Patents Assigned to The Salk Institute
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Patent number: 7510637Abstract: An electrochemical apparatus 1 permits electric-field-assisted fluidic assembly of objects 2 on a patterned silicon substrate 11 by means of electrical addressing. Charged objects 2 such as beads and live cells are moved electrokinetically, like as in electrophoresis, through a solution, typically water 3, towards a micro-patterned charged semiconductor electrode, such as a silicon electrode 11 patterned with silicon dioxide, silicon nitride or agarose gel. The charged objects 2 are thus localized and assembled, most typically into arrays of multiple or single particles, in accordance with the patterning of the electrode 11. Correlating with theoretical predictions, negatively charged polystyrene beads of 20 ?m diameter, or live mammalian cells of 20-30 ?m diameter, can be assembled and disassembled on 100 ?m feature size micro-patterned substrates by means of electrical addressing.Type: GrantFiled: December 8, 2001Date of Patent: March 31, 2009Assignees: The Regents of the University of California, The Salk Institute for Biological StudiesInventors: Carrolee Barlow, Sangeeta N. Bhatia, Mihrimah Ozkan, Sadik C. Esener
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Patent number: 7501487Abstract: The present invention relates to novel receptor polypeptides, which, upon interaction with certain ligands, or activation by certain compounds, modulate transcription of certain genes by binding to cognate response elements associated with promoters of such genes. The novel receptors of the invention modulate transcription in the presence of retinoid compounds. The receptors of the present invention differ significantly from known retinoic acid receptors, in protein primary sequence and in responsiveness to exposure to various retinoids. The invention provides DNAs encoding the novel receptors, expression vectors for expression of the receptors, cells transformed with such expression vectors, cells co-transformed with such expression vectors and with reporter vectors to monitor modulation of transcription by the receptors, and methods of using such co-transformed cells in screening for compounds which are capable, directly or indirectly, of activating the receptors.Type: GrantFiled: June 5, 1995Date of Patent: March 10, 2009Assignee: The Salk Institute for Biological StudiesInventors: David J. Mangelsdorf, Ronald M. Evans
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Patent number: 7498300Abstract: CRF peptide analogs that bind to CRFR1 with an affinity far greater than they bind to CRFR2. These analogs exhibit CRF agonist activity. One exemplary analog that may be made by solid-phase synthesis is (cyclo 31-34)[Ac-Pro4, D-Phe12, Nle21,38, Glu31, Lys34]-r/hCRF(4-41).Type: GrantFiled: January 22, 2004Date of Patent: March 3, 2009Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wyle W. Vale, Jr., Marilyn H. Perrin, Jozsef Gulyas
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Patent number: 7499572Abstract: A method for determining if a first pixel and a second pixel belong to a same surface includes: determining a spatial-difference value for the first pixel and the second pixel; determining one or more vision-difference values for the first pixel and the second pixel; determining, from the spatial-difference value, an initial same-surface probability value for if the first pixel and the second pixel belong to the same surface; determining, from the one or more vision-difference values, a first vision-difference probability value for if the first pixel and the second pixel belong to the same surface; determining, from the spatial-difference value and the one or more vision-difference values, a second vision-difference probability value; determining, from the initial same-surface probability value, the first vision-difference probability value and the second vision-difference probability value, an improved same-surface probability value for if the first pixel and the second pixel belong to the same surface.Type: GrantFiled: June 29, 2004Date of Patent: March 3, 2009Assignee: The Salk Institute for Biological StudiesInventors: Ione Fine, Geoffrey M. Boynton
