Using Fungi Patents (Class 435/911)
  • Patent number: 5998383
    Abstract: A synthetic antisense oligonucleotide comprising at least seven nucleotides or nucleotide analogues having a sequence complementary to the mRNA sequence of ribonucleotide reductase dimeric protein component R2 including SEQ ID Nos:1-102 is disclosed. A synthetic antisense oligonucleotide comprising at least seven nucleotides or nucleotide analogues having a sequence complementary to the mRNA sequence of ribonucleotide reductase dimeric protein component R1 including SEQ ID Nos:103-161 is also disclosed. The invention also discloses pharmaceutical compositions including the synthetic antisense oligonucleotides of the present invention and methods of using the antisense oligonucleotides to modulation proliferative cells including neoplastic cells.
    Type: Grant
    Filed: August 1, 1997
    Date of Patent: December 7, 1999
    Inventors: Jim A. Wright, Aiping H. Young
  • Patent number: 5998141
    Abstract: The present invention is based at least in part on the discovery of the genomic structure of the human SR-BI gene and on the identification of polymorphic regions within the gene. Accordingly, the invention provides nucleic acids having a nucleotide sequence of an allelic variant of an SR-BI gene and nucleic acids having an SR-BI intronic sequence. The invention also provides methods for identifying specific alleles of polymorphic regions of an SR-BI gene, methods for determining whether a subject has or is at risk of developing a disease which is associated with a specific allele of a polymorphic region of an SR-BI gene, and kits for performing such methods.
    Type: Grant
    Filed: July 10, 1997
    Date of Patent: December 7, 1999
    Assignee: Millennium Pharmaceuticals, Inc.
    Inventor: Susan Laurene Acton
  • Patent number: 5994076
    Abstract: Methods and compositions are provided for analyzing differences in the RNA profiles between a plurality of different physiological samples. In the subject methods, a set of a representational number of distinct gene specific primers is used to generate labeled nucleic acids from each of the different physiological samples. The labeled nucleic acids are then compared to each other and differences in the RNA profiles are determined. The subject methods find use in methods of identifying differential gene expression.
    Type: Grant
    Filed: May 21, 1997
    Date of Patent: November 30, 1999
    Assignee: Clontech Laboratories, Inc.
    Inventors: Alex Chenchik, George Jokhadze, Robert Bibilashvilli
  • Patent number: 5994068
    Abstract: A restriction site indexing method for selectively amplifying any fragment generated by a Class II restriction enzyme includes adaptors specific to fragment ends containing adaptor indexing sequences complementary to fragment indexing sequences near the termini of fragments generated by Class II enzyme cleavage. A method for combinatorial indexing facilitates amplification of restriction fragments whose sequence is not known.
    Type: Grant
    Filed: March 11, 1997
    Date of Patent: November 30, 1999
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Richard A. Guilfoyle, Zhen Guo
  • Patent number: 5994523
    Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.
    Type: Grant
    Filed: January 16, 1998
    Date of Patent: November 30, 1999
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: Yutaka Kawakami, Steven A. Rosenberg
  • Patent number: 5993802
    Abstract: The invention disclosed relates to a substantially biologically pure isolate of a low temperature basidiomycelte (LTB) fungus, (.tbd.Coprinus psychromorbidus), to a delivery composition comprising the fungus and an agriculturally acceptable carrier capable of supporting growth of the fungus, and to a method for suppressing the growth of Calmagrostis canadensis and other related weed grasses which are hosts to LTB snow mould.
    Type: Grant
    Filed: July 7, 1997
    Date of Patent: November 30, 1999
    Assignee: Minister of Natural Resources as represented by the Canadian Forest Service
    Inventor: Kenneth I. Mallett
  • Patent number: 5994064
    Abstract: The present invention describes a process of DNA typing performed on human specimens utilizing a specific multiplex reaction which amplifies GATA short tandem repeats in the loci D18S535, D22S683, and D9S302 for the purpose of producing STR genotypes which may be used for identification purposes. This multiplex is an improvement over existing multiplex amplifications for STR typing in that it possesses an extremely high individualization potential for forensic studies and power of exclusion for parentage testing.
    Type: Grant
    Filed: April 24, 1996
    Date of Patent: November 30, 1999
    Assignee: Identigene, Inc.
    Inventors: Rick W. Staub, Michael G. Carrico
  • Patent number: 5994079
    Abstract: Disclosed is a method of detecting RNA molecules of interest in which reverse transcription primers unique to the RNA molecule of interest are used for reverse transcribing the RNA with a reverse transcriptase lacking RNAse H function and the resulting RNA/DNA hybrid is detected with an antibody specific for RNA/DNA hybrids. This method can be used to detect the presence of one or many specific RNA molecules which may be present in a sample, including RNA from different organisms (such as viruses, bacteria, fungi, plants, and animals), or RNA indicative of an infection, a disease state, or predisposition to a disease in an animal. The specificity of detection is increased relative to current detection methods involving probe hybridization since the reverse transcription primers are shorter and less subject to non-specific hybridization. Specificity of the disclosed method can also be increased by using a thermostable reverse transcriptase and performing reverse transcription at a high temperature.
    Type: Grant
    Filed: February 6, 1998
    Date of Patent: November 30, 1999
    Assignee: Digene Corporation
    Inventors: Abel De La Rosa, Clayton D. Collier
  • Patent number: 5994080
    Abstract: Blood clot formation is the key event in myocardial infarction. Besides increased coagulation, failure in blood clot lysis can induce undesired coronary thrombosis. Plasmin is essential for degradation of fibrin clots. Tissue-type plasminogen activator (t-PA) is the serine protease that converts plasminogen into plasmin. The association of the Alu insertion/deletion polymorphism in intron h of the t-pA gene to the risk of myocardial infarction was evaluated. Subjects with a documented history of myocardial infarction (n=162) and controls (n=258) were drawn from the Rotterdam Study, a population-based cohort study of 7983 subjects of 55 years or older. Allele frequencies were 0.54 for the insertion allele (t-PA Alu-h I) and 0.46 for the deletion allele, and were in Hardy Weinberg equilibrium. Among subjects that were homozygous for the insertion (n=138) were more than twice as many subjects with myocardial infarction compared to those homozygous (n=75) for the deletion (relative risk of 2.04, (95% CI 1.03-4.
    Type: Grant
    Filed: February 20, 1998
    Date of Patent: November 30, 1999
    Assignee: Akzo Nobel, N.V.
    Inventors: Diederick Egberstus Grobbee, Cornelis Kluft
  • Patent number: 5989841
    Abstract: Nucleic sequences from the genome of Salmonella Typhi include all or part of the genetic information required for the in vitro infection of cultured HeLa cells by Salmonella bacteria. Polypeptides encoded by these nucleic sequences are also described, as is the use of said polypeptides and nucleic sequences for implementing methods of in vitro Salmonella detection in biological samples which are thought to contain it.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: November 23, 1999
    Assignees: Institut Pasteur, Institut National de la Sante et de la Recherche Medicale
    Inventors: Michel Yvan Popoff, Michel Dion
  • Patent number: 5989912
    Abstract: This invention relates to antisense oligonucleotides that target mRNAs in cells as substrates for the cellular enzyme RNase H and thereby cause specific degradation of the targeted mRNA. The oligonucleotides have three components: a RNase H activating region, a complementarity region and 3' and 5' ends. The invention optimizes each of the components to resist intracellular nucleases, to increase hybridization to target mRNA, to specifically inactivate target mRNA in cells, and to decrease cytotoxicity.
    Type: Grant
    Filed: December 15, 1998
    Date of Patent: November 23, 1999
    Assignees: Oligos Etc. Inc., Tod Mitchell Woolf
    Inventors: Amy Arrow, Roderic M. K. Dale, Tod Mitchell Woolf
  • Patent number: 5989878
    Abstract: The present invention relates to a fermentation process for preparing erythritol with high productivity with novel mutant of Trigonopsis variabilis, more specifically, for preparing erythritol under optimal fermentation conditions for maximum erythritol production by optimizing the environmental conditions of culture such as pH, temperature and controlling osmotic pressure. A two-stage fermentation was performed to control osmotic pressure. Osmotic pressure was adjusted to a low level during growth phase and to a high level during production phase by adding glucose and NaCl. Therefore, erythritol production could be increased due to the increased mutant cells.
    Type: Grant
    Filed: February 10, 1998
    Date of Patent: November 23, 1999
    Assignee: Bolak Co., Ltd.
    Inventors: Sang Yong Kim, Deok Kun Oh, Soo Ryun Jung
  • Patent number: 5989911
    Abstract: The invention features a modified small nucleolar ribonucleic acid (snoRNA) that directs the conversion of a uridine to a pseudouridine in a target nucleic acid, e.g., RNA, that includes first and second flanking regions located on either side of the uridine. The modified snoRNA includes a ribonucleotide sequence of a box H/ACA snoRNA including a Domain A sequence and a Domain B sequence, or a Domain A sequence and a Domain C sequence, wherein the snoRNA is modified in that the Domain A sequence is replaced by a first recognition sequence complementary to at least three consecutive nucleotides in the first flanking region in the target nucleic acid, and the Domain B or C sequence is replaced by a second recognition sequence complementary to at least three consecutive nucleotides in the second flanking region in the target nucleic acid.
    Type: Grant
    Filed: May 8, 1998
    Date of Patent: November 23, 1999
    Assignee: University of Massachusetts
    Inventors: Maurille J. Fournier, Jingwei Ni
  • Patent number: 5990302
    Abstract: A method for isolating a ribonucleic acid, which comprises dissolution of a sample containing the ribonucleic acid, such as cells, in an acidic solution containing a lithium salt and a chaotropic agent, bringing the ribonucleic acid into contact with a nucleic acid-binding carrier such as silica particles, thereby to allow selective adsorption of the ribonucleic acid alone onto said carrier, and eluting the ribonucleic acid from the nucleic acid-bound carrier; a reagent therefor; and a method for producing a cDNA from the ribonucleic acid isolated by this method. According to the present invention, a high purity ribonucleic acid can be isolated quickly and safely from a sample containing the ribonucleic acid.
    Type: Grant
    Filed: July 11, 1997
    Date of Patent: November 23, 1999
    Assignee: Toyo Boseki Kabushiki Kaisha
    Inventors: Toshihiro Kuroita, Hideki Kamimura, Bunsei Kawakami, Yoshihisa Kawamura
  • Patent number: 5989815
    Abstract: The present invention relates to somatic mutations in the Multiple Tumor Suppressor (MTS) gene in human cancers and their use in the diagnosis and prognosis of human cancer. The invention further relates to germ line mutations in the MTS gene and their use in the diagnosis of predisposition to melanoma, leukemia, astrocytoma, glioblastoma, lymphoma, glioma, Hodgkin's lymphoma, CLL, and cancers of the pancreas, breast, thyroid, ovary, uterus, testis, kidney, stomach and rectum. The invention also relates to the therapy of human cancers which have a mutation in the MTS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.
    Type: Grant
    Filed: April 29, 1997
    Date of Patent: November 23, 1999
    Assignees: University of Utah Research Foundation, Myriad Genetics, Inc.
    Inventors: Mark H. Skolnick, Lisa A. Cannon-Albright, Alexander Kamb
  • Patent number: 5989821
    Abstract: The present invention provides oligonucleotide primers and a method of using these primers for identification of the species of an organism, wherein the identification includes amplification of a variable polynucleotide sequence encoding a highly conserved region of a heat shock polypeptide.
    Type: Grant
    Filed: January 5, 1997
    Date of Patent: November 23, 1999
    Assignees: University of British Columbia, The National Research Council of Canada
    Inventors: Swee Han Goh, Anthony Chow, Sean Hemmingsen
  • Patent number: 5989812
    Abstract: An improved method of transcribing nucleic acids wherein the amount of abortive transcripts formed is reduced wherein the improvement comprises an effector sequence in the transcription reaction.
    Type: Grant
    Filed: November 22, 1995
    Date of Patent: November 23, 1999
    Assignee: Boehringer Mannheim GmbH
    Inventors: Viola Rosemeyer, Rudolf Seibl
  • Patent number: 5989817
    Abstract: The present invention provides a rapid and sensitive method for assaying nucleic acids by means of hybridization techniques, wherein the detector probes are modified primers being incorporated into copies of the target nucleic acid before the hybridization reaction and a reagent combination as well as a kit therefor. The invention also provides a method for assaying nucleic acids by means of hybridization techniques, wherein the capturing probes are modified primers being incorporated into copies of the target nucleic acids before the hybridization reaction.
    Type: Grant
    Filed: August 25, 1997
    Date of Patent: November 23, 1999
    Inventors: Hans Erik Soderlund, Arja Marjatta Weckman
  • Patent number: 5990303
    Abstract: The present invention provides 7-deaza-2'-deoxy-guanosine nucleotides of the general formula: ##STR1## wherein R is a --PO.sub.3 H.sub.2, --P.sub.2 O.sub.6 H.sub.3 or --P.sub.3 O.sub.9 H.sub.4 residue or an alkali metal, alkaline earth metal or ammonium salt of the phosphate groups.The present invention also provides processes for the preparation of these nucleotides and is also concerned with the use thereof in the sequencing of DNA.
    Type: Grant
    Filed: May 16, 1997
    Date of Patent: November 23, 1999
    Assignee: Roche Diagnostics GmbH
    Inventor: Frank Seela
  • Patent number: 5989870
    Abstract: A method is described for the identification and cloning of promoters that express under a defined environmental condition, such as growth in glucose medium. Using this method, five Trichodermal promoters capable of the high expression of operably linked coding sequences are identified, one of which is the promoter for T. reesei tef1. Also provided are altered cbh1 promoters, altered so that glucose no longer represses expression from such promoter. The invention further provides vectors and hosts that utilize such promoters, and unique fungal enzyme compositions from such hosts.
    Type: Grant
    Filed: February 16, 1995
    Date of Patent: November 23, 1999
    Assignee: Rohm Enzyme Finland Oy
    Inventors: Tiina Hannele Nakari, Maija-Leena Onnela, Marja Hannele Ilmen, Merja Elisa Penttila
  • Patent number: 5989855
    Abstract: A microorganism having a capability of introducing a 7.beta.-hydroxyl group into a 7-unsubstituted bile acid, and a process for preparing a bile acid having a 7.beta.-hydroxyl group characterized by bringing the above microorganism into contact with a 7-unsubstituted bile acid to convert the acid to a bile acid having a 7.beta.-hydroxyl group. The process permits ursodeoxycholic acid useful as a cholagogue and intermediates therefor to be efficiently prepared.
    Type: Grant
    Filed: September 29, 1998
    Date of Patent: November 23, 1999
    Assignee: Tokyo Tanabe Company Limited
    Inventors: Akio Okamura, Hiroyuki Matsui
  • Patent number: 5989871
    Abstract: Method and composition for detecting one or more selected polynucleotide regions in a target polynucleotide. In the method, a mixture of sequence-specific probes are reacted with the target polynucleotide under hybridization conditions, and the hybridized probes are treated to selectively modify those probes which are bound to the target polynucleotide in a base-specific manner. The resulting labeled probes include a polymer chain which imparts to each different-sequence probe, a distinctive ratio of charge/translational frictional drag, and a detectable label. The labeled probes are fractionated by electrophoresis in a non-sieving matrix, and the presence of one or more selected sequences in the target polynucleotide are detected according to the observed electrophoretic migration rates of the labeled probes in a non-sieiving medium.
    Type: Grant
    Filed: February 14, 1997
    Date of Patent: November 23, 1999
    Assignee: The Perkin-Elmer Corporation
    Inventors: Paul D. Grossman, Steven Fung, Steven M. Menchen, Sam Lee Woo, Emily S. Winn-Deen
  • Patent number: 5985558
    Abstract: Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of Activating Protein 1 (AP-1) expression are provided. In accordance with various embodiments of the present invention, oligonucleotides are provided which are specifically hybridizable with c-fos or c-jun, the genes encoding c-Fos or c-Jun, respectively. In a preferred embodiment, a method of modulating the metastasis of malignant tumors via modulation of one or more of the AP-1 subunits is provided; this method can be effected using the oligonucleotides of the invention or any other agent which modulates AP-1 or AP-1-mediated transcription.
    Type: Grant
    Filed: April 14, 1997
    Date of Patent: November 16, 1999
    Assignee: Isis Pharmaceuticals Inc.
    Inventors: Nicholas M. Dean, Robert McKay, Loren Miraglia, Brenda Baker
  • Patent number: 5985668
    Abstract: The invention relates to sucrose isomerases, to DNA sequences coding therefor, and to novel processes for producing noncariogenic sugars.
    Type: Grant
    Filed: June 27, 1996
    Date of Patent: November 16, 1999
    Assignee: Sudzucker Aktiengesellschaft Mannheim/Ochsenfurt
    Inventors: Ralf Mattes, Kathrin Klein, Sabine Stegmaier
  • Patent number: 5985664
    Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Sentrin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Sentrin. Methods of using these compounds for modulation of Sentrin expression and for treatment of diseases associated with expression of Sentrin are provided.
    Type: Grant
    Filed: December 17, 1998
    Date of Patent: November 16, 1999
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Brenda F. Baker, Lex M. Cowsert
  • Patent number: 5985663
    Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Interleukin-15. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Interleukin-15. Methods of using these compounds for modulation of Interleukin-15 expression and for treatment of diseases associated with expression of Interleukin-15 are provided.
    Type: Grant
    Filed: November 25, 1998
    Date of Patent: November 16, 1999
    Assignee: Isis Pharmaceuticals Inc.
