Patents by Inventor Michael Leuck
Michael Leuck has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 8138330Abstract: The present invention discloses novel methods for the synthesis of oligonucleotides with nucleoside phosphoramidites on solid supports. The methods comprise the stepwise chain assembly of oligonucleotides on supports with 5?-acyl phosphoramidites. The synthesis cycles consist of a front end deprotection step which is conducted with a solution of a primary amine or a phenolate, a phosphoramidite coupling step with a 5?-acyl nucleoside phosphoramidite in the presence of an activator, a phosphite oxidation step and an optional capping step. The novel methods improve the quality of synthetic oligonucleotides due to the irreversibility of the front end deprotection step, which prevents the formation of deletion sequences, and due to the avoidance of acidic reagents in the synthesis cycles, which prevent the formation of depurination side products.Type: GrantFiled: September 11, 2007Date of Patent: March 20, 2012Assignee: Sigma-Aldrich Co. LLCInventors: Michael Leuck, Andreas Wolter, Alfred Stumpe
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Patent number: 7897758Abstract: The present invention discloses novel methods for the synthesis of oligonucleotides and nucleoside phosphoramidites. The methods are based on employing aryl-substituted 5-phenyl-1H-tetrazoles with perfluoroalkyl groups on the aromatic ring as activators. In one aspect the novel activators are used in the synthesis of oligonucleotides via the phosphoramidite approach. In this aspect the activators are highly efficient and can be applied with very short coupling times. In a further aspect, the activators of the invention are used in the synthesis of phosphoramidites through the reaction of nucleosides comprising a free hydroxyl group with phosphitylating agents. In this aspect the activators provide very pure phosphoramidites under mild conditions. The activators of the invention are further characterized by being highly soluble, non-hygroscopic and non-hazardous.Type: GrantFiled: April 26, 2006Date of Patent: March 1, 2011Assignee: Sigma-Aldrich Co.Inventors: Andreas Wolter, Michael Leuck
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Patent number: 7427678Abstract: 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.Type: GrantFiled: May 1, 2001Date of Patent: September 23, 2008Assignee: Sigma-Aldrich Co.Inventors: Wolfgang Pieken, Andreas Wolter, David P. Sebesta, Michael Leuck, Hallie A. Latham-Timmons, John Pilon, Gregory M. Husar
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Publication number: 20080064867Abstract: The present invention discloses novel methods for the synthesis of oligonucleotides with nucleoside phosphoramidites on solid supports. The methods comprise the stepwise chain assembly of oligonucleotides on supports with 5?-acyl phosphoramidites. The synthesis cycles consist of a front end deprotection step which is conducted with a solution of a primary amine or a phenolate, a phosphoramidite coupling step with a 5?-acyl nucleoside phosphoramidite in the presence of an activator, a phosphite oxidation step and an optional capping step. The novel methods improve the quality of synthetic oligonucleotides due to the irreversibility of the front end deprotection step, which prevents the formation of deletion sequences, and due to the avoidance of acidic reagents in the synthesis cycles, which prevent the formation of depurination side products.Type: ApplicationFiled: September 11, 2007Publication date: March 13, 2008Applicant: SIGMA ALDRICH COMPANYInventors: Michael Leuck, Andreas Wolter, Alfred Stumpe
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Patent number: 7329515Abstract: The present invention discloses novel methods and solid supports for the synthesis of 3?-amino oligonucleotides. The novel supports are based on an unsubstituted or ring-substituted hydroxymethylbenzoyl linker element wherein the hydroxymethyl group is esterified to a solid phase bound carboxylic acid and the carbonyl group is linked to an amino alcohol as an amide. Oligonucleotides are conveniently synthesized on the novel supports with no modifications in the standard phosphoramidite synthesis scheme. The ester function of the support is cleaved under the alkaline deprotection conditions for oligonucleotides to provide a free hydroxymethyl group that aids in the release of the 3?-amino oligonucleotide products with a free amino group through neighbor group participation. The free amino group of the oligonucleotides is available for further conjugation reactions to haptens, reporter groups, surfaces or other small molecules or biomolecules.Type: GrantFiled: April 21, 2004Date of Patent: February 12, 2008Assignee: Sigma-Aldrich Co.Inventors: Michael Leuck, Andreas Wolter
