Abstract: The present invention relates to compounds having dual pharmacological activity towards both the sigma (?) receptor, and the ?-opiod receptor and more particularly to diazaspiro undecane compounds having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain. wherein Y is n is 1 or 2; q is 1, 2, 3, 4, 5 or 6; X is a bond, —C(O)O—, —C(O)NR8—, —C(O)—, —O— or —C(R4R4?)—; R1 is C(O)R5 or S(O)2R5.

Abstract: The present invention provides a novel bicyclic or tricyclic heterocyclic compound represented by the formula (I) wherein ring A is an optionally substituted aromatic group, one of X1 and X2 is a carbon atom, and the other is a nitrogen atom, X3 is a nitrogen atom, or CR2, X4 is a nitrogen atom, or CR3, X5 is a sulfur atom, or —CH?CH—, Z1 is an oxygen atom, —C(R6)(R7)—, —NH—, —C(R6)(R7)—NH—, —NH—C(R6)(R7)—, —C(R6)(R7)—O—, —O—C(R6)(R7)—, or a single bond, one of Z2 and Z3 is CH and the other is a nitrogen atom, or both are nitrogen atoms, and other symbols are as defined in the DESCRIPTION, or a pharmacologically acceptable salt thereof.

Abstract: The present invention relates to compounds of formula (I), wherein R1 to R5 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.

Abstract: The invention relates to a novel class of compounds that exhibit activity inhibitory activity toward arginase, and pharmaceutical compositions comprising the compounds of the invention. Also provided herein are methods of treating cancer with the arginase inhibitors of the invention.

Abstract: An amino-containing organosilicon compound having formula (1) is used for surface treatment of an inorganic filler for thereby rendering the filler more compatible with and adhesive to a polymer material. In formula (1), R1 is alkyl, alkenyl, aryl or aralkyl, R2 is alkenyl, aryl or aralkyl, R3 and R4 each are a monovalent hydrocarbon group, and n is 0, 1 or 2.

Abstract: The present disclosure provides Titanium (IV) compounds and methods of making heterocyclic compounds such as pyrroles using Titanium (IV) compounds. In certain embodiments, the Titanium (IV) compound is present in catalytic amounts.

Abstract: Flow batteries incorporating an active material with one or more catecholate ligands can have a number of desirable operating features. Commercial syntheses of catechol produce significant quantities of hydroquinone as a byproduct, which presently has limited value in the battery industry and can represent a significant waste disposal issue at industrial production scales. Using a concerted, high-yield process, low-value hydroquinone can be transformed into high-value 1,2,4-trihydroxybenzene, which can be a desirable ligand for active materials of relevance in the flow battery industry.

Abstract: Compounds are generally provided, along with pharmaceutical compositions including such compounds. Methods are also generally provided for inhibiting ribose 5-phosphate isomerase in a human, such as via administering to the human the pharmaceutical composition that includes such a compound. Methods are also generally provided for treating a mammal that is infected by a parasitic organism, such as via administering to the mammal the pharmaceutical composition that includes such a compound. Methods are also generally provided for forming a pharmaceutical composition.

Abstract: The invention relates to nanoparticles made from organometallic hybrid materials made from iron carboxylates, used for example as contrast agents. The particles can also be used for the encapsulation and vectoring of molecules of interest such as active3 pharmaceutical agents, cosmetically interesting compounds and markers. Apart from the intrinsic properties thereof for imaging, said nanoparticles give good results in terms of capacity for loading with medicaments and in biocompatibility.

Abstract: Various embodiments disclosed relate to bridged phthalocyanine- and napththalocyanine-metal complex catalysts and methods of using and purifying the same. In various embodiments, the present invention provides a method of purifying a catalyst. The method includes contacting a catalyst composition with acid, the catalyst composition including a catalyst, to provide an acidified catalyst composition with the catalyst dissolved therein. The method includes precipitating the catalyst, and removing the precipitated catalyst from solution, to provide a purified catalyst.

