Abstract: The present invention relates to multispecific antibodies comprising at least three antigen binding sites wherein the third binding site is disulfide stabilized by introduction of cysteine, method for their production, pharmaceutical compositions containing said antibodies and uses thereof.

Abstract: The present invention relates to a method for solubilisation or hydrolysis of Municipal Solid Waste (MSW) with an enzyme blend and an enzyme composition for solubilization of Municipal Solid Waste (MSW), the enzyme composition comprising a cellulolytic background composition and a protease, lipase and/or beta-glucanase.

Abstract: Provided herein are, inter alia, humanized 1E9 antibodies capable of binding CD73. The humanized antibodies are useful for the treatment of cancer. Further provided are nucleic acids encoding humanized 1E9 antibodies and methods of inhibiting cell proliferation using the humanized antibodies provided herein.

Abstract: Methods are provided for modulating an abiotic stress response to drought in a plant, for example by introducing a heritable change to the plant, which alters the expression in the plant of an endogenous or exogenous protein that is a member of a particular gene family, the Kanghan genes. Similarly, plants and plants cells having such heritable changes are provided.

Abstract: Disclosed herein are cytomegalovirus vectors encoding fusion proteins comprising Mycobacterium tuberculosis (Mtb) antigens, nucleic acid molecules encoding the same, cytomegalovirus vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.

Abstract: The present invention is based on the discovery of genetic polymorphisms that are associated with psoriasis and related pathologies. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, including groups of nucleic acid molecules that may be used as a signature marker set, such as a haplotype, a diplotype, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Abstract: Embodiments relate to novel vaccines against human papillomavirus (HPV) and HPV-related diseases, including multiple types of cancers. The HPV vaccines are composed of anti-human dendritic cell (DC) surface receptor antibodies, including CD40, and E6/7 proteins of HPV16 and 18. The technology described is not limited to making vaccines against HPV16- and HPV18-related diseases and can be applied to making vaccines carrying E6/7 from any type of HPV. The HPV vaccines described can target DCs, major and professional antigen presenting cells (APCs), and can induce and activate potent HPV E6/7-specific and strong CD4+ and CD8+ T cell responses. The HPV vaccines can be used for the prevention of HPV infection and HPV-related diseases as well as for the treatment of HPV-related diseases, including cancers.

Abstract: The present invention is based on the discovery of genetic polymorphisms that are associated with cardiovascular disorders, particularly acute coronary events such as myocardial infarction and stroke, and genetic polymorphisms that are associated with responsiveness of an individual to treatment of cardiovascular disorders with statin. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Abstract: The invention relates to improved methods, devices, and kits for identifying and implementing an appropriate treatment regimen for subjects suffering from hypertension.

Abstract: The invention relates to a method of isolating an immunoglobulin, comprising the steps of: a) providing a separation matrix comprising at least 15 mg/ml multimers of immunoglobulin-binding alkali-stabilized Protein A domains covalently coupled to a porous support, wherein the porous support comprises cross-linked polymer particles having a volume-weighted median diameter (d50,v) of 56-70 micrometers and a dry solids weight of 55-80 mg/ml; b) contacting a liquid sample comprising an immunoglobulin with the separation matrix; c) washing the separation matrix with a washing liquid; d) eluting the immunoglobulin from the separation matrix with an elution liquid; and e) cleaning the separation matrix with a cleaning liquid comprising at least 0.5 M NaOH.

Abstract: Provided are methods for administering multiple doses of cells, such as T cells, to subjects for cell therapy. Also provided are compositions and articles of manufacture for use in the methods. The cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). The methods generally involve administering a first and at least one consecutive dose of the cells. Timing of the doses relative to one another, and/or size of the doses, in some embodiments provide various advantages such as lower or reduced toxicity and improved efficacy, for example, due to increased exposure of the subject to the administered cells. In some embodiments, the first dose is a relatively low dose, such as one that reduces tumor or disease burden, thereby improving the efficacy of consecutive or subsequent doses, and the consecutive dose is a consolidating dose.

