Abstract: The present invention relates to oncolytic Picornaviruses and methods and compositions for treating subjects having hematologic cancers. These include methods and compositions for treatment of myeloma, using disclosed Picornavirus such as Coxsackievirus, in methods of direct or indirect administration to subjects and ex vivo purging of malignant cells within auto grafts prior to transplantation.

Abstract: A method of treating neurodegenerative conditions is provided. Neural stem cells may be implanted at and/or remote from a region of neuron degeneration. The methods can include isolating neural stem cells from regions where specific types of neurons corresponding to the neurons to be replaced are generated. The methods can include isolating neural stem cells secreting growth factors affecting the growth and/or regeneration of specific types of neuron. In this invention, we disclose a method of treating such disorders, including several neurodegenerative disorders arising from the lack of cells that produce particular neurotransmitters in neural circuitry by transplanting exogenously cultured and expanded neural progenitors which, upon transplantation into a neural tissue, differentiate into neurons capable of integrating and producing neurotransmitters in sufficient quantities and in a sufficient manner to overcome the symptoms associated with the neurodegeneration.

Abstract: A method for treating a renal disease in a subject is disclosed. The method includes administering into a kidney of the subject with an effective amount of a gutless adenoviral vector containing a polynucleotide encoding a therapeutic agent. The gutless adenoviral vector contains the nucleotide sequence of SEQ ID NO:13 or SEQ ID NO:15 and expresses the therapeutic agent in a kidney tissue of the subject.

Abstract: Microbubble-assisted delivery of viruses is disclosed. In particular, methods for targeting a virus to cancer cells in an immunocompetent animal by administering a selectively replicating virus to the immunocompetent animal and disrupting the microbubbles in a location of the animal comprising cancer cells are provided. The virus is encompassed in a suspension of microbubbles, and the surface of the suspension does not include any virus. A suspension of microbubbles comprising a selectively replicating virus that is encompassed in a suspension of microbubbles, which does not include any virus on the surface of the suspension, is also provided.

Abstract: This invention relates to methods and compositions for the treatment of malignancies associated with gamma-herpesvirus infection. Specifically, the invention s relates to the use of gamma-secretase inhibitors to prevent the production of intracellular Notch1 thereby arresting the growth of the infected cells.

Abstract: Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5 and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described, differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.

Abstract: A method for obtaining bacteriophages by stressing bacteria. The method involves isolating bacteria, propagating the bacteria, exposing the bacteria to at least one environmental stressing agent to induce excision of bacteriophage that are present in the bacterial genome. Multiple or individual environmental stressing agents may be applied. These liberated bacteriophages may be collected for purposes of treating pathogenic infections, protecting plants and agricultural products or general sterilization and sanitation.

Abstract: An isolated bacteriophage MR299-2 or NH-4 deposited under NCIMB Deposit Accession Nos. 41729 and 41730, respectively, is described. The phages have lytic activity against P. aeruginosa strains, including mucoid and CF clinical isolate strains. Variant hages are also described, wherein said variants retain the phenotypic characteristics of said phage and wherein said phage and variants thereof have lytic activity against P. aeruginosa strains.

Abstract: The present invention provides recombinant replication-defective adenoviral vectors derived from chimpanzee adenoviruses and methods for generating recombinant adenoviruses in human E1-expressing cell lines. The invention also provides compositions and methods suitable for use for the delivery and expression of transgenes encoding immunogens against which a boosted immune response is desired. The invention further provides methods of generating clinical grade vector stocks suitable for use in humans. In a particular embodiment the invention contemplates the use of vectors comprising transgenes which encode tumor associated antigens in vaccines and pharmaceutical compositions for the prevention and treatment of cancer.

Abstract: The present invention relates to the processes of preparing silkfibroin/polyethylene oxide blended materials, and the resulting materials thereof, which are suitable for biomedical applications such as wound healing. In particular, the electrospun silk fibroin/PEO mats with a silk:PEO blend ratio of 2:1 to 4:1, treated with controlled evaporation, constraint-drying techniques, and/or alcohol treatment, and/or PEO extraction, demonstrate suitable physical and biofunctional properties, such as fiber structure, topography, absorption, water vapor transmission rates, oxygen permeation, and biodegradability, relevant to biomaterial systems with utility for wound dressings.

Abstract: The present invention relates to non-laboratory virus strains, for example of herpes viruses such as HSV, with improved oncolytic and/or gene delivery capabilities as compared to laboratory virus strains.

