Nexstar Pharmaceuticals, Inc.

Diane Tasset

Larry M Gold

Nebojsa Janjic

Gary P Kirschenheuter

Wolfgang A Pieken

Sumedha D Jayasena

Nikos C Pagratis

Torsten Walter Wiegand

Nucleic acid ligands containing modified nucleotides are described as are methods for producing such oligonucleotides. Such ligands enrich the chemical diversity of the candidate mixture for the SELEX process. Specific examples are provided of nucleic acids containing nucleotides modified at the 2&prime;- and 5-position. Specific 2-OH and 2&prime;-NH,modified RNA ligands to thrombin are described.

High affinity nucleic acid ligands containing modified nucleotides

The present invention utilizes the SELEX (Systematic Evolution of Ligands for EXponential Enrichment) method for identifying and preparing nucleic acid ligands to basic fibroblast growth factor (bFGF) and thrombin. Included in the invention are nucleic acid ligands to bFGF which are inhibitors of bFGF and 2&prime;-amino-modified RNA ligands to bFGF. Further included in the present invention are modified nucleotide sequences to thrombin based on the sequences of the RNA ligands identified. The modified RNA ligands to bFGF and thrombin exhibit increased in vivo stability.

High affinity ligands of basic fibroblast growth factor and thrombin

Methods are described for the identification and preparation of high-affinity nucleic acid ligands to cytokines. Included in the invention are specific nucleic acid ligands to IFN-gamma, IL-4, IL-10, TNF-alpha, and RANTES.

High affinity nucleic acid ligands of cytokines

Nucleic acid ligands containing modified nucleotides are described as are methods for producing such oligonucleotides. Such ligands enrich the chemical diversity of the candidate mixture for the SELEX process. Specific examples are provided of nucleic acids containing nucleotides modified at the 2'- and 5-position. Specific 2-OH and 2'-NH.sub.2 modified RNA ligands to thrombin are described.

This invention discloses high-affinity oligonucleotide ligands to human Immunoglobulin E (IgE), specifically RNA and ssDNA ligands having the ability to bind to IgE, and the methods for obtaining such ligands. The ligands are capable of inhibiting the interaction of IgE with its receptor.

High-affinity oligonucleotide ligands to immunoglobulin E (IgE)

This invention discloses high-affinity oligonucleotide ligands to human Immunoglobulin E (IgE), specifically RNA ligands having the ability to bind to IgE, and the methods for obtaining such ligands. The ligands are capable of inhibiting the interaction of IgE with its receptor.

Methods are described for the identification of nucleic acid ligand solutions to thrombin. The present invention utilizes the SELEX (Systematic Evolution of Ligands for EXponential Enrichment) method for identfying and preparing DNA ligands to thrombin. Further included in the present invention are modified nucleotide sequences based on the sequences of the DNA ligands identified. The modified DNA ligands to thrombin exhibit increased in vivo stability.

DNA ligands of thrombin

Methods are described for the identification of nuclei acid ligand solutions to thrombin. The present invention utilizes the SELEX (Systematic Evolution of Ligands for EXponential enrichment) method for identifying and preparing RNA ligands to thrombin. Further included in the present invention are modified nucleotide sequences based on the sequences of the RNA ligands identified. The modified RNA ligands to thrombin exhibit increased in vivo stability.

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Boulder, CO, United States of America

Diane Tasset