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1. 发明授权

US09157084B2 Furin-knockdown bi-functional RNA 有权
标题翻译：呋喃蛋白敲低双功能RNA
公开(公告)号：US09157084B2
公开(公告)日：2015-10-13
申请号：US12973787
申请日：2010-12-20
申请人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
发明人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
IPC分类号： C12N15/00 , C07H21/04 , C07K1/00 , C12N5/00 , C12N15/113 , A61K38/21 , C07K14/535 , C12N15/85
CPC分类号： C12N15/1137 , A61K38/193 , A61K38/217 , A61K48/005 , C07K14/535 , C12N15/85 , C12N2310/14 , C12N2310/141 , C12N2310/3519 , C12N2310/531 , C12N2320/31 , C12N2320/35 , C12N2330/51 , C12N2830/20 , C12N2840/107 , A61K2300/00
摘要： Compositions and methods to attenuate the immunosuppressive activity of TGF-β through the use of bi-functional shRNAs was substituted therefor described herein. The bi-functional shRNAs of the present invention knocks down the expression of furin in cancer cells to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
摘要翻译：降低TGF-β的免疫抑制活性的组合物和方法通过用本文所述的双官能shRNA进行替代。本发明的双功能shRNAs通过表达GM-CSF转基因敲除癌细胞中弗林蛋白酶的表达，以增加肿瘤抗原的表达，呈递和加工。

2. 发明授权

US09132146B2 Furin-knockdown and GM-CSF-augmented (FANG) cancer vaccine 有权
标题翻译：呋喃蛋白降解和GM-CSF增强（FANG）癌症疫苗
公开(公告)号：US09132146B2
公开(公告)日：2015-09-15
申请号：US12973823
申请日：2010-12-20
申请人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
发明人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
IPC分类号： C12N15/11 , C07H21/04 , A61K31/7088 , A61K31/7105
CPC分类号： C12N15/85 , A61K31/7088 , A61K31/7105 , A61K35/13 , A61K38/217 , A61K39/0011
摘要： Compositions and methods for cancer treatment are discloses herein. More specifically the present invention describes an autologous cancer vaccine genetically modified for Furin knockdown and GM-CSF expression. The vaccine described herein attenuates the immunosuppressive activity of TGF-β through the use of bi-functional shRNAs to knock down the expression of furin in cancer cells, and to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
摘要翻译：本文公开了用于癌症治疗的组合物和方法。更具体地，本发明描述了用于Furin敲低和GM-CSF表达遗传修饰的自体癌症疫苗。本文所述的疫苗减弱TGF-β的免疫抑制活性; 通过使用双功能shRNAs敲低癌细胞中弗林蛋白酶的表达，并通过GM-CSF转基因的表达增强肿瘤抗原的表达，表达和加工。

3. 发明申请

US20130078279A1 FURIN-KNOCKDOWN AND GM-CSF-AUGMENTED (FANG) CANCER VACCINE 审中-公开
标题翻译： FURIN-KNOCKDOWN和GM-CSF-AUGMENTED（FANG）CANCER VACCINE
公开(公告)号：US20130078279A1
公开(公告)日：2013-03-28
申请号：US13606476
申请日：2012-09-07
申请人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
发明人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
IPC分类号： A61K31/7088
CPC分类号： C12N15/85 , A61K31/7088 , A61K31/7105 , A61K35/13 , A61K38/217 , A61K39/0011
摘要： Compositions and methods for cancer treatment are discloses herein. More specifically the present invention describes an autologous cancer vaccine genetically modified for Furin knockdown and GM-CSF expression. The vaccine described herein attenuates the immunosuppressive activity of TGF-β through the use of bi-functional shRNAs to knock down the expression of furin in cancer cells, and to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
摘要翻译：本文公开了用于癌症治疗的组合物和方法。更具体地，本发明描述了用于Furin敲低和GM-CSF表达遗传修饰的自体癌症疫苗。本文所述的疫苗减弱TGF-β的免疫抑制活性; 通过使用双功能shRNAs敲低癌细胞中弗林蛋白酶的表达，并通过GM-CSF转基因的表达增强肿瘤抗原的表达，表达和加工。

