公开(公告)号：EP0786005B1

公开(公告)日：2004-12-22

申请号：EP95937598.1

申请日：1995-10-11

申请人： THE UNIVERSITY OF BRITISH COLUMBIA

发明人： HAYDEN, Michael, R. ,  MA, Yuanhong ,  LEWIS, Suzanne ,  LIU, Guoquing

IPC分类号： C12N15/55 ,  C12N9/20 ,  C12N15/86 ,  C12Q1/68 ,  A61K48/00

CPC分类号： C12Q1/6883 ,  A61K38/00 ,  A61K48/00 ,  C12N9/20 ,  C12N2799/022 ,  C12N2799/027 ,  C12Q1/683 ,  C12Q2600/156 ,  C12Y301/01003 ,  Y10S435/81

摘要： A single point mutation in the human lipoprotein lipase gene which results in an A → G nucleotide change at codon 291 (nucleotide 1127) of the lipoprotein lipase gene, and a substitution of serine for the normal asparagine in the lipoprotein lipase gene product is seen with increased frequency in patients with coronary artery disease, and is associated with an increased susceptibility to coronary artery disease, including in particular premature atherosclerosis. This is expressed as a diminished catalytic activity of lipoprotein lipase, lower HDL-cholesterol levels and higher triglyceride levels. Thus, susceptibility of a human individual to premature atherosclerosis can be evaluated by: (a) obtaining a sample of DNA from the individual; and (b) evaluating the sample of DNA for the presence of nucleotides encoding a serin residue as amino acid 291 of the lipoprotein lipase gene product. Patients found to be suffering from or likely to suffer from premature atherosclerosis and other forms of coronary artery disease as a result of a lipoprotein lipase deficiency can be treated using gene therapy.

公开(公告)号：EP0786005A1

公开(公告)日：1997-07-30

申请号：EP95937598.0

申请日：1995-10-11

申请人： THE UNIVERSITY OF BRITISH COLUMBIA

发明人： HAYDEN, Michael, R. ,  MA, Yuanhong ,  LEWIS, Suzanne ,  LIU, Guoquing

IPC分类号： A61K38 ,  C12N9 ,  C12N15 ,  C12Q1 ,  A61K48

CPC分类号： C12Q1/6883 ,  A61K38/00 ,  A61K48/00 ,  C12N9/20 ,  C12N2799/022 ,  C12N2799/027 ,  C12Q1/683 ,  C12Q2600/156 ,  C12Y301/01003 ,  Y10S435/81

摘要： A single point mutation in the human lipoprotein lipase gene which results in an A → G nucleotide change at codon 291 (nucleotide 1127) of the lipoprotein lipase gene, and a substitution of serine for the normal asparagine in the lipoprotein lipase gene product is seen with increased frequency in patients with coronary artery disease, and is associated with an increased susceptibility to coronary artery disease, including in particular premature atherosclerosis. This is expressed as a diminished catalytic activity of lipoprotein lipase, lower HDL-cholesterol levels and higher triglyceride levels. Thus, susceptibility of a human individual to premature atherosclerosis can be evaluated by: (a) obtaining a sample of DNA from the individual; and (b) evaluating the sample of DNA for the presence of nucleotides encoding a serin residue as amino acid 291 of the lipoprotein lipase gene product. Patients found to be suffering from or likely to suffer from premature atherosclerosis and other forms of coronary artery disease as a result of a lipoprotein lipase deficiency can be treated using gene therapy.

公开(公告)号：EP0786005B9

公开(公告)日：2005-11-30

申请号：EP95937598.1

申请日：1995-10-11

申请人： THE UNIVERSITY OF BRITISH COLUMBIA

发明人： HAYDEN, Michael, R. ,  MA, Yuanhong ,  LEWIS, Suzanne ,  LIU, Guoquing

IPC分类号： C12N15/55 ,  C12N9/20 ,  C12N15/86 ,  C12Q1/68 ,  A61K48/00

CPC分类号： C12Q1/6883 ,  A61K38/00 ,  A61K48/00 ,  C12N9/20 ,  C12N2799/022 ,  C12N2799/027 ,  C12Q1/683 ,  C12Q2600/156 ,  C12Y301/01003 ,  Y10S435/81

摘要： A single point mutation in the human lipoprotein lipase gene which results in an A → G nucleotide change at codon 291 (nucleotide 1127) of the lipoprotein lipase gene, and a substitution of serine for the normal asparagine in the lipoprotein lipase gene product is seen with increased frequency in patients with coronary artery disease, and is associated with an increased susceptibility to coronary artery disease, including in particular premature atherosclerosis. This is expressed as a diminished catalytic activity of lipoprotein lipase, lower HDL-cholesterol levels and higher triglyceride levels. Thus, susceptibility of a human individual to premature atherosclerosis can be evaluated by: (a) obtaining a sample of DNA from the individual; and (b) evaluating the sample of DNA for the presence of nucleotides encoding a serin residue as amino acid 291 of the lipoprotein lipase gene product. Patients found to be suffering from or likely to suffer from premature atherosclerosis and other forms of coronary artery disease as a result of a lipoprotein lipase deficiency can be treated using gene therapy.

