Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as anti-IL-6 antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat anemia (e.g., anemia associated with chemotherapy) including persons on a treatment regimen with a drug or chemotherapy and/or radiation for cancer (e.g., head and neck cancer) that is associated with increased risk of anemia.

Abstract: The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Abstract: This application provides, inter alia, antibodies or antigen-binding fragments thereof, targeting cell surface GRP78 expressed on tumor cells, tumor endothelial cells, and tumor initiating cancer cells. These anti-GRP78 antibodies, or antigen-binding fragments thereof, have a high affinity for GRP78 and are less immunogenic compared to their unmodified parent antibodies in a given species, e.g., a human, and function to inhibit GRP78. Importantly, these isolated novel antibodies and antigen-binding fragments thereof, attenuate PI3K signaling and promote apoptosis in tumor cells, while leaving normal cells unaffected. The antibodies and antigen-binding fragments are useful for UPR-targeted cancer therapeutic treatments.

Abstract: An object of the present invention is to provide a monoclonal antibody that recognizes an extracellular region of Claudin-2. A monoclonal antibody that specifically binds to an extracellular region of Claudin-2.

Abstract: Described herein are multi-specific binding agents that bind A33 and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Also provided herein are methods of using multi-specific binding agents or compositions thereof for the detection, prevention, and/or therapeutic treatment of diseases characterized by expression of the A33 glycoprotein antigen, in particular, colorectal cancer.

Abstract: There is provided a chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—GY-AFSSS (SEQ ID No. 1); CDR2—YPGDED (SEQ ID No. 2) CDR3—SLLYGDYLDY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—SASSSVSYMH (SEQ ID No. 4); CDR2—DTSKLAS (SEQ ID No. 5) CDR3—QQWNINPLT (SEQ ID No. 6). There is also provided a cell comprising such a CAR, and the use of such a cell in the treatment of cancer, in particular a B cell malignancy.

Abstract: The present invention provides antibodies that bind to and stabilize human Triggering Receptor Expressed on Myeloid cells 2 (TREM2) protein and methods of using these antibodies.

Abstract: Provided herein are anti-TREM2 antibodies and related methods of making and using anti-TREM2 antibodies. Also provided are methods and compositions for enhancing an immune response and/or for the treatment of an immune-related condition in an individual, e.g., cancer, comprising killing, disabling, or depleting non-stimulatory myeloid cells using an anti-TREM2 antibody or antigen binding fragment thereof.

Abstract: The invention provides multifunctional antibody-ligand traps and methods of using them to counteract immune tolerance and/or immune dysfunction. The multifunctional antibody-ligand traps and fusion proteins of the invention can counteract immune dysfunction in order to restore and unleash antitumor or pathogen-directed immune responses. Provided here are promising immunotherapeutic agents for treatment and prevention of cancers, infectious diseases, and immuno-inflammatory disorders.

Abstract: The disclosure relates to a method of treating or preventing immune (idiopathic) thrombocytopenic purpura (ITP) in a human in need thereof, the method comprising administering to the human in the range of 1 to 5 doses of an anti-FcRn antibody or antigen binding fragment thereof over a treatment period of 1 to 12 weeks, wherein the aggregate dose in the treatment period is in the range of 1 to 30 mg per kg.

Abstract: The present disclosure relates to anti-TRBC1 antigen binding domains characterized by the sequences of the variable chains. The CDRs sequences of the variable chains are: (VH CDR1) GYTFT, (VH CDR2) NPYNDDIQS, (VH CDR3) GAGYNFDGAYRFFDF; and (VL CDR1) RSSQRLVHSNGNTYL, (VL CDR2) RVSNRFP, (VL CDR3) SQSTHVPYT. The claimed humanized antibodies derive from the murine JOVI antibody. Uses in cancer therapy.

Abstract: Antigen binding constructs that bind to CD8, for example antibodies, including antibody fragments (such as scFv, minibodies, and cys-diabodies) that bind to CD8, are described herein. Methods of use are described herein.

