Abstract: The invention provides compositions and methods for brown fat induction and activity through modulation of Fndc5 activity and/or expression. Also provided are methods for preventing or treating metabolic disorders in a subject through modulation of Fndc5 activity and/or expression. Further provided are methods for identifying compounds that are capable of modulating Fndc5 activity and/or expression.

Abstract: The present invention pertains to the function of SGLT5 as a sodium dependent co-transporter of mannose and/or fructose. The invention provides nucleic acids and host cells for inducible expression of SGLT5. Based on an inducible expression system the invention provides methods, assays and test kits for the identification of compounds interacting with SGLT5, especially with human SGLT5.

Abstract: The present invention provides a cell culture medium formulation that supports the in vitro cultivation, particularly in suspension, of mammalian cells, particularly epithelial cells and fibroblast cells, and methods for cultivating mammalian cells in suspension in vitro using these media. The media comprise a basal medium and a polyanionic or polyanionic compound, preferably a polysulfonated or polysulfated compound, and more preferably dextran sulfate. The present invention also provides chemically defined, protein-free eukaryotic cell culture media comprising an iron chelate and zinc, which is capable of supporting the growth (and particularly the high-density growth of mammalian cells) in suspension culture, increasing the level of expression of recombinant protein in cultured cells, and/or increasing virus production in cultured cells.

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 generally to nutritive medium, medium supplement, media subgroup and buffer formulations. Specifically, powdered nutritive medium, supplement, subgroup formulations, cell culture media comprising all of the necessary nutritive factors for in vitro cell cultivation, buffer formulations that produce particular ionic and pH conditions upon reconstitution with a solvent are provided. Particularly, methods of production of these media, supplement, subgroup, buffer formulations and kits, and methods for the cultivation of prokaryotic and eukaryotic cells using these dry powdered nutritive media, supplement, subgroup and buffer formulations are provided. Methods of producing sterile, powdered media or supplement (e.g., powdered FBS, powdered transferrin, powdered insulin, powdered organ extracts, powdered growth factors), media subgroup and buffer formulations by gamma irradiation are provided.

Abstract: The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having ?-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired ?-galactosidase activity by changing the structure of the active site of wild-type human ?-N-acetylgalactosaminidase.

Abstract: The present invention provides methods for using endogenous transcriptional control systems to regulate the expression of heterologous protein(s). In particular, targeted genome editing is used to integrate a sequence encoding the heterologous protein(s) in-frame with an endogenous coding sequence such that the expression of the heterologous and endogenous sequences is regulated by the endogenous control system.

Abstract: The present invention relates a host cell comprising an expression vector comprising a nucleic acid molecule encoding a protein requiring gamma-carboxylation and associated expression control sequences and a nucleic acid molecule encoding a vitamin K epoxido reductase and associated expression control sequences and a nucleic acid molecule encoding a ?-glutamyl carboxylase and associated control sequences. The invention further relates to a method of producing a protein requiring gamma-carboxylation in high yields.

Abstract: Compositions comprising gp350 variant DNA and amino acid sequences are provided, as are vectors and host cells containing such sequences. Also provided is a process for producing homogeneous gp350 protein recombinantly and in the absence of production of gp220 protein, pharmaceutical compositions containing such protein and prophylactic treatments making use of such proteins.

Abstract: Anti-CD22 antibodies and immunoconjugates thereof are provided. Methods of using anti-CD22 antibodies and immunoconjugates thereof are provided.

Abstract: Some embodiments of this invention include methods for treating disease and methods for administering a compound of Formula (I). In some aspects of the invention, diseases can be treated by administration of compositions comprising a compound of Formula (I). Pharmaceutical compositions of some embodiments of the present invention comprise a compound of Formula (I).

Abstract: Expression-enhancing nucleotide sequences for expression in eukaryotic systems are provided that allow for enhanced and stable expression of recombinant proteins in eukaryotic cells. Enhanced expression and stability regions (EESYRs) are provided for expression of a gene of interest in a eukaryotic cell. Chromosomal loci, sequences, and vectors are provided for enhanced and stable expression of genes in eukaryotic cells.

