Patents by Inventor Scott W. Lowe
Scott W. Lowe 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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Patent number: 7993925Abstract: The invention relates to recombinant vectors for inducible and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene. In certain embodiments, the invention relates to the use of Tet (tetracycline)-responsive RNA Polymerase II (Pol II) promoters (e.g., TetON or TetOFF) to direct inducible knockdown in certain cells of an integrated or an endogenous gene, such as p53. The invention also relates to a method for producing transgenic animals (e.g., mice) expressing inducible (such as tetracycline-regulated), reversible, and/or tissue-specific double-stranded RNA molecules that interfere with the expression of a target gene.Type: GrantFiled: June 5, 2008Date of Patent: August 9, 2011Assignee: Cold Spring Harbor LaboratoryInventors: Ross Dickins, Scott W. Lowe, Gregory J. Hannon
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Publication number: 20110105583Abstract: In one aspect, the invention generally relates to use of miR-34 as a biomarker to estimate TP53 function in a cell. In another aspect, the invention generally relates to multiple uses of miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.Type: ApplicationFiled: May 5, 2008Publication date: May 5, 2011Applicants: MERCK & CO., INC., COLD SPRING HARBOR LABORATORYInventors: Michele A. Cleary, Aimee L. Jackson, Peter S. Linsley, Julja Burchard, Lee P. Lim, Jill F. Magnus, Lin He, Xingyue He, Scott W. Lowe, Gregory J. Hannon
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Publication number: 20110035814Abstract: This invention provides methods of diagnosis, drug screening, and treatment based on the discovery that cIAP1 and Yap are co-amplified oncogenes that cooperate to contribute to oncogenesis and tumor maintenance.Type: ApplicationFiled: May 23, 2007Publication date: February 10, 2011Applicant: COLD SPRING HARBOR LABORATORYInventors: Lars Zender, Scott W. Lowe, Mona S. Spector, Wen Xue
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Publication number: 20110015093Abstract: Provided is a single construct combining a sequence encoding an RNAi molecule, a sequence encoding a reporter, and a target sequence specific for the RNAi molecule. The construct can be used to determine the potency of the encoded RNAi molecule in a direct and unbiased way. These results can be used to inform the design of potent RNAi molecules of various types and can be extended to several other applications, including: (1) generation of tiled libraries comprising every possible RNAi molecule-encoding sequence for a given gene target; (2) large-scale parallel validation of RNAi molecules targeting many genes to generate validated RNAi molecule-encoding libraries; (3) experimental comparison of design algorithms and strategies; and (4) investigation of RNAi biology in target site mutagenesis assays by screening pools containing single nucleotide changes in target sites and/or in the RNAi molecule to identify the most relevant sequence characteristics of potent RNAi-target site predictions.Type: ApplicationFiled: October 24, 2008Publication date: January 20, 2011Applicant: Cold Spring Harbor LaboratoryInventors: Christof Fellmann, Scott W. Lowe, Gregory J. Hannon, Johannes Ekkehart Zuber
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Publication number: 20100310504Abstract: Fibrosis arises as part of a wound healing response that maintains organ integrity following catastrophic tissue damage, but can also contribute to a variety of human pathologies, including liver cirrhosis. The invention demonstrates that cellular senescence acts to limit the fibrogenic response to tissue damage, thereby establishing a role for the senescence program in pathophysiological settings beyond cancer. Accordingly, the methods of the invention relate to modulating cellular senescence in disease tissue that have elevated numbers of senescent cells, such as in fibrotic tissues.Type: ApplicationFiled: September 25, 2008Publication date: December 9, 2010Inventors: Scott W. Lowe, Valery Krizhanovsky, Lars Zender
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Publication number: 20100297010Abstract: The present invention is directed to methods of identifying tumor suppressor genes in vivo, tumor suppressors thus found, methods of treatment taking advantage of the identified tumor suppressors, methods of and kits for diagnosis of cancer using the identified tumor suppressor, and pharmaceutical composition comprising an identified tumor suppressor or modulators thereof.Type: ApplicationFiled: May 16, 2008Publication date: November 25, 2010Inventors: Anka Bric, Lars Zender, Cornelius Miething, Uli Bialucha, Scott W. Lowe
