公开(公告)号：US20060188511A1

公开(公告)日：2006-08-24

申请号：US10958624

申请日：2004-10-05

申请人： Steven Foung ,  Kenneth Hadlock ,  Zhenyong Keck

发明人： Steven Foung ,  Kenneth Hadlock ,  Zhenyong Keck

IPC分类号： A61K39/42

CPC分类号： C07K16/109 ,  A61K39/42 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/34 ,  A61K2300/00

摘要： Conformational epitopes of the envelope proteins E1 and E2 of the Hepatitis C virus (HCV) have been identified and characterized using a panel of monoclonal antibodies derived from patients infected with HCV. These conserved conformational and linear epitopes of the HCV protein E1 or E2 have been determined to be important in the immune response of humans to HCV and may be particularly important in neutralizing the virus. Based on the identification of these conformational epitopes, vaccines containing peptides and mimotopes with these conformational epitopes intact may be prepared and administered to patients to prevent and/or treat HCV infection. The identification of four distinct groups of monoclonal antibodies with each directed to a particular epitope of E1 or E2 may be used to stratify patients based on their response to HCV and may be used to determine a proper treatment regimen. Pharmaceutical compositions for prevention and treatment of HCV, comprising one or more the monoclonal antibodies, are provided.

摘要翻译： 已经使用来自感染HCV的患者的一组单克隆抗体鉴定和表征丙型肝炎病毒（HCV）的包膜蛋白E1和E2的构象表位。 已经确定HCV蛋白E1或E2的这些保守的构象和线性表位在人类对HCV的免疫应答中是重要的，并且在中和病毒时尤其重要。 基于这些构象表位的鉴定，可以制备含有具有这些构象表位的肽和模拟表位的疫苗，并将其施用于患者以预防和/或治疗HCV感染。 鉴定四种不同组的单克隆抗体，每种单克隆抗体针对E1或E2的特定表位可用于基于其对HCV的反应来对患者进行分层，并且可用于确定适当的治疗方案。 提供了包含一种或多种单克隆抗体的用于预防和治疗HCV的药物组合物。

公开(公告)号：US20070032635A1

公开(公告)日：2007-02-08

申请号：US11504974

申请日：2006-08-15

申请人： Steven Foung ,  Kenneth Hadlock ,  Zhen-Yong Keck

发明人： Steven Foung ,  Kenneth Hadlock ,  Zhen-Yong Keck

IPC分类号： C07H21/04 ,  C07K14/00 ,  C07K16/00 ,  A61K38/00 ,  C07K17/00 ,  C07K2/00 ,  C07K4/00 ,  C07K5/00 ,  C07K7/00

CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  C07K16/109 ,  C07K2317/21 ,  C12N2710/14143 ,  C12N2710/24143 ,  C12N2770/24222 ,  G01N33/5767

摘要： Conformational epitopes of the envelope protein E2 of the Hepatitis C virus (HCV) have been identified and characterized using a panel of monoclonal antibodies derived from patients infected with HCV. These conformational epitopes have been determined to be important in the immune response of humans to HCV and may be particularly important in neutralizing the virus. Based on the identification of these conformational epitopes, vaccines containing peptides and mimotopes with these conformational epitopes intact may be prepared and administered to patients to prevent and/or treat HCV infection. The identification of four distinct groups of monoclonal antibodies with each directed to a particular epitope of E2 may be used to stratify patients based on their response to HCV and may be used to determine a proper treatment regimen.

摘要翻译： 已经使用来自感染HCV的患者的一组单克隆抗体鉴定和表征丙型肝炎病毒（HCV）的包膜蛋白E2的构象表位。 这些构象表位已经被确定为在人类对HCV的免疫应答中是重要的，并且在中和病毒时尤其重要。 基于这些构象表位的鉴定，可以制备含有具有这些构象表位的肽和模拟表位的疫苗，并将其施用于患者以预防和/或治疗HCV感染。 可以使用鉴定四种不同组的单克隆抗体，每种单克隆抗体针对E2的特定表位，以根据其对HCV的反应来对患者进行分层，并且可用于确定适当的治疗方案。

公开(公告)号：US20060104980A1

公开(公告)日：2006-05-18

申请号：US09728720

申请日：2000-12-01

申请人： Steven Foung ,  Kenneth Hadlock ,  Zhen-Yong Keck

发明人： Steven Foung ,  Kenneth Hadlock ,  Zhen-Yong Keck

IPC分类号： A61K39/42 ,  C12Q1/70 ,  C07K16/08

CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  C07K16/109 ,  C07K2317/21 ,  C12N2710/14143 ,  C12N2710/24143 ,  C12N2770/24222 ,  G01N33/5767

摘要： Conformational epitopes of the envelope protein E2 of the Hepatitis C virus (HCV) have been identified and characterized using a panel of monoclonal antibodies derived from patients infected with HCV. These conformational epitopes have been determined to be important in the immune response of humans to HCV and may be particularly important in neutralizing the virus. Based on the identification of these conformational epitopes, vaccines containing peptides and mimotopes with these conformational epitopes intact may be prepared and administered to patients to prevent and/or treat HCV infection. The identification of four distinct groups of monoclonal antibodies with each directed to a particular epitope of E2 may be used to stratify patients based on their response to HCV and may be used to determine a proper treatment regimen.