Abstract: A method for analyzing L-threonine contained in an specimen, which includes the steps of mixing a sample containing the specimen with an L-threonine dehydrogenase derived from Cupriavidus necator and a coenzyme NAD+ and analyzing the amount of NADH or 2-amino-3-oxobutyric acid after a predetermined period; an L-threonine dehydrogenase derived from Cupriavidus necator, which is a novel L-threonine dehydrogenase (TDH; EC 1.1.1.103) and can be utilized in the above-mentioned analysis method; a method for preparing a gene or the like to be used in the preparation of the enzyme, or a method for preparing the enzyme; an L-threonine analysis kit which includes (A) the L-threonine dehydrogenase and (B) a coenzyme NAD+; an enzyme preparation for use in the analysis of L-threonine, which includes the L-threonine dehydrogenase contained in a buffer solution; and an enzyme sensor utilizing the L-threonine dehydrogenase.

Abstract: The present disclosure relates to non-naturally occurring polypeptides useful for preparing Ezetimibe, polynucleotides encoding the polypeptides, and methods of using the polypeptides.

Abstract: The present invention relates to an arginine deiminase mutant with partial lysine-deficient and preparation and application thereof. The arginine deiminase mutant of the present invention has enzymatic activity of degrading arginine into citruline; compared with the arginine deiminase with the amino acid sequence of SEQ ID NO: 1, the amino acid sequence comprises one or more of K9N, T, K59Q, K66R, A, K93E, A, Q, K111R, A, K119Q, L, M, K121Q, I, K122E, L, K126E, S, R, K178I, E, D, K196I, R, K209G, T, D, K243E, V, R, K249D, Q, K263N, Q, K279Y, T, K293R, H, E, K325V, I, K380T, R, E, and K406E, D, S substitutions. Compared with PEG modified natural derived arginine deiminase, the PEG modified arginine deiminase mutant of the present invention retain better bioactivity; and because the quantity of lysine in arginine deiminase is reduced, the PEG modified products are more uniform and can be applied to clinical treatment of hepatoma, melanoma and the like.

Abstract: The invention relates to a set of genetic constructs which comprises at least a first recombinogenic construct (i) with at least two portions homologous to the genomic regions preceding and following the DNA target site of a site specific endonuclease and also comprising both a negative selection and positive selection mark interposed with the homologous portions as well as a region into which a sequence of interest can be cloned adjacent to the positive selection marker; and a second construct (ii, iii or iv) comprising the meganuclease. The present invention also relates to a kit comprising these constructs and methods to use this set of constructs to introduce into the genome of a target cell, tissue or organism a sequence of interest.

Abstract: Heterodimeric antibody-Fc-containing proteins, such as bispecific antibodies, and novel methods for producing such proteins.

Abstract: The present invention relates to polypeptides transiently activating Ras homolog gene family member A (RhoA) GTPase, polynucleotides encoding said polypeptides and pharmaceutical compositions comprising said polypeptides or said polynucleotides. The present invention further relates to the use of said polypeptides, said polynucleotides or said pharmaceutical compositions for long-term treatment of damage of the peripheral or central nervous system.

Abstract: The disclosure provides novel molecules related to growth and differentiation factor-8 (GDF-8), in particular mouse and humanized antibodies, and antibody fragments, including those that inhibit GDF-8 activity and signaling in vitro and/or in vivo. The disclosure also provides methods for diagnosing, treating, ameliorating, preventing, prognosing, or monitoring degenerative orders of muscle, bone, and insulin metabolism, etc., in particular amyotrophic lateral sclerosis (ALS). In addition, the disclosure provides pharmaceutical compositions for the treatment of such disorders by using the antibodies, polypeptides, polynucleotides, and vectors of the invention.

Abstract: The invention is directed to a method of preparing a nucleic acid sequence with a modified splice site usage profile, which employs the use of a nucleic acid sequence comprising a cryptic splice donor site. The invention also provides a method of producing an alternate form of an RNA molecule encoded by a nucleic acid sequence, which nucleic acid sequence comprises a cryptic splice donor site, a heterologous nucleic acid sequence, and a splice acceptor site.

Abstract: A highly active allene oxide synthase that can be used in the production of a plant growth regulating agent (KODA) is provided.

Abstract: Disclosed is a DNA construct that is useful for efficient generation of recombinant CHO cells useful for the production of target proteins. The DNA construct is a construct comprising, from a 5? end toward a 3? end, a first homologous DNA fragment, a target protein gene, and a second homologous DNA fragment. The first and second homologous DNA fragments have homology allowing for homologous recombination with a part of a hypoxanthine-phosphoribosyltransferase enzyme (hprt) locus in a CHO cell genome and have a chain length of not less than 1 kbp.

