公开(公告)号：US08124351B2

公开(公告)日：2012-02-28

申请号：US12094112

申请日：2006-11-14

申请人： Maher Albitar ,  Hagop Kantarjian ,  Francis Giles ,  Iman Jilani

发明人： Maher Albitar ,  Hagop Kantarjian ,  Francis Giles ,  Iman Jilani

IPC分类号： G01N33/53

CPC分类号： G01N33/573 ,  G01N33/53 ,  G01N33/574 ,  G01N33/57426

摘要： The present invention concerns the detection of gene products resulting from chromosomal translocations, including fusion proteins comprising a first and second region. In particular, the fusion proteins are identified following subjecting a sample comprising the proteins to a bead comprising an antibody to a first region, followed by subjecting the bead-antibody-fusion complex to a second antibody directed against the second region, thereby detecting the fusion protein. In particular aspects, the invention is employed to provide prognosis for an individual with cancer, to identify suitability for a particular cancer therapy, and/or to monitor response of a patient to a therapy, for example.

摘要翻译： 本发明涉及由染色体易位引起的基因产物的检测，包括包含第一和第二区域的融合蛋白。 特别地，在将含有蛋白质的样品经受包含第一区域的抗体的珠粒后，鉴定融合蛋白，然后使珠抗体 - 融合复合物受到针对第二区域的第二抗体的检测，从而检测融合蛋白 蛋白。 在具体方面，本发明用于为患有癌症的个体提供预后，以确定特定癌症治疗的适用性和/或监测患者对治疗的反应。

公开(公告)号：US20090226933A1

公开(公告)日：2009-09-10

申请号：US12094112

申请日：2006-11-14

申请人： Maher Albitar ,  Hagop Kantarjian ,  Francis Giles ,  Iman Jilani

发明人： Maher Albitar ,  Hagop Kantarjian ,  Francis Giles ,  Iman Jilani

IPC分类号： G01N33/53

CPC分类号： G01N33/573 ,  G01N33/53 ,  G01N33/574 ,  G01N33/57426

摘要： The present invention concerns the detection of gene products resulting from chromosomal translocations, including fusion proteins comprising a first and second region. In particular, the fusion proteins are identified following subjecting a sample comprising the proteins to a bead comprising an antibody to a first region, followed by subjecting the bead-antibody-fusion complex to a second antibody directed against the second region, thereby detecting the fusion protein. In particular aspects, the invention is employed to provide prognosis for an individual with cancer, to identify suitability for a particular cancer therapy, and/or to monitor response of a patient to a therapy, for example.

摘要翻译： 本发明涉及由染色体易位引起的基因产物的检测，包括包含第一和第二区域的融合蛋白。 特别地，在将含有蛋白质的样品经受包含第一区域的抗体的珠粒后，鉴定融合蛋白，然后使珠抗体 - 融合复合物接受针对第二区域的第二抗体，从而检测融合蛋白 蛋白。 在具体方面，本发明用于为患有癌症的个体提供预后，以确定特定癌症治疗的适用性和/或监测患者对治疗的反应。

公开(公告)号：US20060073527A1

公开(公告)日：2006-04-06

申请号：US11110374

申请日：2005-04-20

申请人： Maher Albitar ,  Elihu Estey ,  Hagop Kantarjian ,  Francis Giles ,  Michael Keating

发明人： Maher Albitar ,  Elihu Estey ,  Hagop Kantarjian ,  Francis Giles ,  Michael Keating

IPC分类号： G01N33/574 ,  G01N33/00

CPC分类号： G01N33/6851 ,  G01N33/57426 ,  G01N33/6803 ,  G01N33/6848 ,  G01N2800/52 ,  Y10T436/24 ,  Y10T436/25 ,  Y10T436/25625

摘要： The present invention demonstrates that the diagnosis and prediction of clinical behavior in patients with hematologic malignancies, such as leukemia, can be accomplished by analysis of proteins present in a plasma sample. Thus, in particular embodiments the present invention uses plasma to create a diagnostic or prognostic protein profile of a hematologic malignancy comprising collecting plasma samples from a population of patients with hematologic malignancies; generating protein spectra from the plasma samples with or without fractionation; comparing the protein spectra with clinical data; and identifying protein markers in the plasma samples that correlate with the clinical data. Protein markers identified by this approach can then be used to create a protein profile that can be used to diagnose the hematologic malignancy or determine the prognosis of the hematologic malignancy. Potentially these specific proteins can be identified and targeted in the therapy of these malignancies.

