Deprotection Step Patents (Class 536/25.31)
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Publication number: 20040175726Abstract: A hydrocarbyldithiomethyl-modified compound of the Formula:Type: ApplicationFiled: October 27, 2003Publication date: September 9, 2004Applicant: Quiatech AB, a Swedish corporationInventor: Marek Kwiatkowski
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Patent number: 6770436Abstract: Radiation-activated catalysts (RACs), autocatalytic reactions, and protective groups are employed to achieve a highly sensitive, high resolution, radiation directed combinatorial synthesis of pattern arrays of diverse polymers. When irradiated, RACs produce catalysts that can react with enhancers, such as those involved in autocatalytic reactions. The autocatalytic reactions produce at least one product that removes protecting groups from synthesis intermediates. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.Type: GrantFiled: May 25, 2000Date of Patent: August 3, 2004Assignee: Affymetrix, Inc.Inventors: Jody E. Beecher, Martin J. Goldberg, Glenn H. McGall
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Patent number: 6762298Abstract: The invention provides a method of thermally deprotecting the internucleosidic phosphorus linkage of an oligonucleotide, which method comprises heating a protected oligonucleotide in a fluid medium at a substantially neutral pH, so as to deprotect the oligonucleotide. The present invention further provides a method of synthesizing an oligonucleotide using the thermal deprotection method described above, and novel oligonucleotides and intermediates that incorporate the thermolabile protecting group used in accordance with the present invention.Type: GrantFiled: February 23, 2001Date of Patent: July 13, 2004Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Serge L. Beaucage, Andrzej Wilk, Andrzej Grajkowski
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Patent number: 6762281Abstract: Methods of preparing peptide linked oligomeric compounds are provided. The method is useful for preparing larger scale amounts of peptide linked oligomeric compounds. More particularly, the synthesis of peptide linked oligomeric compounds is performed without the problems of aggregation associated with electrostatic interactions. The present method describes using equimolar amounts of oligomeric compounds and peptide reagents providing for an increase in overall efficiency.Type: GrantFiled: September 7, 2001Date of Patent: July 13, 2004Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Andrei P. Guzaev
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Patent number: 6713622Abstract: A set of 4,7-dichlororhodamine compounds useful as fluorescent dyes are disclosed having the structures wherein R1-R6 are hydrogen, fluorine, chlorine, lower alkyl, lower alkene, lower alkyne, sulfonate, sulfone, amino, amido, nitrile, lower alkoxy, linking group, or, when taken together, R1 and R6 is benzo, or, when taken together, R4 and R5 is benzo; R7-R10, R12-R16 and R18 may be hydrogen, fluorine, chlorine, lower alkyl, lower alkene, lower alkyne, sulfonate, sulfone, amino, amido, nitrile, lower alkoxy, linking group; R11 and R17 may be hydrogen, lower alkyl, lower alkene, lower alkyne, phenyl, aryl, linking group; Y1-Y4 are hydrogen, lower alkyl, or cycloalkyl, or, when taken together, Y1 and R2, Y2 and R1 Y3 and R3, and/or Y4 and R4 is propano, ethano, or substituted forms thereof, and X1-X3 taken separately are hydrogen, chlorine, fluorine, lower alkyl, carboxylate, sulfonate, hydroxymethyl, and linking group, or any combinations thereof In another aspect, the invention includes reagType: GrantFiled: May 25, 2000Date of Patent: March 30, 2004Assignee: Applera CorporationInventor: Ronald J. Graham
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Patent number: 6673918Abstract: Method for one-pot deprotection of RNA molecules.Type: GrantFiled: September 21, 2001Date of Patent: January 6, 2004Assignee: Sirna Therapeutics, Inc.Inventors: Laurent Bellon, Christopher T. Workman
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Patent number: 6664388Abstract: The present invention provides a process for the removal of protecting groups, i.e. deprotection, from chemically synthesized oligonucleotides. In one embodiment, the invention provides reagents suitable for use in such a process, and kits incorporating such reagents in a convenient, ready-to-use format. By use of the process and reagents of the invention, side-reactions leading to certain impurities that contaminate the synthesized oligonucleotides can be minimized. Methods and reagents are provided for deprotection of an oligonucleotide by reacting a protected oligonucleotide with a deprotection reagent wherein the deprotection reagent comprises an active methylene compound and an amine reagent. The active methylene compound has the structure: where substituent EWG is an electron-withdrawing group and R is hydrogen, C1-C12 alkyl, C6-C20 aryl, heterocycle or an electron-withdrawing group.Type: GrantFiled: March 4, 2002Date of Patent: December 16, 2003Assignee: Applera CorporationInventor: Jeffrey S. Nelson
