Abstract: The invention is concerned with the systematic elucidation and identification of regulatory sequences. The invention provides among others screenings and detection methods with which regulatory sequences can be identified. The invention further provides regulatory sequences and use thereof in various fields such as, but not limited to, protein production, diagnostics, transgenic plants and animals, and the therapeutic field.

Abstract: The invention is concerned with the systematic elucidation and identification of regulatory sequences. The invention provides among others screenings and detection methods with which regulatory sequences can be identified. The invention further provides regulatory sequences and use thereof in various fields such as, but not limited to, protein production, diagnostics, transgenic plants and animals, and the therapeutic field.

Abstract: The invention is concerned with the systematic elucidation and identification of regulatory sequences. The invention provides among others screenings and detection methods with which regulatory sequences can be identified. The invention further provides regulatory sequences and use thereof in various fields such as, but not limited to, protein production, diagnostics, transgenic plants and animals, and the therapeutic field.

Abstract: We describe (1) a method of enhancing antigen presentation, comprising the step of supplying to an antigen presenting cell such as a dendritic cell, or precursor cell, an inhibitor of Toll-related receptor (TRR) signalling and (2) a method of inhibiting antigen presentation, comprising the step of supplying to an antigen presenting cell such as a dendritic cell, or precursor cell, an enhancer of Toll-related receptor (TRR) signalling. The inhibitor of TRR signalling may be a dominant negative mutant of MyD88, for example MyD881pr.

Abstract: The invention provides methods and compositions for preparing antibodies and antibody derivatives with reduced core fucosylation.

Abstract: The invention is directed to an isolated polypeptide which (a) is obtainable from a teleost; (b) has antimicrobial activity; (c) binds to oligoguanosine and/or CpG (SEQ ID NO:7); (d) comprises 58 strongly basic amino acids selected from the group consisting of K and R; (e) comprises 50 hydrophobic amino acids selected from the group consisting of A, I, L, F, W and V; (f) comprises 50 polar amino acids selected from the group consisting of N, C, Q, S, T and Y and (g) contains 11 lysine-rich motifs and antimicrobial fragments thereof as well as methods for preparing said polypeptides, compositions and libraries comprising said polypeptide(s) and uses of said polypeptide(s), particularly in treating microbial infections. The invention is further directed to a nucleic acid(s) encoding said polypeptide, microarrays comprising said nucleic acid(s) and uses for said nucleic acid(s).

Abstract: The present disclosure features methods relating to conducting a stem cell technology business such as a regenerative medicine business based on induced pluripotent stem cells (iPSCs) and cells differentiated from iPSCs. The present disclosure also provides a database of iPSC-derived cells and methods of using the database for tracking customers and samples, as well as methods for marketing and running the business.

Abstract: The present invention relates to a method for detecting von-Willebrand factor (vWF) activity comprising assaying a sample in the presence of a soluble form or portion of glycoprotein Ib(?) (GPIb(?) and ristocetin, or a functionally equivalent substance. Additionally, the invention relates to the use of the aforementioned soluble form or portion of glycoprotein Ib(?), of ristocetin or a functional equivalent substance, of specifically reacting anti-GPIB(?) antibody(ies) and/or of specific binding partners, like specifically reacting anti-vWF antibody(ies) for carrying out the method of the invention. Furthermore, the present invention relates to kits for carrying out the method of the invention.

Abstract: The invention provides processes for recombinant production of erythropoietin (EPO) in a human embryonic retina cell that expresses at least an adenoviral E1A protein, wherein said EPO is produced at high concentrations and wherein said EPO as produced has a high average sialic acid content per EPO molecule.

Abstract: Therapeutic compositions used in the field of angiogenesis include nucleotide sequences of genes, the involvement of the genes in the angiogenesis mechanism having been demonstrated by the Applicant, and including the complementary sequences thereof, the antisense sequences of same, polypeptide sequences coded by the coding parts of the aforementioned genes and antibodies that are directed against the polypeptide sequences and also relate to genetically-modified cells that underexpress or overexpress the above-mentioned genes and to therapeutic compositions containing the cells, which are used to treat angiogenic disorders, and, moreover, relate to methods of diagnosing and/or prognosticating antigenic disorders and to novel methods of screening active compounds in the treatment of the disorders.

