Abstract: The present invention provides polypeptides with histone H3 lysine 79 methyltransferase activity as well as nucleic acids encoding the same. Also provided are methods of using the polypeptides and nucleic acids of the invention in screening assays to identify compounds of interest. Further provided are diagnostic methods for leukemia and prognostic methods to predict the course of the disease in a subject.

Abstract: Methods and diagnostic agents for identification of subjects for cancer treatment with an anti-hyaluronan agent, such as a hyaluronan-degrading enzyme, are provided. Diagnostic agents for the detection and quantification of hyaluronan in a biological sample and monitoring cancer treatment with an anti-hyaluronan agent, for example a hyaluronan-degrading enzyme, are provided. Combinations and kits for use in practicing the methods also are provided.

Abstract: Provided herein are compositions and methods for the assembly of a bioluminescent complex from two or more non-luminescent (e.g., substantially non-luminescent) peptide and/or polypeptide units. In particular, bioluminescent activity is conferred upon a non-luminescent polypeptide via structural complementation with another, complementary non-luminescent peptide.

Abstract: The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides a soluble FZD receptor comprising an extracellular domain of a human FZD receptor that inhibits growth of tumor cells. The present invention still further provides a soluble receptor comprising a Fri domain of a human FZD receptor that binds a ligand of a human FZD receptor and said soluble receptor is capable of inhibiting tumor growth. The present invention still further provides a method of treating cancer comprising administering a soluble FZD receptor comprising for example, either an extracellular domain of a human FZD receptor or a Fri domain of a human FZD receptor, in an amount effective to inhibit tumor growth.

Abstract: The present invention relates to exosomes comprising a transferrin targeting moiety on their surface, methods of producing them and to the use of such exosomes for delivering genetic material and/or biotherapeutic proteins or peptides or chemotherapeutic agents in vivo, in particular the use of such exosomes in methods of gene therapy or gene silencing, or delivery of other therapeutic agents.

Abstract: The invention relates generally to a new trimerization domain useful for developing multifunctional and multivalent complexes. Particularly, the invention relates to the design of trimeric polypeptide complexes using polypeptide structural elements derived from the collagen XV protein, and their use in diagnostic and therapeutic systems in vivo and in vitro. The invention also relates to nucleic acids and vectors useful for producing said trimeric complexes.

Abstract: Nucleases and methods of using these nucleases for modification of an HPRT locus and for increasing the frequency of gene modification at a targeted locus and clones and for generating animals.

Abstract: The present invention provides a hemojuvelin (HJV) fusion protein (e.g., a human HJV.Fc) protein, polynucleotides and vectors encoding such proteins, and methods for making such proteins. Also provided are methods for treating iron-related disorders which include administration of a HJV fusion protein to a patient in need thereof.

Abstract: The invention relates to a polypeptide comprising: (a) a HC-domain or fragment thereof of the neurotoxic component of a clostridial toxin; and (b) a first LC domain or fragment thereof of the neurotoxic component of a clostridial toxin; and (c) at least one further LC domain or fragment thereof of the neurotoxic component of a clostridial toxin wherein the first and the at least one further LC domain may be the same or different from each other, and wherein each of said fragments of said first and of said at least one further LC domain still exhibits proteolytic activity.

Abstract: High-affinity variants of the DMF5 TCR, and methods of use thereof for the treatment and imaging of cancer in a patient.

Abstract: A cell-killing peptide, more specifically a cell-killing CKP fusion peptide (CTD7:CKP) is disclosed, wherein a cell-killing peptide (CKP) comprising 10 amino acids in MTD of Noxa protein causing cell death, and 7 amino acids targeting a cancer cell are fused. The cell-killing CKP fusion peptide induces strong cell necrosis at various cancer cell lines (HeLa, HCT116, MCF-7, A549, BJAB, CT26, PC3 and the like) and shows strong tumor regression effect at a mouse tumor model using experimental animals, but does not show apoptosis at normal cells. Therefore, it can be broadly used to human body for treating various diseases requiring cell death, particularly, as an anti-cancer drug.

Abstract: Embodiments herein report compositions of alpha-1 antitrypsin fusion polypeptides or peptide derivatives thereof. In certain embodiments, compositions and methods relate to generating a construct of use in pharmaceutically acceptable compositions to treat a subject in need of alpha-1 antitrypsin therapy or treatment. In other embodiments, compositions and methods disclosed herein concern linking alpha-1 antitrypsin or derivative thereof to an immune fragment.

