Viral Vectors and Their Use in Therapeutic Methods

• US 20110070262A1
• Filed: 03/11/2010
• Published: 03/24/2011
• 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: Catherex, Inc. (Amgen Inc.)
• Inventors: Johnson, Paul, Rabkin, Samuel D., Todo, Tomoki, Martuza, Robert L.
• Granted Patent: US 8,470,577 B2
• Time in Patent Office: Days
• US Class Current: 424/205.1
• 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

1-30. -30. (canceled)

31. A herpes simplex virus comprising an inactivating mutation in the ICP47 locus of the virus, wherein said mutation occurs between the BstEII site and the EcoNI site of the BamH1 fragment encompassing the ICP47 region, and wherein said mutation places US11 under control of the ICP47 immediate-early promoter.

32. The virus of claim 31, wherein the mutation is a deletion.

33. The virus of claim 31, further comprising one or more additional mutations selected from the group consisting of an inactivating mutation in the γ

34.5 neurovirulence determination locus and the ICP6 locus.

34. The virus of claim 31, further comprising an inactivating mutation in the γ

34.5 neurovirulence locus of said virus and an inactivating mutation in the ICP6 locus of said virus.

35. The virus of claim 31, further comprising sequences encoding a heterologous gene product.

36. The virus of claim 35, wherein said heterologous gene product comprises a vaccine antigen or an immunomodulatory protein.

37. The virus of claim 36, wherein said immunomodulatory protein is a cytokine.

38. The virus of claim 31, wherein said herpes simplex virus is a herpes simplex-1 virus.

39. A pharmaceutical composition comprising the virus of claim 31 and a pharmaceutically acceptable carrier, adjuvant, or diluent.

40. A method of treating cancer in a patient, comprising administering the virus of claim 31 to said patient in an amount sufficient to treat cancer in said patient.

41. A method of immunizing a patient against an infectious disease, cancer, or an autoimmune disease, said method comprising administering the virus of claim 31 to said patient in an amount sufficient to immunize said patient against an infectious disease, cancer, or an autoimmune disease.

42. A herpes simplex virus comprising a deletion, wherein said deletion comprises the region between the BstEII site and the EcoNI site of the BamH1 fragment encompassing the ICP47 region and wherein the deletion places US11 under control of the ICP47 immediate-early promoter.

43. The virus of claim 42, further comprising one or more additional mutations selected from the group consisting of an inactivating mutation in the γ

34.5 neurovirulence determination locus and the ICP6 locus.

44. The virus of claim 42, further comprising an inactivating mutation in the γ

34.5 neurovirulence locus of said virus and an inactivating mutation in the ICP6 locus of said virus.

45. The virus of claim 42, further comprising sequences encoding a heterologous gene product.

46. The virus of claim 45, wherein said heterologous gene product comprises a vaccine antigen or an immunomodulatory protein.

47. The virus of claim 46, wherein said immunomodulatory protein is a cytokine.

48. The virus of claim 42, wherein said herpes simplex virus is a herpes simplex-1 virus.

49. A pharmaceutical composition comprising the virus of claim 42 and a pharmaceutically acceptable carrier, adjuvant, or diluent.

50. A method of treating cancer in a patient, comprising administering the virus of claim 42 to said patient in an amount sufficient to treat cancer in said patient.

51. A method of immunizing a patient against an infectious disease, cancer, or an autoimmune disease, said method comprising administering the virus of claim 42 to said patient in an amount sufficient to immunize said patient against an infectious disease, cancer, or an autoimmune disease.