Involving A Ligase (6.) Patents (Class 435/91.52)
  • Patent number: 6376184
    Abstract: 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: Grant
    Filed: March 30, 2000
    Date of Patent: April 23, 2002
    Assignee: Hamamatsu Photonics K.K.
    Inventors: Shigeru Hosoi, Michiko Furuki
  • Publication number: 20020034737
    Abstract: 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: Application
    Filed: October 9, 1997
    Publication date: March 21, 2002
    Applicant: Hyseq, Inc.
    Inventor: RADOJE DRMANAC
  • Patent number: 6358712
    Abstract: 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: Grant
    Filed: January 5, 1999
    Date of Patent: March 19, 2002
    Assignee: Trustee of Boston University
    Inventors: Kevin A. Jarrell, Vincent W. Coljee, William Donahue, Svetlana Mikheeva
  • Patent number: 6352825
    Abstract: 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 seq
    Type: Grant
    Filed: November 25, 1996
    Date of Patent: March 5, 2002
    Assignee: Stichting Researchfonds Pathologie
    Inventors: Christophorus Joannes Meijer, Adrianus Johannes van den Brule, Jan Marcus Walboomers, Petrus Josephus Snijders
  • Patent number: 6351690
    Abstract: 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: Grant
    Filed: January 21, 2000
    Date of Patent: February 26, 2002
    Assignee: Virologic, Inc.
    Inventor: Steven J. Lenz
  • Patent number: 6333156
    Abstract: 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: Grant
    Filed: July 16, 1999
    Date of Patent: December 25, 2001
    Assignees: The Institute of Physical and Chemical Research
    Inventor: Yoshihide Hayashizaki
  • Patent number: 6309824
    Abstract: 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: Grant
    Filed: January 16, 1997
    Date of Patent: October 30, 2001
    Assignee: Hyseq, Inc.
    Inventor: Radoje T. Drmanac
  • Patent number: 6297006
    Abstract: 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: Grant
    Filed: March 4, 1997
    Date of Patent: October 2, 2001
    Assignee: Hyseq, Inc.
    Inventors: Radoje T. Drmanac, Snezana Drmanac, Aaron Hou, Brian Hauser
  • Patent number: 6280949
    Abstract: 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: Grant
    Filed: September 17, 1999
    Date of Patent: August 28, 2001
    Assignee: Yale University
    Inventor: Paul M. Lizardi
  • Patent number: 6270966
    Abstract: 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: Grant
    Filed: August 7, 1998
    Date of Patent: August 7, 2001
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: John N. Weinstein, John Buolamwini
  • Patent number: 6261770
    Abstract: 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: Grant
    Filed: May 19, 1998
    Date of Patent: July 17, 2001
    Assignee: Display Systems Biotech ApS
    Inventor: Peter Rolf Warthoe
  • Patent number: 6251608
    Abstract: 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: Grant
    Filed: April 20, 2000
    Date of Patent: June 26, 2001
    Assignee: Technion Research & Development Foundation, Ltd.
    Inventor: Andrew P. Levy
  • Patent number: 6248526
    Abstract: 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: Grant
    Filed: December 14, 1998
    Date of Patent: June 19, 2001
    Assignee: Aventis Behring, GmbH
    Inventor: Thomas Weimer
  • Patent number: 6242211
    Abstract: 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: Grant
    Filed: March 5, 1999
    Date of Patent: June 5, 2001
    Assignee: Terragen Discovery, Inc.
    Inventors: Todd C. Peterson, Paul Brian
  • Patent number: 6238867
    Abstract: 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: Grant
    Filed: February 22, 1999
    Date of Patent: May 29, 2001
    Assignee: InVitro Diagnostics Inc
    Inventors: Igor B. Roninson, Abraham Grossman
  • Patent number: 6203988
    Abstract: 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: Grant
    Filed: January 12, 1999
    Date of Patent: March 20, 2001
    Assignee: Hitachi, Ltd.
    Inventors: Hideki Kambara, Chihiro Uematsu