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1. 发明授权

US08361981B2 Chemo- and radiation-sensitization of cancer by antisense TRPM-2 oligodeoxynucleotides 有权
公开(公告)号：US08361981B2
公开(公告)日：2013-01-29
申请号：US12431997
申请日：2009-04-29
申请人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson , Tobias Zellweger
发明人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson , Tobias Zellweger
IPC分类号： A61K31/70 , C07H21/04
CPC分类号： A61K31/7125 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K45/06 , A61K48/00 , C07K14/775 , A61K2300/00
摘要： Administration of antisense oligodeoxynucleotides (ODN) targeted against the testosterone-repressed prostate message-2 (TRPM-2) gene can reduce the amount of TRPM-2 in renal cell cancer (RCC) cells and other cancer cells, and as a result enhance chemosensitivity of these cells to chemotherapy agents and radiation. Thus, for example, the sensitivity of renal cell cancer cells to a chemotherapeutic agent can be increased by exposing renal cell cancer cells to a chemotherapeutic agent and an agent which reduces the amount of TRPM-2 in the renal cell cancer cells. This provides an improved method for treatment of renal cell cancer, which is generally resistant to treatment with known chemotherapy agents.

2. 发明申请

US20140100261A1 TRPM-2 ANTISENSE THERAPY 有权
标题翻译： TRPM-2抗体治疗
公开(公告)号：US20140100261A1
公开(公告)日：2014-04-10
申请号：US14027693
申请日：2013-09-16
申请人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson
发明人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson
IPC分类号： C12N15/113 , A61K31/337
CPC分类号： C12N15/1135 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K41/0038 , A61K45/06 , A61K48/00 , C07H21/00 , C07K14/775 , C12N15/113 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , A61K2300/00 , C12N2310/3525
摘要： A method for treating an individual suffering from a cancer comprising administering to the individual a chemotherapeutic agent, and ii) one antisense oligonucleotide having nucleotides in the sequence set forth in Seq. ID No. 4 and which antisense oligonucleotide has a phosphorothioate modification that increases the stability thereof in vivo, wherein the cancer expresses testosterone-repressed prostate message-2 (TRPM-2), thereby treating said individual.
摘要翻译：一种用于治疗患有癌症的个体的方法，包括向所述个体施用化学治疗剂，和ii）一种具有Seq。所述序列中具有核苷酸的反义寡核苷酸。 ID No.4，反义寡核苷酸具有增加其在体内的稳定性的硫代磷酸酯修饰，其中癌症表达睾丸激素抑制前列腺消息-2（TRPM-2），从而治疗所述个体。

3. 发明申请

US20120322850A1 TRPM-2 ANTISENSE THERAPY 失效
标题翻译： TRPM-2抗体治疗
公开(公告)号：US20120322850A1
公开(公告)日：2012-12-20
申请号：US13464670
申请日：2012-05-04
申请人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Helson
发明人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Helson
IPC分类号： A61K31/713 , A61P35/00
CPC分类号： C12N15/1135 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K41/0038 , A61K45/06 , A61K48/00 , C07H21/00 , C07K14/775 , C12N15/113 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , A61K2300/00 , C12N2310/3525
摘要： It has now been determined that antisense therapy which reduces the expression of TRPM-2 provides therapeutic benefits in the treatment of cancer. Addition of antisense TRPM-2 ODN to prostatic tumor cells in vivo is effective for delaying the onset of androgen independence. Combined use of antisense TRPM-2 and taxanes synergistically enhances cytotoxic chemosensitivity of androgen-independent prostate cancer. In addition, it has also been found that antisense TRPM-2 has beneficial effect for other cancer types. Specifically, antisense TRPM-2 ODN enhances chemosensitivity in human Renal cell cancer, a normally chemoresistant disease with no active chemotherapeutic agent having an objective response rate higher than 10%. Radiation sensitivity is also enhanced when cells expressing TRPM-2 are treated with antisense TRPM-2 ODN. Thus, the antisense TRPM-2 ODNs can be used to enhance hormone sensitivity, chemosensitivity and radiation sensitivity of a variety of cancer types in which expression of TRPM-2 has been observed.
摘要翻译：现在已经确定减少TRPM-2表达的反义治疗在治疗癌症方面提供了治疗益处。反义TRPM-2 ODN在体内向前列腺肿瘤细胞的添加对于延缓雄激素独立性的发生是有效的。结合使用反义TRPM-2和紫杉烷类物质协同增强雄激素依赖性前列腺癌的细胞毒性化学敏感性。此外，还已经发现反义TRPM-2对其他癌症类型具有有益的作用。具体地，反义TRPM-2 ODN增强了人肾细胞癌的化学敏感性，这是一种没有活性化学治疗剂的客观反应率高于10％的正常化疗耐药性疾病。当用反义TRPM-2 ODN处理表达TRPM-2的细胞时，放射敏感性也增强。因此，反义TRPM-2 ODN可用于增强已经观察到TRPM-2表达的各种癌症类型的激素敏感性，化学敏感性和辐射敏感性。

