Interferon tau compositions and methods of use

Abstract

The present invention describes the production of interferon-τ proteins and polypeptides derived therefrom The antiviral and anticellular proliferation properties of these proteins and polypeptides are disclosed. One advantage of the proteins of the present invention is that they do not have cytotoxic side-effects when used to treat cells. Structure/function relationships for the interferon-τ protein are also described. In one aspect, the invention includes ovine interferon-τ. In another aspect the invention includes multiple forms of human interferon-τ.

It is claimed:  
     
         1 . An isolated nucleic acid molecule that encodes an ovine interferon-τ.  
     
     
         2 . A nucleic acid of  claim 1 , where said nucleic acid molecule has the sequence presented as SEQ ID NO:1.  
     
     
         3 . A nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule encodes a polypeptide having a sequence presented as SEQ ID NO:2.  
     
     
         4 . A nucleic acid of  claim 3 , where said polypeptide includes a leader sequence.  
     
     
         5 . An expression vector comprising 
 (a) a nucleic acid containing an open reading frame that encodes the ovine interferon-τ; and    (b) regulatory sequences effective to express said open reading frame in a host cell.    
     
     
         6 . A method of recombinantly producing ovine interferon-τ, comprising 
 introducing into suitable host cells, a recombinant expression system containing an open reading frame (ORF) having a polynucleotide sequence which encodes an ovine interferon-τ polypeptide, where the vector is designed to express the ORF in said host, and  
 culturing said host under conditions resulting in the expression of the ORF sequence.  
 
     
     
         7 . A recombinantly produced ovine interferon-τ protein.  
     
     
         8 . The recombinantly produced protein of  claim 7 , where said protein has the sequence presented as SEQ ID NO:2.  
     
     
         9 . A method of inhibiting tumor cell growth, comprising 
 contacting the cells with ovine interferon-τ at a concentration effective to inhibit growth of the tumor cells.    
     
     
         10 . A method of inhibiting viral replication, comprising 
 contacting cells infected with a virus with ovine interferon-τ at a concentration effective to inhibit viral replication within said cells.    
     
     
         11 . The method of  claim 10 , where said virus is an RNA virus.  
     
     
         12 . The method of  claim 11 , where said virus is selected from the group consisting of feline leukemia virus, ovine lentivirus, equine infectious anemia virus, bovine immunodeficiency virus, visna-maedi virus, and caprine arthritis encephalitis.  
     
     
         13 . The method of  claim 10 , where said virus is a DNA virus.  
     
     
         14 . The method of  claim 10 , where said interferon-τ has the protein sequence presented as SEQ ID NO:2.  
     
     
         15 . An isolated nucleic acid molecule that encodes a human interferon-τ.  
     
     
         16 . A nucleic acid of  claim 15 , where said nucleic acid molecule includes the sequence presented as SEQ ID NO:43.  
     
     
         17 . A nucleic acid molecule of  claim 15 , wherein said nucleic acid molecule encodes a polypeptide having a sequence presented as SEQ ID NQ:44.  
     
     
         18 . A nucleic acid molecule of  claim 17 , where said polypeptide further includes a leader sequence.  
     
     
         19 . A nucleic acid of  claim 15 , where said nucleic acid molecule includes the sequence presented as SEQ ID NO:29.  
     
     
         20 . A nucleic acid molecule of  claim 15 , wherein said nucleic acid molecule encodes a polypeptide having a sequence presented as SEQ ID NO:30.  
     
     
         21 . A nucleic acid molecule of  claim 20 , where said polypeptide further includes a leader sequence.  
     
     
         22 . A nucleic acid of  claim 15 , where said nucleic acid molecule includes the sequence presented as SEQ ID NO:33.  
     
     
         23 . A nucleic acid molecule of  claim 15 , wherein said nucleic acid molecule encodes a polypeptide having a sequence presented as SEQ ID NO:34.  
     
     
         24 . A nucleic acid molecule of  claim 23 , where said polypeptide further includes a leader sequence.  
     
     
         25 . A nucleic acid of  claim 15 , where said nucleic acid molecule includes the sequence presented as SEQ ID NO:25.  
     
     
         26 . A nucleic acid molecule of  claim 15 , wherein said nucleic acid molecule encodes a polypeptide having a sequence presented as SEQ ID NO:26.  
     
     
         27 . A nucleic acid molecule of  claim 26 , where said polypeptide further includes a leader sequence.  
     
     
         28 . A nucleic acid of  claim 15 , where said nucleic acid molecule includes the sequence presented as SEQ ID NO:27.  
     
