Abstract: Compositions, and uses thereof, which are beneficial for eukaryotic cells in culture, and methods for their use in promoting cell growth, viability and recombinant protein expression. The methods disclosed in the present application are useful, for example, for improving cell viability and in accelerating the rate of cell growth of cells grown in culture. In one aspect, the supplements of the invention are useful for improving or enhancing the yield of the recombinant proteins from the cell cultures.

Abstract: A promoter comprising nucleotides from positions 2489-3038 of FIG. 3.

Abstract: The present invention is directed generally to metal binding compounds which may be added to cell culture media to replace factors required for cultivation of the cells (e.g. transferrin) which are of animal or human origin. More specifically, the invention is directed to metal binding compounds or complexes thereof comprising one or more transition element cations (such as ferrous or ferric ions), which are added to cell and tissue culture medium compositions. The metal binding compounds may be added to the media alone or may be first complexed with a transition metal ion. The invention is also directed to methods of use of such compositions, including, for example, methods for the cultivation of eukaryotic cells, particularly animal cells, in vitro. The invention also relates to compositions comprising such culture media and one or more cells, and to kits comprising one or more of the above-described compositions.

Abstract: The invention provides a novel method for generating stable mammalian cell lines with enhanced protein production capabilities, and to expression vectors and related methods for high level expression of biopharmaceutical proteins of interest.

Abstract: Disclosed herein are methods and compositions for inactivating a FUT8 gene, using fusion proteins comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.

Abstract: This invention is in the general field of recombinant expression of polypeptides in animal cell culture. More particularly, the invention concerns improved selection in cells of recombinantly engineered vectors designed to express polypeptides.

Abstract: The subject of the present invention is a process for producing adherent cells comprising: a. introducing a suspension of adherent cells into a culture vessel containing microcarriers in a culture medium; b. amplifying the cells by performing a plurality of cell passages in the same culture vessel wherein each cell passage subsequent to the first is carried out: i) by using all or part of the cells produced during the previous cell passage after having subjected the cells to enzyme treatment to detach the cells from the microcarriers, and ii) by introducing culture medium and an increasing amount of microcarriers into the culture medium; and c. harvesting the cells produced during the last cell passage, optionally after having subjected the cells to enzyme treatment to detach cells from microcarriers. The invention also relates to the implementation of this process for the production of biological agents, serving in particular to prepare vaccines or drugs.

Abstract: An isolated nucleic acid molecule capable of expressing an human ether-à-go-go related gene (hERG) mutant that enhances hERG inactivation, wherein the mutation is not located in the vicinity of the drug-binding pocket within the cavity of the ion conduction pore of the hERG protein. Use of the isolated nucleic acid molecule in an assay for screening potential drug binding to hERG protein.

Abstract: The present invention relates to a cell-based method for producing influenza virus vaccines by enriching the population of surface-bound ?2,6-sialic acid receptors on a cell surface, such as on a Chinese Hamster Ovary (CHO) cell surface. The host cell therefore presents numerous binding sites to which an influenza virus can bind via its hemagglutinin spike protein and infect the host cell. In contrast to wild-type CHO cells, the surface of the mutated CHO cells of the present invention contains an enriched population of ?2,6-sialic acid receptors which makes the inventive CHO cells highly susceptible to viral infection, and therefore safe, effective, and highly efficient cells for rapidly producing influenza vaccines.

Abstract: Polynucleotide and polypeptide sequences that encode novel variants of mouse or human thyroid stimulating hormone-? proteins are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications to prevent, treat or reduce the severity of thyroid stimulating hormone-?-related disorders.

Abstract: The invention relates to methods for propagating viruses. In particular, the invention provides optimized conditions for propagating viruses. Optimization of the following parameters are provided: lipid concentrates as supplements to the medium, temperature shift from pre-infection to post-infection, multiplicity of infection, direct bead-to-bead transfer and serum supplementation of pre-infection medium. In particular, the invention provides for the first time a method for propagating a virus by culturing cells that are infected with the virus in a medium comprising chemically defined lipid concentrate (CDLC). In another claim, the CDLC is added to medium that is substantially free of serum for culture of virus-infected cells.