Abstract: The present invention relates to new methods to promote sialylation of glycoconjugates, including recombinant glycoproteins, in glycoconjugate production systems. The invention relates to methods to promote efficient glycoconjugate sialylation in recombinant expression systems, by providing simpler and more economical ways to produce large intracellular pools of sialic acid precursors. The invention is directed to nucleic acids, vectors, and cells harboring vectors comprising nucleic acids encoding enzymes involved in the synthesis of sialic acid precursors, and cells harboring these nucleic acids in combination with nucleic acids encoding glycosyltransferases, including sialyltransferases, to facilitate the production of humanized recombinant glycoproteins in bacterial, fungal, plant, and animal cell expression systems.

Abstract: The present invention provides a chimeric protein capable of killing or modifying a cell expressing abnormally high levels of a ligand of a receptor of the TNF/NGF family, comprising the amino acid sequence of at least one polypeptide consisting of an extracellular portion of said receptor connected to an effector molecule. In addition the invention provides pharmaceutical compositions comprising said chimeric protein and use thereof.

Abstract: An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes are alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.

Abstract: The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase possessing endonuclease activity, wherein said PA subunit is from Influenza A 2009 pan-demic H1N1 virus or is a variant thereof. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting.

Abstract: The invention concerns methods and means for preventing the reduction of disulfide bonds during the recombinant production of disulfide-containing polypeptides. In particular, the invention concerns the prevention of disulfide bond reduction during harvesting of disulfide-containing polypeptides, including antibodies, from recombinant host cell cultures.

Abstract: The present invention relates to novel muteins derived from human tear lipocalin. The invention also refers to a corresponding nucleic acid molecule encoding such a mutein and to a method for its generation. The invention further refers to a method for producing such a mutein. Finally, the invention is directed to a pharmaceutical composition comprising such a lipocalin mutein as well as to various uses of the mutein.

Abstract: The present invention provides novel mammalian alpha-kinase proteins: melanoma alpha-kinase (MK), heart alpha-kinase (HK), kidney alpha-kinase (KK), skeletal muscle alpha-kinase (SK), and lymphocyte alpha-kinase (LK). In particular, a novel kinase type is herein provided, characterized by the presence of an alpha-kinase catalytic domain and an ion channel domain. Isolated nucleic acids of the alpha-kinases MK, HK, KK, SK and LK are provided. Methods for making the novel alpha-kinases, cells that express the alpha-kinases and methods for treating an animal in need of either increased or decreased activity of the alpha-kinases are provided.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Abstract: The invention provides a composition comprising transthyretin and an ICAM-1 targeting agent, wherein the transthyretin and ICAM-1 targeting agent are coupled together, as well as methods of preparing such compositions. The invention further provides a diabody capable of binding specifically to ICAM-1 and transthyretin. The invention also provides a method of use of such composition in the manufacture of a medicament for treating an amyloid-? related neurodegenerative disease, comprising administering to a subject a composition comprising transthyretin coupled to an ICAM-1 targeting agent in an amount effective to treat the neurodegenerative disease, wherein the composition is administered to the subject outside of the blood-brain barrier.

Abstract: Isolated protein complexes are provided comprising growth factors such as IGF-I, IGF-II, EGF, bFGF, or KGF and fibronectin, or at least domains thereof that enable binding to and activation of both a growth factor receptor, and an integrin receptor-binding domain of fibronectin. These protein complexes include synthetic proteins where the growth factor and fibronectin sequences are joined by a linker sequence. Also provided are uses of these protein complexes for stimulating or inducing cell migration and/or proliferation in wound healing, tissue engineering, cosmetic and therapeutic treatments such as skin replacement, skin replenishment and treatment of burns where epithelial cell migration is required. In other embodiments, the invention provides inhibition of cancer cell metastasis, particularly in relation to breast cancer.

Abstract: The present invention provides compositions comprising retroviral vectors, transduced cells, and methods of using the same for gene therapy. In particular, the present invention relates to lentiviral vectors and cells transduced with those vectors to provide gene therapy to subjects having an adrenoleukodystrophy and/or adrenomyeloneuropathy.

Abstract: The present invention provides non-human mammalian cell lines that are deficient in CMP-Neu5Ac hydroxylase (Cmah) and/or glycoprotein alpha-1,3-galactosyltransferase (Ggta1). Also provided are methods for using the cells disclosed herein for producing recombinant proteins with human-like patterns of glycosylation.

