Labelled (e.g., Tagged With Radioactive Tracer, Fluorescent Marker, Intercalator, Etc.) Patents (Class 536/26.6)
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Patent number: 8338585Abstract: The present invention provides massively parallel oligonucleotide synthesis and purification for applications that utilize large collections of defined high-fidelity oligonucleotides (e.g., from about 101 to about 105 different sequences, generally between 25-160 bases in length).Type: GrantFiled: December 9, 2011Date of Patent: December 25, 2012Assignee: Affymetrix, Inc.Inventors: Glenn H. McGall, Robert G. Kuimelis
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Patent number: 8324358Abstract: Block copolymers labelled with molecular recognition units and comprising a hydrophobic block and a luminescent block are presented. A method of detecting biomolecules using such block copolymers is also presented. More specifically, the block copolymers of the present invention have the following Formula (I): wherein “A” is a hydrophobic block; “B” is a luminescent block; “C” is a hydrophilic block; “D” is a molecular recognition unit; “n” and “m” are integers ranging from 1 to 75; “x” is either 0 or an integer ranging from 1 to 75; and “Y” is either 0 or 1.Type: GrantFiled: May 26, 2006Date of Patent: December 4, 2012Assignee: McGill UniversityInventors: Hanadi Sleiman, Bingzhi Chen, Kim Metera
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Patent number: 8318436Abstract: The present invention provides a method and compositions for high throughput screening of genetically modified photosynthetic organisms for plasmic state. The present invention provides methods of producing one or more proteins, including biomass degrading enzymes in a plant. Also provided are the methods of producing biomass degradation pathways in alga cells, particularly in the chloroplast. Single enzymes or multiple enzymes may be produced by the methods disclosed. The methods disclosed herein allow for the production of biofuel, including ethanol.Type: GrantFiled: October 7, 2011Date of Patent: November 27, 2012Assignees: Sapphire Energy, Inc., The Scripps Research InstituteInventors: Stephen Mayfield, Bryan O'Neill, Michael Mendez, Yan Poon
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Patent number: 8304259Abstract: A labeling dye of the present invention includes a coloring portion comprising an organic EL-dye, a bonding portion to be bonded with a biomolecule and a spacer portion for linking the coloring portion and the bonding portion. The present invention provides a high incorporation ratio and also high fluorescence intensity in solid state.Type: GrantFiled: July 28, 2006Date of Patent: November 6, 2012Inventor: Shinichiro Isobe
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Patent number: 8299226Abstract: This disclosure provides novel reversibly terminated ribonucleotides which can be used as a reagent for DNA sequencing reactions. Methods of sequencing nucleic acids using the disclosed nucleotides are also provided.Type: GrantFiled: August 10, 2011Date of Patent: October 30, 2012Assignee: Alere San Diego, Inc.Inventors: Olaf Piepenburg, Derek L. Stemple, Niall A. Armes
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Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators
Patent number: 8298792Abstract: This invention provides a process for sequencing single-stranded DNA employing modified nucleotides.Type: GrantFiled: February 8, 2011Date of Patent: October 30, 2012Assignee: The Trustees of Columbia University in the City of New YorkInventors: Jingyue Ju, Dae Hyun Kim, Lanrong Bi, Qinglin Meng, Xiaoxu Li -
Patent number: 8293684Abstract: The present invention relates to labeling kits containing novel non-natural nucleotide monomers and to methods of making and using such compounds. The invention further relates to a method of detecting the presence of a nucleic acid, e.g., RNA, of interest in a sample, the method having the following steps: providing the sample; ligating a nucleic acid of interest with a labeling reagent according to the instant invention; providing a nucleic acid array having probes directed to the nucleic acid of interest; hybridizing the labeled nucleic acid fragments to said nucleic acid array; and determining the extent of hybridization to said probes to determine the presence of the nucleic acid of interest.Type: GrantFiled: November 29, 2007Date of Patent: October 23, 2012Assignee: ExiqonInventors: Peter Mouritzen, Christian Lomholt, Søren Morgenthaler Echwald, Mikkel Noerholm
