Synthesis Of Polynucleotides Or Oligonucleotides Patents (Class 536/25.3)
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Publication number: 20120225088Abstract: Aptamers and improved aptamers are provided with enhanced efficacy for binding to target molecules in vivo or for treating cancer or other diseases. Such improvements in aptamers are provided that enhance in vivo efficacy such as binding to the target molecule or enhancing anti-cancer activity. Such improvements also include stability to serum nucleases, reduced binding to a soluble form of the target molecule, increased avidity, affinity or specificity to the target molecule on a cell surface, increased lifetime in circulation, or any combination of the foregoing. Improvements are provided by truncation, multimerization, including at least one non-natural nucleic acid, adding a 3? or 5? polyethylene glycol, or any combination thereof. Aptamers for treatment of autoimmune diseases are also provided.Type: ApplicationFiled: November 16, 2010Publication date: September 6, 2012Inventors: David A. Scheinberg, Prabodhika Mallikaratchy
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Patent number: 8258199Abstract: Compounds represented by the following structural formulas can be used as photoacid generators: Such compounds are useful, for example, in fabricating arrays of polymers.Type: GrantFiled: May 9, 2011Date of Patent: September 4, 2012Assignee: Affymetrix, Inc.Inventors: Glenn H. McGall, Andrea Cuppoletti
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Publication number: 20120220497Abstract: Methods and devices are provided for manipulating droplets on a support using surface tension properties, moving the droplets along a predetermined path and merging two droplets together enabling a number of chemical reactions. Disclosed are methods for controlling the droplets volumes. Disclosed are methods and devices for synthesizing at least one oligonucleotide having a predefined sequence. Disclosed are methods and devices for synthesizing and/or assembling at least one polynucleotide product having a predefined sequence from a plurality of different oligonucleotides having a predefined sequence.Type: ApplicationFiled: November 3, 2010Publication date: August 30, 2012Applicant: Gen 9, Inc.Inventors: Joseph Jacobson, Larry Li-Yang Chu, Senthil Ramu
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Patent number: 8252910Abstract: Nucleic acid compositions, methods of making and using such compositions that comprise modular functional groups that can be configured to provide desired functionality to different nucleotide types through a swappable and preferably non-covalent linkage component. Such compositions are useful in a variety of applications including nucleic acid analyses.Type: GrantFiled: November 18, 2009Date of Patent: August 28, 2012Assignee: Pacific Biosciences of California, Inc.Inventors: Jonas Korlach, Jeffrey Wegener
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Publication number: 20120214868Abstract: A modified L-nucleic acid, containing an L-nucleic acid part conjugated to a non-L-nucleic acid part is described. The conjugate has extended retention time in and demonstrates a delayed elimination from an organism.Type: ApplicationFiled: March 26, 2012Publication date: August 23, 2012Inventors: Christian Lange, Bernd Eschgfäller, Sven Klussmann
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Patent number: 8247540Abstract: There is disclosed nucleotides and nucleotide analogs having a protecting or “caging” group. There is further disclosed oligonucleotides and oligonucleotides analogs formed having a protecting or “caging” group. There is further disclosed a method for decaging the nucleotides and nucleotide analogs having a protecting or “caging” group and oligonucleotides and oligonucleotide analogs having a caging group.Type: GrantFiled: December 5, 2008Date of Patent: August 21, 2012Inventor: Alexander Deiters
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Publication number: 20120208720Abstract: Provided are linkers suitable for preparing a conjugate of a nucleic acid and a peptide as a translation product thereof in a reconstituted cell-free translation system in genotype-phenotype mapping (display methods), said linkers comprising a single-stranded structure region having a side chain base pairing with the base at the 3?-end of an mRNA at one end and a peptidyl acceptor region containing an amino acid attached to an oligo RNA consisting of a nucleotide sequence of ACCA via an ester bond at the other end, characterized in that the ester bond is formed by using an artificial RNA catalyst. Also provided are display methods using [mRNA]-[linker]-[peptide] conjugates assembled via such linkers.Type: ApplicationFiled: October 21, 2010Publication date: August 16, 2012Inventors: Kenji Kashiwagi, Patrick C. Reid
