Abstract: The invention provides methods for muscle repair or regeneration comprising administering therapeutically effective amounts of RAR agonists or stem cells that are pretreated with contact with a RAR agonist to a subject at a site of muscle damage. Additionally, the invention provides compositions comprising RAR agonist treated stem cells and methods of use of said cells for muscle repair or regeneration. In one embodiment, the stem cells are mesenchymal stem cells. In one embodiment, the RAR agonist is an RAR? agonist. In one embodiment, administration of the RAR agonist is begun during a period of increased endogenous retinoid signaling in the subject resulting from incurrence of the damaged muscle tissue.

Abstract: The present invention relates to the fields of Factor VII (FVII) and Factor VIIa (FVIIa) albumin linked polypeptides. More specifically, the invention relates to cDNA sequences coding for human Factor VII and Factor VIIa and derivatives genetically fused to a cDNA coding for human serum albumin which may be linked by oligonucleotides which code for intervening peptidic linkers such encoded derivatives exhibiting improved stability and extended functional plasma half-life, recombinant expression vectors containing such cDNA sequences, host cells transformed with such recombinant expression vectors, recombinant polypeptides and derivatives which do have biological activities of the unmodified wild type protein but having improved stability and prolonged shelf-life and processes for the manufacture of such recombinant proteins and their derivatives. The invention also covers a transfer vector for use in human gene therapy, which comprises such modified DNA sequences.

Abstract: The present invention relates to a polypeptide comprising a modified von Willebrand Factor (VWF) having a higher Factor VIII binding affinity than non-modified VWF, its pharmaceutical use and method of its preparation.

Abstract: The present disclosure provides engineered transaminase polypeptides having improved properties as compared to naturally occurring transaminases including the ability of converting the substrate, 3?-hydroxyacetophenone to (S)-3-(1-aminoethyl)-phenol in enantiomeric excess and high percentage conversion. Also provided are polynucleotides encoding the engineered transaminases, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases to synthesize (S)-3-(1-aminoethyl)-phenol and related compounds useful in the production of active pharmaceutical ingredients.

Abstract: The present invention relates to a novel method for expanding mesenchymal stem cells (MSCs) in low-density and hypoxic condition as compared to normal air conditions traditionally used in cell culture. The present method provides rapid and efficient expansion of human MSCs without losing cellular proliferation and stem cell properties, including increase in proliferation, decrease in senescence, and increase in differentiation potential both in vitro and in vivo. The expanded MSCs by the present method may maintain normal karyotyping, and will not form tumor when transplanted into mammal.

Abstract: Compositions and methods for swine LDL-R gene knockouts.

Abstract: The disclosure relates to the field of glyco-engineering, more specifically, to eukaryotic cells wherein both an endoglucosaminidase and a glycoprotein are present. These cells can be used to deglycosylate or partly deglycosylate the (exogenous) glycoprotein, in particular, without the need for adding an extra enzyme. Methods are also provided for the application of these cells in protein production. According to one specific aspect, the eukaryotic cells are glyco-engineered yeast cells in which, additionally, at least one exogenous enzyme needed for complex glycosylation is present, e.g., allowing easier separation of differentially glycosylated glycoproteins.

Abstract: The present disclosure relates to transaminase polypeptides capable of aminating a dicarbonyl substrate, and polynucleotides, vectors, host cells, and methods of making and using the transaminase polypeptides.

Abstract: Novel ALK and NTRK1 fusion molecules and uses are disclosed.

Abstract: Provided herein are chimeric influenza hemagglutinin (HA) polypeptides, compositions comprising the same, vaccines comprising the same, and methods of their use.

Abstract: The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method further involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide.

Abstract: The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: Disclosed are methods of promoting and/or enhancing G-Protein Coupled Receptor (GPCR) localization to the cell membrane and/or cell surface; methods of promoting and/or enhancing GPCR functional expression; and methods and assays for screening or identifying ligands (e.g., agonists or antagonists) that bind GPCRs. Also provided are vectors, recombinant cells, and stable cell lines for use in the methods and assays.

Abstract: The present invention belongs to the field of animal health and relates to a nucleic acid sequence which comprises the genome of an infectious genotype I (EU) PRRS virus clone useful for studying Porcine Reproductive and Respiratory Syndrome (PRRS), a viral disease affecting swine, and in the development of vaccines, therapeutics and diagnostics for the prophylaxis, treatment and diagnosis of PRRS.

Abstract: The present provides fusion proteins comprising PDGF and VEGF binding portions, and recombinant viral particles encoding the fusion proteins. Compositions comprising the fusion proteins and viral particles as well as methods of using the same are also provided.

Abstract: This invention relates to the field of therapeutics. Most specifically, the invention provides methods of generating conditionally expressing one or more proteins under the control of a gene expression modulation, system in the presence of activating ligand and uses for therapeutic purposes in animals. The vector may be provided to treat or prevent disease.