4. 发明申请

US20120055909A1 METHOD OF LASER-WELDING AND METHOD OF MANUFACTURING BATTERY INCLUDING THE SAME 审中-公开
标题翻译：激光焊接方法及其制造方法
公开(公告)号：US20120055909A1
公开(公告)日：2012-03-08
申请号：US13319700
申请日：2009-05-15
申请人： Hideaki Miyake , Takahiro Oshima
发明人： Hideaki Miyake , Takahiro Oshima
IPC分类号： B23K26/00
CPC分类号： B23K26/32 , B21K25/00 , B23K26/123 , B23K26/28 , B23K26/3584 , B23K26/60 , B23K33/00 , H01M2/26 , H01M2/30 , H01M10/0525
摘要： Provided is a method of laser-welding that can achieve uniform welding of a member with large laser reflectance on a surface thereof A laser welding step (S1) includes a surface roughening step (S11) in which a first laser processing device irradiates laser light to a surface (each welding portion (31)) of a welding section (30, 30, 30, 30) between a negative electrode terminal (20) (a first member) and a negative electrode lead (21) (a second member) and carries out roughening, thereby forming a laser marker (32) on the surface; and a welding step (S12) in which a second laser processing device irradiates laser light to each welding portion (31) roughened in the surface roughening step (S11) and melts each welding portion (31), thereby carrying out the laser-welding of the negative electrode terminal (20) to the negative electrode lead (21).
摘要翻译：本发明提供一种激光焊接方法，其可以实现在其表面上具有大的激光反射率的部件的均匀焊接。激光焊接步骤（S1）包括表面粗糙化步骤（S11），其中第一激光加工装置将激光照射到在负极端子（20）（第一部件）和负极引线（21）（第二部件）之间的焊接部分（30,30,30,30）的表面（每个焊接部分（31））和进行粗糙化，从而在表面上形成激光标记（32）以及焊接工序（S12），其中第二激光加工装置向在表面粗糙化工序（S11）中粗化的各焊接部分（31）照射激光，熔化各焊接部（31），由此进行激光焊接负极端子（20）连接到负极引线（21）。

5. 发明授权

US07896278B2 Winding apparatus 有权
标题翻译：卷绕装置
公开(公告)号：US07896278B2
公开(公告)日：2011-03-01
申请号：US12279209
申请日：2007-10-10
申请人： Hideaki Miyake , Shingo Hashimoto
发明人： Hideaki Miyake , Shingo Hashimoto
IPC分类号： B65H51/20 , H02K15/04
CPC分类号： H02K15/0435
摘要： A wiring apparatus includes a spool; an annular reel surrounding the spool to be rotatable about an axis common with the spool, the reel being previously wound with a wire in layers to be wound on the spool; a winding arm for guiding the wire from the reel to the spool and placed outside the reel so as to be movable around the spool about the axis; a first motor and others for driving the winding arm and others to move around the spool to wind the wire on the spool; and a second motor and others for driving the reel to rotate on the axis to unreel the wire of a required length from the reel during driving of the first motor.
摘要翻译：布线装置包括：卷轴; 围绕卷轴的环形卷轴可围绕与卷轴共同的轴线旋转，卷轴预先用导线卷绕成卷绕在卷轴上的层; 用于将所述线从所述卷轴引导到所述卷轴并且绕在所述卷轴外侧以绕所述卷轴绕所述轴线运动的卷绕臂; 一个第一马达和其他驱动绕组臂和其他的绕线轴移动以将线缠绕在线轴上; 以及第二电动机和其他驱动卷轴以在轴线旋转以在第一电动机的驱动期间从卷轴退出所需长度的电线。