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Publication number: 20120208705Abstract: Artificial transposon sequences having code tags and target nucleic acids containing such sequences. Methods for making artificial transposons and for using their properties to analyze target nucleic acids.Type: ApplicationFiled: February 10, 2011Publication date: August 16, 2012Inventors: Frank J. Steemers, Kevin Gunderson, Thomas Royce, Natasha Pignatelli
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Patent number: 8236499Abstract: Provided are methods and compositions for the production of linear single-stranded nucleic acids, which can be used as templates in high-throughput sequencing systems. Also provided are methods and compositions for the production of closed single-stranded nucleic acid loops, which can be used as templates in high-throughput sequencing systems.Type: GrantFiled: March 27, 2009Date of Patent: August 7, 2012Assignee: Pacific Biosciences of California, Inc.Inventors: Pranav Patel, Keith Bjornson, Kevin Travers, Cheryl Heiner
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Publication number: 20120192317Abstract: The invention provides methods for selecting nucleotide sequences that yield dsRNA-mediated gene suppression in a target organism and enable their uptake by the target organism. The invention further provides expression constructs that confer stabilized expression of such sequences in a transgenic host cell, and methods for their use. Also provided are organisms, cells and tissues prepared by a method of the invention.Type: ApplicationFiled: November 28, 2011Publication date: July 26, 2012Inventors: GREGORY R. HECK, Tichafa R. I. Munyikwa, Jean C. Goley, James K. Roberts, Scott C. Johnson, Ty T. Vaughn
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Patent number: 8227431Abstract: The present patent application relates to the novel nucleoside derivatives and novel intermediates, which are useful to antiviral, anti tumor and immunomodulatory activity, method of treating diseases, conditions and/or disorders modulated by viral infections with them, and processes for preparing them.Type: GrantFiled: March 12, 2009Date of Patent: July 24, 2012Assignee: Hetero Drugs LimitedInventors: Bandi Parthasaradhi Reddy, Vedula Manohar Sharma, Kura Rathnakar Reddy, Musku Madhanmohan Reddy, Jennepalli Sreenu, Aryasomayajula Ratnakar
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Publication number: 20120184724Abstract: A nucleoside monomer that is protected by a thionocarbamate protecting group and contains one or more 2H, 13C, or 15N isotopes in the ribose and/or base part is provided, as well as a method for making a polynucleotide that uses the same. Also provided is a polynucleotide synthesis method that employs a diamine to deprotect a protected polynucleotide.Type: ApplicationFiled: December 28, 2011Publication date: July 19, 2012Applicant: AGILENT TECHNOLOGIES, INC.Inventors: Agnieszka B. Sierzchala, Brian Phillip Smart, Douglas J. Dellinger, Geraldine Dellinger, Joel Myerson, Zoltan Timar
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Publication number: 20120178647Abstract: A method of designing a multi-zinc-finger polypeptide predicted to bind to a sequence of interest that has at least three subsites includes the steps of: a) providing a nucleotide sequence of interest having first, second, and third consecutive subsites, wherein each of the first and third subsites are adjacent to the second subsite; b) identifying first and second adjacent zinc finger polypeptide sequences previously shown to bind to the first and second subsites in the context of a multi-zinc finger polypeptide; c) identifying a third zinc finger polypeptide previously shown to bind to a third subsite adjacent to the second subsite when present in the context of a multi-zinc finger polypeptide adjacent to the second zinc finger polypeptide; and d) combining the first, second, and third zinc finger polypeptide sequences in linear order, thereby designing a multi-zinc finger polypeptide predicted to bind to the sequence of interest.Type: ApplicationFiled: August 3, 2010Publication date: July 12, 2012Applicant: THE GENERAL HOSPITAL CORPORATIONInventors: J. Keith Joung, Jeffry D. Sander
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Patent number: 8216810Abstract: The present invention provides systems and methods for determining the presence or absence of one or more target nucleic acid sequences in a sample. Also provided are kits comprising these systems, and uses of these systems in such applications as determining the presence or absence of at least one target nucleic acid sequence in a sample, detecting microorganism transcripts and host transcripts, differentiating microorganism transcripts from host transcripts, screening blood products, assaying a food product for contamination, assaying a sample for environmental contamination, detecting genetically-modified organisms, biodefense, forensics, and genetic-comparability studies. The present invention further provides a complex that includes a target nucleic acid sequence, a capture nucleic acid, and a reporter nucleic acid.Type: GrantFiled: April 27, 2004Date of Patent: July 10, 2012Assignee: The Trustees of Columbia University in the City of New YorkInventors: W. Ian Lipkin, Thomas Briese, Gustavo Palacios, Omar Jabado
