Gilead Sciences, Inc.

Isis Pharmaceuticals, Inc.

Genentech, Inc.

Other

Brian C. Froehler

Brian C Froehler

Mark D Matteucci

Arnold J Gutierrez

Robert J Jones

Jeff Pudlo

Rick Wagner

Chris A Buhr

Sylvia Wu

Kenneth M Kent

Mark Mattencci

Norbert W Bischofberger

Kenneth Michael Kent

The present invention provides 2-aminopyridine and 2-pyridone C-nucleosides and oligonucleotides containing the subject nucleosides. The nucleosides are useful in the preparation of the subject oligonucleotides. The oligonucleotides are useful in oligonucleotide-based diagnosis and separation through triplex binding.

2-aminopyridine and 2-pyridone C-nucleosides

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 incorporated into pharmaceutically acceptable carriers and 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 as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines

Novel hydrogen-phosphonodithioate compositions are provided which are particularly useful for forming internucleotide and internucleoside linkages in oligonucleosides or oligonucleotides. The oligonucleotides and analogs thereof made by using the hydrogen-phosphonodithioate compositions may be therapeutically useful as antiviral and anticancer agents and may have other therapeutic or diagnostic uses. A method for making the hydrogen-phosphonodithioates is provided as well as a method for converting same to an activated intermediate for substitution on the phosphorus atom.

Nucleoside hydrogen phosphonodithioate diesters and activated phosphonodithioate analogues

Oligonucleotides including 2-aminopyridine and 2-pyridone C-nucleoside units

2-Aminopyridine and 2-pyridone C-nucleosides, oligonucleotides comprising, and tests using the same oligonucleotides

The present invention describes methods for the production of oligonucleotides under conditions which exploit the desirable characteristics, such as the property of sustaining high degrees of substitution, of functionalized organic polymeric supports while avoiding the sluggish kinetics and low rates of conversion which normally plague syntheses involving such solid supports. By employing the methods and materials disclosed, functionalized support, substituted to a degree of about 250 &mgr;mol/g, can be utilized at greater than 98% conversion levels for each sequential nucleotide coupling cycle, to provide unprecedented amounts of isolated oligonucleotide per gram of solid support.

Large scale synthesis of oligonucleotides and their associated analogs

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 base analog 5-propynyluracil, 5-propynylcytosine 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 may 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.

Enhanced triple-helix and double-helix formation directed by oligonucleotides containing modified pyrimidines

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 incorporated into pharmaceutically acceptable carriers and 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 as pharmaceutical agents to treat various diseases such as those caused by viruses and can be used for diagnostic purposes in order to detect viruses or disease conditions.

Methods of using oligomers containing modified pyrimidines

Oligonucleotides having tandem sequences of inverted polarity, i.e., oligonucleotides comprising regions of the formula:

Oligonucleotides with inverted polarity

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.

Nucleoside 5'-methylene phosphonates

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.

Enhanced triple-helix and double-helix formation with oligomers

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.

Growing community of inventors

Belmont, CA, United States of America

Brian C Froehler