Drug Or Compound Screening Involving Gene Expression Patents (Class 435/6.13)
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Patent number: 8945839Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system.Type: GrantFiled: April 18, 2014Date of Patent: February 3, 2015Assignees: The Broad Institute Inc., Massachusetts Institute of TechnologyInventor: Feng Zhang
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Patent number: 8945846Abstract: Aspects of the present invention include methods, compositions and kits for classifying a subject as having or being predisposed to a hematolymphoid neoplasm or malignancy if they harbor a mutation in the LNK gene. Aspects of the present invention also include screening for candidate agents for treating LNK mutation-based hematolymphoid neoplasms or malignancies in cell-based and cell free assays as well as therapeutic compositions for treating a LNK-mutant based hematolymphoid disorder. Also provided are compositions, systems, kits and computer program products that find use in practicing the subject methods.Type: GrantFiled: January 12, 2011Date of Patent: February 3, 2015Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Jason Robert Gotlib, Garry P. Nolan, James L. Zehnder, Stephen Tracy Oh
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Patent number: 8945828Abstract: The present application relates to methods for identification of foetal cells and generation and isolation of binding members recognizing foetal cells. The methods of the invention may further be used for other purposes relating to characterization of biological samples and biological antigens. The methods are characterized by the applicability in situations where the interesting objects are present in a limited amount, or where the interesting objects are intermixed with other material, thus the methods are suitable for use in situations where the ratio of the interesting material compared to other material is low.Type: GrantFiled: June 27, 2011Date of Patent: February 3, 2015Assignee: Aarhus UniversitetInventors: Sten Kolvraa, Britta Christensen, Palle Schelde, Morten Draeby Sorensen, Peter Kristensen
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Patent number: 8945848Abstract: The invention provides for compositions and methods for identifying and validating modulators of cell fate, such as such as maintenance, cell specification, cell determination, induction of stem cell fate, cell differentiation, cell dedifferentiation, and cell trans-differentiation. The invention relates to reporter nucleic acid constructs, host cells comprising such constructs, and methods using such cells and constructs. The invention relates to methods for making cells comprising one or more reporter nucleic acid constructs using fluorogenic oligonucleotides. The methods relate to high throughput screens.Type: GrantFiled: July 30, 2010Date of Patent: February 3, 2015Assignee: Chromocell CorporationInventors: Kambiz Shekdar, Dennis J. Sawchuk, Jessica C. Langer
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Publication number: 20150031856Abstract: The present invention provides compositions and methods for transforming primary mammalian cells using an oncogenic form of ALK wherein the transformed cells display features of that of a corresponding tumor cell isolated from a cancer subject. The invention also provides a method for immortalizing normal CD4+ T lymphocytes with a lymphoma-characteristic form of ALK such as NPM-ALK.Type: ApplicationFiled: March 5, 2014Publication date: January 29, 2015Inventors: Mariusz Wasik, James L. Riley, Qian Zhang, Fang Wei
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Publication number: 20150031569Abstract: The present invention relates to an in vitro method for diagnosing a complete congenital stationary night blindness (cCSNB) in a subject, which method comprises determining the presence of an alteration in the GPR179 gene in a biological sample of said subject. Screening methods and therapeutic applications are further described.Type: ApplicationFiled: January 23, 2013Publication date: January 29, 2015Inventors: Christina Zeitz, Isabelle Audo, Elise Orhan, Kinga Jakowska, Jose-Alain Sahel
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Publication number: 20150031562Abstract: Biomarkers useful for identifying treatments for and monitoring treatment of patients with multiple sclerosis (MS) are provided, as well as methods for their identification, methods of diagnosing MS, relapse of MS patients and disease progression in MS patients.Type: ApplicationFiled: February 27, 2014Publication date: January 29, 2015Applicant: BIOGEN IDEC MA INC.Inventors: Aaron B. Kantor, Susan E. Goelz, Jun Deng, Hua Lin, Christopher Becker
