公开(公告)号：EP1497438B1

公开(公告)日：2009-10-28

申请号：EP03753568.9

申请日：2003-04-24

申请人： Crucell Holland B.V.

发明人： VOGELS, Ronald ,  BOUT, Abraham

IPC分类号： C12N15/86

CPC分类号： C12N15/86 ,  A61K48/00 ,  A61K2039/525 ,  A61K2039/5256 ,  C12N2710/10343 ,  C12N2810/6018 ,  C12N2830/002

公开(公告)号：EP1325145B1

公开(公告)日：2009-04-15

申请号：EP01981160.3

申请日：2001-09-25

申请人： Crucell Holland B.V.

发明人： HAVENGA, Menzo, Jans, Emco ,  BOUT, Abraham

IPC分类号： C12N15/86 ,  C07K14/075 ,  A61K38/00 ,  A61K48/00 ,  C12N15/00 ,  C12N15/62

CPC分类号： C12N15/86 ,  A61K48/00 ,  C07K14/005 ,  C07K2319/02 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/6018

摘要： The invention provides means and methods for transduction of a skeletal muscle cell and/or a muscle cell specific precursor thereof. Provided is the use of a gene delivery vehicle derived from an adenovirus, having a tropism for said cells, for the preparation of a medicament. In a preferred aspect of the invention, said gene delivery vehicle comprises at least a tropism determining part of an adenoviral fiber protein of subgroup B and/or F. More preferably, said gene delivery vehicle comprises at least part of a fiber protein of an adenovirus of stereotype (11, 16, 35, 40 and/or 51) or a functional part, derivative and/or analogue thereof.

公开(公告)号：EP0787201B1

公开(公告)日：2004-04-28

申请号：EP96926662.6

申请日：1996-08-16

申请人： Crucell Holland B.V. ,  OctoPlus B.V. ,  Universiteit Utrecht

发明人： HENNINK, Wilhelmus, Everhardus ,  BOUT, Abraham

IPC分类号： C12N15/87 ,  A61K47/48 ,  A61K48/00

CPC分类号： C12N15/87 ,  A61K47/605 ,  A61K48/00

摘要： The present invention relates to a synthetic transfection system comprising as a carrier a cationic, water soluble or water dispersible polyphosphazene. In addition, it relates to a method for introducing DNA fragments in target cells, comprising contacting these DNA fragments with a polyphosphazene which is at least partially substituted with cationic substituents and subsequently contacting the obtained transfection system wits target cells. Finally, the invention involves the use of a polyphosphazene which is at least partially substituted with cationic substituents as transfection vehicle.

公开(公告)号：EP1196544A2

公开(公告)日：2002-04-17

申请号：EP00965872.5

申请日：2000-07-19

申请人： Crucell Holland B.V.

发明人： HOEBEN, Robert, C. ,  BOUT, Abraham ,  VALERIO, Domenico ,  VAN DER EB, Alex, J. ,  SCHOUTEN, Govert ,  FALLAUX, Frits, J.

IPC分类号： C12N5/10 ,  C12N15/861 ,  A61K48/00

CPC分类号： C12N7/00 ,  A61K48/00 ,  C07K14/005 ,  C12N15/86 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10352 ,  C12N2830/42

摘要： The problem of replication competent adenovirus in virus production is solved in that we have developed packaging cells that have no overlapping sequences with a new basic vector and thus are suited for safe large scale production of recombinant adenoviruses one of the additional problems associated with the use of recombinant adenovirus vectors is the host-defense reaction against treatment with adenovirus. Another aspect of the invention involves screening recombinant adenovirus vector lots, especially those intended for clinical use, for the presence of adenovirus E1 sequences, as this will reveal replication competent adenovirus, as well as revertant E1 adenoviruses. It is also an aspect of the present invention to molecularly characterize the revertants that are generated in the newer helper/vector combinations.

公开(公告)号：EP1440157B1

公开(公告)日：2012-01-25

申请号：EP02770322.2

申请日：2002-10-29

申请人： Crucell Holland B.V.

发明人： OPSTELTEN, Dirk, Jan, Elbertus ,  KAPTEYN, Johan, Christiaan ,  PASSIER, Petrus, Christianus, Johannes, Josephus ,  BRUS, Ronald, Hendrik, Peter ,  BOUT, Abraham

IPC分类号： C12N15/65 ,  C12N15/86 ,  G01N33/68 ,  G01N33/74 ,  C07K14/505

CPC分类号： C07K14/005 ,  A61K38/00 ,  C07K14/505 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12P21/005

摘要： The present invention provides methods for identifying, selecting and obtaining mammalian cells that are capable of producing proteinaceous molecules comprising predetermined post-translational modifications, wherein said post-translational modifications are brought about by the mammalian cell in which the proteinaceous molecule is expressed. Preferably, said predetermined post-translational modifications comprise glycosylation. The invention further provides methods for obtaining and producing proteinaceous molecules, using mammalian cells obtainable by a method of the present invention. Preferably said proteinaceous molecules comprise erythropoietin (EPO), since the effect of (recombinant) EPO depends heavily on the glycosylation pattern of the oligosaccharides present on the protein. Mammalian cells that have been obtained on the basis of their ability to produce proteins and/or post-translational modifications that are indicative for a predetermined post-translational modification that is desired are also provided. Preferably, said mammalian cells have neural characteristics and properties such that significant amounts of recombinant proteins can be produced that harbor 'neural- or brain-type' properties.

