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1. 发明申请

WO2006034191A2 TEM17 BINDS TO CORTACTIN 审中-公开
标题翻译： TEM17为CORTACTIN
公开(公告)号：WO2006034191A2
公开(公告)日：2006-03-30
申请号：PCT/US2005/033479
申请日：2005-09-20
申请人： THE JOHNS HOPKINS UNIVERSITY , ST. CROIX, Brad , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , NANDA, Akash , BUCKHAULTS, Philip, W.
发明人： ST. CROIX, Brad , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , NANDA, Akash , BUCKHAULTS, Philip, W.
IPC分类号： C07K14/82
CPC分类号： C07K14/4748
摘要： Tumor Endothelial Marker 17 (TEM17) was recently identified as an mRNA transcript overexpressed in the endothelium of vessels in human solid tumors. We have identified several new variants of TEMI7, derived by alternative splicing, that are intracellular (TEM17-I), secreted (TEM17-S), and on the cell surface membrane (TEM17-M) of tumor endothelium. We identified cortactin as a protein capable of binding to the extracellular region of both TEM17 and its closest homologue, TEM3, which is also expressed in tumor endothelium. The binding domain of cortactin is a 9-amino acid residue region in its plexin-like domain. These provide targets for the delivery of therapeutic and imaging agents to the vessels of solid tumors.
摘要翻译：肿瘤内皮标记17（TEM17）最近被鉴定为人类实体瘤血管内皮中过表达的mRNA转录物。我们已经确定了通过选择性剪接（细胞内（TEM17-I），分泌型（TEM17-S））和肿瘤内皮的细胞表面膜（TEM17-M）衍生的几种新的变体TEMI7。我们鉴定了皮质激素作为能够结合TEM17及其最近同源物TEM3的细胞外区域的蛋白质，TEM3也在肿瘤内皮中表达。皮质激素的结合结构域是其plexin样结构域中的9-氨基酸残基区域。这些为将实施肿瘤的血管递送治疗和显像剂提供了目标。

2. 发明申请

WO2002010217A3 ENDOTHELIAL CELL EXPRESSION PATTERNS 审中-公开
公开(公告)号：WO2002010217A3
公开(公告)日：2002-02-07
申请号：PCT/US2001/024031
申请日：2001-08-01
申请人： THE JOHNS HOPKINS UNIVERSITY , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12N15/12
摘要： To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived f rom normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in teh endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.

3. 发明申请

WO2004005883A2 SECRETED AND CYTOPLASMIC TUMOR ENDOTHELIAL MARKERS 审中-公开
标题翻译：分泌和肿瘤肿瘤内皮标记
公开(公告)号：WO2004005883A2
公开(公告)日：2004-01-15
申请号：PCT/US2003/016250
申请日：2003-07-02
申请人： THE JOHNS HOPKINS UNIVERSITY , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： G01N
CPC分类号： G01N33/5011 , A61K38/00 , G01N33/5091 , G01N33/57484
摘要： To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed many differentially expressed genes, including a large nujber of genes that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions fo the liver. Theses results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic.
摘要翻译：为了更好地了解肿瘤血管生成，开发了分离内皮细胞（ECs）和评估基因表达模式的新技术。将来自正常和恶性结肠直肠组织的ECs的转录物与来自非内皮细胞的转录物进行比较，鉴定了主要在内皮中表达的170个以上的基因。正常和肿瘤衍生的内皮的比较显示许多差异表达的基因，包括在肿瘤相关内皮中特异性升高的大量基因。来自该组的代表性基因的实验表明，大多数类似地在原发性肺，乳腺，脑和胰腺癌的内皮以及肝脏的转移性损伤中表达。这些结果表明，人类的肿瘤和正常内皮在分子水平上是不同的，对抗血管生成的发展具有重要意义。

4. 发明申请

WO2002083874A3 ENDOTHELIAL CELL EXPRESSION PATTERNS 审中-公开
公开(公告)号：WO2002083874A3
公开(公告)日：2002-10-24
申请号：PCT/US2002/008253
申请日：2002-04-10
申请人： THE JOHNS HOPKINS UNIVERSITY , CARSON-WALTER, Eleanor , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： CARSON-WALTER, Eleanor , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： A61K39/395
摘要： To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.

5. 发明申请

WO2004001004A2 MEMBRANE ASSOCIATED TUMOR ENDOTHELIUM MARKERS 审中-公开
标题翻译：膜相关肿瘤内皮标记
公开(公告)号：WO2004001004A2
公开(公告)日：2003-12-31
申请号：PCT/US2003/019544
申请日：2003-06-23
申请人： JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12N
CPC分类号： C07K14/705 , A61K38/00 , A61K2039/505 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158
摘要： To gain a better understanding of tumor angiogenesis endothelial cells (Ecs) were isolated and gene expression patterns were evaluated. When transcripts from Ecs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal-and tumor-derived endothelium revealed differentially expressed genes, including many that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level.
摘要翻译：为了更好地了解肿瘤血管生成，分离内皮细胞（Ecs），评估基因表达模式。将来自正常和恶性结肠直肠组织的Ecs的转录物与来自非内皮细胞的转录物进行比较，鉴定出在内皮中主要表达的170个以上的基因。正常和肿瘤衍生的内皮的比较显示差异表达的基因，包括在肿瘤相关内皮中特异性升高的许多基因。来自该组的代表性基因的实验证明，大多数类似物在原发性肺癌，乳腺癌，脑癌和胰腺癌的内皮以及肝转移灶中均表达。这些结果表明，人类的肿瘤和正常内皮在分子水平上是不同的。