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Patent number: 8940497Abstract: A multidimensional profiling strategy that combines activity-based proteomics and metabolomics was used to determine that an active protein, which is a previously uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and the lysophospholipids. Biochemical studies confirmed that the active protein regulates this pathway by hydrolyzing the metabolic intermediate 2-acetyl monoalkylglycerol. Inactivation of the active protein disrupted ether lipid metabolism in cancer cells and impaired cell migration and tumor growth in vivo.Type: GrantFiled: August 14, 2012Date of Patent: January 27, 2015Assignee: The Scripps Research InstituteInventors: Benjamin F. Cravatt, Kyle P. Chiang, Sherry Niessen, Alan Saghatelian
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Publication number: 20150023973Abstract: The present invention provides a pharmaceutical composition for preventing or treating angiogenic diseases comprising inhibitors of NUP153 gene expression or NUP153 activity as active ingredient and a method for screening an agent for preventing or treating angiogenic diseases. According to the present invention, inhibition of the NUP153 gene expression or the NUP153 activity reduces export of mRNA of a pro-angiogenic factor (VEGF, HGF and bFGF) from nucleus. In addition, inhibition of the NUP153 gene expression or the NUP153 activity has effect that angiogenesis are inhibited by inhibition of invasion and tube formation in a dose-dependent manner without showing toxicity. Therefore, the pharmaceutical composition of the present invention may be used for preventing or treating a variety of angiogenesis-related diseases, and the method for screening of the present invention may be valuably used in finding a new agent for preventing or treating angiogenic diseases.Type: ApplicationFiled: July 19, 2014Publication date: January 22, 2015Inventors: Ho Jeong KWON, Nam Hee KIM
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Publication number: 20150025122Abstract: Compositions and methods for down modulating target gene expression with RNA interference, as well as methods for administering said compositions are disclosed. The method comprises administering a first strand to a cell, incubating the cell for a time period suitable for uptake of the first oligo prior to administering a second strand, wherein the first strand and said second strand form an intracellular duplex which is effective to catalyze degradation of gene target mRNA or inhibit translation of said mRNA.Type: ApplicationFiled: January 6, 2014Publication date: January 22, 2015Inventor: Larry J. Smith
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Publication number: 20150024955Abstract: The present invention relates to screening methods that make use of a histone deacetylase interacting with a myosin phosphatase for the identification of novel therapeutics useful for inhibiting or inducing apoptosis and for the treatment of pathological conditions, such as smooth muscle cell disorder, cardiac hypertrophy or asthma. Also disclosed are methods for inhibiting or inducing apoptosis and for treatment of a pathological condition by administering to a mammal a therapeutically effective amount of a compound that inhibits or increases the dephosphorylation of a histone deacetylase by a myosin phosphatase or inhibits or increases the binding of a histone deacetylase to a myosin phosphatase.Type: ApplicationFiled: July 18, 2014Publication date: January 22, 2015Inventors: Eric Verdin, Maribel Parra
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Publication number: 20150018236Abstract: Methods for screening libraries of polypeptides for biologically activity on cells. For example, polypeptides can be synthesized and encapsulated along with their coding sequences in microcapsules of an emulsion. Emulsion microcapsules can then be fused with microcapsules comprising test cells and biological activity on the cells is assessed to identify biologically active polypeptides and nucleic acid molecules encoding the same.Type: ApplicationFiled: February 1, 2013Publication date: January 15, 2015Applicant: Invenra Inc.Inventors: Roland Green, Bryan Glaser, Ivar Meyvantsson, Kimberly Kaufman, Madison Green
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Patent number: 8932814Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.Type: GrantFiled: April 22, 2014Date of Patent: January 13, 2015Assignees: The Broad Institute Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Le Cong, Feng Zhang