Abstract: The present invention provides sialic acid analogs and their compositions useful for the treatment of sialic acid deficiencies.

Abstract: The present invention provides a high-purity acid-form sophorolipid (SL)-containing composition characterized by substantially not containing acetic acid. The high-purity acid-form SL-containing composition can be produced, for example, by the following method: (i) adjusting the pH of a partially purified acid-form SL-containing composition to an acidic range; and (ii-a) subjecting an acidified partially purified acid-form SL-containing composition obtained in step (i) to chromatography to acquire a fraction containing an acid-form SL, or (ii-b) leaving the acidified partially purified acid-form SL-containing composition obtained in step (i) to stand under a low-temperature condition to acquire a resulting gelled object.

Abstract: A method of preparing a base sequence for synthesis of a nucleic acid nanostructure, a method of synthesizing a nucleic acid nanostructure, a candidate base sequence pair, and a nucleic acid nanostructure are provided. A method of preparing a base sequence includes selecting candidate groups of base sequences of 5?-cohesive end having at least 50% GC content, calculating Gibb's free energy values of the selected candidate groups to re-select the candidate groups, and selecting the candidate groups, that have a sequence of 3 different successive bases among the base sequences from the re-selected candidate groups.

Abstract: Provided herein are multiple solid forms of a defined steroid-like compound, and methods for the preparation and use thereof. In one aspect, there is provided a crystalline form of said steroid-like compound, and methods for the preparation and use thereof. In another aspect, there is provided a substantially amorphous form of said steroid-like compound, and methods for the preparation and use thereof. In yet another aspect, there are provided compositions containing compounds according to the present invention. In certain aspects, such compositions are suitable for delivery of active agents according to the present invention to a subject in need thereof. In another aspect of the invention, there are provided methods for the treatment of a variety of indications, including glaucoma, ocular hypertension, and the like. In still another aspect of the present invention, there are provided kits containing compounds according to the present invention and/or compositions containing same.

Abstract: The automated synthesis of clinically relevant amounts of 16?-18F-fluoro-5?-dihydrotestosterone (18F-FDHT) using a commercially available radiosynthesizer. Synthesis was performed in 90 minutes with a decay-corrected radiochemical yield of 29±5%. The specific activity was 4.6 Ci/?mol (170 GBq/?mol) at end of formulation with a starting activity of 1.0 Ci (37 GBq). The formulated 18F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use.

Abstract: Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described.

Abstract: Provided herein are methods for refolding denatured protein (e.g., from inclusion bodies) that do not require the use of a denaturing agent. Exemplary methods use a high pH for solubilizing denatured protein, followed by a decrease in pH for refolding the proteins.

Abstract: Compounds of Formulas I: and shorter variants thereof are described, along with solid supports having such compounds coupled thereto, and the use thereof as affinity ligands for antibodies.

Abstract: The present invention relates to compositions which may comprise a molecular sled linked to cargo and uses thereof. In particular, the present invention relates to a non-naturally occurring or engineered composition which may comprise a molecular sled, linkers and a molecular cargo connected to the sled via the linkers. Methods involving the use of molecular sleds and their cargoes and pharmaceutical compositions, methods for treating cancer, a degenerative disease, a genetic disease or an infectious disease as well as diagnostic methods are also contemplated by the present invention.

Abstract: The present invention relates to a cyclic peptide compound, and a preparation method, pharmaceutical composition and use thereof. In particular, the cyclic peptide compound of the present invention has a structure as shown by general formula (I). The compound of general formula (I), and isomers, racemates, pharmaceutically acceptable salts, crystalline hydrates, solvates or mixtures thereof have a use in the preparation of medicaments for preventing or treating mammalian diseases associated with histone deacetylase dysregulations.

Abstract: The present invention relates to peptides, in particular dodecapeptide-containing coating agents, adhesion promoters or adhesives for oxidic surfaces, a multilayer composite or a coated substrate, containing compounds which are formed entirely or in part of dodecapeptides as adhesion promoters between at least two adjacent layers of the composite or between the coating and the substrate, and to dodecapeptides that can be used as coating agents, adhesion promoters or adhesives for oxidic surfaces.