Abstract: The present invention relates to an ICOS binding protein or antigen binding portion thereof that is an agonist to human ICOS and does not induce complement, ADCC, or CDC when placed in contact with a T cell in vivo and methods of treating cancer, infectious disease and/or sepsis with said ICOS binding protein or antigen binding portion thereof. Further the ICOS binding proteins or antigen binding portions thereof of the present invention are capable of activating a T cell when placed in contact with said T cell; stimulating T cell proliferation when placed in contact with said T cell and/or inducing cytokine production when placed in contact with said T cell. The present invention relates to ICOS binding proteins or antigen binding portions thereof comprising one or more of: SEQ ID NO:1; SEQ ID NO:2; SEQ ID NO:3; SEQ ID NO:4; SEQ ID NO:5; and/or SEQ ID NO:6.

Abstract: The disclosure provides methods of treating viral infection using trispecific binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind a CD38 polypeptide (e.g., human and/or cynomolgus monkey CD38 polypeptides), a CD28 polypeptide, and a CD3 polypeptide.

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 ligand (PD-L1), which can block the binding of PD-L1 to PD-1, and therefore block the inhibitory function of PD-L1 on PD-1 expressing T cells. The antibodies of disclosure provide very potent agents for the treatment of multiple cancers via modulating human immune function.

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: Provided are methods and compositions for treating an individual with cancer or infectious disease. Multivalent Dectin-2 stimulating agents are provided that include: (a) an agent that binds to Dectin-2 and stimulates Dectin-2 signaling; and (b) an antibody and/or an immunomodulatory agent, wherein (a) and (b) are conjugated to one another. In some cases, (a) is a mannobiose glycopolypeptide that binds to Dectin-2. In some cases (b) is a stimulatory ligand for a TLR (e.g., TLR7, TLR8, TLR7/8, TLR2, and the like). Methods of treating an individual with cancer and/or an infectious disease can include administering to the individual an effective amount of a Dectin-2 stimulating composition. In some cases, the Dectin-2 stimulating composition comprises a Dectin-2 stimulating glycopolymer. In some cases the Dectin-2 stimulating composition comprises a multivalent Dectin-2 stimulating agent.

Abstract: The invention provides FGFR1 agonists, including agonistic anti-FGFR1 antibodies, and methods of using the same.

Abstract: The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human EGFRVIII on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Abstract: The present invention relates to methods for treating medical conditions and/or disorders characterized by uncontrolled or abnormal expression of members of the IL1R3 signaling pathway such as IL-1?, IL-I?, IL-33, IL-36, IL1RA and/or IL1R3, as well as variants thereof. More specifically, the present invention relates to anti-IL1R3 antibodies for use in the treatment of an IL1R3-mediated inflammatory condition and/or disorder in a subject. Such conditions and disorders include but are not limited to inflammatory diseases, immune disorders, fibrotic disorders, eosinophilic disorders, infection, pain, a central nervous system disorder, an ophthalmologic disorder, Hereditary Systemic Inflammatory Diseases, and Systemic and Local Inflammatory Diseases and cancer associated chronic inflammation.

Abstract: The present invention relates to the field of cell immunotherapy and more particularly to a new generation of chimeric antigen receptors (CAR). These new CARs are primarily expressed into cells under the form of chimeric polypeptide precursors that can be made active by a protease and switched-off upon addition of a protease inhibitor. Once activated by the protease, such CARs reach the surface of the immune cells and bind specific antigens. More specifically, the presentation of these CARs at the cells' surface is made controllable by inclusion in their polypeptide structure of a protease domain and/or a degradation domain (e.g. degron).

Abstract: Disclosed herein are Interleukin 1 Receptor Accessory Protein (IL1RAP) antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.

Abstract: The present invention relates to a novel antibody and antibody fragment that specifically binds to OX40 and to a composition comprising said antibody or antibody fragment thereof. In addition, the present invention relates to a nucleic acid encoding the antibody or antibody fragment thereof and a host cell comprising the same, and to a related use thereof. In addition, the present invention relates to the use of the antibody and antibody fragment for treatment and diagnosis.

