Abstract: The disclosure provides means and methods for interfering with Programmed Cell Death 1 protein (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) mediated inhibition in a PD-1 and/or TIM-3 positive cell. A method may comprise contacting said cell with an antibody or a functional part, derivative and/or analogue thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of TIM-3, thereby inhibiting PD-1 and/or TIM-3 mediated activity in said cell. The invention also provides antibodies or variants thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of TIM-3.

Abstract: The invention provides means and methods for interfering with Programmed Cell Death 1 protein (PD-1) and Lymphocyte activation 3 (LAG 3) mediated inhibition in a PD-1 and/or LAG3 positive cell. A method may comprise contacting said cell with an antibody or a functional part, derivative and/or analogue thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of LAG3, thereby inhibiting PD-1 and/or LAG3 mediated activity in said cell. The invention also provides antibodies or variants thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of LAG3.

Abstract: Herein described are liquid formulations of antibodies and biologically active fragments thereof that specifically bind to a human ICOS polypeptide, exhibit increased in vivo ADCC activity and undergo reversible self-association in solution.

Abstract: Provided are dosage regimens for combination therapy using PD-1 axis binding antagonists and GPC3 targeting agent. For example, the dosage regimens comprise (i) a loading period within which the GPC3 targeting agent is administered, followed by (ii) a maintenance period within which the PD-1 axis binding antagonist and the GPC3 targeting agent are administered.

Abstract: The present disclosure relates to a chimeric antigen receptor, a nucleic acid, a chimeric antigen receptor expression plasmid, a chimeric antigen receptor expressing cell, a pharmaceutical composition for treating cancer, and use of the chimeric antigen receptor expressing cell. The chimeric antigen receptor is specific to human leukocyte antigen G. The nucleic acid encodes the chimeric antigen receptor. The chimeric antigen receptor expression plasmid expresses the chimeric antigen receptor. The chimeric antigen receptor expressing cell is obtained by transducing the chimeric antigen receptor into an immune cell. The pharmaceutical composition for treating cancer includes the chimeric antigen receptor expressing cell and a pharmaceutically acceptable carrier.

Abstract: Multi-specific binding proteins that bind NKG2D receptor, CD16, and a tumor-associated antigen selected from EGFR, HLA-E, CCR4, and PD-L1 are described, as well pharmaceutical compositions and therapeutic methods useful for the treatment of cancer.

Abstract: The present invention provides new compositions and methods useful for the treatment and potential cure of beta-globinopathies such as sickle cell disease and beta-thalassemia by inhibiting the expression and/or activity of RIOK3.

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) ?-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising ?-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) ?-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising ?-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4.

Abstract: The present invention relates to compositions and methods for treatment of neurological disorders. In particular, the present invention relates to the epidermal growth factor receptor (EGFR) as a clinical target for treatment of neurological disorders, preferably in conjunction with neuropathic pain.

Abstract: This application discloses anti-CCR7 antibodies, antigen binding fragments thereof, and antibody drug conjugates of said antibodies or antigen binding fragments. The invention also relates to methods of treating or preventing cancer using the antibodies, antigen binding fragments, and antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents.

Abstract: Agents that inhibit CX3CL1 in endothelial cells to reduce or inhibit immunosuppression mechanisms that are co-opted by cancer cells to evade host immune system, and that reduce immunosuppression in context of therapies that target VEGF-dependent signaling, and methods of use thereof.

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 present invention discloses novel methods, compositions, and uses thereof for removing or overcoming immunosuppression. More specifically, the methods and compositions disclosed herein target effector Treg cells by modulating ST2 and/or IL-33 signaling using pharmaceutical inhibitors and/or genetic ablation, whereby the levels and/or activities of effector Treg cells in a tumor microenvironment are inhibited, and the infiltration of effector CD8+ cytotoxic T cells into tumor microenvironment increases. As a result, tumor growth is inhibited and tumor volume is reduced. The present invention also provides methods for identifying and isolating effector Treg cells in a population of heterogeneous cells.

