Patents by Inventor Richard P. Rava

Richard P. Rava 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: 20200291478
    Abstract: The present invention relates to methods comprising identifying polymorphisms in samples comprising mixtures of genomes, and for determining and/or monitoring the presence or absence of disorders associated with the identified polymorphisms.
    Type: Application
    Filed: April 27, 2020
    Publication date: September 17, 2020
    Inventor: Richard P. Rava
  • Patent number: 10741269
    Abstract: Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions. In some embodiments, methods are provided for determining copy number variation (CNV) of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some embodiments, methods are provided for determining CNVs known or suspected to be associated with a variety of medical conditions. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by removing within-sample GC-content bias. In some embodiments, removal of within-sample GC-content bias is based on sequence data corrected for systematic variation common across unaffected training samples. Also disclosed are systems and computer program products for evaluation of CNV of sequences of interest.
    Type: Grant
    Filed: October 21, 2014
    Date of Patent: August 11, 2020
    Assignee: Verinata Health, Inc.
    Inventors: Darya I. Chudova, Diana Abdueva, Richard P. Rava
  • Publication number: 20200251180
    Abstract: Methods of reliably estimating genomic fraction (e.g., fetal fraction) from polymorphisms such as small base variations or insertions-deletions are disclosed. Sequenced data from a multigenomic source is used to determine allele counts for one or more of the polymorphisms. For one or more of the polymorphisms, zygosity is assigned, and genomic fraction is determined from the zygosity and allele counts. Certain embodiments employ SNPs as the relevant polymorphism. The disclosed methods can be applied as part of an intentional, pre-designed re-sequencing study targeted against known polymorphisms or can be used in a retrospective analysis of variations found by coincidence in overlapping sequences generated from maternal plasma (or any other setting where a mixture of DNA from several people are present).
    Type: Application
    Filed: April 20, 2020
    Publication date: August 6, 2020
    Inventors: Richard P. Rava, Brian K. Rhees, John P. Burke
  • Patent number: 10718020
    Abstract: Methods and kits for selectively enriching non-random polynucleotide sequences are provided. Methods and kits for generating libraries of sequences are provided. Methods of using selectively enriched non-random polynucleotide sequences for detection of fetal aneuploidy are provided.
    Type: Grant
    Filed: September 28, 2016
    Date of Patent: July 21, 2020
    Assignee: Verinata Health, Inc.
    Inventors: Yue-Jen Chuu, Richard P. Rava
  • Publication number: 20200219588
    Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.
    Type: Application
    Filed: January 24, 2020
    Publication date: July 9, 2020
    Inventors: Richard P. Rava, Anupama Srinivasan
  • Patent number: 10662474
    Abstract: The present invention relates to methods comprising whole genome sequencing for identifying polymorphisms in samples comprising mixtures of genomes, and for determining and/or monitoring the presence or absence of disorders associated with the identified polymorphisms.
    Type: Grant
    Filed: January 19, 2011
    Date of Patent: May 26, 2020
    Assignee: VERINATA HEALTH, INC.
    Inventor: Richard P. Rava
  • Patent number: 10658070
    Abstract: Methods of reliably estimating genomic fraction (e.g., fetal fraction) from polymorphisms such as small base variations or insertions-deletions are disclosed. Sequenced data from a multigenomic source is used to determine allele counts for one or more of the polymorphisms. For one or more of the polymorphisms, zygosity is assigned, and genomic fraction is determined from the zygosity and allele counts. Certain embodiments employ SNPs as the relevant polymorphism. The disclosed methods can be applied as part of an intentional, pre-designed re-sequencing study targeted against known polymorphisms or can be used in a retrospective analysis of variations found by coincidence in overlapping sequences generated from maternal plasma (or any other setting where a mixture of DNA from several people are present).
    Type: Grant
    Filed: August 11, 2016
    Date of Patent: May 19, 2020
    Assignee: Verinata Health, Inc.