公开(公告)号：US20060029574A1

公开(公告)日：2006-02-09

申请号：US10913296

申请日：2004-08-06

申请人： Maher Albitar ,  Hagop Kantarjian ,  Ira Goldknopf ,  Essam Sheta

发明人： Maher Albitar ,  Hagop Kantarjian ,  Ira Goldknopf ,  Essam Sheta

IPC分类号： G01N33/574

CPC分类号： G01N33/5748 ,  G01N33/57407 ,  G01N2333/82

摘要： The present invention provides methods and compositions for identifying cancer cells that are either sensitive or resistant to a particular anti-cancer therapy. Accordingly, the present invention allows for more accurate diagnosis, prognosis, and monitoring of a subject's condition. Furthermore, the ability to assess a subject's resistance or sensitivity to a particular treatment regimen will permit more informed treatment decisions to be made prior to beginning therapy. The present invention also overcomes deficiencies in the prior art concerning the treatment of cancers by providing methods and compositions for treating cancer and improving the effectiveness of other cancer therapies.

摘要翻译： 本发明提供用于鉴定对特定抗癌疗法敏感或抗性的癌细胞的方法和组合物。 因此，本发明允许对受试者的状况进行更准确的诊断，预后和监测。 此外，评估受试者对特定治疗方案的抵抗力或敏感性的能力将允许在开始治疗之前进行更明智的治疗决定。 本发明还通过提供用于治疗癌症的方法和组合物并提高其它癌症疗法的有效性来克服关于癌症治疗的现有技术的缺陷。

公开(公告)号：US06645972B2

公开(公告)日：2003-11-11

申请号：US10286960

申请日：2002-11-04

申请人： Jacques Jolivet ,  Francis Giles ,  Hagop Kantarjian

发明人： Jacques Jolivet ,  Francis Giles ,  Hagop Kantarjian

IPC分类号： A61K31505

CPC分类号： A61K31/506 ,  Y10S514/908 ,  Y10S514/922

摘要： The present invention provides a novel method for treating leukemia in a host that has been previously treated with a Bcr-Abl tyrosine kinase inhibitor comprising administering to the host a therapeutically effective amount of a compound having the formula I: wherein B is cytosine or 5-fluorocytosine and R is selected from H, monophosphate, diphosphate, triphosphate, carbonyl substituted with a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and and where in each Rc is independently selected from the group comprising H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl an hydroxy protecting group.

摘要翻译： 本发明提供了一种用于治疗先前用Bcr-Abl酪氨酸激酶抑制剂治疗的宿主中的白血病的新方法，包括向宿主施用治疗有效量的具有式I的化合物：其中B为胞嘧啶或5- 氟胞嘧啶，R选自H，单磷酸盐，二磷酸盐，三磷酸盐，被C 1-6烷基取代的羰基，C 2-6烯基，C 2-6炔基，C 6-10芳基，并且其中每个R c独立地选自 H，C 1-6烷基，C 2-6烯基，C 2-6炔基，羟基保护基。

公开(公告)号：US20060189687A1

公开(公告)日：2006-08-24

申请号：US11349043

申请日：2006-02-06

申请人： Ralph Zingaro ,  Emil Freireich ,  Hatice Duzkale ,  Hagop Kantarjian ,  Srdan Verstovsek ,  Merida Sotelo-Lerma

发明人： Ralph Zingaro ,  Emil Freireich ,  Hatice Duzkale ,  Hagop Kantarjian ,  Srdan Verstovsek ,  Merida Sotelo-Lerma

IPC分类号： C07F9/90 ,  A61K31/285

CPC分类号： C07F9/72

摘要： Arsenic trioxide, an inorganic compound, is commercially available anti-cancer agent but it carries significant toxicity. Organic arsenicals, on the other hand, are much less toxic, to the extent that the methylation of inorganic arsenic in vivo into organic arsenicals has been considered a detoxification reaction. New organic arsenic derivatives have been synthesized, including S-dimethylarsino-glutathione, S-dimethylarsino-thiosuccinic acid and S-dimethylarsino-thiobenzoic acid, and established its potent in vitro cytotoxic activity against numerous human tumor cell lines, both of solid and hematological origin, as well as against malignant blood cells from patients with leukemia. Results form a basis for the development of S-dimethylarsino-glutathione, S-dimethylarsino-thiosuccinic acid, S-dimethylarsino-thiobenzoic acid, and other organic arsenicals as an anti-cancer therapy, combining high efficacy with very low, if any, toxicity.

