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1. 发明申请

WO2011066583A1 AMYLOID BETA AGGREGATES IN CEREBRO SPINAL FLUID AS BIOMARKERS FOR ALZHEIMER'S DISEASE 审中-公开
标题翻译：作为ALZHEIMER病的生物标志物的CEREBRO脊柱液中的AMYLOID BETA聚集
公开(公告)号：WO2011066583A1
公开(公告)日：2011-06-03
申请号：PCT/US2010/058450
申请日：2010-11-30
申请人： NOVARTIS AG , PERETZ, David , ALLAUZEN, Sophie , WANG, Xuemei , GAO, Man (carol) , YAM, Alice , FEDYNYSHYN, Joseph
发明人： PERETZ, David , ALLAUZEN, Sophie , WANG, Xuemei , GAO, Man (carol) , YAM, Alice , FEDYNYSHYN, Joseph
IPC分类号： G01N33/68 , C07K7/00
CPC分类号： G01N33/543 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： The invention provides methods for assessing increased probability of having Alzheimer's disease in a subject under assessment including a step of obtaining a measurement of Aβ40 aggregates in a biological sample from the subject, where the biological sample does not include brain tissue, a fraction of brain tissue, or brain homogenate. In some embodiments, the invention relates to methods of assessing increased probability of early stage Alzheimer's disease. The invention further provides methods of assessing increased probability of not having Alzheimer's disease, methods of monitoring disease progression in a subject with Alzheimer's disease, and methods of assigning disease stage for a subject with Alzheimer's disease, and methods of assessing increased probability of MCI progressing to Alzheimer's disease.
摘要翻译：本发明提供用于评估在评估受试者中具有阿尔茨海默氏病的可能性增加的方法，包括获得来自受试者的生物样品中Aß40聚集体的测量的步骤，其中生物样品不包括脑组织，脑组织的一部分，或脑匀浆。在一些实施方案中，本发明涉及评估早期阿尔茨海默氏病的概率增加的方法。本发明还提供了评估增加阿尔茨海默氏病的可能性的方法，用阿尔茨海默病监测受试者的疾病进展的方法，以及为阿尔茨海默氏病患者分配疾病阶段的方法，以及评估增加的MCI进展概率的方法阿尔茨海默氏病。

2. 发明申请

WO2009134942A1 ASSAY FOR PATHOGENIC CONFORMERS 审中-公开
标题翻译：病原性制剂的测定
公开(公告)号：WO2009134942A1
公开(公告)日：2009-11-05
申请号：PCT/US2009/042185
申请日：2009-04-29
申请人： NOVARTIS AG. , PERETZ, David , WANG, Xuemei , GAO, Man (Carol) , YAM, Alice , LAU, Anthony , WU, Ping
发明人： PERETZ, David , WANG, Xuemei , GAO, Man (Carol) , YAM, Alice , LAU, Anthony , WU, Ping
IPC分类号： A61K38/00 , G01N33/53
CPC分类号： G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： The invention provides methods for detecting the presence of a non-prion pathogenic conformer in a sample by contacting the sample suspected of containing a non-prion pathogenic conformer with a pathogenic conformer- specific binding reagent under conditions that allow the binding of the reagent to the pathogenic conformer, if present; and detecting the presence the pathogenic conformer, if any, in the sample by its binding to the reagent; where the pathogenic conformer- specific binding reagent is typically derived from a prion protein fragment and interacts preferentially with a pathogenic prion protein. Methods for diagnosis of conformational diseases are also provided.
摘要翻译：本发明提供了通过在怀疑含有非朊病毒致病性构象异构体的样品与致病性构象异构体特异性结合试剂的接触的条件下，将样品中的非朊病毒致病性构象异构体存在的方法，致病性构象异构体，如果存在; 并通过其与试剂的结合来检测样品中致病性构象异构体（如果有的话）的存在; 其中致病性构象异构体特异性结合试剂通常衍生自朊病毒蛋白片段并优先与致病性朊病毒蛋白相互作用。还提供了构象疾病诊断方法。

