Involving A Ligase (6.) Patents (Class 435/91.52)
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Patent number: 6376184Abstract: The base sequence data of a gene is analyzed. A set of degenerate probes are hybridized to a single-stranded nucleic acid analyte derived from a gene, the nucleic acid analyte is used as a template and the probes are used as primers for a thermo-cycled polymerase reaction, the reaction products obtained from the respective probes are separated by gel electrophoresis and the electrophoresis patterns for the probes are compared, to allow for feature extraction of the base sequence of the nucleic acid analyte, including its sequencing.Type: GrantFiled: March 30, 2000Date of Patent: April 23, 2002Assignee: Hamamatsu Photonics K.K.Inventors: Shigeru Hosoi, Michiko Furuki
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Publication number: 20020034737Abstract: The invention relates to oligonucleotide probes attached to discrete particles wherein the particles can be grouped into a plurality of sets based on a physical property. A different probe is attached to the discrete particles of each set, and the identity of the probe is determined by identifying the discrete particles from their physical property. The physical property includes any that can be used to differentiate the discrete particles, and includes, for example, size, flourescence, radioactivity, electromagnetic charge, or absorbance, or label(s) may be attached to the particle such as a dye, a radionuclide, or an EML. In a preferred embodiment, discrete particles are separated by a flow cytometer which detects the size, charge, flourescence, or absorbance of the particle. The invention also relates to methods using the probes complexed with the discrete particles to analyze target nucleic acids.Type: ApplicationFiled: October 9, 1997Publication date: March 21, 2002Applicant: Hyseq, Inc.Inventor: RADOJE DRMANAC
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Patent number: 6358712Abstract: The present invention provides an improved system for linking nucleic acids to one another. In particular, the present invention provides techniques for producing DNA product molecules that may be easily and directly ligated to recipient molecules. The product molecules need not be cleaved with restriction enzymes in order to undergo such ligation. In preferred embodiments of the invention, the DNA product molecules are produced through iterative DNA synthesis reactions, so that the product molecules are amplified products. The invention further provides methods for directed ligation of product molecules (i.e., for selective ligation of certain molecules within a collection of molecules), and also for methods of exon shuffling, in which multiple different product molecules are produced in a single ligation reaction. Preferred embodiments of the invention involve ligation of product molecules encoding functional protein domains, particularly domains naturally found in conserved gene families.Type: GrantFiled: January 5, 1999Date of Patent: March 19, 2002Assignee: Trustee of Boston UniversityInventors: Kevin A. Jarrell, Vincent W. Coljee, William Donahue, Svetlana Mikheeva
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Patent number: 6352825Abstract: The oligonucleotides: (i) the 23-mer 5′-TTTGTTACTGTGGTAGATACTAC-3′ (SEQ ID NO: 1) or the 23-mer which is complementary to it; (ii) a 23-mer derived from (i) by from 1 to 5 nucleotide substitutions; (iii) a 23+-mer having a 3′ terminal sequence consisting of (i) or (ii); (iv) a fragment of (i) or (ii) having a length of from 8 to 18 nucleotides; (v) the 25-mer 5′-GAAAAATAAACTGTAAATCATATTC-3′ (SEQ ID NO: 2) or the 25-mer which is complementary to it; (vi) a 25-mer derived from (v) by from 1 to 5 nucleotide substitutions; (vii) a 25+-mer having a 3′ terminal sequence consisting of (v) or (vi); (viii) the 28-mer 5′-GAAAAATAAACTGTAAATCATATTCTTC-3′ (SEQ ID NO: 10) or the 28-mer which is complementary to it; (ix) the 28-mer 5′-GAAAAATAAACTGTAAATCATATTCCTC-3′ (SEQ ID NO: 18) or the 28-mer which is complementary to it; (x) a 28-mer derived from (viii) or (ix) by from 1 to 5 nucleotide substitutions; (xi) a 28+-mer having a 3′ terminal seqType: GrantFiled: November 25, 1996Date of Patent: March 5, 2002Assignee: Stichting Researchfonds PathologieInventors: Christophorus Joannes Meijer, Adrianus Johannes van den Brule, Jan Marcus Walboomers, Petrus Josephus Snijders
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Patent number: 6351690Abstract: A system for performing antiviral drug susceptibility and resistance testing is automated using software and robotics. The system includes a transfection apparatus, an infection apparatus and a plate reading apparatus. One or more of the apparatuses may be automated.Type: GrantFiled: January 21, 2000Date of Patent: February 26, 2002Assignee: Virologic, Inc.Inventor: Steven J. Lenz
