公开(公告)号：EP0873132A1

公开(公告)日：1998-10-28

申请号：EP96940479.0

申请日：1996-11-15

申请人： THE UNIVERSITY OF BRITISH COLUMBIA

发明人： KALCHMAN, Michael ,  HAYDEN, Michael, R.

IPC分类号： C07K14 ,  C07K16 ,  A61K38

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

摘要： A protein, designated as HIP1, interacts differently with the gene product of a normal (16 CAG repeat) and an expanded (⊃ 44 CAG repeat) HD gene. The HIP1 protein originally isolated from the yeast two-hybrid screen is encoded by a 1.2 kb cDNA, devoid of stop codons, that is expressed as a 400 amino acid polypeptide. By further screening of a human frontal cortex cDNA library, and employing the protocol for 5' Rapid Amplification of cDNA ends (RACE), a total of 4795 nucleotides (with an open reading frame of 914 amino acids) of the 10 kb message HIP1 have been isolated to date. Expression of the HIP1 protein was found to be limited to the brain, where the interaction of the HIP1 with the HD protein appears to be necessary for the association of the HD protein with the membrane or specific cytoskeletal components to render it functional. Because HIP1 interacts with expanded HD protein less well than with normal length HD, introduction of additional HIP1 or overexpression of HIP-1 can lead to increased functionality of the defective or normal HD protein. Alternatively, modified forms of the HIP1 which bind more effectively to expanded HD could be introduced to convert the expanded HD protein into a functional molecule.

公开(公告)号：EP1200117B1

公开(公告)日：2008-08-13

申请号：EP00943499.4

申请日：2000-06-23

申请人： THE UNIVERSITY OF BRITISH COLUMBIA ,  Amsterdam Molecular Therapeutics B.V.

发明人： HAYDEN, Michael, R. ,  KASTELEIN, John, J., P. ,  EXCOFFON, Katherine Julia Diane Ashbourne

IPC分类号： A61K38/46 ,  A61K48/00 ,  C12N15/63 ,  A61P9/10 ,  C12N9/20

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

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：EP1397385A2

公开(公告)日：2004-03-17

申请号：EP02732283.3

申请日：2002-06-07

申请人： Xenon Genetics, Inc. ,  THE UNIVERSITY OF BRITISH COLUMBIA

发明人： WELLINGTON, Cheryl, L. ,  BROOKS-WILSON, Angela, R. ,  HAYDEN, Michael, R.

IPC分类号： C07K14/705

CPC分类号： G01N33/689 ,  G01N33/6893 ,  G01N33/6896 ,  G01N2500/00

摘要： The invention features methods for treating, preventing or modulating a neurological disease or disorder, or for modulating an anaesthetic or a fertility process by administering compounds that modulate ABCA1 expression or activity. The invention also features methods for identifying compounds useful for such methods.

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.