Abstract: The invention provides cell lines which are useful for the rapid detection of enteroviruses. In particular, the invention provides transgenic African green monkey kidney cell lines and buffalo green monkey kidney cell lines. The invention provides cell lines which have increased sensitivity to infection by enteroviruses in single-cell type and mixed-cell type cultures compared to other cell types which are currently used for enterovirus detection. The cells of the invention also are permissive to infection by a larger number of enteroviruses as compared to the cell type from which they were derived.

Abstract: DNAs encoding monkey cathepsin S have been cloned and characterized. The recombinant protein is capable of forming biologically active protein. The cDNA's have been expressed in recombinant host cells that produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified.

Abstract: The present invention provides methods of purification of Hepatitis A Virus from the supernatant of an infected cell culture and production of a preparation of purified HAV antigen. The present invention is also directed to an HAV vaccine composition comprising a preparation consisting of purified mature HAV particles in an amount sufficient to induce a protective immune response in a mammal.

Abstract: Japanese macaques can harbor a virus related to RRV, called Japanese macaque herpesvirus (JMHV). An isolated virus is disclosed herein (Japanese macaque herpesvirus, JMHV) as deposited with ATCC as Deposit Accession No. PTA-1884, deposited May 18, 2000, as are viral particles including this virus and host cells infected with this virus. The entire nucleic acids sequence of this virus is provided herein. Also disclosed are the nucleic acid sequences of unique open reading frames, and the polypeptide sequences encoded by these open reading frames. Pharmaceutical compositions are also disclosed that include the viral nucleic acid, a polypeptide encoded by the viral nucleic acid, an antibody that binds the JMHV polypeptide, or a polynucleotide encoding at least one JMHV polypeptide. Model systems for screening for agents of use in the treatment of MS are also disclosed.

Abstract: Highly efficient gene transfer into primate-derived embryonic stem (ES) cells has successfully been achieved by using a simian immunodeficiency virus vector (SIV) pseudotyped with VSV-G protein, which is a surface glycoprotein of vesicular stomatitis virus (VSV) The present invention provides simian immunodeficiency virus vectors for gene transfer to primate ES cells. The method for gene transfer to primate ES cells using the vectors of the present invention is useful in, for example, research into embryology and disease, clinical applications, and experimental models for primates. The method is also useful in assaying and screening for genes and reagents able to enhance the specific differentiation of tissues or cells, and which are useful in preparing desired cells or tissues differentiated from ES cells.

Abstract: A cell-based assay system in which the detection of the reporter gene activity, or secreted alkaline phosphatase (SEAP), is dependent upon the protease activity of the Hepatitis C virus NS3 gene product. This system can be used to assess the activity of candidate protease inhibitors in a mammalian cell-based assay system. The assay system is simpler than previously described assays due to the use of SEAP which allows the reporter gene activity to be quantified by measuring the amount of secreted gene product in the cell media by monitoring the conversion of luminescent or calorimetric alkaline phosphatase substrate.

Abstract: The present invention provides genes encoding novel matrix metalloproteinases termed MMP; constructs and recombinant host cells incorporating the genes; the MMP polypeptides encoded by the genes; antibodies to the MMP polypeptides; and methods of making and using all of the foregoing.

Abstract: The present invention makes available powerful tools for the study of cancer, based on a novel expression construct for a constitutively active hydrocarbon receptor CA-AhR. The invention further comprises transgenic non-human animals, preferably mammals, expressing CA-AhR in one or more tissues thereof. An animal model based on the transgenic non-human animals forms the basis for novel methods e.g. for the study of cancer; for the screening of compounds, such as drug candidates; for the investigation of the molecular mechanisms of cancer, in particular stomach cancer; for the investigation of the mechanisms of highly differentiated adenocarcinoma etc. Likewise, in vitro models based on transformed cells or cell lines, functionally incorporating the inventive construct are disclosed.

Abstract: A live hepatitis A virus adapted to growth in MRC-5 cells, which HAV is preferably characterized by suitable attenuation for effective vaccine administration to humans and animals without inactivation, methods for adapting HAV to growth in MRC-5, vaccine compositions and method of vaccinating humans against HAV infection.

Abstract: A method of providing papillomavirus like articles which may be used for diagnostic purposes or for incorporation in a vaccine for use in relation to infections causd by papillomavirus. The method includes an initial step of constructing one or more recombinant DNA molecules which each encode papillomavirus L1 protein or a combination of papillomavirus L1 protein and papillomavirus L2 protein followed by a further step of transfecting a suitable host cell with one or more of the recombinant DNA molecules so that virus like particles (VLPs) are produced within the cell after expression of the L1 or combination of L1 and L2 proteins. The VLPs are also claimed per se as well as vaccines incorporating the VLPs.