3. 发明申请

WO2011057029A1 POSITIVELY CHARGED SPECIES AS BINDING REAGENTS IN THE SEPARATION OF PROTEIN AGGREGATES FROM MONOMERS 审中-公开
标题翻译：作为联合试剂在单体分离蛋白质聚集体中的积极物种
公开(公告)号：WO2011057029A1
公开(公告)日：2011-05-12
申请号：PCT/US2010/055528
申请日：2010-11-04
申请人： NOVARTIS AG , SALISBURY, Cleo , PERETZ, David , YAM, Alice , WANG, Xuemei , GAO, Man, (carol)
发明人： SALISBURY, Cleo , PERETZ, David , YAM, Alice , WANG, Xuemei , GAO, Man, (carol)
IPC分类号： G01N33/68 , C07K7/00
CPC分类号： G01N33/6896 , A61K38/00 , C07K7/06 , C07K7/08 , G01N33/531 , G01N2800/2821 , G01N2800/50 , G01N2800/52 , G01N2800/56
摘要： The invention provides methods for detecting the presence of an aggregate in a sample by contacting the sample suspected of containing an aggregate with an aggregate-specific binding reagent under conditions that allow the binding of the reagent to the aggregate, if present; and detecting the presence of the aggregate, if any, in the sample by its binding to the reagent; where the aggregate-specific binding reagent typically has a net charge of at least about positive one at the pH at which the sample is contacted with the ASB reagent, is attached to a solid support at a charge density of at least about 60 nmol net charge per square meter, and binds preferentially with aggregates over monomers when attached to the solid support. Methods for detecting the presence of oligomer are also provided. Compositions for use in the methods arc provided.
摘要翻译：本发明提供了在允许试剂与聚集体结合的条件下（如果有的话），将怀疑含有骨料的样品与聚集体特异性结合试剂接触的方式来检测样品中骨料的存在; 并通过与样品的结合来检测样品中聚集体（如果有的话）的存在; 其中聚集体特异性结合试剂通常在样品与ASB试剂接触的pH下通常具有至少约为1的净电荷，以至少约60nmol净电荷的电荷密度附着于固体支持物当连接到固体支持物上时，优先与聚集体相对于单体结合。还提供了检测低聚物存在的方法。提供了用于方法的组合。

4. 发明申请

WO2008124098A1 PRION ASSAY 审中-公开
标题翻译： PRION测试
公开(公告)号：WO2008124098A1
公开(公告)日：2008-10-16
申请号：PCT/US2008/004454
申请日：2008-04-03
申请人： NOVARTIS AG , PERETZ, David , YAM, Alice
发明人： PERETZ, David , YAM, Alice
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2800/2828
摘要： The invention relates to an assay method for detecting the presence of PrP Sc using at least one sequence-specific protease for a substantially complete digestion of the proteins in a sample, leaving the octarepeat region in both PrP Sc and PrP C intact, leaving the protease-resistant core of PrP Sc intact and remain connected to the octarepeat region, while digesting away at least part of the amino acid sequences in PrP C corresponding to the protease-resistant core in PrP Sc . The method further comprises a step of inhibiting further digestion by the protease, a step of denaruration, and a step of detecting the presence of PrP Sc using at least two binding partners, a first binding partner and a second binding partner, wherein the first binding partner specifically binds an epitope in the amino-proximal region, and the second binding partner specifically binds an epitope within a region of the protease-resistant core of PrP Sc that has been cleaved away in PrP C . The invention also relates to a kit comprising reagents that can be used in the assay method.
摘要翻译：本发明涉及使用至少一种用于基本上完全消化样品中的蛋白质的序列特异性蛋白酶来检测PrP 的存在的测定方法，将Octpepeat区域保留在PrP ^{Sc>和PrP 完整，使得PrP Sc蛋白酶抗性核心完整并保持连接到八边形区域，同时消化掉至少部分 PrP 中对应于蛋白酶抗性核心的PrP 中的氨基酸序列。该方法还包括使用至少两个结合配偶体，第一结合配偶体和第二结合配偶体，抑制蛋白酶进一步消化，脱色步骤和检测PrP 的存在的步骤其中所述第一结合配偶体特异性结合所述氨基邻近区域中的表位，并且所述第二结合配偶体特异性结合已经在所述蛋白酶抗性核心的区域中的表位在PrP 中切断。本发明还涉及包含可用于测定方法的试剂的试剂盒。}

