Pentavalent Phosphorus Compound Utilized Patents (Class 536/25.33)
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Publication number: 20090036660Abstract: In some embodiments, the present disclosure provides methods of making a mixture of nucleic acid molecules, the methods comprising the steps of: synthesizing on a substrate a population of nucleic acid molecules wherein each synthesized nucleic acid molecule comprises a substrate-attached proximal nucleic acid molecule, a distal nucleic acid molecule, and a cleavable linker linking the proximal nucleic acid molecule to the distal nucleic acid molecule, and harvesting distal nucleic acid molecules from the substrate by cleaving the cleavable linker under conditions that do not release the proximal nucleic acid molecule. Related compositions and kits are also provided.Type: ApplicationFiled: July 31, 2007Publication date: February 5, 2009Inventors: Joel Myerson, Emily M. Leproust, Douglas J. Dellinger
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Patent number: 7470783Abstract: 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: April 14, 2005Date of Patent: December 30, 2008Assignee: Affymetrix, Inc.Inventors: Glenn H. McGall, Ngo Q. Nam, Richard P. Rava
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Publication number: 20080254516Abstract: The invention provides efficient methods of isolating specific nucleic acid targets to obtain information from target nucleic acid sequences in a relatively short time period. DNA or cDNA is enzymatically digested into smaller fragments, double-stranded DNA linkers are added onto the ends of the DNA fragments to flank each fragment with a known DNA sequence. The fragments are mixed with an oligonucleotide probe that is bound to a marker and contains a conserved nucleic acid sequence of interest. The fragments that hybridize to the probe through nucleotide base pair complementation become indirectly connected to the marker. These target fragments are captured using a capture agent that specifically recognizes the marker and treated to prevent non-specific binding. Captured fragments are typically cloned prior to sequencing. The captured fragments may also be amplified using PCR to increase the efficiency of the cloning.Type: ApplicationFiled: March 1, 2005Publication date: October 16, 2008Inventors: Judith St. John, Thomas W. Quinn
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Patent number: 7435810Abstract: A method of fabricating polynucleotide arrays includes dissolving a nucleotide monomer, oligonucleotide, or polynucleotide in a solvent containing ionic liquid and depositing the resulting solution on an array substrate. The method has particular application to fabrication of an addressable array of polynucleotides on a substrate that carries substrate bound moieties each with a hydroxyl group. The process may be repeated at specific locations on the array to elongate the polynucleotide deposited on the array.Type: GrantFiled: December 22, 2004Date of Patent: October 14, 2008Assignee: Agilent Technologies, Inc.Inventors: Joel Myerson, Michel G M Perbost, Douglas J Dellinger, Geraldine F Dellinger
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Patent number: 7417139Abstract: Methods of forming an internucleotide bond are disclosed. Such methods find use in synthesis of polynucleotides. The method involves contacting a functionalized support with a precursor having an exocyclic amine triaryl methyl protecting group under conditions and for a time sufficient to result in internucleotide bond formation. The functionalized support includes a solid support, a triaryl methyl linker group, and a nucleoside moiety having a reactive site hydroxyl, the nucleoside moiety attached to the solid support via the triaryl methyl linker group.Type: GrantFiled: August 30, 2003Date of Patent: August 26, 2008Assignee: Agilent Technologies, Inc.Inventors: Douglas J Dellinger, Agnieszka B. Sierzchala, Marvin H Caruthers, Geraldine F Dellinger
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Patent number: 7411061Abstract: A method of synthesizing polynucleotides is disclosed. The method involves contacting a first nucleotide with a selected reactive group in the presence of an ionic liquid. The selected reactive group may be on a second nucleotide, a polynucleotide, or on a moiety on an insoluble substrate, for example in an oligonucleotide synthesizer.Type: GrantFiled: December 22, 2004Date of Patent: August 12, 2008Assignee: Agilent Technologies, Inc.Inventors: Joel Myerson, Michel G. M. Perbost, Douglas J. Dellinger, Geraldine F Dellinger