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Patent number: 6653458Abstract: Modified oligonucleotides containing at least one 2′,5′-internucleotide linkage are provided. The oligonucleotides of the invention may also bear additional substituents at the 2′- and 3′-positions.Type: GrantFiled: November 8, 1999Date of Patent: November 25, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Phillip Dan Cook, Charles J. Guinosso
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Patent number: 6653468Abstract: Compounds for the synthesis of oligomeric compounds, particularly oligonucleotides and oligonucleotide mimetics, are provided. In addition, methods for functionalizing a support medium with a first monomeric subunit and methods for the synthesis of oligomeric compounds utilizing the novel compounds bound to support media are provided.Type: GrantFiled: September 30, 2002Date of Patent: November 25, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Andrei P. Guzaev, Muthiah Manoharan
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Patent number: 6649348Abstract: Apparatus and methods are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. In the present invention at least two of the steps are performed by placing a support having a functionalized surface into a chamber of a flow cell and subjecting the surface to a step of the synthesis and placing the support into a chamber of another flow cell and subjecting the surface to another step of the synthesis. An apparatus generally comprises a plurality of flow cells and one or more fluid dispensing stations are mounted on the platform and are in fluid communication with one or more of the plurality of flow cells. A station for monomer addition to the surface of the support is mounted on the platform. The apparatus further comprises a mechanism for moving a support to and from the station for monomer addition and a flow cell and from one flow cell to another flow cell.Type: GrantFiled: June 29, 2001Date of Patent: November 18, 2003Assignee: Agilent Technologies Inc.Inventors: Jay K. Bass, John F. McEntee, Tim J. Lazaruk, Maryam Mobed-Miremadi
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Patent number: 6649750Abstract: Synthetic processes are provided wherein high purity oligomers are prepared using support bound phosphoramidite protocols starting with a nucleoside or larger synthon linked to a support media through a nucleosidic heterocyclic base moiety. Intermediates undergoing depurination at the support linkage site are removed during the wash cycle. Also provided are compositions useful in such processes.Type: GrantFiled: January 5, 2000Date of Patent: November 18, 2003Assignee: Isis Pharmaceuticals, Inc.Inventors: Daniel C. Capaldi, Vasulinga T. Ravikumar, Douglas L. Cole
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Patent number: 6649751Abstract: Provided is a method for purification and synthesis of RNA molecules that have at least one chemical modification.Type: GrantFiled: May 28, 2002Date of Patent: November 18, 2003Assignee: Sirna Therapeutics, Inc.Inventors: Nassim Usman, Francine Wincott, David Sweedler, Leonid Beigelman, Lech W. Dudycz, Susan Grimm, Anthony DiRenzo, Danuta Tracz
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Patent number: 6646118Abstract: The present invention relates to a support system for solid phase synthesis of oligomers, such as oligonucleotides, wherein the starting compound is bound to the support via a disiloxyl linkage. Furthermore, the invention relates to a method for synthesis of oligonucleotides on a solid support. The support system comprises a stable disiloxyl linkage providing high nucleoside loadings to the support and the method allows convenient non-laborious oligomer synthesis.Type: GrantFiled: March 25, 2002Date of Patent: November 11, 2003Assignee: Quiatech ABInventors: Marek Kwiatkowski, Mats Nilsson, Ulf Landegren
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Patent number: 6632938Abstract: Methods for preparing purified oligonucleotides by treating a solution comprising an oligonucleotide with an aggregating agent and a precipitation enhancer under conditions sufficient to form an oligonucleotide aggregate and isolating the oligonucleotide aggregate to produce a purified oligonucleotide.Type: GrantFiled: June 7, 2001Date of Patent: October 14, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Max N. Moore, John Charles Arthur, Kent Vansooy, Anthony N. Scozzari