Abstract: The present invention relates to a cell line in which an expression construct is introduced into a genomic DNA, the expression construct including: (a) a promoter operable in animal cells and heterologous to adenoviruses; and (b) a modified adenovirus E1 coding gene sequence of SEQ ID NO:1 operatively linked to the promoter. According to the present invention, the cell line of the present invention is a novel cell line which is less likely to produce a replication competent adenovirus (RCA). The adenovirus producing cell line of the present invention has a low possibility of producing RCA due to homologous recombination, when compared with conventional cell lines. Therefore, this makes it possible to regulate the required amount of virus during gene therapy using the adenovirus and prevent tissue damage and toxic effects caused by overproduction of the adenovirus.

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: Provided are pro-coagulant compounds (e.g., pro-coagulant peptides or peptide derivatives) and methods of using and making those compounds. Further provided are conjugates between a pro-coagulant compound of the present disclosure (e.g., pro-coagulant peptide or peptide derivative) and a polypeptide selected from FIX, FVIIa, FVIII, and platelet targeting moieties (e.g., PDG-13), wherein the compound is linked to the polypeptide optionally via a linker. The compounds and conjugates are useful for the treatment of coagulation disorders, such as hemophilia A and hemophilia B. Further provided are methods of using and making the conjugates.

Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Abstract: The present invention refers to the gene cluster and genes comprised by the gene cluster which are involved in the biosynthesis of griselimycin and methylgriselimycin and to the use of the gene cluster, genes comprised thereby and proteins encoded thereby for the production of antibiotic agents.

Abstract: The present invention concerns methods and compositions involving RNase III and polypeptides containing RNase III domains to generate RNA capable of triggering RNA-mediated interference (RNAi) in a cell. In some embodiments, the RNase III is from a prokaryote. RNase III activity will cleave a double-stranded RNA molecule into short RNA molecules that may trigger or mediate RNAi (siRNA). Compositions of the invention include kits that include an RNase III domain-containing polypeptide. The present invention further concerns methods using polypeptides with RNase III activity for generating RNA molecules that effect RNAi, including the generation of a number of RNA molecules to the same target.

Abstract: The present invention generally relates to methods of making cDNA molecules and cDNA libraries. The invention also relates to cDNA molecules and cDNA libraries produced according to these methods, as well as to vectors and host cells containing such cDNA molecules and libraries. The invention also relates to kits for making the cDNA molecules and libraries of the invention.

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: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

Abstract: A heat-resistant NDV live vaccine vector system includes a transcription plasmid, three helper plasmids, and host cells. The transcription plasmid is constructed by through cloning complete genomic cDNA of a heat-resistant NDV vaccine strain to a pBR322 vector. The three helper plasmids are constructed by cloning sequences coding nucleoprotein (NP), phosphoprotein, large polymerase protein of a heat-resistant NDV vaccine strain respectively to pcDNA3.1 vectors. A recombinant NDV artificially obtained by cotransfacting host cells with the transcription plasmid and the three helper plasmids shows heat-resistance.

Abstract: Compositions and methods are disclosed that relate to novel plasmin-inhibiting polypeptides that are structural variants of a human TFPI-2 Kunitz-type proteinase first inhibitor domain (KD1). The polypeptides are potent plasmin inhibitors and in certain embodiments have anti-fibrinolytic activity and/or decreased anti-coagulation activity relative to wild-type TFPI-2 KD1 and are not highly immunogenic. The plasmin-inhibiting polypeptides will find uses as anti-cancer agents, as antifibrinolytic agents, as protease inhibitors, and in other contexts.

Abstract: The present invention relates to nucleic acid sequences coding for modified coagulation factors, preferably coagulation factor VIII, and their derivatives; recombinant expression vectors containing such nucleic acid sequences; host cells transformed with such recombinant expression vectors; and recombinant polypeptides and derivatives coded for by said nucleic acid sequences, whereby said recombinant polypeptides and derivatives have biological activities and prolonged in vivo half-lives compared to the unmodified wild-type proteins. The invention also relates to corresponding sequences that result in improved in vitro stability. The present invention further relates to processes for the manufacture of such recombinant proteins and their derivatives. The invention also relates to a transfer vector for use in human gene therapy, which comprises such nucleic acid sequences.

Abstract: The present disclosure relates to polypeptides, including fusions thereof, nucleic acids, vectors, host cells, immunodiagnostic reagents, kits, and immunoassays for use detecting the presence of HCV antibodies. More specifically, the present invention describes specific NS3 antigens that can be used for the detection of anti-HCV antibodies.

Abstract: The current disclosure provides a method for the creation of a high-density cryopreserved cell bank using perfusion culture techniques and non-centrifugal concentration of cells. Methods of production using this high-density cryopreserved cell bank are also provided.

Abstract: There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them.