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Publication number: 20100273660Abstract: In some aspects, the invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both and by transplanting the resulting hepatocytes into a recipient non-human animal. The present invention also provides methods for identifying and validating tumor suppressor genes by screening pools of shRNAs that target genomic regions deleted in human cancers, such as human hepatocellular carcinomas.Type: ApplicationFiled: November 12, 2009Publication date: October 28, 2010Applicant: Cold Spring Harbor LaboratoryInventors: Lars Zender, Wen Xue, Scott Powers, Scott W. Lowe
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Patent number: 7794941Abstract: The invention provides methods for diagnosing cancers in humans by detecting DNA amplifications in chromosomal region 8p22, which encompasses the FGF-20 gene and the EFHA2 gene. Also provided are cancer treatment methods using inhibitors of FGF-20 and EFHA2. The invention also provides methods for promoting successful regeneration of liver function. These methods can be used therapeutically to improve liver function following transplantation in both recipient and donor subjects.Type: GrantFiled: August 13, 2007Date of Patent: September 14, 2010Assignee: Cold Spring Harbor LaboratoryInventors: Scott Powers, Lars Zender, Rebecca A. Kohnz, Scott W. Lowe
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Publication number: 20100186097Abstract: The invention provides, among other things, methods for performing RNA interference in stem cells and methods for using the stem cells in vivo.Type: ApplicationFiled: July 6, 2009Publication date: July 22, 2010Applicant: Cold Spring Harbor LaboratoryInventors: Scott W. LOWE, Michael HEMANN, Gregory J. HANNON, Patrick J. PADDISON, Jack ZILFOU, Jordan FRIDMAN, Michelle A. CARMELL, Ross DICKINS, Thomas A. ROSENQUIST, Stephen J. ELLEDGE
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Publication number: 20090217404Abstract: The invention provides, among other things, methods for performing RNA interference (RNAi) in stem cells (such as embryonic stem cells) and methods for using such stem cells in vivo. The invention also provides various animal models based on conditional/inducible, reversible, tissue-specific/spacial, and/or developmental stage-specific/temporal RNAi of certain target genes, which animal model may be useful for, e.g., drug target identification and/or validation.Type: ApplicationFiled: February 23, 2008Publication date: August 27, 2009Inventors: Scott W. Lowe, Michelle A. Carmell, Gregory J. Hannon, Patrick Paddison, Jack Zilfou, Jordan Fridman, Ross Dickins, Michael Hemann, Thomas A. Rosenquist, Prem Premsrirut
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Publication number: 20090186839Abstract: The invention provides novel inhibitors of protein translation initiation and inhibitors of eIF4F activity that can increase chemosensitivity or diminish or reverse chemoresistance in growth transformed cells and thereby reduce hyperproliferative conditions, such as cancer progression, in select patient populations having particular tumor genotypes. The invention also provides methods which target translation initiation controls in growth-transformed cells, such as tumor subtypes with altered expression of a gene activity, including the human akt, bcl-2, eIF4E, eIF4A or PTEN activities, to restore drug sensitivity in vivo in a genotype selective manner. In one aspect, the inhibitors of translation initiation of the invention are rocaglates, i.e., cyclopenta[b]benzofurons, which increases chemosensitivity or diminishes or reverses chemoresistance either alone or in combination, additively or synergistically, with other agents that alter growth or death.Type: ApplicationFiled: August 15, 2007Publication date: July 23, 2009Applicants: Cold Spring Harbor Laboratory, McGill UniversityInventors: Scott W. Lowe, Hans G. Wendel, Jerry Pelletier, Marie-Eve Bordeleau, Francis Robert
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Publication number: 20090082298Abstract: The invention relates to recombinant vectors for inducible and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene. In certain embodiments, the invention relates to the use of Tet (tetracycline)-responsive RNA Polymerase II (Pol II) promoters (e.g., TetON or TetOFF) to direct inducible knockdown in certain cells of an integrated or an endogenous gene, such as p53. The invention also relates to a method for producing transgenic animals (e.g., mice) expressing inducible (such as tetracycline-regulated), reversible, and/or tissue-specific double-stranded RNA molecules that interfere with the expression of a target gene.Type: ApplicationFiled: June 5, 2008Publication date: March 26, 2009Applicant: Cold Spring Harbor LaboratoryInventors: Ross Dickins, Gregory J. Hannon, Scott W. Lowe
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Publication number: 20090029872Abstract: This invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both and by transplanting the resulting hepatocytes into a recipient non-human animal. This invention also relates to the use of RNA interference (RNAi) technology in vivo to efficiently identify genes associated with liver cancer, in particular those encoding tumor suppressors, by knocking out candidate genes using RNAi and observing whether tumors would develop.Type: ApplicationFiled: February 21, 2008Publication date: January 29, 2009Applicant: Cold Spring Harbor LaboratoryInventors: Lars Zender, Scott W. Lowe, Mona S. Spector
