Patents Examined by Bradley L. Sisson
  • Patent number: 10253353
    Abstract: This disclosure relates to a method for increasing the hybridization efficiency of a probe and a target RNA in a sample, for example to identify a particular RNA present in the sample. The method includes heating a lysate sample comprising at least one target RNA, such as a tRNA, mRNA or rRNA, at a temperature of about 95° C. for a time sufficient to interfere with secondary structure of the RNA, wherein the time is short enough, such that the RNA in the cell lysate sample are not significantly degraded, and wherein the lysate comprises a cell lysis buffer comprising a chemical denaturant. To detect a target RNA in the lysate, the lysate is contacted with at least one detectable probe, such as a labeled probe, designed to specifically hybridize to the target RNA in the lysate.
    Type: Grant
    Filed: December 5, 2014
    Date of Patent: April 9, 2019
    Assignees: The Broad Institute, Inc., The General Hospital Corporation
    Inventors: Roby Bhattacharyya, Deborah Hung, Milesh Patel
  • Patent number: 10150960
    Abstract: Provided herein is a method for enriching a target nucleic acid molecule. In one embodiment, the method may involve hybridizing a C-probe to a strand of a target nucleic acid to produce a complex, enzymatically removing any 3? overhanging end from the target nucleic acid of the complex to produce a 3? hydroxyl group at the 3? end; extending the 3? end of the first sequence using the oligonucleotide sequence of the C-probe as a template; enzymatically removing any 5? overhanging end from the target nucleic acid, either before or after the extending step, to produce an 5? phosphate group at the end of the second sequence; and ligating the 5? phosphate group at the end of the second sequence to the 3? hydroxyl group at the end of the first sequence to produce a circular DNA molecule that contains the target sequence and the complement of the oligonucleotide sequence.
    Type: Grant
    Filed: February 26, 2013
    Date of Patent: December 11, 2018
    Assignee: AGILENT TECHNOLOGIES, INC.
    Inventor: Brian Jon Peter
  • Patent number: 10150990
    Abstract: The present application provides polynucleotides comprising 5?-tails with sequence segments useful for the detection of target nucleic acid sequences, and methods for their use in detecting target nucleic acids. The polynucleotides are used to amplify a subsequence of a target nucleic acid in the presence of one or more ribonucleotides. The ribonucleotides are incorporated into amplification products at regular intervals complementary to the 5?-tail sequence segments. Cleavage of amplification products at the bond immediately 3? to incorporated ribonucleotides produces detectably distinct fragments indicative of the presence or absence of a target nucleic acid.
    Type: Grant
    Filed: April 9, 2009
    Date of Patent: December 11, 2018
    Assignees: Roche Molecular Systems, Inc., CEA/Institut de Genomique—Centre National de Genotypage
    Inventors: David H. Gelfand, Ivo Glynne Gut, Keith A. Bauer, Florence Mauger
  • Patent number: 10066257
    Abstract: The present invention provides compositions, apparatuses and methods for detecting one or more nucleic acid targets present in a sample. Methods of the invention include utilizing two or more ligation probes that reversibly bind a target nucleic acid in close proximity to each other and possess complementary reactive ligation moieties. When such probes have bound to the target in the proper orientation, they are able to undergo a spontaneous chemical ligation reaction that yields a ligation product that is directly detected or that is amplified to produce amplicons that are then detected. The present invention also provides methods to stabilize sample RNA so that degradation does not significantly affect the results of the analysis.
    Type: Grant
    Filed: May 17, 2012
    Date of Patent: September 4, 2018
    Assignee: DXTERITY DIAGNOSTICS INCORPORATED
    Inventors: Robert Terbrueggen, Yenbou Liu, John Ray Childers, Jr., Chang Hee Kim, Majid R. Abedi
  • Patent number: 10036063
    Abstract: A method of determining the sequence of a target nucleic acid is provided. The method can include the steps of (a) performing a defined number of incremental extension cycles to produce a population of nucleic acid fragments having different portions of the target nucleic acid wherein the individual nucleic acid fragments in the population have a defined length that is correlated with the number of incremental extension cycles; (b) determining the sequence of the first end of individual nucleic acid fragments in the population, thereby providing first end sequences; (c) determining the sequence of the second end of individual nucleic acid fragments in the population, thereby providing second end sequences; and (d) determining the sequence of the target nucleic acid based on the first end sequences, the second end sequences and the defined length.