公开(公告)号：US07879326B2

公开(公告)日：2011-02-01

申请号：US12140151

申请日：2008-06-16

申请人： Steven Foung ,  Zhen-Yong Keck ,  Richard Webby

发明人： Steven Foung ,  Zhen-Yong Keck ,  Richard Webby

IPC分类号： A61K39/42 ,  C07K16/10 ,  C12N15/13 ,  C12N5/24 ,  C12N5/10

CPC分类号： C07K16/1018 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/76

摘要： A panel of IgG1 human monoclonal antibodies (HMAbs) identified by hemagglutination inhibition (HI) assay has been produced from peripheral B cells of an individual immunized with prototype H5N1 vaccine. Sequence analysis of antibody clones showed three clusters of different HMAbs as represented by HMAbs designated as BF1-1, BF1-19 and BF1-10. BF1-1 and BF1-10 have distinct CDR 1, 2 and 3 regions of both heavy and light chains. BF1-19 has the same heavy chain as BF1-1 but the light chain of BF1-10. Antibody binding affinity, KD, studies showed all three HMAbs ranging from at least about 10−8 to at least about 10−9. In vivo protection studies showed that these antibodies afforded significant protection against infection. These findings demonstrate that the antibodies of the invention are cross-neutralizing and therapeutic.

摘要翻译： 已经通过用原型H5N1疫苗免疫的个体的外周B细胞产生了通过血细胞凝集抑制（HI）测定鉴定的一组IgG1人单克隆抗体（HMAb）。 抗体克隆的序列分析显示由称为BF1-1，BF1-19和BF1-10的HMAb表示的三组不同HMAb。 BF1-1和BF1-10具有明显的重链和轻链CDR 1，2和3区。 BF1-19具有与BF1-1相同的重链，但BF1-10的轻链。 抗体结合亲和力KD研究显示所有三种HMAb在至少约10-8至至少约10-9之间。 体内保护研究表明，这些抗体提供了显着的抗感染保护。 这些发现证明本发明的抗体是交叉中和和治疗的。

公开(公告)号：US20130084301A1

公开(公告)日：2013-04-04

申请号：US13599796

申请日：2012-08-30

申请人： Steven Foung ,  Zhen-Yong Keck

发明人： Steven Foung ,  Zhen-Yong Keck

IPC分类号： C07K16/10 ,  A61K39/29 ,  A61K39/42 ,  A61K45/06 ,  G01N33/569 ,  G01N33/68

CPC分类号： C07K16/10 ,  A61K39/12 ,  A61K39/29 ,  A61K39/42 ,  A61K45/06 ,  C07K16/109 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2317/92 ,  C12N2770/24234 ,  G01N33/56983 ,  G01N33/6854

摘要： Compositions and methods are provided relating to human anti-HCV E2 monoclonal antibodies. The antibodies of the invention bind to a conserved region of HCV E2 protein, and neutralize HCV influenza virus across multiple HCV genotypes. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the human anti-HCV monoclonal antibodies; and cell lines that produce these monoclonal antibodies.

摘要翻译： 提供了关于人抗HCV E2单克隆抗体的组合物和方法。 本发明的抗体结合HCV E2蛋白的保守区域，并通过多种HCV基因型中和HCV流感病毒。 本发明的实施方案包括分离的抗体及其衍生物和片段，包含一种或多种人抗HCV单克隆抗体的药物制剂; 和产生这些单克隆抗体的细胞系。

公开(公告)号：US20120039846A1

公开(公告)日：2012-02-16

申请号：US13122598

申请日：2008-10-05

申请人： Steven Foung ,  Zhen-yong Keck

发明人： Steven Foung ,  Zhen-yong Keck

IPC分类号： A61K38/21 ,  C12N5/0781 ,  A61P31/14 ,  C12N5/071 ,  A61K39/42 ,  C07K16/10 ,  C12N5/16

CPC分类号： C07K16/109 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76

摘要： The present invention provides identification and characterization of conformational epitopes of the envelope protein E2 of the Hepatitis C virus (HCV). The present invention provides a panel of human monoclonal antibodies that recognize conformational epitopes of E2. The antibodies are derived from patients infected with HCV. The present invention provides methods for utilizing HCV antibodies as therapeutic, diagnostic, and/or prophylactic agents. The present invention provides mimotopes with conformational epitopes intact and methods of using mimotopes. The present invention provides methods of stratifying patients based on their response to HCV. The present invention provides pharmaceutical compositions for prevention and treatment of HCV comprising one or more HCV antibodies.

