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1. 发明授权

US08859492B2 Metallodrugs having improved pharmacological properties, and methods of manufacture and use thereof 有权
标题翻译：具有改善的药理学性质的金属药物及其制造和使用方法
公开(公告)号：US08859492B2
公开(公告)日：2014-10-14
申请号：US13470299
申请日：2012-05-12
申请人： James A. Cowan , Ada S. Cowan , Donna T. Palmer
发明人： James A. Cowan , Ada S. Cowan , Donna T. Palmer
IPC分类号： C07K19/00 , C07K7/08 , C07K14/46 , C07K2/00 , A61K38/05 , A61K38/10 , A61K38/17 , A61K38/08 , A61P31/00 , C07K5/068 , C07K1/113 , A61K47/48 , C07K7/06 , C07K5/02 , C07H23/00 , A61K38/00
CPC分类号： C07K14/825 , A61K31/424 , A61K38/00 , A61K38/10 , A61K38/16 , A61K47/547 , C07F17/02 , C07H21/00 , C07H23/00 , C07K5/022 , C07K7/06 , C07K2319/20 , C07K2319/70
摘要： It is an object of the present invention to provide improved pharmacological properties to molecules which bind to a target with low affinity (hereinafter referred to as a “ligand moiety”) through linkage of such molecules to a metal binding moiety, thereby generating a combination molecule commonly referred to as a “metallodrug” or “metallotherapeutic.” The metal binding domain of metallodrugs typically catalyzes oxido-reductase chemistry or acts as a Lewis-Acid catalyst, resulting in modification of proteins and nucleic acids that are in close proximity due to binding of the ligand moiety to its target.
摘要翻译：本发明的目的是通过将这些分子连接到金属结合部分来提供与具有低亲和力的靶（以下称为“配体部分”）结合的分子的改善的药理学性质，由此产生组合分子通常称为“金属药物”或“金属治疗剂”。金属药物的金属结合结构域通常催化氧化还原酶化学或作为路易斯酸催化剂，从而导致由于结合而接近的蛋白质和核酸的修饰的配体部分。

2. 发明申请

US20120144635A1 METHODS AND SYSTEMS FOR MANUFACTURING AN AXLE 审中-公开
标题翻译：制造轴的方法和系统
公开(公告)号：US20120144635A1
公开(公告)日：2012-06-14
申请号：US13361756
申请日：2012-01-30
申请人： Richard Gerard Potje , Timothy Dunagan , Jon Edmond Meyer , James A. Cowan
发明人： Richard Gerard Potje , Timothy Dunagan , Jon Edmond Meyer , James A. Cowan
IPC分类号： B23P23/04 , B23P23/06 , B23Q7/00 , B21C43/00
CPC分类号： B23P15/00 , B21J1/06 , B21J5/00 , B21J17/00 , B21K1/10 , C21D1/25 , C21D1/28 , C21D1/62 , C21D1/78 , C21D7/13 , C21D9/28 , F27B9/16 , Y10T29/45 , Y10T29/4544 , Y10T29/49771 , Y10T29/49826 , Y10T29/49829 , Y10T29/49995 , Y10T29/49998 , Y10T29/53022 , Y10T29/534 , Y10T29/53539 , Y10T29/53548
摘要： A continuous system for automatically manufacturing an axle is provided. The system includes a plurality of sub-systems and an automated transport system. The plurality of sub-systems includes a furnace configured to heat a billet to a predetermined forging temperature, a forging system configured to forge an axle from a heated billet, and a machining system configured to form a machined axle from said axle. The automated transport system is configured to automatically transport a product to and from each of the plurality of sub-systems. The product includes the billet, the axle, and the machined axle.
摘要翻译：提供了一种用于自动制造轴的连续系统。该系统包括多个子系统和自动运输系统。所述多个子系统包括构造成将坯料加热到预定锻造温度的炉子，被配置为从加热坯料锻造轴的锻造系统以及被构造成从所述轴部形成加工轴的加工系统。自动传送系统被配置为自动地将产品传送到多个子系统中的每一个子系统。该产品包括坯料，轴和加工轴。