Abstract: Disclosed herein are novel analogs of cyclosporin, pharmaceutical compositions containing them, and methods for their use in the treatment of dry eye and other conditions.

Abstract: The present invention relates to a peptide which consists of more than 50% of sequence sections of the formula -(An-Bm-Co)-, and to a conjugate containing the peptide and at least one covalently bonded active compound, and to a process for the preparation of the conjugate. The present invention furthermore relates to the use of the peptide and the conjugate for targeting of the kidney, and to a medicament comprising the peptide or conjugate.

Abstract: The invention relates to chimeric norovirus VP1 proteins containing the S-domain of VP1 of a first norovirus strain and a P-domain that contains at least a portion of the P-domain of VP1 of a second norovirus strain. The invention also relates to nucleic acids that encode the chimeric VP1 proteins, virus-like particles that contain a chimeric norovirus VP1 protein, and to immunogenic compositions.

Abstract: An object of the present invention is to provide a technique to create novel engineered protein ligands that, when immobilized through a lysine residue (its side chain ?-amino group) which allows for efficient immobilization to a carrier, show the optimum binding capacity and binding efficiency to a target molecule. The present invention provides an engineered protein having a sequence obtained by replacing all the lysine residues in Protein A, which is the most typical protein ligand, with other amino acids, and adding lysine at a terminal; and an affinity separation matrix in which such an engineered protein is immobilized on a water-insoluble carrier by reductive amination or the like. This affinity separation matrix is characterized by its high binding capacity to a target molecule even when the immobilized amount of the ligand is small.

Abstract: The invention concerns novel streptavidin muteins. In one embodiment such a mutein (a) contains at least one mutation in the region of the amino acid positions 115 to 121 with reference to the amino acid sequence of wild type streptavidin as set forth at SEQ ID NO: 15 and (b) has a higher binding affinity than each of (i) a streptavidin mutein that comprises the amino acid sequence Val44-Thr45-Ala46-Arg47 (SEQ ID NO: 98), or (ii) a streptavidin mutein that comprises the amino acid sequence He44-Gly45-Ala46-Arg47 (SEQ ID NO: 99) at amino acid positions 44 to 47, or (iii) wild type-streptavidin (SEQ ID NO: 15) for peptide ligands comprising the amino acid sequence Trp-Ser-His-Pro-Gln-Phe-Glu-Lys (SEQ ID NO: 100).

Abstract: A polypeptide porous body of the present invention is a porous body of a polypeptide derived from spider silk proteins. The polypeptide includes a water-insoluble polypeptide. The polypeptide porous body has an apparent density of 0.1 g/cm3 or less. A method for producing the polypeptide porous body includes: a solution production step in which the polypeptide is dissolved in at least one solvent selected from DMSO, DMF, and these with an inorganic salt, so as to obtain a solution of the polypeptide; a step in which the solution produced in the solution production step is substituted with a water-soluble solvent so as to obtain a polypeptide gel; and a step in which the polypeptide gel is dried. Thereby, the present invention provides a polypeptide porous body having excellent water absorbability and a polypeptide porous body suitable for application to a living body, and a method for producing the same.

Abstract: The present disclosure provides hNGAL muteins that bind a pyoverdine family member or pyochelin and can be used in various application including pharmaceutical applications, for example, to inhibit or reduce growth of P. aeruginosa. The present disclosure also concerns methods of making one or more pyoverdine- or pyochelin-binding muteins described herein as well as compositions comprising one or more of such muteins. The present disclosure further relates to nucleic acid molecules encoding such muteins and to methods for generation of such muteins and nucleic acid molecules. In addition, the application discloses therapeutic and/or diagnostic uses of these muteins as well as compositions comprising one or more of such muteins.

Abstract: The invention features methods of treatment and diagnosis using NRG-2 polypeptides, nucleic acid molecules, and antibodies. The invention also provides novel NRG-2 polypeptides and nucleic acid molecules.

Abstract: High-Yield mammalian transient expression systems can include a cell culture media (particularly serum free, non animal derived, and/or chemically defined media) for introducing macromolecules and compounds (e.g., nucleic acid molecules) into cells (e.g., eukaryotic cells). Cells containing such introduced materials can then be cultured in the cell culture media. In particular, the invention allows introduction of nucleic acid molecules (e.g., vectors) into cells (particularly mammalian cells) and expression of proteins encoded by the nucleic acid molecules in the cells. The invention obviates the need to change the cell culture medium each time a different procedure is performed with the cells (e.g., culturing cells vs. transfecting cells). The invention also relates to compositions and kits useful for culturing and transforming/transfecting cells.

Abstract: A method for purifying rHuEPO through the use of a multi-step filtration process which provides for a rHuEPO product having superior stability and shelf-life.

Abstract: Provided herein are methods of producing a recombinant polypeptide containing two chains, such as an immune mobilizing monoclonal T-cell receptor against cancer (ImmTAC) protein including an alpha chain and a beta chain. In particular, methods are provided for producing heterologous secretory proteins in bacteria through utilization of optimized expression vectors and culture processes.

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: Inhibitor peptides for combinatorial inactivation of ErbB1, ErbB2, and ErbB3 featuring an EGFR-based peptide and a cell penetrating component such as a protein transduction domain (e.g., PTD4) for enhancing penetration of the EGFR-based peptide into a cell. The EGFR peptide may be from 8 to 30 amino acids in length. The inhibitor peptides can inhibit tumor growth, reduce metastasis, activate apoptosis, activate necrosis, disrupt calcium signaling, and/or increase ROS. In some embodiments, the EGFR-based peptide is at least 50% identical to at least 8 consecutive residues of SEQ ID NO: 1.

Abstract: Disclosed embodiments relate to antibodies that recognize redox modulated proteins such as glutathionylated actin. Embodiments relate to a reagent for the immunoassay of glutathionylated actin. Disclosed embodiments also relate to diagnosis of and therapies for the treatment of diseases related to impaired deglutathionylation of peptides. Additionally, disclosed embodiments relate to pharmaceutical compositions containing antibodies which recognize redox modulated proteins and kits for the detection or treatment of diseases related to redox modulated proteins which include antibodies that recognize redox modulated proteins.

Abstract: The present invention relates to a method of detecting a disease characterized by an expansion of genomic hexanucleotide repeats as well as polypeptides of said hexanucleotide repeats, ligands specifically binding to the polypeptides, and to methods of identifying an inhibitor preventing the expression and/or aggregation of said polypeptide.

Abstract: The present invention provides isolated antibodies that bind to 14-3-3 epsilon that are useful in the recognition of tumor cells and tumor specific delivery of drugs and therapies.

Abstract: The present invention is directed to antibodies and fragments thereof having binding specificity for CGRP. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the VH, VL and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-CGRP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-CGRP antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-CGRP antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with CGRP.

Abstract: The present invention relates to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with neurofibrillary tangles. In particular, the invention relates to antibodies, which specifically recognize and bind to phosphorylated pathological protein tau-conformers and to methods and compositions involving said antibodies for the therapeutic and diagnostic use in the treatment of tauopathies including Alzheimer's Disease (AD).

Abstract: Antibodies directed to the antigen Ang-2 and uses of such antibodies are described. In particular, fully human monoclonal antibodies directed to the antigen Ang-2. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies.

