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    Clinical diagnosis of hepatic fibrosis using a novel panel of human serum protein biomarkers
    1.
    发明授权
    Clinical diagnosis of hepatic fibrosis using a novel panel of human serum protein biomarkers 有权
    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。

    Clinical diagnosis of hepatic fibrosis using a novel panel of low abundant human plasma protein biomarkers
    2.
    发明授权
    Clinical diagnosis of hepatic fibrosis using a novel panel of low abundant human plasma protein biomarkers 有权
    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。

    CLINICAL DIAGNOSIS OF HEPATIC FIBROSIS USING A NOVEL PANEL OF LOW ABUNDANT HUMAN PLASMA PROTEIN BIOMARKERS
    3.
    发明申请
    CLINICAL DIAGNOSIS OF HEPATIC FIBROSIS USING A NOVEL PANEL OF LOW ABUNDANT HUMAN PLASMA PROTEIN BIOMARKERS 有权
    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。

    CLINICAL DIAGNOSIS OF HEPATIC FIBROSIS USING A NOVEL PANEL OF HUMAN SERUM PROTEIN BIOMARKERS
    4.
    发明申请
    CLINICAL DIAGNOSIS OF HEPATIC FIBROSIS USING A NOVEL PANEL OF HUMAN SERUM PROTEIN BIOMARKERS 有权
    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。

    Glycosylation markers for cancer diagnosing and monitoring
    6.
    发明授权
    Glycosylation markers for cancer diagnosing and monitoring 失效
    用于癌症诊断和监测的糖基化标记

    公开(公告)号：US07892752B2

    公开(公告)日：2011-02-22

    申请号：US11411246

    申请日：2006-04-26

    申请人： Raymond A. Dwek ,  Umi Marshida Abd Hamid ,  Rafael de Llorens ,  Rosa Peracaula ,  Catherine M. Radcliffe ,  John Robertson ,  Louise Royle ,  Pauline M. Rudd ,  Nicole Zitzmann

    发明人： Raymond A. Dwek ,  Umi Marshida Abd Hamid ,  Rafael de Llorens ,  Rosa Peracaula ,  Catherine M. Radcliffe ,  John Robertson ,  Louise Royle ,  Pauline M. Rudd ,  Nicole Zitzmann

    IPC分类号： G01N33/53

    CPC分类号： G01N33/6842 ,  G01N33/57407 ,  G01N33/57484

    摘要： One can identify and quantify one or more glycosylation markers of cancer by utilizing quantitative HPLC analysis of glycans which have been released from unpurified glycoproteins. The unpurified glycoproteins can be total glycoproteins or a selection of the total glycoproteins. The identified glycosylation marker can be a native glycan or a digestion product which has been segregated and amplified by exoglycosidase digestions. One can utilize the identified glycosylation marker, for example, for diagnosing and/or monitoring cancer in a subject. One can also use the glycosylation marker to identify glycoprotein biomarkers that carry the glycosylation marker. Such biomarkers can also be used for monitoring and/or diagnosing cancer. The biomarker may also be a subset of glycoforms of a glycoprotein that are separated in trains of spots on 2D gel.

    摘要翻译： 通过利用已经从未纯化的糖蛋白释放的聚糖的定量HPLC分析，可以鉴定和定量癌症的一种或多种糖基化标记物。 未纯化的糖蛋白可以是总糖蛋白或总糖蛋白的选择。 鉴定的糖基化标记可以是天然聚糖或消化产物，其通过去糖基酶消化分离和扩增。 可以使用鉴定的糖基化标记，例如用于诊断和/或监测受试者的癌症。 也可以使用糖基化标记来鉴定携带糖基化标记的糖蛋白生物标志物。 此类生物标志物也可用于监测和/或诊断癌症。 生物标志物也可以是在2D凝胶上的斑点列中分离的糖蛋白的糖形成的子集。