    Inventors: C. Frank Bennett, Lex M. Cowsert
  • Patent number: 5985556
    Abstract: A kit and a method of DNA sequencing including digesting a sample DNA with a restriction enzyme to obtain a DNA fragment; introducing an oligonucleotide having a definite base sequence into the DNA fragment at the 3' terminus; and performing a complementary strand extension reaction, using a labeled primer. The complementary strand extension reaction uses as a template, a single strand of the DNA fragment having the oligonucleotide introduced thereinto, to obtain a labeled extended primer having a base sequence complementary to the single strand of the DNA fragment. Next a sequencing reaction with the labeled primer and using the single strand of the DNA fragment having the oligonucleotide introduced thereinto, is performed with the extended labeled primer, using as a template, a part of the single strand of the sample DNA having the base sequence of the single strand of the DNA fragment and a contiguous sequence adjacent thereto, or a single strand of the sample DNA.
    Type: Grant
    Filed: September 18, 1996
    Date of Patent: November 16, 1999
    Assignee: Hitachi, Ltd.
    Inventors: Hideki Kambara, Kazunori Okano
  • Patent number: 5985620
    Abstract: This invention describes compounds active against TNF-.alpha. mRNA. It further describes RNA molecules capable of conferring stability to RNA in vivo through an endogenous ribozyme binding protein(s). Possible mRNA molecules to be stabilized include ribozymes, antisense molecules and mRNA encoding polypeptides useful for protein production. The ribozymes and antisense molecules described herein are useful in mammals and plants, particularly suited for viral diseases. Methods of production and methods of use are also described.
    Type: Grant
    Filed: June 22, 1995
    Date of Patent: November 16, 1999
    Assignee: Gene Shears Pty. Limited
    Inventor: Mouldy Sioud
  • Patent number: 5985568
    Abstract: A method of photoelectro-manipulation of target molecules including providing a photoconductive layer of material having a first and a second electrically conductive contact on a first surface thereof and a probe on an opposed second surface. A solution containing target molecules is positioned in electrical contact with the probe. A positive potential is connected between the solution and the first electrically conductive contact and a negative potential is connected between the solution and the second electrically conductive contact. A beam of light is directed through a portion of the photoconductive layer of material to complete an electrical circuit between one of the first and the second electrically conductive contacts and the solution, whereby target molecules in the solution are attracted to or repelled from the probe which is coupled into the electrical circuit by the beam of light.
    Type: Grant
    Filed: September 4, 1997
    Date of Patent: November 16, 1999
    Assignee: Motorola, Inc.
    Inventors: Michael Krihak, Chan-Long Shieh
  • Patent number: 5985598
    Abstract: The present invention relates to nucleotide sequences of TCL-1 genes and amino acid sequences of their encoded proteins, as well as derivatives and analogs thereof, and antibodies thereto. The TCL-1 gene sequence is preferentially expressed early in T and B lymphocyte differentiation. The present invention further relates to the use of TCL-1 genes and their encoded proteins as diagnostic and therapeutic reagents for the detection and treatment of disease states associated with chromosomal abnormalities.
    Type: Grant
    Filed: October 27, 1994
    Date of Patent: November 16, 1999
    Assignees: Thomas Jefferson University, Raggio-Italgene S.p.A.
    Inventors: Giandomenico Russo, Carlo M. Croce
  • Patent number: 5985555
    Abstract: Method and device for processing nucleic acids in a reaction mixture on a surface that can be temperature-controlled and its immediate vicinity wherein the main space of the reaction mixture remains essentially isothermal. The method has the advantage of a very short processing time.
    Type: Grant
    Filed: September 19, 1996
    Date of Patent: November 16, 1999
    Assignee: Boehringer Mannheim GmbH
    Inventor: Wolf Bertling
  • Patent number: 5985549
    Abstract: Improved methodologies for in-situ hybridization and non-isotopic detection of nucleic acid sequences are provided which offer major increases of resolution, sensitivity, and simplicity unavailable in previously known techniques. The methodology is able to detect even a single-copy of a specific nucleic acid of interest under controlled conditions regardless of whether these are DNA or RNA sequences; or whether the nucleic acid sequence of interest is localized in the chromosomes, nucleus, or cytoplasm of a cell. The methods employ a variety of non-isotopic labels and detection means for rapid and reliable assays. The invention is also provided in kit form for use in the clinical/diagnostic laboratory such that a relatively unskilled person can accurately and reproducibly detect even a single-copy of a specific nucleic acid of interest.
