Systemic treatment of metastatic and/or systemically-disseminated cancers using GM-CSF-expressing poxviruses

• US 9,180,149 B2
• Filed: 09/07/2006
• Issued: 11/10/2015
• Est. Priority Date: 09/07/2005
• Status: Active Grant

• Current Assignee: Sillajen Biotherapeutics Incorporated (SillaJen, Inc.)
• Original Assignee: Sillajen Biotherapeutics Incorporated (SillaJen, Inc.)
• Inventors: Kirn, David
• Primary Examiner(s): HILL, KEVIN KAI
• Application Number:
  US11/470,951
• Publication Number:
  US 20070065411A1
• Time in Patent Office: 3,351 Days
• Field of Search: 424/93.6, 435/235.1, 435/320.1
• US Class Current: 1/1
• CPC Class Codes: A01K 2207/20 Animals treated with compounds which are neither proteins nor nucleic acids
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0331 Animal model for proliferative diseases
• CPC Class Codes: A01K 2267/0393 Animal model comprising a reporter system for screening tests
• CPC Class Codes: A01K 67/0271 Chimeric vertebrates, e.g. comprising exogenous cells
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• 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 35/768 Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 49/0008 Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07K 14/535 Granulocyte CSF; Granulocyte-macrophage CSF
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24111 Orthopoxvirus, e.g. vaccinia virus, variola
• 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 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 concerns methods and compositions for the treatment of cancer and cancer cells using intravascular administration of a vaccinia virus. In some embodiments, methods and compositions involve a replicative vaccinia virus that encodes GM-CSF.

Claims

1. A method of killing a cancer cell in a human subject comprising administering intravascularly to the subject 10⁹ to 10¹⁰ plaque forming units (Pfu) of a replicative Wyeth strain vaccinia virus JX-594.

2. The method of claim 1, wherein the vaccinia virus is administered intravenously.

3. The method of claim 1, wherein the vaccinia virus is administered intraarterially.

4. The method of claim 1, wherein the vaccinia virus is in a pharmaceutically acceptable formulation.

5. The method of claim 1, wherein the subject is administered the vaccinia virus multiple times.

6. The method of claim 5, wherein a second treatment occurs within 3 weeks of a first treatment.

7. The method of claim 6, wherein the second treatment occurs within 2 weeks of the first treatment.

8. The method of claim 5, wherein the same dose is administered.

9. The method of claim 1, wherein the administration occurs intravascularly by injection.

10. The method of claim 1, wherein the administration occurs intravascularly using intravenous drip or bolus.

11. The method of claim 1, wherein the administration occurs intravascularly using a pump.

12. The method of claim 1, wherein the cancer cell is a metastasized cancer cell.

13. The method of claim 1, wherein the subject has lung cancer, colorectal cancer, breast cancer, prostate cancer, pancreatic cancer, hepatocellular cancer, leukemia, lymphoma, myeloma or melanoma.

15. The method of claim 1, wherein expression of a nucleic acid encoding granulocyte-macrophage colony stimulating factor (GM-CSF) is directed by a synthetic vaccinia early/late promoter.

14. A method of treating one or more metastases in a human subject comprising administering intravascularly to the subject 10⁹ to 10¹⁰ plaque forming units (Pfu) of a replicative Wyeth strain vaccinia virus JX-594.