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1. 发明申请

US20070248659A1 Individualized cancer therapy 失效
标题翻译：个性化的癌症治疗
公开(公告)号：US20070248659A1
公开(公告)日：2007-10-25
申请号：US11601431
申请日：2006-11-17
申请人： David Shanahan , John Nemunaitis , Neil Senzer , Phillip Maples , Donald Rao
发明人： David Shanahan , John Nemunaitis , Neil Senzer , Phillip Maples , Donald Rao
IPC分类号： A61K48/00 , A61K31/7105 , A61K9/127 , A61P43/00 , C12N5/08 , C12N5/10
CPC分类号： C12Q1/6886 , A61K31/7105 , A61K31/713 , A61K48/00 , C12N15/111 , C12N15/113 , C12Q2600/156 , C12Q2600/158 , C12Q2600/178 , G01N33/574 , G01N33/57484
摘要： In certain preferred embodiments, the invention provides methods for treating cancer, which comprise (a) obtaining a specimen of cancer tissue from a patient; (b) obtaining a specimen of normal tissue in the proximity of the cancer tissue from such patient; (c) extracting total protein and RNA from the cancer tissue and normal tissue; (d) obtaining a protein expression profile of the cancer tissue and normal tissue using 2D DIGE and mass spectrometry; (e) identifying proteins that are expressed in such cancer tissue at significantly different levels than in the normal tissue; (f) obtaining a gene expression profile of the cancer tissue and normal tissue using microarray technology and comparing the results thereof to the protein expression profile; (g) prioritizing over-expressed proteins by assessing the connectivity thereof to other cancer-related or stimulatory proteins; (h) designing an appropriate RNA interference expression cassette to, directly or indirectly, modulate the expression of genes encoding such prioritized proteins; (i) incorporating said cassette into an appropriate delivery vehicle; and (j) providing the patient with an effective amount of the delivery vehicle to, directly or indirectly, modify the expression (i.e., production) of such proteins.
摘要翻译：在某些优选实施方案中，本发明提供了治疗癌症的方法，其包括（a）从患者获得癌组织标本; （b）在患者的癌组织附近获得正常组织标本; （c）从癌组织和正常组织提取总蛋白和RNA; （d）使用2D DIGE和质谱法获得癌组织和正常组织的蛋白质表达谱; （e）以与正常组织中显着不同的水平鉴定在这样的癌组织中表达的蛋白质; （f）使用微阵列技术获得癌组织和正常组织的基因表达谱，并比较其结果与蛋白质表达谱; （g）通过评估与其他癌症相关或刺激性蛋白质的连通性来优先考虑过表达的蛋白质; （h）设计合适的RNA干扰表达盒直接或间接地调节编码这些优先蛋白质的基因的表达; （i）将所述盒装入合适的运送车辆; 和（j）向患者提供有效量的递送载体直接或间接地修饰这些蛋白质的表达（即生产）。

2. 发明申请

US20100166845A1 INDIVIDUALIZED CANCER THERAPY 有权
公开(公告)号：US20100166845A1
公开(公告)日：2010-07-01
申请号：US12609462
申请日：2009-10-30
申请人： David Shanahan , John Nemunaitis , Neil Senzer , Phillip Maples , Donald Rao
发明人： David Shanahan , John Nemunaitis , Neil Senzer , Phillip Maples , Donald Rao
IPC分类号： A61K9/127 , A61K31/7105 , A61P35/00
CPC分类号： C12N15/1135 , A61K9/1273 , A61K9/513 , A61K31/7105 , A61K31/713 , A61K48/00 , A61K48/005 , C12N2310/14 , C12N2310/531 , C12N2320/32 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158 , G01N33/574 , G01N33/57496 , G01N2800/52
摘要： In certain embodiments, the invention provides methods for treating cancer, comprising: (a) obtaining a specimen of cancer tissue and normal tissue from a patient; (b) extracting total protein and RNA from the cancer tissue and normal tissue; (c) obtaining a protein expression profile of the cancer tissue and normal tissue; (d) identifying over-expressed proteins in the cancer tissue; (e) comparing the protein expression profile to a gene expression profile; (f) identifying at least one prioritized protein target by assessing connectivity of each said over-expressed protein to other cancer-related or stimulatory proteins; (g) designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding the prioritized target protein; (h): designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding a protein of higher priority in the signaling pathway in which the first protein is a component; (i) incorporating the first cassette into a first delivery vehicle; (j) providing a patient with an effective amount of the first delivery vehicle; (k) extracting total protein and RNA from the treated cancer tissue; (l) identifying over-expressed proteins in the treated cancer tissue; (m) designing a second RNA interference expression cassette to modulate the expression of a second prioritized protein in the treated tissue; (n) incorporating the second cassette into a second delivery vehicle; (o) providing the previously treated patient with an effective amount of the second delivery vehicle; (p) identifying a novel protein signal following prior treatment with protein specific knockdown; (q) identifying a gene mutation provided by gene sequencing/microarray on assessment of other protein signals; and (r) identifying of a novel protein signal as a result of determination of the gene mutation and assessment of other protein signals to, directly or indirectly, modify the expression (i.e., production) of such proteins.