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Patent number: 7385050Abstract: Functionalized supports for polynucleotide synthesis are disclosed. The supports have linker moieties that are stable to conditions used in polynucleotide synthesis, but may be cleaved to release synthesized polynucleotides from the support. Methods of making the functionalized supports and methods of using are also disclosed.Type: GrantFiled: August 30, 2003Date of Patent: June 10, 2008Assignee: Agilent Technologies, Inc.Inventors: Douglas J Dellinger, Geraldine F Dellinger, Marvin H Caruthers
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Patent number: 7381820Abstract: A method for producing 2?-deoxy-2?-fluoro-?-D-arabinonucleoside represented by formula (II): (wherein B represents a base), in particular, 2?-deoxy-2?-fluoro-?-D-arabinopurinenucleoside, which method comprises causing a nucleoside phosphorylase to act on ?-1-phosphorylated-2-deoxy-2-fluoroarabinoside represented by formula (I): or a mixture of ?- and ?-isomers of 1-phosphorylated-2-deoxy-2-fluoroarabinoside represented by formula (V?): and on a base. The compound can be produced at high yield and in a convenient and highly stereoselective manner.Type: GrantFiled: October 22, 2004Date of Patent: June 3, 2008Assignee: Yamasa CorporationInventors: Kohei Yamada, Noritake Matsumoto, Hiroyuki Hayakawa
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Patent number: 7378516Abstract: Methods for the formation of sulfurized oligonucleotides are provided. The methods allow for the formation of phosphorothioate linkages in the oligonucleotides or derivatives, without the need for complex solvent mixtures and repeated washing or solvent changes. Oligonucleotides having from about 8, and up to about 50, nucleotides can be sulfurized according to the methods of the invention with higher yields than have been previously reported.Type: GrantFiled: May 17, 2004Date of Patent: May 27, 2008Assignee: ISIS Pharmaceuticals, Inc.Inventors: Douglas L. Cole, Vasulinga T. Ravikumar, Zacharia S. Cheruvallath
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Patent number: 7371852Abstract: Alkyl-linked nucleotide non-homogeneous solid supports and nucleotide affinity media comprising an alkyl-linked nucleotide are provided. The linker is generally a hydrophobic linker that can be a 3, 4, 5, 6, 7, 8, 9, 10, or a longer carbon chain. Also included in the invention are methods for synthesis of an alkyl-linked nucleotide, nucleotide affinity media and methods of use thereof for affinity chromatography and screening methods.Type: GrantFiled: January 21, 2004Date of Patent: May 13, 2008Assignee: Serenex, Inc.Inventors: Klass P. Hardeman, Steven E. Hall, Roy W. Ware, Lindsay A. Hinkley, Matthew G. Jenks
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Patent number: 7355037Abstract: Provided is a hydroxyl-protected alcohol of the formula R—O—Pg, wherein Pg is a protecting group of the formula: wherein Y, Z, W, R1, R1a, R2, R2a, R3, R3a, R4, R4a, a, b, c, d, e and f are defined herein and R is a nucleosidyl group, an oligonucleotidyl group with 2 to about 300 nucleosides, or an oligomer with 2 to about 300 nucleosides. Also provided is a deprotection method, which includes heating the hydroxyl-protected alcohol at a temperature effective to cleave thermally the hydroxyl-protecting group therefrom.Type: GrantFiled: December 3, 2002Date of Patent: April 8, 2008Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Serge L. Beaucage, Andrzej Grajkowski, Andrzej Wilk
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Patent number: 7348391Abstract: The present invention provides solid support media for use in oligomer synthesis, methods of producing the media, and methods of using the media. In some embodiments, the processes of the invention comprise (a) providing an organic phase comprising an olefin monomer, a cross-linker, a functionalizing reagent and an initiator; and (b) contacting the organic phase with an aqueous phase under conditions of time and temperature effective to form the polymeric bead.Type: GrantFiled: September 2, 2005Date of Patent: March 25, 2008Assignees: Isis Pharmaceuticals, Inc., Nitto Denko CorporationInventors: Vasulinga Ravikumar, Raju K. Kumar, Kenjirou Mori, Tatsuya Konishi, Ayako Matsunawa, Takeo Matsumura, Cheiko Kitaura, Gang Zhao