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Patent number: 8288516Abstract: To provide a functional molecule including a modified nucleotide unit having a substituent introduced to a base thereof, wherein the substituent is removably introduced to the base; a functional molecule synthesizing amidite that has a substituent removably introduced to its base and that is used for the manufacture of the functional molecule; and a target substance analysis method including: preparing a random pool of functional molecules using a functional molecule synthesizing amidite; screening a functional molecule having affinity for a target substance from the random pool; amplifying the functional molecules having affinity for the target substance, wherein the method further comprises, prior to the amplification step, removing a substituent from the functional molecule having affinity for the target substance.Type: GrantFiled: March 17, 2008Date of Patent: October 16, 2012Assignee: Fujitsu LimitedInventors: Tsuyoshi Fujihara, Shozo Fujita
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Patent number: 8288098Abstract: This invention relates to agents and conjugates to detect and isolate target components from complex mixtures such as nucleic acids from biological samples, cells from bodily fluids, and nascent proteins from translation reactions. Agents comprise a detectable moiety bound to a photoreactive moiety. Conjugates comprise agents coupled to substrates by covalent bounds which can be selectively cleaved with the administration of electromagnetic radiation. Targets substances labeled with detectable molecules can be easily identified and separated from a heterologous mixture of substances. Exposure of the conjugate to radiation releases the target in a functional form and completely unaltered. Using photocleavable molecular precursors as the conjugates, label can be incorporated into macromolecules, the nascent macromolecules isolated and the label completely removed.Type: GrantFiled: October 27, 2011Date of Patent: October 16, 2012Assignee: AmberGen, Inc.Inventors: Kenneth J. Rothschild, Sanjay M. Sonar, Jerzy Olejnik
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Patent number: 8268977Abstract: Compositions and systems are provided for the high efficiency quenching small water-soluble oligomers, or oligofluors, of from about 1-10 kd in size, where the oligofluors comprise multiple excimeric or exciplex forming fluorophores arranged on a scaffold, which are efficiently quenched by a quencher entity linked to the oligomer through a cleavable moiety. Fluorophores of interest include, without limitation, aromatic fluorophores such as pyrenes, e.g. benzopyrene, perylene, pyrene, etc. In some embodiments the oligofluor/quencher combination provides for a Stern-Vollmer constant (KSV) of greater than about 106 M?1, and may be greater than about 107 M?1, greater than about 108 M?1, or more. In some embodiments of the invention, the scaffold is a phosphodiester/glycoside backbone, e.g. an analog of a polynucleotide.Type: GrantFiled: November 16, 2009Date of Patent: September 18, 2012Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Eric Todd Kool, James N. Wilson, Nan Dai
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Patent number: 8263365Abstract: The present invention relates to a novel method for analyzing nucleic acid sequences based on real-time detection of DNA polymerase-catalyzed incorporation of each of the four nucleotide bases, supplied individually and serially in a microfluidic system, to a reaction cell containing a template system comprising a DNA fragment of unknown sequence and an oligonucleotide primer. Incorporation of a nucleotide base into the template system can be detected by any of a variety of methods including but not limited to fluorescence and chemiluminescence detection. Alternatively, microcalorimetic detection of the heat generated by the incorporation of a nucleotide into the extending template system using thermopile, thermistor and refractive index measurements can be used to detect extension reactions.Type: GrantFiled: January 18, 2011Date of Patent: September 11, 2012Assignee: Arizona Board of RegentsInventors: Peter Williams, Thomas J. Taylor, Daniel J. B. Williams, Ian Gould, Mark A. Hayes
