公开(公告)号：EP1836631A2

公开(公告)日：2007-09-26

申请号：EP05824951.7

申请日：2005-11-22

申请人： Odyssey Thera, Inc.

发明人： MACDONALD, Marnie, L. ,  WESTWICK, John, K. ,  KEON, Brigitte ,  LAMERDIN, Jane ,  MICHNICK, Stephen, W.

IPC分类号： G06F19/00

CPC分类号： G01N33/5008 ,  B82Y10/00 ,  B82Y30/00 ,  C12Q1/025 ,  G01N33/5014 ,  G01N33/5041

摘要： This invention provides principles, methods and compositions for ascertaining the mechanism of action of pharmacologically important compounds in the context of network biology, across the entire scope of the complex pathways of living cells. Importantly, the principles, methods and compositions provided allow a rapid assessment of the on-pathway and off-pathway effects of lead compounds and drug candidates in living cells, and comparisons of lead compounds with well-characterized drugs and toxicants to identify patterns associated with efficacy and toxicity. The invention will be useful in improving the drug discovery process, in particular by identifying drug leads with desired safety and efficacy and in effecting early attrition of compounds with potential adverse effects in man.

公开(公告)号：EP1737972B1

公开(公告)日：2012-02-01

申请号：EP05735396.3

申请日：2005-04-11

申请人： Odyssey Thera, Inc.

发明人： WESTWICK, John, K. ,  KEON, Brigitte ,  MacDONALD, Marnie ,  MICHNICK, Stephen, William, Watson

IPC分类号： G06F19/00 ,  C12Q1/00 ,  G01N33/50

CPC分类号： C40B30/04 ,  G01N33/5008 ,  G01N33/5014 ,  G01N33/502 ,  G01N33/5041 ,  G01N33/68 ,  G01N33/6845 ,  G06F19/12 ,  Y02A90/26

摘要： The present invention provides methods for performing pharmacological profiling of a chemical compound, in particular to improve drug safety and efficacy at an early stage in the drug development process. The chemical compound may be a test compound, drug lead, known drug or toxicant. The compound is profiled against a panel of assays. Preferred embodiments of the invention include high-content assays for protein-protein interactions. The compositions and methods of the invention can be used to identify pathways underlying drug efficacy, safety, and toxicity; and to effect attrition of novel compounds with undesirable or toxic properties. The compositions and methods of the invention can also be used to identify new uses of therapeutic agents, to screen libraries of chemical compounds, to perform lead optimization, and to perform studies of structure-activity relationships in the context of intact cells. The compositions and methods of the invention can be applied to any test compound, drug, drug target, pathway, and therapeutic indication.

公开(公告)号：EP1668161B1

公开(公告)日：2014-01-22

申请号：EP04785127.4

申请日：2004-09-24

申请人： Odyssey Thera Inc.

发明人： WESTWICK, John, K. ,  KEON, Brigitte ,  MACDONALD, Marnie, L.

IPC分类号： C12Q1/68 ,  G01N33/50 ,  G01N33/53 ,  G01N33/566 ,  G01N33/58 ,  G01N21/68 ,  C12P21/02

CPC分类号： G01N33/74 ,  C12Q1/00 ,  G01N33/5041 ,  G01N2333/726 ,  G01N2500/00

公开(公告)号：EP1590476B1

公开(公告)日：2012-09-26

申请号：EP04708966.9

申请日：2004-02-06

申请人： Odyssey Thera Inc.

发明人： MICHNICK, Stephen, William, Watson ,  REMY, Ingrid ,  MACDONALD, Marnie ,  LAMERDIN, Jane ,  YU, Helen ,  WESTWICK, John, K.

IPC分类号： G01N33/50

CPC分类号： G01N33/5011 ,  G01N33/5008 ,  G01N33/5041 ,  G01N33/542 ,  G01N33/6845 ,  G01N2500/02 ,  Y02A90/26

摘要： The present invention provides protein fragment complementation assays for drug discovery, in particular to identify compounds that activate or inhibit cellular pathways. Based on the selection of an interacting protein pair combined with an appropriate PCA reporter, the assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds. The interacting pair may be selected by cDNA library screening; by gene-by-gene interaction mapping; or by prior knowledge of a pathway. Fluorescent and luminescent assays can be constructed using the methods provided herein. The selection of suitable PCA reporters for high-throughput or high-content (high-context) assay formats is described for a diversity of reporters, with particular detail provided for examples of monomeric enzymes and fluorescent proteins. Methods are described for constructing such assays for one or more steps in a biochemical pathway; testing the effects of compounds from combinatorial, natural product, peptide, antibody, nucleic acid or other diverse libraries on the protein or pathway(s) of interest; and using the results of the screening to identify specific compounds that activate or inhibit the protein or pathway(s) of interest. Single-color and multi-color assays are disclosed. Further disclosed are universal expression vectors with cassettes that allow the rapid construction of assays for a large and diverse number of gene/reporter combinations. The development of such assays is shown to be straightforward, providing for a broad, flexible and biologically relevant platform for drug discovery.

