Oncolytic vaccinia virus combination cancer therapy

• US 9,180,151 B2
• Filed: 05/08/2014
• Issued: 11/10/2015
• Est. Priority Date: 09/14/2009
• Status: Active Grant

• Current Assignee: Sillajen Biotherapeutics Incorporated (SillaJen, Inc.)
• Original Assignee: Sillajen Biotherapeutics Incorporated (SillaJen, Inc.)
• Inventors: Kirn, David, Breitbach, Caroline
• Primary Examiner(s): Long, Scott
• Application Number:
  US14/273,476
• Publication Number:
  US 20140322173A1
• Time in Patent Office: 551 Days
• US Class Current: 1/1
• 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 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2710/24132 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent

Abstract

Embodiments of the invention are directed methods that include a thymidine kinase deficient vaccinia virus. The methods include evaluating a tumor for reperfusion after treatment with vaccinia virus and administering an anti-angiogenic agent if reperfusion is detected.

Claims

1. A method for treating cancer in a human subject previously administered a vaccinia virus lacking a thymidine kinase gene and expressing GM-CSF comprising administering to the subject an effective amount of an anti-angiogenic agent that inhibits VEGF-R tyrosine kinase, wherein the inhibitor of VEGF-R tyrosine kinase is administered up to 13 weeks after the vaccinia virus therapy.

2. The method of claim 1, wherein the inhibitor of VEGF-R tyrosine kinase is administered after determining whether a tumor is undergoing re-vascularization.

3. The method of claim 2, wherein determining tumor re-vascularization is by non-invasive imaging of the tumor.

4. The method of claim 3, wherein the non-invasive imaging is magnetic resonance imaging (MRI).

5. The method of claim 4, wherein the magnetic resonance imaging is dynamic contrast-enhanced MRI (dce-MRI).

6. The method of claim 1, wherein the inhibitor of VEGF-R tyrosine kinase is administered at least 1 week after the vaccinia virus administration.

7. The method of claim 1, wherein the cancer is a brain tumor, a head &

neck cancer tumor, an esophageal tumor, a skin tumor, a lung tumor, a thymic tumor, a stomach tumor, a colon tumor, a liver tumor, an ovarian tumor, a uterine tumor, a bladder tumor, a testicular tumor, a rectal tumor, a breast tumor, a kidney tumor, a pancreatic tumor, hepatocellular carcinoma or a renal carcinoma.

8. The method of claim 7, wherein the tumor is a pancreatic tumor, a hepatocellular carcinoma or a renal carcinoma.

9. The method of claim 7 wherein the tumor is a metastasis.

10. The method of claim 9, wherein the metastasis is colon or renal metastasis.

11. The method of claim 1, further comprising first administering to the subject the vaccinia virus therapy.

12. The method of claim 11, wherein the vaccinia virus is administered intratumorally, intravascularly, or both intravascularly and intratumorally.

13. The method of claim 1, wherein the vaccinia virus is a Wyeth strain.

14. The method of claim 13, wherein the vaccinia virus is JX-594.

15. The method of claim 1, wherein the inhibitor of VEGF-R tyrosine kinase is administered at least 2 weeks after the vaccinia virus administration.

16. The method of claim 1, wherein the inhibitor of VEGF-R tyrosine kinase is selected from the group consisting of:

SU5416, SU6668, vatalanib, AEE788, ZD6474, ZD4190, AZD2171, GW786034, CP-547,632, AG013736, and YM-359445.

17. The method of claim 3, wherein the non-invasive imaging is contrast enhanced CT scanning.

18. The method of claim 1, wherein the cancer has failed to respond favorably to or is resistant to treatment with one or more chemotherapeutic agents.

19. The method of claim 18 , wherein the treatment with one or more chemotherapeutic agents comprises administering one or more anti-angiogenic agents.

20. The method of claim 1, wherein the vaccinia virus is administered by intratumoral injection every two weeks.

21. A method for treating cancer in a human subject previously administered a vaccinia virus lacking a thymidine kinase gene and expressing GM-CSF comprising administering to the subject an effective amount of sorafenib, sutent or AG013736 up to 13 weeks after the vaccinia virus therapy.

22. The method of claim 21 , wherein the cancer is a pancreatic tumor, a hepatocellular carcinoma or a renal carcinoma.