Drug Or Compound Screening Involving Gene Expression Patents (Class 435/6.13)
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Publication number: 20140193828Abstract: The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides the necessary information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through one or more metabolic pathways of interest.Type: ApplicationFiled: March 7, 2014Publication date: July 10, 2014Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIAInventor: Marc K. HELLERSTEIN
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Patent number: 8771935Abstract: The present invention provides methods for identifying cognitive enhancers able to enhance CREB pathway function. Cognitive enhancers identified in accordance with the invention can be used in rehabilitating an animal with cognitive dysfunction and for enhancing memory or normal cognitive performance (ability or function) in the animal.Type: GrantFiled: February 2, 2012Date of Patent: July 8, 2014Assignee: Dart Neuroscience (Cayman) Ltd.Inventors: Timothy P Tully, Roderick E. M. Scott, Rusiko Bourtchouladze
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Patent number: 8771945Abstract: 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: February 18, 2014Date of Patent: July 8, 2014Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventor: Feng Zhang
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Patent number: 8771943Abstract: A method and assay for predicting athletic performance potential of a subject, such as a thoroughbred race horse, comprising the steps of assaying a biological sample from a subject for the presence of a single nucleotide polymorphism in one or more genes associated with athletic performance. The athletic performance genes may be selected from one or more of MSTN, COX4I2, PDK4, CKM and COX4I1.Type: GrantFiled: September 11, 2009Date of Patent: July 8, 2014Assignee: University College Dublin—National University of Ireland, DublinInventors: Emmeline Hill, David MacHugh, Nick Orr, JingJing Gu, Lisa Katz
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Publication number: 20140187611Abstract: The present invention relates to methods of increasing lifespan, delaying aging, and/or preventing or treating an age-related disease or a mitochondrial disease in a subject, comprising inducing a nuclear-mitochondrial OXPHOS protein dyssynchrony, including inhibiting the mitochondrial translation machinery function, as well as methods for screening agents that are able to increase lifespan, inhibit or delay aging, and/or prevent or treat an age-related disease or disorder, or a mitochondrial disease or disorder, in a subject.Type: ApplicationFiled: August 20, 2012Publication date: July 3, 2014Applicant: ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNEInventors: Johan Auwerx, Richardus Houtkooper, Laurent Mouchiroud
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Publication number: 20140187615Abstract: This disclosure describes, in one aspect, a composition that generally includes an xNA molecule comprising at least six nucleotides, in an amount effective to improve at least one indicator of myocyte function and a pharmaceutically acceptable carrier. In another aspect, this disclosure describes a method of treating cardiac disease. Generally, the method includes administering to a subject a composition that includes an xNA molecule having at least six nucleotides, in an amount effective to improve at least one indicator of myocyte function, and a pharmaceutically acceptable carrier. In another aspect, this disclosure describes a method for evaluating the efficacy of treatment of cardiac disease. Generally, the method includes administering to a subject a composition that includes a first xNA molecule comprising a predetermined length in an amount effective to increase myocyte relaxation, then selecting a predetermined length of a second xNA molecule for at least one subsequent treatment.Type: ApplicationFiled: December 23, 2013Publication date: July 3, 2014Applicant: Regents of the University of MinnesotaInventors: Michael T. Bowser, Gianluigi Veglia, Meng Jing, Raffaello Verardi, Joseph M. Metzger, Brian Raymond Thompson
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Patent number: 8765377Abstract: The invention pertains to a method of determining a statin dosage for an individual in need of treatment with a statin, comprising determining a SLCO1B1 genotype from a nucleic acid sample of the individual, said genotype comprising the presence or absence of the SLCO1B1-056 polymorphism, and determining an ApoE genotype or phenotype identifying an ApoE polymorphism selected from the group consisting of ApoE2, ApoE3, ApoE4, and any combination thereof, wherein the combination of a SLCO1B1 genotype identifying the presence of the SLCO1B1-056 C polymorphism and the ApoE genotype or phenotype identifying one of the ApoE3/4 or ApoE4/4 genotypes indicates the statin dosage.Type: GrantFiled: October 12, 2012Date of Patent: July 1, 2014Assignee: Boston Heart Diagnostics CorporationInventors: Ernst J. Schaefer, Eliana Polisecki
