Abstract: Modified oxyntomodulin derivatives. Such derivatives can be used for the treatment of metabolic diseases such as diabetes and obesity.

Abstract: A method is described for producing protein compositions having reduced amounts of O-linked glycosylation. The method includes producing the protein in cells cultured in the presence of an inhibitor of Pmt-mediated O-linked glycosylation and/or in the presence of one or more ?-1,2-mannosidases.

Abstract: The present invention relates to conjugates of a polypeptide and an oligosaccharide, wherein the polypeptide is conjugated to at least one oligosaccharide-spacer residue, the oligosaccharide being a synthetic sulfated oligosaccharide comprising 4-18 monosaccharide units and per se having affinity to antithrombin III and the spacer being a bond or an essentially pharmacologically inactive flexible linking residue, or a pharmaceutically acceptable salt thereof. The conjugates of the invention have improved pharmacokinetic properties when compared to the original polypeptides (i.e. the corresponding non-conjugated polypeptides per se).

Abstract: The present inventors conducted a similarity search of the amino acid sequence of known G protein-coupled receptor proteins in GenBank, and obtained a novel human GPCR gene “BG37”, cDNA containing the ORF of the gene was cloned and its nucleotide sequence was determined. Moreover, novel GPCR “BG37” genes from mouse and rat were isolated. Use of the novel GPCR of the present invention enables screening of ligands, compounds inhibiting the binding to a ligand, and candidate compounds of pharmaceuticals which can regulate signal transduction from the “BG37” receptor.

Abstract: Methods for display of recombinant whole immunoglobulins or immunoglobulin libraries on the surface of eukaryote host cells, including yeast and filamentous fungi, are described. The methods are useful for screening libraries of recombinant immunoglobulins in eukaryote host cells to identify immunoglobulins that are specific for an antigen of interest.

Abstract: Modified oxyntomodulin derivatives. Such derivatives can be used for the treatment of metabolic diseases such as diabetes and obesity.

Abstract: The present invention provides methods to reduce or eliminate ?-mannosidase resistant glycans on glycoproteins in yeast. The reduction or elimination of ?-mannosidase resistant glycans on glycoproteins results from the disruption of the newly isolated P. pastoris AMR2 gene encoding ?1,2-mannosyltransferase. The present invention also discloses novel genes, polypeptides, antibodies, vectors and host cells relating to ?-mannosidase resistance on glycans.

Abstract: A Rapid And Sensitive Radiometric Assay For Assessing The Activity Of Cytochrome P-450 (CYP) 2C9 And The Potential Of An Analyte To Inhibit CYP2C9 Activity Or Induce CYP2C9 Expression is described. All the steps of the assay, including incubations, product separation, and radioactivity counting are preferably performed in a multiwell format, which can be automated.

Abstract: Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways.

Abstract: A method for producing human-like glycoproteins by expressing a Class 2 ?-mannosidase having a substrate specificity for Man?1,3 and Man?1,6 glycosidic linkages in a lower eukaryote is disclosed. Hydrolysis of these linkages on oligosaccharides produces substrates for further N-glycan processing in the secretory pathway.

Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIII activity, which produce bisected N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar transporters and mannosidases, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.

Abstract: A novel gene encoding P. pastoris orotate-phosphoribosyl transferase (URA5) is disclosed. Methods for producing and selecting yeast strains capable of stable genetic integration of heterologous sequences into the host genome are also provided.

Abstract: Examination of obesity or emaciation is performed based on expression levels of LCE gene or protein in a test tissue or a test cell or a polymorphism of the gene. Evaluation of compounds including screening of therapeutic agents for obesity or emaciation is performed utilizing the nature of LCE gene or protein.

Abstract: Novel genes encoding P. pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5 and HIS6 are disclosed. A method for inactivating alternately at least two biosynthetic pathways in a methylotrophic yeast is provided. A method for producing and selecting yeast strains characterized as being capable of genetic integration of heterologous sequences into the host genome using the genes involved in the biosynthetic pathways is also disclosed.

Abstract: The present invention provides methods to reduce or eliminate ?-mannosidase resistant glycans on glycoproteins in yeast. The reduction or elimination of ?-mannosidase resistant glycans on glycoproteins results from the disruption of the newly isolated P. pastoris AMR2 gene encoding ?1,2-mannosyltransferase. The present invention also discloses novel genes, polypeptides, antibodies, vectors and host cells relating to ?-mannosidase resistance on glycans.

Abstract: The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities such as those involved in glycosylation to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified oligosaccharides are created or selected. N-glycans made in the engineered host cells have a Man5GlcNAc2 core structure which may then be modified further by heterologous expression of one or more enzymes, e.g.

Abstract: The present invention generally relates to methods of modifying the glycosylation structures of recombinant proteins expressed in fungi or other lower eukaryotes, to more closely resemble the glycosylation of proteins from higher mammals, in particular humans. The present invention also relates to novel enzymes and, nucleic acids encoding them and, hosts engineered to express the enzymes, methods for producing modified glycoproteins in hosts and modified glycoproteins so produced.

Abstract: The present invention relates to the elimination of mannosylphosphorylation on the glycans of glycoproteins in the yeast genus Pichia. The elimination of mannosylphosphorylated glycoproteins results from the disruption of the PNO1 gene and the newly isolated P. pastoris MNN4B gene. The present invention further relates to methods for producing modified glycan structures in host cells that are free of glycan mannosylphosphorylation.

Abstract: A novel receptor, “LDL-receptor-related protein-5” (“LRP-5”), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.

Abstract: The present invention discloses the isolation and characterization of cDNA molecules encoding novel androgen receptor (AR) protein from Macaca mulatta. Also within the scope of the disclosure are recombinant vectors, recombinant host cells, methods of screening for modulators of Macaca mulatta AR (rhAR) activity, purified proteins and fusion proteins which comprise all or a portion of the rhAR protein, transgenic mice comprising a transgene encoding the rhAR protein, as well as production of antibodies against AR, or epitopes thereof.