Patents Represented by Attorney Daryl D. Muenchau
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Patent number: 5792847Abstract: Oligomers which have substituents on the 2' position are resistant to oligonucleases and furthermore can be derivatized to deliver reagents or drugs, to carry label, or to provide other properties.Type: GrantFiled: June 6, 1995Date of Patent: August 11, 1998Assignee: Gilead Sciences, Inc.Inventors: Chris A. Buhr, Mark Matteucci
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Patent number: 5777153Abstract: The present invention is directed to new cationic lipids and intermediates in their synthesis that are useful for transfecting nucleic acids or peptides into prokaryotic or eukaryotic cells. The lipids comprise one or two arginine, lysine or ornithine residues linked to a lipophilic moiety. The lipids form a composition when mixed with polyanions such as nucleic acids. The compositions permit efficient transfer of polyanions into cells without significant toxicity to the cells.Type: GrantFiled: July 8, 1994Date of Patent: July 7, 1998Assignee: Gilead Sciences, Inc.Inventors: Kuei-Ying Lin, Jason G. Lewis, Mark D. Matteucci, Richard W. Wagner
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Patent number: 5763208Abstract: Oligonucleotides that are capable of passive diffusion across cell membranes are disclosed. These oligonucleotides contain at least two nucleotide residues and show a log distribution coefficient in octanol:water of about 0.0-2.5 and a solubility in water of at least 0.001 .mu.g/mL. In preferred embodiments, either at least 80% of the internucleotide linkages are non-ionic, or at least 80% of the bases contain lipophilic hydrocarbyl substitutions, or a combination of these sums to 80%. These oligonucleotides may be conjugated to label and used to visualize cells.Type: GrantFiled: February 28, 1996Date of Patent: June 9, 1998Assignee: Gilead Sciences, Inc.Inventors: Norbert Bischofberger, Ken Kent, Rick Wagner, Chris Buhr, Kuei-Ying Lin
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Patent number: 5763424Abstract: The invention provides compositions and methods to prevent the appearance of visually detectable precipitate in the composition upon storage of an aqueous solution of the composition containing 5-250 mg/mL of the phosphonate nucleotide analog for at least 6 months at 22.degree. where the composition comprises a phosphonate nucleotide analog and a sufficient amount of a divalent or trivalent metal cation sequestering agent such as about 0.1% w/v EDTA, and/or a sufficiently low concentration of a divalent or trivalent metal cation, e.g., about 3-10 ppm, and/or a sufficient pH in water, e.g., a pH of about 7.0-7.5.Type: GrantFiled: March 26, 1996Date of Patent: June 9, 1998Assignee: Gilead Sciences, Inc.Inventor: Lung-Chi J. Yuan
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Patent number: 5721218Abstract: Oligonucleotides having tandem sequences of inverted polarity, i.e., oligonucleotides comprising regions of the formula:3'----------5'----C----5'----------3' (1)or5'----------3'----C----3'----------5' (2)wherein --C-- symbolizes any method of coupling the nucleotide sequence of opposite polarity,are useful for forming an extended triple helix with a double-helical nucleotide duplex. The inverted polarity also stabilizes the single-strand oligonucleotides to exonuclease degradation.Type: GrantFiled: March 11, 1996Date of Patent: February 24, 1998Assignee: Gilead Sciences, Inc.Inventor: Brian Froehler
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Patent number: 5717095Abstract: A cyclic nucleotide phosphonate ester characterized by the presence of an n-butyl salicylate ester group linked to the phosphorus atom of cHPMPC is disclosed. The analog comprises an ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog.Type: GrantFiled: December 27, 1996Date of Patent: February 10, 1998Assignee: Gilead Sciences, Inc.Inventors: Murty N. Arimilli, Robert J. Jones, Ernest J. Prisbe
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Patent number: 5705693Abstract: The present invention is directed to new cationic lipids and intermediates in their synthesis that are useful for transfecting nucleic acids or peptides into prokaryotic or eukaryotic cells. The lipids comprise one or two substituted arginine, lysine or ornithine residues, or derivatives thereof, linked to a lipophilic moiety. The lipids form a complex when mixed with polyanions such as nucleic acids or peptides. The complexes permit efficient transfer of polyanions into cells, usually without significant toxicity to the cells.Type: GrantFiled: July 7, 1995Date of Patent: January 6, 1998Assignee: Gilead Sciences, Inc.Inventors: Randolph B. DePrince, Kevin L. Facchine, George S. Lewis, Jason G. Lewis, Kuei-Ying Lin, Mark D. Matteucci, Robert A. Mook, Jr., Richard W. Wagner
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Patent number: 5672697Abstract: Novel oligonucleotides analogs and nucleoside analogs as well as methods for their synthesis are described. The oligonucleotides are useful in diagnostic and therapeutic applications. The oligonucleotides are stable to nuclease degradation.Type: GrantFiled: February 8, 1991Date of Patent: September 30, 1997Assignee: Gilead Sciences, Inc.Inventors: Chris Buhr, Mark Matteucci, Norbert W. Bischofberger, Brian Froehler
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Patent number: 5656745Abstract: Nucleotide analogs characterized by the presence of an amidate linked amino acid or an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise a phosphoamidate or ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.Type: GrantFiled: September 17, 1993Date of Patent: August 12, 1997Assignee: Gilead Sciences, Inc.Inventors: Norbert Bischofberger, Robert J. Jones, Murty Arimilli, Kuei-Ying Lin, Michael Louie, Lawrence R. McGee, Ernest J. Prisbe
