公开(公告)号：US20100266678A1

公开(公告)日：2010-10-21

申请号：US12732630

申请日：2010-03-26

申请人： Stephanie Pollock ,  Raymond Dwek ,  Nicole Zitzmann

发明人： Stephanie Pollock ,  Raymond Dwek ,  Nicole Zitzmann

IPC分类号： A61K9/127 ,  A61P31/12

CPC分类号： A61K9/127 ,  A61K9/0019 ,  A61K9/1271 ,  A61K31/683 ,  A61K31/685 ,  A61K47/6911 ,  Y02A50/385

摘要： Provided are methods of reducing cellular cholesterol levels using lipid particles that are capable of cellular entry. Such lipid particles may be used for treating or preventing a disease or condition that is caused by or associated with an increased cellular cholesterol level and for treating or preventing a disease or condition, that is caused by or associated with a virus, that relies on cellular cholesterol for its replication.

摘要翻译： 提供使用能够进入细胞的脂质颗粒降低细胞胆固醇水平的方法。 这种脂质颗粒可用于治疗或预防由细胞胆固醇水平升高引起或与细胞胆固醇水平升高相关的疾病或病症，并用于治疗或预防依赖于细胞因子的病毒引起或与之相关的疾病或病症 胆固醇用于其复制。

公开(公告)号：US08703744B2

公开(公告)日：2014-04-22

申请号：US12732630

申请日：2010-03-26

申请人： Stephanie Pollock ,  Raymond Dwek ,  Nicole Zitzmann

发明人： Stephanie Pollock ,  Raymond Dwek ,  Nicole Zitzmann

IPC分类号： A61K9/127 ,  A61P31/12

CPC分类号： A61K9/127 ,  A61K9/0019 ,  A61K9/1271 ,  A61K31/683 ,  A61K31/685 ,  A61K47/6911 ,  Y02A50/385

摘要： Provided are methods of reducing cellular cholesterol levels using lipid particles that are capable of cellular entry. Such lipid particles may be used for treating or preventing a disease or condition that is caused by or associated with an increased cellular cholesterol level and for treating or preventing a disease or condition, that is caused by or associated with a virus, that relies on cellular cholesterol for its replication.

摘要翻译： 提供使用能够进入细胞的脂质颗粒降低细胞胆固醇水平的方法。 这种脂质颗粒可用于治疗或预防由细胞胆固醇水平升高引起或与细胞胆固醇水平升高相关的疾病或病症，并用于治疗或预防依赖于细胞因子的病毒引起或与之相关的疾病或病症 胆固醇用于其复制。

公开(公告)号：US20080280972A1

公开(公告)日：2008-11-13

申请号：US12081661

申请日：2008-04-18

申请人： Raymond Dwek ,  Wanda Buzgariu ,  Anca Hirtopeanu ,  Robert Moriarty ,  Gabriela Negroiu ,  Norica Nichita ,  Livia Zdrentu ,  Nicole Zitzmann

发明人： Raymond Dwek ,  Wanda Buzgariu ,  Anca Hirtopeanu ,  Robert Moriarty ,  Gabriela Negroiu ,  Norica Nichita ,  Livia Zdrentu ,  Nicole Zitzmann

IPC分类号： A61K31/40 ,  C12N5/06 ,  A61K31/075 ,  A61K31/045 ,  A61P43/00

CPC分类号： A61K31/40 ,  A61K31/7004

摘要： A proliferation of cells can be reduced by contacting the cells with a compound having formula (I) where R and R′ are each alkyl groups, R″ is hydrogen or an alkyl group and X3, X4 and X5 are each independently selected from the group consisting of hydrogen, benzyl, t-butyldimethylsiloxy radical and triphenylmethyl. Accordingly, compounds of formula (I) can be used for treatment of tumors including melanoma. Also a secretion of a matrix metalloproteinase (MMP) enzyme by cells can be reduced by contacting the cells with the compound having formula (I). Accordingly, compounds of formula (I) can be used for treatment physiological conditions associated with an elevated MMP level, such as tumors.

