Cytokine receptor chain

Abstract

Polynucleotides encoding the IL-13 receptor and fragments thereof are disclosed. IL-13 receptor proteins, methods for their production, inhibitors of binding of IL-13 and its receptor and methods for their identification are also disclosed. Methods of medical treatment using such molecules and antagonists of the IL-13/IL-13R interaction are also provided.

1 . An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
 (a) the nucleotide sequence of SEQ ID NO:1 from nucleotide 256 to nucleotide 1404;   (b) the nucleotide sequence of SEQ ID NO:3 from nucleotide 103 to nucleotide 1242;   (c) a nucleotide sequence varying from the sequence of the nucleotide sequence specified in (a) or (b) as a result of degeneracy of the genetic code;   (d) a nucleotide sequence capable of hybridizing under stringent conditions to the nucleotide specified in (a) or (b);   (e) a nucleotide sequence encoding a species homologue of the sequence specified in (a) or (b); and   (f) an allelic variant of the nucleotide sequence specified in (a) or (b).   
     
     
         2 . The polynucleotide of  claim 1  wherein said nucleotide sequence encodes for a protein having a biological activity of the IL-13R binding chain. 
     
     
         3 . The polynucleotide of  claim 1  wherein said nucleotide sequence is operably linked to an expression control sequence. 
     
     
         4 . The polynucleotide of  claim 1  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 319 to nucleotide 1257. 
     
     
         5 . The polynucleotide of  claim 1  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 1324 to nucleotide 1404. 
     
     
         6 . The polynucleotide of  claim 1  comprising the nucleotide sequence of SEQ ID NO:3 from nucleotide 178 to nucleotide 1125. 
     
     
         7 . The polynucleotide of  claim 1  comprising the nucleotide sequence of SEQ ID NO:3 from nucleotide 1189 to nucleotide 1242. 
     
     
         8 . A host cell transformed with the polynucleotide of  claim 3 . 
     
     
         9 . The host cell of  claim 8 , wherein said cell is a mammalian cell. 
     
     
         10 . A process for producing a IL-13bc protein, said process comprising:
 (a) growing a culture of the host cell of  claim 8  in a suitable culture medium; and   (b) purifying the IL-13bc protein from the culture.   
     
     
         11 . An isolated IL-13bc protein comprising an amino acid sequence selected from the group consisting of:
 (a) the amino acid sequence of SEQ ID NO:2;   (b) the amino acid sequence of SEQ ID NO:2 from amino acids 22 to 334;   (c) the amino acid sequence of SEQ ID NO:2 from amino acids 357 to 383;   (d) the amino acid sequence of SEQ ID NO:4;   (e) the amino acid sequence of SEQ ID NO:4 from amino acids 26 to 341;   (f) the amino acid sequence of SEQ ID NO:4 from amino acids 363 to 380; and   (g) fragments of (a)-(f) having a biological activity of the IL-13 receptor binding chain.   
     
     
         12 . The protein of  claim 11  comprising the amino acid sequence of SEQ ID NO:2. 
     
     
         13 . The protein of  claim 11  comprising the sequence from amino acid 22 to 334 of SEQ ID NO:2. 
     
     
         14 . The protein of  claim 11  comprising the amino acid sequence of SEQ ID NO:4. 
     
     
         15 . The protein of  claim 11  comprising the sequence from amino acid 26 to 341 of SEQ ID NO:4. 
     
     
         16 . A pharmaceutical composition comprising a protein of  claim 11  and a pharmaceutically acceptable carrier. 
     
     
         17 . A protein produced according to the process of  claim 10 . 
     
     
         18 . A composition comprising an antibody which specifically reacts with a protein of  claim 11 . 
     
     
         19 . A method of identifying an inhibitor of IL-13 binding to the IL-13 receptor which comprises:
 (a) combining a protein of  claim 11  with IL-13 or a fragment thereof, said combination forming a first binding mixture;   (b) measuring the amount of binding between the protein and the IL-13 or fragment in the first binding mixture;   (c) combining a compound with the protein and the IL-13 or fragment to form a second binding mixture;   (d) measuring the amount of binding in the second binding mixture; and   (e) comparing the amount of binding in the first binding mixture with the amount of binding in the second binding mixture;   
       wherein the compound is capable of inhibiting IL-13 binding to the IL-13 receptor when a decrease in the amount of binding of the second binding mixture occurs. 
     
     
         20 . An inhibitor identified by the method of  claim 19 . 
     
     
         21 . A pharmaceutical composition comprising the inhibitor of  claim 20  and a pharmaceutically acceptable carrier. 
     
     
         22 . A method of inhibiting binding of IL-13 to the IL-13 receptor in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 21 . 
     
