Patents by Inventor Paul M. Lizardi

Paul M. Lizardi 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).

  • Publication number: 20210332413
    Abstract: It has been established that one or more large double stranded DNA fragments (each 2,000 to 40,000 base pairs in size) can be captured and isolated from genomic DNA fragments using sequence specific PNA hybridization probes. Compositions and methods for enrichment of a multiplicity of long DNA sequences selected from the genome of any eukaryote are provided. Capture is performed using multiple PNA molecules with gamma-modified chiral backbones, comprising a mixture of neutral and positive chemical groups. Two or more PNA probes with covalently bound haptens, preferably biotin, target each DNA domain of interest for capture, isolation, and subsequent sequencing analysis of the multiplicity of enriched targets, including DNA methylation sequencing. The methods include enhancement of probe-DNA binding specificity through single strand binding proteins (SSB).
    Type: Application
    Filed: June 28, 2021
    Publication date: October 28, 2021
    Inventors: Paul M. Lizardi, Brent W. Ferguson
  • Patent number: 11046999
    Abstract: It has been established that one or more large double stranded DNA fragments (each 2,000 to 40,000 base pairs in size) can be captured and isolated from genomic DNA fragments using sequence specific PNA hybridization probes. Compositions and methods for enrichment of a multiplicity of long DNA sequences selected from the genome of any eukaryote are provided. Capture is performed using multiple PNA molecules with gamma-modified chiral backbones, comprising a mixture of neutral and positive chemical groups. Two or more PNA probes with covalently bound haptens, preferably biotin, target each DNA domain of interest for capture, isolation, and subsequent sequencing analysis of the multiplicity of enriched targets, including DNA methylation sequencing. The methods include enhancement of probe-DNA binding specificity through single strand binding proteins (SSB).
    Type: Grant
    Filed: September 16, 2016
    Date of Patent: June 29, 2021
    Assignee: PetaOmics, Inc.
    Inventors: Paul M. Lizardi, Brent W. Ferguson
  • Publication number: 20170073748
    Abstract: It has been established that one or more large double stranded DNA fragments (each 2,000 to 40,000 base pairs in size) can be captured and isolated from genomic DNA fragments using sequence specific PNA hybridization probes. Compositions and methods for enrichment of a multiplicity of long DNA sequences selected from the genome of any eukaryote are provided. Capture is performed using multiple PNA molecules with gamma-modified chiral backbones, comprising a mixture of neutral and positive chemical groups. Two or more PNA probes with covalently bound haptens, preferably biotin, target each DNA domain of interest for capture, isolation, and subsequent sequencing analysis of the multiplicity of enriched targets, including DNA methylation sequencing. The methods include enhancement of probe-DNA binding specificity through single strand binding proteins (SSB).
    Type: Application
    Filed: September 16, 2016
    Publication date: March 16, 2017
    Inventors: Paul M. Lizardi, Brent W. Ferguson
  • Publication number: 20130137086
    Abstract: Disclosed are methods, compositions, devices, and systems for assessing cancer potential, state, stage, risk of progression, prognosis, etc. of a subject based on determining the methylation state of human papillomavirus (HPV) in a sample from the subject. The cancers assessed generally can be cancer associated with or caused by HPV. For example, cervical cancer, vulvar cancer, penile cancer, anal cancer, and head and neck cancer can be associated with HPV. It has been discovered that certain patterns, profiles, and sets of methylation of HPV genomes are correlated with different cancer potential, state, stage, risk of progression, prognosis, etc.
    Type: Application
    Filed: May 9, 2011
    Publication date: May 30, 2013
    Applicant: YALE UNIVERSITY
    Inventors: Janet L. Brandsma, Paul M. Lizardi
  • Publication number: 20120221249
    Abstract: The invention includes a method of creating a sequence information framework that defines the range of epigenetic configurations of individual DNA strands in any diploid organism in which DNA methylation is prevalent. The invention also includes a method of generating DNA descriptors referred to as long hepitype distributions (LHDs).
    Type: Application
    Filed: May 14, 2010
    Publication date: August 30, 2012
    Inventors: Paul M. Lizardi, Junhyong Kim
  • Publication number: 20120157324
    Abstract: Disclosed are methods and compositions of assessing one or more statuses of a subject. Also disclosed are methods and compositions of identifying status biomarkers associated with a status of a subject. Also disclosed are sets of one or more status biomarkers. Also disclosed are methods and compositions of producing status biomarker capture probes.
    Type: Application
    Filed: August 17, 2010
    Publication date: June 21, 2012
    Applicant: YALE UNIVERSITY
    Inventors: Paul M. Lizardi, Sebastian Szpakowski, Min Chen, Jose Costa, Hongyu Zhao
  • Patent number: 7618776
    Abstract: Disclosed are compositions and a method for of amplifying nucleic acid sequences useful for detecting the presence of molecules of interest. The method is useful for detecting specific nucleic acids in a sample with high specificity and sensitivity. The method also has an inherently low level of background signal. A preferred form of the method consists of a DNA ligation operation, an amplification operation, and a detection operation. The DNA ligation operation circularizes a specially designed nucleic acid probe molecule. This operation is dependent on hybridization of the probe to a target sequence and forms circular probe molecules in proportion to the amount of target sequence present in a sample. The amplification operation is rolling circle replication of the circularized probe. A single round of amplification using rolling circle replication results in a large amplification of the circularized probe sequences.