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Patent number: 7276598Abstract: The present invention discloses novel phosphoramidite reagents for use in oligonucleotide synthesis. The present invention further discloses novel methods for the conversion of terminal hydroxyl groups of oligonucleotides into phosphate monoesters. By employing novel reagents, as also disclosed herein, the methods are fully compatible with standard procedures for solid phase oligonucleotide synthesis and do not require additional processing steps. The inventive reagents to phosphorylate terminal hydroxyl groups of oligonucleotides are superior to the prior art in that they for the first time combine the desired attributes of being a solid compound for facile handling, comprising two ?-eliminating protective groups removable as fast or faster than the standard cyanoethyl group, providing a DMT-group for easy monitoring of the coupling efficiency, and enabling a fast final deprotection of the phosphorylated oligonucleotide without any extra manipulation steps.Type: GrantFiled: April 9, 2004Date of Patent: October 2, 2007Assignee: Sigma-Aldrich Co.Inventors: Kurt Vagle, Michael Leuck, Andreas Wolter
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Publication number: 20060247431Abstract: The present invention discloses novel methods for the synthesis of oligonucleotides and nucleoside phosphoramidites. The methods are based on employing aryl-substituted 5-phenyl-1H-tetrazoles with perfluoroalkyl groups on the aromatic ring as activators. In one aspect the novel activators are used in the synthesis of oligonucleotides via the phosphoramidite approach. In this aspect the activators are highly efficient and can be applied with very short coupling times. In a further aspect, the activators of the invention are used in the synthesis of phosphoramidites through the reaction of nucleosides comprising a free hydroxyl group with phosphitylating agents. In this aspect the activators provide very pure phosphoramidites under mild conditions. The activators of the invention are further characterized by being highly soluble, non-hygroscopic and non-hazardous.Type: ApplicationFiled: April 26, 2006Publication date: November 2, 2006Applicant: Sigma-Aldrich Co.Inventors: Andreas Wolter, Michael Leuck
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Patent number: 7098326Abstract: 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.Type: GrantFiled: January 22, 2003Date of Patent: August 29, 2006Assignee: Sigma-Aldrich Co.Inventors: Wolfgang Pieken, Andreas Wolter, Michael Leuck
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Publication number: 20040230047Abstract: The present invention discloses novel phosphoramidite reagents for use in oligonucleotide synthesis. The present invention further discloses novel methods for the conversion of terminal hydroxyl groups of oligonucleotides into phosphate monoesters. By employing novel reagents, as also disclosed herein, the methods are fully compatible with standard procedures for solid phase oligonucleotide synthesis and do not require additional processing steps. The inventive reagents to phosphorylate terminal hydroxyl groups of oligonucleotides are superior to the prior art in that they for the first time combine the desired attributes of being a solid compound for facile handling, comprising two &bgr;-eliminating protective groups removable as fast or faster than the standard cyanoethyl group, providing a DMT-group for easy monitoring of the coupling efficiency, and enabling a fast final deprotection of the phosphorylated oligonucleotide without any extra manipulation steps.Type: ApplicationFiled: April 9, 2004Publication date: November 18, 2004Applicant: Proligo, LLCInventors: Kurt Vagle, Michael Leuck, Andreas Wolter
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Publication number: 20040220397Abstract: The present invention discloses novel methods and solid supports for the synthesis of 3′-amino oligonucleotides. The novel supports are based on an unsubstituted or ring-substituted hydroxymethylbenzoyl linker element wherein the hydroxymethyl group is esterified to a solid phase bound carboxylic acid and the carbonyl group is linked to an amino alcohol as an amide. Oligonucleotides are conveniently synthesized on the novel supports with no modifications in the standard phosphoramidite synthesis scheme. The ester function of the support is cleaved under the alkaline deprotection conditions for oligonucleotides to provide a free hydroxymethyl group that aids in the release of the 3′-amino oligonucleotide products with a free amino group through neighbor group participation. The free amino group of the oligonucleotides is available for further conjugation reactions to haptens, reporter groups, surfaces or other small molecules or biomolecules.Type: ApplicationFiled: April 21, 2004Publication date: November 4, 2004Applicant: PROLIGO LLCInventors: Michael Leuck, Andreas Wolter
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Publication number: 20030215801Abstract: 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.Type: ApplicationFiled: May 1, 2001Publication date: November 20, 2003Inventors: Wolfgang Pieken, Andreas Wolter, David P. Sebesta, Michael Leuck, Hallie A. Latham-Timmons, John Pilon, Gregory M. Husar
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Publication number: 20030195351Abstract: 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.Type: ApplicationFiled: January 22, 2003Publication date: October 16, 2003Applicant: PROLIGO, LLCInventors: Wolfgang Pieken, Andreas Wolter, Michael Leuck