Soluble Interleukin-1 Receptor Accessory Molecule

Abstract

The present invention relates to a novel soluble IL-1 receptor accessory molecule (IL-1R AcM) protein which is a member of the Ig superfamily. In particular, isolated nucleic acid molecules are provided encoding the human IL-1R AcM protein. IL-1R AcM polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. Screening methods are further provided for identifying agonist and antagonists of IL-1 signal transduction. The invention further relates to methods for treating physiologic and pathologic disease conditions with IL-1R AcM antagonists.

1 . An isolated antibody or fragment thereof that specifically binds to a protein selected from the group consisting of:
 (a) a polypeptide whose amino acid sequence consists of amino acid residues −17 to 339 of SEQ ID NO:2;   (b) a polypeptide whose amino acid sequence consists of amino acid residues 1 to 339 of SEQ ID NO:2;   (c) a polypeptide comprising the full-length IL-1R AcM polypeptide encoded by cDNA clone contained in ATCC™ Deposit No. 97666;   (d) a polypeptide comprising the mature IL-1R AcM polypeptide encoded by cDNA clone contained in ATCC™ Deposit No. 97666;   (e) a polypeptide whose amino acid sequence consists of a portion of SEQ ID NO:2, wherein said portion is at least 30 contiguous amino acid residues in length; and   (f) a polypeptide whose amino acid sequence consists of a portion of SEQ ID NO:2, wherein said portion is at least 50 contiguous amino acid residues in length.   
     
     
         2 . The antibody or fragment thereof of  claim 1  that specifically binds protein (a). 
     
     
         3 . The antibody or fragment thereof of  claim 1  that specifically binds protein (b). 
     
     
         4 . The antibody or fragment thereof of  claim 1  that specifically binds protein (c). 
     
     
         5 . The antibody or fragment thereof of  claim 1  that specifically binds protein (d). 
     
     
         6 . The antibody or fragment thereof of  claim 1  that specifically binds protein (e). 
     
     
         7 . The antibody or fragment thereof of  claim 1  that specifically binds protein (f). 
     
     
         8 . The antibody or fragment thereof of  claim 2  that specifically binds protein (b). 
     
     
         9 . The antibody or fragment thereof of  claim 3  wherein said protein bound by said antibody or fragment thereof is glycosylated. 
     
     
         10 . The antibody or fragment thereof of  claim 3  wherein said antibody or fragment thereof is human. 
     
     
         11 . The antibody or fragment thereof of  claim 3  wherein said antibody or fragment thereof is polyclonal. 
     
     
         12 . The antibody or fragment thereof of  claim 3  wherein said antibody or fragment thereof is monoclonal. 
     
     
         13 . The antibody or fragment thereof of  claim 3  which is selected from the group consisting of:
 (a) a chimeric antibody or fragment thereof;   (b) a humanized antibody or fragment thereof;   (c) a single chain antibody; and   (d) a Fab fragment.   
     
     
         14 . The antibody or fragment thereof of  claim 3  which is labeled. 
     
     
         15 . The antibody or fragment thereof of  claim 3  wherein said antibody or fragment thereof specifically binds to said protein in a Western blot or an ELISA. 
     
     
         16 . An isolated cell that produces the antibody or fragment thereof of  claim 3 . 
     
     
         17 . A hybridoma that produces the antibody or fragment thereof of  claim 3 . 
     
     
         18 . A method of detecting IL-1R AcM protein in a biological sample comprising:
 (a) contacting the biological sample with the antibody or fragment thereof of  claim 3 ; and   (b) detecting the IL-1R AcM protein in the biological sample.   
     
     
         19 . An isolated antibody or fragment thereof that specifically binds a IL-1R AcM protein purified from a cell culture wherein said IL-1R AcM protein is encoded by a polynucleotide encoding amino acids −17 to 339 of SEQ ID NO:2. 
     
     
         20 . The antibody or fragment thereof of  claim 19  wherein said antibody or fragment thereof is monoclonal. 
     
     
         21 . The antibody or fragment thereof of  claim 19  wherein said antibody or fragment thereof is polyclonal. 
     
     
         22 . The antibody or fragment thereof of  claim 19  wherein said antibody or fragment thereof is human. 
     
     
         23 . The antibody or fragment thereof of  claim 19  which is selected from the group consisting of:
 (a) a chimeric antibody or fragment thereof;   (b) a humanized antibody or fragment thereof;   (c) a single chain antibody; and   (d) a Fab fragment.   
     
     
         24 . The antibody or fragment thereof of  claim 19  wherein said antibody or fragment thereof specifically binds to said protein in a Western blot or an ELISA. 
     
     
         25 . The antibody or fragment thereof of  claim 19  wherein the amino acid sequence of said IL-1R AcM protein consists of amino acid residues 1 to 339 of SEQ ID NO:2.