f) HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, and 249.

[0145] In some embodiments, at least one, at least two, or all three V selected from the following: HProvided herein are anti-IL18BP antibodies comprising HVR sequences, options of which include: (a) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 167, 168, and 169; (b) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, (c) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 179, 180, 181, 182, 183, 184, 185, 186, 187 and 188.

[0146] In some embodiments, provided herein are anti-IL18BP antibodies, which comprise at least one, at least two, or all three V selected from the following: L The options include: (a) HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, and 247; (b) HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, and 248; and (c) HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, and 249.

[0147] In some aspects, provided herein is an anti-IL18BP antibody, the anti-IL18BP antibody comprising: (a) V H A domain comprising at least one, at least two, or all three V selected from the following: HHVR sequences, the options being: (i) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 167, 168, and 169; (ii) SEQ ID NOs: 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 170, 171, 172, 173, 174, 175; (b) a VHVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188; and (iii) a VHVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188; L A domain comprising at least one, at least two, or all three V selected from the following: L and (iii) an HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, and 249.

[0148] In some aspects, provided herein are anti-IL18BP antibodies, including (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 60, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 71, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 87, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 112, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122. (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 73, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 88, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 103, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123. HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 62, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 74, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 89, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 104, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 114, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 124, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 75, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 89, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 104, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 114, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 124. (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 63, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 76, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 91, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 106, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 115, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123.and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 77, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 88, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 103, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 64, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 78, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 65, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 79, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 93, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 127. (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 80, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 94, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 108, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 117, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 128, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 66, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 81, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 95 R-H3, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 109, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 118, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 129, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 67, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 82, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 96, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 130,(a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 68, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 83, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 97, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 119, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 131, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 69, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 84, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 98, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 110, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 120, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 132, (a) sequence (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 70, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 85, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 99, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 111, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 121, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 133, as well as (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 70, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 86, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 100, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 111, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 121, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 133.

[0149] In another aspect, the anti-IL18BP antibody comprises a heavy chain variable domain (V) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 and 44. H ) sequence. In certain embodiments, HThe sequence has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44, and contains substitutions (e.g., conservative substitutions), insertions, or deletions compared to the reference sequence, but an anti-IL18BP antibody comprising the sequence retains the ability to bind to IL18BP. In a particular embodiment, a total of 1 to 10 amino acids have been substituted, inserted, and / or deleted in SEQ ID NO: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or 44. In certain aspects, a total of 1 to 5 amino acids have been substituted, inserted, and / or deleted in SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or 44. In certain aspects, the substitutions, insertions, or deletions occur in the regions outside the HVRs (i.e., FRs). Optionally, the anti-IL18BP antibody comprises a V-type or V-type amino acid substitution, insertion, and / or deletion in SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44. H In certain embodiments, V H comprises one, two or three HVRs selected from the following options: (a) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 60, 61, 62, 63, 64, 65, 66, 67, 68, 69 and 70; (b) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85 and 86; and (c) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 and 100.

[0150] In another aspect, an anti-IL18BP antibody is provided, comprising a light chain variable domain (V) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59. L In certain embodiments, V L The sequence has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, and 59, and contains substitutions (e.g., conservative substitutions), insertions, or deletions compared to the reference sequence, although an anti-IL18BP antibody comprising the sequence retains the ability to bind to IL18BP. In some embodiments, a total of 1 to 10 amino acids are substituted, inserted, and / or deleted in SEQ ID NO: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, or 59. In certain embodiments, a total of 1 to 5 amino acids have been substituted, inserted, and / or deleted in SEQ ID NO: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, or 59. In certain embodiments, the substitutions, insertions, or deletions occur in the regions outside the HVRs (i.e., FRs). Optionally, the anti-IL18BP antibody comprises a V-type amino acid sequence of SEQ ID NO: 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, or 210. L In certain embodiments, V Lcomprises one, two, or three HVRs selected from the following options: (a) HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, and 111; (b) HVR-L2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 112, 113, 114, 115, 116, 117, 118, 119, 120, and 121; and (c) HVR-L3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, and 133.

[0151] In some embodiments, an anti-IL18BP antibody is provided, which antibody comprises a V as in any of the embodiments provided above. H and V as in any of the embodiments provided above. L In some embodiments, provided herein is an anti-IL18BP antibody, which comprises a V as in any of the embodiments provided above. H and V as in any of the embodiments provided above. L In one embodiment, the antibody comprises the V of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 and 44, and the V of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59. H and V L sequences, including post-translational modifications of those sequences.

[0152] In some embodiments, the heavy chain variable domain (V H ) and the light chain variable domain (V L ) is provided herein. H and V L is selected from the group consisting of: V comprising the amino acid sequence of SEQ ID NO:29 H and V comprising the amino acid sequence of SEQ ID NO: 45 L , V comprising the amino acid sequence of SEQ ID NO: 30 Hand V comprising the amino acid sequence of SEQ ID NO: 46 L , V comprising the amino acid sequence of SEQ ID NO: 31 H and V comprising the amino acid sequence of SEQ ID NO: 47 L , V comprising the amino acid sequence of SEQ ID NO: 32 H and V comprising the amino acid sequence of SEQ ID NO: 48 L , V comprising the amino acid sequence of SEQ ID NO: 33 H and V comprising the amino acid sequence of SEQ ID NO: 49 L , V comprising the amino acid sequence of SEQ ID NO: 34 H and V comprising the amino acid sequence of SEQ ID NO: 50 L , V comprising the amino acid sequence of SEQ ID NO: 35 H and V comprising the amino acid sequence of SEQ ID NO: 51 L , V comprising the amino acid sequence of SEQ ID NO: 36 H and V comprising the amino acid sequence of SEQ ID NO: 52 L , V comprising the amino acid sequence of SEQ ID NO: 37 H and V comprising the amino acid sequence of SEQ ID NO: 53 L , V comprising the amino acid sequence of SEQ ID NO: 38 H and V comprising the amino acid sequence of SEQ ID NO: 54 L , V comprising the amino acid sequence of SEQ ID NO: 39 H and V comprising the amino acid sequence of SEQ ID NO: 55 L , V comprising the amino acid sequence of SEQ ID NO: 40 H and V comprising the amino acid sequence of SEQ ID NO: 56 L , V comprising the amino acid sequence of SEQ ID NO: 41 H and V comprising the amino acid sequence of SEQ ID NO: 57 L , V comprising the amino acid sequence of SEQ ID NO: 42 H and V comprising the amino acid sequence of SEQ ID NO: 58 L , V comprising the amino acid sequence of SEQ ID NO: 43 H and V comprising the amino acid sequence of SEQ ID NO: 59 L and V comprising the amino acid sequence of SEQ ID NO: 44. H and V comprising the amino acid sequence of SEQ ID NO: 59 L is.

[0153] In some aspects, an anti-IL18BP antibody of the disclosure competitively inhibits the binding of at least one reference antibody selected from anti-IL18BP antibodies BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, and BP-16, and any combination thereof, for binding to IL18BP.

[0154] In some aspects, the anti-IL18BP antibodies of the present disclosure bind to an epitope of human IL18BP that is the same as or overlaps with an IL18BP epitope bound by at least one reference antibody selected from anti-IL18BP antibodies BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, and BP-16. Detailed exemplary methods for mapping antibody-binding epitopes are provided in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology, vol. 66 (Humana Press, Totowa, NJ).

[0155] In some embodiments, an anti-IL18BP antibody of the present disclosure competitively inhibits the binding of at least one reference antibody or binds to an epitope of human IL18BP that is the same as or overlaps with an IL18BP epitope bound by at least one reference antibody, wherein the reference antibody is a heavy chain variable domain (V H ) and the light chain variable domain (V L ), and this V H and V L is selected from the group consisting of: V comprising the amino acid sequence of SEQ ID NO:29 H and V comprising the amino acid sequence of SEQ ID NO: 45 L , V comprising the amino acid sequence of SEQ ID NO: 30 H and V comprising the amino acid sequence of SEQ ID NO: 46 L, V comprising the amino acid sequence of SEQ ID NO: 31 H and V comprising the amino acid sequence of SEQ ID NO: 47 L , V comprising the amino acid sequence of SEQ ID NO: 32 H and V comprising the amino acid sequence of SEQ ID NO: 48 L , V comprising the amino acid sequence of SEQ ID NO: 33 H and V comprising the amino acid sequence of SEQ ID NO: 49 L , V comprising the amino acid sequence of SEQ ID NO: 34 H and V comprising the amino acid sequence of SEQ ID NO: 50 L , V comprising the amino acid sequence of SEQ ID NO: 35 H and V comprising the amino acid sequence of SEQ ID NO: 51 L , V comprising the amino acid sequence of SEQ ID NO: 36 H and V comprising the amino acid sequence of SEQ ID NO: 52 L , V comprising the amino acid sequence of SEQ ID NO: 37 H and V comprising the amino acid sequence of SEQ ID NO: 53 L , V comprising the amino acid sequence of SEQ ID NO: 38 H and V comprising the amino acid sequence of SEQ ID NO: 54 L , V comprising the amino acid sequence of SEQ ID NO: 39 H and V comprising the amino acid sequence of SEQ ID NO: 55 L , V comprising the amino acid sequence of SEQ ID NO: 40 H and V comprising the amino acid sequence of SEQ ID NO: 56 L , V comprising the amino acid sequence of SEQ ID NO: 41 H and V comprising the amino acid sequence of SEQ ID NO: 57 L , V comprising the amino acid sequence of SEQ ID NO: 42 H and V comprising the amino acid sequence of SEQ ID NO: 58 L , V comprising the amino acid sequence of SEQ ID NO: 43 H and V comprising the amino acid sequence of SEQ ID NO: 59 L and V comprising the amino acid sequence of SEQ ID NO: 44. H and V comprising the amino acid sequence of SEQ ID NO: 59 L is.

[0156] In some aspects, provided herein are anti-IL18BP antibodies comprising at least one, two, three, four, five, or six HVRs selected from the following options: (a) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 167, 168, and 169, (b) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 170, 171, 172, 173, 174, 175, 176, 177, and 178, (c) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249.

[0157] In some embodiments, provided herein are anti-IL18BP antibodies, which comprise at least one, at least two, or all three V selected from the following: H The options include: (a) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 167, 168, and 169; (b) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 170, 171, 172, 173, 174, 175, 176, 177, and 178; and (c) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188.

[0158] In some embodiments, provided herein are anti-IL18BP antibodies, which comprise at least one, at least two, or all three V selected from the following: L The options include (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249.

[0159] In some aspects, provided herein is an anti-IL18BP antibody, the anti-IL18BP antibody comprising: (a) V H A domain comprising at least one, at least two, or all three V selected from the following: H (b) a domain comprising HVR sequences, the options being (i) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 167, 168, and 169; (ii) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 170, 171, 172, 173, 174, 175, 176, 177, and 178; and (iii) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188; and L A domain comprising at least one, at least two, or all three V selected from the following: L and a domain comprising an HVR sequence, the options being (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249.

[0160] In some aspects, provided herein are anti-IL18BP antibodies, including (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 167, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 170, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 179, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249; (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 171, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 181, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249. (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 182, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 182, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249. (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 184, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249.and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 174. (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 184, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175 (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 176, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 186, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248,and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 171, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 187, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 171 (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 188, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 171, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 182, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172 (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 184, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248,and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 177, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 177 (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 184, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 177, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 173, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 186, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 178 (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 178, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 184, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248,and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 178, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 175 (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 186, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 171, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 183, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 171, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 184, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 171 (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 185, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 172, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 186, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248,and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 177, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 186, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249, and (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 169, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 178, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 186, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249.

[0161] In another aspect, the anti-IL18BP antibody comprises a heavy chain variable domain (V) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 and 165. H ) sequence. In certain embodiments, HThe sequence has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 and 165, and contains substitutions (e.g., conservative substitutions), insertions or deletions compared to the reference sequence, but wherein an anti-IL18BP antibody comprising the sequence retains the ability to bind to IL18BP. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted, and / or deleted in SEQ ID NO: 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, or 165. In certain embodiments, a total of 1 to 5 amino acids have been substituted, inserted, and / or deleted in SEQ ID NO: 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, or 165. In certain embodiments, the substitutions, insertions, or deletions occur in the regions outside the HVRs (i.e., the FRs). Optionally, the anti-IL18BP antibody comprises the V of SEQ ID NOs: 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 and 165. H In certain embodiments, V Hcomprises one, two, or three HVRs selected from the following options: (a) HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 167, 168, and 169; (b) HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 170, 171, 172, 173, 174, 175, 176, 177, and 178; and (c) HVR-H3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188.