Abstract: Methods of treating autoimmune diseases, such as primary immune thrombocytopenia (ITP), solid organ transplant rejection, graft-related disease, pemphigus vulgaris, systemic sclerosis, and myasthenia gravis using antibody polypeptides that specifically bind human CD40L are provided. The antibody polypeptides do not activate platelets. The methods may comprise at least one administration cycle comprising one dose of the antibody polypeptide. The dose may be administered intravenously at a dose from about 75 mg to about 1500 mg. The method normalizes platelet counts in the human patient.

Abstract: Herein are provided a method for producing a multispecific antibody comprising the steps of providing a mammalian cell expressing the antibody, transfecting said mammalian cell with an expression vector comprising an expression cassette encoding a polypeptide of the antibody that has a domain crossover, cultivating the transfected cell and recovering the antibody from the cell or the cultivation medium and thereby producing the multispecific antibody.

Abstract: Herein are provided bispecific anti-human CD20/human transferrin receptor antibodies and methods of using the same.

Abstract: Disclosed herein are multifunctional antigen-binding proteins comprising at least one multifunctional recombinant protein scaffold and at least one antigen-specific binding domain, Polynucleotides encoding the multifunctional antigen-binding proteins, vectors containing the disclosed polynucleotides, and cells that have been genetically engineered to express the polynucleotide are also provided. Methods of using the multifunctional antigen-binding proteins are disclosed.

Abstract: Methods are provided for identifying and selecting antibodies that are internalized into cells via the macropinocytosis pathway. Additionally antibodies that are internalized via this pathway are provided as well as immunoconjugates comprising such antibodies.

Abstract: Humanized antibodies, capable of specific binding to human CEACAM1 molecules containing human-to-murine back-mutations in non-CDR variable regions, and their encoding polynucleotide sequences are provided. Pharmaceutical compositions comprising these antibodies as well as methods of their use in treating and diagnosing cancer and other conditions are also provided.

Abstract: A panel of human variable heavy (VH) single domain monoclonal antibodies specific for cell-surface glypican-2 (GPC2) are described. Methods for the diagnosis and treatment and GPC2-positive cancer are also described. Recombinant immunotoxins comprised of a GPC2-specific VH domain antibody and a clinically used form of Pseudomonas exotoxin A (PE38) were generated and shown to inhibit GPC2-positive neuroblastoma tumor cell growth and inhibit neuroblastoma xenograft growth in nude mice, without significant toxicity. Chimeric antigen receptors comprising a GPC2-specific VH single domain antibody are also described. T cells expressing the GPC2-specific CARs potently killed GPC2-positive neuroblastoma cells in a dose-dependent manner.

Abstract: The present invention is directed to heterodimeric antibodies that bind CD3 and PSMA.

Abstract: Described herein are anti-MCAM antibodies and antigen binding fragments thereof that are capable of inhibiting the interaction between MCAM and its ligand, a protein comprising a laminin ?-4 chain. These anti-MCAM antibodies and antigen binding fragments thereof may be useful for, for example, treating inflammatory conditions characterized by the infiltration of MCAM-expressing cells into a site of inflammation in the body.

Abstract: This document provides methods and materials related to treating cancer. For example, methods and materials for using particles (e.g., nanoparticles) containing (a) one or more molecules having the ability to bind to a cancer cell (e.g., a human breast cancer cell) and (b) one or more molecules having the ability to bind to an APC (e.g., a human macrophage) to treat cancer are provided.

Abstract: This disclosure provides compositions and methods for expressing and displaying isolated integral membrane proteins (IMPs) or fragments thereof in a native conformation for use in the screening, selecting, and identifying of antibodies or antibody-like molecules that bind to a target IMP of interest.

Abstract: The present application provides a HDAC6 inhibitor for use in treating a degenerative disease associated with the formation of intracellular granules, wherein said granules are formed by the aggregation of a protein selected from the group comprising APP, Tau, Ataxin-2, hnRNPA1, C9orf72, Lamin A/C, Myotilin, Matrin 3, alpha-synuclein, SOD1, FUS, hnRNPA2B1, VCP, TIA1, Desmin and Huntingtin, and wherein said inhibitor inhibits both the CD1 and CD2 of HDAC6.