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Patent number: 8932818Abstract: The present invention relates to compounds that modulate ribosomal frameshifting and nucleic acid constructs for use in methods for identifying or validation of compounds that modulate ribosomal frameshifting. In particular, the present invention relates to the use of nucleic acid constructs to identify or validate compounds capable of modulating the efficiency of programmed ribosomal frameshifting and the use of compounds that modulate the efficiency of programmed ribosomal frameshifting to inhibit the replication or infectivity of viruses that employ programmed ribosomal frameshifting.Type: GrantFiled: August 13, 2009Date of Patent: January 13, 2015Assignee: PTC Therapeutics, Inc.Inventors: Sergey V. Paushkin, Nikolai A. Naryshkin, Ellen Welch
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Patent number: 8932993Abstract: The present invention relates to novel genetic markers associated with endometriosis and risk of developing endometriosis, and methods and materials for determining whether a human subject has endometriosis or is at risk of developing endometriosis and the use of such risk information in selectively administering a treatment that at least partially prevents or compensates for an endometriosis related symptom.Type: GrantFiled: March 7, 2013Date of Patent: January 13, 2015Assignee: Juneau Biosciences, LLC.Inventors: Kenneth Ward, Rakesh N. Chettier, Hans Albertsen
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Publication number: 20150010513Abstract: An isolated human brown adipose tissue stem cell line. In one embodiment, the isolated human brown adipose tissue stem cell line expresses the markers CD9, SSEA4, CD44, CD90, CD166, CD73, but not CD14, CD34, CD45 or STRO-1. In another embodiment, the isolated human brown adipose tissue stem cell line expresses the genes UCP1, PPARGC1A, NRF1, FOXC2, CREB1, SIRT3, and WNT5A (REFX). In still another embodiment, the isolated human brown adipose tissue stem cell line is capable of differentiating into osteoblasts, chondrocytes, and adipocytes.Type: ApplicationFiled: April 17, 2014Publication date: January 8, 2015Inventor: Francisco Javier Silva
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Publication number: 20150010575Abstract: A target substance used for combination treatment with an anti-c-Met antibody, a pharmaceutical composition for combination administration for preventing and/or treating cancer including an anti-c-Met antibody and an inhibitor against the target substance as active ingredients, a method for preventing and/or treating cancer including co-administering an anti-c-Met antibody and an inhibitor against the target substance, and a method for screening a drug for preventing and/or treating cancer using the target substance.Type: ApplicationFiled: July 3, 2014Publication date: January 8, 2015Inventors: Bo Gyou KIM, Shangzi Wang, Ji Min Lee, Kyung Ah Kim, Louis M. Weiner
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Publication number: 20150010485Abstract: At least one microRNA selected from among hsa-miR-330, hsa-miR-7 and hsa-miR-137, the mature forms thereof, and the precursors thereof, for depigmenting the skin, and an in vitro method for identifying depigmenting compounds, which includes the steps of: a) placing at least one test compound in contact with a sample of melanocytes; b) measuring the expression or activity of at least one microRNA selected from among miR-330, miR-7 and miR-137, the mature forms thereof, and the precursors thereof, in the melanocytes; c) selecting the compounds for which at least 20% activation of the expression or of the activity of at least one of the microRNAs is measured in the melanocytes treated in a) by an element for comparing with the untreated melanocytes.Type: ApplicationFiled: December 18, 2012Publication date: January 8, 2015Applicants: CHANEL PARFUMS BEAUTE, INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE), INSTITUTE CURIE, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - CNRSInventors: Gaelle Saintigny, Christian Mahe, Lionel Larue, Florian Rambow
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Patent number: 8927517Abstract: Use of autophagic activity in regulation of the amount of melanin in a keratinocyte, the control of skin or hair color, or selection of an agent for regulating the amount of melanin in a keratinocyte or an agent for controlling skin or hair color.Type: GrantFiled: April 8, 2013Date of Patent: January 6, 2015Assignee: Kao CorporationInventors: Daiki Murase, Akira Hachiya