Abstract: The document provides nucleic acids, polypeptides, and viruses containing nucleic acids and/or polypeptides. The document also provides methods for using viruses to treat cancer patients. Specifically, the document provides nucleic acid molecules encoding viral hemagglutinin (H) polypeptides, viral H polypeptides, and viruses containing nucleic acids and/or H polypeptides. Such viruses are useful for vaccinations and for treating cancer patients as the viruses are not shed.

Abstract: The present invention relates to the cloning, identification and characterization of the unique and entire genomic sequences encoding new porcine DC-SIGN and LSECtin proteins, including the novel nucleotide sequences of the full-length cDNA and genes of both pDC-SIGN gene and pLSECtin. Also provided are the nucleic acid molecules encoding newly discovered porcine ICAM-3 isoforms from porcine monocyte-derived dendritic cells and the use thereof. Specifically, the invention is drawn to an isolated nucleic acid molecule comprising a nucleotide sequence encoding one or more of porcine DC-SIGN, porcine ICAM-3, porcine LSECtin, a complement of the nucleotide sequence or a functional, defined portion of the nucleotide sequence or a protein fusion product linked to a protein that may be of porcine or human origin.

Abstract: Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.

Abstract: Disclosed herein are methods and compositions for inactivating a glutamine synthetase (GS) gene, using fusion proteins comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.

Abstract: Phosphorylated Apoptin is described. Apoptin is tumor-specifically phosphorylated and part of the Apoptin apoptotic pathway in tumor cells is elucidated. New therapeutic possibilities, for example, novel therapeutic compounds that can work alone or, sequentially to, or jointly with other known compounds. Also, the use of tumor-specifically phosphorylation of Apoptin for diagnostic purposes is described. Such a diagnostic purpose can, for example, be a method for detecting the presence of cancer cells or cells that are cancer prone or a method to identify a putative cancer inducing agent or a method for the in vitro treatment effect of Apoptin on tumor cells by testing the phosphorylation state of Apoptin. Even more, the invention provides possibilities to further elucidate the apoptotic pathway and to identify for example crucial mediators of phosphorylation in human tumor cells. Interfering with such a mediator could provide new anti-cancer therapies.

Abstract: The present invention relates to the use of a new isolate of Neospora caninum for the development of diagnostic tests and for the manufacture of products for the treatment and prevention of the infection caused by Neospora. The use of a new isolate of Neospora caninum (filed in the Culture Collection of Algae and Protozoa, with access number CCAP 2051/1), and the extracts obtained therefrom, in the preparation of diagnostic tests and in the manufacture of products for the treatment and prevention of the infection caused by Neospora, is based on the ease with which the new isolate converts from the tachyzoite to the bradyzoite stage under in vitro conditions. Additionally and with the same applications, the polypeptides and the polynucleotides obtained from the new isolate and the immunoreactive antibodies developed against Neospora antigens are used.

Abstract: The present invention provides compositions and methods for the detection of the presence, absence, or quantity of a segmented negative strand RNA virus such as an influenza virus. A genetically engineered vertebrate cell comprising an artificial segment comprising a 5? UTR and a 3? UTR of a segmented negative strand RNA virus and an open reading frame of a reporter gene, preferably in an anti-sense orientation, is contacted with a biological specimen suspected of comprising a segmented negative strand virus. Infection of the cell with a segmented negative strand RNA virus results in expression of a polypeptide encoded by the reporter gene. A genetically engineered cell of the invention can also comprise a recombinant DNA encoding the artificial segment. The recombinant DNA can comprise a promoter for RNA Polymerase I for directing transcription of the artificial segment.

