Fusion proteins comprising tumor necrosis factor receptor

Abstract

Fusion proteins comprise a tumor necrosis factor receptor (TNF-R) polypeptide and at least one additional polypeptide selected from an interleukin-1 receptor (IL-1R) and a second TNF-R polypeptide. One such fusion protein comprises one IL-1R and two TNF-R polypeptides. The fusion proteins have therapeutic use and may be produced via recombinant DNA technology.

What is claimed is:  
     
         1 . A fusion protein comprising a human tumor necrosis factor receptor (TNF-R) and a human interleukin-1 receptor (IL-1R).  
     
     
         2 . A fusion protein according to  claim 1 , comprising two TNF-Rs and one IL-1R, wherein said fusion protein is of a formula selected from:  
       TNF-R−linker−TNF-R−linker−IL-1R and IL-1R−linker−TNF-R−linker−TNF-R  
       wherein each linker is a peptide linker.  
     
     
         3 . A fusion protein according to  claim 2  wherein each of the peptide linkers comprises from 5 to 100 amino acids selected from the group consisting of glycine, asparagine, serine, threonine, and alanine.  
     
     
         4 . A fusion protein according to  claim 2  wherein each TNF-R represents a soluble TNF-R and IL-1R represents a soluble IL-1R.  
     
     
         5 . A fusion protein according to  claim 4  wherein each soluble TNF-R comprises an amino acid sequence selected from the group consisting of amino acids 1-x and −22-x of SEQ ID NO: 1, wherein x represents an integer from 163 to 235.  
     
     
         6 . A fusion protein according to  claim 4  wherein the soluble IL-1R comprises an amino acid sequence selected from the group consisting of amino acids 1-x and −20-x of SEQ ID NO: 5, wherein x is 312-316.  
     
     
         7 . A fusion protein according to  claim 4  wherein the soluble IL-1R comprises an amino acid sequence selected from the group consisting of amino acids 1-x and −13-x of SEQ ID NO: 7, wherein x is 330-333.  
     
     
         8 . A fusion protein of the formula:  
       TNF-R−linker−TNF-R  
       wherein the linker is a peptide linker.  
     
     
         9 . A fusion protein according to  claim 8  wherein said peptide linker comprises from 5 to 100 amino acids selected from the group consisting of glycine, asparagine, serine, threonine, and alanine.  
     
     
         10 . A fusion protein according to  claim 8  wherein each TNF-R represents a soluble TNF-R polypeptide.  
     
     
         11 . A fusion protein according to  claim 10 , wherein each soluble TNF-R comprises an amino acid sequence selected from the group consisting of amino acids 1-x and −22-x of SEQ ID NO: 1, wherein x represents an integer from 163 to 235.  
     
     
         12 . An isolated DNA sequence that encodes a fusion protein according to  claim 1 .  
     
     
         13 . An expression vector comprising a DNA sequence according to  claim 12 .  
     
     
         14 . A host cell containing an expression vector according to  claim 13 .  
     
     
         15 . An isolated DNA sequence that encodes a fusion protein according to  claim 2 .  
     
     
         16 . An expression vector comprising a DNA sequence according to  claim 15 .  
     
     
         17 . A host cell containing an expression vector according to  claim 16 .  
     
     
         18 . An isolated DNA sequence that encodes a fusion protein according to  claim 8 .  
     
     
         19 . An expression vector comprising a DNA sequence according to  claim 18 .  
     
     
         20 . A host cell containing an expression vector according to  claim 19 .  
     
     
         21 . A process for producing a fusion protein of the formula:  
       TNF-R−linker−TNF-R−linker−IL-1R or IL- 1 R−linker−TNF-R−linker−TNF-R  
       comprising culturing a host cell according to  claim 17  under conditions that promote expression of said fusion protein, and recovering said fusion protein.  
     
     
         22 . A process for producing a fusion protein of the formula TNF-R−polypeptide linker−TNF-R comprising culturing a host cell according to  claim 20  under conditions that promote expression of said fusion protein, and recovering said fusion protein.  
     
     
         23 . A pharmaceutical composition comprising a fusion protein according to  claim 2  and a suitable diluent, excipient, or carrier.  
     
     
         24 . A pharmaceutical composition comprising a fusion protein according to  claim 8  and a suitable diluent, excipient, or carrier.  
     
     
         25 . A method for treating a condition mediated by tumor necrosis factor and by interleukin-1, comprising administering a therapeutically effective amount of a pharmaceutical composition according to  claim 23  to a patient afflicted with said condition.  
     
     
         26 . A method for treating a condition mediated by tumor necrosis factor, comprising administering a therapeutically effective amount of a pharmaceutical composition according to  claim 24  to a patient afflicted with said condition.