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Patent number: 7247720Abstract: A process for the phosphitylation of an alcohol or thiol with a phosphitylation agent in the presence of an activator is provided. The activator has the formula: wherein p is 0 or an integer from 1 to 4 and R for each occurrence is a substituent. Preferably X7 is O and p is 0. The activator is commonly employed as a salt complex with an organic base. Preferred alcohols or thiols include nucleosides and oligonucleotides. The process is particularly suited for the synthesis of phosphoramidites.Type: GrantFiled: October 8, 2003Date of Patent: July 24, 2007Assignee: Avecia Biotechnology Inc.Inventor: Nanda Dulal Sinha
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Patent number: 7230095Abstract: A solid support bound polynucleotide, preferably a 3?-O- or 5?-O-substituted polynucleotide, is disclosed. The polynucleotides are of formula: wherein Q is a substantially pure polynucleotide, each X is O or S; Y is an inert spacer group; R represents the solid support. Also disclosed is a method of isolating a target biomolecule, preferably a protein or a polynucleotide, from a mixture.Type: GrantFiled: April 25, 2002Date of Patent: June 12, 2007Assignee: Avecia Biotechnology Inc.Inventor: Nanda Dulal Sinha
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Patent number: 7227015Abstract: Methods for the formation of sulfurized oligonucleotides are provided. The methods allow for the formation of phosphorothioate linkages in the oligonucleotides or derivatives, without the need for complex solvent mixtures and repeated washing or solvent changes. Oligonucleotides having from about 8, and up to about 50, nucleotides can be sulfurized according to the methods of the invention with higher yields than have been previously reported.Type: GrantFiled: January 10, 2001Date of Patent: June 5, 2007Assignee: ISIS Pharmaceuticals, Inc.Inventors: Douglas L. Cole, Vasulinga T. Ravikumar, Zacharia S. Cheruvallath
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Patent number: 7227017Abstract: A process for the synthesis of phosphorothioate oligonucleotides is provided which comprises assembling an oligonucleotide bound to a solid support in the presence of acetonitrile; prior to cleaving the oligonucleotide from the solid support removing the acetonitrile; and cleaving the oligonucleotide from the solid support. The process is particularly suited to the large scale synthesis of nucleotides. The acetonitrile may be removed from the solid support by one or both of drying and by washing with solvents. Preferred washing solvents comprise trialkylamines.Type: GrantFiled: June 5, 2003Date of Patent: June 5, 2007Assignee: Avecia LimitedInventors: Ben James Mellor, Donald Alfred Wellings, Mark Edward Douglas
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Patent number: 7205399Abstract: The present invention features novel compositions, linkers, derivatized solid supports, and methods for the efficient solid phase synthesis of oligonucleotides, including RNA, DNA, RNA-DNA chimeras, and analogs thereof.Type: GrantFiled: July 3, 2002Date of Patent: April 17, 2007Assignee: Sirna Therapeutics, Inc.Inventors: Chandra Vargeese, Weimin Wang
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Patent number: 7199236Abstract: 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: September 14, 2004Date of Patent: April 3, 2007Assignee: 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: 7193077Abstract: Precursors for use in the synthesis of polynucleotides and methods of using the precursors in synthesizing polynucleotides are disclosed. The precursors include a heterocyclic base having an exocyclic amine group and a substituted or unsubstituted triaryl methyl protecting group bound to the exocyclic amine group.Type: GrantFiled: August 30, 2003Date of Patent: March 20, 2007Assignee: Agilent Technologies, Inc.Inventors: Douglas J. Dellinger, Agnieszka B. Sierzchala, Marvin H. Caruthers
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Patent number: 7186822Abstract: 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: December 28, 2004Date of Patent: March 6, 2007Assignee: Isis Pharmaceuticals, Inc.Inventors: Vasulinga Ravikumar, Muthiah Manoharan, Daniel C. Capaldi, Achim Krotz, Douglas L. Cole, Andrei P. Guzaev
