Suppression of malignancy utilizing ribonucleotide reductase R1

Abstract

The present invention provides a method of modulating the malignant properties of a cell in a human or other mammal by contacting a neoplastic cell with a growth modulating amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal. The present invention also provides and uses a growth modulating amount of the ribonucleotide reductase R1 protein or biologically active peptide to modulate the malignant properties of a cell in a human or other mammal. The method provides for a generally elevated expression of the R1 component of mammalian ribonucleotide reductase. The expressible nucleic acid sequence can be in the form of a vector for gene therapy.

What is claimed is:  
     
         1 . The use of an effective amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of a mammal for modulating tumorigenicity of neoplastic cells in a mammal.  
     
     
         2 . The use of a pharmaceutical composition comprising an effective amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of a mammal and a pharmaceutically physiologically acceptable carrier or diluent for modulating tumorigenicity of neoplastic cells in a mammal.  
     
     
         3 . The use of an effective amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of a mammal for inhibiting neoplastic cell growth in a mammal.  
     
     
         4 . The use of a pharmaceutical composition comprising an effective amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of a mammal and a pharmaceutically physiologically acceptable carrier or diluent for inhibiting neoplastic cell growth in a mammal.  
     
     
         5 . The use of an effective amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of a mammal for gene therapy in a mammal.  
     
     
         6 . The use of a pharmaceutical composition comprising an effective amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of a mammal and a pharmaceutically physiologically acceptable carrier or diluent for gene therapy in a mammal.  
     
     
         7 . The use according to any one of the  claims 1  to  6  wherein the nucleic acid sequence is in the form of a vector.  
     
     
         8 . The use according to any one of the  claims 1  to  7  wherein the nucleic acid sequence is SEQ ID No: 1.  
     
     
         9 . The use according to any one of the  claims 1  to  7  wherein the nucleic acid sequence is the coding region for the ribonucleotide reductase R1 protein from SEQ ID No: 1.  
     
     
         10 . The use according to  claim 9  wherein the coding region is modified to code for a biologically active peptide of ribonucleotide reductase R1.  
     
     
         11 . The use according to  claim 9  wherein the coding region is modified to code for a biologically active analogue of ribonucleotide reductase R1.  
     
     
         12 . The use of an effective amount ribonucleotide reductase R1 of a mammal for modulating tumorigenicity of neoplastic cells in a mammal.  
     
     
         13 . The use of a pharmaceutical composition comprising an effective amount of ribonucleotide reductase R1 of a mammal and a pharmaceutically physiologically acceptable carrier or diluent for modulating tumorigenicity of neoplastic cells in a mammal.  
     
     
         14 . The use of an effective amount of ribonucleotide reductase R1 of a mammal for inhibiting neoplastic cell growth in a mammal.  
     
     
         15 . The use of a pharmaceutical composition comprising an effective amount of ribonucleotide reductase R1 of a mammal and a pharmaceutically physiologically acceptable carrier or diluent for inhibiting neoplastic cell growth in a mammal.  
     
     
         16 . The use according to any one of  claims 12  to  15  wherein ribonucleotide reductase R1 is a biologically active analogue or derivative.  
     
     
         17 . The use according to any one of  claims 12  to  16  wherein the ribonucleotide reductase R1 analogue or derivative is recombinantly produced.  
     
     
         18 . The use according to any one of  claims 1  to  17  wherein the mammal is a human.  
     
     
         19 . The use of an effective amount of an expressible nucleic acid sequence having a coding sequence for ribonucleotide reductase R1 as set forth in SEQ ID No: 1 of a mammal for manufacturing a vector for gene therapy.  
     
     
         20 . A pharmaceutical composition for inhibiting neoplastic cell growth in a mammal consisting of an effective amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal and a pharmaceutically physiologically acceptable carrier or diluent.  
     
     
         21 . The pharmaceutical composition as set forth in  claim 20  wherein the expressible nucleic acid sequence is included in a vector for gene therapy.  
     
     
         22 . The pharmaceutical composition as set forth in claims  20  wherein the nucleic acid sequence is SEQ ID No: 1.  
     
     
         23 . The pharmaceutical composition as set forth in claims  20  and  21  wherein the nucleic acid sequence is the coding region for the ribonucleotide reductase R1 protein from SEQ ID No: 1.  
     
     
         24 . A pharmaceutical composition for inhibiting neoplastic cell growth in a mammal consisting of 
 an effective amount of ribonucleotide reductase R1 and a pharmaceutically physiologically acceptable carrier or diluent.    
     
     
         25 . The pharmaceutical composition as set forth in  claim 24  wherein the ribonucleotide reductase R1 is recombinantly produced.  
     
     
         26 . The pharmaceutical composition as set forth in  claim 24  wherein the ribonucleotide reductase R1 is a biologically active analogue or derivative.  
     
     
         27 . The pharmaceutical composition as set forth in  claim 26  wherein the biologically active derivative is a peptide.  
     
     
         28 . A method of modulating the tumorigenicity of neoplastic cells in a mammal by 
 contacting said neoplastic cell with a growth modulating amount of ribonucleotide reductase R1.    
     
     
         29 . The method of  claim 28  wherein the mammal is human.  
     
     
         30 . The method as set forth in  claim 28  wherein the ribonucleotide reductase R1 is recombinantly produced.  
     
     
         31 . The method as set forth in  claim 28  wherein the ribonucleotide reductase R1 is a biologically active analogue or derivative.  
     
     
         32 . A method of modulating the tumorigenicity of neoplastic cells in a mammal by 
 contacting said neoplastic cell with a growth modulating amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal.    
     
     
         33 . The method of  claim 32  wherein the mammal is human.  
     
     
         34 . The method as set forth in  claim 32  wherein the expressible nucleic acid sequence is included in a vector for gene therapy.  
     
     
         35 . The method as set forth in  claim 32  wherein the nucleic acid sequence is SEQ ID No: 1.  
     
     
         36 . The method as set forth in  claim 32  wherein the nucleic acid sequence is the coding region for the ribonucleotide reductase R1 protein from SEQ ID No: 1.  
     
     
         37 . The method as set forth in  claim 32  wherein the coding region is modified to code for a biologically active peptide of ribonucleotide reductase R1.  
     
     
         38 . The method as set forth in  claim 32  wherein the coding region is modified to code for a biologically active analogue of ribonucleotide reductase R1.