Patents by Inventor Srinivasan Yegnasubramanian

Srinivasan Yegnasubramanian 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).

  • Patent number: 12060615
    Abstract: The present invention provides methods for discovering agents that are effective in reversing epigenetic silencing by inhibiting the interaction of methyl-binding (MBD) proteins with methylated genomic DNA. Also provided are methods for reactivating silenced genes having CpG island hypermethylation along with methods for treatment and prevention of diseases, such as cancer and sickle cell anemia, by administering an agent that modulates methyl-binding domain (MBD) protein-mediated transcriptional repression, thereby increasing gene transcription to prevent or treat disease. Additionally, compounds identified by the present invention useful for treatment and prevention of diseases, such as cancer and sickle cell anemia, are provided.
    Type: Grant
    Filed: February 25, 2019
    Date of Patent: August 13, 2024
    Assignee: The Johns Hopkins University
    Inventors: William G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
  • Publication number: 20240009292
    Abstract: The present disclosure relates to a BCG based therapeutic agent using a BCG strain that overexpresses the STING agonist, c-di-AMP. This BCG strain, called BCG-disA-OE, enhances the elevated trained immunity of macrophages and promotes early anti-viral Type I interferon responses in a subject, providing protection against viral infections such as primary respiratory infections and SARS-CoV-2 infection.
    Type: Application
    Filed: October 1, 2021
    Publication date: January 11, 2024
    Inventors: Alok Singh, Peter Um, Keira Cohen, William Bishai, Rullin Wang, Srinivasan Yegnasubramanian, Trinity J. Bivalacqua
  • Publication number: 20230416294
    Abstract: Novel N4-substituted decitabine analogs are disclosed that exhibit promising in vitro and in vivo therapeutic activity. These novel compounds were shown to be resistant to deamination via cytidine deaminase (CDA) metabolism and provide a unique pharmacokinetic profile versus decitabine, while retaining the ability to induce DNA demethylation in target cells. These novel compounds can be used for treating hematological cancers, as well for new therapeutic interventions, including bacterial or viral pneumonia, acute respiratory distress syndrome, pulmonary fibrosis, transplantation and checkpoint inhibitor-induced adverse events, including pneumonitis.
    Type: Application
    Filed: August 10, 2021
    Publication date: December 28, 2023
    Inventors: Barbara Slusher, Rana Rais, Franco D'Alessio, Pavel Majer, Marcela Krecmerova, Srinivasan Yegnasubramanian
  • Publication number: 20230100402
    Abstract: The disclosure generally relates to compositions and methods for the treatment of cancer. In some aspects, disclosed herein are methods for the induction of synthetic lethality with epigenetic therapy (ISLET) using a combination of at least one epigenetic compound and at least one chemotherapeutic agent. Also disclosed herein are screening methods for identifying compounds that induce killing of cancer cells when combined with at least one epigenetic compound. Further disclosed herein are methods of potentiating a therapeutic effect of a chemotherapeutic agent against a cancer, comprising administering to a subject having the cancer an epigenetic compound in an amount effective to potentiate the therapeutic effect of the chemotherapeutic agent against the cancer.
    Type: Application
    Filed: September 16, 2022
    Publication date: March 30, 2023
    Inventors: Srinivasan Yegnasubramanian, William G. Nelson, Ajay Vaghasia, Philipp Nuhn
  • Publication number: 20230003718
    Abstract: Provided herein are methods for determining a rate of DNA double strand repair on a DNA strand in a cell that include (a) delivering a reporter gene, a gene-editing agent, and a gene-repair template into a cell, wherein the gene-editing agent generates a DNA double strand break on the DNA strand; (b) detecting a change in reporter gene expression, wherein the change in reporter gene expression indicates the presence of a DNA double strand repair event; and (c) analyzing the change in reporter gene expression, thereby determining the rate of DNA double strand repair on the DNA strand in the cell.
