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1. 发明申请

US20210161928A1 CANCER THERAPY VIA A COMBINATION OF EPIGENETIC MODULATION AND IMMUNE MODULATION 有权
公开(公告)号：US20210161928A1
公开(公告)日：2021-06-03
申请号：US17167819
申请日：2021-02-04
申请人： Stephen B. Baylin , Drew M. Pardoll , Suzanne L. Topalian
发明人： Stephen B. Baylin , Drew M. Pardoll , Suzanne L. Topalian
IPC分类号： A61K31/706 , A61K38/15 , A61K39/395 , A61K31/167 , C07K16/28 , A61K45/06 , C12Q1/6886
摘要： Cancer therapies that combine epigenetic modulating agent(s) with immune modulating agent(s), which were remarkably identified to provide an improved treatment regimen over single agent therapy, are disclosed. In particular embodiments, the invention provides for improved treatment of NSCLC in patients via administration of exemplary immune modulating agents anti-PD-1 antibody or anti-PD-L1 antibody, which were observed to show enhanced activity in combination with the exemplary epigenetic modulating agent 5-deoxyazacytidine. Further, expression markers of responsive neoplastic cells are also disclosed.

2. 发明授权

US08071290B2 Hypermethylation of GATA-4 and GATA-5 transcription factor genes in cancer 有权
标题翻译： GATA-4和GATA-5转录因子基因在癌症中的高甲基化
公开(公告)号：US08071290B2
公开(公告)日：2011-12-06
申请号：US12119366
申请日：2008-05-12
申请人： Stephen B. Baylin , Yoshimitsu Akiyama , James G. Herman
发明人： Stephen B. Baylin , Yoshimitsu Akiyama , James G. Herman
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6858 , C12Q1/6886 , C12Q2600/154 , C12Q2523/125
摘要： Methods are provided for identifying the presence of cancer cells in a sample by detecting hypermethylation of the promoter region of a GATA-4 transcription factor gene, a GATA-5 transcription factor gene, or both. Methods for ameliorating a cancer by effecting expression of a hypermethylation silenced GATA-4 and/or GATA-5 transcription also are provided.
摘要翻译：提供了通过检测GATA-4转录因子基因，GATA-5转录因子基因或两者的启动子区域的甲基化来鉴定样品中癌细胞存在的方法。还提供了通过进行表达高甲基化沉默的GATA-4和/或GATA-5转录来改善癌症的方法。

3. 发明申请

US20090092976A1 Hypermethylation of GATA-4 and GATA-5 Transcription Factor Genes in Cancer 有权
标题翻译： GATA-4和GATA-5转录因子基因在甲状腺癌中的甲基化
公开(公告)号：US20090092976A1
公开(公告)日：2009-04-09
申请号：US12119366
申请日：2008-05-12
申请人： Stephen B. Baylin , Yoshimitsu Akiyama , James G. Herman
发明人： Stephen B. Baylin , Yoshimitsu Akiyama , James G. Herman
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6858 , C12Q1/6886 , C12Q2600/154 , C12Q2523/125
摘要： Methods are provided for identifying the presence of cancer cells in a sample by detecting hypermethylation of the promoter region of a GATA-4 transcription factor gene, a GATA-5 transcription factor gene, or both. Methods for ameliorating a cancer by effecting expression of a hypermethylation silenced GATA-4 and/or GATA-5 transcription also are provided.
摘要翻译：提供了通过检测GATA-4转录因子基因，GATA-5转录因子基因或两者的启动子区域的甲基化来鉴定样品中癌细胞存在的方法。还提供了通过进行表达高甲基化沉默的GATA-4和/或GATA-5转录来改善癌症的方法。

4. 发明申请

US20080221056A1 Early Detection and Prognosis of Colon Cancers 审中-公开
标题翻译：早期检测和结肠癌预后
公开(公告)号：US20080221056A1
公开(公告)日：2008-09-11
申请号：US12029645
申请日：2008-02-12
申请人： Stephen B. Baylin , Wim Van Criekinge , Kornel E. Schuebel
发明人： Stephen B. Baylin , Wim Van Criekinge , Kornel E. Schuebel
IPC分类号： A61K31/7088 , C12Q1/68 , A61P35/00
CPC分类号： C12Q1/6886 , C12Q2523/125 , C12Q2600/106 , C12Q2600/154
摘要： We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island hypermethylation and transcriptional silencing in colorectal cancer (CRC). By screening cell lines and validating tumor specific hypermethylation in a panel of primary human CRC samples, we estimate that nearly 5% of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find a much larger number of genes hypermethylated in individual tumors, and much higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken. The genes we identified can be used inter alia diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.
摘要翻译：我们已经开发了一种转录组范围的方法来鉴定受启动子CpG岛高甲基化和转录沉默在结肠直肠癌（CRC）中影响的基因。通过筛选细胞系并验证一组原代人CRC样品中的肿瘤特异性高甲基化，我们估计所有已知基因中的近5％可能是单个肿瘤中的启动子甲基化。当与基因突变直接比较时，我们发现在个体肿瘤中超甲基化的基因数量更多，并且在具有遗传或表观遗传变化的个体基因内的高甲基化频率高得多。因此，为了列举人类癌症基因组中的全部变化，并促进最有效的肿瘤分组来鉴定癌症生物标志物并定制治疗方法，应进行遗传和表观遗传筛选。我们确定的基因可以用于诊断上检测癌症，癌前病症和发展癌症的可能性。