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Publication number: 20150005367Abstract: The present invention relates to the field of fibrosis and inflammation and more particularly to the use of ADAM12 (A Disintegrin and Metalloproteinase 12) inhibitors to prevent or treat inflammation-induced fibrosis. The present invention also relates to the use of ADAM12 as a marker for inflammation-induced fibrosis and to the ablation of ADAM12 expressing cells as therapeutic approach to interfere with the development of pro-fibrotic cells.Type: ApplicationFiled: September 5, 2014Publication date: January 1, 2015Applicant: Institut PasteurInventors: Lucie Peduto, Gerard Eberl
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Publication number: 20150005361Abstract: Disclosed herein are compositions and methods to treat and reduce therapeutic resistance in chronic myelogenous leukemia. Also disclosed herein are methods to generate leukemia stem cell like cells (iLSCs) generated from CML patient-derived iPSCs, and methods for utilizing iLSCs in screens to identify modulators of CML drug resistance and gene targets that underlie CML drug resistance.Type: ApplicationFiled: April 11, 2014Publication date: January 1, 2015Applicant: Wisconsin Alumni Research FoundationInventors: Igor I. Slukvin, Kran Suknuntha
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Publication number: 20150004620Abstract: A method of identifying inhibitors of epithelial-mesenchymal transition (EMT). The method may comprise comparing different sets of image data obtained from one or more cell colonies before (T1) and after (T2) exposure to a possible inhibitor of epithelial-mesenchymal transition. The method may further comprise measuring the cell number and a spreading coefficient value in the one or more cell colonies for determining cell count ratio (CCR) and normalized cell dispersion ratio (CDR) for the one or more colonies. The possible inhibitor may then be identified to be an inhibitor of EMT if the determined CCR and CDR indicates that the possible inhibitor i) does not or marginally inhibit growth and inhibits EMT, or ii) inhibits growth and inhibits cell dispersion and optionally inhibits also EMT, or iii) is cytotoxic and inhibits cell dispersion and optionally inhibits also EMT.Type: ApplicationFiled: December 28, 2012Publication date: January 1, 2015Inventors: Jean Paul Thiery, Kian Nigiap Chuo, Wen Jing Sim
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Publication number: 20150004616Abstract: Human skin tissue sample methods and models for identifying and screening test agents as effective for providing skin tone benefits, methods for validating hypotheses for mechanisms driving skin pigmentation as well as methods for driving skin pigment levels in ex-vivo skin tissue. The method includes contacting a cultured human skin tissue sample with a test agent, generating a transcriptional profile from the sample, and comparing the results to a control to determine if the test agent is effective for providing a skin tone benefit.Type: ApplicationFiled: December 20, 2012Publication date: January 1, 2015Inventors: Deborah Ruth Finlay, Tomohiro Hakozaki, Charles Carson Bascom, Heather Eileen Matheny
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Patent number: 8920832Abstract: The invention provides a nucleic-acid-transfecting composition which exhibits low cytotoxicity, which facilitates an effective nucleic acid transfection into a cell, and which improves expression of the nucleic acid in the cell. The composition for transfecting a nucleic acid into a cell, contains a di(C12-16 alkyl)dimethylammonium halide and a phospholipid.Type: GrantFiled: September 29, 2011Date of Patent: December 30, 2014Assignee: Hokkaido System Science Co., Ltd.Inventors: Hiroshi Kikuchi, Hideo Kobayashi, Kouichi Hashimoto, Ayako Iijima, Daigo Asano, Junko Yasuda
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Patent number: 8921056Abstract: The present invention relates to a composition useful for the diagnosis of diseases associated with aberrant expression of the genes encoding the secreted proteins Futrin 1, 2, 3 and/or 4(=R-Spondin 2, 3, 1 and 4, respectively), e.g. in connection with tumors or diseases of the muscle, kidneys or bones. The present invention also relates to a pharmaceutical composition containing a compound which is capable of modifying (a) the expression of the gene encoding Futrin 1, 2, 3 and/or 4 or (b) the activity of the Futrin 1, 2, 3 and/or 4 protein.Type: GrantFiled: April 4, 2014Date of Patent: December 30, 2014Assignee: Deutsches KrebsforschungszentrumInventors: Christof Niehrs, Wei Wu, Andrey Glinka, Olga Kazanskaya