Abstract: Disclosed is an insecticidal suspension concentrate composition comprising by weight based on the total weight of the composition: (a) from about 0.3 to about 30% of 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide; (b) from about 5 to about 70% of a nonionic ethylene oxide-propylene oxide block copolymer component having a water solubility of at least about 5% by weight at 20° C., a hydrophilic-lipophilic balance value ranging from about 5 to about 18 and an average molecular weight ranging from about 900 to about 20000 daltons; and (c) from about 20 to about 95% of water. Also disclosed is a method for controlling an insect pest comprising diluting said suspension concentrate composition with water to form a diluted composition, and contacting the insect pest or its environment with an insecticidally effective amount of said diluted composition.

Abstract: A conformable tissue implant is provided for use in repairing or augmenting a tissue defect or injury site. The tissue implant contains a tissue carrier matrix comprising a plurality of biocompatible, bioresorbable granules and at least one tissue fragment in association with the granules. The tissue fragment contains one or more viable cells that can migrate from the tissue and populate the tissue carrier matrix. Also provided is a method for injectably delivering the tissue implant.

Abstract: The present invention relates to a novel bacteriophage, more particularly, a bacteriophage that has a specific bactericidal activity against Salmonella enteritidis, Salmonella typhimurium, Salmonella gallinarum and Salmonella pullorum, a composition for the prevention or treatment of infectious diseases including salmonellosis and Salmonella food poisoning caused by Salmonella enteritidis or Salmonella typhimurium, Fowl typhoid caused by Salmonella gallinarum, and Pullorum disease caused by Salmonella pullorum, which comprises the bacteriophage as an active ingredient, and an animal feed, drinking water, cleaner, and sanitizer which comprise the bacteriophage as an active ingredient.

Abstract: Methods for treating cell proliferative disorders by administering virus to proliferating cells having an activated Ras-pathway are disclosed. The virus is administered so that it ultimately directly contacts proliferating cells having an activated Ras-pathway. Proliferative disorders include but are not limited to neoplasms. The virus is selected from modified adenovirus, modified HSV, modified vaccinia virus and modified parapoxvirus orf virus. Also disclosed are methods for treating cell proliferative disorders by further administering an immunosuppressive agent.

Abstract: The present invention includes compositions and methods for the use of an encapsulation additive having between about 0.1 to about 30 percent isolated and purified vitelline protein B to provide for mixed and extended release formulations.

Abstract: Described are vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding at least two antigens from one or more tuberculosis-causing bacilli. Also described is the use of specific protease recognition sites linking antigens through which the encoded antigens are separated upon cleavage. After cleavage, the antigens contribute to the immune response in a separate manner. The recombinant vectors may comprise a nucleic acid encoding the protease cleaving the linkers and separating the antigens. Also described is the use of genetic adjuvants encoded by the recombinant vectors, wherein such genetic adjuvants may also be cleaved through the presence of the cleavable linkers and the specific protease.

Abstract: The present invention provides a method for reducing the risk of bacterial infection or sepsis in a susceptible patient by treating the susceptible patient with a pharmaceutical composition containing bacteriophage of one or more strains which produce lytic infections in pathogenic bacteria. Preferably, treatment of the patient reduces the level of colonization with pathogenic bacteria susceptible to the bacteriophage by at least one log. In a typical embodiment, the susceptible patient is an immunocompromised patient selected from the group consisting of leukemia patients, lymphoma patients, carcinoma patients, sarcoma patients, allogeneic transplant patients, congenital or acquired immunodeficiency patients, cystic fibrosis patients, and AIDS patients. In a preferred mode, the patients treated by this method are colonized with the pathogenic bacteria subject to infection by said bacteriophage.

Abstract: The present invention is directed to materials and methods for the treatment of hypertension and ischemia comprising administering at least one therapeutic agent selected from the group consisting of vascular endothelial growth factor-C product and vascular endothelial growth factor-D product, and optionally, when treating hypertension, a standard of care anti-hypertensive agent.

Abstract: Provided herein are liquid viral formulations useful for the stabilization and storage of viruses and methods of preparing these formulations. The liquid viral formulations described herein include a virus (e.g., a purified virus) and a non-viral composition including excipients and a liquid carrier. The formulations can be used, for example, to retain the infectivity or immunogenicity of viruses during periods of storage.

Abstract: The invention relates to the use of an attenuated vaccinal strain of Myxoma virus, in particular the SG33 strain, as an oncolytic agent.