摘要翻译： 本发明提供丙型肝炎病毒（HCV）的包膜蛋白E2的构象表位的鉴定和表征。 本发明提供识别E2的构象表位的一组人单克隆抗体。 抗体来自感染HCV的患者。 本发明提供了使用HCV抗体作为治疗，诊断和/或预防剂的方法。 本发明提供具有构象表位的模拟表位和使用模拟表位的方法。 本发明提供了基于其对HCV的反应来分层患者的方法。 本发明提供了用于预防和治疗包含一种或多种HCV抗体的HCV的药物组合物。

公开(公告)号：US08858947B2

公开(公告)日：2014-10-14

申请号：US13122598

申请日：2008-10-05

申请人： Steven Foung ,  Zhen-yong Keck

发明人： Steven Foung ,  Zhen-yong Keck

IPC分类号： C07K16/00 ,  C07K16/08 ,  C07K16/10 ,  A61K39/42

CPC分类号： C07K16/109 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76

摘要： The present invention provides identification and characterization of conformational epitopes of the envelope protein E2 of the Hepatitis C virus (HCV). The present invention provides a panel of human monoclonal antibodies that recognize conformational epitopes of E2. The antibodies are derived from patients infected with HCV. The present invention provides methods for utilizing HCV antibodies as therapeutic, diagnostic, and/or prophylactic agents. The present invention provides mimotopes with conformational epitopes intact and methods of using mimotopes. The present invention provides methods of stratifying patients based on their response to HCV. The present invention provides pharmaceutical compositions for prevention and treatment of HCV comprising one or more HCV antibodies.

摘要翻译： 本发明提供丙型肝炎病毒（HCV）的包膜蛋白E2的构象表位的鉴定和表征。 本发明提供识别E2的构象表位的一组人单克隆抗体。 抗体来自感染HCV的患者。 本发明提供了使用HCV抗体作为治疗，诊断和/或预防剂的方法。 本发明提供具有构象表位的模拟表位，以及使用模拟表位的方法。 本发明提供了基于其对HCV的反应来分层患者的方法。 本发明提供了用于预防和治疗包含一种或多种HCV抗体的HCV的药物组合物。

公开(公告)号：US20090041679A1

公开(公告)日：2009-02-12

申请号：US12140151

申请日：2008-06-16

申请人： Steven Foung ,  Zhen-Yong Keck ,  Richard Webby

发明人： Steven Foung ,  Zhen-Yong Keck ,  Richard Webby

IPC分类号： A61K9/12 ,  C07K16/18 ,  C12N15/11 ,  G01N33/53 ,  A61P31/00 ,  C12N5/06 ,  A61K39/395

CPC分类号： C07K16/1018 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/76

摘要： A panel of IgG1 human monoclonal antibodies (HMAbs) identified by hemagglutination inhibition (HI) assay has been produced from peripheral B cells of an individual immunized with prototype H5N1 vaccine. Sequence analysis of antibody clones showed three clusters of different HMAbs as represented by HMAbs designated as BF1-1, BF1-19 and BF1-10. BF1-1 and BF1-10 have distinct CDR 1, 2 and 3 regions of both heavy and light chains. BF1-19 has the same heavy chain as BF1-1 but the light chain of BF1-10. Antibody binding affinity, KD, studies showed all three HMAbs ranging from at least about 10−8 to at least about 10−9. In vivo protection studies showed that these antibodies afforded significant protection against infection. These findings demonstrate that the antibodies of the invention are cross-neutralizing and therapeutic.

摘要翻译： 已经通过用原型H5N1疫苗免疫的个体的外周B细胞产生了通过血细胞凝集抑制（HI）测定鉴定的一组IgG1人单克隆抗体（HMAb）。 抗体克隆的序列分析显示由称为BF1-1，BF1-19和BF1-10的HMAb表示的三组不同HMAb。 BF1-1和BF1-10具有明显的重链和轻链CDR 1，2和3区。 BF1-19具有与BF1-1相同的重链，但BF1-10的轻链。 抗体结合亲和力KD研究显示所有三种HMAb在至少约10-8至至少约10-9之间。 体内保护研究表明，这些抗体提供了显着的抗感染保护。 这些发现证明本发明的抗体是交叉中和和治疗的。