Patents by Inventor James G. Nadeau
James G. Nadeau has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 5958700Abstract: A detector oligonucleotide having a sequence which forms an intramolecularly base-paired secondary structure is described for use in detecting nucleic acid target sequences and target sequence amplification. The detector oligonucleotide is further modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned on the detector oligonucleotide such that they are in close spatial proximity in the base-paired, folded secondary structure, thereby causing quenching of donor fluorescence. The detector oligonucleotide may optionally further comprise a restriction endonuclease recognition site (RERS) which remains partially or entirely single-stranded in the base-paired secondary structure. The RERS is flanked by the two dyes. In the presence of target, the base-paired secondary structure is unfolded or linearized, increasing the distance between the donor and acceptor dyes and causing a change in fluorescence of the donor and/or the acceptor.Type: GrantFiled: January 26, 1999Date of Patent: September 28, 1999Assignee: Becton, Dickinson and CompanyInventors: James G. Nadeau, J. Bruce Pitner, C. Preston Linn, James L. Schram
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Patent number: 5935791Abstract: Detector nucleic acids are employed for detection of nucleic acid target sequences by fluorescence quenching mechanisms. The detector nucleic acid comprises at least two oligonucleotides and is partially single-stranded and partially double-stranded. One of the two dyes of a donor/acceptor dye pair is linked to the first oligonucleotide and the other is linked to a second oligonucleotide such that they are in close spatial proximity when the first and second oligonucleotides are base-paired and donor fluorescence is quenched. A single second oligonucleotide may be hybridized to the first oligonucleotide or multiple second oligonucleotides may be hybridized to the first oligonucleotide and to each other, forming a junction structure comprising multiple donor/acceptor dye pairs. The detector oligonucleotide retains its partially single-stranded and partially double-stranded conformation in the absence of target.Type: GrantFiled: September 23, 1997Date of Patent: August 10, 1999Assignee: Becton, Dickinson and CompanyInventors: James G. Nadeau, Helen V. Hsieh, J. Bruce Pitner, C. Preston Linn
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Patent number: 5928869Abstract: A detector oligonucleotide having a sequence which forms an intramolecularly base-paired secondary structure is described for use in detecting nucleic acid target sequences and target sequence amplification. The detector oligonucleotide is further modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned on the detector oligonucleotide such that they are in close spatial proximity in the base-paired, folded secondary structure, thereby causing quenching of donor fluorescence. The detector oligonucleotide may optionally further comprise a restriction endonuclease recognition site (RERS) which remains partially or entirely single-stranded in the base-paired secondary structure. The RERS is flanked by the two dyes. In the presence of target, the base-paired secondary structure is unfolded or linearized, increasing the distance between the donor and acceptor dyes and causing a change in fluorescence of the donor and/or the acceptor.Type: GrantFiled: May 30, 1997Date of Patent: July 27, 1999Assignee: Becton, Dickinson and CompanyInventors: James G. Nadeau, J. Bruce Pitner, C. Preston Linn, James L. Schram
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Patent number: 5919630Abstract: Single-stranded signal primers are modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned in sufficiently close spatial proximity on the signal primer that the fluorescence of the first dye is quenched by the second dye. The signal primer may further comprise a restriction endonuclease recognition site (RERS) between the two dyes. As the signal primer is initially single-stranded and remains single-stranded in the absence of target, the restriction endonuclease recognition site is not cleavable or nickable by the restriction endonuclease. In the presence of target, however, signal primer and the restriction endonuclease recognition site are rendered double-stranded and cleavable or nickable by the restriction endonuclease. Cleavage or nicking separates the two dyes and a change in fluorescence due to decreased quenching is detected as an indication of the presence of the target sequence or of target sequence amplification.Type: GrantFiled: November 4, 1998Date of Patent: July 6, 1999Assignee: Becton, Dickinson and CompanyInventors: James G. Nadeau, J. Bruce Pitner, James L. Schram, C. Preston Linn, Glenn P. Vonk, G. Terrance Walker
