Abstract: In certain embodiments, this disclosure relates to conjugates comprising a polypeptide of GM-CSF and a polypeptide IL-4. Typically, the GM-CSF and IL-4 are connected by a linker, e.g., polypeptide. In certain embodiments, the disclosure relates to isolated nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such nucleic acids.

Abstract: The present disclosure encompasses compositions and methods for targeted cytokine delivery. The compositions disclosed herein comprise a cytokine linked to an NKG2D ligand or PD1 ligand and may improve immunotherapy by limiting side effects associated with immunotherapy. The present disclosure also encompasses compositions and methods for recruiting cytotoxic lymphocytes to target cells using NKG2D receptor ligands or PD1 ligands. The compositions disclosed herein comprise a NKG2D receptor ligand and a targeting molecule and may improve immunotherapy by limiting side effects associated with immunotherapy.

Abstract: Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

Abstract: The present invention has a function of enabling the penetration of the blood-brain barrier and the blood-spinal cord barrier of the central nervous system, which have not been significantly penetrated, with excellent efficiency, thereby enabling a rapid, quick, and more efficient therapeutic effect to be obtained through low dose administration. In addition, the present invention enables local administration unlike conventional therapeutic agents, thereby decreasing side effects, and enables local administration of a therapeutic agent at a high concentration, thereby enabling potentially new treatments and prescriptions.

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: Disclosed herein are methods of increasing numbers of monocytes to a tumor or cancer metastasis site in a subject. Non-limiting embodiments include administering or using a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+ GR1? (Ly6C?)) monocytes; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1? (Ly6C?)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist. Also disclosed herein are methods of increasing, stimulating, activating or promoting monocyte migration to or mobilization against a tumor or cancer metastasis in a subject. Non-limiting embodiments include administering a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1? (Ly6C?)) monocytes; or CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1? (Ly6C?)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist.

Abstract: The present invention relates to a novel epitope to convert T cell to type 2 helper T (TH2) cell. Specifically, the present invention relates to an epitope constituting the 20th to 30th amino acids (SEQ ID No.2) of extracellular domain (ECD) of activation-inducible tumor necrosis factor receptor (AITR), an antibody recognizing the epitope, a polynucleotide encoding the epitope, a polynucleotide encoding the antibody, an expression vector comprising the polynucleotide encoding the epitope or antibody, a transformant introduced with the vector, a composition comprising the antibody for converting T cell to TH2 cell and a method of conversion, a pharmaceutical composition comprising the antibody for preventing or treating autoimmune disease, and a method for treating autoimmune disease using the antibody.

Abstract: Contemplated compositions and methods comprise chimeric molecule complexes that advantageously provide activating signaling to immune competent cells when bound to ALL cells. Furthermore, chimeric molecule complexes include an Fc portion to extend serum half live time and facilitate purification.

Abstract: The disclosure relates to a recombinant membrane span protein complex, comprising (1) a fusion protein, comprising a membrane span protein fused to a kinase domain, preferably a constitutive kinase and (2) a reporter construct comprising a polypeptide, interacting with the membrane span protein, fused to a reporter phosphorylation domain. The disclosure relates further to the uses of such membrane span protein complex for the detection of compounds that interact with the membrane span protein and for the screening and/or detection of inhibitors of the compound-membrane span protein interactions. In a preferred embodiment, the membrane span protein is a G protein coupled receptor (GPCR) and the method is used for the screening and/or detection of inhibitors of the ligand-receptor binding.

Abstract: Described herein are methods and compositions relating to nanodiscs, e.g., phospholipid bilayers with a proteinaceous belt or border. Further provided herein are loopable membrane scaffold proteins, e.g., for forming nanodiscs.

Abstract: The present invention relates to single domain antibodies comprising at least one modification relative to the 4D5 antibody scaffold or human germline VH3 domain, the modifications selected from the group consisting of H35D, A78V, S93V, S93G and W103R, with the position numbering being according to the Kabat numbering scheme. Disulfide-free variants further comprise at least one additional modification selected from the group consisting of C22S, A24I, A24L and C92T, and with the proviso that at least one of C22S and C92T is present. Further encompassed are the multi-modular antibody molecules and antibody conjugates comprising single domain antibodies, as well as methods for producing them. The invention in particular provides a library of the single domain antibodies or multi-modular antibody molecules and a method for selecting an antibody that binds an antigen.