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Publication number: 20140179552Abstract: Methods, compositions and kits for diagnosing osteoarthritis in a feline are disclosed. The methods of the invention comprise detecting differential expression of at least one biomarker in a body sample, preferably a blood sample, where the biomarker is differentially expressed in osteoarthritis.Type: ApplicationFiled: December 18, 2013Publication date: June 26, 2014Applicant: COLGATE-PALMOLIVE COMPANYInventors: Samer Waleed Khedheyer Al-Murrani, William David Schoenherr
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Publication number: 20140171483Abstract: The inventors found that the gene, HOXB7, was frequently overexpressed in breast cancer, and is a major upstream regulator of events leading to tamoxifen resistance. The present invention provides double-stranded short interfering nucleic acid (siNA) molecules that targets the HOXB7 gene in cells, and also provides methods of use of this siNA molecule for methods of screening, diagnosis and prediction of treatment outcomes as well as treatment of cancer.Type: ApplicationFiled: March 1, 2012Publication date: June 19, 2014Applicant: The Johns Hopkins UniversityInventors: Saraswati Sukumar, Kideok Jin
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Publication number: 20140161917Abstract: Methods of using nesprin-2 modulators to impart anti-aging benefits to the skin and/or improve skin conditions.Type: ApplicationFiled: October 30, 2013Publication date: June 12, 2014Applicant: Avon Products, Inc.Inventors: John W. Lyga, Ying Chen, Qian Zheng, Uma Santhanam
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Publication number: 20140163118Abstract: Described herein are expression signatures of genes and coordinately expressed gene networks associated with skin aging, methods used to determine the physiological age of skin, and methods used to screen for compounds used to reduce the visible signs of aging of the skin.Type: ApplicationFiled: May 3, 2012Publication date: June 12, 2014Applicant: DERMACHIP INC.Inventors: Giammaria Giuliani, Raymond Rodriguez, Somen Nandi
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Publication number: 20140161721Abstract: This document provides methods and materials related to genetic variations of developmental disorders. For example, this document provides methods for using such genetic variations to assess susceptibility of developing Autism Spectrum Disorder.Type: ApplicationFiled: February 8, 2013Publication date: June 12, 2014Inventors: Eli Hatchwell, Peggy S. Eis, Stephen Scherer, Aparna Prasad
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Publication number: 20140162968Abstract: The present invention relates to a method for screening and preparing an obesity prevention or treatment agent, and a method for preparing an obesity prevention or treatment agent. Being able to easily detect a substance that has a preventive and therapeutic effect on obesity, the present invention has a wide spectrum of applications in the research and medicine field in the prevention or treatment of obesity.Type: ApplicationFiled: January 20, 2012Publication date: June 12, 2014Inventor: Myeong Ok Kim
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Patent number: 8748087Abstract: The present invention provides an isolated polynucleotide acid comprising a polynucleotide sequence having a substantial amount of sequence identity to the entire length of the polynucleotide sequence as set forth in SEQ ID NO: 1 or its complementary strand (SEQ ID NO: 2), the sequence is derived from RT domain of HBV polymerase gene. The present invention also provides a polypeptide and related compositions, as well as methods for using the same.Type: GrantFiled: December 20, 2006Date of Patent: June 10, 2014Assignee: Fudan UniversityInventors: Yu-Mei Wen, Yong-Xiang Wang, Zhang-Mei Ma
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Patent number: 8748106Abstract: This application is based, inter alia, on the discovery of a binding interaction between the Hn-33 hemagglutinin polypeptide of the type A Clostridium botulinum neurotoxin complex and synaptosomal proteins, including synaptotagmin II (Syt II). Methods of screening for compounds that modulate, e.g., increase or decrease, this interaction are provided. Also provided are compositions and methods for targeting compounds to neuronal and cancer cells by coupling the compounds to Hn-33 or biologically active Hn-33 variants.Type: GrantFiled: April 18, 2006Date of Patent: June 10, 2014Inventors: Bal Ram Singh, Yu Zhou
