Abstract: The invention provides means and methods for inhibiting growth of a cancer. The means in some embodiments comprise proteins and antibodies that binds an extracellular part of a membrane associated member of the epidermal growth factor (EGF) receptor family and an extracellular part of a membrane associated member of a WNT signaling pathway. Further provided are various cells and assays that are helpful in the production of the proteins, antibodies and cells.

Abstract: The present invention provides novel compounds of Formulae (I?) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g.

Abstract: The invention provides antibody formulations and methods useful for prophylaxis or treatment of transthyretin-related amyloidosis.

Abstract: The invention relates generally to multispecific polypeptides having constrained CD3 binding. In some embodiments, the multispecific polypeptides contain cleavable linkers that, when cleaved, results in dual effector functions. Also provided are methods of making and using these multispecific polypeptides in a variety of therapeutic, diagnostic and prophylactic indications.

Abstract: The present invention provides methods for preventing or treating allergy. Also provided are methods for reducing the susceptibility to an allergen in a subject in need thereof. In certain embodiments, the subject has a disease or disorder selected from the group consisting of atopic dermatitis, asthma, allergic rhinitis, and eosinophilic esophagitis. The methods of the present invention comprise administering to a subject in need thereof a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody.

Abstract: Compositions and methods for treating FSHD and for identifying agents useful for the treatment of FSHD.

Abstract: A pharmaceutical composition contains an antibody or a fragment thereof specific for COL6A3 for the treatment of a cancer. A method of treating a cancer includes administering to a subject in need thereof the pharmaceutical composition. A kit includes a container that contains the pharmaceutical composition. A method of producing an antibody or a fragment thereof against a peptide or a MHC/peptide complex. A method for detecting a diseased tissue includes administering to a subject in need thereof an antibody or a fragment thereof conjugated to a radioisotope and detecting a signal from the radioisotope in the subject. A method for treating a diseased tissue includes administering to a subject in need thereof an antibody or a fragment thereof conjugated to a toxin.

Abstract: The present disclosure relates to a bio-manufacturing process that enables continuous production of a therapeutic protein with reduced heterogeneity. The bio-manufacturing process disclosed herein utilizes a multi column chromatography system that performs the unit operations of reducing heterogeneity in a therapeutic protein, capturing the therapeutic protein and inactivating viruses, purifying the therapeutic protein, and polishing the purified therapeutic protein. The process disclosed herein can reduce heterogeneity of a therapeutic protein by reducing a proportion of basic isoforms of the therapeutic protein.

Abstract: The invention is directed to biomarkers for predicting a patient's response, both therapeutic and toxic, to immunotherapy.

Abstract: The present invention relates to compositions and methods for using a minibody. Minibodies described herein comprise a secretion signal, a variable heavy chain fragment, a variable light chain fragment, a constant chain fragment, and a hinge domain between the variable light chain fragment and the constant chain fragment. One aspect includes a nucleic acid encoding a minibody. Other aspects include compositions comprising a minibody and a modified T cell comprising a nucleic acid encoding a minibody. Also included are methods and pharmaceutical compositions comprising the modified T cells for adoptive therapy and treating a condition, such as cancer.

Abstract: The present disclosure provides humanized antibodies that specifically bind to CD3 with an optimized affinity and induce T cell-mediated killing of tumour related target antigen high expressing cells with high potency but have limited killing activity on target antigen low expressing cells. The present disclosure also provides bispecific antibodies comprising a first antigen-binding domain that specifically binds to human CD3 with optimized affinity and a second antigen-binding molecule that specifically binds a tumor-related antigen. The disclosure further relates to methods of generating such humanized antibodies and bispecific antibodies for biological, diagnostic, pharmaceutical and other uses.

Abstract: The present invention relates to thiocarbamate derivatives of Formula (I) which are useful as A2A adenosine receptor (A2AR) inhibitors Especially, the present invention relates to a pharmaceutical composition comprising an A2A inhibitor of Formula (I) and a lipid carrier such as lauroyl macrogol-32 glycerides, D-?-tocopherol-polyethylene glycol-1000 succinate or a mixture thereof. The pharmaceutical composition of the invention is particularly useful for oral dosing in the treatment of cancers. The present invention also relates to a combination comprising an A2A receptor inhibitor of Formula (I) and an anticancer agent. The anticancer agent is for example an immunotherapeutic agent, such as a checkpoint inhibitor. The invention further relates to a pharmaceutical composition and a kit of parts comprising such combination. Additionally, the combination of the invention is particularly useful for the treatment and/or prevention of cancers.

Abstract: The present disclosure relates to stable aqueous solutions comprising a high concentration of an anti-C5 antibody (e.g., ravulizumab) and methods for preparing the solutions. The disclosure also provides methods for treating or preventing complement-associated disorders, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), using the solutions. Also featured were therapeutic kits containing one or more of the solutions and a means for administering the solutions to a patient in need such a treatment.

