公开(公告)号：US5989551A

公开(公告)日：1999-11-23

申请号：US548159

申请日：1995-10-25

申请人： Noel K. Maclaren ,  Abner L. Notkins ,  Michael S. Lan ,  Qing Li

发明人： Noel K. Maclaren ,  Abner L. Notkins ,  Michael S. Lan ,  Qing Li

IPC分类号： A61K38/00 ,  A61K39/00 ,  A61P3/10 ,  A61P37/02 ,  C07K14/47 ,  C07K14/705 ,  C12N9/16

CPC分类号： C07K14/4713 ,  C07K14/705 ,  C12N9/16 ,  A61K38/00 ,  A61K39/00

摘要： The method and compositions of this invention provide an effective and reliable substitute for the currently employed ICA assay for diabetes. By providing a method for detecting autoantibodies to GAD.sub.65, IA-2 and a previously unidentified antigen termed IA-2.beta. herein, the method provides a chemical assay which has improved reliability. In addition, these antigens may be employed in therapeutic regimens aimed at achieving amelioration of the clinical condition.

摘要翻译： 本发明的方法和组合物为目前使用的糖尿病ICA测定提供了有效和可靠的替代物。 通过提供一种用于检测GAD65，IA-2和本来称为IA-2β的先前未鉴定的抗原的自身抗体的方法，该方法提供了具有改善的可靠性的化学测定。 此外，这些抗原可以用于旨在改善临床状况的治疗方案中。

公开(公告)号：US06391651B1

公开(公告)日：2002-05-21

申请号：US08514213

申请日：1995-08-11

申请人： Noel K. Maclaren ,  Abner L. Notkins ,  Michael S. Lan

发明人： Noel K. Maclaren ,  Abner L. Notkins ,  Michael S. Lan

IPC分类号： G01N33564

CPC分类号： C07K14/4713 ,  A61K38/00 ,  A61K39/00 ,  C07K14/705 ,  C12N9/16 ,  Y10S530/845

摘要： The method and compositions of this invention provide an effective and reliable substitute for the currently employed ICA assay for diabetes. By providing a method for detecting autoantibodies to both GAD65 and IA-2 auto-antigens, the method provides a chemical assay which has improved reliability. In addition, these antigens may be employed in therapeutic regimens aimed at achieving immune tolerance and therefore amelioration of the clinical condition.

摘要翻译： 本发明的方法和组合物为目前使用的糖尿病ICA测定提供了有效和可靠的替代物。 通过提供用于检测GAD65和IA-2自身抗原的自身抗体的方法，该方法提供了具有改善的可靠性的化学测定。 此外，这些抗原可以用于旨在实现免疫耐受并因此改善临床状况的治疗方案中。

公开(公告)号：US06225049B1

公开(公告)日：2001-05-01

申请号：US08246489

申请日：1994-05-19

申请人： Michael S. Lan ,  Abner L. Notkins

发明人： Michael S. Lan ,  Abner L. Notkins

IPC分类号： C12Q168

CPC分类号： C07K14/47 ,  C12Q1/6886 ,  C12Q2600/158

摘要： A novel insulinoma-associated, neuroendocrine tumor-associated cDNA sequence is disclosed. The sequence and fragments thereof are useful for the diagnosis and identification of insulinoma and neuroendocrine tumors. The invention relates to a method for identifying a cancer employing the insulinoma-associated nucleic acid, polypeptide and antibody generated thereto.

摘要翻译： 公开了一种新型胰岛素瘤相关神经内分泌肿瘤相关cDNA序列。 其序列和片段可用于诊断和鉴定胰岛素瘤和神经内分泌肿瘤。 本发明涉及使用与之产生的胰岛素相关核酸，多肽和抗体鉴定癌症的方法。

公开(公告)号：US20120316225A1

公开(公告)日：2012-12-13

申请号：US13505823

申请日：2010-11-08

申请人： Mary B. Breslin ,  Michael S. Lan

发明人： Mary B. Breslin ,  Michael S. Lan

IPC分类号： A61K31/7088 ,  A61P35/00 ,  G01N21/76 ,  C12N15/85 ,  C12N15/861

CPC分类号： C12N15/86 ,  C07K14/005 ,  C07K2319/55 ,  C07K2319/61 ,  C12N15/85 ,  C12N2710/10343 ,  C12N2710/16622 ,  C12N2710/16634 ,  C12N2830/008 ,  C12N2830/32 ,  C12N2830/40

摘要： A modification of the existing INSM1 promoter region has been discovered that incorporated DNA elements that silence expression of neuronal genes in non-neuronal cells and that has increased the effectiveness and safety of using the INSM1 promoter for tumor treatment. One modification was addition of one or two tandem copies of neuronal restrictive silencer elements (NRSEs) derived either from the mouse nicotinic acetylcholine receptor (nAChR) or the rat superior cervical ganglion 10 (SCG10) promoters. These NRSEs were placed in the expression construct either directly upstream or downstream of the INSM1 promoter sequence. The most effective expression construct was the nAChR NRSE element positioned downstream of the INSM1 promoter. This expression construct increased the tissue specificity of the INSM1 promoter without a significant decrease in its activity. In addition, the modified INSM1 promoter was placed into a viral vector, adenovirus 5. Constructs with an insulator element, the chicken HS4 β-globin insulator element, with the INSM1 promoter was shown to decrease the interference of the viral genome on its expression. Constructs have been made that do not decrease the INSM1 promoter activity but significantly augment the tumor specificity of the promoter. Linking the construct to a reporter gene allowed for detection of the placement of the viral vector, and this detection can be used for diagnosing or locating neuroendocrine tumors.

