Pentavalent Phosphorus Compound Utilized Patents (Class 536/25.33)
  • Patent number: 10829803
    Abstract: The present invention provides compositions, apparatuses and methods for detecting one or more nucleic acid targets present in a sample. Methods of the invention include utilizing two or more oligonucleotide probes that reversibly bind a target nucleic acid in close proximity to each other and possess complementary reactive ligation moieties. When such probes have bound to the target in the proper orientation, they are able to undergo a spontaneous chemical ligation reaction that yields a ligated oligonucleotide product. In accordance with the invention, the presence of the target(s) of interest can be determined by measuring the presence or amount of ligated oligonucleotide product.
    Type: Grant
    Filed: May 10, 2007
    Date of Patent: November 10, 2020
    Assignee: DXTERITY DIAGNOSTICS INCORPORATED
    Inventor: Robert Terbrueggen
  • Patent number: 10508276
    Abstract: The technology described herein relates to siRNAs, e.g., methods and compositions relating to the production of siRNAs in bacterial cells.
    Type: Grant
    Filed: November 6, 2017
    Date of Patent: December 17, 2019
    Assignee: CHILDREN'S MEDICAL CENTER CORPORATION
    Inventors: Judy Lieberman, Linfeng Huang
  • Patent number: 9605019
    Abstract: The present application, among other things, provides technologies, e.g., reagents, methods, etc. for preparing oligonucleotides comprising phosphorothiotriesters linkages, e.g., oligonucleotides having the structure of IIIa, IIIb or IIIc. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ia or Ib with a silylating reagent to provide a silyloxyphosphonate, and reacting the silyloxyphosphonate with a thiosulfonate reagent of structure IIa or IIb to provide an oligonucleotide of structure IIIa or IIIb.
    Type: Grant
    Filed: July 13, 2012
    Date of Patent: March 28, 2017
    Assignee: WAVE LIFE SCIENCES LTD.
    Inventors: Gregory L. Verdine, Meena, Naoki Iwamoto, David Charles Donnell Butler
  • Patent number: 8901289
    Abstract: The present invention provides a method for preparing nucleotide oligomers, including (a) coupling a nucleotide dimer or nucleotide trimer to a nucleoside attached to solid supports or to universal solid supports as a starting material; (b) sequentially coupling nucleotide monomers to the resulting structures of Step (a) to prepare a nucleotide oligomer; and (c) removing the nucleotide oligomers from the solid supports. The method of the present invention provides nucleotide oligomers having 15-20% higher purity than the conventional art. The present invention enables the efficient and inexpensive synthesis of nucleotide oligomers with high purity within a shorter period of time.
    Type: Grant
    Filed: May 7, 2010
    Date of Patent: December 2, 2014
    Assignee: St. Pharm Co., Ltd.
    Inventors: Kyeong-Eun Jung, Alexei Kayushin, Moon Hee Kim, Kyung-Il Kim, Sungwon Kim, Yumi Ji
  • Patent number: 8895723
    Abstract: Disclosed herein are methods of preparing a phosphorothioate nucleotide analog, which are useful in treating diseases and/or conditions such as viral infections.
    Type: Grant
    Filed: March 18, 2013
    Date of Patent: November 25, 2014
    Assignees: Alios BioPharma, Inc., Vertex Pharmaceuticals Inc.
    Inventors: Vladimir Serebryany, Jyanwei Liu, Leonid Beigelman, Young Chun Jung, Peter Jamison Rose, Shereen Ibrahim, Cavan McKeon Bligh, Luigi Anzalone
  • Patent number: 8859755
    Abstract: A method for preparing a phosphorothioate RNA based on the oxazaphospholidine method, wherein cyanoethoxymethyl group is used instead of tert-butyldimethylsilyl group as a protective group of 2?-hydroxyl group of RNA.
    Type: Grant
    Filed: March 4, 2011
    Date of Patent: October 14, 2014
    Assignee: Chiralgen, Ltd.
    Inventors: Takeshi Wada, Yohei Nukaga
  • Patent number: 8846896
    Abstract: Disclosed herein are methods of preparing a phosphorothioate nucleotide analog, which are useful in treating diseases and/or conditions such as viral infections.
