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公开(公告)号：US20130022598A1
公开(公告)日：2013-01-24
申请号：US13482406
申请日：2012-05-29
IPC分类号： C07K16/30 , G01N33/53 , A61P35/00 , C07K16/46 , A61K39/395
CPC分类号： C07K16/2863 , A61K38/00 , A61K39/39558 , A61K47/6829 , A61K47/6849 , A61K2039/505 , A61K2039/545 , C07K14/21 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/624 , C07K2317/92 , C07K2319/04 , C07K2319/55
摘要： We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.
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公开(公告)号：US20140010829A1
公开(公告)日：2014-01-09
申请号：US13988696
申请日：2011-11-15
申请人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Hailan Piao
发明人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Hailan Piao
IPC分类号： C07K16/30
CPC分类号： A61K39/39558 , A61K47/68 , A61K47/6811 , A61K47/6829 , A61K47/6865 , A61K2039/505 , A61K2039/507 , C07K16/30 , C07K16/3015 , C07K16/303 , C07K16/3038 , C07K16/3069 , C07K16/3084 , C07K16/44 , C07K2317/565 , C07K2317/622 , C07K2317/73 , C07K2317/77 , C07K2317/92 , C07K2319/55 , G01N33/57492
摘要： High affinity antibodies were made to gangliosides expressed on tumor cells. The antibodies can be used analytically, diagnostically, therapeutically, and theranostically. The antibodies may be used to target cytotoxic reagents to tumor cells, thus minimizing full-body toxicity. The antibodies may also be used with out added cytotoxin. The antibodies may be detectably labeled or labelable for analytic and diagnostic purposes. The combination of specificity and affinity of the antibodies render them particularly useful.
摘要翻译： 对肿瘤细胞上表达的神经节苷脂进行高亲和力抗体。 抗体可以在分析，诊断，治疗和治疗上使用。 抗体可用于将细胞毒性试剂靶向肿瘤细胞，从而使全身毒性最小化。 抗体也可以与外加的细胞毒素一起使用。 为了分析和诊断目的，抗体可以被可检测地标记或可标记。 抗体的特异性和亲和力的组合使它们特别有用。
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公开(公告)号：US20100047164A1
公开(公告)日：2010-02-25
申请号：US12418956
申请日：2009-04-06
申请人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Ralph Reisfeld
发明人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Ralph Reisfeld
IPC分类号： A61K51/00 , A61K39/395 , G01N33/574 , C07K16/00
CPC分类号： A61K51/1027 , A61K2039/505 , C07K16/3092 , C07K2317/54 , C07K2317/622 , C07K2319/00 , G01N2800/52
摘要： Chondroition sulfate proteoglycans represent excellent targets for anti-tumor immunotherapy. Antibodies which target such proteoglycans can be used alone, in combinations, armed with a cytotoxic payload or unarmed. Combinations of such antibodies can target different epitopes of the proteoglycans. Internalization of the antibodies can increase the toxicity of the payloads. Single chain variable regions are especially advantageous for such anti-tumor immunotherapy.
摘要翻译： 硫酸软骨素蛋白聚糖代表抗肿瘤免疫治疗的良好靶标。 靶向这种蛋白聚糖的抗体可以单独使用，组合使用，具有细胞毒性有效载荷或非武装。 这些抗体的组合可以靶向蛋白聚糖的不同表位。 抗体的内在化可以增加有效载荷的毒性。 单链可变区对于这种抗肿瘤免疫治疗特别有利。
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公开(公告)号：US20090269343A1
公开(公告)日：2009-10-29
申请号：US12418975
申请日：2009-04-06
IPC分类号： A61K39/395 , C07K16/00 , G01N33/53 , A61P35/00
CPC分类号： C07K16/2863 , A61K38/00 , A61K39/39558 , A61K47/6829 , A61K47/6849 , A61K2039/505 , A61K2039/545 , C07K14/21 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/624 , C07K2317/92 , C07K2319/04 , C07K2319/55
摘要： We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.