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Patent number: 6630581Abstract: The invention provides a method for synthesizing oligonucleotides using carbonate protection of hydroxyl groups and nucleophilic deprotection reagents. The deprotection reagents irreversibly cleave the carbonate protecting groups while simultaneously oxidizing the internucleotide phosphite triester linkage, and can be used in aqueous solution at neutral to mildly basic pH. The method eliminates the need for separate deprotection and oxidation steps, and, since the use of acid to remove protecting groups is unnecessary, acid-induced depurination is avoided. Fluorescent or other readily detectable carbonate protecting groups can be used, enabling monitoring of individual reaction steps during oligonucleotide synthesis. The invention is particularly useful in the highly parallel, microscale synthesis of oligonucleotides. Reagents and kits for carrying out the aforementioned method are provided as well.Type: GrantFiled: January 8, 2001Date of Patent: October 7, 2003Assignee: Agilent Technologies, Inc.Inventors: Douglas J. Dellinger, Marvin H. Caruthers, Jason R. Betley
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Publication number: 20030181712Abstract: The present invention provides a process for the removal of protecting groups, i.e. deprotection, from chemically synthesized oligonucleotides. In one embodiment, the invention provides reagents suitable for use in such a process, and kits incorporating such reagents in a convenient, ready-to-use format. By use of the process and reagents of the invention, side-reactions leading to certain impurities that contaminate the synthesized oligonucleotides can be minimized.Type: ApplicationFiled: March 4, 2002Publication date: September 25, 2003Applicant: PE Corporation (NY)Inventor: Jeffrey S. Nelson
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Publication number: 20030166917Abstract: Method for purification and synthesis of RNA molecules and enzymatic RNA molecules in enzymatically active form.Type: ApplicationFiled: May 28, 2002Publication date: September 4, 2003Inventors: Nassim Usman, Francine Wincott, David Sweedler, Leonid Beigelman, Lech W. Dudycz, Susan Grimm, Anthony DiRenzo, Danuta Tracz
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Patent number: 6610842Abstract: Synthetic processes are provided wherein oligomers are prepared using phosphoramidite compositions. Oligomers having phosphodiester, phosphorothioate, phosphorodithioate covalent linkages are prepared that can include other covalent linkages. Also provided are compositions useful in such processes.Type: GrantFiled: May 6, 1999Date of Patent: August 26, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Vasulinga T. Ravikumar, Daniel C. Capaldi, Douglas L. Cole
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Patent number: 6593464Abstract: The invention relates to a process for deblocking substantially a blocked, detectably labeled oligonucleotide by contacting the blocked detectably labeled oligonucleotide with an effective amount of a nucleophilic amino compound under conditions that result in substantial deblocking of the oligonucleotide, thereby giving the substantially deblocked oligonucleotide.Type: GrantFiled: May 24, 2000Date of Patent: July 15, 2003Assignee: Invitrogen CorporationInventors: Gulilat Gebeyehu, Richard M. Pires
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Publication number: 20030113769Abstract: The present invention provides oligomers which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the nucleoside moieties of the oligomer is modified to include an aminooxy linkage. These oligomers are useful for diagnostic, therapeutic and investigative purposes.Type: ApplicationFiled: September 3, 2002Publication date: June 19, 2003Inventors: Muthiah Manoharan, Harri Lonnberg, Harri Salo, Pasi Virta
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Patent number: 6576752Abstract: The present invention provides oligomers which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the nucleoside moieties of the oligomer is modified to include an aminooxy linkage. These oligomers are useful for diagnostic, therapeutic and investigative purposes.Type: GrantFiled: June 25, 1999Date of Patent: June 10, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Harri Lonnberg, Harri Salo, Pasi Virta