公开(公告)号：EP1812078A2

公开(公告)日：2007-08-01

申请号：EP05851268.2

申请日：2005-10-29

申请人： Odyssey Thera, Inc.

发明人： WESTWICK, John, K. ,  LAMERDIN, Jane ,  OWENS, Stephen ,  MACDONALD, Marnie, L.

IPC分类号： A61K48/00 ,  A61K38/54 ,  A61K39/395

CPC分类号： C12Q1/485 ,  G01N33/502 ,  G01N33/6893 ,  G01N2500/00

摘要： The present invention discloses a method of treating an individual or animal with diabetes and/or obesity. The method comprises administering to the individual or animal a therapeutically effective amount of a protein tyrosine kinase inhibitor. Preferably, the preventative and therapeutic methods of the present invention involve administering - to a mammal in need thereof - a therapeutically effective amount of an inhibitor of a c-Src-family protein tyrosine kinase. The invention pertains to pharmaceutical compositions containing an inhibitor of a c-Src-family protein tyrosine kinase or an analog or metabolite thereof, or an inhibitor of another protein tyrosine kinase, and a pharmaceutically acceptable carrier. Purines and pyrimidines and other molecules useful in the treatment of diabetes and obesity are provided herein, in particular, pyrazolopyrimidines, cyanoquinolines, phenylaminopyrimidines, anilinoquinazolines and related compounds. The invention also provides cellular targets and assay compositions useful for the identification of additional novel therapeutic agents for the treatment of these disorders.

公开(公告)号：EP1784642A2

公开(公告)日：2007-05-16

申请号：EP05788134.4

申请日：2005-08-18

申请人： Odyssey Thera, Inc.

发明人： WESTWICK, John, K. ,  YU, Helen ,  MACDONALD, Marnie, L.

IPC分类号： G01N33/53

CPC分类号： C12Q1/025 ,  G01N33/5023 ,  G01N33/5035 ,  G01N33/5041 ,  G01N33/5097 ,  G01N2440/00 ,  G01N2440/10 ,  G01N2440/12 ,  G01N2440/36 ,  G01N2440/38 ,  G01N2500/10

摘要： The instant invention provides a method for establishing safety profiles for chemical compounds, as well as pharmacological profiling said method comprising (A) testing the effects of said chemical compounds on the amount and/or post-translational modifications of two or more macromolecules in intact cells; (B) constructing a pharmacological profile based on the results of said tests; and (C) comparing said profile to the profile(s) of drugs with established safety characteristics. Additionally, the invention is also directed to a composition comprising an assay panel, said panel comprising at least one high-content assay for the amount and/or post-­translational modification of a protein and at least one high-content assay for the amount and/or subcellular location of a protein-protein interaction.

公开(公告)号：EP1668161A2

公开(公告)日：2006-06-14

申请号：EP04785127.4

申请日：2004-09-24

申请人： Odyssey Thera Inc.

发明人： WESTWICK, John, K. ,  KEON, Brigitte ,  MACDONALD, Marnie, L.

IPC分类号： C12Q1/68 ,  G01N33/53 ,  C12P21/02

CPC分类号： G01N33/74 ,  C12Q1/00 ,  G01N33/5041 ,  G01N2333/726 ,  G01N2500/00

摘要： This invention relates generally to the fields of biology, molecular biology, chemistry and biochemistry. The invention is directed to a large number of novel assays for G-protein-coupled receptors (GPCRs) and their signaling pathways. Methods are described for constructing such assays for one or more steps in a GPCR pathway. The invention can be used for functional characterization of GPCRs, target validation, de-orphanization of receptors, high-throughput screening, high-content screening, pharmacological profiling, and other drug discovery applications. The assays can be used directly to assess whether a compound library or a biological extract contains an agonist or antagonist of a receptor. Assay compositions are also provided. The development of such assays is shown to be straightforward, providing for a broad, flexible and biologically relevant platform for the discovery of novel drugs and natural ligands that act on GPCRs or their cognate pathways.