Abstract: This disclosure concerns compositions and methods for increasing the expression of a polynucleotide of interest. Some embodiments concern novel transactivation polypeptides and variants thereof that have been identified in plants, and methods of using the same. Particular embodiments concern the use of at least one DNA-binding polypeptide in a fusion protein to target at least one transactivation polypeptide or variant thereof to a specific binding site on a nucleic acid comprising the polynucleotide of interest, such that its expression may be increased.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell expressing a CAR having an antigen binding domain, a transmembrane domain, a CD2 signaling domain, and a CD3 zeta signaling domain. The invention also includes incorporating CD2 into the CAR to alter the cytokine production of CAR-T cells in both negative and positive directions.

Abstract: The invention relates to a polypeptide comprising a C3 convertase effector domain, a C5 convertase effector domain and optionally a terminal complex inhibitory effector domain which is resistant to deregulation by physiologic FHR-Proteins and has a dimerization motif, and to its therapeutic use.

Abstract: The application relates to the field of biopharmaceuticals, in particular to tumor-targeting peptides and method for preparation and application thereof. The application discloses a tumor-targeting peptide. The tumor-target peptide displays better binding specificity and capability, thereby alleviates the effect of cancer treatment drugs on normal cells, reduces the incidence of adverse drug reactions, and improves the therapeutic effect.

Abstract: Disclosed herein include methods of reducing the viscosity of a starch slurry during starch processing by the addition of one or more surfactants and one or more amylases. In some embodiments, the unexpected reduction in slurry viscosity results in a surprising increase in corn oil recovery, reduction in residual starch, and increased fermentation rate.

Abstract: The present disclosure describes a method of treating immunological disorders, for example alloimmune and autoimmune diseases, using a pharmaceutical composition comprising at least one mesenchymal stromal cell-derived protein Further disclosed herein is the use of the pharmaceutical composition for immunomodulation.

Abstract: In this invention, a non-infectious particle has been produced, comprising a pathogen antigen protein caused to be expressed on the surface of a virus particle having at least one species of paramyxovirus envelope protein missing from the particle. This particle has been found to hold within the particle a large amount of antigen protein compared to an infectious particle, and to be capable of eliciting a host immune response with extremely high efficiency. The non-infectious particle according to the present invention is useful as a vaccine against a pathogenic virus, or the like.

Abstract: A method of decreasing cytokine production and release is disclosed. In one embodiment, the method comprises the step of providing cytotoxic cells to a subject wherein the cells are preferably natural killer cells or T lymphocytes and are genetically modified to express a chimeric antigen receptor comprising a first element that is an extracellular antigen receptor and a second intracellular element that is a signaling moiety comprising altered ADAP-dependent or Fyn-dependent signaling such that downstream signaling causing cytokine release is decreased. Specific modifications of CD137 and NKG2D cytoplasmic tails are described. Additionally, methods to develop and screen drug compounds capable of compromising the binding between ADAP and Fyn and disrupting the downstream release of cytokines are described.

Abstract: The present invention provides a chimeric antigen receptor (CAR) that recognizes B7-H3 (CD276), as well as methods of use in the treatment of diseases and disorders.

Abstract: Materials and methods related to gene targeting (e.g., gene targeting with transcription activator-like effector nucleases; “TALENS”) are provided.

Abstract: Synthetic HIV envelope proteins, vectors and compositions thereof, and methods for inducing protective immunity against human immunodeficiency virus (HIV) infection are described. Viral expression vectors encoding the synthetic HIV envelope proteins can be used in vaccines to provide improved protective immunity against HIV.

Abstract: The present invention relates in part to nucleic acids encoding proteins, therapeutics comprising nucleic acids encoding proteins, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, and therapeutics produced using these methods, kits, and devices. Methods and products for altering the DNA sequence of a cell are described, as are methods and products for inducing cells to express proteins using synthetic RNA molecules. Therapeutics comprising nucleic acids encoding gene-editing proteins are also described.

Abstract: The invention relates to conjugates that bind to targets, methods of using conjugates that bind to targets and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies that express a target.

Abstract: Disclosed herein are enhanced polypeptides, polynucleotides encoding these polypeptides, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

Abstract: A sugar cane plant cell comprising a recombinant nucleic acid molecule is provided, the recombinant nucleic acid molecule comprising a nucleotide sequence of interest, a promoter and the nucleotide sequence of SEQ ID NO:1, wherein the promoter is downstream of and in operative association with the nucleotide sequence of SEQ ID NO:1 and upstream of and in operative association with the nucleotide sequence of interest, and the nucleotide sequence of interest is expressed at a level at least about 6 times greater than the level of expression of said nucleotide sequence of interest in a control. Additionally, a method of increasing the expression of a nucleotide sequence of interest in a sugar cane plant cell using the recombinant nucleic acid molecule of the invention is provided.