[0162] In another aspect, an anti-IL18BP antibody is provided, which comprises a light chain variable domain (V) having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity to the amino acid sequence of SEQ ID NO: 166. L In certain embodiments, V L The sequence has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 166 and contains substitutions (e.g., conservative substitutions), insertions, or deletions compared to the reference sequence, but an anti-IL18BP antibody comprising the sequence retains the ability to bind to IL18BP. In some embodiments, a total of 1 to 10 amino acids have been substituted, inserted, and / or deleted in SEQ ID NO: 166. In certain embodiments, a total of 1 to 5 amino acids have been substituted, inserted, and / or deleted in SEQ ID NO: 166. In certain embodiments, the substitutions, insertions, or deletions occur in regions outside the HVRs (i.e., FRs). Optionally, the anti-IL18BP antibody comprises a VVR of SEQ ID NO: 166. L In certain embodiments, V L comprises one, two, or three HVRs selected from the following, the options being (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 247, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 248, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 249.

[0163] In some embodiments, an anti-IL18BP antibody is provided, which antibody comprises a V as in any of the embodiments provided above. H and V as in any of the embodiments provided above. L In some embodiments, provided herein is an anti-IL18BP antibody, which comprises a V as in any of the embodiments provided above. H and V as in any of the embodiments provided above. L In one embodiment, the antibody comprises the V of SEQ ID NOs: 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 and 165, and the V of SEQ ID NO: 166. H and V L sequences, including post-translational modifications of those sequences.

[0164] In some embodiments, the heavy chain variable domain (V H ) and the light chain variable domain (V L ) is provided herein. H and V L is selected from the group consisting of: V comprising the amino acid sequence of SEQ ID NO: 134 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 135 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 136 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 137 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 138 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 139 Hand V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 140 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 141 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 142 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 143 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 144 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 145 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 146 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 147 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 148 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 149 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 150 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 151 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 152 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 153 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 154 H and V comprising the amino acid sequence of SEQ ID NO: 166L , V comprising the amino acid sequence of SEQ ID NO: 155 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 156 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 157 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 158 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 159 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 160 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 161 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 162 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 163 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 164 H and V comprising the amino acid sequence of SEQ ID NO: 166 L and V comprising the amino acid sequence of SEQ ID NO: 165. H and V comprising the amino acid sequence of SEQ ID NO: 166 L is.

[0165] In some embodiments, the anti-IL18BP antibodies of the disclosure are selected from the group consisting of anti-IL18BP antibodies BP-04.01, BP-04.02, BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04.14, BP-04.15, BP-04.16, competitively inhibits the binding of at least one reference antibody selected from BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31 and BP-04.32, and any combination thereof.

[0166] In some embodiments, the anti-IL18BP antibodies of the disclosure include the anti-IL18BP antibodies BP-04.01, BP-04.02, BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04.14, BP-04.15, BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31, BP-04.32, BP-04.33, BP-04.34, BP-04.35, BP-04.36, BP-04.37, BP-04.38, BP-04.39, BP-04.40, BP-04.41, BP-04.42, BP-04.43, BP-04.44, BP-04.45, BP-04.46, BP-04.47, BP-04.48, BP-04.49, BP-04.50, BP-04.51, BP-04.52, BP-04.53, BP-04.54, and BP-04.31 and BP-04.32.

[0167] In some embodiments, an anti-IL18BP antibody of the present disclosure competitively inhibits the binding of at least one reference antibody or binds to an epitope of human IL18BP that is the same as or overlaps with an IL18BP epitope bound by at least one reference antibody, wherein the reference antibody is a heavy chain variable domain (V H ) and the light chain variable domain (V L ), and this V H and V L is selected from the group consisting of: V comprising the amino acid sequence of SEQ ID NO: 134 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 135 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 136 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 137 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 138 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 139 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 140 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 141 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 142 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 143 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 144 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 145 Hand V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 146 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 147 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 148 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 149 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 150 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 151 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 152 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 153 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 154 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 155 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 156 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 157 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 158 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 159 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 160 H and V comprising the amino acid sequence of SEQ ID NO: 166L , V comprising the amino acid sequence of SEQ ID NO: 161 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 162 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 163 H and V comprising the amino acid sequence of SEQ ID NO: 166 L , V comprising the amino acid sequence of SEQ ID NO: 164 H and V comprising the amino acid sequence of SEQ ID NO: 166 L and V comprising the amino acid sequence of SEQ ID NO: 165. H and V comprising the amino acid sequence of SEQ ID NO: 166 L is.

[0168] In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 190, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 191, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 192, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 193, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 194, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 195, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 196, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 197, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 198, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 199, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 200 and the light chain comprises the amino acid sequence of SEQ ID NO: 189.In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 201, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 202, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 203, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 204, and the light chain comprises the amino acid sequence of SEQ ID NO: 189.

[0169] In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 205, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 206, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 207, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 208, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 209, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 210, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 211, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 212, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 213, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 214, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 215 and the light chain comprises the amino acid sequence of SEQ ID NO: 189.In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 216, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 217, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 218, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 219, and the light chain comprises the amino acid sequence of SEQ ID NO: 189.

[0170] In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 220, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 221, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 222, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 223, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 224, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 225, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 226, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 227, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 228, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 229, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 230 and the light chain comprises the amino acid sequence of SEQ ID NO: 189.In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 231, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 232, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 233, and the light chain comprises the amino acid sequence of SEQ ID NO: 189. In some aspects, provided herein is an isolated anti-IL18BP antibody comprising a heavy chain and a light chain. The heavy chain comprises the amino acid sequence of SEQ ID NO: 234, and the light chain comprises the amino acid sequence of SEQ ID NO: 189.

[0171] In some embodiments, the anti-IL18BP antibody according to any of the above embodiments is a monoclonal antibody, including a humanized antibody and / or a human antibody. In some embodiments, the anti-IL18BP antibody is an antibody fragment, examples of which include an Fv, Fab, Fab', scFv, diabody, or F(ab')2 fragment. In some embodiments, the anti-IL18BP antibody is a substantially full-length antibody, examples of which include an IgG1 antibody, an IgG2a antibody, or other antibody class or isotype as defined herein.

[0172] In some embodiments, an anti-IL18BP antibody according to any of the above embodiments may incorporate any of the features, alone or in combination, as described below.

[0173] Binding affinity of anti-IL18BP antibodies In some embodiments of any of the antibodies provided herein, the antibody has a cytotoxicity of less than 1 μM, less than 100 nM, less than 10 nM, less than 1 nM, less than 0.1 nM, less than 0.01 nM, or less than 0.001 nM (e.g., less than 10 -8 M or less, e.g., 10 -8 M~10 -13 M, e.g., 10 -9 M~10 -13 Dissociation constant (K D). The dissociation constant may be determined by any analytical technique, including any biochemical or biophysical technique, examples of which include ELISA, surface plasmon resonance (SPR), biolayer interferometry (see, e.g., the Octet System by ForteBio), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), circular dichroism (CD), stopped-flow analysis, and colorimetric or fluorescent protein melting analysis. In one embodiment, Kd is measured by a radiolabeled antigen binding assay (RIA). In some embodiments, an RIA is performed on the Fab version of the antibody of interest and its antigen, e.g., as described in Chen et al. J. Mol. Biol. 293:865-881 (1999). In some embodiments, the K D is measured using a BIACORE surface plasmon resonance assay, e.g., using a BIACORE-2000 or BIACORE-3000 (BIAcore, Inc., Piscataway, NJ) performed at 25°C using an immobilized antigen CM5 chip at approximately 10 response units (RU). In some embodiments, K D is determined using a monovalent antibody (e.g., Fab) or a full-length antibody. In some embodiments, K D is determined using the monovalent form of the full-length antibody.

[0174] antibody fragment In some embodiments of any of the antibodies provided herein, the antibody is an antibody fragment. Antibody fragments include, but are not limited to, Fab, Fab', Fab'-SH, F(ab')2, Fv, and scFv fragments, as well as other fragments described below. For a review of certain antibody fragments, see Hudson et al. Nat. Med. 9:129-134 (2003). For a review of scFv fragments, see, e.g., WO 93 / 16185, and U.S. Pat. Nos. 5,571,894 and 5,587,458. For a discussion of Fab and F(ab')2 fragments that contain salvage receptor-binding epitope residues and have increased in vivo half-lives, see U.S. Pat. No. 5,869,046.

[0175] Diabodies are antibody fragments with two antigen-binding sites, which may be bivalent or bispecific. See, e.g., EP404097, WO 1993 / 01161, Hudson et al. Nat. Med. 9:129-134 (2003). Triabodies and tetrabodies are also described in Hudson et al. Nat. Med. 9:129-134 (2003). Single-domain antibodies are antibody fragments that contain all or part of the heavy chain variable domain or all or part of the light chain variable domain of an antibody. In certain embodiments, single-domain antibodies are human single-domain antibodies (see, e.g., U.S. Pat. No. 6,248,516).

[0176] Antibody fragments can be produced by a variety of techniques, as described herein, including, but not limited to, proteolytic digestion of intact antibodies and production by recombinant host cells (e.g., E. coli or phage).

[0177] Chimeric and humanized antibodies In some embodiments of any of the antibodies provided herein, the antibody is a chimeric antibody. Specific chimeric antibodies are described, for example, in U.S. Patent No. 4,816,567. In one example, a chimeric antibody comprises a non-human variable region (e.g., a variable region derived from a mouse, rat, hamster, rabbit, or non-human primate such as a monkey) and a human constant region. In a further example, a chimeric antibody is a "class-switched" antibody whose class or subclass has been changed from that of the parent antibody. Chimeric antibodies include antigen-binding fragments thereof.

[0178] In some embodiments of any of the antibodies provided herein, the antibody is a humanized antibody. Typically, non-human antibodies are humanized to reduce immunogenicity in humans while retaining the specificity and affinity of the parent non-human antibody. In certain embodiments, humanized antibodies are substantially non-immunogenic in humans. In certain embodiments, humanized antibodies have substantially the same affinity for a target as an antibody from another species from which the humanized antibody is derived. See, e.g., U.S. Patent Nos. 5,530,101, 5,693,761, 5,693,762, and 5,585,089. In certain embodiments, amino acids in antibody variable domains are identified that can be modified to reduce immunogenicity without reducing the native affinity of the antigen-binding domain. See, e.g., U.S. Patent Nos. 5,766,886 and 5,869,619. Generally, humanized antibodies comprise one or more variable domains in which HVRs (or portions thereof) are derived from a non-human antibody and FRs (or portions thereof) are derived from human antibody sequences. A humanized antibody will optionally also comprise at least a portion of a human constant region. 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 HVR residues are derived), e.g., to restore or improve antibody specificity or affinity.

[0179] Humanized antibodies, and methods for making them, are reviewed, for example, in Almagro et al. Front Biosci. 13:161 9-1633 (2008), and are further described, for example, in U.S. Patent Nos. 5,821,337, 7,527,791, 6,982,321, and 7,087,409. Human framework regions that can be used for humanization include, but are not limited to, the following: framework regions selected using the "best-fit" method (see, e.g., Sims et al. J. Immunol. 151:2296 (1993)), framework regions derived from consensus sequences of human antibodies of particular subgroups of light or heavy chain variable regions (see, e.g., Carter et al. Proc. Natl. Acad. Sci. USA 89:4285 (1992) and Presta et al. J. Immunol. 151:2623 (1993)), human mature (somatically mutated) framework regions or human germline framework regions (see, e.g., Almagro and Fransson Front. Biosci. 13:1619-1633 (2008)), and framework regions derived from screening of FR libraries (see, e.g., Baca et al. J. Biol. Chem. 272:10678-10684 (1997) and Rosok et al. J. Biol. Chem. 271:22611-22618 (1996)).

[0180] Human antibodies In some embodiments of any of the antibodies provided herein, the antibody is a human antibody. Human antibodies can be produced using various techniques known in the art. Human antibodies are generally described in van Dijk et al. Curr. Opin. Pharmacol. 5:368-74 (2001) and Lonberg Curr. Opin. Immunol. 20:450-459 (2008).