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Patent number: 7186813Abstract: Biomolecules are provided having multiple binding sites for attachment to a substrate surface. The multiple attachment sites may be produced directly on the biomolecule or through use of branched phosphoramidite moieties that can be added in multiple to form dendritic structures which can in turn provide attachment sites for substrate binding moieties. Substrate binding moieties may include noncovalent binding moieties. For covalent binding moieties oligonucleotides containing hydrazides are provided. These hydrazides can be introduced via protected building blocks such as phosphoramidites or via building blocks containing precursor forms of such hydrazides.Type: GrantFiled: August 11, 2000Date of Patent: March 6, 2007Assignee: Nanogen Recognomics GmbHInventors: Markus Schweitzer, Norbert Windhab, John R. Havens, Thomas J. Onofrey, Charles Greef, Daguang Wang
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Patent number: 7169916Abstract: A process of manufacturing oligonucleotides includes a 5?-deblocking step in which the 5-blocking group is removed with dichloroacetic acid that is essentially free of chloral. The process is useful for making oligonucleotides that are substantially free of chloral adducts.Type: GrantFiled: March 31, 2003Date of Patent: January 30, 2007Assignee: Isis Pharmaceuticals, Inc.Inventors: Achim Krotz, Daniel Capaldi, Hans Gaus, Brett Turney
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Patent number: 7144700Abstract: Methods, employing a polycyclic hydrocarbon or a polycyclic heteroaromatic compound as sensitizers, are provided to increase the efficiency of removing, by irradiation, photolabile protecting groups that mask reactive sites on synthesis intermediaries. Preferred groups of photolabile protecting moieties include: ((?-methyl-2-nitropiperonyl)-oxy)carbonyl (MeNPOC), ((Phenacyl)-oxy)carbonyl (PAOC), O-(9-phenylxanthen-9-yl) (PIXYL), and ((2-methylene-9,10-anthraquinone)-oxy)carbonyl (MAQOC). In conjunction with using the sensitizers and protecting groups described above, a method of forming, from component molecules, a plurality of compounds on a support, each compound occupying a separate predefined region of the support is provided. These resulting solid-phase arrays are useful, for example, to assay for the presence of biochemical products in biological samples.Type: GrantFiled: July 21, 2000Date of Patent: December 5, 2006Assignee: Affymetrix, Inc.Inventors: Glenn McGall, Daniel E. Falvey, Jacqueline A. Fidanza, Brian M. Feldman
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Patent number: 7138384Abstract: A synthetic oligonucleotide comprising a C-5 methylcytosine and which recognizes and binds an allosteric site on DNA methyltransferase thereby inhibiting DNA methyltransferase activity is disclosed. Also disclosed is a composition comprising a synthetic oligonucleotide of the invention. The composition is useful for inhibiting DNA methyltransferase activity, thereby inhibiting the methylation of DNA. The composition can be a pharmaceutical composition useful for treating disorders associated with methylation defects, such as cancer and certain developmental disorders. Also disclosed is a method of inhibiting methylation of DNA. The method involves contacting a DCMTase with a synthetic oligonucleotide of the invention in the presence of the DNA, thereby resulting in an enzyme/synthetic oligonucleotide complex. The presence of the complex prevents catalysis, thereby inhibiting DNA methyltransferase activity.Type: GrantFiled: June 12, 1998Date of Patent: November 21, 2006Assignee: The Regents of the University of CaliforniaInventors: Norbert O. Reich, James Flynn
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Patent number: 7135565Abstract: 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: GrantFiled: July 27, 2001Date of Patent: November 14, 2006Assignees: Agilent Technologies, Inc., University of ColoradoInventors: Douglas J. Dellinger, Michael G. M. Perbost, Marvin H. Caruthers, Jason R. Betley
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Patent number: 7135564Abstract: A reusable linker arm for solid support oligonucleotide synthesis, the linker arm comprising formula (a) wherein Z is a linker moiety and T is an organic radical.Type: GrantFiled: June 30, 1999Date of Patent: November 14, 2006Assignee: University Technologies International Inc.Inventors: Richard T. Pon, Shuyuan Yu