    Type: Grant
    Filed: March 11, 2013
    Date of Patent: September 30, 2014
    Inventors: Vladimir Serebryany, Jyanwei Liu, Leonid Beigelman, Young Chun Jung, Jamison Rose, Shereen Ibrahim, Cavan McKeon, Luigi Anzalone
  • Patent number: 8735569
    Abstract: Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.
    Type: Grant
    Filed: July 8, 2013
    Date of Patent: May 27, 2014
    Assignee: Gilead Pharmasset LLC
    Inventors: Bruce S. Ross, Michael Joseph Sofia, Ganapati Reddy Pamulapati, Suguna Rachakonda, Hai-Ren Zhang, Byoung-Kwon Chun, Peiyuan Wang
  • Patent number: 8642755
    Abstract: A method and compositions for sulfurizing at least one phosphite or thiophosphite linkage in an oligonucleotide. The methods employ a phenylacetyl disulfide reagent (known as PADS), phenylthioacetic acid (PTAA) in the presence or absence or N-alkyl imidazole in industrially preferred solvents or solvents that are derived from renewable resources. The use of PTAA eliminates the need to “age” the PADS solution prior to its use in sulfurization reactions.
    Type: Grant
    Filed: June 30, 2009
    Date of Patent: February 4, 2014
    Assignee: Agilent Technologies, Inc.
    Inventors: Agnieszka B. Sierzchala, Douglas J Dellinger, Victor R Mokler, Zoltan Timar
  • Patent number: 8629263
    Abstract: Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.
    Type: Grant
    Filed: January 25, 2013
    Date of Patent: January 14, 2014
    Assignee: Gilead Pharmasset LLC
    Inventors: Bruce Ross, Michael Joseph Sofia, Ganapati Reddy Pamulapati, Suguna Rachakonda, Hai-Ren Zhang, Byoung-Kwon Chun, Peiyuan Wang
  • Patent number: 8569476
    Abstract: A method for preparing oligonucleotide comprising reacting the compound of Formula (1) with the compound of Formula (2) in a liquid reaction medium under the condition of condensation reaction to obtain the compound of formula (3) is provided. 1-(2-mesitylenesulfonyl)-3-nitro-1H-1,2,4-triazole (MSNT) is applied as condensing agent. Oligonucleotides synthesized in the liquid reaction medium could be obtained on a large scale.
    Type: Grant
    Filed: September 22, 2009
    Date of Patent: October 29, 2013
    Assignee: Suzhou Ribo Life Science Co., Ltd.
    Inventors: Zhen Xi, Jinyu Huang, Junbin Zhang
  • Patent number: 8492536
    Abstract: A method for modifying nucleic acid bases by a chemical means, which enables the discrimination of every base species in plural species of bases in a nucleic acid comprising plural nucleotide units, while retaining the base sequence information of the nucleic acid. A nucleic acid base-modified product provided by the method. The nucleic acid base-modified product is essentially a single strand. In accordance with the invention, a novel means for sequencing a nucleic acid by a microscopic means is provided.
    Type: Grant
    Filed: August 8, 2008
    Date of Patent: July 23, 2013
    Assignees: Inter-University Research Institute Corporation National Institute of Natural Sciences, Nagayama IP Holdings, LLC
    Inventors: Masanori Kataoka, Kuniaki Nagayama
  • Publication number: 20130096291
    Abstract: A method for synthesizing an oligonucleotide which comprises using a sulfurizing agent of general formula (I) for sulfurizing at least one phosphorus internucleotide linkage of a precursor of the oligonucleotide, wherein R is an aryl group or a heteroaryl group, which is bonded to the S-atom through an annular carbon atom; and R1 and R2 are independently organic residues, preferably a C1-C20 hydrocarbon residue. The method may further comprise purifying the oligonucleotide. Also included is a process for the synthesis of the sulfurizing agent.
    Type: Application
    Filed: June 30, 2011
    Publication date: April 18, 2013
    Applicant: GIRINDUS AMERICA, INC.
    Inventors: Yigang He, Victor Sorokin, Wieslaw Adam Mazur
  • Patent number: 8350022
    Abstract: The present invention relates to a method for stereoselective synthesis of phosphorus compounds, whereby in the first reaction step a chiral auxiliary on the phosphorus atom of phosphoryl chloride, thiophosphoryl chloride or phosphorus trichloride is covalently bonded, the product from the first reaction step is reacted in the following step with an alcohol, thiol, or amine as the nucleophile in the presence of a base, and in the last step the chiral auxiliary is displaced from the product of the following step by a nucleophile.
