Abstract: The present invention relates to novel compounds having a function of a peptide in the amylin family, related nucleic acids, expression constructs, host cells, and processes production of the compounds. The compounds of the invention include one or more amino acid sequence modifications. In addition, methods and compositions are disclosed to treat and prevent metabolic disorders such as obesity, diabetes, and increased cardiovascular risk.

Abstract: Disclosed herein are methods and compositions for generation of Bak- and/or Bax-deficient cell lines using engineered nucleases.

Abstract: The present disclosure provides variants of C-type natriuretic peptide (CNP), pharmaceutical compositions comprising CNP variants, and methods of making CNP variants. The CNP variants are useful as therapeutic agents for the treatment of diseases responsive to CNP, including but not limited to bone-related disorders, such as skeletal dysplasias (e.g., achondroplasia), and vascular smooth muscle disorders (e.g., restenosis and arteriosclerosis).

Abstract: The present invention relates to fusion polypeptides including (a) a binding site for a cytoskeleton component and (b1) an effector protein or the catalytic domain thereof or (b2) a binding site for the effector protein, and nucleic acid sequences encoding the fusion polypeptides. Moreover, various therapeutic uses of the fusion polypeptides are described, e.g., the treatment of diseases associated with the presence of an aberrant cell population, preferably cancer or AIDS.

Abstract: Focusing on the fact that antibody molecules with one H chain are not secreted when using the “knobs-into-holes” method, the present inventors revealed that desired bispecific antibodies can be preferentially formed by first expressing the H and L chains of one arm, and then suppressing their expression, followed by expressing the H and L chains of the other arm so that first desired HL molecules (HaLa and HbLb) are constructed, and then the H chains are paired with each other (H2L2). The present invention was thus completed.

Abstract: A protein structure capable of selective interaction with an organic target is provided. The protein structure is a polymer comprising as a repeating structural unit a recombinant fusion protein that is capable of selective interaction with the organic target. The fusion protein is comprising the moieties B, REP and CT, and optionally NT. B is a non-spidroin moiety of more than 30 amino acid residues, which provides the capacity of selective interaction with the organic target. REP is a moiety of from 70 to 300 amino acid residues and is derived from the repetitive fragment of a spider silk protein. CT is a moiety of from 70 to 120 amino acid residues and is derived from the C-terminal fragment of a spider silk protein. NT is an optional moiety of from 100 to 160 amino acid residues and is derived from the N-terminal fragment of a spider silk protein. The fusion protein and protein structure thereof is useful as an affinity medium and a cell scaffold material.

Abstract: The present invention relates to a polypeptide having interleukin-10 function, comprising two interleukin-10 monomer subunits covalently linked by a linker. The present invention further relates to a nucleic acid molecule encoding the polypeptide of the invention, a vector comprising said nucleic acid molecule, a non-human host transformed with the nucleic acid molecule or the vector of the invention as well as a method for the production of a recombinant polypeptide of the invention. The present invention further relates to a pharmaceutical composition as well as to the polypeptide, the nucleic acid molecule, the vector or the host or host cell of the invention for use in treating and/or preventing inflammatory diseases.

Abstract: A strategy to improve protein stability by domain insertion. TEM 1 beta-lactamase (BLA) and exo-inulinase, as model target enzymes, are inserted into a hyperthermophilic maltose binding protein from Pyrococcus furiosus (PfMBP). Unlike conventional protein stabilization methods that employ mutations and recombinations, the inventive approach does not require any modification on a target protein except for its connection with a hyperthermophilic protein scaffold. For that reason, target protein substrate specificity was largely maintained, which is often modified through conventional protein stabilization methods. The insertion was achieved through gene fusion by recombinant DNA techniques.

Abstract: Chemokines may be administered to a patient for immunotolerization. Chemokines include CCL19 and CCL21. Materials and methods for accomplishing tolerization and described.

Abstract: It is intended to provide a polynucleotide comprising a viral base sequence, the viral base sequence containing: a first base sequence encoding a viral replication protein, and a second base sequence encoding a viral movement protein, the second base sequence being located downstream of the first base sequence and having a linking site for linking with an exogenous base sequence encoding a polypeptide to be expressed, the linking site being located downstream of the second base sequence, the second base sequence being obtained by modifying with a base sequence in a native sequence derived from a virus by insertion, substitution, or addition. By using this, a vector containing a viral base sequence is constructed, and a protein is efficiently produced without worsening growth of a host cell containing the vector.

