Oncolytic rhabdovirus

• US 9,896,664 B2
• Filed: 04/24/2015
• Issued: 02/20/2018
• Est. Priority Date: 12/10/2009
• Status: Active Grant

• Current Assignee: Turnstone Limited Partnership
• Original Assignee: Turnstone Limited Partnership
• Inventors: Bell, John C., Stojdl, David F.
• Primary Examiner(s): Horning, Michelle S
• Application Number:
  US14/696,028
• Publication Number:
  US 20150275185A1
• Time in Patent Office: 1,033 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/766 Rhabdovirus, e.g. vesicular stomatitis virus
• CPC Class Codes: A61K 35/768 Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2760/20021 Viruses as such, e.g. new isolates, mutants or their genomic sequences
• CPC Class Codes: C12N 2760/20032 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2760/20062 by genetic engineering
• CPC Class Codes: C12N 2760/20071 Demonstrated in vivo effect
• 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
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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.

Claims

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.

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.

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.

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.

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.

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.

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.

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.