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1. 发明授权

US08650017B2 System and method of evaluation of stochastic interactions of a soluble ligand with a target cell population for optimization of drug design and delivery 失效
标题翻译：评估可溶性配体与靶细胞群体的随机相互作用的系统和方法，以优化药物设计和递送
公开(公告)号：US08650017B2
公开(公告)日：2014-02-11
申请号：US11449648
申请日：2006-06-09
申请人： Oleg U. Kirnasovsky , Vladimir Vainstein , Yuri Kogan , Zvia Agur
发明人： Oleg U. Kirnasovsky , Vladimir Vainstein , Yuri Kogan , Zvia Agur
IPC分类号： G06G7/48 , G06G7/58 , G01N33/48 , G01N31/00
CPC分类号： G06F19/3456 , G01N33/5011 , G06F19/00 , G06F19/12 , G06F19/704 , G16H50/50
摘要： A computer system for recommending an optimal treatment protocol comprising a model of biological processes related to a disease. A treatment protocol generator generates a plurality of treatment protocols for treating a disease using drugs. A selector selects an optimal treatment protocol from the plurality of treatment protocols based on model. The model further comprises a pharmacokinetics macro module adapted to analyze interactions between a ligand and a population of target cells at a tissue level. The model further comprises a pharmacokinetics micro module adapted to analyze interactions between the ligand and a cell at an individual cell level. The pharmacokinetics micro module is adapted to model behavior of the ligand and receptors related to single cell level of ligand-cell interactions, as a stochastic process.
摘要翻译：一种用于推荐包括与疾病相关的生物过程模型的最佳治疗方案的计算机系统。治疗方案生成器产生用于使用药物治疗疾病的多种治疗方案。选择器基于模型从多个处理协议中选择最佳处理协议。该模型还包括适于分析组织水平的配体和靶细胞群体之间的相互作用的药代动力学宏模块。该模型还包括适于分析在单个细胞水平的配体和细胞之间的相互作用的药代动力学微模块。药代动力学微模块适用于模拟与配体 - 细胞相互作用的单细胞水平相关的配体和受体的行为，作为随机过程。

2. 发明申请

US20070054331A1 System and method of evaluation of stochastic interactions of a soluble ligand with a target cell population for optimization of drug design and delivery 失效
标题翻译：评估可溶性配体与靶细胞群体的随机相互作用的系统和方法，以优化药物设计和递送
公开(公告)号：US20070054331A1
公开(公告)日：2007-03-08
申请号：US11449648
申请日：2006-06-09
申请人： Oleg Kirnasovsky , Vladimir Vainstein , Yuri Kogan , Zvia Agur
发明人： Oleg Kirnasovsky , Vladimir Vainstein , Yuri Kogan , Zvia Agur
IPC分类号： G01N33/574 , G06F19/00
CPC分类号： G06F19/3456 , G01N33/5011 , G06F19/00 , G06F19/12 , G06F19/704 , G16H50/50
摘要： A computer system for recommending an optimal treatment protocol comprising a model of biological processes related to a disease. A treatment protocol generator generates a plurality of treatment protocols for treating a disease using drugs. A selector selects an optimal treatment protocol from said plurality of treatment protocols based on model. The model further comprises a pharmacokinetics macro module adapted to analyze interactions between a ligand and a population of target cells at a tissue level. The model further comprises a pharmacokinetics micro module adapted to analyze interactions between the ligand and a cell at an individual cell level. The pharmacokinetics micro module is adapted to model behavior of the ligand and receptors related to single cell level of ligand-cell interactions, as a stochastic process.
摘要翻译：一种用于推荐包括与疾病相关的生物过程模型的最佳治疗方案的计算机系统。治疗方案生成器产生用于使用药物治疗疾病的多种治疗方案。选择器基于模型从所述多个治疗方案中选择最佳治疗方案。该模型还包括适于分析组织水平的配体和靶细胞群体之间的相互作用的药代动力学宏模块。该模型还包括适于分析在单个细胞水平的配体和细胞之间的相互作用的药代动力学微模块。药代动力学微模块适用于模拟与配体 - 细胞相互作用的单细胞水平相关的配体和受体的行为，作为随机过程。

