Treatment of neoplasms with viruses
AssigneePro-Virus, Inc.
InventorsMichael S. Roberts, Robert M. Lorence, William S. Groene, Harvey Rabin, Reid W. von Borstel
Life of this patent
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Abstract
The subject invention relates to viruses that are able to replicate and thereby kill neoplastic cells with a deficiency in the IFN-mediated antiviral response, and their use in treating neoplastic disease including cancer and large tumors. RNA and DNA viruses are useful in this regard. The invention also relates to methods for the selection, design, purification and use of such viruses for cancer therapy.
Claims152
A method of infecting a neoplasm in a mammal with a virus comprising administering an interferon-sensitive, replication-competent clonal RNA virus to said mammal.
A method of infecting a neoplasm in a mammal with a virus comprising administering a replication-competent clonal RNA virus to said mammal wherein said virus has sensitivity to interferon.
A method of treating a neoplasm in a mammal comprising administering to said mammal a therapeutically effective amount of an interferon-sensitive, replication-competent clonal RNA virus.
A method of infecting a neoplasm in a mammal with a virus comprising administering an interferon-sensitive, replication-competent clonal vaccinia virus, having one or more mutations in one or more genes selected from the group consisting of K3L, E3L, and B18R, to said mammal.
A method of infecting a neoplasm in a mammal with a virus comprising administering a replication-competent clonal vaccinia virus, having one or more mutations in one or more genes selected from the group consisting of K3L, E3L, and B18R, to said mammal wherein said virus has sensitivity to interferon.
A method treating a neoplasm in a mammal comprising administering to said mammal a therapeutically effective amount of an interferon-sensitive, replication-competent clonal vaccinia virus, having one or more mutations in one or more genes selected from the group consisting of K3L, E3L, and B18R.
A method of infecting a neoplasm in a mammal with a virus comprising administering an interferon-sensitive, replication-competent clonal DNA virus, selected from the group consisting of Adenoviruses, Parvoviruses, Papovaviruses, and Iridoviruses, to said mammal.
A method of infecting a neoplasm in a mammal with a virus comprising administering a replication-competent clonal DNA virus, selected from the group consisting of Adenoviruses, Parvoviruses, Papovaviruses, and Iridoviruses, to said mammal wherein said virus has sensitivity to interferon.
A method of treating a neoplasm in a mammal comprising administering to said mammal a therapeutically effective amount of an interferon-sensitive, clonal DNA virus selected from the group consisting of Adenoviruses, Parvoviruses, Papovaviruses, and Iridoviruses.
A method of infecting a neoplasm in a mammal with a virus comprising administering an interferon-sensitive, replication-competent clonal Herpesvirus to said mammal.
A method of infecting a neoplasm in a mammal with a virus comprising administering a replication-competent clonal Herpesvirus to said mammal wherein said virus has sensitivity to interferon.
A method treating a neoplasm in a mammal comprising administering to said mammal a therapeutically effective amount of an interferon-sensitive, replication-competent clonal Herpesvirus.
A method of infecting a neoplasm which is at least 1 centimeter in size in a mammal with a virus comprising administering a clonal virus, selected from the group consisting of (1) RNA viruses;
- (2) Hepadenavirus;
- (3) Parvovirus;
- (4) Papovavirus;
- (5) Herpesvirus;
- (6) Poxvirus;
- and (7) Iridovirus, to said mammal.
A method of treating a neoplasm in a mammal, comprising administering to said mammal a therapeutically effective amount of a clonal virus selected from the group consisting of (1) RNA virus;
- (2) Hepadenavirus;
- (3) Parvovirus;
- (4) Papovavirus;
- (5) Herpesvirus;
- (6) Poxvirus;
- and (7) Iridovirus, wherein said neoplasm is at least 1 centimeter in size.
A method of treating a tumor in a mammal, comprising administering to said mammal a therapeutically effective amount of an RNA virus cytocidal to said tumor, wherein said mammal has a tumor burden comprising at least 1.5% of the total body weight of said mammal.
A method of screening tumor cells or tissue freshly removed from the patient to determine the sensitivity of said cells or tissue to killing by a virus comprising subjecting a tissue sample to a differential cytotoxicity assay using an interferon-sensitive virus.