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Publication number: 20120174256Abstract: An object of the present invention is to identify sequence features of the 5? UTR, which are involved in changes in the translational state of plants under environmental stresses, and to provide a recombinant DNA molecule, an expression vector, a transformant, and the like, having the above sequence features.Type: ApplicationFiled: August 19, 2010Publication date: July 5, 2012Inventors: Ko Kato, Shigehiko Kanaya, Hideyuki Matsuura, Shinya Takenami, Tatsuya Nosho, Yuhki Kubo, Kiyotaka Ueda
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Publication number: 20120164692Abstract: The present invention relates to an annealing control primer for improving annealing specificity in nucleic acid amplification and its applications to all fields of nucleic acid amplification-involved technology. The present primer comprises (a) a 3?-end portion having a hybridizing nucleotide sequence substantially complementary to a site on a template nucleic acid to hybridize therewith; (b) a 5?-end portion having a pre-selected arbitrary nucleotide sequence; and (c) a regulator portion positioned between said 3?-end portion and said 5?-end portion comprising at least one universal base or non-discriminatory base analog, whereby said regulator portion is capable of regulating an annealing portion of said primer in association with annealing temperature.Type: ApplicationFiled: February 23, 2012Publication date: June 28, 2012Applicant: Seegene, Inc.Inventor: Jong-Yoon CHUN
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Patent number: 8206952Abstract: In a method for synthesizing a long nucleic acid molecule, a first immobilized nucleic acid has a first 5? region and a first 3? region and a second immobilized nucleic acid has a second 5? region and a second 3? region. The second 3? region and the first 5? region have identical nucleic acid sequences. An oligonucleotide is hybridized to the first 3? region, extending the hybridized oligonucleotide and producing a first extension product having a 3? region that is complementary to the first 5? region. The 3? region of the first extension product is hybridized to the second 3? region, extending the 3? region of the first extension product and producing a synthesized nucleic acid molecule having a 3? region that is complementary to the second 5? region, wherein the synthesized nucleic acid molecule has a sequence complementary to the first and second 3? and 5? regions.Type: GrantFiled: February 1, 2011Date of Patent: June 26, 2012Assignee: Massachusetts Institute of TechnologyInventors: Peter A. Carr, Brian Y. Chow, Joseph M. Jacobson, David W. Mosley, Christopher Emig
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Publication number: 20120157324Abstract: Disclosed are methods and compositions of assessing one or more statuses of a subject. Also disclosed are methods and compositions of identifying status biomarkers associated with a status of a subject. Also disclosed are sets of one or more status biomarkers. Also disclosed are methods and compositions of producing status biomarker capture probes.Type: ApplicationFiled: August 17, 2010Publication date: June 21, 2012Applicant: YALE UNIVERSITYInventors: Paul M. Lizardi, Sebastian Szpakowski, Min Chen, Jose Costa, Hongyu Zhao
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Publication number: 20120159670Abstract: The present invention is in the field of plant molecular biology and provides methods for production of high expressing seed-specific and/or seed-preferential promoters and the production of plants with enhanced seed-specific and/or seed-preferential expression of nucleic acids wherein nucleic acid expression enhancing nucleic acids (NEENAs) are functionally linked to said promoters and/or introduced into plants.Type: ApplicationFiled: August 11, 2010Publication date: June 21, 2012Applicant: BASF PLANT SCIENCE COMPANYInventors: Josef Martin Kuhn, Linda Patricia Loyall, Malte Siebert, Elke Duwenig