Abstract: Isolated human monoclonal antibodies which bind to IL-8 (e.g., human IL-8) are disclosed. The human antibodies can be produced in a hybridoma, transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals, hybridomas, and transfectomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Abstract: This invention provides antibodies or functional fragments thereof that bind to PD-1 with high affinity. The invention provides nucleic acid molecules encoding the antibodies or the fragments thereof according to the present invention, expression vectors and host cells for expressing the antibodies or the functional fragments thereof according to the present invention, as well as methods for producing the antibodies or the functional fragments thereof according to the present invention. The present invention also provides immunoconjugates and pharmaceutical compositions comprising the antibodies or the functional fragments thereof according to the present invention. The present invention additionally provides methods for treating a plurality of diseases (comprising cancers, infectious diseases and inflammatory diseases) by using the antibodies or the functional fragments thereof disclosed herein.

Abstract: An isolated antibody comprising an antigen recognition domain which specifically binds CD84 and (i) down regulates the anti-apoptotic activity of stromal cells on chronic lymphocytic leukemia (CLL) cells; and/or (ii) induces mobilization of CLL cells from the bone marrow. Also provided are antibodies comprising antigen recognition domains comprising complementarity determining regions as indicated and uses thereof.

Abstract: The invention relates to a humanized CD3 binding site, which comprises (a) a variable heavy chain domain (VH) as depicted in SEQ ID NO:8 and a variable light chain domain (VL) as depicted in SEQ ID NO:3; or (b) a variable heavy chain domain (VH) as depicted in SEQ ID NO:9 and a variable light chain domain (VL) as depicted in SEQ ID NO:4, or c) a variable heavy chain domain (VH) as depicted in SEQ ID NO:7 and a variable light chain domain (VL) as depicted in SEQ ID NO:2; or (d) a variable heavy chain domain (VH) as depicted in SEQ ID NO:6 and a variable light chain domain (VL) as depicted in SEQ ID NO:1. The CD3 binding sites have an increased stability, while the binding affinity has been retained due to mutations at positions VH111 and VL49.

Abstract: Disclosed herein are single chain variable fragment CD3 binding proteins with improved binding affinities, and robust aggregation profiles. Also described are multispecific binding proteins comprising a single chain variable fragment CD3 binding protein according to the instant disclosure. Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of using such formulations are provided.

Abstract: The present invention provides methods for decreasing a nasal polyp score in a subject. The methods include administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody or antigen binding fragment thereof.

Abstract: By means of amino acid sequence alterations, the present inventors succeeded in providing constant regions that can confer antibodies with favorable properties, particularly as pharmaceuticals. The variants of the constant regions provided by the present invention will remarkably reduce heterogeneity when applied to antibody production. That is, homogeneity of antibodies can be maintained at a high level by introducing the alterations provided by the present invention into the antibody heavy chain constant regions. More specifically, decrease in homogeneity caused by —SS— bond linkage differences in the heavy chains of antibody molecules can be prevented. Furthermore, in a preferred embodiment of the present invention, pharmacokinetics of antibodies can be improved and decrease in homogeneity caused by deletion of the C terminus in the antibody constant region can be ameliorated.

Abstract: Antibodies of interest comprising a heavy chain signal peptide and/or a light chain signal peptide or combination thereof and compositions are described. The method of determining the signal peptide including creating data set of antibodies signal peptides, clustering, selecting and creating recombinant antibodies for enhanced expression and secretion are described.

Abstract: A method of detecting the presence of glioblastomas and/or recurrent glioblastomas in a subject in need thereof includes isolating CD14+ cells from a blood sample of the subject and determining the ratio of isolated CD14+ cells expressing low levels of HLA-DR to isolated CD14+ cells expressing VNN2, wherein the subject has increased risk of glioblastomas or recurrent glioblastoma if the ratio of isolated CD14+ cells expressing low levels of HLA-DR to isolated CD14+ cells expressing VNN2 is greater than about 2.

Abstract: The invention provides anti-Ly6E antibodies, immunoconjugates and methods of using the same. In some embodiments, the anti-Ly6E antibodies comprise heavy chain HVRs comprising the amino acid sequences of SEQ ID NOs: 32-34 and/or light chain HVRs comprising the amino acid sequences of SEQ ID NOs: 29-31.