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Patent number: 7125982Abstract: The present method describes the use of thio-phosphate as a feed source for micro-organisms and multi-cellular organisms. This compound enters into nucleotide pools and ultimately into polymers of both RNA and DNA forming stable phosphorothioate internucleotide linkages. The method enables the microbial synthesis of both plasmid and phage DNA substituted with phosphorothioate. Furthermore, methods are described for the preparation of phosphorothioate oligo mixtures from recombinant phage DNA grown in modified media for use in antisense studies.Type: GrantFiled: December 5, 2001Date of Patent: October 24, 2006Assignee: Frayne ConsultantsInventor: Elizabeth Gay Frayne
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Patent number: 7087732Abstract: 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 28, 2001Date of Patent: August 8, 2006Assignee: Affymetrix, Inc.Inventors: Stephen P. A. Fodor, Lubert Stryer, J. Leighton Read, Michael C. Pirrung
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Patent number: 7049432Abstract: The present invention provides alkylphosphonate dimers and oligonucleotides prepared therefrom. The invention further provides novel methods for the preparation of these alkylphosphonate dimers. Methods for the preparation of substantially diastereomerically pure alkylphosphonate dimers are also provided.Type: GrantFiled: June 4, 2002Date of Patent: May 23, 2006Assignees: ISIS Pharmaceuticals, Inc., McGill UniversityInventors: Muthiah Manoharan, George Just, Andrei Guzaev, Arlène Roland, Jianchao Wang, Michael E. Jung
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Patent number: 7041816Abstract: 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: January 20, 2004Date of Patent: May 9, 2006Assignee: 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: 7022833Abstract: A process for the synthesis of a phosphorothioate triester is provided. The process comprises the coupling of an H-phosphonate with an alcohol in the presence of a solution comprising both a coupling agent and a sulfur transfer agent. Preferably, the H-phosphonate and alcohol are protected nucleosides or oligonucleotides.Type: GrantFiled: February 23, 2001Date of Patent: April 4, 2006Assignee: Avecia LimitedInventor: Colin Bernard Reese
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Patent number: 7019127Abstract: A process for the synthesis in solution phase of a phosphorothioate triester is provided. The process comprises the solution phase coupling of an H-phosphonate with an alcohol in the presence of a coupling agent to form an H-phosphonate diester. The H-phosphonate diester is oxidised in situ with a sulfur transfer agent to produce the phosphorothioate triester. Preferably, the H-phosphonate and alcohol are protected nucleosides or oligonucleotides. Oligonucleotide H-phosphonates which can be used in the formation of phosphorothioate triesters are also provided.Type: GrantFiled: November 15, 2002Date of Patent: March 28, 2006Assignee: Avecia LimitedInventors: Colin Bernard Reese, Quanlai Song
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Patent number: 6951931Abstract: 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: November 14, 2002Date of Patent: October 4, 2005Assignee: ISIS Pharmaceuticals, Inc.Inventors: Kuei-Ying Lin, Mark D. Matteucci
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Patent number: 6902900Abstract: The invention comprises novel methods and strategies to detect and/or quantify nucleic acid analytes. The methods involve nucleic acid probes with covalently conjugated dyes, which are attached either at adjacent nucleotides or at the same nucleotide of the probe and novel linker molecules to attach the dyes to the probes. The nucleic acid probes generate a fluorescent signal upon hybridization to complementary nucleic acids based on the interaction of one of the attached dyes, which is either an intercalator or a DNA groove binder, with the formed double stranded DNA. The methods can be applied to a variety of applications including homogeneous assays, real-time PCR monitoring, transcription assays, expression analysis on nucleic acid microarrays and other microarray applications such as genotyping (SNP analysis). The methods further include pH-sensitive nucleic acid probes that provide switchable fluorescence signals that are triggered by a change in the pH of the medium.Type: GrantFiled: October 21, 2002Date of Patent: June 7, 2005Assignee: Prolico, LLCInventors: Martin Davies, Ian Bruce, Andreas Wolter