Abstract: Isolated histidyl-tRNA synthetase splice variant polynucleotides and polypeptides having non-canonical biological activities are provided, as well as compositions and methods related thereto.

Abstract: The present invention provides methods for treating hypercholesterolemia. The methods of the present invention comprise administering to patients with heterozygous familial hypercholesterolemia a pharmaceutical composition comprising a PCSK9 inhibitor. In certain embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody such as the exemplary antibody referred to herein as mAb316P. The methods of the present invention are useful for treating patients with heterozygous familial hypercholesterolemia who are not adequately controlled by maximum tolerated dose statin therapy with or without other lipid lowering therapy.

Abstract: The invention relates to antibodies to MASP-2 and functional equivalents thereof. In particular, the invention relates to MASP-2 antibodies capable of inhibiting the function of MASP-2. The invention furthermore discloses MASP-2 epitopes, wherein antibodies recognising said epitopes are in particularly useful for inhibiting MASP-2 activity. The invention also relates to methods of producing said antibodies, methods of inhibiting MASP-2 activity as well as to pharmaceutical compositions comprising the MASP-2 antibodies.

Abstract: The present disclosure relates to cell penetrating anti-DNA binding proteins. Compositions comprising these binding proteins may be may be useful for delivering agents to cells and treating diseases such as cancer.

Abstract: The present disclosure relates to cell penetrating anti-DNA binding proteins. Compositions comprising these binding proteins may be may be useful for delivering agents to cells and treating diseases such as cancer.

Abstract: Contemplated compositions and methods use various immunomodulatory agents to downregulate an autoimmune response and/or to upregulate immune responses against autoantigen presenting cells.

Abstract: The claimed invention is directed to continuous process for dehydrating nanocellulose using a combination of evaporative cooling and sublimation cooling. The continuous process begins with a slurry of nanocellulose material and operates to dehydrate the material without causing agglomeration or loss of structure. Such dehydrated nanocellulose material is very useful when incorporated into structural materials.

Abstract: Several embodiments of NO releasing structures are disclosed. In some embodiments, the structures are covalently modified to store and release nitric oxide. Some embodiments pertain to methods of making and use of these structures. The covalently modified polymer structures may be tailored to release nitric oxide in a controlled manner and are useful for treatment of various medical conditions.

Abstract: Described herein is an octenyl succinic acid modified starch (OSA modified starch) degraded by at least one enzyme capable of cleaving 1,4-linkages of a starch molecule from the non-reducing ends to produce short chain saccharides, wherein the content of non-covalently bound, free octenyl succinic acid in the OSA modified starch is less than about 0.50% by weight, based on total weight of the modified starch, and wherein content of alpha-1,6-glycosidic linkages is higher than 12%, a method of preparing same, and an encapsulation agent comprising same as well as a method of encapsulating an active agent with said encapsulation agent.

Abstract: Methods for the preparation of oligosaccharide products from polysaccharide starting materials are disclosed. The methods include: hydrolyzing a glucosamine-containing polysaccharide starting material, such as heparin or heparosan, under conditions sufficient to form an oligosaccharide intermediate (e.g., a GlcN-IdoA disaccharide intermediate or a GlcA-GlcN disaccharide intermediate), and converting the oligosaccharide intermediate to the oligosaccharide product. Conversion of the oligosaccharide intermediates to the oligosaccharide products may include one or more esterification, acylation, epimerization, protection, and deprotection steps. Preparation of higher-order oligomers is described, as well as methods for selective oligosaccharide sulfation.

Abstract: Provided herein are purified hemicellulose compositions, sweetener compositions including purified hemicellulose compositions, as well as methods for making the same. Also provided are uses of the compositions.

Abstract: The invention deals with a novel process for making intermediates of the pharmaceutically useful product Sugammadex of formula (1).

