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21. 发明授权

US07285541B2 Treatment of melanoma by reduction in clusterin levels 有权
标题翻译：通过降低聚集蛋白水平治疗黑色素瘤
公开(公告)号：US07285541B2
公开(公告)日：2007-10-23
申请号：US10646391
申请日：2003-08-21
申请人： Martin Gleave , Burkhard Jansen
发明人： Martin Gleave , Burkhard Jansen
IPC分类号： A61K48/00 , C07H21/02 , C07H21/04
CPC分类号： C12N15/113 , A61K31/712 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： Treatment of melanoma is achieved through reduction in the effective amount of clusterin in melanoma cells of in a mammalian subject, preferably a human. A therapeutic agent effective to reduce the effective amount of clusterin in the melanoma cells is administered to the subject. The therapeutic agent may be, for example, an antisense ODN or small inhibitory RNA (siRNA) compound targeted to clusterin. bcl-xL in a subject or cell line can also be regulated by administering to the subject or cell line an agent effective to modulate the amount of clusterin expression. In particular, in clusterin expressing cells, the expression of bcl-xL is down-regulated when the effective amount of clusterin is reduced. Such inhibition is significant because bcl-xL is known to act as an inhibitor of apoptosis.
摘要翻译：黑素瘤的治疗通过在哺乳动物受试者，优选人中减少黑素瘤细胞中的聚集蛋白的有效量来实现。向受试者施用有效降低黑素瘤细胞中的聚集蛋白有效量的治疗剂。治疗剂可以是例如靶向簇蛋白的反义ODN或小的抑制性RNA（siRNA）化合物。受试者或细胞系中的bcl-xL也可以通过向受试者或细胞系施用有效调节聚集蛋白表达量的试剂来调节。特别地，在簇蛋白表达细胞中，当有效量的聚集蛋白降低时，bcl-xL的表达下调。这种抑制是显着的，因为已知bcl-xL作为凋亡抑制剂。

22. 发明申请

US20120077861A1 Bispecific Antisense Oligonucleotides that Inhibit IGFBP-2 and IGFBP-5 and Methods of Using Same 有权
标题翻译：抑制IGFBP-2和IGFBP-5的双特异性反义寡核苷酸及其使用方法
公开(公告)号：US20120077861A1
公开(公告)日：2012-03-29
申请号：US12978940
申请日：2010-12-27
申请人： Martin Gleave , Maxim Signaevsky
发明人： Martin Gleave , Maxim Signaevsky
IPC分类号： A61K31/713 , A61P35/00 , C12N5/071
CPC分类号： C12N15/113 , A61K31/713 , A61K38/00 , C07K2319/00 , C12N2310/11 , C12N2310/111 , C12N2310/3519 , C12N2310/51
摘要： Bispecific antisense oligonucleotides which consist essentially of a sequence of bases that is complementary to portions of both the gene encoding human IGFBP-2 and the gene encoding human IGFBP-5 are useful in as antisense therapeutics in the treatment of endocrine-regulated cancers.
摘要翻译：基本上由与编码人IGFBP-2的基因和编码人IGFBP-5的基因的部分互补的碱基序列的双特异性反义寡核苷酸可用作治疗内分泌调节癌症的反义治疗剂。

23. 发明申请

US20110009472A1 RNAi Probes Targeting Cancer-Related Proteins 失效
标题翻译：靶向癌症相关蛋白的RNAi探针
公开(公告)号：US20110009472A1
公开(公告)日：2011-01-13
申请号：US12845521
申请日：2010-07-28
申请人： Martin Gleave , Burkhard Jansen , Ioannis P. Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
发明人： Martin Gleave , Burkhard Jansen , Ioannis P. Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
IPC分类号： A61K31/7088 , A61P35/00 , A61K31/713
CPC分类号： C12N15/113 , A61K31/712 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： RNAi sequences that are useful as therapeutics in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease. These sequences target clusterin, IGFBP-5, IGFBP-2, both IGFBP-2 and -5 simultaneously, Mitf, and B-raf. The invention further provides for the use of these RNAi sequences in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease, and a method of treating such conditions through the administration of the RNA molecules with RNAi activity to an individual, including a human individual in need of such treatment.
摘要翻译：可用作治疗各种类型癌症的RNAi序列，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤 ; 和阿尔茨海默病。这些序列同时靶向簇蛋白，IGFBP-5，IGFBP-2，IGFBP-2和-5两者，Mitf和B-raf。本发明进一步提供这些RNAi序列用于治疗各种类型的癌症，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤; 和阿尔茨海默病，以及通过向包括需要这种治疗的人的个体的个体施用具有RNAi活性的RNA分子来治疗这些病症的方法。

