公开(公告)号：US20120237523A1

公开(公告)日：2012-09-20

申请号：US13429286

申请日：2012-03-23

申请人： John R. Mascola ,  Richard T. Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary J. Nabel ,  Peter D. Kwong ,  Tongqing Zhou ,  Mark Connors ,  Gilad Ofek ,  Lawrence Shapiro ,  Jiang Zhu ,  William R. Schief

发明人： John R. Mascola ,  Richard T. Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary J. Nabel ,  Peter D. Kwong ,  Tongqing Zhou ,  Mark Connors ,  Gilad Ofek ,  Lawrence Shapiro ,  Jiang Zhu ,  William R. Schief

IPC分类号： A61K39/42 ,  C12N15/13 ,  A61P31/18 ,  G01N33/566 ,  G01N33/569 ,  C12N1/21 ,  C12N5/10 ,  C12N1/19 ,  C07K16/10 ,  C12N15/63

CPC分类号： C07K16/1063 ,  A61K39/42 ,  A61K45/06 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C12N2740/10011 ,  C12N2740/16011 ,  C12N2740/16111

摘要： Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

公开(公告)号：US20120244166A1

公开(公告)日：2012-09-27

申请号：US13429279

申请日：2012-03-23

申请人： John R. Mascola ,  Richard T. Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary J. Nabel ,  Peter D. Kwong ,  Tongqing Zhou ,  Mark Connors ,  Gilad Ofek ,  Lawrence Shapiro ,  Jiang Zhu ,  William R. Schief

发明人： John R. Mascola ,  Richard T. Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary J. Nabel ,  Peter D. Kwong ,  Tongqing Zhou ,  Mark Connors ,  Gilad Ofek ,  Lawrence Shapiro ,  Jiang Zhu ,  William R. Schief

IPC分类号： A61K39/395 ,  C12N15/63 ,  C12N1/21 ,  C12N1/19 ,  A61P31/18 ,  C12N15/74 ,  G01N21/64 ,  C07K16/10 ,  C12N15/13 ,  C12N9/96 ,  C12N5/10

CPC分类号： C07K16/1063 ,  A61K39/42 ,  A61K45/06 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C12N2740/10011 ,  C12N2740/16011 ,  C12N2740/16111

摘要： Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and uses of these antibodies, are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

摘要翻译： 公开了特异性结合HIV-1 gp120的CD4结合位点的单克隆中和抗体。 还公开了特异性结合HIV-1 gp41的单克隆中和抗体。 还公开了这些抗体的鉴定以及这些抗体的用途。 还提供了用于增强使用表位支架探针的任何抗体的结合和中和活性的方法。

公开(公告)号：US08637036B2

公开(公告)日：2014-01-28

申请号：US13429286

申请日：2012-03-23

申请人： John R. Mascola ,  Richard T. Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary J. Nabel ,  Peter D. Kwong ,  Tongqing Zhou ,  Mark Connors ,  William R. Schief

发明人： John R. Mascola ,  Richard T. Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary J. Nabel ,  Peter D. Kwong ,  Tongqing Zhou ,  Mark Connors ,  William R. Schief

IPC分类号： A61K39/42 ,  A61K39/21 ,  C12Q1/70

CPC分类号： C07K16/1063 ,  A61K39/42 ,  A61K45/06 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C12N2740/10011 ,  C12N2740/16011 ,  C12N2740/16111

摘要： Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

摘要翻译： 公开了特异性结合HIV-1 gp120的CD4结合位点的单克隆中和抗体。 还公开了特异性结合HIV-1 gp41的单克隆中和抗体。 还公开了这些抗体的鉴定，以及这些抗体的用途。 还提供了用于增强使用表位支架探针的任何抗体的结合和中和活性的方法。

公开(公告)号：US09175070B2

公开(公告)日：2015-11-03

申请号：US13498125

申请日：2010-09-24

申请人： John R. Mascola ,  Richard T. Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary J. Nabel ,  Peter D. Kwong ,  Tongqing Zhou ,  Mark Connors ,  William R. Schief