摘要翻译： 已经发现现有的INSM1启动子区域的修饰是掺入了在非神经元细胞中沉默神经元基因表达的DNA元件，并增加了使用INSM1启动子进行肿瘤治疗的有效性和安全性。 一个修改是从小鼠烟碱乙酰胆碱受体（nAChR）或大鼠上颈部神经节10（SCG10）启动子衍生的神经元限制性消音元件（NRSE）的一个或两个串联拷贝的添加。 将这些NRSEs直接置于INSM1启动子序列的上游或下游的表达构建体中。 最有效的表达构建体是位于INSM1启动子下游的nAChR NRSE元件。 该表达构建体增加了INSM1启动子的组织特异性，而其活性没有显着降低。 此外，将修饰的INSM1启动子置于病毒载体，腺病毒5中。具有绝缘体元件，具有INSM1启动子的鸡HS4和bgr - 球蛋白绝缘子元件的构建体显示可减少病毒基因组对其表达的干扰 。 已经建立了不降低INSM1启动子活性但显着增加启动子的肿瘤特异性的构建体。 将构建体连接到允许检测病毒载体的位置的报告基因，并且该检测可用于诊断或定位神经内分泌肿瘤。

公开(公告)号：US09090907B2

公开(公告)日：2015-07-28

申请号：US13505823

申请日：2010-11-08

申请人： Mary B. Breslin ,  Michael S. Lan

发明人： Mary B. Breslin ,  Michael S. Lan

IPC分类号： A61K48/00 ,  C12Q1/66 ,  C12N15/00 ,  A01N63/00 ,  C12N15/86 ,  C07K14/005 ,  C12N15/85

CPC分类号： C12N15/86 ,  C07K14/005 ,  C07K2319/55 ,  C07K2319/61 ,  C12N15/85 ,  C12N2710/10343 ,  C12N2710/16622 ,  C12N2710/16634 ,  C12N2830/008 ,  C12N2830/32 ,  C12N2830/40

摘要： A modification of the existing INSM1 promoter region has been discovered that incorporated DNA elements that silence expression of neuronal genes in non-neuronal cells and that has increased the effectiveness and safety of using the INSM1 promoter for tumor treatment. One modification was addition of one or two tandem copies of neuronal restrictive silencer elements (NRSEs) derived either from the mouse nicotinic acetylcholine receptor (nAChR) or the rat superior cervical ganglion 10 (SCG10) promoters. These NRSEs were placed in the expression construct either directly upstream or downstream of the INSM1 promoter sequence. The most effective expression construct was the nAChR NRSE element positioned downstream of the INSM1 promoter. This expression construct increased the tissue specificity of the INSM1 promoter without a significant decrease in its activity. In addition, the modified INSM1 promoter was placed into a viral vector, adenovirus 5. Constructs with an insulator element, the chicken HS4 β-globin insulator element, with the INSM1 promoter was shown to decrease the interference of the viral genome on its expression. Constructs have been made that do not decrease the INSM1 promoter activity but significantly augment the tumor specificity of the promoter. Linking the construct to a reporter gene allowed for detection of the placement of the viral vector, and this detection can be used for diagnosing or locating neuroendocrine tumors.

摘要翻译： 已经发现现有的INSM1启动子区域的修饰是掺入了在非神经元细胞中沉默神经元基因表达的DNA元件，并增加了使用INSM1启动子进行肿瘤治疗的有效性和安全性。 一个修改是从小鼠烟碱乙酰胆碱受体（nAChR）或大鼠上颈部神经节10（SCG10）启动子衍生的神经元限制性消音元件（NRSE）的一个或两个串联拷贝的添加。 将这些NRSEs直接置于INSM1启动子序列的上游或下游的表达构建体中。 最有效的表达构建体是位于INSM1启动子下游的nAChR NRSE元件。 该表达构建体增加了INSM1启动子的组织特异性，而其活性没有显着降低。 此外，将修饰的INSM1启动子置于病毒载体，腺病毒5中。具有绝缘体元件，具有INSM1启动子的鸡HS4和bgr - 球蛋白绝缘子元件的构建体显示可减少病毒基因组对其表达的干扰 。 已经建立了不降低INSM1启动子活性但显着增加启动子的肿瘤特异性的构建体。 将构建体连接到允许检测病毒载体的位置的报告基因，并且该检测可用于诊断或定位神经内分泌肿瘤。