Abstract: A new class of synthetic cyclodextrin dimers is described. Exemplary cyclodextrin dimers can treat atherosclerotic plaques by targeting various forms cholesterol both intracellularly and extracellularly. Also provided are methods of depleting atherosclerotic plaques of cholesterol, cholesterol esters, 7-ketocholesterol and 7-ketocholesterol esters by treatment with such cyclodextrins. Further described are subclasses of dimers that have high specificity for 7-ketocholesterol.

Abstract: A glycosaminoglycan derivative which is obtainable by a process that includes the steps of N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan, and oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NH2 to aldehydes. The process further includes reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols, where the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof.

Abstract: The invention relates to a method for producing a modified conjugated diene-based polymer, comprising a step of reacting an organometallic compound with a unit based on a modifying agent, in a conjugated diene-based polymer that has a unit based on a conjugated diene compound-containing monomer and a unit based on a modifying agent having a silicon atom, tin atom, germanium atom or phosphorus atom.

Abstract: Provided are a method for preparing a conjugated diene-based polymer and a method for preparing a graft copolymer including the same. The method for preparing a conjugated diene-based polymer includes enlarging a first conjugated diene-based polymer in multiple stages to prepare a second conjugated diene-based polymer, wherein the multi-stage enlargement includes a primary enlargement stage and a secondary enlargement stage, and a weight ratio of acids added in the primary enlargement stage and the secondary enlargement stage is 70:30 to 90:10. A graft copolymer prepared by the above-described method can be used to form a thermoplastic resin molded article excellent in all of plating characteristics, mechanical properties, surface characteristics, colorability, and processability.

Abstract: The present invention relates to [1] a process for producing a water-based pigment dispersion, including step 1 of subjecting an ionic group-containing monomer (a) and a hydrophobic monomer (b) to polymerization reaction using an ionic group-containing polymerization initiator (x) and an ionic group-containing chain transfer agent (y) to obtain an ionic group-containing polymer A, step 2 of mixing and dispersing the obtained polymer A and a pigment in an aqueous medium to obtain a pigment water dispersion, and step 3 of subjecting the polymer A in the obtained pigment water dispersion to crosslinking reaction with a polyfunctional compound to obtain the water-based pigment dispersion, and [2] a process for producing a water-based ink, including, in addition to the aforementioned steps 1 to 3, step 4 of mixing the obtained water-based pigment dispersion with an organic solvent to obtain the water-based ink.

Abstract: A self-healing polymer network containing a physical crosslinking agent, a composition therefor, and an optical element comprising the same is provided. The self-healing polymer network comprises a polymer derived from monomers including self-healing monomers each having a first polymerizable functional group and at least one of urethane, urea, or amide group chemically linked to the first polymerizable functional group, wherein the polymer has a backbone formed by polymerizing the first polymerizable functional groups of the self-healing monomers and a plurality of side groups each having at least one of urethane, urea, or amide group chemically linked to the backbone. In addition, the self-healing polymer network comprises a physical crosslinking agent which is an alcohol mixture having at least two of monool, diol, triol, and tetraol or the higher polyol and crosslinking the polymer by physically crosslinking the urethane, urea, or amide group of the side groups.

Abstract: This invention relates to a process to polymerize olefins comprising contacting, in solution phase at a temperature of 60° C. to 200° C., ethylene, and at least one olefin comonomer with a catalyst system comprising a non-coordinating anion activator and a metallocene catalyst compound, preferably represented by the formula: and 2) obtaining ethylene polymer having an Mw greater than 100,000 g/mol, preferably greater tha 400,000 g/mol.

Abstract: To provide a modified polytetrafluoroethylene excellent in breaking strength. The modified polytetrafluoroethylene comprises a polymer having units based on tetrafluoroethylene and a polymer having units based on a monomer represented by formula (1), wherein the content of the units based on a monomer represented by formula (1) is from 10 to 500 mass ppm, to all units in the modified polytetrafluoroethylene, and the standard specific gravity is from 2.155 to 2.175, CH2?CR1-L-R2??Formula (1) wherein R1 represents a hydrogen atom or an alkyl group, L represents a single bond, —CO—O—*, —O—CO—*, or —O—, * represents a bonding position to R2, and R2 represents a hydrogen atom, an alkyl group, or a nitrile group.

