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1. 发明申请

WO1994025625A1 MEANS FOR DETECTING FAMILIAL COLON CANCER (FCC) 审中-公开
标题翻译：检测家族性癌症（FCC）的手段
公开(公告)号：WO1994025625A1
公开(公告)日：1994-11-10
申请号：PCT/US1994004785
申请日：1994-05-02
申请人： THE JOHNS HOPKINS UNIVERSITY , DE LA CHAPELLE, Albert
发明人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/683 , A61K38/00 , C07K14/82 , C12Q1/6886 , C12Q2600/112 , C12Q2600/156 , C12Q2600/172
摘要： Markers of chromosome 2 are associated with cancer predisposition, as shown by linkage analysis, in a significant fraction of families with a history of colon and other cancers. Tumors from these patients progressed through the same series of accumulated mutations in oncogenes and tumor suppressor genes found in non-familial cases, but showed no losses of heterozygosity for the linked chromosome 2 markers. DNA from the tumors (but not normal tissues) in most familial cases revealed a consistent and distinct abnormality: rearrangemnets in short repeated sequences throughout their genomes. This abnormality suggests that a large number of replication errors had occurred during tumor development. Methods are presented for detecting the presence of the gene which predisposes people to have a colon and other tumors and for utilizing this information for diagnostic, prognostic, and preventive purposes. DNA markers useful for such methods are also described.
摘要翻译：染色体2的标记与癌症倾向相关，如通过连锁分析所显示的，具有结肠和其他癌症病史的家族的很大一部分。来自这些患者的肿瘤通过在非家族性病例中发现的致癌基因和肿瘤抑制基因的相同序列的累积突变进行，但是对于连锁的2号染色体标记物，没有显示出杂合性的损失。在大多数家族性病例中，肿瘤（但不是正常组织）的DNA显示出一致和明显的异常：在整个基因组中以短的重复序列重新排列。这种异常表明在肿瘤发展过程中发生了大量的复制错误。提出了用于检测易患人群具有结肠和其他肿瘤的基因的存在并用于诊断，预后和预防目的的方法。还描述了对这些方法有用的DNA标记。

2. 发明申请

WO1995015381A3 HUMAN MUTATOR GENE hMSH2 AND HEREDITARY NON POLYPOSIS COLORECTAL CANCER 审中-公开
公开(公告)号：WO1995015381A3
公开(公告)日：1995-06-08
申请号：PCT/US1994013805
申请日：1994-12-02
申请人： THE JOHNS HOPKINS UNIVERSITY , DE LA CHAPELLE, Albert
发明人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W.
IPC分类号： C12N15/12

3. 发明申请

WO2021163546A1 METHODS AND MATERIALS FOR ASSESSING NUCLEIC ACIDS 审中-公开
公开(公告)号：WO2021163546A1
公开(公告)日：2021-08-19
申请号：PCT/US2021/017937
申请日：2021-02-12
申请人： THE JOHNS HOPKINS UNIVERSITY , PAPADOPOULOS, Nickolas , KINZLER, Kenneth W. , VOGELSTEIN, Bert , COHEN, Joshua David
发明人： PAPADOPOULOS, Nickolas , KINZLER, Kenneth W. , VOGELSTEIN, Bert , COHEN, Joshua David
IPC分类号： C12Q1/686
摘要： Provided herein are systems, kits, compositions and methods for sequencing library preparation and sequencing workflow (e.g., for the identification of mutations). In certain embodiments, provides herein systems and methods to identically barcode both strands of templates, and PCR-based enrichment of each strand that does not require hybridization capture.

4. 发明申请

WO2019133245A1 PREVENTING CYTOKINE RELEASE SYNDROME 审中-公开
公开(公告)号：WO2019133245A1
公开(公告)日：2019-07-04
申请号：PCT/US2018/064969
申请日：2018-12-11
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PAPADOPOULOS, Nickolas , ZHOU, Shibin , STAEDTKE, Verena , BAI, Renyuan , RIGGINS, Gregory J.
IPC分类号： A61K31/198 , A61K39/395 , A61K38/22 , A61P19/02 , A61P37/00
摘要： This document relates to methods and materials for preventing cytokine release syndrome (CRS). For example, methods and materials for using one or more catecholamine inhibitors to prevent a mammal from developing CRS are provided.

