Abstract: The present invention relates generally to a novel CREBa polypeptide isoform, polynucleotides encoding the polypeptide, expression constructs comprising the polynucleotides, host cell transformed or transfected with the polynucleotides, methods for producing the polypeptide, and methods to identify inhibitors of binding between the CREBa and other polypeptides or polynucleotides.
Abstract: Methods of screening for substances which affect mammalian MAP kinase pathways, both inhibitors and activators, are provided. Substances identified using the methods as having such an effect are candidate pharmaceuticals for use in treatment of cancer, inflammatory disorders, cardio-vascular disorders or neurological disease. Yeasts are provided for use in the methods. In the yeast, deficiencies in yeast MAPKK kinase and MAPK kinase are complemented by mammalian MAPKK kinase and MAPK kinase. Yeast MAPK may also be replaced with a mammalian homologue and mammalian MAPK phosphatases may be introduced.
Type:
Grant
Filed:
December 14, 1995
Date of Patent:
September 28, 1999
Assignee:
Cancer Research Campaign Technology, Ltd.
Inventors:
Christopher John Marshall, Alan Ashworth, David Anthony Hughes
Abstract: Compositions of antisense oligonucleotides conjugated to peptides of a plurality of N-methylpyrrolecarboxamides linked by peptide bonds is provided. The compositions form stable hybridization complexes with DNA and can be used for any purpose which involves hybridizing an oligonucleotide to a DNA molecule, such as in antisense procedures. A method for enhancing oligonucleotide binding to a target is also provided. The method involves the step of hybridizing the target DNA with an oligonucleotide-peptide composition.
Type:
Grant
Filed:
July 15, 1996
Date of Patent:
September 21, 1999
Assignee:
Worcester Foundation for Biomedical Research
Abstract: A method of preparing a nucleic acid sequence capable of hybridizing to a target DNA sequence without requiring knowledge of this DNA sequence comprises the steps of ligating or otherwise linking a DNA fragment related to the target DNA sequence to a nucleotide sequence containing the recognition motif of an asymmetrically cleaving restriction enzyme, and subjecting the construct to the restriction enzyme to thereby cleave the construct within the target-related DNA fragment part thereof. A vector therefor comprises a site for insertion of the target-related DNA fragment, and a recognition sequence for an asymmetrically cleaving restriction enzyme or enzymes on one or both sides of said insertion site.
Abstract: Oligonucleotides are provided which are targeted to nucleic acids encoding human raf and capable of inhibiting raf expression. In preferred embodiments, the oligonucleotides are targeted to mRNA encoding human c-raf or human A-raf. The oligonucleotides may have chemical modifications at one or more positions and may be chimeric oligonucleotides. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating abnormal proliferative conditions which employ oligonucleotides of the invention.
Abstract: The present invention relates to methods of treating disease-associated cellular proliferation using oligonucleotides. In particular, it relates to the use of oligonulceotides which are substantially complementary to interleukin-6 receptor mRNA sequences. In the form of pharmaceutical compositions, these oligonucleotides are suitable for administration to human subjects for the treatment of abnormal cellular proliferation due to such diseases as cancer, autoimmune disorders and viral infection.
Type:
Grant
Filed:
November 21, 1997
Date of Patent:
August 31, 1999
Assignee:
Gen-Probe Incorporated
Inventors:
Steven Joel Brown, Nanibhushan Dattagupta, Yathi M. Naidu
Abstract: The present invention relates generally to a method for the prophylaxis and/or treatment of skin disorders, and in particular proliferative and/or inflammatory skin disorders, and to genetic molecules useful for same. The present invention is particularly directed to genetic molecules capable of modulating growth factor interaction with its receptor on epidermal keratinocytes to inhibit, reduce or otherwise decrease stimulation of this layer of cells. The present invention contemplates, in a most preferred embodiment, a method for the prophylaxis and/or treatment of psoriasis.