    Type: Grant
    Filed: October 3, 1994
    Date of Patent: November 16, 1999
    Assignee: University of Massachusetts
    Inventors: Robert H. Singer, Jeanne B. Lawrence
  • Patent number: 5981173
    Abstract: The genomes of two novel human papillomavirus (HPV) types, HPV68 and HPV70, were cloned from a low grade cervical intraepithelial neoplasia and a vulvar papilloma, respectively, and sequenced. Both types are related to HPV39, a potentially oncogenic virus. HPV68 and HPV70 were also detected in genital intraepithelial neoplasia from three patients and one patient, respectively. Comparison with sequence data in the literature indicates that the subgenomic ME180-HPV DNA fragment, cloned from a carcinoma cell line, corresponds to an HPV68 subtype and that several HPV DNA fragments amplified by PCR from genital neoplasia represent worldwide distributed variants of HPV68 and HPV70.
    Type: Grant
    Filed: February 11, 1997
    Date of Patent: November 9, 1999
    Assignees: Institut Pasteur, Institut Nationale de la Sante Et de la Recherche Medicale
    Inventors: Gerard Orth, Sylvie Beaudenon, Michele Longuet
  • Patent number: 5981241
    Abstract: A method of producing erythritol is disclosed, in which a microorganism having an ability of producing erythritol is cultivated for generation in a medium containing preferably 5 ppm or more of calcium, and erythritol is collected from the culture, thus producing erythritol efficiently.
    Type: Grant
    Filed: December 4, 1998
    Date of Patent: November 9, 1999
    Assignee: Mitsubishi Chemical Corporation
    Inventors: Hiroshi Cho, Kenji Yamagishi, Shuichi Abe, Satoshi Morioka
  • Patent number: 5981733
    Abstract: An apparatus for the automated synthesis of molecular arrays. A jetting device is employed along with a reaction chamber to dispense reagents used in the synthesis onto the substrate. A positioning system moves the substrate from the jet to the reaction chamber. A controller controls the movement of the substrate and the application of the reagents so that the synthesis is carried out according to a pre-determined procedure. The apparatus will synthesize nucleotides in an array of micron-size spots according to a pattern selected by the operator immediately prior to synthesis.
    Type: Grant
    Filed: September 16, 1996
    Date of Patent: November 9, 1999
    Assignee: Incyte Pharmaceuticals, Inc.
    Inventors: Ronald C. Gamble, Thomas P. Theriault, John D. Baldeschwieler
  • Patent number: 5981186
    Abstract: The sequence of a target nucleic acid polymer can be determined by (a) performing a first chain-extension sequencing reaction on the target nucleic acid polymer in a reaction mixture containing first and second chain-terminators to produce a first product mixture containing commonly-labeled polynucleotide fragments complementary to a first strand of the target nucleic acid polymer, each fragment in the mixture being terminated with the first or second chain-terminator; (b) performing a second chain extension sequencing reaction on the target nucleic acid polymer in a reaction mixture containing the first and a third chain-terminator to produce a second product mixture containing commonly-labeled polynucleotide fragments complementary to the first strand of the target nucleic acid polymer, each fragment in the mixture being terminated with the first or the third chain-terminator, said first, second and third chain-terminators each being different; and (c) evaluating the lengths of the polynucleotide fragments
    Type: Grant
    Filed: July 14, 1997
    Date of Patent: November 9, 1999
    Assignee: Visible Genetics, Inc.
    Inventors: Chris Gabe, Rodney D. Gilchrist
  • Patent number: 5981171
    Abstract: Methods and compositions are provided for a rapid quantitative nucleic acid hybridization assay for detecting a DNA or RNA sequence in a biological sample. The method comprises solution hybridization of a target nucleic acid sequence with a detectably-labeled probe, separation of the target-nucleic acid probe from the unhybridized probe by gel exclusion or affinity chromatography and detection of the amount of labeled probe as an indication of the target nucleic acid present in the biological sample.
    Type: Grant
    Filed: July 6, 1990
    Date of Patent: November 9, 1999
    Assignee: Abbott Laboratories
    Inventor: Mary C. Kuhns
  • Patent number: 5981279
    Abstract: Constructs encoding calmodulin antisense molecules are disclosed. These constructs may be used to advantage to inhibit proliferation of malignant cells. The invention further comprises monoclonal antibody studded liposomes to facilitate cell-type specific delivery of the antisense calmodulin constructs. To enhance cell-type specific expression of calmodulin antisense sequences, cell-type specific promoters are employed to drive expression of the antisense molecules in targeted tissues.
    Type: Grant
    Filed: November 8, 1996
    Date of Patent: November 9, 1999
    Assignee: Allegheny University of the Health Sciences
    Inventor: Benjamin Weiss
  • Patent number: 5981181
    Abstract: There are described DNA sequences, that contain the coding region of an oligosaccharide transporter, whose introduction in a plant genome modifies the formation and transfer of storage materials in transgenic plants, plasmids, bacteria and plants containing these DNA sequences, a process for the preparation and transformation of yeast strains, that makes possible the identification of the DNA sequences of the plant oligosaccharide transporter of the invention, as well as the use of DNA sequences of the invention.