[0181] Human antibodies may be prepared by administering immunogens to transgenic animals modified to produce intact human antibodies or intact antibodies with human variable regions in response to antigen challenge. Mouse strains deficient in mouse antibody production with large fragments of the human Ig loci can be engineered, with the expectation that such mice will produce human antibodies in the absence of mouse antibodies. Large human Ig fragments can preserve the diversity of large variable genes and the proper regulation of antibody production and expression. By exploiting mouse mechanisms for antibody diversification and selection and the lack of immune tolerance to human proteins, the human antibody repertoire recapitulated in these mouse strains can yield high-affinity, fully human antibodies against any antigen of interest, including human antigens. Hybridoma technology can be used to produce and select antigen-specific human MAbs with desired specificity. Certain exemplary methods are described in U.S. Pat. No. 5,545,807, EP 546073, and EP 546073. See also, for example, U.S. Patent Nos. 6,075,181 and 6,150,584, which describe XENOMOUSE™ technology, U.S. Patent No. 5,770,429, which describes HUMAB® technology, U.S. Patent No. 7,041,870, which describes KM MOUSE® technology, and U.S. Patent Application Publication No. 2007 / 0061900, which describes VELOCIMOUSE® technology. The human variable regions from intact antibodies produced by such animals may be further modified, for example, by combining with different human constant regions.

[0182] Human antibodies can also be produced by hybridoma-based methods. Human myeloma cell lines and mouse-human heteromyeloma cell lines for the production of human monoclonal antibodies have been described. (See, e.g., Kozbor J. Immunol. 133:3001 (1984) and Boerner et al. J. Immunol. 147:86 (1991)). Human antibodies generated via human B cell hybridoma technology are also described in Li et al. Proc. Natl. Acad. Sci. USA, 103:3557-3562 (2006). Additional methods include those described, for example, in U.S. Pat. No. 7,189,826, which describes the production of monoclonal human IgM antibodies from hybridoma cell lines. Human hybridoma technology (Trioma technology) is also described in Vollmers et al., Histology and Histopathology 20(3):927-937 (2005) and Vollmers et al., Methods and Findings in Experimental and Clinical Pharmacology 27(3):185-91 (2005). Human antibodies can also be generated by isolating Fv clone variable domain sequences selected from a human-derived phage display library. Such variable domain sequences can then be combined with desired human constant domains. Techniques for selecting human antibodies from antibody libraries are described below.

[0183] In some embodiments of any of the antibodies provided herein, the antibody is a human antibody isolated by in vitro methods and / or screening of combinatorial libraries for antibodies with the desired activity(ies). Suitable examples include, but are not limited to, phage display (CAT, Morphosys, Dyax, Biosite / Medarex, Xoma, Symphogen, Alexion (formerly Proliferon), Affimed), ribosome display (CAT), yeast display (Adimab), and the like. In certain phage display methods, repertoires of VH and VL genes are individually cloned by polymerase chain reaction (PCR) and randomly recombined into phage libraries, which can then be screened for antigen-binding phage, as described in Winter et al. Ann. Rev. Immunol. 12:433-455 (1994). For example, various methods are known in the art for generating phage display libraries and screening such libraries for antibodies with the desired binding characteristics. See also Sidhu et al. J. Mol. Biol. 338(2): 299-310, 2004; Lee et al. J. Mol. Biol. 340(5): 1073-1093, 2004; Fellouse Proc. Natl. Acad. Sci. USA 101(34):12467-12472 (2004); and Lee et al. J. Immunol. Methods 284(-2):119-132 (2004). Phages typically display antibody fragments as either single-chain Fv (scFv) fragments or Fab fragments. Libraries from immunized sources provide high-affinity antibodies against the immunogen without the need to construct hybridomas. Alternatively, as described by Griffiths et al. EMBO J. 12:725-734 (1993), naive repertoires can be cloned (e.g., from humans) to provide a single source of antibodies against a wide range of non-self and even self antigens without immunization.Finally, naive libraries can also be synthetically generated by cloning unrearranged V gene segments from stem cells, encoding the highly variable HVR3 region, and using PCR primers containing random sequences to achieve in vitro rearrangement, as described by Hoogenboom et al. J. Mol. Biol., 227:381-388, 1992. Patent publications describing human antibody phage libraries include, for example, U.S. Pat. No. 5,750,373 and U.S. Patent Publication Nos. 2007 / 0292936 and 2009 / 0002360. Antibodies isolated from human antibody libraries are considered human antibodies or human antibody fragments herein.

[0184] Constant region including the Fc region In some embodiments of any of the antibodies provided herein, the antibody comprises an Fc. In some embodiments, the Fc is a human IgG1, IgG2, IgG3, and / or IgG4 isotype. In some embodiments, the antibody is of the IgG, IgM, or IgA class.

[0185] In certain embodiments of any of the antibodies provided herein, the antibody has an IgG2 isotype. In some embodiments, the antibody contains a human IgG2 constant region. In some embodiments, the human IgG2 constant region comprises an Fc region. In some embodiments, the antibody induces one or more IL18BP activities, or does so independently of binding to an Fc receptor. In some embodiments, the antibody binds an inhibitory Fc receptor. In certain embodiments, the inhibitory Fc receptor is inhibitory Fc gamma receptor IIB (FcγIIB).

[0186] In certain embodiments of any of the antibodies provided herein, the antibody has an IgG1 isotype. In some embodiments, the antibody contains a mouse IgG1 constant region. In some embodiments, the antibody contains a human IgG1 constant region. In some embodiments, the human IgG1 constant region comprises an Fc region. In some embodiments, the antibody binds an inhibitory Fc receptor. In certain embodiments, the inhibitory Fc receptor is inhibitory Fc gamma receptor IIB (FcγIIB).

[0187] In certain embodiments of any of the antibodies provided herein, the antibody has an IgG4 isotype. In some embodiments, the antibody contains a human IgG4 constant region. In some embodiments, the human IgG4 constant region comprises an Fc region. In some embodiments, the antibody binds an inhibitory Fc receptor. In certain embodiments, the inhibitory Fc receptor is inhibitory Fc gamma receptor IIB (FcγIIB).

[0188] In certain embodiments of any of the antibodies provided herein, the antibody has a hybrid IgG2 / 4 isotype. In some embodiments, the antibody comprises an amino acid sequence comprising amino acids 118 to 260, EU numbering, of human IgG2 and amino acids 261 to 447, EU numbering, of human IgG4 (WO 1997 / 11971; WO 2007 / 106585).

[0189] In some embodiments, the Fc region increases cluster formation without activating complement compared to a corresponding antibody comprising an Fc region that does not contain the amino acid substitutions. In some embodiments, the antibody induces one or more activities of a target to which the antibody specifically binds. In some embodiments, the antibody binds to IL18BP.

[0190] It may also be desirable to modify the anti-IL18BP antibodies of the present disclosure to modify effector function and / or increase the serum half-life of the antibody. For example, the Fc receptor binding site in the constant region may be modified or mutated to eliminate or reduce binding affinity for certain Fc receptors (such as FcγRI, FcγRII, and / or FcγRIII, which reduces antibody-dependent cell-mediated cytotoxicity). In some embodiments, effector function is impaired by removing N-glycosylation in the Fc region of the antibody (e.g., within the CH2 domain of IgG). In some embodiments, effector function is impaired by modifying regions such as 233-236, 297, and / or 327-331 of human IgG, as described below. i.e., WO 99 / 58572 and Armour et al. Molecular Immunology 40: 585-593 (2003); Reddy et al. J. Immunology 164:1925-1933 (2000). In other embodiments, it may be desirable to modify the anti-IL18BP antibodies of the present disclosure to modify effector function to enhance ITIM-containing FcgRIIb (CD32b)-directed discovery selectivity and increase clustering of IL18BP antibodies on neighboring cells without activating humoral responses, including antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis.

[0191] To extend the serum half-life of an antibody, a salvage receptor binding epitope may be incorporated into the antibody (particularly an antibody fragment), as described, for example, in U.S. Patent No. 5,739,277. As used herein, the term "salvage receptor binding epitope" refers to an epitope in the Fc region of an IgG molecule (e.g., IgG1, IgG2, IgG3, or IgG4) that is responsible for increasing the in vivo serum half-life of the IgG molecule. Other amino acid sequence modifications.

[0192] Antibody variants In some embodiments of any of the antibodies provided herein, amino acid sequence variants of the antibody are contemplated. For example, it may be desirable to improve the binding affinity and / or other biological properties of the antibody.

[0193] Substitution, insertion and deletion variants In some embodiments of any of the antibodies provided herein, antibody variants with one or more amino acid substitutions are provided. Amino acid sequence variants of antibodies 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. [Table 1]

[0194] Substantial modification of antibody biological properties can be achieved by selecting substitutions that significantly differ in (a) the structure of the polypeptide backbone in the region of the substitution (e.g., sheet or helical conformation), (b) the charge or hydrophobicity of the molecule at the target site, or (c) the effectiveness of maintaining side chain bulk. Naturally occurring residues are classified based on common side chain properties, namely: (1) Hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; (2) Neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) Acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; and (6) Aromatic: Trp, Tyr, Phe.

[0195] For example, non-conservative substitutions can involve exchanging a member of one of these classes for a member of another class. Such substituted residues can be introduced, for example, into regions of the human antibody that are homologous with the non-human antibody, or into the non-homologous regions of the molecule.

[0196] When making changes to the polypeptides or antibodies described herein, according to certain embodiments, the hydropathic index of amino acids can be considered. Each amino acid is assigned a hydropathic index on the basis of its hydrophobicity and charge characteristics. They are isoleucine (+4.5), valine (+4.2), leucine (+3.8), phenylalanine (+2.8), cysteine / cystine (+2.5), methionine (+1.9), alanine (+1.8), glycine (-0.4), threonine (-0.7), serine (-0.8), tryptophan (-0.9), tyrosine (-1.3), proline (-1.6), histidine (-3.2), glutamic acid (-3.5), glutamine (-3.5), aspartic acid (-3.5), asparagine (-3.5), lysine (-3.9), and arginine (-4.5).

[0197] The importance of the hydropathic amino acid index in conferring interactive biological function to a protein is understood in the art. Kyte et al. J. Mol. Biol., 157:105-131 (1982). It is known that certain amino acids can be substituted with other amino acids having a similar hydropathic index or score and still retain similar biological activity. In certain embodiments, modifications based on hydropathic index include substitutions of amino acids whose hydropathic index is within ±2. In certain embodiments, those within ±1 are included, and in certain embodiments, those within ±0.5 are included.

[0198] It is also understood in the art that substitution of equivalent amino acids can be made effectively on the basis of hydrophilicity, particularly when the biologically functional proteins or peptides produced thereby are intended for use in immunological embodiments, such as the present case. In certain embodiments, the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of its adjacent amino acids, correlates with its immunogenicity and antigenicity, i.e., with a biological property of the protein.

[0199] The following hydrophilicity values ​​have been assigned to these amino acid residues: arginine (+3.0), lysine (+3.0±1), aspartic acid (+3.0±1), glutamic acid (+3.0±1), serine (+0.3), asparagine (+0.2), glutamine (+0.2), glycine (0), threonine (−0.4), proline (−0.5±1), alanine (−0.5), histidine (−0.5), cysteine ​​(−1.0), methionine (−1.3), valine (−1.5), leucine (−1.8), isoleucine (−1.8), tyrosine (−2.3), phenylalanine (−2.5), and tryptophan (−3.4). When changes are made based on similar hydrophilicity values, certain embodiments include substitution of amino acids with hydrophilicity values ​​within ±2, certain embodiments include amino acids within ±1, and certain embodiments include amino acids within ±0.5. Epitopes can also be identified from primary amino acid sequences based on hydrophilicity. These regions are also referred to as "epitope core regions."

[0200] In certain embodiments of the variant VH and VL sequences set forth above, each HVR is unaltered.

[0201] Amino acid sequence insertions include amino- and / or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing 100 or more residues, as well as intrasequence insertions of single or multiple amino acid residues. An example of a terminal insertion includes an antibody with an N-terminal methionyl residue. Other insertional variants of antibody molecules include the fusion to the N- or C-terminus of the antibody to an enzyme (e.g., for ADEPT) or a polypeptide which increases the serum half-life of the antibody.

[0202] Also, any cysteine ​​residue outside the HVRs and not involved in maintaining the proper conformation of the antibody may be substituted, generally with serine, to improve the oxidative stability of the molecule and prevent aberrant crosslinking. Conversely, cysteine ​​bond(s) may be added to the antibody to improve stability (particularly where the antibody is an antibody fragment such as an Fv fragment).

[0203] Glycosylation variants In some embodiments of any of the antibodies provided herein, the antibody is altered to increase or decrease the extent to which the antibody is glycosylated. Addition or deletion of glycosylation sites to an antibody may be conveniently accomplished by altering the amino acid sequence such that one or more glycosylation sites are created or removed.

