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1. 发明授权

US09274120B2 Stratification of pancreatic and ovarian cancer patients for susceptibility to therapy with PTK2 inhibitors 有权
公开(公告)号：US09274120B2
公开(公告)日：2016-03-01
申请号：US14221370
申请日：2014-03-21
申请人： Guenther Adolf , Pilar Garin-Chesa , Ulrich Hirt
发明人： Guenther Adolf , Pilar Garin-Chesa , Ulrich Hirt
IPC分类号： G01N33/53 , C12Q1/00 , G01N33/574 , C12Q1/68
CPC分类号： G01N33/57492 , C12Q1/6886 , G01N33/57484 , G01N33/57496 , G01N2333/705 , G01N2333/91205 , G01N2800/52
摘要： The present invention relates to a method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. Said detection of the expression of the E-cadherin protein in a cancer sample of a cancer patient is preferably conducted by way of an immunohistochemistry (IHC) method. Said IHC method preferably employs a primary antibody which is specific for E-cadherin and a secondary antibody which specifically reacts with the primary antibody. The present invention also relates to a method of treating a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2, comprising administering to the patient a therapeutically effective amount of a PTK2 inhibitor. In a further aspect, the present invention relates to a PTK2 inhibitor for use in the treatment of a cancer patient whose cancer is characterized by an E-cadherin protein immunoreactivity score (IRS) of 0-2. The present invention also provides a method of screening for a therapeutically effective PTK2 inhibitor comprising the steps of (a) providing cancer cells or a cancer cell line which are characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being even more preferred); (b) contacting the cancer cell or the cancer cell line of (a) with a PTK2 inhibitor; and (c) evaluating whether the PTK2 inhibitor negatively affects the cancer cell/cancer cell lines. In a further aspect, the present invention relates to a method for stratifying cancer patients that are susceptible to treatment with a PTK2 inhibitor, comprising determining the E-cadherin IRS score in a cancer sample of said patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 (i.e. 2, 1, or 0) indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. The present invention also relates to a pharmaceutical package comprising a PTK2 inhibitor, and (a) instructions and/or an imprint indicating that said PTK2 inhibitor is to be used for the treatment of patients which suffer from a cancer which is characterized by an E-cadherin protein immunoreactivity score of 2, 1, or 0 (1 being preferred and 0 being more preferred); and/or (b) instructions and/or an imprint indicating that said patient is to be stratified by a method of the present invention; and/or (c) means to carry out a method as defined herein.

2. 发明授权

US07714010B2 Pyrrolobenzimidazolones and their use as anti-proliferative agents 有权
标题翻译：吡咯并苯并咪唑酮及其作为抗增殖剂的用途
公开(公告)号：US07714010B2
公开(公告)日：2010-05-11
申请号：US11130542
申请日：2005-05-17
申请人： Darryl McConnel , Steffen Steurer , Bernd Krist , Ulrike Weyer-Czernilofsky , Maria Impagnatiello , Matthias Treu , Iris Kauffmann-Hefner , Pilar Garin-Chesa , Andreas Schnapp
发明人： Darryl McConnel , Steffen Steurer , Bernd Krist , Ulrike Weyer-Czernilofsky , Maria Impagnatiello , Matthias Treu , Iris Kauffmann-Hefner , Pilar Garin-Chesa , Andreas Schnapp
IPC分类号： A61K31/4184 , A61K31/4188 , C07D235/02
CPC分类号： C07D487/04
摘要： The invention relates to pyrrolobenzimidazolone compounds of formula (I), wherein A, T and R1 to R3 are defined as in claim 1, which are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation and the use thereof for preparing a pharmaceutical composition.
摘要翻译：本发明涉及式（I）的吡咯并苯并咪唑酮化合物，其中A，T和R 1至R 3如权利要求1中所定义，其适用于治疗以细胞增殖过度或异常为特征的疾病及其用于制备药物组成。

