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11. 发明授权

US08329889B2 In vivo gene sensors 有权
标题翻译：体内基因传感器
公开(公告)号：US08329889B2
公开(公告)日：2012-12-11
申请号：US12867537
申请日：2009-02-17
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： C07H21/04
CPC分类号： C12N15/1086 , C12N15/111 , C12N15/63 , C12N2310/111 , C12N2320/50
摘要： Described are methods and compositions for the detection of target genes. The inventors have developed a synthetic nucleic acid sensor-effector gene circuit. In cells without a target gene, the circuit suppresses e.g., effector production, but in the presence of the target gene the suppression is subject to competition, such that the synthetic sensor is de-repressed and permits expression of the effector gene. The methods and compositions described further permit the selective expression of an effector gene in those cells expressing the target gene. In this manner, cells expressing a target gene can be selectively targeted for treatment or elimination. In certain aspects, the methods and compositions described permit the selective expression of an agent such as a therapeutic gene product, in a specifically targeted population of cells in an organism.
摘要翻译：描述了用于检测靶基因的方法和组合物。本发明人开发了合成核酸传感器 - 效应子基因电路。在没有靶基因的细胞中，电路抑制例如效应子产生，但是在靶基因的存在下，抑制受到竞争，使得合成传感器被去抑制并且允许效应基因的表达。所描述的方法和组合物进一步允许在表达靶基因的那些细胞中选择性表达效应基因。以这种方式，表达靶基因的细胞可以选择性地靶向用于治疗或消除。在某些方面，所描述的方法和组合允许在生物体中的特定靶细胞群中选择性地表达诸如治疗性基因产物的试剂。

12. 发明授权

US08182804B1 Engineered enzymatically active bacteriophages and methods of uses thereof 有权
标题翻译：工程化酶活性噬菌体及其应用方法
公开(公告)号：US08182804B1
公开(公告)日：2012-05-22
申请号：US11662551
申请日：2005-09-12
申请人： James J Collins , Hideki Kobayashi , Mads Kearn , Michihiro Araki , Ari Friedland , Timothy Kuan-Ta Lu
发明人： James J Collins , Hideki Kobayashi , Mads Kearn , Michihiro Araki , Ari Friedland , Timothy Kuan-Ta Lu
IPC分类号： A01N63/00 , C12N15/74 , A61K48/00
CPC分类号： C12N9/2437 , A61L2/16 , C07K14/005 , C07K2319/00 , C12N7/00 , C12N2795/10222 , C12N2795/10243 , C12Y302/01004
摘要： The present invention provides engineered bacteriophages that express at least one biofilm degrading enzyme on their surface and uses thereof for degrading bacterial biofilms. The invention also provides genetically engineered bacteriophages expressing the biofilm degrading enzymes and proteins necessary for the phage to replicate in different naturally occurring biofilm producing bacteria. The phages of the invention allow a method of biofilm degradation by the use of one or only a few administration of the phage because the system using these phages is self perpetuating, and capable of degrading biofilm even when the concentration of bacteria within the biofilm is low.
摘要翻译：本发明提供了在其表面上表达至少一种生物膜降解酶的工程化噬菌体及其用于降解细菌生物膜的工程噬菌体。本发明还提供表达生物膜降解酶和蛋白质在不同天然存在的生物膜产生细菌中复制的噬菌体所需的遗传工程化噬菌体。本发明的噬菌体允许通过使用一种或仅少量的噬菌体施用来生物膜降解的方法，因为使用这些噬菌体的系统是自我延续的，并且即使当生物膜内的细菌浓度低时也能降解生物膜。

13. 发明授权

US08153119B2 Engineered enzymatically active bacteriophage and methods for dispersing biofilms 有权
标题翻译：工程化的酶活性噬菌体和分散生物膜的方法
公开(公告)号：US08153119B2
公开(公告)日：2012-04-10
申请号：US12337677
申请日：2008-12-18
申请人： James J Collins , Timothy Kuan-Ta Lu
发明人： James J Collins , Timothy Kuan-Ta Lu
IPC分类号： A01N63/00 , A61K38/43 , C12P21/06 , C12P21/04 , C12N15/09 , C12N15/00 , C12N1/00
CPC分类号： A01N63/02 , C12N7/00 , C12N9/2402 , C12N2795/10211 , C12N2795/10221 , C12N2795/10232 , C12Y207/07006 , C12Y302/01052
摘要： The present invention is directed to engineered enzymatically active bacteriophages that are both capable of killing the bacteria by lysis and dispersing the bacterial biofilm because they have been also engineered to express biofilm-degrading enzymes, particularly dispersin B (DspB), an enzyme that hydrolyzes β-1,6-N-acetyl-D-glucosamine, a crucial adhesion molecule needed for biofilm formation and integrity in Staphylococcus and E. coli, including E. coli K-12, as well as clinical isolates.
摘要翻译：本发明涉及工程化的酶活性噬菌体，其能够通过裂解和分散细菌生物膜来杀死细菌，因为它们也被工程化以表达生物降膜酶，特别是分解B（DspB），其是水解＆bgr的酶 ; -1,6-N-乙酰基-D-葡糖胺，生物膜形成所需的关键粘附分子和葡萄球菌和大肠杆菌（包括大肠杆菌K-12）以及临床分离物中的完整性。