Abstract: The present invention relates to a method to enhance cell growth in culture comprising adding an alkyl-amine-n-oxide (AANOx), such as dodecyldimethylamine oxide (DDAO), into the culture medium in an amount sufficient to improve cell growth.

Abstract: The invention relates to means and methods for regulating gene expression and production of proteinaceous molecules. The invention provides a method for producing a proteinaceous molecule in a cell comprising selecting a cell for its suitability for producing the proteinaceous molecule, providing a nucleic acid encoding the proteinaceous molecule with a nucleic acid comprising a STAR (STabilizing Anti-Repression) sequence, expressing the resulting nucleic acid in the cell and collecting the proteinaceous molecule. Providing at least one STAR sequence to a nucleic acid encoding a proteinaceous molecule will enhance production (yield) of the proteinaceous molecule by a host cell, increase the proportion of host cells with acceptable expression levels, and/or increase stability of a gene expression level.

Abstract: In this application is described isolated, recombinant CapD and recombinant PghP for use in digesting capsule comprising polyglutamate polymers and for treatment of infections caused by bacilli having a polyglutamate capsule, such as anthrax.

Abstract: Antigen binding proteins that bind to human CGRP receptor (CGRP R) are provided. Nucleic acids encoding the antigen binding protein, vectors, and cells encoding the same are also provided. The antigen binding proteins can inhibit binding of CGRP R to CGRP, and are useful in a number of CGRP R related disorders, including the treatment and/or prevention of migraine headaches.

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 organisms to antimicrobial agents.

Abstract: Virus-like particles (VLPs) of mammalian-hosted viruses, such as SARS-CoV and influenza viruses, have been recombinantly produced from Vero cells. The VLPs closely emulate the exterior of authentic virus particles and are highly immunogenic. They can elicit not only humoral but also cellular immune responses in a mammal. Compositions and methods related to the VLPs are also described.

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that bind to CD44, and that function to inhibit CD44. The invention also relates to heavy and light chain immunoglobulins derived from human CD44 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human CD44 antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions or medicaments for treatment.

Abstract: This invention relates to the general field of recombinant expression of polypeptides in animal cell culture. More particularly, the invention concerns improved selection in cells of recombinantly engineered vectors designed to express polypeptides.

Abstract: The present invention relates to an isolated novel virus causing Severe Acute Respiratory Syndrome (SARS) in humans (“hSARS virus”). The hSARS virus is identified to be morphologically and phylogenetically similar to known member of Coronaviridae. The present invention provides the complete genomic sequence of the hSARS virus. Furthermore, the invention provides the nucleic acids and peptides encoded by and/or derived from the hSARS virus and their use in diagnostic methods and therapeutic methods, including vaccines. In addition, the invention provides chimeric or recombinant viruses encoded by said nucleotide sequences and antibodies immunospecific to the polypeptides encoded by the nucleotide sequences.

Abstract: The present invention provides an isolated polynucleotide comprising or consisting of the nucleotide sequence encoding the G protein of human respiratory syncytial virus (RSV), wherein the nucleotide sequence is codon optimised for expression in mammalian cells and wherein the polynucleotide provides increased expression of the G protein in mammalian cells relative to expression of the wildtype RSV-G gene. Preferably, the polynucleotide comprises or consists of the nucleotide sequence of SEQ ID NO:2. Further aspects of the invention provide pharmaceutical compositions, in particular vaccines, for use in methods of immunising a subject against RSV infection.

Abstract: The present invention provides a system for analyzing interactions between glycans and interaction partners that bind to them. The present invention also provides HA polypeptides that bind to umbrella-topology glycans, and reagents and methods relating thereto.

Abstract: A serum-free Vero cell banking process provides a standardized and consistent way to generate reliable and stable cell banks for viral vaccine production. The substitution of animal-derived substances with plant-derived substances in the growth and freezing media increases the viability of the cells upon thawing and reduces their recovery time, thereby allowing a more precise schedule for manufacturing and more consistent processes.