Abstract: Methods for treating proliferative disorders, by administering reovirus to a Ras-mediated proliferative disorder, are disclosed. The reovirus is administered so that it ultimately directly contacts ras-mediated proliferating cells. Proliferative disorders include but are not limited to neoplasms. Human reovirus, non-human mammalian reovirus, and/or avian reovirus can be used. If the reovirus is human reovirus, serotype 1 (e.g., strain Lang), serotype 2 (e.g., strain Jones), serotype 3 (e.g., strain Dearing or strain Abney), as well as other serotypes or strains of reovirus can be used. Combinations of more than one type and/or strain of reovirus can be used, as can reovirus from different species of animal. Either solid neoplasms or hematopoietic neoplasms can be treated.

Abstract: Provided herein are lyophilized viral formulations useful for the stabilization and storage of viruses and methods of preparing these formulations. The lyophilized viral formulations described herein include a virus (e.g., a purified virus) and a non-viral composition including excipients. The formulations can be used, for example, to retain the infectivity or immunogenicity of viruses during periods of storage.

Abstract: The embodiment of the invention is a virus-like particle vector, a process for the manufacture thereof, use of the virus-like particle vector and a pharmaceutical composition, which contains the virus-like particle vector. The vector is intended for the delivery of therapeutic agents into specific mammalian tissues, especially low molecular weight agents, in particular low molecular weight anti-cancer drugs into cancer tissues. More specifically, the invention relates to the virus-like particle vector, which constitutes an adenoviral dodecahedron with the therapeutic substance encapsulated or covalently linked.

Abstract: The invention relates to compositions and methods that employ OX40 (CD134), a TNFR superfamily protein, agonists. The invention includes among other things administering an OX40 agonist alone or in combination with a viral antigen, or live or attenuated virus, to treat a viral infection, or for vaccination or immunization.

Abstract: Provided are viral sensitizing compounds that enhance the efficacy of viruses by increasing spread of the virus in cells, increasing the titer of virus in cells, or increasing the cytotoxicity of virus to cells. Other uses, compositions and methods of using same are also provided.

Abstract: The present invention provides isolated polypeptides comprising a fragment of the amino acid sequence of SEQ ID NO:1, or a variant, derivative or fusion thereof, which is capable of binding specifically to and lysing cells of Clostridium difficile, wherein the polypeptide exhibits greater lytic activity on cells of Clostridium difficile than the polypeptide of SEQ ID NO: 1. The invention further provides means for producing the same, methods for killing bacterial cells such as cells of Clostridium difficile, as well as methods for diagnosing, treating and preventing diseases and conditions associated with infection of the same.

Abstract: The present invention discloses a method of treating cancer in a subject. This involves co-administering a replicating virus and a matrix metalloproteinase to the subject under conditions effective to treat cancer. It also relates to a method of enhancing the delivery to and distribution within a tumor mass of therapeutic viruses. This involves co-administering a replicating virus and a matrix metalloproteinase to the tumor mass under conditions effective to enhance the delivery to and distribution within the tumor mass of therapeutic viruses. Another aspect relates to a cancer therapeutic. This involves a replicating virus and a matrix metalloproteinase.

Abstract: The present invention relates to nucleic acids encoding the novel parvoviral protein “assembly activating protein” (AAP), the encoded polypeptides, methods of producing the polypeptides, antibodies specific for AAP, the use of the nucleic acids for the preparation of the polypeptides, the use of the nucleic acids or the polypeptides for the preparation of the parvoviral particle and methods of producing parvoviral particles essentially consisting of VP3 by providing in addition to the coding sequence of the parvoviral structural protein VP3 a sequence fragment Z/a nucleic acid encoding AAP in the cell and expressing VP3 and fragment Z under control of a rep-independent promoter. Furthermore, the present invention relates to parvoviral particles essentially consisting of VP3 and/or obtainable by the above method as well as expression cassettes comprising (i) a heterologous promoter and (ii) VP3 coding sequence and/or fragment Z.

Abstract: Methods of inducing apoptosis in hyperproliferative cells, particularly cancer cells are provided. Such method involves increasing the levels of a potassium channel modulatory protein in the cell. Examples of such proteins are native KChAP protein, a biologically active variant of native KChAP protein, or a biologically active KChAP-related protein (collectively referred to hereinafter as “KChAP protein”). In one embodiment, the cells are contacted with the KChAP protein under conditions permitting uptake of the protein by the cells. In another embodiment, the cells are contacted with (i) a nucleic acid encoding the KChAP protein, and (ii) a promoter active in the cancer cell, wherein the promoter is operably linked to the region encoding the KChAP protein, under conditions permitting the uptake of the nucleic acid by the cancer cell. Methods of detecting cancerous cells in a biological sample selected from the group consisting of a colorectal tissue sample or brain tissue sample are also provided.

