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1. 发明授权

US09012162B2 Clinical diagnosis of hepatic fibrosis using a novel panel of human serum protein biomarkers 有权
标题翻译：使用人血清蛋白生物标志物的新型小组对肝纤维化进行临床诊断
公开(公告)号：US09012162B2
公开(公告)日：2015-04-21
申请号：US11851619
申请日：2007-09-07
申请人： Bevin Gangadharan , Nicole Zitzmann , Raymond A. Dwek
发明人： Bevin Gangadharan , Nicole Zitzmann , Raymond A. Dwek
IPC分类号： G01N33/00 , G01N33/576
CPC分类号： G01N33/6893 , G01N33/576 , G01N33/5767 , G01N2333/775 , G01N2800/085 , Y10S436/811
摘要： The inventors have proposed a novel panel of human serum protein biomarkers for diagnosing hepatic fibrosis and cirrhosis. Presently there is no reliable non-invasive way of assessing liver fibrosis. A 2D-PAGE based proteomics study was used to identify potential fibrosis biomarkers. Serum from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) was analyzed. Several proteins associated with liver scarring and/or viral infection were identified. These proteins include the inter-α-trypsin inhibitor heavy chain H4 fragments, complement factor H-related protein 1, CD5L, Apo L1, and β2GPI. Increased and decreased thiolester cleavage of a2M and Complement C3, respectively, was also detected. The concentrations of these novel biomarkers can be determined using an immunoassay where the concentrations would reflect the extent of fibrosis. A fibrosis scoring scale for each of the novel biomarkers is proposed. The additive result from the scores of all the novel biomarkers would give a more reliable indication of the degree of fibrosis rather than examining individual biomarkers.
摘要翻译：本发明人提出了用于诊断肝纤维化和肝硬化的人类血清蛋白生物标志物的新颖小组。目前尚无可靠的非侵入性肝纤维化评估方法。使用基于2D-PAGE的蛋白质组学研究来鉴定潜在的纤维化生物标志物。分析了丙型肝炎病毒（HCV）感染引起肝脏瘢痕形成程度不同的患者血清。鉴定了与肝脏瘢痕形成和/或病毒感染相关的几种蛋白质。这些蛋白质包括α-间胰蛋白酶抑制剂重链H4片段，补体因子H相关蛋白1，CD5L，Apo L1和＆bgr; 2GPI。还检测到了分别增加和减少的a2M和补体C3的硫醇裂解。这些新型生物标志物的浓度可以使用免疫测定来确定，其中浓度将反映纤维化程度。提出了每种新型生物标志物的纤维化评分量表。所有新生物标志物的得分的添加剂结果将给出更可靠的纤维化程度的指示，而不是检查个体生物标志物。

2. 发明申请

US20080085526A1 CLINICAL DIAGNOSIS OF HEPATIC FIBROSIS USING A NOVEL PANEL OF HUMAN SERUM PROTEIN BIOMARKERS 有权
标题翻译：使用人类血清蛋白生物标志物的新面板进行的肝脏纤维化的临床诊断
公开(公告)号：US20080085526A1
公开(公告)日：2008-04-10
申请号：US11851619
申请日：2007-09-07
申请人： Bevin Gangadharan , Nicole Zitzmann , Raymond Dwek
发明人： Bevin Gangadharan , Nicole Zitzmann , Raymond Dwek
IPC分类号： G01N33/53 , G01N33/68
CPC分类号： G01N33/6893 , G01N33/576 , G01N33/5767 , G01N2333/775 , G01N2800/085 , Y10S436/811
摘要： The inventors have proposed a novel panel of human serum protein biomarkers for diagnosing hepatic fibrosis and cirrhosis. Presently there is no reliable non-invasive way of assessing liver fibrosis. A 2D-PAGE based proteomics study was used to identify potential fibrosis biomarkers. Serum from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) was analysed. Several proteins associated with liver scarring and/or viral infection were identified. These proteins include the inter-α-trypsin inhibitor heavy chain H4 fragments, complement factor H-related protein 1, CD5L, Apo L1, and β2GPI. Increased and decreased thiolester cleavage of a2M and Complement C3, respectively, was also detected. The concentrations of these novel biomarkers can be determined using an immunoassay where the concentrations would reflect the extent of fibrosis. A fibrosis scoring scale for each of the novel biomarkers is proposed. The additive result from the scores of all the novel biomarkers would give a more reliable indication of the degree of fibrosis rather than examining individual biomarkers.
摘要翻译：本发明人提出了用于诊断肝纤维化和肝硬化的人类血清蛋白生物标志物的新颖小组。目前尚无可靠的非侵入性肝纤维化评估方法。使用基于2D-PAGE的蛋白质组学研究来鉴定潜在的纤维化生物标志物。分析了丙型肝炎病毒（HCV）感染引起肝脏瘢痕形成程度不同的患者血清。鉴定了与肝脏瘢痕形成和/或病毒感染相关的几种蛋白质。这些蛋白质包括α间胰蛋白酶抑制剂重链H4片段，补体因子H相关蛋白1，CD5L，Apo L1和β2GPI。还检测到了分别增加和减少的a2M和补体C3的硫醇裂解。这些新型生物标志物的浓度可以使用免疫测定来确定，其中浓度将反映纤维化程度。提出了每种新型生物标志物的纤维化评分量表。所有新生物标志物的得分的添加剂结果将给出更可靠的纤维化程度的指示，而不是检查个体生物标志物。