Abstract: A highly efficient method of making a primary cell derived biologic by purifying mononuclear cells (MNCs) in a automated cell processor to remove contaminating cells by loading leukocytes onto lymphocyte separation medium (LSM) and centrifuging the medium to obtain purified MNCs, storing the MNCs overnight in a closed sterile bag system, stimulating an induction mixture of the MNCs with phytohemagglutinin (PHA) or other mitogen and ciprofloxacin in a scalable cell culture device and producing a primary cell derived biologic from the MNCs, removing the mitogen from the induction mixture by filtering, incubating the induction mixture, clarifying the induction mixture by filtering to obtain a primary cell derived biologic supernatant, and clearing the primary cell derived biologic supernatant from adventitious agents by anion exchange chromatography, filtration. A closed system prevents contamination of the resulting primary cell derived biologic. An automated method of purifying cells.

Abstract: The present invention provides a biomass which comprises avian embryonic particles having a particle size of about 0.5 mm to 10.0 mm and the use thereof in a method for the production of virus antigens. Also provided is a method for the preparation of a vaccine useful for the amelioration and prevention of viral disease.

Abstract: The present invention relates to a process for producing a desired polypeptide using rat cells. Specifically, the present invention relates to a process for producing the polypeptide which comprises culturing rat cells such as YB2/3HL.P2.G11.16Ag.20 (hereinafter referred to as YB2/0), preferably rat cells to which a recombinant DNA comprising DNA encoding a desired polypeptide such as an immunologically functional molecule is introduced, in a medium which does not contain serum (hereinafter referred to as a serum-free medium). Among the desired polypeptides obtained by the process of the present invention, an antibody obtained by using a transformant of YB2/0 has a high antibody-dependent cell-mediated cytotoxic activity (hereinafter sometimes referred to as ADCC activity) and is useful as a pharmaceutical agent.

Abstract: The present invention relates to a new polynucleotide that encodes a polypeptide involved in cellular entrance of PRRSV, to a recombinant vector comprising said polynucleotide, to a cell capable of expressing said polypeptide, a method of producing said polypeptide as well as to cell culture and to a novel method of producing the PRRSV virus. The present invention further relates to a method of identifying compounds that affect the PRRSV receptor function of the polypeptide as well as to the use of the polypeptide or identified compounds in the manufacture of medicaments. The present inventors have succeeded in isolating a protein from PAM membranes that seems to play a crucial role in virus entry into the cell. The elucidated nucleotide sequence encoding the protein, as well as the amino acid sequence of the protein, were compared with sequences stored in sequence databases.

Abstract: Modified porcine factor VIII is disclosed in which most of the B domain has been removed through genetic engineering. This modified factor VIII is particularly useful for treatment of hemophiliacs, especially those undergoing bleeding episodes.

Abstract: A method of inducing dendritic cell (DC) development by administering Macrophage-Colony Stimulating Factor Receptor Ligand is provided. M-CSF receptor ligands induce DCs to differentiate into subtypes, for example plasmacytoid DCs and conventional DCs. Induction with an M-CSF receptor ligand can be achieved in vitro from hematopoietic precursors, such as bone marrow cells, or in vivo. In vitro, M-CSF receptor ligand-derived DCs can be used to produce cytokines and to stimulate other immune response cells. M-CSF receptor ligands can also be used to induce precursor cells removed from an animal to develop into DCs. In addition, these isolated DCs can be exposed to antigens to stimulate a specific immune response when reintroduced into the animal. Treatments for cancers, such as Acute Myeloid Leukemia, and autoimmune diseases such as Systemic Lupus Erythematosus, are also provided in the invention.

Abstract: There is disclosed an isolated nucleic acid molecule encoding a human neurotrophic growth factor designated enovin and having the amino acid sequence illustrated in FIG. 1, 21, 23 or 24 or encoding a functional equivalent, derivative or bioprecursor of said growth factor. The growth factor preferably comprises the amino acid sequence from position 27 to 139 of the sequence illustrated in FIG. 1, or a functional equivalent, derivative or bioprecursor thereof. The nucleic acid molecule encoding enovin can be used to transform a host cell, tissue or organism by including it in an appropriate vector. The host cell, tissue or organism and the vector also form part of the invention.

