Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Nexstar Pharmaceuticals, Inc.

Proligo, LLC

Sigma-aldrich Co. LLC

Wolfgang A Pieken

Larry M Gold

David Brian Olsen

Fritz Eckstein

Fritz Benseler

David M Williams

Nebojsa Janjic

Gary P Kirschenheuter

Diane Tasset

Danny P McGee

Andreas Wolter

Michael Leuck

Yansheng Zhai

Olaf Heindenreich

Olaf Heidenreich

Bruce Eaton

Kurt Vagle

Andrew Stephens

Gregory M Husar

Hallie A Latham-Timmons

Jianping Huang

John Pilon

Alecia Settle

David P Sebesta

Ken Hill

This invention discloses a novel method for immobilizing molecules to a support. Specifically, this invention discloses a method of immobilizing derivatized biomolecules, such as oligonucleotides, using cycloaddition reactions, such as the Diels-Alder reaction. Included in this invention are the novel immobilized biomolecules that can be prepared according to the method of this invention.

Method for immobilizing oligonucleotides employing the cycloaddition bioconjugation method

The present invention discloses novel methods for the integrated synthesis and purification of oligonucleotides. The methods employ novel capping reagents carrying two functional groups. The first functional group provides for a smooth and efficient capping process and incorporates the second functional group into contaminant oligonucleotides during solid phase oligonucleotide synthesis. The second functional group functions as a chemical purification handle in the trapping of truncated oligonucleotides (failure sequences) on a solid support. The trapping process creates covalent bonds between the solid support and the truncated oligonucleotides and therefore allows the removal of the truncated sequences from the desired full length oligonucleotide product by filtration. The chemical trapping process employed in this invention is based on cycloaddition reactions, particularly Diels-Alder reactions between the truncated oligonucleotides and the trapping agent. The invention includes novel solid support compositions that carry covalently attached Diels-Alder reaction components.

Methods for the integrated synthesis and purification of oligonucleotides

The present invention refers to an RNA molecule with catalytic activity comprising at least one modified nucleoside, wherein the hydroxy group at the 2'-position of the ribose sugar is replaced by a modifier group, selected from halo, sulfhydryl, azido, amino, monosubstituted amino and disubstituted amino groups, a process for the preparation of modified RNA molecules and the use of modified RNA molecules as therapeutic agents and biocatalysts.

Modified ribozymes

This invention discloses a novel method for conjugating macromolecules to other molecular entities. Specifically, this invention discloses a method for conjugating or derivatizing macromolecules, such as oligonucleotides and proteins, using cycloaddition reactions, such as the Diels-Alder reaction or 1,3-dipolar cycloadditions. Included in the invention are the novel bioconjugated macromolecules that can be prepared according to the method of the invention.

Bioconjugation of macromolecules

This invention discloses an improved method for the sequential solution phase synthesis of oligonucleotides. The method lends itself to automation and is ideally suited for large scale manufacture of oligonucleotides with high efficiency.

Method for solution phase synthesis of oligonucleotides

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

Method of preparation of known and novel 2'-modified nucleosides by

This invention discloses an improved method for the sequential solution phase synthesis of oligonucleotides and peptides. The method lends itself to automation and is ideally suited for large scale manufacture oligonucleotides with high efficiency.

Method for solution phase synthesis of oligonucleotides and peptides

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.

The claimed invention is drawn to RNA molecules with catalytic activity comprising at least one modified nucleoside having a modifier group replacing the hydroxy group at the 2'-position of the ribose sugar where the modifier group is an halo, amino, mono- or disubstituted amino, or an azido group, and methods of use in vivo.

The present invention refers to an RNA molecule with catalytic activity comprising at least one modified nucleoside, wherein the hydroxy group at the 2'-position of the fibose sugar is replaced by a modifier group, selected from halo, sulfhydryl, azido, amino, monosubstituted amino, and disubstituted andno groups, a process for the preparation of modified KNA molecules and the use of modified KNA molecules as therapeutic agents and biocatalysts.

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Longmont, CO, United States of America

Wolfgang A Pieken