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Patent number: 6576426Abstract: This invention provides reagents, libraries and sets of the reagents, and assay methods using the reagents, the reagents comprising an analyte moiety and a tag moiety, wherein the tag moiety contains information defining the identify and location of the analyte residues of the analyte moiety which is detectable by mass spectrometry.Type: GrantFiled: December 6, 2001Date of Patent: June 10, 2003Assignee: Oxford Gene Technology LimitedInventors: Edwin Southern, William Jonathan Cummins
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Patent number: 6566495Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.Type: GrantFiled: December 17, 1999Date of Patent: May 20, 2003Assignee: Affymetrix, Inc.Inventors: Stephen P. A. Fodor, Lubert Stryer, J. Leighton Read, Michael C. Pirrung
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Patent number: 6566515Abstract: Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Ar—C(R1)(R2)—O—C(O)— wherein: Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative thereof; R1 and R2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, optionally substituted aryl or optionally substituted heteroaromatic, or a vinylogous derivative of the foregoing; and X is a leaving group, a chemical fragment linked to Ar—C(R1)(R2)—O—C(O)— via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R1 and R2 are H, X is not linked to Ar—C(R1)(R2)—O—C(O)— via a nitrogen atom.Type: GrantFiled: March 14, 2000Date of Patent: May 20, 2003Assignee: Affymetrix, Inc.Inventors: Glenn H. McGall, Ngo Q. Nam, Richard P. Rava
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Patent number: 6559279Abstract: Methods of preparing peptide linked oligomeric compounds are provided. The method is useful for preparing larger scale amounts of peptide linked oligomeric compounds. More particularly, the synthesis of peptide linked oligomeric compounds is performed without the problems of aggregation associated with electrostatic interactions. The present method describes using equimolar amounts of oligomeric compounds and peptide reagents providing for an increase in overall efficiency.Type: GrantFiled: September 8, 2000Date of Patent: May 6, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Andrei P. Guzaev
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Patent number: 6538128Abstract: The invention provides improved processes for oligonucleotide synthesis utilizing arenes as solvents for detritylation of oligonucleotides.Type: GrantFiled: March 22, 1999Date of Patent: March 25, 2003Assignee: Avecia Biotechnology, Inc.Inventors: Guangrong Zhang, Jin-Yan Tang
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Patent number: 6531584Abstract: Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.Type: GrantFiled: September 2, 1999Date of Patent: March 11, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventors: Phillip Dan Cook, Andrew Mamoru Kawasaki
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Patent number: 6531589Abstract: The invention provides new methods for synthesizing oligonucleotides that allow for deprotection of the oligonucleotides under more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups.Type: GrantFiled: February 8, 1996Date of Patent: March 11, 2003Assignee: Hybridon, Inc.Inventors: Radhakrishnan P. Iyer, Theresa Devlin, Ivan Habus, Dong Yu, Sudhir Agrawal, Nan-Hui Ho
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Patent number: 6512107Abstract: The present invention relates to a novel and improved process for preparing 2′-fluoro-5-methyl-&bgr;-L-arabinofuranosyluridine represented by formula (I) which shows anti-viral activity, especially potent anti-viral activity against hepatitis B-virus and Epstein-Barr virus:Type: GrantFiled: July 23, 1998Date of Patent: January 28, 2003Assignee: The University of Georgia Research FoundationInventors: Chung K. Chu, Jinfa Du, Yongseok Choi
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Patent number: 6509459Abstract: The invention provides new processes for synthesizing oligonucleotides that allow for deprotection of the oligonucleotide under more rapid and/or more mild conditions than existing methods. The invention further provides a nucleoside base protecting group that is stable under oligonucleotide synthesis conditions, but which can be removed under more mild conditions than existing protecting groups, as well as nucleoside synthons having such base protecting groups. The invention also provides oligonucleotides containing any of a variety of base labile functionalities and methods for using such oligonucleotides.Type: GrantFiled: April 30, 1997Date of Patent: January 21, 2003Assignee: Hybridon, Inc.Inventors: Sudhir Agrawal, Radhakrishnan P. Iyer, Ivan Habus, Dong Yu