3. 发明申请

US20090320263A1 METHODS AND SYSTEMS FOR MANUFACTURING AN AXLE 有权
标题翻译：制造轴的方法和系统
公开(公告)号：US20090320263A1
公开(公告)日：2009-12-31
申请号：US12146776
申请日：2008-06-26
申请人： Richard Gerard Potje , Timothy Dunagan , Jon Edmond Meyer , James A. Cowan
发明人： Richard Gerard Potje , Timothy Dunagan , Jon Edmond Meyer , James A. Cowan
IPC分类号： B23P11/00 , B23P19/00
CPC分类号： B23P15/00 , B21J1/06 , B21J5/00 , B21J17/00 , B21K1/10 , C21D1/25 , C21D1/28 , C21D1/62 , C21D1/78 , C21D7/13 , C21D9/28 , F27B9/16 , Y10T29/45 , Y10T29/4544 , Y10T29/49771 , Y10T29/49826 , Y10T29/49829 , Y10T29/49995 , Y10T29/49998 , Y10T29/53022 , Y10T29/534 , Y10T29/53539 , Y10T29/53548
摘要： A method for manufacturing an axle is provided. The method includes heating a billet at a heating station to a predetermined temperature, forging the heated billet at a forging station to form an axle, and machining the axle at a machining station to form a machined axle. A product is automatically transported to and from each station using a product transport system, wherein the product includes the billet, the axle and the machined axle.
摘要翻译：提供一种制造轴的方法。该方法包括将加热站的坯料加热到预定温度，在锻造站锻造加热坯料以形成轴，并且在加工台处加工轴以形成加工轴。产品使用产品运输系统自动运往每个车站，其中产品包括坯料，轴和加工轴。

4. 发明申请

US20120289454A1 METALLODRUGS HAVING IMPROVED PHARMACOLOGICAL PROPERTIES, AND METHODS OF MANUFACTURE AND USE THEREOF 有权
标题翻译：具有改善的药理特性的金属及其制造方法及其用途
公开(公告)号：US20120289454A1
公开(公告)日：2012-11-15
申请号：US13470299
申请日：2012-05-12
申请人： James A. Cowan , Ada S. Cowan , Donna T. Palmer
发明人： James A. Cowan , Ada S. Cowan , Donna T. Palmer
IPC分类号： C07K19/00 , C07K7/08 , C07K14/46 , C07H23/00 , C07K2/00 , C07H1/00 , C12N9/99 , A61K38/05 , A61K38/10 , A61K38/17 , A61K38/08 , A61P31/00 , C07K5/068 , C07K1/113
CPC分类号： C07K14/825 , A61K31/424 , A61K38/00 , A61K38/10 , A61K38/16 , A61K47/547 , C07F17/02 , C07H21/00 , C07H23/00 , C07K5/022 , C07K7/06 , C07K2319/20 , C07K2319/70
摘要： It is an object of the present invention to provide improved pharmacological properties to molecules which bind to a target with low affinity (hereinafter referred to as a “ligand moiety”) through linkage of such molecules to a metal binding moiety, thereby generating a combination molecule commonly referred to as a “metallodrug” or “metallotherapeutic.” The metal binding domain of metallodrugs typically catalyzes oxido-reductase chemistry or acts as a Lewis-Acid catalyst, resulting in modification of proteins and nucleic acids that are in close proximity due to binding of the ligand moiety to its target.
摘要翻译：本发明的一个目的是通过将这些分子连接到金属结合部分来提供与具有低亲和力的靶（以下称为配体部分）结合的分子的改进的药理学性质，由此产生通常称为的组合分子作为金属药物或金属治疗剂。金属药物的金属结合结构域通常催化氧化还原酶化学或用作路易斯酸催化剂，导致由于配体部分与其靶标的结合而非常接近的蛋白质和核酸的修饰。

5. 发明申请

US20080188422A1 Ligands Having Metal Binding Ability and Targeting Properties 有权
标题翻译：具有金属结合能力和靶向性质的配体
公开(公告)号：US20080188422A1
公开(公告)日：2008-08-07
申请号：US11569919
申请日：2005-06-01
申请人： James A. Cowan , Yan Jin , Seth Bradford , Nikhil Gokhale , Ada Cowan , Chun-An Chen
发明人： James A. Cowan , Yan Jin , Seth Bradford , Nikhil Gokhale , Ada Cowan , Chun-An Chen
IPC分类号： A61K38/00 , C07K14/00 , C07D257/00 , A61P9/00 , A61P3/10 , A61P37/00 , C07K7/00
CPC分类号： A61K47/64
摘要： Ligands having a metal binding domain and a targeting domain are provided. The ligands can be used to target, inhibit, and catalytically degrade or inactivate a desired target. Methods of treating a disease or condition using the ligands are also provided.
摘要翻译：提供了具有金属结合结构域和靶向结构域的配体。配体可用于靶向，抑制和催化降解或灭活所需靶。还提供了使用配体治疗疾病或病症的方法。