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Patent number: 5888739Abstract: G-quartet structures have been found to be useful in fluorescence assays to detect a selected nucleic acid sequence. When oligonucleotides containing these structures are labeled with a donor fluorophore and an acceptor dye, the folding or interaction of the oligonucleotides in the G-quartet structure brings the donor-acceptor pair into close proximity, allowing an interaction between the two labels which results in quenching of donor fluorescence or a change in other fluorescence properties which are the result of the interaction of two dyes in close proximity. The G-quartet structure unfolds or is otherwise disrupted upon hybridization to its complementary sequence, increasing the distance between the two dye labels. This results in decreased donor quenching or a change in another proximity-related fluorescence parameter.Type: GrantFiled: September 9, 1997Date of Patent: March 30, 1999Assignee: Becton, Dickinson and CompanyInventors: J. Bruce Pitner, James G. Nadeau, Glenn P. Vonk
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Patent number: 5882870Abstract: The present invention relates to a system for the reversible anticoagulation of blood utilizing a nucleic acid ligand which binds thrombin and a reversing agent which has greater affinity for the nucleic acid ligand than does thrombin. When used with a blood sample, the nucleic acid ligand binds thrombin, preventing it from converting fibrinogen to fibrin, and thus anticoagulating the blood. Subsequently, the reversing agent may be added to the anticoagulated blood sample, and by competitive binding, replaces thrombin bound to the ligand, thus freeing the thrombin to convert fibrinogen to fibrin and allowing the blood to coagulate.Type: GrantFiled: January 14, 1998Date of Patent: March 16, 1999Assignee: Becton Dickinson and CompanyInventors: James G. Nadeau, Erwin A. Vogler
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Patent number: 5846726Abstract: Single-stranded signal primers are modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned in sufficiently close spatial proximity on the signal primer that the fluorescence of the first dye is quenched by the second dye. The signal primer may further comprise a restriction endonuclease recognition site (RERS) between the two dyes. As the signal primer is initially single-stranded and remains single-stranded in the absence of target, the restriction endonuclease recognition site is not cleavable or nickable by the restriction endonuclease. In the presence of target, however, signal primer and the restriction endonuclease recognition site are rendered double-stranded and cleavable or nickable by the restriction endonuclease. Cleavage or nicking separates the two dyes and a change in fluorescence due to decreased quenching is detected as an indication of the presence of the target sequence or of target sequence amplification.Type: GrantFiled: May 13, 1997Date of Patent: December 8, 1998Assignee: Becton, Dickinson and CompanyInventors: James G. Nadeau, J. Bruce Pitner, James L. Schram, C. Preston Linn, Glenn P. Vonk, G. Terrance Walker
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Patent number: 5840487Abstract: Methods employing internal oligonucleotide standards in isothermal nucleic acid amplification reactions to determine the efficacy of the amplification reaction and to quantify pre-amplification target levels.Type: GrantFiled: February 18, 1997Date of Patent: November 24, 1998Assignee: Becton, Dickinson and CompanyInventors: James G. Nadeau, Michael C. Little
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Patent number: 5811269Abstract: Primers and methods for adapter-mediated multiplex amplification of the IS6110 insertion element of the Mycobacterium tuberculosis (M.tb) complex and a 16S rDNA target common to essentially all mycobacteria are described. In certain embodiments, the primers are optimized for efficient multiplex amplification in thermophilic SDA. The multiplex Strand Displacement Amplification methods of the invention are capable, in a single amplification reaction, of simultaneously identifying M. tuberculosis and providing a screen for substantially all of the clinically relevant species of mycobacteria. Also disclosed are internal control sequences designed for coamplification with the two targets, allowing assessment of amplification efficiency and/or quantitation of the targets.Type: GrantFiled: April 30, 1996Date of Patent: September 22, 1998Assignee: Becton, Dickinson and CompanyInventors: James G. Nadeau, Cheryl H. Dean, James L. Schram, Deborah R. Howard, Margaret S. Dey, David J. Wright
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Patent number: 5736365Abstract: Primers and methods for adapter-mediated multiplex amplification of the IS6110 insertion element of Mycobacterium tuberculosis (M.tb) and the 16S ribosomal gene of Mycobacterium tuberculosis, useful for simultaneously detecting and/or identifying species of the M. tuberculosis complex and other clinically relevant Mycobacterium species. Multiplex Strand Displacement Amplification (SDA) is used in a single amplification reaction which is capable of simultaneously identifying M. tuberculosis and providing a screen for substantially all of the clinically relevant species of Mycobacteria. Also disclosed are methods for adapter-mediated multiplex amplification of multiple target sequences and a single internal control sequence for determination of sample efficacy or quantitation of the targets.Type: GrantFiled: August 29, 1996Date of Patent: April 7, 1998Assignee: Becton, Dickinson and CompanyInventors: George Terrance Walker, James G. Nadeau, Patricia Anne Spears, Colleen M. Nycz, Daryl Dee Shank, James L. Schram, Stewart Russel Jurgensen