[0204] Glycosylation of antibodies is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain. Thus, the presence of either of these tripeptide sequences in a polypeptide creates a potential glycosylation site. O-linked glycosylation refers to the attachment of N-acetylgalactosamine, galactose, or xylose sugars to a single hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.

[0205] Addition of glycosylation sites to an antibody is conveniently accomplished by altering the amino acid sequence so that it contains one or more of the above-described tripeptide sequences (for N-linked glycosylation sites). The alteration may also be made by adding, or substituting, one or more serine or threonine residues to the sequence of the original antibody (for O-linked glycosylation sites).

[0206] If the antibody comprises an Fc region, the carbohydrate attached thereto may be altered. Natural antibodies produced by mammalian cells typically comprise branched, biantennary oligosaccharides attached by an N-linkage to the CH2 domain of the Fc region, generally to Asn297 according to the Kabat numbering system. The oligosaccharides may include various carbohydrates, such as mannose, N-acetylglucosamine (GlcNAc), galactose, and sialic acid, as well as fucose attached to GlcNAc at the "stem" of the biantennary oligosaccharide structure. In some embodiments, modifications of the oligosaccharides in the antibodies of the present disclosure may be made to generate antibody variants with specific improved properties.

[0207] In one embodiment, antibody variants are provided that have carbohydrate structures lacking fucose attached (directly or indirectly) to the Fc region. See, e.g., U.S. Patent Publication Nos. 2003 / 0157108 and 2004 / 0093621. Examples of publications related to "defucosylated" or "fucose-deficient" antibody variants include US 2003 / 0157108; US 2003 / 0115614; US 2002 / 0164328; US 2004 / 0093621; US ​​2004 / 0132140; US 2004 / 0110704; US 2004 / 0110282; US 2004 / 0109865; Okazaki et al. J. Mol. Biol. 336:1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004). Examples of cell lines capable of producing defucosylated antibodies include Led 3 CHO cells, which are deficient in protein fucosylation (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US 2003 / 0157108), and knockout cell lines (such as α-1,6-fucosyltransferase gene, FUT8, knockout CHO cells) (see, e.g., Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004) and Kanda et al. Biotechnol. Bioeng. 94(4):680-688 (2006)).

[0208] Modified constant region In some embodiments of any of the antibodies provided herein, the antibody Fc is an antibody, Fc isotype and / or modification, hi some embodiments, the antibody Fc isotype and / or modification is capable of binding to an Fc gamma receptor.

[0209] In some embodiments of any of the antibodies provided herein, the modified antibody Fc is an IgG1-modified Fc. In some embodiments, the IgG1-modified Fc comprises one or more modifications. For example, in some embodiments, the IgG1-modified Fc comprises one or more amino acid substitutions (e.g., compared to a wild-type Fc region of the same isotype). In some embodiments, the one or more amino acid substitutions are selected from the following: The choices are N297A (Bolt S et al. (1993) Eur J Immunol 23:403-411), D265A (Shields et al. (2001) RJ Biol. Chem. 276, 6591-6604), L234A, L235A (Hutchins et al. (1995) Proc Natl Acad Sci USA, 92:11980-11984; Alegre et al., (1994) Transplantation 57:1537-1543. 31; 31;Xu et al. (2000) Cell Immunol, 200:16-26), C226S, C229S, E233P, L234V, L234F, L235E (McEarchern et al., (2007) Blood, 109:1185-1192), P331S (Sazinsky et al., (2008) Proc Natl Acad Sci USA 2008, 105:20167-20172), S267E, L328F, A330L, M252Y, S254T and / or T256E, where the amino acid positions are according to the EU numbering convention.

[0210] In some embodiments of any of the IgG1-modified Fcs, the Fc comprises an N297A mutation (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises D265A and N297A mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises a D270A mutation (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises L234A and L235A mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises L234A and G237A mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises L234A, L235A, and G237A mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises one or more (including all) of the P238D, L328E, E233, G237D, H268D, P271G, and A330R mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises one or more of the S267E / L328F mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises the P238D, L328E, E233D, G237D, H268D, P271G, and A330R (according to EU numbering) mutations. In some embodiments of any of the IgG1-modified Fcs, the Fc comprises the P238D, L328E, G237D, H268D, P271G, and A330R mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises P238D, S267E, L328E, E233D, G237D, H268D, P271G, and A330R mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises P238D, S267E, L328E, G237D, H268D, P271G, and A330R mutations (according to EU numbering).In some embodiments of any of the IgG1-modified Fcs, the Fc comprises C226S, C229S, E233P, L234V, and L235A mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises L234F, L235E, and P331S mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises S267E and L328F mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises N325S and L328F mutations (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises a K322A mutation (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises a P331S mutation (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises a S267E mutation (according to EU numbering). In some embodiments of any of the IgG1-modified Fcs, the Fc comprises a substitution of the constant heavy chain 1 (CH1) and hinge region of IgG1 with CH1 and the hinge region of IgG2 with a kappa light chain (amino acids 118-230 (according to EU numbering) of IgG2).

[0211] In some embodiments of any of the IgG1-modified Fcs, the Fc comprises two or more amino acid substitutions that increase antibody clustering without activating complement, compared to a corresponding antibody having an Fc region that does not comprise the two or more amino acid substitutions. Thus, in some embodiments of any of the IgG1-modified Fcs, the IgG1-modified Fc is an antibody comprising an Fc region, wherein the antibody comprises an amino acid substitution at position E430G and one or more amino acid substitutions in the Fc region at residue positions selected from L234F, L235A, L235E, S267E, K322A, L328F, A330S, P331S, P331G, and any combination thereof (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions E430G, L243A, L235A, and P331S (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions E430G and P331S (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions E430G and K322A (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions E430G, A330S, and P331S (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions E430G, K322A, A330S, and P331S (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions E430G, K322A, and A330S (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions E430G, K322A, and A330S (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions E430G, K322A, and P331S (according to EU numbering). In some embodiments, the IgG1 modified Fc comprises amino acid substitutions at positions L234A, L235A and P331S (according to EU numbering). In some embodiments, the IgG1 modified Fc comprises amino acid substitutions at positions L234A, L235A and P331G (according to EU numbering). In some embodiments, the IgG1 modified Fc comprises amino acid substitutions at positions L234A, L235A and P329S (according to EU numbering).In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions L234A, L235A, and P329G (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions P331S and E430G (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions N325S and L328F (according to EU numbering). In some embodiments, the IgG1-modified Fc comprises amino acid substitutions at positions S267E and L328F (according to EU numbering).

[0212] In some embodiments of any of the IgG1-modified Fcs, the IgG1-modified Fc referred to herein may further comprise, and may be combined with, one or more of the A330L mutation (Lazar et al. Proc Natl Acad Sci USA, 103:4005-4010 (2006)), or the L234F, L235E, and / or P331S mutations (Sazinsky et al. Proc Natl Acad Sci USA, 105:20167-20172 (2008)) (according to the EU numbering convention) to eliminate complement activation. In some embodiments of any of the IgG1-modified Fcs, the IgG1-modified Fc may further comprise one or more of the A330L, A330S, L234F, L235E, and / or P331S (according to the EU numbering convention). In some embodiments of any of the IgG1-modified Fcs, the IgG1-modified Fc may further comprise one or more mutations that extend the antibody half-life in human serum (e.g., one or more (including all) of M252Y, S254T, and T256E mutations (according to EU numbering)). In some embodiments of any of the IgG1-modified Fcs, the IgG1-modified Fc may further comprise one or more of E430G, E430S, E430F, E430T, E345K, E345Q, E345R, E345Y, S440Y, and / or S440W (according to EU numbering).

[0213] Another aspect of the present disclosure relates to antibodies with modified constant regions (i.e., Fc regions). Antibodies that activate target receptors dependent on binding to FcgR receptors may lose their agonistic activity if engineered to eliminate FcgR binding (see, e.g., Wilson et al. Cancer Cell 19:101-113 (2011); Armour at al. Immunology 40:585-593 (2003); and White et al. Cancer Cell 27:138-148 (2015)). Therefore, it is believed that anti-IL18BP antibodies of the present disclosure with the correct epitope specificity can activate target antigens with minimal side effects if the antibody has an Fc domain from the human IgG2 isotype (CH1 and hinge region), or another type of Fc domain that can preferentially bind the inhibitory FcgRIIBr receptor, or a variant thereof.

[0214] In some embodiments of any of the antibodies provided herein, the modified antibody Fc is an IgG2-modified Fc. In some embodiments, the IgG2-modified Fc comprises one or more modifications. For example, in some embodiments, the IgG2-modified Fc comprises one or more amino acid substitutions (e.g., compared to a wild-type Fc region of the same isotype). In some embodiments of any of the IgG2-modified Fcs, the one or more amino acid substitutions are selected from the following: The options are V234A (Alegre et al. Transplantation 57:1537-1543 (1994); Xu et al. Cell Immunol, 200:16-26 (2000)); G237A (Cole et al. (1999));H268Q, V309L, A330S, P331S (US 2007 / 0148167;Armour et al. Eur J Immunol 29: 2613-2624 (1999);Armour et al. The Haematology Journal 1(Suppl.1):27 (2000);Armour et al. The Haematology Journal 1(Suppl.1):27 (2000)), C219S and C220S (White et al. Cancer Cell 27, 138-148 (2015)); S267E, L328F (Chu et al. Mol Immunol, 45:3926-3933 (2008)); and M252Y, S254T and / or T256E (according to EU numbering). In some embodiments of any of the IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions V234A and G237A (according to EU numbering). In some embodiments of any of the IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions C219S or C220S (according to EU numbering). In some embodiments of any of the IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions A330S and P331S (according to EU numbering).In some embodiments of any of the IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions S267E and L328F (according to EU numbering).

[0215] In some embodiments of any of the IgG2-modified Fcs, the Fc comprises a C127S amino acid substitution (according to EU numbering) (White et al., (2015) Cancer Cell 27, 138-148; Lightle et al. Protein Sci. 19:753-762 (2010); and WO2008 / 079246). In some embodiments of any of the IgG2-modified Fcs, the antibody has an IgG2 isotype with a kappa light chain constant domain comprising a C214S amino acid substitution (according to EU numbering) (White et al. Cancer Cell 27:138-148 (2015); Lightle et al. Protein Sci. 19:753-762 (2010); and WO2008 / 079246).

[0216] In some embodiments of any of the IgG2-modified Fcs, the Fc comprises a C220S amino acid substitution (according to EU numbering). In some embodiments of any of the IgG2-modified Fcs, the antibody has an IgG2 isotype with a kappa light chain constant domain comprising a C214S amino acid substitution (according to EU numbering).

[0217] In some embodiments of any of the IgG2-modified Fcs, the Fc comprises a C219S amino acid substitution (according to EU numbering). In some embodiments of any of the IgG2-modified Fcs, the antibody has an IgG2 isotype with a kappa light chain constant domain comprising a C214S amino acid substitution (according to EU numbering).

[0218] In some embodiments of any of the IgG2-modified Fcs, the Fc comprises an IgG2 isotype heavy chain constant domain 1 (CH1) and hinge region (White et al. Cancer Cell 27:138-148 (2015)). In specific embodiments of any of the IgG2-modified Fcs, the IgG2 isotype CH1 and hinge region comprise the amino acid sequence of 118-230 (according to EU numbering). In some embodiments of any of the IgG2-modified Fcs, the antibody Fc region comprises an S267E amino acid substitution, an L328F amino acid substitution, or both, and / or an N297A or N297Q amino acid substitution (according to EU numbering).

[0219] In some embodiments of any of the IgG2-modified Fcs, the Fc further comprises one or more amino acid substitutions at positions E430G, E430S, E430F, E430T, E345K, E345Q, E345R, E345Y, S440Y, and S440W (according to EU numbering). In some embodiments of any of the IgG2-modified Fcs, the Fc may further comprise one or more mutations that extend the antibody half-life in human serum (e.g., one or more (including all) of the M252Y, S254T, and T256E mutations (according to EU numbering)). In some embodiments of any of the IgG2-modified Fcs, the Fc may further comprise A330S and P331S.

[0220] In some embodiments of any of the IgG2-modified Fcs, the Fc is an IgG2 / 4 hybrid Fc. In some embodiments, the IgG2 / 4 hybrid Fc comprises IgG2 aas 118-260 and IgG4 aas 261-447. In some embodiments of any of the IgG2-modified Fcs, the Fc comprises one or more amino acid substitutions at positions H268Q, V309L, A330S, and P331S (according to EU numbering).

