Abstract: Disclosed is a method of synthesizing linaclotide through completely selective formation of three disulfide bonds, comprising the steps of: 1) synthesizing linaclotide precursor resin through solid-phase synthesis; 2) forming the first disulfide bond through solid phase oxidation; 3) forming the second disulfide bond through liquid phase oxidation; and 4) deprotecting methyl in the methyl-protected cysteine, and oxidatively coupling the third disulfide bond to obtain linaclotide. The method has mild reaction conditions with low cost, high yield and high purity product, is a simple and stable process and is suitable for large-scale production.

Abstract: Nucleic acid molecules encoding monomeric near-infrared fluorescent proteins, variants and derivatives thereof are provided, as well as proteins and peptides encoded by these nucleic acids. Also provided are proteins that are substantially similar to, or derivatives, homologues, or mutants of, the above-referenced specific proteins. Also provided are fragments of the nucleic acids and the peptides encoded thereby, specifically split fluorescent proteins. In addition, host-cells, stable cell lines and transgenic organisms comprising above-referenced nucleic acid molecules are provided. The invention also refers to methods of making and using monomeric fluorescent proteins derived from bacterial phytochromes. The subject protein and nucleic acid compositions find use in a variety of different applications and methods, particularly for labeling of biomolecules, cells or cell organelles, and for detecting protein-protein interactions. Finally, kits for use in such methods and applications are provided.

Abstract: The invention relates to artificial forisome bodies including a fusion protein of at least one SEO-F protein or an at least 50-amino acid portion thereof, and at least one additional protein or peptide, with the exception of GFP and the Venus protein, wherein in an embodiment the forisome body further includes an unfused SEO-F protein or a form of the protein having C-terminal deletions of up to 45 amino acids and/or N-terminal deletions of up to 13 amino acids, wherein the unfused SEO-F protein is selected from proteins having the property of being capable of forming homomeric forisome bodies in the absence of additional SEO-F proteins.

Abstract: An isolated protein that is highly abundant in the seed of wheat varieties with desirable breadmaking qualities is provided. Associated promoters and promoter active fragments are also provided. Further provided are plants or plant parts with improved or enhanced breadmaking properties, and methods of producing such plants, wherein the abundance of the isolated protein is increased or enhanced. Such plants and/or plant parts may be used in the production of plant products, for example bread and read products.

Abstract: Photoluminescent proteins resistant to protein cleavage reagents are described herein. In being resistant to cleavage reagents, such photoluminesncent proteins can reduce the number of digestion or cleavage products, thereby simplifying quantification and purification of recombinant protein compositions. In some embodiments, a photoluminescent protein described herein comprises an amino acid sequence having an absence of internal methionine residues.

Abstract: It has been believed that promoting the assembly of polysomes composed of many ribosomes attached to mRNA is very effective for highly efficient protein synthesis. However, the mechanism for p180 protein's capability of promoting polysome formation has been yet to be elucidated. The inventors of the present application newly discovered SF3b4 protein as a protein that specifically interacts with the coiled-coil domain of p180 protein, a responsible region for its capability of promoting polysome formation, and which is capable of promoting mRNA localization to an endoplasmic reticulum (ER). The inventors also found that, in cells capable of highly expressing both p180 protein and a protein promoting mRNA localization to an endoplasmic reticulum (ER) (e.g., SF3b4 protein), the mRNA localization to the endoplasmic reticulum can be significantly elevated so that the secretory capacity in cultured cells can be enhanced.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T-cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: The invention relates to the field of medicine. Among others, it relates to biologically active analogs of interferons (IFNs) which show less unwanted side-effects and to the therapeutic uses thereof. Provided is an IFN analog, wherein the moiety mediating binding to its natural receptor is at least functionally disrupted and wherein the analog comprises a signaling moiety capable of mediating intracellular IFN activity, said signaling moiety being provided at its N-terminus, optionally via a linker, with at least one targeting domain capable of binding to a cell surface receptor other than the IFN receptor.