3. 发明申请

US20110286960A1 CANCER THERAPY BY DOCETAXEL AND GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF) 审中-公开
标题翻译： DOCETAXEL和GRANULOCYTE COLONY-STIMULATING FACTOR（G-CSF）治疗癌症
公开(公告)号：US20110286960A1
公开(公告)日：2011-11-24
申请号：US13126929
申请日：2009-11-02
申请人： Oded Vainas , Vladimir Vainstein , Ori Inbar , Marina Kleiman , Radel Ben-av , Zvia Agur
发明人： Oded Vainas , Vladimir Vainstein , Ori Inbar , Marina Kleiman , Radel Ben-av , Zvia Agur
IPC分类号： A61K38/19 , A61P37/00 , G06G7/60 , A61P35/00
CPC分类号： A61K45/06 , A61K38/193 , G16C20/30 , A61K2300/00
摘要： Neutropenia is the dose-limiting toxicity of the tri-weekly docetaxel (Taxotere®) schedule. Here, we evaluate in Metastatic Breast Cancer (MBC) patients (N=38) a computerized method for predicting docetaxel-induced neutropenia, and use the model to identify improved docetaxel and Granulocyte Colony Stimulating Factor (G-CSF) regimens. Pharmacokinetics/pharmacodynamics (PK/PD) models were created and simulated concomitantly with a mathematical granulopoiesis model. Individual baseline neutrophil counts and docetaxel schedules served as inputs. Our trial validated the model accuracy in predicting nadir timings (r=0.99), grade 3/4 neutropenia (86% success) and neutrophil profiles (r=0.62). Model was robust to CYP3A-induced variability, except for slightly less accurate grade 3/4 neutropenia predictions. Simulations confirm smaller toxicity of the weekly docetaxel regimen than the tri-weekly one, and suggest an optimal G-CSF support for alleviating neutropenia, 60 μg/day QD×3, 6-7 days post-docetaxel, administered tri- and bi-weekly, and 4 days post weekly docetaxel>33 mg/m2.
摘要翻译：中性粒细胞减少是三周多西他赛（Taxotere®）计划的剂量限制性毒性。在这里，我们评估转移性乳腺癌（MBC）患者（N = 38）一种预测多西紫杉醇诱导的中性粒细胞减少的计算机化方法，并使用该模型来鉴定改良的多西他赛和粒细胞集落刺激因子（G-CSF）方案。药物动力学/药效学（PK / PD）模型被创建并模拟与数学粒子学模型。单个基线嗜中性粒细胞计数和多西他赛计划作为输入。我们的试验验证了模型准确性预测最低点时间（r = 0.99），3/4级中性粒细胞减少（86％成功）和嗜中性粒细胞分布（r = 0.62）。模型对CYP3A诱导的变异性是稳健的，除了稍微不太准确的3/4级中性粒细胞减少预测。模拟证实每周多西紫杉醇方案的毒性小于三周一次，并建议最佳的G-CSF支持减轻中性粒细胞减少，60μg/天QD×3,6-天后多西紫杉醇，给予三 - 和二 - 每周，每周多西紫杉醇> 33 mg / m2。

4. 发明授权

US07418374B2 Treatment protocol generation for diseases related to angiogenesis 失效
标题翻译：与血管生成相关的疾病的治疗方案生成
公开(公告)号：US07418374B2
公开(公告)日：2008-08-26
申请号：US10207772
申请日：2002-07-31
申请人： Zvia Agur , Levon Arakelyan , Vladimir Vainstein
发明人： Zvia Agur , Levon Arakelyan , Vladimir Vainstein
IPC分类号： G06N3/00
CPC分类号： G01N33/74 , G01F1/3218 , G01F1/3263 , G01F1/3272 , G01F1/86 , G01N2333/515
摘要： A computer-implemented method for determining an optimal treatment protocol for a disease related to angiogenesis, comprising creating an angiogenesis model including pro-angiogenic and anti-angiogenic factors. Effective vessel density (EVD) is incorporated as a factor regulating switching on and switching off of at least one component in the angiogenesis model. Effects of vasculature maturation and mature vessel destabilization are incorporated. Pro-angiogenic and anti-angiogenic factors, which can influence changes in state of a tissue, are selected. Effects of drugs in the pro-angiogenic and anti-angiogenic factors are incorporated. A plurality of treatment protocols in a protocol space is generated. A best treatment protocol based on a pre-determined criteria is selected.
摘要翻译：一种用于确定与血管发生相关的疾病的最佳治疗方案的计算机实现的方法，包括产生包括促血管生成和抗血管生成因子的血管生成模型。有效血管密度（EVD）作为调节血管生成模型中至少一种成分的开启和关闭的因子而被引入。纳入血管成熟和成熟血管不稳定的作用。选择可影响组织状态变化的促血管生成因子和抗血管生成因子。药物在促血管生成因子和抗血管生成因子中的作用被并入。生成协议空间中的多个处理协议。选择基于预定标准的最佳治疗方案。