[0221] In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises one or more additional amino acid substitutions selected from the following, the options being A330L, L234F; L235E or P331S (according to EU numbering); and any combination thereof.

[0222] In certain embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises one or more amino acid substitutions at residue positions selected from C127S, L234A, L234F, L235A, L235E, S267E, K322A, L328F, A330S, P331S, E345R, E430G, S440Y, and any combination thereof (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions E430G, L243A, L235A, and P331S (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions E430G and P331S (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions E430G and K322A (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions E430G, A330S, and P331S (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions E430G, K322A, A330S, and P331S (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions E430G, K322A, A330S, and P331S (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions E430G, K322A, and P331S (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises amino acid substitutions at positions S267E and L328F (according to EU numbering). In some embodiments of any of the IgG1 and / or IgG2-modified Fcs, the Fc comprises an amino acid substitution at position C127S (according to EU numbering).In some embodiments of any of the IgG1 and / or IgG2 modified Fcs, the Fc comprises amino acid substitutions at positions E345R, E430G and S440Y (according to EU numbering).

[0223] In some embodiments of any of the antibodies provided herein, the modified antibody Fc is an IgG4-modified Fc. In some embodiments, the IgG4-modified Fc comprises one or more modifications. For example, in some embodiments, the IgG4-modified Fc comprises one or more amino acid substitutions (e.g., compared to a wild-type Fc region of the same isotype). In some embodiments of any of the IgG4-modified Fcs, the one or more amino acid substitutions are selected from L235A, G237A, S229P, L236E (Reddy et al. J Immunol 164:1925-1933 (2000)), S267E, E318A, L328F, M252Y, S254T, and / or T256E (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc may further comprise L235A, G237A, and E318A (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc may further comprise S228P and L235E (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the IgG4-modified Fc may further comprise S267E and L328F (according to EU numbering).

[0224] In some embodiments of any of the IgG4-modified Fcs, the IgG4-modified Fc may comprise an S228P substitution or may be combined with the S228P mutation (according to the EU numbering convention) (Angal et al. Mol Immunol. 30:105-108 (1993)) and / or one or more of the mutations described in (Peters et al. J Biol Chem. 287(29):24525-33 (2012)) to enhance antibody stability.

[0225] In some embodiments of any of the IgG4-modified Fcs, the IgG4-modified Fc may further comprise one or more mutations that extend the antibody half-life in human serum (e.g., one or more (including all) of the M252Y, S254T and T256E mutations (according to the EU numbering rules)).

[0226] In some embodiments of any of the IgG4-modified Fcs, the Fc comprises L235E (according to EU numbering). In specific embodiments of any of the IgG4-modified Fcs, the Fc comprises one or more amino acid substitutions at residue positions selected from C127S, F234A, L235A, L235E, S267E, K322A, L328F, E345R, E430G, S440Y, and any combination thereof (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc comprises amino acid substitutions at positions E430G, L243A, L235A, and P331S (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc comprises amino acid substitutions at positions E430G and P331S (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc comprises amino acid substitutions at positions E430G and K322A (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc comprises an amino acid substitution at position E430 (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc region comprises amino acid substitutions at positions E430G and K322A (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc comprises amino acid substitutions at positions S267E and L328F (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc comprises amino acid substitutions at position C127S (according to EU numbering). In some embodiments of any of the IgG4-modified Fcs, the Fc comprises amino acid substitutions at positions E345R, E430G, and S440Y (according to EU numbering).

[0227] Other antibody modifications In some embodiments of any of the antibodies, the antibody is a derivative. The term "derivative" refers to a molecule that contains a chemical modification other than an amino acid (or nucleic acid) insertion, deletion, or substitution. In certain embodiments, a derivative includes a covalent modification, including, but not limited to, chemical conjugation with a polymer, lipid, or other organic or inorganic moiety. In certain embodiments, a chemically modified antigen binding protein may have a longer circulating half-life than an antigen binding protein that is not chemically modified. In certain embodiments, a chemically modified antigen binding protein may have improved targeting ability to desired cells, tissues, and / or organs. In some embodiments, a derivative antigen binding protein is covalently modified to include one or more water-soluble polymer linkages, including, but not limited to, polyethylene glycol, polyoxyethylene glycol, or polypropylene glycol. See, e.g., U.S. Patent Nos. 4,640,835, 4,496,689, 4,301,144, 4,670,417, 4,791,192, and 4,179,337. In certain embodiments, the derivative antigen binding proteins comprise one or more polymers, including, but not limited to, monomethoxy-polyethylene glycol, dextran, cellulose, ethylene glycol / propylene glycol copolymers, carboxymethylcellulose, polyvinylpyrrolidone, poly-1,3-dioxolane, poly-1,3,6-trioxane, ethylene / maleic anhydride copolymers, polyamino acids (either homopolymers or random copolymers), poly-(N-vinylpyrrolidone)-polyethylene glycol, propylene glycol homopolymer, polypropylene oxide / ethylene oxide copolymer, polyoxyethylated polyols (e.g., glycerol), and polyvinyl alcohol, as well as mixtures of such polymers.

[0228] In certain embodiments, the derivatives are covalently modified with polyethylene glycol (PEG) subunits. In certain embodiments, one or more water-soluble polymers are attached to one or more specific positions of the derivative, e.g., the amino terminus. In certain embodiments, one or more water-soluble polymers are randomly attached to one or more side chains of the derivative. In certain embodiments, PEG is used to improve the therapeutic potential of antigen-binding proteins. In certain embodiments, PEG is used to improve the therapeutic potential of humanized antibodies. Certain such methods are discussed, for example, in U.S. Patent No. 6,133,426, which is hereby incorporated by reference for all purposes.

[0229] Peptide analogs are commonly used in the pharmaceutical industry as non-peptide drugs with properties similar to those of the template peptide. These types of non-peptide compounds are called "peptide mimetics" (peptidomimetics). Fauchere, J. Adv. Drug Res., 15:29 (1986); and Evans et al. J. Med. Chem., 30:1229 (1987), which are incorporated herein by reference for all purposes. Such compounds are often developed with the aid of computer molecular modeling. Peptide mimetics that are structurally similar to therapeutically useful peptides can be used to achieve similar therapeutic effects. Generally, peptidomimetics are structurally similar to a paradigm polypeptide (i.e., a polypeptide having biochemical properties or pharmacological activity), such as a human antibody, but have one or more peptide linkages optionally replaced by linkages selected from -CHNH-, -CHS-, -CH-CH-, -CH=CH- (cis and trans), -COCH-, -CH(OH)CH-, and -CHSO-, by methods well known in the art. In certain embodiments, systematic substitution of one or more amino acids of a consensus sequence with a D-amino acid of the same type (e.g., D-lysine in place of L-lysine) can be used to generate more stable peptides. Additionally, constrained peptides containing the consensus sequence or substantially identical consensus sequence variations can be generated by methods known in the art (Rizo and Gierasch Ann. Rev. Biochem., 61:387 (1992), incorporated herein by reference for all purposes), for example, by adding internal cysteine ​​residues capable of forming intramolecular disulfide bridges that cyclize the peptide.

[0230] Drug conjugates involve coupling a biologically active cytotoxic (anticancer) payload or drug to an antibody that specifically targets a particular tumor marker (e.g., a polypeptide ideally present only in or on tumor cells). The antibody tracks these proteins in the body and binds them to the surface of cancer cells. A biochemical reaction between the antibody and the target protein (antigen) triggers a signal within the tumor cell, which then absorbs or internalizes the antibody along with a cytotoxin. After the ADC is internalized, the cytotoxic agent is released, killing the cancer. This targeting ideally allows the drug to have fewer side effects and a wider therapeutic window than other chemotherapeutic agents. Techniques for conjugating antibodies are disclosed and known in the art (see, e.g., Jane de Lartigue Onc...

Claims

1. An isolated anti-interleukin-18 binding protein (IL18BP) antibody, which blocks IL-18 from binding to IL18BP.

2. The anti-IL18BP antibody according to claim 1, wherein the anti-IL18BP antibody increases the expression level of interferon-gamma (IFNγ) in peripheral blood mononuclear cells.

3. The anti-IL18BP antibody according to claim 1 or 2, wherein the anti-IL18BP antibody increases IFNγ expression in natural killer cells.

4. The anti-IL18BP antibody according to any one of claims 1 to 3, wherein the anti-IL18BP antibody increases the level of inflammatory cytokines in serum.

5. The anti-IL18BP antibody according to any one of claims 1 to 4, which increases serum IFNγ levels.

6. The anti-IL18BP antibody according to any one of claims 1 to 5, which increases serum IL-10 levels.

7. The anti-IL18BP antibody according to any one of claims 1 to 6, which increases serum IL-6 levels.

8. The anti-IL18BP antibody according to any one of claims 1 to 7, wherein the anti-IL18BP antibody increases serum tumor necrosis factor alpha (TNFα) levels.

9. The anti-IL18BP antibody according to any one of claims 1 to 8, wherein said anti-IL18BP antibody reduces the percentage of CD3+ T cells in vivo.

10. The anti-IL18BP antibody according to any one of claims 1 to 9, wherein said anti-IL18BP antibody reduces the percentage of CD19+ B cells in vivo.

11. The anti-IL18BP antibody according to any one of claims 1 to 10, wherein the anti-IL18BP antibody reduces the percentage of CD11b+ cells in vivo.

12. The anti-IL18BP antibody according to any one of claims 1 to 11, wherein the anti-IL18BP antibody increases the percentage of macrophages in vivo.

13. BP-10, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-1 0, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-04.01, BP-04.02, BP -04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04. 09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04.14, BP-04.15, BP 13. The anti-IL18BP antibody of claim 1, which competes for binding to IL18BP with one or more antibodies selected from BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31 and BP-04.32, and any combination thereof.

14. The anti-IL18BP antibody comprises a light chain variable domain and a heavy chain variable domain, and the light chain variable domain, the heavy chain variable domain, or both are selected from the group consisting of BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-17, BP-18, BP-19, BP-20, BP-21, BP-22, BP-23, BP-24, BP-25, BP-26, BP-27, BP-28, BP-29, BP-30, BP-31, BP-32, BP-33, BP-34, BP-35, BP-36, BP-37, BP-38, BP-39, BP-40, BP-41, BP-42, BP-43, BP-44, BP-45, BP-46, BP-47, BP-48, BP-49, BP-50, BP-51, BP-52, BP-53, BP-54, BP-55, BP-56, BP-57, BP-58, BP-59, BP-60, BP-61, BP-62, BP-63, BP-64, BP-65, BP-66, BP-67, BP-68, BP-69, BP-70, BP-71, BP-72, BP-73, BP-74, BP-75, BP-76, BP-77, BP-78, 4, BP-15, BP-16, BP-04.01, BP-04.02, BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04 .07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04.14, BP-04.1 5, BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23 , BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31 and The anti-IL18BP antibody according to any one of claims 1 to 13, comprising at least one, at least two, at least three, at least four, at least five, or six HVRs selected from HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, and HVR-H3 of an antibody selected from IL18BP-04.

32.

15. a. the HVR-H1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 167, 168, and 169; b. the HVR-H2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 170, 171, 172, 173, 174, 175, 176, 177, and 178; c. the HVR-H3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188; d. the HVR-L1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, and 247; e. the HVR-L2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, and 248; and / or The anti-IL18BP antibody of claim 14, wherein the HVR-L3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, and 249.

16. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 60, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 71, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 87, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 112, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 122, or b. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 61, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 72, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 88, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 102, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 113, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 123, or c. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 61, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 73, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 88, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 103, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 113, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 123, or d. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 62, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 74, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 89, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 104, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 114, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 124, or e. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 61, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 75, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 90, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 105, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 113, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 123, or f. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 63, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 76, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 91, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 106, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 115, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 125, or g. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 61, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 77, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 88, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 103, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 113, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 123; or h. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 64, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 78, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 92, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 107, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 116, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 126, or i. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 65, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 79, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 93, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 116, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 127, or j. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 66, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 80, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 94, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 108, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 117, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 128; or k. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 66, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 81, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 95, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 109, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 118, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 129; or l. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 67, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 82, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 96, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 116, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 130, or m. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 68, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 83, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 97, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 101, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 119, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 131, or n. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 69, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 84, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 98, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 110, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 120, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 132; or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 70, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 85, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 99, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 111, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 121, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 133, or p. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 70, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 86, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 100, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 111, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 121, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 133, or q. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 167, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 170, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 179, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 168, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 180, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 181, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 182, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or v. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or x. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 1704, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or y. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or z. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 176, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 187, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 188, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 182, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or hh. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or ii. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or ll. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or The anti-IL18BP antibody according to claim 14 or 15, wherein the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO:

249.

