Patents by Inventor Lawrence A. Haff
Lawrence A. Haff 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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Publication number: 20130084561Abstract: The invention provides compositions and methods for the detection of biological targets, (e.g. nucleic acids and proteins) by nucleic acid templated chemistry, for example, by generating fluorescent, chemiluminescent and/or chromophoric signals.Type: ApplicationFiled: May 9, 2012Publication date: April 4, 2013Inventors: James M. Coull, Andrew M. Stern, Lawrence A. Haff, Barbara S. Fox, Yumei Huang
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Patent number: 7968289Abstract: The invention provides turnover probes for use in a variety of detection assays, for example, nucleic acid detection assays. In addition, the invention provides assays, for example, nucleic acid detection assays, using such turnover probes.Type: GrantFiled: May 3, 2006Date of Patent: June 28, 2011Assignee: Ensemble Therapeutics CorporationInventors: James M. Coull, Lawrence A. Haff, Joshua A. Bittker, Xiaoyu Li, Larry W. McLaughlin
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Publication number: 20100159446Abstract: The invention provides compositions and methods for the detection and/or quantification of biological targets (e.g., nucleic acids and proteins) by the nucleic acid-templated creation of one or more reaction products, for example, epitopes, enzyme substrates, enzyme activators, and ligands. The reaction products can be detected and/or quantitated after signal amplification using an amplification system.Type: ApplicationFiled: July 21, 2008Publication date: June 24, 2010Inventors: Lawrence A. Haff, Yumei Huang, Richard A. Martinelli, Benjamin A. Seigal, David J. Livingston, Wei-Chuan Sun
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Publication number: 20090280477Abstract: The invention provides turnover probes for use in a variety of detection assays, for example, nucleic acid detection assays. In addition, the invention provides assays, for example, nucleic acid detection assays, using such turnover probes.Type: ApplicationFiled: May 3, 2006Publication date: November 12, 2009Inventors: James M. Coull, Lawrence A. Haff, Joshua A. Bittker, Xiaoyu Li, Alexander F. Rosenberg, Larry W. McLaughlin
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Publication number: 20070154899Abstract: The invention provides compositions and methods for the detection of biological targets, (e.g. nucleic acids and proteins) by nucleic acid templated chemistry, for example, by generating fluorescent, chemiluminescent and/or chromophoric signals.Type: ApplicationFiled: May 26, 2006Publication date: July 5, 2007Inventors: James Coull, Andrew Stern, Lawrence Haff, Barbara Fox, Yumei Huang
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Publication number: 20050130178Abstract: An asynchronous thermal cycling protocol for nucleic acid amplification uses two primers with thermal melting temperatures different by about 10 to 30° C. After the higher melting primer has annealed and polymerase mediated extension, the uncopied, single-stranded target sequence may be hybridized and detected by a probe. DNA probes may be cleaved by the exonuclease activity of a polymerase. The probe may be a non-cleaving analog such as PNA. When a probe is labelled with a reporter dye and a quencher selected to undergo energy transfer, e.g. FRET, fluorescence from the reporter dye may be effectively quenched when the probe is unbound. Upon hybridization of the probe to complementary target or upon cleavage while bound to target, the reporter dye is no longer quenched, resulting in a detectable amount of fluorescence. The second, lower-melting primer may be annealed and extended to generate a double-stranded nucleic acid. Amplification may be monitored in real time, including each cycle, or at the end point.Type: ApplicationFiled: June 9, 2004Publication date: June 16, 2005Applicant: Applera CorporationInventors: Caifu Chen, Michael Egholm, Lawrence Haff