3. 发明授权

US06455677B1 FAP&agr;-specific antibody with improved producibility 有权
标题翻译：具有提高生产力的FAPα特异性抗体
公开(公告)号：US06455677B1
公开(公告)日：2002-09-24
申请号：US09301593
申请日：1999-04-29
申请人： John Edward Park , Pilar Garin-Chesa , Uwe Bamberger , Wolfgang J. Rettig , Olivier Lèger , Jose William Saldanha
发明人： John Edward Park , Pilar Garin-Chesa , Uwe Bamberger , Wolfgang J. Rettig , Olivier Lèger , Jose William Saldanha
IPC分类号： C07K1630
CPC分类号： C07K16/40 , A61K38/00 , A61K2039/505 , C07K2317/24 , C07K2317/567 , C07K2319/00 , C12N2799/026
摘要： Recombinant antibody proteins are provided that specifically bind fibroblast activation protein alpha (FAP&agr;) and comprise framework modifications resulting in the improved producibility in host cells. The invention also relates to the use of said antibodies for diagnostic and therapeutic purposes and methods of producing said antibodies.
摘要翻译：提供重组抗体蛋白质，其特异性结合成纤维细胞活化蛋白α（FAPalpha）并且包含框架修饰，导致提高宿主细胞的生产性。本发明还涉及所述抗体用于诊断和治疗目的的用途以及产生所述抗体的方法。

4. 发明授权

US06348195B1 Method for treating cancers 有权
标题翻译：治疗癌症的方法
公开(公告)号：US06348195B1
公开(公告)日：2002-02-19
申请号：US09602709
申请日：2000-06-26
申请人： Thomas Paul Wallace , William Joseph Harris , Francis Joseph Carr , Wolfgang J. Rettig , Pilar Garin-Chesa , Lloyd J. Old
发明人： Thomas Paul Wallace , William Joseph Harris , Francis Joseph Carr , Wolfgang J. Rettig , Pilar Garin-Chesa , Lloyd J. Old
IPC分类号： A61K39395
CPC分类号： G01N33/6854 , G01N33/57484 , G01N33/6833
摘要： The invention provides for the production of several humanized murine antibodies specific for the antigen LK26, which is recognized by the murine antibody LK26. This antigen is expressed on all choriocarcinoma, teratocarcinoma and renal cancer cell lines whereas it is not expressed on cell lines of leukaemias, lymphomas, neuroectodermally-derived and epithelial tumor cell lines (excepting a small subset of epithelial cell lines). Furthermore, whereas renal cancer cell lines express the LK26 antigen, normal renal epithelial cells do not. Similarly, with the exception of the trophoblast, all normal adult and fetal tissues tested are negative for the LK26 phenotype. The invention also provides for numerous polynucleotide encoding humanized LK26 specific antibodies, expression vectors for producing humanized LK26 specific antibodies, and host cells for the recombinant production of the humanized antibodies. The invention also provides methods for detecting cancerous cells (in vitro and in vivo) using humanized LK26 specific antibodies. Additionally, the invention provides methods of treating cancer using LK26 specific antibodies.
摘要翻译：本发明提供了针对抗原LK26特异的几种人源化鼠抗体的产生，其被鼠抗体LK26识别。该抗原在所有绒毛膜癌，畸胎癌和肾癌细胞系中表达，而不在白血病，淋巴瘤，神经外胚层衍生的和上皮性肿瘤细胞系的细胞系（除了上皮细胞系的一小部分之外）上表达。此外，肾癌细胞株表达LK26抗原时，肾上皮细胞不正常。类似地，除了滋养层之外，所有正常的成年和胎儿组织都检测到LK26表型阴性。本发明还提供编码人源化LK26特异性抗体的许多多核苷酸，用于产生人源化LK26特异性抗体的表达载体和用于重组产生人源化抗体的宿主细胞。本发明还提供了使用人源化LK26特异性抗体检测癌细胞（体外和体内）的方法。另外，本发明提供使用LK26特异性抗体治疗癌症的方法。

5. 发明授权

US06217868B1 Methods for detecting cancer cells by using humanized antibodies which bind specifically to FB5 antigen 有权
标题翻译：通过使用特异性结合FB5抗原的人源化抗体检测癌细胞的方法
公开(公告)号：US06217868B1
公开(公告)日：2001-04-17
申请号：US09184198
申请日：1998-11-02
申请人： Thomas Paul Wallace , Francis Carr , Wolfgang J. Rettig , Pilar Garin-Chesa , Lloyd J. Old
发明人： Thomas Paul Wallace , Francis Carr , Wolfgang J. Rettig , Pilar Garin-Chesa , Lloyd J. Old
IPC分类号： A61K39395
CPC分类号： C07K16/30 , C07K2317/24 , C07K2319/00
摘要： The invention provides for the production of several humanized murine antibodies specific for the antigen FB5, which is recognized by the murine antibody FB5. The FB5 antigen is expressed on the luminal surface of vascular endothelial cells of a wide range of malignant tumors. The invention also provides for numerous polynucleotide encoding humanized FB5 specific antibodies, expression vectors for producing humanized FB5 specific antibodies, and host cells for the recombinant production of the humanized antibodies. The invention also provides methods for detecting cancerous cells (in vitro and in vivo) using humanized FB5 specific antibodies. Additionally, the invention provides methods of treating cancer using FB5 specific antibodies.
摘要翻译：本发明提供了针对抗原FB5特异的几种人源化鼠抗体的产生，其被鼠抗体FB5识别。 FB5抗原在广泛恶性肿瘤的血管内皮细胞的腔表面上表达。本发明还提供编码人源化FB5特异性抗体的许多多核苷酸，用于产生人源化FB5特异性抗体的表达载体和用于重组产生人源化抗体的宿主细胞。本发明还提供使用人源化FB5特异性抗体检测癌细胞（体外和体内）的方法。另外，本发明提供了使用FB5特异性抗体治疗癌症的方法。

