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11. 发明专利

CA2665343C WATER-DISPERSIBLE ORAL, PARENTERAL, AND TOPICAL FORMULATIONS FOR POORLY WATER SOLUBLE DRUGS USING SMART POLYMERIC NANOPARTICLES 未知
公开(公告)号：CA2665343C
公开(公告)日：2014-12-16
申请号：CA2665343
申请日：2007-10-05
申请人： UNIV JOHNS HOPKINS
发明人： MAITRA ANIRBAN , FELDMANN GEORG , BISHT SAVITA
IPC分类号： A61K9/14 , A61K9/107 , A61K31/7068 , A61K47/30 , A61K47/48 , A61K49/00 , A61K51/08
摘要： Polymeric nanoparticles with a hydrophobic core and a hydrophilic shell are formed from: 1) N-isopropyl acrylamide (NIPAAM), at a molar ratio of about 50% to about 90%, and preferably 60% for specific delivery routes such as oral or parenteral; either water-soluble vinyl derivatives like vinylpyrolidone (VP) or vinyl acetate (VA), or water insoluble vinyl derivatives like methyl methacrylate (MMA) or styrene (ST), at a molar ratio of about 10% to about 30%;, and acrylic acid (AA), at a molar ratio of about 10% to about 30%. The formed nanoparticles may be optionally surface functional using reactive groups present in AA, including PEGylation, or conjugation of moieties such as chemotherapeutics, contrasting agents, antibodies, radionucleides, ligands, and sugars, for diagnostic, therapeutic, and imaging purposes. The polymeric nanoparticles are preferably dispersed in aqueous solutions. The polymeric nanoparticles incorporate one or more types of medicines or bioactive agents in the hydrophobic core; on occasion, the medicine or bioactive agent may be conjugated to the nanoparticle surface via reactive functional groups. The polymeric nanoparticles are capable of delivering the said medicines or bioactive agents through oral, parenteral, or topical routes. The polymeric nanoparticles allow poorly water soluble medicines or bioactive agents, or those with poor oral bioavailability, to be formulated in an aqueous solution, and enable their convenient delivery into the systemic circulation.

12. 发明专利

CA2644136A1 CANCER TREATMENT WITH GAMMA-SECRETASE INHIBITORS 未知
公开(公告)号：CA2644136A1
公开(公告)日：2007-09-07
申请号：CA2644136
申请日：2007-02-27
申请人： UNIV JOHNS HOPKINS
发明人： EBERHART CHARLES , MAITRA ANIRBAN , FAN XING
IPC分类号： A61K31/38
摘要： Provided are methods for treating cancer in a patient, comprising administering to a patient in need thereof a therapeutically effective regimen, the regimen comprising administering a gamma-secretase inhibitor, wherein the regimen results in a reduction in the cancer cell population in the patient. In some embodiments of the methods, the therapeutically effective regimen stabilizes, reduces or eliminates the cancer stem cell population. Also provided are compounds of the formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , and X are as herein described.

13. 发明专利

AU2012339835B2 Differential identification of pancreatic cysts 未知
公开(公告)号：AU2012339835B2
公开(公告)日：2016-01-28
申请号：AU2012339835
申请日：2012-11-12
申请人： UNIV JOHNS HOPKINS
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , PAPADOPOULOS NICKOLAS , WU JIAN , HRUBAN RALPH , MAITRA ANIRBAN , DAL MOLIN MARCO
IPC分类号： C12Q1/68 , C12N15/11
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 (ß-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.