Abstract: The present invention provides a method of producing sclareol, said method comprising contacting a particular polypeptide having a sclareol synthase activity with labdenediol diphosphate (LPP). In particular, said method may be carried out in vitro or in vivo to produce sclareol, a very useful compound in the fields of perfumery and flavoring. The present invention also provides the amino acid sequence of the polypeptide used in the method. A nucleic acid derived from Salvia sclarea and encoding the polypeptide of the invention, an expression vector containing said nucleic acid, as well as a non-human host organism or a cell transformed to harbor the same nucleic acid, are also part of the present invention.

Abstract: The invention related to chimeric peptides including a penetrating peptide and a binding domain of PP2A catalytic subunit to caspase-9 which have pro-apoptotic activity. These chimeric peptides may be used for the treatment of hyperproliferative disorders.

Abstract: A recombinant galectin 9 (rGal 9) is provided which exhibits an immune system-mediated action and a direct action on tumor cells (i.e., activity of inducing the intercellular adhesion and apoptosis of the tumor cells), thereby potent in inducing the inhibition of cancer metastasis and reduction. Moreover, the rGal 9 exerts no efficacy on non-activated lymphocytes but can induce apoptosis in activated T cells, in particular, CD4-positive T cells causing an excessive immune response.

Abstract: The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.

Abstract: The present invention relates to the production of sugar hydrolysates from cellulosic material. The method may be used, for example for producing fermentable sugars for the production of bioethanol from lignocellulosic material. Cellulolytic enzymes and their production by recombinant technology are described, as well as uses of the enzymes and enzyme preparations.

Abstract: Described are specific-binding therapeutic and/or diagnostic proteins directed against Glypican-3 (GPC3), which proteins include muteins of a lipocalin protein, such as lipocalin 2 (Lcn2 or NGAL). The invention also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, the invention also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

Abstract: Methods for demannosylating phosphorylated N-glycans on a glycoprotein are described that use a mannosidase capable of hydrolyzing a terminal alpha-1,2 mannose linkage when the underlying mannose is phosphorylated.

Abstract: As a substance which pharmacologically regulates the function of a cell surface functional molecule, a substance which has specificity and an activity or efficacy equal or superior to an antibody and does not require an advanced production technique and facility for application thereof to a pharmaceutical product has been demanded. The invention relates to a multimer of an extracellular domain of a cell surface functional molecule, particularly a tetramer of an extracellular domain of PD-1 or PD-L1. Further, the invention relates to an application of such a tetramer as a preventive and/or therapeutic agent for cancer, cancer metastasis, immunodeficiency, an infectious disease or the like and an application of PD-1 or PD-L1 as a testing or diagnostic agent or a research agent for such a disease.

Abstract: The invention relates to a fusion protein and a method for the generation of the fusion protein of the invention. Further, the invention relates to the use of the fusion protein of the invention for the generation of induced pluripotent cells. Moreover, the invention relates to a composition comprising at least one fusion protein of the invention.

Abstract: The invention relates generally to G protein coupled receptors and in particular to agonists and antagonists of G protein receptors and methods of using the same.

Abstract: The invention relates to a nucleic acid molecule encoding a multimeric precursor which after transcription is specifically cleaved in vivo to form multiple copies of a protein of interest. The invention further relates to a cell comprising this nucleic acid molecule and a method for producing a protein of interest using this cell.

Abstract: This invention relates to a recombinant human G-CSF (rhG-CSF) dimer and its use in the treatment of neurological disorder. In particular, upon ischemic neural injury in animal, this invention can be used to protect neurons with the use of rhG-CSF dimer such that function of injured nerves can be restored. Serum half-life of G-CSF dimer of this invention is prolonged and the biological activity thereof is increased.

Abstract: The invention relates to phosphatases and more in specific to (genetically) modified phosphatases, pharmaceutical compositions comprising (genetically) modified phosphatases and the use of (genetically) modified phosphatases for treating or curing for example sepsis, inflammatory bowel disease or other inflammatory diseases, or renal failure. The invention further relates to a method for producing phosphatases.

Abstract: The present disclosure relates to an improved method for the manufacture of immunoglobulin single variable domains. More specifically, the present disclosure relates to a method of producing immunoglobulin single variable domains in which the proportion of carbamylated variants is strongly reduced or absent and to improved immunoglobulin single variable domains obtainable by methods of the present disclosure.

Abstract: The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

Abstract: Mutations of the epidermal growth factor receptor (EGFr), of phosphatidylinositol 3?-kinase (“PI3K”), and of B-Raf are described. Methods of treating tumors containing mutated EGFr with human monoclonal antibodies against EGFr are described. Methods and kits for ascertaining the presence of one or more mutant EGFr, mutant PI3K, and/or mutant B-Raf in a sample and for treating disorders or conditions related to the presence of mutant EGFr, mutant PI3K, and/or mutant B-Raf are also described. Methods of treating tumors containing mutant EGFr, mutant PI3K, and/or mutant B-Raf are also described.