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Patent number: 8263364Abstract: The present invention relates to a novel method for analyzing nucleic acid sequences based on real-time detection of DNA polymerase-catalyzed incorporation of each of the four nucleotide bases, supplied individually and serially in a microfluidic system, to a reaction cell containing a template system comprising a DNA fragment of unknown sequence and an oligonucleotide primer. Incorporation of a nucleotide base into the template system can be detected by any of a variety of methods including but not limited to fluorescence and chemiluminescence detection. Alternatively, microcalorimetic detection of the heat generated by the incorporation of a nucleotide into the extending template system using thermopile, thermistor and refractive index measurements can be used to detect extension reactions.Type: GrantFiled: January 18, 2011Date of Patent: September 11, 2012Assignee: Arizona Board of RegentsInventors: Peter Williams, Thomas J. Taylor, Daniel J. B. Williams, Ian Gould, Mark A. Hayes
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Patent number: 8258276Abstract: A compound having the general formula shown below: where R1-6 are independently selected from the group consisting of an electron withdrawing group, an alkyl group, an aryl group, hydrogen, a heteroaryl group, and a five or six member ring structure formed from the R1 and R2 pair, the R3 and R4 pair, the R4 and R5 pair, or the R5 and R6 pair; R7 is a substituted or unsubstituted aryl group; and Y is a nucleophile.Type: GrantFiled: September 2, 2011Date of Patent: September 4, 2012Assignee: Integrated DNA Technologies, Inc.Inventors: Andrei Laikhter, Joseph A. Walder, Mark Behlke, Mikhail Podyminogin, Yawfui Yong
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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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Patent number: 8241852Abstract: Embodiments of the present invention provide methods and nucleic acid reporter molecules for the detection of nucleic acid in a sample. The nucleic acid reporter molecule comprises two unsymmetrical cyanine monomer moieties, which may be the same or different, that are covalently attached by a linker comprising at least one aromatic, heteroaromatic, cyclic or heterocyclic moiety comprising 3-20 non-hydrogen atoms selected from the group consisting of O, N, S, P and C. The linker may be rigid, relatively flexible or some degree thereof. The unsymmetrical cyanine monomer moieties comprise a substituted or unsubstituted benzazolium moiety and a substituted or unsubstituted pyridinium or quinolinium moiety that is connected by a methine bridge that is monomethine, trimethine or pentamethine. The linkers form the cyanine dimer compounds by attaching to the pyridinium or quinolinium moiety of the monomer moieties.Type: GrantFiled: January 31, 2011Date of Patent: August 14, 2012Assignee: Life Technologies CorporationInventors: Stephen Yue, Ching-Ying Cheung
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Patent number: 8242251Abstract: Embodiments of the present invention provide methods and nucleic acid reporter molecules for the detection of nucleic acid in a sample. The nucleic acid reporter molecule comprises two unsymmetrical cyanine monomer moieties, which may be the same or different, that are covalently attached by a linker comprising at least one aromatic, heteroaromatic, cyclic or heterocyclic moiety comprising 3-20 non-hydrogen atoms selected from the group consisting of O, N, S, P and C. The linker may be rigid, relatively flexible or some degree thereof. The unsymmetrical cyanine monomer moieties comprise a substituted or unsubstituted benzazolium moiety and a substituted or unsubstituted pyridinium or quinolinium moiety that is connected by a methine bridge that is monomethine, trimethine or pentamethine. The linkers form the cyanine dimer compounds by attaching to the pyridinium or quinolinium moiety of the monomer moieties.Type: GrantFiled: February 2, 2011Date of Patent: August 14, 2012Assignee: Life Technologies CorporationInventors: Stephen Yue, Ching-Ying Cheung
