Method for sequencing polynucleotides

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United States of America Patent

PATENT NO

5302509

SERIAL NO

07661750

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Abstract

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A method is provided for determining the sequence of nucleotides on a single strand DNA molecule. The single strand DNA molecule is attached to a leader oligonucleotide and its complementary strand to a solid state support. Fluorescently-labeled 3'-blocked nucleotide triphosphates, with each of the bases A, G, C, T having a different fluorescent label, are mixed with the bound DNA molecule in the presence of DNA polymerase. The DNA polymerase causes selective addition of only the complementary labeled NTP, thus identifying the next unpaired base in the unknown DNA strand. The 3'-blocking group is then removed, setting the system up for the next NTP addition and so on. The sequence is repeated until no more fluorescently-labeled NTPs can be detected as being added by the polymerase.

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Patent Owner(s)

Patent OwnerAddressTotal Patents
BECKMAN INSTRUMENTS, INC.FULLERTON, CA103

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Inventor(s)

Inventor Name Address # of filed Patents Total Citations
Cheeseman, Peter C Palo Alto, CA 1 401

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Patent Info (Count) # Cites Year
 
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NATIONAL SCIENCE FOUNDATION (3)
* 2006/0154,288 Methods for analyzing nucleic acid sequences 6 2006
* 2007/0134,716 Zero-mode metal clad waveguides for performing spectroscopy with confined effective observation volumes 2 2007
* 2008/0131,895 Massive parallel method for decoding DNA and RNA 10 2007
 
NANOFLUIDICS, INC. (2)
7170050 Apparatus and methods for optical analysis of molecules 120 2004
* 2006/0060,766 Apparatus and methods for optical analysis of molecules 19 2004
 
Whitehead Institute for Biomedical Research (1)
6203993 Methods for the detection of nucleic acids 122 2000
 
Focus Technologies, Inc. (4)
6867004 Methods of using oxidized fungal antigens in antibody testing 1 2001
* 2003/0124,630 Oxidized fungal antigens and methods of making and using thereof 0 2001
7205114 Oxidized fungal antigens and methods of making and using thereof 0 2004
* 2005/0112,708 Oxidized fungal antigens and methods of making and using thereof 0 2004
 
BECKMAN COULTER, INC. (10)
* 5837860 Covalent attachment of nucleic acid molecules onto solid-phases via disulfide bonds 66 1997
6322968 De novo or "universal" sequencing array 28 1997
* 6030782 Covalent attachment of nucleic acid molecules onto solid-phases via disulfide bonds 43 1997
6872521 Polymerase signaling assay 2 1998
* 6136962 Covalent attachment of unmodified nucleic acids to silanized solid phase surfaces 29 1998
6387626 Covalent attachment of unmodified nucleic acids to silanized solid phase surfaces 19 2000
6337188 De novo or "universal" sequencing array 24 2000
6946249 De novo or "universal" sequencing array 8 2001
* 2004/0126,765 Method and compositions for sequencing nucleic acid molecules 17 2002
* 2005/0094,807 Accuracy array assay system and method 0 2003
 
The Governors of the University of Alberta (2)
7037687 Method of determining the nucleotide sequence of oligonucleotides and DNA molecules 151 2002
* 2003/0138,809 Method of determining the nucleotide sequence of oligonucleotides and DNA molecules 60 2002
 
SPECTRAGEN, INC. (5)
* 5695934 Massively parallel sequencing of sorted polynucleotides 217 1994
* 5604097 Methods for sorting polynucleotides using oligonucleotide tags 293 1994
* 5863722 Method of sorting polynucleotides 157 1995
* 5654413 Compositions for sorting polynucleotides 95 1995
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Orchid Bio Computer, Inc. (1)
* 5919626 Attachment of unmodified nucleic acids to silanized solid phase surfaces 67 1997
 
HOWARD HUGHES MEDICAL INSTITUTE (1)
6326489 Surface-bound, bimolecular, double-stranded DNA arrays 62 1997
 