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Patent number: 8202982Abstract: Methods for obtaining antisense oligonucleotides with activity against a desired target are provided. Methods of identifying oligonucleotide sequence motifs which are predictive of antisense oligonucleotide activity are provided, as are motifs identified according to this method. Methods of selecting effective antisense oligonucleotide sequences and effective antisense target sequences are provided, as are sequences selected according to these methods. In other methods of the invention, oligonucleotides are designed to hybridize to target sequences containing one or more activity-enhancing motifs. Antisense oligonucleotides designed according to these methods are also provided.Type: GrantFiled: September 10, 2009Date of Patent: June 19, 2012Assignee: Isis Phramaceuticals, Inc.Inventors: Susan M. Freier, Olga Matveeva, Alexander Tsodikov, Michael C. Giddings, Jacqueline R. Wyatt
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Patent number: 8198418Abstract: A novel nucleoside triphosphate derivative, a nucleic acid probe, and a multilabeled nucleic acid probe that can detect a target nucleic acid conveniently and with high sensitivity, as well as a method for producing the multilabeled nucleic acid probe, and a method for detecting a target nucleic acid using the multilabeled nucleic acid probe or the nucleic acid probe. A target nucleic acid can be detected conveniently and with high sensitivity by using a transglutaminase (TGase), and by using a multilabeled nucleic acid probe in which a plurality of labeling portions have been introduced in advance by covalent binding, or by introducing a plurality of labeling portions by covalent binding into a nucleic acid probe that has been hybridized with the target nucleic acid.Type: GrantFiled: July 22, 2009Date of Patent: June 12, 2012Assignees: Kyushu University, National University Corporation, The University of Tokushima, Hitachi Aloka Medical, Ltd.Inventors: Noriho Kamiya, Sumihare Noji, Yoshiyuki Hiraishi
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Publication number: 20120142011Abstract: The present invention pertains to the use of at least one abasic modification within the first 8 nucleotide positions of the 5? region of the antisense strand of a small interfering nucleic acid (siNA) molecule for reducing off-target effects. Provided are suitable modified siNAs, compositions and methods for producing respective siNAs, as well as kits comprising respective siNAs.Type: ApplicationFiled: June 11, 2010Publication date: June 7, 2012Inventors: Peter Hahn, Eric fat Lader, Wolfgang Bielke, Alexander Azzawi, Jie Kang
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Patent number: 8193335Abstract: The present invention relates to methods for producing reporter molecules suitable for the detection of analytes, e.g. nucleic acids. Further, the present invention relates to methods and regions for detecting analytes.Type: GrantFiled: October 31, 2007Date of Patent: June 5, 2012Assignee: baseclick GmbHInventors: Thomas Carell, Anja Schwögler
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Patent number: 8193336Abstract: A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.Type: GrantFiled: June 19, 2009Date of Patent: June 5, 2012Inventor: Robert S. Foote
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Patent number: 8193337Abstract: A process for the preparation of an oligonucleotide having at least one phosphate internucleotide linkage I provided. The process comprises the steps of: a) forming a nascent oligonucleotide comprising a phosphorus (III) internucleotide linkage; and b) oxidation of the nascent oligonucleotide with aqueous iodine solution thereby to form a phosphorus (V) internucleotide linkage; wherein the oxidation is carried out in the presence of a base, the conjugate acid of said base having a pKa higher than the pKa of the conjugate acid of pyridine. Preferably the base is N-methylimidazole.Type: GrantFiled: July 14, 2008Date of Patent: June 5, 2012Assignee: Avecia Biotechnology, Inc.Inventor: Nanda D. Sinha
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Patent number: 8188269Abstract: The present invention relates to improved covalent coupling of two or more entities such as biomolecules, polymer compositions, organic/inorganic molecules/materials, and the like, including their combinations, through one or more novel reactive groups attached to linker groups of 2-1000 atoms length. The present invention also contemplates the use of bifunctional bridge molecules to link two or more entities, wherein the functional groups of the bridge molecules are the novel reactive groups of the present invention.Type: GrantFiled: May 12, 2008Date of Patent: May 29, 2012Assignee: Luminex CorporationInventors: Ananda G. Lugade, Kurt D. Hoffacker, Adam J. Jenkins, Karri L. Michael-Ballard, Leonid Patsenker, Ewald Terpetschnig, Veronica D. Thomason, Ralph McDade
