Oncolytic rhabdovirus

Patent metadata

Field	Value
Publication number	US-9896664-B2
Application number	US-201514696028-A
Country	US
Kind code	B2
Filing date	Apr 24, 2015
Priority date	Dec 10, 2009
Publication date	Feb 20, 2018
Grant date	Feb 20, 2018

Abstract

Embodiments of the invention include compositions and methods related to Maraba virus and their use as anti-cancer therapeutics. Such rhabdoviruses possess tumor cell killing properties in vitro and in vivo.

First claim

The invention claimed is:

1. An attenuated Maraba virus comprising:
a G protein having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:5 and an arginine at the position corresponding to position 242 of SEQ ID NO:5.

2. A method of killing a hyperproliferative cell comprising contacting the cell with an isolated oncolytic Maraba virus encoding:
a G protein having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:5 and an arginine at the position corresponding to position 242 of SEQ ID NO:5.

3. The method of claim 2 , wherein the cell is comprised in a patient.

4. The method of claim 3 , wherein the cell is a cancer cell.

5. The method of claim 4 , wherein the cancer cell is a metastatic cancer cell.

6. The method of claim 3 , wherein the oncolytic Maraba virus is administered to the patient.

7. The method of claim 6 , wherein the oncolytic Maraba virus is administered by intraperitoneal, intravenous, intra-arterial, intramuscular, intradermal, intratumoral subcutaneous, or intranasal administration.

8. The method of claim 2 , further comprising administering a second anti-cancer therapy.

9. The method of claim 8 , wherein the second cancer therapy is chemotherapeutic, radiotherapeutic, or immunotherapeutic.

10. A method for treating a cancer patient comprising administering an effective amount of an isolated oncolytic Maraba virus encoding:
a G protein having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:5 and an arginine at the position corresponding to position 242 of SEQ ID NO:5.

11. The method of claim 10 , wherein the oncolytic Maraba virus is administered intraperitoneal, intravenous, intra-arterial, intramuscular, intradermal, intratumoral, subcutaneous, or intranasal administration.

12. The method of claim 10 , further comprising administering a second cancer therapy.

13. The method of claim 12 , wherein the second cancer therapy is chemotherapy, radiotherapy, immunotherapy, or surgery.

14. A composition comprising an isolated oncolytic Maraba virus having a nucleic acid segment encoding:
a G protein having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:5 and an arginine at the position corresponding to position 242 of SEQ ID NO:5.

15. The composition of claim 14 , wherein the composition is a pharmaceutically acceptable composition.

16. The composition of claim 15 , further comprising a second anti-cancer agent.

17. The composition of claim 16 , wherein the second anti-cancer agent is a chemotherapeutic, radiotherapeutic, or immunotherapeutic.

18. The attenuated Maraba virus of claim 1 , wherein the G protein has an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5 except for an arginine at the position corresponding to position 242 of SEQ ID NO: 5.

19. The method of claim 2 , wherein the G protein has an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5 except for an arginine at the position corresponding to position 242 of SEQ ID NO: 5.

20. The method of claim 10 , wherein the G protein has an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5 except for an arginine at the position corresponding to position 242 of SEQ ID NO: 5.

21. The composition of claim 14 , wherein the G protein has an amino acid sequence that is 100% identical to the amino acid sequence of SEQ ID NO: 5 except for an arginine at the position corresponding to position 242 of SEQ ID NO: 5.

Assignees

• Ottawa Hospital Res Inst
• Childrens Hospital Of Eastern Ontario Res Institute Inc
• Turnstone Lp

Inventors

• Bell John C
• Stojdl David F

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12N7/00 Primary

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C12N2760/20032

  Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent · CPC title

• C12N2760/20062

  by genetic engineering · CPC title