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Patent number: 5645985Abstract: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used used for diagnostic purposes in order to detect viruses or disease conditions.Type: GrantFiled: November 25, 1992Date of Patent: July 8, 1997Assignee: Gilead Sciences, Inc.Inventors: Brian Froehler, Rick Wagner, Mark Matteucci, Robert J. Jones, Arnold J. Gutierrez, Jeff Pudlo
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Patent number: 5646269Abstract: The present invention is directed to improved methods to synthesize oligonucleotide analogs having an acetal linkage, such as a 3',5'-formacetal (3' --O--CH.sub.2 --O-- 5'), 3',5'-thioformacetal (3' --S--CH.sub.2 --O-- 5') or an analogous 2',5' linkage between adjacent nucleoside analog residues. Compositions comprising 5', 3' and 2' phosphinate nucleoside analogs useful in the methods are also provided.Type: GrantFiled: April 28, 1994Date of Patent: July 8, 1997Assignee: Gilead Sciences, Inc.Inventors: Mark D. Matteucci, Jiancun Zhang
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Patent number: 5633360Abstract: Oligonucleotides that are capable of passive diffusion across cell membranes are disclosed. These oligonucleotides contain at least two nucleotide residues and show a log distribution coefficient in octanol:water of about 0.0-2.5 and a solubility in water of at least 0.001 .mu.g/mL. In preferred embodiments, either at least 80% of the internucleotide linkages are non-ionic, or at least 80% of the bases contain lipophilic hydrocarbyl substitutions, or a combination of these sums to 80%. These oligonucleotides may be conjugated to label and used to visualize cells.Type: GrantFiled: April 14, 1992Date of Patent: May 27, 1997Assignee: Gilead Sciences, Inc.Inventors: Norbert Bischofberger, Ken Kent, Rick Wagner, Chris Buhr, Kuei-Ying Lin
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Patent number: 5596086Abstract: Oligonucleotide analogs are disclosed wherein one or more phosphodiester linkages between adjacent nucleotides are replaced by a backbone linkage resistant to nucleases. The modified oligonucleotides are capable of strong hybridization to target RNA or DNA. The oligomers of the invention may be used as diagnostic reagents to detect the presence or absence of the target DNA or RNA sequences to which they bind.Type: GrantFiled: September 20, 1991Date of Patent: January 21, 1997Assignee: Gilead Sciences, Inc.Inventors: Mark Matteucci, Robert J. Jones, John Munger
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Patent number: 5594121Abstract: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain 7-deaza-7-substituted purines or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention. Compositions of the invention can be used for diagnostic purposes in order to detect viruses or disease conditions.Type: GrantFiled: June 7, 1995Date of Patent: January 14, 1997Assignee: Gilead Sciences, Inc.Inventors: Brian Froehler, Mark Matteucci
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Patent number: 5582981Abstract: A method for identifying oligomer sequences which specifically bind target biomolecules is described. The technique involves complexation of the support-bound target molecule with a mixture of oligonucleotides containing random sequences and sequences which serve as primer for PCR under conditions wherein a complex is formed with the specifically binding sequences, but not with the other members of the oligonucleotide mixture. The target-oligonucleotide complexes are then separated from both the support and the uncomplexed oligonucleotides and the complexed members of the oligonucleotide mixture are recovered from the separated complex and subsequently amplified using the polymerase chain reaction. The recovered oligonucleotides may be sequenced, and successive rounds of selection using complexation, separation, amplification and recovery can be employed.Type: GrantFiled: April 28, 1994Date of Patent: December 10, 1996Assignee: Gilead Sciences, Inc.Inventors: John J. Toole, John Latham, Louis C. Bock, Linda C. Griffin
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Patent number: 5484908Abstract: Oligonucleotides with enhanced hybridization binding possessing 5-propynyluracil and/or 5-propynylcytosine in place of uracil and cytosine, respectively. These oligonucleotides are useful in traditional hybridization assays for detection of a specific DNA sequence.Type: GrantFiled: November 26, 1991Date of Patent: January 16, 1996Assignee: Gilead Sciences, Inc.Inventors: Brian Froehler, Robert J. Jones
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Patent number: 5434257Abstract: Oligonucleotide analogs having one or more substitute linkages of the formula 2'/3'--S--CH.sub.2 --CH.dbd.5' or 2'/3'--O--CH.sub.2 --CH.dbd.5' between adjacent nucleomonomers are disclosed. The substitute linkage replace the usual phosphodiester linkage found in unmodified nucleic acids. The oligonucleotide analogs are easy to synthesize, stable in vivo, resistant to endogenous nucleases and are able to hybridize to target nucleic acid sequences in a sequence specific manner.Type: GrantFiled: October 26, 1993Date of Patent: July 18, 1995Assignee: Gilead Sciences, Inc.Inventors: Mark D. Matteucci, Xiaodong Cao
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Patent number: 5386030Abstract: The present invention concerns nucleotide analogs and their compositions and use. In particular it relates to novel (phosphonomethoxy) methoxy purine/pyrimidine derivatives.Type: GrantFiled: February 11, 1993Date of Patent: January 31, 1995Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Science of the Czech Republic, Rega Stichting v.z.w.Inventors: Choung U. Kim, John C. Martin, Bing Y. Luh, Peter F. Misco