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Patent number: 8232050Abstract: Methods of using dyes and associated technology are provided. A dye, such as a monomeric dye or a dimeric dye, may be used in a nucleic acid gel staining application and/or a nucleic acid detection application. Such a dye and a salt that comprises an anion that is associated with a strong acid and a cation that is associated with a strong base may be used in such an application. A dimeric dye, such as a dimeric dye capable of forming a hairpin-like structure, may be used to stain and/or detect nucleic acids via a release-on-demand mechanism. A dimeric dye having low background fluorescence in the absence of nucleic acids and high fluorescence in the presence of nucleic acids, upon binding therewith, may be used to stain and/or detect nucleic acids.Type: GrantFiled: August 11, 2010Date of Patent: July 31, 2012Assignee: Biotium, Inc.Inventors: Fei Mao, Wai-Yee Leung
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Patent number: 8227187Abstract: Methods, compositions and articles of manufacture for assaying a sample for a target polynucleotide are provided. A sample suspected of containing the target polynucleotide is contacted with a polycationic multichromophore and a sensor polynucleotide complementary to the target polynucleotide. The sensor polynucleotide comprises a signaling chromophore to receive energy from the excited multichromophore and increase emission in the presence of the target polynucleotide. The methods can be used in multiplex form. Kits comprising reagents for performing such methods are also provided.Type: GrantFiled: December 7, 2009Date of Patent: July 24, 2012Assignee: The Regents of the University of CaliforniaInventors: Guillermo C. Bazan, Brent S. Gaylord, Shu Wang
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Patent number: 8221972Abstract: The invention concerns a method for determining at least one target molecule map in a tissue section, using at least one (A-X)n-B conjugate, wherein A is a tag molecule of known molecular weight, X is a linker that is cleaved during sample desorption/ionization, n is an integer of at least 1, and B is a binding molecule that binds specifically to said target molecule. When using MALDI mass spectrometry, said linker molecule X may be cleaved by photodissociation during sample laser irradiation if photocleavable at the wavelength of said MALDI laser. Alternatively, when using UV-MALDI, IR-MALDI, SIMS or DESI mass spectrometry, said linker molecule X may be cleaved by fragmentation during sample desorption/ionization.Type: GrantFiled: June 7, 2006Date of Patent: July 17, 2012Assignees: Centre National de la Recherche Scientifique (CNRS), Universite des Sciences et Technologies de Lille, Eurogentec S.A.Inventors: Rémi Lemaire, Isabelle Fournier, Michel Salzet, Michel Dechamps, Jean-Claude Edmond Tabet, Gottfried Proess, Ivo Rudloff, Marc Lemaitre
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Patent number: 8216514Abstract: The present invention relates to a novel method for analyzing nucleic acid sequences based on real-time detection of DNA polymerase-catalyzed incorporation of each of the four nucleotide bases, supplied individually and serially in a microfluidic system, to a reaction cell containing a template system comprising a DNA fragment of unknown sequence and an oligonucleotide primer. Incorporation of a nucleotide base into the template system can be detected by any of a variety of methods including but not limited to fluorescence and chemiluminescence detection. Alternatively, microcalorimetic detection of the heat generated by the incorporation of a nucleotide into the extending template system using thermopile, thermistor and refractive index measurements can be used to detect extension reactions.Type: GrantFiled: June 8, 2011Date of Patent: July 10, 2012Assignee: Arizona Board of RegentsInventors: Peter Williams, Thomas J. Taylor, Daniel J. B. Williams, Ian Gould, Mark A. Hayes
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Publication number: 20120172583Abstract: Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers facilitate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R21Z1C(O)R22R28 where R21 is a C1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z1 is either NH, sulfur or oxygen, R22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R28 includes a functional group which attaches the linker to the acceptor dye.Type: ApplicationFiled: September 14, 2010Publication date: July 5, 2012Applicant: LIFE TECHNOLOGIES CORPORATIONInventors: Linda G. Lee, Sandra L. Spurgeon, Barnett B. Rosenblum