Abstract: Provided is a fusion protein comprising circularly permuted form of TRAIL, and the fusion protein contains circularly permuted form of TRAIL and oligopeptides located at the N-terminus and/or C-terminus of the permuted form. The oligopeptides contain a repeating sequence consisting of 3-10 histidines. The components of the circularly permuted form of TRAIL from N-terminus to C-terminus are: (a) amino acids 135-281 of TRAIL, (b) a linker, and (c) amino acids 121-135 of TRAIL or amino acids 114-135 of TRAIL or amino acids 95-135 of TRAIL or any fragments of amino acids 95-135 of TRAIL containing amino acids 121-135 of TRAIL. Also provided is a method for treating cancer by using the fusion protein.

Abstract: The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Abstract: A fusion protein that includes a polypeptide binding specifically to a constant region of an antibody and a stabilization protein linked to a terminus of the polypeptide, a polynucleotide encoding the fusion protein, a cell including the polynucleotide, a method of preparing the fusion protein, and a method of isolating an antibody by using the fusion protein.

Abstract: Fusion proteins including a type-II cohesin module that are capable of integrating into native and designer cellulosomes. ?-glucosidases modified to include a type-II cohesin module and polynucleotides encoding same. Multi-enzyme complexes including the fusion proteins, and methods for biomass degradation utilizing same.

Abstract: We disclose growth hormone fusion proteins that have increased in vivo stability and activity; nucleic acid molecules encoding said proteins and methods of treatment of growth hormone related diseases that would benefit from growth hormone agonists or antagonists.

Abstract: The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of amyloid proteins. The compositions may also be used to detect amyloid.

Abstract: The present invention relates to LRP6 constructs that bind to LRP6 receptor. The LRP6 constructs comprise at least one LRP6 binding moiety and a half-life extender molecule such that the LRP6 construct inhibit the Wnt signaling pathway without potentiation of the Wnt signal. The LRP6 constructs also have an increased half-life to provide more time for the therapeutic benefit.

Abstract: The present disclosure provides a fusion protein comprising IL-1 receptor antagonist fused to a hybrid Fc. Particularly the present disclosure relates to a fusion protein comprising IL-1 receptor antagonist fused to a human immunoglobulin hybrid Fc fragment. In one embodiment, the hybrid Fc fragment comprises IgD and IgG4. Also provided is a pharmaceutical composition comprising the present fusion protein, which are useful for treating autoimmune disease including rheumatoid arthritis, inflammatory bowel disease (Crohn's disease, ulcerative colitis), psoriasis and diabetes and the like. The present fusion protein with excellent efficacy and reduced side effects is qualified for clinical development as therapeutic antibodies to treat autoimmune disease.

Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating or preventing diseases, disorders or conditions related to diabetes mellitus using albumin fusion proteins of the invention.

Abstract: The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Abstract: The present invention relates to DYAD genes, mutants thereof, and use of them for making plants that retain heterozygosity of the female parent plant. The invention also encompasses plants, plant tissues, and seeds of plants that have a dyad phenotype and so retain heterozygosity of the female parent, either constitutively or conditionally. The invention is useful for propagating desired hybrid phenotypes in a manner of an apomictic plant and for increasing the ploidy of a plant genotype, which may result in plants having increased biomass.

Abstract: Transgenic plants that express CIVPS or intein modified proteins, compositions of matter comprising them, products of diverse applications made from the transgenic plants, methods to construct the transgenic plants containing CIVPS or intein modified genes, methods to express CIVPS or intein modified proteins in plants, and methods of using the transgenic plants.

Abstract: Disclosed are yeast-based immunotherapeutic compositions, hepatitis B virus (HBV) antigens, and fusion proteins for the treatment and/or prevention of HBV infection and symptoms thereof, as well as methods of using the yeast-based immunotherapeutic compositions, HBV antigens, and fusion proteins for the prophylactic and/or therapeutic treatment of HBV and/or symptoms thereof.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of EGFRvIII. The invention also relates to chimeric antigen receptor (CAR) specific to EGFRvIII, vectors encoding the same, and recombinant T cells comprising the anti-EGFRvIII CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an anti-EGFRvIII binding domain.