    Type: Grant
    Filed: April 3, 2009
    Date of Patent: January 8, 2013
    Assignee: Universitaet Hamburg
    Inventors: Chris Meier, Jens O. Thomann
  • Patent number: 8344132
    Abstract: Methods for the preparation of the ? isomer of a 9-deazapurine derivatives using benzyl protecting groups as the protecting groups for the 2 and 3 hydroxyl groups in ribose are provided.
    Type: Grant
    Filed: June 21, 2006
    Date of Patent: January 1, 2013
    Assignee: BioCryst Pharmaceticals, Inc.
    Inventors: Pooran Chand, Minwan Wu, Pravin L. Kotian, V. Satish Kumar, Tsu-Hsing Lin
  • Publication number: 20120322993
    Abstract: Disclosed are a novel phosphorylating reagent and related methods. Specifically disclosed is a compound represented by general formula (A). In the formula, WG1 and WG2 independently represent a cyano group, a nitro group, a halogen atom, an alkylsulfonyl group or an arylsulfonyl group; X1, X2, X3 and X4 independently represent CR or N; and R represents H, a methyl group, a halogen atom, a trifluoromethyl group, a cyano group, a nitro group, an alkoxycarbonyl group, a carbamoyl group, a monoalkylcarbamoyl group, a dialkylcarbamoyl group, a sulfamoyl group, a monoalkylsulfamoyl group, a dialkylsulfamoyl group, or an alkylsulfonyl group.
    Type: Application
    Filed: January 19, 2011
    Publication date: December 20, 2012
    Applicants: NIPPON SHINYAKU CO., LTD., THE UNIVERSITY OF TOKYO
    Inventors: Takeshi Wada, Seigo Nagata, Koichi Uetake
  • Publication number: 20120220761
    Abstract: The present invention describes simple, efficient, and enzyme-free method of making oligonucleotides with 5?-triphosphate. This invention presents novel process for synthesizing triphosphate oligonucleotides using a diaryl phosphonate as reagent. The process of the present invention is amenable to large-scale, economic 5?-triphosphate oligonucleotide synthesis.
    Type: Application
    Filed: December 22, 2009
    Publication date: August 30, 2012
    Applicant: ALNYLAM PHARMACEUTICALS, INC.
    Inventors: Ivan Zlatev, Francois Morvan, Jean-Jacques Vasseur, Francoise Debart, Muthiah Manoharan
  • Publication number: 20120178710
    Abstract: The invention provides methods for the synthesis of cyclic dinucleotides and thiophosphate analogs thereof as well as a new family of analogs of cyclic diguanosine monophosphate that includes a series of seven phosphorothioate derivatives that includes diastereomers of mono-, di-, and trithiophosphates.
    Type: Application
    Filed: July 1, 2010
    Publication date: July 12, 2012
    Applicant: Rutgers, The State University of New Jersey
    Inventors: Roger A. Jones, Barbara L. Gaffney
  • Patent number: 8212020
    Abstract: This invention relates to the field of nucleic acid chemistry, more specifically to the field of compositions of matter that comprise triphosphates of modified 2?-deoxynucleosides and oligonucleotides that are formed when these are appended to the 3?-end of a primer, wherein said modifications comprise NH2 moiety attached to their 3?-hydroxyl group and a fluorescent species in a form of a tag affixed to the nucleobase via a linker that can be cleaved. Such compositions and their associated processes enable and improve the sequencing of oligonucleotides using a strategy of cyclic reversible termination, as outlined in U.S. Pat. No. 6,664,079. Most specifically, the invention concerns compositions of matter that are 5?-triphosphates of ribo- and 2?-deoxyribonucleosides carrying detectable tags and oligonucleotides that might be derived from them.
    Type: Grant
    Filed: March 23, 2009
    Date of Patent: July 3, 2012
    Inventors: Steven Albert Benner, Daniel Hutter, Nicole Aurora Leal, Fei Chen
  • Patent number: 8193337
    Abstract: A process for the preparation of an oligonucleotide having at least one phosphate internucleotide linkage I provided. The process comprises the steps of: a) forming a nascent oligonucleotide comprising a phosphorus (III) internucleotide linkage; and b) oxidation of the nascent oligonucleotide with aqueous iodine solution thereby to form a phosphorus (V) internucleotide linkage; wherein the oxidation is carried out in the presence of a base, the conjugate acid of said base having a pKa higher than the pKa of the conjugate acid of pyridine. Preferably the base is N-methylimidazole.
