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1. 发明申请

US20140206544A1 RNAi-Based Method of Screening and Characterizing Drug Combinations 有权
标题翻译：基于RNAi的筛选和表征药物组合的方法
公开(公告)号：US20140206544A1
公开(公告)日：2014-07-24
申请号：US13994057
申请日：2011-12-16
申请人： Justin Pritchard , Douglas A. Lauffenburger , Michael Hemann
发明人： Justin Pritchard , Douglas A. Lauffenburger , Michael Hemann
IPC分类号： C12N15/10 , C12Q1/68 , G01N33/50
CPC分类号： C12N15/1079 , C12Q1/6883 , C12Q1/6886 , C12Q2600/136 , C12Q2600/178 , G01N33/5023
摘要： In one aspect, the invention is directed to a method of characterizing a mechanism of action of a combination of agents. The method comprises contacting a plurality of populations of cells with a combination of agents to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein the gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the combination of agents is determined, thereby obtaining an shRNA signature of the combination of agents so as to identify one or more genes that mediate a response to the combination of agents, thereby characterizing the mechanism of action of the combination of agents. In another aspect, the invention is directed to a method of determining whether a patient population treated with a first agent would benefit from a treatment using the first agent in combination with one or more additional agents. In yet another aspect, the invention is directed to method of determining whether a formulation of one or more agents maintains a mechanism of action of the one or more agents when unformulated.
摘要翻译：一方面，本发明涉及一种表征药剂组合的作用机理的方法。所述方法包括使多个细胞群与待评估的试剂的组合接触，其中每个细胞群具有一个由小发夹RNA（shRNA）靶向的感兴趣基因，并且其中感兴趣的基因调节细胞死亡和多个的调节细胞死亡的基因被靶向于多个细胞群体。确定每种细胞群与药剂组合的反应性，从而获得试剂组合的shRNA标签，以鉴定介导对试剂组合的反应的一种或多种基因，从而表征代理商的组合。在另一方面，本发明涉及一种确定用第一药剂治疗的患者群体是否将受益于使用第一药剂与一种或多种另外的药剂联合治疗的方法。在另一方面，本发明涉及确定一种或多种试剂的制剂是否在未配制时维持所述一种或多种试剂的作用机制的方法。

2. 发明授权

US09670486B2 RNAi-based method of screening and characterizing drug combinations 有权
公开(公告)号：US09670486B2
公开(公告)日：2017-06-06
申请号：US13994057
申请日：2011-12-16
申请人： Justin Pritchard , Douglas A. Lauffenburger , Michael Hemann
发明人： Justin Pritchard , Douglas A. Lauffenburger , Michael Hemann
IPC分类号： C12Q1/68 , G01N33/50 , C12N15/10
CPC分类号： C12N15/1079 , C12Q1/6883 , C12Q1/6886 , C12Q2600/136 , C12Q2600/178 , G01N33/5023
摘要： In one aspect, the invention is directed to a method of characterizing a mechanism of action of a combination of agents. The method comprises contacting a plurality of populations of cells with a combination of agents to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein the gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the combination of agents is determined, thereby obtaining an shRNA signature of the combination of agents so as to identify one or more genes that mediate a response to the combination of agents, thereby characterizing the mechanism of action of the combination of agents. In another aspect, the invention is directed to a method of determining whether a patient population treated with a first agent would benefit from a treatment using the first agent in combination with one or more additional agents. In yet another aspect, the invention is directed to method of determining whether a formulation of one or more agents maintains a mechanism of action of the one or more agents when unformulated.