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Publication number: 20120128761Abstract: Disclosed are lipophilic polynucleotide conjugates including polynucleotide-cholesterol conjugates and methods of delivering therapeutic polynucleotides to a mammalian cell or patient in need of treatment using said conjugates. The disclosure further provides methods of synthesizing the lipophilic polynucleotide conjugates. The conjugates are designed to mimic or target cellular miRNAs. The lipophilic moiety, such as cholesterol or cholesterol derivative, is spaced from the polynucleotide by a substantially linear hydrocarbon group. Due to an absence of significantly polar groups and/or exchangeable protons in the vicinity of the lipophilic moiety, the interaction between the lipophilic moiety and cell membranes is enhanced to provide for efficient entry into cells.Type: ApplicationFiled: May 5, 2010Publication date: May 24, 2012Applicant: MiRagen Therapeutics, Inc.Inventors: Kurt Vagle, William S. Marshall
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Publication number: 20120130060Abstract: This invention may be used in human and veterinary medicine for the creation of a drug that is effective in the treatment of oncological illnesses in animals and humans. Summary of the Invention Modified antisense oligonucleotides with anticancer properties and methods of obtaining them, distinct in that in the capacity of oligonucleotides, a mixture of the products of the hydrolysis of polynucleotides is used, and modification is done through changing the molecular charges of the nucleotide bases to their opposites; they thereby obtain antisense properties. The hydrolysis of polynucleotides leads to the application of natural or synthetic nucleases, acid or alkaline hydrolysis, and modification of the structure through the acylation of the amino groups of mononucleotides in the structure of oligonucleotides by dicarboxylic acids or through their alkylation by halogen-carboxylic acids.Type: ApplicationFiled: February 1, 2011Publication date: May 24, 2012Inventors: Artur Martynov, Boris S. Farber, Sonya Sophya Farber
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Publication number: 20120129704Abstract: Methods of generating nucleic acid fragments of substantially uniform length from sample nucleic acids comprising linearly stretching the sample nucleic acids over a substrate having a plurality of cleavage regions separated by relatively consistent distances, cleaving the linearly stretched sample nucleic acids at the cleavage regions, and collecting the resulting nucleic acid fragments. The method may further include collecting and concentrating the resultant nucleic acid fragments of substantially uniform length.Type: ApplicationFiled: April 2, 2010Publication date: May 24, 2012Applicant: Illumina, Inc.Inventors: Kevin Gunderson, Michal Lebl, David L. Heiner
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Patent number: 8183355Abstract: Method for the synthesis of nucleotide derivatives wherein molecules of interest are grafted on the oligonucleotide with the help of a “click chemistry” reaction between an azide function on the molecule of interest and an alkyne function on the oligonucleotide, or between an alkyne function on the molecule of interest and an azide function on the oligonucleotide. Intermediate molecules, notably alkyne functionalized oligonucleotides, grafted oligonucleotides, azide functionalized oligonucleotides, oligonucleotide micro arrays containing them and the use of those grafted oligonucleotides for biological investigation and for cell targeting.Type: GrantFiled: April 7, 2011Date of Patent: May 22, 2012Assignee: Centre National de la Recherche Scientifique (CNRS)Inventors: François Morvan, Albert Meyer, Jean-Jacques Vasseur, Sébastien Vidal, Jean-Pierre Cloarec, Yann Chevolot, Eliane Souteyrand
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Publication number: 20120123107Abstract: A nucleic acid cleavage complex is disclosed, which includes: a nanoparticle, a nucleic acid cleavage reagent, and a polynucleotide chain specifically recognizing a sequence of a target nucleic acid and having a first terminal and a second terminal opposite to the first terminal, wherein the first terminal is connected to the nanoparticle, the second terminal is connected to the nucleic acid cleavage reagent, and the first terminal sequence and the second terminal sequence are base-paired to make the polynucleotide chain form a hairpin. Also, a method for using the nucleic acid cleavage complex is also disclosed.Type: ApplicationFiled: November 3, 2011Publication date: May 17, 2012Applicant: National Cheng Kung UniversityInventors: Dar-Bin Shieh, Ying-Ying Li, Hung-Ching Lu
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Publication number: 20120122800Abstract: This invention provides a unique composition which includes a DNA dendrimer combined with siRNA molecule. Further, methods of preparing a composition which includes a DNA dendrimer combined with a siRNA molecule, methods of protecting a DNA dendrimer siRNA complex against degradation in body fluids, methods of protecting a DNA dendrimer against degradation in bodily fluids, and methods of delivering a DNA dendrimer into bodily fluids are provided.Type: ApplicationFiled: August 10, 2009Publication date: May 17, 2012Inventors: James Kadushin, Robert C. Getts