Abstract: An enzyme solution for subculturing primate embryonic stem (ES) cells and a method of culturing primate ES cells is described herein. The enzyme solution comprises trypsin, calcium chloride and a serum substitute. The culturing method comprises the step of culturing primate ES cells in a solution comprising trypsin and calcium chloride, and optionally a serum substitute. The solution and method of this invention enable one to stably maintain and propagate ES cells derived from a primate, such as monkey or human, for a long period in an undifferentiated state and with a normal karyotype.

Abstract: In accordance with the present invention, there are provided nucleic acids encoding human metabotropic glutamate receptor subtypes and the proteins encoded thereby. In a particular embodiment, the invention nucleic acids encode mGluR1, mGluR2, mGluR3 and mGluR5 subtypes of human metabotropic glutamate receptors. In addition to being useful for the production of metabotropic glutamate receptor subtypes, these nucleic acids are also useful as probes, thus enabling those skilled in the art, without undue experimentation, to identify and isolate related human receptor subunits. In addition to disclosing novel metabotropic glutamate receptor subtypes, the present invention also comprises methods for using such receptor subtypes to identify and characterize compounds which affect the function of such receptors, e.g., agonists, antagonists, and modulators of glutamate receptor function.

Abstract: The present invention provides a human polypeptide homolog of human tankyrase protein (THP) and polynucleotides which identify and encode THP. In addition, the invention provides expression vectors, host cells and methods for its production. The invention also provides methods for the identification of THP agonists/antagonists, useful for the treatment of human diseases, such as human cancer and age related diseases.

Abstract: The present invention relates to the determination of an authentic HCV genome RNA sequences, to construction of infectious HCV DNA clones, and to use of the clones, or their derivatives, in therapeutic, vaccines, and diagnostic applications. The invention is also directed to HCV vectors, e.g., for gene therapy of gene vaccines.

Abstract: The invention is directed to novel systems for the high level production of purified recombinant adeno-associated virus (rAAV) vector stocks comprising producer cell lines and helper adenoviruses. These systems provide high level production of rAAV vector stocks that are not contaminated by helper viruses or have very minimal contamination with helper virus. The invention is also directed to methods for the production of high yield, purified rAAV vector stocks using the systems of the invention.

Abstract: The present invention generally relates to the field of diagnostic microbiology, and, more particularly, to compositions and methods for detecting and differentiating one or more viruses or other intracellular parasites present in a specimen. The present invention also provides compositions and methods to evaluate the susceptibility of a organisms to antimicrobial agents.

Abstract: A cell culture medium which is low in dissolved carbon dioxide is disclosed. The medium contains less than about 1 g/L added sodium bicarbonate and includes an organic buffer and a metal complexing agent. The medium is preferably essentially free of added sodium bicarbonate. Methods of use of the medium in culturing mammalian cells, particularly cells engineered to produce recombinant factor VIII, are also disclosed.

Abstract: The invention is directed to novel systems for the high level production of purified recombinant adeno-associated virus (rAAV) vector stocks comprising producer cell lines and helper adenoviruses. These systems provide high level production of rAAV vector stocks that are not contaminated by helper viruses or have very minimal contamination with helper virus. The invention is also directed to methods for the production of high yield, purified rAAV vector stocks using the systems of the invention.

Abstract: The present invention discloses a novel secreted polypeptide, termed Osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding Osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind Osteoprotegerin, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis.

Abstract: The DNA encoding the cell surface receptor for thrombin has been cloned and sequenced. The availability of this DNA permits the recombinant production of thrombin receptor which can be produced at cell surfaces and is useful in assay systems both for the detection of thrombin and for the evaluation of candidate thrombin agonists and antagonists. Further, the elucidation of the structure of the thrombin receptor permits the design of agonist and antagonist compounds which are useful diagnostically and therapeutically. The availability of the thrombin receptor also permits production of antibodies specifically immunoreactive with the receptor per se or with specific regions thereof which are also useful diagnostically or therapeutically.

Abstract: Embodiments of the present invention are directed to non-naturally occurring cells and methods for screening compositions and genes which interact with interleukin 1 beta and interleukin-1 beta converting enzyme (ICE) processing, methods and non-naturally occurring cells for making ICE, and agonists and inhibitors of ICE.

