Method for treatment of tumors using nucleic acid ligands to PDGF
Granted: March 2, 2004
Patent Number:
6699843
A method is provided for treating solid tumors comprising administering a composition comprising a PDGF aptamer and a cytotoxic agent. In a preferred embodiment the PDGF aptamer is identified using the SELEX process for the Systematic Evolution of Ligands by Exponential enrichment. A method is also provided for reducing the interstitial fluid pressure (IFP) of a solid tumor comprising administering a PDGF aptamer. Finally, a method is provided for increasing the uptake of cytotoxic…
High-affinity oligonucleotide ligands to vascular endothelial growth factor (VEGF)
Granted: February 24, 2004
Patent Number:
6696252
Methods are described for the identification and preparation of nucleic acid ligand ligands to vascular endothelial growth factor (VEGF). Included in the invention are specific RNA ligands to VEGF identified by the SELEX method.
Bivalent binding molecules of 7 transmembrane G protein-coupled receptors
Granted: January 27, 2004
Patent Number:
6682886
Described herein are methods for identifying and preparing bivalent binding molecules to 7 transmembrane G protein-coupled receptors. The methods disclosed herein are based on the SELEX method for generating high affinity nucleic acid ligands. SELEX is an acronym for Systematic Evolution of Ligands by EXponential enrichment. The methods of this invention combine two or more binding domains to two or more different epitopes of the same 7 transmembrane G protein-coupled receptor. These…
2?-fluoropyrimidine anti-calf intestinal phosphatase nucleic acid ligands
Granted: January 6, 2004
Patent Number:
6673553
Methods are described for the identification and preparation of nucleic acid ligands to calf intestinal phosphatase. Included in the invention are specific RNA ligands to calf intestinal phosphatase identified by the SELEX method.
Determining non-nucleic acid molecule binding to target by competition with nucleic acid ligand
Granted: December 30, 2003
Patent Number:
6670132
A competitive binding assay is used to determine whether a non-nucleic acid molecule from a library of non-nucleic acid molecules binds to a target. The non-nucleic acid molecule competes with a nucleic acid ligand for binding to the target which may be immobilized. Detecting displacement of nucleic acid ligand from a complex of the nucleic acid ligand and the target determines binding of the non-nucleic acid molecule to the target. The nucleic acid ligand may be immobilized and…
Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability
Granted: November 25, 2003
Patent Number:
RE38333
Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure —OC(R2)2OC(O)X(R)a, wherein R2 independently is H, C1-C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR3 in which R3 is C1-C12 alkyl; X is N or O; R is independently H, C1-C12 alkyl, aryl, alkenyl,…
Pharmaceutical formulations
Granted: October 21, 2003
Patent Number:
6635278
The invention provides compositions comprising the nucleotide analog 9-[2-[[bis[(pivaloyloxy)methyl]phosphono]methoxy]ethyl]adenine and an alkaline excipient with or without L-carnitine-L-tartrate. The compositions are more stable those previously described. The invention also provides methods to make the compositions and their intermediates.
Systematic evolution of ligands by exponential enrichment: tissue selex
Granted: September 2, 2003
Patent Number:
6613526
This invention discloses high-affinity oligonucleotide ligands to complex tissue targets, specifically nucleic acid ligands having the ability to bind to complex tissue targets, and the methods for obtaining such ligands. Tissue targets comprise cells, subcellular components, aggregates or cells, collections of cells, and higher ordered structures. Specifically, nucleic acid ligands to red blood cells ghosts, endothelia of the blood brain and CSF-blood barriers, glioblastomas, and…
Nucleotide-based prodrugs
Granted: August 26, 2003
Patent Number:
6610841
This invention relates to nucleotide-based prodrugs and their drug-delivery applications. The nucleotide-based prodrugs of the present invention comprise a drug component covalently attached via junctional ester bond(s) to one or more nucleotide components. Release and activation of the drug component of a nucleotide-based prodrug arises from hydrolysis of the junctional ester bond joining the nucleotide component to the drug component. The active drug component may be a nucleoside…
Tenascin-C nucleic acid ligands
Granted: July 22, 2003
Patent Number:
6596491
Methods are described for the identification and preparation of nucleic acid ligands to tenascin-C. Included in the invention are specific RNA ligands to tenascin-C identified by the SELEX method. Further included in the invention are methods for detecting the presence of a disease condition in a biological tissue in which tenascin-C is expressed.
