Abstract: Provided herein is a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein R1a, R1b, R2a, R2b, R3, R4a, R4b, R5, R6a, R6b, R7a, R7a, R11a, R11b, R12a, R12b, R16a, R16b, R19, R11a, R22, RX, RY and n are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds, e.g., in the treatment of CNS-related disorders.

Abstract: The present invention discloses a polypeptide compound, a pharmaceutical composition, and a preparation method and use thereof. The structural formula of the polypeptide compound is shown in general formula (I): Such polypeptide compounds as ?-opioid receptor agonists have the advantages of better activity and the potential to become clinical candidate compounds.

Abstract: An isolated cancer-targeting peptide that includes at least two copies of the amino acid sequence PFLP (SEQ ID NO: 1) or PFLF (SEQ ID NO: 2). Also disclosed is a pharmaceutical composition for treating cancer. The composition contains the isolated cancer-targeting peptide and an anti-cancer agent. Further disclosed is a bispecific anti-cancer antibody that includes the isolated cancer-targeting peptide and an antigen-binding peptide that stimulates T cell activity. Methods are provided for treating cancer by administering the pharmaceutical composition or the bispecific anti-cancer antibody. Further provided is a method for diagnosing cancer by administering a radionuclide-labeled cancer-targeting peptide to an individual and imaging a location of the radionuclide.

Abstract: Cyclic depsipeptide-class molecules, referred to herein as persephacins (including analogs thereof), having similarities to aureobasidin A, are described. The persephacins have antimicrobial activity, such as antifungal activity against a diverse range of clinically-relevant fungal pathogens, antiprotozoan parasite activity, and antibacterial activity, and can be used for example in treatments of difficult-to-treat ocular fungal infections at lower concentrations than natamycin. The active compounds may be combined with a secondary compound in a composition.

Abstract: Provided is a multi-target compound with anticoagulation and platelet GPIIb/IIIa receptor antagonism. The formula of the multi-target compound is as follows: A-L-B-L?-C. A and B are binding sites with a thrombin, C is a binding site with a platelet GPIIb/IIIa receptor, L is a first linking group, and L? is a second linking group. Also provided are a preparation method for the compound and use of the compound. The compound has the effects on inhibiting human thrombin activity and a platelet GPIIb/IIIa receptor in vitro, and has the effects on antiplatelet aggregation in vitro/in vivo, and anticoagulation and antithrombosis in vivo.

Abstract: Novel peptides that bind to human PAC1 are provided. These peptides that are antagonists of PAC1 are useful in a number of PAC1 related disorders, including the treatment and/or prevention of headache disorders, including migraine, such as acute migraine.

Abstract: Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include at least one RNA polynucleotides having an open reading frame encoding at least one varicella zoster virus (VZV) antigen. Methods for preparing and using such vaccines are also described.

Abstract: The treatment of bacterial respiratory infections using bacterially-originating antibiotics known as pyocins. In particular, S type pyocins are administered by pulmonary administration for the treatment of such infections.

Abstract: Methods of making engineered protein-based materials, nanofibers, and biofilms from bacterial amyloid-based structures that are capable of mediating long-range electron transport are provided.

Abstract: The present invention, in some aspects, provides compositions including a solution comprising a plurality of exfoliated silk microfibrils and/or exfoliated silk nanofibrils, wherein the micro- or nano-fibrils are characterized as having a substantially nematic structure, as well as methods for making and using the same.

Abstract: Disclosed are high-porosity protein particles useful for carrying one or more agents of interest, methods for their manufacture and use, and products comprising them.

Abstract: Provided herein are progranulin variants and fusion proteins that comprise a progranulin variant and an Fc polypeptide. Methods of using such proteins to treat progranulin-associated disorders (e.g., a neurodegenerative disease, such as frontotemporal dementia (FTD)) are also provided herein.

Abstract: The present technology relates, inter alia, to compositions and methods, including heterodimeric proteins that find use in the treatment of disease, such as immunotherapies for cancer and autoimmunity.