3. 发明授权

US09273300B2 Methods and compositions for modulating sialic acid production and treating hereditary inclusion body myopathy 有权
标题翻译：调节唾液酸生产和治疗遗传性包涵体肌病的方法和组合物
公开(公告)号：US09273300B2
公开(公告)日：2016-03-01
申请号：US12526239
申请日：2008-02-07
申请人： Phillip Maples , Chris Jay , John J. Nemunaitis
发明人： Phillip Maples , Chris Jay , John J. Nemunaitis
IPC分类号： A61K48/00 , A61K9/16 , A61K9/50 , C12N9/90 , C12N15/85
CPC分类号： A61K48/005 , C12N9/90 , C12N15/85 , C12Y501/03014
摘要： According to certain embodiments of the present invention, methods for modulating the production of sialic acid in a system are provided, which comprise providing the system with a wild-type GNE-encoding nucleic acid sequence. According to such embodiments, the system may comprise a cell, muscular tissue, or other desirable targets. Similarly, the present invention encompasses methods for producing wild-type GNE in a system that comprises a mutated endogenous GNE-encoding sequence. In other words, the present invention includes providing, for example, a cell or muscular tissue that harbors a mutated (defective) GNE-encoding sequence with a functional wild-type GNE encoding sequence.
摘要翻译：根据本发明的某些实施方案，提供了调节系统中唾液酸生产的方法，其包括向系统提供编码野生型GNE的核酸序列。根据这样的实施例，该系统可以包括细胞，肌肉组织或其它期望的靶。类似地，本发明包括在包含突变的内源GNE编码序列的系统中产生野生型GNE的方法。换句话说，本发明包括例如提供具有功能性野生型GNE编码序列的突变（缺陷）GNE编码序列的细胞或肌肉组织。

4. 发明授权

US08916530B2 Individualized cancer therapy 有权
公开(公告)号：US08916530B2
公开(公告)日：2014-12-23
申请号：US12609462
申请日：2009-10-30
申请人： David Shanahan , John Nemunaitis , Neil Senzer , Phillip Maples , Donald Rao
发明人： David Shanahan , John Nemunaitis , Neil Senzer , Phillip Maples , Donald Rao
IPC分类号： A01N43/04 , A61K31/713 , C12N15/113 , C07H21/04
CPC分类号： C12N15/1135 , A61K9/1273 , A61K9/513 , A61K31/7105 , A61K31/713 , A61K48/00 , A61K48/005 , C12N2310/14 , C12N2310/531 , C12N2320/32 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158 , G01N33/574 , G01N33/57496 , G01N2800/52
摘要： In certain embodiments, the invention provides methods for treating cancer, comprising: (a) obtaining a specimen of cancer tissue and normal tissue from a patient; (b) extracting total protein and RNA from the cancer tissue and normal tissue; (c) obtaining a protein expression profile of the cancer tissue and normal tissue; (d) identifying over-expressed proteins in the cancer tissue; (e) comparing the protein expression profile to a gene expression profile; (f) identifying at least one prioritized protein target by assessing connectivity of each said over-expressed protein to other cancer-related or stimulatory proteins; (g) designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding the prioritized target protein; (h): designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding a protein of higher priority in the signaling pathway in which the first protein is a component; (i) incorporating the first cassette into a first delivery vehicle; (j) providing a patient with an effective amount of the first delivery vehicle; (k) extracting total protein and RNA from the treated cancer tissue; (l) identifying over-expressed proteins in the treated cancer tissue; (m) designing a second RNA interference expression cassette to modulate the expression of a second prioritized protein in the treated tissue; (n) incorporating the second cassette into a second delivery vehicle; (o) providing the previously treated patient with an effective amount of the second delivery vehicle; (p) identifying a novel protein signal following prior treatment with protein specific knockdown; (q) identifying a gene mutation provided by gene sequencing/microarray on assessment of other protein signals; and (r) identifying of a novel protein signal as a result of determination of the gene mutation and assessment of other protein signals to, directly or indirectly, modify the expression (i.e., production) of such proteins.

