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1. 发明公开

EP3125938A1 USE OF BACTERIA, BACTERIAL PRODUCTS, AND OTHER IMMUNOREGULATORY ENTITIES IN COMBINATION WITH ANTI-CTLA-4 AND/OR ANTI-PD-1 ANTIBODIES TO TREAT SOLID TUMOR MALIGNANCIES 审中-实审
标题翻译：菌细菌产物和其他免疫调节单位组合使用的抗CTLA-4和/或抗PD-1抗体用于实体瘤恶性肿瘤的治疗
公开(公告)号：EP3125938A1
公开(公告)日：2017-02-08
申请号：EP15773992.1
申请日：2015-03-31
申请人： The Johns Hopkins University , Biomed Valley Discoveries, Inc.
发明人： ZHOU, Shibin , VOGELSTEIN, Bert , KINZLER, Kenneth , KIM, Kibem , SAHA, Saurabh
IPC分类号： A61K39/395 , A61K35/74 , A61P35/00
CPC分类号： A61K35/744 , A61K9/0019 , A61K35/74 , A61K35/742 , A61K39/3955 , A61K39/39558 , A61K2035/115 , A61K2039/505 , A61K2039/54 , A61K2039/545 , C07K16/2803 , C07K16/2818 , A61K2300/00
摘要： The presently disclosed subject matter provides methods and kits for treating solid tumors in a subject by using a combination of anti-CTLA-4 and/or anti-PD-1 antibodies with at least one member of the group consisting of a bacterium, bacterial product, and an immunoregulatory entity. In particular embodiments, the bacteria are toxin-depleted, anaerobic bacteria, such as Clostridium novyi-NT.
摘要翻译：当前盘游离缺失的主题通过使用抗CTLA-4和/或抗PD-1抗体与组由细菌中的至少一个构件，细菌产物的组合提供用于在受试者中治疗实体瘤的方法和试剂盒和免疫调节实体。在具体实施方案中，细菌是毒素耗尽，厌氧细菌，梭菌属诺氏：如NT。

2. 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。

3. 发明申请

WO1996037611A1 EB1 GENE PRODUCT BINDS TO APC 审中-公开
标题翻译： EB1基因产品绑定到APC
公开(公告)号：WO1996037611A1
公开(公告)日：1996-11-28
申请号：PCT/US1996007747
申请日：1996-05-22
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth
IPC分类号： C12N15/12
CPC分类号： C07K14/47 , A61K38/00 , C07K2319/00
摘要： Inactivation of the APC tumor suppressor gene plays an important role in the development of both sporadic and familial forms of colorectal cancers. The majority of these mutations result in the loss of the carboxyl terminus of the APC protein. A cellular protein, EB1, that associates with the carboxyl terminus of APC both in vitro and in vivo has been identified. The EB1 gene is predicted to encode a 268 amino acid protein without significant homology to any protein with known function.
摘要翻译： APC肿瘤抑制基因的失活在结肠直肠癌的散发和家族形式的发展中起重要作用。这些突变中的大多数导致APC蛋白的羧基末端的损失。已经鉴定了在体外和体内与APC的羧基末端缔合的细胞蛋白质EB1。 EB1基因被预测编码268个氨基酸的蛋白质，而与具有已知功能的任何蛋白质没有显着的同源性。

4. 发明公开

EP3296407A1 MUTATIONS OF THE PIK3CA GENE IN HUMAN CANCERS 有权
标题翻译： PIK3CA基因在人类癌症中的突变
公开(公告)号：EP3296407A1
公开(公告)日：2018-03-21
申请号：EP17197306.8
申请日：2005-02-18
申请人： The Johns Hopkins University
发明人： SAMUELS, Yardena , VELCULESCU, Victor , KINZLER, Kenneth , VOGELSTEIN, Bert
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the P13K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the P13K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.
摘要翻译：已知磷脂酰肌醇3-激酶（PI3K）是信号传导途径的重要调节剂。为了确定PI3K是否在癌症中被遗传改变，我们分析了P13K基因家族的序列并发现一个家族成员PIK3CA在结肠和其他器官的癌症中经常发生突变。大部分突变聚集在P13K螺旋或激酶结构域内的两个位置附近。 PIK3CA代表人类癌症中鉴定的突变最严重的癌基因之一，并且可用作诊断和治疗靶标。

5. 发明申请

WO2012054717A2 DETECTING AND TREATING SOLID TUMORS THROUGH SELECTIVE DISRUPTION OF TUMOR VASCULATURE 审中-公开
标题翻译：通过选择性破坏肿瘤血管检测和治疗实体肿瘤
公开(公告)号：WO2012054717A2
公开(公告)日：2012-04-26
申请号：PCT/US2011/057086
申请日：2011-10-20
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , QIAO, Yuan , HUANG, Xin , KINZLER, Kenneth , ZHOU, Shibin , DIAZ, Luis
发明人： VOGELSTEIN, Bert , QIAO, Yuan , HUANG, Xin , KINZLER, Kenneth , ZHOU, Shibin , DIAZ, Luis
IPC分类号： A61K9/127 , A61K47/48 , A61K49/18 , A61K39/395 , A61P35/00
CPC分类号： A61K51/1045 , A61K9/1271 , A61K39/395 , A61K45/06 , A61K51/1009 , C07K16/2887 , C07K16/40 , A61K2300/00
摘要： Several agents capable of inducing vascular responses akin to those observed in inflammatory processes enhance the accumulation of nanoparticles in tumors. Exemplary vascular-active agents include a bacterium, a pro-inflammatory cytokine, and microtubule-destabilizing drugs. Such agents can increase the tumor to blood ratio of radioactivity by more than 20-fold compared to nanoparticles alone. Moreover, vascular-active agents dramatically improved the therapeutic effect of nanoparticles containing radioactive isotopes or chemotherapeutic agents.
摘要翻译：能够诱导类似于在炎症过程中观察到的血管反应的几种试剂增强了纳米颗粒在肿瘤中的积聚。示例性血管活性剂包括细菌，促炎细胞因子和微管去稳定化药物。与单独的纳米颗粒相比，这种药物可以使放射性肿瘤与血液的比例增加20倍以上。此外，血管活性剂显着改善含有放射性同位素或化学治疗剂的纳米颗粒的治疗效果。