Abstract: An oncolytic virus (for example a replication competent virus) comprising a transgene cassette encoding an anti-CD40 antibody or binding fragment thereof, wherein the transgene cassette comprises an amino acid sequence given in SEQ ID NO: 12 or a sequence at least 95% identical thereto (such as 96, 97, 98 or 99% identical thereto), in particular a cassette of SEQ ID NO: 12; pharmaceutical compositions comprising the same, methods of preparing said oncolytic virus and compositions and use of the oncolytic virus or composition in treatment, in particular in the treatment of cancer. Also provided is the treatment of a patient population characterised as having a cancer expressing CD40, in particular a cancer over expressing CD40, with a therapy according to the present disclosure.

Abstract: Provided are binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof, comprising a CH1 domain (e.g., a human IgG1 CH1 domain), wherein the CH1 domain has an engineered N-linked glycosylation site at amino acid position 114, according to Kabat numbering. Also provided are nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

Abstract: The present invention provides novel CD47 antibodies or immunologically active fragments thereof that have low immunogenicity in humans and cause low or no level of red blood cell depletion or hemagglutination, as well as pharmaceutical compositions containing such antibodies that can be used for treatment diseases mediated by CD47 or inhibition of phagocytosis or platelet aggregation.

Abstract: A method of treating a T-cell mediated disease in a subject by administering to the subject a therapeutically effective amount of an antibody or fragment thereof that specifically binds to CD6 is described. Humanized antibodies useful for the method are also described.

Abstract: The invention is directed to methods of reducing growth of prostate cancer cells and breast cancer cells, which comprises treating such cancer cells with a combination of androgen or endocrine deprivation therapy (e.g., enzalutamide, abiraterone, and tamoxifen) and immunotherapy.

Abstract: The present invention relates to bispecific or multi-specific antibody molecules with two or more paratopes. At least one paratope is Fv or scFv, while the other paratope is in a mono-valent or bivalent Fab. These novel molecules also have an Fc moiety that allows extended half-life in vivo.

Abstract: The present disclosure relates to specific binding agents binding to different PIVKA-II forms as compared to antibodies known so far in the art. The present disclosure also relates to methods of using the specific binding agents to detect the presence of PIVKA-II.

Abstract: In one aspect, the invention provides compositions and methods for preventing, reducing, and/or treating a disease, disorder or condition associated with fibrin-induced activation of the complement system and the associated activation of the coagulation and/or contact systems comprising administering a therapeutic amount of a MASP-2 inhibitory antibody to a subject in need thereof. In some embodiments, the methods of the invention provide anticoagulation and/or antithrombosis and/or antithrombogenesis without affecting hemostasis. In one embodiment of this aspect of the invention, the compositions and methods are useful for treating a subject is suffering from, or at risk of developing, a disease, disorder or condition associated with complement-related inflammation, excessive coagulation or contact system activation initiated by fibrin or activated platelets.

Abstract: Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Abstract: A monomeric bispecific polyethylene glycol (PEG) engager that includes an anti-PEG Fab fused to a disulfide stabilized scFv that specifically binds to a cell surface antigen. The PEG engager, in the absence of PEG, remains monomeric upon binding to the cell surface antigen on a cell and remains on the surface of the cell. Also provided is a method for treating cancer by administering a PEG engager followed by a PEGylated anti-cancer agent. A kit that contains a PEG engager and a PEGylated anti-cancer agent is also disclosed. Further disclosed are methods for imaging cells and diagnosing cancer by administering a PEG engager followed by a PEGylated imaging agent. Another kit is provided that includes the PEG engager and the PEGylated imaging agent.

Abstract: Methods for identifying a polypeptide of interest with desired properties, like specific binding affinity to a molecule of interest or greater stability or improved solubility, from vast numbers of variants. The polypeptides of interest can be antibodies that are selected from an antibody library.

