公开(公告)号：US06399743B1

公开(公告)日：2002-06-04

申请号：US09570454

申请日：2000-05-12

申请人： Adhip P. N. Majumdar

发明人： Adhip P. N. Majumdar

IPC分类号： C07K1400

CPC分类号： C07K14/71 ,  A61K38/00 ,  C07K2319/00

摘要： A cDNA fragment clone of 1583 base pairs with 90-95% sequence homology to the mouse EGFR and a truncated rat EGFR is described. The isolated cDNA is termed ERRP (EFG-Receptor Related Protein). In Northern-blot analysis with poly A+ RNA from different rat tissues, ERRP cDNA hybridized strongly to a mRNA transcript of about 1.8 kb. Maximal expression was noted in the small intestine, followed by colon, liver, gastric mucosa and other tissues. Transfection of ERRP cDNA in HCT-116 cells, a colon cancer cell line, markedly inhibits proliferation in monolayer and in soft agar and attenuates EGF-R tyrosine kinase activity. Transfection of ERRP in HCT-116 also delays tumor growth in SCID mice injected with these cells compared to the vector-transfector control cells. On the other hand, proliferation of the vector-transfected control, but not ERRP transfected HCT cells could be stimulated by TGF-&agr; (10−10M and 10−9M). The ERRP cDNA represents a new member of the EGFR gene family, and its protein product plays a key role in modulating the function of EGFR.

摘要翻译： 描述了与小鼠EGFR和截短的大鼠EGFR具有90-95％序列同源性的1583个碱基对的cDNA片段克隆。 分离的cDNA被称为ERRP（EFG-受体相关蛋白）。 在来自不同大鼠组织的聚A + RNA的Northern印迹分析中，ERRP cDNA与约1.8kb的mRNA转录物强烈杂交。 在小肠中注意到最大的表达，其次是结肠，肝，胃粘膜和其他组织。 结肠癌细胞系HCT-116细胞中ERRP cDNA的转染显着抑制单层和软琼脂中的增殖，并减弱EGF-R酪氨酸激酶的活性。 与载体转染对照细胞相比，HCT-116中ERRP的转染也延缓了注射这些细胞的SCID小鼠的肿瘤生长。 另一方面，载体转染的对照但不是ERRP转染的HCT细胞的增殖可以被TGF-α（10-10M和10-9M）刺激。 ERRP cDNA表达EGFR基因家族的新成员，其蛋白质产物在调节EGFR功能中起关键作用。

公开(公告)号：US07049410B2

公开(公告)日：2006-05-23

申请号：US10302868

申请日：2002-11-25

申请人： Adhip P. N. Majumdar ,  Fazlul H. Sarkar

发明人： Adhip P. N. Majumdar ,  Fazlul H. Sarkar

IPC分类号： C07K16/00

CPC分类号： C07K14/71 ,  C07K16/2863

摘要： This invention relates to ERRP (EGF-Receptor Related Protein) specific antibodies that could be used 1) to study the functional properties of ERRP and; 2) as a diagnostic and prognostic tool for malignancies. Preferably, the antibody reacts with a segment of ERRP containing 15 amino acids (SEQ ID NO: 4) that possesses the most antigenic property.

公开(公告)号：US06582934B2

公开(公告)日：2003-06-24

申请号：US09867521

申请日：2001-05-31

申请人： Adhip P. N. Majumdar

发明人： Adhip P. N. Majumdar

IPC分类号： C12N1500

CPC分类号： C07K14/71 ,  A61K38/00 ,  C07K2319/00

摘要： A cDNA fragment clone of 1583 base pairs with 90-95% sequence homology to the mouse EGFR and a truncated rat EGFR is described. The isolated cDNA is termed ERRP (EFG-Receptor Related Protein). In Northern-blot analysis with poly A+RNA from different rat tissues, ERRP cDNA hybridized strongly to a mRNA transcript of about 1.8 kb. Maximal expression was noted in the small intestine, followed by colon, liver, gastric mucosa and other tissues. Transfection of ERRP cDNA in HCT-116 cells, a colon cancer cell line, markedly inhibits proliferation in monolayer and in soft agar and attenuates EGF-R tyrosine kinase activity. Transfection of ERRP in HCT-116 also delays tumor growth in SCID mice injected with these cells compared to the vector-transfector control cells. On the other hand, proliferation of the vector-transfected control, but not ERRP transfected HCT cells could be stimulated by TGF-&agr; (10−10M and 10−9M). The ERRP cDNA represents a new member of the EGFR gene family, and its protein product plays a key role in modulating the function of EGFR.

摘要翻译： 描述了与小鼠EGFR和截短的大鼠EGFR具有90-95％序列同源性的1583个碱基对的cDNA片段克隆。 分离的cDNA被称为ERRP（EFG-受体相关蛋白）。 在来自不同大鼠组织的聚A + RNA的Northern印迹分析中，ERRP cDNA与约1.8kb的mRNA转录物强烈杂交。 在小肠中注意到最大的表达，其次是结肠，肝，胃粘膜和其他组织。 结肠癌细胞系HCT-116细胞中ERRP cDNA的转染显着抑制单层和软琼脂中的增殖，并减弱EGF-R酪氨酸激酶的活性。 与载体转染对照细胞相比，HCT-116中ERRP的转染也延缓了注射这些细胞的SCID小鼠的肿瘤生长。 另一方面，载体转染的对照但不是ERRP转染的HCT细胞的增殖可以被TGF-α（10-10M和10-9M）刺激。 ERRP cDNA表达EGFR基因家族的新成员，其蛋白质产物在调节EGFR功能中起关键作用。

公开(公告)号：US20120121589A1

公开(公告)日：2012-05-17

申请号：US13383536

申请日：2010-07-13

申请人： Adhip P. N. Majumdar ,  Arun K. Rishi ,  Yingjie Yu

发明人： Adhip P. N. Majumdar ,  Arun K. Rishi ,  Yingjie Yu

IPC分类号： A61K39/395 ,  A61K38/02 ,  A61P35/02 ,  C12N15/63 ,  C12N5/071 ,  A61P35/00 ,  C07K14/71 ,  C12N15/54

CPC分类号： C07K14/705 ,  C07K2319/32

摘要： A protein that attenuates EGFR and/or EGFR family members comprises a modified EGFR ectodomain. The protein inhibits signaling via the EGFR and/or EGFR family members. The protein includes a portion of the EGFR (or EGFR family member) and the “U” region epitope of EGFR related protein (ERRP), wherein the portion of the EGFR is operable to bind a ligand of EGFR. Also included are nucleic acids encoding such proteins. Attenuating EGFR signaling can include inhibiting the EGFR and/or EGFR family members and to provide antiproliferative activity. The present proteins and expression of nucleic acids encoding these proteins can regulate cellular growth and can be used to treat tumors and cancerous cells that express one or more of the EGFR and EGFR family members.

摘要翻译： 减弱EGFR和/或EGFR家族成员的蛋白质包含修饰的EGFR胞外域。 该蛋白通过EGFR和/或EGFR家族成员抑制信号传导。 该蛋白质包括一部分EGFR（或EGFR家族成员）和EGFR相关蛋白（ERRP）的“U”区表位，其中该部分EGFR可操作地结合EGFR配体。 还包括编码这种蛋白质的核酸。 衰减性EGFR信号传导可以包括抑制EGFR和/或EGFR家族成员并提供抗增殖活性。 本发明的蛋白质和编码这些蛋白质的核酸的表达可以调节细胞生长并且可以用于治疗表达一种或多种EGFR和EGFR家族成员的肿瘤和癌细胞。