    Type: Application
    Filed: June 21, 2022
    Publication date: January 5, 2023
    Inventors: Srinivasan Yegnasubramanian, Chaya Steinberg, William G. Nelson
  • Patent number: 11491174
    Abstract: The disclosure generally relates to compositions and methods for the treatment of cancer. In some aspects, disclosed herein are methods for the induction of synthetic lethality with epigenetic therapy (ISLET) using a combination of at least one epigenetic compound and at least one chemotherapeutic agent. Also disclosed herein are screening methods for identifying compounds that induce killing of cancer cells when combined with at least one epigenetic compound. Further disclosed herein are methods of potentiating a therapeutic effect of a chemotherapeutic agent against a cancer, comprising administering to a subject having the cancer an epigenetic compound in an amount effective to potentiate the therapeutic effect of the chemotherapeutic agent against the cancer.
    Type: Grant
    Filed: June 6, 2018
    Date of Patent: November 8, 2022
    Assignee: The Johns Hopkins University
    Inventors: Srinivasan Yegnasubramanian, William G. Nelson, Ajay Vaghasia, Philipp Nuhn
  • Patent number: 11035850
    Abstract: This application provides methods to quantitate drug incorporation into DNA and of simultaneously measuring DNA methylation levels. Drugs include nucleoside analog DNA methyltransferase inhibitors.
    Type: Grant
    Filed: April 10, 2017
    Date of Patent: June 15, 2021
    Assignee: The Johns Hopkins University
    Inventors: Michelle A. Rudek-Renaut, Srinivasan Yegnasubramanian, Nicole Anders
  • Publication number: 20210130879
    Abstract: BiSeqS (bisulfite sequencing system) is a technology that can increase the specificity of sequencing by at least two orders of magnitude over and above that achieved with molecular barcoding and can be applied to any massively parallel sequencing instrument. BiSeqS employs bisulfite treatment to distinguish the two strands of molecularly barcoded DNA. Its specificity arises from the requirement for the same mutation to be identified in both strands. Because no library preparation is required, the technology permits very efficient use of the template DNA as well as sequence reads, which are nearly all confined to the amplicons of interest. Such efficiency is critical for clinical samples, such as plasma, in which only tiny amounts of DNA are often available. BiSeqS can be applied to evaluate transversions, as well as small insertions or deletions, and can reliably detect one mutation among >10,000 wild type molecules.
    Type: Application
    Filed: March 15, 2018
    Publication date: May 6, 2021
    Inventors: Bert VOGELSTEIN, Kenneth W. KINZLER, Nickolas PAPADOPOULOS, Austin MATTOX, Srinivasan YEGNASUBRAMANIAN, William G. NELSON
  • Publication number: 20210106603
    Abstract: The disclosure generally relates to compositions and methods for the treatment of cancer. In some aspects, disclosed herein are methods for the induction of synthetic lethality with epigenetic therapy (ISLET) using a combination of at least one epigenetic compound and at least one chemotherapeutic agent. Also disclosed herein are screening methods for identifying compounds that induce killing of cancer cells when combined with at least one epigenetic compound. Further disclosed herein are methods of potentiating a therapeutic effect of a chemotherapeutic agent against a cancer, comprising administering to a subject having the cancer an epigenetic compound in an amount effective to potentiate the therapeutic effect of the chemotherapeutic agent against the cancer.
    Type: Application
    Filed: June 6, 2018
    Publication date: April 15, 2021
    Inventors: Srinivasan Yegnasubramanian, William G. Nelson, Ajay Vaghasia, Philipp Nuhn
  • Publication number: 20200149112
    Abstract: The present invention provides methods for discovering agents that are effective in reversing epigenetic silencing by inhibiting the interaction of methyl-binding (MBD) proteins with methylated genomic DNA. Also provided are methods for reactivating silenced genes having CpG island hypermethylation along with methods for treatment and prevention of diseases, such as cancer and sickle cell anemia, by administering an agent that modulates methyl-binding domain (MBD) protein-mediated transcriptional repression, thereby increasing gene transcription to prevent or treat disease. Additionally, compounds identified by the present invention useful for treatment and prevention of diseases, such as cancer and sickle cell anemia, are provided.