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Patent number: 6881836Abstract: 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: January 22, 2003Date of Patent: April 19, 2005Assignee: Affymetrix, IncInventors: Glenn H. McGall, Ngo Q. Nam, Richard P. Rava
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Patent number: 6858720Abstract: A method of synthesizing polynucleotides is disclosed. The method involves contacting a first nucleotide with a selected reactive group in the presence of an ionic liquid. The selected reactive group may be on a second nucleotide, a polynucleotide, or on a moiety on an insoluble substrate, for example in an oligonucleotide synthesizer.Type: GrantFiled: October 31, 2001Date of Patent: February 22, 2005Assignee: Agilent Technologies, Inc.Inventors: Joel Myerson, Michel G. M. Perobost, Douglas J. Dellinger, Geraldine F Dellinger
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Patent number: 6858722Abstract: 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 23, 2003Date of Patent: February 22, 2005Assignee: Isis Pharmaceuticals, Inc.Inventors: Vasulinga T. Ravikumar, Daniel C. Capaldi, Douglas L. Cole
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Patent number: 6852850Abstract: A method of fabricating polynucleotide arrays includes dissolving a nucleotide monomer, oligonucleotide, or polynucleotide in a solvent containing ionic liquid and depositing the resulting solution on an array substrate. The method has particular application to fabrication of an addressable array of polynucleotides on a substrate that carries substrate bound moieties each with a hydroxyl group. The process may be repeated at specific locations on the array to elongate the polynucleotide deposited on the array.Type: GrantFiled: October 31, 2001Date of Patent: February 8, 2005Assignee: Agilent Technologies, Inc.Inventors: Joel Myerson, Michel G M Perbost, Douglas J Dellinger, Geraldine F. Dellinger
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Patent number: 6825338Abstract: Selectively functionalized oligonucleotides, methods for making same, and compounds useful therefor are disclosed. The oligonucleotides can be selectively functionalized with a first conjugate group at the 3′-terminial position and optionally functionalized with a second conjugate group at the 5′-terminal position and/or one or more internucleotides. Alternatively, the oligonucleotides can be selectively functionalized with a first conjugate group at the 5′-terminal position and optionally functionalized with a second conjugate group at one or more internucleotides. In yet another embodiment, the oligonucleotides can be functionalized with a first conjugate group at one or more internucleotides and with a second conjugate group at one or more different internucleotides.Type: GrantFiled: March 30, 2001Date of Patent: November 30, 2004Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Andrei P. Guzaev
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Patent number: 6825331Abstract: 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: September 3, 2002Date of Patent: November 30, 2004Assignee: ISIS Pharmaceuticals, Inc.Inventors: Muthiah Manoharan, Harri Lonnberg, Harri Salo, Pasi Virta
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Patent number: 6822088Abstract: The present invention relates to methods for synthesizing an oligomeric compound on a solid support comprising contacting a solid support with a filling material to produce a mixture thereof; placing the mixture in a reaction vessel; and synthesizing the oligomeric compound. The present invention also relates to (a) reaction vessels for synthesizing oligomeric compounds comprising a solid support; and a filling material, (b) apparatuses for synthesizing oligomeric compounds comprising a reagent source, and a reaction vessel comprising a solid support; and a filling material, and (c) compositions comprising a solid support and a filling material mixed therewith.Type: GrantFiled: July 16, 2002Date of Patent: November 23, 2004Assignee: ISIS Pharmaceuticals, Inc.Inventors: Max Moore, Achim H. Krotz, Mark Andrade, Anthony N. Scozzari