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Patent number: 7485434Abstract: In accordance with the present invention, it has been discovered that glucose and incretin hormones promote pancreatic islet cell survival via the calcium and cAMP dependent induction, respectively, of the transcription factor CREB. Specifically, a signaling module has been identified which mediates cooperative effects of calcium and cAMP on islet cell gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a cytoplasmic CREB coactivator. The module comprises a cAMP regulated snf1-like kinase called SIK2 and the calcium regulated phosphatase calcineurin, both of which associate with TORC2 in the cytoplasm. TORC2 is repressed under basal conditions through a phosphorylation dependent interaction with 14-3-3 proteins. cAMP and calcium signals stimulate CREB target gene expression via complementary effects on TORC2 dephosphorylation; cAMP disrupts TORC2-associated activity of SIK2 or related family members, whereas calcium induces TORC2 dephosphorylation via calcineurin.Type: GrantFiled: April 4, 2006Date of Patent: February 3, 2009Assignee: The Salk Institute for Biological StudiesInventor: Marc R. Montminy
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Publication number: 20090013433Abstract: This invention provides recombinant cells and transgenic plants that display selectively increased or decreased response to brassinosteroids, resulting in increased yield. Methods of modulating brassinosteroid responses, and of modulating plant phenotypes, are provided.Type: ApplicationFiled: January 9, 2008Publication date: January 8, 2009Applicant: The Salk Institute for Biological StudiesInventors: Xuelu Wang, Joanne Chory
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Publication number: 20080299148Abstract: Antitoxin and vaccine compositions based on nodavirus VLPs are provided. Anthrax antitoxin and vaccine compositions are provided. Methods of treating toxins with VLP-based antitoxins are provided. Methods of raising an immune response with immunogen decorated VLPs are provided.Type: ApplicationFiled: February 14, 2008Publication date: December 4, 2008Applicants: The Salk Institute for Biological Studies, The Scripps Research InstituteInventors: John Young, Anette Schneemann, Marianne Manchester, Kelly Dryden, John M. Marlett, Darly Joseph Manayani, Godfrey Jonah Anderson Rainey, Vijay Reddy, Marc E. Siladi, Heather M. Scobie, Diane Thomas, Mark Yeager
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Publication number: 20080292591Abstract: This invention provides model systems for study of tumors. Model cells and model animals are prepared to mimic characteristics of natural clinical tumors. The tumor models can be contacted with putative modulators to screen for therapeutics and to help understand tumorigenic processes. Model animals can include model cells, closely correlated to the characteristics of clinical tumors, in an environment closely mimicking that of the tumors in patients. Thus, the animal models are highly representative for use in clinical and pharmacological studies.Type: ApplicationFiled: March 5, 2008Publication date: November 27, 2008Applicant: The Salk Institute for Biological StudiesInventors: Tomotoshi Marumoto, Inder Verma, Yasushi Soda, Yifeng Xia
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Publication number: 20080260638Abstract: SRIF peptide antagonists, which are selective for SSTR2 in contrast to the other cloned SRIF receptors and which bind with high affinity to the cloned human receptor SSTR2 but do not activate the receptor, have many useful functions. Because they do not bind with significant affinity to SSTR1, SSTR3, SSTR4 or SSTR5, their administration avoids potential undesirable side effects. Because they block the receptor function, they can be used therapeutically to block certain physiological effects which SSTR2 mediates. By incorporating radioiodine or the like in these SSTR2-selective SRIF antagonists, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, highly radioactive moieties can be N-terminally coupled, complexed or chelated thereto.Type: ApplicationFiled: October 15, 2007Publication date: October 23, 2008Applicant: The Salk Institute for Biological StudiesInventors: Jean E.F. Rivier, Judit Erchegyi, Jean Claude Reubi, Helmut R. Maecke
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Patent number: 7439027Abstract: Farnesyl pyrophosphate, the metabolically active form of farnesol, is a key precursor in the synthesis of cholesterol, carotenoids, steroid hormones, bile acids and other molecules involved in cellular growth and metabolism. A nuclear receptor has been identified that is transcriptionally activated by farnesol and related molecules. This novel signaling pathway can be modulated by the use of key metabolic intermediates (or analogs and/or derivatives thereof) as transcriptional regulatory signals.Type: GrantFiled: April 28, 2006Date of Patent: October 21, 2008Assignees: The Salk Institute for Biological Studies, Ligand Pharmaceuticals, Inc., United States of AmericaInventors: Ronald M Evans, Barry M Forman, Cary A Weinberger