     
         29 . A nucleic acid molecule of  claim 15 , wherein said nucleic acid molecule encodes a polypeptide having a sequence presented as SEQ ID NO:28.  
     
     
         30 . A nucleic acid molecule of  claim 29 , where said polypeptide further includes a leader sequence.  
     
     
         31 . A nucleic acid of  claim 15 , where said nucleic acid molecule includes the sequence presented as SEQ ID NO:21.  
     
     
         32 . A nucleic acid molecule of  claim 15 , wherein said nucleic acid molecule encodes a polypeptide having a sequence presented as SEQ ID NO:22.  
     
     
         33 . A nucleic acid molecule of  claim 32 , where said polypeptide further includes a leader sequence.  
     
     
         34 . A nucleic acid of  claim 15 , where said nucleic acid molecule includes the sequence presented as SEQ ID NO:23.  
     
     
         35 . A nucleic acid molecule of  claim 15 , wherein said nucleic acid molecule encodes a polypeptide having a sequence presented as SEQ ID NQ:24.  
     
     
         36 . A nucleic acid molecule of  claim 35 , where said polypeptide further includes a leader sequence.  
     
     
         37 . An expression vector comprising 
 (a) a nucleic acid containing an open reading frame that encodes a human interferon-τ; and    (b) regulatory sequences effective to express said open reading frame in a host cell.    
     
     
         38 . An expression vector of  claim 37 , where said human interferon-τ contains a polypeptide having a sequence presented as SEQ ID NO:44.  
     
     
         39 . An expression vector of  claim 37 , where said human interferon-τ contains a polypeptide having a sequence presented as SEQ ID NO:30.  
     
     
         40 . An expression vector of  claim 37 , where said human interferon-τ contains a polypeptide having a sequence presented as SEQ ID NO:34.  
     
     
         41 . An expression vector of  claim 37 , where said human interferon-τ contains a polypeptide having a sequence presented as SEQ ID NO:26.  
     
     
         42 . An expression vector of  claim 37 , where said human interferon-τ contains a polypeptide having a sequence presented as SEQ ID NO:28.  
     
     
         43 . An expression vector of  claim 37 , where said human interferon-τ contains a polypeptide having a sequence presented as SEQ ID NO:22.  
     
     
         44 . An expression vector of  claim 37 , where said human interferon-τ contains a polypeptide having a sequence presented as SEQ ID NO:24.  
     
     
         45 . A method of recombinantly producing human interferon-τ, comprising 
 introducing into suitable host cells, a recombinant expression system containing an open reading frame (ORF) having a polynucleotide sequence which encodes a human interferon-τ polypeptide, where the vector is designed to express the ORF in said host, and  
 culturing said host under conditions resulting in the expression of the ORF sequence.  
 
     
     
         46 . An isolated human interferon-τ protein.  
     
     
         47 . A protein of  claim 46 , where said protein is recombinantly produced.  
     
     
         48 . A protein of  claim 46 , where said protein contains the sequence presented as SEQ ID NO:44.  
     
     
         49 . A protein of  claim 46 , where said protein contains the sequence presented as SEQ ID NO:30.  
     
     
         50 . A protein of  claim 46 , where said protein contains the sequence presented as SEQ ID NO:34.  
     
     
         51 . A protein of  claim 46 , where said protein contains the sequence presented as SEQ ID NO:26.  
     
     
         52 . A protein of  claim 46 , where said protein contains the sequence presented as SEQ ID NO:28.  
     
     
         53 . A protein of  claim 46 , where said protein contains the sequence presented as SEQ ID NO:22.  
     
     
         54 . A protein of  claim 46 , where said protein contains the sequence presented as SEQ ID NO:24.  
     
     
         55 . A method of inhibiting tumor cell growth, comprising 
 contacting the cells with human interferon-τ at a concentration effective to inhibit growth of the tumor cells.    
     
     
         56 . A method of  claim 55 , wherein said cells are human carcinoma cells, human leukemia cells, human T-lymphoma cells, and human melanoma cells.  
     
     
         57 . A method of  claim 56 , wherein said cells are steroid-sensitive tumor cells.  
     
     
         58 . A method of  claim 57 , wherein said cells are mammary tumor cells.  
     
     
         59 . A method of  claim 55 , where said protein contains the sequence presented as SEQ ID NO:44.  
     
     
         60 . A method of  claim 55 , where said protein contains the sequence presented as SEQ ID NO:30.  
     
     
         61 . A method of  claim 55 , where said protein contains the sequence presented as SEQ ID NO:34.  
     