Platelet derived growth factor (PDGF) nucleic acid ligand complexes
Granted: June 24, 2003
Patent Number:
6582918
This invention discloses a method for preparing a complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a PDGF Nucleic Acid Ligand by SELEX methodology and associating the PDGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more PDGF Nucleic Acid Ligands in association with a Non-Immunogenic,…
High affinity nucleic acid ligands of complement system proteins
Granted: May 20, 2003
Patent Number:
6566343
Methods are described for the identification and preparation of high-affinity Nucleic Acid Ligands to Complement System Proteins. Methods are described for the identification and preparation of high affinity Nucleic Acid Ligands to Complement System Proteins C1q, C3 and C5. Included in the invention are specific RNA ligands to C1q, C3 and C5 identified by the SELEX method.
High affinity nucleic acid ligands to lectins
Granted: April 8, 2003
Patent Number:
6544959
This invention discloses high-affinity oligonucleotide ligands to lectins, specifically nucleic acid ligands having the ability to bind to the lectins, wheat germ agglutinin, L-selectin, E-selectin and P-selectin. Also disclosed are the methods for obtaining such ligands.
Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction
Granted: March 11, 2003
Patent Number:
6531286
A homogeneous assay that utilizes molecular beacons as the reporter and nucleic acid ligands as the sensor is described. This assay, called the ligand beacon assay, is for the detection of target molecules in a test mixture. The concept of the ligand beacon assay was tested using several proteins to which high affinity and specific nucleic acid ligands are available. The assay specifically detects the molecular target that binds the nucleic acid ligand with high affinity and specificity.…
Preparation of cyclohexene carboxylate derivatives
Granted: February 11, 2003
Patent Number:
6518438
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.
Nucleoside modifications by palladium catalyzed methods
Granted: January 28, 2003
Patent Number:
6512106
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.
Fluorescence-based assay for the interaction of small molecules with the human renal organic anion transporter 1 (hOAT1)
Granted: November 12, 2002
Patent Number:
6479231
Secretion of small molecules from systemic blood circulation into urine is one of the physiologically essential functions of the kidney. Human organic anion transporter (hOAT1) is a key component in the renal tubular secretion of negatively charged molecules including a variety of important therapeutics. In some cases, compounds interacting with hOAT1 may induce pharmacokinetic drug-drug interactions or cause nephrotoxicity. We developed a fluorescence-based, 96-well format assay using…
Nucleic acid ligand complexes
Granted: October 15, 2002
Patent Number:
6465188
This invention discloses a method for preparing a therapeutic or diagnostic complex comprised of a nucleic acid ligand and a lipophilic compound or non-immunogenic, high molecular weight compound by identifying a nucleic acid ligand by SELEX methodology and associating the nucleic acid ligand with a lipophilic compound or a non-immunogenic, high molecular weight compound. The invention further discloses complexes comprising one or more nucleic acid ligands in association with a…
Systematic evolution of ligands by exponential enrichment: blended selex
Granted: October 15, 2002
Patent Number:
6465189
A method is described for generating blended nucleic acid ligands containing non-nucleic acid functional units. Specifically, a SELEX identified RNA ligand to the integrin gpIIbIIIa is conjugated to the peptide Gly-Arg-Gly-Asp-Thr-Pro (SEQ ID NO:1). This blended RNA ligand inhibits the biological activity of gpIIbIIIa with high specificity. Also described is a single-stranded DNA ligand to elastase coupled to N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethyl ketone (SEQ ID NO:2). This…
Methods for the dealkylation of phosphonate esters
Granted: October 15, 2002
Patent Number:
6465649
Disclosed are methods for the dealkylation of phosphonate esters by use of trimethylchlorosilane as the dealkylating agent. In particular, this invention is directed to the discovery that high yields for the dealkylation of phosphonate esters can be achieved within relatively short reaction times by the use of trimethylchlorosilane provided that the dealkylation procedure occurs in a sealed vessel containing a compatible solvent.
