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1. 发明授权

US08039208B2 Automated strategy for identifying physiological glycosylation markers(s) 有权
标题翻译：识别生理糖基化标记的自动化策略
公开(公告)号：US08039208B2
公开(公告)日：2011-10-18
申请号：US11411232
申请日：2006-04-26
申请人： Raymond A. Dwek , Louise Royle , Nicole Zitzmann , Catherine M. Radcliffe , Pauline Rudd
发明人： Raymond A. Dwek , Louise Royle , Nicole Zitzmann , Catherine M. Radcliffe , Pauline Rudd
IPC分类号： C12Q1/00
CPC分类号： C12Q1/34 , G01N33/582 , G01N33/6842 , G01N2333/924 , G01N2400/14
摘要： One can identify and quantify one or more glycosylation markers of a physiological condition such as a disease or a stage of disease 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. This strategy is compatible with a high throughput format and glycan data base searching. One can utilize the identified glycosylation marker, for example, for monitoring the physiological condition in a subject. One can also use the glycosylation marker to identify glycoproteins that carry the glycosylation marker which can also be used to monitor the physiological condition. 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，可以鉴定和定量生理条件如疾病或疾病阶段的一个或多个糖基化标记物。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。此策略与高吞吐量格式和聚糖数据库搜索兼容。可以使用鉴定的糖基化标记，例如，用于监测受试者的生理状况。还可以使用糖基化标记来鉴定携带糖基化标记的糖蛋白，其也可以用于监测生理状况。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。

2. 发明授权

US07892752B2 Glycosylation markers for cancer diagnosing and monitoring 失效
标题翻译：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。

3. 发明申请

US20110182982A1 LIPOSOME TREATMENT OF VIRAL INFECTIONS 审中-公开
标题翻译： LIPOSOME治疗病毒感染
公开(公告)号：US20110182982A1
公开(公告)日：2011-07-28
申请号：US13069603
申请日：2011-03-23
申请人： Raymond A. Dwek , Norica Nichita-Branza , Stefana Petrescu , Stephanie Pollock , Pauline Rudd , Christopher Scanlan , Nicole Zitzmann
发明人： Raymond A. Dwek , Norica Nichita-Branza , Stefana Petrescu , Stephanie Pollock , Pauline Rudd , Christopher Scanlan , Nicole Zitzmann
IPC分类号： A61K9/127 , A61K31/445 , A61K31/7056 , A61K38/21 , A61P31/12
CPC分类号： A61K31/70 , A61K9/1271 , A61K9/1272 , A61K38/212 , A61K47/6425 , A61K47/6911 , A61K2300/00
摘要： One can treat a viral infection such as hepatitis B (HBV), hepatitis C(HCV), and bovine viral diarrhea virus (BVDV) infections via the delivery of pH sensitive liposomes directly into the endoplasmic reticulum (ER) membrane. Two exemplary liposome formulations are DOPE/CHEMS (DC liposomes) and DOPE/CHEMS/PEG-PE (DCPP liposomes). DC and DCPP liposomes can optimize the intracellular delivery of N-butyl deoxynojirimycin (NB-DNJ), and consequently increase the in vivo activity of this iminosugar several orders of magnitude, and could be used in combination with other therapeutic agents such as interferon and/or ribavirin. The optimized release of NB-DNJ directly into the ER can be also applied for the treatment of other viruses, for which NB-DNJ is known to be an effective antiviral, such as human immunodeficiency virus (HIV).
摘要翻译：通过将pH敏感的脂质体直接递送到内质网（ER）膜中，可以治疗乙型肝炎（HBV），丙型肝炎（HCV）和牛病毒性腹泻病毒（BVDV）感染的病毒感染。两种示例性的脂质体制剂是DOPE / CHEMS（DC脂质体）和DOPE / CHEMS / PEG-PE（DCPP脂质体）。 DC和DCPP脂质体可以优化N-丁基脱氧野尻霉素（NB-DNJ）的细胞内递送，从而增加这种亚氨基二糖的体内活性几个数量级，并且可以与其它治疗剂如干扰素和/ 或利巴韦林。 NB-DNJ直接进入ER的优化释放也可以用于其他病毒的治疗，已知NB-DNJ是有效的抗病毒药物，如人类免疫缺陷病毒（HIV）。