摘要翻译： 我们测试了识别EGFR重组和肿瘤特异性EGFRvIII受体的重组双特异性免疫毒素的体外和体内功效。 从杂交瘤中克隆单链抗体并与毒素融合，携带增加细胞内保留的C-末端肽。 测量了重组双特异性免疫毒素对EGFRwt和EGFRvIII蛋白的结合亲和力和特异性。 测量体外细胞毒性。 在皮下模型中评估重组双特异性免疫毒素的体内活性，并与已建立的单特异性免疫毒素的体内活性进行比较。 在我们的临床前研究中，双特异性重组免疫毒素显示出显着的治疗脑肿瘤的潜力。
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公开(公告)号：US09441048B2
公开(公告)日：2016-09-13
申请号：US13988696
申请日：2011-11-15
申请人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Hailan Piao
发明人： Darell Bigner , Chien-Tsun Kuan , Ira H. Pastan , Hailan Piao
CPC分类号： A61K39/39558 , A61K47/68 , A61K47/6811 , A61K47/6829 , A61K47/6865 , A61K2039/505 , A61K2039/507 , C07K16/30 , C07K16/3015 , C07K16/303 , C07K16/3038 , C07K16/3069 , C07K16/3084 , C07K16/44 , C07K2317/565 , C07K2317/622 , C07K2317/73 , C07K2317/77 , C07K2317/92 , C07K2319/55 , G01N33/57492
摘要： High affinity antibodies were made to gangliosides expressed on tumor cells. The antibodies can be used analytically, diagnostically, therapeutically, and theranostically. The antibodies may be used to target cytotoxic reagents to tumor cells, thus minimizing full-body toxicity. The antibodies may also be used with out added cytotoxin. The antibodies may be detectably labeled or labelable for analytic and diagnostic purposes. The combination of specificity and affinity of the antibodies render them particularly useful.
摘要翻译： 对肿瘤细胞上表达的神经节苷脂进行高亲和力抗体。 抗体可以在分析，诊断，治疗和治疗上使用。 抗体可用于将细胞毒性试剂靶向肿瘤细胞，从而使全身毒性最小化。 抗体也可以与外加的细胞毒素一起使用。 为了分析和诊断目的，抗体可以被可检测地标记或可标记。 抗体的特异性和亲和力的组合使它们特别有用。
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6.发明申请公开(公告)号：US20090252750A1
公开(公告)日：2009-10-08
申请号：US12092228
申请日：2006-10-31
申请人： Chien-Tsun Kuan , Darell Bigner , Ira H. Pastan
发明人： Chien-Tsun Kuan , Darell Bigner , Ira H. Pastan
IPC分类号： A61K39/395 , C07K16/18 , C12N15/11 , C12N5/06 , G01N33/574
CPC分类号： C07K16/28 , A61K47/6817 , A61K2039/505 , C07K16/1214 , C07K16/30 , C07K2317/565 , C12N15/00 , G01N33/57484
摘要： The invention provides high affinity antibodies suitable for forming immunotoxins that inhibit the growth of cells expressing human glycoprotein NMB, including glioblastoma multiform cells, anaplastic astrocytoma cells, anaplastic oligodendroglioma cells, oligodendroglioma cells, and melanoma cells.
摘要翻译： 本发明提供了适合于形成抑制表达人糖蛋白NMB的细胞生长的免疫毒素的高亲和力抗体，包括成胶质细胞瘤多形细胞，间变性星形细胞瘤细胞，间变性少突神经胶质瘤细胞，少突胶质细胞瘤细胞和黑素瘤细胞。
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公开(公告)号：US20140017266A1
公开(公告)日：2014-01-16
申请号：US13991308
申请日：2011-12-05
CPC分类号： C07K16/30 , A61K47/6829 , A61K47/6849 , A61K2039/505 , C07K14/21 , C07K16/18 , C07K16/28 , C07K2317/622 , C07K2317/73 , C07K2317/92 , C07K2319/55
摘要： Recombinant scFv-immunotoxins target tumor cells expressing human podoplanin but not podoplanin-negative or normal cells. The immunotoxins can be used for treatment of malignant glioma patients or any malignant tumor expressing podoplanin. One such immunotoxin comprises a modified Pseudomonas exotoxin (PE38) attached to the scFv antibody fragment. This immunotoxin can be used as a therapeutic drug for the treatment of malignant gliomas and other cancers.
