Patents by Inventor Stephen Michnick
Stephen Michnick has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20070254373Abstract: 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 desired 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 (KFP1 PCA) derived from Anemonia sulcata.Type: ApplicationFiled: January 23, 2007Publication date: November 1, 2007Applicant: Odyssey Pharmaceuticals, Inc.Inventors: Stephen Michnick, Marnie MacDonald, Jane Lamerdin
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Publication number: 20070212677Abstract: 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.Type: ApplicationFiled: August 31, 2006Publication date: September 13, 2007Applicant: Odyssey Thera, Inc.Inventors: Marnie MacDonald, Jane Lamerdin, Stephen Owens, Brigitte Keon, Graham Bilter, Zhidi Shang, Zhengping Huang, Helen Yu, Jennifer Dias, Tomoe Minami, Stephen Michnick, John Westwick
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Publication number: 20070148682Abstract: We describe a strategy for designing and implementing protein-fragment complementation assays (PCAs) to detect biomolecular interactions in vivo and in vitro. The design, implementation and broad applications of this strategy are illustrated with a large number of enzymes with particular detail provided for the example of murine dihydrofolate reductase (DHFR). Fusion peptides consisting of N- and C-terminal fragments of murine DHFR fused to GCN4 leucine zipper sequences were coexpressed in Escherichia coli grown in minimal medium, where the endogenous DHFR activity was inhibited with trimethoprim. Coexpression of the complementary fusion products restored colony formation. Survival only occurred when both DHFR fragments were present and contained leucine-zipper forming sequences, demonstrating that reconstitution of enzyme activity requires assistance of leucine zipper formation. DHFR fragment-interface point mutants of increasing severity (Ile to Val, Ala and Gly) resulted in a sequential increase in E.Type: ApplicationFiled: January 8, 2007Publication date: June 28, 2007Applicant: Odyssey Pharmaceuticals, Inc.Inventors: Stephen Michnick, Joelle Pelletier, Ingrid Remy
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Publication number: 20060160109Abstract: 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.Type: ApplicationFiled: November 21, 2005Publication date: July 20, 2006Applicant: Odyssey Thera, Inc.Inventors: Marnie MacDonald, John Westwick, Brigitte Keon, Jane Lamerdin, Stephen Michnick
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Publication number: 20060147948Abstract: New methods are provided for the post-genomic era that will permit the analysis of the dynamic expression and localization of gene products in living cells. Herein we propose the development of such a method from a bioorganic approach involving organic synthesis and protein engineering. Specifically, novel compounds bearing two maleimide groups attached directly to fluorescent cores will be prepared, whose latent fluorescence is quenched until their maleimide groups undergo a specific thiol addition reaction. Complementary a-helical proteins are designed bearing two cysteine residues appropriately positioned to react with our novel fluorogens. Genetically fusing our helical probe peptides to test proteins of interest, we can selectively label the target sequence in living cells with our small synthetic fluorogenic molecules. The scope of this technique is described in the context of studying protein localization and protein-protein interactions in living cells.Type: ApplicationFiled: June 16, 2005Publication date: July 6, 2006Inventors: Jeffrey Keillor, Stephen Michnick, Stephane Girouard
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Publication number: 20060094059Abstract: 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.Type: ApplicationFiled: September 21, 2005Publication date: May 4, 2006Applicant: Odyssey Thera, Inc.Inventors: John Westwick, Marnie MacDonald, Helen Yu, Stephen Owens, Stephen Michnick
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Publication number: 20050255452Abstract: The present invention describes a method of expressing PCA interacting partners in plant material comprising: (A) transforming said material with: (1) a first construct coding for a first fusion product comprising (a) a first fragment of a first molecule whose fragments can exhibit a detectable activity when associated and (b) a first protein-protein interacting domain; and (2) a second construct coding for a second fusion product comprising (a) a second fragment of said first molecule and (b) a second protein-protein interacting domain that can bind (1)(b); (B) culturing said material under conditions allowing expression of said PCA interacting partners; and (C) detecting said activity.Type: ApplicationFiled: March 28, 2005Publication date: November 17, 2005Applicant: Odyssey Thera, Inc.Inventors: Normand Brisson, Stephen Michnick
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Publication number: 20050208577Abstract: The present invention describes a rapid and efficient in vivo library-versus-library screening strategy for identifying optimally interacting pairs of heterodimerizing polypeptides. It allows for the screening of a protein library against a second protein library, rather than against a single bait protein, and thus has numerous applications in the study of protein-protein interactions. Additionally, it allows for the application of different selection stringencies. Two leucine zipper libraries, semi-randomized at the positions adjacent to the hydrophobic core, were genetically fused to either one of two designed fragments of the enzyme murine dihydrofolate reductase (mDHFR), and cotransformed into E. coli. Interaction between the library polypeptides was required for reconstitution of the enzymatic activity of mDHFR, allowing bacterial growth.Type: ApplicationFiled: May 23, 2005Publication date: September 22, 2005Applicant: Adyssey Thera, Inc.Inventors: Stephen Michnick, Joelle Pelletier, Katja Arndt, Andreas Pluckthun
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Publication number: 20050079547Abstract: The instant invention describes a method for detecting protein-protein interactions in living organisms and/or cells, said method comprising: (a) synthesizing probe protein fragments from a protein which enables fluorescent or luminescent detection by dissecting the gene coding for the fluorescent or luminescent protein into a least two fragments; (2) constructing fusion proteins consisting of the probe protein fragments linked to protein domains that are to be tested for interactions; (3) coexpressing the fusion proteins; and (d) detecting reconstitution of the fluorescence or luminescence signal.Type: ApplicationFiled: July 2, 2004Publication date: April 14, 2005Inventors: Stephen Michnick, Marnie MacDonald, John Westwick
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Patent number: 5659012Abstract: Novel assays for identifying agents which alter the effect of erythropoietin on proliferation of erythroid cells and agents identified thereby. Novel peptide comprising the erythropoietin receptor binding site for SH-PTP1.Type: GrantFiled: March 10, 1995Date of Patent: August 19, 1997Assignee: Whitehead Institute for Biomedical ResearchInventors: Ursula Klingmuller, Stephen Michnick, Benjamin G. Neel, Ulrike Lorenz, Harvey F. Lodish