Abstract: Methods and compositions for producing therapeutic agents using chondrocytes are provided. The genetically engineered chondrocytes can be used to express the therapeutic agent in a subject, including in an environment typically associated with chondrocytes and in an environment not typically associated with chondrocytes.

Abstract: Described herein are methods to enhance protein secretion in a host cell. In preferred embodiment, the host cell is a gram-positive microorganism such as a Bacillus. In another preferred embodiment, the host cell is a gram-negative microorganism. Preferably the gram-negative microorganism is an Escherichia coli or a member of the genus Pantoea. Protein secretion may be enhanced by the overexpression of protein components of the Tat pathway. Alternatively, secretion of foreign proteins can be selectively enhanced by forming a chimeric polypeptide comprising a tat signal sequence and the protein of interest. In a preferred embodiment, the tat signal sequence is selected from phoD or LipA.

Abstract: The invention relates to cell lines from differentiated cells with hepatocytic phenotypes capable of producing albumin and blood coagulation factors, said cells being derived from a human leukaemia cell line, preferably the human THP1 cell line, and preserving the characteristics of immortality. Among the cell lines of the invention, the cell lines known as PSC-THP1-EP, PSC-THP1-EP-FAST, PSC-THP1-HEP and PSC-THP1-EPEP are preferred. The invention also relates to methods for obtaining the cell lines of the invention and the uses of said cell lines, particularly for the production of albumin and/or blood coagulation factors.

Abstract: Method for providing a hypoallergenic glycoprotein includes growing at least one of a mutated plant, a part of the mutated plant, plant cells produced from the mutated plant, a transgenic plant, a part of the transgenic plant and plant cells produced from the transgenic plant wherein an activity of an enzyme Golgi ?-mannosidase II has been eliminated or decreased so as to obtain a grown material. The hypoallergenic glycoprotein is isolated from the grown material.

Abstract: Response element regions, DNA constructs comprising response element regions, host cells comprising response element regions, and methods of using response element regions are provided.

Abstract: Human G-protein chemokine receptor polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides for identifying antagonists and agonists to such polypeptides and methods of using the agonists and antagonists therapeutically to treat conditions related to the underexpression and overexpression of the G-protein chemokine receptor polypeptides, respectively. Also disclosed are diagnostic methods for detecting a mutation in the G-protein chemokine receptor nucleic acid sequences and detecting a level of the soluble form of the receptors in a sample derived from a host.

Abstract: The present invention provides compositions and methods relating to or derived from anti-PAR-2 antibodies. In particular embodiments, the invention provides antibodies that bind human PAR-2, PAR-2-binding fragments and derivatives of such antibodies, and PAR-2-binding polypeptides comprising such fragments. Other embodiments provide nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having PAR-2-related disorders or conditions.

Abstract: A microorganism which produces compounds useful as an antifungal agent, particularly a therapeutic agent for deep-seated mycoses, such as mycotic sinusitis, is provided. The present inventors have conducted intensive studies on naturally-occurring microorganisms as a research for antifungal compounds, and found a fungus Acremonium persicinum which produces cyclic compounds having a potent antifungal activity and useful as a medicament, particularly an antifungal agent, and the present invention was completed.

Abstract: A compound useful as an antifungal agent, particularly a therapeutic agent for deep-seated mycoses, is provided. A fungus Acremonium persicinum was collected, and cyclic compounds were isolated from culture liquids thereof. The present inventors confirmed that the cyclic compounds or salts thereof have a potent antifungal activity and are useful as medicaments, particularly an antifungal agent, and thus the present invention was completed. The cyclic compound and the salt thereof according to the present invention can be used as an agent for preventing or treating mycoses, particularly deep-seated mycoses.

Abstract: The invention provides a recombinant vector comprising an ovine adenovirus genome and a sequence encoding a heterologous polypeptide, wherein the sequence encoding the heterologous polypeptide is inserted between E4 and E3 transcription units of the ovine adenovirus genome.

Abstract: The invention provides a novel therapeutic composition comprising of insulin producing mesenchymal stem cells obtained from human adipose tissue along with Hematopoietic stem cells for the treatment of diabetic patients especially insulinopenic patients. The invention also describes a simple and efficient process for the isolation, proliferation and differentiation of insulin producing mesenchymall stem cells from human adipose tissue. Unfiltered extract of adipose tissue is used in the process with a medium totally free from xenogenic material; the serial passages of the cells are avoided in the process.