Abstract: Methyl-lysine affinity reagents created by engineering the 3×MBT methyl-lysine binding domain repeat of lethal (3) malignant brain tumor-like protein 1 (L3MBTL1) are disclosed. In particular, the invention relates to affinity reagents and affinity chromatography media comprising the 3×MBT domain repeat and methods of using such affinity reagents in detection, purification, and proteomic profiling of methylated proteins and peptides.

Abstract: A blood coagulation factor VII derivative, a blood coagulation factor VIIa derivative, FacVII and FacVIIa conjugates are prepared by linking a polymer capable of extending the blood half-life to the derivative. FacVII and VIIa complexes each prepared by linking a carrier to the conjugate, genes encoding the FacVII and FacVIIa derivatives, expression vectors comprising the genes, transformants introduced with the expression vectors, a method for preparing the FacVII and FacVIIa derivatives using the transformants, a method for preparing the FacVIIa conjugate and complex, a FacVIIa complex prepared by the method, a pharmaceutical composition for the prevention or treatment of hemophilia comprising the derivative, conjugate, or complex as an active ingredient, and a pharmaceutical composition for blood coagulation comprising the derivative, conjugate, or complex as an active ingredient are described.

Abstract: Disclosed herein are methods and compositions for inactivating a FUT8 gene, using fusion proteins comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Abstract: The present invention provides isolated polynucleotides that can serve as translation enhancing elements and their use in protein expression reagents and methods.

Abstract: The invention concerns the field of recombinant gene engineering. It concerns novel introns and compositions comprising such introns as well as a method to improve expression of polypeptides from nucleic acids such as cloned genes with heterologous introns, especially genes encoding antibodies and antibody derived fragments, and the production of various polypeptides in eukaryotic host cells using said novel intron sequences as heterologous introns.

Abstract: The invention concerns the field of recombinant gene engineering. It concerns novel introns and compositions comprising such introns as well as a method to improve expression of polypeptides from nucleic acids such as cloned genes with heterologous introns, especially genes encoding antibodies and antibody derived fragments, and the production of various polypeptides in eukaryotic host cells using said novel intron sequences as heterologous introns.

Abstract: A conditioned cell culture medium of cells derived from Spalax or naked mole rat (Heterocephalus glaber) and methods for preparing it are provided. Pharmaceutical compositions comprising the conditioned cell culture medium and its use in the treatment of cancer as well as methods for identifying anti-cancer agents are also provided.

Abstract: The present invention provides novel nucleotides sequences, protein sequences, immunogenic compositions, vaccines, and methods that relate to making and using new porcine parvovirus 5B (PPV5B) that infects, inter alia, domestic swine. The compositions and methods provide for the detection of infections by said new virus, monitoring genetic changes in the viral sequences in wild and domestic animals and herds, and making and using novel vaccines for protecting animals from infection by the virus.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration, and reduced immunogenicity. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, Short Bowel Syndrome, Parkinson's disease, and cardiovascular disease.

Abstract: Methods and cell lines for overexpressing functional gamma-carboxylated proteins are disclosed.

Abstract: The present invention relates to polynucleotides encoding immunogenic HIV polypeptides. Uses of the polypeptides in applications including immunization, generation of packaging cell lines, and production of HIV polypeptides are also described. Polynucleotides encoding antigenic HIV polypeptides are described, as are uses of these polynucleotides and polypeptide products therefrom, including formulations of immunogenic compositions and uses thereof.

Abstract: Targeted coagulation factors comprising a coagulation factor linked with at least one domain that specifically binds to a membrane protein on a blood cell is provided. The disclosed targeted coagulation factors increase the efficiency of coagulation factors and prolong their duration of action and thus, are an improvement for the treatment of hematological diseases such as hemophilia A.

Abstract: Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.

Abstract: The present invention relates to a system and methods for identifying a compound for de-fatting and functional recovery of macrosteatotic hepatocytes.

Abstract: The present invention is concerned with nuclease fusion proteins and various uses thereof. Specifically, it relates to a polynucleotide encoding a polypeptide comprising (i) a first module comprising at least a first DNA binding domain derived from a homing endonuclease, (ii) a linker, and (iii) a second module comprising at least a second DNA binding domain and a cleavage domain derived from a restriction endonuclease, wherein said polypeptide functionally interacts only with DNA comprising a DNA recognition site for the first DNA binding domain and a DNA recognition site for the second DNA binding domain, and wherein said cleavage domain cleaves DNA within a specific DNA cleavage site upon binding of the polypeptide. Further contemplated are a vector and a non-human transgenic organism comprising said polynucleotide as well as a polypeptide encoded by the polynucleotide of the invention.

Abstract: IL4/IL13-binding proteins comprise binding domains, which inhibit IL4/IL13 binding to IL4Ralpha and common gamma chain complexes (Type 1) and inhibit IL4 binding to IL4Ralpha and IL13Ralpha1 complexes (Type 2), and IL13 binding to IL13Ralpha1 and/or IL13Ralpha2, are useful in the treatment of cancer, inflammatory, and other pathological conditions, such as allergic or fibrotic conditions, especially pulmonary conditions.

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.