Abstract: The invention provides an A? peptide aggregation inhibitor, an A? peptide toxicity reducing agent, and a preventive and/or therapeutic agent for Alzheimer's disease. The oxidized A? peptide in which one or more amino acid residues of A? peptide have been oxidized (excluding an oxidized A? peptide in which only Met has been oxidized).

Abstract: The disclosure pertains to the field of molecular means capable of binding calcium, in particular peptides which are calcium chelators, appropriate for use in vitro or in vivo and preferably capable of targeting specific cellular compartments. Polypeptide comprising a first calcium-binding domain, a peptide linker and a second calcium binding domain, wherein the first and second binding domains are linked through the peptide linker, and wherein: the first calcium-binding domain and the second calcium binding domain each comprise at least one calcium-binding site derived from a EF-hand motif; and, the first calcium-binding domain and the second calcium binding domain differ in at least one calcium-binding site.

Abstract: The present invention provides for recombinant Endo-S mutants that exhibit reduced hydrolysis activity and increased transglycosylation activity for the synthesis of glycoproteins wherein a desired sialylated oxazoline or synthetic oligosaccharide oxazoline is added to a core fucosylated or nonfucosylated GlcNAc-protein acceptor. Such recombinant Endo-S mutants are useful for efficient glycosylation remodeling of IgG1-Fc domain to provide different antibody glycoforms carrying structurally well-defined Fc N-glycans.

Abstract: TCR The present invention relates to an engineered T cell receptor (TCR). In particular, the present invention relates to methods for expression of a TCR when expressed as an exogenous TCR, to methods for selecting a TCR with high cell surface expression when expressed as an exogenous TCR and to methods for identifying residues which contribute to the cell surface expression level of a TCR. The present invention also relates to an engineered TCR which has a high level of cell surface expression when expressed as an exogenous TCR compared to the corresponding germline TCR sequence.

Abstract: Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of Fc?RI?. Notably, CAR constructs with an intracellular domain of Fc?RI? had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.

Abstract: The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and (ii) a polypeptide capable of co-localizing a beta-2 microglobulin component of a MHC class I molecule with an intracellular signalling domain within the cell.

Abstract: Provided are p97 (melanotransferrin)-trastuzumab fusion proteins and related methods of use thereof, for instance, to facilitate delivery of trastuzumab across the blood-brain barrier (BBB) and/or improve tissue penetration of the antibody in CNS and peripheral tissues, and thereby treat and/or diagnose HER2-positive cancers, including those of the central nervous system (CNS).

Abstract: Provided are high affinity Mycobacterium tuberculosis capsule-specific antibodies and fragments thereof, as well as methods of use and devices employing such antibodies and/or fragments.

Abstract: Pharmaceutical composition comprising antibodies or antigen binding fragments thereof that bind to Globo H, stage-specific embryonic antigen 3 (SSEA-3) and stage-specific embryonic antigen 4 (SSEA-4) are disclosed herein, as well as methods of use thereof. Methods of use include, without limitation, cancer therapies and diagnostics. The antibodies of the disclosure can bind to certain cancer cell surfaces. Exemplary targets of the antibodies disclosed herein can include carcinomas, such as sarcoma, skin cancer, leukemia, lymphoma, brain cancer, glioblastoma, lung cancer, breast cancer, oral cancer, head-and-neck cancer, nasopharyngeal cancer, esophagus cancer, stomach cancer, liver cancer, bile duct cancer, gallbladder cancer, bladder cancer, pancreatic cancer, intestinal cancer, colorectal cancer, kidney cancer, cervix cancer, endometrial cancer, ovarian cancer, testical cancer, buccal cancer, oropharyngeal cancer, laryngeal cancer and prostate cancer.

Abstract: The invention provides antibodies to tau. The antibodies inhibit or delay tau-associated pathologies and associated symptomatic deterioration.

Abstract: Objective of the present invention is to provide a novel monoclonal antibody against Nav1.7. The present invention discloses a monoclonal antibody against Nav1.7 or its antibody fragment, having specific six CDRs (CDR1 to CDR3 of a heavy chain and CDR1 to CDR3 of a light chain) or specific heavy/light chain variable regions. The monoclonal antibody and the like can be used for treating or preventing pain, pruritus and so on.