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Patent number: 8212015Abstract: The invention is directed to modified guanine-containing nucleosides and nucleotides and uses thereof. More specifically, the invention relates to modified fluorescently labelled guanine-containing nucleosides and nucleotides which exhibit enhanced fluorophore intensity by virtue of reduced quenching effects.Type: GrantFiled: October 6, 2010Date of Patent: July 3, 2012Assignee: Illumina Cambridge LimitedInventors: John Milton, Xiaohai Liu
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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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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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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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Patent number: 8158346Abstract: Nucleosides and nucleotides are disclosed that are linked to detectable labels via a cleavable linker group.Type: GrantFiled: July 13, 2010Date of Patent: April 17, 2012Assignee: Illumina Cambridge LimitedInventors: Shankar Balasubramanian, Colin Barnes, Xiaohai Liu
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Patent number: 8153780Abstract: The invention relates to a reporter unit for detecting a target molecule comprising at least one component attached to a target molecule specific probe, wherein said at least one component is liberated from said probe by the activity of a first enzyme thereby making the at least one component available as a substrate for a second enzyme which employs the substrate in a polymerization reaction to obtain a detectable structure.Type: GrantFiled: February 6, 2008Date of Patent: April 10, 2012Assignee: Atonomics A/SInventor: Peter Warthoe
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Publication number: 20120083599Abstract: Novel biotin analogues, such as 2-Azidobiotin, comprising the ureido ring of natural biotin with the thiophene ring, optionally modified, and a modified sidechain having a functional end group, preferably selected from the group consisting of a carboxylic acid, amine, alcohol, thiol, aldehyde and a halide, and at least one bio-orthogonally reactive chemical group located elsewhere in the sidechain. The analogues are used for labelling target structures and biomolecules, such as peptides and proteins in vitro or in vivo.Type: ApplicationFiled: March 22, 2010Publication date: April 5, 2012Applicant: UNIVERSITY OF NOTTINGHAMInventors: Neil R. Thomas, Yang Yong-Qing, William C. Drewe
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Patent number: 8148064Abstract: Nucleosides and nucleotides are disclosed that are linked to detectable labels via a cleavable linker group.Type: GrantFiled: July 19, 2010Date of Patent: April 3, 2012Assignee: Illumina Cambridge LimitedInventors: Shankar Balasubramanian, Colin Barnes, Xiaohai Liu, John Milton
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Patent number: 8148516Abstract: The present invention provides compounds, methods and systems for sequencing nucleic acid using single molecule detection. Using labeled NPs that exhibit charge-switching behavior, single-molecule DNA sequencing in a microchannel sorting system is realized. In operation, sequencing products are detected enabling real-time sequencing as successive detectable moieties flow through a detection channel. By electrically sorting charged molecules, the cleaved product molecules are detected in isolation without interference from unincorporated NPs and without illuminating the polymerase-DNA complex.Type: GrantFiled: August 10, 2010Date of Patent: April 3, 2012Assignee: Pacific Biosciences of California, Inc.Inventors: John G. K. Williams, Gregory R Bashford, Jiyan Chen, Dan Draney, Nara Narayanan, Bambi L. Reynolds, Pamela Sheaff
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Patent number: 8148515Abstract: The present invention relates to dyes in general. The present invention provides a wide range of dyes and kits containing the same, which are applicable for labeling a variety of biomolecules such as nucleic acids, cells and microorganisms. The present invention also provides various methods of using the dyes for research and development, forensic identification, environmental studies, diagnosis, prognosis, and/or treatment of disease conditions.Type: GrantFiled: June 2, 2010Date of Patent: April 3, 2012Assignee: Biotium, Inc.Inventors: Fei Mao, Wai-Yee Leung, Hye Eun Hoover