Abstract: Isolated pluralities of T cells which recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen and pharmaceutical compositions comprising the same are disclosed. Methods of making a plurality of T cells that recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen are also disclosed. Methods of treating an individual who has been diagnosed with cancer of a mucosal tissue or preventing such cancer in an individual at elevated risk are disclosed as are nucleic acid molecules that comprise a nucleotide sequence that encode proteins that recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen and T cells comprising such nucleic acid molecules.

Abstract: This disclosure provides compositions and related methods providing targeted cell-specific inhibition of Notch receptor signaling. The disclosure provides a bi-specific molecule with separate domains that target the intended cell-type and the Notch receptor on that cell-type. The disclosure also provides for nucleic acids, vectors, and cells allowing for the expression of the bi-specific fusion molecules. The disclosure also provides related methods of making and using the bi-specific fusion molecule to inhibit Notch signaling in target cells of interest, including for the treatment of diseases characterized by a dysregulation of Notch signaling.

Abstract: Provided herein are compositions for preventing, ameliorating, and/or reducing tissue ischemia and/or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease, coronary artery disease, stroke and influencing other conditions, by suppressing CD47 and/or blocking TSP1 and/or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of blood vessel diameter and blood flow, and permits modification of blood pressure and cardiac function. Under conditions of decreased blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue perfusion and tissue survival.

Abstract: An object of the present invention is to provide a pharmaceutical composition or food or drink composition comprising an active ingredient that suppresses functional expression of Oscar protein. Another object of the present invention is to provide a pharmaceutical composition or food composition for preventing or treating kidney disease. A further object of the present invention is to provide a pharmaceutical composition or food or drink composition that suppresses functional expression of Oscar in a living organism in order to suppress functional expression of FGF23. A still further object of the present invention is to provide a method for evaluating an effect, in the body, of an active ingredient that suppresses functional expression of Oscar protein.

Abstract: [Problem] To provide, in place of injected agents (such as Vidaza® and Dacogen®) clinically used as therapeutic drugs for high-risk myelodysplastic syndromes, a medicine as a therapeutic drug or a prophylactic drug for various advanced solid tumors, said medicine having high stability with respect to cytidine deaminase which is a hydrolytic metabolic enzyme, being absorbed into the body even by oral administration, and having an effect of being integrated into a nucleic acid biosynthetic route and inhibiting DNA methyltransferases, i.e., DNMTs. [Solution] The aforementioned problem is solved by a novel compound represented by formula (I). (In the formula, R is a hydroxyl group or a hydrogen atom, and R1 and R2 are each a benzyl group that may have a substituent.

Abstract: The current disclosure provides binding polypeptides (e.g., antibodies), and targeting moiety conjugates thereof, comprising a site-specifically engineered glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides 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 disclosure provides antibody agents that bind to a programmed death-1 (PD-1) protein. Particular immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide sequences are explicitly provided. Also provided are related nucleic acids, vectors, compositions, and methods of using the anti-PD-1 antibody agent to treat a disorder or disease that is responsive to PD-1 inhibition, such as cancer or an infectious disease.

Abstract: A composition comprising at least one AAV vector formulated for intrathecal delivery to the central nervous system is described. The composition comprises at least one expression cassette which contains sequences encoding an immunoglobulin construct linked to expression control sequences therefor and a pharmaceutically acceptable carrier. The immunoglobulin construct may be an immunoglobulin modified to have decreased or no measurable affinity for neonatal Fc receptor (FcRn).

Abstract: The present invention relates to a composition and a method for inducing CD4+ T cells to differentiate into regulatory T cells and proliferate through an induced T cell co-stimulator ligand (ICOSL) or an ICOSL-overexpressing mesenchymal stem cell and for preventing or treating regulatory T cell-mediated diseases. The induced T cell co-stimulator ligand (ICOSL) or ICOSL-overexpressing mesenchymal stem cell according to the present invention effectively suppresses the proliferation of PBMCs, induces the expression of an ICOS in regulatory T cells, thereby inducing the differentiation and proliferation of the regulatory T cells through a PI3K-Akt mechanism, and thus can effectively prevent, treat, or enhance regulatory T cell-mediated diseases.

Abstract: This invention relates to methods for promoting reinnervation of auditory hair cells, specifically, by inhibiting Repulsive Guidance Molecule a (RGMa), a repulsive axonal guidance molecule that is expressed in the cochlea, or its receptor, neogenin.

Abstract: The present invention relates to methods of immunomodulation and treating patients having solid tumors with antibodies that specifically bind CD38.