Abstract: The present invention relates to a labeled chimeric non-therapeutic antibodylike protein comprising, in a hypervariable region thereof, an enzyme cleavable peptide sequence derived from a hypervariable region of a reference therapeutic antibody.

Abstract: This disclosure provides antibodies and antigen-binding fragments that are derived from 6nb6 and that can be administered to an individual that is infected or suspected of being infected with a virus. Antibodies and antigen-binding fragments herein can be capable of treating or curing the virus, and which may provide protection against the virus for up to several weeks. Antibodies and antigen-binding fragments herein can be used to diagnose a SARS CoV 2 infection.

Abstract: Provided herein are fusion protein constructs that can bind a complement-associated antigen, comprising a targeting moiety and a complement modulator protein, or a fragment thereof or a variant thereof. The targeting moiety is an antibody or an antigen binding fragment thereof, in some examples. Further provided are methods of using the fusion protein constructs, for example, in treating complement mediation conditions.

Abstract: Provided herein are fusion protein constructs that can bind a complement-associated antigen, comprising a targeting moiety and a complement modulator protein, or a fragment thereof or a variant thereof. The targeting moiety is an antibody or an antigen binding fragment thereof, in some examples. Further provided are methods of using the fusion protein constructs, for example, in treating complement mediation conditions.

Abstract: This disclosure provides compositions and methods for controlling pain. In particular the disclosure provides a method for controlling pain comprising co-administration of an NGF antagonist and a TNF? antagonist. The NGF antagonist and the TNF? antagonist can be separate molecules or part of a multifunctional polypeptide, e.g., a multispecific binding molecule that comprises an NGF antagonist domain and a TNF? antagonist domain. This disclosure also provides multifunctional polypeptides, e.g., multispecific binding molecules, comprising an NGF antagonist domain, and a TNF? antagonist domain. The method provides improved pain control. Administration of an NGF antagonist and a TNF? antagonist as provided herein can control pain in the subject more effectively than an equivalent amount of the NGF antagonist or the TNF? antagonist administered alone.

Abstract: For example, therapeutic methods and the like for novel IL-8-related diseases using an IL-8 signal inhibitor are provided. Alternatively, for example, therapeutic methods and the like for known or novel IL-8-related diseases using a novel anti-IL-8 antibody are provided.

Abstract: The present invention provides methods for treating, preventing or reducing the severity of active eosinophilic esophagitis. In certain embodiments, the present invention provides methods of increasing esophageal distensibility. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4/interleukin-13 (IL-4/IL-13) pathway inhibitor such as an anti-IL-4R antibody.

Abstract: Provided herein are novel anti-EMP2 antibodies useful for the treatment and diagnosis of cancers that express or overexpress EMP2. In one aspect, provided herein is an isolated antibody that binds to Epithelial Membrane Protein 2 (EMP2), that includes heavy chain variable region and a light chain variable region. The heavy chain variable region includes three heavy chain complementary determining regions (HCDRs) and the light chain variable region includes three light chain variable regions (LCDRs). In some embodiments, the sequence of HCDR1 is SEQ ID NO: 11, the sequence of HCDR2 is SEQ ID NO: 12, the sequence of HCDR3 is SEQ ID NO: 13, the sequence of LCDR1 is SEQ ID NO:14, the sequence of LCDR2 is SEQ ID NO: 15, and the sequence of LCDR3 is SEQ ID NO: 16.

Abstract: The present disclosure provides a human antibody or antigen binding fragment thereof or an antibody construct comprising a human binding domain or antigen binding fragment thereof capable of binding to human CDH19 on the surface of a target cell. The disclosure relates to a nucleic acid sequence encoding the antibody or antigen binding fragment thereof contained in the antibody construct, a vector comprising the nucleic acid sequence and a host cell transformed or transfected with the vector. Furthermore, the disclosure relates to a process for the production of the antibody construct of the disclosure, a medical use or a method of treatment using the antibody construct and a kit comprising the antibody or antigen binding fragment thereof or the antibody construct.

Abstract: In accordance with the present invention, there are provided functionally modulated tool receptors which are useful for drug discovery and development. In certain aspects and embodiments as described herein, a sophisticated and powerful approach has been designed that allows the rapid development of enhanced receptors, while simultaneously exploring millions of possibilities for improved properties with respect to such properties as protein expression, homogeneity, stabilization, conformational and activation pathway selectivity, antigenicity, immunogenicity, and the like. Indeed, the new methodology described herein represents a breakthrough by leveraging a full range of combinatorial amino acid replacements, in multiple positions simultaneously, in order to generate modified membrane-spanning proteins.