Abstract: A method for producing L-glutamic acid by culturing a coryneform bacterium which has L-glutamic acid producing ability and which has been modified so that expression of the fasR gene is enhanced in a medium to produce and accumulate L-glutamic acid in the medium or cells, and collecting L-glutamic acid from the medium or cells.

Abstract: The present invention provides polynucleotides, as well as polypeptides encoded thereby, that are differentially expressed in cancer cells. These polynucleotides are useful in a variety of diagnostic and therapeutic methods. The present invention further provides methods of reducing growth of cancer cells. These methods are useful for treating cancer.

Abstract: A method for prognosing the status of a tumor patient is provided, wherein the level of antibodies against Saccharomyces cerevisiae, Candida sp., especially Candida albicans, Aspergillus fumigatus or Klebsiella pneumoniae is determined in said the patient, and prognosing the status of the patient upon the level of these antibodies determined in the patient by determining a better status for a patient with a lower level of these antibodies compared to the average level or by determining a worse status for a patient with a higher level of these antibodies compared to the average level.

Abstract: The present invention relates to G-CSF polypeptides and their uses, particularly for therapeutic or prophylactic treatment in human subjects. The invention also relates to nucleic acids encoding said polypeptides, vectors comprising such nucleic acids and recombinant cells containing the same. The invention further discloses methods of producing such polypeptides, as well as methods and tools for detecting or dosing these polypeptides in any sample.

Abstract: Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

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: This invention provides a novel receptor expressed on neuronal cells in a developmentally-specific manner. Accordingly, this invention provides the amino acid sequences of selected portions of the receptor and polynucleotides encoding these portions as well as antibodies that bind to the polypeptide portions of the receptor. Compositions and methods for using the compositions are also provided.

Abstract: A cell extract for cell-free protein synthesis is produced by removing substances, which bind to an affinity support to be used in purification or interaction analysis, from a cell extract having protein synthetic activity. Then, a target protein is synthesized by using the cell extract for cell-free protein synthesis. The synthesized target protein can be purified by using the affinity support and used in interaction analysis.

Abstract: The present invention relates to a hybrid Hepatocyte Growth Factor (HGF) gene which is prepared by inserting an inherent or foreign intron between exons 4 and 5 in HGF cDNA, which has a base sequence of SEQ ID NO: 2. The gene has high expression efficiency and simultaneously expresses two heterotypes of HGF and dHGF (deleted variant HGF). Further the gene may be used for treating or preventing ischemic or liver diseases.

Abstract: Nucleic acid molecules which encode a branching enzyme from a bacterium of the genus Neisseria, vectors, host cell, plant cells and plants containing said nucleic acid molecules as well as starch obtainable from the plants described are described. Furthermore, an in-vitro method for producing ?-1,6-branched ?-1,4-glucans on the basis of sucrose and a combination of enzymes of an amylosucrase and a branching enzyme as well as the ?-1,6-branched ?-1,4-glucans obtainable by said method are described.

Abstract: The present invention provides artificial enzymes comprising, e.g., an N-terminal domain derived from E. coli FkpA that allows for dimerization and provides a substrate binding region, and a C-terminal thioredoxin domain derived from E. coli DsbA. Similar to DsbC, such de novo designed chimeric (hybrid) FkpA-DsbA enzymes function, as disulfide reductases, oxidases, or isomerases, and chaperones in vivo and in vitro, despite lacking similarity to DsbC-related polypeptide sequence.

Abstract: A fibrinolytic enzyme isolated from a culture broth of a mushroom has a characteristic of degrading a fibrin and a fibrinogen without activating an activity of a plasminogen. The plasminogen is activated to generate a plasmin to degrade the fibrin and/or fibrinogen, so that the fibrinolytic enzyme be used for the thrombosis-related diseases to degrade the fibrin and fibrinogen of blood clots without activate the plasminogen, so as to avoid a hemorrhage due to the over activation the plasminogen to over generate the plasmin.

Abstract: Provided herein are methods for refolding proteins. The methods involve covalently modifying a denatured protein with a nonproteinaceous polymer and then renaturing the modified protein.

Abstract: The invention provides composition and methods for producing proteins of interest which comprise at least one disulfide bond, include proteins which in their mature form do not contain disulfide bonds, but whose precursor molecule contained at least one disulfide bond. The methods employ a host cell modified to more efficiently produce properly folded disulfide bond containing proteins. The host cells generally contain a mutation in one or more reductase genes, and can be further genetically modified to increase their growth rate, and are further optionally modified to increase the expression of a catalyst of disulfide bond formation. Host cells, methods for u sing such to produce proteins of interest, proteins of interest produced by these methods are within the scope of the invention.

