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1. 发明授权

US06660467B1 Variant of ciliary neurotrophic factor and DNA encoding the variant 有权
标题翻译：睫状神经营养因子的变体和编码变体的DNA
公开(公告)号：US06660467B1
公开(公告)日：2003-12-09
申请号：US09381393
申请日：1999-09-20
申请人： Isabelle Gloaguen , Annalise Di Marco , Anna De Martis , Ralph Laufer , Isabella Saggio
发明人： Isabelle Gloaguen , Annalise Di Marco , Anna De Martis , Ralph Laufer , Isabella Saggio
IPC分类号： C12N500
CPC分类号： C07K14/475 , A61K38/00
摘要： The subject of the present invention are variants of ciliary neurotrophic factor with enhanced receptor selectivity (CNTFR), useful for the treatment of diseases and disorders including motor neuron diseases and muscle degenerative diseases. Another subject of the invention is to provide a method for identifying the above mentioned CNTF variants. The hCNTF variants with the amino acid substitutions in accordance with the present invention, have a reduced ability, as compared to the human CNTF, to elicit biological effects through soluble CNTFR, without affecting its ability to activate membrane-bound neuronal CNTF receptors, thereby improving its therapeutic properties. FIG. 1 shows the reduced CNTFR binding affinity of a CNTF variant according to the invention (IA-CNTF; SEQ ID NO: 2). It is evident that the binding affinity of this variant to the CNTFR is reduced as compared to the wild-type human CNTF molecule.
摘要翻译：本发明的主题是具有增强的受体选择性（CNTFR）的睫状神经营养因子的变体，其可用于治疗疾病和病症，包括运动神经元疾病和肌肉退行性疾病。本发明的另一主题是提供一种鉴定上述CNTF变体的方法。根据本发明具有氨基酸取代的hCNTF变体与人CNTF相比具有降低的能力，通过可溶性CNTFR引起生物学效应，而不影响其活化膜结合的神经元CNTF受体的能力，从而改善其治疗性质。图。图1显示根据本发明的CNTF变体（IA-CNTF; SEQ ID NO：2）的CNTFR结合亲和力降低。显然，与野生型人CNTF分子相比，该变体与CNTFR的结合亲和力降低。

2. 发明授权

US06565869B1 Use of CNTF (ciliary neurotrophic factor) receptor activators for the treatment of obesity 有权
标题翻译：使用CNTF（睫状神经营养因子）受体激活剂治疗肥胖
公开(公告)号：US06565869B1
公开(公告)日：2003-05-20
申请号：US09308368
申请日：1999-07-19
申请人： Gennaro Ciliberto , Patrizia Costa , Giacomo Paonessa , Domenico Lazzaro , Isabelle Gloaguen , Annalise Di Marco , Anna De Martis , Ralph Laufer , Riccardo Cortese
发明人： Gennaro Ciliberto , Patrizia Costa , Giacomo Paonessa , Domenico Lazzaro , Isabelle Gloaguen , Annalise Di Marco , Anna De Martis , Ralph Laufer , Riccardo Cortese
IPC分类号： A61F202
CPC分类号： A61K38/185 , A61K38/2264 , A61K48/00 , A61K2300/00
摘要： The present invention refers to the use of hCNTF (human ciliary neurotrophic factor), mutants thereof or other molecules that activate the CNTF receptor, for the preparation of drugs for the treatment of obesity and associated disease, for example hyperglycemia. FIG. 1 shows the anti-obesity effect of hCNTF and leptin on body weight (left panels) and on food intake (right panels) in genetically obese mice and in mice with diet-induced obesity (DIO).
摘要翻译：本发明涉及hCNTF（人纤维神经营养因子），其突变体或活化CNTF受体的其它分子用于制备用于治疗肥胖症和相关疾病例如高血糖症的药物的用途。图。图1显示了基因肥胖小鼠和饮食诱导的肥胖（DIO）小鼠中hCNTF和瘦素对体重（左图）和食物摄取（右图）的抗肥胖作用。

3. 发明申请

US20080193950A1 Assay for Cytochrome P450 Isoform 2C9 失效
标题翻译：细胞色素P450异构体2C9的测定
公开(公告)号：US20080193950A1
公开(公告)日：2008-08-14
申请号：US11663587
申请日：2005-10-04
申请人： Ralph Laufer , Annalise Di Marco , Ashok Chaudhary
发明人： Ralph Laufer , Annalise Di Marco , Ashok Chaudhary
IPC分类号： G01N33/53 , G01N33/566 , C12Q1/02
CPC分类号： C12Q1/26 , G01N2333/90245 , G01N2500/02
摘要： A Rapid And Sensitive Radiometric Assay For Assessing The Activity Of Cytochrome P-450 (CYP) 2C9 And The Potential Of An Analyte To Inhibit CYP2C9 Activity Or Induce CYP2C9 Expression is described. All the steps of the assay, including incubations, product separation, and radioactivity counting are preferably performed in a multiwell format, which can be automated.
摘要翻译：描述了用于评估细胞色素P-450（CYP）2C9的活性的快速和敏感的辐射测定以及分析物抑制CYP2C9活性或诱导CYP2C9表达的潜力。测定的所有步骤，包括孵育，产物分离和放射性计数优选以可以自动化的多孔格式进行。