5. 发明申请

WO2021216478A1 HUMAN INTERLEUKIN-2 CONJUGATES BIASED FOR THE INTERLEUKIN-2 RECEPTOR BETA GAMMAc DIMER AND CONJUGATED TO A NONPEPTIDIC, WATER-SOLUBLE POLYMER 审中-公开
公开(公告)号：WO2021216478A1
公开(公告)日：2021-10-28
申请号：PCT/US2021/028054
申请日：2021-04-20
申请人： MERCK SHARP & DOHME CORP. , ABRAHAMS, Cristina , BOWMAN, Edward , LI, Xiaofan , LIN, Songnian , SOLIS, Willy , STAFFORD, Ryan , WILLINGHAM, Aarron , YAM, Alice , YANG, Junhao , YIN, Gang
发明人： ABRAHAMS, Cristina , BOWMAN, Edward , LI, Xiaofan , LIN, Songnian , SOLIS, Willy , STAFFORD, Ryan , WILLINGHAM, Aarron , YAM, Alice , YANG, Junhao , YIN, Gang
IPC分类号： C07K14/55 , A61K38/03 , A61K38/20 , A61K47/60
摘要： Interleukin-2 (IL-2) conjugates comprising at least one or more amino acid substitutions that bias binding to the IL-2 receptor βγc dimer over binding the IL-2 receptor αβγc trimer and a non-natural amino acid at or near the N-terminus conjugated to a water-soluble polymer are described. The IL-2 conjugates are useful for treatment and prevention of cell proliferation and cancer in a patient.

6. 发明公开

EP2142934A1 PRION ASSAY 有权
标题翻译： PRIONENTEST
公开(公告)号：EP2142934A1
公开(公告)日：2010-01-13
申请号：EP08754072.0
申请日：2008-04-03
申请人： Novartis AG
发明人： PERETZ, David , YAM, Alice
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2800/2828
摘要： The invention relates to an assay method for detecting the presence of PrPSc using at least one sequence-specific protease for a substantially complete digestion of the proteins in a sample, leaving the octarepeat region in both PrPSc and PrPC intact, leaving the protease-resistant core of PrPSc intact and remain connected to the octarepeat region, while digesting away at least part of the amino acid sequences in PrPC corresponding to the protease-resistant core in PrPSc. The method further comprises a step of inhibiting further digestion by the protease, a step of denaruration, and a step of detecting the presence of PrPSc using at least two binding partners, a first binding partner and a second binding partner, wherein the first binding partner specifically binds an epitope in the amino-proximal region, and the second binding partner specifically binds an epitope within a region of the protease-resistant core of PrPSc that has been cleaved away in PrPC. The invention also relates to a kit comprising reagents that can be used in the assay method.

7. 发明公开

EP2496947A1 POSITIVELY CHARGED SPECIES AS BINDING REAGENTS IN THE SEPARATION OF PROTEIN AGGREGATES FROM MONOMERS 审中-公开
标题翻译：正被装载的货物载波位置作为约束性试剂分离蛋白聚集体和低聚物中
公开(公告)号：EP2496947A1
公开(公告)日：2012-09-12
申请号：EP10785247.7
申请日：2010-11-04
申请人： Novartis AG
发明人： SALISBURY, Cleo , PERETZ, David , YAM, Alice , WANG, Xuemei , GAO, Man, (carol)
IPC分类号： G01N33/68 , C07K7/00
CPC分类号： G01N33/6896 , A61K38/00 , C07K7/06 , C07K7/08 , G01N33/531 , G01N2800/2821 , G01N2800/50 , G01N2800/52 , G01N2800/56
摘要： The invention provides methods for detecting the presence of an aggregate in a sample by contacting the sample suspected of containing an aggregate with an aggregate-specific binding reagent under conditions that allow the binding of the reagent to the aggregate, if present; and detecting the presence of the aggregate, if any, in the sample by its binding to the reagent; where the aggregate-specific binding reagent typically has a net charge of at least about positive one at the pH at which the sample is contacted with the ASB reagent, is attached to a solid support at a charge density of at least about 60 nmol net charge per square meter, and binds preferentially with aggregates over monomers when attached to the solid support. Methods for detecting the presence of oligomer are also provided. Compositions for use in the methods arc provided.