CALIFORNIA INSTITUTE OF TECHNOLOGY (10)
6818395 Methods and apparatus for analyzing polynucleotide sequences 189 2000
6911345 Methods and apparatus for analyzing polynucleotide sequences 163 2001
* 2002/0025,529 Methods and apparatus for analyzing polynucleotide sequences 30 2001
7297518 Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension 110 2002
* 2002/0164,629 Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension 64 2002
7462449 Methods and apparatuses for analyzing polynucleotide sequences 14 2004
* 2005/0147,992 Methods and apparatus for analyzing polynucleotide sequences 22 2004
* 2006/0172,408 Device for immobilizing chemical and biochemical species and methods of using same 74 2004
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VISIGEN, INC. (1)
* 2003/0064,366 Real-time sequence determination 151 2001
 
Intelligent BioSystems, Inc. (6)
* 8612161 Methods and compositions for base calling nucleic acids 3 2009
8481259 Methods and devices for sequencing nucleic acids in smaller batches 6 2010
* 2010/0323,350 Methods And Devices For Sequencing Nucleic Acids In Smaller Batches 23 2010
9017973 Methods and compositions for incorporating nucleotides 0 2011
9145589 Methods and devices for sequencing nucleic acids in smaller batches 0 2014
9399799 Methods and compositions for incorporating nucleotides 0 2014
 
INDUSTRIAL TECHNOLOGY RESEARCH INSTITUTE (4)
7767441 Bioassay system including optical detection apparatuses, and method for detecting biomolecules 18 2008
* 2009/0146,076 BIOASSAY SYSTEM INCLUDING OPTICAL DETECTION APPARATUSES, AND METHOD FOR DETECTING BIOMOLECULES 18 2008
7811810 Bioassay system including optical detection apparatuses, and method for detecting biomolecules 14 2009
9482615 Single-molecule detection system and methods 0 2011
 
HELICOS BIOSCIENCES CORPORATION (3)
* 2005/0239,085 Methods for nucleic acid sequence determination 22 2004
* 2005/0170,367 Fluorescently labeled nucleoside triphosphates and analogs thereof for sequencing nucleic acids 26 2004
* 2006/0118,754 Stabilizing a polyelectrolyte multilayer 1 2004
 
BP CORPORATION NORTH AMERICA INC. (2)
7291460 Multiplexed systems for nucleic acid sequencing 0 2003
* 2003/0224,439 Multiplexed systems for nucleic acid sequencing 4 2003
 
Arroyo Optics, Inc. (1)
* 2003/0092,051 Pyrophosphorolysis activated polymerization (PAP): application to allele-specific amplification and nucleic acid sequence determination 0 2002
 
Dynex Technologies (1)
9244069 Sample plate systems and methods 1 2012
 
MDS ANALYTICAL TECHNOLOGIES (US) INC (2)
6297018 Methods and apparatus for detecting nucleic acid polymorphisms 125 2000
* 2005/0227,294 Molecular modification assays involving lipids 2 2005
 
ALERE SAN DIEGO, INC. (1)
7270951 Method for direct nucleic acid sequencing 36 2000
 
Pacific Biosciences (1)
* 2009/0082,212 SYSTEM AND METHODS FOR NUCLEIC ACID SEQUENCING OF SINGLE MOLECULES BY POLYMERASE SYNTHESIS 4 2007
 
APPLIED BIOSYSTEMS, LLC (10)
* 5945284 Length determination of nucleic acid repeat sequences by discontinuous primer extension 43 1997
6309829 Length determination of nucleic acid repeat sequences by discontinuous primer extension 13 1998
6773887 Length determination of nucleic acid repeat sequences by discontinuous primer extension 2 2001
7414115 Length determination of nucleic acid repeat sequences by discontinuous primer extension 2 2007
* 2009/0062,129 REAGENTS, METHODS, AND LIBRARIES FOR GEL-FREE BEAD-BASED SEQUENCING 22 2007
8431691 Reagents, methods, and libraries for bead-based sequencing 2 2008
* 2009/0062,132 ALTERNATIVE NUCLEIC ACID SEQUENCING METHODS 87 2008
8329404 Reagents, methods, and libraries for bead-based sequencing 3 2012
9217177 Methods for bead-based sequencing 0 2013
9493830 Reagents, methods, and libraries for bead-based sequencing 0 2013
 