14. 发明专利

CA2665343A1 WATER-DISPERSIBLE ORAL, PARENTERAL, AND TOPICAL FORMULATIONSFOR POORLY WATER SOLUBLE DRUGS USING SMART POLYMERIC NANOPARTICLES 未知
公开(公告)号：CA2665343A1
公开(公告)日：2008-06-19
申请号：CA2665343
申请日：2007-10-05
申请人： UNIV JOHNS HOPKINS
发明人： FELDMANN GEORG , BISHT SAVITA , MAITRA ANIRBAN
IPC分类号： A61K47/30
摘要： Polymeric nanoparticles with a hydrophobic core and a hydrophilic shell a re formed from: 1) N-isopropyl acrylamide (NIPAAM), at a molar ratio of abou t 50% to about 90%, and preferably 60% for specific delivery routes such as oral or parenteral; either water-soluble vinyl derivatives like vinylpyrolid one (VP) or vinyl acetate (VA), or water insoluble vinyl derivatives like me thyl methacrylate (MMA) or styrene (ST), at a molar ratio of about 10% to ab out 30%;, and acrylic acid (AA), at a molar ratio of about 10% to about 30%. The formed nanoparticles may be optionally surface functional using reactiv e groups present in AA, including PEGylation, or conjugation of moieties suc h as chemotherapeutics, contrasting agents, antibodies, radionucleides, liga nds, and sugars, for diagnostic, therapeutic, and imaging purposes. The poly meric nanoparticles are preferably dispersed in aqueous solutions. The polym eric nanoparticles incorporate one or more types of medicines or bioactive a gents in the hydrophobic core; on occasion, the medicine or bioactive agent may be conjugated to the nanoparticle surface via reactive functional groups . The polymeric nanoparticles are capable of delivering the said medicines o r bioactive agents through oral, parenteral, or topical routes. The polymeri c nanoparticles allow poorly water soluble medicines or bioactive agents, or those with poor oral bioavailability, to be formulated in an aqueous soluti on, and enable their convenient delivery into the systemic circulation.

15. 发明申请

WO2011014872A3 COMPOSITIONS AND METHODS FOR DIAGNOSING, TREATING OR PREVENTING NEOPLASIAS 审中-公开
标题翻译：用于诊断，治疗或预防NEOPLASIAS的组合物和方法
公开(公告)号：WO2011014872A3
公开(公告)日：2011-05-26
申请号：PCT/US2010044118
申请日：2010-08-02
申请人： UNIV JOHNS HOPKINS , MAITRA ANIRBAN , ALVAREZ HECTOR
发明人： MAITRA ANIRBAN , ALVAREZ HECTOR
IPC分类号： A61K39/395 , A61K31/7105 , A61K38/16 , A61P35/00
CPC分类号： A61K45/06 , A61K31/7105 , A61K39/395 , C12Q1/6886 , C12Q2600/158 , A61K2300/00
摘要： As described below, the present invention features compositions and methods for diagnosing, treating and preventing neoplasias.
摘要翻译：如下所述，本发明的特征在于用于诊断，治疗和预防肿瘤的组合物和方法。

16. 发明申请

WO2005013800A2 ELEVATED HEDGEHOG PATHWAY ACTIVITY IN DIGESTIVE SYSTEM TUMORS, AND METHODS OF TREATING DIGESTIVE SYSTEM TUMORS HAVING ELEVATED HEDGEHOG PATHWAY ACTIVITY 审中-公开
标题翻译：消化系统肿瘤中的高位通路障碍通路活性以及治疗具有高度障碍性通路活性的消化系统肿瘤的方法
公开(公告)号：WO2005013800A2
公开(公告)日：2005-02-17
申请号：PCT/US2004022698
申请日：2004-07-15
申请人： UNIV JOHNS HOPKINS , BEACHY PHILIP A , BERMAN DAVID MONTY , KARHADKAR SUNIL S , MAITRA ANIRBAN
发明人： BEACHY PHILIP A , BERMAN DAVID MONTY , KARHADKAR SUNIL S , MAITRA ANIRBAN
IPC分类号： A61B20060101 , A61K38/00 , C07K16/18 , A61B
CPC分类号： C07K16/18 , A61K31/4355 , C07K2317/73 , C07K2317/76 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158 , G01N33/57419 , G01N33/57446 , G01N2500/04
摘要： Elevated Hedgehog (Hh) pathway activity, including ligand stimulated Hh pathway activity, was detected in digestive tract cancers, including esophagus, stomach, biliary tract, and pancreatic cancer, and determined to be associated with growth and proliferation of the cancer cells. Accordingly, methods are provided for treating a digestive tract cancer associated with elevated Hh pathway activity by reducing or inhibiting the Hh pathway activity. Also provided are methods of determining the responsiveness of a digestive tract tumor to treatment with an Hh pathway antagonist.
摘要翻译：在包括食道，胃，胆道和胰腺癌的消化道癌症中检测到升高的Hedgehog（Hh）途径活性，包括配体刺激的Hh途径活性，并确定其与癌细胞的生长和增殖相关。因此，提供了通过降低或抑制Hh途径活性来治疗与升高的Hh途径活性相关的消化道癌症的方法。还提供了确定消化道肿瘤对用Hh途径拮抗剂治疗的响应性的方法。