发明人： John R. Mascola ,  Richard T. Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary J. Nabel ,  Peter D. Kwong ,  Tongqing Zhou ,  Mark Connors ,  William R. Schief

IPC分类号： C07K16/10 ,  A61K31/517 ,  A61K45/06

CPC分类号： C07K16/1063 ,  A61K39/42 ,  A61K45/06 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C12N2740/10011 ,  C12N2740/16011 ,  C12N2740/16111

摘要： Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

摘要翻译： 公开了特异性结合HIV-1 gp120的CD4结合位点的单克隆中和抗体。 还公开了特异性结合HIV-1 gp41的单克隆中和抗体。 还公开了这些抗体的鉴定，以及这些抗体的用途。 还提供了用于增强使用表位支架探针的任何抗体的结合和中和活性的方法。

公开(公告)号：US20120282264A1

公开(公告)日：2012-11-08

申请号：US13498125

申请日：2010-09-24

申请人： John R. Mascola ,  Richard Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary Nabel ,  Peter Kwong ,  Tongqing Zhou ,  Mark Connors ,  Gilad Ofek ,  Lawrence Shapiro ,  Jiang Zhu ,  William R. Schief

发明人： John R. Mascola ,  Richard Wyatt ,  Xueling Wu ,  Yuxing Li ,  Carl-Magnus Hogerkorp ,  Mario Roederer ,  Zhi-yong Yang ,  Gary Nabel ,  Peter Kwong ,  Tongqing Zhou ,  Mark Connors ,  Gilad Ofek ,  Lawrence Shapiro ,  Jiang Zhu ,  William R. Schief

IPC分类号： C07K16/10 ,  A61K39/42 ,  C12N15/13 ,  C12N1/21 ,  C12N15/74 ,  G01N33/569 ,  A61P31/18 ,  G01N33/577 ,  C12N9/96 ,  C12N15/63

CPC分类号： C07K16/1063 ,  A61K39/42 ,  A61K45/06 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C12N2740/10011 ,  C12N2740/16011 ,  C12N2740/16111

摘要： Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

摘要翻译： 公开了特异性结合HIV-1 gp120的CD4结合位点的单克隆中和抗体。 还公开了特异性结合HIV-1 gp41的单克隆中和抗体。 还公开了这些抗体的鉴定，以及这些抗体的用途。 还提供了用于增强使用表位支架探针的任何抗体的结合和中和活性的方法。

公开(公告)号：US20130251726A1

公开(公告)日：2013-09-26

申请号：US13792098

申请日：2013-03-10

申请人： John Mascola ,  Dennis R. Burton ,  Wayne Koff ,  Peter Kwong ,  Gary Nabel ,  Sanjay K. Phogat ,  Pascal Raymond Georges Poignard ,  Melissa Danielle De Jean St. Marcel Simek-Lemos ,  Xueling Wu ,  Tongqing Zhou ,  Zhi-Yong Yang

发明人： John Mascola ,  Dennis R. Burton ,  Wayne Koff ,  Peter Kwong ,  Gary Nabel ,  Sanjay K. Phogat ,  Pascal Raymond Georges Poignard ,  Melissa Danielle De Jean St. Marcel Simek-Lemos ,  Xueling Wu ,  Tongqing Zhou ,  Zhi-Yong Yang

IPC分类号： C07K16/10 ,  A61K45/06 ,  A61K39/42

CPC分类号： C07K16/1063 ,  A61K39/42 ,  A61K45/06 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/76 ,  C07K2317/92 ,  G01N33/56988

摘要： The present application relates novel HIV-1 broadly neutralizing antibodies. The antibodies of the present invention are further characterized by their ability to bind epitopes from the Env proteins. The invention also provides light and heavy chain variable region sequences. Compositions for prophylaxis, diagnosis and treatment of HIV infection are provided.

