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11. 发明申请

US20190256920A1 Differential Identification of Pancreatic Cysts 审中-公开
公开(公告)号：US20190256920A1
公开(公告)日：2019-08-22
申请号：US15583141
申请日：2017-05-01
申请人： The Johns Hopkins University
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Jian Wu , Ralph Hruban , Anirban Maitra , Marco Dal Molin
IPC分类号： C12Q1/6886 , C12Q1/6883
摘要： More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations, but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.

12. 发明授权

US10350282B2 Mesothelin vaccines and model systems 有权
公开(公告)号：US10350282B2
公开(公告)日：2019-07-16
申请号：US15333518
申请日：2016-10-25
申请人： The Johns Hopkins University
发明人： Elizabeth A. Jaffee , Tzyy-Choou Wu , Chien-Fu Hung , Ralph Hruban
IPC分类号： A61K39/02 , A61K39/00 , C07K16/30 , C12N15/85 , C07K7/06 , C12N15/74 , C07K14/47
摘要： Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

13. 发明申请

US20160032406A1 Diagnostic Method Using PALB2/US 审中-公开
标题翻译：诊断方法使用PALB2 / US
公开(公告)号：US20160032406A1
公开(公告)日：2016-02-04
申请号：US14820844
申请日：2015-08-07
申请人： The Johns Hopkins University
发明人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Sian Jones , Scott Kern , Ralph Hruban , James R. Eshleman , Michael Goggins , Alison Klein , Manuel Hidalgo , Victor Velculescu
IPC分类号： C12Q1/68 , G01N33/574 , A61K31/407
CPC分类号： C12Q1/6886 , A61K31/407 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , G01N33/57438 , G01N2333/47
摘要： 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.
摘要翻译：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。

14. 发明授权

US11667976B2 TERT promoter mutations in urothelial neoplasia 有权
公开(公告)号：US11667976B2
公开(公告)日：2023-06-06
申请号：US17097510
申请日：2020-11-13
申请人： The Johns Hopkins University
发明人： Bert Vogelstein , Kenneth W. Kinzler , Luis Diaz , Nickolas Papadopoulos , George J. Netto , Ralph Hruban , Isaac A. Kinde
IPC分类号： C12Q1/6886
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： TERT promoter mutations occur in both papillary and flat lesion bladder cancers, are the most frequent genetic alterations identified to date in noninvasive precursor lesions of the bladder, are detectable in urine, and appear to be strongly associated with bladder cancer recurrence. The TERT promoter mutations are useful urinary biomarker for both the early detection and monitoring of bladder neoplasia.

15. 发明授权

US09637796B2 Differential identification of pancreatic cysts 有权
公开(公告)号：US09637796B2
公开(公告)日：2017-05-02
申请号：US14359149
申请日：2012-11-12
申请人： THE JOHNS HOPKINS UNIVERSITY
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Jian Wu , Ralph Hruban , Anirban Maitra , Marco Dal Molin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6883 , C12Q2600/156
摘要： More than 2% of adults harbor a pancreatic cyst, a subset of which progress to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs) and solid pseudo-papillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10=4.6, 27=12, 16=7.6, and 2.9=2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of VHL, a key component of the VHL ubiquitin ligase complex that has previously been associated both with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations, but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.

16. 发明申请

US20160199473A1 Mesothelin Vaccines and Model Systems 审中-公开
公开(公告)号：US20160199473A1
公开(公告)日：2016-07-14
申请号：US15069047
申请日：2016-03-14
申请人： The Johns Hopkins University
发明人： Elizabeth A. Jaffee , Ralph Hruban
IPC分类号： A61K39/00
CPC分类号： A61K39/0208 , A01K2267/0331 , A61K39/0011 , A61K2039/505 , A61K2039/5154 , A61K2039/52 , A61K2039/522 , A61K2039/523 , A61K2039/53 , A61K2039/55511 , A61K2039/55522 , A61K2039/57 , A61K2039/6031 , C07K7/06 , C07K14/4748 , C07K16/30 , C12N15/74 , C12N15/8509 , C12N2710/16522 , C12N2740/13043 , Y02A50/484
摘要： Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.

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