Abstract: The invention relates to a Vero cell line that can be grown in serum-free and protein-free culture and in suspension culture in the absence of carrier for its adherence, and to production of viral vaccines using said cell line. More particularly, the present invention relates to establishment of a cell line that can be grown in suspension culture without need of the cells to be adhered to any supporting material. Furthermore, the present invention provides a process to obtain said Vero cell line and a process for producing viral vaccines with said cell line. The present invention further relates to the viruses obtained using the inventive method and to the vaccines formulated with said viruses.

Abstract: The present invention relates to the field of animal health and in particular of Equine Herpes Viruses (EHV) wherein the gene encoding the protein gM is absent, and which is free of heterologous elements. Further aspects of the invention relate to pharmaceutical compositions comprising said viruses, uses thereof, and methods for the prophylaxis and treatment of EHV infections. The invention also relates to pharmaceutical compositions comprising the combination of EHV-1 and EHV-4 viruses wherein the gene encoding the protein gM is absent and which is free of heterologous elements.

Abstract: Isolated nucleic acids encoding T2R76 polypeptides, recombinantly expressed T2R76 polypeptides, heterologous expression systems for recombinant expression of T2R76 polypeptides, assay methods employing the same, and methods for altering taste perception via administration of a T2R76 modulator. These T22R76 polypeptides can be expressed alone or co-expressed with another T2R polypeptide, preferably a different human T2R polypeptide.

Abstract: The invention provides adenovirus and retrovirus vectors useful to prepare influenza virus. Also provided is a canine RNA polymerase I promoter and vectors having that promoter.

Abstract: The present invention relates to the identification of the cytosolic phosphoprotein CRMP4b as a protein that physically and functionally interacts with RhoA to mediate neurite outgrowth inhibition. siRNA-mediated knockdown of CRMP4 promotes neurite outgrowth on myelin substrates indicating a critical role for CRMP4 in neurite outgrowth inhibition. Disruption of CRMP4b-RhoA binding with a competitive inhibitor attenuates neurite outgrowth inhibition on myelin and aggrecan substrates. Stimulation of neuronal growth cones with Nogo leads to co-localization of CRMP4b and RhoA at discrete regions within the actin-rich central and peripheral domains of the growth cone indicative of a potential function in cytoskeletal rearrangements during neurite outgrowth inhibition. Together these data indicate that a RhoA-CRMP4b complex forms in response to inhibitory challenges in the growth cone environment and regulate cytoskeletal dynamics at distinct sites necessary for axon outgrowth inhibition.

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: The invention relates to means and methods for regulating gene expression and production of proteinaceous molecules. The invention provides a method for producing a proteinaceous molecule in a cell comprising selecting a cell for its suitability for producing the proteinaceous molecule, providing a nucleic acid encoding the proteinaceous molecule with a nucleic acid comprising a STAR (STabilizing Anti-Repression) sequence, expressing the resulting nucleic acid in the cell and collecting the proteinaceous molecule. Providing at least one STAR sequence to a nucleic acid encoding a proteinaceous molecule will enhance production (yield) of the proteinaceous molecule by a host cell, increase the proportion of host cells with acceptable expression levels, and/or increase stability of a gene expression level.

Abstract: The present invention relates to the discovery that the T1R receptors assemble to form functional taste receptors. Particularly, it has been discovered that co-expression of T1R1 and T1R3 results in a taste receptor that responds to umami taste stimuli, including monosodium glutamate. Also, it has been discovered that co-expression of the T1R2 and T1R3 receptors results in a taste receptor that responds to sweet taste stimuli including naturally occurring and artificial sweeteners. Also the present invention relates to the use of hetero-oligomeric taste receptors comprising T1R1/T1R3 and T1R2/T1R3 in assays to identify compounds that respectively respond to umami taste stimuli and sweet taste stimuli. Further, the invention relates to the constitutive of cell lines that stably or transiently co-express a combination of T1R1 and T1R3; or T1R2 and T1R3; under constitutive or inducible conditions.