5. 发明申请

WO2019100059A1 METHODS AND MATERIALS FOR ASSESSING AND TREATING CANCER 审中-公开
公开(公告)号：WO2019100059A1
公开(公告)日：2019-05-23
申请号：PCT/US2018/062007
申请日：2018-11-20
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , WANG, Qing , PAPADOPOULOS, Nickolas , ZHANG, Ming
IPC分类号： G01N33/574
摘要： This document provides methods and materials for identifying biomarkers (e.g., peptide biomarkers) that can be used to identify a mammal as having a disease (e.g., cancer). This document also provides methods and materials for identifying and/or treating cancer. For example, this document provides methods and materials for using one or more peptide fragments derived from a peptidyl-prolyl cis-trans isomerase A (PPIA) polypeptide to identify a mammal as having cancer (e.g., ovarian cancer).

6. 发明申请

WO2019067092A1 METHODS AND MATERIALS FOR ASSESSING AND TREATING CANCER 审中-公开
公开(公告)号：WO2019067092A1
公开(公告)日：2019-04-04
申请号：PCT/US2018/045669
申请日：2018-08-07
申请人： THE JOHNS HOPKINS UNIVERSITY , BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEMS , THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , COHEN, Joshua , PAPADOPOULOS, Nickolas , LENNON, Anne Marie , TOMASETTI, Cristian , WANG, Yuxuan , NETTO, Georges Jabboure , KARCHIN, Rachel , DOUVILLE, Chris , HANASH, Samir , SPRINGER, Simeon , GROLLMAN, Arthur , DICKMAN, Kathleen
IPC分类号： C12Q1/6886
摘要： Provided herein are methods and materials for detecting and/or treating subject (e.g. a human) having cancer. In some embodiments, methods and materials for identifying a subject as having cancer (e.g., a localized cancer) are provided in which the presence of member(s) of two or more classes of biomarkers are detected. In some embodiments, methods and materials for identifying a subject as having cancer (e.g. a localized cancer) are provided in which the presence of member(s) of at least one class of biomarkers and the presence of aneuploidy are detected. In some embodiments, methods described herein provide increased sensitivity and/or specificity in the detection of cancer in a subject (e.g. a human).

7. 发明申请

WO2016010879A1 SUPPRESSION OF MYELOID DERIVED SUPPRESSOR CELLS AND IMMUNE CHECKPOINT BLOCKADE 审中-公开
标题翻译：抑制髓磷脂抑制细胞和免疫检测点块
公开(公告)号：WO2016010879A1
公开(公告)日：2016-01-21
申请号：PCT/US2015/040107
申请日：2015-07-13
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： ZHOU, Shibin , VOGELSTEIN, Bert , KINZLER, Kenneth W. , KIM, KiBem
IPC分类号： A61K31/44 , A61K31/706 , A61K39/395 , A61P35/00
CPC分类号： A61K39/39558 , A61K31/437 , A61K31/4406 , A61K31/706 , A61K35/742 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K16/2818 , C07K2317/34 , C07K2317/92 , A61K2300/00
摘要： Impressive responses have been observed in patients treated with checkpoint inhibitory anti-PD-1 or anti-CTLA-4 antibodies. However, immunotherapy against poorly immunogenic cancers remains a challenge. Treatment with both anti-PD-1 and anti-CTLA-4 antibodies were unable to eradicate large, modestly immunogenic CT26 tumors or metastatic 4T1 tumors. However, co-treatment with epigenetic modulating drugs and checkpoint inhibitors markedly improved treatment outcomes, curing more than 80% of them. Functional studies revealed that the primary targets of the epigenetic modulators were myeloid-derived suppressor cells (MDSCs). A PI3K-inhibitor that reduced circulating MDSCs also cured 80% of mice with metastatic 4T1 tumors when combined with immune checkpoint inhibitors. Thus, cancers resistant to immune checkpoint blockade can be cured by eliminating MDSCs.
摘要翻译：在使用检查点抑制性抗PD-1或抗CTLA-4抗体治疗的患者中观察到令人印象深刻的反应。然而，针对不良免疫原性癌症的免疫治疗仍然是一个挑战。用抗PD-1和抗CTLA-4抗体的治疗不能消除大的，适度的免疫原性CT26肿瘤或转移性4T1肿瘤。然而，与表观遗传调节药物和检查点抑制剂的共同治疗显着改善了治疗结果，治愈了其中80％以上。功能研究表明，表观遗传调节剂的主要靶标是骨髓来源的抑制细胞（MDSCs）。结合免疫检查点抑制剂，减少循环MDSCs的PI3K抑制剂也可治愈80％转移性4T1肿瘤小鼠。因此，通过消除MDSC可以治愈抗免疫检查点阻断的癌症。