Abstract: The present invention provides Interferon-Like (IFN-L) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing IFN-L polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with IFN-L polypeptides.

Abstract: The present invention relates to a hybrid Hepatocyte Growth Factor (HGF) gene which is prepared by inserting an inherent or foreign intron between exons 4 and 5 in HGF cDNA, which has a base sequence of SEQ ID NO: 2. The gene has high expression efficiency and simultaneously expresses two heterotypes of HGF and dHGF (deleted variant HGF). Further the gene may be used for treating or preventing ischemic or liver diseases.

Abstract: The disclosure relates to compounds of the formula (I): wherein R1, R2, R3, and R4 are as defined in the disclosure, or a pharmaceutically acceptable salt thereof; which is formed by the microorganism ST 201196 (DSM 18870); the use thereof for the treatment and/or prophylaxis of fungal disorders; medicaments containing a compound of formula (I); processes for production thereof; and the microorganism ST 201196 (DSM 18870).

Abstract: Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production. The invention also provides methods for increasing the effector function of monoclonal antibodies and monoclonal antibodies with increased effector function.

Abstract: A hybrid type I polyketide synthase gene typically containing a starter module and a plurality of heterologous extender modules is used to synthesise novel polyketides. It is preferably under the control of type II polypolyketide synthase promoter e.g. act I or S. coelicolor.

Abstract: The invention relates to the discovery of a selective cell surface marker that permits the selection of a unique subset of pancreatic stem cells having a high propensity to differentiate into insulin-producing cells or into insulin-producing cell aggregates.

Abstract: The present invention relates to improved Nanobodies™ against von Willebrand Factor (vWF), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.

Abstract: An object of the present invention is to provide a medium supplement for animal cell culture and an animal cell culture medium. The present invention relates to a medium supplement for animal cell culture comprising sericin or a sericin derivative and an animal cell culture medium comprising at least said medium supplement and a basal medium composition.

Abstract: A method of preparing molecules of interest for delivery to eukaryotic cells is shown, wherein a ricin B chain subunit not having a ribosome inactivating subunit and retaining lectin activity is modified by modifying the first cysteine residue to be absent or substituted with an amino acid other than cysteine, or removing a protease sensitive site at the N-terminal of the subunit, or adding an endoplasmic reticulum retrieval signal, and operatively associating the subunit with a molecule of interest. Methods of operatively associating the subunit and molecule of interest include chemical conjugation at primary amines, conjugation with N-glycans of the subunit, a disulfide bond, and assembly of immunoglobulin domains. The invention provides for operatively associating multiple molecules of interest with a ricin B chain subunit, and delivery into targeted cells, cell components, and combination of cells.

Abstract: A drug product comprising a combination of highly purified collagenase I and collagenase II from Colostridium histolyticum is disclosed. The drug product includes collagenase I and collagenase II in a ratio of about 1 to 1, with a purity of greater than at least 95%. The invention further disclosed improved fermentation and purification processes for preparing the said drug product.

Abstract: Recombinant expression vectors are provided comprising a 3?UTR of a light chain and an Epstein-Barr virus origin of replication. Also provided are host cells comprising such vectors and methods of producing recombinant protein with such vectors. Additional methods of producing a recombinant protein involve contacting cells with a first and second vector, each of which encode a different polypeptide chain, and wherein the second vector is present in an amount which is about 1.5 to 2.5 times as much as that of the first vector. Cells also can be transfected with a recombinant transient expression vector encoding a protein and are cultured in a medium in a membrane-enhanced culturing vessel to produce recombinant protein.

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 invention relates to a process for the manufacturing of a protein in mammalian cells cultured in a serum-free medium.

Abstract: The invention described herein relates to a method for combining antigen fragments of Toxoplasma gondii proteins, in the form of chimeric fusion products, and their use as diagnostic and immunogenic agents.