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Publication number: 20140155271Abstract: This document provides methods and materials related to genetic variations of neurological disorders. For example, this document provides methods for using such genetic variations to assess susceptibility of developing Parkinson's disease.Type: ApplicationFiled: November 2, 2012Publication date: June 5, 2014Applicants: Population Diagnostics, Inc., The Research Foundation of State of University of New YorkInventors: ELI HATCHWELL, PEGGY S. EIS
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Publication number: 20140155290Abstract: Improved host cells and culture methods involving overexpression of MAN1C1 activity to improve protein production are provided.Type: ApplicationFiled: February 6, 2014Publication date: June 5, 2014Applicant: AMGEN INC.Inventor: Christopher Kenyon Crowell
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Publication number: 20140154343Abstract: Methods for preventing, ameliorating, or reducing dermatological signs of aging are provided which employ active agents, other than a retinoid, that stimulate thymosin beta-4 expression in the skin. Also provided are methods for screening for substances which stimulate thymosin beta-4 expression levels and the methods of using active agents identified by the screening protocol in the treatment of skin.Type: ApplicationFiled: December 9, 2013Publication date: June 5, 2014Applicant: Avon Products, Inc.Inventors: Siming W. Chen, Qian Zheng, Satish Parimoo
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Publication number: 20140154326Abstract: The invention provides a micro-organ composite which comprises a core group of cells and an outer layer of cells, wherein the cells of the core group are mesenchymal cells and the cells of the outer layer are epithelial cells or wherein the cells of the core group are epithelial cells and the cells of the outer layer are mesenchymal cells, and wherein the core group of cells is at least partially encapsulated by the outer layer of cells.Type: ApplicationFiled: July 23, 2012Publication date: June 5, 2014Applicant: University of DurhamInventors: Aihua Guo, Colin Albert Buchanan Jahoda
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Patent number: 8744778Abstract: In one aspect, the present invention provides methods of determining whether an agent is more like a partial agonist of a target molecule than a full agonist of the same target molecule. In another aspect, the present invention provides methods to select a candidate compound that may reduce blood plasma glucose concentration in a mammal. Populations of genes are provided that are useful in the practice of the present invention.Type: GrantFiled: August 12, 2011Date of Patent: June 3, 2014Assignee: Merck Sharp & Dohme Corp.Inventors: Yejun Tan, Hongyue Dai, Pek Yee Lum, John Ryan Thompson, Joel Peter Berger, Eric Stanley Muise, Richard F. Raubertas, Kenny Kin Chung Wong
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Patent number: 8741572Abstract: The present invention provides compounds and assays for the identification and validation of compounds for use in the treatment of muscular mystrophy (MD), or a form thereof, in which said compounds increase the post-transcriptional expression of a target gene (i.e., mIGF1, ITGA7, or UTRN).Type: GrantFiled: October 8, 2012Date of Patent: June 3, 2014Assignee: PTC Therapeutics, Inc.Inventors: Westley J. Friesen, Nikolai Naryshkin, Meenal Patel, Charles Romfo, Yuki Tomizawa, Ellen Welch, Jin Zhou
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Publication number: 20140148496Abstract: ATM kinase is shown to regulate proteasome-mediated protein turnover through suppression of the expression of the ubiquitin-like protein ISG15 (Interferon Stimulated Gene 15). Silencing of the ISG15 pathway restored both the ubiquitin and autophagy pathways, and the UV-mediated degradation of their substrates in A-T cells. The ATM kinase negatively regulates the ISG15 pathway, and the constitutively elevated ISG15 pathway induces proteinopathy in A-T cells, and in A-T patients. These findings indicate that proteasome-mediated protein degradation is impaired in A-T cells due to elevated expression of the ISG15 conjugation pathway, which contributes to progressive neurodegeneration in A-T patients. The ISG15 pathway is a new target for both detection and treatment of A-T Inhibitors if ISG15 expression can be used to inhibit or attenuate neurodegeneration in A-T patients.Type: ApplicationFiled: November 29, 2012Publication date: May 29, 2014Inventor: Shyamal D. Desai