4. 发明申请

US20080138351A1 LIPOSOME TREATMENT OF VIRAL INFECTIONS 审中-公开
标题翻译： LIPOSOME治疗病毒感染
公开(公告)号：US20080138351A1
公开(公告)日：2008-06-12
申请号：US11832891
申请日：2007-08-02
申请人： Raymond A. Dwek , Norica Nichita-Branza , Stefana Petrescu , Stephanie Pollock , Pauline Rudd , Christopher Scanlan , Nicole Zitzmann
发明人： Raymond A. Dwek , Norica Nichita-Branza , Stefana Petrescu , Stephanie Pollock , Pauline Rudd , Christopher Scanlan , Nicole Zitzmann
IPC分类号： A61K39/395 , A61K9/127 , A61K31/70 , A61K38/02 , A61K38/08
CPC分类号： A61K31/70 , A61K9/1271 , A61K9/1272 , A61K38/212 , A61K47/6425 , A61K47/6911 , A61K2300/00
摘要： One can treat a viral infection such as hepatitis B (HBV), hepatitis C (HCV), and bovine viral diarrhea virus (BVDV) infections via the delivery of pH sensitive liposomes directly into the endoplasmic reticulum (ER) membrane. Two exemplary liposome formulations are DOPE/CHEMS (DC liposomes) and DOPE/CHEMS/PEG-PE (DCPP liposomes). DC and DCPP liposomes can optimize the intracellular delivery of N-butyl deoxynojirimycin (NB-DNJ), and consequently increase the in vivo activity of this iminosugar several orders of magnitude, and could be used in combination with other therapeutic agents such as interferon and/or ribavirin. The optimized release of NB-DNJ directly into the ER can be also applied for the treatment of other viruses, for which NB-DNJ is known to be an effective antiviral, such as human immunodeficiency virus (HIV).
摘要翻译：通过将pH敏感的脂质体直接递送到内质网（ER）膜中，可以治疗乙型肝炎（HBV），丙型肝炎（HCV）和牛病毒性腹泻病毒（BVDV）感染的病毒感染。两种示例性的脂质体制剂是DOPE / CHEMS（DC脂质体）和DOPE / CHEMS / PEG-PE（DCPP脂质体）。 DC和DCPP脂质体可以优化N-丁基脱氧野尻霉素（NB-DNJ）的细胞内递送，从而增加这种亚氨基二糖的体内活性几个数量级，并且可以与其它治疗剂如干扰素和/ 或利巴韦林。 NB-DNJ直接进入ER的优化释放也可以用于其他病毒的治疗，已知NB-DNJ是有效的抗病毒药物，如人类免疫缺陷病毒（HIV）。

5. 发明申请

US20060269974A1 Glycosylation markers for cancer diagnosing and monitoring 失效
标题翻译：用于癌症诊断和监测的糖基化标记
公开(公告)号：US20060269974A1
公开(公告)日：2006-11-30
申请号：US11411246
申请日：2006-04-26
申请人： Raymond Dwek , Umi Hamid , Rafael Llorens , Rosa Peracaula , Catherine Radcliffe , John Robertson , Louise Royle , Pauline Rudd , Nicole Zitzmann
发明人： Raymond Dwek , Umi Hamid , Rafael Llorens , Rosa Peracaula , Catherine Radcliffe , John Robertson , Louise Royle , Pauline Rudd , Nicole Zitzmann
IPC分类号： G01N33/574 , C12Q1/37 , G01N33/00
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。

6. 发明授权

US08367705B2 Iminosugars and methods of treating bunyaviral and togaviral diseases 有权
公开(公告)号：US08367705B2
公开(公告)日：2013-02-05
申请号：US12813882
申请日：2010-06-11
申请人： Urban Ramstedt , Brennan Klose , Nicole Zitzmann , Raymond A. Dwek , Terry D. Butters
发明人： Urban Ramstedt , Brennan Klose , Nicole Zitzmann , Raymond A. Dwek , Terry D. Butters
IPC分类号： A61K31/445
摘要： Provided are novel methods of treating and/or preventing a disease or condition caused by or associated with a virus belonging to the Bunyaviridae or Togaviridae family using iminosugars, such as DNJ derivatives.