Genway Biotech Inc. (2)
6951742 Methods and vectors for generating antibodies in avian species and uses therefor 1 2000
* 2005/0208,628 Methods and vectors for generating antibodies in avian species and uses therefor 0 2005
 
CITY OF HOPE (13)
6534269 Pyrophosphorolysis activated polymerization (PAP): application to allele-specific amplification and nucleic acid sequence determination 16 2001
7105298 Serial coupling of restriction cleavage and extension for nucleic acid amplification 2 2002
7033763 Pyrophosphorolysis activated polymerization (PAP) 4 2003
* 2004/0009,515 Pyrophosphorolysis activated polymerization (PAP) 2 2003
7238480 Pyrophosphorolysis activated polymerization (PAP) 2 2004
* 2005/0095,608 Pyrophosphorolysis activated polymerization (PAP) 0 2004
7504221 Pyrophosphorolysis activated polymerization (PAP) 4 2007
* 2007/0298,428 PYROPHOSPHOROLYSIS ACTIVATED POLYMERIZATION (PAP) 0 2007
7914995 Reaction mixture for pyrophosphorolysis activated polymerization (PAP) 0 2009
7919253 Serial coupling of nucleic acid metabolism and extension for nucleic acid amplification 2 2009
* 2010/0129,871 PYROPHOSPHOROLYSIS ACTIVATED POLYMERIZATION (PAP) 2 2009
8173371 Serial coupling of nucleic acid metabolism and extension for nucleic acid amplification 0 2010
* 2011/0124,051 PYROPHOSPHOROLYSIS ACTIVATED POLYMERIZATION (PAP) 1 2010
 
454 LIFE SCIENCES CORPORATION (7)
6274320 Method of sequencing a nucleic acid 293 1999
7244559 Method of sequencing a nucleic acid 187 2001
7335762 Apparatus and method for sequencing a nucleic acid 129 2002
* 2007/0092,872 Apparatus and method for sequencing a nucleic acid 106 2002
7264929 Method of sequencing a nucleic acid 170 2002
7211390 Method of sequencing a nucleic acid 146 2004
* 2004/0248,161 Method of sequencing a nucleic acid 122 2004
 
EXACT LABORATORIES, INC. (1)
* 2010/0173,320 Methods for Detecting Nucleic Acids Indicative of Cancer 0 2010
 
ROCHE MOLECULAR SYSTEMS, INC. (1)
9322062 Process for biosensor well formation 0 2014
 
VERIZON PATENT AND LICENSING INC. (1)
* 2008/0235,019 AGE DETERMINATION USING SPEECH 2 2007
 
ESOTERIX GENETIC LABORATORIES, LLC (26)
* 5928870 Methods for the detection of loss of heterozygosity 115 1997
* 6100029 Methods for the detection of chromosomal aberrations 74 1997
* 6146828 Methods for detecting differences in RNA expression levels and uses therefor 64 1998
* 6020137 Methods for the detection of loss of heterozygosity 46 1998
6280947 Methods for detecting nucleotide insertion or deletion using primer extension 29 1999
6919174 Methods for disease detection 18 2000
6300077 Methods for the detection of nucleic acids 43 2000
6849403 Apparatus and method for drug screening 10 2000
6503718 Methods for detecting mutations using primer extension for detecting disease 19 2001
6428964 Method for alteration detection 26 2001
6498012 Methods for detecting mutations using primer extension for detecting disease 14 2001
6475738 Methods for detecting mutations using primer extension for detecting disease 66 2001
6482595 Methods for detecting mutations using primer extension 18 2001
6750020 Method for alteration detection 5 2001
7776524 Methods for analysis of molecular events 1 2003
* 2003/0203,382 Methods for analysis of molecular events 0 2003
* 2008/0241,827 Methods For Detecting A Mutant Nucleic Acid 0 2005
7981607 Method for detecting recombinant event 1 2005
* 2009/0170,077 Method for detecting recombinant event 0 2005
9109256 Method for monitoring disease progression or recurrence 0 2005
* 2009/0325,153 ANALYSIS OF HETEROGENEOUS NUCLEIC ACID SAMPLES 1 2006
7811757 Methods for disease detection 3 2006
* 2007/0202,513 Methods for disease detection 6 2006
* 2008/0248,471 Methods for disease detection 0 2007
8409829 Methods for analysis of molecular events 0 2010
8389220 Method for detecting a recombinant event 0 2011
 
