公开(公告)号：US20060233742A1

公开(公告)日：2006-10-19

申请号：US10499458

申请日：2002-12-04

申请人： Silvio Rodriguez ,  Osvaldo Reyes Acosta ,  Nelson Santiago Vispo ,  Yaquelin Puchades Izaguirre ,  Ricardo Silva Rodriguez ,  Alejandro Moro Soria ,  Alicia Santos Savio ,  Luis González López ,  Belkis González Barrios

发明人： Silvio Rodriguez ,  Osvaldo Reyes Acosta ,  Nelson Santiago Vispo ,  Yaquelin Puchades Izaguirre ,  Ricardo Silva Rodriguez ,  Alejandro Moro Soria ,  Alicia Santos Savio ,  Luis González López ,  Belkis González Barrios

IPC分类号： A61K38/19 ,  A61K38/10 ,  A61K38/12 ,  A61K38/21

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。

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。

公开(公告)号：US07947287B2

公开(公告)日：2011-05-24

申请号：US12099646

申请日：2008-04-08

申请人： Silvio Ernesto Perea Rodriquez ,  Osvaldo Reyes Acosta ,  Nelson Francisco Santiago Vispo ,  Yaquelin Puchades Izaguirre ,  Ricardo Silva Rodriguez ,  Alejandro Moro Soria ,  Alicia Santos Savio ,  Luis Javier Gonzalez Lopez ,  Belkis Gonzalez Barrios

发明人： Silvio Ernesto Perea Rodriquez ,  Osvaldo Reyes Acosta ,  Nelson Francisco Santiago Vispo ,  Yaquelin Puchades Izaguirre ,  Ricardo Silva Rodriguez ,  Alejandro Moro Soria ,  Alicia Santos Savio ,  Luis Javier Gonzalez Lopez ,  Belkis Gonzalez 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。

公开(公告)号：US20090005294A1

公开(公告)日：2009-01-01

申请号：US12099646

申请日：2008-04-08

申请人： Silvio Ernesto Perea Rodriquez ,  Osvaldo Reyes Acosta ,  Nelson Francisco Santiago Vispo ,  Yaquelin Puchades Izaguirre ,  Ricardo Silva Rodriguez ,  Alejandro Moro Soria ,  Alicia Santos Savio ,  Luis Javier Gonzalez Lopez ,  Belkis Gonzalez Barrios

发明人： Silvio Ernesto Perea Rodriquez ,  Osvaldo Reyes Acosta ,  Nelson Francisco Santiago Vispo ,  Yaquelin Puchades Izaguirre ,  Ricardo Silva Rodriguez ,  Alejandro Moro Soria ,  Alicia Santos Savio ,  Luis Javier Gonzalez Lopez ,  Belkis Gonzalez Barrios

IPC分类号： A61K38/12 ,  C07K7/64 ,  C12N15/63 ,  C07K14/00

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。

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。

公开(公告)号：US08431524B2

公开(公告)日：2013-04-30

申请号：US13120855

申请日：2009-09-30

申请人： Alicia Santos Savio ,  Osvaldo Reyes Acosta ,  Haydee Geronimo Perez ,  Hilda Elisa Garay Perez ,  Yunier Rodriguez Alvarez ,  Gerardo Enríque Guillen Nieto

发明人： Alicia Santos Savio ,  Osvaldo Reyes Acosta ,  Haydee Geronimo Perez ,  Hilda Elisa Garay Perez ,  Yunier Rodriguez Alvarez ,  Gerardo Enríque Guillen Nieto

IPC分类号： A61K38/04 ,  C12Q1/68

CPC分类号： C07K14/5443 ,  A61K38/00

摘要： The present invention is related to the field of molecular immunology, particularly to a peptide derived from the sequence of interleukine-15 (IL-15), wherein said peptide was optimized to inhibit the biological activity of this molecule. In the present invention, it is shown that this peptide inhibits IL-15-induced T cell proliferation, Tumor Necrosis Factor α (TNFα) induction and the expression of IL-8 and IL-6 by the IL-15 receptor α subunit (IL-15Rα), all these effects mediated by the binding of the peptide to the IL-15Rα. The invention is also related to the use of the peptide to treat pathologies where the abnormal expression of IL-15 or IL-15Rα is related to the course of the disease, such as rheumatoid arthritis (RA) and prostate cancer.

摘要翻译： 本发明涉及分子免疫学领域，特别涉及衍生自白介素-15（IL-15）序列的肽，其中所述肽被优化以抑制该分子的生物学活性。 在本发明中，显示该肽抑制IL-15诱导的T细胞增殖，肿瘤坏死因子α（TNFalpha）诱导和IL-8受体α亚基（IL）的IL-8和IL-6的表达 -15Rα），所有这些作用由肽与IL-15Rα的结合介导。 本发明还涉及使用肽来治疗其中IL-15或IL-15Rα异常表达与疾病进程如类风湿性关节炎（RA）和前列腺癌相关的病理学。

公开(公告)号：US20110251140A1

公开(公告)日：2011-10-13

申请号：US13120855

申请日：2009-09-30

申请人： Alicia Santos Savio ,  Osvaldo Reyes Acosta ,  Haydee Geronimo Perez ,  Hilda Elisa Garay Perez ,  Yunier Rodriguez Alvarez ,  Gerardo Enrique Guillen Nieto

发明人： Alicia Santos Savio ,  Osvaldo Reyes Acosta ,  Haydee Geronimo Perez ,  Hilda Elisa Garay Perez ,  Yunier Rodriguez Alvarez ,  Gerardo Enrique Guillen Nieto

IPC分类号： A61K38/08 ,  C07H21/00 ,  A61P19/02 ,  A61P35/00 ,  A61P17/06 ,  A61P29/00 ,  C07K7/06 ,  C12N15/63

CPC分类号： C07K14/5443 ,  A61K38/00

摘要： The present invention is related to the field of molecular immunology, particularly to a peptide derived from the sequence of interleukine-15 (IL-15), wherein said peptide was optimized to inhibit the biological activity of this molecule. In the present invention, it is shown that this peptide inhibits IL-15-induced T cell proliferation, Tumor Necrosis Factor α (TNFα) induction and the expression of IL-8 and IL-6 by the IL-15 receptor a subunit (IL-15Rα), all these effects mediated by the binding of the peptide to the IL-15Rα. The invention is also related to the use of the peptide to treat pathologies where the abnormal expression of IL-15 or IL-15Rα is related to the course of the disease, such as rheumatoid arthritis (RA) and prostate cancer.

摘要翻译： 本发明涉及分子免疫学领域，特别涉及衍生自白介素-15（IL-15）序列的肽，其中所述肽被优化以抑制该分子的生物学活性。 在本发明中，表明该肽抑制IL-15诱导的T细胞增殖，肿瘤坏死因子α（TNFα）诱导和IL-8受体a亚基（IL）的IL-8和IL-6的表达 -15Rα），所有这些作用由肽与IL-15Rα的结合介导。 本发明还涉及使用肽治疗其中IL-15或IL-15Rα的异常表达与疾病进程相关的病症，例如类风湿性关节炎（RA）和前列腺癌。

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。

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

IPC分类号： A61K38/20 ,  C12N15/06 ,  C07K14/54 ,  C12N5/02 ,  C12P21/02

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。