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Publication number: 20140150124Abstract: A construct system for expressing a reporter protein, as well as a transgenic animal and a screening method employing the same, are provided. In certain embodiments, the construct system is a three component system in which expression of a reporter protein from a reporter construct is induced by a transcription factor that is produced using two other constructs, each producing a different part of the transcription factor. The parts of the transcription factor are ligated together. Expression of the reporter only occurs in tissues in which both of the parts of the transcription factor are produced.Type: ApplicationFiled: September 26, 2011Publication date: May 29, 2014Applicant: RIGEL PHARMACEUTICALS, INC.Inventor: Todd M Kinsella
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Publication number: 20140148380Abstract: The present invention relates to, inter alia, a method for repressing transcription and/or gene expression from RpoN binding sites (or promoters) or cryptic promoters upstream of RpoN binding sites. The method comprises providing an agent that specifically and selectively binds to RpoN promoter sequences to inhibit or repress the expression of genes downstream of that promoter; and contacting the RpoN promoter with the agent. Agents for repressing transcription and/or gene expression from RpoN promoters are also provided. The agent can be a composition that binds specifically to the ?24, ?12, or ?24/?12 site(s) for RpoN promoter interference. Synthetic peptides, vectors, and host cells are also provided.Type: ApplicationFiled: May 7, 2012Publication date: May 29, 2014Applicant: THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORKInventors: Christopher T. Nomura, Benjamin R. Lundgren
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Patent number: 8735073Abstract: Cannabinoid receptor 2 (CB2) is expressed in B lymphocytes and is involved in immune regulation. Mouse splenic B cells express three CB2 transcripts utilizing two different first exons. Human peripheral blood B cells express one CB2 transcript utilizing one first exon. Alignment of sequenced RACE products to either the mouse or human genome reveals that isolated transcripts contain previously unidentified transcriptional start sites (TSS). B cells from mouse and human preferentially express one transcript, exon 1a in mouse and exon 1 in human. Multiple CB2 TSSs are utilized in mouse splenic B cells and one TSS in human peripheral blood B cells. The defining of the receptor gene TSSs in these cells provides materials and methods for therapeutically regulating immune function, including antibody isotype switching, using compounds such as inhibitory nucleic acids that down-regulate expression of the B cell CB2 gene (e.g., RNAi molecules).Type: GrantFiled: September 23, 2013Date of Patent: May 27, 2014Assignee: University of South FloridaInventors: Thomas W. Klein, Tracy Sherwood, Liang Nong, Cathy Newton
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Patent number: 8735071Abstract: The invention features compositions and methods for modulating the expression of Gadd45 and the use of such compositions and methods as neuroprotectants, to enhance neurogenesis, and for the treatment of mood disorders.Type: GrantFiled: December 23, 2009Date of Patent: May 27, 2014Assignee: The Johns Hopkins UniversityInventors: Hongjun Song, Dengke K. Ma, Guo-li Ming
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Patent number: 8735072Abstract: Methods of screening candidate agents to identify lead compounds for the development of therapeutic agents for the treatment of a neurodegenerative disease, such as Huntington's Disease and Parkinson's Disease and methods for identifying a mutation in, or changes in expression of, a gene associated with neurodegenerative disease, such as Huntington's Disease and Parkinson's Disease, are provided.Type: GrantFiled: March 13, 2012Date of Patent: May 27, 2014Assignees: Whitehead Institute for Biomedical Research, University of WashingtonInventors: Paul J. Muchowski, Susan L. Lindquist, Tiago Outeiro
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Publication number: 20140141017Abstract: The present invention provides methods and compositions for identifying compounds which inhibit ApoCI and which are useful in the treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction. The invention further provides methods for treating subjects suffering from or at risk of developing atherosclerosis, plaque rupture, apoptosis, or myocardial infarction. The invention further provides methods for diagnosing subjects at suffering from or at risk of developing treatment or prevention of atherosclerosis, plaque rupture, apoptosis, or myocardial infarction.Type: ApplicationFiled: November 14, 2013Publication date: May 22, 2014Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Subroto Chatterjee, Peter O. Kwiterovich