Abstract: The present invention relates, inter alia, to certain hepcidin peptide analogs, including peptides and dimers thereof, and to the use of the peptides and peptide dimers in the treatment and/or prevention of a variety of diseases, conditions or disorders, including treatment and/or prevention of iron overload diseases, which include hereditary hemochromatosis and iron-loading anemias, and other conditions and disorders described herein.

Abstract: The present invention relates to glucagon analogs and their medical use, for example in the treatment of hypoglycaemia. In particular, the present invention relates to stable glucagon analogs suitable for use in a liquid formulation.

Abstract: The present invention relates to a novel peptide showing more excellent activities on a glucagon like peptide-1 receptor and a glucagon receptor than native oxyntomodulin, and a composition for the prevention or treatment of obesity comprising the peptide as an active ingredient. Unlike native oxyntomodulin, the novel peptide of the present invention reduces food intake, suppresses gastric emptying, and facilitates lipolysis with reduced side-effects, and also shows excellent receptor-activating effects. Thus, it can be widely used in the treatment of obesity with safety and efficacy.

Abstract: Provided herein are T-cell receptor (TCR) fusion proteins (TFPs), T-cells engineered to express one or more TFPs, and methods of use thereof for the treatment of diseases, including cancer.

Abstract: Factor VIII variants and methods of use thereof are disclosed.

Abstract: The present invention relates to polypeptides which include tenth fibronectin type III domains (10Fn3) that binds to serum albumin, with south pole loop substitutions. The invention further relates to fusion molecules comprising a serum albumin-binding 10Fn3 joined to a heterologous protein for use in diagnostic and therapeutic applications.

Abstract: Methods and compositions are provided for the treatment of a patient with intracranial hemorrhage (ICH). Methods include the use of the products of recombinant constructs such as those that contain lactoferrin, as well as fusion protein constructs of lactoferrin and Fc domain for IgG.

Abstract: Provided herein are various processes for the improved production of antibody producing organisms, antibody producing tissues, antibody producing cells and antibodies. In certain embodiments, provided herein are methods for rapidly producing antibody producing organisms, tissues, cells and antibodies derived from humans, organisms, plants or cells that are genetically altered to over-express certain proteins.

Abstract: Binding molecules, including bispecific antibodies that include at least two anti-influenza binding domains are disclosed, including binding molecules having a first binding domain that specifically binds influenza A virus and a second binding domain that specifically binds influenza B virus.

Abstract: The invention provides antibodies that specifically bind to medin. The antibodies have the capacity to bind to monomeric, misfolded, aggregated, fibril or deposited forms of medin. The antibodies can be used for treating or effecting prophylaxis of diseases associated with medin, medin accumulation or accumulation of medin deposits (e.g., medin amyloidosis). The antibodies can also be used for diagnosing medin amyloidosis and inhibiting or reducing aggregation of medin, among other applications.

Abstract: The present invention provides antibodies that bind to ANGPTL8 and methods of using the same. According to certain embodiments, the invention includes methods of using anti-ANGPTL8 antibodies that bind human ANGPTL8 with high affinity to treat obesity, reduce body fat, reduce body weight, increase energy expenditure, and increase HDL-C, in a subject.

Abstract: The present invention relates to the field of medicine, and specifically to the field of monoclonal antibodies against human IL-17. More specifically, the invention relates to monoclonal antibodies/antagonists of IL-17A, which bind with high affinity to an IL-17 epitope, wherein the antibodies contain amino acid substitutions in hypervariable regions of heavy and light chains. The antibodies according to this invention can be chimeric, humanized or human antibodies or antigen-binding fragments thereof, and can be used as a medicinal agent for treating autoimmune and inflammatory disorders and disorders of cell proliferation and development. The invention also relates to methods for producing said antibodies.

Abstract: Disclosed herein are anti-CD47 antibody molecules, their manufacture and use in treating disorders associated with CD47 expression, for example, certain hematological cancers and solid tumors.

