Abstract: The invention relates to anti-Tau nanobodies.

Abstract: The invention provides novel compositions, methods, and therapeutic uses related to fusogenic protein MINION (microprotein inducer of fusion).

Abstract: M-CSF-specific RX1-based or RX-1 derived antibodies are provided, along with pharmaceutical compositions containing such antibody, kits containing a pharmaceutical composition, and methods of preventing and treating bone loss in a subject afflicted with an osteolytic disease.

Abstract: Disclosed herein are novel compositions and methods for the inhibition of Plexin B2-mediated Angiogenin activity. Such compositions and methods are useful, for example, for the treatment of cancer, the treatment of wet AMD and the inhibition of angiogenesis. Also disclosed herein are methods of determining whether a test agent is a modulator of Plexin B2 activity.

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: This invention provides a method for treating a subject afflicted with a hematologic malignancy comprising administering to the subject an agent targeting a hematologic malignancy-associated antigen, wherein the subject has a low peripheral cancerous cell burden. This invention also provides a method for treating a subject afflicted with a hematologic malignancy and having a high peripheral cancerous cell burden, comprising (i) medically lowering the subject's peripheral cancerous cell burden, and (ii) while the subject's peripheral cancerous cell burden is still low, administering to the subject an agent targeting a hematologic malignancy-associated antigen. Particularly envisioned are the subject methods for treating acute myeloid leukemia using an anti-CD33 antibody labeled with an alpha-emitting isotope, such as 225Ac-HuM195.

Abstract: The present invention relates to novel human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.

Abstract: The present invention relates to an anti-CD66c antibody and its use for treating cancer, and more particularly, it is possible to induce T-cell activation or humoral immune response using an antibody specifically recognizing CD66c. A nucleic acid molecule encoding the antibody or antigen-binding fragment thereof, a vector comprising the nucleic acid molecule, a host cell and the antibody or antigen-binding fragment thereof is used for alleviation, prevention, treatment or diagnosis of CD66c-related disease.

Abstract: The present invention pertains to novel modulators of resistance against T-cell mediated cytotoxic immune responses. The invention provides antagonists of immune escape mechanisms and therefore offers a novel approach for treating, or aiding a treatment, of various proliferative diseases such as cancerous diseases, in particular melanoma, pancreatic cancer and colorectal cancer. The invention specifically discloses the receptor Olfactory Receptor, Family 10, Subfamily H, Member 1 (OR10H1)as a checkpoint molecule in tumor resistance against cytotoxic T-cells. Provided is the inhibition of OR10H1 expression and/or function as a strategy for enhancing tumor susceptibility to a patients T-cell mediated immune response. Provided are antigen binding constructs for the detection of the OR10H1 protein, as well as inhibitory compounds, such as siRNA/shRNA molecules targeting OR10H1 and anti-OR10H1 antibodies, forimpairing the immune escape mediated by OR10H1.

Abstract: The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 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 invention is in the field of medicine and relates to immunology, and relates in particular to human V?9V?2 T cell receptor binding immunoglobulin molecules.

Abstract: The present invention is directed to bispecific, heterodimeric checkpoint antibodies.

Abstract: Molecular determinants of cancer response to immunotherapy are described, as are systems and tools for identifying and/or characterizing cancers likely to respond to immunotherapy.

Abstract: The present invention relates to a combination comprising anti-BAG3 antibodies and inhibitors of the immune check-point, to pharmaceutical formulation comprising said combination, optionally with an pharmaceutically acceptable excipient and to its use in the treatment of neoplastic diseases.

Abstract: An atlas of intestinal epithelial cells, intestinal epithelial stem cells and intestinal immune cells identifies new cell populations, markers, networks, and responses to stimuli. Intestinal T cells drive intestinal epithelial cell differentiation and activity. Accordingly, disclosed are methods of modulating intestinal epithelial cell differentiation, maintenance and/or function, related methods for the treatment of disease, including IBD. Also disclosed are methods and kits for identifying cell types, their differentiation, homeostasis and activation.

Abstract: The invention is directed to the treatment of prostate cancer by means of antibodies. Above all, the invention relates to the administration of an anti-alpha-v integrin (receptor) antibody to patients suffering from prostate cancer, especially castration-resistant prostate cancer (CRPC), optionally accompanied by lymph node and bone tissue metastases (mCRPC). In particular, the invention relates to the therapy of said patients by means of the anti-angiogenic antibody DI17E6 and structural mutants thereof.

