Patents Assigned to Worcester Foundation for Experimental Biology
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Publication number: 20030148980Abstract: The invention provides hybrid oligonucleotides having phosphorothioate or phosphorodithioate internucleotide linkages, and both deoxyribonucleosides and ribonucleosides or 2′-substituted ribonucleosides. Such hybrid oligonucleotides have superior properties of duplex formation with RNA, nuclease resistance, and RNase H activation.Type: ApplicationFiled: October 8, 2002Publication date: August 7, 2003Applicant: Worcester Foundation for Experimental BiologyInventors: Valeri Metelev, Sudhir Agrawal
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Publication number: 20020099192Abstract: The invention provides hybrid oligonucleotides having phosphorothioate or phosphorodithioate internucleotide linkages, and both deoxyribonucleosides and ribonucleosides or 2′-substituted ribonucleosides. Such hybrid oligonucleotides have superior properties of duplex formation with RNA, nuclease resistance, and RNase H activation.Type: ApplicationFiled: June 22, 2001Publication date: July 25, 2002Applicant: Worcester Foundation for Experimental BiologyInventors: Valeri Metelev, Sudhir Agrawal
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Patent number: 5824776Abstract: A chimeric compound that contains a cell-specific ligand linked to a pore-forming agent capable of lysing a cell.Type: GrantFiled: December 5, 1996Date of Patent: October 20, 1998Assignee: Worcester Foundation for Experimental BiologyInventors: Hagen Bayley, Barbara J. Walker
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Patent number: 5817771Abstract: A chimeric compound that contains a cell-specific ligand linked to a pore-forming agent capable of lysing a cell.Type: GrantFiled: December 27, 1994Date of Patent: October 6, 1998Assignee: Worcester Foundation for Experimental BiologyInventors: Hagen Bayley, Barbara J. Walker
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Patent number: 5789187Abstract: Disclosed is a method of reducing or inhibiting the tumorigenicity of a tumor cell in which a vector including a nucleotide sequence encoding a differentiation factor receptor, or a polypeptide portion thereof, is transferred to the tumor cell such that the nucleotide sequence is expressed. Tumorigenicity is monitored by cell growth and colony formation in a semi-soft medium, a reduction in proliferation being indicative of the reduction or inhibition of tumorigenicity of the treated tumor cell.Type: GrantFiled: September 21, 1994Date of Patent: August 4, 1998Assignee: Worcester Foundation for Experimental BiologyInventors: Alonzo H. Ross, Wojciech Poluha, Mahesh B. Lachyankar, Dorota K. Poluha
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Patent number: 5777078Abstract: An inactive pore-forming agent which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell.Type: GrantFiled: June 7, 1995Date of Patent: July 7, 1998Assignee: Worcester Foundation for Experimental BiologyInventors: Hagan Bayley, Barbara J. Walker, Chung-yu Chang, Brett Niblack, Rekha Panchal
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Patent number: 5652355Abstract: The invention provides hybrid oligonucleotides having phosphorothioate or phosphorodithioate internucleotide linkages, and both deoxyribonucleosides and ribonueleosides or 2'-substituted ribonucleosides. Such hybrid oligonucleotides have superior properties of duplex formation with RNA, nuclease resistance, and RNase H activation.Type: GrantFiled: July 23, 1992Date of Patent: July 29, 1997Assignee: Worcester Foundation for Experimental BiologyInventors: Valeri Metelev, Sudhir Agrawal
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Patent number: 5635377Abstract: A method of site-directed alteration (removal or removal followed by replacement) of selected nucleotides in an RNA molecule, as well as to mixed phosphate backbone oligonucleotides useful in the method. It further relates to a method of producing polypeptides or proteins encoded by the RNA molecule altered by the present method. Through use of the present method, site-directed cleavage of an RNA molecule is effected, followed by excision of the selected or target segment of the RNA molecule.Type: GrantFiled: November 18, 1994Date of Patent: June 3, 1997Assignee: Worcester Foundation for Experimental Biology, Inc.Inventors: Thoru Pederson, Sudhir Agrawal, Sandra Mayrand, Paul C. Zamecnik
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Patent number: 5612469Abstract: Methods are disclosed for increasing ribozyme catalytic activity without reducing specificity, which methods comprise contacting an RNA molecule with a ribozyme and a facilitator oligonucleotide.The present invention further provides compositions comprising a ribozyme and an effective amount of a facilitator oligonucleotide.Type: GrantFiled: May 1, 1995Date of Patent: March 18, 1997Assignee: Worcester Foundation for Experimental BiologyInventor: John Goodchild