6. 发明授权

US06403777B1 Metalloligands for cleaving nucleic acids 失效
标题翻译：用于切割核酸的金属配体
公开(公告)号：US06403777B1
公开(公告)日：2002-06-11
申请号：US09348225
申请日：1999-07-06
申请人： James A. Cowan
发明人： James A. Cowan
IPC分类号： C07H1500
CPC分类号： C07H23/00
摘要： Transition metal complexes, referred to hereinafter as “metalloligands”, that catalyze the degradation of DNA and the cleavage of RNA at select sites are provided. In one embodiment, the metalloligand has the following structure: wherein R1 is an amino group, i.e. an NH, or an alkylamino group comprising 1 or 2 carbon atoms; wherein R2 is selected from the group consisting of an amino group, a hydroxyl group, i.e., O(H), an alkylamino group comprising 1 or 2 carbon atoms; and an alkylhydroxyl group comprising 1 or 2 carbon atoms; wherein J is a ligand which comprises at least one carbon-containing five-membered or six-membered ring structure; and wherein M is a transition metal ion which is bound via coordinate bonds to R1 and R2. In another embodiment the metalloligand has the following structure: wherein R1′ and R1″ are the same or different and wherein R1′ and R1″ are an amino group or an alkylamino group comprising 1 or 2 carbon atoms; wherein R2′ and R2″ are the same or different and wherein R2′ and R2″ are selected from the group consisting of an amino group, a hydroxyl group, an alkylamino group comprising 1 or 2 carbon atoms, and an alkylhydroxyl group comprising one or two carbon atoms; wherein J′ and J″ are the same or different and wherein J′ and J″ are ligands which comprise at least one carbon-containing five-membered or six-membered ring structure; and wherein M is a transition metal ion which is bound via coordinate bonds to R1′, R1″, R2′ and R2″. Methods of cleaving nucleic acids using the metalloligands are also provided.
摘要翻译：提供了以下称为“金属配体”的过渡金属络合物，其催化DNA的降解和选择位点处的RNA的切割。在一个实施方案中，金属配体具有以下结构：其中R 1是氨基，即NH，或包含1或2个碳原子的烷基氨基; 其中R2选自氨基，羟基，即O（H），含有1或2个碳原子的烷基氨基; 和含有1或2个碳原子的烷基羟基; 其中J是包含至少一个含碳的五元或六元环结构的配体; 并且其中M是通过配位键与R 1和R 2结合的过渡金属离子。在另一个实施方案中，金属配体具有以下结构：其中R1'和R1“相同或不同，并且其中R1'和R1” 氨基或含有1或2个碳原子的烷基氨基; 其中R2'和R2“相同或不同，并且其中R2'和R2”选自氨基，羟基，包含1或2个碳原子的烷基氨基，和烷基羟基，包括一个或两个碳原子; 其中J'和J“相同或不同，并且其中J'和J”是包含至少一个含碳五元或六元环结构的配体; 并且其中M是通过配位键与R1'，R1“，R2'和R2”结合的过渡金属离子。还提供了使用金属配体切割核酸的方法。

7. 发明授权

US08122580B2 Methods for manufacturing an axle 有权
标题翻译：轴的制造方法
公开(公告)号：US08122580B2
公开(公告)日：2012-02-28
申请号：US12146776
申请日：2008-06-26
申请人： Richard Gerard Potje , Timothy Dunagan , Jon Edmond Meyer , James A. Cowan
发明人： Richard Gerard Potje , Timothy Dunagan , Jon Edmond Meyer , James A. Cowan
IPC分类号： B23P25/00 , B23P17/00 , B23Q7/00 , C21D8/00
CPC分类号： B23P15/00 , B21J1/06 , B21J5/00 , B21J17/00 , B21K1/10 , C21D1/25 , C21D1/28 , C21D1/62 , C21D1/78 , C21D7/13 , C21D9/28 , F27B9/16 , Y10T29/45 , Y10T29/4544 , Y10T29/49771 , Y10T29/49826 , Y10T29/49829 , Y10T29/49995 , Y10T29/49998 , Y10T29/53022 , Y10T29/534 , Y10T29/53539 , Y10T29/53548
摘要： A method for manufacturing an axle is provided. The method includes heating a billet at a heating station to a predetermined temperature, forging the heated billet at a forging station to form an axle, and machining the axle at a machining station to form a machined axle. A product is automatically transported to and from each station using a product transport system, wherein the product includes the billet, the axle and the machined axle.
摘要翻译：提供一种制造轴的方法。该方法包括将加热站的坯料加热到预定温度，在锻造站锻造加热坯料以形成轴，并且在加工台处加工轴以形成加工轴。产品使用产品运输系统自动运往每个车站，其中产品包括坯料，轴和加工轴。