    Type: Grant
    Filed: June 30, 2010
    Date of Patent: July 31, 2018
    Assignee: ILLUMINA, INC.
    Inventor: John Stephen West
  • Patent number: 9976177
    Abstract: The present invention provides compositions, apparatuses and methods for detecting one or more nucleic acid targets present in a sample. Methods of the invention include utilizing two or more oligonucleotide probes that reversibly bind a target nucleic acid in close proximity to each other and possess complementary reactive ligation moieties. When such probes have bound to the target in the proper orientation, they are able to undergo a spontaneous chemical ligation reaction that yields a ligated oligonucleotide product. In one aspect, the ligation product is of variable length that correlates with a particular target. Following chemical ligation, the probes may be amplified and detected by capillary electrophoresis or microarray analysis.
    Type: Grant
    Filed: March 29, 2010
    Date of Patent: May 22, 2018
    Assignee: DXTERITY DIAGNOSTICS INCORPORATED
    Inventor: Robert Terbrueggen
  • Patent number: 9970050
    Abstract: Methods and compositions for the detection and quantification of nucleic acids are provided. In one embodiment, a sample is contacted with a primer complementary to a first region of a target nucleic acid and a probe complementary to a second region of the target nucleic acid downstream of the first region under conditions suitable for hybridization of the target nucleic acid with the primer and the probe. The probe in this embodiment comprises a fluorophore and is attached to a solid support. The hybridized probe is cleaved with a nucleic acid polymerase having exonuclease activity to release the reporter from the solid support. The presence of the target nucleic acid is then detected and optionally quantified by detecting a decrease in signal from the reporter on the solid support.
    Type: Grant
    Filed: January 22, 2015
    Date of Patent: May 15, 2018
    Assignee: LUMINEX CORPORATION
    Inventors: Brian Schrader, Douglas F. Whitman
  • Patent number: 9957502
    Abstract: The present invention relates to a single-stranded nucleic acid molecule for use in a method for the production of a nucleic acid, whereby the nucleic acid molecule comprises a part A and a part B, whereby part A comprises a sequence, which corresponds at least to a partial sequence of the recognition site of a type IIS restriction enzyme, and part B comprises an arbitrary but defined sequence of nucleotides. By using such nucleic acid molecules it is possible to assemble different fragments in a sequence-independent manner and thus conduct the synthesis of a nucleic acid with recourse to standardized elements.
    Type: Grant
    Filed: November 22, 2002
    Date of Patent: May 1, 2018
    Assignee: SLONING BIOTECHNOLOGY GMBH
    Inventors: Octavian Schatz, Timothy O'Connell
  • Patent number: 9880089
    Abstract: An array chip design is provided where the chip includes a field region arranged with sites according to a first pitch and at least one track region having a one-dimensional site pattern arranged according to a second pitch that is less dense and is an integer multiple of the first pitch so that observation through pixel-based sensors using one-dimensional quad-cell averaging can be applied in the track region, thereby to attain alignment of the chip to pixel-based optical instrumentation with a higher density of sites.
    Type: Grant
    Filed: November 26, 2013
    Date of Patent: January 30, 2018
    Assignee: Complete Genomics, Inc.
    Inventors: Bryan P. Staker, Paul Heilman
  • Patent number: 9745616
    Abstract: The present invention provides compositions, apparatuses and methods for detecting one or more nucleic acid targets present in a sample. Methods of the invention include utilizing two or more ligation probes that reversibly bind a target nucleic acid in close proximity to each other and possess complementary reactive ligation moieties. When such probes have bound to the target in the proper orientation, they are able to undergo a spontaneous chemical ligation reaction that yields a ligation product that is directly detected or that is amplified to produce amplicons that are then detected. The present invention also provides methods to stabilize sample RNA so that degradation does not significantly affect the results of the analysis.
