Abstract: The invention concerns a method and device for the rapid, simultaneous isolation of genomic desoxyribonucleic acid (DNA) and cellular total ribonucleic acid (RNA), free of genomic DNA from various starting materials. The fields of application are molecular biology, biochemistry, gene technology (in particular gene therapy), medicine, biomedical diagnosis, veterinary medicine, food analysis and all related fields. The method proposed is characterized in that materials containing DNA and RNA are lysed in a special buffer, the lysate incubated with a mineral carrier, the carrier with the DNA bound to it separated off and washed with buffer solution, and the DNA subsequently separated from the carrier with a buffer of lower salt concentration. The lysate left after separating off the DNA bound to the carrier is mixed with phenol, chloroform and sodium acetate in defined proportions, the phases allowed to separate, and the total RNA precipitated from the aqueous phase by adding isopropanol.
Abstract: A process for the preparation of 4"-deoxyerythromycins, having the formula: ##STR1## wherein R is H or OH, R.sup.1 is H or loweralkyl, and R.sup.2 is H or CH.sub.3 by treatment of the starting material, 2'-O-acetyl-4"-imidazolylthiocarbamoyl-erythromycin, with a hypophosphite reagent, in a water-miscible protic solvent optionally comprising a phase transfer agent. In a preferred embodiment, the water-miscible solvent is an alcohol and the starting material is reacted with sodium hypophosphite, ACVA and tetra-n-butylammonium hydroxide.
Type:
Grant
Filed:
March 6, 1998
Date of Patent:
March 21, 2000
Assignee:
Abbott Laboratories
Inventors:
Alexandra E. Graham, Albert V. Thomas, Rachel R. P. Yang
Abstract: 5,5'-Pyrophosphates of non-naturally occurring nucleosides selected from 1-(1-thyminyl)-3-azido-2, 3-dideoxy-D-riboside, 1(5-fluoro-1-uracilyl)-2, 3-dideoxy-D-riboside, 1-(1-uracilyl)-3-azido-2, 3-dideoxy-D-riboside, 1-(9-guaninyl)-2, 3-dideoxy-D-riboside, 1-(9-hypoxanthinyl)-2, 3-dideoxy-D-riboside, 1-(1-cytosinyl)-2, 3-dideoxy-D-riboside, and 1-(9-adeninyl)-2, 3-dideoxy-D-riboside, are described as well as their manufacture and use as therapeutic agents against tumors and retroviral infections including HIV infections. The compounds may be administered as the active ingredients of pharmaceutical compositions or as prodrugs encapsulated within biological carriers, e.g. transformed erythrocytes, for targeting to specific cell populations responsible for the development of the noted pathological disorders.
Type:
Grant
Filed:
January 14, 1997
Date of Patent:
March 21, 2000
Assignees:
Biosearch Italia, S.p.A., Gruppo Lepetit, S.p.A.
Inventors:
Antonio De Flora, Umberto Benatti, Marco Giovine
Abstract: The present invention provides a practical method capable of chemically synthesizing a 100-mer or more long-chain oligonucleotide easily and reliably and a novel compound used in said method. The present invention relates to a method for chemical synthesis of an oligonucleotide by the phosphoroamidite method, which comprises preparing a base moiety-unprotected nucleoside phosphoroamidite from a base moiety-unprotected nucleoside by use of an imidazole trifluoromethanesulfonate represented by the following chemical formula, and coupling said base moiety-unprotected nucleotide phosphoroamidite in a predetermined order to chemically synthesize an oligonucleotide consisting of a specific nucleotide sequence, as well as to an imidazole trifluoromethanesulfonate represented by the chemical formula.
Type:
Grant
Filed:
September 3, 1998
Date of Patent:
March 21, 2000
Assignee:
Japan Science and Technology Corporation
Abstract: The present invention is directed to a method of synthesizing sulfurized oligonucleotide analogs by reacting an oligonucleotide analog containing a phosphorous(III) linkage with a dithiocarbonic acid diester polysulfide having the formula ##STR1## to produce a sulfurized oligonucleotide analog. The diester polysulfide reagent is useful in solution and solid phase oligonucleotide analog synthesis.
Type:
Grant
Filed:
June 25, 1998
Date of Patent:
March 21, 2000
Assignee:
ISIS Pharmaceuticals, Inc.
Inventors:
Zacharia S. Cheruvallath, Vasulinga T. Ravikumar, Douglas L. Cole, Daniel C. Capaldi
Abstract: Methods of modulating the activity of the TAR element of HIV are provided. Oligonucleotides having 6 to 50 bases and at least one 2'-O alkyl modification and selected sequences are disclosed.
Abstract: Replacement of the natural nucleotides with unnatural zwitterionic nucleotides having a cationic moiety tethered to the base (or analog thereof) results in oligodeoxynucleotides with diminished charge but undiminished ability to complex with DNA at low ionic strengths. We have now discovered that DNA can be made fully zwitterionic by introducing tethered cationic moieties to the bases without affecting duplex formation. The resulting oligonucleotides have the further advantages of being nuclease resistant.
Type:
Grant
Filed:
July 26, 1996
Date of Patent:
February 29, 2000
Assignee:
The Regents of the University of California
Abstract: Antimicrobial compounds having the formula ##STR1## as well as pharmaceutically acceptable salts, esters or prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.