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Patent number: 8729041Abstract: The present invention provides compositions and methods featuring miR-26 microRNA polynucleotides for the diagnosis, treatment or prevention of hepatic neoplasia.Type: GrantFiled: December 2, 2009Date of Patent: May 20, 2014Assignees: The Johns Hopkins University, Nationwide Children's Hospital, Inc.Inventors: Joshua T. Mendell, Kathryn A. Mendell, Raghu R. Chivukula, Erik A. Wentzel, Jerry R. Mendell, K. Reed Clark, Janaiah Kota
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Patent number: 8728797Abstract: The invention relates to an in vitro cell based expression system for overexpressing heterologous pump proteins associated with drug resistance into the membrane of the host cell for drug screening applications.Type: GrantFiled: May 27, 2008Date of Patent: May 20, 2014Assignee: LA SA SopartecInventors: Brian Charles Monk, Richard David Cannon, Kenjirou Nakamura, Masakazu Niimi, Kyoko Niimi, Ann Rachel Holmes, Erwin Lamping, David Roger Kay Harding, Andre Goffeau, Anabelle Decottignies
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Publication number: 20140137274Abstract: PROBLEM There 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.Type: ApplicationFiled: November 30, 2012Publication date: May 15, 2014Applicants: LSIP, LLC, National Cancer CenterInventors: National Cancer Center, LSIP, LLC
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Publication number: 20140134636Abstract: Disclosed is a composition for a whitening effect or for the prevention of gray hair, which includes antisense nucleic acid molecules of SEQ ID NO: 2, wherein the composition has an miRNA of SEQ ID NO: 1 or a base sequence complementary thereto. Also disclosed is a method for controlling chromogenesis in test materials and for screening for expression control materials of chromogenic genes. The composition and the screening method can be used for the whitening effect or for the prevention of gray hair.Type: ApplicationFiled: June 13, 2012Publication date: May 15, 2014Applicant: AMOREPACIFIC CORPORATIONInventors: Kyu Han Kim, Hyun Jung Choi, Bum Ho Bin, Tae Ryong Lee
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Publication number: 20140134635Abstract: The invention is directed to a method of characterizing a mechanism of action of an agent (e.g., a chemotherapeutic agent, a genotoxic agent). The method comprises contacting a plurality of populations of cells with an agent to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein said gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the agent is determined, thereby obtaining an shRNA signature of the agent, so as to identify one or more genes that mediate a response to the agent, thereby characterizing the mechanism of action of the agent. The invention is also directed an article of manufacture for characterizing a mechanism of action of a chemotherapeutic or genotoxic agent.Type: ApplicationFiled: December 16, 2011Publication date: May 15, 2014Inventors: Hai Jiang, Justin Pritchard, Douglas A. Lauffenburger, Michael Hemann
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Patent number: 8722338Abstract: Genome-wide association studies (GWAS) was recently used to identify SNPs in a genomic region on chromosome 4 that associate with serum urate levels and gout. The present disclosure shows that human ATP-binding cassette, subfamily G, 2 (ABCG2), encoded by the ABCG2 gene contained in this region, is a hitherto unknown urate efflux transporter. The present disclosure further shows that native ABCG2 is located in the brush border membrane of kidney proximal tubule cells, where it mediates renal urate secretion. Introduction of the mutation Q141K encoded by the common SNP rs2231142 by site-directed mutagenesis resulted in reduced urate transport rates compared to wild-type ABCG2. Data from a population-based study of 14,783 individuals support rs2231142 as the causal variant in the region and show highly significant associations with urate levels and gout.Type: GrantFiled: March 11, 2010Date of Patent: May 13, 2014Assignee: The Johns Hopkins UniversityInventors: Michael Kottgen, Josef Coresh, William Guggino, Anna Kottgen, Owen Woodward
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Publication number: 20140128272Abstract: Provided are a method for retaining in a dormant state a cancer tissue-derived cell mass that can reflect accurately the in vivo behavior of cancer cells, and an evaluation method for examining the sensitivity to various treatments including a drug sensitivity test by using a cancer tissue-derived cell mass in such a dormant state. The cancer tissue-derived cell mass is prepared from an individual. Such a cancer tissue-derived cell mass is cultured in vitro under the conditions of hypoxia and low levels of growth factors. Furthermore, a treatment with a drug, etc. is applied in vitro to the cancer tissue-derived cell mass in the dormant state so that evaluation is achieved by examination of its proliferation state, determination of life and death, and analysis of signals.Type: ApplicationFiled: February 15, 2013Publication date: May 8, 2014Inventor: Masahiro Inoue