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Patent number: 6900061Abstract: A sample plate for a MALDI process is provided which comprises an electrically conductive substrate having a hydrophobic coating whose thickness and hydrophobic character can be modified by changing the coating substrate and/or the concentration of the substrate. Different coating substances that have provided optimal performance of the sample plate for reproducible deposition and analysis by MALDI-MS and MALDI-MS/MS processes of analyte mixtures include synthetic waxes such as paraffin compositions, lipids, organic acids, silicon-containing compounds, silica polymers and natural waxes. Metal polishes that have been used to clean and regenerate plate surfaces have also provided a sample plate that has optimal performance for reproducible deposition and analysis by MALDI-MS and MALDI-MS/MS processes of analyte mixtures.Type: GrantFiled: August 23, 2002Date of Patent: May 31, 2005Assignees: PerSeptive BioSystems, Inc., MDS Inc.Inventors: Igor P. Smirnov, Andrew J. Tomlinson, Lawrence A. Haff, Jennifer M. Campbell, Cheryl E. Murphy
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Patent number: 6887664Abstract: An asynchronous thermal cycling protocol for nucleic acid amplification uses two primers with thermal melting temperatures different by about 10 to 30° C. After the higher melting primer has annealed and polymerase mediated extension, the uncopied, single-stranded target sequence may be hybridized and detected by a probe. DNA probes may be cleaved by the exonuclease activity of a polymerase. The probe may be a non-cleaving analog such as PNA. When a probe is labelled with a reporter dye and a quencher selected to undergo energy transfer, e.g. FRET, fluorescence from the reporter dye may be effectively quenched when the probe is unbound. Upon hybridization of the probe to complementary target or upon cleavage while bound to target, the reporter dye is no longer quenched, resulting in a detectable amount of fluorescence. The second, lower-melting primer may be annealed and extended to generate a double-stranded nucleic acid. Amplification may be monitored in real time, including each cycle, or at the end point.Type: GrantFiled: June 5, 2001Date of Patent: May 3, 2005Assignee: Applera CorporationInventors: Caifu Chen, Michael Egholm, Lawrence A. Haff
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Publication number: 20040038423Abstract: A sample plate for a MALDI process is provided which comprises an electrically conductive substrate having a hydrophobic coating whose thickness and hydrophobic character can be modified by changing the coating substrate and/or the concentration of the substrate. Different coating substances that have provided optimal performance of the sample plate for reproducible deposition and analysis by MALDI-MS and MALDI-MS/MS processes of analyte mixtures include synthetic waxes such as paraffin compositions, lipids, organic acids, silicon-containing compounds, silica polymers and natural waxes. Metal polishes that have been used to clean and regenerate plate surfaces have also provided a sample plate that has optimal performance for reproducible deposition and analysis by MALDI-MS and MALDI-MS/MS processes of analyte mixtures.Type: ApplicationFiled: August 23, 2002Publication date: February 26, 2004Inventors: Igor P. Smirnov, Andrew J. Tomlinson, Lawrence A. Haff, Jennifer M. Campbell, Cheryl E. Murphy
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Publication number: 20030207266Abstract: An asynchronous thermal cycling protocol for nucleic acid amplification uses two primers with thermal melting temperatures different by about 10 to 30° C. After the higher melting primer has annealed and polymerase mediated extension, the uncopied, single-stranded target sequence may be hybridized and detected by a probe. DNA probes may be cleaved by the exonuclease activity of a polymerase. The probe may be a non-cleaving analog such as PNA. When a probe is labelled with a reporter dye and a quencher selected to undergo energy transfer, e.g. FRET, fluorescence from the reporter dye may be effectively quenched when the probe is unbound. Upon hybridization of the probe to complementary target or upon cleavage while bound to target, the reporter dye is no longer quenched, resulting in a detectable amount of fluorescence. The second, lower-melting primer may be annealed and extended to generate a double-stranded nucleic acid.Type: ApplicationFiled: June 5, 2001Publication date: November 6, 2003Inventors: Caifu Chen, Michael Egholm, Lawrence A. Haff
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Publication number: 20030039976Abstract: Methods are provided for determining polynucleotide sequence information using mass-modified bases incorporated into amplification products. A sample including a target nucleic acid is amplified in the presence of a mass-modified nucleobase to produce an amplified product incorporating the mass-modified nucleobase. The mass of one strand of the amplified product is compared with the mass of one strand of a reference nucleic acid.Type: ApplicationFiled: August 14, 2001Publication date: February 27, 2003Inventor: Lawrence A. Haff