Abstract: A polyvinyl alcohol has a number-average molecular weight (Mn) from 4,400 to 440,000, a molecular weight distribution (Mw/Mn) from 1.05 to 1.70, a degree of saponification from 80 to 99.99 mol %, wherein the polyvinyl alcohol contains an end group represented by a formula (I) below, and a molar ratio (X) of the end group based on total monomer units and the number-average molecular weight (Mn) satisfy a formula (1) below. Such a polyvinyl alcohol has a narrow molecular weight distribution and a high number-average molecular weight with hue good. (In the formula, R1 denotes an optionally substituted aromatic group having a carbon number from 6 to 20, and R2 denotes a hydrogen atom, an alkyl group having a carbon number from 1 to 20, or an optionally substituted aromatic group having a carbon number from 6 to 20.) X·Mn/44?0.

Abstract: A method for manufacturing a fluorine-free water repellent includes: mixing a paraffin, an inorganic nanopowder and a first reactive monomer to form a first mixture, in which the first reactive monomer includes a structure represented by formula (A), formula (B) or a combination thereof, the formula (A) is wherein X1 is a benzene, and the formula (B) is wherein X2 is CH3 or H and X3 is an alkyl group having 18 or more carbon atoms; mixing an emulsifier, a cosolvent and water to form a second mixture; mixing the first mixture and the second mixture to form a pre-emulsion; and adding an initiator and a second reactive monomer into the pre-emulsion, in which the first reactive monomer and the second reactive monomer are polymerized to form a water repellent, wherein the second reactive monomer is vinylidene chloride.

Abstract: This invention relates to plasticized poly(vinyl chloride) compounds formulated to provide sufficient flexibility and flame retardance to be suitable for building and construction polymeric articles. One aspect of the present invention is a flame retardant poly(vinyl chloride) compound, comprising a mixture of: poly(vinyl chloride); a plasticizer selected from the group consisting of polymeric plasticizer, alkyl aryl fire retardant plasticizer, and combinations thereof; and optionally functional additives, wherein the mixture has i) a Limiting Oxygen Index of greater than 50% according to ASTM D2863; ii) an Elongation at Break of at least 10% according to ASTM D638 (Type IV); and iii) a Modulus of Elasticity of less than about 15,000 psi according to ASTM 638 (Type IV).

Abstract: A propylene ethylene copolymer having: i) xylene soluble fraction at 25° C. ranging from 14 wt % to 27 wt %; ii) intrinsic viscosity of the fraction soluble in xylene at 25° C. ranging from 1.0 to 2.4 dl/g; iii) melt flow rate, MFR, ranging from 1.0 g/10 min to 50.0 g/10 min; iv) an ethylene derived units content ranging from 5.0 wt % to 12.0 wt %; v) the ethylene derived units content on the fraction insoluble in xylene at 25° C. ranging from 2.5 wt % to 6.0 wt %; vi) the ethylene derived units content on the fraction soluble in xylene at 25° C. ranging from 15.2. wt % to 30.2 wt %; and vii) C13 NMR sequences PEP measured on the fraction insoluble in xylene at 25° C. ranging from 3.5 mol % to 5.5 mol % and C13 NMR sequences PEP measured on the fraction soluble in xylene at 25° C. ranging from 11.0 mol % to 14.2 mol %.

Abstract: A process for the polymerization of olefins in gas phase carried out in a reactor having two interconnected polymerization zones, a first zone (riser) and a second zone (downcomer), wherein growing polymer particles: a) flow through the riser under fast fluidization conditions established by feeding a mixture of gas and liquid; b) leave the riser and enter the downcomer, through which the growing polymer particles flow downward in a densified form; and c) leave the downcomer and are reintroduced into the riser, thereby establishing a circulation of polymer between the riser and the downcomer; the reactor is operated at a temperature between 0° C. and 5° C. above the dew point of the riser gas at the operating pressure, and in the riser, besides the growing polymer particles and gas flow, an amount of liquid is present.