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Patent number: 6506895Abstract: A photoactivatable nucleic acid derivative composition in which one or more photoreactive group(s) are bound to a natural or synthetic nucleic acid. The photoreactive groups can be bound to the nucleic acid before, during or after its formation, and can thereafter be activated in order to attach the nucleic acid to another molecule, e.g., to the surface of a solid support. Also described is a method of preparing such a composition, and a method of using such a composition to attach the nucleic acid to a another molecule, such as that provided by the surface of a substrate used to prepare a nucleic acid chip by photolithographic techniques.Type: GrantFiled: February 24, 1998Date of Patent: January 14, 2003Assignee: SurModics, Inc.Inventors: Patrick E. Guire, Melvin J. Swanson, Gary W. Opperman
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Patent number: 6495676Abstract: Methods and compositions are provided for detecting nucleic acid sequences. Probes comprising a crosslinking agent are combined with a sample which may comprise a target sequence which is complementary to the probe. Hybridization is allowed to occur between complementary sequences. The crosslinking agent is activated. Covalent bonds are formed between the probe and the target sequence if they are hybridized to one another. The crosslinked nucleic acids can then be detected to indicate the presence of the target sequence. Also provided are kits comprising reagents.Type: GrantFiled: September 3, 1999Date of Patent: December 17, 2002Assignee: NaxcorInventors: Michael L. Wood, David Albagli, Reuel B. Van Atta, Douglas Y. Thien, Peter C. Cheng, Bingfang Huan
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Patent number: 6489466Abstract: Immobilized nucleotide primers of this invention include a modified nucleotide tethered to a support substrate through a linking group. In particular, the modified nucleotide is constructed such that the C-5′ end of the nucleotide is tetherable to the linking group and the protected C-3′ end is available for further controlled modification, e.g., addition of other nucleotides in specific sequences to the immobilized nucleotide primer. Additionally, the linking group is of sufficient length to allow the immobilized nucleotide primer to be used to synthesize and screen arrays of oligonucleotides, e.g., enzymatic C-3′ primer extension.Type: GrantFiled: January 26, 2001Date of Patent: December 3, 2002Assignee: Linden Technologies, Inc.Inventors: Yih Huang, Tai-Nang Huang, Ming Shen
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Patent number: 6479262Abstract: The present invention provides methods of preparing large polynucleotides of arbitrary sequence and in a manner that will readily lend itself to automation. The present invention provides methods of preparing a polynucleotide having at least 200 nucleotides in either a 5′ to 3′ or 3′ to 5′ direction by ligating a plurality of oligonucleotides, the assembly of which, represents the nucleotide sequence of the desired polynucleotide.Type: GrantFiled: May 16, 2000Date of Patent: November 12, 2002Assignee: Hercules, IncorporatedInventor: Simon Delagrave
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Publication number: 20020156268Abstract: The present invention discloses improved methods for oligonucleotide synthesis and purification. In the methods of the invention, a half-life is determined for deprotection of the 5′-OH protecting group at the 5′-terminus of an oligonucleotide post-synthesis. The half-life is used to determine an optimal reaction time for removal of the 5′-OH protecting group. The methods of the invention are amenable to the large-scale synthesis and purification of oligonucleotides.Type: ApplicationFiled: March 22, 2002Publication date: October 24, 2002Inventors: Achim H. Krotz, Bethany M. McElroy, Anthony N. Scozzari
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Patent number: 6468740Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. In one particular embodiment, an array of rotated cyclic polymers is formed. In another embodiment, an array of polymers is formed based on a target polymer. The array includes systematically substituted versions of the target molecule. In another embodiment, rotated and systematically substituted cyclic polymers are formed on a substrate.Type: GrantFiled: April 8, 1998Date of Patent: October 22, 2002Assignee: Affymetrix, Inc.Inventor: Christopher P. Holmes