3. 发明申请

US20120251528A1 Non-Human Mammal Model Of Human Hematopoietic Cancer 审中-公开
标题翻译：人类造血癌非人类哺乳动物模型
公开(公告)号：US20120251528A1
公开(公告)日：2012-10-04
申请号：US13381307
申请日：2010-06-28
申请人： Ilya B. Leskov , Adam C. Drake , Maroun Khoury , Jianzhu Chen , Christian Pallasch , Michael Hemann
发明人： Ilya B. Leskov , Adam C. Drake , Maroun Khoury , Jianzhu Chen , Christian Pallasch , Michael Hemann
IPC分类号： A01K67/027 , A61K39/395 , A61P35/02 , C12Q1/06
CPC分类号： A61K39/3955 , A01K67/027 , A01K67/0271 , A01K2207/12 , A01K2227/105 , A01K2267/0331 , A01K2267/0381 , A61K2039/505 , C07K16/2893 , C07K2317/24 , A61K2300/00
摘要： The present invention describes Photolabile Compounds methods for use of the compounds. The Photolabile Compounds have a photoreleasable ligand, which can be biologically active, and which is photoreleased from the compound upon exposure to light. In some embodiments, the Photolabile Compounds comprise a light antenna, such as a labeling molecule or an active derivative thereof. In one embodiment, the light is visible light, which is not detrimental to the viability of biological samples, such as cells and tissues, in which the released organic molecule is bioactive and can have a therapeutic effect. In another embodiment, the photoreleasable ligand can be a labeling molecule, such as a fluorescent molecule.
摘要翻译：本发明描述了使用该化合物的光不稳定化合物方法。光不稳定化合物具有光可释放的配体，其可以是生物活性的，并且其在暴露于光时从化合物中光分解。在一些实施方案中，光不稳定化合物包含光天线，例如标记分子或其活性衍生物。在一个实施方案中，光是可见光，其对生物样品（例如细胞和组织）的活力无害，其中释放的有机分子是生物活性的并且可以具有治疗效果。在另一个实施方案中，光可释放配体可以是标记分子，例如荧光分子。

4. 发明申请

US20090217404A1 Cell-based RNA interference and related methods and compositions 审中-公开
标题翻译：基于细胞的RNA干扰及相关方法和组成
公开(公告)号：US20090217404A1
公开(公告)日：2009-08-27
申请号：US12072124
申请日：2008-02-23
申请人： Scott W. Lowe , Michelle A. Carmell , Gregory J. Hannon , Patrick Paddison , Jack Zilfou , Jordan Fridman , Ross Dickins , Michael Hemann , Thomas A. Rosenquist , Prem Premsrirut
发明人： Scott W. Lowe , Michelle A. Carmell , Gregory J. Hannon , Patrick Paddison , Jack Zilfou , Jordan Fridman , Ross Dickins , Michael Hemann , Thomas A. Rosenquist , Prem Premsrirut
IPC分类号： A01K67/027 , C12Q1/68 , C12N5/00 , C12N5/06 , C12N5/08 , C07H21/00
CPC分类号： A01K67/0271 , A01K2267/0331 , C07K14/82 , C12N15/1135 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/50 , C12N2799/027 , C12N2830/006
摘要： The invention provides, among other things, methods for performing RNA interference (RNAi) in stem cells (such as embryonic stem cells) and methods for using such stem cells in vivo. The invention also provides various animal models based on conditional/inducible, reversible, tissue-specific/spacial, and/or developmental stage-specific/temporal RNAi of certain target genes, which animal model may be useful for, e.g., drug target identification and/or validation.
摘要翻译：本发明尤其提供了用于在干细胞（例如胚胎干细胞）中进行RNA干扰（RNAi）的方法以及在体内使用这种干细胞的方法。本发明还提供了基于某些靶基因的条件/诱导型，可逆性，组织特异性/空间和/或发育阶段特异性/时间RNAi的各种动物模型，所述动物模型可用于例如药物靶标鉴定和 /或验证。

5. 发明授权

US09683231B2 RNAi-based method of drug screening and characterization 有权
公开(公告)号：US09683231B2
公开(公告)日：2017-06-20
申请号：US13993930
申请日：2011-12-16
申请人： Hai Jiang , Justin Pritchard , Douglas A. Lauffenburger , Michael Hemann
发明人： Hai Jiang , Justin Pritchard , Douglas A. Lauffenburger , Michael Hemann
IPC分类号： C12N15/10 , C12Q1/68 , G01N33/50
CPC分类号： C12N15/1079 , C12Q1/6883 , C12Q1/6886 , C12Q2600/136 , C12Q2600/178 , G01N33/5023
摘要： The invention is directed to a method of characterizing a mechanism of action of an agent (e.g., a chemotherapeutic agent, a genotoxic agent). The method comprises contacting a plurality of populations of cells with an agent to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein said gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the agent is determined, thereby obtaining an shRNA signature of the agent, so as to identify one or more genes that mediate a response to the agent, thereby characterizing the mechanism of action of the agent. The invention is also directed an article of manufacture for characterizing a mechanism of action of a chemotherapeutic or genotoxic agent.

