Abstract: This disclosure describes related novel methods for Recombinase-Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed methods have the advantage of not requiring thermocycling or thermophilic enzymes, thus offering easy and affordable implementation and portability relative to other amplification methods. Further disclosed are conditions to enable real-time monitoring of RPA reactions, methods to regulate RPA reactions using light and otherwise, methods to determine the nature of amplified species without a need for gel electrophoresis, methods to improve and optimize signal to noise ratios in RPA reactions, methods to optimize oligonucleotide primer function, methods to control carry-over contamination, and methods to employ sequence-specific third ‘specificity’ probes.
Type:
Grant
Filed:
January 30, 2015
Date of Patent:
April 12, 2016
Assignee:
Alere San Diego Inc.
Inventors:
Olaf Piepenburg, Colin H. Williams, Niall A. Armes, Derek L. Stemple
Abstract: A process includes providing a mixture that includes a recombinase, a single-strand binding protein, and one or more oligonucleotides; and detecting particles in the reaction mixture.
Type:
Grant
Filed:
February 18, 2014
Date of Patent:
October 13, 2015
Assignee:
Alere San Diego Inc.
Inventors:
Niall A. Armes, Olaf Piepenburg, Catherine Jean Greenwood
Abstract: The present invention provides methods and compositions for monitoring of subjects suffering from, or being evaluated for, heart failure. A filtered Natriuretic peptide time-series, alone or in combination with other clinical indicia such as weight gain, can be used to estimate a patient's hazard (risk of decompensation). The cumulative integral of Natriuretic peptide concentration can be used to estimate cumulative hazard (risk times exposure) over longer periods of exposure, e.g., 14 day periods, or 30 day periods.
Type:
Application
Filed:
August 3, 2012
Publication date:
June 18, 2015
Applicant:
Alere San Diego, Inc.
Inventors:
Kenneth Kupfer, Richard C. Sangeorge, Jerome Mcaleer, Kevin Keegen, David Kinniburgh Lang
Abstract: This disclosure describes kits, reagents and methods for Recombinase Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed kits, reagents and methods have the advantage of not requiring thermocycling or thermophilic enzymes, thus offering easy and affordable implementation and portability relative to other amplification methods.
Abstract: The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects. In particular, the invention relates to methods and compositions selected to monitor cardiorenal syndrome using assays that detect NGAL, preferably together with assays that detect natriuretic peptides such as BNP. Such methods and compositions can provide early indications of a deterioration in cardiorenal syndrome status, including prognosis regarding mortality and worsening renal function.
Abstract: This disclosure describes related novel methods for Recombinase-Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed methods have the advantage of not requiring thermocycling or thermophilic enzymes. Further, the improved processivity of the disclosed methods may allow amplification of DNA up to hundreds of megabases in length.
Type:
Grant
Filed:
September 23, 2013
Date of Patent:
February 24, 2015
Assignee:
Alere San Diego, Inc.
Inventors:
Olaf Piepenburg, Colin H. Williams, Niall A. Armes, Derek L. Stemple
Abstract: This disclosure describes related novel methods for Recombinase-Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed methods have the advantage of not requiring thermocycling or thermophilic enzymes, thus offering easy and affordable implementation and portability relative to other amplification methods. Further disclosed are conditions to enable real-time monitoring of RPA reactions, methods to regulate RPA reactions using light and otherwise, methods to determine the nature of amplified species without a need for gel electrophoresis, methods to improve and optimize signal to noise ratios in RPA reactions, methods to optimize oligonucleotide primer function, methods to control carry-over contamination, and methods to employ sequence-specific third ‘specificity’ probes.
Type:
Grant
Filed:
March 27, 2013
Date of Patent:
February 3, 2015
Assignee:
Alere San Diego Inc.
Inventors:
Olaf Piepenburg, Colin H. Williams, Niall A. Armes, Derek L. Stemple
Abstract: A process includes providing a mixture that includes a recombinase, a single-strand binding protein, and one or more oligonucleotides; and detecting particles in the reaction mixture.
Type:
Application
Filed:
February 18, 2014
Publication date:
January 22, 2015
Applicant:
Alere San Diego, Inc.
Inventors:
Niall A. Armes, Olaf Piepenburg, Catherine Jean Greenwood
Abstract: The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects. In particular, the invention relates to methods and compositions selected to monitor cardiorenal syndrome using assays that detect NGAL, preferably together with assays that detect natriuretic peptides such as BNP. Such methods and compositions can provide early indications of a deterioration in cardiorenal syndrome status, including prognosis regarding mortality and worsening renal function.
Abstract: The invention encompasses diagnosis and prognosis in the context of heart or renal failure, particularly in subjects who exhibit a normal body fluid level of a natriuretic peptide. The invention also relates to methods of assigning an increased likelihood that a subject having AKI is susceptible to AKI progression. The invention relates in part to assigning a diagnosis of heart and/or renal failure, and/or an outcome risk (e.g., worsening cardiac and/or renal function or a mortality risk) to a subject based, at least in part, on the result(s) obtained from an assay that detects WAP four-disulfide core domain protein 2 performed on a body fluid sample obtained from a subject.
Type:
Application
Filed:
July 3, 2012
Publication date:
October 23, 2014
Applicant:
ALERE SAN DIEGO INC.
Inventors:
William D. Arnold, Christelle Jost, Brian Noland, Jonathan Gary, Joseph Buechler, Vance Wong, Scott Harold Rongey, Uday Kumar Veeramallu, Kelline Marie Rodems
Abstract: This disclosure provides for methods and reagents for rapid multiplex RPA reactions and improved methods for detection of multiplex RPA reaction products. In addition, the disclosure provides new methods for eliminating carryover contamination between RPA processes.
