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11. 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。

12. 发明授权

US09074209B2 TRPM-2 antisense therapy 有权
标题翻译： TRPM-2反义治疗
公开(公告)号：US09074209B2
公开(公告)日：2015-07-07
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 , A61K31/00 , A61K31/337 , A61K31/66 , A61K31/704 , A61K41/00 , A61K45/06 , C07H21/00 , C07K14/775 , A61K48/00
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： A method for treating an individual suffering from a cancer comprising administering to the individual i) 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，包括向个体施用i）化学治疗剂，和ii）一种具有Seq。所列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。

13. 发明授权

US08536149B2 TRPM-2 antisense therapy 失效
标题翻译： TRPM-2反义治疗
公开(公告)号：US08536149B2
公开(公告)日：2013-09-17
申请号：US13464670
申请日：2012-05-04
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 , 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. 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。

14. 发明授权

US07732422B2 TRPM-2 antisense therapy 失效
标题翻译： TRPM-2反义治疗
公开(公告)号：US07732422B2
公开(公告)日：2010-06-08
申请号：US11875226
申请日：2007-10-19
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. Seq ID No. 4 (cagcagcagagtcttcatcat) is an antisense oligonucleotide which inhibits expression of TRPM-2 by tumor cells, and which can be combined with a pharmaceutically acceptable carrier suitable for human administration.
摘要翻译：降低TRPM-2表达的反义疗法在治疗癌症方面提供治疗益处。 Seq ID No.4（cagcagcagagtcttcatcat）是抑制肿瘤细胞表达TRPM-2的反义寡核苷酸，其可以与适于人给药的药学上可接受的载体组合。

15. 发明授权

US07196067B2 Antisense insulin-like growth factor binding protein (IGFBP)-2-oligodeoxynucleotides for prostate and other endocrine tumor therapy 有权
标题翻译：用于前列腺和其他内分泌肿瘤治疗的反义胰岛素样生长因子结合蛋白（IGFBP）-2-寡脱氧核苷酸
公开(公告)号：US07196067B2
公开(公告)日：2007-03-27
申请号：US10380195
申请日：2001-09-13
申请人： Martin Gleave , Paul S. Rennie , Kiyama Satoshi , Colleen Nelson
发明人： Martin Gleave , Paul S. Rennie , Kiyama Satoshi , Colleen Nelson
IPC分类号： A61K31/70 , C07H21/04
CPC分类号： C12N15/113 , A61K38/00 , A61K48/00 , C07K14/4743
摘要： Compositions and a method are provided for the treatment of prostate and other endocrine tumors in mammals, including humans, by administration of an antisense oligodeoxynucleotide (ODN) which is complementary to a portion of the gene encoding IGFBP-2. Using the Shionogi tumor model in vitro and in vivo, the administration of such an ODN was shown to reduce proliferation of tumor cells, and also to delay the progression to androgen independence. Thus, treatment of prostate and other hormone-regulated cancer in mammals, including humans, and delay of the progression of prostate tumors to androgen independence is accomplished by administering to the mammal a therapeutically effective amount of an antisense oligodeoxynucleotide which is complementary to a portion of the nucleic acid sequence encoding IGFBP-2 and which reduces the amount of IGFBP-2 in the treated cells.
摘要翻译：提供组合物和方法，用于通过施用与编码IGFBP-2的基因的一部分互补的反义寡脱氧核苷酸（ODN）来治疗哺乳动物（包括人）中的前列腺和其它内分泌肿瘤。在体外和体内使用Shionogi肿瘤模型，这种ODN的施用显示可以减少肿瘤细胞的增殖，并且也延缓进展到雄激素的独立性。因此，通过向哺乳动物施用治疗有效量的反义寡脱氧核苷酸来实现哺乳动物（包括人）中前列腺和其他激素调节癌症的治疗以及前列腺肿瘤进展到雄激素独立性的治疗，所述反义寡脱氧核苷酸与编码IGFBP-2的核酸序列并减少处理细胞中IGFBP-2的量。

