Abstract: A process for the purification of viruses from a cell lysate preparation is described, consisting of preferably two successive chromatographic steps; the first a clarification step utilizing size exclusion chromatography, and the second, a virus capture and release step using anion exchange chromatography, which successive chromatographic steps have the advantage of purifying virus, and avoiding chromatography buffer conductivity adjustments.

Abstract: A new cytosine deaminase gene and protein from Candida kefyr are provided. This protein has increased ability to convert the 5-fluorocytosine prodrug to its toxic form when compared against the E. coli enzyme.

Abstract: Provided are replication competent, recombinant adenovirus vectors containing mutations in the E1B region which permit the easy deletion of a gene or genes therein, and optionally the substitution therefore of a heterologous gene that substantially exhibits the temporal expression pattern of the E1b region gene(s) deleted. Such vectors have applications for the treatment of disease, and preferably for the treatment of neoplastic disease.

Abstract: Identification, characterization and expression of nucleotides that encode phosphatidylinositol-3′kinase associated protein(s) that bind to the intermediate SH2 domain on the regulatory subunit of PI3K, p85, by the associated protein(s) C-terminal amino acids, and that exhibit a bromodomain are described, as well as methods of using such proteins for medical applications, including diagnosis and treatment cell growth disorders.

Abstract: The present invention relates to pharmaceutical compositions, kits, and methods of use thereof, comprising, a mutant human herpes simplex virus, which is cytopathic to susceptible target cells, such as neoplastic cells. Preferably, the virus does not produce a functionally active wild-type gC polypeptide coded for the UL44 gene.

Abstract: Compositions and methods are described that are useful to assay for compouds that affect PKB kinase activity which have medical applications for the diagnosis and treatment of disease.

Abstract: The present invention relates to pharmaceutical compositions, kits, and methods of use thereof, comprising, a mutant human herpes simplex-type 1 virus, which is cytopathic to susceptible hyperproliferative cells, such as neoplastic cells. Preferably, the virus does not produce a fully functionally active wild-type ICP0 polypeptide coded for the IE gene 1.

Abstract: Adenoviral mutants are described that have single amino acid mutations in the E1B-55K protein which mutations effect the p53 binding/inactivation and the late functions of the E1B-55K protein in a manner that enhances the efficacy of such viruses for treating cancer when compared to adenoviral mutants that have the E1B-55K region deleted.

Abstract: The present invention relates to all aspects of a guanine exchange factor (GEF), for example, a Rho-GEF, such as p115 Rho-GEF. A GEF modulates cell signaling pathways, both in in vitro and in vivo, by modulating the activity of a GTPase. By way of illustration, a p115 Rho-GEF, which modulates the activity of a Rho GTPase, is described. However, the present invention relates to other GEFs, especially other Rho-GEFs. The present invention particularly relates to an isolated p115 Rho-GEF polypeptide or fragments of it, a nucleic acid coding for p115 Rho-GEF or fragments of it, and derivatives of the polypeptide and nucleic acid. The invention also relates to methods of using such polypeptides, nucleic acids, or derivatives thereof, e.g., in therapeutics, diagnostics, and as research tools.

Abstract: The present invention relates to nucleic acid molecules, including antisense and enzymatic nucleic acid molecules, such as hammerhead ribozymes, DNAzymes, and antisense, which modulate the expression of the Chk-1 gene.

Abstract: Compositions of matter consisting of a family of related nucleic acid sequences that encode proteins, termed Cell Growth Regulatory Proteins, that phosphorylate cell cycle targets, and methods of using the nucleotide sequences and the proteins encoded thereby, to diagnose and/or treat disease where the Cell Growth Regulatory Proteins have an apparent molecular weight of about 54.6 kdaltons.

Abstract: The present invention relates to an isolated SRK polypeptide, biologically-active polypeptide fragments thereof, and nucleic acids which code for it. This polypeptide has various activities in regulating cell signaling and signal transduction pathways, including, e.g., a protein kinase activity; an autophosphorylating activity; a cell survival promoting activity; a HAX-1 binding activity; an apoptosis suppression activity; a MAPKK stimulatory activity; a transcription modulatory activity, and a SRK-specific immunogenic activity. The invention relates to all aspects of SRK, or homologs thereof, including assays for modulators, activators, ligands, etc. The invention also relates to a cytolic or soluble HAX-1 which produces apoptosis when expressed in cells.

