Papilloma virus sequences

Abstract

The present invention relates to methods and compositions useful in the treatment and prevention of human papilloma virus infections and the symptoms and diseases associated therewith. More particularly, the invention relates to polynucleotide sequences which encode human papilloma virus (HPV) amino acid amino acid sequences, wherein the codon usage pattern of the polynucleotide sequences resemble those of highly expressed mammalian genes.

1 . A polynucleotide sequence which encodes a HPV amino acid sequence, wherein the codon usage pattern of the polynucleotide sequence resembles that of highly expressed mammalian genes.  
     
     
         2 . The polynucleotide sequence according to  claim 1  in which the codon usage pattern of the polynucleotide sequence resembles that of highly expressed human genes.  
     
     
         3 . The polynucleotide sequence according to  claim 1  in which the codon usage pattern of the polynucleotide sequence also resembles that of highly expressed  E. coli  genes.  
     
     
         4 . The polynucleotide sequence according to  claim 1  which is a DNA sequence.  
     
     
         5 . The polynucleotide sequence according to  claim 1  which encodes a HPV polypeptide of an HPV type or sub-type associated with cervical cancer, benign cutaneous warts or genital warts.  
     
     
         6 . The polynucleotide sequence according to  claim 5  which encodes a HPV polypeptide of one oftypes 1-4, 6, 7, 10, 11, 16, 18, 26-29, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68.  
     
     
         7 . The polynucleotide sequence according to  claim 6  which encodes a HPV polypeptide of an HPV type or sub-type which is associated particularly with cervical cancer or genital warts.  
     
     
         8 . The polynucleotide sequence according to  claim 7  which encodes a HPV polypeptide of one of types 6, 11, 16, 18, 33 or 45, or a fusion of two or more polypeptides of one or more of HPV virus types 6, 11, 16, 18, 33 or 45.  
     
     
         9 . The polynucleotide sequence according to  claim 8  which encodes a HPV polypeptide of a HPV type or sub-type selected from HPV 11, 6a or 6b.  
     
     
         10 . The polynucleotide sequence according to  claim 1  which encodes a mutated HPV polypeptide having reduced biological function.  
     
     
         11 . The polynucleotide sequence according to  claim 10  which encodes a mutated HPV polypeptide comprising one or more point mutations by which one or more of the polypeptide's natural biological functions is inactivated.  
     
     
         12 . The polynucleotide sequence according to  claim 1  in which the encoded HPV polypeptide comprises the whole or a part of a HPV early gene product.  
     
     
         13 . The polynucleotide sequence according to  claim 12  in which the encoded HPV polypeptide comprises the whole or a part of E1 or E2, or a fusion of the whole or a part of E1 or E2 with another HPV polypeptide.  
     
     
         14 . The polynucleotide sequence according to  claim 2  having a codon usage coefficient for highly expressed human genes of greater than 0.3 but less than 1.  
     
     
         15 . The polynucleotide sequence according to  claim 2  having a codon usage coefficient for highly expressed human genes of greater than 0.4 but less than 1.  
     
     
         16 . The polynucleotide sequence according to  claim 2  having a codon usage coefficient for highly expressed human genes of greater than 0.5 but less than 1.  
     
     
         17 . The polynucleotide sequence according to  claim 3  having a codon usage coefficient for highly expressed  E. coli  genes of greater than 0.6.  
     
     
         18 . A polynucleotide sequence as set out in FIG. 5 a  and  5   b , or a fragment or analogue thereof which maintains the codon usage pattern thereof.  
     
     
         19 . A polynucleotide sequence as set out in FIG. 6, or a fragment or analogue thereof which maintains the codon usage pattern thereof.  
     
     
         20 . An expression vector comprising a polynucleotide sequence according to  claim 1  operably linked to a control sequence which is capable of providing for the expression of the polynucleotide sequence by a host cell.  
     
     
         21 . The expression vector according to  claim 20  which is capable of directing the expression of the polynucleotide sequence in bacterial, insect or mammalian cells.  
     
     
         22 . The expression vector according to  claim 20  which is p7313PLc.  
     
     
         23 . A host cell comprising a polynucleotide sequence according to  claim 1 .  
     
     
         24 . A host cell comprising an expression vector according to  claim 20 .  
     
     
         25 . A host cell according to  claim 23  or  claim 24  which is a bacterial, mammalian, or insect cell.  
     
     
         26 . A pharmaceutical composition comprising a polynucleotide sequence according to  claim 1 .  
     
     
         27 . A pharmaceutical composition comprising a vector according to  claim 20 .  
     
     
         28 . A pharmaceutical composition according to  claim 26  or  claim 27  comprising a plurality of particles, preferably gold particles, coated with DNA.  
     
     
         29 . A pharmaceutical composition according to  claim 27  further comprising a pharmaceutically acceptable excipient.  
     
     
         30 . A pharmaceutical composition according to any one of claims  26 , 27, or 29 further comprising an adjuvant.  
     
     
         31 . A pharmaceutical composition according to  claim 28  further comprising an adjuvant.  
     
     
         32 . A pharmaceutical composition according to  claim 30  in which the adjuvant is encoded as a fusion with the HPV polypeptide encoded by the polynucleotide.  
     
     
         33 . A pharmaceutical composition according to  claim 31  in which the adjuvant is encoded as a fusion with the HPV polypeptide encoded by the polynucleotide.  
     
     
         34 . A method of treating or preventing HPV infections or any symptoms or diseases associated therewith, comprising administering an effective amount of a polynucleotide according to  claim 1 , a vector according to  claim 20  or a pharmaceutical composition according to  claim 26  or  27 .  
     
     
         35 . A method of treating or preventing HPV infections or any symptoms or diseases associated therewith, comprising administering a pharmaceutical composition according to any one of claims  26  or  27  in a prime-boost dosage regime with a recombinant viral vector or non-viral based system comprising a polynucleotide according to  claim 1.