     
         23 . A method of inhibiting binding of IL-13 to the IL-13 receptor in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 16 . 
     
     
         24 . A method of inhibiting binding of IL-13 to the IL-13 receptor in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 18 . 
     
     
         25 . An isolated polynucleotide comprising a nucleotide sequence encoding a peptide or protein comprising an amino acid sequence selected from the group consisting of:
 (a) the amino acid sequence of SEQ ID NO:2;   (b) the amino acid sequence of SEQ ID NO:2 from amino acids 22 to 334;   (c) the amino acid sequence of SEQ ID NO:2 from amino acids 357 to 383;   (d) the amino acid sequence of SEQ ID NO:4;   (e) the amino acid sequence of SEQ ID NO:4 from amino acids 26 to 341;   (f) the amino acid sequence of SEQ ID NO:4 from amino acids 363 to 380; and   (g) fragments of (a)-(f) having a biological activity of the IL-13 receptor binding chain.   
     
     
         26 . The protein of  claim 11  wherein said amino acid sequence is part of a fusion protein. 
     
     
         27 . The protein of  claim 26  comprising an Fc fragment. 
     
     
         28 . A method of treating an IL-13-related condition in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 16 . 
     
     
         29 . The method of  claim 28  wherein said condition is an IgE-mediated condition. 
     
     
         30 . The method of  claim 29  wherein said condition is selected from the group consisting of atopy, an allergic condition, asthma and an immune complex disease. 
     
     
         31 . The method of  claim 30  wherein said condition is selected from the group consisting of lupus, nephritis, thyroiditis and Grave's disease. 
     
     
         32 . A method for potentiating IL-13 activity, said method comprising combining a protein having IL-13 activity with a protein of  claim 11  and contacting such combination with a cell expressing at least one chain of IL-13R other than IL-13bc. 
     
     
         33 . The method of  claim 32  wherein the contacting step is performed by administering a therapeutically effective amount of such combination to a mammalian subject. 
     
     
         34 . The protein of  claim 11  comprising the amino acid sequence of SEQ ID NO:2 from amino acids 1 to 331. 
     
     
         35 . The protein of  claim 11  comprising the amino acid sequence of SEQ ID NO:2 from amino acids 26 to 331. 
     
     
         36 . The polynucleotide of  claim 25  encoding a peptide or protein comprising the amino acid sequence of SEQ ID NO:2 from amino acids 1 to 331 
     
     
         37 . The polynucleotide of  claim 25  encoding a peptide or protein comprising the amino acid sequence of SEQ ID NO:2 from amino acids 26 to 331. 
     
     
         38 . The method of  claim 28  wherein said condition is an inflammatory condition of the lung. 
     
     
         39 . A method of treating an IL-13-related condition in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition comprising an IL-13 antagonist and a pharmaceutically acceptable carrier. 
     
     
         40 . The method of  claim 39  wherein said condition is an IgE-mediated condition. 
     
     
         41 . The method of  claim 40  wherein said condition is selected from the group consisting of atopy, an allergic condition, asthma and an immune complex disease. 
     
     
         42 . The method of  claim 41  wherein said condition is selected from the group consisting of lupus, nephritis, thyroiditis and Grave's disease. 
     
     
         43 . The method of  claim 39  wherein said antagonist is selected from the group consisting of an IL-13bc protein, a soluble form of IL-13Rα1, an antibody to IL-13 or an IL-13-binding fragment thereof, an antibody to IL-13bc or an IL-13bc-binding fragment thereof, an antibody to IL-13Rα1 or an IL-13Rα1-binding fragment thereof, IL-13R-binding mutants of IL-4, a small molecule capable of inhibiting the interaction of IL-13 with IL-13bc and a small molecule capable of inhibiting the interaction of IL-13 with IL-13Rα1. 
     
     
         44 . The method of  claim 43  wherein said IL-13bc protein is a protein of  claim 11 . 
     
     
         45 . A method of inhibiting the interaction of IL-13 with an IL-13bc protein in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition comprising an IL-13 antagonist and a pharmaceutically acceptable carrier. 
     
     
         46 . The method of  claim 45  wherein said antagonist is selected from the group consisting of an IL-13bc protein, a soluble form of IL-13Rα1, an antibody to IL-13 or an IL-13-binding fragment thereof, an antibody to IL-13bc or an IL-13bc-binding fragment thereof, an antibody to IL-13Rα1 or an IL-13Rα1-binding fragment thereof, IL-13R-binding mutants of IL-4, a small molecule capable of inhibiting the interaction of IL-13 with IL-13bc and a small molecule capable of inhibiting the interaction of IL-13 with EL-13Rα1. 
     
     
         47 . The method of  claim 46  wherein said IL-13bc protein is a protein of  claim 11 .