Abstract: The present invention relates to methods for producing a recombinant polypeptide of interest, the method comprising the steps of: a) providing a polynucleotide library encoding one or more polypeptides of interest, wherein the library was prepared in an expression cloning vector comprising at least the following elements: i) a polynucleotide encoding a selectable marker; ii) a fungal replication initiation sequence, preferably an autonomously replicating sequence (ARS); and iii) a polynucleotide comprising in sequential order: a promoter derived from a fungal cell, a cloning-site into which the library is cloned, and a transcription terminator; b) transforming a mutant of a parent filamentous fungal host cell with the library, wherein the frequency of non-homologous recombination in the mutant has been decreased compared to the parent; c) culturing the transformed host cell obtained in (b) under conditions suitable for expression of the polynucleotide library; and d) selecting a transformed host cell which pr

Abstract: An isolated protein complex is provided which includes a growth factor, growth factor binding protein and vitronectin. Preferably, the isolated protein complex includes an insulin-like growth factor-I, insulin-like growth factor binding protein-3 or insulin-like growth factor binding protein-5 and vitronectin. Also provided are methods of modulating cell proliferation and/or migration by administering said protein complex for the purposes of wound healing, skin repair and tissue replacement therapy. Conversely, by using agents that disrupt growth factor protein complexes formed in vivo, growth factor-driven cell proliferation and/or migration may be suppressed such as for the purposes of treating cancers, psoriasis, atherosclerosis and wounds prone to hypertrophic scarring.

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: The present invention relates to novel amino acid and nucleic acid sequences of cyclic nucleotide-specific phosphodiesterases from the parasite Leishmania major. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the nucleic acid sequences as well as methods for producing and using the amino acid and nucleic acid sequences. The invention further relates to the use of these sequences, and of antibodies directed against these sequences, in the diagnosis and treatment of disorders related to the infection of Leishmania major, including the identification of compounds that form complexes with the polypeptides and nucleic acids of the present invention.

Abstract: Compositions comprising osteogenic factors fused with membrane transduction domains of viral proteins are provided. Also provided are methods of expression and use of such compositions. Further, the methods of making such compositions are also provided. The methods involve transfecting the cells with an isolated nucleic acid comprising a nucleotide sequence encoding a LIM mineralization protein operably linked to a promoter and optionally a membrane transduction domain of a viral protein. Transfection may be accomplished ex vivo or in vivo by direct injection of virus or naked DNA, or by a nonviral vector such as a plasmid. Methods for treating disc disease associated with trauma or disc degeneration are also described.

Abstract: The present invention provides Epstein-Barr virus (EBV)-negative NK cell lines. The NK cell lines of the present invention are useful for screening factors associated with the proliferation and expression functions of NK cells and to discover factors produced by the NK cells. In addition, the cell lines are immortalized despite the fact that they are EBV-negative. Thus, unknown mechanisms of oncogenesis may be elucidated through an understanding of the mechanisms underlying the immortalization of the cell lines of the present invention.

Abstract: A description is given of a bioreactor (1), in particular for NMR spectroscopy, comprising a container (7) capable of containing a cell culture, a first inlet line (6) for the inward flow of a culture medium to the inside of the container and a second outlet line (9, 10) for the outward flow of the culture medium from the container (7). The first line (6), an inlet line, is connected to a spiral-shaped device (12) which has a form such that when the medium is made to flow inside the first line (6) and made to flow out of the second line (9; 10), hydrostatic thrust and hydrodynamic forces produce with respect to the cells a condition of simulated reduced gravity inside the container (7).

Abstract: The invention discloses a family of neuronal migration-inducing, proliferation-promoting and neurite outgrowth promoting factors, termed NRP compounds, and provides compositions and methods for the use of NRP compounds in the treatment of brain injury and neurodegenerative disease. NRP compounds induce neurons and neuroblasts to proliferate and migrate into areas of damage caused by acute brain injury or chronic neurodegenerative disease, such as stroke, trauma, nervous system infections, demyelinating diseases, dementias, and metabolic disorders. NRP compounds may be administered directly to a subject or to a subject's cells by a variety of means including orally, intraperitoneally, intravascularly, and directly into the nervous system of a patient.

Abstract: Antibodies directed to the C-terminal side of ?-amyloid peptide and methods of using these antibodies for diagnosing and treatment of Alzheimer's disease and A? peptide associated diseases are described.

Abstract: Methods for controlling the level of dissolved carbon dioxide and limiting osmolality in a mammalian cell culture process to enhance cell growth, viability and density, and increase biologic product concentration and yield are provided. Such control of the level of dissolved carbon dioxide and pH as well as the resulting ability to limit osmolality in a mammalian cell culture process is achieved by adopting alternative pH control strategies and CO2 stripping techniques during a mammalian cell culture process. Such pH control techniques and carbon dioxide stripping occur without foam and with little or no damage to the mammalian cells.

Abstract: Disclosed are libraries of DNA sequences encoding zinc finger binding motifs for display on a particle, together with methods of designing zinc finger binding polypeptides for binding to a particular target sequence and, inter alia, use of designed zinc finger polypeptides for various in vitro or in vivo applications.