    Type: Application
    Filed: February 25, 2019
    Publication date: May 14, 2020
    Inventors: William G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
  • Publication number: 20200041488
    Abstract: This application provides methods to quantitate drug incorporation into DNA and of simultaneously measuring DNA methylation levels. Drugs include nucleoside analog DNA methyltransferase inhibitors.
    Type: Application
    Filed: April 10, 2017
    Publication date: February 6, 2020
    Inventors: Michelle A. Rudek-Renaut, Srinivasan Yegnasubramanian, Nicole Anders
  • Publication number: 20190367990
    Abstract: The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for assessing prostate cancer. In a specific embodiment, present inventors have developed and applied a new technology and associated computation methods enabling simultaneous genome-scale analysis of genetic (copy number) and epigenetic (total methylation (TM) and allele-specific methylation (ASM) alternation, This method, called MBD-SNP, features affinity enrichment or methylated genomic DNA fragments using a methyl-binding domain polypeptide.
    Type: Application
    Filed: December 20, 2018
    Publication date: December 5, 2019
    Inventors: Srinivasan Yegnasubramanian, G. Steven Bova, Martin Aryee, William B. Isaacs, William G. Nelson
  • Patent number: 10227654
    Abstract: The present invention provides methods for discovering agents that are effective in reversing epigenetic silencing by inhibiting the interaction of methyl-binding (MBD) proteins with methylated genomic DNA. Also provided are methods for reactivating silenced genes having CpG island hypermethylation along with methods for treatment and prevention of diseases, such as cancer and sickle cell anemia, by administering an agent that modulates methyl-binding domain (MBD) protein-mediated transcriptional repression, thereby increasing gene transcription to prevent or treat disease. Additionally, compounds identified by the present invention useful for treatment and prevention of diseases, such as cancer and sickle cell anemia, are provided.
    Type: Grant
    Filed: May 8, 2015
    Date of Patent: March 12, 2019
    Assignee: The Johns Hopkins University
    Inventors: William G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
  • Patent number: 10196698
    Abstract: The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for assessing prostate cancer. In a specific embodiment, present inventors have developed and applied a new technology and associated computation methods enabling simultaneous genome-scale analysis of genetic (copy number) and epigenetic (total methylation (TM) and allele-specific methylation (ASM) alternation, This method, called MBD-SNP, features affinity enrichment or methylated genomic DNA fragments using a methyl-binding domain polypeptide.
    Type: Grant
    Filed: May 18, 2017
    Date of Patent: February 5, 2019
    Assignee: The Johns Hopkins University
    Inventors: Srinivasan Yegnasubramanian, G. Steven Bova, Martin Aryee, William B. Isaacs, William G. Nelson
  • Publication number: 20180100196
    Abstract: The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for assessing prostate cancer. In a specific embodiment, present inventors have developed and applied a new technology and associated computation methods enabling simultaneous genome-scale analysis of genetic (copy number) and epigenetic (total methylation (TM) and allele-specific methylation (ASM) alternation, This method, called MBD-SNP, features affinity enrichment or methylated genomic DNA fragments using a methyl-binding domain polypeptide.
    Type: Application
    Filed: May 18, 2017
    Publication date: April 12, 2018
    Inventors: Srinivasan Yegnasubramanian, G. Steven Bova, Martin Aryee, William B. Isaacs, William G. Nelson
  • Patent number: 9297806
    Abstract: The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for diagnosing or predicting cancer in a patient. In one embodiment, a method for identifying a patient as having cancer comprises the steps of (a) providing a formalin-fixed, paraffin-embedded or fresh frozen sample of patient tissue; (b) steaming the sample in antigen retrieval buffer; (c) incubating the sample in hydrochloric acid (HCl); (d) incubating the sample with an affinity reagent specific for 5hmC under conditions to form a complex between the affinity reagent and 5-hydroxymethylcytosine (5hmC) present in the sample; (e) detecting the complexes formed between 5hmC and the affinity reagent with secondary detection reagents; (f) quantifying 5hmC levels; and (g) identifying the patient as having cancer if the 5hmC levels in the sample are reduced as compared to a control.
