Human interleukin-11 receptor

Abstract

Polynucleotides encoding the human IL-11 receptor and fragments thereof are disclosed. IL-11 receptor proteins, methods for their production, inhibitors of binding of human IL-11 and its receptor and methods for their identification are also disclosed.

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 803 to nucleotide 1999;    (b) a nucleotide sequence varying from the sequence of the nucleotide sequence specified in (a) as a result of degeneracy of the genetic code;    (c) an allelic variant of the nucleotide sequence specified in (a); and    (d) a fragment of (a) or (b) encoding a protein having the ability to bind IL-11.    
     
     
         2 . The polynucleotide of  claim 1  wherein said nucleotide sequence encodes for a protein having a biological activity of the human IL-11 receptor.  
     
     
         3 . The polynucleotide of  claim 1  wherein said nucleotide sequence is operably linked to an expression control sequence.  
     
     
         4 . The polynucleotide of  claim 2  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 803 to nucleotide 1999.  
     
     
         5 . The polynucleotide of  claim 2  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 803 to nucleotide 1828 or a fragment thereof.  
     
     
         6 . The polynucleotide of  claim 2  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 1907 to nucleotide 1999 or a fragment thereof.  
     
     
         7 . The polynucleotide of  claim 1  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 734 to nucleotide 1999.  
     
     
         8 . The polynucleotide of  claim 1  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 1067 to nucleotide 1828.  
     
     
         9 . The polynucleotide of  claim 1  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 1067 to nucleotide 1999.  
     
     
         10 . A host cell transformed with the polynucleotide of  claim 3 .  
     
     
         11 . The host cell of  claim 8 , wherein said cell is a mammalian cell.  
     
     
         12 . A process for producing a human IL-11R protein, said process comprising: 
 (a) growing a culture of the host cell of  claim 10  in a suitable culture medium; and    (b) purifying the human IL-11R protein from the culture.    
     
     
         13 . An isolated human IL-11R 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 24 to 422;    (c) the amino acid sequence of SEQ ID NO:2 from amino acids 24 to 365;    (d) the amino acid sequence of SEQ ID NO:2 from amino acids 391 to 422;    (e) the amino acid sequence of SEQ ID NO:2 from amino acids 102 to 422;    (f) the amino acid sequence of SEQ ID NO:2 from amino acids 102 to 365;    (g) the amino acid sequence of SEQ ID NO:2 from amino acids 24 to 359;    (h) the amino acid sequence of SEQ ID NO:2 from amino acids 24 to 345;    (i) the amino acid sequence of SEQ ID NO:2 from amino acids 24 to 324; and    (j) fragments of (a)-(i) having a biological activity of the human IL-11 receptor.    
     
     
         14 . The protein of  claim 13  comprising the amino acid sequence of SEQ ID NO:2.  
     
     
         15 . The protein of  claim 13  comprising the sequence from amino acid 24 to 365 of SEQ ID NO:2.  
     
     
         16 . A pharmaceutical composition comprising a protein of  claim 13  and a pharmaceutically acceptable carrier.  
     
     
         17 . A protein produced according to the process of  claim 12 .  
     
     
         18 . A composition comprising an antibody which specifically reacts with a protein of  claim 13 .  
     
     
         19 . A method of identifying an inhibitor of IL-11 binding to the human IL-11 receptor which comprises: 
 (a) combining a protein of  claim 13  with IL-1 or a fragment thereof, said combination forming a first binding mixture;    (b) measuring the amount of binding between the protein and the IL-11 or fragment in the first binding mixture;    (c) combining a compound with the protein and the IL-11 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-11 binding to the human IL-11 receptor when a decrease in the amount of binding of the second binding mixture occurs.    
     
     
         20 . The method of  claim 19  wherein the first and second binding mixture comprise gp130 or a fragment thereof capable of binding to the protein of  claim 13  or the IL-11 or fragment used therein.  
     
     
         21 . An inhibitor identified by the method of  claim 19 .  
     
     
         22 . A pharmaceutical composition comprising the inhibitor of  claim 21  and a pharmaceutically acceptable carrier.  
     
     
         23 . A method of inhibiting binding of IL-11 to the human IL-11 receptor in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 22 .  
     
     
         24 . A method of inhibiting binding of IL-11 to the human IL-11 receptor in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 16 .  
     
     
         25 . A method of inhibiting binding of IL-11 to the human IL-11 receptor in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 18 .  
     
     
         26 . A method of treating or preventing loss of bone mass in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 22 .  
     
     
         27 . A method of treating or preventing loss of bone mass in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 16 .  
     
     
         28 . A method of treating or preventing loss of bone mass in a mammalian subject, said method comprising administering a therapeutically effective amount of a composition of  claim 18 .  
     
     
         29 . An isolated polynucleotide comprising a nucleotide sequence capable of hybridizing under stringent conditions to polynucleotide of  claim 4 .  
     
     
         30 . 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 24 to 422;    (c) the amino acid sequence of SEQ ID NO:2 from amino acids 24 to 365;    (d) the amino acid sequence of SEQ ID NO:2 from amino acids 391 to 422;    (e) the amino acid sequence of SEQ ID NO:2 from amino acids 112 to 422;    (f) the amino acid sequence of SEQ ID NO:2 from amino acids 112 to 365;    (g) the amino acid sequence of SEQ ID NO:2 from amino acids 24 to 359;    (h) the amino acid sequence of SEQ ID NO:2 from amino acids 24 to 345;    (i) the amino acid sequence of SEQ ID NO:2 from amino acids 24 to 324; and    (j) fragments of (a)-(i) having a biological activity of the human IL-11 receptor.    
     
     
         31 . The polynucleotide of  claim 2  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 734 to nucleotide 1828.  
     
     
         32 . The polynucleotide of  claim 2  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 734 to nucleotide 1810.  
     
     
         33 . The polynucleotide of  claim 2  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 734 to nucleotide 1768.  
     
     
         34 . The polynucleotide of  claim 2  comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 734 to nucleotide 1705.  
     
     
         35 . The protein of  claim 13  comprising an amino acid sequence beginning at amino acid 26 of SEQ ID NO:2.  
     
     
         36 . The protein of  claim 13  comprising an amino acid sequence beginning at amino acid 23 of SEQ ID NO:2.  
     
     
         37 . The protein of  claim 13  comprising an amino acid sequence beginning at amino acid 1 of SEQ ID NO:2.