公开(公告)号：US07619000B2

公开(公告)日：2009-11-17

申请号：US11349043

申请日：2006-02-06

申请人： Ralph A. Zingaro ,  Emil J. Freireich ,  Hatice Duzkale ,  Hagop Kantarjian ,  Srdan Verstovsek ,  Merida Sotelo-Lerma

发明人： Ralph A. Zingaro ,  Emil J. Freireich ,  Hatice Duzkale ,  Hagop Kantarjian ,  Srdan Verstovsek ,  Merida Sotelo-Lerma

IPC分类号： A61K31/285 ,  A61K33/36 ,  C07F9/00

CPC分类号： C07F9/72

摘要： Arsenic trioxide, an inorganic compound, is commercially available anti-cancer agent but it carries significant toxicity. Organic arsenicals, on the other hand, are much less toxic, to the extent that the methylation of inorganic arsenic in vivo into organic arsenicals has been considered a detoxification reaction. New organic arsenic derivatives have been synthesized, including S-dimethylarsino-glutathione, S-dimethylarsino-thiosuccinic acid and S-dimethylarsino-thiobenzoic acid, and established its potent in vitro cytotoxic activity against numerous human tumor cell lines, both of solid and hematological origin, as well as against malignant blood cells from patients with leukemia. Results form a basis for the development of S-dimethylarsino-glutathione, S-dimethylarsino-thiosuccinic acid, S-dimethylarsino-thiobenzoic acid, and other organic arsenicals as an anti-cancer therapy, combining high efficacy with very low, if any, toxicity.

摘要翻译： 三氧化二砷（无机化合物）是市售的抗癌剂，但具有显着的毒性。 另一方面，有机砷的毒性远低于体内无机砷甲基化成有机砷被认为是解毒反应的程度。 已经合成了新的有机砷衍生物，包括S-二甲基胂基 - 谷胱甘肽，S-二甲基胂基 - 硫代琥珀酸和S-二甲基胂基 - 硫代苯甲酸，并建立了其对许多人类肿瘤细胞系的有效体外细胞毒活性，包括固体和血液学起源 ，以及来自白血病患者的恶性血细胞。 结果形成了开发S-二甲基胂基 - 谷胱甘肽，S-二甲基胂基 - 硫代琥珀酸，S-二甲基胂基 - 硫代苯甲酸和其他有机砷作为抗癌治疗的基础，将高效率与非常低（如果有的话）毒性相结合 。

公开(公告)号：US07405314B2

公开(公告)日：2008-07-29

申请号：US11252966

申请日：2005-10-17

申请人： Ralph A. Zingaro ,  Hatice Duzkale ,  Emil J. Freireich ,  Hagop Kantarjian ,  Merida Sotelo-Lerma ,  Srdan Verstovsek ,  Mingzhang Gao

发明人： Ralph A. Zingaro ,  Hatice Duzkale ,  Emil J. Freireich ,  Hagop Kantarjian ,  Merida Sotelo-Lerma ,  Srdan Verstovsek ,  Mingzhang Gao

IPC分类号： A61K61/285 ,  C07F9/00

CPC分类号： C07F9/72 ,  C07F9/74

摘要： The present invention provides organic arsenicals. Many of these compounds have potent in vitro cytotoxic activity against numerous human tumor cell lines, both of solid and hematological origin, as well as against malignant blood cells from patients with leukemia.

公开(公告)号：US06911471B2

公开(公告)日：2005-06-28

申请号：US10337969

申请日：2003-01-07

申请人： Ralph A. Zingaro ,  Emil J. Freireich ,  Hatice Duzkale ,  Hagop Kantarjian ,  Srdan Verstovsek ,  Merida Sotelo-Lerma

发明人： Ralph A. Zingaro ,  Emil J. Freireich ,  Hatice Duzkale ,  Hagop Kantarjian ,  Srdan Verstovsek ,  Merida Sotelo-Lerma

IPC分类号： A61K38/00 ,  A61K31/203 ,  A61K31/285 ,  A61P35/00 ,  A61P35/02 ,  C07F9/72 ,  C07F9/74 ,  C07F9/78 ,  A61K33/36 ,  C07F9/70