3. 发明授权

US08889364B2 Clinical diagnosis of hepatic fibrosis using a novel panel of low abundant human plasma protein biomarkers 有权
标题翻译：使用低浓度人血浆蛋白生物标志物的新型小组对肝纤维化进行临床诊断
公开(公告)号：US08889364B2
公开(公告)日：2014-11-18
申请号：US12779349
申请日：2010-05-13
申请人： Bevin Gangadharan , Nicole Zitzmann , Raymond A. Dwek
发明人： Bevin Gangadharan , Nicole Zitzmann , Raymond A. Dwek
IPC分类号： G01N33/53 , G01N33/574 , G01N33/68 , G01N33/576
CPC分类号： G01N33/5767 , G01N33/57438 , G01N33/6893 , G01N2333/47 , G01N2333/4728 , G01N2333/775 , G01N2333/924 , G01N2500/00 , G01N2800/085 , G01N2800/52 , G01N2800/54 , G01N2800/56 , G01N2800/7057
摘要： The inventors have proposed a novel panel of human plasma protein biomarkers for diagnosing hepatic fibrosis and cirrhosis. Presently there is no reliable non-invasive way of assessing liver fibrosis. A 2D-PAGE based proteomics study was used to identify potential fibrosis biomarkers. Plasma from patients with hepatic cirrhosis induced by infection with the hepatitis C virus (HCV) were analyzed. Several proteins associated with liver scarring and potentially also related to viral infection were identified. These proteins include 14-3-3 protein zeta/delta, adiponectin, afamin, alpha-1-antitrypsin, alpha-2-HS-glycoprotein, apolipoprotein C-III, apolipoprotein E, C4b-binding protein beta chain, intact/cleaved complement C3dg, corticosteroid-binding globulin, fibrinogen gamma chain, beta haptoglobin at pH 5.46-5.49, haptoglobin-related protein, hemopexin, immunoglobulin J chain, leucine-rich alpha-2-glycoprotein, lipid transfer inhibitor protein, retinol-binding protein 4, serum paraoxonase/arylesterase 1, sex hormone-binding globulin and zinc-alpha-2-glycoprotein. These biomarkers can be used in conjunction with polypeptides in WO/2008/031051. The concentrations of these novel biomarkers can be determined using an immunoassay where the concentrations would reflect the extent of fibrosis. A fibrosis scoring scale for each of the novel biomarkers is proposed. The additive result from the scores of all the novel biomarkers would give a more reliable indication of the degree of fibrosis rather than examining individual biomarkers.
摘要翻译：本发明人提出了用于诊断肝纤维化和肝硬化的人血浆蛋白生物标志物的新颖小组。目前尚无可靠的非侵入性肝纤维化评估方法。使用基于2D-PAGE的蛋白质组学研究来鉴定潜在的纤维化生物标志物。对丙型肝炎病毒（HCV）感染引起的肝硬化患者血浆进行了分析。鉴定了与肝脏瘢痕形成相关并且潜在地也与病毒感染相关的几种蛋白质。这些蛋白质包括14-3-3蛋白ζ/δ，脂连蛋白，afamin，α-1-抗胰蛋白酶，α-2-HS-糖蛋白，载脂蛋白C-III，载脂蛋白E，C4b结合蛋白β链，完整/切割补体 C3dg，皮质类固醇结合球蛋白，纤维蛋白原γ链，β接触珠蛋白，pH 5.46-5.49，触珠蛋白相关蛋白，血红蛋白，免疫球蛋白J链，富含亮氨酸的α-2-糖蛋白，脂质转移抑制蛋白，视黄醇结合蛋白4，血清对氧磷酶/芳基酯酶1，性激素结合球蛋白和锌-α-2-糖蛋白。这些生物标志物可以与WO / 2008/031051中的多肽结合使用。这些新型生物标志物的浓度可以使用免疫测定来确定，其中浓度将反映纤维化程度。提出了每种新型生物标志物的纤维化评分量表。所有新生物标志物的得分的添加剂结果将给出更可靠的纤维化程度的指示，而不是检查个体生物标志物。