14. 发明申请

US20100322903A1 ENGINEERED BACTERIOPHAGES AS ADJUVANTS FOR ANTIMICROBIAL AGENTS AND COMPOSITIONS AND METHODS OF USE THEREOF 有权
标题翻译：工程化杀菌剂作为抗菌药物及其组合物的使用方法及其使用方法
公开(公告)号：US20100322903A1
公开(公告)日：2010-12-23
申请号：US12812212
申请日：2009-01-12
申请人： James J Collins , Timothy Kuan-Ta Lu
发明人： James J Collins , Timothy Kuan-Ta Lu
IPC分类号： A61K35/76 , C12N7/01 , A61P31/04
CPC分类号： C07K14/005 , A61K35/76 , C12N15/113 , C12N2320/32 , C12N2330/30 , C12N2795/14122 , C12N2795/14132
摘要： The present invention relates to the treatment and prevention of bacteria and bacterial infections. In particular, the present invention relates to engineered bacteriophages used in combination with antimicrobial agents to potentiate the antimicrobial effect and bacterial killing by the antimicrobial agent. The present invention generally relates to methods and compositions comprising engineered bacteriophages and antimicrobial agents for the treatment of bacteria, and more particularly to bacteriophages comprising agents that inhibit antibiotic resistance genes and/or cell survival genes, and/or bacteriophages comprising repressors of SOS response genes or inhibitors of antimicrobial defense genes and/or expressing an agent which increases the sensitivity of bacteria to an antimicrobial agent in combination with at least one antimicrobial agent, and their use thereof.
摘要翻译：本发明涉及细菌和细菌感染的治疗和预防。特别地，本发明涉及与抗微生物剂组合使用的工程化噬菌体，以增强抗微生物效果和抗微生物剂的细菌杀伤作用。本发明一般涉及包含工程化噬菌体和用于治疗细菌的抗微生物剂的方法和组合物，更具体地涉及包含抑制抗生素抗性基因和/或细胞存活基因的试剂和/或包含SOS应答基因阻遏物的噬菌体的噬菌体或抗微生物防御基因的抑制剂和/或表达增加细菌对抗微生物剂与至少一种抗微生物剂的敏感性的试剂及其用途。

15. 发明申请

US20090312716A1 MEDICATION CARTRIDGE PISTON 审中-公开
标题翻译：药品盒活塞
公开(公告)号：US20090312716A1
公开(公告)日：2009-12-17
申请号：US12307788
申请日：2007-06-27
申请人： Ari Tao Adler , James J. Collins, JR. , Jose Colucci, JR. , Jared Alden Judson
发明人： Ari Tao Adler , James J. Collins, JR. , Jose Colucci, JR. , Jared Alden Judson
IPC分类号： A61M5/315
CPC分类号： A61M5/31513 , A61J1/065 , A61M5/31515 , A61M2005/31516
摘要： A medication cartridge piston of a cartridge for an injection device. In one form, the piston includes a body (32) formed of a first material and including an interior hollow with a rearward facing mouth allowing for insertion of a drive member of the injection device. The body includes a first portion and a second portion disposed rearwared of the first portion, a sealing gland (34) secured to the body and formed of a material that is less rigid than the first material, the sealing gland ringing at least an axial segment of the second portion and having at least one exterior periphery region for sealingly engaging an interior surface of the cartridge barrel, and the body first portion including a thrust surface (4S) within the interior hollow for direct abutment by the drive member, at least a portion of the thrust surface disposed forward of a forward edge of a forwardmost sealing gland exterior periphery region of the at least one exterior periphery region. This piston can be operatively pulled by the drive member in a forward direction within the cartridge barrel to dispense medication from the cartridge. In an alternate embodiment, a piston is provided which is adapted for use with different drive members of injection devices.
摘要翻译：用于注射装置的药筒的药筒活塞。在一种形式中，活塞包括由第一材料形成并包括具有向后的嘴的内部空腔的主体（32），其允许插入注射装置的驱动构件。本体包括第一部分和第二部分，该第一部分和第二部分设置在第一部分的后部，密封压盖（34）固定到主体并且由比第一材料刚性小的材料形成，密封压盖至少振动至少一个轴向部分并且具有用于密封地接合盒筒的内表面的至少一个外周边区域，并且主体第一部分包括内部空心内的推力表面（4S），用于由驱动构件直接邻接，至少一个推力表面的一部分设置在至少一个外周边区域的最前面的密封压盖外周边区域的前边缘的前方。该活塞可以由驱动构件在筒筒内沿向前方向可操作地拉动，以从药筒分配药物。在替代实施例中，提供适于与注射装置的不同驱动构件一起使用的活塞。

