公开(公告)号：WO2021127184A1

公开(公告)日：2021-06-24

申请号：PCT/US2020/065617

申请日：2020-12-17

Applicant: THE JOHNS HOPKINS UNIVERSITY ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth W. ,  HSIUE, Emily Han-Chung ,  DOUGLASS, Jacqueline ,  HWANG, Michael S. ,  PEARLMAN, Alexander ,  PAPADOPOULOS, Nickolas ,  ZHOU, Shibin ,  MOG, Brian ,  WRIGHT, Katharine M. ,  GABELLI, Sandra B.

Inventor： VOGELSTEIN, Bert ,  KINZLER, Kenneth W. ,  HSIUE, Emily Han-Chung ,  DOUGLASS, Jacqueline ,  HWANG, Michael S. ,  PEARLMAN, Alexander ,  PAPADOPOULOS, Nickolas ,  ZHOU, Shibin ,  MOG, Brian ,  WRIGHT, Katharine M. ,  GABELLI, Sandra B.

IPC: C07K14/82 ,  C07K16/32 ,  A61K39/395 ,  A61P35/00

Abstract: This document provides methods and materials for assessing a mammal having or suspected of having cancer and/or for treating a mammal having cancer. For example, molecules including one or more antigen-binding domains (e.g., a single-chain variable fragment (scFv)) that can bind to a modified peptide (e.g., a tumor antigen), as well as method for using such molecules, are provided.

公开(公告)号：WO2013006791A3

公开(公告)日：2013-01-10

申请号：PCT/US2012/045757

申请日：2012-07-06

Applicant: THE JOHNS HOPKINS UNIVERSITY ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth W.

Inventor： VOGELSTEIN, Bert ,  KINZLER, Kenneth W.

IPC: C12Q1/68 ,  C12N15/11

Abstract: Assays for detecting mutant sequences at particular locations, especially against a background of non-mutant sequences, employ thermocycling ligase reactions. Differentially labeled or sized probes can be used to distinguish wild-type and mutant sequences. Physico-chemical properties of the probes can be critical to successful detection. Mutation detection can be used for diagnosis, monitoring, or prognosticating diseases such as cancers.

公开(公告)号：WO2010102160A3

公开(公告)日：2011-01-13

申请号：PCT/US2010026290

申请日：2010-03-05

Applicant: UNIV JOHNS HOPKINS ,  VOGELSTEIN BERT ,  KINZLER KENNETH W ,  PARSONS D WILLIAMS ,  JONES SIAN ,  KERN SCOTT ,  HRUBAN RALPH ,  ESHLEMAN JAMES R ,  GOGGINS MICHAEL ,  KLEIN ALISON ,  HIDALGO MANUEL ,  VELCULESCU VICTOR E

Inventor： VOGELSTEIN BERT ,  KINZLER KENNETH W ,  PARSONS D WILLIAMS ,  JONES SIAN ,  KERN SCOTT ,  HRUBAN RALPH ,  ESHLEMAN JAMES R ,  GOGGINS MICHAEL ,  KLEIN ALISON ,  HIDALGO MANUEL ,  VELCULESCU VICTOR E

IPC: C12Q1/68 ,  G01N33/574 ,  G01N33/68

CPC classification number: C12Q1/6886 ,  A61K31/407 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/57438 ,  G01N2333/47

Abstract: The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.

Abstract translation: 本发明提供了一种检测胰腺癌患者和具有胰腺癌家族史的个体中PALB2基因突变的方法。 还提供了用于诊断患有胰腺癌的倾向，用于预测患者对胰腺癌治疗的反应以及用于治疗患者胰腺癌的方法，其基于在患者体内PALB2突变或异常PALB2基因表达的存在。

公开(公告)号：WO2005091849A3

公开(公告)日：2009-04-16

申请号：PCT/US2005005193

申请日：2005-02-18

Applicant: UNIV JOHNS HOPKINS ,  SAMUELS YARDENA ,  VELCULESCU VICTOR ,  KINZLER KENNETH W ,  VOGELSTEIN BERT

Inventor： SAMUELS YARDENA ,  VELCULESCU VICTOR ,  KINZLER KENNETH W ,  VOGELSTEIN BERT

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q2600/156

Abstract: 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.