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Patent number: 5559221Abstract: A method of purifying full length synthetic target oligonucleotides from a mixture of oligonucleotides, particularly from a mixture containing truncated or failed sequences. The method involves attaching a short nucleotide sequence complementary to the 5' end of a target oligonucleotide to a solid support. The complementary between the most 5' nucleotides of the target oligonucleotide and the bound oligonucleotide results in hybridization which serves to retain the target oligonucleotide. Truncated or failed sequences lacking 5' sequences complementary to the attached oligonucleotide, fail to hybridize and therefore are not retained. The method makes it possible to purify gram quantities of synthetic deoxyribonucleic acids or ribonucleic acids and sequences which have modifications, such as on the phosphate backbone. The support-bound nucleotide sequences are stable under conditions of purification and therefore can be reused.Type: GrantFiled: May 10, 1994Date of Patent: September 24, 1996Assignee: Worcester Foundation for Experimental BiologyInventors: Sudhir Agrawal, Paul C. Zamecnik
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Patent number: 5387520Abstract: Disclosed are methods and compositions for treating neuroblastoma cells. The methods include contacting the neuroblastoma cells with a neurotrophic factor and less than a lethal dose of an inhibitor of cell proliferation for about 1 to 15 days, and then maintaining the neuroblastoma cells in contact with the neurotrophic factor for an additional 1 to 15 days. The composition includes a neurotrophic factor such as the neurotropin, nerve growth factor, and an inhibitor of cell proliferation such as aphidicolin, thymidine, or hydroxyurea. Also disclosed are methods for inducing the remission or differentiation of, or eliminating, neuroblastoma cells.Type: GrantFiled: August 27, 1992Date of Patent: February 7, 1995Assignee: Worcester Foundation for Experimental BiologyInventors: Patrizia LoPresti, Wojciech Poluha, Dorota K. Poluha, Alonzo H. Ross
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Patent number: 5366878Abstract: A method of site-directed alteration (removal or removal followed by replacement) of selected nucleotides in an RNA molecule, as well as to mixed phosphate backbone oligonucleotides useful in the method. It further relates to a method of producing polypeptides or proteins encoded by the RNA molecule altered by the present method. Through use of the present method, site-directed cleavage of an RNA molecule is effected, followed by excision of the selected or target segment of the RNA molecule.Type: GrantFiled: March 24, 1993Date of Patent: November 22, 1994Assignee: The Worcester Foundation for Experimental BiologyInventors: Thoru Pederson, Sudhir Agrawal, Sandra Mayrand, Paul C. Zamecnik
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Patent number: 5352578Abstract: A method of purifying full length synthetic target oligonucleotides from a mixture of oligonucleotides, particularly from a mixture containing truncated or failed sequences is disclosed. The method involves attaching a short nucleotide sequence complementary to the 5' end of a target oligonucleotide to a solid support. The complementarity between the most 5' nucleotides of the target oligonucleotide and the bound oligonucleotide results in hybridization which serves to retain the target oligonucleotide. Truncated or failed sequences lacking 5' sequences complementary to the attached oligonucleotide, fail to hybridize and therefore are not retained. The method makes it possible to purify gram quantities of synthetic deoxyribonucleic acids or ribonucleic acids and sequences which have modifications, such as on the phosphate backbone. The support-bound nucleotide sequences are stable under conditions of purification and therefore can be reused.Type: GrantFiled: February 15, 1989Date of Patent: October 4, 1994Assignee: Worcester Foundation for Experimental BiologyInventors: Sudhir Agrawal, Paul C. Zamecnik
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Patent number: 5220007Abstract: A method of site-directed alteration (removal or removal followed by replacement) of selected nucleotides in an RNA molecule, as well as to mixed phosphate backbone oligonucleotides useful in the method. It further relates to a method of producing polypeptides or proteins encoded by the RNA molecule altered by the present method. Through use of the present method, site-directed cleavage of an RNA molecule is effected, followed by excision of the selected or target segment of the RNA molecule.Type: GrantFiled: February 19, 1992Date of Patent: June 15, 1993Assignee: The Worcester Foundation for Experimental BiologyInventors: Thoru Pederson, Sudhir Agrawal, Sandra Mayrand, Paul C. Zamecnik