    Inventors: Richard P. Rava, Brian K. Rhees, John P. Burke
  • Patent number: 10612096
    Abstract: The invention provides compositions and methods for determining the fraction of fetal nucleic acids in a maternal sample comprising a mixture of fetal and maternal nucleic acids. The fraction of fetal nucleic acids can be used in determining the presence or absence of fetal aneuploidy.
    Type: Grant
    Filed: October 20, 2016
    Date of Patent: April 7, 2020
    Assignee: VERINATA HEALTH, INC.
    Inventors: Richard P. Rava, Yue-Jen Chuu, Manjula Chinnappa, David A. Comstock, Gabrielle Heilek, Michael Hunkapiller
  • Patent number: 10586610
    Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.
    Type: Grant
    Filed: March 16, 2016
    Date of Patent: March 10, 2020
    Assignee: Verinata Health, Inc.
    Inventors: Richard P. Rava, Anupama Srinivasan
  • Publication number: 20200048704
    Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.
    Type: Application
    Filed: July 26, 2019
    Publication date: February 13, 2020
    Inventors: Richard P. Rava, Brian K. Rhees
  • Publication number: 20200035327
    Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.
    Type: Application
    Filed: September 18, 2019
    Publication date: January 30, 2020
    Applicant: Verinata Health, Inc.
    Inventors: Richard P. Rava, Brian K. Rhees
  • Patent number: 10482993
    Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.
    Type: Grant
    Filed: February 5, 2016
    Date of Patent: November 19, 2019
    Assignee: Verinata Health, Inc.
    Inventors: Richard P. Rava, Brian K. Rhees
  • Publication number: 20190338345
    Abstract: The disclosure provides methods and kits for preparing sequencing library to detect chromosomal abnormality using cell-free DNA (cfDNA) without the need of first isolating the cfDNA from a liquid fraction of a test sample. In some embodiments, the method involves reducing the binding between the cfDNA and nucleosomal proteins without unwinding the cfDNA from the nucleosomal proteins. In some embodiments, the reduction of binding may be achieved by treating with a detergent or heating. In some embodiments, the method further involves freezing and thawing the test sample before reducing the binding between the cfDNA and the nucleosomal proteins. In some embodiments, the test sample is a peripheral blood sample from a pregnant woman including cfDNA of both a mother and a fetus. In other embodiments, the test sample is a peripheral blood sample from a patient known or suspected to have cancer.
    Type: Application
    Filed: July 17, 2019
    Publication date: November 7, 2019
    Inventors: Anupama Srinivasan, Richard P. Rava
  • Patent number: 10415089
    Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.
    Type: Grant
    Filed: December 29, 2015
    Date of Patent: September 17, 2019
    Assignee: Verinata Health, Inc.
    Inventors: Richard P. Rava, Brian K. Rhees
  • Patent number: 10400267
    Abstract: The disclosure provides methods and kits for preparing sequencing library to detect chromosomal abnormality using cell-free DNA (cfDNA) without the need of first isolating the cfDNA from a liquid fraction of a test sample. In some embodiments, the method involves reducing the binding between the cfDNA and nucleosomal proteins without unwinding the cfDNA from the nucleosomal proteins. In some embodiments, the reduction of binding may be achieved by treating with a detergent or heating. In some embodiments, the method further involves freezing and thawing the test sample before reducing the binding between the cfDNA and the nucleosomal proteins. In some embodiments, the test sample is a peripheral blood sample from a pregnant woman including cfDNA of both a mother and a fetus. In other embodiments, the test sample is a peripheral blood sample from a patient known or suspected to have cancer.
    Type: Grant
    Filed: June 11, 2018
    Date of Patent: September 3, 2019
    Assignee: Verinata Health, Inc.