Abstract: Compositions and methods relating to regulatable chimeric antigen receptors (RCARs), where the intracellular signaling or proliferation of the RCAR can be controlled to optimize the use of an RCAR-expressing cell to provide an immune response, are provided. For example, a RCAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.

Abstract: This invention relates generally to molecules that specifically engage OX40, a member of the TNF receptor superfamily (TNFRSF). More specifically this invention relates to multivalent and multispecific molecules that bind at least OX40.

Abstract: Provided herein are T cells expressing a chimeric antigen receptor (CAR) targeted to B cell activating factor receptor (BAFF-R). The CAR targeted to BAFF-R (BAFF-R CAR) described herein includes a domain that binds BAFF-R. Methods of making and using the BAFF-R CAR are also provided.

Abstract: Provided herein is a heavy chain constant region comprising a CH1 domain, a hinge region, a CH2 domain and a CH3 domain, wherein the sequences of said CH1 domain and hinge region derive from the sequences of CH1 domain and hinge region in human IgG2, the sequences of said CH2 domain and CH3 domain derive from the sequences of CH2 domain and CH3 domain in human IgGs; and wherein, said antibody heavy chain constant region has an affinity to human Fc?RIIB equal to or higher than the affinity of human IgG1 to human Fc?RIIB, said antibody heavy chain constant region has an I/A ratio equal to or higher than human IgG1 has. Also provided are antibodies or fusion proteins based on a heavy chain constant region according to the above, wherein the antibody heavy chain constant region significantly enhances agonistic activity of the antibodies or fusion proteins and improves efficacy of the antibodies or fusion proteins in treating diseases like tumors and autoimmune diseases.

Abstract: The present disclosure relates to methods of using glucocorticoid-induced TNFR-related protein (GITR) agonists as anti-tumor agents, for example in combination with CpG oligodeoxynucleotides. A specific antibody, characterized by its CDRs is described as agonist.

Abstract: The invention relates to a bispecific antibody specifically binding to human B cell maturation antigen (BCMA) and to human CD3? (CD3) together with an immunotherapeutic drug for combined use in treating multiple myeloma.

Abstract: The present invention relates generally to glutamine-free cell culture media supplemented with asparagine. The invention further concerns the production of recombinant proteins, such as antibodies, in asparagine-supplemented glutamine-free mammalian cell culture.

Abstract: The invention is related to CD20 antibodies with improved characteristics. Some embodiments describe antibodies comprising a mouse IgG2; a human IgG1, IgA1 or IgA2 constant region and a variable domain that can bind the epitope “EPANpSEK” on human CD20 expressed on Ramos cells and which antibody has an increased PCD functionality when compared to Rituximab with a constant region of the same isotype.

Abstract: This disclosure provides a method for treating a subject afflicted with a renal cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an anti-cancer agent which is an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) another anti-cancer agent. The other anti-cancer agent may be an anti-angiogenic tyrosine kinase inhibitor or an anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) antibody. The disclosure also provides a kit for treating a subject afflicted with a renal cancer, the kit comprising a dosage of an anti-PD-1 antibody, a dosage of another anti-cancer agent which is an anti-angiogenic tyrosine kinase inhibitor or an anti-CTLA-4 antibody, and instructions for using the anti-PD-1 antibody and the other anti-cancer agent in any of the disclosed methods for treating a renal cancer.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

Abstract: The present invention provides a combination therapy for treatment of a tumour in a subject. The combination therapy comprises administration of (i) an antibody directed against cancer stem cells and (ii) a checkpoint inhibitor.

Abstract: The invention provides methods for the treatment of subjects having or at risk of having kidney injuries using antibodies that specifically bind Metalloproteinase inhibitor 2 (TIMP-2). Specifically, the methods can be used for the treatment of a subject having chronic kidney disease (CKD), acute kidney injury (AKI), or a subject having an existing diagnosis of one or more of congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, glomerular filtration below the normal range, cirrhosis, serum creatinine above the normal range, sepsis, or acute renal failure (ARP).

Abstract: The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and eribulin or a pharmaceutically acceptable salt thereof, and the use of the combination therapies for the treatment of urothelial cancer.

Abstract: Embodiments of the disclosure include methods and compositions that allow for development of efficient chimeric antigen receptors (CARs) by selecting appropriate spacer content and/or length by balancing the effects of tonic signaling with the efficacy of antigen recognition for the spacer. In specific embodiments, the CH3 domain from IgG2 is utilized as a spacer. In specific embodiments, T cell metabolic activity is utilized as a measure of tonic signaling to facilitate determination of suitable CAR constructs. In other embodiments, cells bearing chimeric Fc receptor target molecules are utilized to target Fc gamma receptor (FcR)-bearing for the purpose of their destruction.