Abstract translation: 已知磷脂酰肌醇3-激酶（PI3K）是信号传导途径的重要调控因子。 为了确定PI3K在癌症中的遗传改变，我们分析了P13K基因家族的序列，发现一个家族成员PIK3CA在结肠癌和其他器官的癌症中经常发生突变。 大多数突变聚集在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出来的最突变的癌基因之一，可用作诊断和治疗靶点。

公开(公告)号：WO2007149432A3

公开(公告)日：2008-12-31

申请号：PCT/US2007014273

申请日：2007-06-19

Applicant: UNIV JOHNS HOPKINS ,  DIEHL FRANK ,  KINZLER KENNETH W ,  VOGELSTEIN BERT

Inventor： DIEHL FRANK ,  KINZLER KENNETH W ,  VOGELSTEIN BERT

IPC: C12Q1/68 ,  C07H21/02

CPC classification number: C12Q1/686 ,  C12Q1/6876 ,  C12Q2600/16 ,  C12Q2527/125 ,  C12Q2527/153 ,  C12Q2565/537

Abstract: Modulation of the viscosity of the oil phase of a microemulsion used for amplification of DNA on a bead increases the homogeneity of product beads and the amount of amplified DNA per bead. Moreover the number of separate microemulsion populations that can be formed in parallel is increased using multi-well plates and mixer mill disruptor machines designed to lyse biological samples.

Abstract translation: 用于在珠上扩增DNA的微乳液的油相的粘度的调节增加了产物珠的均匀性和每个珠的扩增DNA的量。 此外，可以使用设计用于裂解生物样品的多孔板和混合机研磨破碎机来增加可以平行形成的单独的微乳液种群的数量。

公开(公告)号：WO2008021288A2

公开(公告)日：2008-02-21

申请号：PCT/US2007/017866

申请日：2007-08-13

Applicant: JOHNS HOPKINS UNIVERSITY ,  SJOBLOM, Tobias ,  JONES, Sian ,  PARSONS, D., Williams ,  WOOD, Laura, D. ,  LIN, Jimmy ,  BARBER, Thomas ,  MANDELKER, Diana ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W. ,  VELCULESU, Victor, E.

Inventor： SJOBLOM, Tobias ,  JONES, Sian ,  PARSONS, D., Williams ,  WOOD, Laura, D. ,  LIN, Jimmy ,  BARBER, Thomas ,  MANDELKER, Diana ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W. ,  VELCULESU, Victor, E.

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156

Abstract: Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of ~90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention and monitoring.

Abstract translation: 分析11个乳房和11个结直肠癌中的13,023个基因显示，个体肿瘤平均累积了〜90个突变基因，但只有其中一个子集对肿瘤过程有贡献。 使用严格的标准来描绘这一亚型，我们确定了189个基因（平均每个肿瘤11个），以显着的频率突变。 这些基因绝大多数不知道在肿瘤中被遗传改变，并被预测会影响广泛的细胞功能，包括转录，粘附和侵袭。 这些数据定义了两种人类癌症类型的遗传景观，为诊断和治疗干预和监测提供了新的目标。

公开(公告)号：WO2007050465A3

公开(公告)日：2007-10-25

申请号：PCT/US2006041115

申请日：2006-10-20

Applicant: UNIV JOHNS HOPKINS ,  VOGELSTEIN BERT ,  DIEHL FRANK ,  KINZLER KENNETH W ,  LI MING

Inventor： VOGELSTEIN BERT ,  DIEHL FRANK ,  KINZLER KENNETH W ,  LI MING

IPC: C12P19/34

CPC classification number: C12Q1/6858 ,  G01R31/025 ,  G01R31/3277 ,  C12Q2565/537 ,  C12Q2563/155 ,  C12Q2527/125

Abstract: Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.

