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1. 发明授权

US08383599B2 Methods and compositions for RNA interference 有权
标题翻译： RNA干扰的方法和组成
公开(公告)号：US08383599B2
公开(公告)日：2013-02-26
申请号：US12152837
申请日：2008-05-16
申请人： Gregory J. Hannon , Patrick J. Paddison , Emily Bernstein , Amy Caudy , Douglas S. Conklin , Scott Hammond
发明人： Gregory J. Hannon , Patrick J. Paddison , Emily Bernstein , Amy Caudy , Douglas S. Conklin , Scott Hammond
IPC分类号： A61K48/00
CPC分类号： C12N15/1034 , A01K2217/05 , C12N15/102 , C12N15/111 , C12N2310/14 , C12N2310/53 , C12N2320/12
摘要： The present invention provides methods for attenuating gene expression in a cell using gene-targeted double stranded RNA (dsRNA). The dsRNA contains a nucleotide sequence that hybridizes under physiologic conditions of the cell to the nucleotide sequence of at least a portion of the gene to be inhibited (the “target” gene).
摘要翻译：本发明提供使用基因靶向双链RNA（dsRNA）减弱细胞中基因表达的方法。 dsRNA含有在细胞的生理条件下与要抑制的基因的至少一部分（靶基因）的核苷酸序列杂交的核苷酸序列。

2. 发明申请

US20100267803A1 Regulators Of Fat Metabolism As Anti-Cancer Targets 审中-公开
标题翻译：脂肪代谢调节剂作为抗癌靶标
公开(公告)号：US20100267803A1
公开(公告)日：2010-10-21
申请号：US12613953
申请日：2009-11-06
申请人： Douglas S. Conklin , Antonis Kourtidis
发明人： Douglas S. Conklin , Antonis Kourtidis
IPC分类号： A61K31/7105 , C12Q1/25 , C12Q1/48 , C12Q1/02 , A61P35/00
CPC分类号： G01N33/5011 , A61K31/7105 , G01N33/57415
摘要： Embodiments of the invention provide methods of identifying agents that reduce or prevent the proliferation of breast cancer cells, or kill them, in particular by interfering with the expression of the transcription factors NR1D1 and PPARγ or the expression of genes whose transcription they activate or the activity of the proteins translated from those transcripts.
摘要翻译：本发明的实施方案提供鉴定减少或预防乳腺癌细胞增殖或杀死它们的药剂的方法，特别是通过干扰转录因子NR1D1和PPARγ的表达或其激活转录的基因的表达或活性的蛋白质从这些转录物翻译。

3. 发明申请

US20100261776A1 BRUTON'S TYROSINE KINASE AS ANTI-CANCER DRUG TARGET 审中-公开
标题翻译： BRUTON'S TYROSINE KINASE作为抗癌药物目标
公开(公告)号：US20100261776A1
公开(公告)日：2010-10-14
申请号：US12613937
申请日：2009-11-06
申请人： Douglas S. Conklin , Cheryl Eifert , Antonis Kourtidis
发明人： Douglas S. Conklin , Cheryl Eifert , Antonis Kourtidis
IPC分类号： A61K31/7088 , A61P35/00 , G01N33/53 , C12N9/12
CPC分类号： A61K31/7088 , C12N9/1205 , C12N15/1137 , C12N2310/14 , C12Y207/10001 , C12Y207/10002 , G01N33/573 , G01N33/57415 , G01N2333/9121
摘要： Receptor protein tyrosine kinases (RPTKs) transmit extracellular signals across the plasma membrane to cytosolic proteins, stimulating the formation of complexes that regulate key cellular functions. Over half of the 90 tyrosine kinases have been implicated in human cancers and are for this reason considered highly promising drug targets. To gain insight into the tyrosine kinases that contribute to breast cancer related cellular mechanisms, we carried out a large-scale loss-of-function analysis of the tyrosine kinases, using RNA interference, in the clinically relevant Erb-B2 positive, BT474 breast cancer cell line. The cytosolic, non-receptor tyrosine kinase Bruton's tyrosine kinase (BTK), which has been extensively studied for its role in B cell development, was among those tyrosine kinase genes required for BT474 breast cancer cell survival. The BTK protein identified was an alternative form containing an amino-terminal extension. This alternative form of the Btk message is also present in tumorigenic breast cells at significantly higher levels than in normal breast cells.
摘要翻译：受体蛋白酪氨酸激酶（RPTKs）通过质膜将细胞外信号传递到胞质蛋白，刺激调节关键细胞功能的复合物的形成。 90种酪氨酸激酶中有一半已经涉及人类癌症，因此被认为是非常有希望的药物靶点。为了深入了解有助于乳腺癌相关细胞机制的酪氨酸激酶，我们在临床相关的Erb-B2阳性，BT474乳腺癌中使用RNA干扰对酪氨酸激酶进行了大规模的功能丧失功能分析细胞系。已经广泛研究其在B细胞发育中的作用的细胞溶质非受体酪氨酸激酶Bruton酪氨酸激酶（BTK）是BT474乳腺癌细胞存活所需的酪氨酸激酶基因之一。鉴定的BTK蛋白是含有氨基末端延伸的替代形式。这种替代形式的Btk信息也以明显高于正常乳腺细胞的水平存在于致瘤性乳腺细胞中。

