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公开(公告)号：US08748411B2
公开(公告)日：2014-06-10
申请号：US11920031
申请日：2006-05-05
申请人： Rolando Eduardo Rodriguez Fernandez , Roberto Vera Alvarez , Ania De La Nuez Veulens , Yuliet Mazola Reyes , Silvio Ernesto Perea Rodriguez , Boris Ernesto Acevedo Castro , Alexis Musacchio Lasa , Raimundo Ubieta Gómez
发明人： Rolando Eduardo Rodriguez Fernandez , Roberto Vera Alvarez , Ania De La Nuez Veulens , Yuliet Mazola Reyes , Silvio Ernesto Perea Rodriguez , Boris Ernesto Acevedo Castro , Alexis Musacchio Lasa , Raimundo Ubieta Gómez
IPC分类号： A61K31/66 , A61K31/53 , A61K31/505 , A61K31/47 , A61K31/415 , A61K31/40 , C07D251/42 , C07D473/00 , C07D239/02 , C07D215/38 , C07D235/00 , C07D233/96 , C07D209/14 , C07D307/02 , C07D229/00 , C07F9/02 , C07C281/02 , C07C273/02 , C07C303/00 , C07C241/00
CPC分类号： C07C211/14 , C07C237/06 , C07C237/22 , C07C243/28 , C07C255/42 , C07C257/14 , C07C271/22 , C07C271/64 , C07C275/08 , C07C275/16 , C07C275/24 , C07C281/12 , C07C317/28 , C07C327/42 , C07C337/08 , C07D207/34 , C07D209/14 , C07D213/81 , C07D213/82 , C07D215/46 , C07D233/88 , C07D233/91 , C07D235/14 , C07D239/36 , C07D239/46 , C07D239/54 , C07D251/22 , C07D307/52 , C07D487/04 , C07F9/224
摘要： Chemical compounds derived by in silico molecular modelling, having a well defined structure suitable for the blocking of the phosphorylation event, through the specific interaction of the chemical with the Casein Kinase 2 enzyme substrate phosphorylation domain or it's neighbourhood. This invention comprises also the pharmaceutical compositions containing such compounds, and their use in the preparation of medicines or agents for the treatment of diseases or conditions related with neoplasic processes.
摘要翻译： 通过在硅分子模拟中得到的化学化合物通过化学物质与酪蛋白激酶2酶底物磷酸化结构域或其邻域的特异性相互作用具有适合于阻断磷酸化事件的良好定义的结构。 本发明还包含含有这些化合物的药物组合物及其在制备用于治疗与肿瘤过程相关的疾病或病症的药物或试剂中的用途。
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2.发明授权Pharmaceutical combination for the treatment and/or chemosensibilization of refractory tumors to anticancer drugs 有权用于治疗和/或耐药肿瘤对抗癌药物的化学敏化的药物组合公开(公告)号：US08871725B2
公开(公告)日：2014-10-28
申请号：US12280629
申请日：2007-02-28
申请人： Silvio Ernesto Perea Rodriguez , Yasser Perera Negrin , Arielis Rodriguez Ulloa , Jeovanis Gil Valdés , Yassel Ramos Gómez , Lila Rosa Castellanos Serra , Lázaro Hiram Betancourt Núñez , Aniel Sánchez Puente , Jorge Fernández de Cossio Dorta Duque , Boris Ernesto Acevedo Castro , Luis Javier González López , Vladimir Besada Pérez , Daniel Fernando Alonso , Daniel Eduardo Gomez
发明人： Silvio Ernesto Perea Rodriguez , Yasser Perera Negrin , Arielis Rodriguez Ulloa , Jeovanis Gil Valdés , Yassel Ramos Gómez , Lila Rosa Castellanos Serra , Lázaro Hiram Betancourt Núñez , Aniel Sánchez Puente , Jorge Fernández de Cossio Dorta Duque , Boris Ernesto Acevedo Castro , Luis Javier González López , Vladimir Besada Pérez , Daniel Fernando Alonso , Daniel Eduardo Gomez
CPC分类号： A61K38/08 , A61K31/136 , A61K31/282 , A61K31/337 , A61K31/407 , A61K31/475 , A61K31/506 , A61K31/513 , A61K31/5377 , A61K31/555 , A61K31/675 , A61K31/69 , A61K31/704 , A61K31/7048 , A61K31/7068 , A61K31/7076 , A61K33/24 , A61K45/06 , A61K2300/00
摘要： This invention is related to a pharmaceutical combination that contains a Casein kinase 2 (CK2) peptide inhibitor (termed P15) along with the standard chemotherapeutic drugs used in cancer treatment and which are administered together, separated or sequentially. The chemotherapeutic drugs include cisplatin, taxol, alkaloids from Vinca, 5-fluorouracil, doxorubicin, cyclophosphamide, etoposide, mitomicin C, imatinib, iressa and velcade (vortezomib). The synergism between the P15 peptide and the anticancer drugs achieves an efficient concentration of each cytostatic drug in the combination which is from 10- to 100-fold lower than that for each cytostatic drug alone. The pharmaceutical combination described in this invention exhibits lower toxicity compared to that reported by the anticancer therapeutics and therefore, it represents a crucial advantage for its use in cancer therapy. Furthermore, the sequential administration of this pharmaceutical combination through the pretreatment with the P15 peptide leads to the chemo sensibilization of refractory tumors to the anticancer therapeutics.