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Patent number: 7413853Abstract: In accordance with the present invention, there are provided methods for modulating Phase II conjugating enzymes such as, for example, UGTs. Phase II conjugating enzymes such as UGTs function in concert with Phase I monooxygenase enzymes such as cytochrome P450 enzymes (CYPs) to eliminate steroids and xenobiotics. Nuclear receptors SXR/PXR and CAR are xenosensors regulating expression of CYP genes such as CYP3A and 2B. The ability of this group of receptors to regulate expression of UGT in response to steroids and/or xenobiotics provides novel approaches for direct regulation/activation of a glucuronidation pathway, thereby providing methods to achieve physiologic homeostasis with respect to steroids and/or xenobiotics. SXR/PXR and CAR regulation/activation of UGT represents the first evidence of receptors that can transduce/transactivate both Phase I and Phase II adaptive hepatic response. In another aspect, the present invention also provides transgenic rodents expressing one or more of SXR, CAR or PXR.Type: GrantFiled: July 9, 2002Date of Patent: August 19, 2008Assignee: The Salk Institute for Biological StudiesInventors: Ronald M. Evans, Wen Xie
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Patent number: 7384759Abstract: The invention provides crystalline O-methyltransferases and isolated non-native O-methyltransferases as well as sets of their structural coordinates. Also provided are methods of predicting the activity or substrate specificity of putative O-methyltransferases, methods of identifying potential substrates of O-methyltransferases, and methods of identifying potential inhibitors of methyltranferases.Type: GrantFiled: December 11, 2001Date of Patent: June 10, 2008Assignees: The Salk Institute for Biological Studies, The Samuel Roberts Noble FoundationInventors: Joseph P. Noel, Chloe Zubieta, Richard Dixon
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Patent number: 7371577Abstract: A gene activation/inactivation and site-specific integration system has been developed for mammalian cells. The invention system is based on the recombination of transfected sequences by FLP, a recombinase derived from Saccharomyces. In several cell lines, FLP has been shown to rapidly and precisely recombine copies of its specific target sequence. For example, a chromosomally integrated, silent ?-galactosidase reporter gene was activated for expression by FLP-mediated removal of intervening sequences to generate clones of marked cells. Alternatively, the reverse reaction can be used to target transfected DNA to specific chromosomal sites. These results demonstrate that FLP can be used, for example, to mosaically activate or inactivate transgenes for a variety of therapeutic purposes, as well as for analysis of vertebrate development.Type: GrantFiled: July 18, 2005Date of Patent: May 13, 2008Assignee: The Salk Institute for Biological StudiesInventors: Geoffrey M. Wahl, Stephen V. O'Gorman
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Patent number: 7361483Abstract: In accordance with the present invention, a novel aromatic prenyltransferase, Orf2 from Streptomyces sp. strain CL190, involved in naphterpin biosynthesis has been identified and the structure thereof elucidated. This prenyltransferase catalyzes the formation of a C—C bond between a prenyl group and a compound containing an aromatic nucleus, and also displays C—O bond formation activity. Numerous crystallographic structures of the prenyltransferase have been solved and refined, e.g., (1) prenyltransferase complexed with a buffer molecule (TAPS), (2) prenyltransferase as a binary complex with geranyl diphosphate (GPP) and Mg2+, and prenyltransferase as ternary complexes with a non-hydrolyzable substrate analogue, geranyl S-thiolodiphosphate (GSPP) and either (3) 1,6-dihydroxynaphthalene (1,6-DHN), or (4) flaviolin (i.e., 2,5,7-trihydroxy-1,4-naphthoquinone, which is the oxidized product of 1,3,6,8-tetrahydroxynaphthalene (THN)). These structures have been solved and refined to 1.5 ?, 2.25 ?, 1.95 ? and 2.Type: GrantFiled: January 27, 2006Date of Patent: April 22, 2008Assignees: The Salk Institute for Biological Studies, Toudai TLO, Ltd.Inventors: Tomohisa Kuzuyama, Joseph P. Noel, Stephane P. Richard
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Patent number: 7358225Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of £ 10 nM of CRF occupy 350% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.Type: GrantFiled: August 26, 2003Date of Patent: April 15, 2008Assignee: The Salk Institute for Biological StudiesInventors: Marilyn H. Perrin, Ruoping Chen, Kathy A. Lewis, Wylie W. Vale, Jr., Cynthia J. Donaldson, Paul Sawchenko
