Odyssey Thera Inc.

San Ramon, CA, United States

Odyssey Thera Inc.

San Ramon, CA, United States
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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.


Patent
Odyssey Thera Inc. | Date: 2011-07-06

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.


Patent
Odyssey Thera Inc. | Date: 2011-09-07

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.


Patent
Odyssey Thera Inc. | Date: 2011-03-23

The present invention describes an assay method comprising: (A) generating (1) at least a first fragment of a reporter molecule linked to a first interacting domain and at least a second fragment of a reporter molecule linked to a second interacting domain, or (2) nucleic acid molecules that code for (A)(1) and subsequently allowing said nucleic acid molecules to produce their coded products; then, (B) allowing interaction of said domains; and (C) detecting reconstituted reporter molecule activity; where said reporter molecule can react with a penicillin- or a cephalosporin-class substrate.


Patent
Odyssey Thera Inc. | Date: 2011-08-29

The cell-based assays described in the present invention can be used to directly assess the sensitivity and specificity of the gene annotation reagent against its target, mapping genes and to determine if a non-targeted gene participates in a pathway of interest or is functionally linked to another gene or protein. Preferred assay embodiments include fluorescence or luminescence assays in intact (live or fixed) cells. Such fluorescence or luminescence assays include high-throughput or high-content assays for protein activity, subcellular localization, post-translational modifications, or interactions of proteins. Suitable assays may include protein-protein interaction assays; protein translocation assays; and post-translational modification assays. The invention can be used to assess the efficacy of any gene silencing experiment, and to map novel genes into biochemical pathways, and to identify novel pharmaceutical targets. The results also demonstrate the feasibility of employing this strategy in genome-wide functional annotation efforts.


The present invention is directed to Protein-fragment Complementation Assays (PCAs) and assay compositions based on fluorescent proteins. The invention provides methods for fragmenting fluorescent proteins and generating mutant fragments with desir4 spectral characteristics for PCA. The invention encompasses assays and compositions based on fluorescent proteins from the species Aequorea, Anemonia and Anthozoa. In particular, the invention is directed to fragments of mutant fluorescent proteins having improved spectral properties over the wild-type proteins. The invention encompasses fragments of mutant versions of A. Victoria green fluorescent protein (GFP), in particular yellow fluorescent proteins (EYFP and super-EYFP), Venus, cyan, citrine, blue, cyan-green, and photoactivatable variants of GFP.; The invention also encompasses red fluorescent PCAs based on Discosoma red fluorescent protein (RFP PCA)and a kindling fluorescent protein PCA (KFP 1 PCA) derived from Anemonia sulcata. Any useful mutation of a fluorescent protein can be engineered into a fragment, generating a wide range of assays useful for drug discovery, target validation, high-throughput screening, high-content screening, pathway mapping, drug mechanism-of-action studies, blosensors, and diagnostics.


Patent
Odyssey Thera Inc. | Date: 2010-09-10

The present invention provides functional annotation of novel genes by detection of interactions of their encoded proteins with known proteins followed by assays to validate that the gene participates in a specific cellular function. The instant invention also provides an experimental strategy that allows for detection of protein interactions and functional assays with a single reporter system. Interactions among network component proteins are detected and probed with stimulators and inhibitors of the network and subcellular location of the interacting proteins is determined. Additionally, applicants use this strategy to map a signal transduction network that controls the G_(0 )to G_(1 )transition in eukaryotes. Analysis of 148 combinations of 65 protein pairs in mammalian cells allows applicants to propose a model of network architecture. The results demonstrate the feasibility of employing this strategy in genome-wide functional annotation efforts.


Patent
Odyssey Thera Inc. | Date: 2012-06-20

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.


Patent
Odyssey Thera Inc. | Date: 2012-05-09

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.


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