摘要翻译： 通过使细胞与具有式（I）的化合物（其中R和R'各自为烷基，R“为氢或烷基，X 3，X S 4和X 5各自独立地选自氢，苄基，叔丁基二甲基甲硅烷氧基和三苯基甲基。 因此，式（I）化合物可用于治疗包括黑素瘤的肿瘤。 通过使细胞与式（I）的化合物接触，也可以通过细胞分泌基质金属蛋白酶（MMP）酶。 因此，式（I）化合物可用于与升高的MMP水平例如肿瘤相关的治疗生理条件。

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。

公开(公告)号：US08957106B2

公开(公告)日：2015-02-17

申请号：US12081661

申请日：2008-04-18

申请人： Raymond Dwek ,  Wanda Buzgariu ,  Anca Hirtopeanu ,  Robert Moriarty ,  Gabriela Negroiu ,  Norica Nichita ,  Livia Zdrentu ,  Nicole Zitzmann

发明人： Raymond Dwek ,  Wanda Buzgariu ,  Anca Hirtopeanu ,  Robert Moriarty ,  Gabriela Negroiu ,  Norica Nichita ,  Livia Zdrentu ,  Nicole Zitzmann

IPC分类号： A01N43/36 ,  A61K31/40 ,  A01N31/00 ,  A61K31/045 ,  C12N5/071 ,  A61K31/7004

CPC分类号： A61K31/40 ,  A61K31/7004

摘要： A proliferation of cells can be reduced by contacting the cells with a compound having formula (I) where R and R′ are each alkyl groups, R″ is hydrogen or an alkyl group and X3, X4 and X5 are each independently selected from the group consisting of hydrogen, benzyl, t-butyldimethylsiloxy radical and triphenylmethyl. Accordingly, compounds of formula (I) can be used for treatment of tumors including melanoma. Also a secretion of a matrix metalloproteinase (MMP) enzyme by cells can be reduced by contacting the cells with the compound having formula (I). Accordingly, compounds of formula (I) can be used for treatment physiological conditions associated with an elevated MMP level, such as tumors.

摘要翻译： 通过使细胞与具有式（I）的化合物（其中R和R'各自为烷基，R“是氢或烷基）并且X 3，X 4和X 5各自独立地选自基团 由氢，苄基，叔丁基二甲基甲硅烷氧基和三苯基甲基组成。 因此，式（I）化合物可用于治疗包括黑素瘤的肿瘤。 通过使细胞与式（I）的化合物接触，也可以通过细胞分泌基质金属蛋白酶（MMP）酶。 因此，式（I）化合物可用于与升高的MMP水平例如肿瘤相关的治疗生理条件。

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。

公开(公告)号：US20090252785A1

公开(公告)日：2009-10-08

申请号：US12410750

申请日：2009-03-25

申请人： Stephanie Pollock ,  Raymond Allen Dwek ,  Nicole Zitzmann

发明人： Stephanie Pollock ,  Raymond Allen Dwek ,  Nicole Zitzmann

IPC分类号： A61K9/127 ,  A61K31/70 ,  C12Q1/70

CPC分类号： A61K9/127 ,  A61K9/0019 ,  A61K9/1271 ,  A61K31/445

摘要： Provided are compositions that include lipid particles, such as liposomes, that can fuse with the ER membrane of a cell. The lipid particles can also deliver a cargo, such as a therapeutic or an imaging agent, encapsulated inside the particles inside the ER lumen of the cell. The compositions can be useful for treating and/or preventing diseases or conditions caused by or associated with a virus, such as viral infections, including HIV and HCV infections.

摘要翻译： 提供的是包含可以与细胞的ER膜融合的脂质颗粒（例如脂质体）的组合物。 脂质颗粒还可以递送包封在细胞的ER腔内的颗粒内的货物，例如治疗剂或显像剂。 该组合物可用于治疗和/或预防由病毒引起或与之相关的疾病或病症，例如包括HIV和HCV感染在内的病毒感染。

公开(公告)号：US20120237592A1

公开(公告)日：2012-09-20

申请号：US13483383

申请日：2012-05-30

申请人： Stephanie Pollock ,  Raymond Allen Dwek ,  Nicole Zitzmann

发明人： Stephanie Pollock ,  Raymond Allen Dwek ,  Nicole Zitzmann

IPC分类号： A61K9/127 ,  A61K31/655 ,  A61P31/12 ,  A61K31/45

CPC分类号： A61K9/127 ,  A61K9/0019 ,  A61K9/1271 ,  A61K31/445

摘要： Provided are compositions that include lipid particles, such as liposomes, that can fuse with the ER membrane of a cell. The lipid particles can also deliver a cargo, such as a therapeutic or an imaging agent, encapsulated inside the particles inside the ER lumen of the cell. The compositions can be useful for treating and/or preventing diseases or conditions caused by or associated with a virus, such as viral infections, including HIV and HCV infections.

摘要翻译： 提供的是包含可以与细胞的ER膜融合的脂质颗粒（例如脂质体）的组合物。 脂质颗粒还可以递送包封在细胞的ER腔内的颗粒内的货物，例如治疗剂或显像剂。 该组合物可用于治疗和/或预防由病毒引起或与之相关的疾病或病症，例如包括HIV和HCV感染在内的病毒感染。

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）。

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）。