Abstract: In part, the disclosure relates to methods of treating fibrotic cancers by administering one or more Serum Amyloid Protein (SAP) agonists. In certain aspects, the method further comprises the conjoint administration of an anti-cancer therapeutic, e.g., a chemotherapeutic agent. In certain aspects, the disclosure relates to methods of treating myelofibrosis by administering an SAP agonist and optionally one or more anti-cancer therapeutic agents.

Abstract: The invention provides compositions comprising bacterial strains for treating and preventing cancer.

Abstract: The present invention is based on the identification of novel biomarkers predictive of responsiveness of esophagogastric cancers to inhibitors of the PD-1 pathway.

Abstract: The present invention provides antibodies and antigen binding fragments thereof that bind to human Follistatin-Like-3 (FSTL3) protein, compositions comprising such antibodies, and methods of making and using such antibodies.

Abstract: A method of treating root avulsion injury in a subject in need thereof includes administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTP?.

Abstract: The present invention relates to compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein X, Y, Z, Q, W, m, u, ring (A), R2, R3, R4, R5 and R6, are as defined in the specification and claims. The present invention provides a pharmaceutical composition containing the compounds of Formula (I) and a therapeutic method of treating and/or preventing Downs syndrome, 3-amyloid angiopathy, disorders associated with cognitive impairment, Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegenerative diseases, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, Alzheimer's disease and/or Down syndrome, age-related macular degeneration (AMD), glaucoma, olfactory function impairment, traumatic brain injury, progressive muscle diseases, Type II diabetes mellitus and cardiovascular diseases (stroke).

Abstract: Methods of treatment comprising administering a compound having structure (I), or a pharmaceutically acceptable salt thereof, or administering a pharmaceutical composition comprising the compound of structure (I) or pharmaceutically acceptable salt thereof, are provided.

Abstract: This present disclosure relates to a method of treating autoimmune, respiratory and/or inflammatory diseases or conditions, e.g., asthma, COPD, rheumatoid arthritis and idiopathic Pulmonary Fibrosis (IPF). The method comprises administering a dual PI3K delta and gamma inhibitor and a corticosteroid. The present invention also relates to pharmaceutical compositions containing a dual PI3K delta and gamma inhibitor and a corticosteroid.

Abstract: Provided is an approach for differentially determining the histological type of a lung cancer lesion objectively and rapidly with high accuracy. A method for differentially assessing a lesion in a lung cancer patient as squamous cell carcinoma or adenocarcinoma, comprising a step of measuring an expression level of an expression product of at least one DNA comprising a transcription start site in a biological sample collected from the lesion, wherein the DNA comprises a base at an arbitrary position in the transcription start site and at least one or more bases located immediately downstream thereof in any of nucleotide sequences represented by SEQ ID NOs: 1 to 213, and the transcription start site is a region wherein both ends thereof are defined by the first base and the 101st base counted from the 3? end in any of the nucleotide sequences represented by SEQ ID NOs: 1 to 213.

Abstract: The present disclosure relates, in general, to methods of treating or preventing post-prandial hypoglycemia after gastric bypass surgery using a negative modulator antibody that binds to the insulin receptor and modulates the action of insulin at the insulin receptor.

Abstract: The present invention provides monoclonal antibodies that bind to the complement factor 5 (C5) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to C5 protein. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing C5 activity, thus providing a means of treating or preventing a C5-related disease or disorder in humans. In some embodiments, the invention provides for an anti-C5 antibody that has improved pharmacokinetic and pharmacodynamic properties, e.g., a half-life of more than 10 days.

Abstract: This disclosure relates to methods of assaying and scoring PD-L1 expression in tumors. Tumor samples are labeled with an antibody or antibody fragment that specifically binds to human PD-L1 and binding is detected. Binding intensity is compared to background, and tumor cells having membrane staining above background are counted. The percentage of tumor cells containing membrane staining of PD-L1 is determined and the tumor is classified as “PD-L1 positive” if the percentage of tumor cells falls above a predefined level.

Abstract: The present disclosure provides methods of treating multiple myeloma in an individual, the methods comprising genotyping an HLA allele and a KIR allele in the individual; and, depending on the outcome of the genotyping, administering a multiple myeloma therapy to the individual. In some embodiments, the multiple myeloma therapy comprises an anti-CD38 antibody, lenalidomide, and dexamethasone. The present disclosure provides methods for selecting a multiple myeloma patient for a multiple myeloma therapy. The present disclosure provides methods for identifying a multiple myeloma patient as likely to experience a beneficial clinical outcome from a multiple myeloma therapy.

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 homeopathic pain topical analgesic composition based on snake venom is disclosed. The study product also contained of Arnica montana, a homeopathic remedy most frequently used for fractures, bruises, and muscle strains due to its analgesic and anti-inflammatory effects. The composition also contained a penetrant component to enhance penetration of the ingredients as well as an analgesic/anti-inflammatory component. The snake venoms used may include those of Naja naja, Crotalus horridus and Lachesis muta. A clinical study of a product formulated in this way was effective in promoting relief from muscle pain and discomfort.