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Patent number: 5194428Abstract: A method of inhibiting influenza virus replication through the activity of natural (unmodified) or modified oligonucleotides (oligodeoxynucleotides or oligoribonucleotides) which hybridize to a selected region of the influenza virus RNA and interfere with its ability to serve as a template for synthesis of encoded products. Oligonucleotides (unmodified or modified) which have antiviral activity against influenza virus as a result of their ability to hydridze to a selected region of influenza virus RNA and inhibit its ability to serve as a template for synthesis of encoded products, as well as compositions which include the oligonucleotides.Type: GrantFiled: April 30, 1990Date of Patent: March 16, 1993Assignees: Worcester Foundation for Experimental Biology, Mt. Sinai School of MedicineInventors: Sudhir Agrawal, Josef M. E. Leiter, Peter Palese, Paul C. Zamecnik
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Patent number: 5149797Abstract: A method of site-directed alteration (removal or removal followed by replacement) of selected nucleotides in an RNA molecule, as well as to mixed phosphate backbone oligonucleotides useful in the method. It further relates to a method of producing polypeptides or proteins encoded by the RNA molecule altered by the present method. Through use of the present method, site-directed cleavage of an RNA molecule is effected, followed by excision of the selected or target segment of the RNA molecule.Type: GrantFiled: February 15, 1990Date of Patent: September 22, 1992Assignee: The Worcester Foundation for Experimental BiologyInventors: Thoru Pederson, Sudhir Agrawal, Sandra Mayrand, Paul C. Zamecnik
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Patent number: 5149798Abstract: A process of producing synthetic oligonucleotides on a small or large scale using H-phosphonate nucleoside monomers is described. The process can be used to synthesize oligonucleotides of any length, including oligodeoxyribonucleotides and oligoribonucleotides. The process results in a coupling efficiency of greater than 97% and consumes only two to three equivalents of monomer to activator per coupling reaction. In addition, the process does not require a separate capping step and capping reagent because the activating reagent serves a self-capping function thereby preventing elongation of failed sequences. The H-phosphonate linkages of the fully synthesized oligonucleotide can be oxidized with a variety of reagents to obtain either phosphate diester or other types of modified oligonucleotides.Type: GrantFiled: April 6, 1989Date of Patent: September 22, 1992Assignee: Worcester Foundation for Experimental BiologyInventors: Sudhir Agrawal, Paul C. Zamecnik
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Patent number: 5109126Abstract: A method of assaying, detecting, monitoring, and influencing in vitro and in vivo activity of glycosyltransferase and sugar nucleotides which are analogs of the naturally-occurring sugar nucleotides for which the glycosyltransferases are specific. These sugar nucleotide analogs include those labeled with a fluorogenic moiety at the 2' or 3' position of the ribose or at another location (e.g., on a constituent phosphate or in the nucleotide backbone), such as the UDP-galactose analog, 2'(or 3')-O-(2,4,6-trinitrophenyl)-5'-uridine diphosphate galactose (TUG). A highly specific assay for soluble glycosyltransferase has been developed which utilizes the fluorogenic sugar-nucleotide analogs. These assays rely on changes in spectral properties resulting from specific binding events of the sugar nucleotide analog and the glycosyltransferase. Assays of this invention do not rely on the use of radio-isotopes and can be used to assess glycosyltransferase activity in living cells.Type: GrantFiled: December 6, 1988Date of Patent: April 28, 1992Assignee: Worcester Foundation for Experimental BiologyInventors: Sudhir Agrawal, Richard A. Cardullo, David E. Wolf
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Patent number: 5049550Abstract: A component of blood platelets analogues thereof are described. The invention is based on the discovery that this component, a dinucleotide, as well as several of its chemically synthesized analogues, is an effective anti-platelet and antithrombotic agent.Type: GrantFiled: November 21, 1988Date of Patent: September 17, 1991Assignee: Worcester Foundation for Experimental BiologyInventor: Paul C. Zamecnik
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Patent number: 4806463Abstract: Inhibition of HTLV-III by adminstration of an oligonucleotide complementary to highly conserved regions of the HTLV-III genome necessary for HTLV-III replication and/or gene expression is described, as are oligodeoxynucleotide sequences which are complementary to those regions, methods of inhibiting HTLV-III replication and gene expression and methods of determining the presence or absence of HTLV-III virus in samples such as blood, saliva, urine and tears.Type: GrantFiled: May 23, 1986Date of Patent: February 21, 1989Assignee: Worcester Foundation for Experimental BiologyInventors: John Goodchild, Paul C. Zamecnik