公开(公告)号：EP1546315A1

公开(公告)日：2005-06-29

申请号：EP03750632.6

申请日：2003-09-25

申请人： Novartis AG ,  Novartis Pharma GmbH

发明人： GEISER, Martin ,  GEISSE, Sabine ,  OSTERMEIER, Christian ,  RAMAGE, Paul ,  RAULF, Friedrich ,  ZENKE, Gerhard

IPC分类号： C12N9/12 ,  G01N23/20 ,  G01N33/573

CPC分类号： C12N9/12 ,  A61K38/00 ,  C07K2299/00 ,  C12N9/1205

摘要： The present invention relates to the three dimensional structure of ZAP-70 protein tyrosine kinase and describes methods of making a crystal of ZAP-70 and purification of the catalytic domain of ZAP-70 for use in crystallisation. The invention also relates to the use of the three dimensional structure of the catalytic domain of ZAP-70 for identifying and designing ligands which inhibit the biological function of ZAP-70.

公开(公告)号：EP1836296A1

公开(公告)日：2007-09-26

申请号：EP06703258.1

申请日：2006-01-02

申请人： Novartis AG ,  NOVARTIS-PHARMA GMBH

发明人： JAHNKE, Wolfgang ,  RONDEAU, Jean-michel ,  GEISER, Martin ,  RAMAGE, Paul ,  STRAUSS, Andre

IPC分类号： C12N9/10 ,  C30B29/58 ,  C12Q1/48 ,  A61K38/00

CPC分类号： C12N9/1085 ,  C07K2299/00

摘要： The present invention relates to crystalline human farnesyl diphosphate synthase (FPPS), to the three-dimensional structure of free FPPS, as well as the three-dimensional structures of FPPS in complex with substrates such as IPP (isopentenyl diphosphate) and/or with inhibitors, such as Zometa® or Aredia®. Further, methods for preparing crystals of human FPPS are described. According to the invention the crystals can be used to determine the structures of FPPS homologs, mutants, complexes with ligands, FPPS crystal forms and similar molecules of unknown structure. The invention further relates to the use of FPPS crystals to select new FPPS ligands, e.g., by X-ray screening and to design and/or identify inhibitors against FPPS. Furthermore, the invention relates to NMR methods for selecting and/or identifying new low molecular weight binders to FPPS, which represent new therapeutic agents.

公开(公告)号：EP0672057B1

公开(公告)日：2000-09-20

申请号：EP93915814.3

申请日：1993-07-06

申请人： Novartis AG

发明人： BAUER, Wilfried ,  BRECKENRIDGE, Robin ,  CARDINAUX, François ,  GOMBERT, Frank ,  GRAM, Hermann ,  RAMAGE, Paul ,  SCHNEIDER, Helmut ,  WAELCHLI, Rudolf ,  ALBERT, Rainer ,  LEWIS, Ian

IPC分类号： C07K14/635 ,  C12N15/62 ,  C12P21/02 ,  C12N1/20 ,  A61K38/29

CPC分类号： C07K14/005 ,  A61K38/00 ,  C07K14/635 ,  C07K2319/00 ,  C07K2319/50 ,  C07K2319/75 ,  C12N2795/10222

摘要： PTH compounds having PTH-like activity and comprising at least one modification, said modification being either 1) at least one radical selected from an L- or D-α-amino acid, C2-6alcoxycarbonyl and optionally substituted C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aralkyl, aralkenyl or C3-6cycloalkyl-C1-4alkyl and attached to the terminal amino group of the PTH compound, and/or at least one radical selected from C2-6alcoxycarbonyl and optionally substituted C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aralkyl, aralkenyl or C3-6cycloalkyl-C1-4alkyl and attached to one or more side chain amino groups of the PTH compound; or 2) at least one α-amino acid unit in the positions 1 to 38 of a naturally occurring PTH sequence being replaced by a natural or unnatural amino acid unit optionally in protected form, whereby the α-amino acid units present in positions 1 and 2 at the amino terminus of the PTH sequence may be replaced by a pseudo-peptide, or a combination of such modifications, in free form or in salt form, have pharmacological activity, e.g. for preventing or treating all bone conditions which are associated with increased calcium depletion or resorption or in which calcium fixation in the bone is desirable.

公开(公告)号：EP0670907B1

公开(公告)日：1997-05-07

申请号：EP94901914.5

申请日：1993-11-29

申请人： SANDOZ-ERFINDUNGEN Verwaltungsgesellschaft m.b.H. ,  SANDOZ-PATENT-GMBH ,  Novartis AG

发明人： HEITZMANN, Markus ,  MOVVA, Rao ,  RAMAGE, Paul

IPC分类号： C12P21/06 ,  C07K14/52 ,  C07K14/54

CPC分类号： C12N15/10 ,  C07K14/54 ,  C07K14/5412 ,  C12P21/06

摘要： A process for the recombinant preparation in a bacterial host of the mature form of a mammalian protein or peptide of formula X-Pro-Z, which is subject to processing by endogenous bacterial aminopeptidases is provided. In the formula X-Pro-Z, X is a single N-terminal amino acid other than proline, and Z is the remaining sequence of amino acid residues of the protein or peptide. The process comprises inserting into a cell of the bacterial host an appropriate vector containing DNA coding for Met-Y-X-Pro-Z, in which Y is a natural amino acid that is specifically cleavable in vitro from X-Pro-Z by an aminopeptidase and that imparts resistance to in vivo processing by endogenous bacterial aminopeptidases. The cell is then induced to express the expression product Met-Y-X-Pro-Z which is then treated with an appropriate aminopeptidase to cleave off Met and Y.