公开(公告)号：EP1200117A2

公开(公告)日：2002-05-02

申请号：EP00943499.4

申请日：2000-06-23

申请人： THE UNIVERSITY OF BRITISH COLUMBIA ,  Amsterdam Molecular Therapeutics B.V. (AMT) ,  Academic Hospital at the University of Amsterdam

发明人： HAYDEN, Michael, R. ,  KASTELEIN, John, J., P.

IPC分类号： A61K38/46 ,  A61K48/00 ,  C12N15/63 ,  A61P9/10

CPC分类号： C12N9/20 ,  A61K38/00 ,  A61K48/00 ,  C12Y301/01034

摘要： The invention provides for the use of a therapeutic derived from a truncated lipoprotein lipase protein (LPL S447X), including nucleic acids encoding such proteins, for the treatment of conditions including LPL responsive conditions, such as cardiovascular disease, hypertension, LPL deficiency, high triglyceride levels, low HDL-cholesterol levels or atherosclerosis.

公开(公告)号：EP1082336A2

公开(公告)日：2001-03-14

申请号：EP99925933.6

申请日：1999-05-27

申请人： UNIVERSITY OF BRITISH COLUMBIA ,  Merck Frosst Canada & Co.

发明人： KALCHMAN, Michael ,  HAYDEN, Michael, R. ,  HACKAM, Abigail ,  CHOPRA, Vikramjit ,  NICHOLSON, Donald, W. ,  VALLAINCOURT, John, P. ,  RASPER, Dita, M. ,  GOLDBERG, Paul

IPC分类号： C07H21/04 ,  C12Q1/68 ,  C07K5/00

CPC分类号： C07K16/18 ,  A61K38/00 ,  C07K14/47 ,  C07K14/4747

摘要： A family of proteins, including a specific human protein designated as HIP1, has been identified that interact differently with the gene product of a normal (16 CAG repeat) and an expanded (⊃44 CAG repeat) HD gene. Expression of the HIP1 protein was found to be enriched in the brain. Analysis of the sequence of the HIP1 protein indicated that it includes a death effector domain (DED), suggesting an apoptotic function. Thus, it appears that a normal function of Huntingtin may be to bind HIP1 and related apoptosis modulators, reducing its effectiveness in stimulating cell death. Since expanded huntingtin performs this function less well, there is an increase in HIP1-modulated cell death in individuals with an expanded repeat in the HD gene. This understanding of the likely role of huntingtin and HIP1 or related proteins (collectively 'HIP-apoptosis modulating proteins') in the pathology of Huntington's disease offers several possibilities for therapy. First, because the function of huntingtin apparently depends at least in part on the ability to interact with HIP-apoptosis modulating proteins, added expression (e.g., via gene therapy) of normal (non-expanded) huntingtin or of the HIP-binding region of huntingtin should provide a therapeutic benefit. Other DED-interacting peptides could also be used to mask and reduce the interaction of HIP-apoptosis modulating proteins with the death signaling complex. Alternatively, a mutant form of HIP-protein from which the DED has been deleted might be introduced, for example using gene therapy techniques. Because HIP-apoptosis modulating proteins have been shown to self-associate, a protein with a deleted DED may compete with endogenous HIP-protein in the formation of these associations, thereby reducing the amount of apoptotically-active HIP-protein.

公开(公告)号：EP1551856A2

公开(公告)日：2005-07-13

申请号：EP03762177.8

申请日：2003-06-27

申请人： Xenon Genetics, Inc. ,  Warner-Lambert Company LLC

发明人： BROWNLIE, Alison, J. ,  TAFURI,Sherrie, Rae ,  BRINKMAN, Ryan, R. ,  CHAGNOVICH, Daniel ,  CHATTERJEE, Aurobindo ,  DONALDSON, Gary, C. ,  DUBE, Marie-Pierre ,  GOLDBERG, Yigal, P. ,  JERVA, Leonard, F. ,  LAFRENIER, Ronald, G. ,  LUDWIG, Erwin ,  SAMUELS, Mark, E. ,  WU, Chenyan ,  HAYDEN, Michael, R.

IPC分类号： C07H21/04 ,  C12Q1/00 ,  C12Q1/68 ,  C12P21/06 ,  C12N15/63

CPC分类号： C07K14/47

摘要： The invention features compositions and methods for modulating HDL levels and/or treating a vascular disease, dyslipidemia or a related disorder in a patient in need thereof. The invention also includes methods for identifying therapeutic agents for such treating disorders based on the identification of novel therapeutic targets herein. The invention also includes diagnostic and pharmacogenomic compositions and methods which employ the therapeutic targets named herein.