Use of a vector expressing DNA polymerase β as medicine

• US 6,475,996 B1
• Filed: 07/06/1999
• Issued: 11/05/2002
• Est. Priority Date: 12/13/1996
• Status: Expired due to Fees

• Current Assignee: Centre National De La Recherche Scientifique
• Original Assignee: Centre National De La Recherche Scientifique
• Inventors: Hoffmann, Jean-Sébastien, Tiraby, Gérard Jean, Fons, Pascal, Cazaux, Christophe
• Primary Examiner(s): Nguyen, Dave T.
• Assistant Examiner(s): Nguyen, Quang
• Application Number:
  US09/319,265
• Time in Patent Office: 1,218 Days
• Field of Search: 424/93.1, 424/83.2, 435/69.1, 435/320.1, 435/6, 435/183, 435/325, 435/455, 435/456, 514/44
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 38/45 Transferases (2)
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 2799/021 for the expression of a heterologous nucleic acid
• CPC Class Codes: C12N 9/1252 DNA-directed DNA polymerase (2.7.7.7), i.e. DNA replicase

Abstract

The invention concerns the use of a vector expressing DNA polymerase β for the treatment of cancer or viral diseases such as AIDS.

Claims

1. An expression vector comprising a polynucleotide sequence encoding DNA polymerase β

and a polynucleotide sequence encoding thymidine kinase or thymidilate kinase, wherein said polynucleotide sequences are under the control of an expression system which is effective in expressing said polymerase β

in a cell.

2. The vector according to claim 1, wherein the vector is a viral vector derived from a virus selected from the group consisting of an adenovirus, adeno-associated virus, retrovirus, herpesvirus, poxvirus, parvovirus, plasmovirus, Semliki Forest virus, and Sinbis virus.

3. The vector of claim 1 which is pZH tk pol β

.

4. An isolated cell which is transformed with the expression vector according to claim 1.

5. A pharmaceutical composition comprising the expression vector according to claim 1 and at least one nucleoside analog.

6. The pharmaceutical composition according to claim 5, wherein said nucleoside analog is AZT or ddC.

7. A pharmaceutical composition comprising an expression vector comprising a polynucleotide sequence encoding DNA polymerase β

and at least one nucleoside analog, wherein said polynucleotide sequence is under the control of an expression system which is effective in expressing said DNA polymerase β and

induces overproduction of said DNA polymerase β

in tumor cells or cells infected by a virus.

8. The pharmaceutical composition according to claim 7, further comprising an expression vector comprising a polynucleotide sequence coding for thymidine kinase or thymidilate kinase which is under the control of an expression system which is effective for the expression of said thymidine kinase or thymidiiate kinase in sad cell.

9. The pharmaceutical composition according to claim 8, wherein said nucleoside analog is AZY or ddC.

10. The pharmaceutical composition according to claim 7, wherein said nucleoside analog is AZT or ddC.

11. A method for enhancing the capability of a tumor cell in incorporating a nucleoside analog having antiviral or antitumor activity into DNA of said cell, comprising introducing directly into said cell with an expression vector, thereby inducing overproduction of DNA polymerase β

in said cell, wherein said expression vector comprises a polynucleotide sequence encoding DNA polymerase β

under the control of an expression system which is effective in expressing said DNA polymerase β and

induces overproduction of said DNA polymerase β

in said tumor cell.

12. The method according to claim 11, wherein said vector is used in combination with a vector expressing thymidine kinase or thymidilate kinase.

13. The method according to claim 11, wherein said vector is used in combination with at least one nucleoside analog.