公开(公告)号：EP1633381A2

公开(公告)日：2006-03-15

申请号：EP04751045.8

申请日：2004-04-30

申请人： Merck & Co., Inc.

发明人： HAZUDA, Daria, Jean ,  DODSON, Elizabeth, Chen ,  LAI, Ming-Tain ,  XU, Min ,  SHI, Xiao-Ping ,  SIMON, Adam, J. ,  WU, Guoxin ,  LI, Yueming ,  REGISTER, Robert, Bruce

IPC分类号： A61K38/00 ,  A61K38/07 ,  A61K38/08

CPC分类号： C07K7/06 ,  A01K2217/05 ,  A01K2267/0306 ,  A61K38/00 ,  C07K5/1016 ,  C07K5/1019 ,  C07K5/1021 ,  C07K14/4711 ,  C07K16/18 ,  C12P21/06 ,  C12Q1/37 ,  G01N33/5088 ,  G01N33/6896 ,  G01N2500/00 ,  G01N2800/52

摘要： Provided are methods of identifying inhibitors of β-secretase that employ modified β-secretase substrates. The modified β-secretase substrates have β-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered β-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1'-P2' of the β-secretase cleavage site. Many of the modified β-secretase substrates are more efficient substrates for β-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by β-secretase. Recombinant polynucleotide molecules encoding the modified β-secretase substrates are provided. Antibodies that recognize cleavage products of the modified β-secretase substrates are provided. Stable cell lines expressing the modified β-secretase substrates are provided. Transgenic animals expressing the modified β-secretase substrates are provided.

公开(公告)号：EP1292359A2

公开(公告)日：2003-03-19

申请号：EP01939219.0

申请日：2001-05-22

申请人： MERCK & CO., INC.

发明人： SIMON, Adam, J.

IPC分类号： A61N1/00 ,  A61N1/04 ,  A61N1/18 ,  A61N1/30 ,  A61N1/32 ,  C12M1/42 ,  C12N13/00

CPC分类号： A61N1/325 ,  A61K49/0002 ,  A61N1/306

摘要： A system and method for assessing the performance of a system for delivering a pharmaceutical agent to a portion of a body. A pair of electrodes are applied to the portion of the body. A pharmaceutical agent is infused into the portion of the body and the electrodes are energized by a signal generator, electrically stimulating the portion of the body. The voltage and current delivered to the portion of the body are measured using a data acquisition system thereby generating electrical parameter data. An immune response, gene expression level or other biological response to the pharmaceutical agent is measured and the electrical test data is correlated with the biological response to assess the performance of the system.

公开(公告)号：EP1631661A2

公开(公告)日：2006-03-08

申请号：EP04753635.4

申请日：2004-05-28

申请人： Merck & Co., Inc.

发明人： CHEN, Richard, Z. ,  SIMON, Adam, J. ,  VOGT, Thomas, F.

IPC分类号： C12N5/00 ,  C12N15/00 ,  A01K67/00 ,  G01N33/00

CPC分类号： C07K14/4711 ,  A01K67/0275 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/0312 ,  C07K16/18 ,  C12N15/8509 ,  C12N2800/30

摘要： The present invention provides transgenic animals having an amyloid precursor protein wherein the amino acids flanking the β secretase cleavage site are NF and EV. The invention also provides tissues and cell lines derived from such animals. The invention further provides methods of screening candidate compounds to determine whether the compounds can alter the rate of cleavage of amyloid precursor protein by β secretase.

公开(公告)号：EP1578356A2

公开(公告)日：2005-09-28

申请号：EP03743199.6

申请日：2003-02-23

申请人： Merck & Co., Inc.

发明人： ESPESETH, Amy, S. ,  FERRER, Marc ,  FLORES, Osvaldo, A. ,  HAZUDA, Daria, J. ,  INGLESE, James ,  MILLER, Michael, D. ,  REGISTER, Bruce ,  SHI, Xiao-Ping ,  SIMON, Adam, J. ,  ZUCK, Paul, D.

IPC分类号： A61K6/00

CPC分类号： C07K14/47 ,  C07K14/4702 ,  C07K14/4711 ,  C07K2319/00 ,  C07K2319/50 ,  G01N2500/10

摘要： The present invention provides DNA constructs, genetically engineered host cells, and methods for identifying inhibitors of amyloid precursor protein (APP) processing. The methods provide for the convenient identification, in a single assay, of inhibitors of β-secretase and Ϝ-secretase as well as other forms of APP processing. The methods rely on fusion proteins of APP and transcription factors in which APP processing releases the transcription factors, allowing the transcription factors to activate transcription of a reporter gene. Inhibitors are identified as substances that block or diminish transcription factor release from the fusion protein, thereby causing a diminution of reporter gene readout.

公开(公告)号：EP1368058A2

公开(公告)日：2003-12-10

申请号：EP02748361.9

申请日：2002-02-26

申请人： Merck & Co., Inc.

发明人： HAZUDA, Daria, J. ,  LINEBERGER, Janet, E. ,  MILLER, Michael, D. ,  SIMON, Adam, J.

IPC分类号： A61K39/00

CPC分类号： C12N15/86 ,  C07K14/005 ,  C07K2319/00 ,  C07K2319/40 ,  C07K2319/61 ,  C12N9/86 ,  C12N15/62 ,  C12N2740/16043 ,  C12N2740/16122 ,  C12N2740/16322 ,  C12Y305/02006

摘要： The present invention features a chimeric protein containing a β-lactamase region and either a Vpr region or a Vpx region. The chimeric protein can be packaged into a viral reporter particle, introduced into a cell recognized by the viral particle and provide intracellular β-lactamase activity.