Abstract: The present invention is directed to antagonists of CS1 that bind to and neutralize at least one biological activity of CS1. The invention also includes a pharmaceutical composition comprising such antibodies or antigen-binding fragments thereof. The present invention also provides for a method of preventing or treating disease states, including autoimmune disorders and cancer, in a subject in need thereof, comprising administering into said subject an effective amount of such antagonists.

Abstract: The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immunosuppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-?)) and regulatory T cells and/or immunosuppressive myeloid dendritic cells (DCs). By counteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment.

Abstract: The present disclosure provides various molecular constructs having a targeting element and an effector element. Methods for treating various diseases using such molecular constructs are also disclosed.

Abstract: The present invention relates to methods for treating gastric neoplasias, in particular treating patients who have been previously determined to have an EGFR biomarker. Gastric carcinoma (GC) is one of the most common and deadest cancers with ?1 million diagnoses and ?0.7 million deaths each year worldwide, with high incidence in Eastern Asia.

Abstract: Described is a construct comprising (a) a targeting moiety; (b) a fusogenic moiety consisting one or more fusogenic sequence(s) derived from dengue virus glycoprotein E comprising the sequence DRGWGNGCGLFGKGGI (SEQ ID NO:1) or a sequence which shows 1 to 8 substitutions, deletions, or insertions in comparison to SEQ ID NO:1; and (c) a molecule which is to be delivered into the cytoplasm of a cell. Moreover, described is a pharmaceutical composition comprising the construct according to the invention and optionally a pharmaceutical acceptable carrier. Further, described is a kit comprising one or more fusogenic sequence(s) derived from dengue virus glycoprotein E comprising the sequence as shown in SEQ ID NO:1 or a sequence which shows 1 to 8 substitutions, deletions, or insertions in comparison to SEQ ID NO:1.

Abstract: The present invention provides antibodies that bind to Tie2 and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human Tie2 and block the interaction between Tie2 and one or more Tie2 ligands such as angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), angiopoietin 3 (Ang3) and/or angiopoietin 4 (Ang4). The antibodies of the invention are useful, inter alia, for the treatment of diseases and disorders associated with one or more Tie2 biological activities including angiogenesis.

Abstract: The present invention generally relates to antibodies, antigen-binding fragments thereof, polypeptides, and immunoconjugates that bind to CD123 antigen (the a chain of the interleukine 3 receptor, or IL-3R?). The present invention also relates to methods of using such CD123-binding molecules for diagnosing and treating diseases, such as B-cell malignancies.

Abstract: An isolated monoclonal antibody that specifically binds human OX40. A nucleic acid molecule encoding the antibody, an expression vector, a host cell and a method for expressing the antibody are also provided. The present invention further provides an immunoconjugate, a bispecific molecule, a chimeric antigen receptor, an oncolytic virus and a pharmaceutical composition comprising the antibody, as well as a treatment method using an anti-OX40 antibody of the invention.

Abstract: Chimeric antigen receptors containing CD19/CD20 or CD20/CD19 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Abstract: The specification provides compositions and methods of reducing a risk of a HBV infection in a subject and of treating a subject infected with HBV.

Abstract: The monoclonal IgG-type antibodies were suggested comprising variable domains represented by a combination of VHH-derivative with a variable domain of the light chain VL. Said antibodies can comprise amino acid substitutions at positions 44 and 45 (Kabat numbering) or combinations thereof. Antibodies of the invention possess increased affinity and improved aggregation stability.

Abstract: Provided is a novel cellulose derivative having excellent water resistance. This is a cellulose acylate oxoalkanoate which is a cellulose derivative corresponding to cellulose, except with substituents replacing part or all of hydrogen atoms in the hydroxy groups of the cellulose. The substituents includes a group represented by General Formula (1) and a group represented by General Formula (2). The cellulose acylate oxoalkanoate has a degree x of substitution with the group represented by General Formula (1), a degree y of substitution with the group represented by General Formula (2), and a degree z of unsubstitution, where x, y, and z meet conditions specified by Expressions (A), (B), and (C): 0.1?x?2.99??(A) 0.01?y?2.

