Receptor for oncostatin M

Abstract

A novel polypeptide functions as the β chain of an oncostatin M receptor and is thus designated OSM-Rβ. Heterodimeric receptor proteins comprising OSM-Rβ and gp130 bind oncostatin M and find use in inhibiting biological activities mediated by oncostatin M.

What is claimed is:  
     
         1 . A receptor capable of binding oncostatin M, comprising a gp130 polypeptide covalently linked to an oncostatin M receptor B-chain (OSM-RB) polypeptide, wherein said gp130 polypeptide is a biologically active polypeptide encoded by a DNA selected from the group consisting of: 
 a) DNA comprising the coding region of the nucleotide sequence presented in SEQ ID NO:1;    b) DNA capable of hybridizing under highly stringent conditions to the DNA of (a); and    c) DNA that encodes the amino acid sequence presented in SEQ ID NO:2; and    wherein said OSM-Rβ polypeptide is a biologically active polypeptide encoded by a DNA selected from the group consisting of:    a′) DNA comprising the coding region of the nucleotide sequence presented in SEQ ID NO:5;    b′) DNA capable of hybridizing under highly stringent conditions to the DNA of (a′); and    c′) DNA that encodes the amino acid sequence presented in SEQ ID NO:6.    
     
     
         2 . A receptor according to  claim 1 , wherein said receptor comprises a soluble gp130 polypeptide covalently linked to a soluble OSM-Rβ polypeptide.  
     
     
         3 . A receptor according to  claim 1  wherein said receptor comprises gp130 covalently linked to OSM-Rβ via a peptide linker.  
     
     
         4 . A receptor according to  claim 3 , wherein said receptor is a recombinant fusion protein of the formula:  
       R 1 -L-R 2  or R 2 -L-R 1    
       wherein R 1  represents a soluble gp130; R 2  represents a soluble OSM-Rβ, and L represents a peptide linker.  
     
     
         5 . A receptor according to  claim 4 , wherein said soluble gp130 comprises amino acids −22 to y or 1 to y of SEQ ID NO:2, wherein y represents an integer between 308 and 597, inclusive; and said soluble OSM-Rβ comprises amino acids −27 to x or 1 to x of SEQ ID NO:6, wherein x is an integer between 432 and 714, inclusive.  
     
     
         6 . An isolated DNA sequence encoding the receptor of  claim 4 .  
     
     
         7 . A recombinant expression vector comprising the DNA sequence of  claim 6 .  
     
     
         8 . A process for preparing a receptor according to  claim 4 , comprising culturing a host cell transformed with an expression vector comprising a DNA sequence that encodes said fusion protein under conditions that promote expression of said fusion protein, and recovering said fusion protein.  
     
     
         9 . A receptor according to  claim 2  comprising a first fusion polypeptide that comprises an antibody Fc region polypeptide attached to the C-terminus of a soluble gp130, and a second fusion polypeptide that comprises an antibody Fc region polypeptide attached to the C-terminus of a soluble OSM-Rβ, wherein said first fusion polypeptide is linked to said second fusion polypeptide via disulfide bonds between the Fc region polypeptides.  
     
     
         10 . A process for preparing a receptor according to  claim 9 , comprising culturing a host cell co-transfected with a first expression vector encoding said first fusion polypeptide and with a second expression vector encoding said second fusion polypeptide under conditions that promote expression of said first and second fusion polypeptides, and recovering said receptor.  
     
     
         11 . A receptor according to  claim 9 , wherein said soluble gp130 comprises amino acids −22 to y or 1 to y of SEQ ID NO:2, wherein y represents an integer between 308 and 597, inclusive; and said soluble OSM-Rβ comprises amino acids −27 to x or 1 to x of SEQ ID NO:6, wherein x is an integer between 432 and 714, inclusive.  
     
     
         12 . A composition comprising a receptor of  claim 2  and a suitable diluent or carrier.  
     
     
         13 . An isolated DNA encoding an OSM-Rβ polypeptide, wherein said DNA is selected from the group consisting of: 
 a) DNA comprising the coding region of the nucleotide sequence presented in SEQ ID NO:5;  
 b) DNA capable of hybridizing under highly stringent conditions to the DNA of (a), and encoding a biologically active OSM-Rβ polypeptide; and  
 c) DNA that encodes the amino acid sequence presented in SEQ ID NO:6.  
 
     
     
         14 . An isolated DNA according to  claim 13 , wherein said OSM-Rβ comprises an amino acid sequence selected from the group consisting of amino acids −27 to 952 and amino acids 1 to 952 of SEQ ID NO:6.  
     
     
         15 . An isolated DNA according to  claim 13 , wherein said DNA encodes a soluble OSM-Rβ polypeptide.  
     
     
         16 . A DNA according to  claim 15 , where said soluble OSM-Rβ polypeptide comprises amino acids −27 to x or 1 to x of SEQ ID NO:6, wherein x is an integer between 432 and 714, inclusive.  
     
     
         17 . An isolated DNA encoding an OSM-Rβ polypeptide, wherein said OSM-Rβ polypeptide is characterized by the N-terminal amino acid sequence Glu Arg Leu Pro Leu Thr Pro Val Ser Leu Lys Val.  
     
     
         18 . An expression vector comprising a DNA according to  claim 13 .  
     
     
         19 . An expression vector comprising a DNA according to  claim 15 .  
     
     
         20 . A process for preparing an OSM-Rβ polypeptide, comprising culturing a host cell transformed with a vector according to  claim 18  under conditions promoting expression of OSM-Rβ and recovering the OSM-Rβ polypeptide from the culture.  
     
     
         21 . A process for preparing an OSM-Rβ polypeptide, comprising culturing a host cell transformed with a vector according to  claim 19  under conditions promoting expression of OSM-Rβ and recovering the OSM-R]3 polypeptide from the culture.  
     
     
         22 . A purified OSM-Rβ polypeptide encoded by a DNA according to  claim 13 .  
     
     
         23 . An OSM-Rβ polypeptide according to  claim 22 , wherein said OSM-Rβ is a soluble OSM-Rβ polypeptide.  
     
     
         24 . A soluble OSM-Rβ according to  claim 23 , comprising amino acids −27 to x or 1 to x of SEQ ID NO:6, wherein x is an integer between 432 and 714, inclusive.  
     
     
         25 . A purified OSM-Rβ polypeptide, wherein said OSM-Rβ polypeptide is characterized by the N-terminal amino acid sequence Glu Arg Leu Pro Leu Thr Pro Val Ser Leu Lys Val.  
     
     
         26 . An OSM-Rβ polypeptide according to  claim 25 , comprising amino acids 1 to 952 of SEQ ID NO:6.  
     
     
         27 . An OSM-Rβ polypeptide according to  claim 22 , wherein said OSM-Rβ is encoded by the OSM-Rβ cDNA in the recombinant vector deposited in strain ATCC 69675.  
     
     
         28 . A soluble OSM-Rβ polypeptide according to  claim 15 , wherein said polypeptide additionally comprises an Fc polypeptide fused to the C-terminus of said OSM-Rβ polypeptide.  
     
     
         29 . An antibody that is immunoreactive with an OSM-Rβ polypeptide according to  claim 13 .  
     
     
         30 . An antibody according to  claim 29 , wherein said antibody is a monoclonal antibody.  
     
     
         31 . An isolated nucleic acid molecule comprising a sequence of at least about 14 nucleotides of the coding region of the DNA sequence presented in SEQ ID NO:5, or its DNA or RNA complement.