Abstract: The present invention provides immortalized eukaryotic cells and methods useful for the production of immunologically active bivalent antibody fragments, such as F(ab?)2 fragments. The methods and cells of the invention result in a desirable ratio of bivalent to monovalent antibody fragments.

Abstract: Methods for producing a protein extract from cells, such as cells or cellular samples containing viral proteins, are provided. In general terms, the methods may involve: increasing the pH of the cells to a pH of at least about pH 10.0 to produce an intermediate composition, and then, in the presence of a non-ionic detergent such as a polyoxyethylene alkyl ether, neutralizing the pH of the intermediate composition to produce the protein extract. Such methods can be used in conjunction with methods for detecting one or more target proteins in a sample, such as viral proteins. Systems, kits and compositions for practicing the subject methods are also provided.

Abstract: The invention provides stable feed media containing pyruvate and methods for stabilizing feed media by adding pyruvate. The invention further provides methods for producing proteins using such media and proteins produced through the use of such methods.

Abstract: Disclosed herein 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. By transfecting cells in culture with an apoptosis-inhibiting gene or vector, cells in culture can survive longer, resulting in extension of the state and yield of protein biosynthesis. Expression of the apoptosis-inhibitor within the cells, because it does not kill the cells, allows the cells, or an increased fraction thereof, to be maintained in culture for longer periods. This invention then allows for controlled, enhanced protein production of cell lines for commercial and research uses, particularly the enhanced production of growth factors, interferons, interleukins, hormones, enzymes, and monoclonal antibodies, and the like.

Abstract: Compositions and methods for the inducible expression of genes in eukaryotic cells. Expression of a nucleotide sequence of interest is controlled by a regulatory fusion protein that consists of a transcription blocking domain and a ligand-binding domain. When the cognate ligand for the ligand-binding domain is present, transcription of the nucleotide sequence of interest is blocked. Upon removal of the cognate ligand, the nucleotide sequence of interest is transcribed. The method is useful for large scale production of a desired product in eukaryotic cells.

Abstract: The present invention provides isolated nucleic acid and amino acid sequences of sweet taste receptors comprising two heterologous G-protein coupled receptor polypeptides from the T1R family of sensory G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of sweet taste receptors.

Abstract: The invention relates to methods for cultivating mammalian cells and for producing recombinant proteins in large-scale cultures of such cells. The proteins are, e.g., Factor VII or Factor VII-related polypeptides.

Abstract: Compounds and methods for the diagnosis and treatment of Chlamydial infection are disclosed. The compounds provided include polypeptides that contain at least one antigenic portion of a Chlamydia antigen and DNA sequences encoding such polypeptides. Pharmaceutical compositions and vaccines comprising such polypeptides or DNA sequences are also provided, together with antibodies directed against such polypeptides. Diagnostic kits containing such polypeptides or DNA sequences and a suitable detection reagent may be used for the detection of Chlamydial infection in patients and in biological samples.

Abstract: The invention relates to methods of improving protein production, e.g., large-scale commercial protein production, e.g., antibody production, utilizing a modified fed-batch cell culture method comprising a cell growth phase and a polypeptide production phase. The modified fed-batch cell culture method combines both cell culture perfusion and fed-batch methods to achieve higher titers of polypeptide products. Because the modified fed-batch cell culture method of the invention produces higher polypeptide product titers than fed-batch culture alone, it will substantially improve commercial-scale protein production. The invention also relates to a perfusion bioreactor apparatus comprising a fresh medium reservoir connected to a bioreactor by a feed pump, a recirculation loop connected to the bioreactor, wherein the recirculation loop comprises a filtration device, e.g., ultrafiltration or microfiltration, and a permeate pump connecting the filtration device to a permeate collection container.

Abstract: A serum-free C3A clonal cell line and methods for generating the same are provided. The C3A cell line has a reduced doubling time in serum-free medium compared to a corresponding C3A cell line from which it is derived. Methods using the cells of the serum-free C3A clonal cell line for the production, expression and recovery of harvestable polypeptides, screening compounds for metabolic activity, studying enteric disease and for use in a bio-artificial liver device are also provided.