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Publication number: 20140127704Abstract: The present invention provides a kit for diagnosing the cardiomyopathy comprising an antibody or oligonucleotide for measuring an expression level of nuclear receptor interaction protein (NRIP). The present invention also provides a method of predicting a risk of cardiomyopathy for a subject. The present invention further provides a method of screening an agent for treating cardiomyopathy.Type: ApplicationFiled: November 5, 2012Publication date: May 8, 2014Applicant: NATIONAL TAIWAN UNIVERSITYInventors: Show-Li CHEN, Ssu-Yu LIN, Szu-Wei CHANG, Hsin-Hsiung CHEN
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Publication number: 20140127706Abstract: A method for measuring human CYP3A inducibility upon administration of a test drug, characterized in that a non-human animal to which a test drug is administered or a population of human cells cultured in a medium containing a test drug is infected with viruses (A) and (B); virus (A) being an adenovirus which is used as a vector and engineered by incorporating thereto a detectable reporter gene an;d at least 3 human PXR binding regions falling within an untranslated region of a human CYP3A gene, and virus (B) being an adenovirus which is used as a vector and engineered by incorporating thereto a human PXR cDNA; and subsequently expression level of the reporter gene is determined in the non-human animal or the cultured human cells.Type: ApplicationFiled: December 20, 2013Publication date: May 8, 2014Applicant: SEKISUI MEDICAL CO., LTD.Inventors: Yasushi YAMAZOE, Kiyoshi Nagata
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Publication number: 20140127705Abstract: The present invention relates to a method for screening substances having weight-regulating action.Type: ApplicationFiled: June 22, 2012Publication date: May 8, 2014Inventor: Toshihiro Nakajima
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Patent number: 8715643Abstract: Disclosed is a transformed cell (a cell model) which can form a cytoplasmic inclusion body derived from TAR DNA-binding protein of 43 kDa (TDP-43) that is found in the brain of a patient suffering from a neurodegenerative disease such as FTLD and ALS. The transformed cell is characterized by having, introduced therein, a promoter capable of functioning in a host cell and a mutant TDP-43 gene.Type: GrantFiled: March 6, 2009Date of Patent: May 6, 2014Assignee: Tokyo Metropolitan Institute of Medical ScienceInventors: Takashi Nonaka, Tetsuaki Arai, Haruhiko Akiyama, Masato Hasegawa, Makiko Yamashita
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Patent number: 8715927Abstract: Disclosed herein is the identification of human DNA polymerase ? (pol ?) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL -inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol ?. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol ? sufficient to enhance the efficacy of the ICL-inducing agent. Further provided is a method of identifying a DNA polymerase inhibitor.Type: GrantFiled: April 22, 2009Date of Patent: May 6, 2014Assignee: Oregon Health & Science UniversityInventors: R. Stephen Lloyd, Irina G. Minko, Amanda K. McCullough
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Publication number: 20140113954Abstract: MicroRNAs (miR-NAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. The miRNAs are useful to diagnose and treat cancers.Type: ApplicationFiled: November 19, 2013Publication date: April 24, 2014Applicant: The Johns Hopkins UniversityInventors: Jordan CUMMINS, Victor VELCULESCU, Kenneth W. KINZLER, Bert VOGELSTEIN
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Patent number: 8703424Abstract: The invention provides biomarker profiles of metabolites and methods for screening chemical compounds including pharmaceutical agents, lead and candidate drug compounds and other chemicals using human stem-like cells (hSLCs) or lineage-specific cells produced therefrom. The inventive methods are useful for testing toxicity, particularly developmental toxicity and detecting teratogenic effects of such chemical compounds. Specifically, a more predictive developmental toxicity model, based on an in vitro method that utilizes both hSLCs and metabolomics to discover biomarkers of developmental toxicity is disclosed.Type: GrantFiled: March 22, 2011Date of Patent: April 22, 2014Assignee: Stemina Biomarker Discovery, Inc.Inventors: Paul R. West, April M. Weir-Hauptman, Alan M. Smith, Elizabeth L. R. Donley, Gabriela G. Cezar