16. 发明授权

US07349739B2 Method and apparatus for neurophysiologic performance 有权
标题翻译：神经生理学表现的方法和装置
公开(公告)号：US07349739B2
公开(公告)日：2008-03-25
申请号：US10429252
申请日：2003-05-05
申请人： Jason D Harry , Stephen J Kleshinski , James B Niemi , Gregg R Draudt , Dirk Ahlgrim , James J. Collins
发明人： Jason D Harry , Stephen J Kleshinski , James B Niemi , Gregg R Draudt , Dirk Ahlgrim , James J. Collins
IPC分类号： A61N1/18
CPC分类号： A61N1/32 , A61N1/0452 , A61N1/0456 , A61N1/0472 , A61N1/0476 , A61N1/0484 , A61N1/0492 , A61N1/0551 , A61N1/08
摘要： The invention features methods and apparatus for enhancing neurophysiologic performance, such as sensorimotor control and neuroplasticity. A preferred method involves inputting bias signals to sensory cells of a subject, thereby improving sensory cell function, while the subject is performing a predefined physical activity. A system used to practice the method of the invention includes a wearable device to which is secured at least one repositionable signal input device and a signal generator that is communicatively coupled to the signal input devices.
摘要翻译：本发明的特征在于增强神经生理学性能的方法和装置，例如感觉运动控制和神经可塑性。一种优选的方法包括将偏倚信号输入到受试者的感觉细胞，从而改善感觉细胞功能，同时对象正在执行预定的身体活动。用于实施本发明的方法的系统包括可穿戴设备，至少一个可重新定位的信号输入设备和通信地耦合到信号输入设备的信号发生器。

17. 发明授权

US06737269B2 Multi-state genetic oscillator 有权
标题翻译：多态遗传振荡器
公开(公告)号：US06737269B2
公开(公告)日：2004-05-18
申请号：US09872338
申请日：2001-06-01
申请人： Timothy Gardner , James J. Collins
发明人： Timothy Gardner , James J. Collins
IPC分类号： C12N1509
CPC分类号： C12N15/635 , C12N15/63
摘要： Provided are methods and compositions for regulating gene expression in a cell. The invention provides recombinant multi-state genetic oscillators containing an adjustable-threshold genetic switch that is periodically activated by an oscillating amount of an activator agent. The activating agent is a gene product expressed from a promoter regulated by the adjustable-threshold switch and thus forms a feedback loop that causes periodic switching of the adjustable-threshold switch between an “on” state and an “off” state. Multi-state genetic oscillators are useful to express one or more genes of interest in a periodic manner without requiring a periodic application of an external activating agent.
摘要翻译：提供用于调节细胞中基因表达的方法和组合物。本发明提供了包含可调节阈值遗传开关的重组多态遗传振荡器，其由振荡量的活化剂周期性地激活。活化剂是由可调节阈值开关调节的启动子表达的基因产物，因此形成反馈环路，其导致可调节阈值开关在“接通”状态和“关闭”状态之间的周期性切换。多状态遗传振荡器可用于周期性地表达一种或多种感兴趣的基因而不需要周期性施用外部活化剂。

18. 发明授权

US09697460B2 Biological analog-to-digital and digital-to-analog converters 有权
公开(公告)号：US09697460B2
公开(公告)日：2017-07-04
申请号：US13512449
申请日：2010-11-30
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： C12P21/06 , C07H21/04 , G06N3/00 , H03M1/36 , H03M1/74
CPC分类号： G06N3/002 , H03M1/361 , H03M1/74
摘要： Described herein are novel biological converter switches that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for converting analog inputs to digital outputs, and digital inputs to analog outputs, in cells and cellular systems. Flexibility in these biological converter switches is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create circuits that act, for example, as switchboards, and regulate the production of an output product(s) based on the combination and nature of input signals received.