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Patent number: 6333156Abstract: Disclosed are a method which can simultaneously analyze a plurality of analytes and can realize the determination of the base sequence of a large quantity of gene information in a short time, and an apparatus for the method. The method comprises the steps of: preparing four samples, for each of a plurality of nucleic acid analytes, containing analyte nucleic acid-derived oligonucleotide fragments with the end bases having been base-specifically fragmented; labeling the oligonucleotide fragments with a different label for each of the analyte nucleic acids; and subjecting the four samples to an analytical method which can distinguish oligonucleotide fragments based on a difference in length of one base, thereby determining the base sequence of the target nucleic acids.Type: GrantFiled: July 16, 1999Date of Patent: December 25, 2001Assignees: The Institute of Physical and Chemical ResearchInventor: Yoshihide Hayashizaki
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Patent number: 6309824Abstract: The present invention provides a method for detecting a target nucleic acid species including the steps of providing an array of probes affixed to a substrate and a plurality of labeled probes wherein each labeled probe is selected to have a first nucleic acid sequence which is complementary to a first portion of a target nucleic acid and wherein the nucleic acid sequence of at least one probe affixed to the substrate is complementary to a second portion of the nucleic acid sequence of the target, the second portion being adjacent to the first portion; applying a target nucleic acid to the array under suitable conditions for hybridization of probe sequences to complementary sequences; introducing a labeled probe to the array; hybridizing a probe affixed to the substrate to the target nucleic acid; hybridizing the labeled probe to the target nucleic acid; affixing the labeled probe to an adjacently hybridized probe in the array; and detecting the labeled probe affixed to the probe in the array.Type: GrantFiled: January 16, 1997Date of Patent: October 30, 2001Assignee: Hyseq, Inc.Inventor: Radoje T. Drmanac
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Patent number: 6297006Abstract: The present invention provides a method for detecting a target nucleic acid species including the steps of providing an array of probes affixed to a substrate and a plurality of labeled probes wherein each labeled probe is selected to have a first nucleic acid sequence which is complementary to a first portion of a target nucleic acid and wherein the nucleic acid sequence of at least one probe affixed to the substrate is complementary to a second portion of the nucleic acid sequence of the target, the second portion being adjacent to the first portion; applying a target nucleic acid to the array under suitable conditions for hybridization of probe sequences to complementary sequences; introducing a labeled probe to the array; hybridizing a probe affixed to the substrate to the target nucleic acid; hybridizing the labeled probe to the target nucleic acid; affixing the labeled probe to an adjacently hybridized probe in the array; and detecting the labeled probe affixed to the probe in the array.Type: GrantFiled: March 4, 1997Date of Patent: October 2, 2001Assignee: Hyseq, Inc.Inventors: Radoje T. Drmanac, Snezana Drmanac, Aaron Hou, Brian Hauser
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Patent number: 6280949Abstract: Disclosed are compositions and a method for amplification of nucleic acid sequences of interest. The method is based on stand displacement replication of the nucleic acid sequences of interest by multiple primers. In one preferred form of the method, referred to as multiple strand displacement amplification, two sets of primers are used, a right set and a left set. The primers in the right set are complementary to one strand of the nucleic acid molecule to be amplified and the primers in the left set are complementary to the opposite strand. The 5′ end of primers in both sets are distal to the nucleic acid sequence of interest when the primers have hybridized to the nucleic acid sequence molecule to be amplified. Amplification proceeds by replication initiated at each primer and continuing through the nucleic acid sequence of interest. A key feature of this method is the displacement of intervening primers during replication by the polymerase.Type: GrantFiled: September 17, 1999Date of Patent: August 28, 2001Assignee: Yale UniversityInventor: Paul M. Lizardi
