Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
  • A61K35/66—Microorganisms or materials therefrom
  • A61K35/76—Viruses; Subviral particles; Bacteriophages
  • A61K35/765—Reovirus; Rotavirus
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/04—Centrally acting analgesics, e.g. opioids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
  • A61P35/04—Antineoplastic agents specific for metastasis
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
  • C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
  • C12N2720/00011—Details
  • C12N2720/12011—Reoviridae
  • C12N2720/12211—Orthoreovirus, e.g. mammalian orthoreovirus
  • C12N2720/12232—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent

Definitions

• analgesic therapies are considered. These therapies include anesthesiologic, surgical, and
• neurostimulatory interventions For example, destructive neurolysis using phenol or alcohol is considered when other nondestructive approaches are not possible or have failed, the pain is well localized, and the block will not compromise strength or sphincter function.
• some neurostimulatory techniques can be relatively noninvasive (for example, transcutaneous electrical nerve stimulation and acupuncture), others are still.
• the oncolytic virus is reovirus.
• the reovirus may be a mammalian reovirus or an avian reovirus.
• the reovirus is a human reovirus.
• the human reovirus may be any of the three serotypes: type 1 (strain Lang or TIL), type 2 (strain Jones, T2J) and type 3 (strain Dearing or strain Abney, T3D).
• the human reovirus is serotype 3 reovirus.
• the reovirus may be modified such that the outer capsid is removed, the virion is packaged in a liposome or micelle, or the proteins of the outer capsid have been mutated.
• the recombinant reovirus may also result from reassortment of reovirases from different serotypes, such as selected from the group consisting of serotype 1 reovirus, serotype 2 reovirus and serotype 3 reovirus.
• the recombinant reovirus may comprise naturally-occurring variant coat protein coding sequences or mutated coat protein coding sequences.
• the neoplasm may be a solid neoplasm.
• the neoplasm may be metastatic and/or terminal.
• the virus may be administered by injection into or near a solid neoplasm, or by any other methods known in the art, such as systemic administration.
• the recombinant reovirus may be from two or more strains of reovirus, particularly two or more strains of reovirus selected from the group consisting of strain Dearing, strain Abney, strain Jones, and strain Lang.
• the recombinant reovirus may also result from reassortment of reo viruses from different serotypes, such as selected from the group consisting of serotype 1 reovirus, serotype 2 reovirus and serotype 3 reovirus.
• the recombinant reovirus may comprise naturally-occurring variant coat protein coding sequences or mutated coat protein coding sequences.
• a second component which is a second pharmaceutical composition comprising an effective amount of an analgesic.
• the amount of the analgesic is less than that required if the first component is absent.
• kits that comprises an oncolytic virus and an analgesic.
• the kit may further comprise any component that can be used to practice the present invention as disclosed herein.
• the kit may further comprise at least one additional oncolytic virus, a chemotherapeutic agent, an immunosuppresive agent, a means for suppressing the immune system, an anti-antivirus antibody, a means for administering any of the components of the kit, and/or an instruction for using the kit.
• Neuroopathic pain is pain that is believed to be sustained by aberrant somatosensory processing in the peripheral or central nervous system.
• Neuropathic pain may present as a burning, tingling sensation with a lancinating component. It can be further subdivided into deafferentation pains (such as central pain, phantom pain, and postherpetic neuralgia), peripheral mononeuropathies and polyneuropathies, and the complex regional pain syndromes (reflex sympathetic dystrophy or causalgia).
• Neuropathic pain syndromes respond less well to opioid drugs than nociceptive pain syndromes. Pain syndromes can be "acute” or "chronic.”
• Chronic pain syndromes result primarily from a direct effect of the neoplasm. They also may be therapy-related or represent disorders unrelated to the disease or its treatment.
• Non-opioid analgesics are natural or synthetic substances that reduce pain but are not opioid analgesics. Non-opioid analgesics are known in the art (see, e.g. , The Merck Manual, 1999).
• Ras-activated neoplastic cells or “ras-mediated neoplastic cells” refer to cells which proliferate at an abnormally high rate due to, at least in part, activation of the ras pathway.
• the ras pathway may be activated by way of ras gene structural mutation, elevated level of ras gene expression, elevated stability of the ras gene message, or any mutation or other mechanism which leads to the activation of ras or a factor or factors downstream or upstream from ras in the ras pathway, thereby increasing the ras pathway activity.
• EGF receptor PDGF receptor or sos results in activation of the ras pathway.
• Ras-mediated neoplastic cells include, but are not limited to, ras-mediated cancer cells, which are cells proliferating in a malignant manner due to activation of the ras pathway.
• oncolytic viruses are replication-competent viruses with experimentally determined replicative advantages in tumor cells compared with normal tissue.