Type:
Grant
Filed:
November 4, 1998
Date of Patent:
February 22, 2000
Assignee:
Abbott Laboratories
Inventors:
Yat Sun Or, Zhenkun Ma, Richard F. Clark, Daniel T. Chu, Jacob J. Plattner, George Griesgraber
Abstract: The present invention relates to the discovery that certain .beta.-L-dioxolane nucleoside analogs which contain a uracil base, and preferably, a 5-halosubstituted uracil base, exhibit unexpectedly high activity against Epstein-Barr virus (EBV), Varciella-Zoster virus (VZV) and Herpes Virus 8 (HV-8). In particular, the compounds according to the present invention show potent inhibition of the replication of the virus (viral growth) in combination with very low toxicity to the host cells (i.e., animal or human tissue). Compounds are useful for treating EBV, VZV and HV-8 infections in humans.
Type:
Grant
Filed:
October 21, 1997
Date of Patent:
February 8, 2000
Assignee:
Yale University
Inventors:
Chung K. Chu, Fucheng Qu, Yung-Chi Cheng
Abstract: Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, and phosphorodithioate covalent linkages. Also provided are synthetic intermediates useful in such processes.
Type:
Grant
Filed:
February 10, 1998
Date of Patent:
February 1, 2000
Assignee:
Isis Pharmeuticals, Inc.
Inventors:
Daniel C. Capaldi, Vasulinga T. Ravikumar
Abstract: This invention discloses a method for the preparation of 2'-modified nucleosides, using a palladium catalyst and an alkene functionalized with a heteroatom. Included in the invention are the novel pyrimidines and purines that can be prepared according to the method of the invention and oligonucleotides containing said modified pyrimidines and purines.
Abstract: A method for inhibiting replication of HIV, which comprises subjecting HIV-infected cells to a composition (a) comprising as a primary component a polysaccharide derived from a hot aqueous solvent extract of tubercle bacillus.
Abstract: The object of the present invention is a pharmaceutical composition, which comprises, as active principle, a combination of an adenosinergic agonist and a compound selected from the opiates, benzodiazepines and NMDA antagonists.
Type:
Grant
Filed:
December 7, 1998
Date of Patent:
January 18, 2000
Assignee:
Laboratoires UPSA
Inventors:
Francoise Camborde, Alix Cloarec, Timur Gungor, Jean-Marie Teulon
Abstract: The present invention relates to a method for treating AIDS, which comprises administering to an HIV-infected patient (a) a composition containing as the primary component a polysaccharide derived from a hot water extract of human-type tubercle bacillus and (b) a nucleoside-type anti-HIV agent. Due to the incorporation of composition (a), the present invention enhances the therapeutic effect of nucleoside-type anti-HIV agents on AIDS.
Abstract: This invention relates to synthetic oligonucleotides that are useful for antisense based therapeutic applications. The synthetic oligonucleotides of this invention have modifications in the sugar phosphate backbone for improved antisense properties.
Type:
Grant
Filed:
February 5, 1997
Date of Patent:
January 18, 2000
Assignees:
ChemGenes Corporation, Oligos Etc., Inc.
Inventors:
Roderic M. K. Dale, Amy Arrow, Suresh C. Srivastava, Syed K. Raza
Abstract: A linker arm for solid support oligonucleotide synthesis, the linker arm comprising formula (1), wherein: X.sup.1 is selected from the group consisting of --O--, --S--, --S(O).sub.2 --, --C(O)-- and --N(R.sup.12)--; R.sup.12 is selected from the group comprising hydrogen, a substituted or unsubstituted C.sub.1 -C.sub.20 alkyl group, a substituted or unsubstituted C.sub.5 -C.sub.30 aryl group and a substituted or unsubstituted C.sub.5 -C.sub.40 alkaryl group, X.sup.3 is --O-- or --N(H)--; R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different and are selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C.sub.1 -C.sub.20 alkyl group, a substituted or unsubstituted C.sub.5 -C.sub.30 aryl group and a substituted or unsubstituted C.sub.5 -C.sub.40 alkylaryl group; n is 0, 1 or 2; and one of A' and B' is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C.sub.1 -C.sub.20 alkyl group, a substituted or unsubstituted C.sub.5 -C.
Type:
Grant
Filed:
June 19, 1998
Date of Patent:
January 18, 2000
Assignee:
University Technologies International Inc.
Abstract: The invention provides a cationic polynucleoside chain having multiple nucleosides, the nucleosides being coupled together by positively charged guanidyl linkages.
Type:
Grant
Filed:
January 5, 1996
Date of Patent:
January 11, 2000
Assignee:
The Regents of The University of California
Inventors:
Thomas C. Bruice, Robert O. Dempcy, Orn Almarsson
Abstract: Provided is an artificial nucleic acid which has a double-stranded structure made of two oligonucleotides, where the oligonucleotide has in a sugar-phosphate backbone structure thereof a sugar moiety having a group having a metal-coordinating site, and the two oligonucleotides are bound together through a metal complex structure formed by coordination of the metal-coordinating site to a metal ion. Also provided is a nucleotide useful for synthesizing the artificial nucleic acid.
Abstract: There is described a polycarboxylic acid or a salt thereof obtained by oxidation of a polysaccharide containing an anhydrous glucose as a constituent unit, wherein the carboxyl group content thereof is high and the weight average molecular weight thereof is not less than 2000. This polycarboxylic acid is suitable for use as a builder for detergent because the amount of an alkali required to perform neutralization titration of the polycarboxylic acid is not less than 435 mg in terms of sodium hydroxide and because the chelate force thereof to a polyvalent cation is high.The polycarboxylic acid is produced by oxidizing a polysaccharide with an oxidizing agent in the presence of a transition metal catalyst.
Abstract: The present invention is related to a novel class of decarboxylase enzyme inhibitors consisting of .alpha.-oxiranyl amino acids and derivatives thereof and a method of synthesizing such compounds.
Type:
Grant
Filed:
July 22, 1997
Date of Patent:
December 28, 1999
Assignee:
Board of Regents University of Nebraska-Lincoln
Inventors:
David B. Berkowitz, Michelle L. Pedersen