AFFYMETRIX, INC. (7)
7329496 Sequencing of surface immobilized polymers utilizing microflourescence detection 21 2006
* 2006/0172,327 Sequencing of surface immobilized polymers utilizing microflourescence detection 1 2006
* 7459275 Sequencing of surface immobilized polymers utilizing microfluorescence detection 24 2006
* 2007/0105,131 Sequencing of surface immobilized polymers utilizing microfluorescence detection 1 2006
8796186 System and method for processing large number of biological microarrays 5 2009
* 2010/0081,583 FLUDIC SYSTEM AND METHOD FOR PROCESSING BIOLOGICAL MICROARRAYS IN PERSONAL INSTRUMENTATION 1 2009
* 2011/0009,297 Consumable elements for use with fluid processing and detection systems 3 2010
 
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY (4)
7622281 Methods and compositions for clonal amplification of nucleic acid 7 2005
7932034 Heat and pH measurement for sequencing of DNA 102 2007
* 2008/0166,727 Heat and pH Measurement for Sequencing of DNA 101 2007
* 2011/0171,655 PH MEASUREMENT FOR SEQUENCING OF DNA 9 2011
 
MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH (3)
7368233 Methods of screening for lung neoplasm based on stool samples containing a nucleic acid marker indicative of a neoplasm 27 2000
* 2004/0043,467 Supracolonic aerodigestive neoplasm detection 9 2003
7981612 Methods of screening for supracolonic neoplasms based on stool samples containing a nucleic acid marker indicative of a neoplasm 0 2008
 
MOLECULAR DEVICES, INC. (4)
6982431 Sample analysis systems 164 2002
7745142 Molecular modification assays 1 2003
* 2004/0249,586 Molecular modification assays 4 2003
7632651 Molecular modification assays 5 2005
 
APPLERA CORPORATION (2)
7294464 Length determination of nucleic acid repeat sequences by discontinuous primer extension 0 2004
* 2005/0112,619 Length determination of nucleic acid repeat sequences by discontinuous primer extension 0 2004
 
Pacific Biosciences of California, Inc. (21)
6255083 System and methods for nucleic acid sequencing of single molecules by polymerase synthesis 171 1999
6762048 System and apparatus for nucleic acid sequencing of single molecules by polymerase synthesis 67 2001
7229799 System and method for nucleic acid sequencing by polymerase synthesis 68 2003
* 2003/0194,740 System and method for nucleic acid sequencing by polymerase synthesis 74 2003
7476503 Apparatus and method for performing nucleic acid analysis 63 2005
7315019 Arrays of optical confinements and uses thereof 102 2005
7302146 Apparatus and method for analysis of molecules 65 2005
* 2006/0061,755 Apparatus and method for analysis of molecules 4 2005
* 2006/0063,264 Apparatus and method for performing nucleic acid analysis 34 2005
* 2006/0061,754 Arrays of optical confinements and uses thereof 23 2005
7476504 Use of reversible extension terminator in nucleic acid sequencing 49 2006
* 2006/0183,145 Use of reversible extension terminator in nucleic acid sequencing 78 2006
8530154 System and method for nucleic acid sequencing by polymerase synthesis 0 2006
7313308 Optical analysis of molecules 36 2007
* 2007/0206,189 Optical analysis of molecules 0 2007
* 2008/0241,833 SYSTEM AND METHOD FOR NUCLEIC ACID SEQUENCING BY POLYMERASE SYNTHESIS 7 2007
* 2008/0009,007 CONTROLLED INITIATION OF PRIMER EXTENSION 16 2007
8980584 System and methods for nucleic acid sequencing of single molecules by polymerase synthesis 0 2007
8192961 System and methods for nucleic acid sequencing of single molecules by polymerase synthesis 20 2007
8709725 Arrays of optical confinements and uses thereof 0 2007
7906284 Arrays of optical confinements and uses thereof 9 2007
 