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Publication number: 20140107028Abstract: Methods and compositions are provided for evaluating a diabetic patient for treatment with an incretin-based therapy. In certain embodiments, evaluation is ongoing and the patient is evaluated at multiple times. In additional embodiments, a diabetic patient is treated with an incretin-based therapy after the patient has been evaluated for expression levels of GLP-1R in a biological sample. In some aspects, the biological sample is specifically a blood sample that has been enriched for peripheral blood monocytes.Type: ApplicationFiled: March 12, 2013Publication date: April 17, 2014Inventors: Sindhu RAJAN, Louis H. Philipson, John B. Ancsin
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Publication number: 20140105896Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.Type: ApplicationFiled: September 12, 2013Publication date: April 17, 2014Applicant: BRISTOL-MYERS SQUIBB COMPANYInventors: Sharon CLOAD, Linda ENGLE, Dasa LIPOVSEK, Malavi MADIREDDI, Ginger Chao RAKESTRAW, Joanna SWAIN, Wenjun ZHAO
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Publication number: 20140106348Abstract: The present invention provides a culture method of cells and/or tissues including culturing cells and/or tissues in a suspended state by using a medium composition wherein indeterminate structures are formed in a liquid medium, the structures are uniformly dispersed in the solution and substantially retain the cells and/or tissues without substantially increasing the viscosity of the solution, thus affording an effect of preventing sedimentation thereof, and the like.Type: ApplicationFiled: July 24, 2013Publication date: April 17, 2014Inventors: Taito NISHINO, Tatsuro KANAKI, Ayako OTANI, Koichiro SARUHASHI, Misayo Tomura, Takehisa IWAMA, Masato HORIKAWA, Norio NAKATSUJI, Tomomi OTSUJI
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Publication number: 20140106366Abstract: The present invention relates to methods for determining the efficiency of an ion channel ligand comprising (a) contacting a cell expressing the ion channel with (i) plasma of an animal and (ii) the ion channel ligand and (b) determining the effect of the ion channel ligand on the cell.Type: ApplicationFiled: September 4, 2013Publication date: April 17, 2014Applicant: SANOFIInventors: Thomas LICHER, Hans-Willi JANSEN, Ursula SCHINDLER, Stefan SCHAEFER
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Publication number: 20140105887Abstract: Provided herein are methods of modulating IL-33 activity, e.g., for the purpose of treating immune diseases and conditions, as well as methods of screening for compounds capable antagonizing IL-33 signaling.Type: ApplicationFiled: August 9, 2013Publication date: April 17, 2014Applicant: Merck Sharp & Dohme Corp.Inventors: Alissa A. Chackerian, Robert A. Kastelein
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Publication number: 20140106365Abstract: The present invention provides compositions and methods of use in investigations of the formation of multiprotein assemblies implicated in disease. Also provided are assays for screening candidate compounds of potential utility in preventing and/or treating such diseases by preventing the assembly of or disrupting the function of multiprotein assemblies.Type: ApplicationFiled: July 24, 2013Publication date: April 17, 2014Applicant: Prosetta Antiviral, Inc.Inventors: Vishwanath R. LINGAPPA, Debendranath Dey
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Patent number: 8697359Abstract: 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: October 15, 2013Date of Patent: April 15, 2014Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventor: Feng Zhang
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Patent number: 8697729Abstract: Disclosed are methods and compositions for modulating the function of transcription factors, especially transcription factors that recruit epigenetic regulators (histone modifying enzymes) to specific DNA promoters. The targeted transcription factors include but are not limited to the myocyte enhancing factor (MEF2), the forkhead/winged helix transcription factor FOXP3 and the transcription factor GATA3. Also disclosed are small molecule modulators of MEF2 and its associated factors that include but not limited to histone deacetylases (HDACs), p300/CBP and Cabin1 and the therapeutic applications thereof.Type: GrantFiled: November 5, 2009Date of Patent: April 15, 2014Assignee: University of Southern CaliforniaInventors: Lin Chen, Nimanthi Jayathilaka, Aidong Han, Nicos Petasis