Abstract: Disclosed herein are methods and compositions for insertion of Factor IX (FIX) sequences into the genome of a cell for treating hemophilia B.

Abstract: The present invention describes the isolation and characterization of the novel biopesticide compositions and/or biopesticide formulations obtained from Eucalyptus species capable of serving as effective biocontrol agents and/or pest control management agents. The invention focuses on the isolation of these biopesticide compositions and formulations that are known to possess pesticidal properties and are derived from natural sources having biological origin. The invention more particularly describes the isolation and characterization, including but not confined to, novel biopesticide compositions possessing pesticidal attributes along with other pharmaceutically important attributes so as to also function as effective biocontrol agents.

Abstract: The present invention provides engineered bacteriophages that express at least one biofilm degrading enzyme on their surface and uses thereof for degrading bacterial biofilms. The invention also provides genetically engineered bacteriophages expressing the biofilm degrading enzymes and proteins necessary for the phage to replicate in different naturally occurring biofilm producing bacteria. The phages of the invention allow a method of biofilm degradation by the use of one or only a few administration of the phage because the system using these phages is self perpetuating, and capable of degrading biofilm even when the concentration of bacteria within the biofilm is low.

Abstract: Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein X is O or S; Y is O or S; Z is a direct bond, O, S(O)n, NR6, C(R7)2O, OC(R7)2, C(?X1), C(?X1)E, EC(?X1), C(?NOR8) or C(?NN(R6)2); a is 0, 1, 2 or 3; and R1, R2, R3, R4, R5a, R5b, R6, R7, R8, X1 and E are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.

Abstract: Disclosed are compounds of Formula 1, N-oxides and salts thereof, wherein X is O or S; Y is O or S; Z is a direct bond, O, S(O)n, NR6, C(R7)2O, OC(R7)2, EC(?X1); a is 1, 2 or 3; and R1, R2, R3, R4, R5a, R5b, R6, R7, X1 and E are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.

Abstract: Disclosed are compositions comprising (a) at least one compound selected from compounds of Formula 1, N-oxides, and salt thereof, wherein R1 is phenyl optionally substituted with up to 5 substituents independently selected from R3, or pyridinyl optionally substituted with up to 4 substituents independently selected from R3; R2 is C1-C4 haloalkyl; or thiazolyl, pyridinyl or pyrimidinyl, each optionally substituted with up to 2 substituents independently selected from the group consisting of halogen and C1-C4 alkyl; each R3 is independently halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C(R4)?NOR4 or Q; each R4 is independently C1-C4 alkyl; Z is CH?CH or S; and each Q is independently phenyl or pyridinyl, each optionally substituted with up to 3 substituents independently selected from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy; and (b) at least one invertebrate pest control agent.

Abstract: Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein Z is O or S; and R1, R2, R3, Q and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling a parasitic nematode comprising contacting the parasitic nematode or its environment with a biologically effective amount of a compound or a composition of the invention.

Abstract: The present invention relates in its broadest aspect to combined phage/antibiotic therapy. More particularly, it relates to use of (i) one or more bacteriophages and (ii) one or more antibiotics in the manufacture of a combined product for simultaneous, separate or sequential administration of (i) and (ii) to treat a bacterial infection characterized by biofilm formation, for example an infection comprising or consisting of P. aeruginosa. Treatment in this context may be either therapeutic or prophylactic treatment. Also provided are deposited bacteriophages each exhibiting different strain specificity against P. aeruginosa and combinations of such bacteriophages, e.g. a panel of six deposited bacteriophages which was found to be effective against a high percentage of clinical isolates of P. aeruginosa from canine ear infections.

Abstract: The disclosure provides mutant ribonucleotide reductase strains of poxviruses including for example vaccinia viruses. The disclosure also provides methods and for the use of these mutant ribonucleotide reductase strains of vaccinia viruses in oncolytic virotherapy.