Type:
Application
Filed:
October 29, 2013
Publication date:
October 2, 2014
Applicant:
ALERE SAN DIEGO, INC.
Inventors:
Olaf Piepenburg, Colin H. Williams, Niall A. Armes
Abstract: The present invention relates to novel 2-hydroxyhippuric acid analogs, and methods for their synthesis and use. Such analogs are designed to provide a protected or functional moiety such as a free thiol (—SH) group or a protected thiol group, thereby providing a convenient linkage chemistry for coupling under mild conditions to a suitable group on a target protein, polypeptide, solid phase or detectable label.
Abstract: This disclosure describes related novel methods for Recombinase-Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed methods have the advantage of not requiring thermocycling or thermophilic enzymes. Further, the improved processivity of the disclosed methods may allow amplification of DNA up to hundreds of megabases in length.
Type:
Application
Filed:
September 23, 2013
Publication date:
August 21, 2014
Applicant:
Alere San Diego, Inc.
Inventors:
Olaf Piepenburg, Colin H. Williams, Niall A. Armes, Derek L. Stemple
Abstract: A process includes providing a mixture that includes a recombinase, a single-strand binding protein, and one or more oligonucleotides; and detecting particles in the reaction mixture.
Type:
Grant
Filed:
April 6, 2012
Date of Patent:
August 19, 2014
Assignee:
Alere San Diego Inc.
Inventors:
Niall A. Armes, Olaf Piepenburg, Catherine Jean Greenwood
Abstract: The present invention relates in part to diagnosing the occurrence of heart failure, particularly in subjects who exhibit a normal body fluid level of a natriuretic peptide. The present invention further relates in part to assigning an outcome risk (e.g., worsening cardiac function or a mortality risk, a risk of rehospitalization) to a subject. The methods comprise performing one or more assays that detect one or more biomarkers selected from the group consisting of WAP4C, ESAM, LTBR, Mesothelin, and Syndecan-1 performed on a body fluid sample obtained from a subject, and assigning diagnosis or risk based, at least in part, on the result(s) obtained thereby.
Type:
Grant
Filed:
November 25, 2011
Date of Patent:
August 5, 2014
Assignee:
Alere San Diego, Inc.
Inventors:
William D. Arnold, Christelle Jost, Brian Noland, Jonathan Gary, Joseph Buechler, Vance Wong, Scott Harold Rongey, Uday Kumar Veeramallu, Kelline Marie Rodems
Abstract: The present invention relates in part to diagnosing the occurrence of heart failure, particularly in subjects who exhibit a normal body fluid level of a natriuretic peptide. The present invention further relates in part to assigning an outcome risk (e.g., worsening cardiac function or a mortality risk, a risk of rehospitalization) to a subject. The methods comprise performing one or more assays that detect one or more biomarkers selected from the group consisting of WAP4C, ESAM, LTBR, Mesothelin, and Syndecan-1 performed on a body fluid sample obtained from a subject, and assigning diagnosis or risk based, at least in part, on the result(s) obtained thereby.
Type:
Application
Filed:
November 25, 2011
Publication date:
May 29, 2014
Applicant:
ALERE SAN DIEGO, INC.
Inventors:
William D. Arnold, Christelle Jost, Brian Noland, Jonathan Gary, Joseph Buechler, Vance Wong, Scott Harold Rongey, Uday Kumar Veeramallu, Kelline Marie Rodems
Abstract: This disclosure describes related novel methods for Recombinase-Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed methods have the advantage of not requiring thermocycling or thermophilic enzymes, thus offering easy and affordable implementation and portability relative to other amplification methods. Further disclosed are conditions to enable real-time monitoring of RPA reactions, methods to regulate RPA reactions using light and otherwise, methods to determine the nature of amplified species without a need for gel electrophoresis, methods to improve and optimize signal to noise ratios in RPA reactions, methods to optimize oligonucleotide primer function, methods to control carry-over contamination, and methods to employ sequence-specific third ‘specificity’ probes.
Type:
Application
Filed:
March 27, 2013
Publication date:
April 10, 2014
Applicant:
Alere San Diego Inc.
Inventors:
Olaf Piepenburg, Colin H. Williams, Niall A. Armes, Derek L. Stemple
Abstract: The present invention features novel, diverse, hybrid and engineered recombinase enzymes, and the utility of such proteins with associated recombination factors for carrying out DNA amplification assays. The present invention also features different recombinase ‘systems’ having distinct biochemical activities in DNA amplification assays, and differing requirements for loading factors, single-stranded DNA binding proteins (SSBs), and the quantity of crowding agent employed.
Type:
Grant
Filed:
November 30, 2011
Date of Patent:
January 28, 2014
Assignee:
Alere San Diego, Inc.
Inventors:
Olaf Piepenburg, Niall A. Armes, Mathew James David Parker
Abstract: This disclosure provides for methods and reagents for rapid multiplex RPA reactions and improved methods for detection of multiplex RPA reaction products. In addition, the disclosure provides new methods for eliminating carryover contamination between RPA processes.
Type:
Grant
Filed:
July 6, 2011
Date of Patent:
November 12, 2013
Assignee:
Alere San Diego, Inc.
Inventors:
Olaf Piepenburg, Colin H. Williams, Niall A. Armes
Abstract: This disclosure describes related novel methods for Recombinase-Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed methods have the advantage of not requiring thermocycling or thermophilic enzymes. Further, the improved processivity of the disclosed methods may allow amplification of DNA up to hundres of megabases in length.
Type:
Grant
Filed:
August 4, 2011
Date of Patent:
November 5, 2013
Assignee:
Alere San Diego, Inc.
Inventors:
Olaf Piepenburg, Colin H. Williams, Niall A. Armes, Derek L. Stemple