6. 发明申请

WO2012065161A2 ANTIBODIES TO TUMOR ENDOTHELIAL MARKER 8 审中-公开
标题翻译：抗肿瘤内皮标记物8
公开(公告)号：WO2012065161A2
公开(公告)日：2012-05-18
申请号：PCT/US2011/060583
申请日：2011-11-14
申请人： SCOTT & WHITE HEALTHCARE , THE GOVERNMENT OF THE UNITED STATES OF AMERICA , WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE , FRANKEL, Arthur, E. , SU, Yunpeng , ST. CROIX, Brad
发明人： FRANKEL, Arthur, E. , SU, Yunpeng , ST. CROIX, Brad
IPC分类号： A61K51/10
CPC分类号： C07K16/28 , A61K9/0019 , A61K39/39558 , A61K45/06 , A61K47/6809 , A61K47/6811 , A61K47/6849 , A61K47/6851 , C07K2317/24 , C07K2317/33 , C07K2317/35 , C07K2317/56 , C07K2317/622 , C07K2317/73 , C07K2317/92
摘要： The present invention is directed to particular antibodies and fragments thereof that find use in the detection, prevention and treatment of diseases and disorders associated with abnormal angiogenesis. In particular, these antibodies detect tumor endothelial marker 8 (TEM8) in its native and cell-surface expressed form. Also disclosed are improved methods for producing monoclonal antibodies, as well as pharmaceutical compositions and kits.
摘要翻译：本发明涉及可用于检测，预防和治疗与异常血管生成相关的疾病和病症的特定抗体及其片段。具体而言，这些抗体以其天然和细胞表面表达形式检测肿瘤内皮标志物8（TEM8）。还公开了生产单克隆抗体的改进方法，以及药物组合物和试剂盒。

7. 发明申请

WO2012174160A1 TEM8 ANTIBODIES, CONJUGATES THEREOF, AND THEIR USE 审中-公开
标题翻译： TEM8抗体，与其结合使用及其使用
公开(公告)号：WO2012174160A1
公开(公告)日：2012-12-20
申请号：PCT/US2012/042315
申请日：2012-06-13
申请人： THE UNITED STATES OF AMERICA , as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , ST. CROIX, Brad , FLEMING, Tony , CHAUDHARY, Amit , SAHA, Saurabh , ZHANG, Xiaoyan, Michelle , KWONG, Rou-fun , NOVARTIS AG
发明人： ST. CROIX, Brad , FLEMING, Tony , CHAUDHARY, Amit , SAHA, Saurabh , ZHANG, Xiaoyan, Michelle , KWONG, Rou-fun
IPC分类号： C07K16/30 , C07K16/46 , A61K39/395 , A61P35/00 , A61P31/04
CPC分类号： C07K16/28 , A61K2039/505 , A61K2039/507 , C07K16/2863 , C07K16/30 , C07K2317/21 , C07K2317/24 , C07K2317/33 , C07K2317/55 , C07K2317/732 , C07K2317/734 , C07K2317/76
摘要： Antibodies that specifically bind TEM8 protein, and conjugates thereof, are disclosed herein. In some examples the conjugates and antibodies are useful for methods of detecting and treating pathogenic angiogenesis. In other examples the conjugates and antibodies are useful for methods of detecting and treating cancer. In additional examples, the conjugates and antibodies are useful for methods of decreasing binding of Anthrax protective antigen to a cell.
摘要翻译：本文公开了特异性结合TEM8蛋白的抗体及其缀合物。在一些实例中，缀合物和抗体可用于检测和治疗病原性血管发生的方法。在其它实例中，缀合物和抗体可用于检测和治疗癌症的方法。在另外的实例中，缀合物和抗体可用于减少炭疽保护性抗原与细胞结合的方法。

8. 发明申请

WO2012172495A1 COMPOSITIONS AND METHODS FOR ANTIBODIES TARGETING TEM8 审中-公开
标题翻译：抗生素靶向组合物和方法TEM8
公开(公告)号：WO2012172495A1
公开(公告)日：2012-12-20
申请号：PCT/IB2012/052990
申请日：2012-06-13
申请人： NOVARTIS AG , NATIONAL INSTITUTES OF HEALTH , FLEMING, Tony , KWONG, Rou-Fun , SAHA, Saurabh , ST. CROIX, Brad , ZHANG, Xiaoyan Michelle
发明人： FLEMING, Tony , KWONG, Rou-Fun , SAHA, Saurabh , ST. CROIX, Brad , ZHANG, Xiaoyan Michelle
IPC分类号： C07K16/28 , C07K16/30
CPC分类号： C07K16/30 , C07K16/28 , C07K2317/21 , C07K2317/55 , C07K2317/64
摘要： The present invention relates to antibodies and antigen binding fragments thereof that bind to both human and mouse TME8, as well as compositions and methods of use thereof.
摘要翻译：本发明涉及结合人和小鼠TME8的抗体及其抗原结合片段，以及其组合物和使用方法。

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