4. 发明申请

US20110286979A1 CHEMOSENSITIZATION BY BI-FUNCTIONAL SMALL HAIRPIN RNA (bi-shRNA) 审中-公开
标题翻译：双功能小毛发RNA（bi-shRNA）的化学发光
公开(公告)号：US20110286979A1
公开(公告)日：2011-11-24
申请号：US13111677
申请日：2011-05-19
申请人： Alex W. Tong , Yu Yang , Donald Rao , Phillip B. Maples , Neil Senzer , John J. Nemunaitis , Zhaohui Wang
发明人： Alex W. Tong , Yu Yang , Donald Rao , Phillip B. Maples , Neil Senzer , John J. Nemunaitis , Zhaohui Wang
IPC分类号： A61K35/12 , A61K31/7105 , A61K31/7088 , A61P35/00 , A61P35/04
CPC分类号： A61K31/337 , A61K31/7088 , A61K31/7105 , A61K45/06 , C12N15/113 , C12N15/1135 , C12N2310/14 , C12N2320/31 , C12N2330/50 , A61K2300/00 , C12N2310/531
摘要： Compositions and methods of augmenting the anti-tumor activities of docetaxel and other taxanes by combination with a bi-functional small hairpin RNA (bi-shRNA) is described herein. The instant invention describes the interactive outcome of STMN1 knockdown with docetaxel. In vitro docetaxel (DOC) dose response assessments with or without co-treatment with bi-shRNASTMN1 in CCL-247 and SK-MEL-28 melanoma cells indicated that STMN1 knockdown significantly reduced DOC concentration needed to inhibit cancer cell growth by 50% (IC50) of CCL-247 cells from 1.8±0.2 to 0.6±0.4 nm (n=3, p 10-fold reduction in DOC IC50 suggest that bi-shRNASTMN1 can markedly enhance the effectiveness of docetaxel for human cancer cells.
摘要翻译：本文描述了通过与双功能小发夹RNA（双shRNA）组合增强多西他赛和其他紫杉烷类抗肿瘤活性的组合物和方法。本发明描述了使用多西紫杉醇的STMN1敲低的交互结果。在CCL-247和SK-MEL-28黑素瘤细胞中，用或者与双shRNASTMN1进行共处理的体外多西紫杉醇（DOC）剂量反应评估表明STMN1敲低显着降低抑制癌细胞生长所需的DOC浓度50％（IC50 ）CCL-247细胞从1.8±0.2到0.6±0.4nm（n = 3，p <0.05），SK-MEL-28细胞从1.7±0.2nm到0.1±0.0（n = 3，p <0.05）。 DOC IC50的3〜10倍降低表明bi-shRNASTMN1可以显着增强多西紫杉醇对人类癌细胞的有效性。

5. 发明申请

US20110262408A1 FURIN-KNOCKDOWN AND GM-CSF-AUGMENTED (FANG) CANCER VACCINE 有权
标题翻译： FURIN-KNOCKDOWN和GM-CSF-AUGMENTED（FANG）CANCER VACCINE
公开(公告)号：US20110262408A1
公开(公告)日：2011-10-27
申请号：US12973823
申请日：2010-12-20
申请人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
发明人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
IPC分类号： A61K35/12 , C12N5/09 , A61P35/00 , A61K31/7105 , A61P37/04 , C12N15/85 , C12P21/00
CPC分类号： C12N15/85 , A61K31/7088 , A61K31/7105 , A61K35/13 , A61K38/217 , A61K39/0011
摘要： Compositions and methods for cancer treatment are discloses herein. More specifically the present invention describes an autologous cancer vaccine genetically modified for Furin knockdown and GM-CSF expression. The vaccine described herein attenuates the immunosuppressive activity of TGF-β through the use of bi-functional shRNAs to knock down the expression of furin in cancer cells, and to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
摘要翻译：本文公开了用于癌症治疗的组合物和方法。更具体地，本发明描述了用于Furin敲低和GM-CSF表达遗传修饰的自体癌症疫苗。本文所述的疫苗减弱TGF-β的免疫抑制活性; 通过使用双功能shRNAs敲低癌细胞中弗林蛋白酶的表达，并通过GM-CSF转基因的表达增强肿瘤抗原的表达，表达和加工。

