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IL-18 binding proteins

A technology for binding proteins and binding domains, which can be used in antifungal agents, antibacterial agents, sugar derivatives, etc., and can solve problems such as inability to signal transduction

Inactive Publication Date: 2007-01-24
ABBVIE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The IL-18Rα subunit directly binds IL-18 but cannot signal

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0285] Example 1: Preparation and characterization of recombinant IL-18

Embodiment 11

[0286] Example 1.1: IL-18 biological activity determination test

[0287] In Example 1 and Example 2, unless otherwise specified, the following test was used to determine the biological activity of IL-18.

Embodiment 11A

[0288] Example 1.1.A: KG-1 bioassay

[0289] KG-1 (ATCC#CCL-246) is a human bone marrow mononuclear cell line that constitutively expresses low-level functional IL-18 receptors. The use of TNF therapy up-regulates the IL-18R alpha and beta subunits of the functional IL-18 receptor on these cells. By ELISA, TNF-treated KG-1 cells were incubated with recombinant human IL-18 (rhu-IL-18) for KG-1 bioassay to determine the level of IL-18-induced human IFNγ production (Konishi, K ., et al. (1997) J. Immunol. Methods 209:187-191). The KG-1 bioassay was used to determine the neutralizing ability of IL-18 antagonists. For example, anti-IL-18 antibodies are incubated with different concentrations of rhu-IL-18, and then incubated with TNF-treated KG-1 cells in a 96-well plate at 37°C for 16-18 hours. The supernatant was collected and the human IFNγ level was determined by ELISA. The test measured IL-18 antagonists as low as 4×10 -11 To 6×10 -11 M's IC 50 value

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PUM

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Abstract

The present invention encompasses IL-18 binding proteins, particularly antibodies that bind human interleukin-18 (hIL-18). Specifically, the invention relates to antibodies that are entirely human antibodies. Preferred antibodies have high affinity for hIL-18 and / or that neutralize hIL-18 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-18 and for inhibiting hIL-18 activity, e.g., in a human subject suffering from a disorder in which hIL-18 activity is detrimental.

Description

[0001] Cross-documentation of related applications [0002] This application claims the priority benefit of U.S. Application No. 10 / 706,689 filed on November 12, 2003. Technical field [0003] The present invention relates to interleukin 18 (IL-18) binding proteins, in particular to their use in the prevention and / or treatment of acute and chronic inflammatory diseases. Background technique [0004] Interleukin-18 (IL-18) was first described as gamma-interferon-inducing factor (IGIF) in 1989, and is a pro-inflammatory cytokine. In addition to its ability to induce gamma-interferon, it also has many functions . These biological properties include activation of NF-κb, expression of Fas ligand, induction of CC and CXC chemokines, and increased production of competent human immunodeficiency virus. Since IL-18 has the function of inducing the production of γ-interferon in T cells and macrophages, it plays an important role in Th1-type immune response and participating in innate and acq...

Claims

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Application Information

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IPC IPC(8): C07K16/00C12N15/00C07H21/04G01N33/53A61K39/395C07K16/24G01N33/68
CPCC07K2317/33C07K2317/52C07K2317/92C07K2317/71G01N33/6869C07K2317/94C07K16/244A61K2039/505C07K2317/76C07K2317/55A61P1/00A61P1/02A61P1/04A61P1/16A61P11/00A61P11/06A61P11/08A61P13/00A61P13/12A61P15/00A61P15/08A61P17/00A61P17/02A61P17/04A61P17/06A61P17/14A61P19/00A61P19/02A61P19/04A61P19/06A61P21/00A61P25/00A61P25/04A61P25/14A61P25/16A61P25/18A61P25/24A61P25/28A61P27/02A61P29/00A61P3/00A61P3/02A61P31/00A61P31/04A61P31/10A61P31/14A61P31/16A61P31/18A61P31/20A61P33/00A61P35/00A61P35/02A61P3/08A61P37/00A61P37/02A61P37/04A61P37/06A61P37/08A61P43/00A61P5/00A61P5/14A61P5/16A61P5/50A61P7/00A61P7/06A61P9/00A61P9/04A61P9/10A61P9/12A61P3/10Y02A50/30C07K19/00C07K16/18C07K16/24
Inventor T·加于尔B·拉布科夫斯基J·W·沃斯L·格林J·巴布库克X·-C·贾J·韦勒J·S·康B·赫德伯格
Owner ABBVIE INC
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