Abstract: A novel polypeptide, designated neuronal factor (NF), has been identified by PCR amplification of human genomic DNA. Provided herein is nucleic acid encoding NF useful in diagnostics and in the recombinant preparation of NF. NF is used in the treatment of nerve cells and in diagnostic assays.

Abstract: The replication machinery of polio virus is used to express heterologous gene products, such as chloramphenicol acetyl transferase, in mammalian cells. Detectable expression following DNA transfection demonstrated that a polio replicon containing a foreign gene in the P1 region transcribed from an inducible promoter can be exported from the nucleus to the cytoplasm. The proteins in the P2/P3 region of the RNA can be translated and thereby render the RNA capable of replication. A stable cell line harbouring the polio replicon in the genome results in constitutive expression of chloramphenicol acetyl transferase or other heterologous gene product.

Abstract: Viruses from the family Orthomyxoviridae, particularly influenza virus, can grown in monkey kidney cells, particularly Vero Cells, after passaging the cells in a serum-free or protein-free medium. The use of a proteolytic enzyme, especially trypsin, also aids in the propagation of the virus. The method allows for the virus to be produced to be used in a vaccine.

Abstract: The present invention provides a method for producing a rotavirus antigen which the mass culture is difficult, comprising cloning a cell highly permitting the proliferation of rotavirus from a cell culture; preparing a cloned cell adapted-rotavirus strain by passaging a rotavirus in the resulting cloned cell strain and adapting the rotavirus to the cloned cell strain; culturing as a seed virus the adapted rotavirus strain or a reassortant prepared by using the adapted rotavirus strain as a parent strain; and isolating and purifying the rotavirus antigen from the culture medium of the seed virus; and additionally provides an rotavirus antigen, a vaccine against rotavirus infections, and a diagnostic agent of the diseases, as produced by using the antigen. These antigen, vaccine and diagnostic agent can make great contributions to individual fields of the fundamental research works and clinical application, relating to rotavirus infections.

Abstract: Isolated DNA encoding each of human calcium channel .alpha..sub.1 -, .alpha..sub.2 -, .beta.- and .gamma.-subunits, including subunits that arise as splice variants of primary transcripts, is provided. In particular DNA clones encoding each of the .alpha..sub.1A-1, .alpha..sub.1A-2, .alpha..sub.1E-1, .alpha..sub.1C-2, .alpha..sub.1E-3, .beta..sub.3-1, .beta..sub.2C, .beta..sub.2D, .beta..sub.2E and .beta..sub.4 subunits of human calcium channels are provided. Cells and vectors containing the DNA, subunit specific antibodies and nucleic acid probes and methods for identifying compounds that modulate the activity of human calcium channels are also provided.

Abstract: Methods, including culture media conditions, which provide for isolation and purification of renal tubule stem cells and for in vitro kidney tubulogenesis are disclosed. The methods rely on culturing adult kidney cells in a culture media treated with combinations of transforming growth factor-.beta..sub.1, epidermal growth factor, and all-trans retinoic acid.

Abstract: This invention provides a method for obtaining a recombinant retroviral packaging cell capable of producing retroviral vectors as well as the recombinant packaging cell obtained by the method. Also provided is a method of producing recombinant retroviral particles obtained by introducing into the packaging cells obtained according to the methods disclosed herein, a recombinant retroviral vector and propagating the resulting producer cells under conditions favorable for the production and secretion of retroviral vector supernatant. The retroviral supernatant produced by these methods also is claimed herein. This invention further provides a method for screening retroviral vector supernatant for high transduction efficiency and methods for producing retroviral vector supernatant for transducing cells with high efficiency in gene therapy applications.

Abstract: An isolated and purified nucleic acid comprising:a nucleotide sequence which has at least 50% sequence identity, with any of the nucleotide sequences coding for polypeptides containing in their pepridic chains:the amino acid sequence of 311 amino acids of FIGS. 2 or 3,or a fragment of this sequence being such that it is able to produce antibodies capable of forming a complex with the amino acid sequence of FIG. 2 or 3,or an amino acid sequence having a percentage of homology of at least 50%, with the amino acid sequence of FIG. 2 or 3,or a sequence able to form a complex with antibodies raised against the amino acid sequence of FIG.

Abstract: Methods and compositions are provided for expression of mammalian genes in culture. An amplifiable gene is introduced by homologous recombination in juxtaposition to a target gene, the resulting combination of amplifiable gene and target gene transferred to a convenient host and the target gene amplified by means of the amplifiable gene. The resulting expression host may then be grown in culture with enhanced expression of the target gene.

Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of weight, and to the diagnostic and therapeutic uses to which such modulators may be put. In its broadest aspect, the present invention relates to the elucidation and discovery of nucleotide sequences, and proteins putatively expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight. The nucleotide sequences in object represent the genes corresponding to the murine and human ob gene, that have been postulated to play a critical role in the regulation of body weight and adiposity. Preliminary data, presented herein, suggests that the polypeptide product of the gene in question functions as a hormone.

Abstract: This invention relates to novel mammalian excitatory amino acid transporter proteins and genes encoding such proteins. The invention is directed towards the isolation, characterization and use of human excitatory amino acid transporter proteins for pharmacological screening of analogues, agonists, antagonists, inhibitors, modulators and facilitators of excitatory amino acid transport in a variety of tissues, particularly neuronal tissues. This invention provides isolated nucleic acid encoding a novel excitatory amino acid transporter subtype that is specifically expressed in retina. Also provided are recombinant expression constructs capable of expressing this novel transporter in transformed prokaryotic and eukaryotic cells, and also provides such transformed cell cultures producing the novel human transporter. Purified transporter protein and membranes comprising the transporter protein are also provided.

Abstract: Antigens derived from Taenia crassiceps have been isolated which have specificity and sensitivity in their reactivity with antibodies against Taenia saginata and Taenia solium. These antigens may therefor be used in diagnostic testing for the serological screening of livestock for cysticercosis, rather than relying upon methods involving dissection and visual examination.

Abstract: Novel peroxisome proliferator-activated receptor subunits designated PPAR.gamma. and PPAR.delta. are described. Nucleic acid sequences encoding the receptor subunits, expression vectors containing such sequences and host cells transformed with such vectors are also disclosed, as are heterodimeric PPAR receptors comprising at least one of the invention subunits, and methods for the expression of such novel receptors, and various uses therefor.

Abstract: Isolated DNA encoding each of human calcium channel .alpha..sub.1 -, .alpha..sub.2 -, .beta.- and .gamma.-subunits, including subunits that arise as splice variants of primary transcripts, is provided. Cells and vectors containing the DNA and methods for identifying compounds that modulate the activity of human calcium channels are also provided.

Abstract: A novel HSV mini viral vector is disclosed. The vector comprises HSV and EBV genes which allow it to remain in episomal state, to have very high transfection and infection, and to tolerate up to 140 kb of foreign DNA. Techniques and genetic constructs for producing the vectors, for constructing the vectors and transfection and infection to recipient cells are disclosed.

Abstract: Cell lines that express complementing levels of herpes simplex virus (HSV) essential immediate early proteins ICP4 and ICP27 as well as ICP4, ICP27 and ICP0 and a method of producing the novel cell lines are disclosed. These cell lines are utilized to provide HSV strains deficient for both (a) ICP4 and ICP27; (b) ICP4, ICP27, ICP22; (c) ICP4, ICP27, ICP0; and, (d) ICP4, ICP27, ICP22 and ICP0, and their generation, and HSV strains deficient for (a) ICP4 and ICP27; (b) ICP4, ICP27, ICP22; (c) ICP4, ICP27, ICP0; and, (d) ICP4, ICP27, ICP22 and ICP0, and one or more additional genes, and their generation. Vectors are provided from these methods of using these HSV strains for gene transfer and for producing site-specific homologous recombination with cellular DNA.

Abstract: The invention relates to polynucleotides which contain pseudorabies virus sequences, in particular sequences from the gII region of PRV, in the antisense orientation, their preparation and their use.

Abstract: The invention relates to Arginase II polypeptides, polynucleotides encoding the polypeptides, methods for producing the polypeptides, in particular by expressing the polynucleotides, and agonists and antagonists of the polypeptides. The invention further relates to methods for utilizing such polynucleotides, polypeptides, agonists and antagonists for applications, which relate, in part, to research, diagnostic and clinical arts.

Abstract: The present invention relates to the acid sphingomyelinase gene and to methods of diagnosing Niemann-Pick disease. It is based, at least in part, on the cloning and expression of the full-length cDNA encoding acid sphingomyelinase and on the discovery of mutations in the acid sphingomyelinase gene of Ashkenazi Jewish Niemann-Pick disease patients.

Abstract: A method for introducing a mutation into a desired site in Herpes Simplex Virus Type 1 uses a set of starting vectors, where each starting vector has a fragment of the substantially complete HSV-1 genome and also DNA which overlaps with a sequential genomic fragment contained in other starting vectors, so that upon co-transfection of a host cell, replication of viral DNA, and recombination, a mutated replicable virus is formed. The starting vector containing a gene which is to be mutated is replaced by a replacement vectors. The replacement vectors contain a copy of the mutated gene and overlapping DNA, and genomic DNA which was present in the starting vector. A host cell is transformed with the replacement vectors and the remaining starting vectors under conditions allowing replication of viral DNA and recombination to form a replicating mutated virus. In preferred embodiments, the protease gene is mutated.