Abstract: A process for the production of a non-derivatized nanocellulose material from a cellulosic fibrous material, comprising the steps of providing a suspension of cellulosic fibrous material in a continuous phase of a non-aqueous process liquid comprising a swelling agent and a processing solvent; forming a suspension of swollen cellulosic fibrous material in a continuous phase of non-aqueous process liquid; forming a suspension of cellulosic fibrous material in a continuous phase of processing solvent; forming a dispersion of non-derivatized nanocellulose material in a continuous phase of a processing solvent; isolating the non-derivatized nanocellulose material, characterized in that the swelling agent is a low-transition-temperature mixture (LTTM) and in particular a deep eutectic solvent and said low-transition-temperature mixture and in particular said deep eutectic solvent is soluble in the processing solvent and wherein the processing solvent is non-solubilizing for the cellulosic fibrous material and the

Abstract: The present disclosure describes tunable methods of treating cellulosic materials with a composition that provides increased hydrophobicity and/or lipophobicity to such materials without sacrificing the biodegradability thereof. The methods as disclosed provide for binding of saccharide fatty acid esters on cellulosic materials, including that the disclosure provides products made by such methods. The materials thus treated display higher hydrophobicity, lipophobicity, barrier function, and mechanical properties, and may be used in any application where such features are desired.

Abstract: To provide a method for producing a multicomponent copolymer with which a multicomponent copolymer having excellent rupture strength can be obtained, and a multicomponent copolymer, a rubber composition and a tire having excellent rupture strength. The method is a method for producing a multicomponent copolymer having a conjugated diene unit, a non-conjugated olefin unit and an aromatic vinyl unit, comprising adding continuously or intermittently continuously a conjugated diene compound into a reactor containing a catalyst and at least one selected from the group consisting of a non-conjugated olefin compound and an aromatic vinyl compound. The multicomponent copolymer is obtained with the production method. The rubber composition comprises the multicomponent copolymer as a rubber component. The tire uses the rubber composition.

Abstract: A catalyst for polymerization of an olefin is disclosed, including a compound represented by the general formula R1R2Si(NHR3)2 wherein R1 is a cycloalkyl group having 3 to 12 carbon atoms or an aromatic hydrocarbon group having 6 to 12 carbon atoms; R2 is a linear alkyl group having 1 to 10 carbon atoms or a branched alkyl group having 3 to 10 carbon atoms; the number of carbon atoms of R1 is larger by 2 or more than that of R2; and R3 is a linear alkyl group having 2 to 6 carbon atoms, a branched alkyl group having 3 to 6 carbon atoms or a cycloalkyl group having 3 to 6 carbon atoms, as an external electron-donating compound. The catalyst can prepare a polymer having excellent hydrogen activity and high stereoregularity and melt flow rate even in homopolymerization at a high temperature, with high productivity.

Abstract: There is provided a method for producing a modified polyvinyl alcohol resin, comprising step (A) of acetalizing polyvinyl alcohol particles swollen with a solvent capable of swelling the polyvinyl alcohol particles by reacting them with a carbonyl compound and/or an acetalized carbonyl compound in the presence of the solvent, wherein a content of an organic solvent in the solvent is 5% by mass or more.

Abstract: The present invention relates to a process for determining a set of one or more operating conditions of an olefin polymerization reactor for the synthesis of a polyolefin in slurry condition, comprising the steps of: a1) introducing a polyolefin into a volume of at least one diluent, said diluent being agitated by a powered agitator at a first temperature T1; b1) monitoring the power consumed by the agitator as a function of the concentration, for at least three concentrations C1, C2, and Cn, which are different from each other; c1) repeating steps a1) and b1) at two or more subsequent temperatures T2 and Tn, which are different from each other and from T1; d1) determining from the power consumed by the agitator as a function of concentration, said set of one or more stable operating conditions for the synthesis of the polyolefin in the olefin polymerization reactor.

Abstract: A process to form an ethylene-based polymer in a reactor system, said process comprising at least the following steps: a) injecting a first initiator mixture into the tubular reactor at location L along the reactor, b) injecting a compressed make-up CTA system at the location L1, at a distance (L?L1) from 145*Dprehehater to 1000*Dpreheater, upstream from L, and wherein Dpreheater=the inner diameter of the pre-heater in meter (m); and wherein L1 is located in the preheater, and c) optionally, injecting one or more additional compressed make-up CTA system(s) into the preheater, at one or more location: LiLi+1, Ln (2?i and 2?n), upstream from L1, and each location is, independently, at a distance from 145*Dprehehater to 1000*Dpreheater, and wherein n equals the total number of injection locations of the make-up CTA system(s) injected into the preheater, upstream from L1, and wherein (L?L1) is less than each (L?Li), (L?Li+1), (L?Ln); and d) polymerizing a reaction mixture comprising at least ethylene, the first i