CPC分类号： C07F9/72

摘要： Arsenic trioxide, an inorganic compound, is commercially available anti-cancer agent but it carries significant toxicity. Organic arsenicals, on the other hand, are much less toxic, to the extent that the methylation of inorganic arsenic in vivo into organic arsenicals has been considered a detoxification reaction. New organic arsenic derivatives have been synthesized, including S-dimethylarsino-glutathione, S-dimethylarsino-thiosuccinic acid and S-dimethylarsino-thiobenzoic acid, and established its potent in vitro cytotoxic activity against numerous human tumor cell lines, both of solid and hematological origin, as well as against malignant blood cells from patients with leukemia. Results form a basis for the development of S-dimethylarsino-glutathione, S-dimethylarsino-thiosuccinic acid, S-dimethylarsino-thiobenzoic acid, and other organic arsenicals as an anti-cancer therapy, combining high efficacy with very low, if any, toxicity.

摘要翻译： 三氧化二砷（无机化合物）是市售的抗癌剂，但具有显着的毒性。 另一方面，有机砷的毒性远低于体内无机砷甲基化成有机砷被认为是解毒反应的程度。 已经合成了新的有机砷衍生物，包括S-二甲基胂基 - 谷胱甘肽，S-二甲基胂基 - 硫代琥珀酸和S-二甲基胂基 - 硫代苯甲酸，并建立了其对许多人类肿瘤细胞系的有效体外细胞毒活性，包括固体和血液学起源 ，以及来自白血病患者的恶性血细胞。 结果形成了开发S-二甲基胂基 - 谷胱甘肽，S-二甲基胂基 - 硫代琥珀酸，S-二甲基胂基 - 硫代苯甲酸和其他有机砷作为抗癌治疗的基础，将高效率与非常低（如果有的话）毒性相结合 。

公开(公告)号：US20080090904A1

公开(公告)日：2008-04-17

申请号：US11894807

申请日：2007-08-20

申请人： Ralph Zingaro ,  Emil Freireich ,  Hatice Duzkale ,  Hagop Kantarjian ,  Srdan Verstovsek ,  Merida Sotelo-Lerma

发明人： Ralph Zingaro ,  Emil Freireich ,  Hatice Duzkale ,  Hagop Kantarjian ,  Srdan Verstovsek ,  Merida Sotelo-Lerma

IPC分类号： A61K31/285 ,  A61P35/00 ,  C07F9/66

CPC分类号： C07F9/72

摘要： Arsenic trioxide, an inorganic compound, is commercially available anti-cancer agent but it carries significant toxicity. Organic arsenicals, on the other hand, are much less toxic, to the extent that the methylation of inorganic arsenic in vivo into organic arsenicals has been considered a detoxification reaction. New organic arsenic derivatives have been synthesized, including S-dimethylarsino-glutathione, S-dimethylarsino-thiosuccinic acid and S-dimethylarsino-thiobenzoic acid, and established its potent in vitro cytotoxic activity against numerous human tumor cell lines, both of solid and hematological origin, as well as against malignant blood cells from patients with leukemia. Results form a basis for the development of S-dimethylarsino-glutathione, S-dimethylarsino-thiosuccinic acid, S-dimethylarsino-thiobenzoic acid, and other organic arsenicals as an anti-cancer therapy, combining high efficacy with very low, if any, toxicity.

摘要翻译： 三氧化二砷（无机化合物）是市售的抗癌剂，但具有显着的毒性。 另一方面，有机砷的毒性远低于体内无机砷甲基化成有机砷被认为是解毒反应的程度。 已经合成了新的有机砷衍生物，包括S-二甲基胂基 - 谷胱甘肽，S-二甲基胂基 - 硫代琥珀酸和S-二甲基胂基 - 硫代苯甲酸，并建立了其对许多人类肿瘤细胞系的有效体外细胞毒活性，包括固体和血液学起源 ，以及来自白血病患者的恶性血细胞。 结果形成了开发S-二甲基胂基 - 谷胱甘肽，S-二甲基胂基 - 硫代琥珀酸，S-二甲基胂基 - 硫代苯甲酸和其他有机砷作为抗癌治疗的基础，将高效率与非常低（如果有的话）毒性相结合 。