    Type: Grant
    Filed: July 14, 2008
    Date of Patent: June 5, 2012
    Assignee: Avecia Biotechnology, Inc.
    Inventor: Nanda D. Sinha
  • Publication number: 20110282044
    Abstract: The present invention describes simple, efficient, and enzyme-free method of making oligonucleotide phosphate derivatives. This invention presents novel process using automated synthesizer for synthesizing oligonucleotide phosphate derivatives using a diaryl phosphonate as reagent.
    Type: Application
    Filed: July 30, 2010
    Publication date: November 17, 2011
    Applicant: ALNYLAM PHARMACEUTICALS
    Inventors: Muthiah MANOHARAN, Ivan ZLATEV
  • Publication number: 20110237786
    Abstract: A method for preparing oligonucleotide comprising reacting the compound of Formula (1) with the compound of Formula (2) in a liquid reaction medium under the condition of condensation reaction to obtain the compound of formula (3). In the method according to the present invention, the functional groups are protected by suitable protective groups to only expose the 5?-OH of the compound of Formula (1) (OH-component) and the 3?-phosphate of the compound of Formula (2) (P-component) which are to be connected, so that the condensation reaction is carried out in a liquid reaction medium to bond the OH-component and P-component to obtain DNA or RNA short chain. The method of the present invention does not need a solid phase column and can be carried out in a liquid reaction medium. Thus, oligonucleotides can be synthesized on a large scale.
    Type: Application
    Filed: September 22, 2009
    Publication date: September 29, 2011
    Applicant: SUZHOU RIBO LIFE SCIENCE CO., LTD
    Inventors: Zhen Xi, Jinyu Huang, Junbin Zhang
  • Patent number: 7999098
    Abstract: Hydrazino, oxyamino and carbonyl-based monomers and methods for incorporation into oligonucleotides during enzymatic synthesis are provided. Modified oligonucleotides are provided that incorporate the monomers provided herein. Immobilized oligonucleotides and oligonucleotide conjugates that contain covalent hydrazone or oxime linkages are provided. Methods for preparation of surface bound oligonucleotides are provided. Methods for the preparation of oligonucleotide conjugates are also provided.
    Type: Grant
    Filed: December 11, 2006
    Date of Patent: August 16, 2011
    Assignee: Solulink Biosciences, Inc.
    Inventors: David A. Schwartz, Richard I. Hogrefe
  • Publication number: 20110165226
    Abstract: The invention comprises a viral cap-leader sequence which comprises at least three bases complementary to the 3?-ultimate residues of a (?)ssRNA virus template sequence. Preferably said consensus sequence is represented by the general formula 7mG(N)6-10-(A/U/G)?A/U?AGC, more preferably 7mG(N)7-8-(A/U/G)?A/U?AGC. Further comprised are modified cap-leader sequences that are able to block elongation by the viral polymerase or cleavage by the viral endonuclase. Such modified cap-leader sequences comprise a 3?-terminal phosphate group, one or more phosphorothioate or phosphorodiamidate bonds or one ore more morpholino rings. Also pharmaceutical products comprising such a modified cap-leader sequence are disclosed. Further, the invention comprises methods for inhibiting virus transcription, especially for influenza virus, using such a modified cap-leader sequence or pharmaceutical product.
    Type: Application
    Filed: May 20, 2009
    Publication date: July 7, 2011
    Inventor: Richard Jozef Maria Kormelink
  • Patent number: 7923550
    Abstract: The present invention describes novel compounds and methods for capping reactive groups on support and during multistep synthesis. These new capping reagents are also useful for high quality synthesis on solid supports and surfaces used as microarrays, biosensors, or in general as biochips. The compounds are also useful for controlling surface density of reactive groups on a support. The compounds may also be used to modify the hydrophilic/hydrophobic characteristics of a surface or a molecule. The compounds have functional utility in various applications in the fields of genomics, proteomics, diagnostics and medicine.
    Type: Grant
    Filed: April 14, 2004
    Date of Patent: April 12, 2011
    Inventors: Xiaolian Gao, Peilin Yu
  • Patent number: 7893249
    Abstract: Method for synthesis, deprotection, and/or purification of nucleic acid molecules, such as oligonucleotides comprising one or more ribonucleotides. Such nucleic acid molecules include siRNA, dsRNA, ribozymes, antisense, and aptamers.
