公开(公告)号：US20050048476A1

公开(公告)日：2005-03-03

申请号：US10006305

申请日：2001-12-06

申请人： Charles Prussak ,  Thomas Kipps ,  Mark Cantwell

发明人： Charles Prussak ,  Thomas Kipps ,  Mark Cantwell

IPC分类号： C12N15/09 ,  A61K31/7088 ,  A61K38/00 ,  A61K48/00 ,  A61P35/00 ,  C07K14/525 ,  C07K19/00 ,  C12N5/10 ,  C12P21/02 ,  C12P21/04 ,  C12Q1/68 ,  C07H21/04 ,  C07K14/52 ,  C12N5/06

CPC分类号： C07K14/525 ,  A61K38/00 ,  C07K2319/00

摘要： The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNFα, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNFα, wherein the encoded domain or subdomain replaces a cleavage site of native TNFα, and a second nucleotide sequence encoding a domain or subdomain of native TNFα that binds to a TNFα receptor. The encoded chimeric TNFα is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNFα receptor on the surface of a cell. The chimeric TNFα is therefore useful in methods for inducing apoptosis of a cell expressing a TNFα receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNFα that is expressed on the surface of the cell.

摘要翻译： 本发明涉及编码嵌合TNFα的分离的多核苷酸序列，其包含编码除TNFalpha之外的肿瘤坏死因子配体的结构域或亚结构域的第一核苷酸序列，其中编码的结构域或亚结构域替代天然TNFα的切割位点，以及 编码结合TNFα受体的天然TNFα的结构域或亚结构域的第二核苷酸序列。 编码的嵌合TNFα对于细胞表面的切割显着较不敏感，因此可以增加能够结合细胞表面的TNFα受体的配体的浓度。 因此，嵌合TNFα可用于诱导表达TNFα受体的细胞凋亡的方法，诱导免疫系统细胞的活化和治疗肿瘤细胞，通过将感兴趣的细胞引入编码嵌合TNFα的分离的多核苷酸序列，所述多核苷酸序列表达于 电池的表面。

公开(公告)号：US20060183199A1

公开(公告)日：2006-08-17

申请号：US11015117

申请日：2004-12-17

申请人： Thomas Kipps ,  Sanjai Sharma ,  Mark Cantwell

发明人： Thomas Kipps ,  Sanjai Sharma ,  Mark Cantwell

IPC分类号： C07H21/04 ,  C12P21/02 ,  C07K14/525

CPC分类号： C07K14/48 ,  A61K48/00 ,  A61K2039/51 ,  C07K14/52 ,  C07K14/525 ,  C07K14/5255 ,  C07K14/705 ,  C07K14/70575 ,  C07K2319/00 ,  C12N2799/021

摘要： This invention relates to genes which encode accessory molecule ligands and their use for immunomodulation, vaccination and treatments of various human diseases, including malignancies and autoimmune diseases. This invention also describes the use of accessory molecule ligands which are made up of various domains and subdomain portions of molecules derived from the tumor necrosis factor family. The chimeric molecules of this invention contain unique properties which lead to the stabilization of their activities and thus greater usefulness in the treatment of diseases. Vectors for expressing genes which encode the accessory molecule ligands of this invention are also disclosed.

摘要翻译： 本发明涉及编码辅助分子配体的基因及其用于免疫调节，疫苗接种和治疗各种人类疾病（包括恶性肿瘤和自身免疫性疾病）的用途。 本发明还描述了由衍生自肿瘤坏死因子家族的分子的各种结构域和亚结构域部分构成的辅助分子配体的用途。 本发明的嵌合分子含有独特的性质，其导致其活性的稳定，因此在治疗疾病方面更有用。 还公开了用于表达编码本发明的辅助分子配体的基因的载体。

公开(公告)号：US20070207510A1

公开(公告)日：2007-09-06

申请号：US11709917

申请日：2007-02-21

申请人： Thomas Kipps ,  Tetsuya Fukuda ,  Tomoyuki Endo

发明人： Thomas Kipps ,  Tetsuya Fukuda ,  Tomoyuki Endo

IPC分类号： G01N33/574 ,  C07K16/30

CPC分类号： G01N33/57426 ,  A61K39/0011 ,  A61K2039/53 ,  C07K16/081 ,  C07K16/3061 ,  G01N33/57415 ,  G01N33/57419

摘要： Compositions comprising a purified, isolated antibody, humanized antibodies and precipitates directed against ROR-1, wherein the antibody binds ROR-1 with moderate to high affinity. The compositions may be used for detecting and isolating an amount of ROR-1 in a subject sample, and to evaluate the appearance, status, course, or treatment of a ROR-1 cancer in a subject. The ROR-1 antibodies are especially useful in identifying lymphomas and ademocarcinomas. Vaccines and related methods for protecting a subject against diseases that involve expression of ROR-1 are also provided.

