663 results about "Drug discovery" patented technology

The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and stimulate cells that maximizes stimulation and / or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and / or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and / or receptor signaling enhancement. Also provided are methods for producing phenotypically tailored cells, including T-cells for the use in diagnostics, drug discovery, and the treatment of a variety of indications, including cancer, viral infection, and immune related disorders. Compositions of cells having specific phenotypic properties produced by these processes are further provided.

The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and / or stimulate cells that maximizes stimulation and / or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and / or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and / or receptor signaling enhancement. Also provided are methods for producing phenotypically tailored cells, including T-cells for the use in diagnostics, drug discovery, and the treatment of a variety of indications, including cancer, viral infection, and immune related disorders. Compositions of cells having specific phenotypic properties produced by these processes are further provided.

Stem cells, including mammalian, and particularly primate primordial stem cells (pPSCs) such as human embryonic stem cells (hESCs), hold great promise for restoring cell, tissue, and organ function. However, cultivation of stem cells, particularly undifferentiated hESCs, in serum-free, feeder-free, and conditioned-medium-free conditions remains crucial for large-scale, uniform production of pluripotent cells for cell-based therapies, as well as for controlling conditions for efficiently directing their lineage-specific differentiation. This instant invention is based on the discovery of the formulation of minimal essential components necessary for maintaining the long-term growth of pPSCs, particularly undifferentiated hESCs. Basic fibroblast growth factor (bFGF), insulin, ascorbic acid, and laminin were identified to be both sufficient and necessary for maintaining hESCs in a healthy self-renewing undifferentiated state capable of both prolonged propagation and then directed differentiation. Having discerned these minimal molecular requirements, conditions that would permit the substitution of poorly-characterized and unspecified biological additives and substrates were derived and optimized with entirely defined constituents, providing a “biologics”-free (i.e., animal-, feeder-, serum-, and conditioned-medium-free) system for the efficient long-term cultivation of pPSCs, particularly pluripotent hESCs. Such culture systems allow the derivation and large-scale production of stem cells such as pPSCs, particularly pluripotent hESCs, in optimal yet well-defined biologics-free culture conditions from which they can be efficiently directed towards a lineage-specific differentiated fate in vitro, and thus are important, for instance, in connection with clinical applications based on stem cell therapy and in drug discovery processes.

Stem cells, including mammalian, and particularly primate primordial stem cells (pPSCs) such as human embryonic stem cells (hESCs), hold great promise for restoring cell, tissue, and organ function. However, cultivation of stem cells, particularly undifferentiated hESCs, in serum-free, feeder-free, and conditioned-medium-free conditions remains crucial for large-scale, uniform production of pluripotent cells for cell-based therapies, as well as for controlling conditions for efficiently directing their lineage-specific differentiation. This instant invention is based on the discovery of the formulation of minimal essential components necessary for maintaining the long-term growth of pPSCs, particularly undifferentiated hESCs. Basic fibroblast growth factor (bFGF), insulin, ascorbic acid, and laminin were identified to be both sufficient and necessary for maintaining hESCs in a healthy self-renewing undifferentiated state capable of both prolonged propagation and then directed differentiation. Having discerned these minimal molecular requirements, conditions that would permit the substitution of poorly-characterized and unspecified biological additives and substrates were derived and optimized with entirely defined constituents, providing a “biologics”-free (i.e., animal-, feeder-, serum-, and conditioned-medium-free) system for the efficient long-term cultivation of pPSCs, particularly pluripotent hESCs. Such culture systems allow the derivation and large-scale production of stem cells such as pPSCs, particularly pluripotent hESCs, in optimal yet well-defined biologics-free culture conditions from which they can be efficiently directed towards a lineage-specific differentiated fate in vitro, and thus are important, for instance, in connection with clinical applications based on stem cell therapy and in drug discovery processes.