    Type: Grant
    Filed: December 7, 2009
    Date of Patent: February 22, 2011
    Assignee: Sirna Therapeutics, Inc.
    Inventors: Keith Bowman, Christopher Shaffer, Chandra Vargeese
  • Patent number: 7872120
    Abstract: Methods for synthesizing a collection of partially identical polynucleotides are disclosed.
    Type: Grant
    Filed: August 10, 2007
    Date of Patent: January 18, 2011
    Inventor: Venkata Chalapathi Rao Koka
  • Patent number: 7858772
    Abstract: The present invention provides methods of extending nucleic acids and purifying target nucleic acids. The methods include the use of capping reagents to effect chain termination and provide a handle for purification via fluorous affinity methods.
    Type: Grant
    Filed: December 18, 2007
    Date of Patent: December 28, 2010
    Assignee: Roche Molecular Systems, Inc.
    Inventors: Amar Gupta, Stephen Will
  • Patent number: 7855285
    Abstract: A process for providing regiospecific and highly stereoselective synthesis of 9-? anomeric purine nucleoside analogs is described. The introduction of the sugar moiety on to 6-(azolyl)-substituted purine bases is performed so that highly stereoselective formation of the ? anomers of only the 9 position regioisomers of the purine nucleoside analogs (either D or L enantiomers) is obtained. This regiospecific and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs, and in particular 2?-deoxy, 3?-deoxy, 2?-deoxy-2?-halo-arabino and 2?,3?-dideoxy-2?-halo-threo purine nucleoside analogs, in high yields without formation of the 7-positional regioisomers. Processes for providing novel 6-(azolyl)purines for the regiospecific and highly stereoselective synthesis of 9-? anomeric purine nucleoside analogs are described. The compounds are drugs or intermediates to drugs.
    Type: Grant
    Filed: June 14, 2006
    Date of Patent: December 21, 2010
    Assignee: Brigham Young University
    Inventors: Morris J. Robins, Minghong Zhong
  • Patent number: 7795423
    Abstract: The present invention provides a new labeling reagent for preparing modified oligonucleotides and processes for their production wherein these oligonucleotides contain at least once the structure P?N—SO2-benzole-L-M-X, characterized in that L is either —(CH2)n- or polyethylene glycol, M is selected from a group consisting of —NH—, —O—, —S—, and —COO—, and X is either a protecting group or a detectable unit. L is preferably either —(CH2)n- or polyethylene glycol.
    Type: Grant
    Filed: May 20, 2008
    Date of Patent: September 14, 2010
    Assignee: Roche Diagnostics Operations, Inc.
    Inventor: Dieter Heindl
  • Patent number: 7786294
    Abstract: A method of producing a polydeoxyribonucleotide molecule by reverse transcriptase polymerase chain reaction wherein the polydeoxyribonucleotide molecule has a length of greater than 5,000 base-pairs is disclosed. The method involves combining two reverse transcriptases followed by two protocols of polymerase chain reaction. This method enable the amplification of large DNAs, such as viruses, from a sample while preserving genetic diversity of the large DNA.
    Type: Grant
    Filed: May 31, 2007
    Date of Patent: August 31, 2010
    Assignee: Saint Louis University
    Inventors: Xiaofeng Fan, Adrian M. Di Bisceglie
  • Patent number: 7777013
    Abstract: Labeled nucleotide analogs used in place of naturally occurring nucleoside triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions, and various analyses based thereon, including DNA sequencing, single base identification, hybridization assays and others.
    Type: Grant
    Filed: May 15, 2008
    Date of Patent: August 17, 2010
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Yue Xu, Jeffrey Wegener, Arek Bibillo
  • Patent number: 7759480
    Abstract: 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: Grant
    Filed: January 29, 2007
    Date of Patent: July 20, 2010
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Achim Krotz, Daniel C. Capaldi, Hans-Joachim Josef Gaus, Brett Turney
  • Patent number: 7741471
    Abstract: The present invention provides the combination of the O-2 diphenylcarbamoyl (“DPC”) and N-6 dimethylaminomethylidene (“DMF”) protecting groups for isoguanosine nucleosides that can be utilized in oligonucleotide synthesis.
    Type: Grant
    Filed: May 26, 2005
    Date of Patent: June 22, 2010
    Assignee: EraGen Biosciences, Inc.
    Inventors: James R. Prudent, Christopher B. Sherrill
  • Patent number: 7741472
    Abstract: The present invention concerns modified oligonucleotides and processes for their production wherein these oligonucleotides contain at least once the structure P?N-Acc where Acc is an electron acceptor or an electron acceptor substituted with a residue R and R is any organic substituent.
    Type: Grant
    Filed: May 16, 2008
    Date of Patent: June 22, 2010
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Dieter Heindl, Dirk Kessler
  • Patent number: 7723511
    Abstract: 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: Grant
    Filed: April 21, 2008
    Date of Patent: May 25, 2010
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Douglas L. Cole, Vasulinga Ravikumar, Zacharia S. Cheruvallath
  • Patent number: 7700706
    Abstract: 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: Grant
    Filed: December 17, 2007
    Date of Patent: April 20, 2010
    Assignee: Isis Pharmaceuticals, Inc.
    Inventors: Vasulinga Ravikumar, Raju K. Kumar, Kenjirou Mori, Tatsuya Konishi, Ayako Matsunawa, Takeo Matsumura, Cheiko Kitaura, Gang Zhao
  • Patent number: 7700761
    Abstract: Provided are processes for preparing a 3?-deoxypentopyranosyl oligomers with linkers for linking biomolecules. The processes can the steps of: bonding a 4?-protected-3?-deoxypentopyranosyl nucleoside to a solid support by coupling the 2?-OH group with a CPG support or other similar support with an amide linkage; deprotecting the 4?-protected-3?-deoxypentopyranosyl nucleoside at the 4? position; deprotecting the 4?-protected-3?-deoxypentopyranosyl nucleoside at the 4? position; and conjugating a linker to the free 4? position. The resulting product can be conjugated via the linker to a biomolecule. The method can include, prior to addition of the linker, reacting the 4?-OH group of the 4?-protected-3?-deoxypentopyranosyl nucleoside that is linked to the solid support with a 4?-protected-3?-deoxypentopyranosyl nucleoside phosphoramidite in the presence of a coupling reagent, and oxidizing the reaction product. This step can be repeated one or more times to produce an oligomer of desired length.
    Type: Grant
    Filed: May 31, 2006
    Date of Patent: April 20, 2010
    Assignee: Nanogen Recognomics GmbH
    Inventors: Christian Miculka, Thomas Wagner, Norbert Windhab
  • Patent number: 7678554
    Abstract: Disclosed is a method of altering a nucleic acid. The method includes fragmenting a parent nucleic acid strand to generate nucleic acid fragments. At least a subset of the fragments are ligated to generate shuffled nucleic acid strands. A selected strand is identified from the shuffled nucleic acid strands for a criterion.
    Type: Grant
    Filed: March 19, 2002
    Date of Patent: March 16, 2010
    Assignee: President and Fellows of Harvard College
    Inventors: David R. Liu, Joshua A. Bittker
  • Patent number: 7655790
    Abstract: Method for synthesis, deprotection, and/or purification of nucleic acid molecules, such as oligonucleotides comprising one or more ribonucleotides. Such nucleic acid molecules include siRNA, dsRNA, ribozymes, antisense, and aptamers.
    Type: Grant
    Filed: January 12, 2005
    Date of Patent: February 2, 2010
    Assignee: Sirna Therapeutics, Inc.
    Inventors: Chandra Vargeese, Christopher Shaffer, Keith Bowman
  • Patent number: 7635772
    Abstract: A process for the synthesis of an oligonucleotide is provided in which an oligonucleotide is assembled on a swellable solid support using the phosphoramidite approach in the presence of an activator, wherein the activator is not tetrazole or a substituted tetrazole. Preferred activators are pyridinium, imidazolinium and benzimidazolinium salts; benzotriazole and derivatives thereof; and saccharin or a saccharin derivative. Preferred swellable solid supports comprise functionalised polystyrene, partially hydrolysed polyvinylacetate or poly(acrylamide).
    Type: Grant
    Filed: December 16, 2003
    Date of Patent: December 22, 2009
    Assignee: Avecia Biotechnology Inc.
    Inventor: Paul McCormac
  • Patent number: 7585970
    Abstract: A method for synthesizing a polynucleotide is disclosed. The method comprises providing a functionalized support comprising a triaryl methyl linker bound to the solid support through a substitution on one of the aryl groups, a nucleotide chain bound to the central methyl carbon of the triaryl methyl group and a nucleoside with a reactive site hydroxyl. The method further provides contacting that functionalized support with a precursor having a hydroxyl protecting group and a phosphorous derivative reactive group to produce internucleotide linkage. The resulting compound is then treated to both remove the hydroxyl protecting group on the precursor, and to oxidize the internucleotide bond.
    Type: Grant
    Filed: August 30, 2003
    Date of Patent: September 8, 2009
    Assignee: Agilent Technologies, Inc.
    Inventors: Douglas J Dellinger, Geraldine F Dellinger, John S Hargreaves
  • Publication number: 20090216003
    Abstract: The present invention describes a flexible basestacking monomer that can be incorporated into an oligonucleotide or oligonucleotide analogue, as well as triplex forming oligonucleotides comprising the flexible basestacking monomer. Triplex forming oligonucleotides of the invention are capable of binding sequence specifically to doublestranded target nucleic acids and are therefore of interest for modulation of the activity of target nucleic acids and also detection of target nucleic acids.
    Type: Application
    Filed: May 24, 2006
    Publication date: August 27, 2009
    Inventors: Vyachelsav V Filichev, Erik Bjerregaard Pedersen
  • Patent number: 7579459
    Abstract: The present invention relates to improved methods for the preparation of nucleic acids. More particularly, conventional solid supports used for nucleic acid synthesis are derivatized with activators having pKas within the 4 to 7 range. Preferentially, CPG-based solid supports are reacted with trialkoxysilanes containing an activator moiety such as pyridine. During each deblocking step of the nucleic acid synthesis cycle, bound pyridiniums are generated, yielding a weak acidic medium spreads throughout the solid support. The bound activators efficiently activate the phosphoramidite reagents towards coupling with 5?-hydroxynucleosides bound to the solid supports, thus eliminating or supplementing external deliveries of activator during the coupling steps.
    Type: Grant
    Filed: December 12, 2005
    Date of Patent: August 25, 2009
    Inventors: Nam Q. Ngo, Laurent Jaquinod
  • Patent number: 7572907
    Abstract: Methods of forming polynucleotides are disclosed.
    Type: Grant
    Filed: April 29, 2005
    Date of Patent: August 11, 2009
    Assignees: Agilent Technologies, Inc., The Regents of the University of Colorado
    Inventors: Douglas J. Dellinger, Geraldine Dellinger, Marvin H. Caruthers, Zoltan Kupihar
  • Publication number: 20090137790
    Abstract: The present invention relates to a method for producing an oligonucleic acid derivative characterized by using a phenoxyacetic acid derivative anhydride as an acylating agent and a pyridine derivative as the acylation reaction activator, in a capping step for protecting the 5?-hydroxyl group of a ribose of an oligonucleic acid derivative.
    Type: Application
    Filed: February 26, 2007
    Publication date: May 28, 2009
    Applicant: Nippon Shinyaku Co., Ltd.
    Inventor: Yukiko Enya
  • Patent number: 7524950
    Abstract: Inkjet printhead solvents and methods of forming an addressable nucleotide array are disclosed.
    Type: Grant
    Filed: April 29, 2005
    Date of Patent: April 28, 2009
    Assignee: Agilent Technologies, Inc.
    Inventors: Douglas J. Dellinger, Eric LeProust, Bill Peck, Marvin H. Caruthers, Peter Cogan
  • Patent number: 7511125
    Abstract: 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: Grant
    Filed: August 19, 2004
    Date of Patent: March 31, 2009
    Assignee: Carlsbad
    Inventors: Kuei-Ying Lin, Mark D. Matteucci
  • Publication number: 20090036660
    Abstract: 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: Application
    Filed: July 31, 2007
    Publication date: February 5, 2009
    Inventors: Joel Myerson, Emily M. Leproust, Douglas J. Dellinger
  • Patent number: 7470783
    Abstract: 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: Grant
    Filed: April 14, 2005
    Date of Patent: December 30, 2008
    Assignee: Affymetrix, Inc.
    Inventors: Glenn H. McGall, Ngo Q. Nam, Richard P. Rava