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Publication number: 20140377768Abstract: The present invention provides a novel antitumor agent that acts through a novel mechanism. The novel antitumor agent contains as an active ingredient a substance capable of inhibiting a cell cycle-dependent Rho GTPase activating protein (RhoGAP). The RhoGAP is cell cycle-dependent and plays an important role in a process through which cancer cells acquire invasive capacity and/or metastatic capacity. The invasion and/or metastasis of cancer cells can be controlled by targeting the RhoGAP. Examples of the substance capable of inhibiting a cell cycle-dependent RhoGAP include an antisense oligonucleotide against a gene encoding the RhoGAP and an oligonucleotide that induces RNA interference of the gene. As the oligonucleotide, one containing an artificial nucleic acid such as BNA is preferred because of its excellent stability. The present invention also provides a screening method including selecting an antitumor agent capable of suppressing cancer cell invasion and/or metastasis through a novel mechanism.Type: ApplicationFiled: January 28, 2013Publication date: December 25, 2014Applicant: Osaka UniversityInventors: Masaru Ishii, Yoshinori Kagawa, Masaki Mori, Hideshi Ishii
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Publication number: 20140378548Abstract: The invention relates to a compound which is effective in inhibiting the function of the TRPM4 ion channel and the use of such compound in treating or preventing a neurodegenerative disease, such as Multiple Sclerosis, Parkinson's disease, Alzheimer's disease, or a myotrophic lateral sclerosis, in a subject. The invention also provides a pharmaceutical composition comprising a TRPM4 inhibitory compound. The invention further relates to in vitro methods for identifying pharmaceutically active compounds that are useful for treating or preventing a neurodegenerative disease.Type: ApplicationFiled: December 21, 2012Publication date: December 25, 2014Inventors: Manuel Friese, Benjamin Schattling, Karin Steinbach, Marc Freichel, Veit Flockerzi, Rudi Vennekens, Doron Merkler
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Publication number: 20140377233Abstract: The present invention is directed to a method of preparing an artificial tooth primordium in vitro, comprising the steps: a) providing isolated mesenchymal dental pulp cells; and b) culturing the mesenchymal dental pulp cells under non-adherent conditions to form a cell aggregate representing an artificial tooth primordium; as well as to an artificial tooth primordium derived therefrom.Type: ApplicationFiled: February 20, 2013Publication date: December 25, 2014Inventors: Roland Lauster, Uwe Marx, Jennifer Binder, Mark Rosowski
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Publication number: 20140378529Abstract: Methods for treating a subject determined to have a cancer comprising a heterozygous inactivation of a housekeeping gene (or a homozygous deletion of a functionally redundant housekeeping gene) by treating the subject with an inhibitor of the gene. For example, a subject having a cancer with an ENO gene deletion can be treated with a glycolysis inhibitor, such as an enolase inhibitor. In some aspects, a subject having a cancer with an ARS gene deletion can be treated with an ARS inhibitor.Type: ApplicationFiled: December 14, 2012Publication date: December 25, 2014Applicants: DANA-FARBER CANCER INSTITUTE, INC., BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEMInventors: Florian L. Muller, Eliot Fletcher-Sananikone, Simona Colla, Elisa Aquilanti, Ronald DePinho
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Publication number: 20140371157Abstract: Disclosed herein are novel methods and compositions useful for inhibiting interaction between a bromodomain protein and an immunoglobulin (Ig) regulatory element. The methods and compositions are particularly useful for downregulating expression of an oncogene translocated with an Ig locus, as well as for treating a cancer (e.g., hematological malignancy) characterized by increased expression of an oncogene which is translocated with an Ig locus.Type: ApplicationFiled: August 30, 2012Publication date: December 18, 2014Applicants: DANA-FARBER CANCER INSTITUTE, INC., WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCHInventors: Richard A. Young, Peter B. Rahl, James Bradner
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Publication number: 20140364402Abstract: The present invention provides, inter alia, a method for identifying an agent that selectively decreases the number of cancer stem cells (CSCs). This method includes (a) contacting a CSC from a population of cells with a candidate agent; and (b) determining whether the candidate agent reduces the survival or growth of the CSC or increases differentiation of the CSC relative to a CSC that has not been contacted with the candidate agent. The method may be used as a high throughput screen.Type: ApplicationFiled: March 22, 2012Publication date: December 11, 2014Applicant: THE ROGOSIN INSTITUTEInventors: Barry Smith, Carlos Cordon-Cardo, Daniel Petrylak, Josep Domenech, Mireia Castilla Martin
