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1. 发明申请

WO2010141135A3 BACTERIOPHAGES EXPRESSING ANTIMICROBIAL PEPTIDES AND USES THEREOF 审中-公开
标题翻译：表达抗真菌肽的特异性及其用途
公开(公告)号：WO2010141135A3
公开(公告)日：2014-04-03
申请号：PCT/US2010026357
申请日：2010-03-05
申请人： UNIV BOSTON , MASSACHUSETTS INST TECHNOLOGY , COLLINS JAMES J , KOERIS MICHAEL , LU TIMOTHY KUAN-TA , CHAU TANGUY MY , STEPHANOPOULOS GREGORY
发明人： COLLINS JAMES J , KOERIS MICHAEL , LU TIMOTHY KUAN-TA , CHAU TANGUY MY , STEPHANOPOULOS GREGORY
IPC分类号： C12P21/06 , C07H21/04
CPC分类号： C12N7/00 , A61K35/76 , A61K38/1767 , C07K14/43504 , C07K14/43563 , C07K14/463 , C12N9/503 , C12N2795/10221 , C12N2795/10231 , C12N2795/10232 , C12N2795/12032 , C12N2795/12043 , C12N2795/14132 , C12N2795/14143
摘要： The present invention is generally related to engineered bacteriophages expressing antimicrobial peptides or lytic enymes or fragments thereof for targeting a broad spectum of bacterial hosts, and for the long-term suppression of bacterial phage resistance for reducing bacterial infections. In some embodiments, bacteriophages express antimicrobial peptides or antimicrobial polypeptides (e.g. phage lytic enzymes) which are secreted from the host bacteria, or alternatively released upon lysis of the bacterial host cell. Aspects of the present invention also relate to the use of the engineered bacteriophages for the reduction of bacterial infections, both in a subject or for bioremediation purposes, in clinical settings and wound healing.
摘要翻译：本发明通常涉及表达抗微生物肽或溶解酶或其片段的工程化噬菌体，用于靶向细菌宿主的宽谱，以及用于长期抑制细菌噬菌体抗性以减少细菌感染。在一些实施方案中，噬菌体表达从宿主细菌分泌的抗微生物肽或抗微生物多肽（例如噬菌体裂解酶），或者在细菌宿主细胞裂解时释放。本发明的方面还涉及在临床环境和伤口愈合中使用工程化噬菌体来减少细菌感染，在受试者中或用于生物修复目的。

2. 发明申请

WO2012151474A3 PROTON-MOTIVE FORCE STIMULATION TO POTENTIATE AMINOGLYCOSIDE ANTIBIOTICS AGAINST PERSISTENT BACTERIA 审中-公开
标题翻译：原始动力学刺激阻止氨基甲酸酯抗生素对抗细菌性细菌
公开(公告)号：WO2012151474A3
公开(公告)日：2013-01-10
申请号：PCT/US2012036492
申请日：2012-05-04
申请人： UNIV BOSTON , COLLINS JAMES J , ALLISON KYLE R , BRYNILDSEN MARK P
发明人： COLLINS JAMES J , ALLISON KYLE R , BRYNILDSEN MARK P
IPC分类号： A61K31/00 , A61K31/7036 , A61P31/00
CPC分类号： A61K31/7036 , A61K9/0019 , A61K31/047 , A61K31/19 , A61K31/7004 , A61K45/06 , A61K2300/00
摘要： Provided herein are compositions and methods to improve treatment of chronic infections, and reduce, delay, or inhibit formation of biofilms, using specific combinations of aminoglycoside antibiotics and high, localized concentrations of one or more PMF stimulating compounds. These novel methods are easily adapted to clinical settings as toxicity and efficacy of the antibiotics and metabolites used have already been studied in vivo, and as dosing for both the antibiotics and metabolites are known. These approaches and therapeutic methods are also useful with non-metabolic chemicals that induce proton-motive force in bacteria.
摘要翻译：本文提供了使用氨基糖苷类抗生素的特定组合以及一种或多种PMF刺激化合物的高定量浓度来改善慢性感染治疗并减少，延迟或抑制生物膜形成的组合物和方法。这些新颖的方法很容易适应于临床环境，因为所用的抗生素和代谢物的毒性和功效已经在体内进行了研究，并且因为抗生素和代谢物的给药都是已知的。这些方法和治疗方法对于在细菌中诱导质子运动力的非代谢化学物质也是有用的。