24. 发明申请

US20080274996A1 RNAi Probes Targeting Cancer-Related Proteins 有权
标题翻译：靶向癌症相关蛋白的RNAi探针
公开(公告)号：US20080274996A1
公开(公告)日：2008-11-06
申请号：US12116083
申请日：2008-05-06
申请人： Martin Gleave , Burkhard Jansen , Ioannis P. Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
发明人： Martin Gleave , Burkhard Jansen , Ioannis P. Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
IPC分类号： A61K31/7105 , C07H21/02 , A61P35/00
CPC分类号： C12N15/113 , A61K31/712 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： RNAi sequences that are useful as therapeutics in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease. These sequences target clusterin, IGFBP-5, IGFBP-2, both IGFBP-2 and -5 simultaneously, Mitf, and B-raf. The invention further provides for the use of these RNAi sequences in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease, and a method of treating such conditions through the administration of the RNA molecules with RNAi activity to an individual, including a human individual in need of such treatment.
摘要翻译：可用作治疗各种类型癌症的RNAi序列，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤 ; 和阿尔茨海默病。这些序列同时靶向簇蛋白，IGFBP-5，IGFBP-2，IGFBP-2和-5两者，Mitf和B-raf。本发明进一步提供这些RNAi序列用于治疗各种类型的癌症，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤; 和阿尔茨海默病，以及通过向包括需要这种治疗的人的个体的个体施用具有RNAi活性的RNA分子来治疗这些病症的方法。

25. 发明授权

US08759308B2 RNAi probes targeting cancer-related proteins 失效
标题翻译：针对癌症相关蛋白的RNAi探针
公开(公告)号：US08759308B2
公开(公告)日：2014-06-24
申请号：US12845521
申请日：2010-07-28
申请人： Martin Gleave , Burkhard Jansen , Ioannis P Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
发明人： Martin Gleave , Burkhard Jansen , Ioannis P Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
IPC分类号： A61K48/00
CPC分类号： C12N15/113 , A61K31/712 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： RNAi sequences that are useful as therapeutics in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease. These sequences target clusterin, IGFBP-5, IGFBP-2, both IGFBP-2 and -5 simultaneously, Mitf, and B-raf. The invention further provides for the use of these RNAi sequences in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease, and a method of treating such conditions through the administration of the RNA molecules with RNAi activity to an individual, including a human individual in need of such treatment.
摘要翻译：可用作治疗各种类型癌症的RNAi序列，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤 ; 和阿尔茨海默病。这些序列同时靶向簇蛋白，IGFBP-5，IGFBP-2，IGFBP-2和-5两者，Mitf和B-raf。本发明进一步提供这些RNAi序列用于治疗各种类型的癌症，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤; 和阿尔茨海默病，以及通过向包括需要这种治疗的人的个体的个体施用具有RNAi活性的RNA分子来治疗这些病症的方法。

26. 发明申请

US20120202873A1 RNAi Probes Targeting Cancer-Related Proteins 有权
标题翻译：靶向癌症相关蛋白的RNAi探针
公开(公告)号：US20120202873A1
公开(公告)日：2012-08-09
申请号：US13404741
申请日：2012-02-24
申请人： Martin Gleave , Burkhard Jansen , Ioannis P. Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
发明人： Martin Gleave , Burkhard Jansen , Ioannis P. Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
IPC分类号： C07H21/02 , A61P35/04 , A61K31/7105
CPC分类号： C12N15/113 , A61K31/712 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： RNAi sequences that are useful as therapeutics in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease. These sequences target clusterin, IGFBP-5, IGFBP-2, both IGFBP-2 and -5 simultaneously, Mitf, and B-raf. The invention further provides for the use of these RNAi sequences in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease, and a method of treating such conditions through the administration of the RNA molecules with RNAi activity to an individual, including a human individual in need of such treatment.
摘要翻译：可用作治疗各种类型癌症的RNAi序列，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤 ; 和阿尔茨海默病。这些序列同时靶向簇蛋白，IGFBP-5，IGFBP-2，IGFBP-2和-5两者，Mitf和B-raf。本发明进一步提供这些RNAi序列用于治疗各种类型的癌症，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤; 和阿尔茨海默病，以及通过向包括需要这种治疗的人的个体的个体施用具有RNAi活性的RNA分子来治疗这些病症的方法。