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Patent number: 8906629Abstract: The present invention provides a method for screening and evaluating ameliorants of dry skin caused by atopic dermatitis, comprising: evaluating a candidate drug as being an ameliorant of dry skin caused by atopic dermatitis in the case the candidate drug significantly increases expression and/or activity of bleomycin hydrolase in comparison with a control drug.Type: GrantFiled: December 2, 2010Date of Patent: December 9, 2014Assignee: Shiseido Company, Ltd.Inventors: Toshihiko Hibino, Yayoi Kamata, Mami Yamamoto
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Publication number: 20140357521Abstract: The disclosure relates cells or cellular systems that express both a membrane protein and a binding domain directed to the membrane protein. Also, methods are provided that use such cells or cellular systems to produce higher amounts of the membrane proteins. Further, the cells or cellular systems can be used as tools for the structural and functional characterization of membrane proteins, as well as for screening and drug discovery efforts targeting membrane proteins.Type: ApplicationFiled: January 21, 2013Publication date: December 4, 2014Inventors: Jan Steyaert, Nico Callewaert, Toon Laeremans, Els Pardon, Kristof Vandewalle, Katrien Claes
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Publication number: 20140357510Abstract: The present invention relates to a composition useful for the diagnosis of diseases associated with aberrant expression of the genes encoding the secreted proteins Futrin 1, 2, 3 and/or 4 (=R-Spondin 2, 3, 1 and 4, respectively), e.g. in connection with tumors or diseases of the muscle, kidneys or bones. The present invention also relates to a pharmaceutical composition containing a compound which is capable of modifying (a) the expression of the gene encoding Futrin 1, 2, 3 and/or 4 or (b) the activity of the Futrin 1, 2, 3 and/or 4 protein.Type: ApplicationFiled: April 4, 2014Publication date: December 4, 2014Applicant: Deutsches KrebsforschungszentrumInventors: Christof Niehrs, Wei Wu, Andrey Glinka, Olga Kazanskaya
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Publication number: 20140357578Abstract: Compositions, methods, and kits are provided for reduction of (CAG)n-RNA mediated toxicity. Compositions, methods, and kits are also provided for treatment of polyglutamine diseases.Type: ApplicationFiled: June 2, 2014Publication date: December 4, 2014Applicant: The Chinese University of Hong KongInventor: Ho Yin Edwin Chan
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Patent number: 8901040Abstract: The invention relates to a method of finding compounds which increase the tolerance of plants to abiotic stress factors acting on this plant, such as, for example, temperature (such as chill, frost or heat), water (such as dryness, drought or anoxia), or the chemical load (such as lack of or excess of mineral salts, heavy metals, gaseous noxious substances) by increasing the expression of plant-endogenous proteins, and to the use of these compounds for increasing the tolerance in plants to abiotic stress factors.Type: GrantFiled: June 30, 2010Date of Patent: December 2, 2014Assignee: Bayer Intellectual Property GmbHInventors: Arno Schulz, Klaus Bartsch, Hansjörg Krähmer, Martin Hills, Erwin Hacker, Chris Rosinger
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Publication number: 20140348840Abstract: The present invention relates to methods and compositions for treating and reducing the risk of Acute Myelogenous Leukemia (AML). In particular, the invention provides methods for identifying novel treatments for AML based on reproducible and detectable changes in AML1-ETO acetylation. The present invention further provides methods of using these treatments.Type: ApplicationFiled: July 13, 2012Publication date: November 27, 2014Applicant: MEMORIAL SLOAN-KETTING CANCER CENTERInventors: Stephen D. Nimer, Lan Wang
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Publication number: 20140348744Abstract: The use of luteinizing hormone receptor (LHR) as a treatment target in cancer is provided. Data demonstrates that LHR plays an important role in androgen synthesis and signaling pathways critical for prostate cancer progression. When LHR is silenced, there is a significant downregulation of androgen receptor (AR) mRNA and protein expression with a subsequent suppression of PSA expression. Data suggesting that the LH-LHR signaling cascade may be an upstream and viable therapeutic target in castration-resistant prostate cancer (CRPC) is presented.Type: ApplicationFiled: May 27, 2014Publication date: November 27, 2014Inventor: Jacek K. Pinski