The invention herein disclosed provides for devices and methods that can detect and control an individual polymer in a mixture is acted upon by another compound, for example, an enzyme, in a nanopore in the absence of requiring a terminating nucleotide. The devices and methods are also used to determine rapidly (˜>50 Hz) the nucleotide base sequence of a polynucleotide under feedback control or using signals generated by the interactions between the polynucleotide and the nanopore. The invention is of particular use in the fields of drug discovery, molecular biology, structural biology, cell biology, molecular switches, molecular circuits, and molecular computational devices, and the manufacture thereof.

A bioelectronic microchip formed on a substrate (16) includes a plurality of field effect transistors (10), each including first (12) and second (14) electrodes on the substrate; and a channel (18) extending between the first and second electrodes. An organic semiconducting material fills the channel (18); and a dielectric layer (20) formed atop the first and second electrodes and the channel. An electrolyte (22) to hold a probe molecule may be formed on the dielectric. A third electrode (24) in proximity with the first and second electrodes and isolated therefrom contacts the dielectric. Capture of target molecules may be detected at each transistor through changes in source to drain characteristics. The method provides high density and low cost sensors, particularly in diagonistic and drug discovery applications.

Articles comprising substantially uniform porous coatings, which may be photopatterned, are provided. The use of such porous coatings increases the surface density of attached compounds within, for example, ligand arrays prepared by methods such as regionally selective solid-phase chemical synthesis. Arrays prepared using the porous coatings may be used within a variety of diagnostic and drug discovery assays.

The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and / or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis / cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

An Agile-Beam Laser Array Transmitter (ABLAT) uses an array of emitters and an array of lenses to project electromagnetic beams over a wide angular coverage area in the far field. Differences in the separation pitches of the two arrays allows the ABLAT to project beams to contiguous and / or overlapping positions, depending on the ratio of the separation pitches and the lens focal length. Compared to other beam steering technology, the ABLAT is a smaller, lighter, and more efficient means of projecting beams over wider angular coverage areas. Various embodiments can be used in any beam steering application, including, but not limited to: free-space optical communications; light detection and ranging (lidar); optical scanning (e.g., retinal or bar-code scanning); display projection; image capture; optical character recognition; scanning laser microscopy; non-destructive testing; printing; facsimiles; map making; web inspection; color print processing; phototypesetting and platemaking; laser marking; material processing; DNA analysis; and drug discovery.

This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

An Agile-Beam Laser Array Transmitter (ABLAT) uses an array of emitters and an array of lenses to project electromagnetic beams over a wide angular coverage area in the far field. Differences in the separation pitches of the two arrays allows the ABLAT to project beams to contiguous and / or overlapping positions, depending on the ratio of the separation pitches and the lens focal length. Compared to other beam steering technology, the ABLAT is a smaller, lighter, and more efficient means of projecting beams over wider angular coverage areas. Various embodiments can be used in any beam steering application, including, but not limited to: free-space optical communications; light detection and ranging (lidar); optical scanning (e.g., retinal or bar-code scanning); display projection; image capture; optical character recognition; scanning laser microscopy; non-destructive testing; printing; facsimiles; map making; web inspection; color print processing; phototypesetting and platemaking; laser marking; material processing; DNA analysis; and drug discovery.

The present invention generally relates to a combination of the fields of tissue engineering, drug discovery and drug development. It more specifically provides new methods and materials for testing the efficacy and safety of experimental drugs, defining the metabolic pathways of experimental drugs and characterizing the properties (e.g., side effects, new uses) of existing drugs. Preferably, evaluation is carried out in three-dimensional tissue-engineered systems, wherein drug toxicity, metabolism, interaction and / or efficacy can be determined.

The present invention relates to systems and methods for biomedical drug research, addressing major molecular, cell biological and biochemical information management issues within drug discovery and basic biomedical science. The invention allows scientists to enter biological, chemical, and / or molecular data into a central database, analyze the data entries according to entry attributes, and graphically view the results. A group of web-enabled researchers can enter, share and analyze molecular and cellular data and information from the resources using standardized vocabularies and ontologies. This application describes in detail components of the databasing system, including but not limited to annotation modules, reference managers, advanced search algorithms, ontology browsers, molecular network builders, and text processing scripts. Ultimately, the information gathered, viewed, and analyzed by this relational databasing system is relevant to research ranging from basic researchers to advanced research in applied technologies within pharmaceutical development and biotech fields.