8. 发明公开

EP2282753A1 ASSAY FOR PATHOGENIC CONFORMERS 审中-公开
标题翻译：分析法的致病性构
公开(公告)号：EP2282753A1
公开(公告)日：2011-02-16
申请号：EP09739744.2
申请日：2009-04-29
申请人： Novartis AG
发明人： PERETZ, David , WANG, Xuemei , GAO, Man (Carol) , YAM, Alice , LAU, Anthony , WU, Ping
IPC分类号： A61K38/00 , G01N33/53
CPC分类号： G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： The invention provides methods for detecting the presence of a non-prion pathogenic conformer in a sample by contacting the sample suspected of containing a non-prion pathogenic conformer with a pathogenic conformer- specific binding reagent under conditions that allow the binding of the reagent to the pathogenic conformer, if present; and detecting the presence the pathogenic conformer, if any, in the sample by its binding to the reagent; where the pathogenic conformer- specific binding reagent is typically derived from a prion protein fragment and interacts preferentially with a pathogenic prion protein. Methods for diagnosis of conformational diseases are also provided.

9. 发明公开

EP2507637A1 AMYLOID BETA AGGREGATES IN CEREBRO SPINAL FLUID AS BIOMARKERS FOR ALZHEIMER'S DISEASE 审中-公开
标题翻译：在液体中的淀粉样蛋白聚合物生物标记FÜRMORBUS ALZHEIMER
公开(公告)号：EP2507637A1
公开(公告)日：2012-10-10
申请号：EP10787232.7
申请日：2010-11-30
申请人： Novartis AG
发明人： PERETZ, David , ALLAUZEN, Sophie , WANG, Xuemei , GAO, Man (carol) , YAM, Alice , FEDYNYSHYN, Joseph
IPC分类号： G01N33/68 , C07K7/00
CPC分类号： G01N33/543 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： The invention provides methods for assessing increased probability of having Alzheimer's disease in a subject under assessment including a step of obtaining a measurement of Aβ40 aggregates in a biological sample from the subject, where the biological sample does not include brain tissue, a fraction of brain tissue, or brain homogenate. In some embodiments, the invention relates to methods of assessing increased probability of early stage Alzheimer's disease. The invention further provides methods of assessing increased probability of not having Alzheimer's disease, methods of monitoring disease progression in a subject with Alzheimer's disease, and methods of assigning disease stage for a subject with Alzheimer's disease, and methods of assessing increased probability of MCI progressing to Alzheimer's disease.

10. 发明授权

EP2142934B1 PRION ASSAY 有权
标题翻译：朊病毒TEST
公开(公告)号：EP2142934B1
公开(公告)日：2011-10-26
申请号：EP08754072.0
申请日：2008-04-03
申请人： Novartis AG
发明人： PERETZ, David , YAM, Alice
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2800/2828
摘要： The invention relates to an assay method for detecting the presence of PrPSc using at least one sequence-specific protease for a substantially complete digestion of the proteins in a sample, leaving the octarepeat region in both PrPSc and PrPC intact, leaving the protease-resistant core of PrPSc intact and remain connected to the octarepeat region, while digesting away at least part of the amino acid sequences in PrPC corresponding to the protease-resistant core in PrPSc. The method further comprises a step of inhibiting further digestion by the protease, a step of denaruration, and a step of detecting the presence of PrPSc using at least two binding partners, a first binding partner and a second binding partner, wherein the first binding partner specifically binds an epitope in the amino-proximal region, and the second binding partner specifically binds an epitope within a region of the protease-resistant core of PrPSc that has been cleaved away in PrPC. The invention also relates to a kit comprising reagents that can be used in the assay method.

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