6. 发明申请

WO2017132438A1 BOTTLENECK SEQUENCING 审中-公开
标题翻译： BOTTLENECK测序
公开(公告)号：WO2017132438A1
公开(公告)日：2017-08-03
申请号：PCT/US2017/015229
申请日：2017-01-27
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth , HOANG, Margaret , PAPADOPOULOS, Nickolas
IPC分类号： C12Q1/68 , C40B20/04
CPC分类号： C12Q1/6869 , C12Q1/6844 , C40B20/04 , C12Q2525/151 , C12Q2525/191 , C12Q2565/514
摘要： Bottleneck Sequencing System (BotSeqS) is a next-generation sequencing method that simultaneously quantifies rare somatic point mutations across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately prior to library amplification. BotSeqS can be used to show age and tissue-dependent accumulations of rare mutations and demonstrate that somatic mutational burden in normal tissues can vary by several orders of magnitude, depending on biologic and environmental factors. BotSeqS has been used to show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, BotSeqS has shown that the mutation spectra of normal tissues were different from each other, but similar to those of the cancers that arose in them.
摘要翻译：瓶颈测序系统（BotSeqS）是一种新一代测序方法，可同时量化线粒体和核基因组中的罕见体细胞点突变。 BotSeqS在文库扩增之前将分子条形码与简单稀释步骤结合在一起。 BotSeqS可以用于显示年龄和组织依赖性罕见突变的累积，并且证明正常组织中的体细胞突变负荷可以根据生物和环境因素而变化几个数量级。 BotSeqS已被用于显示正常组织中线粒体和核基因组的突变模式之间的主要差异。最后，BotSeqS已经表明，正常组织的突变谱彼此不同，但与它们中出现的癌症的突变谱相似。

7. 发明申请

WO2015153639A1 USE OF BACTERIA, BACTERIAL PRODUCTS, AND OTHER IMMUNOREGULATORY ENTITIES IN COMBINATION WITH ANTI-CTLA-4 AND/OR ANTI-PD-1 ANTIBODIES TO TREAT SOLID TUMOR MALIGNANCIES 审中-公开
标题翻译：使用细菌，细菌产品和其他免疫组织化学实验结合抗CTLA-4和/或抗PD-1抗体治疗实体肿瘤恶性肿瘤
公开(公告)号：WO2015153639A1
公开(公告)日：2015-10-08
申请号：PCT/US2015/023633
申请日：2015-03-31
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： ZHOU, Shibin , VOGELSTEIN, Bert , KINZLER, Kenneth , KIM, Kibem
IPC分类号： A61K39/395 , A61K35/74 , A61P35/00
CPC分类号： A61K35/744 , A61K9/0019 , A61K35/74 , A61K35/742 , A61K39/3955 , A61K39/39558 , A61K2035/115 , A61K2039/505 , A61K2039/54 , A61K2039/545 , C07K16/2803 , C07K16/2818 , A61K2300/00
摘要： The presently disclosed subject matter provides methods and kits for treating solid tumors in a subject by using a combination of anti-CTLA-4 and/or anti-PD-1 antibodies with at least one member of the group consisting of a bacterium, bacterial product, and an immunoregulatory entity. In particular embodiments, the bacteria are toxin-depleted, anaerobic bacteria, such as Clostridium novyi-NT.
摘要翻译：目前公开的主题提供了通过使用抗CTLA-4和/或抗-PD-1抗体与至少一种由细菌，细菌产物组成的组合来治疗受试者的实体瘤的方法和试剂盒和免疫调节实体。在具体实施方案中，细菌是无毒素的厌氧细菌，例如梭菌（NTN）NT。

8. 发明公开

EP3360979A1 TERT PROMOTER MUTATIONS IN GLIOMAS AND A SUBSET OF TUMORS 有权转让
公开(公告)号：EP3360979A1
公开(公告)日：2018-08-15
申请号：EP18164632.4
申请日：2014-02-18
申请人： Duke University , The Johns Hopkins University
发明人： YAN, Hai , VOGELSTEIN, Bert , KINZLER, Kenneth , PAPADOPOULOS, Nickolas , BIGNER, Darell , JIAO, Yuchen , BETTEGOWDA, Chetan
IPC分类号： C12Q1/6886 , C12N15/12
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/156
摘要： We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (

9. 发明授权

EP3296407B1 MUTATIONS OF THE PIK3CA GENE IN HUMAN CANCERS 有权
公开(公告)号：EP3296407B1
公开(公告)日：2019-05-22
申请号：EP17197306.8
申请日：2005-02-18
申请人： The Johns Hopkins University
发明人： SAMUELS, Yardena , VELCULESCU, Victor , KINZLER, Kenneth , VOGELSTEIN, Bert
IPC分类号： C12Q1/6886

10. 发明公开

EP3907299A1 SAFE SEQUENCING SYSTEM 审中-实审
公开(公告)号：EP3907299A1
公开(公告)日：2021-11-10
申请号：EP21173115.3
申请日：2012-04-12
申请人： The Johns Hopkins University
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth , PAPADOPOULOS, Nickolas , KINDE, Isaac
IPC分类号： C12Q1/6874 , C12N15/11 , C12Q1/6806
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.

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