TRUSTEES OF TUFTS COLLEGE (20)
6200737 Photodeposition method for fabricating a three-dimensional, patterned polymer microstructure 159 1995
6406845 Fiber optic biosensor for selectively detecting oligonucleotide species in a mixed fluid sample 52 1997
7115884 Self-encoding fiber optic sensor 215 1997
6327410 Target analyte sensors utilizing Microspheres 252 1998
6482593 Fiber optic biosensor for selectively detecting oligonucleotide species in a mixed fluid sample 87 1998
6377721 Biosensor array comprising cell populations confined to microcavities 155 1999
7348181 Self-encoding sensor with microspheres 33 1999
6266459 Fiber optic sensor with encoded microspheres 164 1999
6667159 Optical fiber biosensor array comprising cell populations confined to microcavities 83 2000
* 2003/0027,126 Methods for detecting target analytes and enzymatic reactions 37 2001
6859570 Target analyte sensors utilizing microspheres 168 2001
7622294 Methods for detecting target analytes and enzymatic reactions 39 2004
* 2005/0130,188 Methods for detecting target analytes and enzymatic reactions 90 2004
7754498 Self-encoding sensor with microspheres 5 2005
* 2005/0196,317 Self-encoding sensor with microspheres 9 2005
* 2009/0170,728 METHODS FOR DETECTING TARGET ANALYTES AND ENZYMATIC REACTIONS 103 2009
8030094 Self-encoding sensor with microspheres 3 2010
9377388 Methods for detecting target analytes and enzymatic reactions 0 2011
8426217 Self-encoding sensor with microspheres 1 2011
8691591 Self-encoding sensor with microspheres 0 2013
 
MOLECULAR DEVICES, LLC (2)
7070921 Molecular modification assays 6 2001
* 2010/0304,404 MOLECULAR MODIFICATION ASSAYS 1 2009
 
GENIA TECHNOLOGIES, INC. (12)
* 2011/0193,249 Systems and methods for forming a nanopore in a lipid bilayer 13 2010
* 2011/0192,723 Systems and methods for manipulating a molecule in a nanopore 14 2010
8962242 System for detecting electrical properties of a molecular complex 3 2011
9110478 Temperature regulation of measurement arrays 1 2011
9121059 Nanopore-based single molecule characterization 0 2011
8845880 Nanopore-based single DNA molecule characterization, identification and isolation using speed bumps 0 2011
8986629 Sensor circuit for controlling, detecting, and measuring a molecular complex 0 2013
9041420 Systems and methods for characterizing a molecule 0 2013
9494554 Chip set-up and high-accuracy nucleic acid sequencing 0 2013
9551697 Non-faradaic, capacitively coupled measurement in a nanopore cell array 0 2013
9377437 Systems and methods for characterizing a molecule 0 2014
9567630 Methods for forming lipid bilayers on biochips 0 2014
 
SMITH, BRUCE F. (1)
* 6060288 Method for performing amplification of nucleic acid on supports 91 1997
 