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Patent number: 8178360Abstract: Novel rhodamine dye compounds, labelled conjugates comprising the dyes are described, together with methods for their use. The dyes and labelled conjugates are useful as molecular probes in a variety of applications, such as in assays involving staining of cells, protein binding, and analysis of nucleic acids, such as hybridization assays and nucleic acid sequencing.Type: GrantFiled: May 16, 2007Date of Patent: May 15, 2012Assignee: Illumina Cambridge LimitedInventors: Colin Barnes, Nikolai Nikolaevich Romanov
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Publication number: 20120115164Abstract: Purified genes encoding a cytokine or composite cytokine from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding these molecules are provided. Methods of using said reagents and diagnostic kits are also provided.Type: ApplicationFiled: December 20, 2011Publication date: May 10, 2012Applicant: Schering CorporationInventors: Jacqueline C. Timans, Stefan Karl-Heinz Pflanz, Robert A. Kastelein, J. Fernando Bazan, Donna Rennick, Rene de Waal Malefyt, Jeanne Cheung
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Publication number: 20120115154Abstract: DNA oligomers comprising sequences that are absent from the genome of one or more organisms of interest are used as reference markers (RMs). The RMs are added to biological samples to “tag” and subsequently identify the samples as authentic and to distinguish tagged samples from samples obtained without said markers, for example, in forensic, medical, legal and other applications.Type: ApplicationFiled: October 17, 2011Publication date: May 10, 2012Inventor: Greg Hampikian
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Patent number: 8173620Abstract: The disclosure encompasses caged compounds such as caged nucleoside phosphoesters (caged nucleotides). In an embodiment, the caged nucleotides include compounds corresponding to those described by formula (I) that may be activated by two-photon excitation, and methods of synthesis of such compounds. 8-Bromo-7-hydroxyquinoline-caged ATP was synthesized and examined for its photochemistry as a biologically useful, temporally and spatially controlled ATP-releasing reagent. The combination of two-photon excitation hydrolysis and activation of caged ATP enables methods for finely focusing ATP activation at the sub-cellular level or to a greater depth of activation, thereby providing improved resolution of ATP-dependent processes at the cellular level.Type: GrantFiled: August 20, 2009Date of Patent: May 8, 2012Assignee: University of Georgia Research Foundation, Inc.Inventors: Timothy M. Dore, Yue Zhu, Khalilah G. Reddie, James D. Lauderdale
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Publication number: 20120110685Abstract: The present invention refers to methods for selectively recognizing a base pair in a DNA sequence by a polypeptide, to modified polypeptides which specifically recognize one or more base pairs in a DNA sequence and, to DNA which is modified so that it can be specifically recognized by a polypeptide and to uses of the polypeptide and DNA in specific DNA targeting as well as to methods of modulating expression of target genes in a cell.Type: ApplicationFiled: August 25, 2011Publication date: May 3, 2012Inventors: Ulla Bonas, Jens Boch, Sebastian Schornack, Thomas Lahaye
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Publication number: 20120107355Abstract: A method of quickly producing a vaccine for a biotype of pathogenic microorganism is described, where a nucleic acid molecule or fragment thereof is obtained from a biological sample from an animal exposed to the microorganism, a protective molecule is prepared based on the nucleic acid molecule of interest or fragment thereof, and administered to an animal which has been or is as risk of being exposed to the microorganism. A protective response to the biotype of the microorganism is obtained in the animal.Type: ApplicationFiled: October 19, 2011Publication date: May 3, 2012Applicant: HARRISVACCINES, INC.Inventors: Delbert Linn Harris, Matthew Erdman, Kurt Iver Kamrud, Jonathan Smith, John Dustin Loy, Lyric Colleen Bartholomay, Ed Scura