Abstract: The present invention features mutant stromal cell derived factor-1 (SDF-1) peptides that have been mutated to make them resistant to digestion by, for example, the proteases dipeptidyl peptidase IV (DPPIV), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), leukocyte elastase, cathepsin G, carboxypeptidase M, and carboxypeptidase N, but which retain chemoattractant activity.

Abstract: The present invention concerns the endonucleases capable of cleaving a target sequence located in a “safe harbor loci”, i.e. a loci allowing safe expression of a transgene. The present invention further concerns the use of such endonucleases for inserting transgenes into a cell, tissue or individual.

Abstract: The invention provides polynucleotides and methods for expressing light-activated proteins in animal cells and altering an action potential of the cells by optical stimulation. The invention also provides animal cells and non-human animals comprising cells expressing the light-activated proteins.

Abstract: The present invention relates to blood products, and more particularly to compositions comprising a modified oxygenated hemoglobin having a high affinity for oxygen and methods for making such compositions. Such compositions according to the present invention have better stability to auto oxidation and superior oxygen carrying characteristics.

Abstract: This invention features a kit containing multiple expression vectors for producing tag-cleavable fusion proteins in various expression systems, or for producing fusion proteins in E. coli inclusion bodies.

Abstract: The invention provides compositions and methods for delivering a bioactive moiety comprising at least one non-natural component into a cell cytosol of an eukaryotic cell. The bioactive moiety is linked to an A component of a bacterial toxin, a functional wild-type or modified fragment thereof, or an A component surrogate or mimetic. For delivery, the cell is contacted with the linked bioactive moiety and a corresponding B component of the bacterial toxin or a functional fragment thereof.

Abstract: The present invention is directed to pharmaceutical agents and compositions useful for the treatment and prevention of amyloid disease in a subject. The invention further relates to isolated antibodies that recognize a common conformational epitope of amyloidogenic proteins or peptides that are useful for the diagnosis, treatment, and prevention of amyloid disease.

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 a novel ecdysone receptor/chimeric retinoid X receptor-based inducible gene expression system and methods of modulating gene expression 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: A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also disclosed.

Abstract: The present invention provides, in part, an antibody display system that simultaneously uses a secretion and a display mode. Embodiments of the invention provide a system in which a bait complexed with a monovalent antibody fragment can be captured prior to secretion in a host cell by virtue of surface displaying an antibody light chain and utilizing the covalent interaction of this light chain with the heavy chain of an antibody molecule that is co-expressed in the same host. Polypeptides, polynucleotides and host cells useful for making the antibody display system are also provided along with methods of using the system for identifying antibodies that bind specifically to an antigen of interest.

Abstract: This invention relates to compositions and methods for eliciting an immune response against a parasite of the genus Plasmodium in a mammal.

Abstract: The invention concerns a system for modulating tissue physiology, for example, to prevent or reverse tissue damage caused by disease. The system utilizes vigilant cells that include stable vectors containing a gene switch/biosensor and a gene amplification system. The vectors allow expression of a transgene (such as a cardioprotective gene) in the vigilant cells to be regulated in response to a physiological signal, to be switched on or off, and to provide sufficient levels of the transgene product to achieve a desired result, e.g., prevention or reversal of myocardial cell damage. In addition to myocardial infarction, the vectors can be used to treat cells in a number of other disease states, including diabetes, cancer, stroke, and atherosclerosis. These approaches to stem cell-based gene therapy provide a novel strategy not only for treatment but for prevention of cell destruction.

Abstract: A compound comprising a photosensitizer covalently coupled to a protein selected from the group consisting of antibodies or their derivatives or fragments thereof, synthetic peptides such as scFv, mimotopes which bind CD antigens, cytokine receptors, interleukin receptors, hormone receptors, growth factor receptors, more particularly tyrosine kinase growth factor receptor of the ErbB family, wherein the photosensitizer is coupled to the binding protein via O6-alkylguanine-DNA alkyltransferase (hAGTm), a modified human DNA repair protein.