4. 发明授权

US06960558B2 Method of screening for anti-obesity agents using ciliary neutrophic factor receptor 有权
标题翻译：筛选使用睫状中性白细胞因子受体的抗肥胖剂的方法
公开(公告)号：US06960558B2
公开(公告)日：2005-11-01
申请号：US10356191
申请日：2003-01-31
申请人： Gennaro Ciliberto , Isabelle Gloaguen , Annalise Di Marco , Anna Demartis , Ralph Laufer , Riccardo Cortese
发明人： Gennaro Ciliberto , Isabelle Gloaguen , Annalise Di Marco , Anna Demartis , Ralph Laufer , Riccardo Cortese
IPC分类号： A61K45/00 , A61K38/00 , A61K38/18 , A61K38/22 , A61K48/00 , A61P3/04 , A61P3/10 , A61P43/00 , A61K31/00 , G01N33/53
CPC分类号： A61K38/185 , A61K38/2264 , A61K48/00 , A61K2300/00
摘要： The present invention relates to methods for screening for anti-obesity agents using the ciliary neutrophic factor receptor.
摘要翻译：本发明涉及使用睫状中性因子受体筛选抗肥胖剂的方法。

5. 发明授权

US07629140B2 Assay for cytochrome P450 isoform 2C9 失效
标题翻译：细胞色素P450同工型2C9的测定
公开(公告)号：US07629140B2
公开(公告)日：2009-12-08
申请号：US11663587
申请日：2005-10-04
申请人： Ralph Laufer , Annalise Di Marco , Ashok Chaudhary
发明人： Ralph Laufer , Annalise Di Marco , Ashok Chaudhary
IPC分类号： C12Q1/26
CPC分类号： C12Q1/26 , G01N2333/90245 , G01N2500/02
摘要： A Rapid And Sensitive Radiometric Assay For Assessing The Activity Of Cytochrome P-450 (CYP) 2C9 And The Potential Of An Analyte To Inhibit CYP2C9 Activity Or Induce CYP2C9 Expression is described. All the steps of the assay, including incubations, product separation, and radioactivity counting are preferably performed in a multiwell format, which can be automated.
摘要翻译：描述了用于评估细胞色素P-450（CYP）2C9的活性的快速和敏感的辐射测定以及分析物抑制CYP2C9活性或诱导CYP2C9表达的潜力。测定的所有步骤，包括孵育，产物分离和放射性计数优选以可以自动化的多孔格式进行。

6. 发明申请

US20080145886A1 Assay for Cytochrome P450 Isoforms 3A4 and 3A5 审中-公开
标题翻译：细胞色素P450同工型3A4和3A5的测定
公开(公告)号：US20080145886A1
公开(公告)日：2008-06-19
申请号：US11663579
申请日：2005-10-03
申请人： Ralph Laufer , Annalise Di Marco
发明人： Ralph Laufer , Annalise Di Marco
IPC分类号： C12Q1/30
CPC分类号： C12Q1/26 , G01N2500/00
摘要： A rapid and sensitive radiometric assay for assessing the activity of cytochrome P450 (CYP) 3A4/5 and the potential of an analyte to inhibit CYP3A4/5 activity or induce CYP3A4/5 expression is described. All the steps of the assay, including incubations, product separation, and radioactivity counting are preferably performed in a multiwell format, which can be automated.
摘要翻译：描述了用于评估细胞色素P450（CYP）3A4 / 5的活性和分析物抑制CYP3A4 / 5活性或诱导CYP3A4 / 5表达的潜力的快速和灵敏的辐射测定法。测定的所有步骤，包括孵育，产物分离和放射性计数优选以可以自动化的多孔格式进行。

7. 发明授权

US06756357B1 Variants of human ciliary neurotrophic factor (hCNTF) 失效
标题翻译：人类睫状神经营养因子（hCNTF）的变异
公开(公告)号：US06756357B1
公开(公告)日：2004-06-29
申请号：US09214718
申请日：1999-07-06
申请人： Ralph Laufer , Annalise Di Marco
发明人： Ralph Laufer , Annalise Di Marco
IPC分类号： C07K14475
CPC分类号： C07K14/475 , A61K38/00 , Y10S930/12
摘要： The variants of human ciliary neutrophic factor (hCNTF) according to the present invention are characterized by substitution of phenylalanine 152 and/or lysine 155 with alanine. These variants have biological properties that render them important as the active principles of drugs for the treatment of diseases and pathologies involving the nervous system or other pathologies involving cells responding to the CNTF. FIG. 2 shows the results of simulation of haptoglobin secretion from HepG2 cells by CNTF and the variants described in the invention.
摘要翻译：根据本发明的人睫状中性白细胞因子（hCNTF）的变体的特征在于用丙氨酸取代苯丙氨酸152和/或赖氨酸155。这些变体具有使其作为用于治疗涉及神经系统的疾病和病理学的药物的活性成分或涉及对CNTF起反应的细胞的其它病理学的重要作用。图。图2显示了通过CNTF和本发明描述的变体模拟来自HepG2细胞的触珠蛋白分泌的结果。

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