5. 发明申请

US20110027373A1 METHODS AND COMPOSITIONS FOR MODULATING SIALIC ACID PRODUCTION AND TREATING HEREDITARY INCLUSION BODY MYOPATHY 有权
标题翻译：调节酸乳酸生产和治疗包括身体肌肉酸痛的方法和组合物
公开(公告)号：US20110027373A1
公开(公告)日：2011-02-03
申请号：US12526239
申请日：2008-02-07
申请人： Phillip Maples , Chris Jay , John J. Nemunaitis
发明人： Phillip Maples , Chris Jay , John J. Nemunaitis
IPC分类号： A61K9/00 , A61K31/711 , A61P21/00
CPC分类号： A61K48/005 , C12N9/90 , C12N15/85 , C12Y501/03014
摘要： According to certain embodiments of the present invention, methods for modulating the production of sialic acid in a system are provided, which comprise providing the system with a wild-type GNE-encoding nucleic acid sequence. According to such embodiments, the system may comprise a cell, muscular tissue, or other desirable targets. Similarly, the present invention encompasses methods for producing wild-type GNE in a system that comprises a mutated endogenous GNE-encoding sequence. In other words, the present invention includes providing, for example, a cell or muscular tissue that harbors a mutated (defective) GNE-encoding sequence with a functional wild-type GNE encoding sequence.
摘要翻译：根据本发明的某些实施方案，提供了调节系统中唾液酸生产的方法，其包括向系统提供编码野生型GNE的核酸序列。根据这样的实施例，该系统可以包括细胞，肌肉组织或其它期望的靶。类似地，本发明包括在包含突变的内源GNE编码序列的系统中产生野生型GNE的方法。换句话说，本发明包括例如提供具有功能性野生型GNE编码序列的突变（缺陷）GNE编码序列的细胞或肌肉组织。

6. 发明授权

US08603991B2 Individualized cancer therapy 失效
标题翻译：个性化的癌症治疗
公开(公告)号：US08603991B2
公开(公告)日：2013-12-10
申请号：US11601431
申请日：2006-11-17
申请人： David Shanahan , John Nemunaitis , Neil Senzer , Phillip Maples , Donald Rao
发明人： David Shanahan , John Nemunaitis , Neil Senzer , Phillip Maples , Donald Rao
IPC分类号： A61K31/70 , C12Q1/68 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6886 , A61K31/7105 , A61K31/713 , A61K48/00 , C12N15/111 , C12N15/113 , C12Q2600/156 , C12Q2600/158 , C12Q2600/178 , G01N33/574 , G01N33/57484
摘要： Methods for treating cancer that include (a) obtaining a specimen of cancer issue from a patient; (b) obtaining a specimen of normal tissue in the proximity of the cancer tissue; (c) extracting total protein from the cancer tissue and normal tissue; (d) obtaining a protein expression profile of the cancer tissue and normal tissue; (e) identifying a group of proteins that are expressed in the cancer tissue at significantly different levels than in the normal tissue; (f) identifying one or more prioritized proteins from the group of proteins, which will serve as the target for an RNA interference molecule (RNAi), which, when provided to a patient, will reduce the expression level of the one or more prioritized proteins using both cleavage-dependent and cleavage-independent pathways of the RNA-induced silencing complex (RISC).
摘要翻译：治疗癌症的方法包括：（a）从患者获得癌症问题标本; （b）获得在癌组织附近的正常组织标本; （c）从癌组织和正常组织提取总蛋白; （d）获得癌组织和正常组织的蛋白质表达谱; （e）以与正常组织中显着不同的水平鉴定在癌组织中表达的一组蛋白质; （f）鉴定来自蛋白质组中的一种或多种优先化蛋白质，其将用作RNA干扰分子（RNAi）的靶标，当提供给患者时，其将降低一种或多种优先蛋白质的表达水平使用RNA诱导的沉默复合物（RISC）的切割依赖性和切割独立的途径。

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