Oncolytic Vaccinia Virus

• US 20170020938A1
• Filed: 04/01/2015
• Published: 01/26/2017
• Est. Priority Date: 04/01/2014
• Status: Abandoned Application

• Current Assignee: Queen Mary University Of London (University of London)
• Original Assignee: Queen Mary University Of London (University of London)
• Inventors: Yuan, Ming, Ahmed, Jahangir, Lemoine, Nicholas Robert, Wang, Yaohe
• Application Number:
  US15/301,304
• Publication Number:
  US 20170020938A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 35/768 Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 38/208 IL-12
• CPC Class Codes: A61K 39/285 Vaccinia virus or variola virus
• CPC Class Codes: A61K 48/0066 Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/535 Granulocyte CSF; Granulocyte-macrophage CSF
• CPC Class Codes: C07K 14/54 Interleukins [IL]
• CPC Class Codes: C07K 14/5434 IL-12
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24121 Viruses as such, e.g. new isolates, mutants or their genomic sequences
• CPC Class Codes: C12N 2710/24132 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/24162 by genetic engineering
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention relates to an oncolytic vaccinia virus and virus vectors for use in cancer therapy where in the virus comprises at least three vaccinia virus promoters which are positioned in the same orientation.

Claims

1. A nucleic acid sequence comprising at least three vaccinia virus promoters wherein the at least three promoters are positioned in the same orientation.

2. A nucleic acid sequence according to claim 1 wherein the promoters are promoters having activity in the early and/or late phase of the viral life cycle.

3. A nucleic acid sequence according to claim 2 wherein the promoters are selected from the group consisting of mH5, H5, P7.5 and PE/L.

4. A nucleic acid sequence according to claim 1 wherein the nucleic acid sequence encodes a heterologous polypeptide.

5. A nucleic acid sequence according to claim 4 wherein the polypeptide is a cytokine or reporter polypeptide.

6. A nucleic acid sequence according to claim 5 wherein the cytokine is selected from the group consisting of GM-CSF, IL-12 and IL-21.

7. A nucleic acid sequence according to claim 1 wherein said nucleic acid sequence comprises one or more restriction sites.

8. A nucleic acid sequence according to claim 7 wherein the one or more restriction sites are selected from the group consisting of SalI, BglII, HindIII, SmaI, BamHI and MluI.

10. A nucleic acid sequence according to claim 1 wherein said nucleic acid sequence comprises a sequence substantially homologous to the nucleic acid sequence depicted in FIG. 1.

11. A vaccinia virus vector comprising a nucleic acid sequence according to claim 1.

12. A vaccinia virus comprising a nucleic acid sequence according to claim 1, or a vector comprising the same, wherein the vector or nucleic acid sequence is inserted into the N1L gene.

19. A method of treating cancer in a subject comprising administering to said subject a nucleic acid sequence according to claim 1, or a vaccinia virus or vaccinia virus vector comprising the same.

9. (canceled)

13. A TK-deficient vaccinia virus comprising an inactivated N1L gene.

14. A TK-deficient vaccinia virus according to claim 13 wherein the N1L gene is inactivated by the insertion of a nucleic acid sequence encoding a heterologous polypeptide.

15. A TK-deficient vaccinia virus according to claim 14 wherein the polypeptide is a cytokine.

16. A TK-deficient vaccinia virus according to claim 14 wherein the polypeptide is selected from the group consisting of GM-CSF, IL-12 and IL-21.

17. A TK-deficient vaccinia virus according to claim 14 wherein the nucleic acid sequence comprises at least three promoters, said promoters positioned in the same orientation.

18. A TK-deficient vaccinia virus according to claim 17 wherein the promoters are selected from the group consisting of mH5, H5, P7.5 and PE/L.

20. A composition comprising a TK-deficient vaccinia virus, wherein the virus comprises an inactivated N1L gene, said N1L gene inactivated by the insertion of a vector or nucleic acid sequence encoding a heterologous polypeptide, optionally in the presence of a pharmaceutically acceptable carrier or excipient.

21. A composition according to claim 20 wherein the polypeptide is a cytokine selected from the group consisting of GM-CSF, IL-12 and IL-21.

22-23. -23. (canceled)

24. A method of treating cancer comprising administering to a subject a TK-deficient vaccinia virus wherein the virus comprises an inactivated N1L gene, said N1L gene inactivated by the insertion of a vector or nucleic acid sequence encoding a heterologous polypeptide.

25. A method according to claim 24 wherein the polypeptide is a cytokine.

26. A method according to claim 25 wherein the cytokine is selected from the group consisting of GM-CSF, IL-12 and IL-21.