Abstract: The present invention refers to recombinant DNA molecules codifying fused peptides from different allergens from Blomia tropicalis and Dermatophagoides pteronyssinus having potential usefulness in prevention and treatment of allergies caused by domestic mites. Specifically, the invention discloses fusion proteins composed by different fragments of allergens Der p 1, Der p 2, Der p 7, Der p 8, Blo t 5, Blo t 8, Blo t 18, Blo t 12 and Blo t 13 with reduced serum IgE reactivity in allergic and non allergic individuals. It also discloses methods for production of these molecules in an expression system based on E. coli and purification. The invention refers also to effective and safe vaccines.

Abstract: Intramolecular biosensors are disclosed, including PBP-based biosensors, comprising a ligand binding domain fused to donor and fluorescent moieties that permit detection and measurement of Fluorescence Resonance Energy Transfer upon binding ligand. At least one of the donor and fluorescent moieties may be internally fused to the biosensor such that both ends of the internally fused fluorophore are fixed. In addition, methods of improving the sensitivity of terminally fused biosensors are provided. The biosensors of the invention are useful for the detection and quantification of ligands in vivo and in culture.

Abstract: The invention provides compositions and methods for treating leukemia, for example, acute myeloid leukemia (AML) and B-cell acute lymphoid leukemia (B-ALL). The invention also relates to at least one chimeric antigen receptor (CAR) specific to CD123, vectors comprising the same, and recombinant T cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD123 binding domain. The invention also includes methods of bone marrow ablation for use in treatments necessitating bone marrow reconditioning or transplant.

Abstract: The present invention provides methods for light-dependent gene regulation using a light-responsive DNA-binding protein. Also provided are related nucleic acid molecules, and protein molecules, such as those encoding or comprising the light-responsive DNA-binding protein or DNA-binding sites recognizing the light-responsive DNA-binding protein. Kits using the present light-dependent gene regulation system are further provided by the present invention.

Abstract: The present invention provides compositions and methods for regulating the specificity and activity of T cells. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a “KIR-CAR” which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

Abstract: The invention provides compositions and methods of use thereof for labeling peptide and proteins in vitro or in vivo. The methods described herein employ lipoic acid ligase or mutants thereof, and lipoic acid analogs recognized by lipoic acid ligase and lipoic acid ligase mutants.

Abstract: The invention relates to applications of the cellulase Cel5H of Saccharophagus degradans and its homologues, functional fragments and/or variants and engineered forms thereof, in the context of recombinant, more particularly solventogenic microorganisms, more particularly C. acetobutylicum. The invention also characterizes a novel domain of the Cel5H cellulase with a putative cellulose-binding module function, and its uses in chimeric proteins for depolymerization of cellulose containing substrates.

Abstract: Disclosed herein are methods and compositions for modulating activity of CXCR4 genes, for example using zinc finger transcription factors (ZF-TFs) or zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZF-TFs or ZFNs, vectors comprising polynucleotides encoding ZF-TFs or ZFNs and cells comprising polynucleotides encoding ZF-TFs or ZFNs and/or cells comprising ZF-TF or ZFNs are also provided.

Abstract: The invention provides a fusion protein comprising, from N-terminus to C-terminus: a) a first portion of a Family B G-protein coupled receptor (GPCR) that comprises transmembrane helix (TM)-1, TM2 and TM3 of the GPCR; b) a stable protein domain; and c) a second portion of the GPCR comprising TM4, TM5, TM6 and TM7 of the GPCR. The invention also provides a method of crystallising a GPCR comprising providing the fusion protein of the invention and crystallising it to obtain crystals.

Abstract: The present invention is directed to a polypeptide which comprises: (i) an Rv2386c protein sequence; (ii) a variant of an Rv2386c protein sequence; of (iii) an immunogenic fragment of an Rv2386c protein sequence. In other aspects the invention is directed to associated polynucleotides, fusion proteins and methods for the treatment or prevention of tuberculosis.

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 invention relates to IL-22 polypeptides, IL-22 Fc fusion proteins and IL-22 agonists, composition comprising the same, methods of making and methods of using the composition for the treatment of diseases. The invention also relates to IL-22 receptor associated reagents and methods of use thereof.

Abstract: Methods and products (e.g., recombinant proteins) are described for increasing frataxin expression/levels in a cell, as well as uses of such methods and products, for example for the treatment of Friedreich ataxia in a subject suffering therefrom.