8. 发明授权

US08445431B2 Ligands having metal binding ability and targeting properties 有权
标题翻译：具有金属结合能力和靶向特性的配体
公开(公告)号：US08445431B2
公开(公告)日：2013-05-21
申请号：US11569919
申请日：2005-06-01
申请人： James A. Cowan , Yan Jin , Seth Bradford , Nikhil Gokhale , Ada Cowan , Chun-An Chen
发明人： James A. Cowan , Yan Jin , Seth Bradford , Nikhil Gokhale , Ada Cowan , Chun-An Chen
IPC分类号： A61P31/18 , A61K38/03
CPC分类号： A61K47/64
摘要： Ligands having a metal binding domain and a targeting domain are provided. The ligands can be used to target, inhibit, and catalytically degrade or inactivate a desired target. Methods of treating a disease or condition using the ligands are also provided.
摘要翻译：提供了具有金属结合结构域和靶向结构域的配体。配体可用于靶向，抑制和催化降解或灭活所需靶。还提供了使用配体治疗疾病或病症的方法。

9. 发明授权

US6138578A Freight container ventilation system 失效
标题翻译：货运集装箱通风系统
公开(公告)号：US6138578A
公开(公告)日：2000-10-31
申请号：US024810
申请日：1998-02-17
申请人： James A. Cowan, Jr. , Michael D. Gaikowski , John K. Deveikis , Richard J. Kloster
发明人： James A. Cowan, Jr. , Michael D. Gaikowski , John K. Deveikis , Richard J. Kloster
IPC分类号： B61D27/00 , B61D11/00 , B61D3/00
CPC分类号： B61D27/009
摘要： A ventilated transportable freight container is disclosed. The container is ventilated by natural convection through at least one lower side vent comprising a lower plenum chamber for distributing air into the container and restricting entry of moisture in the form of rain, sleet or snow into the container and at least one upper top vent, including a plenum chamber. The upper top vent or vents may be formed in the sidewall of the enclosure or in the roof of the enclosure depending upon the structure of the container and the particular application. The use of one or more upper top vents enhances circulation of air by natural convection. The invention also incorporates sidewall and endwall spacers extending from the sidewalls and endwalls into the enclosure to provide passageways for the circulation of air to ventilate the enclosure and a path for condensation drainage. In one embodiment of the invention, the transportable freight container of present invention comprises a rail freight car. In another embodiment of the invention, at least one of the lower plenum chambers of the container extends lower than the floor of the enclosure to allow drainage from the enclosure. The container may also incorporate a layer of insulating material on the interior surface of the roof of the container to inhibit condensation of moisture. The freight container of the present invention is particularly adapted to the transport of baled material, such as pulp, which is typically shipped or transported in bales of approximately one cubic yard.
摘要翻译：公开了一种通风运输货物集装箱。容器通过自然对流通过至少一个下侧通风口通风，该至少一个下侧通风口包括用于将空气分配到容器中的下部增压室，并限制雨水，雨夹雪或雪形式的水分进入容器和至少一个上部顶部排气口，包括一个集会厅。根据容器的结构和特定应用，顶部顶部通风孔或通风口可以形成在外壳的侧壁或外壳的顶部中。使用一个或多个上部顶部通风口可以通过自然对流增强空气的循环。本发明还包括从侧壁和端壁延伸到外壳中的侧壁和端壁间隔件，以提供用于循环空气以使外壳通风和冷凝排水路径的通道。在本发明的一个实施例中，本发明的可运输货物集装箱包括铁路货车。在本发明的另一个实施例中，容器的下部增压室中的至少一个延伸低于外壳的底板，以允许从外壳排出。容器还可以在容器的顶部的内表面上并入绝缘材料层，以抑制水分的冷凝。本发明的货物容器特别适用于运输包装材料，例如纸浆，其通常以大约一立方码包的方式运输或运输。

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