Abstract: Disclosed herein are immunoglobulins, such as antibodies, and antigen binding portions thereof, that specifically bind complexes of GARP-TGF?1, LTBP1-TGF?1, LTBP3-TGF?1, and/or LRRC33-TGF?1. The application also provides methods of use of these immunoglobulins for, for example, inhibiting TGF?1 activity, and treating subjects suffering from TGF?1-related disorders, such as cancer and fibrosis.

Abstract: The present invention provides a method for treating or delaying the onset of an autoimmune condition in a human subject. An effective oral dose of ustekinumab is administered to the subject. Oral administration of ustekinumab also is useful in a method of decreasing innate inflammatory cytokines, such as Interleukin-1? and Tumor Necrosis Factor-?, Th1-like cytokines Interleukin-2 and Interferon-?, Interleukin-17 (Teff), Interleukin-12p70, and increasing Th2-like counter-regulatory cytokine Interleukin-13 in a subject.

Abstract: Humanized, mouse or chimeric anti-CD47 monoclonal antibodies are provided. The antibodies bind to human glycosylated and deglycosylated CD47 with an optimized Koff value, they disrupt the human CD47-SIRP? interaction, and find use in various therapeutic, preventive or diagnostic methods. The invention includes isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized or chimeric anti-CD47 monoclonal antibodies; and cell lines that produce these monoclonal antibodies. Also provided are amino acid and nucleotide sequences of the antibodies.

Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Abstract: The present invention provides CTLA-4 monoclonal antibodies, particularly humanized monoclonal antibodies specifically binding to CTLA-4 with high affinity. The present invention also provides functional monoclonal antibodies cross-reactive to CTLA-4 of human, cynomolgus monkey and mouse. The present invention further provides amino acid sequences of the antibodies of the invention, cloning or expression vectors, host cells and methods for expressing or isolating the antibodies. The epitopes of the antibodies are identified. Therapeutic compositions comprising the antibodies of the invention are also provided. The invention also provides methods for treating cancers and other diseases with anti-CTLA-4 antibodies.

Abstract: The present specification discloses a pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS. The pharmaceutical composition is administered by a dosage regimen comprising at least one course of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session of non-treatment.

Abstract: The present disclosure provides monoclonal antibodies against protein programmed cell death 1 (PD-1), which can block the binding of PD-1 ligands to PD-1, and therefore block the inhibitory function of PD-1 ligands on PD-1 expressing T cells.

Abstract: The present disclosure provides isolated binding molecules that bind to and blocks PD-L1, vectors comprising a nucleic acid molecules encoding an amino acid sequence of the binding molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease requiring stimulation of immune responses including cancer.

Abstract: The present disclosure relates to monoclonal antibodies anti-FGFR4 and their use as medicaments and diagnostic agents. In particular, it relates to an antibody which specifically binds to the acid box domain of FGFR4 and to specific portions thereof. Nucleic acids coding for said antibody, vectors and host cells for their expression and production, antibody-drug conjugates and pharmaceutical compositions comprising said antibody are also within the scope of the present disclosure. The present disclosure also relates to antibodies anti-FGFR4 for use for detecting, killing, affecting or inhibiting development and/or differentiation of colon cancer stem cells.

Abstract: An isolated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen-binding domain, comprising an antibody or antibody fragment that binds a human CXC chemokine receptor type 5 (CXCR5) protein. Also disclosed is a nucleic acid molecule encoding the CAR of the invention, a genetically modified immune cell, preferably a T cell, expressing the CAR of the invention and the use of said cell in the treatment of a medical disorder associated with the presence of pathogenic cells expressing CXCR5, preferably pathogenic mature B cells and/or memory B cells, and/or pathogenic T cells and/or T follicular helper cells, in particular mature B cell non-Hodgkin's lymphoma (B-NHL), T cell non-Hodgkin's lymphoma, or autoantibody-dependent autoimmune disease, preferably selected from systemic lupus erythematosus (SLE) or rheumatoid arthritis.