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Publication number: 20020150937Abstract: Disclosed are methods and compositions for extracting nucleic acids from a biological sample. In particular, disclosed is a nucleic acid extraction solution together with methods using such a solution for extracting nucleic acid sequences from biological samples containing cells, cellular debris or both. The nucleic acid extraction solution contains a molecule having the formula R1O—CH2—CH2—OR2, wherein R1 and R2 independently are selected from the group consisting of hydrogen and an alkyl group.Type: ApplicationFiled: January 15, 2002Publication date: October 17, 2002Inventors: Brian Lentrichia, Menashi A. Cohenford
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Patent number: 6465628Abstract: Synthetic processes are provided wherein oligomeric compounds are prepared having phosphodiester, phosphorothioate, phosphorodithioate, or other covalent linkages. The oligomers have substantially reduced exocyclic adducts deriving from acrylonitrile or related contaminants.Type: GrantFiled: April 9, 1999Date of Patent: October 15, 2002Assignee: ISIS Pharmaceuticals, Inc.Inventors: Vasulinga T. Ravikumar, Muthiah Manoharan, Daniel C. Capaldi, Achim Krotz, Douglas L. Cole, Andrei Guzaev
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Patent number: 6451998Abstract: A method of capping a hydroxy group of a moiety, comprising coupling the moiety to a phosphor or phosphite derivative of a protected alcohol, so as to form the corresponding phosphate or phosphite between the hydroxy and phosphor or phosphite groups. The hydroxy group may be later de-capped by hydrolyzing the resulting compound to deprotect the protected alcohol and cleave the phosphate from the moiety so as to regenerate the hydroxy group of the moiety. The method has particular application to fabrication of addressable polynucleotide arrays and allows failed sequences, as well as inter-feature regions, to be left with a free hydroxy group at the ends of the molecules (failed sequences or linkers) at such locations.Type: GrantFiled: October 18, 1999Date of Patent: September 17, 2002Assignee: Agilent Technologies, Inc.Inventor: Michael G. M. Perbost
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Publication number: 20020120128Abstract: In a process and a device for the parallel preparation of at least 4n oligonucleotides, at least four inserts each with n reaction vessels are first arranged on a plate (16), each reaction vessel containing a nucleotide initiator base bound to an inert carrier. Particular operations are then carried out in parallel with one another at four stations (28, 30, 32, 34), and in particular a deblocking operation simultaneously in all n reaction vessels of the insert at the first station (28), a first washing operation simultaneously in all n reaction vessels of the insert at the second station (30), a coupling operation in all n reaction vessels of the insert at the third station (32), and, simultaneously in all n reaction vessels of the insert at the fourth station (34), a second washing operation followed by a capping operation followed by a third washing operation followed by an oxidation operation followed by a fourth washing operation.Type: ApplicationFiled: October 26, 2001Publication date: August 29, 2002Applicant: METABION Gesellschaft fur angewandte Biotechnologie mbHInventor: Ludwig Stockl
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Patent number: 6441150Abstract: This invention presents novel methods for recovery of phosphoramidites from the waste products of oligonucleotide synthesis. The methods include reacting a tribromophenoxydichlorophosphorane with an H-phosphonate in the presence of an amine.Type: GrantFiled: August 23, 1999Date of Patent: August 27, 2002Assignee: ISIS Pharmaceuticals, Inc.Inventors: Richard H. Griffey, Douglas L. Cole, Vasulinga Ravikumar
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Patent number: 6429309Abstract: The present invention relates to a support system for the solid phase synthesis of oligomers, such as oligonucleotide, wherein the starting compound is bound to the support via a disiloxyl linkage. Furthermore, the invention relates to a method for synthesis of oligonucleotides on a solid support. The support system comprises a stable disiloxyl linkage providing high nucleoside loadings to the support and the method allows convenient non-laborious oligomer synthesis.Type: GrantFiled: August 2, 2001Date of Patent: August 6, 2002Assignee: Quiatech ABInventors: Marek Kwiatkowski, Mats Nilsson, Ulf Landegren
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Publication number: 20020103366Abstract: Method for one-pot deprotection of RNA molecules.Type: ApplicationFiled: September 21, 2001Publication date: August 1, 2002Applicant: Ribozyme Pharmaceuticals, Inc.Inventors: Laurent Bellon, Christopher T. Workman
