Method for dosing therapeutic compounds
Granted: May 26, 1998
Patent Number:
5756486
The internally cyclized congeners of hydroxy-substituted nucleotide analogues have been found to exhibit substantially lower toxicity in vivo than their uncyclized analogues, while retaining essentially the same antiviral activity. This was unexpected because the prior art suggested that the cyclic analogues offered no significant advantages in respect to toxicity. This finding permits the administration of much greater doses of the cyclic congeners than otherwise would have been…
Aptamers specific for biomolecules and methods of making
Granted: May 26, 1998
Patent Number:
5756291
A method for identifying oligomer sequences, optionally comprising modified base, which specifically bind target molecules such as serum proteins, kinins, eicosanoids and extracellular proteins is described. The method is used to generate aptamers that bind to serum Factor X, PDGF, FGF, ICAM, VCAM, E-selectin, thrombin, bradykinin, PGF2 and cell surface molecules. The technique involves complexation of the target molecule with a mixture of oligonucleotides containing random sequences and…
Compounds and methods for making and using same
Granted: May 12, 1998
Patent Number:
5750729
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.
PMPA preparation
Granted: March 31, 1998
Patent Number:
5733788
Purified preparations of PMPA are provided, together with analytical methods for the detection of undesired contaminants in PMPA preparations. The PMPA compositions of the invention are of particular utility in therapeutics intended for the treatment or prophylaxis of viral infections.
Oligonucleotides with inverted polarity
Granted: February 24, 1998
Patent Number:
5721218
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.
Nucleotide analogs
Granted: February 10, 1998
Patent Number:
5717095
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.
Thiepane compounds
Granted: January 6, 1998
Patent Number:
5705524
Tri- and tetra substituted thiepane and 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…
Cationic lipids
Granted: January 6, 1998
Patent Number:
5705693
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…
Methods for making nucleoside analogs
Granted: December 2, 1997
Patent Number:
5693771
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.
Method and cyclic carbonates for nucleotide analogues
Granted: November 11, 1997
Patent Number:
5686629
An improved method for the preparation of acyclic nucleotide analogues comprises first condensing a cyclic carbonate with a purine or pyrimidine base and then reacting the alkylated base with an activated phosphonate. Novel cyclic carbonates are employed to yield the desired phosphonylmethoxyalkyl nucleotide analogues.
Nucleoside 5'-methylene phosphonates
Granted: September 30, 1997
Patent Number:
5672697
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.
Nucleotide analogues
Granted: August 19, 1997
Patent Number:
5659023
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.
Nucleotide analogs
Granted: August 12, 1997
Patent Number:
5656745
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.
Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
Granted: July 8, 1997
Patent Number:
5645985
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…
Method for oligonucleotide analog synthesis
Granted: July 8, 1997
Patent Number:
5646269
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.
Oligonucleotide analogs capable of passive cell membrane permeation
Granted: May 27, 1997
Patent Number:
5633360
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%.…
Modified internucleoside linkages having one nitrogen and two carbon atoms
Granted: January 21, 1997
Patent Number:
5596086
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.
Enhanced triple-helix and double-helix formation with oligomers containing modified purines
Granted: January 14, 1997
Patent Number:
5594121
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…
Method for synthesis
Granted: January 7, 1997
Patent Number:
5591851
The internally cyclized congeners of hydroxy-substituted nucleotide analogues have been found to exhibit substantially lower toxicity in vivo than their uncyclized analogues, while retaining essentially the same antiviral activity. This was unexpected because the prior art suggested that the cyclic analogues offered no significant advantages in respect to toxicity. This finding permits the administration of much greater doses of the cyclic congeners than otherwise would have been…
Method for identifying an oligonucleotide aptamer specific for a target
Granted: December 10, 1996
Patent Number:
5582981
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…