Abstract: The invention relates to specific Antibody-Drug-Conjugates (ADCs) with KSP inhibitors and anti-CD123-antibodies, to the use of these conjugates for the treatment and/or prophylaxis of diseases and to the use of these conjugates for preparing medicaments for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases. Such treatments can be carried out as monotherapy or else in combination with other medicaments or further therapeutic measures.

Abstract: Provided are monospecific and bispecific proteins that bind specifically to OX40 and/or PD-L1. Exemplary proteins release the inhibition through PD-L1 and stimulate T cell through OX40. Exemplary polyvalent proteins comprise at least one OX40 binding site and at least one PD-L1 binding site. In certain embodiments, the binding sites may be linked through an immunoglobulin constant region. Anti-OX40 and anti-PD-L1 antibodies are also provided.

Abstract: Disclosed herein are humanized antibodies, antigen-binding fragments thereof, and antibody conjugates, that are capable of specifically binding to certain biantennary Lewis antigens, which antigens are expressed in a variety of cancers. The presently disclosed antibodies are useful to target antigen-expressing cells for treatment or detection of disease, including various cancers. Also provided are polynucleotides, vectors, and host cells for producing the disclosed antibodies and antigen-binding fragments thereof. Pharmaceutical compositions, methods of treatment and detection, and uses of the antibodies, antigen-binding fragments, antibody conjugates, and compositions are also provided.

Abstract: A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. The ligand that binds a protein associated with a TCR complex is UCHT1 with a Y182T mutation. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

Abstract: The disclosure provides antibody immune cell inhibitor fusion proteins comprising four polypeptide chains that form two antigen binding sites and at least two immune cell receptor binding sites that inhibit or diminish activation of an immune effector cell when bound to a target antigen. The disclosure also provides antibody immune cell inhibitor fusion proteins comprising two polypeptide chains that form one antigen binding site and at least one immune cell receptor binding site that inhibit or diminish activation of an immune effector cell when bound to a target antigen. The disclosure further provides pharmaceutical compositions and kits that comprise such antibody immune cell inhibitor fusion proteins, and methods of treatment using such proteins.

Abstract: An object of the present invention is to provide a method by which a peptide having a specific binding capability that can be used for purification of a target molecule can be produced at a low cost, and specifically relates to a peptide fusion protein including one or more peptides having specific binding capability and a scaffold protein, the peptide being inserted into the amino acid sequence of the scaffold protein directly or via a peptide linker, and/or being linked to the N-terminal and/or C-terminal of the scaffold protein.

Abstract: It is an object of the present invention to provide a thickener capable of exhibiting excellent light resistance. The present invention relates to a thickener comprising cellulose fibers having a fiber width of 8 nm or less and water, wherein the thickener is a slurry or a gel, and when the thickener is filled in a colorless and transparent glass cell having an inside dimension of 1 cm in depth×4 cm in width×4.5 cm in height and the thickener is then irradiated with ultraviolet rays with a wavelength of 300 nm or more and 400 nm or less, using a xenon lamp, from the side of the maximum area surface of the glass cell, so as to be an irradiance of 180 W/m2 and an integrated light amount of 500 mJ/m2, the amount of a change in the yellowness before and after ultraviolet irradiation measured in accordance with JIS K 7373 is 10 or less.

Abstract: A cellulose ester, wherein, in a structural formula of the following general formula (I), a degree of substitution where X is an acyl group is from 2.91 to 3.0; the acyl group includes benzoyl group (A) optionally having a substituent, and benzoyl group (B) optionally having a substituent different from that of benzoyl group (A); and when the degree of substitution is 3.0, a degree of substitution of benzoyl group (A) is from 1.5 to 2.9, and a degree of substitution of benzoyl group (B) is from 0.1 to 1.5, wherein all or some of X represents an acyl group; when some of X represents an acyl group, the remainder represents a group selected from a hydrogen atom and an alkyl group; and n represents an integer of from 20 to 20,000.

Abstract: Regioselectively substituted cellulose esters having a plurality of pivaloyl substituents and a plurality of aryl-acyl substituents are disclosed along with methods for making the same. Such cellulose esters may be suitable for use in films, such as +A optical films, and/or +C optical films. Optical films prepared employing such cellulose esters have a variety of commercial applications, such as, for example, as compensation films in liquid crystal displays and/or waveplates in creating circular polarized light used in 3-D technology.