6. 发明申请

US20120136004A1 NEW COMBINATION THERAPY IN TREATMENT OF CANCER AND FIBROTIC DISEASES 审中-公开
标题翻译：治疗癌症和纤维性疾病的新组合治疗
公开(公告)号：US20120136004A1
公开(公告)日：2012-05-31
申请号：US13318395
申请日：2010-05-11
申请人： Joanne Van Ryn , Pilar Garin-Chesa , Flavio Solca
发明人： Joanne Van Ryn , Pilar Garin-Chesa , Flavio Solca
IPC分类号： A61K31/517 , A61P35/02 , A61P43/00 , A61P35/00
CPC分类号： A61K31/517 , A61K31/4439 , A61K31/496 , A61K2300/00
摘要： The invention relates to new methods for the treatment of oncological and fibrotic diseases comprising the combined administration of a receptor tyrosine kinase inhibitor in conjunction with a thrombin inhibitor.
摘要翻译：本发明涉及用于治疗肿瘤和纤维化疾病的新方法，其包括与凝血酶抑制剂联合施用受体酪氨酸激酶抑制剂。

7. 发明申请

US20050261350A1 Pyrrolobenzimidazolones and their use as anti-proliferative agents 有权
标题翻译：吡咯并苯并咪唑酮及其作为抗增殖剂的用途
公开(公告)号：US20050261350A1
公开(公告)日：2005-11-24
申请号：US11130542
申请日：2005-05-17
申请人： Darryl McConnel , Steffen Steurer , Bernd Krist , Ulrike Weyer-Czernilofsky , Maria Impagnatiello , Matthias Treu , Iris Kauffmann-Hefner , Pilar Garin-Chesa , Andreas Schnapp
发明人： Darryl McConnel , Steffen Steurer , Bernd Krist , Ulrike Weyer-Czernilofsky , Maria Impagnatiello , Matthias Treu , Iris Kauffmann-Hefner , Pilar Garin-Chesa , Andreas Schnapp
IPC分类号： C07D487/04 , A61K31/4188 , C07D487/02
CPC分类号： C07D487/04
摘要： The invention relates to pyrrolobenzimidazolone compounds of formula (I), wherein A, T and R1 to R3 are defined as in claim 1, which are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation and the use thereof for preparing a pharmaceutical composition.
摘要翻译：本发明涉及式（I）的吡咯并苯并咪唑酮化合物，其中A，T和R 1至R 3定义如权利要求1，其适用于治疗以细胞增殖过多或异常为特征的疾病及其用于制备药物组合物的用途。

8. 发明授权

US6090930A Recombinant human anti-FB5 antibodies 失效
标题翻译：重组人抗FB5抗体
公开(公告)号：US6090930A
公开(公告)日：2000-07-18
申请号：US013872
申请日：1998-01-27
申请人： Thomas Paul Wallace , Francis Carr , Wolfgang J. Rettig , Pilar Garin-Chesa , Lloyd J. Old
发明人： Thomas Paul Wallace , Francis Carr , Wolfgang J. Rettig , Pilar Garin-Chesa , Lloyd J. Old
IPC分类号： C07K16/30 , C12N15/13 , C07H21/04 , C12N1/20
CPC分类号： C07K16/30 , C07K2317/24 , C07K2319/00
摘要： The invention provides for the production of several humanized murine antibodies specific for the antigen FB5, which is recognized by the murine antibody FB5. The FB5 antigen is expressed on the luminal surface of vascular endothelial cells of a wide range of malignant tumors. The invention also provides for numerous polynucleotide encoding humanized FB5 specific antibodies, expression vectors for producing humanized FB5 specific antibodies, and host cells for the recombinant production of the humanized antibodies. The invention also provides methods for detecting cancerous cells (in vitro and in vivo) using humanized FB5 specific antibodies. Additionally, the invention provides methods of treating cancer using FB5 specific antibodies.
摘要翻译：本发明提供了针对抗原FB5特异的几种人源化鼠抗体的产生，其被鼠抗体FB5识别。 FB5抗原在广泛恶性肿瘤的血管内皮细胞的腔表面上表达。本发明还提供编码人源化FB5特异性抗体的许多多核苷酸，用于产生人源化FB5特异性抗体的表达载体和用于重组产生人源化抗体的宿主细胞。本发明还提供使用人源化FB5特异性抗体检测癌细胞（体外和体内）的方法。另外，本发明提供了使用FB5特异性抗体治疗癌症的方法。