摘要翻译： 本发明涉及含有酪蛋白激酶2（CK2）肽抑制剂（称为P15）以及癌症治疗中使用的标准化学治疗药物并且分开或依次给药的药物组合。 化疗药物包括顺铂，紫杉醇，长春花生物碱，5-氟尿嘧啶，多柔比星，环磷酰胺，依托泊苷，mitomicin C，伊马替尼，iressa和velcade（vortezomib）。 P15肽与抗癌药物之间的协同作用实现了组合中每种细胞抑制药物的有效浓缩，其比单独的每种细胞抑制药物低10至100倍。 本发明中描述的药物组合物与抗癌治疗剂报道的药物组合物相比表现出较低的毒性，因此它代表其用于癌症治疗的关键优势。 此外，通过用P15肽进行预处理，该药物组合的连续施用导致难治性肿瘤对抗癌治疗剂的化学敏感性。
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公开(公告)号：US07736638B2
公开(公告)日：2010-06-15
申请号：US11662844
申请日：2005-09-16
申请人： Alicia Santos Savio , Ania Cabrales Rico , Osvaldo Reyes Acosta , Haydee Geronimo Perez , Celia Aurora Arrieta Aguero , Silvio Ernesto Perea Rodriguez
发明人： Alicia Santos Savio , Ania Cabrales Rico , Osvaldo Reyes Acosta , Haydee Geronimo Perez , Celia Aurora Arrieta Aguero , Silvio Ernesto Perea Rodriguez
CPC分类号： C07K14/5443 , A61K38/00 , A61K39/00 , C07K16/244
摘要： Current invention is related to the molecular pharmacology branch particularly to a peptide belonging to the Interleukin-15 sequence (IL-15) which is able to inhibit IL-15 biological activity, analogues or mimetic of such peptides. In the current invention it is shown that the peptide inhibits both IL-15-induced T cells proliferation upon binding to the IL15 receptor a subunit (IL15Rα) and TNFα-mediated apoptosis.Besides, this invention is related to the use of this peptide in the treatment of several pathologies where aberrant IL-15 or IL-15Rα expression is associated to the disease progression.
