公开(公告)号：EP3218004A4

公开(公告)日：2018-06-13

申请号：EP15858277

申请日：2015-11-12

申请人： UNIV JOHNS HOPKINS

发明人： DIAZ LUIS ,  VOGELSTEIN BERT ,  KINZLER KENNETH W ,  PAPADOPOULOS NICKOLAS ,  LE DUNG

IPC分类号： A61K39/395 ,  A61P35/00

CPC分类号： C07K16/2803 ,  A61K2039/505 ,  A61K2039/55 ,  C07K16/2818 ,  C07K16/2827 ,  C07K16/30 ,  C07K16/40 ,  C07K2317/00 ,  C07K2317/24 ,  C07K2317/76 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Y113/11052

摘要： Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

公开(公告)号：EP2697397A4

公开(公告)日：2014-10-15

申请号：EP12772013

申请日：2012-04-12

申请人： UNIV JOHNS HOPKINS

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

公开(公告)号：EP2326734A4

公开(公告)日：2012-07-11

申请号：EP09812193

申请日：2009-09-03

申请人： UNIV JOHNS HOPKINS

发明人： VOGELSTEIN BERT ,  KINZLER KENNETH W ,  PARSONS DONALD WILLIAM ,  JONES SIAN ,  ZHANG XIAOSONG ,  LIN JIMMY CHANG-HO ,  LEARY REBECCA J ,  ANGENENDT PHILIPP ,  PAPADOPOULOS NICKOLAS ,  VELCULESCU VICTOR ,  PARMIGIANI GIOVANNI ,  KARCHIN RACHEL ,  KERN SCOTT ,  HRUBAN RALPH ,  ESHLEMAN JAMES R ,  GOGGINS MICHAEL ,  KLEIN ALISON

IPC分类号： C12Q1/68

CPC分类号： G01N33/57438 ,  C12Q1/6886 ,  C12Q2600/156 ,  G01N2800/50

公开(公告)号：EP2315849A4

公开(公告)日：2012-02-22

申请号：EP09803662

申请日：2009-07-31

申请人： UNIV JOHNS HOPKINS

发明人： DIEHL FRANK ,  DIAZ LUIS ,  KINZLER KENNETH W ,  VOGELSTEIN BERT ,  SCHMIDT KERSTIN

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2525/197 ,  C12Q2535/131 ,  C12Q2549/119 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/136

公开(公告)号：EP0672181A4

公开(公告)日：1997-03-26

申请号：EP93909210

申请日：1993-03-31

申请人： UNIV JOHNS HOPKINS MED

发明人： VOGELSTEIN BERT ,  KINZLER KENNETH W

IPC分类号： C12N15/09 ,  C07H21/04 ,  C12Q1/34 ,  C12Q1/68 ,  G01N33/50 ,  C12P19/34

CPC分类号： G01N33/50 ,  C12Q1/6806 ,  C12Q1/6886 ,  C12Q2600/156 ,  Y10S435/81 ,  Y10T436/143333 ,  C12Q2527/137

摘要： A method to isolate nucleic acids from stool specimen which is used to detect mutations associated with gastrointestinal neoplasia. An exemplary result obtained is shown in the Figure. Reagents used to carry out the isolation of nucleic acids are also disclosed.

公开(公告)号：EP3169326A4

公开(公告)日：2018-04-04

申请号：EP15822398

申请日：2015-07-13

申请人： UNIV JOHNS HOPKINS

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.

公开(公告)号：EP2912468A4

公开(公告)日：2016-06-29

申请号：EP13851273

申请日：2013-10-17

申请人： UNIV JOHNS HOPKINS

发明人： KINDE ISAAC ,  KINZLER KENNETH W ,  VOGELSTEIN BERT ,  PAPADOPOULOS NICKOLAS ,  DIAZ LUIS ,  BETTEGOWDA CHETAN ,  WANG YUXUAN

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

CPC分类号： C12Q1/6886 ,  C12Q2600/154 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Q2600/16 ,  G01N33/57442 ,  G01N33/57449

摘要： The recently developed liquid-based Papanicolaou (Pap) smear allows not only cytologic evaluation but also collection of DNA for detection of HPV, the causative agent of cervical cancer. We tested these samples to detect somatic mutations present in rare tumor cells that might accumulate in the cervix once shed from endometrial and ovarian cancers. A panel of commonly mutated genes in endometrial and ovarian cancers was assembled and used to identify mutations in all 46 endometrial or cervical cancer tissue samples. We were able also able to identify the same mutations in the DNA from liquid Pap smears in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). We developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear without prior knowledge of the tumor's genotype.

摘要翻译： 最近开发的基于液体的Papanicolaou（Pap）涂片不仅允许细胞学评估，还允许DNA的检测用于检测宫颈癌的致病因子HPV。 我们测试了这些样品，以检测罕见的肿瘤细胞中存在的体细胞突变，其可能在子宫内膜和卵巢癌中从子宫颈积聚。 组装了一组在子宫内膜和卵巢癌中常见突变的基因，用于鉴定所有46例子宫内膜癌或子宫颈癌组织样本中的突变。 我们还能够在100％的子宫内膜癌（24例24例）和41％的卵巢癌（22例中的9例）中鉴定出来自液体巴氏涂片的DNA中的相同突变。 我们开发了一种基于序列的方法来查询单个液体巴氏涂片中12个基因的突变，而无需了解肿瘤的基因型。

公开(公告)号：EP2831279A4

公开(公告)日：2015-12-30

申请号：EP13768366

申请日：2013-03-22

申请人： UNIV JOHNS HOPKINS

发明人： VOGELSTEIN BERT ,  KINZLER KENNETH W ,  PAPADOPOULOS NICKOLAS ,  KINDE ISAAC

IPC分类号： C12Q1/68 ,  C12N15/11 ,  G01N33/48 ,  G01N33/53

CPC分类号： C12Q1/6869 ,  C12Q1/6811 ,  C12Q1/6827 ,  C12Q1/6883 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/16 ,  C12Q2535/122 ,  C12Q2537/16 ,  C12Q2537/165 ,  C12Q2545/114

摘要： Massively parallel sequencing of cell-free, maternal plasma DNA was recently demonstrated to be a safe and effective screening method for fetal chromosomal aneuploidies. Here, we report an improved sequencing method achieving significantly increased throughput and decreased cost by replacing laborious sequencing library preparation steps with PCR employing a single primer pair. Using this approach, samples containing as little as 4% trisomy 21 DNA could be readily distinguished from euploid samples.

公开(公告)号：EP2417270A4

公开(公告)日：2012-09-12

申请号：EP10762298

申请日：2010-04-06

申请人： UNIV JOHNS HOPKINS ,  UNIV CASE WESTERN RESERVE

发明人： VOGELSTEIN BERT ,  KINZLER KENNETH W ,  LI MENG ,  DIAZ LUIS ,  PAPADOPOULOS NICKOLAS ,  MARKOWITZ SANFORD

IPC分类号： C12Q1/68 ,  C12N15/11 ,  G01N33/52

CPC分类号： C12Q1/6816 ,  C12Q1/6886 ,  C12Q2600/154 ,  C12Q2565/501 ,  C12Q2527/125 ,  C12Q2523/125

公开(公告)号：EP1730303A4

公开(公告)日：2009-09-09

申请号：EP05723277

申请日：2005-02-18

申请人： UNIV JOHNS HOPKINS

发明人： SAMUELS YARDENA ,  VELCULESCU VICTOR ,  KINZLER KENNETH W ,  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.