    Inventors: Anupama Srinivasan, Richard P. Rava
  • Patent number: 10388403
    Abstract: The invention provides a method for determining copy number variations (CNV) of a sequence of interest in a test sample that comprises a mixture of nucleic acids that are known or are suspected to differ in the amount of one or more sequence of interest. The method comprises a statistical approach that accounts for accrued variability stemming from process-related, interchromosomal and inter-sequencing variability. The method is applicable to determining CNV of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. CNV that can be determined according to the method include trisomies and monosomies of any one or more of chromosomes 1-22, X and Y, other chromosomal polysomies, and deletions and/or duplications of segments of any one or more of the chromosomes, which can be detected by sequencing only once the nucleic acids of a test sample.
    Type: Grant
    Filed: July 20, 2012
    Date of Patent: August 20, 2019
    Assignee: Verinata Health, Inc.
    Inventors: Richard P. Rava, Brian K. Rhees
  • Publication number: 20190144919
    Abstract: Provided herein, are matrices and methods for the stabilization of proteins and nucleic acids. The stabilized proteins and nucleic acids described herein can be in a sample taken from a subject and can be subsequently stabilized and stored on the matrix. An analyte of interest can be concentrated and eluted for analysis from this sample. The stabilized proteins and nucleic acids described herein can be components of a sample preparation reagent, and the reagent is stored on the matrix and hydration of the matrix with a sample can result in a reaction occurring.
    Type: Application
    Filed: December 6, 2018
    Publication date: May 16, 2019
    Inventors: Alicia Jackson, Dagmar Beyerlein, Sonya Clark, Richard P. Rava
  • Publication number: 20190062832
    Abstract: Disclosed are methods for determining at least one sequence of interest of a fetus of a pregnant mother. In various embodiments, the method can determine one or more sequences of interest in a test sample that comprises a mixture of maternal cellular DNA and mother-and-fetus cfDNA. In some embodiments, methods are provided for determining whether the fetus has a genetic disease. In some embodiments, methods are provided for determining whether the fetus is homozygous in a disease causing allele when the mother is heterozygous of the same allele. In some embodiments, methods are provided for determining whether the fetus has a copy number variation (CNV) or a non-CNV genetic sequence anomaly.
    Type: Application
    Filed: August 9, 2018
    Publication date: February 28, 2019
    Inventors: Anupama Srinivasan, Darya I. Chudova, Richard P. Rava
  • Publication number: 20190065676
    Abstract: Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions. In some embodiments, methods are provided for determining copy number variation of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some embodiments, methods are provided for determining CNVs known or suspected to be associated with a variety of medical conditions. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by deriving a fragment size parameter. In some implementations, information from fragments of different sizes are used to evaluate copy number variations. In some implementations, one or more t-statistics obtained from coverage information of the sequence of interest is used to evaluate copy number variations. In some implementations, one or more fetal fraction estimates are combined with one or more t-statistics to determine copy number variations.
    Type: Application
    Filed: August 31, 2018
    Publication date: February 28, 2019
    Inventors: Sven Duenwald, David A. Comstock, Catalin Barbacioru, Darya I. Chudova, Richard P. Rava, Keith W. Jones, Gengxin Chen, Dimitri Skvortsov
  • Publication number: 20180346967
    Abstract: The disclosure provides methods and kits for preparing sequencing library to detect chromosomal abnormality using cell-free DNA (cfDNA) without the need of first isolating the cfDNA from a liquid fraction of a test sample. In some embodiments, the method involves reducing the binding between the cfDNA and nucleosomal proteins without unwinding the cfDNA from the nucleosomal proteins. In some embodiments, the reduction of binding may be achieved by treating with a detergent or heating. In some embodiments, the method further involves freezing and thawing the test sample before reducing the binding between the cfDNA and the nucleosomal proteins. In some embodiments, the test sample is a peripheral blood sample from a pregnant woman including cfDNA of both a mother and a fetus. In other embodiments, the test sample is a peripheral blood sample from a patient known or suspected to have cancer.
    Type: Application
    Filed: June 11, 2018
    Publication date: December 6, 2018
    Inventors: Anupama Srinivasan, Richard P. Rava