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Publication number: 20020086989Abstract: A photoactivatable nucleic acid derivative composition in which one or more photoreactive group(s) are bound to a natural or synthetic nucleic acid. The photoreactive groups can be bound to the nucleic acid before, during or after its formation, and can thereafter be activated in order to attach the nucleic acid to another molecule, e.g., to the surface of a solid support. Also described is a method of preparing such a composition, and a method of using such a composition to attach the nucleic acid to a another molecule, such as that provided by the surface of a substrate used to prepare a nucleic acid chip by photolithographic techniques.Type: ApplicationFiled: February 24, 1998Publication date: July 4, 2002Inventors: PATRICK E. GUIRE, MELVIN J. SWANSON, GARY W. OPPERMAN
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Patent number: 6414127Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.Type: GrantFiled: September 21, 1999Date of Patent: July 2, 2002Assignee: ISIS Pharmaceuticals, Inc.Inventors: Kuei-Ying Lin, Mark D. Matteucci
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Patent number: 6407223Abstract: The process of the instant invention is drawn to the synthesis of modified P-chiral nucleotide analogues in the form of pure diastereomers possessing preselected configuration at the P-atom. Oligonucleotides prepared by the method of the invention containing P-chiral compounds have enhanced hybridization and transporting properties.Type: GrantFiled: October 14, 1999Date of Patent: June 18, 2002Assignee: Polska Akademia Nauk Cenirum Badan Molekularnych i MakromlekularnychInventors: Wojciech J. Stec, Lucyna A. Woźniak, Arkadiusz Chworoś, Jaroslaw Pyzowski
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Publication number: 20020072593Abstract: The present invention relates to a method of preventing modification of a synthetic oligonucleotide or oligonucleotide analog during removal of at least one &bgr;-cyanoethyl protecting group from the oligonucleotide or oligonucleotide analog. The method involves contacting the oligonucleotide or oligonucleotide analog with a basic solution having at least one acrylonitrile scavenger, such as t-butylamine, at a sufficient temperature and for a sufficient period of time to remove at least one &bgr;-cyanoethyl protecting group. The present invention also relates to a method of producing a synthetic oligonucleotide or oligonucleotide analog.Type: ApplicationFiled: June 12, 2001Publication date: June 13, 2002Applicant: Avecia Biotechnology Inc.Inventor: Nanda D. Sinha
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Patent number: 6403781Abstract: This invention presents novel methods for synthesizing phosphorothioate oligonucleotides, using support-bound phosphoramidites. Novel intermediates useful in the methods are also provided.Type: GrantFiled: January 8, 2001Date of Patent: June 11, 2002Assignee: ISIS Pharmaceuticals, Inc.Inventors: Douglas L. Cole, Vasulinga Ravikumar
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Patent number: 6399765Abstract: The present invention discloses improved methods for oligonucleotide synthesis and purification. In the methods of the invention, a half-life is determined for deprotection of the 5′-OH protecting group at the 5′-terminus of an oligonucleotide post-synthesis. The half-life is used to determine an optimal reaction time for removal of the 5′-OH protecting group. The methods of the invention are amenable to the large-scale synthesis and purification of oligonucleotides.Type: GrantFiled: March 17, 1999Date of Patent: June 4, 2002Assignee: ISIS Pharmaceuticals, Inc.Inventors: Achim H. Krotz, Bethany M. McElroy, Anthony N. Scozzari
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Publication number: 20020058802Abstract: A method of synthesizing a polynucleotide which can, for example, be used during fabrication of an array. A second nucleoside is coupled to a first nucleoside through a phosphite linkage, with the second nucleoside having a hydroxyl protecting group that is a non-carbonate protecting group. The product of the foregoing step is exposed to a composition which both oxidizes the formed phosphite to a phosphate and deprotects the protected hydroxyl of the coupled nucleoside. The method has particular application to fabricating an addressable array of polynucleotides on a substrate which carries substrate bound moieties each with a hydroxyl group.Type: ApplicationFiled: July 27, 2001Publication date: May 16, 2002Inventors: Douglas J. Dellinger, Michael G. M. Perbost, Marvin H. Caruthers, Jason R. Betley