Abstract: Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Abstract: The invention is concerned with a fusion protein comprising interleukin 10 and interleukin 4, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of osteoarthritis, chronic pain, a condition characterized by local or systemic inflammation, immune activation, and/or lymphoproliferation.

Abstract: Disclosed is a recombinant polypeptide for facilitating membrane fusion. The recombinant polypeptide having a sequence with at least 80% sequence identity with the ectodomain of p14 fusion-associated small transmembrane (FAST) protein and having a functional myristoylation motif, a transmembrane domain from a FAST protein and a sequence with at least 80% sequence identity with the endodomain of p15 FAST protein. A targeting ligand can be added to the recombinant polypeptide for selective fusion. The recombinant polypeptide can be included in the membrane of a liposome, or the like, to facilitate the delivery of bioactive compounds, such as siRNA, or the recombinant polypeptide can be mixed with a lipid carrier and added to cultured cells to induce cell-cell fusion and heterokaryon formation.

Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.

Abstract: The present disclosure relates to a soluble CD52 glycoprotein and its use in treating diseases regulated by effector T-cells, for example autoimmune diseases such as type 1 diabetes. The present disclosure also relates to fusion proteins comprising the soluble glycoprotein, to cells expressing high levels of CD52, and to diagnostic methods based on the detection of CD52 expression levels in a subject.

Abstract: A recombinant fusion interferon for animals. The recombinant fusion interferon comprises an animal interferon and a Fc region of an animal immunoglobulin G (IgG). The animal interferon and the Fc region of the animal immunoglobulin G can be further joined by a linker. A polynucleotide that encodes the recombinant fusion interferon for animals, a method for producing the recombinant fusion interferon, and the use of the recombinant fusion interferon.

Abstract: Influenza virus-like particles (VLPs) comprising the structural proteins HA, NA, M1 and M2 are described. VLPs are also generated containing M1 alone, as are VLPs with M1 and any one or two of HA, NA and M2. VLPs with HA from one influenza subtype and NA from a different influenza subtype are also described, as are VLPs in which a portion or all of HA or NA is replaced by a heterologous moiety not produced by influenza virus, so as to comprise chimeric VLPs.

Abstract: In one embodiment, the present invention provides a new isoform of human PD1 (?42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain. ?42PD1 does not engage PD-L1/PD-L2, and can induce the production of pro-inflammatory cytokines In one embodiment, ?42PD1 can be used as an intramolecular adjuvant to develop a fusion DNA vaccine for enhancing antigen-specific CD8+ T cell immunity and for prevention of pathogenic infection and/or cancer. In one embodiment, soluble ?42PD1 protein could be a therapeutic target for autoimmune diseases. In other embodiments, proteins or peptides or nucleic acids encoding proteins or peptides containing ?42PD1 could be used as immunogens for developing antibodies binding specifically to ?42PD1. In yet another embodiment, neutralizing antibodies could block s?42PD1 function and accordingly could be used as treatment for autoimmune disorders.

Abstract: The present invention relates to compositions comprising biologically active proteins linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of glucose-related diseases, metabolic diseases, coagulation disorders, and growth hormone-related disorders and conditions.

Abstract: Provided are chimeric VEGF-binding proteins and nucleic acids (e.g., a vector) encoding chimeric VEGF-binding proteins, methods and host cells for producing these proteins and nucleic acids, and pharmaceutical compositions containing these proteins and nucleic acids. Also provided are methods of treating an angiogenic disease or disorder that include administering at least one of the chimeric VEGF-binding proteins or at least one of the nucleic acids (e.g., a vector) encoding a chimeric VEGF-bind ing protein.

Abstract: Provided herein are tandem Fcs and tandem Fc antibodies (“TFcAs”), e.g., tandem Fc bispecific antibodies (“TFcBAs”), which comprise one or at least two binding sites that specifically bind to one or more cell surface receptors. The binding sites are connected through a TFc, which TFc comprises a first Fc region and a second Fc region, wherein the first and the second Fc regions are linked through a TFc linker to form a contiguous polypeptide and dimerize to form an Fc dimer. Exemplary TFcBAs bind to the cell surface receptors c-Met and EpCam and inhibit signal transduction through the cell surface receptor(s) for which the binding sites of the TFcBA are specific.