FLUIDIGM CORPORATION (26)
6255475 Chain terminators, the use thereof for nucleic acid sequencing and synthesis and a method of their preparation 74 1997
7169560 Short cycle methods for sequencing polynucleotides 178 2004
* 2005/0260,609 Methods and devices for sequencing nucleic acids 5 2004
* 2006/0024,678 Use of single-stranded nucleic acid binding proteins in sequencing 14 2004
7220549 Stabilizing a nucleic acid for nucleic acid sequencing 68 2004
7482120 Methods and compositions for improving fidelity in a nucleic acid synthesis reaction 14 2005
* 2006/0172,313 Methods and compositions for improving fidelity in a nucleic acid synthesis reaction 4 2005
* 2006/0046,258 Applications of single molecule sequencing 64 2005
* 2006/0263,790 Methods for improving fidelity in a nucleic acid synthesis reaction 4 2005
7635562 Methods and devices for nucleic acid sequence determination 36 2005
7666593 Single molecule sequencing of captured nucleic acids 44 2005
* 2007/0048,744 Single molecule sequencing of captured nucleic acids 9 2005
* 2007/0117,103 Nucleotide analogs 4 2005
* 2007/0117,102 Nucleotide analogs 6 2005
* 2007/0117,104 Nucleotide analogs 13 2005
7476734 Nucleotide analogs 13 2005
* 2007/0128,614 Nucleotide analogs 2 2005
* 2007/0196,832 Methods for mutation detection 4 2006
7397546 Systems and methods for reducing detected intensity non-uniformity in a laser beam 4 2006
* 2007/0211,467 Systems and methods for reducing detected intensity non-uniformity in a laser beam 0 2006
7491498 Short cycle methods for sequencing polynucleotides 14 2006
* 2009/0305,248 METHODS FOR INCREASING ACCURACY OF NUCLEIC ACID SEQUENCING 24 2006
7897345 Short cycle methods for sequencing polynucleotides 3 2009
* 2010/0184,045 Methods for sequencing degraded or modified nucleic acids 0 2009
9012144 Short cycle methods for sequencing polynucleotides 0 2011
* 2011/0152,114 SHORT CYCLE METHODS FOR SEQUENCING POLYNUCLEOTIDES 0 2011
 
TRUSTEES OF BOSTON UNIVERSITY (2)
8288098 Bioreactive agents 0 2011
8742084 Bioreactive agents 0 2012
 
LINGVITAE AS (1)
* 2009/0239,213 Identifying a target polynucleotide 0 2005
 
GENAISSANCE PHARMACEUTICALS, INC. (2)
6355433 Determination of nucleotide sequence variations through limited primer extension 13 2000
6458544 Methods for determining single nucleotide variations and genotyping 22 2000
 
EUROPAEISCHES LABORATORIUM FUER MOLEKULARBIOLOGIE (EMBL) (1)
* 5976802 Simultaneous sequencing of nucleic acids 81 1997
 
MANTEIA SA (1)
8143008 Method of nucleic acid amplification 10 2010
 
AGILENT TECHNOLOGIES, INC. (11)
6613508 Methods and compositions for analyzing nucleic acid molecules utilizing sizing techniques 82 1997
6312893 Methods and compositions for determining the sequence of nucleic acid molecules 186 1997
6623928 Methods and compositions for determining the sequence of nucleic acid molecules 92 2001
6613523 Method of DNA sequencing using cleavable tags 21 2001
6815212 Methods and compositions for enhancing sensitivity in the analysis of biological-based assays 16 2001
7052846 Methods and compositions for analyzing nucleic acid molecules utilizing sizing techniques 8 2003
* 2006/0057,566 METHODS AND COMPOSITIONS FOR ANALYZING NUCLEIC ACID MOLECULES UTILIZING SIZING TECHNIQUES 3 2003
* 7816079 Method of DNA sequencing using cleavable tags 3 2003
7247434 Methods and compositions for determining the sequence of nucleic acid molecules 0 2003
* 2004/0115,694 Methods and compositions for determining the sequence of nucleic acid molecules 1 2003
7642344 Methods and compositions for determining the sequence of nucleic acid molecules 1 2007
 
PRESIDENT AND FELLOWS OF HARVARD COLLEGE (5)
6548021 Surface-bound, double-stranded DNA protein arrays 14 1998
6432360 Replica amplification of nucleic acid arrays 166 1998
6485944 Replica amplification of nucleic acid arrays 206 1999
* 2003/0124,594 Replica amplification of nucleic acid arrays 9 2002
7785790 Replica amplification of nucleic acid arrays 127 2007
* Cited By Examiner