Abstract: The present invention relates to polynucleotide and polypeptide molecules for Zcyto21, an interferon-like protein, which is most closely related to interferon-? at the amino acid sequence level. The present invention also includes antibodies to the Zcyto21 polypeptides, and methods of using the polynucleotides and polypeptides.

Abstract: Culturing cells for the commercial production of proteins for diagnosis and therapy is a costly and time consuming process. The equipment required is expensive, and production cost are high. In order to provide commercially viable processes it is desirable to use cell lines which produce large quantities of product with each production run. However, most cells do not produce large quantities of desired product per se either because they do not produce a large quantity of product per unit of time (specific productivity) or because they do not survive long enough in the culture medium (time). Here, we identified that addition of a valproic acid compound to the culture medium increases overall (batch) yield and titer. More importantly, compared to the widely used sodium butyrate, batch yields using a valproic acid compound as a medium additive are significantly higher.

Abstract: The invention relates to a method of detecting a DNA sequence which at least partially contributes to promote the stable expression of a gene. To this end the DNA fragment to be examined is cloned in a vector between i) a DNA sequence involved in the induction of gene transcription repressing chromatin and ii) a reporter gene. The invention also relates to the detected DNA sequence, and the application of a stable expression-enhancing DNA sequence for the stable expression of a gene.

Abstract: A method of screening a novel BAFF suppressor or inhibitor. More specifically speaking, a method which comprises adding a combination of TPA with ionomycin and/or an anti-CD3 antibody to a cultured human cell to thereby induce the production of BAFF by the cell; a method of screening a substance capable of suppressing the expression or activity of BAFF which comprises adding a test substance to a BAFF-production system prepared by adding a combination of TPA with ionomycin and/or an anti-CD3 antibody to a cultured human cell and measuring the expression amount and/or the activity of BAFF in the BAFF-production system; and a BAFF production inducer for a BAFF-producing cell which contains a combination of TPA with ionomycin and/or an anti-CD3 antibody.

Abstract: Compositions and methods for the inducible expression of genes in eukaryotic cells. Expression of a nucleotide sequence of interest is controlled by a regulatory fusion protein that consists of a transcription blocking domain and a legends-binding domain. When the cognate ligand for the ligand-binding domain is present, transcription of the nucleotide sequence of interest is blocked. Upon removal of the cognate ligand, the nucleotide sequence of interest is transcribed. The method is useful for large scale production of a desired product in eukaryotic cells.

Abstract: Use of aminoglycoside resistance gene product for achieving high-density growth of animal cells.

Abstract: A method of detecting and isolating cells that produce any secreted protein of interest (POI), comprising: a) constructing a cell line transiently or stably expressing a cell surface capture molecule, which binds the POI, by transfecting the cell line with a nucleic acid that encodes such cell surface capture molecule; b) transfecting said cell simultaneously or subsequently with a second nucleic acid that encodes a POI wherein such POI is secreted; c) detecting the surface-displayed POI by contacting the cells with a detection molecule, which binds the POI; and d) isolating cells based on the detection molecule.

Abstract: The present invention relates to a method for obtaining highly purified hydrophobic proteins from cells by extraction using a buffer containing a detergent and removal of said detergent by hydroxyapatite (HA) column chromatography.

Abstract: A method for identifying compounds that inhibit amyloidal-beta precursor protein processing in cells, comprising contacting a test compound with a GPCR polypeptide, or fragment thereof, and measuring a compound-GPCR property related to the production of amyloidal-beta peptide. Cellular assays of the method measure indicators including second messenger and/or amyloid beta peptide levels. Therapeutic methods,and pharmaceutical compositions including effective amyloidal-beta precursor processing-inhibiting amounts of GPCR expression inhibitors, are useful for treating conditions involving cognitive impairment such as Alzheimers Disease.

Abstract: The invention describes improved methods and compositions for producing a recombinant protein, e.g., an antibody, in mammalian cell culture. In addition, the invention provides improved cell culture media, including improved production media, feed solutions, and combination feeds, which may be used to improve protein productivity in mammalian cell culture.

Abstract: The invention comprises a process for producing a protein of interest in a perfusion system using induction agents without a substantial loss of cell viability. The invention also comprises methods of growing cells in a perfusion system using induction agents without a substantial loss of cell viability.