摘要翻译： 包含纯化的分离的抗体，针对ROR-1的人源化抗体和沉淀物的组合物，其中所述抗体以中等至高亲和力结合ROR-1。 该组合物可用于检测和分离受试者样品中ROR-1的量，并评估受试者中ROR-1癌症的外观，状态，疗程或治疗。 ROR-1抗体特别可用于鉴定淋巴瘤和腺癌。 还提供了用于保护受试者免受涉及ROR-1表达的疾病的疫苗和相关方法。

公开(公告)号：US08114590B2

公开(公告)日：2012-02-14

申请号：US12960955

申请日：2010-12-06

申请人： Paul A. Insel ,  Lingzhi Zhang ,  Fionna Murray ,  Joan R. Kanter ,  Thomas Kipps ,  Laura Rassenti

发明人： Paul A. Insel ,  Lingzhi Zhang ,  Fionna Murray ,  Joan R. Kanter ,  Thomas Kipps ,  Laura Rassenti

IPC分类号： C12Q1/68 ,  C07H21/04

CPC分类号： C12Q1/6886 ,  C12Q2600/158

摘要： The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL, particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

摘要翻译： 本发明通过测定与CLL，特别是PDE7B和/或PDE3B相关的环状核苷酸磷酸二酯酶（PDEs）的同种型的表达水平以及PDE7B的mRNA表达的比例来提供用于诊断慢性淋巴细胞性白血病（CLL）的诊断方法和试剂盒 到PDE3B。 本发明提供了CLL淋巴细胞相对于正常淋巴细胞均匀表达高水平的PDE7B和低水平的PDE3B。 还提供了一种治疗方法和用于CLL的药物组合物，其包含一种或多种能够调节与CLL相关的PDE的同种型的表达或活性水平和/或逆转PDE7B / PDE3B mRNA表达水平的比例的治疗剂。

公开(公告)号：US20090131353A1

公开(公告)日：2009-05-21

申请号：US12096628

申请日：2006-12-07

申请人： Paul A. Insel ,  Lingzhi Zhang ,  Fiona Murray ,  Joan R. Kanter ,  Thomas Kipps ,  Laura Rassenti

发明人： Paul A. Insel ,  Lingzhi Zhang ,  Fiona Murray ,  Joan R. Kanter ,  Thomas Kipps ,  Laura Rassenti

IPC分类号： A61K48/00 ,  C12Q1/68 ,  A61K31/7105 ,  A61P35/02 ,  A61K31/711

CPC分类号： C12Q1/6886 ,  C12Q2600/158

摘要： The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

摘要翻译： 本发明通过确定与CLL特别是PDE7B和/或PDE3B相关的环核苷酸磷酸二酯酶（PDE）的同种型的表达水平，以及PDE7B的mRNA表达比例与PDE7B的mRNA表达的比例，提供了用于诊断慢性淋巴细胞性白血病（CLL）的诊断方法和试剂盒 PDE3B。 本发明提供了CLL淋巴细胞相对于正常淋巴细胞均匀表达高水平的PDE7B和低水平的PDE3B。 还提供了一种治疗方法和用于CLL的药物组合物，其包含一种或多种能够调节与CLL相关的PDE的同种型的表达或活性水平和/或逆转PDE7B / PDE3B mRNA表达水平的比例的治疗剂。

公开(公告)号：US07846664B2

公开(公告)日：2010-12-07

申请号：US12096628

申请日：2006-12-07

申请人： Paul A. Insel ,  Lingzhi Zhang ,  Fiona Murray ,  Joan R. Kanter ,  Thomas Kipps ,  Laura Rassenti

发明人： Paul A. Insel ,  Lingzhi Zhang ,  Fiona Murray ,  Joan R. Kanter ,  Thomas Kipps ,  Laura Rassenti

IPC分类号： C12Q1/68 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12Q1/6886 ,  C12Q2600/158