4. 发明授权

US08513212B2 Bruton's tyrosine kinase as anti-cancer drug target 有权
标题翻译： Bruton的酪氨酸激酶作为抗癌药物靶点
公开(公告)号：US08513212B2
公开(公告)日：2013-08-20
申请号：US13330062
申请日：2011-12-19
申请人： Douglas S. Conklin , Cheryl Eifert , Antonis Kourtidis
发明人： Douglas S. Conklin , Cheryl Eifert , Antonis Kourtidis
IPC分类号： C12N15/11
CPC分类号： A61K31/7088 , C12N9/1205 , C12N15/1137 , C12N2310/14 , C12Y207/10001 , C12Y207/10002 , G01N33/573 , G01N33/57415 , G01N2333/9121
摘要： Receptor protein tyrosine kinases (RPTKs) transmit extracellular signals across the plasma membrane to cytosolic proteins, stimulating formation of complexes that regulate key cellular functions. Over half of the known tyrosine kinases are implicated in human cancers and are therefore highly promising drug targets. A large-scale loss-of-function analysis of the tyrosine kinases using RNA interference in the clinically relevant Erb-B2 positive, BT474 breast cancer cell line showed that Bruton's tyrosine kinase (BTK), a cytosolic, non-receptor tyrosine kinase that has been extensively studied for its role in B cell development, is required, in altered form, for BT474 breast cancer cell survival. This alternative form contains an amino-terminal extension that is also present in tumorigenic breast cells at significantly higher levels than in normal breast cells.
摘要翻译：受体蛋白酪氨酸激酶（RPTKs）通过质膜将细胞外信号传递到胞质蛋白，刺激调节关键细胞功能的复合物的形成。已知的一半以上酪氨酸激酶与人类癌症有关，因此是非常有希望的药物靶点。在临床相关的Erb-B2阳性，BT474乳腺癌细胞系中使用RNA干扰的酪氨酸激酶的大规模功能丧失功能分析显示，Bruton的酪氨酸激酶（BTK）是一种细胞溶质，非受体酪氨酸激酶被广泛研究其在B细胞发育中的作用，需要以BT474型乳腺癌细胞存活的形式。这种替代形式包含氨基末端延伸，其也以与正常乳腺细胞相比显着更高的水平存在于致瘤性乳腺细胞中。

5. 发明申请

US20120165395A1 Bruton's Tyrosine Kinase As Anti-Cancer Drug Target 有权
标题翻译： Bruton的酪氨酸激酶作为抗癌药物靶点
公开(公告)号：US20120165395A1
公开(公告)日：2012-06-28
申请号：US13330062
申请日：2011-12-19
申请人： Douglas S. Conklin , Cheryl Eifert , Antonis Kourtidis
发明人： Douglas S. Conklin , Cheryl Eifert , Antonis Kourtidis
IPC分类号： A61K31/713 , C12N5/09 , C12N9/12 , C12N9/96 , A61P35/00 , G01N33/574
CPC分类号： A61K31/7088 , C12N9/1205 , C12N15/1137 , C12N2310/14 , C12Y207/10001 , C12Y207/10002 , G01N33/573 , G01N33/57415 , G01N2333/9121
摘要： Receptor protein tyrosine kinases (RPTKs) transmit extracellular signals across the plasma membrane to cytosolic proteins, stimulating formation of complexes that regulate key cellular functions. Over half of the known tyrosine kinases are implicated in human cancers and are therefore highly promising drug targets. A large-scale loss-of-function analysis of the tyrosine kinases using RNA interference in the clinically relevant Erb-B2 positive, BT474 breast cancer cell line showed that Bruton's tyrosine kinase (BTK), a cytosolic, non-receptor tyrosine kinase that has been extensively studied for its role in B cell development, is required, in altered form, for BT474 breast cancer cell survival. This alternative form contains an amino-terminal extension that is also present in tumorigenic breast cells at significantly higher levels than in normal breast cells.
摘要翻译：受体蛋白酪氨酸激酶（RPTKs）通过质膜将细胞外信号传递到胞质蛋白，刺激调节关键细胞功能的复合物的形成。已知的一半以上酪氨酸激酶与人类癌症有关，因此是非常有希望的药物靶点。在临床相关的Erb-B2阳性，BT474乳腺癌细胞系中使用RNA干扰的酪氨酸激酶的大规模功能丧失功能分析显示，Bruton的酪氨酸激酶（BTK）是一种细胞溶质，非受体酪氨酸激酶被广泛研究其在B细胞发育中的作用，需要以BT474型乳腺癌细胞存活的形式。这种替代形式包含氨基末端延伸，其也以与正常乳腺细胞相比显着更高的水平存在于致瘤性乳腺细胞中。

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