Abstract: Provided is a low-molecular-weight holothurian glycosarninoglycan, with the constituent units thereof being a glucuronic acid group, an N-acetaminogalactose group and a fucose group, and a sulfate ester group or acetyl ester group thereof. Glucuronic acid and N-acetaminogalactose are interconnected via ?(1-3) and ?(1-4) glucosidic bonds to form a backbone of a disaccharide repeating structural unit, and a fucose group is connected to the backbone as a side chain. On a molar ratio basis, the ratio of the glucuronic acid group:the N-acetaminogalactose group:the fucose group is 1:(0.8-1.2):(0.6-1.2). In the structure of the low-molecular-weight holothurian glycosaminoglycan, 10-30% of glucuronic acid groups are modified, on the 2-position, with a sulfate ester group, and the rest are hydroxyl groups; and a proportion of 10-30% of fucose groups is modified, on the 2-position, with an acetyl ester group, and the rest are hydroxyl or sulfate ester groups.

Abstract: A method for producing an article in which a layer with a radically cross-linkable resin is selectively crosslinked at least partially. This takes place according to a selected cross section of the article to be formed by means of selective application of a radical initiator. The at least partially crosslinked material is added on layer by layer to a carrier or to previous layers bonded to the carrier. A system that is suitable for carrying out the method according to the invention has a substrate, a control unit, an application unit for applying the resin to the substrate, an application unit for applying an initiator to the resin, an energy exposure unit and a contacting unit.

Abstract: The present invention makes it possible to maintain a high 180-degree peel strength of a photocurable composition having a film shape at 25° C. in the state of not being cured against untreated PET as an adherend when bonding is performed by lamination at normal temperature. A photocurable composition having a film shape at 25° C. in a state of not being cured, which contains the following components (A) to (C) and in which the photocurable composition contains 1 to 45 parts by mass of the component (B) with respect to 100 parts by mass of the component (A), a temperature of tan ?=1 is 30° C. to 60° C. before curing, a storage elastic modulus at 25° C. is 10.0×105 Pa or less after curing.

Abstract: The present invention provides polymer compositions having improved corrosivity, color stability and clarity. Also disclosed is a process of preparing the polymers. The process may comprise incorporating into the polymer an acid neutralizing amount of an amorphous aluminum silicate. The amorphous aluminum silicate may be present in the polymer in an amount such that the polymer composition having a Corrosivity Index of less than 6. A refractive index of the amorphous aluminum silicate may be the same or substantially the same as a refractive index of the polymer.

Abstract: A POSS modified polyacrylate fluorine-free waterproofing agent includes following components: 1-10 wt % of a functionalized POSS monomer, 2-20 wt % of methyl methacrylate, 3-26 wt % of butyl acrylate, 1-10 wt % of a long-chain acrylate monomer, 0.5-3.5 wt % of an initiator, 0.5-4 wt % of a reactive cationic emulsifier, and 50-80 wt % of deionized water. A method of preparing a POSS modified polyacrylate fluorine-free waterproofing agent is also disclosed.

Abstract: The polyethylene according to the present disclosure has a molecular structure having a narrow particle distribution and a low content of ultra-high molecular weight, so that a chlorinated polyethylene having excellent chlorination productivity and thermal stability may be prepared by reacting the polyethylene with chlorine. And, a PVC composition including the same with improved impact strength may also be prepared.

Abstract: The invention relates to fluoropolymers that have been modified with low molecular weight, polymeric chain transfer agents, and uses of the modified fluoropolymers. The modified fluoropolymers provide enhanced properties to the fluoropolymer, such as increased adhesion, and hydrophilic characteristics. The modified functional fluoropolymers are useful in many applications, including as binders in electrode-forming compositions and separator compositions, for hydrophilic membranes and hollow fiber membranes, as an aqueous and a solvent cast coating for baked decorative and protective coatings, and as a tie layer between a fluoropolymer layer and an incompatible polymer layer.