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).
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Patent number: 12060615Abstract: 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: GrantFiled: February 25, 2019Date of Patent: August 13, 2024Assignee: The Johns Hopkins UniversityInventors: William G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
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Publication number: 20240009292Abstract: 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: ApplicationFiled: October 1, 2021Publication date: January 11, 2024Inventors: Alok Singh, Peter Um, Keira Cohen, William Bishai, Rullin Wang, Srinivasan Yegnasubramanian, Trinity J. Bivalacqua
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Publication number: 20230416294Abstract: 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: ApplicationFiled: August 10, 2021Publication date: December 28, 2023Inventors: Barbara Slusher, Rana Rais, Franco D'Alessio, Pavel Majer, Marcela Krecmerova, Srinivasan Yegnasubramanian
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Publication number: 20230100402Abstract: 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: ApplicationFiled: September 16, 2022Publication date: March 30, 2023Inventors: Srinivasan Yegnasubramanian, William G. Nelson, Ajay Vaghasia, Philipp Nuhn
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Publication number: 20230003718Abstract: 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: ApplicationFiled: June 21, 2022Publication date: January 5, 2023Inventors: Srinivasan Yegnasubramanian, Chaya Steinberg, William G. Nelson
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Patent number: 11491174Abstract: 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: GrantFiled: June 6, 2018Date of Patent: November 8, 2022Assignee: The Johns Hopkins UniversityInventors: Srinivasan Yegnasubramanian, William G. Nelson, Ajay Vaghasia, Philipp Nuhn
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Patent number: 11035850Abstract: 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: GrantFiled: April 10, 2017Date of Patent: June 15, 2021Assignee: The Johns Hopkins UniversityInventors: Michelle A. Rudek-Renaut, Srinivasan Yegnasubramanian, Nicole Anders
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Publication number: 20210130879Abstract: 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: ApplicationFiled: March 15, 2018Publication date: May 6, 2021Inventors: Bert VOGELSTEIN, Kenneth W. KINZLER, Nickolas PAPADOPOULOS, Austin MATTOX, Srinivasan YEGNASUBRAMANIAN, William G. NELSON
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Publication number: 20210106603Abstract: 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: ApplicationFiled: June 6, 2018Publication date: April 15, 2021Inventors: Srinivasan Yegnasubramanian, William G. Nelson, Ajay Vaghasia, Philipp Nuhn
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Publication number: 20200149112Abstract: 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: ApplicationFiled: February 25, 2019Publication date: May 14, 2020Inventors: William G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
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Publication number: 20200041488Abstract: 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: ApplicationFiled: April 10, 2017Publication date: February 6, 2020Inventors: Michelle A. Rudek-Renaut, Srinivasan Yegnasubramanian, Nicole Anders
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Publication number: 20190367990Abstract: 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: ApplicationFiled: December 20, 2018Publication date: December 5, 2019Inventors: Srinivasan Yegnasubramanian, G. Steven Bova, Martin Aryee, William B. Isaacs, William G. Nelson
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Patent number: 10227654Abstract: 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: GrantFiled: May 8, 2015Date of Patent: March 12, 2019Assignee: The Johns Hopkins UniversityInventors: William G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
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Patent number: 10196698Abstract: 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: GrantFiled: May 18, 2017Date of Patent: February 5, 2019Assignee: The Johns Hopkins UniversityInventors: Srinivasan Yegnasubramanian, G. Steven Bova, Martin Aryee, William B. Isaacs, William G. Nelson
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Publication number: 20180100196Abstract: 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: ApplicationFiled: May 18, 2017Publication date: April 12, 2018Inventors: Srinivasan Yegnasubramanian, G. Steven Bova, Martin Aryee, William B. Isaacs, William G. Nelson
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Patent number: 9297806Abstract: 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: GrantFiled: August 1, 2013Date of Patent: March 29, 2016Assignee: The Johns Hopkins UniversityInventors: Srinivasan Yegnasubramanian, Michael Christoph Haffner, Alcides Chaux, William G. Nelson, Angelo M. DeMarzo
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Publication number: 20150252438Abstract: 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: ApplicationFiled: May 8, 2015Publication date: September 10, 2015Inventors: Wiliam G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
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Patent number: 9034574Abstract: 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: GrantFiled: December 21, 2007Date of Patent: May 19, 2015Assignee: The Johns Hopkins UniversityInventors: William G. Nelson, Srinivasan Yegnasubramanian, Xiaohui Lin, Traci J. Speed, Zachery Reichert
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Publication number: 20140274767Abstract: 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: ApplicationFiled: January 23, 2014Publication date: September 18, 2014Applicant: THE JOHNS HOPKINS UNIVERSITYInventors: Srinivasan Yegnasubramanian, G. Steven Bova, Martin Aryee, William B. Isaacs, William G. Nelson
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Publication number: 20140038183Abstract: 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: ApplicationFiled: August 1, 2013Publication date: February 6, 2014Applicant: The Johns Hopkins UniversityInventors: Srinivasan Yegnasubramanian, Michael Christoph Haffner, Alcides Chaux, William G. Nelson, Angelo M. DeMarzo