Abstract: Novel thioalkylcarboxylate-modified CDs and pharmaceutical compositions comprising these thioalkylcarboxylate-modified CDs are disclosed, as well as methods of using the disclosed thioalkylcarboxylate-modified CDs and pharmaceutical compositions thereof to neutralize or reduce undesired effects or symptoms associated with one or more fentanyl related compounds in a subject in need thereof. The use of the disclosed thioalkylcarboxylate-modified CDs to detect the presence of one or more fentanyl related compounds in a sample is also disclosed, which comprises contacting the sample with said thioalkylcarboxylate-modified CDs or a composition comprising these CDs.

Abstract: Disclosed is a biosourced polymer obtained by dual chemical functionalization of chitosan, usable for catalytic carbonation of cyclic ethers by carbon dioxide, and a binder composition for creating layers and/or coatings for road construction and/or civil engineering, marking materials, or sealing or insulation materials. The composition contains a polyhydroxyurethane polymer binder resulting from the reaction of at least one polyamine with at least one polycyclocarbonate. The polycyclocarbonate was obtained by carbonating a (cyclic) poly(ether) with carbon dioxide catalyzed by the biosourced polymer.

Abstract: A radical polymerization method that enables synthesis, at a high conversion rate, of polymers having a relatively uniform molecular weight and is applicable to various monomers, and an apparatus used for the method. A reaction solution containing monomer and initiator is continuously or intermittently circulated in the apparatus and is heated in a heating-initiation unit to a predetermined temperature simultaneously across a radial direction of a cross section of the flow path whereby the initiator located in a particular volume of the reaction solution is cleaved all at once. The apparatus includes a heating medium production unit 10, a heating medium-reaction solution mixing unit 20, a cooling unit 30, and a recovery unit 40 for a reaction mixture, all communicatively connected by the flow path and optionally a heating reaction unit 60, a cooling unit 70, and a recovery unit 80, all communicatively connected by the flow path.

Abstract: Heterocyclic organic compounds are used as electron donors in conjunction with solid Ziegler-Natta type catalyst in processes in which polyolefins such as polypropylene are produced. The electron donors may be used in the preparation of solid catalyst system, thus serving as “internal electron donors,” or they may be employed during or prior to polymerization with the co-catalyst as “external electron donors.

Abstract: Compositions and methods for selective olefin (e.g., ethylene) polymerization comprising metal organic frameworks (MOFs) are generally provided. In some embodiments, a MOF comprises a plurality of metal ions, each coordinated with at least one ligand comprising at least two unsaturated N-heterocyclic aromatic groups arranged about an organic core.

Abstract: The invention provides novel bromine-containing polymers which have excellent heat resistance and are capable of imparting flame retardance or novel flame-retardant, bromine-containing polymers which have excellent heat resistance and optical characteristics, and methods for producing such polymers. The invention relates to a polymer which includes structural units of the following general formula (1): wherein R1s, R2s, m, p and the asterisks are as defined in the specification and the claims, and to a method for producing such polymers.

Abstract: Disclosed are RAFT agents, a method of polymerizing alkenes, dienes, vinyl compounds, and/or vinylidene compounds using at least one RAFT agent, polymers prepared by the methods, sulfur-crosslinkable rubber mixtures prepared by the methods, and motor vehicle tires, cords, belts, or hoses incorporating the sulfur-crosslinkable rubber mixtures. In one embodiment, the RAFT agent has the formula Z—C(?S)—S—R—S—P or P—S—Z—C(?S)—S—R—S—P, wherein P is a protecting group, and Z and R are typical RAFT Z and R groups.

Abstract: The invention provides an ethylene-based polymer formed from reacting at least the following: ethylene and at least one asymmetrical polyene, comprising an “alpha, beta unsaturated end” and a “C—C double bond end,” and wherein the reaction takes place in the presence of at least one free-radical initiator.