3. 发明申请

WO2011066541A3 BIOLOGICAL CIRCUIT CHEMOTACTIC CONVERTERS 审中-公开
标题翻译：生物电路化学转换器
公开(公告)号：WO2011066541A3
公开(公告)日：2011-10-20
申请号：PCT/US2010058341
申请日：2010-11-30
申请人： UNIV BOSTON , MASSACHUSETTS INST TECHNOLOGY , COLLINS JAMES J , LU TIMOTHY KUAN-TA
发明人： COLLINS JAMES J , LU TIMOTHY KUAN-TA
IPC分类号： C12N15/09 , C12N15/63 , C12Q1/02 , C12Q1/68
CPC分类号： C12N15/63 , C12N15/635
摘要： Described herein are novel biological circuit chemotactic converter that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for detecting and converting external inputs, such as chemoattractants, into outputs that allow for autonomous chemotaxis in cellular systems. Flexibility in these biological circuit chemotactic converter 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 network systems that regulate chemotactic responses based on the combination and nature of input signals received.
摘要翻译：这里描述的是利用诸如遗传拨动开关和单一转换存储器模块（SIMM）等模块化组件的新型生物电路趋化转换器，用于检测和转换诸如化学引诱剂的外部输入到允许在细胞系统中自主趋化的输出。这些生物电路趋化转换器的灵活性通过将各个模块化组件即SIMM和遗传拨动开关组合在一起来提供。这些生物转换器开关可以组合在各种网络拓扑中，以创建基于所接收的输入信号的组合和性质来调节趋化反应的网络系统。

4. 发明申请

WO2011066541A2 BIOLOGICAL CIRCUIT CHEMOTACTIC CONVERTERS 审中-公开
标题翻译：生物电路化学转换器
公开(公告)号：WO2011066541A2
公开(公告)日：2011-06-03
申请号：PCT/US2010/058341
申请日：2010-11-30
申请人： TRUSTEES OF BOSTON UNIVERSITY , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , COLLINS, James, J. , LU, Timothy Kuan-Ta
发明人： COLLINS, James, J. , LU, Timothy Kuan-Ta
IPC分类号： C12N15/09 , C12N15/63 , C12Q1/68 , C12Q1/02
CPC分类号： C12N15/63 , C12N15/635
摘要： Described herein are novel biological circuit chemotactic converter that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for detecting and converting external inputs, such as chemoattractants, into outputs that allow for autonomous chemotaxis in cellular systems. Flexibility in these biological circuit chemotactic converter 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 network systems that regulate chemotactic responses based on the combination and nature of input signals received.
摘要翻译：这里描述的是利用诸如遗传切换开关和单转化酶存储器模块（SIMM）之类的模块化组件的新型生物电路趋化转换器，用于检测外部输入（例如化学引诱物）并将其转换成允许用于细胞系统中的自主趋化。这些生物电路趋化转换器的灵活性是通过将各个模块化组件，即SIMM和遗传切换开关组合在一起提供的。这些生物转换器开关可以组合在各种网络拓扑中，以创建基于所接收的输入信号的组合和性质来调节趋化响应的网络系统。