     
         62 . A method of  claim 55 , where said protein contains the sequence presented as SEQ ID NO:26.  
     
     
         63 . A method of  claim 55 , where said protein contains the sequence presented as SEQ ID NO:28.  
     
     
         64 . A method of  claim 55 , where said protein contains the sequence presented as SEQ ID NO:22.  
     
     
         65 . A method of  claim 55 , where said protein contains the sequence presented as SEQ ID NO:24.  
     
     
         66 . A method of inhibiting viral replication, comprising 
 contacting cells infected with a virus with human interferon-τ at a concentration effective to inhibit viral replication within said cells.    
     
     
         67 . A method of  claim 66 , where said virus is an RNA virus.  
     
     
         68 . A method of  claim 67 , where said virus is human immunodeficiency virus, or hepatitis c virus.  
     
     
         69 . A method of  claim 66 , where said virus is a DNA virus.  
     
     
         70 . A method of  claim 69 , where said virus is hepatitis B virus.  
     
     
         71 . A method of  claim 66 , where said protein contains the sequence presented as SEQ ID NO:44.  
     
     
         72 . A method of  claim 66 , where said protein contains the sequence presented as SEQ ID NO:30.  
     
     
         73 . A method of  claim 66 , where said protein contains the sequence presented as SEQ ID NO:34.  
     
     
         74 . A method of  claim 66 , where said protein contains the sequence presented as SEQ ID NO:26.  
     
     
         75 . A method of  claim 66 , where said protein contains the sequence presented as SEQ ID NO:28.  
     
     
         76 . A method of  claim 66 , where said protein contains the sequence presented as SEQ ID NO:22.  
     
     
         77 . A method of  claim 66 , where said protein contains the sequence presented as SEQ ID NO:24.  
     
     
         78 . A method of enhancing fertility in a female mammal, comprising 
 administering to said mammal an effective mammalian fertility enhancing amount of human interferon-τ in a pharmaceutically acceptable carrier.    
     
     
         79 . A method of  claim 78 , where said protein contains the sequence presented as SEQ ID NO:44.  
     
     
         80 . A method of  claim 78 , where said protein contains the sequence presented as SEQ ID NO:30.  
     
     
         81 . A method of  claim 78 , where said protein contains the sequence presented as SEQ ID NO:34.  
     
     
         82 . A method of  claim 78 , where said protein contains the sequence presented as SEQ ID NO:26.  
     
     
         83 . A method of  claim 78 , where said protein contains the sequence presented as SEQ ID NQ:28.  
     
     
         84 . A method of  claim 78 , where said protein contains the sequence presented as SEQ ID NO:22.  
     
     
         85 . A method of  claim 78 , where said protein contains the sequence presented as SEQ ID NO:24.  
     
     
         86 . A fused polypeptide, comprising: 
 (a) an interferon-τ polypeptide, where said polypeptide is (i) derived from an interferon-τ amino acid coding sequence, and (ii) between 15 and 172 amino acids long; and    (b) a second soluble polypeptide.    
     
     
         87 . The fused polypeptide of  claim 86 , wherein said interferon-τ polypeptide is selected from the group consisting of SEQ ID NO:5 and SEQ ID NO:15.  
     
     
         88 . The fused polypeptide of  claim 86 , wherein said second soluble polypeptide is interferon-α.  
     
     
         89 . The fused polypeptide of  claim 86 , wherein said second soluble polypeptide is interferon-β.  
     
     
         90 . An interferon-τ/type I interferon fusion protein comprising: 
 a type I interferon protein wherein the N-terminal cytotoxic region of said type I interferon is replaced by an N-terminal region of interferon-τ within a sequence spanning residues 1 to 37 of interferon-τ, and the fusion protein has reduced cytotoxicity relative to the cytotoxicity of the type I interferon.  
 
     
     
         91 . The fusion protein of  claim 90 , wherein said type I interferon is interferon-α.  
     
     
         92 . The fusion protein of  claim 90 , wherein said type I interferon is interferon-β.  
     
     
         93 . The fusion protein of  claim 90 , wherein said interferon-τ is ovine, bovine, or human interferon-τ.  
     
     
         94 . The fusion protein of  claim 90 , wherein the sequence from residues 1 to 37 is SEQ ID NO:5 and the sequence from residues 38 to the C-terminal residue is the corresponding sequence of said type I interferon.  
     
     
         95 . The fusion protein of  claim 90 , wherein the sequence from residues 1 to 37 is SEQ ID NO:15 and the sequence from residues 38 to the C-terminal residue is the corresponding sequence of said type I interferon.