Abstract: The present invention is a novel nucleic acid sequence which hybridizes to SEQ ID NO:6 or fragments thereof under stringent conditions, or fragments thereof. The invention also includes diagnostic assays, expression vectors, control sequences, antisense molecules, ribozymes, and host cells to express the polypeptide encoded by the nucleic acid sequence. The present invention also includes claims to the polypeptide sequence coded by the nucleic acid sequences.

Abstract: The invention concerns the use of cells capable of carrying out a process of prenylation of proteins coded by the hepatitis C virus (HCV) genome, such as prenylation of the NS5A protein, for replicating and, if required, the production of HCV or derivative viable mutants, in a suitable culture medium.

Abstract: This invention provides a novel transformed cell useful in constructing an anti-aging agent screening system, a screening method which uses the same and an anti-aging agent, and it relates to a transformed cell in which a gene coding for (a) a protein capable of phosphorylating p38 protein, or (b) p38 protein, a mutant of p38 protein, a kinase domain of p38 protein, a kinase domain of p38 protein mutant or a fusion protein containing them is transformed into a normal cell, a screening method which uses this transformed cell and an anti-aging agent which uses a compound obtained by the screening method as the active ingredient.

Abstract: The invention relates to means and methods for regulating gene expression and production of proteinaceous molecules. The invention provides a method for producing a proteinaceous molecule in a cell comprising selecting a cell for its suitability for producing the proteinaceous molecule, providing a nucleic acid encoding the proteinaceous molecule with a nucleic acid comprising a STAR (STabilizing Anti-Repression) sequence, expressing the resulting nucleic acid in the cell and collecting the proteinaceous molecule. Providing at least one STAR sequence to a nucleic acid encoding a proteinaceous molecule will enhance production (yield) of the proteinaceous molecule by a host cell, increase the proportion of host cells with acceptable expression levels, and/or increase stability of a gene expression level.

Abstract: Purified BMP-11 proteins and processes for producing them are disclosed. Recombinant DNA molecules encoding the BMP-11 proteins are also disclosed. The proteins may be useful in regulating follicle stimulating hormone, such as for contraception. In addition, the proteins may be useful for the induction of bone, cartilage and/or other connective tissue.

Abstract: A novel gene expressed selectively by osteoblast lines is provided. Expression of the gene is highly restricted to cells of osteoblast lineage, including precursor cells. Also provided is a method for promoting bone formation by providing agents that bind to the novel gene within osteoblast cells to stimulate bone formation.

Abstract: The present invention provides compositions useful in and methods for producing populations of infectious, replication-defective alphavirus replicon particles that contain no replication-competent alphavirus particles, as determined by passage on cells in culture. The compositions include helper and replicon nucleic acid molecules that can further reduce the predicted frequency for formation of replication-competent virus and can optimize manufacturing strategies and costs.

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: The present invention provides methods of large scale production of Hepatitis A Virus (HAV) on VERO cells bound to microcarrier. The invention also provides for methods of isolation of HAV from the cell culture supernatant of HAV infected VERO cells.

Abstract: The invention provides isolated nucleic acids molecules, designated 47153 nucleic acid molecules, which encode novel glycosyltransferase family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 47153 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 47153 gene has been introduced or disrupted. The invention still further provides isolated 47153 proteins, fusion proteins, antigenic peptides and anti-47153 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The present invention is directed to a cell line capable of supporting replication of a growth-defective Herpes Simplex Virus strain; specifically a replication-defective HSV-2 double mutant. Particularly disclosed is a cell line that expresses the ICP8 protein and the UL5 protein of Herpes Simplex Virus. This cell line is useful to propagate a replication-defective HSV-2 vaccine strain that contains mutations and/or deletions in the ICP8 and UL5 genes.