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Patent number: 6033880Abstract: Apparatus and method for performing a nucleic acid amplification reaction and preferably a polymerase chain reaction (PCR) in a reaction mixture in at least one capillary tube. Several different embodiments are disclosed. One embodiment cycles a sample through a capillary tube loop passing through two thermostatted fluid baths. Another embodiment has the capillary tube routed alternatingly between two heat exchangers to that the sample makes only one pass through the tube. Other embodiments maintain the heat exchangers stationary and translate the samples between them. Still further embodiments maintain the samples stationary and either automatically translate or rotate the heat exchangers past the samples contained within the capillary tubes to perform the thermal cycles necessary for the amplification reaction.Type: GrantFiled: February 23, 1998Date of Patent: March 7, 2000Assignee: The Perkin-Elmer CorporationInventors: Lawrence A. Haff, Enrico Picozza, Will Bloch, Robert Ragusa, Joseph DiCesare, David Tracy, Paul Saviano, Timothy M. Woudenberg, Richard W. Noreiks
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Patent number: 5885775Abstract: The invention relates to methods for determining sequence information in polynucleotides by combining the recent disparate technologies of mass spectrometry and polynucleotide hybridization, amplification, extension and/or ligation techniques. Broadly, in a first step, the method for determining sequence information in a sample polynucleotide includes hybridizing with a sample nucleotide one or a mixture of oligonucleotide probes having a nucleotide sequence complementary to a portion of the sample polynucleotide, thereby forming a complex. Then, in a second step, the complex is contacted with at least a member selected from the group consisting of nucleosides, dideoxynucleosides, polymerases, nucleases, transcriptases, ligases and restriction enzymes to alter at least a subset of said oligonucleotide probes.Type: GrantFiled: October 4, 1996Date of Patent: March 23, 1999Assignee: PerSeptive Biosystems, Inc.Inventors: Lawrence A. Haff, Igor Pavlovich Smirnov
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Patent number: 5827480Abstract: Apparatus and method for performing a nucleic acid amplification reaction and preferably a polymerase chain reaction (PCR) in a reaction mixture in at least one capillary tube. Several different embodiments are disclosed. One embodiment cycles a sample through a capillary tube loop passing through two thermostatted fluid baths. Another embodiment has the capillary tube routed alternatingly between two heat exchangers to that the sample makes only one pass through the tube. Other embodiments maintain the heat exchangers stationary and translate the samples between them. Still further embodiments maintain the samples stationary and either automatically translate or rotate the heat exchangers past the samples contained within the capillary tubes to perform the thermal cycles necessary for the amplification reaction.Type: GrantFiled: March 25, 1997Date of Patent: October 27, 1998Assignee: The Perkin-Elmer CorporationInventors: Lawrence A. Haff, Enrico Picozza, Will Bloch, Timothy M. Woudenberg
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Patent number: 5779977Abstract: Apparatus and method for performing a nucleic acid amplification reaction and preferably a polymerase chain reaction (PCR) in a reaction mixture in at least one capillary tube. Several different embodiments are disclosed. One embodiment cycles a sample through a capillary tube loop passing through two thermostatted fluid baths. Another embodiment has the capillary tube routed alternatingly between two heat exchangers to that the sample makes only one pass through the tube. Other embodiments maintain the heat exchangers stationary and translate the samples between them. Still further embodiments maintain the samples stationary and either automatically translate or rotate the heat exchangers past the samples contained within the capillary tubes to perform the thermal cycles necessary for the amplification reaction.Type: GrantFiled: March 26, 1997Date of Patent: July 14, 1998Assignee: The Perkin-Elmer CorporationInventors: Lawrence A. Haff, Enrico Picozza, Will Bloch, Timothy M. Woudenberg