Abstract: An object of the present invention is to provide a novel molecule which has high specificity to CLDN-5 and recognizes an extracellular domain of CLDN-5. The object is achieved by an antibody which specifically recognizes a three-dimensional structure or a primary structure of an extracellular domain of a Claudin-5 protein.

Abstract: Described herein is the discovery that cancer stem cells (CSCs) can be induced to differentiate by altering CD47 signaling. Provided herein are methods and compositions for inducing differentiation of cancer stem cells, for instance irreversible differentiation, including methods of treating subjects with cancer such as breast cancer, colon cancer, lung cancer, ovarian cancer, or melanoma, and including metastatic as well as primary cancer. Also provided are methods for treating subjects with triple negative breast cancers involving forcing differentiation of bCSCs of the subjects through targeting of CD47.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that bind to ILT4 (immunoglobulin-like transcript 4) and combinations thereof, e.g., with an anti-PD1 antibody. Also provided are methods of use thereof, for example, for treating or preventing cancer in a subject; and methods of making such antibodies and fragments.

Abstract: The present invention is directed to optimized anti-CD3 variable sequences for use in a variety of bispecific formats, including those that utilize scFv components. The invention further relates to nucleic acids encoding for the polypeptide, to vectors comprising the same and to host cells comprising the vector. In another aspect, the invention provides for a pharmaceutical composition comprising the mentioned polypeptide and medical uses of the polypeptide.

Abstract: Disclosed is a pharmaceutical preparation comprising a CD147 monoclonal antibody, a buffer, a protein protectant and a surfactant. The pharmaceutical preparation can maintain the stability of the CD147 monoclonal antibody over a long period of time. Also disclosed are the use of the pharmaceutical preparation in the preparation of a drug for treating CD147-related diseases, in particular non-small cell lung cancer, and a method for preparing the pharmaceutical preparation.

Abstract: The present invention provides a bispecific construct comprising a first binding domain specifically binding to CD33 and a second binding domain specifically binding to CD3 for use in a method for the treatment of myeloid leukemia, wherein the construct is administered for a maximal period of 14 days followed by a period of at least 14 days without administration of the construct. Moreover, the invention provides a method for the treatment of myeloid leukemia comprising the administration of a therapeutically efficient amount of such bispecific construct and the use of such bispecific construct for the preparation of a pharmaceutical composition for the treatment of myeloid leukemia.

Abstract: The invention relates to CXCR2, to antibodies and related fragments thereof for binding to CXCR2, to production of said antibodies and fragments and to use of said antibodies and fragments for detection and therapy of various conditions.

Abstract: Use of an inhibitor of the ErbB2 receptor for treatment or repair of nerves and/or nerve tissues is provided. The inhibitor includes an antibody, in particular, a monoclonal antibody, for example, Herceptin. A medicament for treatment or repair of nerves and/or nerve tissues can be formulated which includes an inhibitor of the ErbB2 receptor. A pharmaceutical kit may include a medicament having an inhibitor of the ErbB2 receptor and dosing instructions for administrating the medicament for treatment or repair of nerves and/or nerve tissues. Also provided are uses of an inhibitor of the ErbB2 receptor for increasing axon regeneration, preventing neuron or glial cell death, and/or stimulating Schwann cell proliferation in a nerve stump.

Abstract: The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R)n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a polyethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

Abstract: A process for dissolving modified cellulose includes contacting modified cellulose solution with at least one multivalent cation to form a plurality of modified cellulose particles.

Abstract: Objects of the present invention are to provide a phosphoric acid-esterified fine cellulose fiber of which slurry shows superior transparency, and to provide a method for producing a phosphorylated fine cellulose fiber showing superior transparency with good efficiency and high yield. According to the present invention, there is provided a phosphoric acid-esterified fine cellulose fiber, of which 0.2 mass % aqueous dispersion shows a solution haze of 15% or lower.

Abstract: A method for stabilizing a natural rubber such as guayule. The method includes the step of introducing at least one of an Extraction Curves for Guayule Rubber Samples amine and a phenolic anti-oxidant, such as MADA, to a latex form of the rubber under conditions such that the anti-oxidant becomes chemically bound to the rubber. The method includes the further step of subsequently treating the rubber to remove at least a substantial portion of entrained resins. The method can yield a rubber composition of, for example, guayule rubber and including an anti-oxidant chemically bound thereto. The resultant rubber can be suitable for use in tire construction.