    Type: Grant
    Filed: May 17, 2012
    Date of Patent: August 29, 2017
    Assignee: DXTERITY DIAGNOSTICS INCORPORATED
    Inventors: Robert Terbrueggen, Yenbou Liu, John Ray Childers, Jr., Chang Hee Kim, Majid R. Abedi
  • Patent number: 9730637
    Abstract: In alternative embodiments, the invention provides compositions such as devices, pills, beads, capsules, products of manufacture, particles, microparticles, nanoparticles, gels, liquid gels, liquid gel capsules, capsules, tablets, geltabs, liquids, sprays, emulsions, suspensions, pastes or yogurts, for the detection and isolation of biomarkers, nucleic acids, proteins or peptides, proteoglycans, lipids, fats, sugars or polysaccharides in the gastrointestinal tract for e.g., detecting the presence of particular exogenous or endogenous nucleic acids, e.g., DNA or RNA, or proteins, in the gastrointestinal tract, for example, to diagnose the presence of an infectious or exogenous agent such as a virus, a fungus, a parasite, a bacteria, intestinal helminths and protozoan parasites, and the like, or a biomarker such as a cancer-causing or cancer-predisposing allele, e.g., mutations of the KRAS2 oncogene in pancreatic cancer.
    Type: Grant
    Filed: August 17, 2012
    Date of Patent: August 15, 2017
    Assignee: The Regents of the University of California
    Inventors: Dmitri Simberg, Yu-Tsueng Liu
  • Patent number: 9733185
    Abstract: The present invention relates to a device for interfacing nanofluidic and microfluidic components suitable for use in performing high throughput macromolecular analysis. Diffraction gradient lithography (DGL) is used to form a gradient interface between a microfluidic area and a nanofluidic area. The gradient interface area reduces the local entropic barrier to nanochannels formed in the nanofluidic area. In one embodiment, the gradient interface area is formed of lateral spatial gradient structures for narrowing the cross section of a value from the micron to the nanometer length scale. In another embodiment, the gradient interface area is formed of a vertical sloped gradient structure. Additionally, the gradient structure can provide both a lateral and vertical gradient.
    Type: Grant
    Filed: November 13, 2012
    Date of Patent: August 15, 2017
    Assignee: Princeton University
    Inventors: Han Cao, Jonas O. Tegenfeldt, Stephen Chou, Robert H. Austin
  • Patent number: 9528143
    Abstract: A composition suitable for formulation of an enzymatic reaction mixture, the composition comprising a reaction component essential for an ex-vivo non-polymerase enzymatic reaction in which a substrate is catalyzed by an enzyme in a reaction mixture to form a product, and a tracer compatible with the enzyme, the composition being substantially free of the substrate.
    Type: Grant
    Filed: April 12, 2007
    Date of Patent: December 27, 2016
    Assignee: Sigma-Aldrich Co. LLC
    Inventors: Brian W. Ward, David M. Ornitz, Michael G. Deines, Thomas F. Bittick
  • Patent number: 9499866
    Abstract: Described herein are nucleic acid based probes and methods for discriminating and detecting single nucleotide variants in nucleic acid molecules (e.g., DNA). The methods include use of a pair of probes can be used to detect and identify polymorphisms, for example single nucleotide polymorphism in DNA. The pair of probes emit a different fluorescent wavelength of light depending on the association and alignment of the probes when hybridized to a target nucleic acid molecule. Each pair of probes is capable of discriminating at least two different nucleic acid molecules that differ by at least a single nucleotide difference. The methods can probes can be used, for example, for detection of DNA polymorphisms that are indicative of a particular disease or condition.
    Type: Grant
    Filed: May 22, 2014
    Date of Patent: November 22, 2016
    Assignee: Los Alamos National Security, LLC
    Inventors: Hsin-Chih Yeh, James Werner, Jennifer S. Martinez
  • Patent number: 9464281
    Abstract: A method for concentrating viruses includes applying a magnetic force to a mixture containing: sugar chain-immobilized magnetic metal nano-particles each having a structure in which a sugar chain-immobilized metal nano-particle is bound to a first magnetic nano-particle; second magnetic particles with mean particle size larger than that of the sugar chain-immobilized magnetic metal nano-particles; and a specimen. Each sugar chain-immobilized metal nano-particle has a structure where a ligand-conjugate is bound to a metal nano-particle via sulfur atoms. The ligand-conjugate has a structure where a linker compound's amino group is connected to a sugar chain having a reducing terminal. The linker compound includes, in molecules thereof, an amino group, sulfur atoms, and a hydrocarbon chain having carbon-nitrogen bonds.
