C-terminally truncated interferon

Abstract

The invention described herein provides a C-terminally truncated interferon having enhanced biological activity and the polynucleotides encoding such interferon. Also provided are methods for producing and using such truncated interferon.

1 . A polypeptide comprising a C-terminally truncated interferon having enhanced biological activity.  
     
     
         2 . The polypeptide of  claim 1  wherein the enhanced biological activity is antiproliferative activity.  
     
     
         3 . The polypeptide of  claim 1  wherein the C-terminally truncated interferon is interferon alpha 2a.  
     
     
         4 . The polypeptide of  claim 1  wherein the C-terminally truncated interferon is interferon alpha 2b.  
     
     
         5 . The polypeptide of  claim 1  comprising 156 amino acids, 157 amino acids, or 158 amino acids.  
     
     
         6 . The polypeptide of  claim 1  having an amino acid sequence selected from the group consisting of residues #1-156 of SEQ ID NO:2, residues #1-157 of SEQ ID NO:2, and residues #1-158 of SEQ ID NO:2.  
     
     
         7 . A composition comprising the polypeptide of  claim 1  associated with a molecule capable of stabilizing the composition.  
     
     
         8 . The composition of  claim 7  wherein the molecule is selected from the group consisting of polyethylene glycol and polyethylene glycol derivatives.  
     
     
         9 . A composition comprising the polypeptide of  claim 1  fused to a heterologous amino acid sequence.  
     
     
         10 . The composition of  claim 9  wherein the heterologous amino acid sequence is a signal peptide.  
     
     
         11 . The composition of  claim 10  wherein the signal peptide is extensin.  
     
     
         12 . The polypeptide of  claim 1  wherein the polypeptide is plant produced.  
     
     
         13 . The polypeptide of  claim 1  wherein the polypeptide is produced by fermentation or microbially.  
     
     
         14 . A pharmaceutical composition comprising the composition of  claim 1 .  
     
     
         15 . The polypeptide of  claim 12  having 1.56 amino acids, 157 amino acids or 158 amino acids and exhibiting enhanced processing qualities.  
     
     
         16 . The polypeptide of  claim 15  wherein the enhanced processing qualities comprise enhanced stability in plant extracts.  
     
     
         17 . The polypeptide of  claim 15  wherein the enhanced processing qualities comprise enhanced yield.  
     
     
         18 . The polypeptide of  claim 15  wherein the enhanced processing qualities comprise enhanced homogeneity at the C-terminus.  
     
     
         19 . An artificial polynucleotide encoding a polypeptide comprising a C-terminally truncated interferon having enhanced biological activity.  
     
     
         20 . The artificial polynucleotide of  claim 19  further comprising a nucleotide sequence that encodes the amino acid sequence of an extensin signal peptide.  
     
     
         21 . The artificial polynucleotide of  claim 20  wherein the nucleotide sequence that encodes the amino acid sequence of an extensin signal peptide is linked to the 5′ end of the C-terminally truncated interferon.  
     
     
         22 . The artificial polynucleotide of  claim 19 , wherein the polypeptide comprises 156 amino acids, 157 amino acids, or 158 amino acids.  
     
     
         23 . The artificial polynucleotide of  claim 19  with a sequence selected from the group consisting of nucleotides #1-468 of SEQ ID NO:1, nucleotides #1-471 of SEQ ID NO:1, and nucleotides #1-474 of SEQ ID NO:1.  
     
     
         24 . An expression vector comprising the polynucleotide of  claim 19 .  
     
     
         25 . The expression vector of  claim 24  wherein the vector is selected from the group consisting of a plasmid and a viral vector.  
     
     
         26 . A host cell comprising the expression vector of  claim 24 .  
     
     
         27 . The host cell of  claim 26  wherein the host cell is selected from the group consisting of a plant cell, a CHO cell, a bacterial cell and a yeast cell.  
     
     
         28 . A process for producing a polypeptide comprising a C-terminally truncated interferon having enhanced biological activity comprising transforming a plant with the expression vector of  claim 24 .  
     
     
         29 . The process of  claim 28  comprising infecting the plant with a viral vector comprising the expression construct.  
     
     
         30 . The process of  claim 29  further comprising recovering the polypeptide from the plant.  
     
     
         31 . The process of  claim 28  wherein the expression construct further comprises a nucleotide sequence that encodes the amino acid sequence of an extensin signal peptide.  
     
     
         32 . The process of  claim 28  comprising stably incorporating the expression construct into the genome of the plant.  
     
     
         33 . A process for producing a polypeptide comprising a C-terminally truncated interferon having enhanced antiproliferative activity comprising culturing the host cell of  claim 26  and recovering the polypeptide from the host cell.  
     
     
         34 . A polypeptide produced by the method of  claim 28 .  
     
     
         35 . A polypeptide produced by the method of  claim 33   
     
     
         36 . A plant comprising the expression vector of  claim 24 .  
     
     
         37 . The plant of  claim 36  wherein the expression construct is delivered by a viral vector.  
     
     
         38 . The plant of  claim 36  wherein the expression construct is stably incorporated into the plant genome.  
     
     
         39 . The plant of  claim 37  wherein the plant is  N. benthamiana.    
     
     
         40 . A plant containing a C-terminally truncated interferon having enhanced biological activity.  
     
     
         41 . A method for treating an interferon affected disorder comprising administering to a patient a therapeutically effective amount of a pharmaceutical composition comprising the polypeptide of  claim 1 .  
     
     
         42 . The method of  claim 41  wherein the therapeutically effective amount comprises between 5-20 ug.  
     
     
         43 . The method of  claim 41  wherein the pharmaceutical composition is administered subcutaneously.