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Publication number: 20120107871Abstract: A method for generating human IgG1 antibodies with enhanced Fc effector function is disclosed. In practicing the method, an IgG1 Fc look-through mutagenesis (LTM) coding library directed at four receptor-contact regions of the Fc CH2 portion in human IgG1. Fc is expressed in a system in which the mutated Fc fragments are displayed on the surfaces of the expression cells. The fragments are then screened for altered binding affinity to a selected Fc receptor or other Fc-binding protein. The selected mutations may be used, in turn, to guide the selection of multiple substitutions in the construction of a walk-through mutation (WTM) library, for generating additional Fc fragment mutations with desired binding properties. The antibodies so produced have a variety of therapeutic and diagnostic applications.Type: ApplicationFiled: October 7, 2011Publication date: May 3, 2012Inventors: Roberto Crea, Guido Cappuccilli, Toshihiko Takeuchi, Arvind Rajpal, Ramesh Bhatt, Randy Shen
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Patent number: 8168776Abstract: The present invention provides methods and compositions for inhibiting gene expression using double stranded RNA molecules that are between 15 and 21 nucleotides in length and are complementary to a target gene sequence.Type: GrantFiled: March 6, 2003Date of Patent: May 1, 2012Assignee: Alnylam Pharmaceuticals, Inc.Inventors: Roland Kreutzer, Stefan Limmer
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Patent number: 8168777Abstract: Methods for treating nucleic acid including: (a) providing an alkali environment to a nucleic acid sample; (b) reacting the nucleic acid sample with a bisulphite reagent and incubating the reaction so as to form a treated nucleic acid sample where methylated nucleotides in the nucleic acid sample remain unchanged while unmethylated nucleotides are converted to another form; (c) removing unwanted reagents or diluents from the treated nucleic acid sample; and (d) carrying out de-sulphonation of the precipitated treated nucleic acid at a temperature from 70° C. to 95° C. by adjusting the precipitated treated nucleic acid to a pH of between 10 and less than 12.5 to remove sulphonate groups present on the treated nucleic acid and obtain a nucleic acid sample substantially free of sulphonate groups.Type: GrantFiled: March 27, 2009Date of Patent: May 1, 2012Assignee: Human Genetic Signatures Pty. Ltd.Inventors: Douglas Spencer Millar, Cassandra Jean Vockler, Neralie Ann Coulston
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Publication number: 20120101007Abstract: A sensor for detecting of an analyte in a solution phase comprises a plurality of functionalised silver nanoplates wherein a functionalising agent is directly bonded to the surfaces of the nanoplates. The nanoplates provide a detectable wavelength shift change in their local surface plasmon resonance spectrum in response to the binding of an analyte. Two or more of the nanoplates may be electromagnetically coupled.Type: ApplicationFiled: April 8, 2010Publication date: April 26, 2012Applicants: PROVOST FELLOWS AND SCHOLARS OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZEBETH NEA, NATIONAL UNIVERSITY OF IRELAND, GALWAYInventors: Damian Ahern, Margaret Brennan Fournet, Denise Charles, Stephen Michael Cunningham, Patrick Fournet, John Moffat Kelly, Deirdre Marie Ledwith, Muriel Celine Voisin
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Publication number: 20120100633Abstract: The present invention relates to new methods and reagents for coupling molecules by a Click reaction using a heterogeneous catalyst system.Type: ApplicationFiled: April 8, 2010Publication date: April 26, 2012Applicant: BASECLICK GMBHInventors: Antonio Manetto, Philipp Mathias Edwin Gramlich, Simon Warncke
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Patent number: 8163891Abstract: A process for the preparation of a poly(alkoxylated) oligonucleotide is provided. The process comprises reacting an oligonucleotide which has been purified by ultrafiltration with a poly(alkoxide) thereby to form a poly(alkoxylated) oligonucleotide. The poly(alkoxyalted) oligonucleotide may be separated from non-poly(alkoxyalted) oligonucleotide by ultrafiltration under denaturing conditions, such as the presence of organic solvents, for example, ethanol; the presence of urea; the addition of chaotropic salts, for example perchlorate and guanidinium salts; the presence of formamide; and the application of heat, for example a temperature of up to about 70° C.Type: GrantFiled: November 20, 2006Date of Patent: April 24, 2012Assignee: Avecia Biotechnology IncInventors: Nanda Dulal Sinha, Saied Shaikh, Satya Kuchimanchi
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Patent number: 8163897Abstract: 5-bromo-2?-deoxy-uridine (BrdU) labeled nucleotide triphosphates and nucleic acid probes are described herein. The BrdU labeled nucleotide triphosphates include a linker between the nucleotide triphosphate and the BrdU moiety. The linker can be cleavable or non-cleavable. The nucleotide triphosphates can be a ribonucleotide triphosphates, 2?-deoxyribonucleotide triphosphates or 2?,3?-dideoxyribonucleotide triphosphates. The nucleic acid probes can be used for in situ hybridization.Type: GrantFiled: March 1, 2011Date of Patent: April 24, 2012Assignee: Applied Biosystems, LLCInventors: Anilkumar R. Kore, Zhongting Hu
