Polynucleotides and polypeptides of the erythropoietin gene

Abstract

The present invention relates to new polynucleotides deriving from the nucleotide sequence of the EPO gene and comprising new SNPs, new polypeptides derived from the natural EPO protein and comprising at least one mutation caused by the SNPs of the invention as well as their therapeutic uses.

1 . An isolated polynucleotide comprising a nucleotide sequence at least 90% identical to SEQ ID NO. 1, wherein said nucleotide further comprises at least one SNP selected from the group consisting of 465-486 (deletion), c577t, g602c, c1288t, c1347t, g1644a, g2228a, g2357a, c2502t, c2621 g, and g2634a.  
     
     
         2 . The isolated polynucleotide of  claim 1 , wherein said polynucleotide comprises a nucleotide sequence at least 90% identical to nucleotides 615 to 2763 of SEQ ID NO. 1, and wherein said nucleotide sequence comprises at least one coding SNP selected from the group consisting of g1644a, g2357a, and c2621g.  
     
     
         3 . The isolated polynucleotide of  claim 1 , wherein said polynucleotide comprises the SNP g2357a.  
     
     
         4 . An isolated polynucleotide consisting of a part of the polynucleotide of  claim 1 , wherein said polynucleotide comprises at least 10 nucleotides and at least one SNP selected from the group consisting of g1644a, g2357a, and c2621g.  
     
     
         5 . The isolated polynucleotide of  claim 1 , wherein said nucleotide sequence is at least 95% identical to SEQ ID NO. 1.  
     
     
         6 . The isolated polynucleotide of  claim 1 , wherein said nucleotide sequence is at least 99% identical to SEQ ID NO. 1.  
     
     
         7 . The isolated polynucleotide of  claim 2 , wherein said nucleotide sequence is at least 95% identical to nucleotides 615 to 2763 of SEQ ID NO. 1.  
     
     
         8 . The isolated polynucleotide of  claim 2 , wherein said nucleotide sequence is at least 99% identical to nucleotides 615 to 2763 of SEQ ID NO. 1.  
     
     
         9 . The isolated polynucleotide of  claim 2 , wherein said polynucleotide comprises the SNP g2357a.  
     
     
         10 . An isolated polynucleotide consisting of a part of the polynucleotide of  claim 2 , wherein said polynucleotide comprises at least 10 nucleotides and at least one SNP selected from the group consisting of g1644a, g2357a, and c2621g.  
     
     
         11 . The isolated polynucleotide of  claim 10 , wherein said polynucleotide comprises the SNP g2357a.  
     
     
         12 . An isolated polynucleotide encoding a polypeptide, wherein said polypeptide comprises the amino acid sequence SEQ ID NO. 2 or a fragment thereof, said polypeptide further comprising at least one coding SNP selected from the group consisting of D70N, G104S, and S147C.  
     
     
         13 . The isolated polynucleotide of  claim 12 , wherein said polypeptide comprises the SNP G104S.  
     
     
         14 . An isolated polynucleotide, wherein said polynucleotide comprises a nucleotide sequence that is complementary to a polynucleotide according to  claim 2 .  
     
     
         15 . An isolated polynucleotide, wherein said polynucleotide comprises a nucleotide sequence that is complementary to a polynucleotide according to  claim 9 .  
     
     
         16 . An isolated polynucleotide, wherein said polynucleotide comprises a nucleotide sequence that is complementary to a polynucleotide according to  claim 10 .  
     
     
         17 . An isolated polynucleotide, wherein said polynucleotide comprises a nucleotide sequence that is complementary to a polynucleotide according to  claim 11 .  
     
     
         18 . A recombinant vector comprising a polynucleotide according to  claim 2 .  
     
     
         19 . A recombinant vector comprising a polynucleotide according to  claim 9 .  
     
     
         20 . A host cell comprising a recombinant vector according to  claim 18 .  
     
     
         21 . A host cell comprising a recombinant vector according to  claim 19 .  
     
     
         22 . A method for separating a polypeptide, comprising cultivating a host cell according to  claim 19  in a culture medium and separating said polypeptide from the culture medium.  
     
     
         23 . The polypeptide encoded by the isolated polynucleotide of  claim 2  or  claim 9 .  
     
     
         24 . A method for preventing or treating in an individual a disease selected from the group consisting of cancers and tumors, infectious diseases, venereal diseases, immunologically related diseases and autoimmune diseases and disorders, cardiovascular diseases, metabolic diseases, central nervous system diseases, gastrointestinal disorders, and disorders connected with chemotherapy treatments, said method comprising administering to said individual a therapeutically effective amount of an agent comprising a polynucleotide of any of claims  1  or  2 , plus a pharmaceutically acceptable excipient.  
     
     
         25 . A method for preventing or treating anemias in an individual, said method comprising administering to said individual a therapeutically effective amount of an agent comprising a polynucleotide of any of claims  1  or  2 , plus a pharmaceutically acceptable excipient.  
     
     
         26 . The method of  claim 25 , wherein said anemias include anemia in patients under dialysis in renal insufficiency, as well as anemia resulting from chronic infections, inflammatory processes, radiotherapies, and chemotherapies.  
     
     
         27 . A method for increasing the production of autologous blood, notably in patients participating in a differed autologous blood collection program, comprising administering to said individual a therapeutically effective amount of an agent comprising a polynucleotide of  claim 1  or  claim 2 , plus a pharmaceutically acceptable excipient.  
     
     
         28 . A method for preventing or treating in an individual a disease selected from the group consisting of cancers and tumors, infectious diseases, venereal diseases, immunologically related diseases and autoimmune diseases and disorders, cardiovascular diseases, metabolic diseases, central nervous system diseases, gastrointestinal disorders, and disorders connected with chemotherapy treatments, said method comprising administering to said individual a therapeutically effective amount of an agent comprising a polynucleotide of  claim 9 , plus a pharmaceutically acceptable excipient.  
     
     
         29 . A method for preventing or treating anemias in an individual, said method comprising administering to said individual a therapeutically effective amount of an agent comprising a polynucleotide of  claim 9 , plus a pharmaceutically acceptable excipient.  
     
     
         30 . The method of  claim 29 , wherein said anemias include anemia in patients under dialysis in renal insufficiency, as well as anemia resulting from chronic infections, inflammatory processes, radiotherapies, and chemotherapies.  
     
     
         31 . A method for increasing the production of autologous blood, notably in patients participating in a differed autologous blood collection program, comprising administering to said individual a therapeutically effective amount of an agent comprising a polynucleotide of  claim 9 , plus a pharmaceutically acceptable excipient.