Abstract: The present invention provides cell culture compositions capable of producing fusion polypeptides that bind vascular endothelial growth factor (VEGF). The cell culture compositions of the invention comprise cells which contain an expression vector comprising a nucleic acid molecule encoding a fusion polypeptide that binds VEGF. The fusion polypeptides may comprise a VEGF receptor component having an immunoglobulin-like (Ig) domain 2 of a first VEGF receptor, an Ig domain 3 of a second VEGF receptor, and a multimerizing component.

Abstract: The invention relates to anti-Factor D antibodies, their nucleic acid and amino acid sequences, the cells and vectors that harbor these antibodies and their production and their use in the preparation of compositions and medicaments for treatment of diseases and disorders associated with excessive or uncontrolled complement activation. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

Abstract: The present invention provides methods and materials by which glycosylation of glycoproteins can be regulated. Methods include the monitoring and regulation of parameters such that a glycoprotein having a desired product quality is obtained.

Abstract: The present invention provides DNA polymerases having increased efficiency of amplification of long amplicons. The present invention also provides for methods of amplifying target nucleic acid molecules with the DNA polymerases for increasing the efficiency of amplification of long amplicons.

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: An isolated human antibody or antigen binding fragment thereof which binds to human interleukin-4 receptor alpha (hIL-4R?) with an affinity constant (KD) of less than 200 pM, as measured by surface plasmon resonance, is provided.

Abstract: The invention relates to variants of a parent albumin having altered plasma half-life compared with the parent albumin. The invention also relates to fusion polypeptides and conjugates comprising said variant albumin.

Abstract: The present invention is directed to novel nucleotide and amino acid sequences of Torque teno virus (“TTV”), including novel genotypes thereof, all of which are useful in the preparation of vaccines for treating and preventing diseases in swine and other animals. Vaccines provided according to the practice of the invention are effective against multiple swine TTV genotypes and isolates. Diagnostic and therapeutic polyclonal and monoclonal antibodies are also a feature of the present invention, as are infectious clones useful in the propagation of the virus and in the preparation of vaccines. Particularly important aspects of the invention include vaccines that provide TTV ORF1 protein, or peptide fragments thereof, as antigen.

Abstract: The present invention provides isolated polypeptides having an amino acid sequence having at least 70% identity to SEQ ID NO:20, wherein the polypeptide has ER-?36 activity. The invention further provides methods for identifying agents that bind to such polypeptides, methods for detecting such polypeptides, and methods for altering the activity of such polypeptides. Also provided are antibodies that specifically bind to an amino acid sequence depicted at SEQ ID NO:1, or an immunogenic fragment thereof, and methods for making and using such antibodies.

Abstract: The present disclosure relates generally to multi-specific Fab fusion proteins (MSFP) which comprise an antibody Fab fragment with both N-termini fused to a fusion moiety (fusion moiety A or B). MSFP containing the Fab fragment exhibit significantly reduced binding ability of the Fab fragment to the Fab target. Binding of the Fab to its target is restored when the MSFP is clustered on a cell surface by binding of the fusion moieties to their target. The reduced binding of the Fab to its target, especially when presented on a cell surface in its native state, absent fusion moiety binding provides advantages such as: reduced side effects and allows desirable pharmacological effects of selectivity and specificity in a controlled manner.

Abstract: The present invention relates to a Factor VII (FVII) fusion polypeptide with a prolonged half-life, wherein the FVII polypeptide can be activated or is in the activated form.

Abstract: The present invention relates to cell culture media containing combinations of proteins, as well as methods of making the cell culture media, and methods of using the cell culture media to improve growth characteristics of cultured cells.

Abstract: A monomer of an I-CreI meganuclease variant wherein said monomer when in dimeric form binds and cleaves DNA.

Abstract: The invention refers to the use of transforming growth factor-beta 1 (TGF-?1) inhibitor peptides or polynucleotides encoding said peptides for the prevention and/or treatment of corneal fibrosis and/or corneal haze.

Abstract: Described are cell surface and circulating markers for aging related disorders (specific isoforms of NADH oxidase (arNOX)). Recombinant age-related NADH oxidase isoforms and their coding sequences and methods for detecting arNOX isoform presence and quantitation in tissues and in blood, sera, urine, saliva, perspiration and in other body fluids, are provided. Recombinant arNOX proteins are useful in preparing antigens for use in the generation of monoclonal and polyclonal antibodies as well as immunogenic compositions for diagnosis and treatment of aging disorders. DNA probes based on the DNA sequence information provide may be used to identify individuals at risk for aging disorders and for development of therapeutic interventions or anti-aging cosmetic or other formulations of benefit in slowing the aging process in mammals.

Abstract: The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependent cell-mediated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof.