Abstract: A method is provided for simultaneously determining the positions of a selected nucleotide base in a target region of both strands of a denatured duplex nucleic acid polymer. The nucleic acid polymer is combined with a reactant mixture comprising first and second oligonucleotide primers, said primers binding to the sense and antisense strands, respectively, of the nucleic acid polymer at a location flanking the target region; a thermostable DNA polymerase; a chain-terminating nucleotide triphosphate complementary to the selected nucleotide base; and other reagents for synthesis of chain extension products to form a reaction mixture. This mixture is processed through a plurality of thermal cycles, each including at least a chain extension phase and a denaturation phase to produce chain extension products. These chain extension products are evaluated to determine the positions of the selected bases.
Type:
Grant
Filed:
January 20, 1998
Date of Patent:
July 4, 2000
Assignee:
Visible Genetics Inc.
Inventors:
James Leushner, May Hui, James M. Dunn, Marina T. Larson, Jean-Michel Lacroix, Robert Shipman
Abstract: The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA which is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA which is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism a toxin which causes killing of the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon/intron boundaries of pre-mRNA molecules using an exon tagging method.
Type:
Grant
Filed:
August 13, 1998
Date of Patent:
July 4, 2000
Assignee:
Intronn Holdings LLC
Inventors:
Lloyd G. Mitchell, Mariano A. Garcia-Blanco
Abstract: The invention generally provides for compositions and methods of inhibiting the proliferation of human melanoma cancer cells. By administering a therapeutically effective amount of a c-myc oligonucleotide to a human melanoma cancer cell, melanoma cancer cell proliferation can be arrested or inhibited, metastases reduced from a tumor, and apoptosis induced in melanoma cancer cells. Oligonucleotides that are complementary to c-myc polynucleotides are referred to herein as "c-myc oligonucleotides." A particularly efficacious embodiment of the invention relates to compositions and methods concerning the co-administration of c-myc oligonucleotides and cisplatin.
Abstract: Compositions and methods for the diagnosis, prevention and treatment of immune states and disorders amenable to treatment through modulation of T cell activation are provided. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding B7 proteins.
Abstract: The invention provides fast and highly accurate mass spectrometer based processes for directly sequencing a target nucleic acid (or fragments generated from the target nucleic acid), which by means of protection, specificity of enzymatic activity, or immobilization, are unilaterally degraded in a stepwise manner via exonuclease digestion and the nucleotides, derivatives or truncated sequences detected by mass spectrometry.
Abstract: Conjugated compounds which comprise an ST receptor binding moiety and a radiostable active moiety are disclosed. Pharmaceutical compositions comprising conjugated compound which comprises an ST receptor binding moiety and a radiostable active moiety or an ST receptor binding moiety and a radioactive active moiety are disclosed. Methods of treating an individual suspected of suffering from metastasized colorectal cancer are disclosed. Methods of radioimaging metastasized colorectal cancer cells are disclosed. In vitro methods, kits and reagents are disclosed for determining whether or not an individual has metastasized colorectal cancer cells, for determining whether tumor cells are colorectal in origin and for analyzing tissue samples from the colon tissue to evaluate the extent of metastasis of colorectal tumor cells.
Abstract: The present invention provides compositions with high affinity for a target transcription factor, that can be introduced into cells as decoy cis-elements to bind the factor and alter gene expression. Specifically, the present invention provides nucleic acid molecules that compete with cAMP response element (CRE) enhancers for binding to transcription factors.
Type:
Grant
Filed:
November 24, 1997
Date of Patent:
May 9, 2000
Assignee:
The United States of America as represented by the Department of Health and Human Services
Abstract: The present invention provides a single-stranded oligodeoxyribonucleotide, which (i) comprises from about 5 to 11 bases, at least one of which is a substituted or an unsubstituted O.sup.6 -benzylguanine, and (ii) inactivates human AGT. The present invention also provides a single-stranded oligodeoxyribonucleotide, which can inactivate a mutant human AGT, which either is not inactivated by O.sup.6 -benzylguanine or is less inactivated by O.sup.6 -benzylguanine than by said single-stranded oligodeoxyribonucleotide. A phosphate of the single-stranded oligodeoxyribonucleotide can be replaced by a methylphosphonate or a phosphorothioate. The present invention also provides a composition comprising such an oligodeoxyribonucleotide. In addition, the present invention provides a method of enhancing the effect of an antineoplastic alkylating agent, which alkylates the O.sup.
Type:
Grant
Filed:
February 13, 1998
Date of Patent:
May 9, 2000
Assignees:
The United States of America as represented by the Department of Health and Human Services, The Penn State Research Foundation, Arch Development Corporation
Inventors:
Robert C. Moschel, Gary T. Pauly, Anthony E. Pegg, M. Eileen Dolan
Abstract: A method of inhibiting interleukin-5 expression using an antisense oligonucleotide which contains at least one non-natural internucleoside linkage.
Abstract: The method of this invention relates to the use of improved anchor primers and a novel purification process to increase the efficiency and accuracy of the differential display technique.
Type:
Grant
Filed:
April 2, 1997
Date of Patent:
April 4, 2000
Assignee:
Johnson & Johnson Consumer Products, Inc.