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Patent number: 5720923Abstract: Apparatus and method for performing a nucleic acid amplification reaction and preferably a polymerase chain reaction (PCR) in a reaction mixture in at least one capillary tube. Several different embodiments are disclosed. One embodiment cycles a sample through a capillary tube loop passing through two thermostatted fluid baths. Another embodiment has the capillary tube routed alternatingly between two heat exchangers to that the sample makes only one pass through the tube. Other embodiments maintain the heat exchangers stationary and translate the samples between them. Still further embodiments maintain the samples stationary and either automatically translate or rotate the heat exchangers past the samples contained within the capillary tubes to perform the thermal cycles necessary for the amplification reaction.Type: GrantFiled: August 31, 1994Date of Patent: February 24, 1998Assignee: The Perkin-Elmer CorporationInventors: Lawrence A. Haff, Enrico Picozza, Will Bloch, Robert Ragusa, Joseph DiCesare, David Tracy, Paul Saviano, Timothy M. Woudenberg
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Patent number: 5675700Abstract: A complete in situ PCR system for amplification of nucleic acids contained in a prepared cell or tissue sample. The containment system for the PCR sample comprises a glass microscope slide, a specimen sample containing the target nucleic acid sequence mounted on the slide, a flexible plastic cover over the sample, and a retaining assembly fastened to the slide and to the cover to retain and seal a reaction mixture against the sample during thermal cycling.The retaining assembly includes a rigid ring on a rim portion of the cover, a cross beam having spaced parallel rails joined by opposite flat ends, and a pair of clips which are pressed over the ends and opposite sides of the slide to fasten the cross beam and cover to the slide.Type: GrantFiled: June 5, 1995Date of Patent: October 7, 1997Assignee: The Perkin-Elmer CorporationInventors: John G. Atwood, Lawrence A. Haff
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Patent number: 5527510Abstract: A complete in situ PCR system for amplification of nucleic acids contained in a prepared cell or tissue sample. The containment system for the PCR sample comprises a glass microscope slide, a specimen sample containing the target nucleic acid sequence mounted on the slide, a flexible plastic cover over the sample, and a retaining assembly fastened to the slide and to the cover to retain and seal a reaction mixture against the sample during thermal cycling. The retaining assembly includes a rigid ring on a rim portion of the cover, a cross beam having spaced parallel rails joined by opposite flat ends, and a pair of clips which are pressed over the ends and opposite sides of the slide to fasten the cross beam and cover to the slide.Type: GrantFiled: June 5, 1995Date of Patent: June 18, 1996Assignee: The Perkin-Elmer CorporationInventors: John G. Atwood, Lawrence A. Haff
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Patent number: 5480783Abstract: A kit and method for reduction of primer-independent background signals in a DNA replication/detection assay, particularly in a direct in situ PCR amplification/detection assay, for a target DNA sequence in DNA sample, comprising pretreating the DNA sample, containing the target DNA sequence to be replicated/amplified and assayed, with DNA polymerase and one or more dideoxynucleoside triphosphates prior to conducting the replication/amplification steps.Type: GrantFiled: March 31, 1994Date of Patent: January 2, 1996Assignee: The Perkin-Elmer CorporationInventor: Lawrence A. Haff
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Patent number: 5364790Abstract: A complete in situ PCR system for amplification of nucleic acids contained in a prepared cell or tissue sample. The containment system for the PCR sample comprises a glass microscope slide, a specimen sample containing the target nucleic acid sequence mounted on the slide, a flexible plastic cover over the sample, and a retaining assembly fastened to the slide and to the cover to retain and seal a reaction mixture against the sample during thermal cycling. The retaining assembly includes a rigid ring on a rim portion of the cover, a cross beam having spaced parallel rails joined by opposite flat ends, and a pair of clips which are pressed over the ends and opposite sides of the slide to fasten the cross beam and cover to the slide.Type: GrantFiled: February 16, 1993Date of Patent: November 15, 1994Assignee: The Perkin-Elmer CorporationInventors: John G. Atwood, Lawrence A. Haff