# US 2009/0202489 A2 · Adenoviruses mutated in the va genes for cancer treatment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2009/0202489 A2 - Document ID: US20090202489A2 - Status: Published application - Kind: A2 - Application number: 11/809,191 - Filed: 2007-05-31 - Published: 2009-08-13 - Earliest claimed: 2002-03-26 - Assignees: Oncolytics Biotech Inc. - Inventors: Ramon Bonastre; Manel Piqueras - Web page: https://patentgrep.com/patent/US20090202489A2 ## CPC - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - A61K 35/761: Adenovirus - A61P 35/00: Antineoplastic agents - C12N 15/86: Viral vectors - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - C12N 2710/10322: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2710/10332: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent - C12N 2710/10343: viral genome or elements thereof as genetic vector - C12N 2710/10361: Methods of inactivation or attenuation - C12N 2710/10364: by serial passage - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract This invention refers to the use of an adenovirus for cancer treatment, being this adenovirus defective in its virus-associated (VA) RNAs. Said adenovirus has a mutation in the VAI or VAII gene sequence or both. This adenovirus may also have mutations in the sequences controlling expression of the VA RNAs. ## Claims ### Claim at position 1 -11. (canceled) ### Claim 12 An adenovirus having mutated VAI and VAII RNA genes, wherein said adenovirus is defective in its VAI and VAII virus-associated RNAs and will selectively replicate in cells of said cancer, and wherein said adenovirus further has one or more additional mutations to obtain selective replication in tumors. ### Claim 13 (depends on 12) The adenovirus according to claim 12, wherein one or more of said additional mutations to obtain selective replication in tumors is a mutation in one or both of E1a or E1b. ### Claim 14 (depends on 13) The adenovirus according to claim 13, wherein said mutation in one or both of E1a or E1b is a mutation in a promoter region. ### Claim 15 (depends on 12) The adenovirus according to claim 12, wherein said adenovirus further has mutations in the VA RNA genes to obtain selective replication in tumor cells. ### Claim 16 (depends on 12) The adenovirus according to claim 12, wherein said adenovirus further has mutations in the VA RNA genes to obtain selective replication in tumor cells with an active Ras pathway or unresponsive to interferon. ### Claim 17 (depends on 12) The adenovirus according to claim 12, wherein said adenovirus has at least one modification in its capsid to increase its infectivity or to direct it to a receptor present on a tumor cell. ### Claim 18 (depends on 12) The adenovirus according to claim 12, wherein at least one of said additional mutations to obtain selective replication in tumors is an insertion of a promoter that is selectively active in tumor cells, wherein said insertion is in one or more genes of the group E1a, E1b, and E4. ### Claim 19 (depends on 12) The adenovirus according to claim 12, wherein the adenovirus is a human adenovirus. ### Claim 20 (depends on 19) The adenovirus according to claim 19, wherein said adenovirus is a human adenovirus derived from a serotype between 1 and 50, inclusive, that has both a VAI gene and a VAII gene. ### Claim 21 (depends on 19) The adenovirus according to claim 19, wherein said adenovirus is a human adenovirus derived from serotype 5. ### Claim 22 (depends on 12) The adenovirus according to claim 12, wherein said adenovirus further comprises at least one other gene useful in cancer gene therapy. ### Claim 23 (depends on 22) The adenovirus according to claim 22, wherein said gene useful in cancer gene therapy is selected from the group consisting of prodrug activators, tumor suppressors, and immunostimulants. ### Claim 24 An adenovirus comprising: (A) one or a combination of (i) a mutation within a VAI gene; (ii) a mutation in a sequence before a VAI gene that controls the expression of said gene; or (iii) a mutation in a sequence after a VAI gene that controls termination of transcription of said gene; (B) one or a combination of (i) a mutation within a VAII gene; (ii) a mutation in a sequence before a VAII gene that controls the expression of said gene; or (iii) a mutation in a sequence after a VAII gene that controls termination of transcription of said gene; and (C) one or more additional mutations to obtain selective replication in tumors. wherein said mutations (A) and (B) result in defective VAI and VAII virus-associated RNAs, and wherein said adenovirus will selectively replicate in cells of said cancer. ### Claim 25 (depends on 24) The adenovirus according to claim 24, wherein one or more of said additional mutations to obtain selective replication in tumors is a mutation in one or both of E1 a or E1b. ### Claim 26 (depends on 25) The adenovirus according to claim 25, wherein said mutation in one or both of E1a or E1b is a mutation in a promoter region. ### Claim 27 (depends on 24) The adenovirus according to claim 24, wherein said adenovirus further has mutations in the VA RNA genes to obtain selective replication in tumor cells. ### Claim 28 (depends on 24) The adenovirus according to claim 24, wherein said adenovirus further has mutations in the VA RNA genes to obtain selective replication in tumor cells with an active Ras pathway or unresponsive to interferon. ### Claim 29 (depends on 24) The adenovirus according to claim 24, wherein said adenovirus has at least one modification in its capsid to increase its infectivity or to direct it to a receptor present on a tumor cell. ### Claim 30 (depends on 24) The adenovirus according to claim 24, wherein at least one of said additional mutations to obtain selective replication in tumors is an insertion of a promoter that is selectively active in tumor cells, wherein said insertion is in one or more genes of the group E1a, E1b, and E4. ### Claim 31 (depends on 24) The adenovirus according to claim 24, wherein the adenovirus is a human adenovirus. ### Claim 32 (depends on 31) The adenovirus according to claim 31, wherein said adenovirus is a human adenovirus derived from a serotype between 1 and 50, inclusive, that has both a VAI gene and a VAII gene. ### Claim 33 (depends on 31) The adenovirus according to claim 31, wherein said adenovirus is a human adenovirus derived from serotype 5. ### Claim 34 (depends on 24) The adenovirus according to claim 24, wherein said adenovirus further comprises at least one other gene useful in cancer gene therapy. ### Claim 35 (depends on 34) The adenovirus according to claim 34, wherein said gene useful in cancer gene therapy is selected from the group consisting of prodrug activators, tumor suppressors, and immunostimulants.