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Publication number: 20140349964Abstract: The invention provides a method for producing an orexin neuron by culturing a pluripotent stem cell or a neural progenitor cell in the presence of N-acetyl-D-mannosamine and optionally in the presence of at least one inhibitor selected from the group consisting of a Sirtuin 1 inhibitor and an O-linked ?-N-acetylglucosamine transferase inhibitor. The invention also provides a therapeutic agent for narcolepsy or eating disorders, such as anorexia, containing N-acetyl-D-mannosamine, which is based on the induction of orexin neuron in vivo.Type: ApplicationFiled: March 25, 2014Publication date: November 27, 2014Inventors: Kunio SHIOTA, Shintaro YAGI, Koji HAYAKAWA, Mitsuko HIROSAWA-TAKAMORI, Daisuke ARAI, Keiji HIRABAYASHI
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Publication number: 20140349866Abstract: Methods are described for using genes crucial in TH17 differentiation, IL-12Rbeta 1/IL-23R, CCR6, BATF, AHR, STAT3 and IRF4 as new markers for rosacea. Also described, are methods of their use to diagnose rosacea, to screen inhibitors of Th17 differentiation. In particular, method are described for inhibiting at least one of these genes and using the screened inhibitors in rosacea treatment.Type: ApplicationFiled: June 25, 2012Publication date: November 27, 2014Applicant: GALDERMA RESEARCH & DEVELOPMENTInventor: Martin Steinhoff
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Patent number: 8895245Abstract: The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.Type: GrantFiled: September 12, 2011Date of Patent: November 25, 2014Assignee: Epizyme, Inc.Inventors: Robert A. Copeland, Victoria M. Richon, Margaret D. Scott, Christopher J. Sneeringer, Kevin W. Kuntz, Sarah K. Knutson, Roy M. Pollock
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Patent number: 8898149Abstract: A computer system maintains a biological data structure having molecular feature data. The system receives data elements indicating biological molecular features and knowledge elements that represent biological concepts. The system individually associates unique identifiers with the elements. For individual elements, the system maintains an internal element set of the other unique identifiers for the other elements that are directly associated with that one individual element. For the individual elements, the system maintains an external element set of the other unique identifiers for the other elements that have that one individual element in their own internal element sets. Although not required, the computer system may process a query indicating a search scope and a molecular feature for an individual biological entity, and responsively process the molecular feature and the elements based on the search scope to induce a knowledge sub-graph for the individual biological entity.Type: GrantFiled: May 3, 2012Date of Patent: November 25, 2014Assignees: The Translational Genomics Research Institute, Arizona Board of Regents on Behalf of Arizona State UniversityInventors: Spyro Mousses, Toni R. Farley, Jeffrey A. Kiefer, Charles J. Colbourn, Preston Victor Lee
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Publication number: 20140342944Abstract: A kit and method for evaluating in vitro the effect of a xenobiotic (e.g., a biologic drug) on drug metabolism in hepatocytes. The kit comprises a first culture of hepatocytes, a portion of in vitro xenobiotic-stimulated biological sample, and instructions for incubating the first culture of hepatocytes with the portion of in vitro xenobiotic-stimulated biological sample, and analyzing the activity, expression, or a combination thereof of a biomarker in the hepatocytes to evaluate the effect of the xenobiotic on drug metabolism in the hepatocytes.Type: ApplicationFiled: July 31, 2014Publication date: November 20, 2014Inventors: Maciej Czerwinski, David Benjamin Buckley, Faraz Kazmi
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Publication number: 20140342357Abstract: The presently-disclosed subject matter includes methods of identifying an Alu RNA inhibitor, and methods and compositions for inhibiting Alu RNA. Methods and compositions can be used for the treatment of geographic atrophy and other conditions of interest.Type: ApplicationFiled: July 3, 2014Publication date: November 20, 2014Applicant: UNIVERSITY OF KENTUCKY RESEARCH FOUNDATIONInventor: Jayakrishna Ambati