16. 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。

17. 发明申请

US20080064651A1 TRPM-2 Antisense Therapy 失效
标题翻译： TRPM-2反义治疗
公开(公告)号：US20080064651A1
公开(公告)日：2008-03-13
申请号：US11875226
申请日：2007-10-19
申请人： Martin Gleave , Paul Rennie , Hideaki Miyake , Colleen Nelson
发明人： Martin Gleave , Paul Rennie , Hideaki Miyake , Colleen Nelson
IPC分类号： A61K31/7088 , A61P35/00 , C07H21/02
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组合使用反义TRPM-2和紫杉烷类药物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。

18. 发明授权

US07297684B1 Antisense therapy for hormone-regulated tumors 有权
标题翻译：激素调节性肿瘤的反义疗法
公开(公告)号：US07297684B1
公开(公告)日：2007-11-20
申请号：US09619908
申请日：2000-07-19
申请人： Martin Gleave , Hideaki Miyake
发明人： Martin Gleave , Hideaki Miyake
IPC分类号： A01N43/04 , A61K31/70 , C07H21/04 , C12Q1/68 , C12N5/00
CPC分类号： C12N15/113 , A61K38/00 , C12N2310/315 , C12Q1/6886 , C12Q2600/106
摘要： A method is provided for treating hormone-regulated tumors (for example, breast and prostatic tumors) in mammals, including humans, by administration of an antisense ODN which is complementary to a portion of the gene encoding IGFBP-5. Using the Shionogi tumor model in vitro and in vivo, the administration of such an ODN was shown to reduce proliferation of tumor cells, and also to delay the progression to androgen independence. Thus, treatment of prostate cancer in mammals, including humans, and delay of the progression of prostate tumors to androgen independence is accomplished by administering to the mammal a therapeutically effective amount of an antisense oligodeoxynucleotide which is complementary to a portion of the nucleic acid sequence encoding IGFBP-5 and which hybridizes with such a sequence to inhibit expression of IGFBP-5. Specific antisense ODN's which are suitable for use in the method are GACCACGCTGATCACCAT (Seq. ID. No. 1), which is derived from the murine gene sequence, and CGCGGTGAGCAACACCAT (Seq. ID. No. 3) and AGGTCATGCAGCAGCCGC (Seq. ID No 4), which are derived from the human gene sequence.
摘要翻译：提供了通过施用与编码IGFBP-5的基因的一部分互补的反义ODN来治疗哺乳动物（包括人）中激素调节的肿瘤（例如乳腺和前列腺肿瘤）的方法。在体外和体内使用Shionogi肿瘤模型，这种ODN的施用显示可以减少肿瘤细胞的增殖，并且也延缓进展到雄激素的独立性。因此，通过向哺乳动物施用治疗有效量的反义寡脱氧核苷酸来完成前列腺癌在包括人类的哺乳动物中的治疗以及前列腺肿瘤的进展延迟到雄激素独立性，所述反义寡核苷酸与编码的核酸序列的一部分互补 IGFBP-5，其与这样的序列杂交以抑制IGFBP-5的表达。适用于该方法的特异性反义ODN可以衍生自鼠基因序列的GACCACGCTGATCACCAT（Seq.ID.1号）和CGCGGTGAGCAACACCAT（Seq.ID.3号）和AGGTCATGCAGCAGCCGC（Seq.ID No 4），其源自人基因序列。