Type:
Grant
Filed:
August 20, 1996
Date of Patent:
July 27, 1999
Assignee:
Royal Children's Hospital Research Foundation
Inventors:
George Arthur Werther, Christopher John Wraight
Abstract: Compositions and methods are provided for the treatment and diagnosis of diseases associated with protein kinase C. Oligonucleotides are provided which are targeted to nucleic acids encoding PKC. Oligonucleotides specifically hybridizable with a translation initiation site, 5'-untranslated region or 3'-untranslated region are provided. Oligonucleotides specifically hybridizable with a particular PKC isozyme or set of isozymes are also provided. In preferred embodiments, the oligonucleotides contain one or more chemical modifications. Methods of modulating PKC expression and of treating animals suffering from disease amenable to therapeutic intervention by modulating protein kinase C expression using oligonucleotides targeted to PKC are disclosed.
Abstract: The present invention features compounds and methods for inhibiting propagation of human immunodeficiency virus (HIV). Preferred HIV target sites are identified and oligonucleotides designed to hybridize to a target site are described. The preferred use of the oligonucleotides is as an anti-HIV agent to inhibit HIV propagation in a patient infected with HIV. Other uses of the present invention include detecting the presence of HIV by using the oligonucleotides as detection probes or amplification primers, and measuring the ability of an oligonucleotide to inhibit HIV propagation to evaluate its suitability as an anti-HIV agent for a phenotype of HIV or diagnose the presence of HIV in a patient.
Abstract: Oligonucleotides are provided which are targeted to nucleic acids encoding human c-raf and capable of inhibiting raf expression. The oligonucleotides contain a methoxyethoxy (2'--O--CH.sub.2 CH.sub.2 OCH.sub.3) modification at the 2' position of at least one nucleotide. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating abnormal proliferative conditions which employ oligonucleotides of the invention.
Abstract: Identified are genetic regulatory elements which are part of a natural antisense RNA negative regulatory system in eukaryotic cells. The genetic regulatory elements, designated an antisense initiator sequence, when downstream of and operably linked to a DNA molecule can transcribe the DNA molecule into RNA transcripts of negative strand polarity that function to bind to, in forming an RNA duplex with, sense RNA transcripts being produced from a target gene to be regulated. The invention relates to recombinant vectors useful for introduction into eukaryotic cells, and methods of using the vectors to regulate expression of a target gene comprising introducing the recombinant vectors into host eukaryotic cells.
Type:
Grant
Filed:
May 9, 1997
Date of Patent:
July 6, 1999
Assignee:
The Research Foundation of State University of New York
Abstract: The peptide X-Arg-Gly-Asp-R-Y wherein X is H or at least one amino acid and Y is OH or at least one amino acid, and R is an amino acid selected from Thr or Cys, or other amino acid, having the same cell-attachment activity as fibronectin and the peptide X-Arg-Gly-Asp-Ser-Y, wherein X and Y, having said activity are disclosed.
Abstract: Recombinant nucleic acids which encode aminoacyl-tRNA sythetases of pneumocystis origin or portions of such enzymes, have been isolated. These nucleic acids can be used to make expression constructs and transformed host cells for the production of pneumocystis aminoacyl-tRNA synthetases. They can also be used in the further isolation of nucleic acids related by DNA sequence similarities, which also encode pneumocystis aminoacyl-tRNA synthetases, or portions thereof. A further embodiment of the invention is antisense nucleic acid which can hybridize to the nucleic acid which encodes the aminoacyl-tRNA synthetase of pneumocystis. The invention also relates to enzymes, isolated and/or recombinant pneumocystis aminoacyl-tRNA synthetases. Antibodies which bind to these enzymes can be made and can be used in the purification and study of the enzymes.
Type:
Grant
Filed:
April 3, 1995
Date of Patent:
June 15, 1999
Assignee:
Cubist Pharmaceuticals, Inc.
Inventors:
Susan K. Whoriskey, Cheryl L. Quinn, Niajun Tao, Karen I. Politis-Virk, Paul R. Schimmel
Abstract: The invention pertains to a multimeric self-cleaving ribozyme comprising multiple repeating units, wherein each unit comprises a ribozyme containing a catalytic domain and an antisense domain, and a target recognition sequence or portion thereof recognized by the antisense domain of the ribozyme and comprising a ribozyme cleavage site to facilitate self-cleavage. The invention also pertains to constructs comprising DNA encoding the multimeric self-cleaving ribozyme, cells stably transformed with these constructs, and methods of cleaving RNA, regulating gene expression and generating molecular weight ladders utilizing the multimeric self-cleaving ribozyme.