Abstract: The present disclosure provides a method of maintaining a target value of a melt flow index of a polyethylene polymer product being synthesized with a metallocene catalyst in a fluidized bed gas phase reactor. The method includes producing the polyethylene polymer product at the target value of the melt flow index with a metallocene catalyst in a fluidized bed gas phase reactor at a steady state in which the fluidized bed gas phase reactor is at a first reactor temperature and receives feeds of hydrogen and ethylene at a hydrogen to ethylene feed ratio at a first ratio value. When a change in reactor temperature is detected, the hydrogen to ethylene feed ratio is changed from the first ratio value to a second ratio value so as to maintain the melt flow index value of the polyethylene polymer product at the target value.

Abstract: A method for manufacturing a liquid formulation for reaction injection molding for polymerizing a norbornene-based monomer in the presence of a metathesis polymerization catalyst comprising tungsten as a center metal, the liquid formulation comprising a norbornene-based monomer, provided that in case where the norbornene-based monomer includes exo-dicyclopentadiene, a content of exo-dicyclopentadiene is from 0 to 2% by mass of the norbornene-based monomer, an activator of the catalyst, and a specific ether compound.

Abstract: The present invention provides a homopolypropylene having high strength and a low content of low molecular weights together with excellent processability, and a preparation method thereof.

Abstract: Disclosed is a polypropylene with an MFR of at least 20 g/10 min comprising a homopolypropylene and optionally within a range from 2 wt % to 30 wt % of an propylene-?-olefin copolymer by weight of the polypropylene; wherein the homopolypropylene has a MFR within a range from 30 g/10 min to 200 g/10 min, an Mw/Mn within a range from 7 to 16, and comprising 1.1 wt % or less atactic polypropylene based on the total weight of the homopolypropylene and atactic polypropylene, where the propylene-?-olefin copolymer has within a range from 30 wt % to 50 wt % ?-olefin derived units by weight of the propylene-?-olefin copolymer, and an intrinsic viscosity within a range from 4 to 8 dL/g. The impact copolymer may be obtained by combining a Ziegler-Natta catalyst having at least two different internal electron donors with propylene in reactors in series to produce the homopolypropylene followed by a gas phase reactor to produce a propylene-?-olefin copolymer.

Abstract: A thermoplastic elastomer composition contains components (A) to (D), wherein the content of the component (A), (B), (C) and (D) is, respectively, 26% by weight or more and 59% by weight or less, 2% by weight or more and 9% by weight or less, 16% by weight or more and 61% by weight or less and 11% by weight or more and 56% by weight or less, when the total amount of the components (A) to (D) is 100% by weight, and the ratio of the content of the component (C) to the content of the component (D) is over 1 and 5 or less.

Abstract: An ethylene vinyl acetate copolymer with a high degree of cross-linking and a method of preparing the same are provided, by controlling a temperature and polymerization heat in an autoclave reactor during polymerization, even when a reduced amount of a cross-linking agent is used.

Abstract: An ethylene/1,3-butadiene copolymer containing ethylene units, butadiene units and UD units of cyclic, 1,2-cyclohexanediyl structure, and bearing, at one of its chain ends, an alkoxysilyl or silanol function, functional group F1 is provided.

Abstract: To provide an aqueous coating material capable of forming a coating film which is excellent in the weather resistance and has a stable coating film surface, and a substrate with a coating film which is excellent in the weather resistance and which has a stable coating film surface. An aqueous coating material comprising particles of a fluorinated polymer having units based on a fluoroolefin and units having a hydrophilic group; a specific aminosilane and a specific silane, or a condensate thereof, and water; and a substrate with a coating film, which comprises a substrate and a coating film comprising a hydrolysable silane or a condensate thereof formed on a surface of the substrate, wherein the content of silicon atoms in the coating film to the total mass of the coating film is from 0.01 to 10 mass %, and the molar ratio of fluorine atoms to silicon atoms in the coating film surface is from 1 to 300.