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Patent number: 8163524Abstract: The invention provides methods for detecting tumor-associated RNA in plasma, serum, and other bodily fluids. In particular, the invention provides methods for detecting translocated gene RNA, including fusion gene RNA, in plasma or serum or other bodily fluids.Type: GrantFiled: September 18, 2007Date of Patent: April 24, 2012Assignee: OncoMedx, Inc.Inventor: Michael S. Kopreski
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Publication number: 20120096583Abstract: The present invention provides a method for selecting an intron for enhanced expression of a nucleotide sequence encoding a polypeptide, comprising: a) determining a mean free energy value per base pair of one or more introns; b) determining a mean IMEter score of the one or more introns of (a); and c) selecting an intron having a mean free energy value per base pair of below about ?0.268 kcal/mol/bp and a mean IMEter score of at least about ?0.034/bp, thereby selecting an intron for enhanced expression of a nucleotide sequence encoding the polypeptide, wherein expression of a nucleotide sequence operably associated with the selected intron is enhanced as compared to expression of a nucleotide sequence not operably associated with an intron having a mean free energy value per base pair of below about ?0.268 kcal/mol/bp and a mean IMEter score of at least about ?0.034/bp.Type: ApplicationFiled: September 15, 2011Publication date: April 19, 2012Inventors: Kasimalai Azhakanandam, Thomas Z. McNeill
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Patent number: 8158774Abstract: The present invention relates to a simple, economical method for introducing substituent (I) at the 2?-hydroxyl group of the ribose of a ribonucleic acid derivative whose 3?-hydroxyl group and 5?-hydroxyl group are protected with a silicon protecting group, wherein WG1 represents an electron-withdrawing group: The invention also relates to a method for producing a ribonucleic acid derivative of formula (3), comprising the reaction of a ribonucleic acid derivative of formula (1) with a monothioacetal compound of formula (2) to produce the ribonucleic acid derivative of formula (3), using iodine as the reagent for halogenating the sulfur atom of the monothioacetal compound of formula (2) in the presence of an acid: In formulae (1), (2), and (3), Bz represents a nucleobase which may or may not have a protecting group; WG1 represents an electron-withdrawing group; R3 represents alkyl or aryl; and A represents a silicon substituent.Type: GrantFiled: August 1, 2007Date of Patent: April 17, 2012Assignee: Nippon Shinyaku Co., Ltd.Inventors: Hidetoshi Kitagawa, Kouichi Uetake
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Patent number: 8158341Abstract: A method is provided for identifying viral positive biological fluid donations in the fewest number of test cycles. The method comprises providing biological fluid donations and defining an n-dimensional matrix comprising a multiplicity of elements, each element being identified by a matrix notation comprising an index for each dimension of the array. Samples are taken from each fluid donation and mapped to a matrix element with each sample identified by its corresponding element's notation; n aliquots being taken from each sample and subpools formed from the aliquots with each subpool containing an aliquot from all samples mapped to elements in which one of the dimensional indices is fixed. Subpools are tested for viral indication and the dimensional index of each subpool that returns a positive viral indication is determined. The dimensional indices are combined to identify a subset of matrix elements that contain a viral positive sample.Type: GrantFiled: March 9, 2006Date of Patent: April 17, 2012Assignee: Baxter International Inc.Inventors: Lorraine B. Peddada, Charles M. Heldebrant, Andrew J. Conrad, Peter Schmid
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Publication number: 20120088815Abstract: The present invention relates to a modified oligonucleotide, its preparation and application. The invention enables stabilizing the oligonucleotide by introducing a relatively small amount of modified nucleotide at specific UA/UA and/or CA/UG and/or UG/CA site of the oligonucleotide, therefore to decrease the modification-related cytotoxicity and compromising effects on the biological activity.Type: ApplicationFiled: March 30, 2010Publication date: April 12, 2012Applicant: BIOMICS BIOTECHNOLOGIES CO. LTDInventor: Zicai Liang