摘要： The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

摘要翻译： 本发明通过确定与CLL特别是PDE7B和/或PDE3B相关的环核苷酸磷酸二酯酶（PDE）的同种型的表达水平，以及PDE7B的mRNA表达比例与PDE7B的mRNA表达的比例，提供了用于诊断慢性淋巴细胞性白血病（CLL）的诊断方法和试剂盒 PDE3B。 本发明提供了CLL淋巴细胞相对于正常淋巴细胞均匀表达高水平的PDE7B和低水平的PDE3B。 还提供了一种治疗方法和用于CLL的药物组合物，其包含一种或多种能够调节与CLL相关的PDE的同种型的表达或活性水平和/或逆转PDE7B / PDE3B mRNA表达水平的比例的治疗剂。

公开(公告)号：US20070243561A1

公开(公告)日：2007-10-18

申请号：US11675958

申请日：2007-02-16

申请人： Ben Geeraerts ,  Laura Rassenti ,  Fritz Offner ,  Thomas Kipps ,  Dieter Deforce

发明人： Ben Geeraerts ,  Laura Rassenti ,  Fritz Offner ,  Thomas Kipps ,  Dieter Deforce

IPC分类号： G01N33/53

CPC分类号： G01N33/57426

摘要： Methods and compositions for detecting a form of chronic lymphocytic leukemia in a subject are described which allow for distinguishing more aggressive forms of the disease from less aggressive forms. Particularly described methods include assaying a sample obtained from the subject having or suspected of having chronic lymphocytic leukemia for a marker selected from a vimentin cleavage product, annexin 5 and 6-phosphogluconolactonase. A combination of any of these markers may be assayed in particular embodiments of a method according to the present invention. In particular embodiments, detection of an intermediate weight vimentin cleavage product is indicative of a less aggressive form of CLL associated with good prognosis.

摘要翻译： 描述了用于检测受试者中慢性淋巴细胞性白血病形式的方法和组合物，其允许将更具侵略性的形式的疾病与较不具侵略性的形式区分开。 特别描述的方法包括测定从具有或疑似具有慢性淋巴细胞性白血病的受试者获得的样品用于选自波形蛋白裂解产物，膜联蛋白5和6-磷酸葡萄糖聚糖内切酶的标记。 任何这些标记物的组合可以在根据本发明的方法的具体实施方案中进行测定。 在具体实施方案中，中等重量波形蛋白切割产物的检测指示与良好预后相关的较低侵袭性的CLL形式。

公开(公告)号：US20110117562A1

公开(公告)日：2011-05-19

申请号：US12960955

申请日：2010-12-06

申请人： Paul A. Insel ,  Lingzhi Zhang ,  Fionna Murray ,  Joan R. Kanter ,  Thomas Kipps ,  Laura Rassenti

发明人： Paul A. Insel ,  Lingzhi Zhang ,  Fionna Murray ,  Joan R. Kanter ,  Thomas Kipps ,  Laura Rassenti

IPC分类号： C12Q1/44 ,  C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/158

摘要： The present invention provides diagnostic methods and kits for diagnosis of chronic lymphocytic leukemia (CLL) by determining expression levels of isoforms of cyclic nucleotide phosphodiesterases (PDEs) associated with CLL, particularly, PDE7B and/or PDE3B, and a ratio of mRNA expression of PDE7B to PDE3B. The present invention provides that CLL lymphocytes uniformly expressed high levels of PDE7B and low levels of PDE3B relative to those of normal lymphocytes. A method of treatment and a pharmaceutical composition for CLL comprising one or more therapeutic agents capable of modulating expression or activity levels of isoforms of PDEs associated with CLL, and/or reversing the ratio of PDE7B/PDE3B mRNA expression levels are also provided.

摘要翻译： 本发明通过测定与CLL，特别是PDE7B和/或PDE3B相关的环状核苷酸磷酸二酯酶（PDEs）的同种型的表达水平以及PDE7B的mRNA表达的比例来提供用于诊断慢性淋巴细胞性白血病（CLL）的诊断方法和试剂盒 到PDE3B。 本发明提供了CLL淋巴细胞相对于正常淋巴细胞均匀表达高水平的PDE7B和低水平的PDE3B。 还提供了一种治疗方法和用于CLL的药物组合物，其包含一种或多种能够调节与CLL相关的PDE的同种型的表达或活性水平和/或逆转PDE7B / PDE3B mRNA表达水平的比例的治疗剂。