6. 发明申请

US20100186097A1 CELL-BASED RNA INTERFERENCE AND RELATED METHODS AND COMPOSITIONS 审中-公开
标题翻译：基于细胞的RNA干扰及相关方法和组合物
公开(公告)号：US20100186097A1
公开(公告)日：2010-07-22
申请号：US12497967
申请日：2009-07-06
申请人： Scott W. LOWE , Michael HEMANN , Gregory J. HANNON , Patrick J. PADDISON , Jack ZILFOU , Jordan FRIDMAN , Michelle A. CARMELL , Ross DICKINS , Thomas A. ROSENQUIST , Stephen J. ELLEDGE
发明人： Scott W. LOWE , Michael HEMANN , Gregory J. HANNON , Patrick J. PADDISON , Jack ZILFOU , Jordan FRIDMAN , Michelle A. CARMELL , Ross DICKINS , Thomas A. ROSENQUIST , Stephen J. ELLEDGE
IPC分类号： A61K49/00 , A61K35/12 , A01K67/033 , C40B40/06 , C12N5/071 , A61P43/00
CPC分类号： C12N15/1135 , A61K48/00 , C12N15/111 , C12N15/1137 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2330/30 , C12N2330/31
摘要： The invention provides, among other things, methods for performing RNA interference in stem cells and methods for using the stem cells in vivo.
摘要翻译：本发明尤其提供了用于在干细胞中进行RNA干扰的方法以及在体内使用干细胞的方法。

7. 发明申请

US20140134635A1 RNAi-Based Method of Drug Screening and Characterization 有权
标题翻译：基于RNAi的药物筛选和表征方法
公开(公告)号：US20140134635A1
公开(公告)日：2014-05-15
申请号：US13993930
申请日：2011-12-16
申请人： Hai Jiang , Justin Pritchard , Douglas A. Lauffenburger , Michael Hemann
发明人： Hai Jiang , Justin Pritchard , Douglas A. Lauffenburger , Michael Hemann
IPC分类号： G01N33/50
CPC分类号： C12N15/1079 , C12Q1/6883 , C12Q1/6886 , C12Q2600/136 , C12Q2600/178 , G01N33/5023
摘要： The invention is directed to a method of characterizing a mechanism of action of an agent (e.g., a chemotherapeutic agent, a genotoxic agent). The method comprises contacting a plurality of populations of cells with an agent to be assessed, wherein each population of cells have one gene of interest targeted by a small hairpin RNA (shRNA) and wherein said gene of interest regulates cell death and a plurality of genes that regulate cell death are targeted in the plurality of populations of cells. A responsiveness of each population of cells to the agent is determined, thereby obtaining an shRNA signature of the agent, so as to identify one or more genes that mediate a response to the agent, thereby characterizing the mechanism of action of the agent. The invention is also directed an article of manufacture for characterizing a mechanism of action of a chemotherapeutic or genotoxic agent.
摘要翻译：本发明涉及一种表征药剂（例如，化学治疗剂，遗传毒性剂）的作用机制的方法。该方法包括使多个细胞群与待评估的试剂接触，其中每个细胞群具有一个由小发夹RNA（shRNA）靶向的感兴趣基因，其中所述感兴趣的基因调节细胞死亡和多个基因调节细胞死亡的目标在多个细胞群体中。确定每种细胞群体对试剂的反应性，从而获得试剂的shRNA标签，以鉴定介导对试剂的反应的一种或多种基因，从而表征试剂的作用机制。本发明还涉及用于表征化学治疗剂或遗传毒性剂的作用机制的制品。

8. 发明申请

US20080242622A1 Identification of genetic alterations that modulate drug sensitivity in cancer treatments 审中-公开
标题翻译：鉴定在癌症治疗中调节药物敏感性的遗传改变
公开(公告)号：US20080242622A1
公开(公告)日：2008-10-02
申请号：US12077737
申请日：2008-03-19
申请人： Scott W. Lowe , Michael Hemann , Gregory J. Hannon , Darren Burgess
发明人： Scott W. Lowe , Michael Hemann , Gregory J. Hannon , Darren Burgess
IPC分类号： A61K31/7028 , C40B30/06 , C12Q1/68 , A61K31/7105 , A61K31/704 , C12Q1/02
CPC分类号： G01N33/5011 , C12N15/1079 , C12N15/111 , C12N15/113 , C12N15/1137 , C12N2310/14 , C12N2320/12 , C12N2320/31 , C12N2330/31 , C12Y599/01003
摘要： This invention features methods of identifying genetic alterations that can modulate cancer cells' sensitivity to an anti-cancer drug. Information on such genetic alterations can be used to predict cancer therapeutic outcomes and to stratify patient populations to maximize therapeutic efficacy.
摘要翻译：本发明的特征在于鉴定可调节癌细胞对抗癌药物的敏感性的遗传改变的方法。关于这种遗传改变的信息可用于预测癌症治疗结果并分层患者群体以最大化治疗功效。

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