Patents Assigned to Worcester Foundation for Experimental Biology
  • Publication number: 20030148980
    Abstract: 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: Application
    Filed: October 8, 2002
    Publication date: August 7, 2003
    Applicant: Worcester Foundation for Experimental Biology
    Inventors: Valeri Metelev, Sudhir Agrawal
  • Publication number: 20020099192
    Abstract: 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: Application
    Filed: June 22, 2001
    Publication date: July 25, 2002
    Applicant: Worcester Foundation for Experimental Biology
    Inventors: Valeri Metelev, Sudhir Agrawal
  • Patent number: 5824776
    Abstract: A chimeric compound that contains a cell-specific ligand linked to a pore-forming agent capable of lysing a cell.
    Type: Grant
    Filed: December 5, 1996
    Date of Patent: October 20, 1998
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Hagen Bayley, Barbara J. Walker
  • Patent number: 5817771
    Abstract: A chimeric compound that contains a cell-specific ligand linked to a pore-forming agent capable of lysing a cell.
    Type: Grant
    Filed: December 27, 1994
    Date of Patent: October 6, 1998
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Hagen Bayley, Barbara J. Walker
  • Patent number: 5789187
    Abstract: 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: Grant
    Filed: September 21, 1994
    Date of Patent: August 4, 1998
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Alonzo H. Ross, Wojciech Poluha, Mahesh B. Lachyankar, Dorota K. Poluha
  • Patent number: 5777078
    Abstract: 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: Grant
    Filed: June 7, 1995
    Date of Patent: July 7, 1998
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Hagan Bayley, Barbara J. Walker, Chung-yu Chang, Brett Niblack, Rekha Panchal
  • Patent number: 5652355
    Abstract: 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: Grant
    Filed: July 23, 1992
    Date of Patent: July 29, 1997
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Valeri Metelev, Sudhir Agrawal
  • Patent number: 5635377
    Abstract: 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: Grant
    Filed: November 18, 1994
    Date of Patent: June 3, 1997
    Assignee: Worcester Foundation for Experimental Biology, Inc.
    Inventors: Thoru Pederson, Sudhir Agrawal, Sandra Mayrand, Paul C. Zamecnik
  • Patent number: 5612469
    Abstract: 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: Grant
    Filed: May 1, 1995
    Date of Patent: March 18, 1997
    Assignee: Worcester Foundation for Experimental Biology
    Inventor: John Goodchild
  • Patent number: 5559221
    Abstract: 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: Grant
    Filed: May 10, 1994
    Date of Patent: September 24, 1996
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Sudhir Agrawal, Paul C. Zamecnik
  • Patent number: 5387520
    Abstract: 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: Grant
    Filed: August 27, 1992
    Date of Patent: February 7, 1995
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Patrizia LoPresti, Wojciech Poluha, Dorota K. Poluha, Alonzo H. Ross
  • Patent number: 5366878
    Abstract: 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: Grant
    Filed: March 24, 1993
    Date of Patent: November 22, 1994
    Assignee: The Worcester Foundation for Experimental Biology
    Inventors: Thoru Pederson, Sudhir Agrawal, Sandra Mayrand, Paul C. Zamecnik
  • Patent number: 5352578
    Abstract: 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: Grant
    Filed: February 15, 1989
    Date of Patent: October 4, 1994
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Sudhir Agrawal, Paul C. Zamecnik
  • Patent number: 5220007
    Abstract: 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: Grant
    Filed: February 19, 1992
    Date of Patent: June 15, 1993
    Assignee: The Worcester Foundation for Experimental Biology
    Inventors: Thoru Pederson, Sudhir Agrawal, Sandra Mayrand, Paul C. Zamecnik
  • Patent number: 5194428
    Abstract: 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: Grant
    Filed: April 30, 1990
    Date of Patent: March 16, 1993
    Assignees: Worcester Foundation for Experimental Biology, Mt. Sinai School of Medicine
    Inventors: Sudhir Agrawal, Josef M. E. Leiter, Peter Palese, Paul C. Zamecnik
  • Patent number: 5149797
    Abstract: 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: Grant
    Filed: February 15, 1990
    Date of Patent: September 22, 1992
    Assignee: The Worcester Foundation for Experimental Biology
    Inventors: Thoru Pederson, Sudhir Agrawal, Sandra Mayrand, Paul C. Zamecnik
  • Patent number: 5149798
    Abstract: 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: Grant
    Filed: April 6, 1989
    Date of Patent: September 22, 1992
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Sudhir Agrawal, Paul C. Zamecnik
  • Patent number: 5109126
    Abstract: 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: Grant
    Filed: December 6, 1988
    Date of Patent: April 28, 1992
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: Sudhir Agrawal, Richard A. Cardullo, David E. Wolf
  • Patent number: 5049550
    Abstract: 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: Grant
    Filed: November 21, 1988
    Date of Patent: September 17, 1991
    Assignee: Worcester Foundation for Experimental Biology
    Inventor: Paul C. Zamecnik
  • Patent number: 4806463
    Abstract: 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: Grant
    Filed: May 23, 1986
    Date of Patent: February 21, 1989
    Assignee: Worcester Foundation for Experimental Biology
    Inventors: John Goodchild, Paul C. Zamecnik