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Patent number: 6809195Abstract: The present invention discloses methods for synthesizing oligomeric compounds. The methods include a modified phosphoramidite protocol wherein the oxidation and capping steps are combined into a single step. The methods result in increased efficiency and are especially amenable to the large scale synthesis of oligomeric compounds.Type: GrantFiled: August 16, 2000Date of Patent: October 26, 2004Assignee: ISIS Pharmaceuticals, Inc.Inventors: Yogesh S. Sanghvi, Quanlai Song
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Patent number: 6800743Abstract: 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: May 21, 2002Date of Patent: October 5, 2004Assignee: ISIS Pharmaceuticals, Inc.Inventors: Kuei-Ying Lin, Mark D. Matteucci
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Patent number: 6790946Abstract: A method of preparing an immobilized oligonucleotide having a free 3′-end comprises the steps of: i) preparing an oligonucleotide attached in a first position to a solid support via its 3′-end and having a free 5′-end; ii) binding said oligonucleotide in a second position remote from the 3′-end to the solid support; and iii) selectively releasing the 3′-end of the oligonucleotide from the solid support to obta the oligonucleotide attached to the support in said second position in a reversed orientation with a free 3′-end.Type: GrantFiled: September 12, 2001Date of Patent: September 14, 2004Assignee: Quiatech ABInventors: Marek Kwiatkowski, Ulf Landegren, Mats Nilsson
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Patent number: 6790945Abstract: Oligonucleotide probes containing two labels are provided and are useful in hybridization assays. The probes can also contain a minor groove binding group.Type: GrantFiled: June 6, 2001Date of Patent: September 14, 2004Assignee: Epoch Biosciences, Inc.Inventors: Eugeny A. Lukhtanov, Alexander A. Gall, Robert O. Dempcy, Nicolaas M. J. Vermeulen
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Patent number: 6780982Abstract: The present invention relates to novel phosphoramidites, including positive and neutrally charged compounds. The present invention also provides charge tags for attachment to materials including solid supports and nucleic acids, wherein the charge tags increase or decrease the net charge of the material. The present invention further provides methods for separating and characterizing molecules based on the charge differentials between modified and unmodified materials.Type: GrantFiled: February 6, 2001Date of Patent: August 24, 2004Assignee: Third Wave Technologies, Inc.Inventors: Victor Lyamichev, Zbigniew Skrzpczynski, Hatim T. Allawi, Sarah R. Wayland, Tsetska Takova, Bruce P. Neri
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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: 6683167Abstract: The invention provides hybrid oligonucleotides having phosphorothioate or phosphorodithioate internucleotide linkages, and both deoxyribonucleosides and ribonucleosides or 2′-substituted ribonucleosides. Such hybrid oligonucleotides have superior properties of duplex formation with RNA, nuclease resistance, and RNase H activation.Type: GrantFiled: June 22, 2001Date of Patent: January 27, 2004Assignee: University of Massachusetts WorcesterInventors: Valeri Metelev, Sudhir Agrawal
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Patent number: 6673940Abstract: The design, synthesis, and use of cyclic compounds, including cyclic polyamides, is described. Such compounds comprise at least two polymer portions, one of which comprises at least three molecular units, and the other comprises at least four molecular units. At least one molecular unit of such a compound is a hydrogen bond donor or acceptor. The polymer portions are covalently linked to form a cycle. These compounds are capable of targeting specific nucleotide sequences in double-stranded nucleic acids, particularly double-stranded DNA. Accordingly, such compounds can be used to modulate, e.g., increase or decrease, the expression of one or more genes in vitro or in vivo.Type: GrantFiled: January 6, 2000Date of Patent: January 6, 2004Assignee: California Institute of TechnologyInventors: Peter B. Dervan, Eldon E. Baird
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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