Abstract: The present invention relates to an isolated full-length Chp polypeptide, a biologically-active polypeptide fragment thereof, and nucleic acids which code for it. This polypeptide has various activities in regulating cell signaling and signal transduction pathways, including, e.g., a PAK regulatory domain binding activity, a PAK kinase stimulatory activity, a JNK kinase stimulatory activity, a cytoskeletal-reorganizing activity, or a Chp-specific immunogenic activity. The invention relates to all aspects of Chp, or homologs thereof, including assays for modulators, activators, ligands, etc.

Abstract: The present invention provides a novel method for producing recombinant baculoviruses expressing genes of interest by inserting a selectable marker gene, specifically the puromycin resistance (pac) gene, adjacent to the gene of interest into the baculovirus genome, and selecting for viruses that express the selectable marker. Selection of the recombinant virus in the presence of a selection condition, such as puromycin-containing cell culture media, simplifies virus production by eliminating the need for cloning, and testing the virus for gene expression. Such expression systems are readily adapted to an automated method for expression foreign genetic material in a high throughput manner.

Abstract: Methods and compositions for determining the tumor suppressor status of cells are described, preferably as pertaining to the p53 status of tumor cells, and preferably in vivo using a recombinant construct consisting of a first polynucleotide sequence that encodes a reporter molecule and a second p53 binding polynucleotide sequence that is operably linked to the first polynucleotide sequence such that binding of p53 to the second polynucleotide sequence causes the expression of the reporter molecule which can be detected or quantified.

Abstract: Provided are novel phospholipase D DNA and amino acid sequences. The sequences are useful in methods and compositions for identifying phospholipase D mediator molecules which are in turn useful in therapeutic pharmaceutical compositions for treating rheumatoid arthritis, psoriasis, ulcerative colitis, in wound healing and for treating other diseases or conditions characterized by exhibition of an inflammatory response or in the treatment of cancer and other diseases characterized by pathogenic mitogenicity.

Abstract: Methods and compositions are described that affect the GTPase activity of members of the Ras superfamily, preferably Rac, such compositions include guanine nucleotide exchange factors that modulate the GTPase activity, preferably in the presence of GEF enhancers, exemplary guanine nucleotide exchange factors being Rac-GEF and Tiam-1, which are encoded by certain nucleic acid sequences that are herein described, along with uses for the guanine nucleotide exchange factors and the nucleic acid sequences including screening for ligands which recognize Rac-GEF, regulators of Rac-GEF activity, and methods of treating pathological conditions associated or related to a Ras superfamily GTPase, including Rac.

Abstract: Methods and compositions for treating and diagnosing neoplastic disease using viruses are provided. Preferably, mutant adenovirus lacking viral proteins which bind and/or inactivate p53 are administered to a patient having a neoplasm which comprises cells exhibiting p53 and lacking, or substantially devoid of mismatch repair activity. The mutant virus is able to substantially produce a replication phenotype in such neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 function. The preferential generation of a replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.

Abstract: The present invention relates to all aspects of a guanine exchange factor (GEF), for example, a Rho-GEF, such as p115 Rho-GEF. A GEF modulates cell signaling pathways, both in in vitro and in vivo, by modulating the activity of a GTPase. By way of illustration, a p115 Rho-GEF, which modulates the activity of a Rho GTPase, is described. However, the present invention relates to other GEFs, especially other Rho-GEFs. The present invention particularly relates to an isolated p115 Rho-GEF polypeptide or fragments of it, a nucleic acid coding for p115 Rho-GEF or fragments of it, and derivatives of the polypeptide and nucleic acid. The invention also relates to methods of using such polypeptides, nucleic acids, or derivatives thereof, e.g., in therapeutics, diagnostics, and as research tools.

Abstract: The present invention provides novel recombinant baculovirus expression systems for expressing foreign genetic material in a host cell. Such expression systems are readily adapted to an automated method for expression foreign genetic material in a high throughput manner. In other aspects, the present invention features a novel automated method for determining the function of foreign genetic material by transfecting the same into a host by way of the recombinant baculovirus expression systems according to the present invention.