4. 发明申请

US20100291602A1 CLINICAL DIAGNOSIS OF HEPATIC FIBROSIS USING A NOVEL PANEL OF LOW ABUNDANT HUMAN PLASMA PROTEIN BIOMARKERS 有权
标题翻译：使用低等离子人血浆蛋白生物标志物的新面板进行的皮肤纤维化临床诊断
公开(公告)号：US20100291602A1
公开(公告)日：2010-11-18
申请号：US12779349
申请日：2010-05-13
申请人： Bevin GANGADHARAN , Nicole Zitzmann , Raymond A. Dwek
发明人： Bevin GANGADHARAN , Nicole Zitzmann , Raymond A. Dwek
IPC分类号： G01N33/53 , G01N33/566 , G01N33/00
CPC分类号： G01N33/5767 , G01N33/57438 , G01N33/6893 , G01N2333/47 , G01N2333/4728 , G01N2333/775 , G01N2333/924 , G01N2500/00 , G01N2800/085 , G01N2800/52 , G01N2800/54 , G01N2800/56 , G01N2800/7057
摘要： The inventors have proposed a novel panel of human plasma protein biomarkers for diagnosing hepatic fibrosis and cirrhosis. Presently there is no reliable non-invasive way of assessing liver fibrosis. A 2D-PAGE based proteomics study was used to identify potential fibrosis biomarkers. Plasma from patients with hepatic cirrhosis induced by infection with the hepatitis C virus (HCV) were analysed. Several proteins associated with liver scarring and potentially also related to viral infection were identified. These proteins include 14-3-3 protein zeta/delta, adiponectin, afamin, alpha-1-antitrypsin, alpha-2-HS-glycoprotein, apolipoprotein C-III, apolipoprotein E, C4b-binding protein beta chain, intact/cleaved complement C3dg, corticosteroid-binding globulin, fibrinogen gamma chain, beta haptoglobin at pH 5.46-5.49, haptoglobin-related protein, hemopexin, immunoglobulin J chain, leucine-rich alpha-2-glycoprotein, lipid transfer inhibitor protein, retinol-binding protein 4, serum paraoxonase/arylesterase 1, sex hormone-binding globulin and zinc-alpha-2-glycoprotein. These biomarkers can be used in conjunction with polypeptides in WO/2008/031051. The concentrations of these novel biomarkers can be determined using an immunoassay where the concentrations would reflect the extent of fibrosis. A fibrosis scoring scale for each of the novel biomarkers is proposed. The additive result from the scores of all the novel biomarkers would give a more reliable indication of the degree of fibrosis rather than examining individual biomarkers.
摘要翻译：本发明人提出了用于诊断肝纤维化和肝硬化的人血浆蛋白生物标志物的新颖小组。目前尚无可靠的非侵入性肝纤维化评估方法。使用基于2D-PAGE的蛋白质组学研究来鉴定潜在的纤维化生物标志物。对丙型肝炎病毒（HCV）感染引起的肝硬化患者血浆进行了分析。鉴定了与肝脏瘢痕形成相关并且潜在地也与病毒感染相关的几种蛋白质。这些蛋白质包括14-3-3蛋白ζ/δ，脂连蛋白，afamin，α-1-抗胰蛋白酶，α-2-HS-糖蛋白，载脂蛋白C-III，载脂蛋白E，C4b结合蛋白β链，完整/切割补体 C3dg，皮质类固醇结合球蛋白，纤维蛋白原γ链，β接触珠蛋白，pH 5.46-5.49，触珠蛋白相关蛋白，血红蛋白，免疫球蛋白J链，富含亮氨酸的α-2-糖蛋白，脂质转移抑制蛋白，视黄醇结合蛋白4，血清对氧磷酶/芳基酯酶1，性激素结合球蛋白和锌-α-2-糖蛋白。这些生物标志物可以与WO / 2008/031051中的多肽结合使用。这些新型生物标志物的浓度可以使用免疫测定来确定，其中浓度将反映纤维化程度。提出了每种新型生物标志物的纤维化评分量表。所有新生物标志物的得分的添加剂结果将给出更可靠的纤维化程度的指示，而不是检查个体生物标志物。

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