Abstract: Engineered fusion proteins comprising photochromic protein domains are disclosed. In particular, the inventors have constructed fusion proteins containing photoswitchable photochromic fluorescent protein domains linked to selected proteins and shown that such fusion proteins can be used to control the activity or localization of selected proteins with light.

Abstract: The invention relates to cellular localization signals. In particular, the invention relates to endoplasmic reticulum localization signals in monomeric or multimeric form. The localization signals are utilized as research tools or are linked to therapeutics. Disclosed are methods of making and using polypeptides and modified polypeptides as signals to localize therapeutics, experimental compounds, peptides, proteins and/or other macromolecules to the endoplasmic reticulum of eukaryotic cells. The polypeptides of the invention optionally include linkage to reporters, epitopes and/or other experimental or therapeutic molecules. The invention also encompasses polynucleotides encoding the localization signals and vectors comprising these polynucleotides.

Abstract: The invention relates to the field of compounds, especially peptides or polypeptides, that have thrombopoietic activity. The peptides and polypeptides of the invention may be used to increase platelets or platelet precursors (e.g., megakaryocytes) in a mammal.

Abstract: This application is directed to chemokine-immunoglobulin fusion polypeptides and chemokine-polymer conjugates. The fusion polypeptides and conjugates can be used for treating chemokine receptor-mediated disorders and modulating inflammation, inflammatory cell motility, cancer cell motility, or cancer cell survival.

Abstract: SARS (severe acute respiratory syndrome virus, a coronavirus) immunogens, antigens, or epitopes, nucleic acid molecules encoding such immunogens, antigens, or epitopes; vectors containing such nucleic acid molecules, e.g., viral vectors such as baculovirus vectors, DNA vectors, such as DNA plasmid vectors, e.g., DNA plasmids that express a nucleic acid molecule in a mammalian cell, uses for such immunogens, antigens or epitopes and vectors, e.g., as an active component immunogenic, immunological or vaccine compositions, or to generate antibodies, such as monoclonal antibodies, and methods for making, and using such immunogens, antigens or epitopes, vectors, antibodies, including in methods for eliciting an immunological or immunogenic or vaccine response, as well as in assays or diagnostic kits or methods, are discussed, as well as a seamless fusion of sequences in a plasmid or vector, e.g., a sequence encoding a leader sequence and a sequence encoding a protein, epitope or immunogen or antigen.

Abstract: A protein comprising (I) an anti-CD14 antibody or its active fragment, or a derivative thereof and (II) an inhibitor for a protease, or its active fragment, or a derivative thereof is provided.

Abstract: The present invention is to provide a new detection method that is superior in detection sensitivity and allows a simple operation. A nucleic acid construct that includes a cloning region, an encoding nucleic acid of a peptide tag, an encoding nucleic acid of an aptamer that is bindable to the peptide tag is used. By inserting the encoding nucleic acid of arbitrary peptide into the cloning region of the nucleic acid construct, the nucleic acid construct is expressed in vivo. Thereby, a complex of a fusion transcript having the base sequence that includes the encoding nucleic acid of arbitrary peptide, the encoding nucleic acid of a peptide tag, and the encoding nucleic acid of the aptamer and a fusion translation that includes the arbitrary peptide and the peptide tag is formed.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level or a reduced serum albumin level prior to treatment. In another preferred embodiment, the patient's Glasgow Prognostic Score will be increased and survivability will preferably be improved.

Abstract: The present invention is directed to novel chimeric fibroblast growth factor (FGF) polypeptides, novel DNA encoding chimeric FGF polypeptides, and to the recombinant production of chimeric FGF polypeptides, and to methods, compositions and assays utilizing chimeric FGF polypeptides for the therapeutic treatment of metabolic-related disorders and other conditions, and for producing pharmaceutically active compositions including chimeric FGF polypeptides, the compositions having therapeutic and pharmacologic properties including those associated with the treatment of metabolic-related disorders and other conditions.

Abstract: The present invention relates to an inhibitor protein of the wnt signal path, a DNA encoding such a protein and a process for the preparation of such a protein. In addition, this invention concerns the use of the DNA and the protein as well as antibodies directed against the protein.

Abstract: The present invention relates to a trimeric fusion protein comprising three polypeptide chains, wherein each polypeptide chain comprises a eukaryotic collagen or collagen-like domain and a prokaryotic or viral trimerisation domain (PVTD). Also provided is a fusion polypeptide comprising a eukaryotic collagen or collagen-like domain and a PVTD. A suitable PVTD of a fusion polypeptide or protein of the invention is preferably derived from a collagen-like protein sequence found in the genome of the E. coli strain O157:H7 and other E. coli strains, and in bacteriophages or prophages infecting these strains or embedded in their genomes. A PVTD mediates trimerisation of collagen or collagen like polypeptides.