• An ideal oncolytic virus introduced by a single intratumor inoculation replicates and lyses the infected cell, and subsequently infects the surrounding tumor cells until it reaches the boundary between malignant and normal tissue.
• Oncolytic viruses include, for example, adenoviras derivatives, HSV-1 derivatives, autonomous parvovirus, poxvirus, Newcastle disease virus, polio virus derivatives, vesicular stomatitis virus, influenza virus derivatives and reovirus.
• the virus may be naturally occurring or modified.
• the virus is "naturally- occurring": when it can be isolated from a source in nature and has not been intentionally modified by humans in the laboratory.
• the virus can be from a "field source", that is, from an infected animal.
• Pain may be nociceptive (somatic or visceral) or neuropathic.
• Tumor-related nociceptive pain syndromes can be due to neoplastic invasion of bone, joint, muscle or connective tissue. Bone pain syndromes are the most prevalent. Bone metastases are often painless, and the factors that distinguish a painful lesion from a painless one are poorly understood. Multifocal bone pain is usually caused by widespread metastases.
• the present invention provides a method for reducing cancer pains using oncolytic viruses.
• the pain is reduced to the extent that a lower amount or frequency of analgesic measures is required, or a lesser step in the analgesic ladder is necessary, as compared to the amount, frequency or step required in the absence of the viruses.
• virus is administered to an individual mammal.
• reoviras is used.
• Representative types of human reoviras that can be used include type 1 (e.g., strain Lang or TIL); type 2 (e.g., strain Jones or T2J); and type 3 (e.g., strain Dearing or strain Abney, T3D or T3A); other strains of reovirus can also be used.
• the reovirus is human reovirus serotype 3, more preferably the reoviras is human reovirus serotype 3, strain Dearing.
• oligonucleotide site directed mutagenesis of the gene encoding for one of the coat proteins could result in the generation of the desired mutant coat protein.
• Expression of the mutated protein in reovirus infected mammalian cells in vitro such as COS1 cells will result in the incorporation of the mutated protein into the reovirus virion particle (Turner and Duncan, (1992); Duncan et al., (1991); Mah et al., (1990).
• dsRNA double stranded RNA
• Ras-activated neoplastic cells are not subject to protein synthesis inhibition by PKR, because ras inactivates PKR. These cells are therefore susceptible to viral infection even if the virus does not have a PKR inhibitory system. Accordingly, if the PKR inhibitors in adenoviras, vaccinia viras, herpex simplex viras or parapoxvirus orf virus is mutated so as not to block PKR function anymore, the resulting viruses do not infect normal cells due to protein synthesis inhibition by PKR, but they replicate in ras-activated neoplastic cells which lack PKR activities.
• VSV vesicular stomatitis viras
• HSV-1 herpes simplex virus 1
• hrR3 herpes simplex virus 1
• NDV Newcastle disease viras
• Vaccinia virus propagated in several malignant tumor cell lines.
• a course of viras therapy is administered one or more times. Following the first administration of viras therapy particular immune constituents that may interfere with subsequent administrations of virus are removed from the patient. These immune constituents include B cells, T cells, antibodies, and the like.
• the i pharmaceutically acceptable excipient when it serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier or medium for the active ingredients.
• the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments containing, for example, up to 10% by weight of the active
• the viras is administered in an amount that is sufficient to reduce pain (e.g., an "effective amount"). Lessening of pain may occur with or without actual tumor regression.
• the reduction of pain may be concomitant with reduction in size of the neoplasm, or elimination of the neoplasm.
• the reduction in size of the neoplasm, or in a complete elimination of the neoplasm is generally caused by lysis of neoplastic cells ("oncolysis") by the viras (U.S. Patents 6,110,461; 6,136,307; 6,261,555; and 6,344,195).
• viras of the present invention may be administered in conjunction with or in addition to known anticancer compounds or chemotherapeutic agents.
• Chemotherapeutic agents are compounds which may inhibit the growth of tumors. Such agents, include, but are not limited to, 5-fluorouracil, mitomycin C, methotrexate, hydroxyurea, cyclophosphamide, dacarbazine, mitoxantrone, anthracyclins (Epirabicin and Doxurabicin), antibodies to receptors, such as herceptm, etopside, pregnasome, platinum compounds such as carboplatin and cisplatin, taxanes such as taxol and taxotere, hormone therapies such as tamoxifen and anti-estrogens, interferons, aromatase inhibitors, progestational agents and LHRH analogs.
• EGF epidermal growth factor

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• Organic Chemistry (AREA)
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• Virology (AREA)
• Pain & Pain Management (AREA)
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• Rheumatology (AREA)
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• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 2003
  • 2003-05-07 DE DE03722131T patent/DE03722131T1/de active Pending
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