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公开(公告)号:US20140274767A1
公开(公告)日:2014-09-18
申请号:US14162180
申请日:2014-01-23
发明人: Srinivasan Yegnasubramanian , G. Steven Bova , Martin Aryee , William B. Isaacs , William G. Nelson
IPC分类号: C12Q1/68
CPC分类号: C12Q1/6886 , C12Q1/6855 , C12Q2600/154 , C12Q2537/164 , C12Q2565/501 , C12Q2565/531
摘要: 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.
摘要翻译: 本发明涉及癌症领域。 更具体地,本发明提供了可用于评估前列腺癌的方法和组合物。 在一个具体的实施方案中,本发明人已经开发并应用了一种能够同时进行基因组(拷贝数)和表观遗传学(总甲基化(TM))和等位基因特异性甲基化(ASM)交替的基因组大规模分析的新技术和相关计算方法。 称为MBD-SNP,使用甲基结合结构域多肽具有亲和力富集或甲基化基因组DNA片段。
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公开(公告)号:US11491174B2
公开(公告)日:2022-11-08
申请号:US16618845
申请日:2018-06-06
IPC分类号: A61K31/7068 , A61P35/00 , A61K31/203 , A61K31/4188 , A61K31/55
摘要: 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.
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公开(公告)号:US20200149112A1
公开(公告)日:2020-05-14
申请号:US16285019
申请日:2019-02-25
发明人: William G. Nelson , Srinivasan Yegnasubramanian , Xiaohui Lin , Traci J. Speed , Zachery Reichert
IPC分类号: C12Q1/6886 , A61K31/517 , A61K31/4184 , A61K31/4188 , A61K31/381 , A61K31/4439 , G01N33/50 , A61K31/519 , A61K31/444 , A61K31/433 , A61K31/136 , A61K31/404 , A61K31/4245 , G01N33/68
摘要: 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.
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公开(公告)号:US09297806B2
公开(公告)日:2016-03-29
申请号:US13956879
申请日:2013-08-01
发明人: Srinivasan Yegnasubramanian , Michael Christoph Haffner , Alcides Chaux , William G. Nelson , Angelo M. DeMarzo
IPC分类号: G01N33/53 , G01N33/574
CPC分类号: G01N33/57496 , G01N2800/50
摘要: 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.
摘要翻译: 本发明涉及癌症领域。 更具体地,本发明提供了可用于诊断或预测患者中的癌症的方法和组合物。 在一个实施方案中,用于鉴定患者具有癌症的方法包括以下步骤:(a)提供患有组织的福尔马林固定,石蜡包埋或新鲜冷冻的样品; (b)在抗原检索缓冲液中蒸煮样品; (c)将样品在盐酸(HCl)中孵育; (d)在条件下用特异于5hmC的亲和试剂培养样品,以形成样品中存在的亲和试剂和5-羟甲基胞嘧啶(5hmC)之间的复合物; (e)用二级检测试剂检测在5hmC与亲和试剂之间形成的复合物; (f)量化5hmC水平; 如果与对照相比,如果样品中的5hmC水平降低,则鉴定患者具有癌症。
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公开(公告)号:US20240009292A1
公开(公告)日:2024-01-11
申请号:US18029599
申请日:2021-10-01
发明人: Alok Singh , Peter Um , Keira Cohen , William Bishai , Rullin Wang , Srinivasan Yegnasubramanian , Trinity J. Bivalacqua
CPC分类号: A61K39/04 , A61P31/14 , A61K35/74 , A61K2039/58
摘要: 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.
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公开(公告)号:US20230416294A1
公开(公告)日:2023-12-28
申请号:US18041124
申请日:2021-08-10
发明人: Barbara Slusher , Rana Rais , Franco D'Alessio , Pavel Majer , Marcela Krecmerova , Srinivasan Yegnasubramanian
IPC分类号: C07H19/12 , A61P37/06 , A61P29/00 , A61K45/06 , A61K31/706
CPC分类号: C07H19/12 , A61P37/06 , A61K31/706 , A61K45/06 , A61P29/00
摘要: 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.
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公开(公告)号:US10227654B2
公开(公告)日:2019-03-12
申请号:US14708045
申请日:2015-05-08
发明人: William G. Nelson , Srinivasan Yegnasubramanian , Xiaohui Lin , Traci J. Speed , Zachery Reichert
IPC分类号: A61K31/444 , A61K31/404 , A61K31/4188 , A61K31/381 , A61K31/4439 , C12Q1/6886 , A61K31/4245 , A61K31/433 , A61K31/136 , A61K31/517 , A61K31/519 , G01N33/68 , G01N33/50 , A61K31/4184
摘要: 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.
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公开(公告)号:US12060615B2
公开(公告)日:2024-08-13
申请号:US16285019
申请日:2019-02-25
发明人: William G. Nelson , Srinivasan Yegnasubramanian , Xiaohui Lin , Traci J. Speed , Zachery Reichert
IPC分类号: A61K31/4184 , A61K31/136 , A61K31/381 , A61K31/404 , A61K31/4188 , A61K31/4245 , A61K31/433 , A61K31/4439 , A61K31/444 , A61K31/517 , A61K31/519 , C12Q1/6886 , G01N33/50 , G01N33/68
CPC分类号: C12Q1/6886 , A61K31/136 , A61K31/381 , A61K31/404 , A61K31/4184 , A61K31/4188 , A61K31/4245 , A61K31/433 , A61K31/4439 , A61K31/444 , A61K31/517 , A61K31/519 , G01N33/5011 , G01N33/6875 , C12Q2600/136 , C12Q2600/154 , C12Q2600/158 , G01N2500/00
摘要: 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.
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公开(公告)号:US20230100402A1
公开(公告)日:2023-03-30
申请号:US17946416
申请日:2022-09-16
IPC分类号: A61K31/7068 , A61P35/00 , A61K31/203 , A61K31/4188 , A61K31/55
摘要: 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.
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公开(公告)号:US11035850B2
公开(公告)日:2021-06-15
申请号:US16092233
申请日:2017-04-10
IPC分类号: G01N33/50 , A61K31/706 , A61K31/708 , A61K31/7072 , C12Q1/6872 , A61K31/7076 , A61K31/7064 , A61P35/00 , G01N30/72
摘要: This application provides methods to quantitate drug incorporation into DNA and of simultaneously measuring DNA methylation levels. Drugs include nucleoside analog DNA methyltransferase inhibitors.
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