Abstract translation: 用于BEAMing的基本方法的改进提高了灵敏度并提高了信噪比。 这些改进允许确定各种DNA聚合酶的固有错误率，并允许检测从癌症患者血浆中分离的DNA中罕见且微妙的突变。

公开(公告)号：WO2007050465A2

公开(公告)日：2007-05-03

申请号：PCT/US2006/041115

申请日：2006-10-20

Applicant: THE JOHNS HOPKINS UNIVERSITY ,  VOGELSTEIN, Bert ,  DIEHL, Frank ,  KINZLER, Kenneth, W. ,  LI, Ming

Inventor： VOGELSTEIN, Bert ,  DIEHL, Frank ,  KINZLER, Kenneth, W. ,  LI, Ming

IPC: C12Q1/68

CPC classification number: C12Q1/6858 ,  G01R31/025 ,  G01R31/3277 ,  C12Q2565/537 ,  C12Q2563/155 ,  C12Q2527/125

Abstract: Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.

Abstract translation:

于用于整经增加的灵敏度和增加的信噪比的基本方法的改进。 这些改进已批准的各种DNA聚合酶的固有误差率的确定和已批准来自癌症患者的血浆中分离的DNA中稀有和微妙的突变的检测。

公开(公告)号：WO2005062812A2

公开(公告)日：2005-07-14

申请号：PCT/US2004042597

申请日：2004-12-21

Applicant: UNIV JOHNS HOPKINS ,  VOGELSTEIN BERT ,  KINZLER KENNETH W ,  KOHLI MANU ,  RAGO CARLO

Inventor： VOGELSTEIN BERT ,  KINZLER KENNETH W ,  KOHLI MANU ,  RAGO CARLO

IPC: C12N15/63 ,  C12N15/64 ,  C12N15/86 ,  C12N15/864 ,  C12N15/90

CPC classification number: C12N15/86 ,  C12N15/902 ,  C12N2750/14143 ,  C12N2800/30

Abstract: Emerging evidence suggests that recombinant adeno-associated viral (rAAV) vectors can be used for specific gene targeting in human somatic cells. We have developed an rAAV vector construction procedure employing fusion PCR and a single cloning step that considerably simplifies the knockout process. We demonstrate its utility by disrupting genes at specific positions within human colon cancer cells as well as within immortalized normal epithelial cells. This technology should be broadly applicable to in vitro studies that require the manipulation of the human genome.

Abstract translation: 新出现的证据表明重组腺相关病毒（rAAV）载体可用于人体细胞的特定基因靶向。 我们开发了rAAV载体构建程序，采用融合PCR和单克隆步骤，大大简化了敲除过程。 我们通过破坏人类结肠癌细胞内以及永生化正常上皮细胞内特定位置的基因来证明其实用性。 该技术应广泛适用于需要操作人类基因组的体外研究。

公开(公告)号：WO2005039492A2

公开(公告)日：2005-05-06

申请号：PCT/US2004/034625

申请日：2004-10-21

Applicant: THE JOHN HOPKINS UNIVERSITY ,  DANG, Long ,  BETTEGOWDA, Chetan ,  KINZLER, Kenneth, W. ,  VOGELSTEIN, Bert

Inventor： DANG, Long ,  BETTEGOWDA, Chetan ,  KINZLER, Kenneth, W. ,  VOGELSTEIN, Bert

IPC: A61K

CPC classification number: A61K35/742 ,  A61K31/337 ,  A61K31/427 ,  A61K45/06 ,  Y10S435/842 ,  A61K2300/00

Abstract: Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.

Abstract translation: 目前用于治疗癌症的方法在一定程度上受到药物不能影响肿瘤血管不足的区域的限制。 我们已经发现，厌氧细菌的孢子与与微管相互作用的药物组合可能导致肿瘤的血管和非血管性腔室的破坏。 发现两类微管抑制剂发挥显着不同的作用。 抑制微管合成的一些药物，如长春瑞滨，当与孢子结合使用时，引起快速，大规模的出血性坏死。 相比之下，稳定微管（如紫杉烷多西紫杉醇）的药物导致肿瘤消退缓慢，导致大多数肿瘤细胞死亡。 肿瘤不良灌注区域中的剩余细胞可以被杂音细菌消灭。 机理研究表明，微管不稳定剂，而不是微管稳定剂，从根本上减少了流向肿瘤的血液，从而扩大了孢子可以发芽的缺氧生态位。 在没有过量毒性的情况下，单次静脉注射孢子加选择的微管相互作用剂能够引起几种肿瘤的回归。