    Type: Grant
    Filed: January 21, 1997
    Date of Patent: November 9, 1999
    Assignee: Hoechst Schering AgrEvo GmbH
    Inventors: Wolf-Bernd Frommer, Jorg Riesmeier
  • Patent number: 5981183
    Abstract: In a method for amplifying the specific nucleic acid sequence, a highly specific amplification which has low possibility of non-specific hybridization can be carried out. Highly stable reagents, the activities of which do not decrease in case of supply and storage, are also provided. Thermostable enzymes are used as RNA dependent DNA polymerase, DNA dependent DNA polymerase, DNA dependent RNA polymerase and ribonuclease H, which are required for the amplification system based on replicated RNA. Especially, it is preferable that a thermostable enzyme derived from Thermus thermophilus which has RNA dependent DNA polymerase activity, DNA dependent DNA polymerase activity and ribonuclease H activity, and thermostable DNA dependent RNA polymerase are used together. By this method, inactivation of enzymes are prevented by using thermostable enzymes, and the amplification can be carried out without sequential addition of enzymes.
    Type: Grant
    Filed: March 20, 1997
    Date of Patent: November 9, 1999
    Assignee: Toyo Boseki Kabushiki Kaisha
    Inventors: Yutaka Takarada, Hiroaki Inoue, Shuji Shibata, Yoshihisa Kawamura
  • Patent number: 5981235
    Abstract: Solutions containing nucleic acids are treated with an alkaline protease to digest proteins such as nucleases that degrade the nucleic acids. In the isolation of nucleic acids, a biological sample containing nucleic acids is suspended in a solution containing water, buffer and chelating agent, the pH of the solution is adjusted to at least about 10 by adding a solution of sodium hydroxide and anionic detergent, an alkaline protease is incubated in the solution until nucleases are degraded, the pH of the solution is lowered to reduce activity of the alkaline protease by adding a solution having a pH between 3.5 and 4.5 and the alkaline protease is heat inactivated. Lowering of the pH may produce a cloudy solution which is cleared by centrifuging. Nucleic acids are isolated from the cleared solution by alcohol precipitation, or by using paramagnetic particles or a resin matrix containing silica particles. A chaotropic salt can be used to reversibly bind DNA to the resin matrix.
    Type: Grant
    Filed: July 29, 1996
    Date of Patent: November 9, 1999
    Assignee: Promega Corporation
    Inventors: John Shultz, Craig E. Smith, Douglas R. Storts, Paula Brisco, Judy Frederiksen, Susanne Selman, Josephine Grosch
  • Patent number: 5981726
    Abstract: This invention provides for recombinant single chain antibodies capable of specifically binding to a Lewis.sup.Y -related carbohydrate antigen and fusion proteins comprising these antibodies. More particularly, the invention provides for single chain Fv regions of the monoclonal antibodies B1 and B5. The invention also provides for a number of stabilizing mutations of the Lewis.sup.Y -binding monoclonal antibody B3. In addition, the invention provides for methods of detecting cells bearing a Lewis.sup.Y antigen in a patient and for methods of killing or inhibiting the growth of cells bearing a Lewis.sup.Y antigen in a patient.
    Type: Grant
    Filed: October 28, 1994
    Date of Patent: November 9, 1999
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: Ira Pastan, Itai Benhar
  • Patent number: 5976874
    Abstract: External guide sequences ("EGS") can be used to promote RNAase P-mediated cleavage of RNA transcribed from plasmids and other genetic elements which confer drug resistance on bacterial cells. Such cleavage can render the bacteria drug sensitive. In a preferred embodiment, a vector encoding an EGS is administered to an animal or human harboring antibiotic resistant bacterial cells such that the EGS is expressed in the bacterial cells, the EGS promotes RNAase P-mediated cleavage of RNA involved in conferring antibiotic resistance to the cells, and the cells are rendered antibiotic sensitive. A preferred form of administration is via inoculation of the animal or human with cells containing genes for appropriate EGSs on promiscuous plasmids. These plasmids will spread quickly through the antibiotic-resistant population of bacterial cells, thereby making the cells susceptible to antibiotic therapy.
    Type: Grant
    Filed: August 15, 1997
    Date of Patent: November 2, 1999
    Assignee: Yale University
    Inventors: Sidney Altman, Cecilia Guerrier-Takada
  • Patent number: 5976842
    Abstract: Methods and compositions are provided for performing high fidelity polymerase chain reactions. In the subject methods, primer extension products are produced with a low error frequency rate through the use of at least one of unequal concentrations of dNTPs or a melting point reducing agent. Also provided are kits and reagent mixtures for use in the subject methods. The subject invention finds use in a variety of applications, particularly in applications where high fidelity PCR is desired.