Abstract: A liquid composition that contains a polymerizable compound and a solvent, and that can form a porous resin. The liquid composition, when stirred, transmits at least 30 percent of incident light having a wavelength of 550 nm. The haze value of an containing the liquid composition increases by 1.0 percent or more when the element containing the liquid composition is cured.

Abstract: Provided is a photocurable composition including a component (A) which is an acrylic ester compound containing one or more acryloyl groups in one molecule; a component (B) which is an acrylic ester compound containing one or more acryloyl groups and one or more epoxy groups in one molecule; a component (C) which is a compound containing two or more thiol groups in one molecule; a component (D) which is a photoradical generator; and a component (E) which is a photobase generator, in which a ratio between a total mass of the component (A) and the component (B) and a mass of the component (C) is in a range of 67.8:32.2 to 88.0:12.0, inclusive.

Abstract: This invention relates to production of propylene-predominant copolymers using a transition metal complex and at least two different non-coordinating anion activators. An olefinic feed comprising a C3-C40 alpha olefin, ethylene, and a diene monomer is contacted under polymerization reaction conditions with a catalyst system comprising a first non-coordinating anion activator, a second non-coordinating borate activator differing from the first non-coordinating anion activator, and a transition metal complex comprising a tetrahydro-s-indacenyl or tetrahydro-as-indacenyl group bound to a group 3-6 transition metal. A molar ratio of the first non-coordinating anion activator to the second non-coordinating anion activator is sufficient to produce a melt flow rate under the polymerization reaction conditions for the resulting copolymer of about 30 g/10 min or below as determined by ASTM D-1238 (230° C., 2.16 kg).

Abstract: An esterification method of a copolymer is disclosed. The esterification method includes the steps of: (A) mixing a copolymer having a carboxylic acid group, an alcohol or an aminoalcohol compound, a catalyst of formula (I), and a first solvent to obtain a first mixture; (B) reacting the first mixture at a predetermined temperature to obtain a second mixture; and (C) adding the second mixture into a second solvent; wherein the catalyst of formula (I) is shown below: [M(O)a]m+Xbn???(I) wherein M, X, a, b, in, and n are defined in the specification.

Abstract: The present invention relates to a cascade process useful for (fast) ionic polymerisation of liquid monomer(s) containing reaction mixture for the production of the corresponding polymer(s).

Abstract: Embodiments of the invention described herein relate to a polyethylene polymer composition suitable for use in the manufacture of packaging articles, flexible films and/or sheets. In one embodiment, the copolymer comprises a polyethylene resin with density 0.918 g/cm3 to about 0.935 g/cm3, G? at G?(500 Pa) value, as determined from Dynamic Mechanical Analysis at 190° C., of less than 40 Pa, Mz/Mw of greater than 2, CDBI50 of greater than 60. Other embodiments relate to polymer compositions with defined molecular characteristics and formulations suitable for use in the manufacture of articles including films, sheets, bags and pouches with improved creep resistance and high toughness and a good balance of film stiffness and processability in monolayer and/or multi-layer film structures.

Abstract: The presently claimed invention relates to novel monomers which can be used for preparing polymers which are useful as dispersants for pigments and fillers, as wetting agent and as thickening agents in liquid compositions.

Abstract: Novel methods and materials particularly useful for ophthalmic applications and to methods for making and using the same are disclosed herein. More particularly, relatively soft, optically transparent, foldable, high refractive index materials particularly suited for use in the production of intraocular lenses, contact lenses, and other ocular implants and to methods for manufacturing and implanting IOLs made therefrom are disclosed.

Abstract: A method for manufacturing high heat resistant and high scratch resistant water-based polyurethane, which can improve the mechanical strength and water resistance of water-based polyurethane by using acrylate graft modification, is provided. In particular, 2-hydroxyethyl acrylate (2-HEA), methyl methacrylate (MMA), ethyl acrylate (EA), acrylic acid (AA), glycidyl methacrylate (GMA) and triallyl isocyanuric acid ester (TAIC) are used to dilute polyurethane prepolymer. As a result, the prepolymer has a good dispersing effect, and further, waterborne bridging agent and cellulose nanofiber are added to the water-based polyurethane to obtain water-based polyurethane which has high heat resistance and scratch resistance.

