Compounds and methods for synthesis and therapy
Granted: September 14, 1999
Patent Number:
5952375
Novel compounds are described. The compounds generally comprise an acidic group, a basic group, a substituted amino or N-acyl and a group having an optionally hydroxylated alkane moiety. Pharmaceutical compositions comprising the inhibitors of the invention are also described. Methods of inhibiting neuraminidase in samples suspected of containing neuraminidase are also described. Antigenic materials, polymers, antibodies, conjugates of the compounds of the invention with labels, and…
Nucleotide analog composition and synthesis method
Granted: August 10, 1999
Patent Number:
5935946
The invention provides a composition comprising bis(POC)PMPA and fumaric acid (1:1). The composition is useful as an intermediate for the preparation of antiviral compounds, or is useful for administration to patients for antiviral therapy or prophylaxis. The composition is particularly useful when administered orally. The invention also provides methods to make PMPA and intermediates in PMPA synthesis. Embodiments include lithium t-butoxide, 9-(2-hydroxypropyl) adenine and diethyl…
Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability
Granted: July 13, 1999
Patent Number:
5922695
Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C12 alkyl; X is N or O; R is…
Nucleotide analogs
Granted: March 23, 1999
Patent Number:
5886179
Nucleotide phosphonate esters characterized by the presence of an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise an ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.
Preparation of carbocyclic compounds
Granted: March 23, 1999
Patent Number:
5886213
The present invention provides new synthetic methods and compositions. In particular, new methods of preparing intermediates useful in the synthesis of neuraminidase inhibitors and compositions useful as intermediates that are themselves useful in the synthesis of neuraminidase inhibitors are provided.
Carbocyclic compounds
Granted: February 2, 1999
Patent Number:
5866601
Novel carbocyclic compounds are described. The compounds generally comprise an acidic group, a basic group, a substituted amino or N-acyl and a group having an optionally hydroxylated alkane moiety. Pharmaceutical compositions comprising the inhibitors of the invention are also described. Methods of inhibiting neuraminidase in samples suspected of containing neuraminidase are also described. Antigenic materials, polymers, antibodies, conjugates of the compounds of the invention with…
Preparation of carbocyclic compounds
Granted: January 12, 1999
Patent Number:
5859284
The present invention provides new synthetic methods and compositions. In particular, new methods of preparing intermediates useful in the synthesis of neuraminidase inhibitors and compositions useful as intermediates that are themselves useful in the synthesis of neuraminidase inhibitors are provided.
Aptamer analogs specific for biomolecules
Granted: November 24, 1998
Patent Number:
5840867
Oligonucleotide sequences that mediate specific binding to selected target molecules and contain modified base, sugars, or sugar linkages are disclosed. Single-stranded DNA oligomers are obtained that bind to a series of biomolecules that differ in both size and composition. The range of target molecules that may be bound permits generation of binding oligomers that are specific for binding to nearly any biomolecule that is composed of amino acids, lipids and/or carbohydrates. The…
Methods of using oligomers containing modified pyrimidines
Granted: November 3, 1998
Patent Number:
5830653
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…
Modified internucleoside linkages (II)
Granted: October 6, 1998
Patent Number:
5817781
The invention relates to novel modified oligonucleotides, the construction thereof, and their use in oligonucleotide-based therapies. More specifically, the invention is to novel oligonucleotides having modified internucleoside linkages which are resistant to nucleases, having enhanced ability to penetrate cells, and which are capable of binding target oligonucleotide sequences in vitro and in vivo. The modified oligonucleotides of the invention are particularly useful in…
Thiepane compounds
Granted: September 22, 1998
Patent Number:
5811450
Tri- and tetra substituted thiepane compositions having use as immunogens, therapeutics, diagnostics and for other industrial purposes are disclosed. The compositions inhibit proteolytic activity of viral enzymes and are useful for the inhibition of such enzymes as well as in assays for the detection of such enzymes. Embodiments in which antigenic polypeptides are bonded to the compositions are useful in raising antibodies against the thiepane haptens or the polypeptide. Labeled…
Nucleotide analogs
Granted: August 25, 1998
Patent Number:
5798340
Nucleotide analogs characterized by the presence of an amidate lirked 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 hydrolysed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for the synthesis and use are described.
Nuclease stable and binding competent oligomers and methods for their use
Granted: August 11, 1998
Patent Number:
5792608
Oligomers are disclosed which have modified internucleotide linkages and can form triplex and duplex structures by binding to complementary nucleic acid sequences. The oligomers of the invention may be incorporated into carriers and may be constructed to have any desired sequence. Compositions of the invention can be used for diagnostic purposes in order to detect viruses or disease conditions.
2' Modified Oligonucleotides
Granted: August 11, 1998
Patent Number:
5792847
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.
Cationic lipids
Granted: July 7, 1998
Patent Number:
5777153
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.
Compounds and methods for making and using same
Granted: June 16, 1998
Patent Number:
5767100
In accordance with this invention novel compounds are provided that are selected from saturated and unsaturated pyrans and furans substituted with at least a phosphonate group and a heterocyclic base. These compounds are useful as antiinfectives, flame retardants, diagnostic oligonucleotides and immunogens.
Oligonucleotides and their analogs capable of passive cell membrane permeation
Granted: June 9, 1998
Patent Number:
5763208
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%.…
Composition and method for storing nucleotide analogs
Granted: June 9, 1998
Patent Number:
5763424
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…
Carbocyclic compounds
Granted: June 9, 1998
Patent Number:
5763483
Novel carbocyclic compounds are described. The compounds generally comprise an acidic group, a basic group, a substituted amino or N-acyl and a group having an optionally hydroxylated alkane moiety. Pharmaceutical compositions comprising the inhibitors of the invention are also described. Methods of inhibiting neuraminidase in samples suspected of containing neuraminidase are also described. Antigenic materials, polymers, antibodies, conjugates of the compounds of the invention with…
Pyrimidine derivatives for labeled binding partners
Granted: June 9, 1998
Patent Number:
5763588
Compounds having particular interest as labels and various novel uses in diagnostics and therapeutics are provided which have structure (1) ##STR1## wherein R.sup.1 is a binding partner, a linker or H; a and b are 0 or 1, provided that the total of a and b is 0 or 1;A is N or C;X is S, O, --C(O)--, NH or NCH.sub.2 R.sup.6 ;Y is --C(O)--;Z is taken together with A to form an aryl or heteroaryl ring structure comprising 5 or 6 ring atoms wherein the heteroaryl ring comprises a single O…