5. 发明申请

US20080275684A1 TREATMENT PROTOCOL GENERATION FOR DISEASES RELATED TO ANGIOGENESIS 审中-公开
标题翻译：治疗方案产生与血液生成相关的疾病
公开(公告)号：US20080275684A1
公开(公告)日：2008-11-06
申请号：US12132300
申请日：2008-06-03
申请人： Zvia Agur , Levon Arakelyan , Vladimir Vainstein
发明人： Zvia Agur , Levon Arakelyan , Vladimir Vainstein
IPC分类号： G06G7/58
CPC分类号： G01N33/74 , G01F1/3218 , G01F1/3263 , G01F1/3272 , G01F1/86 , G01N2333/515
摘要： A computer-implemented method for determining an optimal treatment protocol for a disease related to angiogenesis, comprising creating an angiogenesis model including pro-angiogenesis and anti-angiogenesis factors. Effective vessel density (EVD) is incorporated as a factor regulating switching on and switching off of at least one component in the angiogenesis model. Effects of vasculature maturation and mature vessels destabilization are incorporated. Pro-angiogenesis and anti-angiogenesis factors, which can influence changes in state of a tissue are selected. Effects of drugs in the pro-angiogenesis and anti-angiogenesis factors are incorporated. A plurality of treatment protocols in a protocol space is generated. A best treatment protocol based on a pre-determined criteria.
摘要翻译：一种用于确定与血管发生相关的疾病的最佳治疗方案的计算机实现的方法，包括产生包括促血管生成和抗血管生成因子的血管生成模型。有效血管密度（EVD）作为调节血管生成模型中至少一种成分的开启和关闭的因子而被纳入。引入脉管系统成熟和成熟血管不稳定的作用。选择可影响组织状态变化的促血管发生和抗血管生成因子。药物在促血管生成和抗血管生成因子中的作用被纳入。生成协议空间中的多个处理协议。基于预先确定的标准的最佳治疗方案。

6. 发明申请

US20050148521A1 Anti-cancer combination and use thereof 审中-公开
标题翻译：抗癌组合及其用途
公开(公告)号：US20050148521A1
公开(公告)日：2005-07-07
申请号：US10898721
申请日：2004-07-23
申请人： Shmuel Ben-Sasson , Lilia Tsirulnikov , Vladimir Vainstein
发明人： Shmuel Ben-Sasson , Lilia Tsirulnikov , Vladimir Vainstein
IPC分类号： A61K31/12 , A61K31/122 , A61K31/195 , A61K31/196 , A61K31/337 , A61K31/405 , A61K31/4745 , A61K31/522 , A61K31/525 , A61K31/573 , A61K31/65 , A61K31/663 , A61K31/675 , A61K31/704 , A61K45/06 , A61P3/06 , A61P9/00 , A61P35/00 , A61P43/00
CPC分类号： A61K45/06
摘要： The present invention relates to the surprising discovery that the combination of several agents, each well known for its established role in treating cancer, inflammation, hemostasis, bone resorption or serving as a solubilizing vehicle, results in a synergistic anti-cancer composition. Furthermore, the combination of at least three agents allows the cytotoxic agent, such as cyclophosphamide, to be used at a lower dosage than when administered alone. One predicted consequence of this treatment, therefore, is a highly desirable reduction in toxic side effects due to the cytotoxic agent.
摘要翻译：本发明涉及令人惊奇的发现，即由治疗癌症，炎症，止血，骨吸收或用作增溶载体的众所周知的几种药剂的组合导致协同抗癌组合物。此外，至少三种试剂的组合允许细胞毒剂如环磷酰胺以比单独施用时更低的剂量使用。因此，这种治疗的一个预测结果是由于细胞毒性剂而引起的毒性副作用的非常理想的降低。

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