    Type: Grant
    Filed: August 1, 2013
    Date of Patent: March 29, 2016
    Assignee: The Johns Hopkins University
    Inventors: Srinivasan Yegnasubramanian, Michael Christoph Haffner, Alcides Chaux, William G. Nelson, Angelo M. DeMarzo
  • Publication number: 20150252438
    Abstract: The present invention provides methods for discovering agents that are effective in reversing epigenetic silencing by inhibiting the interaction of methyl-binding (MBD) proteins with methylated genomic DNA. Also provided are methods for reactivating silenced genes having CpG island hypermethylation along with methods for treatment and prevention of diseases, such as cancer and sickle cell anemia, by administering an agent that modulates methyl-binding domain (MBD) protein-mediated transcriptional repression, thereby increasing gene transcription to prevent or treat disease. Additionally, compounds identified by the present invention useful for treatment and prevention of diseases, such as cancer and sickle cell anemia, are provided.
    Type: Application
    Filed: May 8, 2015
    Publication date: September 10, 2015
    Inventors: Wiliam G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
  • Patent number: 9034574
    Abstract: The present invention provides methods for discovering agents that are effective in reversing epigenetic silencing by inhibiting the interaction of methyl-binding (MBD) proteins with methylated genomic DNA. Also provided are methods for reactivating silenced genes having CpG island hypermethylation along with methods for treatment and prevention of diseases, such as cancer and sickle cell anemia, by administering an agent that modulates methyl-binding domain (MBD) protein-mediated transcriptional repression, thereby increasing gene transcription to prevent or treat disease. Additionally, compounds identified by the present invention useful for treatment and prevention of diseases, such as cancer and sickle cell anemia, are provided.
    Type: Grant
    Filed: December 21, 2007
    Date of Patent: May 19, 2015
    Assignee: The Johns Hopkins University
    Inventors: William G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
  • Publication number: 20140274767
    Abstract: The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for assessing prostate cancer. In a specific embodiment, present inventors have developed and applied a new technology and associated computation methods enabling simultaneous genome-scale analysis of genetic (copy number) and epigenetic (total methylation (TM) and allele-specific methylation (ASM) alternation, This method, called MBD-SNP, features affinity enrichment or methylated genomic DNA fragments using a methyl-binding domain polypeptide.
    Type: Application
    Filed: January 23, 2014
    Publication date: September 18, 2014
    Applicant: THE JOHNS HOPKINS UNIVERSITY
    Inventors: Srinivasan Yegnasubramanian, G. Steven Bova, Martin Aryee, William B. Isaacs, William G. Nelson
  • Publication number: 20140038183
    Abstract: The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for diagnosing or predicting cancer in a patient. In one embodiment, a method for identifying a patient as having cancer comprises the steps of (a) providing a formalin-fixed, paraffin-embedded or fresh frozen sample of patient tissue; (b) steaming the sample in antigen retrieval buffer; (c) incubating the sample in hydrochloric acid (HCl); (d) incubating the sample with an affinity reagent specific for 5hmC under conditions to form a complex between the affinity reagent and 5-hydroxymethylcytosine (5hmC) present in the sample; (e) detecting the complexes formed between 5hmC and the affinity reagent with secondary detection reagents; (f) quantifying 5hmC levels; and (g) identifying the patient as having cancer if the 5hmC levels in the sample are reduced as compared to a control.
    Type: Application
    Filed: August 1, 2013
    Publication date: February 6, 2014
    Applicant: The Johns Hopkins University
    Inventors: Srinivasan Yegnasubramanian, Michael Christoph Haffner, Alcides Chaux, William G. Nelson, Angelo M. DeMarzo