Abstract: Disclosed are fusion proteins comprising a biologically active molecule and an immunoglobulin (Ig) Fc domain which is linked to the biologically active molecule. The Fc domain is a hybrid human Fc domain of (i) IgG1, IgG2 or IgG4 or (ii) IgG4 and IgD. The hybrid Fc is useful as a carrier of biologically active molecules.

Abstract: The present invention relates to a polypeptide derived from a highly conserved region (HCR) I-III of an extracellular region of a CD99 and CD99 family such as CD99L2 and PBDX(or XG), which are a kind of transmembrane protein, or a fused protein thereof. The polypeptide or the fused protein thereof has an activating function of inhibiting the extravasation of white blood cells, or inhibiting the growth and/or metastasis of cancer cells. The present invention also provides a polynucleotide coding the polypeptide, a vector including same, and a transformant transformed by the vector. In addition, the present invention provides a pharmaceutical composition including the polypeptide or the fused protein thereof for preventing or treating inflammatory diseases. Further, the present invention provides a is pharmaceutical composition including the polypeptide or the fused protein thereof inhibiting the growth and/or metastasis of cancer cells, i.e., a pharmaceutical composition for preventing or treating cancer.

Abstract: A drug composition comprising a charged moiety coupled to a therapeutic compound is disclosed. The charged moiety is configured to interact with at least one type of component of opposite charge in a biological tissue to create an in situ depot for prolonged drug delivery. The biological tissue may be eye tissue or any tissue containing charged components.

Abstract: The invention includes a GAS antigen, GAS 40, which is particularly suitable for use either alone or in combinations with additional GAS antigens, such as GAS 117, GAS 130, GAS 277, GAS 236, GAS 40, GAS 389, GAS 504, GAS 509, GAS 366, GAS 159, GAS 217, GAS 309, GAS 372, GAS 039, GAS 042, GAS 058, GAS 290, GAS 511, GAS 533, GAS 527, GAS 294, GAS 253, GAS 529, GAS 045, GAS 095, GAS 193, GAS 137, GAS 084, GAS 384, GAS 202, and GAS 057.

Abstract: This invention relates to a fusion protein comprising the TMD of the transcription factor and PTD, an inhibitor for transcription factor function comprising the same, and a method for producing the same. Various diseases associated with malfunctions or defects of the transcription factor are effectively treated using the fusion protein according to the present invention.

Abstract: Molecules that interfere with the binding of a tumor necrosis factor receptor with its ligand, such as a soluble receptor, have proven usefulness in both basic research and as therapeutics. The present invention provides improved soluble transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI) receptors.

Abstract: A conjugate protein comprising a GM-CSF or a fragment thereof and a truncated CCL2 is described. The conjugate protein has unexpected immune suppressive, anti-obesity and tumoricidal properties and is useful in a variety of therapeutic applications.

Abstract: The invention features recombinant exotoxins from Vibrio cholerae are for the therapeutic treatment of a variety of human diseases, particularly diseases characterized by an abundance or excess of undesired cells.

Abstract: The present invention relates to recombinant factor H and variants and conjugates thereof and methods of their production, as well as uses and methods of treatment involving the materials.

Abstract: Methods of making a protein that stimulates a protective immune response in a subject include separating a portion of a protein from a naturally occurring influenza viral hemagglutinin to form a protein portion. The protein portion includes at least a portion of a globular head, and at least a portion of at least one secondary structure having at least one ?-sheet at a bottom of the globular head that causes the globular head to essentially retain its tertiary structure. The protein portion made by the methods of the invention lacks a transmembrane domain, a cytoplasmic domain and an HA2 subunit. A nucleic acid sequence encoding the protein portion is transformed into a prokaryotic host cell.

Abstract: Methods for detection of the activity of proteolytic enzymes, particularly isopeptidases, are disclosed.

Abstract: A binding partner, especially an antibody fragment that specifically recognizes an antigen-antibody immune complex between anti-THC and THC (tetrahydrocannabinol), is disclosed. The binding partner facilitates a non-competitive homogenous immunoassay for detection of cannabis use. A test kit comprising the binding partner is also described. Preferably the immunoassay is applied for roadside testing of saliva from suspected drivers.

Abstract: The invention provides conjugates, comprising an organ, tissue or tumor cell homing molecule linked to a moiety. Such a moiety can be, for example, an oligonucleotide, small interfering RNA, gene, virus, protein, pharmaceutical or detectable agent. In addition the invention provides methods to diagnose or treat a pathology of the muscle or heart, by administrating to a subject having or suspected of having a pathology a molecule or conjugate that homes to, binds to and is taken up by the muscle cells or heart cells.