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Patent number: 8889356Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.Type: GrantFiled: February 18, 2014Date of Patent: November 18, 2014Assignees: The Broad Institute Inc., Massachusetts Institute of TechnologyInventor: Feng Zhang
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Publication number: 20140336138Abstract: Compositions and methods for treatment of Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome, Port-Wine Stains and related neurocutaneous disorders are provided. Cell lines having the somatic mutation GNAQ p.Arg183Gln amino acid substitution, which was found to be the cause of port-wine stains (prevalence 1 in 300) and Sturge-Weber syndrome are also provided. Compositions and methods for treatment of uveal melanoma are also provided herein. Methods of screening novel compounds and compositions useful in increasing RGS2 and/or RGS4 expression and function in vitro, and for treatment of Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome, Port-Wine Stains and related neurocutaneous disorders are provided are also provided.Type: ApplicationFiled: May 7, 2014Publication date: November 13, 2014Applicants: The Johns Hopkins University, Kennedy Krieger Institute, Inc.Inventors: Anne M. Comi, Jonathan Pevsner, Douglas Marchuk
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Publication number: 20140335516Abstract: Isolated transduced cells exhibiting FRDA characteristics in an inducible fashion are disclosed. Isolated transduced cells comprise an expression vector having a nucleic acid sequence encoding an shRNA for frataxin protein knockdown and a heterologous expression control sequence. Additionally, methods of screening for a candidate therapeutic agent for treating Friedreich's Ataxia using isolated transduced cells are disclosed. Further, a recombinant nucleic acid construct for frataxin knockdown is disclosed that comprises a nucleic acid encoding an shRNA operably linked to a heterologous expression control sequence and expressing an shRNA molecule in a dose-responsive fashion.Type: ApplicationFiled: May 13, 2014Publication date: November 13, 2014Inventors: Ronald Mark Payne, Clifford M. Babbey
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Publication number: 20140336282Abstract: Carcinomas typically invade as a cohesive multicellular unit, a process termed collective invasion. It remains unclear how different subpopulations of cancer cells contribute to this process. We developed three-dimensional (3D) organoid assays to identify the most invasive cancer cells in primary breast tumors. Collective invasion was led by specialized cancer cells that were defined by their expression of basal epithelial genes, such as cytokeratin-14 (K14) and p63. Furthermore, K14+ cells led collective invasion in the major human breast cancer subtypes. Importantly, lumenal cancer cells were observed to convert phenotypically to invasive leaders following induction of basal epithelial genes. Although only a minority of cells within lumenal tumors expressed basal epithelial genes, knockdown of either K14 or p63 was sufficient to block collective invasion. Our data reveal that heterotypic interactions between epithelial subpopulations are critical to collective invasion.Type: ApplicationFiled: May 13, 2014Publication date: November 13, 2014Applicant: The Johns Hopkins UniversityInventors: Andrew Josef Ewald, Kevin Cheung
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Publication number: 20140336240Abstract: This disclosure provides a novel role for microRNA (miR) regulation of lipid metabolism via the MTP pathway, leading to reductions in apoB secretion and blood lipid levels. MiR regulation of the MTP pathway is shown herein to reduce hyperlipidemia and atherosclerosis in vivo. Therefore, inhibition of MTP expression and activity by miR regulation is identified as a new therapeutic target for treatment of cardiovascular disease and conditions or diseases associated with cardiovascular disease such as hyperlipidemia, atherosclerosis, and metabolic syndrome. Treatment of cardiovascular disease and associated conditions or diseases with the novel MTP inhibitors of the invention, such as miR-30c homologs or miR-30c agonists, reduces MTP-associated lipid production without side effects that occur with other methods of MTP inhibition.Type: ApplicationFiled: January 9, 2013Publication date: November 13, 2014Applicant: THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORKInventors: Mahmood Hussain, James Soh
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Publication number: 20140335074Abstract: Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.Type: ApplicationFiled: December 13, 2012Publication date: November 13, 2014Inventors: Judith Campisi, Marco Demaria