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Patent number: 8133701Abstract: The present invention is directed in part to a method for detecting a target nucleic acid using detector oligonucleotides detectable by mass spectrometry. This method uses the 5? to 3? nuclease activity of a nucleic acid polymerase to cleave annealed oligonucleotide probes from hybridized duplexes and release labels for detection by mass spectrometry. This process is easily incorporated into a PCR amplification assay. The method also includes embodiments directed to quantitative analysis of target nucleic acids.Type: GrantFiled: December 4, 2007Date of Patent: March 13, 2012Assignee: Sequenom, Inc.Inventor: Dirk Johannes Van Den Boom
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Patent number: 8133669Abstract: Provided herein are methods and compositions for nucleic acid replication. These methods involve the use of 3?-substituted nucleoside 5?-triphosphates or 3?-substituted terminated primers in nucleic acid replication reactions. In certain aspects, the methods are accomplished by use of 3?-substituted NTPs and/or 3?-substituted terminated primers which provide utility in nucleic acid replication. In preferred embodiments, the NTPs and/or primers are substituted at the 3?-position with particular heat labile chemical groups such as ethers, esters or carbonate esters.Type: GrantFiled: May 21, 2009Date of Patent: March 13, 2012Assignee: Trilink BiotechnologiesInventors: Alexandre Lebedev, Inna Koukhareva
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Publication number: 20120058476Abstract: The invention provides a novel method of labeling oligonucleotides, with reporter moieties, including but not limited to, quenchers, fluorophores, biotin, digoxigenin, peptides and proteins. In addition, this invention provides a method of detecting hybridization of oligonucleotides. This invention also provides novel azo quenchers having the general formula shown below. The invention further provides compositions comprising labeled oligonucleotides and solid supports. The invention also provides kits comprising at least one composition of the present invention.Type: ApplicationFiled: May 5, 2010Publication date: March 8, 2012Inventors: Andrei Laikhter, Suresh C. Srivastava, Naveen P. Srivastava
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Patent number: 8129509Abstract: Compounds and methods are provided for a single-step covalent attachment of a label to a molecule comprising forming a covalently attachable labeling reagent for alkylating the molecule. Then, combining the covalently attachable labeling reagent with a mixture containing the molecule, under conditions wherein the labeling reagent has reactivity with the molecule thereby forming a covalent bond.Type: GrantFiled: April 15, 2003Date of Patent: March 6, 2012Assignee: Mirus Bio LLCInventors: Paul M. Slattum, Jon A. Wolff, James E. Hagstrom, Vladimir G. Budker
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Patent number: 8129529Abstract: Novel energy transfer dyes which can be used with shorter wavelength light sources are provided. These dyes include a donor dye with an absorption maxima at a wavelength between about 250 to 450 nm and an acceptor dye which is capable of absorbing energy emitted from the donor dye. One of the energy transfer dyes has a donor dye which is a member of a class of dyes having a coumarin or pyrene ring structure and an acceptor dye which is capable of absorbing energy emitted from the donor dye, wherein the donor dye has an absorption maxima between about 250 and 450 nm and the acceptor dye has an emission maxima at a wavelength greater than about 500 nm.Type: GrantFiled: December 2, 2010Date of Patent: March 6, 2012Assignee: Applied Biosystems, LLCInventor: Linda G. Lee
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Patent number: 8129106Abstract: A method for detecting sequence specific methylation in a biomolecule, comprising: (a) contacting the biomolecule with an S-adenosyl-L-methionine-dependent methyltransferase in the presence of a detectable cofactor of said methyltransferase; and (b) detecting whether the recognition sequence of said methyltransferase has been modified with the cofactor or a derivative thereof, wherein modification of the recognition sequence of said methyltransferase is indicative of an absence of methylation at said recognition sequence. Also disclosed is a cofactor specific for S-adenosyl-L-methionine-dependent methyltransferases, wherein said cofactor is an N-adenosylaziridine derivative with a reporter group attached to the 6 or 7 position of the adenine ring or attached to the aziridine ring. A complex of the cofactor and a methyltransferase a composition comprising the cofactor or the complex and the use of the cofactor or the complex for detecting sequence-specific methylation in DNA molecules are also disclosed.Type: GrantFiled: June 14, 2005Date of Patent: March 6, 2012Assignee: Max-Planck-Geselischaft zur Forderung der Wissenschaften E.V.Inventors: Elmar Weinhold, Thomas Meier, Hartmut Düfel, Christine Markert-Hahn, Rainer Schmuck