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Patent number: 5723296Abstract: Methods for identification or detection of a species of an organism or a group of related species of an organism by species non-specific amplification of a target sequence followed by species- or group-specific detection of the amplification products. Also provided are a target sequence which is amplifiable in multiple species of mycobacteria using a single pair of amplification primers and species- and group-specific detector probes for hybridization to the assay regioin of the amplified target. Blocking oligonucleotides are employed to allow discrimination among species in which the amplified target sequences are sufficiently similar that they cross-hybridize to an assay probe.Type: GrantFiled: May 10, 1996Date of Patent: March 3, 1998Assignee: Becton, Dickinson and CompanyInventors: Colleen Marie Nycz, James G. Nadeau, Patricia Brinkley Scott, Daryl Dee Shank, Patricia Anne Spears
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Patent number: 5691145Abstract: Oligonucleotides which form G-quartet structures have been found to be useful in fluorescence assays to detect a selected nucleic acid sequence. When one end of the oligonucleotide is labeled with a donor fluorophore and the other end is labeled with an acceptor dye, the folding of the molecule in the G-quartet structure brings the donor-acceptor pair into close proximity, allowing an interaction between the two labels which results in quenching of donor fluorescence or a change in other fluorescence properties which are the result of the interaction of two dyes in close proximity. The G-quartet structure unfolds upon hybridization to its complementary sequence, increasing the distance between the two dye labels. This results in decreased donor quenching or a change in another proximity-related fluorescence parameter. The associated increase in donor fluorescence intensity or the change in another fluorescence parameter may be monitored as an indication of the presence of a selected nucleic acid sequence.Type: GrantFiled: August 27, 1996Date of Patent: November 25, 1997Assignee: Becton, Dickinson and CompanyInventors: J. Bruce Pitner, Glenn P. Vonk, James G. Nadeau
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Patent number: 5681705Abstract: Amplification primers and methods are disclosed for complex-specific amplification of target sequences in the dnaJ genes of the Mycobacterium Avium Complex species. Also provided are assay probes for detection of the amplification products and/or identification of the MAC species which is present.Type: GrantFiled: August 28, 1995Date of Patent: October 28, 1997Inventors: James L. Schram, James G. Nadeau, Cheryl H. Dean
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Patent number: 5668265Abstract: The present invention relates to bi-directional nucleic acid ligand compounds wherein at least two oligonucleotides of opposite sequence polarity are linked to a connecting compound at their same respective terminii; either the 5' terminii or the 3 ' terminii. These compounds are useful for binding protein or small molecule targets and thus may be used as diagnostic or therapeutic agents.Type: GrantFiled: March 12, 1996Date of Patent: September 16, 1997Assignee: Becton Dickinson and CompanyInventors: James G. Nadeau, Mary Lee Ciolkowski, Erwin A. Vogler
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Patent number: 5658738Abstract: The present invention relates to bi-directional nucleic acid ligand compounds wherein at least two oligonucleotides of opposite sequence polarity are linked to a connecting compound at their same respective terminii; either the 5' terminii or the 3' terminii. These compounds are useful for binding protein or small molecule targets and thus may be used as diagnostic or therapeutic agents.Type: GrantFiled: December 11, 1995Date of Patent: August 19, 1997Assignee: Becton Dickinson and CompanyInventors: James G. Nadeau, Mary Lee Ciolkowski, Erwin A. Vogler
