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IL-18 binding proteins
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A technology for binding proteins and binding domains, which can be used in fungi, introduction of foreign genetic material using vectors, antifungal agents, etc., and can solve problems such as inability to signal transduction
Inactive Publication Date: 2011-02-23
ABBVIE INC
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The IL-18Rα subunit directly binds IL-18 but cannot signal
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[0176] A. Preparation method of anti-IL-18 antibody
[0177] Antibodies of the invention can be prepared by a variety of techniques well known in the art. A particularly preferred method of preparing the anti-IL-18 antibody of the present invention includes using XENOMOUSE transgenic mice, and using hybridoma and SLAM cell manipulation techniques known in the art for the preparation of antibodies (Abgenix, Inc., Fremont, CA) , and an antigen comprising the IL-18 peptide described in Example 3.2, ie, human IL-18 comprising the amino acid sequence of SEQ ID NO. 1 and fragments thereof, was used.
[0184] Example 2.2.A provides a protocol for immunization of XENOMOUSE transgenic mice with human IL-18 in phosphate buffered saline.
[0185] B. Production of Antibodies and Antibody-Producing Cell Lines
[0186] Following immunization of an animal with IL-18 antigen, antibodies and / or antibody-producing cells can be obtained from the animal. Serum containing anti-IL-18 antibodies is obtained from animals by bled or sacrificed from the animals. Serum obtained from animals, immunoglobulin fractions obtained from serum, or anti-IL-18 antibodies purified from serum can be used. The sera or immunoglobulins obtained in this way are polyclonal and therefore have a range of heterogeneous properties.
[0187] In another embodiment, antibody-producing immortalized hybridomas can be prepared from immunized animals. Following immunization the animals are sacrificed and the B splenocytes are fused with immortalized myeloma cells as is well known in the art. See, eg, Harlow and Lane, ...
Embodiment 3
[0284] Example 3 discloses methods for the identification of genes regulated by IL-18. These studies demonstrate that IL-18 is a true pro-inflammatory cytokine and can directly regulate the expression of several genes encoding other inflammatory mediators. Studies using human blood samples showed that many responses to IL-18 occur widely in the population and confirmed their use as biochemical markers, and consequently anti-IL18 function.
[0285] Modulators of IL-18 can be agonists and antagonists. Preferably, the modulator is a binding protein or a neutralizing binding protein.
[0286] Exemplary IL-18 inhibitors include, but are not limited to, antibodies and fragments thereof that bind IL-18; antibodies that bind IL-18R; antibodies that bind IL-18RAcP; IL-18bp; IL-18R fragments (e.g., IL-18 lytic extracellular domain of the receptor); peptides that bind IL-18 and reduce or prevent its interaction with IL-18R; bind IL-18R and reduce or prevent its interaction with IL-18 or ...
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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] This application is a divisional application of the invention patent application with the application number 200480039948.2 and the application date of November 12, 2004. [0002] Cross References to Related Applications [0003] This application claims the benefit of priority to US Application Serial No. 10 / 706,689, filed November 12,2003. technical field [0004] 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 [0005] Interleukin-18 (IL-18) was first described in 1989 as gamma-interferon-inducible factor (IGIF) and is a pro-inflammatory cytokine with multifaceted functions in addition to its ability to induce gamma-interferon . These biological properties include activation of NF-κb, Fas ligand expression, induction of CC and CXC chemokines, and increased production of competent human immunodeficiencyvirus. Sin...
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