This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Single-molecule selection methods are provided for identifying target-binding molecules from diverse sequence and shape libraries. Complexes and imprints of selected target-binding molecules are also provided. The subject selection methods are used to identify oligonucleotide and nonnucleotide molecules with desirable properties for use in pharmaceuticals, drug discovery, drug delivery, diagnostics, medical devices, cosmetics, agriculture, environmental remediation, smart materials, packaging, microelectronics and nanofabrication. Single oligonucleotide molecules with desirable binding properties are selected from diverse sequence libraries and identified by amplification and sequencing. Alternatively, selected oligonucleotide molecules are identified by sequencing without amplification. Nonnucleotide molecules with desirable properties are identified by single-molecule selection from libraries of conjugated molecules or nucleotide-encoded nonnucleotide molecules. Alternatively, target-specific nonnucleotide molecules are prepared by imprinting selected oligonucleotide molecules into nonnucleotide molecular media. Complexes and imprints of molecules identified by single-molecule selection are shown to have broad utility as drugs, prodrugs, drug delivery systems, willfully reversible cosmetics, diagnostic reagents, sensors, transducers, actuators, adhesives, adherents and novel multimolecular devices.

PROBLEMThere are provided induced malignant stem cells capable of in vitro proliferation that are useful in cancer research and drug discovery for cancer therapy, as well as processes for production thereof, cancer cells derived from these cells, and applications of these cells.MEANS FOR SOLVINGAn induced malignant stem cell capable of in vitro proliferation are characterized by satisfying the following two requirements:(1) having at least one aberration selected from among (a) an aberration of methylation (high or low degree of methylation) in a tumor suppressor gene or a cancer-related genetic region in endogenous genomic DNA, (b) a somatic mutation of a tumor suppressor gene or a somatic mutation of an endogenous cancer-related gene in endogenous genomic DNA, (c) abnormal expression (increased or reduced / lost expression) of an endogenous oncogene or an endogenous tumor suppressor gene, (d) abnormal expression (increased or reduced / lost expression) of a noncoding RNA such as an endogenous cancer-related microRNA, (e) abnormal expression of an endogenous cancer-related protein, (f) an aberration of endogenous cancer-related metabolism (hypermetabolism or hypometabolism), (g) an aberration of endogenous cancer-related sugar chain, (h) an aberration of copy number variations in endogenous genomic DNA, and (i) instability of microsatellites in endogenous genomic DNA in an induced malignant stem cell; and(2) expressing genes including POU5F1 gene, NANOG gene, SOX2 gene, and ZFP42 gene.

A method for making a plurality of low-cost microelectrode arrays (MEAs) on one substrate utilizing certain unmodified printed circuit board (PCB) fabrication processes and selected materials. In some embodiments, a MEA device is composed of a thin polymer substrate containing patterned conductive traces. Coverlays on both sides of the substrate insulate the conductive traces and defines the electrodes. Preferably, flexible PCB technology is utilized to simultaneously define the microelectrode arrays. In an embodiment, the sensor is an integrated temperature sensor / heater in which the MEA device operates to record extracellular electrical signals from electrically active cell cultures. The present invention enables economical and efficient mass production of MEA devices, making them particularly suitable for disposable applications such as drug discovery, biosensors, etc.

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.

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.

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.

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to fill-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.

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.

Provided are histidyl-tRNA synthetase variant polypeptides, X-ray crystallographic and NMR spectroscopy structures of HRS polypeptides, and related compositions and methods for therapy and drug discovery.

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.

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.

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.

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.

Methods for substantially improved detection and analysis in nucleic acid hybridization assays are described. The methods provide the reliable estimation of background signal which derives primarily from nonspecific hybridization. The invention is useful in chemical, biological, medical and diagnostic techniques, as well as for drug discovery.