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Publication number: 20120052507Abstract: In various embodiments, the present invention provides fluorescent dyes that are linked to another species through an amino acid or peptide linker. In an exemplary embodiment, the dye is linked to a polyphosphate nucleic acid through an amino acid or peptide linker. These conjugates find use in single molecule DNA sequencing and other applications. In various embodiments, the dye moiety is a cyanine dye. Cyanine dyes that are highly charged, such as those including muliple sulfonate, alkylsulfonate, carboxylate and/or alkylcarboxylate moieties are examples of cyanine dyes of use in the compounds of the invention.Type: ApplicationFiled: August 25, 2011Publication date: March 1, 2012Applicant: Pacific Biosciences of California, Inc.Inventor: Gene Shen
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Patent number: 8124333Abstract: A method to link a light emitting reporter to biomolecules with nucleotide oligomers is described. The light reporter particles are silylated and functionalized to produce a coated light reporter particle, prior to covalently linking the biomolecules to the light reporter particle. The light reporter particle generated by the methods of the invention can be excited by a light excitation source such as UV or IR light, and when the biomolecule is DNA, the attached DNA molecule(s) are detectable by amplification techniques such as PCR.Type: GrantFiled: December 11, 2007Date of Patent: February 28, 2012Assignee: APDN, Inc.Inventors: Thomas Kwok, Ming-Hwa Liang, Stephane Shu Kin So
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Patent number: 8114636Abstract: Provided in certain embodiments are new methods for forming azido modified nucleic acid conjugates of reporter molecules, carrier molecules or solid support. In other embodiments are provided methods for enzymatically labeling nucleic acids with an azide group.Type: GrantFiled: February 13, 2007Date of Patent: February 14, 2012Assignee: Life Technologies CorporationInventors: Brian Agnew, Maura J. Ford, Kyle R. Gee, Kapil Kumar
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Patent number: 8114973Abstract: The invention provides for nucleotide analogs and methods of using the same, e.g., for sequencing nucleic acids.Type: GrantFiled: October 2, 2008Date of Patent: February 14, 2012Assignee: Helicos Biosciences CorporationInventors: Suhaib Siddiqi, Subramanian Marappan, Judith Mitchell, Edyta Krzymanska-Olejnik, Atanu Roy, Xiaopeng Bai
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Patent number: 8110554Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.Type: GrantFiled: October 2, 2008Date of Patent: February 7, 2012Assignee: The Regents of the University of CaliforniaInventors: Tao Jiang, Roger Y. Tsien
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Patent number: 8105770Abstract: [PROBLEMS] To provide a CGH method, in particular a CGH microarray method, enabling detection at an elevated accuracy and elevated sensitivity.Type: GrantFiled: January 28, 2008Date of Patent: January 31, 2012Assignee: Wako Pure Chemical Industries, Ltd.Inventors: Makoto Amano, Naoyuki Yamamoto
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Patent number: 8101416Abstract: Methods, compositions and articles of manufacture for assaying a sample for a target polynucleotide are provided. A sample suspected of containing the target polynucleotide is contacted with a polycationic multichromophore and a sensor PNA complementary to the target polynucleotide. A signaling chromophore absorbs energy from the excited multichromophore and emits light in the presence of the target polynucleotide. The methods can be used in multiplex form. Kits having reagents for performing such methods are also provided.Type: GrantFiled: May 8, 2007Date of Patent: January 24, 2012Assignee: The Regents of the University of CaliforniaInventors: Guillermo C. Bazan, Brent S. Gaylord