Abstract: Compositions and methods are provided for identifying proteins and other agents that modulate transactivation of HCMV early genes. In particular, agents that inhibit the cell-type specific transactivation of HCMV DNA polymerase are provided. Such agents may be used, for example, in the treatment of patients infected with HCMV.
Abstract: Disclosed are novel bifunctional nucleoside analogs and oligonucleosides of 3-4 bases (trimers and tetramers) and longer containing at least two consecutive internucleoside linkages of two carbon-one nitrogen atom or two carbon-one oxygen atom (3'-NCC-5', 3'-CNC-5', 3'-OCC-5') internucleoside linkages. The bifunctional nucleosides are useful for preparing the trimers and tetramers, which, in turn, are useful, together with the nucleosides, in preparing oligonucleosides as well as chimeric oligonucleotide analogs, preferably antisense oligonucleosides and oligonucleotide analogs, of 6 to about 60 bases having at least two consecutive internucleoside linkages of two carbon atoms and one nitrogen atom or 2 carbon atoms and one oxygen atom in the oligonucleoside backbone.
Type:
Grant
Filed:
March 13, 1997
Date of Patent:
April 6, 1999
Assignee:
Sanofi
Inventors:
Prasad Venkata Chala Chaturvedula, Ashis Kumar Saha
Abstract: An improvement in adaptor-based sequence analysis is provided that addresses the problems created by self-ligation of target polynucleotides that have complementary ends. The improvement includes preparation of target polynucleotides with dephosphorylated 5' strands and the use of adaptors having a 3' blocking group. In a preferred embodiment, adaptors are ligated to target polynucleotides by a single strand, 3' blocking groups are removed, the adjacent 5' hydroxyl of the target polynucleotide is phosphorylated, and the ligation of the adaptor is completed by treatment with a ligase.
Type:
Grant
Filed:
April 15, 1997
Date of Patent:
March 30, 1999
Assignee:
Lynx Therapeutics, Inc.
Inventors:
Robert B. DuBridge, Glenn Albrecht, Sydney Brenner, Sergei M. Gryaznov, Sarah N. McCurdy
Abstract: Evaluation of a sample for the presence and qualitative nature of a microorganism can be performed in a single vessel by combining a natural abundance DNA sample with a sequencing mixture containing a primer pair, a thermally stable polymerase such as ThermoSequenase.TM. which incorporates dideoxynucleotides into an extending nucleic acid polymer at a rate which is no less than about 0.4 times the rate of incorporation of deoxynucleotides, nucleotide triphosphate feedstocks, and a chain terminating nucleotide triphosphate. The mixture is processed through multiple thermal cycles for annealing, extension and denaturation to produce a product mixture which is analyzed by electrophoresis.
Type:
Grant
Filed:
February 27, 1997
Date of Patent:
March 30, 1999
Assignee:
Visible Genetics, Inc.
Inventors:
Jean-Michel Lacroix, James Leushner, May Hui, James M. Dunn, Marina T. Larson
Abstract: A novel human radiation protecting checkpoint (RAP-1) gene and the RAP-1 protein encoded by the gene are disclosed. RAP-1 is believed to be involved in the regulation of cell cycle progression and/or programmed cell death (apoptosis). A human antisense RNA which can bind to the mRNA of the human RAP-1 protein, as well as the DNA from which the antisense RNA is transcribed are also disclosed. Additionally, a method for isolating DNA damage-monitoring checkpoint genes is described. The use of the DNA and RNA sequences and of the protein of the invention for the eary detection, prevention and/or treatment of cancer, AIDS and other diseases is also discussed.
Type:
Grant
Filed:
June 11, 1997
Date of Patent:
March 16, 1999
Assignee:
Ramot University Authority for Applied and Industrial Development Ltd.
Abstract: Protein disulfide isomerase, which catalyzes the exchange reaction between sulfhydryl and disulfide in a protein for formation of the most stable natural type disulfide bonds, is useful for formation of natural type disulfide bonds in a protein which is produced in a prokaryotic cell.