Abstract: This disclosure relates to diagnostic assays useful to detect a carcinoma from a sample and antibodies or binding fragments thereof useful in the diagnostic tests. In certain embodiments, this disclosure relates to antibodies or fragments that bind HCA, epiglycanin, and/or fragments thereof. In certain embodiments, this disclosure relates to anti-idiotypic antibodies or fragments that bind the variable regions of antibodies that bind HCA and/or epiglycanin.

Abstract: The present invention relates to binding proteins that bind to HER-3 and polynucleotides encoding the same. Expression vectors and host cells comprising the same for the production of the binding protein of the invention are also provided. In addition, the invention provides compositions and methods for diagnosing and treating diseases associated with HER-3 mediated signal transduction and/or its ligand heregulin.

Abstract: This invention generally pertains to antibodies and antigen-binding fragments thereof, e.g., humanized, chimeric, and human antibodies and antigen-binding fragments thereof, and fusion proteins, compositions containing such antibodies and antigen-binding fragments thereof and fusion proteins, wherein such antibodies and antigen-binding fragments thereof and fusion proteins specifically bind to MCT1, e.g., human or non-human MCT1 and antagonize, inhibit or block one or more MCT1-associated functions in vitro and/or in vivo. The invention also relates to therapeutic and diagnostic uses of these anti-MCT1 antibodies, antigen-binding fragments, fusion proteins and compositions containing optionally wherein these anti-MCT1 antibodies, antigen-binding fragments, fusion proteins and compositions containing are used in therapeutic regimens that further include the administration of other therapeutic agents, e.g., mitochondrial inhibitors and/or biguanides or small molecule MCT1 inhibitors.

Abstract: Antibodies to tropomysin receptor kinase (TrkA), compositions including such antibodies, and methods of using such antibodies for the treatment of pain including post-surgical pain, rheumatoid arthritis pain, neuropathic pain and osteoarthritis pain.

Abstract: Methods of inhibiting platelet activation and aggregation using antibodies or peptide vaccines having binding specificity for the a subunit of the (Na++K+)-ATPase are provided, along with methods for inhibiting or preventing or treating thrombosis in a subject using such antibodies.

Abstract: The present disclosure provides binding polypeptides (e.g., antibodies and immunoadhesins) comprising a modified Fc domain. The present disclosure also provides nucleic acids encoding the binding polypeptides, recombinant expression vectors, and host cells for making such binding polypeptides. Methods of using the binding polypeptides disclosed herein to treat disease are also provided.

Abstract: This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups.

Abstract: The present invention relates to a method for producing a population of nucleic acids encoding at least one protein comprising at least one immunoglobulin variable domain having a non-human-derived CDR3 amino acid sequence embedded in essentially human framework sequences, as well as to a population of nucleic acids and a population of proteins relates thereto and uses thereof.

Abstract: This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antibodies including bispecifc antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing an expression-enhancing locus.

Abstract: A water-soluble hydroxyethyl cellulose is produced by reacting ethylene oxide with an alkali cellulose such that an average additional molar number of ethylene oxide per glucose unit of the alkali cellulose is 0.1 to 1.0 mol to prepare hydroxyethyl cellulose, and mechanically pulverizing the prepared hydroxyethyl cellulose. According to this producing method, it is possible to produce a water-soluble hydroxyethyl cellulose from an alkali cellulose with the usage of ethylene oxide reduced. In addition, the water-soluble hydroxyethyl cellulose produced by this producing method has a loss tangent (tan ?) of a 2% by mass aqueous solution of less than 1.0 in a frequency range of 0.1 to 100 rad/s in general, and exhibits a gel physical property.

Abstract: A water soluble iron carbohydrate complex obtainable from an aqueous solution of iron (III) salt and an aqueous solution of the oxidation product of one or more maltodextrins using an aqueous hypochlorite solution at a pH-value within the alkaline range, where, when one maltodextrin is applied, its dextrose equivalent lies between 5 and 20, and when a mixture of several maltodextrins is applied, the dextrose equivalent of the mixture lies between 5 and 20 and the dextrose equivalent of each individual maltodextrin contained in the mixture lies between 2 and 40, process for its production and a medicament for the treatment and prophylaxis of iron deficiency conditions.