    Type: Grant
    Filed: July 22, 2004
    Date of Patent: November 17, 2009
    Assignee: Yale University
    Inventor: Paul M. Lizardi
  • Publication number: 20040265888
    Abstract: Disclosed is a method for the comprehensive analysis of nucleic acid samples and a detector composition for use in the method. The method, referred to as Binary Encoded Sequence Tags (BEST), involves generation of a set of nucleic acid fragments; adding an adaptor to the ends containing recognition site for cleavage at a site offset from the recognition site; cleaving the fragment to generate fragments having a plurality sticky ends; indexing of the fragments into sets based on the sequence of sticky ends. The fragments are indexed by adding a offset adaptor to newly generated ends. A different adaptor will be coupled to each different sticky end. The resulting fragments—which will have defined ends, be of equal lengths (in preferred embodiment), and a central sequence derived from the source nucleic acid molecule—are binary sequence tags. The binary sequence tags can be used and further analyzed in numerous ways.
    Type: Application
    Filed: June 21, 2004
    Publication date: December 30, 2004
    Inventors: Joseph C. Kaufman, Matthew E. Roth, Paul M. Lizardi, Li Feng, Darin R. Latimer
  • Publication number: 20040265897
    Abstract: Disclosed are compositions and a method for of amplifying nucleic acid sequences useful for detecting the presence of molecules of interest. The method is useful for detecting specific nucleic acids in a sample with high specificity and sensitivity. The method also has an inherently low level of background signal. A preferred form of the method consists of a DNA ligation operation, an amplification operation, and a detection operation. The DNA ligation operation circularizes a specially designed nucleic acid probe molecule. This operation is dependent on hybridization of the probe to a target sequence and forms circular probe molecules in proportion to the amount of target sequence present in a sample. The amplification operation is rolling circle replication of the circularized probe. A single round of amplification using rolling circle replication results in a large amplification of the circularized probe sequences.
    Type: Application
    Filed: July 22, 2004
    Publication date: December 30, 2004
    Inventor: Paul M. Lizardi
  • Patent number: 6824981
    Abstract: Disclosed are compositions and methods for sensitive detection of one or multiple analytes. In general, the methods involve the use of special label components, referred to as reporter signals, that can be associated with, incorporated into, or otherwise linked to the analytes. In some embodiments, the reporter signals can be altered such that the altered forms of different reporter signals can be distinguished from each other. In some embodiments, sets of reporter signals can be used where two or more of the reporter signals in a set have one or more common properties that allow the reporter signals having the common property to be distinguished and/or separated from other molecules lacking the common property.
    Type: Grant
    Filed: August 13, 2001
    Date of Patent: November 30, 2004
    Assignee: Agilix Corporation
    Inventors: Brian T. Chait, Darin R. Latimer, Paul M. Lizardi, Eric R. Kershnar, Jon S. Morrow, Matthew E. Roth, Martin J. Mattessich, Kevin J. McConnell
  • Patent number: 6797474
    Abstract: Disclosed are compositions and a method for of amplifying nucleic acid sequences useful for detecting the presence of molecules of interest. The method is useful for detecting specific nucleic acids in a sample with high specificity and sensitivity. The method also has an inherently low level of background signal. A preferred form of the method consists of a DNA ligation operation, an amplification operation, and a detection operation. The DNA ligation operation circularizes a specially designed nucleic acid probe molecule. This operation is dependent on hybridization of the probe to a target sequence and forms circular probe molecules in proportion to the amount of target sequence present in a sample. The amplification operation is rolling circle replication of the circularized probe. A single round of amplification using rolling circle replication results in a large amplification of the circularized probe sequences.
    Type: Grant
    Filed: January 2, 2002
    Date of Patent: September 28, 2004
    Assignee: Yale University
    Inventor: Paul M. Lizardi
  • Publication number: 20040170968
    Abstract: Disclosed are compositions and an in vitro method for cloning and/or amplification of nucleic acid sequences of interest. The method is based on strand displacement replication of the nucleic acid sequences by multiple priming on artificial long terminal repeat (ALTR) sequences appended to the ends of the nucleic acid molecule of interest. The nucleic acid molecules for cloning and amplification can be very long, up to 40 to 80 Kb or longer. In a preferred form of the method, a single primer is used to prime strand displacement replication at multiple sites in artificial long terminal repeat sequences, flanking a target nucleic acid, containing multiple tandem repeats of a primer complement sequence. Amplification proceeds by replication initiated at each primer and continuing through the target nucleic acid sequence. This nested replication of multiple copies significantly increases the amplification yield for extremely long nucleic acid molecules.