17. An isolated anti-IL18BP antibody, the anti-IL18BP antibody comprising a heavy chain variable region (VH) and a light chain variable region (VL), the heavy chain variable region (VH) comprising: a. HVR-H1 comprising an amino acid sequence selected from any one of SEQ ID NOs: 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 167, 168, and 169; b. HVR-H2 comprising an amino acid sequence selected from any one of SEQ ID NOs: 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 170, 171, 172, 173, 174, 175, 176, 177, and 178; and c. HVR-H3 comprising an amino acid sequence selected from any one of SEQ ID NOs: 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 179, 180, 181, 182, 183, 184, 185, 186, 187, and 188; The anti-IL18BP antibody comprising:

18. The light chain variable region a. HVR-L1 comprising an amino acid sequence selected from any one of SEQ ID NOs: 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, and 247; b. HVR-L2 comprising an amino acid sequence selected from any one of SEQ ID NOs: 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, and 248; and c. HVR-L3 comprising an amino acid sequence selected from any one of SEQ ID NOs: 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, and 249; The antibody of claim 17, comprising:

19. 19. The antibody of claim 17 or 18, comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to an amino acid sequence selected from any one of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, and 165.

20. 20. The antibody of any one of claims 17 to 19, comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to an amino acid sequence selected from any one of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, and 166.

21. 21. The antibody of any one of claims 17 to 20, wherein the VH comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions, insertions and / or deletions compared to an amino acid sequence selected from any one of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 and 165.

22. 22. The antibody of any one of claims 17 to 21, wherein the VL comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid substitutions, insertions and / or deletions compared to an amino acid sequence selected from any one of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 and 166.

23. The antibody of any one of claims 17 to 22, comprising a VH comprising an amino acid sequence selected from any one of SEQ ID NOs: 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 and 165.

24. The antibody of any one of claims 17 to 23, comprising a VL comprising an amino acid sequence selected from any one of SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 and 166.

25. 1. An isolated anti-IL18BP antibody, comprising: a. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 60, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 71, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 87, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 112, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 122; b. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 72, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 102, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123; c. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 73, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 103, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123; d. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 62, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 74, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 89, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 104, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 114, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 124; e. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 75, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 90, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 105, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123; f. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 63, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 76, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 91, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 106, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 115, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 125; g. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 61, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 77, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 88, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 103, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 113, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 123; h. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 64, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 78, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 92, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 107, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 126; i. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 65, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 79, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 93, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 127; j. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 66, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 80, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 94, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 108, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 117, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 128; k. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 66, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 81, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 95, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 109, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 118, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 129; l. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 67, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 82, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 96, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 116, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 130; m. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 68, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 83, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 97, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 101, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 119, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 131; n. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 69, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 84, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 98, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 110, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 120, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 132; HVR-H1 comprising the amino acid sequence of SEQ ID NO:70, HVR-H2 comprising the amino acid sequence of SEQ ID NO:85, HVR-H3 comprising the amino acid sequence of SEQ ID NO:99, HVR-L1 comprising the amino acid sequence of SEQ ID NO:111, HVR-L2 comprising the amino acid sequence of SEQ ID NO:121, and HVR-L3 comprising the amino acid sequence of SEQ ID NO:133; p. HVR-H1 comprising the amino acid sequence of SEQ ID NO: 70, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 86, HVR-H3 comprising the amino acid sequence of SEQ ID NO: 100, HVR-L1 comprising the amino acid sequence of SEQ ID NO: 111, HVR-L2 comprising the amino acid sequence of SEQ ID NO: 121, and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 133; q. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 167, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 170, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 179, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; r. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 168, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 180, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 181, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 182, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; v. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; x. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 1704, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; y. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; z. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; aa. The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; bb. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 176, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 187, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; dd. The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 188, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 182, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ff. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; hh. The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ii. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; jj. The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; kk. The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ll. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 173, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; mm. The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; pp. The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 175, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 183, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; The HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 184, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; ss. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 171, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 185, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 172, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 177, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249, or vv. the HVR-H1 comprises the amino acid sequence of SEQ ID NO: 169, the HVR-H2 comprises the amino acid sequence of SEQ ID NO: 178, the HVR-H3 comprises the amino acid sequence of SEQ ID NO: 186, the HVR-L1 comprises the amino acid sequence of SEQ ID NO: 247, the HVR-L2 comprises the amino acid sequence of SEQ ID NO: 248, and the HVR-L3 comprises the amino acid sequence of SEQ ID NO: 249; The anti-IL18BP antibody.

26. a. The method of claim 25a, further comprising: HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 29; b. The method of claim 25 b, further comprising: HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 30; c. The method of claim 25c, further comprising: HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 31; d. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 32; e. The method of claim 25e, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 33; f. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 34; g. The method according to claim 25, further comprising: HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 35; h. The method of claim 25h, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 36; i. The method of claim 25 i, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 37; j. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 38; k. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 39; 1. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 40; m. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 41; n. The method according to claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 42; o. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 43; p. The method according to claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 44; q. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 134; r. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 135; s. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 136; t. In addition to the description of t of claim 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 137; u. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 138; v. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 139; w. In addition to the description of w of claim 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 140; x. In addition to the description of x of claim 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 141; y. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 142; z. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 143; aa. In addition to the aa of claim 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 144; bb. 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 145; cc. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 146; dd. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 147; ee. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 148; ff. 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 149; gg. In addition to the recited gg of claim 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 150; hh. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 151; ii. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 152; jj. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 153; kk. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 154; 11. The method of claim 11 of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 155; mm. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 156; nn. In addition to the description of nn of claim 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 157; oo.

25. The method of claim oo, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 158; pp. 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 159; qq. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 160; rr. The rr of claim 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 161; ss. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 162; tt. The method of claim 25, further comprising: an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 163; uu. The method of claim 25, further comprising: a HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 164; vv. The vv of claim 25, further comprising an HVR comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 165; 26. The antibody of claim 25, comprising:

27. a. The method of claim 25a, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 45; b. The HVR according to claim 25b, further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

46. c. The HVR according to claim 25c, further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

47. d. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 48; e. The method of claim 25e, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 49; f. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 50; g. The invention according to claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

51. h. The method of claim 25h, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 52; i. The method of claim 25 i, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 53; j. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 54; k. The HVR according to claim 25, further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

55.

1. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 56; m. The HVR according to claim 25, further comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

57. n. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 58; o. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 59; p. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 59; q. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; r. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; s. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; t. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; u. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; v. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; w. In addition to the description of w of claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; x. In addition to the description of x of claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; y. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; z. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; aa. In addition to the aa of claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; bb. 25, further comprising a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

166. cc. The invention of claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; dd. The invention as set forth in claim dd, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; ee. The method of claim ee of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; ff. 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; gg. The method of claim 25, further comprising: providing a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; hh. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; ii. The invention according to claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

166. jj. The invention of claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

166. kk. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; 11. The method of claim 11 of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; mm. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; nn. In addition to the description of nn of claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; oo.

25. The method of claim oo, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; pp.

25. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; qq. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; rr. The rr of claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; ss. The method of claim 25, further comprising: a HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; tt. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; uu. The method of claim 25, further comprising: an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; vv. The vv of claim 25, further comprising an HVR comprising a VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 166; 27. The antibody of claim 25 or 26, comprising:

28. a. A HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 29, in addition to the description of claim 25a. b. HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 30, in addition to the description of b of claim 25; c. In addition to the description of claim 25c, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 31; d. In addition to the description of claim 25d, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 32; e. In addition to the description of claim 25e, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 33; f. In addition to the description of f of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 34; g. In addition to the description of g of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 35; h. In addition to the above, a HVR comprising a VH having the amino acid sequence of SEQ ID NO: 36; i. In addition to the description of i of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 37; j. In addition to the description of j of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 38; k. In addition to the above item k of claim 25, the HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 39; 1. The method according to claim 25, further comprising: HVR comprising a VH having the amino acid sequence of SEQ ID NO: 40; m. In addition to the description of m of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 41; n. In addition to the description of n of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 42; o. In addition to the description of o of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 43; p. In addition to the description of p of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 44; q. In addition to the description of q of claim 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 134; r. In addition to the description of r of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 135; s. In addition to the description of s of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 136; t. In addition to the description of t of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 137; u. In addition to the description of u of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 138; v. In addition to the description of v of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 139; w. In addition to the description of w of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 140; x. In addition to the description of x in claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 141; y. In addition to the description of y of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 142; z. In addition to the description of z of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 143; aa. In addition to the aa of claim 25, a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 144; bb. In addition to the description of bb of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 145; cc. In addition to the description of cc of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 146; dd. In addition to the description of dd of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 147; ee. The method of claim 25, further comprising: HVR comprising a VH having the amino acid sequence of SEQ ID NO: 148; ff. In addition to the description of ff of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 149; gg. In addition to the description of gg of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 150; hh. In addition to the description of hh of claim 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 151; ii. In addition to the above, a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 152; jj. In addition to the description of jj of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 153; kk. The HVR according to claim 25, further comprising a VH that is at least 90%, at least 95%, at least 97%, or at least 99% identical to a VH comprising the amino acid sequence of SEQ ID NO:

154.

11. The method of claim 11, further comprising: a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 155; mm. In addition to the description of mm of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 156; nn. In addition to the nn of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 157; oo. In addition to the description of oo of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 158; pp.

25. In addition to the description of pp. 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 159; qq. In addition to the above, a HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 160; rr. In addition to the rr of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 161; ss. In addition to the description of ss of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 162; tt. In addition to the tt of claim 25, further comprising an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 163; uu. In addition to the description of uu of claim 25, an HVR comprising a VH comprising the amino acid sequence of SEQ ID NO: 164; or vv. In addition to the vv of claim 25, HVR further comprises a VH comprising the amino acid sequence of SEQ ID NO: 165; The antibody of any one of claims 25 to 27, comprising:

29. a. A HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 45, in addition to the description of claim 25a. b. HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 46, in addition to the description of b of claim 25; c. A HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 47, in addition to the description of c of claim 25; d. The HVR according to claim 25 d, further comprising a VL comprising the amino acid sequence of SEQ ID NO: 48; e. A HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 49, in addition to the description of e of claim 25. f. In addition to the description of f of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 50; g. In addition to the description of g of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 51; h. In addition to the above, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO:

52. i. The HVR according to claim 25 i, further comprising a VL comprising the amino acid sequence of SEQ ID NO: 53; j. In addition to the above j of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 54; k. In addition to the above k of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 55; 1. The HVR according to claim 25, further comprising a VL comprising the amino acid sequence of SEQ ID NO: 56; m. In addition to the description of m of claim 25, an HVR further comprising a VL comprising the amino acid sequence of SEQ ID NO: 57; n. In addition to the n of claim 25, an HVR further comprising a VL comprising the amino acid sequence of SEQ ID NO: 58; o. In addition to the description of o of claim 25, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 59; p. In addition to the description of p of claim 25, an HVR further comprising a VL comprising the amino acid sequence of SEQ ID NO: 59; q. In addition to the description of q of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; r. In addition to the description of r of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; s. In addition to the description of claim 25 s, an HVR further comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; t. In addition to the description of t of claim 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; u. In addition to the description of u of claim 25, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; v. In addition to the description of v of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; w. In addition to the description of w of claim 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; x. In addition to the description of x in claim 25, an HVR further comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; y. In addition to the above, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; z. In addition to the description of z of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; aa. In addition to the aa of claim 25, a HVR further comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; bb. In addition to the description of bb of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; cc. In addition to the description of cc. of claim 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; dd. In addition to the description of dd of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; ee. The method of claim 25, further comprising: a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; ff. In addition to the description of ff of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; gg. In addition to the description of gg of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; hh. In addition to the description of hh of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; ii. In addition to the above, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; jj. In addition to the description of jj of claim 25, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; kk. The HVR comprising the VL comprising the amino acid sequence of SEQ ID NO: 166 in addition to the kk of claim 25; 11. The method of claim 11, further comprising: mm. In addition to the description of mm of claim 25, further comprising an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; nn. In addition to the nn of claim 25, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; oo. In addition to the above description of claim 25, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; pp.