摘要翻译： 本发明涉及分子药理学分支，特别是涉及能够抑制IL-15生物活性，类似物或模拟这些肽的白细胞介素-15序列（IL-15）的肽。 在本发明中，显示肽结合IL15受体a亚基（IL15Rα）和TNFα介导的细胞凋亡后，抑制IL-15诱导的T细胞增殖。 此外，本发明涉及该肽用于治疗其中异常IL-15或IL-15Rα表达与疾病进展相关的几种病症的用途。
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4.发明申请PHARMACEUTICAL COMBINATION FOR THE TREATMENT AND OR CHEMOSENSIBILIZATION OF REFRACTORY TUMORS TO ANTICANCER DRUGS 有权用于治疗和/或将抗肿瘤药物化学治疗给药物药物的药物组合公开(公告)号：US20090130228A1
公开(公告)日：2009-05-21
申请号：US12280629
申请日：2007-02-28
申请人： Silvio Ernesto Perea Rodriguez , Yasser Perera Negrin , Arielis Rodriguez Ulloa , Jeovanis Gil Valdes , Yassel Ramos Gomez , Lila Rosa Castellanos Serra , Lazaro Hiram Betancourt Nunez , Aniel Sanchez Puente , Jorge Fernandez de Cossio Dorta Duque , Boris Ernesto Acevedo Castro , Luis Javier Gonzalez Lopez , Vladimir Besada Perez , Daniel Fernando Alonso , Daniel Eduardo Gomez
发明人： Silvio Ernesto Perea Rodriguez , Yasser Perera Negrin , Arielis Rodriguez Ulloa , Jeovanis Gil Valdes , Yassel Ramos Gomez , Lila Rosa Castellanos Serra , Lazaro Hiram Betancourt Nunez , Aniel Sanchez Puente , Jorge Fernandez de Cossio Dorta Duque , Boris Ernesto Acevedo Castro , Luis Javier Gonzalez Lopez , Vladimir Besada Perez , Daniel Fernando Alonso , Daniel Eduardo Gomez
IPC分类号： A61K33/24 , A61K38/08 , A61K31/282 , A61K31/337 , A61K31/4745 , A61K31/505 , A61K31/704 , A61K31/675 , A61K31/407 , A61K31/4965 , A61K31/506 , A61K31/7088 , A61P35/00
CPC分类号： A61K38/08 , A61K31/136 , A61K31/282 , A61K31/337 , A61K31/407 , A61K31/475 , A61K31/506 , A61K31/513 , A61K31/5377 , A61K31/555 , A61K31/675 , A61K31/69 , A61K31/704 , A61K31/7048 , A61K31/7068 , A61K31/7076 , A61K33/24 , A61K45/06 , A61K2300/00
摘要： This invention is related to a pharmaceutical combination that contains a Casein kinase 2 (CK2) peptide inhibitor (termed P15) along with the standard chemotherapeutic drugs used in cancer treatment and which are administered together, separated or sequentially. The chemothearapeutic drugs include cisplatin, taxol, alkaloids from Vinca, 5-fluorouracil, doxorubicin, cyclophosphamide, etoposide, mitomicin C, imatinib, iressa and velcade (vortezomib). The synergism between the P15 peptide and the anticancer drugs achieves an efficient concentration of each cytostatic drug in the combination which is from 10- to 100-fold lower than that for each cytostatic drug alone. The pharmaceutical combination described in this invention exhibits lower toxicity compared to that reported by the anticancer therapeutics and therefore, it represents a crucial advantage for its use in cancer therapy. Furthermore, the sequential administration of this pharmaceutical combination through the pretreatment with the P15 peptide leads to the chemo sensibilization of refractory tumors to the anticancer therapeutics.
摘要翻译： 本发明涉及含有酪蛋白激酶2（CK2）肽抑制剂（称为P15）以及癌症治疗中使用的标准化学治疗药物并且分开或依次给药的药物组合。 化疗药物包括顺铂，紫杉醇，长春花生物碱，5-氟尿嘧啶，多柔比星，环磷酰胺，依托泊苷，mitomicin C，伊马替尼，iressa和velcade（vortezomib）。 P15肽与抗癌药物之间的协同作用实现了组合中每种细胞抑制药物的有效浓缩，其比单独的每种细胞抑制药物低10至100倍。 本发明中描述的药物组合物与抗癌治疗剂报道的药物组合物相比表现出较低的毒性，因此它代表其用于癌症治疗的关键优势。 此外，通过用P15肽进行预处理，该药物组合的连续施用导致难治性肿瘤对抗癌治疗剂的化学敏感性。
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5.发明授权Peptides for the treatment of cancer associated with the human papilloma virus (HPV) and other epithelial tumors 有权用于治疗与人乳头状瘤病毒（HPV）和其他上皮肿瘤相关的癌症的肽公开(公告)号：US07374767B2
公开(公告)日：2008-05-20
申请号：US10499458
申请日：2002-12-04
申请人： Silvio Ernesto Perea Rodriguez , Osvaldo Reyes Acosta , Nelson Francisco Santiago Vispo , Yaquelin Puchades Izaguirre , Ricardo Silva Rodriguez , Alejandro Moro Soria , Alicia Santos Savio , Luis Javier González López , Belkis González Barrios
发明人： Silvio Ernesto Perea Rodriguez , Osvaldo Reyes Acosta , Nelson Francisco Santiago Vispo , Yaquelin Puchades Izaguirre , Ricardo Silva Rodriguez , Alejandro Moro Soria , Alicia Santos Savio , Luis Javier González López , Belkis González Barrios
IPC分类号： A61K39/12
CPC分类号： C07K14/005 , A61K38/00 , A61K48/00 , C07K7/06 , C07K2319/10 , C12N7/00 , C12N2710/20022 , C12N2710/20032
摘要： This invention is related to the Molecular Pharmacology field and especially to the development of peptides useful for treating epithelial tumors and mainly those associated to oncogenic types of HPVs. The main objective of this invention is to identify peptides whose structure permits to block the Casein Kinase II (CKII) phosphorylation domain by direct interaction with such a site. In the present invention it is shown eleven cyclic peptides with different aminoacid sequences which inhibit the CKII phosphorylation in vitro, exhibit cytotoxicity on HPV-16 transformed cells (CaSki) and also increase the sensitivity of these cells to the cytostatic effect of interferon (IFN). Furthermore, the invention relates to the use of these peptides conjugated or fused to other peptides and chemical compounds which penetrates into cells as well as with the use of both peptide and chemical mimetic molecules.