A method for identifying a virus with antineoplastic activity in a mammal comprising:
- a) using said test virus to infect i) cells deficient in an interferon-mediated antiviral activity, and ii) cells competent in an interferon-mediated antiviral activity, and
- b) determining whether said test virus kills said cells deficient in an interferon-mediated antiviral activity preferentially to said cells competent in interferon-mediated antiviral activity.
A method of making viruses for use in antineoplastic therapy comprising:
- (a) modifying an existing virus by diminishing or ablating a viral mechanism for the inactivation of the antiviral effects of IFN, and optionally
- (b) creating an attenuating mutation
A method of controlling viral replication in a mammal treated with a virus selected from the group consisting of RNA viruses, Adenoviruses, Poxviruses, Iridoviruses, Parvoviruses, Hepadnaviruses, Varicellaviruses, Betaherpesviruses, and Gammaherpesviruses comprising administering an antiviral compound.
A clonal Paramyxovirus purified by ultracentrifugation without pelleting.
A clonal Paramyxovirus purified to a level of at least 2×109 PFU/mg protein.
A clonal Paramyxovirus purified to a level of at least 1×1010 PFU/mg protein.
A clonal Paramyxovirus purified to a level of at least 6×1010 PFU/mg protein.
A clonal RNA virus purified to a level of at least 2×109 PFU/mg protein.
A replication-competent cytocidal virus which is interferon-sensitive and purified to a level of at least 2×109 PFU/mg protein.
A Clonal cytocidal DNA virus which is interferon-sensitive and purified to a level of at least 2×109 PFU/mg protein.
A replication-competent vaccinia virus having a) one or more mutations in one or more of the K3L, E3L and B18R genes, and b) an attenuating mutation in one or more of the genes encoding thymidine kinase, ribonucleotide reductase, vaccinia growth factor, thymidylate kinase, DNA ligase, dUTPase.
A replication-competent vaccinia virus having one or more mutations in two or more genes selected from the group consisting of K3L, E3L, and B18R.
A Herpesvirus having a modification in the expression of the (2′-5′)A analog.
A Reovirus having a mutation at omega 3 and purified to a level of at least 2×109 PFU/mg protein.
A Reovirus having mutations at omega 1 and omega 3.
A method of purifying an RNA virus comprising the steps of:
- a) generating a clonal virus, and
- b) purifying said clonal virus by ultracentrifugation without pelleting.
A method of purifying a Paramyxovirus comprising purifying said virus by ultracentrifugation without pelleting.
A method of infecting a neoplasm in a mammal with a virus comprising administering an interferon-sensitive, replication-competent RNA virus to said mammal.
A method of infecting a neoplasm in a mammal with a virus comprising administering a clonal virus selected from the group consisting of the Newcastle disease virus strain MK107, Newcastle disease virus strain NJRoakin, Sindbis virus, and Vesicular stomatitis virus.
A method of treating a neoplasm in a mammal comprising subjecting a sample from said mammal to an immunoassay to detect the amount of virus receptor present, and if said receptor is present, administering an interferon-sensitive, replication competent clonal virus, which bind said receptor, to said mammal.
A method of treating tumor ascites comprising administering an interferon-sensitive, replication-competent clonal virus.
A method of reducing pain in a mammal comprising administering an interferon-sensitive, replication competent clonal virus.
A method of infecting a neoplasm in a mammal comprising administering a virus selected from the group of families consisting of Paramyxoviridae, Orthomyxoviridae, Rhabdoviridae, Togaviridae, Flaviviridae, Picornaviridae, Coronaviridae, Reoviridae, Poxviridae, Herpesviridae, and Parvoviridae
A method of treating a disease of viral etiology in a mammal comprising administering to said mammal a therapeutically effective amount of a replication-competent clonal virus.
A method of infecting a neoplasm in a mammal with a virus comprising administering an interferon-responsive, replication-competent clonal RNA virus to said mammal.
A method as in claim1 wherein said virus is administered greater than two weeks after the first administration of the virus.
Dependencies are inferred from the claim text.