Abstract: A gene coding for any of the following estrogen receptors (a) to (c): (a) an estrogen receptor comprising the amino acid sequence represented by amino acid numbers 153 to 602 in the amino acid sequence of SEQ ID NO: 1, (b) an estrogen receptor comprising the amino acid sequence of SEQ ID NO: 1, and (c) an estrogen receptor comprising an amino acid sequence exhibiting 95% or more amino acid identity to the amino acid sequence represented by amino acid numbers 153 to 602 in the amino acid sequence of SEQ ID NO: 1; and the like.

Abstract: A peptide comprising the amino acid sequence RMFPNAPYL or a portion or variant thereof provided that the peptide is not intact human WT-1 polypeptide or a peptide comprising the amino acid sequence CMTWNQMNL or a portion or variant thereof provided that the peptide is not intact human WT-1 polypeptide or a peptide comprising the amino acid sequence HLMPFPGPLL or a portion or variant thereof provided that the peptide is not intact human gata-1 polypeptide, and polynucleotides encoding these peptides. The peptides and polynucleotides are useful as cancer vaccines.

Abstract: This invention relates to methods for controlling deamidation of at least one type of heterologously expressed polypeptide in cell culture.

Abstract: The field of this invention is the development of therapeutic agents having immunogenic efficacy against Campylobacter. The present invention is directed to a method of producing monoclonal antibodies that are highly specific for epitopes of Campylobacter jejuni outer membrane proteins; to specific monoclonal antibodies made by using the epitopes; and to uses thereof. The invention is drawn further to immunogens comprising certain outer membrane proteins or portions thereof from C. jejuni.

Abstract: The invention relates to a process for the culturing of cells by continuous perfusion culturing of a cell culture comprising cell culture medium and cells, wherein cell culture medium is added to the cell culture, the cell culture is circulated over a filter module comprising hollow fibers resulting in an outflow of liquid having a lower cell density than the cell culture and the flow within the filter module is an alternating tangential flow. Preferably, culture medium is added at a particular perfusion rate and/or biomass is removed form the culture at least once. The method is especially suitable for the culturing of aggregating cells. The invention also relates to such a process wherein a biological substance, preferably an antibody, is produced by the cells, which biological substance may be further purified in downstream processing.

Abstract: This invention relates to the discovery that the transcription factors Pbx1 and HMG I are involved in retrovirus, e.g., HIV, replication. Thus, the invention provides methods of identifying modulators of these proteins. Such modulators can be used as reagents in in vitro assays to modulate expression of retroviral sequences and may be used to inhibit HIV replication in vivo.

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: The invention provides processes for culturing cells derived from embryonic retinoblast cells immortalized by adenovirus E1 sequences, preferably PER.C6® (human embryonic retina) cells, to improve product yields from such cells. Feed strategies for such cells and cultures with very high cell densities are provided, resulting in high yields of products, such as recombinant antibodies.

Abstract: The present invention provides methods for inducing insulin gene expression in cultured pancreas cells, the method comprising contacting a culture of endocrine pancreas cells expressing a PDX-1 gene with a GLP-1 receptor agonist, wherein the cells have been cultured under conditions such that the cells are in contact with other cells in the culture, thereby inducing insulin gene expression in the ceils. The invention also provides methods of treating a diabetic human subject using the methods of the invention.

Abstract: An improved process for recovery of virus from allantoic fluid of virus-infected chick embryos. Virus associated with granular and fibrous debris in the allantoic fluid can be disassociated from the debris and recovered, thereby increasing viral yield. Dissociation can be achieved by subjecting the virus-debris complex to conditions of increased salt concentrations, e.g., 0.5 M or greater.

Abstract: A norovirus-permissive cell culture infected with a norovirus, and methods of culturing a norovirus, are disclosed. Norovirus-permissive cells include dendritic cell-lineage cells, and macrophage-lineage cells, such as dendritic cells, and macrophages having a deficiency in a cellular anti-viral pathway such as a STAT-1-dependent pathway, an interferon receptor-dependent pathway, or a PKR-dependent pathway. Also disclosed are methods of screening anti-viral compounds against norovirus-permissive cells infected with norovirus, and norovirus adapted to grow in fibroblasts as well as macrophages that are not deficient in a cellular anti-viral pathway. Methods of making a norovirus vaccine are also disclosed.