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Patent number: 5624825Abstract: Methods for multiplex amplification of target nucleic acid sequences using a single pair of primers. Defined sequences are appended to the ends of multiple target sequences as part of the amplification reaction so that no steps in addition to amplification are required. The target sequences with the appended defined sequences need not be isolated prior to amplification. In one embodiment for coamplification of two target sequences, a sequence corresponding to a terminal segment of the first target sequence is appended to one end of the second target sequence and a sequence corresponding to a terminal segment of the second target sequence is appended to one end of the first target sequence. Amplification of the two targets then requires only a single pair of primers. Alternatively, a single defined sequence may be appended to the 5' and 3' ends of any number of selected targets. All such modified target sequences may then be amplified using a single pair of primers which hybridize to the defined end-sequences.Type: GrantFiled: May 26, 1995Date of Patent: April 29, 1997Assignee: Becton, Dickinson and CompanyInventors: George T. Walker, James G. Nadeau, Michael C. Little
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Patent number: 5593867Abstract: Fluorescence polarization methods for detection of nucleic acid amplification. A fluorescently labelled oligodeoxynucleotide probe is converted from single- to double-stranded form in a target dependent manner during amplification of the target sequence. This conformational change is accompanied by an increase in fluorescence polarization values. The increase in fluorescence polarization can be measured on a transient-state fluorometer in real-time during the amplification reaction without any physical manipulation of the sample. The inventive methods therefore provide a closed, homogeneous system for both amplification of target sequences and detection of amplification. Alternatively, amplification may be detected in the fluorometer after the amplification reaction is completed.Type: GrantFiled: September 23, 1994Date of Patent: January 14, 1997Assignee: Becton, Dickinson and CompanyInventors: G. Terrance Walker, James G. Nadeau, C. Preston Linn
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Patent number: 5561044Abstract: Primers and methods for adapter-mediated multiplex amplification of the IS6110 insertion element of Mycobacterium tuberculosis (M.tb) and the 16S ribosomal gene of Mycobacterium tuberculosis, useful for simultaneously detecting and/or identifying species of the M. tuberculosis complex and other clinically relevant Mycobacterium species. Multiplex Strand Displacement Amplification (SDA) is used in a single amplification reaction which is capable of simultaneously identifying M. tuberculosis and providing a screen for substantially all of the clinically relevant species of Mycobacteria. Also disclosed are methods for adapter-mediated multiplex amplification of multiple target sequences and a single internal control sequence for determination of sample efficacy or quantitation of the targets.Type: GrantFiled: March 3, 1995Date of Patent: October 1, 1996Assignee: Becton, Dickinson and CompanyInventors: George T. Walker, James G. Nadeau, Patricia A. Spears, Colleen M. Nycz, Daryl D. Shank, James L. Schram, Stewart R. Jurgensen
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Patent number: 5547861Abstract: Methods for detecting, immobilizing or localizing primer extension products of a Strand Displacement Amplification reaction which are coupled to, and an indication of, amplification of the target sequence. The primer extension products are secondary, target-specific DNA products generated concurrently with SDA of the target sequence and can therefore be used to detect and/or measure target sequence amplification in real-time. In general, the secondary amplification products are not amplifiable and remain inert in the SDA reaction after they are formed without interfering with amplification of the target sequence. The secondary amplification products may be designed or modified to contain special features to facilitate their detection, immobilization or localization.Type: GrantFiled: April 18, 1994Date of Patent: August 20, 1996Assignee: Becton, Dickinson and CompanyInventors: James G. Nadeau, George T. Walker
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Patent number: 5470723Abstract: Primers and methods for adapter-mediated multiplex amplification of the IS6110 insertion element of Mycobacterium tuberculosis (M.tb) and the 16S ribosomal gene of Mycobacterium tuberculosis, useful for simultaneously detecting and/or identifying species of the M. tuberculosis complex and other clinically relevant Mycobacterium species. Multiplex Strand Displacement Amplification (SDA) is used in a single amplification reaction which is capable of simultaneously identifying M. tuberculosis and providing a screen for substantially all of the clinically relevant species of Mycobacteria. Also disclosed are methods for adapter-mediated multiplex amplification of multiple target sequences and a single internal control sequence for determination of sample efficacy or quantitation of the targets.Type: GrantFiled: August 24, 1993Date of Patent: November 28, 1995Assignee: Becton, Dickinson and CompanyInventors: George T. Walker, James G. Nadeau, Patricia A. Spears, Colleen M. Nycz, Daryl D. Shank, James L. Schram, Stewart R. Jurgensen