公开(公告)号：EP1161548B1

公开(公告)日：2005-02-16

申请号：EP00921175.6

申请日：2000-04-17

申请人： Crucell Holland B.V.

发明人： HATEBOER, Guus ,  VERHULST, Karina, Cornelia ,  SCHOUTEN, Govert, Johan ,  UYTDEHAAG, Alphonsus, Gerardus, Cornelis, Maria ,  BOUT, Abraham

IPC分类号： C12N15/85 ,  C07K14/505 ,  C12N15/86

CPC分类号： C07K14/505 ,  C12N7/00 ,  C12N15/85 ,  C12N2510/02 ,  C12N2510/04 ,  C12N2710/10343 ,  C12N2800/108 ,  C12N2830/00 ,  C12N2830/15 ,  C12N2830/60 ,  C12N2840/20

摘要： The present invention provides methods and compositions for the production of recombinant proteins in a human cell line, using sequences encoding at least one E1 protein of an adenovirus where the cells does not encode a structural adenoviral protein from its genome. The methods and compositions are particularly useful for generating stable expression of human recombinant proteins of interest that are modified post-translationally, e.g. by glycosylation. Such proteins may have advantageous properties in comparison with their counterparts produced in non-human systems like Chinese Hamster Ovary (CHO) cells.

公开(公告)号：EP1406666A2

公开(公告)日：2004-04-14

申请号：EP02746193.8

申请日：2002-07-05

申请人： Crucell Holland B.V.

发明人： HAVENGA, Menzo, Jans, Emco ,  BOUT, Abraham ,  VOGELS, Ronald

IPC分类号： A61K48/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  C12N2710/10343

摘要： The present invention provides novel methods and means for delivering a heterologous nucleic acid of interest to mesenchymal stem cells by providing recombinant adenoviral vectors provided with, or having a natural tropism for mesenchymal stem cells, typically in combination with a reduced tropism for other kinds of cells, in particular liver cells. The invention also provides mesenchymal stem cells provided with a heterologous nucleic acid through the use of a recombinant adenoviral vector according to the invention, and the use of such mesenchymal stem cells for the preparation of medicaments for the treatment of multiple sclerosis, rheumatoid arthritis, angiogenesis and bone related disorders, for instance in treatments that involve bone (re)generation.

公开(公告)号：EP1124976A1

公开(公告)日：2001-08-22

申请号：EP99971042.9

申请日：1999-10-27

申请人： Crucell Holland B.V.

发明人： SCHOUTEN, Govert, Johan ,  BOUT, Abraham ,  PAU, Maria, Grazia

IPC分类号： C12N15/86 ,  C12N5/10

CPC分类号： C12N15/86 ,  C12N2750/14143

摘要： The invention relates to the field of genetically engineered viral vectors, more specifically to adeno-associated virus (AAV) vectors, for use in gene therapy. The present invention provides a process for the production of high titer recombinant adeno-associated virus vectors that are essentially free of helper virus such as adenovirus. The invention provides an adeno-associated virus (AAV) packaging cell having been provided with nucleic acid encoding a gene product providing AAV helper function allowing generating recombinant AAV without concomitant helper virus production.

公开(公告)号：EP1159438B1

公开(公告)日：2008-07-30

申请号：EP00908116.7

申请日：2000-03-03

申请人： Crucell Holland B.V.

发明人： VOGELS, Ronald ,  SCHOUTEN, Govert, Johan ,  BOUT, Abraham

IPC分类号： C12N15/861 ,  C12N15/62 ,  C07K14/075 ,  A61K48/00

CPC分类号： C12N7/00 ,  C07K14/005 ,  C12N9/1211 ,  C12N15/86 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10352

摘要： The invention provides a nucleic acid delivery vehicle with or having been provided with at least a tissue tropism for fibroblast-like or macrophage-like cells, preferably synoviocytes. In one aspect said nucleic acid delivery vehicle is a virus capsid or a functional part, derivative and/or analogue thereof. Preferably said virus capsid is an adenovirus capsid. Preferably said adenovirus is a subgroup B adenovirus, preferably adenovirus 16. Preferably said tissue tropism is provided by at least a tissue tropism determining part of an adenovirus fiber protein or a functional derivative and/or analogue thereof. The invention further presents methods for the treatment of diseases, preferably joint related diseases.

公开(公告)号：EP1307573B1

公开(公告)日：2006-01-04

申请号：EP01974977.9

申请日：2001-08-09

申请人： Crucell Holland B.V.

发明人： HAVENGA, Menzo, Jans, Emco ,  VOGELS, Ronald ,  BOUT, Abraham

IPC分类号： C12N15/861 ,  A61K48/00 ,  C12N5/10 ,  A61P19/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/6018

摘要： The present invention relates to a gene delivery vehicle comprising a recombinant adenovirus having a tropism for a primary human chondrocyte. By efficiently transducing a nucleic acid of interest into a primary chondrocyte, said gene delivery vehicle is able to at least in part improve the counteraction of cartilage disease. In one embodiment said recombinant adenovirus comprises a deletion in the gene encoding for fiber protein, which is replaced by a nucleic acid sequence encoding at least part of a fiber protein of a B-type adenovirus.