19. 发明授权

US09056899B2 Engineered bacteriophages as adjuvants for antimicrobial agents and compositions and methods of use thereof 有权
标题翻译：工程化噬菌体作为抗微生物剂的佐剂及其组合物及其使用方法
公开(公告)号：US09056899B2
公开(公告)日：2015-06-16
申请号：US12812212
申请日：2009-01-12
申请人： James J Collins , Timothy Kuan-Ta Lu
发明人： James J Collins , Timothy Kuan-Ta Lu
IPC分类号： A01N63/00 , C12N7/01 , C07K14/005 , A61K35/76 , C12N15/113
CPC分类号： C07K14/005 , A61K35/76 , C12N15/113 , C12N2320/32 , C12N2330/30 , C12N2795/14122 , C12N2795/14132
摘要： The present invention relates to the treatment and prevention of bacteria and bacterial infections. In particular, the present invention relates to engineered bacteriophages used in combination with antimicrobial agents to potentiate the antimicrobial effect and bacterial killing by the antimicrobial agent. The present invention generally relates to methods and compositions comprising engineered bacteriophages and antimicrobial agents for the treatment of bacteria, and more particularly to bacteriophages comprising agents that inhibit antibiotic resistance genes and/or cell survival genes, and/or bacteriophages comprising repressors of SOS response genes or inhibitors of antimicrobial defense genes and/or expressing an agent which increases the sensitivity of bacteria to an antimicrobial agent in combination with at least one antimicrobial agent, and their use thereof.
摘要翻译：本发明涉及细菌和细菌感染的治疗和预防。特别地，本发明涉及与抗微生物剂组合使用的工程化噬菌体，以增强抗微生物效果和抗微生物剂的细菌杀伤作用。本发明一般涉及包含工程化噬菌体和用于治疗细菌的抗微生物剂的方法和组合物，更具体地涉及包含抑制抗生素抗性基因和/或细胞存活基因的试剂和/或包含SOS应答基因阻遏物的噬菌体的噬菌体或抗微生物防御基因的抑制剂和/或表达增加细菌对抗微生物剂与至少一种抗微生物剂的敏感性的试剂及其用途。

20. 发明申请

US20140178864A1 MODULAR NUCLEIC ACID-BASED CIRCUITS FOR COUNTERS, BINARY OPERATIONS, MEMORY, AND LOGIC 有权
标题翻译：用于计数器，二进制运算，存储器和逻辑的基于核酸的基于电路的电路
公开(公告)号：US20140178864A1
公开(公告)日：2014-06-26
申请号：US14135009
申请日：2013-12-19
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6897 , C12N15/63 , C12N15/635 , C12Q2521/507
摘要： We have created novel engineered genetic counter designs and methods of use thereof that utilize DNA recombinases to provide modular systems, termed single invertase memory modules (SIMMs), for encoding memory in cells and cellular systems. Our designs are easily extended to compute to high numbers, by utilizing the >100 known recombinases to create subsequent modules. Flexibility in our engineered genetic counter designs is provided by daisy-chaining individual modular components, i.e., SIMMs together. These modular components of the engineered genetic counters can be combined in other network topologies to create circuits that perform, amongst other things, logic and memory. Our novel engineered genetic counter designs allow for the maintenance of memory and provide the ability to count between discrete states by expressing the recombinases between their cognate recognition sites.
摘要翻译：我们已经创建了新颖的遗传算法设计及其使用方法，其利用DNA重组酶来提供称为单一转换酶存储器模块（SIMM）的模块化系统，用于对细胞和细胞系统中的存储器进行编码。通过使用> 100个已知重组酶来创建后续模块，我们的设计可以轻松扩展到高数量计算。我们设计的基因计数器设计中的灵活性是通过菊花链连接单个模块化组件（即SIMM）来提供的。设计的遗传计数器的这些模块化组件可以组合在其他网络拓扑中，以创建执行逻辑和存储器的电路。我们的新颖设计的基因计数器设计允许维持记忆，并提供通过在其同源识别位点之间表达重组酶来提供离散状态之间的计数能力。

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