6. 发明授权

US06900187B2 TRPM-2 antisense therapy using an oligonucleotide having 2′-O-(2-methoxy)ethyl modifications 失效
标题翻译：使用具有2'-O-（2-甲氧基）乙基修饰的寡核苷酸的TRPM-2反义治疗
公开(公告)号：US06900187B2
公开(公告)日：2005-05-31
申请号：US10080794
申请日：2002-02-22
申请人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson , Brett P. Monia
发明人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson , Brett P. Monia
IPC分类号： C12N15/09 , A61K31/00 , A61K31/136 , A61K31/337 , A61K31/66 , A61K31/704 , A61K31/7125 , A61K38/00 , A61K41/00 , A61K45/00 , A61K45/06 , A61K48/00 , A61P43/00 , C07H21/00 , C07K14/775 , C12N15/113 , A61K31/70
CPC分类号： C12N15/113 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K41/0038 , A61K45/06 , A61K48/00 , C07H21/00 , C07K14/775 , C12N15/1135 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2310/3525 , A61K2300/00
摘要： A compound consisting of an oligonucleotide of sequence CAGCAGCAGAGTCTTCATCAT, where the oligonucleotide has a phosphorothioate backbone throughout, the sugar moieties of nucleotides 1-4 and 18-21 bear 2′-O-methoxyethyl modifications, and the remaining nucleotides (nucleotides 5-17) are 2′-deoxynucleotides, and where the cytosines of nucleotides 1, 4 and 19 are 5-methylcytosines. The compound has increased stability in vivo and improved in vitro and in vivo antitumor activity.
摘要翻译：由序列CAGCAGCAGAGTCTTCATCAT的寡核苷酸组成的化合物，其寡核苷酸全部具有硫代磷酸酯主链，核苷酸1-4和18-21的糖部分具有2'-O-甲氧基乙基修饰，剩余的核苷酸（核苷酸5-17）是2'-脱氧核苷酸，其中核苷酸1,4和19的胞嘧啶是5-甲基胞嘧啶。该化合物具有增加的体内稳定性和改善的体外和体内抗肿瘤活性。

7. 发明授权

US4596315A Disc brake device 失效
标题翻译：盘式制动装置
公开(公告)号：US4596315A
公开(公告)日：1986-06-24
申请号：US644408
申请日：1984-08-27
申请人： Hiroo Takeuchi , Hideaki Miyake , Yoshito Hanazato , Kimio Koyano
发明人： Hiroo Takeuchi , Hideaki Miyake , Yoshito Hanazato , Kimio Koyano
IPC分类号： F16D65/18 , F16D55/227 , F16D65/14 , F16D65/56
CPC分类号： F16D65/18 , F16D55/227 , F16D65/567 , F16D2121/02 , F16D2121/14 , F16D2123/00 , F16D2125/26
摘要： A disc brake device including a piston, an automatic adjuster and a sleeve piston within the cylinder of a caliper body, wherein braking and automatic braking-gap adjustment are achieved by a hydraulic input, and said piston is pushed by a mechanical input through said sleeve piston and said automatic adjuster for braking.
摘要翻译：一种盘式制动装置，包括活塞，自动调节器和套筒活塞，其位于制动钳体的气缸内，其中通过液压输入实现制动和自动制动间隙调节，并且所述活塞由机械输入件通过所述套筒活塞和所述自动调节器用于制动。

8. 发明授权

US09095602B2 Chemo- and radiation-sensitization of cancer by antisense TRPM-2 oligodeoxynucleotides 有权
公开(公告)号：US09095602B2
公开(公告)日：2015-08-04
申请号：US13737630
申请日：2013-01-09
申请人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson , Tobias Zellweger
发明人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson , Tobias Zellweger
IPC分类号： C12N15/113 , A61K31/7125 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K45/06 , C07K14/775 , A61K48/00
CPC分类号： A61K31/7125 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K45/06 , A61K48/00 , C07K14/775 , A61K2300/00
摘要： Administration of antisense oligodeoxynucleotides (ODN) targeted against the testosterone-repressed prostate message-2 (TRPM-2) gene can reduce the amount of TRPM-2 in renal cell cancer (RCC) cells and other cancer cells, and as a result enhance chemosensitivity of these cells to chemotherapy agents and radiation. Thus, for example, the sensitivity of renal cell cancer cells to a chemotherapeutic agent can be increased by exposing renal cell cancer cells to a chemotherapeutic agent and an agent which reduces the amount of TRPM-2 in the renal cell cancer cells. This provides an improved method for treatment of renal cell cancer, which is generally resistant to treatment with known chemotherapy agents.