25. In addition to the description of pp. 25, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; qq. In addition to the description of qq of claim 25, the HVR further comprises a VL comprising the amino acid sequence of SEQ ID NO: 166; rr. In addition to the rr of claim 25, an HVR further comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; ss. The HVR according to claim 25, further comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; tt. In addition to the tt of claim 25, a HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; uu. In addition to the description of uu of claim 25, an HVR comprising a VL comprising the amino acid sequence of SEQ ID NO: 166; or vv. The HVR comprising the VL comprising the amino acid sequence of SEQ ID NO: 166 in addition to the vv of claim 25; The antibody of any one of claims 25 to 28, comprising:

30. a. a VH comprising the amino acid sequence of SEQ ID NO: 29, and a VL comprising the amino acid sequence of SEQ ID NO: 45; b. A VH comprising the amino acid sequence of SEQ ID NO: 30, and a VL comprising the amino acid sequence of SEQ ID NO: 46; c. A VH comprising the amino acid sequence of SEQ ID NO: 31, and a VL comprising the amino acid sequence of SEQ ID NO: 47; d. A VH comprising the amino acid sequence of SEQ ID NO: 32, and a VL comprising the amino acid sequence of SEQ ID NO: 48; e. a VH comprising the amino acid sequence of SEQ ID NO: 33, and a VL comprising the amino acid sequence of SEQ ID NO: 49; f. A VH comprising the amino acid sequence of SEQ ID NO: 34, and a VL comprising the amino acid sequence of SEQ ID NO: 50; g. A VH comprising the amino acid sequence of SEQ ID NO: 35, and a VL comprising the amino acid sequence of SEQ ID NO: 51; h. A VH comprising the amino acid sequence of SEQ ID NO: 36, and a VL comprising the amino acid sequence of SEQ ID NO: 52; i. a VH comprising the amino acid sequence of SEQ ID NO: 37, and a VL comprising the amino acid sequence of SEQ ID NO: 53; j. A VH comprising the amino acid sequence of SEQ ID NO: 38, and a VL comprising the amino acid sequence of SEQ ID NO: 54; k. a VH comprising the amino acid sequence of SEQ ID NO: 39, and a VL comprising the amino acid sequence of SEQ ID NO: 55; l. VH comprising the amino acid sequence of SEQ ID NO: 40, and VL comprising the amino acid sequence of SEQ ID NO: 56; m. a VH comprising the amino acid sequence of SEQ ID NO: 41, and a VL comprising the amino acid sequence of SEQ ID NO: 57; n. VH comprising the amino acid sequence of SEQ ID NO: 42, and VL comprising the amino acid sequence of SEQ ID NO: 58; o. A VH comprising the amino acid sequence of SEQ ID NO: 43, and a VL comprising the amino acid sequence of SEQ ID NO: 59; p. VH comprising the amino acid sequence of SEQ ID NO: 44, and VL comprising the amino acid sequence of SEQ ID NO: 59; q. a VH comprising the amino acid sequence of SEQ ID NO: 134, and a VL comprising the amino acid sequence of SEQ ID NO: 166; r. A VH comprising the amino acid sequence of SEQ ID NO: 135, and a VL comprising the amino acid sequence of SEQ ID NO: 166; s. a VH comprising the amino acid sequence of SEQ ID NO: 136, and a VL comprising the amino acid sequence of SEQ ID NO: 166; t. VH comprising the amino acid sequence of SEQ ID NO: 137, and VL comprising the amino acid sequence of SEQ ID NO: 166; u. A VH comprising the amino acid sequence of SEQ ID NO: 138, and a VL comprising the amino acid sequence of SEQ ID NO: 166; v. A VH comprising the amino acid sequence of SEQ ID NO: 139, and a VL comprising the amino acid sequence of SEQ ID NO: 166; w. a VH comprising the amino acid sequence of SEQ ID NO: 140, and a VL comprising the amino acid sequence of SEQ ID NO: 166; x. A VH comprising the amino acid sequence of SEQ ID NO: 141, and a VL comprising the amino acid sequence of SEQ ID NO: 166; y. a VH comprising the amino acid sequence of SEQ ID NO: 142, and a VL comprising the amino acid sequence of SEQ ID NO: 166; z. A VH comprising the amino acid sequence of SEQ ID NO: 143, and a VL comprising the amino acid sequence of SEQ ID NO: 166; aa. VH comprising the amino acid sequence of SEQ ID NO: 144, and VL comprising the amino acid sequence of SEQ ID NO: 166; bb. VH comprising the amino acid sequence of SEQ ID NO: 145, and VL comprising the amino acid sequence of SEQ ID NO: 166; cc. VH comprising the amino acid sequence of SEQ ID NO: 146, and VL comprising the amino acid sequence of SEQ ID NO: 166; dd. VH comprising the amino acid sequence of SEQ ID NO: 147, and VL comprising the amino acid sequence of SEQ ID NO: 166; ee. VH comprising the amino acid sequence of SEQ ID NO: 148, and VL comprising the amino acid sequence of SEQ ID NO: 166; ff. VH comprising the amino acid sequence of SEQ ID NO: 149, and VL comprising the amino acid sequence of SEQ ID NO: 166; VH comprising the amino acid sequence of SEQ ID NO: 150, and VL comprising the amino acid sequence of SEQ ID NO: 166; hh. VH comprising the amino acid sequence of SEQ ID NO: 151, and VL comprising the amino acid sequence of SEQ ID NO: 166; ii. a VH comprising the amino acid sequence of SEQ ID NO: 152, and a VL comprising the amino acid sequence of SEQ ID NO: 166; jj. VH comprising the amino acid sequence of SEQ ID NO: 153, and VL comprising the amino acid sequence of SEQ ID NO: 166; kk. VH comprising the amino acid sequence of SEQ ID NO: 154, and VL comprising the amino acid sequence of SEQ ID NO: 166; ll. A VH comprising the amino acid sequence of SEQ ID NO: 155, and a VL comprising the amino acid sequence of SEQ ID NO: 166; mm. VH comprising the amino acid sequence of SEQ ID NO: 156, and VL comprising the amino acid sequence of SEQ ID NO: 166; nn. VH comprising the amino acid sequence of SEQ ID NO: 157, and VL comprising the amino acid sequence of SEQ ID NO: 166; VH comprising the amino acid sequence of SEQ ID NO: 158, and VL comprising the amino acid sequence of SEQ ID NO: 166; pp. VH comprising the amino acid sequence of SEQ ID NO: 159, and VL comprising the amino acid sequence of SEQ ID NO: 166; qq. VH comprising the amino acid sequence of SEQ ID NO: 160, and VL comprising the amino acid sequence of SEQ ID NO: 166; rr. VH comprising the amino acid sequence of SEQ ID NO: 161, and VL comprising the amino acid sequence of SEQ ID NO: 166; ss. VH comprising the amino acid sequence of SEQ ID NO: 162, and VL comprising the amino acid sequence of SEQ ID NO: 166; VH comprising the amino acid sequence of SEQ ID NO: 163, and VL comprising the amino acid sequence of SEQ ID NO: 166; a VH comprising the amino acid sequence of SEQ ID NO: 164 and a VL comprising the amino acid sequence of SEQ ID NO: 166, or VH comprising the amino acid sequence of SEQ ID NO: 165, and VL comprising the amino acid sequence of SEQ ID NO: 166; 26. The antibody of claim 25, comprising:

31. a. the method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 190; b. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 191; c. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 192; d. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

193. e. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

194. f. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

195. g. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

196. h. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

197. i. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 198; j. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

199. k. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

200.

1. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 201; m. HVRs according to claim 25, further comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 202; n. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 203; o. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 204; p. the method of claim 25, further comprising: an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 205; q. The method of claim 25, further comprising: an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 206; r. The method of claim 25, further comprising: an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 207; s. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 208; t. The method of claim 25, further comprising: an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 209; u. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 210; v. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 211; w. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 212; x. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 213; y. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 214; z. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 215; aa. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 216; bb. 25u of claim 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 217; cc. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

218. dd. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 219; ee. The method of claim 25 further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 220; ff.

25. The method of claim 25 further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 221; gg. The method of claim 25 further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 222; hh. The method of claim 25, further comprising: an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 223; ii. The method of claim 25 further comprising: providing a heavy chain HVR that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 224; jj. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 225; kk. The method of claim 25 further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 226; 11. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 227; mm. 25, further comprising: a heavy chain HVR that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 228; nn. The method of claim 25 further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 229; oo. The method of claim 25 further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

230. pp. 26-28, further comprising: a heavy chain HVR comprising at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 231; qq. The method of claim 25, further comprising: HVRs comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 232; rr. rr. according to claim 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 233; ss. The antibody of claim 25, further comprising an HVR comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:234, in addition to the recited item w of claim 25.

32. a. HVRs according to claim 25, further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; b. HVRs according to claim 25u, further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; c. HVRs according to claim 25, further comprising a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

189.

32. The antibody of claim 25 or claim 31, comprising:

33. a. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 190, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; b. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 191, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; c. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 192, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; d. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 193, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; e. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 194, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; f. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 195, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; g. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 196, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; h. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 197, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; i. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 198, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; j. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 199, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; k. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 200, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; l. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 201, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; m. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 202, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; n. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 203, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 204, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; p. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 205, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; q. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 206, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; r. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 207, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; s. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 208, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; t. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 209, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 210, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; v. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:211, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:189; w. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 212, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; x. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 213, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; y. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 214, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; z. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 215, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; aa. a heavy chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 216, and a light chain at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 217, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 218, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; dd. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 219, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 220, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; ff. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 221, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 222, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; hh. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 223, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; ii. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 224, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; jj. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 225, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; kk. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 226, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; ll. a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 227, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 228, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 229, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 230, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; pp. A heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 231, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 232, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189; a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 233, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 189, or ss. The antibody of claim 25, comprising a heavy chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO: 234, and a light chain that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the amino acid sequence of SEQ ID NO:

189.

34. 1. An isolated anti-IL18BP antibody, comprising: a. a heavy chain comprising the amino acid sequence of SEQ ID NO: 190, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; b. a heavy chain comprising the amino acid sequence of SEQ ID NO: 191, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; c. a heavy chain comprising the amino acid sequence of SEQ ID NO: 192, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; d. a heavy chain comprising the amino acid sequence of SEQ ID NO: 193, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; e. a heavy chain comprising the amino acid sequence of SEQ ID NO: 194, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; f. a heavy chain comprising the amino acid sequence of SEQ ID NO: 195, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; g. a heavy chain comprising the amino acid sequence of SEQ ID NO: 196, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; h. a heavy chain comprising the amino acid sequence of SEQ ID NO: 197, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; i. a heavy chain comprising the amino acid sequence of SEQ ID NO: 198, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; j. a heavy chain comprising the amino acid sequence of SEQ ID NO: 199, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; k. a heavy chain comprising the amino acid sequence of SEQ ID NO: 200, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; l. a heavy chain comprising the amino acid sequence of SEQ ID NO: 201, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; m. a heavy chain comprising the amino acid sequence of SEQ ID NO: 202, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; n. a heavy chain comprising the amino acid sequence of SEQ ID NO: 203, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; o. a heavy chain comprising the amino acid sequence of SEQ ID NO: 204, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; p. a heavy chain comprising the amino acid sequence of SEQ ID NO: 205, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; q. a heavy chain comprising the amino acid sequence of SEQ ID NO: 206, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; r. a heavy chain comprising the amino acid sequence of SEQ ID NO: 207, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; s. a heavy chain comprising the amino acid sequence of SEQ ID NO: 208, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; t. a heavy chain comprising the amino acid sequence of SEQ ID NO: 209, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; a heavy chain comprising the amino acid sequence of SEQ ID NO: 210, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; v. a heavy chain comprising the amino acid sequence of SEQ ID NO: 211, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; w. a heavy chain comprising the amino acid sequence of SEQ ID NO: 212, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; x. a heavy chain comprising the amino acid sequence of SEQ ID NO: 213, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; y. a heavy chain comprising the amino acid sequence of SEQ ID NO: 214, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; z. a heavy chain comprising the amino acid sequence of SEQ ID NO: 215, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; aa. a heavy chain comprising the amino acid sequence of SEQ ID NO: 216, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; bb. a heavy chain comprising the amino acid sequence of SEQ ID NO: 217, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; cc. a heavy chain comprising the amino acid sequence of SEQ ID NO: 218, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; dd. a heavy chain comprising the amino acid sequence of SEQ ID NO: 219, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; ee. a heavy chain comprising the amino acid sequence of SEQ ID NO: 220, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; ff. a heavy chain comprising the amino acid sequence of SEQ ID NO: 221, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; a heavy chain comprising the amino acid sequence of SEQ ID NO: 222 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; hh. a heavy chain comprising the amino acid sequence of SEQ ID NO: 223 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; ii. a heavy chain comprising the amino acid sequence of SEQ ID NO: 224, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; jj. a heavy chain comprising the amino acid sequence of SEQ ID NO: 225 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; kk. a heavy chain comprising the amino acid sequence of SEQ ID NO: 226, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; ll. a heavy chain comprising the amino acid sequence of SEQ ID NO: 227, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; mm. a heavy chain comprising the amino acid sequence of SEQ ID NO: 228 and a light chain comprising the amino acid sequence of SEQ ID NO: 189; a heavy chain comprising the amino acid sequence of SEQ ID NO: 229, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; a heavy chain comprising the amino acid sequence of SEQ ID NO: 230, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; pp. A heavy chain comprising the amino acid sequence of SEQ ID NO: 321, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; a heavy chain comprising the amino acid sequence of SEQ ID NO: 232, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; a heavy chain comprising the amino acid sequence of SEQ ID NO: 233 and a light chain comprising the amino acid sequence of SEQ ID NO: 189, or ss. a heavy chain comprising the amino acid sequence of SEQ ID NO: 234, and a light chain comprising the amino acid sequence of SEQ ID NO: 189; The anti-IL18BP antibody comprising:

35. 1. An isolated anti-IL18BP antibody, comprising: antibodies BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-04.01, BP-04.02, BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04.14, The anti-IL18BP antibody comprises a VH comprising HVR-H1, HVR-H2, and HVR-H3 of any one of BP-04.15, BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31, and BP-04.32, and a VL comprising HVR-L1, HVR-L2, and HVR-L3.

36. Antibodies BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-1 0, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-04.01, BP-04.02, BP-0 4.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, B P-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04.14, BP-04.15, BP-04.1 36. The isolated antibody of claim 35, comprising a VH and / or VL that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the VH and / or VL of any one of BP-04.6, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31, and BP-04.

32.

37. Antibodies BP-01, BP-02, BP-03, BP-04, BP-05, BP-06, BP-07, BP-08, BP-09, BP-10, BP-11, BP-12, BP-13, BP-14, BP-15, BP-16, BP-04.01, BP- 04.02, BP-04.03, BP-04.04, BP-04.05, BP-04.06, BP-04.07, BP-04.08, BP-04.09, BP-04.10, BP-04.11, BP-04.12, BP-04.13, BP-04 37. The isolated antibody of claim 35 or claim 36, comprising the VH and / or VL of any one of BP-04.14, BP-04.15, BP-04.16, BP-04.17, BP-04.18, BP-04.19, BP-04.20, BP-04.21, BP-04.22, BP-04.23, BP-04.24, BP-04.25, BP-04.26, BP-04.27, BP-04.28, BP-04.29, BP-04.30, BP-04.31 and BP-04.

32.

38. 1. An isolated anti-IL18BP antibody, comprising: a. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-01 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-01 (as shown in Table 2); b. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-02 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-02 (as shown in Table 2); c. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-03 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-03 (as shown in Table 2); d. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04 (as shown in Table 2); e. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-05 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-05 (as shown in Table 2); f. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-06 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-06 (as shown in Table 2); g. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-07 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-07 (as shown in Table 2); h. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-08 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-08 (as shown in Table 2); i. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-09 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-09 (as shown in Table 2); j. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-10 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-10 (as shown in Table 2); k. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-11 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-11 (as shown in Table 2); l. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-12 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-12 (as shown in Table 2); m. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-13 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-13 (as shown in Table 2); n. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-14 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-14 (as shown in Table 2); a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-15 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-15 (as shown in Table 2); p. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-16 (as shown in Table 1), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-16 (as shown in Table 2); q. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.01 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); r. A VH comprising HVR-H1, HVR-H2, and HVR-H3 (as shown in Table 12) of antibody BP-04.02, and a VL comprising HVR-L1, HVR-L2, and HVR-L3 (as shown in Table 13) of antibody BP-04.LC; s. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.03 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); t. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.04 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); u. A VH comprising HVR-H1, HVR-H2, and HVR-H3 (as shown in Table 12) of antibody BP-04.05, and a VL comprising HVR-L1, HVR-L2, and HVR-L3 (as shown in Table 13) of antibody BP-04.LC; v. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.06 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); w. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.07 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); x. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.08 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); y. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.09 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); z. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.10 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.11 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); bb. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.12 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); cc. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.13 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); dd. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.14 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); ee. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.15 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); ff. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.16 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); gg. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.17 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); hh. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.18 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); ii. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.19 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); jj. A VH comprising HVR-H1, HVR-H2, and HVR-H3 (as shown in Table 12) of antibody BP-04.20, and a VL comprising HVR-L1, HVR-L2, and HVR-L3 (as shown in Table 13) of antibody BP-04.LC; kk. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.21 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); 11. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.22 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); mm. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.23 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); nn. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.24 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); oo. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.25 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); pp. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.26 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); qq. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.27 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.28 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); ss. A VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.29 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.30 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.31 (as shown in Table 12) and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); or vv. a VH comprising HVR-H1, HVR-H2, and HVR-H3 of antibody BP-04.32 (as shown in Table 12), and a VL comprising HVR-L1, HVR-L2, and HVR-L3 of antibody BP-04.LC (as shown in Table 13); The anti-IL18BP antibody comprising:

39. The antibody according to any one of claims 25 to 38, wherein the anti-IL18BP antibody blocks the binding of IL-18 to IL18BP.

40. The following properties: a. The anti-IL18BP antibody increases the expression level of interferon-gamma (IFNγ) in peripheral blood mononuclear cells; b. The anti-IL18BP antibody increases the expression of IFNγ in natural killer cells. c. The anti-IL18BP antibody increases the level of inflammatory cytokines in serum. d. The anti-IL18BP antibody increases serum IFNγ levels. e. The anti-IL18BP antibody increases the level of IL-10 in serum. f. The anti-IL18BP antibody increases serum IL-6 levels. g. The anti-IL18BP antibody increases serum tumor necrosis factor alpha (TNFα) levels. h. The anti-IL18BP antibody reduces the percentage of CD3+ T cells in vivo. i. the anti-IL18BP antibody reduces the percentage of CD19+ B cells in vivo; j. The anti-IL18BP antibody reduces the percentage of CD11b+ cells in vivo. k. The anti-IL18BP antibody increases the percentage of macrophages in vivo. l. The anti-IL18BP antibody increases the serum level of free IL-18; m. the anti-IL18BP antibody reduces the serum level of IL-18BP; n. The anti-IL18BP antibody increases IFNγ levels in tumor lysates; o. The anti-IL18BP antibody increases IL-1β levels in tumor lysates; p. The anti-IL18BP antibody increases IL-15 levels in tumor lysates. q. the anti-IL18BP antibody increases IL-27 levels in tumor lysates; r. The anti-IL18BP antibody increases MIP-1α levels in tumor lysates, and The antibody of any one of claims 25 to 39, wherein the anti-IL18BP antibody has one or more of the following properties: (a) reducing tumor volume;

41. The antibody according to any one of claims 1 to 30 and 35 to 40, which is a monoclonal antibody.

42. The antibody of any one of claims 1 to 41, which is a humanized antibody.

43. 43. The antibody of any one of claims 1 to 42, which is an antigen-binding fragment such as a Fab, Fab', Fab'-SH, F(ab')2, Fv or scFv fragment.

44. The antibody of any one of claims 1 to 43, which is a bispecific or multispecific antibody.

45. An antibody according to any one of claims 1 to 44, which is of the IgG class, IgM class or IgA class.

46. 46. ​​The antibody of claim 45, which is of the IgG class and is of a human IgG1, IgG2, IgG3 or IgG4 isotype, or a mouse IgG1 or IgG2 isotype.

47. Human or mouse IgG1 isotype, and N297A, D265A, D270A, L234A, L235A, G237A, P238D, L328E, E233D, G237D, H268D, P271G, A330R, C226S, C229S, E233P, L234V, L234F, L235E, P331S, P331G, S267E, L328F, A330L, M252Y, S254T, T256E, N297Q, P238S, P238A, A327Q , A327G, P329A, P329S, P329G, K322A, N325S, T394D, A330S, E430G, E430S, E430F, E430T, E345K, E345Q, E345R, E345Y, S440Y, S440W, and any combination thereof, wherein the numbering of said residues is according to EU numbering.

48. 47. The antibody of any one of claims 1-30 or 35-46, having a human or murine IgG2 isotype and comprising one or more amino acid substitutions in the Fc region at amino acid residues selected from the group consisting of A330S, C127S, C214S, C219S, C220S, E345K, E345Q, E345R, E345Y, E430F, E430G, E430S, E430T, G237A, H268Q, L328F, M252Y, P331S, S254T, S267E, S440W, S440Y, T256E, V234A, V309L, and any combination thereof, wherein the numbering of said residues is according to EU numbering.

49. 47. The antibody of any one of claims 1 to 46, having a human or murine IgG4 isotype and comprising one or more amino acid substitutions in the Fc region at amino acid residues selected from the group consisting of C127S, E318A, E345R, E430G, F234A, G237A, K322A, L235A, L235E, L236E, L243A, L328F, M252Y, P331S, S228P, S229P, S254T, S267E, S440Y, T256E, and any combination thereof, wherein the numbering of said residues is according to EU numbering.

50. 50. The antibody of any one of claims 1 to 49, comprising one or more amino acid substitutions in the Fc region at residue positions selected from the group consisting of A330L, A330S, C127S, E345R, E430G, K322A, L234A, L234F, L235A, L235E, L243A, L328F, P331S, P331G, S267E, S440Y, and any combination thereof, wherein the amino acid residues are numbered according to EU numbering or Kabat numbering.

51. The antibody of any one of claims 1 to 50, wherein the IgG Fc amino acid sequence is selected from the group consisting of SEQ ID NOs: 8-27 and 235-246.

52. A pharmaceutical composition comprising the anti-IL18BP antibody according to any one of claims 1 to 51 and a pharmaceutically acceptable carrier.

53. An isolated nucleic acid comprising a nucleic acid sequence encoding the anti-IL18BP antibody of any one of claims 1 to 51.

54. 54. An isolated vector comprising the nucleic acid of claim 53.

55. 55. An isolated host cell comprising the nucleic acid of claim 53 or the vector of claim 54.

56. 56. A method for producing an anti-IL18BP antibody, comprising culturing the cell of claim 55 so as to produce the antibody.

57. 57. The method of claim 56, further comprising recovering the antibody produced by the cells.

58. 52. A method of treating cancer in a subject in need thereof, comprising administering to an individual in need thereof a therapeutically effective amount of an anti-IL18BP antibody of any one of claims 1 to 51, thereby treating said cancer.

59. 59. The method of claim 58, further comprising administering one or more therapeutic agents.

60. 60. The method of claim 59, wherein at least one therapeutic agent is a checkpoint inhibitor.

61. 61. The method of claim 60, wherein the checkpoint inhibitor is selected from a PD1, PD-L1, and PD-L2 inhibitor.

62. 61. The method of claim 60, wherein the checkpoint inhibitor is selected from an anti-PD-L1 antibody, an anti-PD-L2 antibody, and an anti-PD-1 antibody.

63. 63. The method of any one of claims 58 to 62, wherein the cancer is bile duct carcinoma, diffuse large B-cell lymphoma, glioblastoma multiforme, head and neck squamous cell carcinoma, renal clear cell carcinoma, sarcoma, bladder cancer, breast cancer, colorectal cancer, endometrial cancer, kidney cancer, renal carcinoma, pancreatic adenocarcinoma, cutaneous melanoma, gastric adenocarcinoma, lung cancer, non-small cell lung cancer, melanoma, lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, gastric cancer, thyroid cancer, uterine cancer, liver cancer, cervical cancer, testicular cancer, squamous cell carcinoma, glioma, glioblastoma, adenoma, neuroblastoma, bladder carcinoma, esophageal carcinoma, or triple-negative breast carcinoma.

64. A method for detecting the presence of IL18BP in a sample or in an individual in vitro, said method comprising an anti-IL18BP antibody according to any one of claims 1 to 51.

65. 65. The method of claim 64, further comprising quantitating antigen-binding anti-IL18BP antibodies.

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