5. 发明授权

US5846712A Tumor suppressor gene, HIC-1 失效
公开(公告)号：US5846712A
公开(公告)日：1998-12-08
申请号：US452567
申请日：1995-05-25
申请人： Stephen B. Baylin , Michele Makos Wales
发明人： Stephen B. Baylin , Michele Makos Wales
IPC分类号： G01N33/53 , A61K35/76 , A61K38/00 , A61K48/00 , A61P1/00 , A61P7/00 , A61P13/02 , A61P15/00 , A61P25/00 , A61P31/12 , A61P35/00 , C07K14/47 , C07K16/32 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/12 , C12P21/08 , C12Q1/68 , C07H21/02
CPC分类号： C07K14/4703 , A61K38/00 , A61K48/00 , C12N2799/027
摘要： Polynucleotide and polypeptide sequences encoding a novel tumor suppressor, HIC-1, are provided. Also included is a method for detecting a cell proliferative disorder associated with HIC-1. HIC-1 is a marker which can be used diagnostically, prognostically and therapeutically over the course of such disorders.

6. 发明授权

US5786146A Method of detection of methylated nucleic acid using agents which modify unmethylated cytosine and distinguishing modified methylated and non-methylated nucleic acids 失效
标题翻译：使用修饰非甲基化胞嘧啶并鉴别修饰的甲基化和非甲基化核酸的试剂检测甲基化核酸的方法
公开(公告)号：US5786146A
公开(公告)日：1998-07-28
申请号：US656716
申请日：1996-06-03
申请人： James G. Herman , Stephen B. Baylin
发明人： James G. Herman , Stephen B. Baylin
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6827 , C12Q1/6886 , C12Q2600/154
摘要： The present invention provides a method of PCR, methylation specific PCR (MSP), for rapid identification of DNA methylation patterns in a CpG-containing nucleic acid. MSP uses agents to modify unmethylated cytosine in a nucleic acid of interest, and then uses the PCR reaction to amplify the CpG-containing nucleic acid in the specimen by means of CpG-specific oligonucleotide primers. The oligonecleotide primers distinguish between modified methylated and nonmethylated nucleic acid. Kits utilizing MSP for the detection of methylated CpG-containing nucleic acids are also provided.
摘要翻译：本发明提供了PCR，甲基化特异性PCR（MSP）的方法，用于快速鉴定含CpG的核酸中的DNA甲基化模式。 MSP使用试剂来修饰感兴趣的核酸中的未甲基化胞嘧啶，然后使用PCR反应通过CpG特异性寡核苷酸引物扩增样品中含CpG的核酸。寡核苷酸引物区分修饰甲基化和非甲基化核酸。还提供了使用MSP检测含甲基化CpG的核酸的试剂盒。

7. 发明申请

US20090099037A1 Genomic Screen for Epigenetically Silenced Genes Associated With Cancer 审中-公开
标题翻译：与癌症相关的表观遗传学沉默基因的基因组筛选
公开(公告)号：US20090099037A1
公开(公告)日：2009-04-16
申请号：US12253802
申请日：2008-10-17
申请人： Stephen B. Baylin , James Herman , Hiromu Suzuki
发明人： Stephen B. Baylin , James Herman , Hiromu Suzuki
IPC分类号： C12Q1/68 , C40B30/06
CPC分类号： C12Q1/6886 , C12Q1/6809 , C12Q2600/154 , C12Q2537/164
摘要： A method of identifying epigenetically silenced genes, e.g., methylation silenced genes, in cancer cells is provided. In addition, methods of identifying a cancer by detecting epigenetic silencing of gene expression are provided, as are methods of treating a subject having such a cancer, for example, a colorectal cancer and/or gastric cancer. Reagents for practicing such methods also are provided.
摘要翻译：提供了一种在癌细胞中鉴定表观基因沉默基因，例如甲基化沉默基因的方法。此外，提供了通过检测基因表达的表观遗传学沉默来鉴定癌症的方法，以及治疗患有这种癌症的受试者例如结肠直肠癌和/或胃癌的方法。也提供了实施这种方法的试剂。