Abstract: The invention resides in a matrix, i.e. in a carrier material, with human or animal cells adherently bound thereto, the cells being infected with virus. It has shown that surface-dependent cells suitable for virus propagation remain adherently bound to a matrix even in the virus-infected state, continuously produce virus antigen over relatively long periods of time and deliver them into the culture medium. For producing TBE virus antigen by growing tick-borne encephalitis (TBE) virus in cell cultures, a surface-dependent permanent cell line, preferably the Vero cell line ATCC CCL 81, is inoculated with TBE virus, and the cells are kept bound to carriers in a non-lyric serum-free system while maintaining the cell growth, so as to maintain antigen formation, whereupon the antigen-containing medium is separated form the carrier-bound cells and, in a known manner, is processed to a galencially acceptable preparation by concentration, inactivation and purification.

Abstract: A method is provided for increasing the fertilization potential of oocytes comprising culturing oocytes in vitro with an effective amount of inhibin, activin, or a combination of inhibin and activin. Preferably the oocytes being cultured are immature. After the culturing step, the oocytes can be fertilized. The oocytes are suitably cryopreserved and thawed before the culturing step.

Abstract: Packaging defective and packaging proficient HIV vectors are disclosed. These vectors can be used to establish HIV packaging defective cell lines, and to package desired genes. These cell lines can be used in developing a vaccine, HIV antibodies and as part of a system for gene transfer. The packaging proficient vector can be used to target HIV target cells.

Abstract: DNA encoding the prepro inhibin .alpha. and .beta. chains has been isolated. This DNA is ligated into expression vectors and used to transform host cells for the preparation of inhibin or activin. Also provided are prohormone domains and other inhibin .alpha. or .beta. chain derivatives having therapeutic or diagnostic interest. The compositions provided herein are useful in the manipulation of fertility in animals.

Abstract: Disclosed is an isolated and purified feline immunodeficiency virus (FIV) culture having the identifying characteristics of FIV isolate NCSU.sub.1. A biologically pure culture of host cells containing a FIV having the identifying characteristics of FIV isolate NCSU.sub.1 is also disclosed, along with isolated and purified DNA coding for (a) an FIV having the identifying characteristics of FIV isolate NCSU.sub.1, or (b) an antigenic fragment of an FIV having the identifying characteristics of FIV isolate NCSU.sub.1. Various vaccine formulations containing active agents derived from the foregoing FIV virus, DNA encoding the virus, and DNA encoding antigenic fragments of the virus are also disclosed herein.Also disclosed are immunodeficient mice containing feline tissue, which feline tissue is capable of infection with a feline immunodeficiency virus such as (but not limited to) FIV isolate NCSU.sub.1.

Abstract: Purified bone morphogenetic protein-9 (BMP-9) proteins and processes for producing them are disclosed, The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair.

Abstract: The present invention relates to novel mammalian amino acid transporter proteins and the genes that encode such proteins. The invention is directed toward the isolation, characterization and pharmacological use of the human amino acid transporter proteins EAAT1, EAAT2, EAAT3 and ASCT1. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to each of these transporter genes. Also provided are recombinant expression constructs capable of expressing each of the amino acid transporter genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the human amino acid transporter proteins encoded therein. The invention also provides methods for screening in vitro compounds having transport-modulating properties using preparations of transporter proteins from such cultures of cells transformed with recombinant expression constructs.

Abstract: The present invention relates to a novel mammalian methadone-specific opioid receptor protein and genes that encode a such protein. The invention is directed toward the isolation, characterization and pharmacological use of mammalian methadone-specific opioid receptor proteins. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to the rat homologue or the mammalian methadone-specific opioid receptor gene. Also provided are recombinant expression constructs capable of expressing the mammalian methadone-specific opioid receptor genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the mammalian methadone-specific opioid receptor proteins encoded therein.

Abstract: Novel cell lines that express complementing levels of herpes simplex virus (HSV) essential immediate early proteins ICP4 and ICP27 and a method of producing the novel cell lines. These novel cell lines are utilized to provide novel HSV strains deficient for both ICP4 and ICP27, and their generation, and novel HSV strains deficient for ICP4 and ICP27 and one or more additional genes, and their generation. Vectors are provided from these methods of using these vectors for gene transfer and for producing site-specific homologous recombinations with cellular DNA.