9. 发明授权

US08173615B2 TRPM-2 antisense therapy 有权
标题翻译： TRPM-2反义治疗
公开(公告)号：US08173615B2
公开(公告)日：2012-05-08
申请号：US12753995
申请日：2010-04-05
申请人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson
发明人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson
IPC分类号： A61K31/70 , C07H21/04
CPC分类号： C12N15/1135 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K41/0038 , A61K45/06 , A61K48/00 , C07H21/00 , C07K14/775 , C12N15/113 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , A61K2300/00 , C12N2310/3525
摘要： It has now been determined that antisense therapy which reduces the expression of TRPM-2 provides therapeutic benefits in the treatment of cancer. In particular, such antisense therapy can be applied in treatment of prostate cancer and renal cell cancer. Addition of antisense TRPM-2 ODN to prostatic tumor cells in vivo is effective for delaying the onset of androgen independence. Thus, prostate cancer can be treated in an individual suffering from prostate cancer by initiating androgen-withdrawal to induce apoptotic cell death of prostatic tumor cells in the individual, and administering to the individual a composition effective to inhibit expression of TRPM-2 by the tumor cells, thereby delaying the progression of prostatic tumor cells to an androgen-independent state in an individual. Combined use of antisense TRPM-2 and taxanes synergistically enhances cytotoxic chemosensitivity of androgen-independent prostate cancer. In addition, it has also been found that antisense TRPM-2 has beneficial effect for other cancer types. Specifically, antisense TRPM-2 ODN enhances chemosensitivity in human Renal cell cancer, a normally chemoresistant disease with no active chemotherapeutic agent having an objective response rate higher than 10%. Radiation sensitivity is also enhanced when cells expressing TRPM-2 are treated with antisense TRPM-2 ODN. Thus, the antisense TRPM-2 ODNs can be used to enhance hormone sensitivity, chemosensitivity and radiation sensitivity of a variety of cancer types in which expression of TRPM-2 has been observed.
摘要翻译：现在已经确定减少TRPM-2表达的反义治疗在治疗癌症方面提供了治疗益处。特别地，这种反义治疗可以应用于前列腺癌和肾细胞癌的治疗。反义TRPM-2 ODN在体内向前列腺肿瘤细胞的添加对于延缓雄激素独立性的发生是有效的。因此，前列腺癌可以通过引发雄激素停止以诱导个体中前列腺肿瘤细胞的凋亡性细胞死亡而在患有前列腺癌的个体中治疗，并且向该个体施用有效抑制肿瘤中TRPM-2表达的组合物细胞，从而将前列腺肿瘤细胞的进展延迟到个体中与雄激素无关的状态。结合使用反义TRPM-2和紫杉烷类物质协同增强雄激素依赖性前列腺癌的细胞毒性化学敏感性。此外，还已经发现反义TRPM-2对其他癌症类型具有有益的作用。具体地，反义TRPM-2 ODN增强了人肾细胞癌的化学敏感性，这是一种没有活性化学治疗剂的客观反应率高于10％的正常化疗耐药性疾病。当用反义TRPM-2 ODN处理表达TRPM-2的细胞时，放射敏感性也增强。因此，反义TRPM-2 ODN可用于增强已经观察到TRPM-2表达的各种癌症类型的激素敏感性，化学敏感性和辐射敏感性。

10. 发明授权

US07534773B1 TRPM-2 antisense therapy 失效
标题翻译： TRPM-2反义治疗
公开(公告)号：US07534773B1
公开(公告)日：2009-05-19
申请号：US09913325
申请日：2000-02-25
申请人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson
发明人： Martin Gleave , Paul S. Rennie , Hideaki Miyake , Colleen Nelson
IPC分类号： A61K31/70 , C07H21/04
CPC分类号： C12N15/1135 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K41/0038 , A61K45/06 , A61K48/00 , C07H21/00 , C07K14/775 , C12N15/113 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , A61K2300/00 , C12N2310/3525
摘要： Antisense therapy which reduces the expression of TRPM-2 provides therapeutic benefits in the treatment of cancer for example prostate cancer and renal cell cancer. Antisense TRPM-2 ODN treatment of prostatic tumor cells in vivo is effective for delaying the onset of androgen independence and can be used in combination with androgen-withdrawal to induce apoptotic cell death of prostatic tumor cells in the individual. Combined use of antisense TRPM-2 and taxanes synergistically enhances cytotoxic chemosensitivity of androgen-independent prostate cancer. Radiation sensitivity is also enhanced when cells expressing TRPM-2 are treated with antisense TRPM-2 ODN. Thus, the antisense TRPM-2 ODNs can be used to enhance hormone sensitivity, chemosensitivity and radiation sensitivity of a variety of cancer types in which expression of TRPM-2 has been observed.
摘要翻译：降低TRPM-2表达的反义疗法在治疗癌症中具有治疗益处，例如前列腺癌和肾细胞癌。反义TRPM-2 ODN治疗前列腺肿瘤细胞在体内是有效的延迟雄激素独立的发作，可以与雄激素停用联合使用以诱导个体前列腺肿瘤细胞的凋亡性细胞死亡。结合使用反义TRPM-2和紫杉烷类物质协同增强雄激素依赖性前列腺癌的细胞毒性化学敏感性。当用反义TRPM-2 ODN处理表达TRPM-2的细胞时，放射敏感性也增强。因此，反义TRPM-2 ODN可用于增强已经观察到TRPM-2表达的各种癌症类型的激素敏感性，化学敏感性和辐射敏感性。

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