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Patent number: 8093367Abstract: The synthesis of capped/tagged RNA, methods of use and kits providing same are contemplated. Tagged RNA permits isolation of RNA transcripts in vitro. The ability to isolate and purify capped RNA results in improved transcription and translation and provides a tool for identifying RNA-protein interactions. Such capped RNA finds use in therapeutic applications, diagnosis and prognosis and in the treatment of cancers and HIV.Type: GrantFiled: April 30, 2010Date of Patent: January 10, 2012Assignee: Applied Biosystems, LLCInventors: Anilkumar Kore, Shanmugasundaram Muthian, Irudaya Charles
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Patent number: 8088575Abstract: This invention provides methods for attaching a nucleic acid to a solid surface and for sequencing nucleic acid by detecting the identity of each nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction. The invention also provides nucleotide analogues which comprise unique labels attached to the nucleotide analogue through a cleavable linker, and a cleavable chemical group to cap the —OH group at the 3?-position of the deoxyribose.Type: GrantFiled: July 19, 2010Date of Patent: January 3, 2012Assignee: The Trustees of Columbia University in the City of New YorkInventors: Jingyue Ju, Zengmin Li, John Robert Edwards, Yasuhiro Itagaki
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Patent number: 8084201Abstract: It is an object of the present invention to provide an on-off type fluorescent compound (a fluorescence-producing molecule system) used in gene analyses, which is highly stable (namely, being active for a long period of time) and highly sensitive, and which enables amplification of a trace amount of gene signal and observation thereof. The present invention provides a nonfluorescent molecule having a fluorescent substance skeleton such as fluorescein skeleton and having a group represented by —O—C(Y1)(Y2)-N3 wherein each of Y1 and Y2 represents a hydrogen atom, an alkyl group containing 1 to 6 carbon atoms, an alkoxy group containing 1 to 6 carbon atoms, an aryl group containing 6 to 10 carbon atoms, or a cyano group, in the molecule.Type: GrantFiled: August 1, 2008Date of Patent: December 27, 2011Assignee: RikenInventors: Hiroshi Abe, Yoshihiro Ito, Kazuhiro Furukawa
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Patent number: 8084590Abstract: The invention provides a nucleotide or nucleoside having a base attached to a detectable label via a cleavable linker, characterised in that the cleavable linker contains a moiety selected from the group comprising: Formula (I) (wherein X is selected from the group comprising O, S, NH and NQ wherein Q is a C1-10 substituted or unsubstituted alkyl group, Y is selected from the group comprising O, S, NH and N(allyl). T is hydrogen or a C1-10 substituted or unsubstituted alkyl group and * indicates where the moiety is connected to the remainder of the nucleotide or nucleoside).Type: GrantFiled: June 21, 2010Date of Patent: December 27, 2011Assignee: Illumina Cambridge LimitedInventors: John Milton, Silke Ruediger, Xiaohai Liu
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Patent number: 8080235Abstract: Protein kinase A reporters useful for obtaining measurements of protein kinase A activity with high spatial and temporal resolution can be used in high throughput assays to identify potentially therapeutic compounds.Type: GrantFiled: October 26, 2006Date of Patent: December 20, 2011Assignee: The Johns Hopkins UniversityInventors: Jin Zhang, Qiang Ni, Michael David Allen
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Patent number: RE43096Abstract: This invention provides a duplex comprising an oligonucleotide primer and a template, wherein the primer is coupled chemically to a chromophore or fluorophore so as to allow chain extension by a polymerase. In one embodiment, the primer is extended by a polymerase to generate the complement of the template. In a further embodiment, the extended primer is separated from the template for use in a number of methods, including sequencing reactions. Methods of generating these compositions of matter are further provided.Type: GrantFiled: March 13, 2003Date of Patent: January 10, 2012Assignee: California Institute of TechnologyInventors: Lloyd M. Smith, Leroy E. Hood, Michael W. Hunkapiller, Timothy Hunkapiller, Charles R. Connell