摘要翻译： 重组scFv免疫毒素靶向表达人podoplanin但不是podoplanin阴性或正常细胞的肿瘤细胞。 免疫毒素可用于治疗恶性胶质瘤患者或任何恶性肿瘤表达平聚蛋白。 一种这样的免疫毒素包含与scFv抗体片段连接的修饰的假单胞菌外毒素（PE38）。 该免疫毒素可用作治疗恶性胶质瘤和其它癌症的治疗药物。
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8.发明授权Genetic alterations in isocitrate dehydrogenase and other genes in malignant glioma 有权异柠檬酸脱氢酶和恶性胶质瘤中其他基因的遗传改变公开(公告)号：US08685660B2
公开(公告)日：2014-04-01
申请号：US13060191
申请日：2009-09-03
申请人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Xiaosong Zhang , Jimmy Cheng-Ho Lin , Rebecca J. Leary , Philipp Angenendt , Nickolas Papadopoulos , Victor Velculescu , Giovanni Parmigiani , Rachel Karchin , Sian Jones , Hai Yan , Darell Bigner , Chien-Tsun Kuan , Gregory J. Riggins
发明人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Xiaosong Zhang , Jimmy Cheng-Ho Lin , Rebecca J. Leary , Philipp Angenendt , Nickolas Papadopoulos , Victor Velculescu , Giovanni Parmigiani , Rachel Karchin , Sian Jones , Hai Yan , Darell Bigner , Chien-Tsun Kuan , Gregory J. Riggins
IPC分类号： G01N33/574
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/156
摘要： We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.
摘要翻译： 我们发现大多数II级和III级星形细胞瘤和少突胶质细胞瘤中异柠檬酸脱氢酶1（IDH1）的R132残基突变以及从这些较低级别病变发展的成胶质细胞瘤。 那些没有IDH1突变的肿瘤在紧密相关的IDH2基因的类似R172残基中经常具有突变。 这些发现对恶性胶质瘤的发病机制和诊断具有重要意义。
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9.发明申请公开(公告)号：US20060115862A1
公开(公告)日：2006-06-01
申请号：US11282117
申请日：2005-11-16
申请人： Darell Bigner , Charles Pegram , Chien-Tsun Kuan
发明人： Darell Bigner , Charles Pegram , Chien-Tsun Kuan
IPC分类号： G01N33/574
CPC分类号： C07K16/28 , C07K16/18 , C07K16/30 , G01N33/57426 , G01N33/57484 , G01N33/57492 , G01N2333/78
摘要： The present invention provides immunoassays for detecting a tumor in a subject, comprising producing an antibody that specifically binds to tenascin, contacting the antibody with a biological sample suspected of containing tumor cells and determining the binding of the antibody to the biological sample. The present invention further provides methods of identifying a subject for treatment of a tumor. Kits for direct or indirect immunohistochemical or immunocytochemical assays are also provided. A novel polyclonal antibody that binds to tenascin domain TNfn C-D is further provided.
摘要翻译： 本发明提供了用于检测受试者中的肿瘤的免疫测定，其包括产生特异性结合腱生蛋白的抗体，使所述抗体与怀疑含有肿瘤细胞的生物样品接触并测定抗体与生物样品的结合。 本发明还提供鉴定受试者治疗肿瘤的方法。 还提供了用于直接或间接免疫组化或免疫细胞化学测定的试剂盒。 进一步提供了结合腱生蛋白结构域TNfn C-D的新型多克隆抗体。
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公开(公告)号：US08039593B2
公开(公告)日：2011-10-18
申请号：US12092228
申请日：2006-10-31
申请人： Chien-Tsun Kuan , Darell D Bigner , Ira H Pastan
发明人： Chien-Tsun Kuan , Darell D Bigner , Ira H Pastan
IPC分类号： C07K16/00 , A61K39/395
CPC分类号： C07K16/28 , A61K47/6817 , A61K2039/505 , C07K16/1214 , C07K16/30 , C07K2317/565 , C12N15/00 , G01N33/57484
摘要： The invention provides high affinity antibodies suitable for forming immunotoxins that inhibit the growth of cells expressing human glycoprotein NMB, including glioblastoma multiform cells, anaplastic astrocytoma cells, anaplastic oligodendroglioma cells, oligodendroglioma cells, and melanoma cells.
摘要翻译： 本发明提供了适合于形成抑制表达人糖蛋白NMB的细胞生长的免疫毒素的高亲和力抗体，包括成胶质细胞瘤多形细胞，间变性星形细胞瘤细胞，间变性少突神经胶质瘤细胞，少突胶质细胞瘤细胞和黑素瘤细胞。
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