The present invention relates to substituted purine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

Isolated human monoclonal antibodies which bind to and inhibit human CD25, and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced by a hybridoma, a transfectoma or in a nonhuman transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, nonhuman transgenic animals, hybridomas and transfectomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Provided are a method and means permitting the simultaneous measurement of the reactive properties of more than 10,000 of antigen-stimulated lymphocytes being held on a chip and the separate determination of the states of individual cells. A microwell array comprises multiple wells and a coating layer on one of the principal surfaces of a base member, the wells being of a size permitting the entry of only a single cell into each well. A coating layer of a substance capable of binding to a substance produced by the cells contained in the wells is present on the principal surface around the wells. A method of screening for a target cell, comprises: causing specimen cells and a cell culture broth to be contained in the wells of the above microwell array; immersing the coating layer and the wells in the culture broth and culturing the cells in a state permitting the diffusion of substances in the culture broth from the wells into the coating layer; feeding a label substance binding specifically to a substance produced by a target cell present among the specimen cells onto the coating layer; and detecting the substance produced by the target cell that has bound to the substance in the coating layer by the label substance to specify the target cell.

The present disclosure relates to to compositions and methods relating to cytokine agonists and their engineered polypeptides. The engineered polypeptides have specificity to receptors in immune systems including IL-2/15, Type I IFN and IL-10. The present disclosure also relates to methods for identifying surrogate cytokine agonists and to a system for engineering ligands that can compel formation of non-naturally-occurring cytokine receptor heterodimers. The present disclosure also relates to methods and system for identifying surrogate agonists for cell surface receptors including dimeric and trimeric receptors.

The invention provides compositions and methods for diagnosing a patient as having a myeloproliferative disease by identifying mutations in the MPL gene or gene products.

The present invention provides, among other things, methods of treating pruritic or inflammatory skin diseases or disorders, or pruritus associated with a disease or disorder, with an anti-OSMR antibody, including methods of treating pruritus, associated with atopic dermatitis, chronic kidney disease-associated pruritus, uremic pruritus or prurigo nodularis, chronic idiopathic pruritus, chronic idiopathic urticaria, chronic spontaneous urticaria, cutaneous amyloidosis, lichen simplex chronicus, plaque psoriasis, lichens planus, inflammatory ichthyosis, mastocytosis and bullous pemphigoid, comprising a step of administering to a subject in need of treatment an anti-OSMR antibody at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce one or more symptoms of the disease or disorder relative to a control.

The present disclosure includes compositions and methods for detecting the presence of: a coronavirus or an immune response relevant to a coronavirus infection including T cells responsive to one or more coronavirus peptides or proteins comprising, consisting of, or consisting essentially of: one or more amino acid sequences selected from those sequences set forth in Tables 1 to 10 (SEQ ID NOS: 1 to 3522), or a subsequence, portion, homologue, variant or derivative thereof; a fusion protein; a pool of 2 or more peptides; or a polynucleotide that encodes one or more peptides or proteins, comprising, consisting of, or consisting essentially of one or more amino acid sequences set forth in Tables 1 to 10 (SEQ ID NOS: 1 to 3522), or a subsequence, portion, homologue, variant or derivative thereof. The disclosure further provides vaccines, diagnostics, therapies, and kits, comprising such proteins or peptides.

Methods for identifying, isolating and enriching neural stem and progenitor cells (NSPC) such as ventricular radial glia, outer radial glia, astrocytes, pre-oligodendrocyte precursor cells, oligodendrocyte precursor cells, oligodendrocytes, early excitatory neurons, late excitatory neurons, bipotent glial progenitors, and inhibitory neurons are provided. These methods find use in transplantation, to eliminate specific cell subsets, for experimental evaluation, as a source of lineage and cell-specific products, and the like, for example for use in treating human disorders of the central nervous system (CNS).

The invention provides methods and compositions for identifying a subject who will responds to a reno-protective agent for treating or preventing progressive kidney function decline based on the level of a renal associated protein.

The present disclosure relates to anti-EphA2 antibody and cancer detection (or diagnosis) and treatment using the anti-EphA2 antibody. The present invention creates anti-EphA2 antibodies, particularly, a single-chain antibody fragments (scFv) and humanized antibody, which have ability in binding to anti-EphA2 and in inhibiting angiogenesis, migration and cancer cell growth.