Abstract: The present invention relates to an improved process for the production of sulfated hyaluronic acid (HA), sulfated HA-derivatives and/or mixtures thereof, having a high purity and a sulfation degree ranging from 1 to 3, which comprises the following steps: a) solubilization of HA-Na or HA-derivative-Na, in an aprotic solvent in the presence of an organic sulfonic acid; b) sulfation of the solution obtained by the addition of an excess of sulfating agents; c) precipitation in ethanol until a precipitate is obtained; d) solubilization of the precipitate thus obtained in a mixture of water and the aprotic solvent used in step a), in the presence of an excess of NaCl, with a pH adjustment within a range of 3 to 4; e) further precipitation with ethanol until a powder is obtained; f) washings of the powder coming from step c) and drying the product thus obtained under vacuum.

Abstract: A process for producing aqueous polymer dispersions and the use thereof as binder for coatings having high solvent stability and a low tendency to soiling.

Abstract: The present invention relates to a hybrid supported metallocene catalyst including at least first metallocene compound, at least one second metallocene compound, at least one cocatalyst compound, and a carrier, a preparation method therefor, and a polyolefin resin polymerized in the presence of the catalyst, wherein the second metallocene compound is a compound of a bridged structure having a ligand of an asymmetric structure, and the polyolefin resin has a density of 0.910 g/cm3 to 0.960 g/cm3, a molecular weight density in a unimodal distribution of 3 to 5, a melt index of 0.05 to 100 at 2.16 kg, and a melt flow rate of 20 to 40.

Abstract: A method of determining multimodal polyethylene quality comprising the steps of (a) providing a multimodal polyethylene resin sample; (b) determining, in any sequence, the following: that the multimodal polyethylene resin sample has a melt index within 30% of a target melt index; that the multimodal polyethylene resin sample has a density within 2.5% of a target density; that the multimodal polyethylene resin sample has a dynamic viscosity deviation (% MVD) from a target dynamic viscosity of less than about 100%; that the multimodal polyethylene resin sample has a weight average molecular weight (Mw) deviation (% MwD) from a target Mw of less than about 20%; and that the multimodal polyethylene resin sample has a gel permeation chromatography (GPC) curve profile deviation (% GPCD) from a target GPC curve profile of less than about 15%; and (c) responsive to step (b), designating the multimodal polyethylene resin sample as a high quality resin.

Abstract: Embodiments of the present disclosure directed towards polymerization catalysts having improved ethylene enchainment and/or improved catalyst productivity.

Abstract: Provided are a novel catalyst component for producing an ?-olefin (co)polymer, and a production method using the same. A metal complex is obtainable by contacting a compound represented by the general formula [I] or [II] with a transition metal compound containing a transition metal belonging to 9th to 11th group: wherein R1, R2, R3 and R4 represent (i) hydrogen, (ii) a halogen, (iii) a linear alkyl or the like, or (iv) OR9 or the like; R5 and R6 represent a linear alkyl group or the like; any one of R1-R6 may have a heteroatom or a heteroatom containing group; E1 represents phosphorus, arsenic or antimony; X1 represents oxygen or sulfur; Z represents hydrogen or a leaving group.

Abstract: This invention discloses a process for preparing a branched polymer via emulsion polymerization at room temperature and is related to the field of polymer synthesis and preparation of functional polymers. A mixture of water as medium, anionic surfactant as emulsifier, sodium bicarbonate as pH regulator, the reductant monomer containing both polymerizable double bond and the reducing group combined with the persulfate as the oxidant to be useful as initiator, styrene, (meth) acrylate or vinyl acetate as monomer, is reacted to synthesize the branched polymers via a free radical in-situ emulsion polymerization at room temperature and ambient pressure. The monomer conversion can be above 85% in a range of about 10 mins to 10 hours of the reaction time. The process for preparing a branched polymer is carried out under the conditions of emulsion polymerization at room temperature and normal pressure without the addition or assistance of the branched monomer and other initiators.

Abstract: The present invention relates to a process for the preparation of a polyethylene wax, the process comprising the steps of providing a catalyst solution, wherein the catalyst solution comprises at least one activating compound, an alkylaluminoxane and a me-tallocene complex, wherein the molar ratio of the activating compound to aluminum comprised in the alkylaluminoxane is from 0.0005 to 0.20; and polymerizing ethylene, by contacting the ethylene and the catalyst solution.