摘要翻译： 本发明涉及分子药理学领域，特别涉及可用于治疗上皮肿瘤和主要与致癌型HPV相关的肽的发展。 本发明的主要目的是鉴定其结构允许通过与这种位点的直接相互作用阻断酪蛋白激酶II（CKII）磷酸化结构域的肽。 在本发明中，显示了11种具有不同氨基酸序列的环肽，其在体外抑制CKII磷酸化，对HPV-16转化细胞（CaSki）表现出细胞毒性，并且还增加了这些细胞对干扰素（IFN）的细胞抑制作用的敏感性， 。 此外，本发明涉及这些肽与其它肽和化合物共轭或融合的用途，这些肽和化合物可以渗入细胞以及使用肽和化学模拟分子。
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公开(公告)号：US08007776B2
公开(公告)日：2011-08-30
申请号：US10529923
申请日：2003-10-08
申请人： Alicia Santos Savio , Ricardo Silva Rodriguez , Yanelis Morera Diaz , Armando Alexei Rodriquez Alfonso , Jose Rafael Martinez Castillo , Haydee Geronimo Perez , Alejandro Moro Soria , Silvio Ernesto Perea Rodriguez
发明人： Alicia Santos Savio , Ricardo Silva Rodriguez , Yanelis Morera Diaz , Armando Alexei Rodriquez Alfonso , Jose Rafael Martinez Castillo , Haydee Geronimo Perez , Alejandro Moro Soria , Silvio Ernesto Perea Rodriguez
IPC分类号： A61K38/20
CPC分类号： A61K39/0005
摘要： Vaccine composition containing IL-15 for active immunization to treatment diseases related to over-expression of this cytokine. The technical aim pursued in this invention is to inhibit IL-15 activity through development of a therapeutic vaccine which elicits IL-15 neutralizing antibodies in the immunized host.IL-15 can be presented in this vaccine composition either alone or coupled to a carrier such as the P64k protein with a vaccine adjuvant such as Aluminum hydroxide.Besides, this invention is related to the use of this vaccine for treatment of Rheumatoid arthritis and other IL-15 over-expressing related diseases, and leukemia, where this cytokine acts as a growth factor.