6. 发明申请

US20110150832A1 FURIN-KNOCKDOWN BI-FUNCTIONAL RNA 有权
标题翻译： FURIN-KNOCKDOWN双功能RNA
公开(公告)号：US20110150832A1
公开(公告)日：2011-06-23
申请号：US12973787
申请日：2010-12-20
申请人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
发明人： John J. Nemunaitis , Neil Senzer , Phillip B. Maples , Donald Rao
IPC分类号： A61K39/00 , C12N15/85 , A61K38/21 , A61P35/04
CPC分类号： C12N15/1137 , A61K38/193 , A61K38/217 , A61K48/005 , C07K14/535 , C12N15/85 , C12N2310/14 , C12N2310/141 , C12N2310/3519 , C12N2310/531 , C12N2320/31 , C12N2320/35 , C12N2330/51 , C12N2830/20 , C12N2840/107 , A61K2300/00
摘要： Compositions and methods to attenuate the immunosuppressive activity of TGF-β through the use of bi-functional shRNAs is described herein. The bi-functional shRNAs of the present invention knocks down the expression of furin in cancer cells to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
摘要翻译：降低TGF-β的免疫抑制活性的组合物和方法通过使用双功能shRNAs在本文中描述。本发明的双功能shRNAs通过表达GM-CSF转基因敲除癌细胞中弗林蛋白酶的表达，以增加肿瘤抗原的表达，呈递和加工。

7. 发明授权

US08906874B2 Bi-functional shRNA targeting Stathmin 1 and uses thereof 有权
标题翻译：靶向Stathmin 1的双功能shRNA及其用途
公开(公告)号：US08906874B2
公开(公告)日：2014-12-09
申请号：US13410130
申请日：2012-03-01
申请人： Donald Rao , John J. Nemunaitis , Neil Senzer
发明人： Donald Rao , John J. Nemunaitis , Neil Senzer
IPC分类号： A01N43/04 , A61K48/00 , C07H21/04
CPC分类号： A61K48/00 , A61K9/0019 , A61K9/127 , C12N15/113 , C12N15/85 , C12N2310/3519 , C12N2310/51 , C12N2310/53 , C12N2310/531 , C12N2320/31
摘要： The present invention includes bifunctional shRNAs capable of reducing an expression of a Stathmin 1 gene; wherein at least one target site sequence of the bifunctional RNA molecule is located within the Stathmin 1 gene, wherein the bifunctional RNA molecule is capable of activating a cleavage-dependent and a cleavage-independent RNA-induced silencing complex for reducing the expression level of Stathmin 1.
摘要翻译：本发明包括能够降低Stathmin1基因表达的双功能shRNA; 其中双功能RNA分子的至少一个靶位点序列位于Stathmin1基因内，其中双功能RNA分子能够激活切割依赖性和切割独立的RNA诱导的沉默复合物，以降低Stathmin的表达水平 1。

8. 发明申请

US20090246196A1 COMBINED TARGETED THERAPY FOR THE TREATMENT OF PROLIFERATIVE DISEASE 审中-公开
标题翻译：用于治疗增殖性疾病的综合疗法
公开(公告)号：US20090246196A1
公开(公告)日：2009-10-01
申请号：US12282618
申请日：2007-03-15
申请人： Leo Linbeck, III , Martin Lindenberg , John J. Nemunaitis , Neil Senzer , David Shanahan
发明人： Leo Linbeck, III , Martin Lindenberg , John J. Nemunaitis , Neil Senzer , David Shanahan
IPC分类号： A61K39/395 , A61K38/45 , A61K38/16 , A61K31/66 , A61K31/517
CPC分类号： A61K45/06 , A61K31/685 , A61K2300/00
摘要： A method of treating an individual comprising: evaluating the disease state of said individual through quantitative and/or qualitative assays; administering in amounts sufficient to treat said disease at least three agents wherein at least one agent is an inhibitor of the human epidermal receptor pathway, at least one agent is signal transduction inhibitor and at least one agent is an angiogenesis inhibitor and; reevaluating the disease state of said individual presenting through quantitative and/or qualitative assays. A composition comprising a first agent that is an inhibitor of the human epidermal receptor pathway, a second agent that is an angiogenesis inhibitor and a third agent that is an inhibitor of Akt wherein said first agent, second agent, third agent and combinations thereof are present in amounts that when administered to an individual in a diseased state are sufficient to treat said disease.
摘要翻译：一种治疗个体的方法，包括：通过定量和/或定性测定来评估所述个体的疾病状态; 施用足以治疗所述疾病的至少三种试剂，其中至少一种试剂是人表皮受体途径的抑制剂，至少一种试剂是信号转导抑制剂，至少一种试剂是血管发生抑制剂; 通过定量和/或定性测定重新评估所述个体呈递的疾病状态。包含作为人表皮受体途径的抑制剂的第一药剂，作为血管生成抑制剂的第二药剂和作为Akt抑制剂的第三药剂的组合物，其中所述第一药剂，第二药剂，第三药剂及其组合存在当给予患病状态的个体足以治疗所述疾病时。

9. 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.

10. 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）。

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