5. 发明申请

WO2011014693A3 BACTERIOPHAGES EXPRESSING AMYLOID PEPTIDES AND USES THEREOF 审中-公开
标题翻译：表达淀粉样蛋白的特异性及其用途
公开(公告)号：WO2011014693A3
公开(公告)日：2011-06-03
申请号：PCT/US2010043770
申请日：2010-07-29
申请人： WHITEHEAD BIOMEDICAL INST , UNIV BOSTON , LU TIMOTHY KUAN-TA , LINDQUIST SUSAN , KRISHNAN RAJARAMAN , COLLINS JAMES , O'DONNELL CHARLES W , LEIGHTON BONNIE BERGER , DEVADAS SRINIVAS
发明人： LU TIMOTHY KUAN-TA , LINDQUIST SUSAN , KRISHNAN RAJARAMAN , COLLINS JAMES , O'DONNELL CHARLES W , LEIGHTON BONNIE BERGER , DEVADAS SRINIVAS
IPC分类号： C12N15/63 , A61K38/17 , A61P25/28 , C07K14/47 , C12N7/01 , C12N15/12
CPC分类号： C07K14/4711 , A61K35/76 , A61K38/00 , C07K2319/735 , C12N2795/10232 , C12N2795/10243 , C12N2795/14132 , C12N2795/14143 , A61K2300/00
摘要： The present invention generally relates to engineered bacteriophages which express amyloid peptides for the modulation (e.g. increase or decrease) of protein aggregates and amyloid formation. In some embodiments, the engineered bacteriophages express anti-amyloid peptides for inhibiting protein aggregation and amyloid formation, which can be useful in the treatment and prevention of and bacterial infections and biofilms. In some embodiments, the engineered bacteriophages express amyloid peptides for promoting amyloid formation, which are useful for increasing amyloid formation such as promoting bacterial biofilms. Other aspects relate to methods to inhibit bacteria biofilms, and methods for the treatment of amyloid related disorders, e.g., Alzheimer's disease using an anti-amyloid peptide engineered bacteriophages. Other aspects of the invention relate to engineered bacteriophages to express the amyloid peptides on the bacteriophage surface and/or secrete the amyloid peptides, e.g., anti-amyloid peptides and pro-amyloid peptides, and uses thereof for modulating protein aggregates and amyloid formation.
摘要翻译：本发明一般涉及表达淀粉样肽用于调节（例如增加或减少）蛋白质聚集体和淀粉样蛋白形成的工程化噬菌体。在一些实施方案中，工程改造的噬菌体表达用于抑制蛋白质聚集和淀粉样蛋白形成的抗淀粉样肽，其可用于治疗和预防细菌感染和生物膜。在一些实施方案中，工程改造的噬菌体表达用于促进淀粉样蛋白形成的淀粉样肽，其可用于增加淀粉样蛋白形成，例如促进细菌生物膜。其它方面涉及抑制细菌生物膜的方法，以及使用抗淀粉样蛋白肽工程化噬菌体治疗淀粉样蛋白相关病症例如阿尔茨海默氏病的方法。本发明的其它方面涉及在噬菌体表面上表达淀粉样肽和/或分泌淀粉样蛋白肽的工程化噬菌体，例如抗淀粉样肽和原淀粉状蛋白肽，以及其用于调节蛋白质聚集体和淀粉样蛋白形成的用途。

6. 发明申请

WO2010075441A1 MODULAR NUCLEIC ACID-BASED CIRCUITS FOR COUNTERS, BINARY OPERATIONS, MEMORY, AND LOGIC 审中-公开
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：WO2010075441A1
公开(公告)日：2010-07-01
申请号：PCT/US2009/069288
申请日：2009-12-22
申请人： TRUSTEES OF BOSTON UNIVERSITY , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , COLLINS, James, J. , LU, Timothy Kuan-Ta
发明人： COLLINS, James, J. , LU, Timothy Kuan-Ta
IPC分类号： C12Q1/68 , C12N15/63
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。

7. 发明申请

WO2009137136A2 IN VIVO GENE SENSORS 审中-公开
标题翻译： VIVO基因传感器
公开(公告)号：WO2009137136A2
公开(公告)日：2009-11-12
申请号：PCT/US2009/034296
申请日：2009-02-17
申请人： TRUSTEES OF BOSTON UNIVERSITY , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , COLLINS, James, J. , LU, Timothy, Kuan-Ta
发明人： COLLINS, James, J. , LU, Timothy, Kuan-Ta
IPC分类号： C12Q1/68
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。

8. 发明申请

WO2009108406A3 ENGINEERED BACTERIOPHAGES AS ADJUVANTS FOR ANTIMICROBIAL AGENTS AND COMPOSITIONS AND METHODS OF USE THEREOF 审中-公开
公开(公告)号：WO2009108406A3
公开(公告)日：2009-09-03
申请号：PCT/US2009/030755
申请日：2009-01-12
申请人： TRUSTEES OF BOSTON UNIVERSITY , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , COLLINS, James, J. , LU, Timothy, Kuan-Ta
发明人： COLLINS, James, J. , LU, Timothy, Kuan-Ta
IPC分类号： C07K14/01 , A61K35/76
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.

10. 发明申请

WO2008127345A1 MEDICATION CARTRIDGE PISTON 审中-公开
标题翻译：药品盒活塞
公开(公告)号：WO2008127345A1
公开(公告)日：2008-10-23
申请号：PCT/US2007/072173
申请日：2007-06-27
申请人： ELI LILLY AND COMPANY , ADLER, Ari, Tao , COLLINS, James, J., Jr. , COLUCCI, Jose, Jr. , JUDSON, Jared, Alden
发明人： ADLER, Ari, Tao , COLLINS, James, J., Jr. , COLUCCI, Jose, Jr. , JUDSON, Jared, Alden
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中空的主体（32），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。

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