    Type: Application
    Filed: May 14, 2001
    Publication date: September 2, 2004
    Applicant: Yale University
    Inventor: Paul M. Lizardi
  • Patent number: 6773886
    Abstract: Disclosed is a method for the comprehensive analysis of nucleic acid samples and a detector composition for use in the method. The method, referred to as Binary Encoded Sequence Tags (BEST), involves generation of a set of nucleic acid fragments; adding an adaptor to the ends containing recognition site for cleavage at a site offset from the recognition site; cleaving the fragment to generate fragments having a plurality sticky ends; indexing of the fragments into sets based on the sequence of sticky ends. The fragments are indexed by adding a offset adaptor to newly generated ends. A different adaptor will be coupled to each different sticky end. The resulting fragments—which will have defined ends, be of equal lengths (in preferred embodiment), and a central sequence derived from the source nucleic acid molecule—are binary sequence tags. The binary sequence tags can be used and further analyzed in numerous ways.
    Type: Grant
    Filed: November 26, 2001
    Date of Patent: August 10, 2004
    Assignees: Yale University, Agilix Corporation
    Inventors: Joseph C. Kaufman, Matthew E. Roth, Paul M. Lizardi, Li Feng, Darin R. Latimer
  • Publication number: 20040115643
    Abstract: Disclosed is a method and materials for amplifying nucleic acid sequences by limited primer extension. The disclosed method involves association of a primer with a template, extension of the primer for a short distance, termination of extension, and dissociation of the primer from the template, whereupon the events repeat with a new primer. The repeated association, extension, and dissociation of primers from a single template sequence results in amplification of the extended sequences. The termination of extension can be effected by a feature of the template sequence. The reaction can be carried under a single set of conditions, such as isothermal conditions, based on the thermodynamics of dissociation of the extended primers. The disclosed method is particularly suited to detection of nucleic acid sequences. Multiple sequences can be amplified and detected in the same reaction by targeting multiple sequences with extension primers.
    Type: Application
    Filed: December 12, 2002
    Publication date: June 17, 2004
    Inventors: Paul M. Lizardi, Oleg G. Gribanov
  • Publication number: 20040063144
    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: Application
    Filed: November 3, 2003
    Publication date: April 1, 2004
    Inventor: Paul M. Lizardi
  • Patent number: 6677121
    Abstract: Disclosed is a method for the comprehensive analysis of nucleic acid samples and a detector composition for use in the method. The method, referred to as Fixed Address Analysis of Sequence Tags (FAAST), involves generation of a set of nucleic acid fragments having a variety of sticky end sequences; indexing of the fragments into sets based on the sequence of sticky ends; associating a detector sequence with the fragments; sequence-based capture of the indexed fragments on a detector array; and detection of the fragment labels. Generation of the multiple sticky end sequences is accomplished by incubating the nucleic acid sample with one or more nucleic acid cleaving reagents. The indexed fragments are captured by hybridization and coupling, preferably by ligation, to a probe. The method allows a complex sample of nucleic acid to be quickly and easily cataloged in a reproducible and sequence-specific manner.
    Type: Grant
    Filed: May 15, 2001
    Date of Patent: January 13, 2004
    Assignees: Agilix Corporation, Yale University
    Inventors: Paul M. Lizardi, Matthew E. Roth, Li Feng, Cesar E. Guerra, Shane C. Weber, Joseph C. Kaufman, Darin R. Latimer
  • Publication number: 20030235849
    Abstract: Disclosed are compositions and a method for amplification of and multiplex detection of molecules of interest involving rolling circle replication. The method is useful for simultaneously detecting multiple specific nucleic acids in a sample with high specificity and sensitivity. The method also has an inherently low level of background signal. A preferred form of the method consists of an association operation, an amplification operation, and a detection operation. The association operation involves association of one or more specially designed probe molecules, either wholly or partly nucleic acid, to target molecules of interest. This operation associates the probe molecules to a target molecules present in a sample. The amplification operation is rolling circle replication of circular nucleic acid molecules, termed amplification target circles, that are either a part of, or hybridized to, the probe molecules.
    Type: Application
    Filed: April 10, 2003
    Publication date: December 25, 2003
    Inventors: Paul M. Lizardi, Michael Caplan
  • Patent number: 6642034
    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: July 23, 2001
    Date of Patent: November 4, 2003
    Assignee: Yale University
    Inventor: Paul M. Lizardi
  • Patent number: 6632609
    Abstract: Disclosed are compositions and a method for amplification of and multiplex detection of molecules of interest involving rolling circle replication. The method is useful for simultaneously detecting multiple specific nucleic acids in a sample with high specificity and sensitivity. The method also has an inherently low level of background signal. A preferred form of the method consists of an association operation, an amplification operation, and a detection operation. The association operation involves association of one or more specially designed probe molecules, either wholly or partly nucleic acid, to target molecules of interest. This operation associates the probe molecules to a target molecules present in a sample. The amplification operation is rolling circle replication of circular nucleic acid molecules, termed amplification target circles, that are either a part of, or hybridized to, the probe molecules.
    Type: Grant
    Filed: April 24, 2001
    Date of Patent: October 14, 2003
    Assignee: Yale University
    Inventor: Paul M. Lizardi
  • Publication number: 20030143536
    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: Application
    Filed: July 23, 2001
    Publication date: July 31, 2003
    Applicant: Yale University
    Inventor: Paul M. Lizardi