9. 发明授权

US5342757A Monoclonal antibodies which specifically binds to endosialin, a 165 Kd glycoprotein found on tumor vascular endothelium, and uses thereof 失效
标题翻译：特异性结合内皮糖蛋白的单克隆抗体，在肿瘤血管内皮上发现的165Kd糖蛋白及其用途
公开(公告)号：US5342757A
公开(公告)日：1994-08-30
申请号：US976405
申请日：1992-11-13
申请人： Pilar Garin-Chesa , Wolfgang J. Rettig , Lloyd J. Old
发明人： Pilar Garin-Chesa , Wolfgang J. Rettig , Lloyd J. Old
IPC分类号： G01N33/53 , A61K9/127 , A61K38/00 , A61K39/00 , A61K39/395 , A61K45/00 , A61P35/00 , C07H21/04 , C07K14/47 , C07K16/30 , C12N5/10 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/574 , C07K15/28
CPC分类号： C07K16/30 , A61K38/00 , Y10S530/857
摘要： The invention involves monoclonal antibodies which specifically bind to a cell surface antigen characteristic of tumor vascular endothelium. The antigen, referred to as endosialin, is a glycoprotein and has a molecular weight of about 165 kDa as determined by SDS-PAGE. The protein portion of the molecule has a molecular weight of about 95 kDa. Also disclosed are various uses of the monoclonal antibody and the antigen.
摘要翻译：本发明涉及特异性结合肿瘤血管内皮细胞表面抗原特征的单克隆抗体。被称为内皮唾液酸的抗原是糖蛋白，通过SDS-PAGE测定具有约165kDa的分子量。分子的蛋白质部分具有约95kDa的分子量。还公开了单克隆抗体和抗原的各种用途。

10. 发明申请

US20120244141A1 Stratification of cancer patients for susceptibility to therapy with PTK2 inhibitors 审中-公开
标题翻译：癌症患者对PTK2抑制剂治疗易感性的分层
公开(公告)号：US20120244141A1
公开(公告)日：2012-09-27
申请号：US13237833
申请日：2011-09-20
申请人： Guenther ADOLF , Pilar GARIN-CHESA , Ulrich HIRT
发明人： Guenther ADOLF , Pilar GARIN-CHESA , Ulrich HIRT
IPC分类号： A61K39/395 , A61P35/00 , A61K31/713 , A61K31/7105 , G01N21/76 , G01N33/574
CPC分类号： G01N33/57492 , C12Q1/6886 , G01N33/57484 , G01N33/57496 , G01N2333/705 , G01N2333/91205 , G01N2800/52
摘要： A method for determining whether a cancer patient is susceptible to treatment with a protein tyrosine kinase 2 (PTK2) inhibitor, comprising detecting the expression of the E-cadherin protein in a cancer sample of said cancer patient, wherein an E-cadherin protein immunoreactivity score (IRS) of 0-2 indicates that the cancer patient is susceptible to treatment with a PTK2 inhibitor. The invention further encompasses treatment of a patient with a protein tyrosine kinase 2 (PTK2) inhibitor if it has been so determined that said patient is susceptible to such treatment.
摘要翻译：一种确定癌症患者是否易于用蛋白酪氨酸激酶2（PTK2）抑制剂治疗的方法，包括检测所述癌症患者的癌症样品中E-钙粘蛋白蛋白的表达，其中E-钙粘蛋白蛋白免疫反应性评分（IRS）为0-2表示癌症患者易于用PTK2抑制剂治疗。如果已经确定所述患者易于进行这种治疗，本发明还包括治疗患有蛋白酪氨酸激酶2（PTK2）抑制剂的患者。

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