Abstract: The disclosure relates to a thermoset omniphobic composition, which includes a thermoset polymer with first, second, and third backbone segments, first urethane groups linking the first and third backbone segments, and second urethane groups linking the first and second backbone segments. The first, second, and third backbone segments generally correspond to urethane reaction products of polyisocyanate(s), hydroxy-functional hydrophobic polymer(s), and polyol(s), respectively. The thermoset omniphobic composition has favorable omniphobic properties, for example as characterized by water and/or oil contact and/or sliding angles. The thermoset omniphobic composition can be used as a coating on any of a variety of substrates to provide omniphobic properties to a surface of the substrate. Such omniphobic coatings can be scratch-resistant, ink/paint resistant, dirt-repellent, and optically clear.

Abstract: An isocyanate reactive composition comprising At least one component selected from the group consisting of a polyether polyol, a polyester polyol, a polyether polyamide and a polyester polyamide; one or more amine components, each of said amine components having a given structure. In some embodiments, the average number of nitrogen atoms of said amine components is in the range of 5 to 10.

Abstract: Disclosed herein are polyurethanes useful for polishing layers, where the polyurethane is a polyurethane having a Schiff base. Also disclosed herein are polishing layers containing the polyurethanes, polishing methods that use the polishing layers, and a modification method including a step of converting the Schiff base into at least one functional group selected from an aldehyde group, a carboxylic acid group, a hydroxyl group, and an amino group.

Abstract: Disclosed are HCFO-containing isocyanate-reactive compositions, foam-forming compositions containing such isocyanate-reactive compositions, rigid PUR-PIR foams made using such foam-forming compositions, and methods for producing such foams, including use of such foams as insulation in discontinuous foam panel applications. The isocyanate-reactive composition can exhibit a long shelf life, be shelf-stable, and produce a foam with good physical properties.

Abstract: A rigid polyurethane foam comprises the reaction product of an isocyanate and a thixotropic composition. The thixotropic composition comprises: a first polyether polyoi which is aromatic amine initiated and has ethylene and propylene oxide end capping; a second polyether polyoi having a viscosity at 25° C. of from about 500 to about 15,000 cps; a third polyether polyoi having a viscosity at 25° C. of from about 18,000 to about 60,000 cps and a functionality of from about 5 to about 7; and a hydrofluoroolefin. The thixotropic composition has a viscosity at 25° C. of from about 350 to about 5,000 cps. A method of forming a composite article comprising a substrate and the rigid polyurethane foam includes the steps of providing the thixotropic composition, providing an isocyanate, combining the thixotropic composition and the isocyanate to form a reaction mixture, and applying the reaction mixture to the substrate to form the composite article.

Abstract: The present disclosure provides soft block copolymer segments of Formula 1 for thermoplastic polyurethane or polyurethaneurea elastomer materials and their reaction products with divalent compounds, such as diisocyanates, chain extenders and optional additional polyols or polyamines. Also disclosed herein are methods for the production of the soft block copolymer segments, and possible applications of these materials in the formation of biomaterials for articles including medical devices such as implants, heart valves and drug delivery devices.

Abstract: Provided is a thermoplastic resin composition which has improved ultraviolet absorbing capability, mechanical characteristics, hydrolysis resistance, transparency, and blooming resistance and is used for protecting an article used outdoors from ultraviolet light. A problem is solved by a thermoplastic polyurethane resin composition which is a reaction product of an isocyanate component (A1) containing an aliphatic polyisocyanate, a chain extender (A2), and a polyol component (A3) containing a polycarbonate diol having a side-chain alkyl group and contains an ultraviolet absorber (B1) having a benzotriazole skeleton, an ultraviolet absorber (B2) having a maximum absorption wavelength in a range from greater than or equal to 250 nm to less than or equal to 290 nm and having a triazine skeleton, a hindered amine light stabilizer (C), and an antioxidant (D).

Abstract: A hybrid composition includes an isocyanate, a polyester having at least one carbon-carbon double bond and at least one hydroxyl group, castor oil present in an amount of from 5 to 30 weight percent, a catalyst, and a solvent. The hybrid composition can be formed using various methods. The method may include combining the isocyanate and the castor oil to form a first adduct, combining the polyester, the solvent, and the catalyst to form a second adduct, and combining the first adduct and the second adduct. The method may alternatively include combining the castor oil, the solvent, and the polyester to form a third adduct, combining the third adduct with the isocyanate, and combining the catalyst with the third adduct and the isocyanate. The method may alternatively include combining the catalyst and the isocyanate component to form a fourth adduct, and combining the third and fourth adducts.