摘要翻译： 含有IL-15的疫苗组合物用于主动免疫治疗与该细胞因子的过表达有关的疾病。 在本发明中追求的技术目的是通过开发在免疫宿主中引发IL-15中和抗体的治疗性疫苗来抑制IL-15活性。 IL-15可以单独存在于该疫苗组合物中，也可以与诸如氢氧化铝等疫苗佐剂的载体例如P64k蛋白偶联。 此外，本发明涉及该疫苗用于治疗类风湿性关节炎和其它IL-15过表达相关疾病和白血病，其中该细胞因子作为生长因子。
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公开(公告)号：US20090215730A1
公开(公告)日：2009-08-27
申请号：US11920031
申请日：2006-05-05
申请人： Rolando Eduardo Rodriguez Fernandez , Roberto Vera Alvarez , Ania De La Nuez Veulens , Yuliet Mazola Reyes , Silvio Ernesto Perea Rodriguez , Boris Ernesto Acevedo Castro , Alexis Musacchio Lasa , Raimundo Ubieta Gomez
发明人： Rolando Eduardo Rodriguez Fernandez , Roberto Vera Alvarez , Ania De La Nuez Veulens , Yuliet Mazola Reyes , Silvio Ernesto Perea Rodriguez , Boris Ernesto Acevedo Castro , Alexis Musacchio Lasa , Raimundo Ubieta Gomez
IPC分类号： A61K31/17 , A61K31/66 , A61K31/53 , A61K31/505 , A61K31/47 , A61K31/415 , A61K31/40 , A61K31/34 , A61K31/27 , A61K31/16 , A61K31/175 , A61K31/13 , C07D251/02 , C07D473/00 , C07D239/02 , C07D215/38 , C07D235/00 , C07D233/96 , C07D209/14 , C07D307/02 , C07C229/00 , C07F9/02 , C07C281/02 , C07C273/02 , C07C303/00 , C07C241/00
CPC分类号： C07C211/14 , C07C237/06 , C07C237/22 , C07C243/28 , C07C255/42 , C07C257/14 , C07C271/22 , C07C271/64 , C07C275/08 , C07C275/16 , C07C275/24 , C07C281/12 , C07C317/28 , C07C327/42 , C07C337/08 , C07D207/34 , C07D209/14 , C07D213/81 , C07D213/82 , C07D215/46 , C07D233/88 , C07D233/91 , C07D235/14 , C07D239/36 , C07D239/46 , C07D239/54 , C07D251/22 , C07D307/52 , C07D487/04 , C07F9/224
摘要： Chemical compounds derived by in silico molecular modelling, having a well defined structure suitable for the blocking of the phosphorylation event, through the specific interaction of the chemical with the Casein Kinase 2 enzyme substrate phosphorylation domain or it's neighbourhood. This invention comprises also the pharmaceutical compositions containing such compounds, and their use in the preparation of medicines or agents for the treatment of diseases or conditions related with neoplasic processes.
摘要翻译： 通过在硅分子模拟中得到的化学化合物通过化学物质与酪蛋白激酶2酶底物磷酸化结构域或其邻域的特异性相互作用具有适合于阻断磷酸化事件的良好定义的结构。 本发明还包含含有这些化合物的药物组合物及其在制备用于治疗与肿瘤过程相关的疾病或病症的药物或试剂中的用途。
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公开(公告)号：US20090136511A1
公开(公告)日：2009-05-28
申请号：US11662844
申请日：2005-09-16
申请人： Alicia Santos Savio , Ania Cabrales Rico , Osvaldo Reyes Acosta , Haydee Geronimo Perez , Celia Aurora Arrieta Aguero , Silvio Ernesto Perea Rodriguez
发明人： Alicia Santos Savio , Ania Cabrales Rico , Osvaldo Reyes Acosta , Haydee Geronimo Perez , Celia Aurora Arrieta Aguero , Silvio Ernesto Perea Rodriguez
IPC分类号： A61K38/08 , C07K7/06 , A61K39/00 , A61K39/395 , A61P19/02 , A61P17/06 , C07K16/00 , C07H21/00
CPC分类号： C07K14/5443 , A61K38/00 , A61K39/00 , C07K16/244
摘要： Current invention is related to the molecular pharmacology branch particularly to a peptide belonging to the Interleukin-15 sequence (IL-15) which is able to inhibit IL-15 biological activity, analogues or mimetic of such peptides. In the current invention it is shown that the peptide inhibits both IL-15-induced T cells proliferation upon binding to the IL15 receptor α subunit (IL15Rα) and TNFα-mediated apoptosis.Besides, this invention is related to the use of this peptide in the treatment of several pathologies where aberrant IL-15 or IL-15Rα expression is associated to the disease progression.
摘要翻译： 本发明涉及分子药理学分支，特别是涉及能够抑制IL-15生物活性，类似物或模拟这些肽的白细胞介素-15序列（IL-15）的肽。 在本发明中，显示该肽在结合IL15受体α亚基（IL15Rα）和TNFα介导的细胞凋亡时抑制IL-15诱导的T细胞增殖。 此外，本发明涉及该肽用于治疗其中异常IL-15或IL-15Rα表达与疾病进展相关的若干病理学的用途。
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