27. 发明授权

US07973017B2 Treatment of cancer by inhibition of IGFBP's and clusterin 有权
标题翻译：通过抑制IGFBP和聚集蛋白治疗癌症
公开(公告)号：US07973017B2
公开(公告)日：2011-07-05
申请号：US11287334
申请日：2005-11-23
申请人： Martin Gleave
发明人： Martin Gleave
IPC分类号： A01N43/04 , C07H21/02 , C07H21/04 , C12Q1/68 , C12P19/34
CPC分类号： C12N15/113 , A61K31/713 , A61K38/00 , C07K2319/00 , C12N2310/11 , C12N2310/111 , C12N2310/3519 , C12N2310/51
摘要： Agents that reduce the amount of IGFBP-2 and/or IGFBP-5 and that are known to be useful in the treatment of cancer 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. In overcoming this, the present invention provides a combination of therapeutic agents that is useful in the treatment of cancer. The combination includes an agent that reduces the amount of IGFBP-2 and/or IGFBP-5 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. In some embodiments of the invention, the agent that reduces IGFBP-2 and/or IGFBP-5 is a bispecific antisense species. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.
摘要翻译：降低IGFBP-2和/或IGFBP-5的量并且已知可用于治疗癌症的药物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。克服这一点，本发明提供了可用于治疗癌症的治疗剂的组合。该组合包括减少IGFBP-2和/或IGFBP-5的量并刺激簇蛋白表达作为次要作用的试剂，以及有效降低癌细胞中的簇蛋白的量的寡核苷酸。在本发明的一些实施方案中，减少IGFBP-2和/或IGFBP-5的药剂是双特异性反义物质。寡核苷酸可以是反义寡核苷酸或RNAi寡核苷酸。

28. 发明授权

US07820635B2 RNAi probes targeting cancer-related proteins 有权
标题翻译：针对癌症相关蛋白的RNAi探针
公开(公告)号：US07820635B2
公开(公告)日：2010-10-26
申请号：US12116083
申请日：2008-05-06
申请人： Martin Gleave , Burkhard Jansen , Ioannis P Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
发明人： Martin Gleave , Burkhard Jansen , Ioannis P Trougakos , Efstathios Gonos , Maxim Signaevsky , Eliana Beraldi
IPC分类号： A61K48/00
CPC分类号： C12N15/113 , A61K31/712 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： RNAi sequences that are useful as therapeutics in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease. These sequences target clusterin, IGFBP-5, IGFBP-2, both IGFBP-2 and -5 simultaneously, Mitf, and B-raf. The invention further provides for the use of these RNAi sequences in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease, and a method of treating such conditions through the administration of the RNA molecules with RNAi activity to an individual, including a human individual in need of such treatment.
摘要翻译：可用作治疗各种类型癌症的RNAi序列，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤 ; 和阿尔茨海默病。这些序列同时靶向簇蛋白，IGFBP-5，IGFBP-2，IGFBP-2和-5两者，Mitf和B-raf。本发明进一步提供这些RNAi序列用于治疗各种类型的癌症，包括前列腺癌，肉瘤如骨肉瘤，肾细胞癌，乳腺癌，膀胱癌，肺癌，结肠癌，卵巢癌，间变性大细胞淋巴瘤和黑素瘤; 和阿尔茨海默病，以及通过向包括需要这种治疗的人的个体的个体施用具有RNAi活性的RNA分子来治疗这些病症的方法。

29. 发明申请

US20080014198A1 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：治疗癌症与抑制EGF信号传导途径的药剂和减少Clusterin水平的寡核苷酸的组合
公开(公告)号：US20080014198A1
公开(公告)日：2008-01-17
申请号：US11718815
申请日：2005-11-22
申请人： Martin Gleave , Gabriella Zupi
发明人： Martin Gleave , Gabriella Zupi
IPC分类号： A61K31/7088 , 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 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HER-2的小分子抑制剂，对HER-2特异性的反义寡核苷酸或能干扰HER-2蛋白的肽试剂。寡核苷酸可以是反义寡核苷酸或RNAi寡核苷酸。

30. 发明申请

US20060276424A1 Compositions and Methods for Treatment of Prostate and Other Cancers 有权
公开(公告)号：US20060276424A1
公开(公告)日：2006-12-07
申请号：US11422481
申请日：2006-06-06
申请人： Martin Gleave , Palma Rocchi , Maxim Signaevsky , Eliana Beraldi
发明人： Martin Gleave , Palma Rocchi , Maxim Signaevsky , Eliana Beraldi
IPC分类号： A61K48/00
CPC分类号： C12N15/113 , A61K31/337 , A61K31/7068 , A61K31/7088 , A61K31/7125 , A61K31/713 , A61K48/005 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2320/30 , C12N2320/31
摘要： Therapeutic agents which target heat shock protein (hsp) 27 in vivo are used to provide treatment to individuals, particularly human individuals, suffering from prostate cancer and other cancers that overexpress hsp27. A therapeutic agent, for example an antisense oligonucleotide or RNAi nucleotide inhibitor with sequence specificity for hsp27 mRNA, for example human hsp27 mRNA, is administered to an individual suffering from prostate cancer or some other cancer expressing elevated levels of hsp 27 in a therapeutically effective amount. The therapeutic agent is suitably formulated into a pharmaceutical composition which includes a pharmaceutically acceptable carrier, and packaged in dosage unit form. A preferred dosage unit form is an injectable dosage unit form.

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