19. 发明申请

US20080051362A1 Antisense Therapy for Hormone-Regulated Tumors 有权
标题翻译：激素调节性肿瘤的反义治疗
公开(公告)号：US20080051362A1
公开(公告)日：2008-02-28
申请号：US11849845
申请日：2007-09-04
申请人： Martin Gleave , Hideaki Miyake
发明人： Martin Gleave , Hideaki Miyake
IPC分类号： A61K31/70 , C07H21/04 , C12N5/06
CPC分类号： C12Q1/6886 , C12Q2600/106
摘要： A method is provided for treating hormone-regulated tumors (for example, breast and prostatic tumors) in mammals, including humans, by administration of an antisense ODN which is complementary to a portion of the gene encoding IGFBP-5. Using the Shionogi tumor model in vitro and in vivo, the administration of such an ODN was shown to reduce proliferation of tumor cells, and also to delay the progression to androgen independence. Thus, treatment of prostate cancer in mammals, including humans, and delay of the progression of prostate tumors to androgen independence is accomplished by administering to the mammal a therapeutically effective amount of an antisense oligodeoxynucleotide which is complementary to a portion of the nucleic acid sequence encoding IGFBP-5 and which hybridizes with such a sequence to inhibit expression of IGFBP-5. Specific antisense ODN's which are suitable for use in the method are GACCACGCTGATCACCAT (Seq. ID. No. 1), which is derived from the murine gene sequence, and CGCCGTGAGCAACACCAT (Seq. ID. No. 3) and AGGTCATGCACCAGCCGC (Seq. ID No 4), which are derived from the human gene sequence.
摘要翻译：提供了通过施用与编码IGFBP-5的基因的一部分互补的反义ODN来治疗哺乳动物（包括人）中激素调节的肿瘤（例如乳腺和前列腺肿瘤）的方法。在体外和体内使用Shionogi肿瘤模型，这种ODN的施用显示可以减少肿瘤细胞的增殖，并且也延缓进展到雄激素的独立性。因此，通过向哺乳动物施用治疗有效量的反义寡脱氧核苷酸来完成前列腺癌在包括人类的哺乳动物中的治疗以及前列腺肿瘤的进展延迟到雄激素独立性，所述反义寡核苷酸与编码的核酸序列的一部分互补 IGFBP-5，其与这样的序列杂交以抑制IGFBP-5的表达。适用于该方法的特异性反义ODN是来自鼠基因序列的GACCACGCTGATCACCAT（Seq.ID.1），CGCCGTGAGCAACACCAT（Seq.ID.3号）和AGGTCATGCACCAGCCGC（Seq.ID No 4），其源自人基因序列。

20. 发明申请

US20110142827A1 TREATMENT OF CANCER WITH A COMBINATION OF AN AGENT THAT PERTURBS THE EGF SIGNALING PATHWAY AND AN OLIGONUCLEOTIDE THAT REDUCES CLUSTERIN LEVELS 审中-公开
标题翻译：治疗癌症与治疗EGF信号途径和降低CLUSTERIN水平的寡核苷酸的药物的组合
公开(公告)号：US20110142827A1
公开(公告)日：2011-06-16
申请号：US12886027
申请日：2010-09-20
申请人： Martin Gleave , Gabriella Zupi
发明人： Martin Gleave , Gabriella Zupi
IPC分类号： A61K39/395 , A61P35/00
CPC分类号： C07K16/32 , A61K39/39558 , A61K2039/505 , C07K2317/24 , A61K2300/00
摘要： Agents that perturb the EGF signaling pathway and that are known to be useful in the treatment of cancer are found also to result in increased expression of the protein clusterin. Since clusterin can provide protection against apoptosis, this secondary effect detracts from the efficacy of the therapeutic agent. This is overcome using a combination of an agent that has known therapeutic efficacy against the cancer to be treated by perturbation of the EGF signaling pathway and that stimulates expression of clusterin as a secondary effect, and an oligonucleotide that is effective to reduce the amount of clusterin in cancer cells. For example, the agent may be an antibody specific for HER-2, a small molecule inhibitor of HER-2, an antisense oligonucleotide specific for HER-2, or a peptide agent capable of interfering with HER-2 protein. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.
摘要翻译：发现干扰EGF信号通路并且已知可用于治疗癌症的试剂也导致蛋白质簇的表达增加。由于簇蛋白可以提供针对细胞凋亡的保护作用，所以这种二次效应会降低治疗剂的功效。使用具有已知治疗功效的药剂与通过EGF信号通路的扰动来治疗并刺激簇蛋白表达作为次要作用的药物的组合克服，以及有效降低簇的量的寡核苷酸在癌细胞中。例如，该试剂可以是对HER-2特异的抗体，HER-2的小分子抑制剂，对HER-2特异性的反义寡核苷酸，或能够干扰HER-2蛋白质的肽试剂。寡核苷酸可以是反义寡核苷酸或RNAi寡核苷酸。

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