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Patent number: 6270966Abstract: A method for detecting gene expression in cells by reverse transcribing mRNA molecules into cDNA, cutting the cDNA with at least one restriction endonuclease, adding adaptor sequences to the cDNA fragments and selectively amplifying a subset of the cDNA by a polymerase chain reaction (PCR) to present a two-dimensional display of the DNA fragments or for cloning the DNA fragments into a vector is disclosed. In one embodiment, cDNA corresponding to the 3′ end of the mRNA is amplified and displayed or cloned, whereas in another embodiment, cDNA corresponding to the entire mRNA molecule is amplified and displayed or cloned.Type: GrantFiled: August 7, 1998Date of Patent: August 7, 2001Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: John N. Weinstein, John Buolamwini
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Patent number: 6261770Abstract: Disclosed and claimed is a method for preparing a normalized sub-divided library of amplified cDNA fragments from the coding region of mRNAs contained in a sample.Type: GrantFiled: May 19, 1998Date of Patent: July 17, 2001Assignee: Display Systems Biotech ApSInventor: Peter Rolf Warthoe
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Patent number: 6251608Abstract: Methods for determining a potential of a hyperglycemic patient to develop vascular complications in response to oxidative stress and for determining the importance of reducing oxidative stress in a specific hyperglycemic patient are disclosed. Each method includes the step of determining a haptoglobin phenotype of the patient. A variety of means of making this determination are further disclosed.Type: GrantFiled: April 20, 2000Date of Patent: June 26, 2001Assignee: Technion Research & Development Foundation, Ltd.Inventor: Andrew P. Levy
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Patent number: 6248526Abstract: A labeled primer for use in detection of nucleic acid is described, which primer is labeled at the two ends of the oligonucleotide strand with a reporter dye molecule and a quencher molecule, and in which labeled primer, at least one base at the 3′ end is deliberately not complementary to the nucleic acid sequence to be amplified. A process for detecting a nucleic acid sequence using a labeled primer is also described. The process can also be used in amplification processes.Type: GrantFiled: December 14, 1998Date of Patent: June 19, 2001Assignee: Aventis Behring, GmbHInventor: Thomas Weimer
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Patent number: 6242211Abstract: The present invention relates to a novel drug discovery system for generating molecular diversity. The system provides methods for subjecting the genetic materials from a plurality of species of organisms to homologous or homeologous recombination to create novel genes and metabolic pathways. The recombined genetic materials are cloned to form recombined combinatorial gene expression libraries. Methods for screening such gene expression libraries containing recombined genes and metabolic pathways for novel activities and compounds are also provided.Type: GrantFiled: March 5, 1999Date of Patent: June 5, 2001Assignee: Terragen Discovery, Inc.Inventors: Todd C. Peterson, Paul Brian
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Patent number: 6238867Abstract: The present invention is directed to methods, compositions, kits and apparatus to identify and detect the presence or absence of target analytes. The embodiments of the present invention have utility in identification of protein and measurement of its levels in specimens and samples, as well as the design of test kits and apparatus for implementing such methods.Type: GrantFiled: February 22, 1999Date of Patent: May 29, 2001Assignee: InVitro Diagnostics IncInventors: Igor B. Roninson, Abraham Grossman
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Patent number: 6203988Abstract: A DNA fragment preparation method for DNA analysis comprising, i) preparing a plurality of DNA fragments from a sample DNA, and ii) amplifying a specific DNA fragment by PCR, using a pair of primers which hybridize with terminus sequences of the DNA fragments, and a specific primer which hybridizes specifically with a base sequence of the specific DNA fragment at a position between a priming site of one of primer the pair of primers and a priming site of another primer of the pair of primers. The specific primer hybridizes specifically with a base sequence at a middle position of the specific DNA fragment. Products of PCR are separated, by electrophoresis, and signals from DNA fragments originated in a known genes and signals from DNA fragments originated in a unknown genes are displayed separately on a display.Type: GrantFiled: January 12, 1999Date of Patent: March 20, 2001Assignee: Hitachi, Ltd.Inventors: Hideki Kambara, Chihiro Uematsu