    Type: Grant
    Filed: July 27, 2010
    Date of Patent: October 11, 2016
    Assignees: SUDx-Biotec Corporation, National University Corporation Kagoshima University, Neat Co., Ltd.
    Inventors: Yasuo Suda, Masahiro Wakao, Takashi Kodama
  • Patent number: 9423405
    Abstract: Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.
    Type: Grant
    Filed: December 5, 2008
    Date of Patent: August 23, 2016
    Assignee: The Cleveland Clinic Foundation
    Inventors: Stanley L. Hazen, Zeneng Wang, Bruce S. Levison
  • Patent number: 9416401
    Abstract: The invention is related to a method and test kits for quantitative determination of polynucleotide amounts present in a sample. The test kit comprises organized pools with polynucleotide probes having distinct sizes and optionally provided with tracer tags or primer tags. The probes are allowed to hybridize with affinity tagged analyte polynucleotides from the sample. The result is hybrids, which can be recovered on a separation aiding tool provided with the pair of the affinity tag. After the quantitative release of the probes, the probes are either directly recorded, or if primer tagged, they are amplified and optionally provided with a tracer tag before recording. The invention provides a sensitive and quantitative determination of the amount polynucleotides present in a cell or tissue sample and allows a quantitative assessment of variations in the amounts of polynucleotides as a response to inherent changes or due to external stimuli.
    Type: Grant
    Filed: January 10, 2002
    Date of Patent: August 16, 2016
    Assignee: VALTION TEKNILLINEN TUTKIMUSKESKUS
    Inventors: Hans Söderlund, Kari Kataja, Marja Paloheimo, Marja Ilmen, Kristiina Takkinen
  • Patent number: 9080285
    Abstract: The present invention relates to biological substance-immobilized fibers wherein a biological substance is immobilized on a fiber, fibers retaining a biological substance-immobilized gel, and fiber alignments having bundles of the above-described fibers and slices of the same.
    Type: Grant
    Filed: September 1, 2006
    Date of Patent: July 14, 2015
    Assignee: MITSUBISHI RAYON CO., LTD.
    Inventor: Teruta Ishimaru
  • Patent number: 9074262
    Abstract: The present invention is related to nucleic acid sequences that can be used in the field of virus diagnostics, more specifically the diagnosis of infections with the AIDS causing Human Immuno-deficiency Virus (HIV). With the present invention nucleotide sequences are provided that can be used as primers and probes in the amplification and detection of HIV-1 nucleic acid. The oligonucleotide sequences provided with the present invention are located in the LTR part of the HIV viral genome. It has been found that, by using the sequences of the present invention in methods for the amplification and detection of nucleic acid a sensitive and specific detection of HIV-1 can be obtained. The benefit of the sequences of the present invention primarily resides in the fact that, with the aid of primers and probes comprising the sequences according to the invention the nucleic acid of all presently known subtypes of HIV-1 can be detected with high accuracy and sensitivity.
    Type: Grant
    Filed: March 27, 2014
    Date of Patent: July 7, 2015
    Assignee: bioMerieux, B. V.
    Inventors: Jaap Goudsmit, Pieter Oudshoorn, Suzanne Jurriaans, Vladimir Vladimirovich Lukashov
  • Patent number: 9068221
    Abstract: A method of analyzing genetic markers includes binding a set of probes to a segment of single stranded nucleic acids. The segment of single stranded nucleic acids includes a repeat region formed of at least two of a repeat unit. The repeat unit can include at least two nucleic acids. The set of probes includes a first probe complementary to the repeat unit. The method can further include directing the segment through a nanopore device and measuring a signal through the nanopore device. The signal can be indicative of the number of repeat units.
    Type: Grant
    Filed: February 9, 2012
    Date of Patent: June 30, 2015
    Assignee: Life Technologies Corporation
    Inventors: Barry Merriman, Paul Mola