摘要翻译： 本申请涉及新型HIV-1广泛中和抗体。 本发明的抗体的特征还在于它们能够结合来自Env蛋白的表位。 本发明还提供轻链和重链可变区序列。 提供了预防，诊断和治疗艾滋病毒感染的组合。

公开(公告)号：US10273291B2

公开(公告)日：2019-04-30

申请号：US14116710

申请日：2012-03-23

申请人： John R. Mascola ,  Gary Nabel ,  Barton F. Haynes ,  Xueling Wu ,  Thomas B. Kepler ,  Peter Kwong

发明人： John R. Mascola ,  Gary Nabel ,  Barton F. Haynes ,  Xueling Wu ,  Thomas B. Kepler ,  Peter Kwong

IPC分类号： C07K16/10 ,  A61K39/42 ,  G01N33/569

摘要： Antibody VRC01 represents a human immunoglobulin that neutralizes—˜90% of diverse HIV-1 isolates. To understand how such broadly neutralizing HIV-1 antibodies develop and recognize the viral envelope, we used X-ray crystallography and 454 pyrosequencing to characterize additional antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding of different antibodies to the same CD4-binding-site epitope. Antibody recognition was achieved through the evolution of complementary contact domains that were generated in diverse ways. Phylogenetic analysis of expressed heavy and light chains determined by deep sequencing revealed a common pathway of antibody heavy chain maturation confined to IGHV1-2*02 lineage that could pair with different light chains. The maturation pathway inferred by antibodyomics reveals that diverse antibodies evolve to a highly affinity-matured state to recognize an invariant viral structure, providing insight into the development and evolution of broadly neutralizing HIV-1 immunity.

公开(公告)号：US20140205607A1

公开(公告)日：2014-07-24

申请号：US14116710

申请日：2012-03-23

申请人： John R. Mascola ,  Gary Nabel ,  Barton F. Haynes ,  Xueling Wu ,  Thomas B. Kepler ,  Peter Kwong

发明人： John R. Mascola ,  Gary Nabel ,  Barton F. Haynes ,  Xueling Wu ,  Thomas B. Kepler ,  Peter Kwong

IPC分类号： C07K16/10 ,  G01N33/569

CPC分类号： C07K16/1063 ,  A61K39/42 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76 ,  G01N33/56988

摘要： Antibody VRC01 represents a human immunoglobulin that neutralizes—˜90% of diverse HIV-1 isolates. To understand how such broadly neutralizing HIV-1 antibodies develop and recognize the viral envelope, we used X-ray crystallography and 454 pyrosequencing to characterize additional antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding of different antibodies to the same CD4-binding-site epitope. Antibody recognition was achieved through the evolution of complementary contact domains that were generated in diverse ways. Phylogenetic analysis of expressed heavy and light chains determined by deep sequencing revealed a common pathway of antibody heavy chain maturation confined to IGHV1-2*02 lineage that could pair with different light chains. The maturation pathway inferred by antibodyomics reveals that diverse antibodies evolve to a highly affinity-matured state to recognize an invariant viral structure, providing insight into the development and evolution of broadly neutralizing HIV-1 immunity.

摘要翻译： 抗体VRC01代表一种人类免疫球蛋白，可中和〜90％的不同HIV-1分离株。 为了了解这种广泛中和的HIV-1抗体如何发展和识别病毒包膜，我们使用X射线晶体学和454焦磷酸测序来鉴定HIV-1感染个体的其他抗体。 晶体结构揭示了不同抗体与相同CD4结合位点表位结合的收敛模式。 通过以不同方式产生的互补接触域的发展，实现了抗体识别。 通过深度测序确定的表达重链和轻链的系统发育分析揭示了限制在可与不同轻链配对的IGHV1-2 * 02谱系的抗体重链成熟的共同途径。 通过抗体学推断的成熟途径揭示了多种抗体进化到高度亲和力成熟的状态，以识别不变的病毒结构，提供对广泛中和HIV-1免疫的发展和进化的洞察。