公开(公告)号：EP2707388B1

公开(公告)日：2019-06-12

申请号：EP12782672.5

申请日：2012-03-23

申请人： Duke University ,  The Government of The United States of America, as represented by The Secretary, Department of Health and Human Services

发明人： MASCOLA, John, R. ,  NABEL, Gary ,  HAYNES, Barton, F. ,  WU, Xueling ,  KEPLER, Thomas, B. ,  KWONG, Peter

IPC分类号： C07K16/10 ,  C12N15/13 ,  A61K39/42 ,  A61P31/18

公开(公告)号：EP2480572B1

公开(公告)日：2019-01-30

申请号：EP10760878.8

申请日：2010-09-24

申请人： The United States of America, as represented by The Secretary, Department of Health and Human Services ,  University of Washington through its Center for Commercialization

发明人： MASCOLA, John, R. ,  WYATT, Richard ,  WU, Xueling ,  LI, Yuxing ,  HOGERKORP, Carl-Magnus ,  ROEDERER, Mario ,  YANG, Zhi-yong ,  NABEL, Gary ,  KWONG, Peter ,  ZHOU, Tongqing ,  CONNORS, Mark ,  OFEK, Gilad ,  SHAPIRO, Lawrence ,  ZHU, Jiang ,  SCHIEF, William R.

IPC分类号： C07K16/10

公开(公告)号：EP2828294A1

公开(公告)日：2015-01-28

申请号：EP13763664.3

申请日：2013-03-15

申请人： The United States of America, as represented by The Secretary, Department of Health and Human Services

发明人： MASCOLA, John, R. ,  LYNCH, Rebecca, M. ,  WU, Xueling ,  CONNORS, Mark ,  ZHOU, Tongqing ,  CASAZZA, Joseph ,  KWONG, Peter, D.

IPC分类号： C07K16/10 ,  A61K39/42 ,  A61P31/18

CPC分类号： C07K16/1063 ,  A61K39/42 ,  A61K45/06 ,  A61K49/0004 ,  A61K2039/505 ,  A61K2039/545 ,  C07K2317/31 ,  C07K2317/76 ,  G01N33/56983

摘要： Neutralizing antibodies that specifically bind to HIV-1 gpl20 and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV infection is disclosed.

公开(公告)号：EP2707388A2

公开(公告)日：2014-03-19

申请号：EP12782672.5

申请日：2012-03-23

申请人： Duke University ,  The Government of The United States of America, as represented by The Secretary, Department of Health and Human Services

发明人： MASCOLA, John, R. ,  NABEL, Gary ,  HAYNES, Barton, F. ,  WU, Xueling ,  KEPLER, Thomas, B. ,  KWONG, Peter

IPC分类号： C07K16/10 ,  C12N15/13 ,  A61K39/42 ,  A61P31/18

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.