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Patent number: 7314747Abstract: The present invention relates to isolated polynucleotides encoding a family of silencing mediators of retinoic acid and thyroid hormone receptor (SMRT) isoforms, including vertebrate and invertebrate isoforms thereof. The invention also relates to polypeptide SMRT co-repressors encoded by invention SMRT polynucleotides, and to peptide portions thereof that can modulate transcriptional potential of a nuclear receptor. In addition, the invention relates to chimeric molecules and to complexes containing a SMRT co-repressor or peptide portion thereof, to antibodies that specifically bind such compositions, and to methods for identifying an agent that modulates the repressor potential of a SMRT co-repressor.Type: GrantFiled: March 10, 2000Date of Patent: January 1, 2008Assignee: The Salk Institute for Biological StudiesInventors: Ronald M. Evans, J. Don Chen, Peter Ordentlich, Michael R. Downes
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Patent number: 7312031Abstract: The present invention relates to the use of an alpha complementation assay as a quick, effective, and safe method for the detection of cell fusion mediated by viral proteins. Additionally, the method disclosed herein permits the identification of inhibitors of cell fusion using an alpha complementation assay.Type: GrantFiled: December 4, 2003Date of Patent: December 25, 2007Assignee: The Salk Institute for Biological StudiesInventors: Carsten Muenk, Anne Holland, Nathaniel Landau
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Patent number: 7288385Abstract: The Smek (Suppressor of mek null) gene is described and characterized. Smek acts in the stress response pathway of animals by binding to and enhancing the transcription of FOXO, thereby providing the link between the stress response pathway and the insulin/IGF-1 pathway. Given the link between both the stress response pathway and the insulin/IGF-1 pathway and longevity, Smek1 represents an essential target for modulation of life span and the stress response. Methods of increasing life span and stress tolerance by modulation of Smek activity are disclosed, as are screening methods for identifying compounds that modulate Smek activity. In addition, recombinant animals expressing the Smek gene that have a longer life span and enhanced stress tolerance, and methods of using the Smek genet to modulate both longevity and stress tolerance, are described.Type: GrantFiled: June 24, 2005Date of Patent: October 30, 2007Assignee: The Salk Institute for Biological StudiesInventors: Hui Ma, Tony Hunter, Suzanne C. Wolff, Andrew Dillin
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Patent number: 7285380Abstract: The present invention comprises crystalline polyketide synthases, isolated non-native polyketide synthases having the structural coordinates of said crystalline polyketide synthases, and nucleic acids encoding such non-native polyketide synthases. Also disclosed are methods of producing mutant polyketide synthases, and methods of altering the activity and/or substrate specificity of putative polyketide synthases.Type: GrantFiled: December 14, 2001Date of Patent: October 23, 2007Assignee: The Salk Institute for Biological StudiesInventors: Joseph P. Noel, Michael B. Austin, Marianne E. Bowman
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Patent number: 7286712Abstract: A method and apparatus for efficiently encoding images using a set of non-orthogonal basis functions, thereby allowing reduction of file size, shorter transmission time, and improved accuracy. The non-orthogonal basis functions include homogenous color basis functions, luminance-encoding basis functions that have luminance edges and chromatic basis functions that exhibit color opponency. Some of the basis functions are non-orthogonal with respect to each other. Using these basis functions, a source vector is calculated to provide a number of coefficients, each coefficient associated with one basis function. The source vector is compressed by selecting a subset of the calculated coefficients, thereby providing an encoded vector. Because the method is highly efficient, the image data is substantially represented by a small number of coefficients. In some embodiments, the non-orthogonal basis functions include two or more classes. A wavelet approach can also be utilized.Type: GrantFiled: March 21, 2005Date of Patent: October 23, 2007Assignee: The Salk Institute for Biological StudiesInventors: Te-Won Lee, Thomas Wachtler, Terrence J. Sejnowski