Antibodies that bind il-18 and methods of inhibiting il-18 activity

Abstract

Antibodies that bind human interleukin-18 (hIL-18) are provided, in particular antibodies that bind epitope(s) of human IL-18. The antibodies can be, for example, entirely human antibodies, recombinant antibodies, or monoclonal antibodies. Preferred antibodies have high affinity for hIL-18 and 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

RELATED APPLICATIONS[0001]This application is a continuation of, and claims priority from, U.S. patent application Ser. No. 09 / 780,035, filed on Feb. 9, 2001, entitled, “Antibodies that Bind IL-18 and Methods of Inhibiting IL-18 Activity,” which claims the benefit of U.S. Provisional Application No. 60 / 181,608, filed Feb. 10, 2000, entitled, “Antibodies that Bind Human Interleukin-18 and Methods of Making and Using,” the contents of each which are hereby incorporated by reference.BACKGROUND OF THE INVENTION[0002]Interleukin-18 (IL-18) was originally described in 1989 as interferon-gamma inducing factor (IGIF) and is a pro-inflammatory cytokine with various functions in addition to an ability to induce interferon gamma. These biological properties include activation of NF-κb, Fas ligand expression, the induction of both CC and CXC chemokines, and increased production of competent human immunodeficiency virus.[0003]Due to the ability of IL-18 to induce interferon gamma production in T...

AI Technical Summary

Benefits of technology

[0087]The antibodies and antibody portions of the invention preferably are capable of neutralizing hIL-18 activity both in vitro and in vivo. Accordingly, such antibodies and antibody portions of the invention can be used to inhibit hIL-18 activity, e.g., in a cell culture containing hIL-18, in human subjects or in other mammalian subjects having IL-18 with which an antibody of the invention cross-reacts. In one embodiment, the invention provides a method for inhibiting IL-18 activity comprising contacting IL-18 with an antibody or antibody portion of the invention such that IL-18 activity is inhibited. Preferably, the IL-18 is human IL-18. For example, in a cell culture containing, or suspected of containing hIL-18, an antibody or antibody portion of the invention can be added to the culture medium to inhibit hIL-18 activity in the culture.

Problems solved by technology

Moreover, murine IL-18 antibodies are limited for their use in vivo due to problems associated with administration of mouse antibodies to humans, such as short serum half life, an inability to trigger certain human effector functions and elicitation of an unwanted immune response against the mouse antibody in a human (the “human anti-mouse antibody” (HAMA) reaction).

However, because these chimeric and humanized antibodies still retain some murine sequences, they still may elicit an unwanted immune reaction, the human anti-chimeric antibody (HAMA) reaction, especially when administered for prolonged periods.

However, such antibodies have not been described in the art and, therefore are still needed.

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