    Type: Grant
    Filed: October 30, 1997
    Date of Patent: November 2, 1999
    Assignee: Clontech Laboratories, Inc.
    Inventor: Helmut Wurst
  • Patent number: 5976802
    Abstract: The invention concerns a method for the sequence-specific labelling of nucleic acids comprising the generation of labelled nucleic acid fragments by an enzymatic labelling reaction in which a labelled deoxyribonucleoside triphosphate is attached to a nucleic acid primer molecule and the nucleic acid sequence is determined by means of the label, wherein the labelling reaction is carried out in a single reaction vessel with the simultaneous presence of one or several nucleic acid primer molecules and at least two labelled deoxyribonucleoside triphosphates which each contain different labelling groups and different bases and under conditions in which only one single type of labelled deoxyribonucleoside triphosphate can be attached to a nucleic acid primer molecule.
    Type: Grant
    Filed: September 29, 1997
    Date of Patent: November 2, 1999
    Assignee: Europasches Laboratorium fur Molekularbiologie (EMBL)
    Inventors: Wilhelm Ansorge, Hartmut Voss, Josef Stegemann, Stefan Wiemann
  • Patent number: 5977343
    Abstract: Method for purification and synthesis of RNA molecules and enzymatic RNA molecules in enzymatically active form.
    Type: Grant
    Filed: August 15, 1997
    Date of Patent: November 2, 1999
    Assignee: Ribozyme Pharmaceuticals, Inc.
    Inventor: Danuta Tracz
  • Patent number: 5976851
    Abstract: Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. The nucleotide and amino acid sequences of the .alpha. and .beta. subunits of both rat and human farnesyl transferase are disclosed, as are methods and compositions for the preparation of farnesyl transferase by recombinant means, following the molecular cloning and co-expression of its two subunits, for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21.sup.ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme.
    Type: Grant
    Filed: February 16, 1993
    Date of Patent: November 2, 1999
    Assignee: Board of Regents, The University of Texas System
    Inventors: Michael S. Brown, Joseph L. Goldstein, Yuval Reiss
  • Patent number: 5976855
    Abstract: The present invention relates to a method of preparing a variant of a parent lipolytic enzyme, comprising (a) subjecting a DNA sequence encoding the parent lipolytic enzyme to random mutagenesis, (b) expressing the mutated DNA sequence obtained in step (a) in a host cell, and (c) screening for host cells expressing a mutated lipolytic enzyme which has a decreased dependance to calcium and/or an improved tolerance towards a detergent or a detergent component as compared to the parent lipolytic enzyme.
    Type: Grant
    Filed: August 22, 1996
    Date of Patent: November 2, 1999
    Assignee: Novo Nordisk A/S
    Inventors: Allan Svendsen, Ib Groth Clausen, Jens Sigurd Okkels, Marianne Thellersen
  • Patent number: 5976879
    Abstract: A method of combatting aberrant splicing in a pre-mRNA molecule containing a mutation is disclosed. When present in the pre-mRNA, the mutation causes the pre-mRNA to splice incorrectly and produce an aberrant mRNA or mRNA fragment different from the mRNA ordinarily encoded by the pre-mRNA. The method comprises hybridizing an antisense oligonucleotide to the pre-mRNA molecule to create a duplex molecule under conditions which permit splicing. The antisense oligonucleotide is one which does not activate RNase H, and is selected to block a member of the aberrant set of splice elements created by the mutation so that the native intron is removed by splicing and the first mRNA molecule encoding a native protein is produced. Oligonucleotides useful for carrying out the method are also disclosed.
    Type: Grant
    Filed: April 30, 1999
    Date of Patent: November 2, 1999
    Assignee: The University of North Carolina at Chapel Hill
    Inventors: Ryszard Kole, Zbigniew Dominski
  • Patent number: 5977341
    Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Inhibitor-kappa B Kinase-beta. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Inhibitor-kappa B Kinase-beta. Methods of using these compounds for modulation of Inhibitor-kappa B Kinase-beta expression and for treatment of diseases associated with expression of Inhibitor-kappa B Kinase-beta are provided.
    Type: Grant
    Filed: November 20, 1998
    Date of Patent: November 2, 1999
    Assignee: Isis Pharmaceuticals Inc.
    Inventors: Brett P. Monia, Lex M. Cowsert