17. 发明申请

WO2012078831A3 SMART POLYMERIC NANOPARTICLES WHICH OVERCOME MULTIDRUG RESISTANCE TO CANCER CHEMOTHERAPEUTICS AND TREATMENT-RELATED SYSTEMIC TOXICITY 审中-公开
标题翻译：智能聚合纳米粒子，其具有耐多药结核病和治疗相关系统毒性
公开(公告)号：WO2012078831A3
公开(公告)日：2012-11-15
申请号：PCT/US2011063870
申请日：2011-12-08
申请人： UNIV JOHNS HOPKINS , MAITRA ANIRBAN , PRAMANIK DIPANKAR
发明人： MAITRA ANIRBAN , PRAMANIK DIPANKAR
IPC分类号： A61K47/48 , A61K9/127 , A61K31/704 , A61K31/7042 , A61P35/00 , C08F20/06 , C08F20/56
CPC分类号： A61K31/12 , A61K9/0019 , A61K9/5138 , A61K31/704 , A61K31/7042 , A61K45/06 , C08F220/06 , C08F220/56 , C08F226/10 , A61K2300/00
摘要： Polymeric nanoparticles with a hydrophobic core that encapsulates curcumin and a hydrophilic shell with one or more chemotherapeutic agents (e.g., doxorubicin) associated with the shell surface are formed from N-isopropylacryl amide (NEPAAM), acrylic acid (AA), and at least one vinyl monomer selected from the group consisting of vinyl acetate, 4-vinyl benzoic acid, methylmethacrylate, vinylmethacrylate, N-vinylpyrrolidone, N-vinyl piperidone, N-vinyl caprolacum, N-vinyl carbazole, and styrene, where the ?G????, the AA, and the vinyl monomer are present at molar ratios of 50-70:10-30: 10-30 for NIPAAM:AA:vmyl monomer. These nanoparticles effectively overcome multidrug resistance and ameliorate cardiomyopathy in vivo.
摘要翻译：具有与外壳表面相关的一种或多种化学治疗剂（例如，多柔比星）封装姜黄素和亲水壳的疏水性核心的聚合物纳米颗粒由N-异丙基丙烯酰胺（NEPAAM），丙烯酸（AA）和至少一种乙烯基单体，选自乙酸乙烯酯，4-乙烯基苯甲酸，甲基丙烯酸甲酯，甲基丙烯酸乙烯酯，N-乙烯基吡咯烷酮，N-乙烯基哌啶酮，N-乙烯基caprolacum，N-乙烯基咔唑和苯乙烯，其中γG 对于NIPAAM：AA：vmyl单体，α，乙烯基单体的摩尔比为50-70:10-30:10-30。这些纳米粒子有效地克服了多药耐药，改善了体内心肌病。