Abstract: Aspects of the disclosure relate to methods that involve activating the Protein Kinase A (PKA) pathway to induce cancer stem cells (CSCs) to undergo a mesenchymal to epithelial transition. Methods provided herein are useful, in some embodiments, because they render CSCs amenable to treatment with conventional cancer therapies. In some embodiments, methods are provided that involve assaying PKA pathway activity to identify compounds that selectively target CSCs.

Abstract: The present invention relates to the use of a CD24 protein for lowering low-density lipoprotein cholesterol levels, treating and preventing atherosclerosis, and for reducing risk of cardiovascular disease.

Abstract: The current disclosure describes methods of expanding precursor cells for hematopoietic transplantation in subjects. The methods culture precursor cells in media containing an immobilized high molecular weight LILRB2 agonist or an LILRB2 agonist in combination with a Notch agonist. The expanded cells can be used to treat a variety of hematopoietic disorders.

Abstract: The present invention relates to, in part, compositions comprising improved flagellin derived constructs and methods of using for vaccination, including adjuvants comprising flagellin-based agents.

Abstract: This invention relates, e.g., to a molecular delivery system comprising A. a substrate having a nanostructured surface region which comprises a plurality of nanostructures and, covalently attached to the substrate, multiple copies of a first member of a binding pair; and B. at least one vector nanoparticle which comprises, encapsulated therein, a molecule of interest, and on its surface, multiple copies of second member of the binding pair. Methods of using the molecular delivery system to deliver a molecule of interest to a cell are also described.

Abstract: The present invention provides methods for enhancing the efficacy and/or safety of a vaccine. In certain embodiments, the invention provides methods to increase or potentiate the immune response to a vaccine in a subject in need thereof. The methods of the present invention comprise administering to a subject in need thereof an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody in combination with said vaccine. In certain embodiments, the methods of the present invention are used to afford enhanced protection to an infectious disease such as whooping cough.

Abstract: This disclosure relates to materials and methods useful for vaccinating mammals against the effects of envenomation by venomous organisms (including the Western Rattlesnake) by making use of venom from multiple distinct populations, subspecies or species of the organism, to make a vaccine more broadly protective against other populations, subspecies or species. This disclosure also relates to a method for determining which organisms which are capable of envenomation should be pooled for optimizing the coverage and efficacy of a vaccine which is produced from the venoms (or toxoid derivatives) in the combination.

Abstract: The present invention aims to obtain an anti-repulsive guidance molecule a (RGMa) antibody having a high binding activity and few side effects which can be used as a medicine for preventing, treating, or preventing the relapse of neurological or immunological diseases. The problem is solved by providing an isolated RGMa binding protein which does not inhibit binding between RGMa and neogenin but neutralizes the neurite outgrowth inhibiting activity of RGMa, preferably by providing an anti-RGMa antibody which has complementarity determining regions having amino acid sequences of SEQ ID NOS: 30-35 or SEQ ID NOS: 36-40 in Sequence Listing, and SFG.

Abstract: The present disclosure describes an IHC assay for detecting and quantifying spatially proximal pairs of PD-1-expressing cells (PD-1+ cells) and PD-Ligand-expressing cells (PD-L+ cells) in tumor tissue, and the use of the assay to generate proximity biomarkers that are predictive of which cancer patients are most likely to benefit from treatment with a PD-1 antagonist. The disclosure also provides methods for testing tumor samples for the proximity biomarkers, as well as methods for treating subjects with a PD-1 antagonist based on the test results.

Abstract: This document provides methods and materials related to treating myelomas. For example, methods and materials relating to the use of a composition containing albumin-containing nanoparticle/antibody complexes (e.g., ABRAXANE®/anti-CD38 polypeptide antibody complexes) to treat myelomas are provided.

Abstract: An erbB2 antibody is provided that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density. The erbB2 antibody comprises a heavy chain and a light chain. Each chain has a constant region and a variable region. Each variable region comprises framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below: For the heavy chain: CDR1 GFNIKDTYIH (SEQ ID No. 1) CDR2 RIYPTNGY57TR59 YADSVKG (SEQ ID No. 2) CDR3 WGGDGFYAMDY (SEQ ID No. 3) For the light chain: CDR1 RASQDVN30TAVA (SEQ ID No. 4) CDR2 SASF53LYS (SEQ ID No. 5) CDR3 QQHY92TTPPT (SEQ ID No. 6). At least one of Y57, R59, N30, F53, and Y92 is substituted by an amino acid that confers on said antibody a reduced erbB2 binding affinity (Kd) that is in the range from 0.1 nM to 100 nM. The substitution is other than N30A, F53N, Y92A and Y92F when there is a single substitution in the antibody light chain.