8. 发明申请

WO2012142213A2 SAFE SEQUENCING SYSTEM 审中-公开
标题翻译：安全排序系统
公开(公告)号：WO2012142213A2
公开(公告)日：2012-10-18
申请号：PCT/US2012/033207
申请日：2012-04-12
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , PAPADOPOULOS, Nickolas , KINDE, Isaac
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PAPADOPOULOS, Nickolas , KINDE, Isaac
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6874 , C12Q1/6806 , C12Q1/6869 , C12Q1/6876 , C12Q2563/179 , C12Q2600/158 , C12Q2535/122 , C12Q2565/514
摘要： The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called "Safe-SeqS" for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant ("super-mutants") if ≥95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro , and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.
摘要翻译：存在于DNA模板的一小部分中的突变的鉴定对于在几个生物医学研究领域的进展是必不可少的。尽管大规模并行测序仪器原则上非常适合于此任务，但是这些仪器中的错误率通常太高，无法确定罕见的变体。我们在这里描述了一种可以显着增加大规模并行测序仪器对此目的的灵敏度的方法。这种方法的一个例子是（Safe-Sequencing System），称为“Safe-SeqS”，包括（i）将唯一标识符（UID）分配给每个模板分子; （ii）每个唯一标记的模板分子的扩增以产生UID家族; 和（iii）扩增产物的冗余测序。具有相同UID的PCR片段是真正的突变体（“超突变体”），如果其中95％含有相同的突变。我们说明了这种方法用于确定聚合酶的保真度，体外合成的寡核苷酸的准确性以及正常细胞的核和线粒体基因组中突变的流行率的效用。

9. 发明申请

WO2012071096A2 ARID1A AND PPP2R1A MUTATIONS IN CANCER 审中-公开
标题翻译： ARID1A和PPP2R1A突变在癌症中
公开(公告)号：WO2012071096A2
公开(公告)日：2012-05-31
申请号：PCT/US2011/050487
申请日：2011-09-06
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , VELCULESCU, Victor , PAPADOPOULOS, Nickolas , JONES, Sian
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , VELCULESCU, Victor , PAPADOPOULOS, Nickolas , JONES, Sian
IPC分类号： C12Q1/68 , C12N5/09 , G01N33/68 , A61K31/7088 , C12N15/11
CPC分类号： C12Q1/6886 , A61K31/7088 , A61K31/711 , C12Q2600/156 , G01N33/5011
摘要： Two genes, ARID1A (AT-rich interactive domain-containing protein 1A) and PPP2R1A (protein-phosphatase 2, regulatory subunit 1, alpha), can be used in methods which are useful for detecting cancer, diagnosing cancer, contributing to a diagnosis of cancer, confirming a diagnosis of cancer, identifying appropriate treatments for cancer, monitoring treatment of cancer, and evaluating treatment protocols for cancer, including ovarian clear cell carcinoma, breast cancer, colon cancer, gastric cancer, lung cancer, medulloblastoma, pancreatic cancer, and prostate cancer.
摘要翻译：在可用于检测癌症的方法中可以使用两种基因，即ARID1A（富含AT的交互结构域的蛋白质1A）和PPP2R1A（蛋白质磷酸酶2，调节亚基1，α）诊断癌症，有助于诊断癌症，确认癌症的诊断，鉴别癌症的适当治疗，监测癌症的治疗，以及评估癌症的治疗方案，包括卵巢透明细胞癌，乳腺癌，结肠癌，胃癌，肺癌癌症，成神经管细胞瘤，胰腺癌和前列腺癌。

10. 发明申请

WO2006002142A2 IMAGING INFECTION WITH COMPOUNDS THAT BIND TO THYMIDINE KINASE 审中-公开
标题翻译：用与甲状腺素激酶结合的化合物成像感染
公开(公告)号：WO2006002142A2
公开(公告)日：2006-01-05
申请号：PCT/US2005/021888
申请日：2005-06-20
申请人： THE JOHNS HOPKINS UNIVERSITY , POMPER, Martin, G. , BETTEGOWDA, Chetan , FOSS, Catherine , ZHOU, Shibin , KINZLER, Kenneth , VOGELSTEIN, Bert
发明人： POMPER, Martin, G. , BETTEGOWDA, Chetan , FOSS, Catherine , ZHOU, Shibin , KINZLER, Kenneth , VOGELSTEIN, Bert
IPC分类号： A61K49/00
CPC分类号： A61K51/1241 , A61K51/0491 , A61K51/1231
摘要： The instant invention provides a method for diagnosing an infection in a subject by administering to the subject a compound suitable for imaging which binds to a thymidine kinase present in the infecting organism, and obtaining an image of the subject to determine the presence and location of the compound, wherein a localization of the compound is indicative that the subject has an infection.
摘要翻译：本发明提供了一种用于诊断受试者感染的方法，其通过向受试者施用适合于成像的化合物，其与存在于感染生物体中的胸苷激酶结合，并获得受试者的图像以确定化合物的存在和位置，其中化合物的定位表明该对象具有感染。

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