8. 发明授权

US07371527B1 Hypermethylation of GATA-4 and GATA-5 transcription factor genes in cancer 有权
标题翻译： GATA-4和GATA-5转录因子基因在癌症中的高甲基化
公开(公告)号：US07371527B1
公开(公告)日：2008-05-13
申请号：US10972066
申请日：2004-10-21
申请人： Stephen B. Baylin , Yoshimitsu Akiyama , James G. Herman
发明人： Stephen B. Baylin , Yoshimitsu Akiyama , James G. Herman
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6858 , C12Q1/6886 , C12Q2600/154 , C12Q2523/125
摘要： Methods are provided for identifying the presence of cancer cells in a sample by detecting hypermethylation of the promoter region of a GATA-4 transcription factor gene, a GATA-5 transcription factor gene, or both. Methods for ameliorating a cancer by effecting expression of a hypermethylation silenced GATA-4 and/or GATA-5 transcription also are provided.
摘要翻译：提供了通过检测GATA-4转录因子基因，GATA-5转录因子基因或两者的启动子区域的甲基化来鉴定样品中癌细胞存在的方法。还提供了通过进行表达高甲基化沉默的GATA-4和/或GATA-5转录来改善癌症的方法。

9. 发明申请

US20080057071A1 Use Of Hedgehog Pathway Inhibitors In Small-Cell Lung Cancer 审中-公开
标题翻译：在小细胞肺癌中使用刺猬通路抑制剂
公开(公告)号：US20080057071A1
公开(公告)日：2008-03-06
申请号：US10576149
申请日：2004-10-20
申请人： David N. Watkins , David M. Berman , Stephen B. Baylin , Philip A. Beachy
发明人： David N. Watkins , David M. Berman , Stephen B. Baylin , Philip A. Beachy
IPC分类号： A61K39/395 , A61K31/42 , A61P35/00 , C12N5/08 , C12Q1/68 , G01N33/53
CPC分类号： G01N33/57423 , G01N33/5011 , G01N2800/52
摘要： Elevated Hedgehog (Hh) pathway activity, including ligand stimulated Hh pathway activity, was detected in small-cell lung cancer (SCLQ cells, and determined to be associated with growth and proliferation of the cancer cells. Accordingly, methods are provided for treating SCLC associated with elevated Hh pathway activity by reducing or inhibiting the Hh pathway activity. Also provided are methods of determining the responsiveness of SCLC to treatment with a Hh pathway antagonist.
摘要翻译：在小细胞肺癌（SCLQ细胞）中检测到高刺猬（Hh）通路活性，包括配体刺激的Hh通路活性，并确定与癌细胞的生长和增殖相关，因此提供了用于治疗SCLC相关的方法通过降低或抑制Hh通路活性，具有升高的Hh通路活性。还提供了确定SCLC对用Hh途径拮抗剂治疗的反应性的方法。

10. 发明授权

US06773897B2 Method of predicting the clinical response to chemotherapeutic treatment with alkylating agents 有权
标题翻译：预测用烷化剂对化学治疗的临床反应的方法
公开(公告)号：US06773897B2
公开(公告)日：2004-08-10
申请号：US09969131
申请日：2001-10-01
申请人： James G. Herman , Stephen B. Baylin , Manel Esteller
发明人： James G. Herman , Stephen B. Baylin , Manel Esteller
IPC分类号： C12Q148
CPC分类号： C07K16/40 , C12Q1/683 , C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , Y10S435/975 , C12Q2523/125
摘要： The present invention provides methods relating to chemotherapeutic treatment of a cell proliferative disorder. In particular, a method is provided for predicting the clinical response to certain types of chemotherapeutic agents. Alkylating agents, used for the treatment of certain types of tumors including tumors of the nervous system and lymph system, are efficacious agents when the damage they do to tumor cell DNA is not repaired by cellular DNA repair mechanisms. The present invention provides a method for determining the activity of a gene encoding a DNA repair enzyme, thus providing a prediction of the clinical response to alkylating agents.
摘要翻译：本发明提供了与细胞增殖性疾病的化学治疗有关的方法。特别地，提供了一种用于预测对某些类型的化学治疗剂的临床反应的方法。用于治疗某些类型肿瘤（包括神经系统和淋巴系统的肿瘤）的烷化剂是当它们对肿瘤细胞DNA的损伤不被细胞DNA修复机制修复时是有效的试剂。本发明提供了确定编码DNA修复酶的基因的活性的方法，从而提供了对烷化剂的临床应答的预测。

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