Abstract: The present invention relates to a therapeutic polypeptide and methods for its creation and use for modulating an immune response in a host organism in need thereof. In particular, the invention relates to the administration to an organism in need thereof, of an effective amount of a pre-coupled polypeptide complex comprising a lymphokine polypeptide portion, for example IL-15 (SEQ ID NO: 5, 6), IL-2 (SEQ ID NO: 10, 12) or combinations of both, and an interleukin receptor polypeptide portion, for example IL-15Ra (SEQ ID NO: 7, 8), IL-2Ra (SEQ ID NO: 9, 11) or combinations of both, for augmenting the immune system in, for example, cancer, SCID, AIDS, or vaccination; or inhibiting the immune system in, for example, rheumatoid arthritis, or Lupus. The therapeutic complex of the invention surprisingly demonstrates increased half-life, and efficacy in vivo.

Abstract: The invention provides, inter alia, conjugates comprising a coagulating agent conjugated to an antibody, where the antibody specifically binds an extracellular domain epitope of a mammalian PLVAP protein. These agents specifically target HCC tumors and treat the HCC. The invention also provides methods of using these conjugates, such as methods of treating HCC by administering the conjugates provided by the invention or compositions provided by the invention, such as pharmaceutical compositions.

Abstract: Disclosed herein are chimeric receptors comprising an extracellular domain with affinity and specific for the Fc portion of an immunoglobulin molecule (Ig) (e.g., an extracellular ligand-binding domain of F158 FCGR3A or V158 FCGR3A variant); a transmembrane domain (e.g., a transmembrane domain of CD8?); at least one co-stimulatory signaling domain (e.g., a co-stimulatory signaling domain of 4-1BB); and a cytoplasmic signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM) (e.g., a cytoplasmic signaling domain of CD3?). Also provided herein are nucleic acids encoding such chimeric receptors and immune cells expressing the chimeric receptors. Such immune cells can be used to enhance antibody-dependent cell-mediated cytotoxicity and/or to enhance antibody-based immunotherapy, such as cancer immunotherapy.

Abstract: The invention relates to the design of trimeric polypeptide complexes using polypeptide structural elements derived from the collagen XVIII 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: The present invention provide purified Flt4 receptor tyrosine kinase polypeptides and fragments thereof, polynucleotides encoding such polypeptides, antibodies that specifically bind such polypeptides, and uses therefor.

Abstract: Described are compositions and methods useful for modulating the immune system of a subject. Also included are diagnostic methods for monitoring an immunologic condition. In particular the invention relates to antagonists of interferon proteins and associated methods of use as well as methods to develop neutralizing antibodies against IFN antagonists to treat viral infections.

Abstract: Intermolecular disulfide stabilized foldon polypeptides are provided.

Abstract: A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also disclosed.

Abstract: The present disclosure provides immunogenic compositions, such as vaccines, including DNA vaccines, and uses thereof, e.g., to suppress or prevent an immune response and/or to treat or prevent an autoimmune disease.

Abstract: Fluorescent protein voltage sensors for measuring membrane potential and imaging high-frequency neuronal electrical activity are disclosed. In particular, the invention relates to engineered protein voltage sensors that comprise a voltage-sensing domain comprising four transmembrane domains linked to a circularly permuted fluorescent protein, which is inserted into the extracellular loop between the third (S3) and fourth (S4) transmembrane segments of the voltage-sensing domain. Such fluorescent protein voltage sensors can be used for measuring the electrical activity of neurons, including single action potentials, trains of action potentials, and subthreshold potential changes and, in particular, for imaging high-frequency neuronal electrical activity.

Abstract: The present invention relates to a fusion protein comprising a skin-penetrating peptide, a polynucleotide encoding the fusion protein, an expression vector comprising the polynucleotide, a transformant comprising the expression vector, a method for preparing the fusion protein, a cosmetic composition for improving skin conditions, which comprises the fusion protein, and a pharmaceutical composition for external skin use, which comprises the fusion protein. The fusion protein of the invention comprises a skin-penetrating peptide bound to a physiologically active protein. The fusion protein significantly enhances the skin penetration and skin retention of the physiologically active protein while maintaining or enhancing the ability of the physiologically active protein to synthesize a material showing physiologically active effects. Thus, it can be widely used as an active ingredient in functional cosmetic compositions and pharmaceutical compositions for external skin use.