18. 发明申请

WO2007100895A3 CANCER TREATMENT WITH GAMMA-SECRETASE INHIBITORS 审中-公开
标题翻译：癌症治疗用药物抑制剂
公开(公告)号：WO2007100895A3
公开(公告)日：2008-07-17
申请号：PCT/US2007005362
申请日：2007-02-27
申请人： UNIV JOHNS HOPKINS , EBERHART CHARLES , FAN XING , MAITRA ANIRBAN
发明人： EBERHART CHARLES , FAN XING , MAITRA ANIRBAN
IPC分类号： A61K31/38
CPC分类号： C07D333/34 , A61K31/38 , A61K31/381 , A61K31/5513 , A61K45/06 , A61N5/10 , C07D409/12
摘要： Provided are methods for treating cancer in a patient, comprising administering to a patient in need thereof a therapeutically effective regimen, the regimen comprising administering a gamma-secretase inhibitor, wherein the regimen results in a reduction in the cancer cell population in the patient In some embodiments of the methods, the therapeutically effective regimen stabilizes, reduces or eliminates the cancer stem cell population.
摘要翻译：本发明提供了一种治疗患者癌症的方法，其包括向有需要的患者施用治疗有效的方案，该方案包括施用γ-分泌酶抑制剂，其中该方案导致患者中癌细胞群的减少在一些方法的实施方案，治疗有效的方案稳定，减少或消除癌症干细胞群体。

19. 发明申请

WO2005020795A3 METHOD OF DIAGNOSIS AND TREATMENT OF PANCREATIC ENDOCRINE NEOPLASMS BASED ON DIFFERNTIAL GENE EXPRESSION ANALYSIS 审中-公开
标题翻译：基于差异基因表达分析诊断和治疗胰腺内皮细胞的方法
公开(公告)号：WO2005020795A3
公开(公告)日：2006-04-27
申请号：PCT/US2004027665
申请日：2004-08-25
申请人： UNIV JOHNS HOPKINS , MAITRA ANIRBAN , YEO CHARLES J , HANSEL DONNA E
发明人： MAITRA ANIRBAN , YEO CHARLES J , HANSEL DONNA E
IPC分类号： C12Q1/68 , A61B20060101 , A61K49/00 , C07H21/04 , C12M1/34 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/136
摘要： Methods for diagnosing pancreatic endocrine neoplasms are provided. Methods include obtaining a nucleic acid sample from the subject contacting nucleic acids of the sample with an array comprising a plurality of DNAs under conditions to form one or more hybridization complexes; detecting the hybridization complexes; and comparing the levels of the hybridization complexes detected with the level of hybridization complexes detected in a non-diseased sample, wherein an altered level of hybridization complexes detected compared with the level of hybridization complexes of a nondiseased sample correlates with the presence of PEN in the subject. Nearly 200 differentially expressed genes identified in well -differentiated PENs versus enriched normal islet cells are provided, and a subset of these genes was validated at the protein level using PEN tissue microarrays.
摘要翻译：提供诊断胰腺内分泌肿瘤的方法。方法包括在条件下从包含多个DNA的阵列获得来自所述受试者的核酸样品与所述样品的核酸接触以形成一种或多种杂交复合物; 检测杂交复合物; 将检测到的杂交复合物的水平与在非病变样品中检测到的杂交复合物的水平进行比较，其中检测到的杂交复合物的水平与未分离样品的杂交复合物的水平相比变化与PEN的存在相关学科。提供了在富分化的PEN中鉴定的近200个差异表达的基因与富集的正常胰岛细胞，并且使用PEN组织微阵列在蛋白质水平上验证了这些基因的一个子集。

20. 发明专利

AU2012339835A1 Differential identification of pancreatic cysts 未知
公开(公告)号：AU2012339835A1
公开(公告)日：2014-06-12
申请号：AU2012339835
申请日：2012-11-12
申请人： UNIV JOHNS HOPKINS
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , PAPADOPOULOS NICKOLAS , WU JIAN , HRUBAN RALPH , MAITRA ANIRBAN , DAL MOLIN MARCO
IPC分类号： C12Q1/68 , C12N15/11
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 (ß-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.

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