Abstract: An impact copolymer comprising a polypropylene comprising at least 50 mol % propylene, and having a molecular weight distribution (MwMALLS/Mn) greater than 10, a branching index (g?) of less than 0.97, and a melt strength greater than 40 cN, and an elastomer. Also disclosed is a method of making an impact copolymer composition comprising melt-blending the components, sequentially or simultaneously a polypropylene resin comprising at least 50 mol % propylene, and having a molecular weight distribution (Mw/Mn) greater than 6, a branching index (g?) of at least 0.97, and a melt strength greater than 10 cN determined using an extensional rheometer at 190° C.; and within the range from 0.01 to 3 wt % of at least one organic peroxide; and an elastomer.

Abstract: The various embodiments of the invention provide, a magnesium titanium polymerization procatalyst, methods for making and using the same.

Abstract: Disclosed herein are ethylene-based polymers generally characterized by a Mw ranging from 70,000 to 200,000 g/mol, a ratio of Mz/Mw ranging from 1.8 to 20, an 1B parameter ranging from 0.92 to 1.05, and an ATREF profile characterized by one large peak. These polymers have the dart impact, tear strength, and optical properties of a metallocene-catalyzed LLDPE, but with improved processability, melt strength, and bubble stability, and can be used in blown film and other end-use applications.

Abstract: A process for forming voided latex particles is improved by combining swelling and polymerization of an outer shell into a single step. The process includes contacting multi-stage emulsion polymer particles comprising a core, at least one intermediate shell, with a swelling agent, and polymerizing an outer shell after said contacting with swelling agent wherein the core and the at least one intermediate shell are contacted with swelling agent in the presence of less than 0.5% monomer based on the weight of the multi-stage emulsion polymer particles, and substantially all of the swelling occurs during polymerization of the outer shell.

Abstract: The invention is related to a new soft heterophasic random propylene copolymer with improved optical properties, as well as the process by which the heterophasic random propylene copolymer is produced.

Abstract: A polyurethane dispersant is described that comprises a reaction product of a polyisocyanate with a) a component supplying a anchoring imide group wherein the carbonyl groups of the imide are bonded to a fused or non-fused aromatic ring, b) at least one solvent-solubilizing chain, and other optional components to build molecular weight or modify the interaction of the dispersant with various particulates or continuous media.

Abstract: A process for producing a polyurethane-coated conduit element includes mixing a) a mixture of aromatic and aliphatic polyisocyanate with, b) at least one polymeric compound having at least two hydrogen atoms which are reactive toward isocyanate, c) at least one chain extender, d) a catalyst, and e) optionally at least one other auxiliary, additive, or both, to form a reaction mixture; applying the reaction mixture to a conduit element; and allowing the reaction mixture to react to form a polyurethane layer. The polyurethane-coating conduit element is suitable for maritime applications in the oil and gas industry, which polyurethane has improved hydrolysis stability at high temperatures and nevertheless satisfies the high mechanical demands in the oil and gas industry.

Abstract: Provided is a mechanochromic resin by which a stress applied to a material can be visualized in real time, and a mechanochromic luminescent material that is used in the synthesis of the mechanochromic resin. Stress can be visualized in real time by means of a mechanochromic luminescent material represented by formula (1) or formula (2) and a mechanochromic resin obtained by crosslinking the mechanochromic luminescent material. [Chemical formula 1] (In the formula, Y1 and Y2 each denote a substituent group that inhibits aggregation of the mechanochromic luminescent material represented by formula (1), and Y1 and Y2 may be same as or different from each other. Z1 and Z2 each denote a polymerizable group, and may be same as or different from each other.) [Chemical formula 2] (In the formula, Y1 and Y2 each denote a substituent group that inhibits aggregation of the mechanochromic luminescent material represented by formula (2), and Y1 and Y2 may be same as or different from each other.

Abstract: The present invention relates to functionalized polymers including a poly(phenylene) structure. The structure can include any useful modifications, such as the inclusion of one or more reactive handles having an aryl group. Methods and uses of such structures and polymers are also described herein.