Inventors:
Nicholas Combates, Jose R. Pardinas, Satish Parimoo, Stephen M. Prouty, Kurt S. Stenn
Abstract: The invention provides genetic suppressor elements that confer upon a cell resistance to one or more chemotherapeutic drug, methods for identifying and obtaining such elements, and methods of using such elements. The invention also provides cloned genes associated with sensitivity to chemotherapeutic drugs, particularly a cloned human kinesin heavy chain gene involved in resistance to DNA damaging agents.
Abstract: Enzymatic RNA molecules have been designed that cleave mutant N-ras mRNA, preferably at a NUX cleavage site (N=any base, X=A, C or U). Preferred ribozymes have nucleotide sequences 5'-CCAACACCUGAUGAGCGUUAGCGAAACCUGCU-3' or 5'-UCCCAACCUGAUGAGCGUUAGCGAAACACCUG-3' (SEQ ID NOS:1 and 2), and derivatives thereof. The present invention also provides pharmaceuticals containing such molecules and the use of such molecules for the preparation of pharmaceuticals for the treatment of diseases involving abnormal cell growth and/or differentiation.
Type:
Grant
Filed:
May 23, 1997
Date of Patent:
March 14, 2000
Assignee:
Hoechst Aktiengesellschaft
Inventors:
Eugen Uhlmann, Joachim Engels, Michaela Scherr, Arnold Ganser
Abstract: This invention relates to methods and compositions for producing a fusion protein comprised of Haemophilus influenzae P2 amino acid sequences, wherein in place of loop 5, or a portion thereof, is displayed a heterologous or homologous peptide sequence having biological activity. The fusion protein may be expressed on the surface of the host cell, such as in H. influenzae, which has been transformed with a fusion sequence that is operatively linked to at least one regulatory control element for expression of the fusion protein. Alternatively, the fusion protein can be purified from the host cell in the expression system, if the fusion protein remains associated with the host cell; or from the media of the expression system, if the fusion protein is a secreted form.
Type:
Grant
Filed:
October 31, 1996
Date of Patent:
March 7, 2000
Assignee:
Research Foundation of State University of New York
Abstract: This invention provides methods of amplifying a sequence of interest present within a nucleic acid molecule. In addition, this invention provides a method of determining the nucleotide sequence of a sequence of interest present within a nucleic acid molecule (e.g. GAWTS and RAWTS) which can be used to sequence tissue specific genes (e.g. tsRAWTS) and genes accross species (e.g. zooRAWTS).In addition, this invention provides a method of synthesizing a polypeptide encoded for by a nucleic acid molecule (RAWIT). Further, the subject invention provides a method of determining an internal nucleotide sequence present within a nucleic acid molecule, and a method of determining a terminal nucleotide sequence present within a nucleic acid molecule (e.g. PLATS).Also provided for is a method of determining the nucleotide sequence of sequences present within a nucleic acid molecule which are adjacent to areas of known sequence (e.
Abstract: The invention provides recombinant nucleic acids comprising nucleic acid sequences from the genomic DNA methyltransferase gene. The invention further provides sequence information for such nucleic acid sequences. In addition, the invention provides antisense oligonucleotides complementary to special regions of the genomic DNA methyltransferase gene or its RNA transcript. Finally, the invention provides methods for using such antisense oligonucleotides as analytical and diagnostic tools, as potentiators of transgenic plant and animal studies and gene therapy approaches, and as potential therapeutic agents.
Abstract: The invention relates to oligonucleotide sequences (or initiators) derived from the HIV-2 ROD virus genome and from that of the SIV-mac 142 virus, as well as their use in an in vitro method for the diagnosis of the infection of an individual by a HIV-2 type virus.
Type:
Grant
Filed:
November 18, 1994
Date of Patent:
February 1, 2000
Assignees:
Institut Pasteur, Institut National de la Sante et de la Recherche Medicale
Inventors:
Pierre Sonigo, Christian Brechot, Valerie Courgnaud
Abstract: The invention relates to deoxyribo- and ribo-oligonucleotides and derivatives thereof, as well as pharmaceutical preparations, therapies, diagnostics and commercial research reagents in relation to disease states which respond to modulation of the synthesis of the enzyme S-adenosylmethionine decarboxylase (SAMDC). In particular, the invention relates to antisense oligonucleotides and oligonucleotide derivatives specifically hybridizable with nucleic acids relating to (preferably human) SAMDC. These oligonucleotides and their derivatives have been found to modulate the synthesis of SAMDC in cells.
Type:
Grant
Filed:
August 20, 1997
Date of Patent:
January 25, 2000
Assignee:
Novartis AG
Inventors:
Helmut Mett, Robert Haner, Nicholas Mark Dean
Abstract: Compositions and methods are provided for the treatment and diagnosis of diseases amenable to treatment through modulation of the synthesis or metabolism of intercellular adhesion molecules. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with nucleic acids encoding intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequences, 3'-untranslated sequences, and intervening sequences.
Type:
Grant
Filed:
December 2, 1997
Date of Patent:
January 18, 2000
Assignee:
Isis Pharmaceuticals Inc.
Inventors:
C. Frank Bennett, Christopher K. Mirabelli