7. 发明申请

US20100137365A1 Long chain N-alkyl compounds and oxa-derivatives thereof 审中-公开
标题翻译：长链N-烷基化合物及其氧杂衍生物
公开(公告)号：US20100137365A1
公开(公告)日：2010-06-03
申请号：US12656370
申请日：2010-01-28
申请人： Nicole Zitzmann , Terry D. Butters , Frances M. Platt , Gary S. Jacob , Donald H. Picker , Sandra Carrouee , George W.J. Fleet , Raymond A. Dwek , David Durantel , Anand Mehta , Timothy M. Block
发明人： Nicole Zitzmann , Terry D. Butters , Frances M. Platt , Gary S. Jacob , Donald H. Picker , Sandra Carrouee , George W.J. Fleet , Raymond A. Dwek , David Durantel , Anand Mehta , Timothy M. Block
IPC分类号： A61K31/445 , A61P31/12 , A61P31/14 , C07D211/46 , C07D207/12 , C07C237/42 , A61K31/402 , A61K31/166
CPC分类号： A61K31/13 , A61K31/00 , A61K31/166 , A61K31/40 , A61K31/445 , Y02A50/385 , Y02A50/387 , Y02A50/389 , Y02A50/393 , Y02A50/395
摘要： Long chain N-alkyl amino and imino compounds, oxa-substituted derivatives thereof, and pharmaceutical compositions including such compounds are described. The long chain N-alkyl group is a C8-C16 alkyl group. The long chain N-alkyl compounds and oxa-substituted derivatives thereof can be used in the treatment of viral infections, in particular hepatitis B virus or hepatitis C virus, in a cell or an individual. For example, the long chain N-alkyl compounds or oxa-substituted derivatives thereof can be derived from piperidines, pyrrolidines, phenylamines, pyridines, pyrroles, or amino acids.
摘要翻译：描述了长链N-烷基氨基和亚氨基化合物，其氧杂取代的衍生物和包括这些化合物的药物组合物。长链N-烷基是C8-C16烷基。长链N-烷基化合物及其氧杂取代的衍生物可用于治疗细胞或个体中的病毒感染，特别是乙型肝炎病毒或丙型肝炎病毒。例如，长链N-烷基化合物或其氧杂取代的衍生物可衍生自哌啶，吡咯烷，苯胺，吡啶，吡咯或氨基酸。

8. 发明申请

US20110065752A1 METHODS OF TREATING ORTHOMYXOVIRAL INFECTIONS 审中-公开
标题翻译：治疗口腔感染的方法
公开(公告)号：US20110065752A1
公开(公告)日：2011-03-17
申请号：US12873704
申请日：2010-09-01
申请人： Urban Ramstedt , Brennan Klose , Nicole Zitzmann , Raymond A. Dwek , Terry D. Butters
发明人： Urban Ramstedt , Brennan Klose , Nicole Zitzmann , Raymond A. Dwek , Terry D. Butters
IPC分类号： A61K31/445 , A61P31/14 , C12N5/02
CPC分类号： A61K31/445 , A61K31/655 , C07D211/46
摘要： Provided are novel iminosugars and methods of treating and/or preventing a disease or condition caused by or associated with a virus belonging to the Orthomyxoviridae family using iminosugars, such as DNJ derivatives.
摘要翻译：提供了新的亚氨基糖苷以及使用亚氨基二糖如DNJ衍生物治疗和/或预防由属于正粘病毒科的病毒引起或与之相关的疾病或病症的方法。

9. 发明申请

US20100222384A1 Iminosugars and methods of treating arenaviral infections 审中-公开
标题翻译：伊米诺糖和治疗异种病毒感染的方法
公开(公告)号：US20100222384A1
公开(公告)日：2010-09-02
申请号：US12656993
申请日：2010-02-22
申请人： Urban Ramstedt , Brennan Klose , Nicole Zitzmann , Raymond A. Dwek , Terry D. Butters
发明人： Urban Ramstedt , Brennan Klose , Nicole Zitzmann , Raymond A. Dwek , Terry D. Butters
IPC分类号： A61K31/445 , A61P31/12
CPC分类号： A61K31/445
摘要： Provided are methods of treating a disease or condition caused by or associated with a virus belonging to the Arenaviridae family using iminosugars, such as DNJ derivatives.
摘要翻译：本发明提供了使用亚氨基二糖（例如DNJ衍生物）治疗由属于该病毒属（Arenaviridae）家族的病毒引起或与之相关的疾病或病症的方法。

10. 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。

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