Abstract: The present invention is directed to the administration of an HSV derived oncolytic virus and a PI3K/AKT/mTOR pathway inhibitor to treat various types of resistant tumors. Therapy-resistant tumor formation is one of the main causes for treatment failure in the clinic. The treatment methods and compositions disclosed herein sensitize resistant tumors to the treatment of herpes simplex virus (HSV)-based oncolytic virotherapy. Pre or co-treatment of resistant tumor cells with the mTOR inhibitor, rapamycin, or certain PI3K inhibitors, such as LY294002, can efficiently sensitize the tumors to HSV derived oncolytic viruses, whereby the replication and spread of the viruses are dramatically enhanced.

Abstract: Methods are provide to allow for the preparation of adenoviral vectors with altered tropism. Compositions comprising such vectors and methods of use thereof also are provided.

Abstract: The present invention relates to compositions and pharmaceutical compositions comprising poxviruses and more particularly extracellular enveloped viruses. The present invention also relates to a process for producing poxviruses and poxviruses obtained thereof. Moreover, the present invention also relates to the use of said poxvirus and said composition for the preparation of a medicament.

Abstract: Embodiments of surgical grafts, and methods, for the delivery of therapeutic agents to a target tissue via acellular matrices, are described. In some embodiments, nonviable matrices are successful in preventing or lessening adhesion formation by guiding tissue repair and remodeling, while also providing the target tissue with therapeutic agents that can act as repair and remodeling factors. An exemplary method to modulate flexor tendon healing and provide elimination or reduction of fibrotic adhesions involves loading a freeze-dried flexor digitorum longus allograft with recombinant adeno-associated viral (rAAV) vectors for the targeted and transient expression of growth/differentiation factor 5 (GDF5).

Abstract: A composition is disclosed comprising virus in a formulation comprising a polyhydroxy hydrocarbon buffered to maintain a pH in a range from about 7 to about 8.5 at a temperature in the range from about 2° C. to 27° C. Methods for concentrating and purifying virus preparations are also disclosed.

Abstract: The present invention relates, in general, to a methodology for the generation of nonsegmented negative-strand RNA viruses (Pringle, 1991) from cloned deoxyribonucleic acid (cDNA). Such rescued viruses are suitable for use as vaccines, or alternatively, as plasmids in somatic gene therapy applications. The invention also relates to cDNA molecules suitable as tools in this methodology and to helper cell lines allowing the direct rescue of such viruses. Measles virus (MV) is used as a mode for other representatives of the Mononegavirales, in particular the family Paramyxoviridae.

Abstract: Novel hydroxylated 1,2,4-oxadiazole benzoic acid compounds, methods of using and pharmaceutical compositions comprising a hydroxylated 1,2,4-oxadiazole benzoic acid derivative are disclosed. The methods include methods of treating or preventing a disease ameliorated by modulation of premature translation termination or nonsense-mediated mRNA decay, or ameliorating one or more symptoms associated therewith.

Abstract: The invention provides virus-like particles for treatment of viral infections based on the virus causing the infection. The virus-like particles comprise the virus recombinant proteins that form a capsid, recombinant virus membrane proteins attached to the capsid and vRNA packaged within said capsid. The vRNA is generated from a DNA sequence encoding a polypeptide capable of specifically binding to a constant region of a nonstructural protein of the virus that is essential for propagation of the virus.

Abstract: The present invention is directed to engineered enzymatically active bacteriophages that are both capable of killing the bacteria by lysis and dispersing the bacterial biofilm because they have been also engineered to express biofilm-degrading enzymes, particularly dispersin B (DspB), an enzyme that hydrolyzes ?-1,6-N-acetyl-D-glucosamine, a crucial adhesion molecule needed for biofilm formation and integrity in Staphylococcus and E. coli, including E. coli K-12, as well as clinical isolates.

Abstract: A method of killing a cell that is lacking in effective p53 protein activity, particularly as compared to wild type, is provided characterised in that it comprises delivering to the cell a single stranded DNA including a portion with at least one base, internally located with respect to any 3? and 5? ends of the DNA, that is unbasepaired with another base in a form that is capable of being internalised by the cell.

Abstract: The present invention generally relates to compositions and methods of delivering substances in a dry mode, wherein the compositions include a surface layer disposed on the outer surface of the composition that is permeable to carbon dioxide and oxygen. The compositions may be used to deliver microorganisms to remove contaminates, such as oil, chemical, waste, or sewage, from soil, water, or air. In other embodiments, the compositions can also be used for delivering liquid food, liquid food additives, liquid biotech agricultural ingredients, conventional liquid agricultural ingredients, liquid human wellness and dietary supplements, and liquid fragrances and beauty products.