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Publication number: 20090022685Abstract: This invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations (e.g., in oncogenes and tumor suppressor genes) that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both, preferably by inducible, reversible, and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene, and by transplanting the resulting hepatocytes into a recipient non-human animal. The invention further provides a method to treat cancer involving cooperative interactions between a tumor cell senescence program and the innate immune system.Type: ApplicationFiled: August 15, 2007Publication date: January 22, 2009Inventors: Scott W. Lowe, Gregory J. Hannon, Lars Zender, Wen Xue, Ross Dickins
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Publication number: 20080242622Abstract: This invention features methods of identifying genetic alterations that can modulate cancer cells' sensitivity to an anti-cancer drug. Information on such genetic alterations can be used to predict cancer therapeutic outcomes and to stratify patient populations to maximize therapeutic efficacy.Type: ApplicationFiled: March 19, 2008Publication date: October 2, 2008Applicant: Cold Spring Harbor LaboratoryInventors: Scott W. Lowe, Michael Hemann, Gregory J. Hannon, Darren Burgess
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Publication number: 20080226553Abstract: This invention provides, among other things, methods for performing RNA interference in stem cells and methods for using stem cells in vivo.Type: ApplicationFiled: September 29, 2003Publication date: September 18, 2008Applicant: Cold Spring Harbor LaboratoryInventors: Scott W. Lowe, Michelle A. Carmell, Gregory J. Hannon, Patrick J. Paddison, Jack Zilfou, Jordan Fridman, Michelle A. Carmell, Ross Dickins, Thomas A. Rosenquist, Stephen J. Elledge
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Publication number: 20080188434Abstract: The invention provides methods for diagnosing cancers in humans by detecting DNA amplifications in chromosomal region 8p22, which encompasses the FGF-20 gene and the EFHA2 gene. Also provided are cancer treatment methods using inhibitors of FGF-20 and EFHA2. The invention also provides methods for promoting successful regeneration of liver function. These methods can be used therapeutically to improve liver function following transplantation in both recipient and donor subjects.Type: ApplicationFiled: August 13, 2007Publication date: August 7, 2008Inventors: Scott Powers, Lars Zender, Rebecca A. Kohnz, Scott W. Lowe
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Publication number: 20040048821Abstract: Described herein are mutant forms of the adenovirus E1A oncoprotein which are unable to bind and inactivate retinoblastoma (Rb) protein and are defective in promoting apoptosis and chemosensitivity in normal (non-tumorigenic or nonmalignant) cells, but enhance apoptosis and sensitivity to toxic agents (e.g., chemotherapeutic agents, radiation) in Rb protein deficient mutant cells. Such E1A mutant oncoproteins are useful to enhance apoptosis and sensitivity to toxic agents in Rb protein deficient mammalian cells. Also described are agents, useful to promote apoptosis and chemosensitivity in Rb deficient cells, which mimic the activity of an E1A region involved in binding p300 and CBP proteins. Such E1A mimics are, for example, polypeptides which consist essentially of the amino acid residues of such an E1A region (e.g., the N-terminal region, CR1), DNA encoding the E1A region or small organic molecules which mimic the activity of the E1A region.Type: ApplicationFiled: March 26, 2003Publication date: March 11, 2004Applicant: Cold Spring Harbor LaboratoryInventor: Scott W. Lowe
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Patent number: 6583333Abstract: A mouse expressing myc in B cells, because of defective function of one or more tumor suppressor genes, is useful for the testing of anti-lymphoma agents and for the testing of genes which may have an effect on the apoptotic pathway. Preferred embodiments include mice of genotypes E&mgr;-myc/p53+/−, E&mgr;-myc/Rb+/− and E&mgr;-myc/p16+/−, and cells derived from lymphomas arising in these mice, wherein the cells may have undergone further genetic alteration. Mouse strains, lymphoma cells and cell lines of the invention can be used in methods to discover new anti-lymphoma agents, methods to characterize tumors, and to characterize genes which may affect the development of resistance to anti-tumor agents. Such methods are also part of the invention.Type: GrantFiled: May 12, 1998Date of Patent: June 24, 2003Assignee: Cold Spring Harbor LaboratoryInventors: Scott W. Lowe, Rachel R. Wallace-Brodeur