公开(公告)号：EP1797427A2

公开(公告)日：2007-06-20

申请号：EP05813818.1

申请日：2005-09-22

申请人： Odyssey Thera, Inc.

发明人： WESTWICK, John, K. ,  MACDONALD, Marnie, L. ,  YU, Helen ,  OWENS, Stephen ,  MICHNICK, Stephen, W.

IPC分类号： G01N33/53

CPC分类号： G01N33/5011 ,  A61K31/00 ,  C12N5/00 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5035 ,  G01N33/5041 ,  G01N33/6845 ,  G01N2500/00

摘要： The screening system utilizes dynamic measurements of pathway activity to detect the activities of drugs within cellular pathways. The methods of the invention can be used to identify previously unknown drug activities and therapeutic uses, even for drugs that have been well characterized with standard biochemical assays. We demonstrated the utility of the invention by screening a portion of the known pharmacopeia. We identified dozens of drugs, previously or currently marked for a variety of indications, with surprising and previously-unsuspected activity against “hallmark” cancer pathways. We also showed that over 20 of these drugs indeed have anti-proliferative activity in human tumor cells, underscoring the utility and predictability of the screening system. The methodology will extend the utility of the current pharmacopeia and provide the basis for de novo discovery of drugs with a broad range of therapeutic indications.

公开(公告)号：EP1737972A2

公开(公告)日：2007-01-03

申请号：EP05735396.3

申请日：2005-04-11

申请人： Odyssey Thera, Inc.

发明人： WESTWICK, John, K. ,  KEON, Brigitte ,  MacDONALD, Marnie ,  MICHNICK, Stephen, William, Watson

IPC分类号： C12Q1/00

CPC分类号： C40B30/04 ,  G01N33/5008 ,  G01N33/5014 ,  G01N33/502 ,  G01N33/5041 ,  G01N33/68 ,  G01N33/6845 ,  G06F19/12 ,  Y02A90/26

摘要： The present invention provides methods for performing pharmacological profiling of a chemical compound, in particular to improve drug safety and efficacy at an early stage in the drug development process. The chemical compound may be a test compound, drug lead, known drug or toxicant. The compound is profiled against a panel of assays. Preferred embodiments of the invention include high-content assays for protein-protein interactions. The compositions and methods of the invention can be used to identify pathways underlying drug efficacy, safety, and toxicity; and to effect attrition of novel compounds with undesirable or toxic properties. The compositions and methods of the invention can also be used to identify new uses of therapeutic agents, to screen libraries of chemical compounds, to perform lead optimization, and to perform studies of structure-activity relationships in the context of intact cells. The compositions and methods of the invention can be applied to any test compound, drug, drug target, pathway, and therapeutic indication.

公开(公告)号：EP1590476A2

公开(公告)日：2005-11-02

申请号：EP04708966.9

申请日：2004-02-06

申请人： Odyssey Thera Inc.

发明人： MICHNICK, Stephen, William, Watson ,  REMY, Ingrid ,  MACDONALD, Marnie ,  LAMERDIN, Jane ,  YU, Helen ,  WESTWICK, John, K.

IPC分类号： C12Q1/00 ,  C12Q1/68 ,  C07K14/00 ,  C12N15/11

CPC分类号： G01N33/5011 ,  G01N33/5008 ,  G01N33/5041 ,  G01N33/542 ,  G01N33/6845 ,  G01N2500/02 ,  Y02A90/26

摘要： The present invention provides protein fragment complementation assays for drug discovery, in particular to identify compounds that activate or inhibit cellular pathways. Based on the selection of an interacting protein pair combined with an appropriate PCA reporter, the assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds. The interacting pair may be selected by cDNA library screening; by gene-by-gene interaction mapping; or by prior knowledge of a pathway. Fluorescent and luminescent assays can be constructed using the methods provided herein. The selection of suitable PCA reporters for high-throughput or high-content (high-context) assay formats is described for a diversity of reporters, with particular detail provided for examples of monomeric enzymes and fluorescent proteins. Methods are described for constructing such assays for one or more steps in a biochemical pathway; testing the effects of compounds from combinatorial, natural product, peptide, antibody, nucleic acid or other diverse libraries on the protein or pathway(s) of interest; and using the results of the screening to identify specific compounds that activate or inhibit the protein or pathway(s) of interest. Single-color and multi-color assays are disclosed. Further disclosed are universal expression vectors with cassettes that allow the rapid construction of assays for a large and diverse number of gene/reporter combinations. The development of such assays is shown to be straightforward, providing for a broad, flexible and biologically relevant platform for drug discovery.