Viral vectors and their use in therapeutic methods

• US 7,749,745 B2
• Filed: 03/27/2002
• Issued: 07/06/2010
• Est. Priority Date: 03/27/2001
• Status: Active Grant

• Current Assignee: Catherex, Inc. (Amgen Inc.), Georgetown University, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Georgetown University, The General Hospital Corporation (Mass General Brigham, Inc.), Medigene, Inc. (Medigene AG)
• Inventors: Johnson, Paul, Rabkin, Samuel D., Todo, Tomoki, Martuza, Robert L.
• Primary Examiner(s): Mosher; Mary E
• Assistant Examiner(s): Hill; Myron G
• Application Number:
  US10/107,036
• Publication Number:
  US 20020187163A1
• Time in Patent Office: 3,023 Days
• Field of Search: 435/320.1, 435/235, 435/440, 435/455, 435/235.1
• US Class Current: 435/235.1
• CPC Class Codes: A61K 2039/5254 avirulent or attenuated
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 35/763 Herpes virus
• CPC Class Codes: A61K 35/768 Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
• CPC Class Codes: A61K 38/162 from virus
• CPC Class Codes: A61K 39/245 Herpetoviridae, e.g. herpes simplex virus
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/16632 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
• CPC Class Codes: C12N 2710/16634 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2710/16643 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/16662 : by genetic engineering
• CPC Class Codes: C12N 2710/16671 : 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

Abstract

The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

Claims

1. A herpes simplex-1 virus comprising (i) a mutation that consists of a deletion of the region of said virus corresponding to the BstEII-EcoNI fragment of the BamHI x fragment of F strain of herpes simplex virus I, and (ii) an inactivating mutation in the γ

34.5 neurovirulence locus of said virus and optionally an inactivating mutation elsewhere in the genome of said virus.

2. The virus of claim 1, wherein said virus comprises said inactivating mutation elsewhere in the genome of said virus and said inactivating mutation elsewhere in the genome of said virus is an inactivating mutation in the ICP6 locus of said virus.

3. The virus of claim 1, further comprising sequences encoding a heterologous gene product.

4. The virus of claim 3, wherein said heterologous gene product comprises a vaccine antigen or an immunomodulatory protein.

5. A pharmaceutical composition comprising the virus of claim 1, and a pharmaceutically acceptable carrier, adjuvant, or diluent.

6. The virus of claim 1, wherein said virus is R47Δ

.

7. The virus of claim 1, wherein said virus is G47Δ

.

8. The virus of claim 1, wherein said deletion results in the coding sequence of the US11 gene of said virus being under control of the ICP47 promoter of said virus.