Deprotection Step Patents (Class 536/25.31)
  • Patent number: 9896472
    Abstract: A method of deprotecting a solid support bound polynucleotide includes the step of contacting the polynucleotide with a composition comprising a diamine under conditions sufficient to deprotect the 2?-protected ribonucleotide residue. The solid support bound polynucleotide has at least one 2?-protected ribonucleotide residue, which has the following structure: wherein BP is a protected or unprotected heterocycle; R12 is a protecting group selected from a hydrocarbyl, a substituted hydrocarbyl, an aryl, and a substituted aryl; X is O or S; and PG is a thionocarbamate protecting group.
    Type: Grant
    Filed: September 14, 2015
    Date of Patent: February 20, 2018
    Assignee: Agilent Technologies, Inc.
    Inventors: Douglas J. Dellinger, Joel Myerson, Agnieszka Sierzchala, Geraldine F. Dellinger, Zoltan Timar
  • Patent number: 9758546
    Abstract: Provided herein are methods for the synthesis of oligomeric compounds wherein removal of the 5?-terminal trityl group is performed at reduced temperature and lower pH relative to standard methods. In certain embodiments, the present methods provide detritylated oligomeric compounds having a reduced percentage of depurination relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present methods provide detritylated oligomeric compounds with increased purity relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present method provide an increased rate of detritylation compared to standard methods.
    Type: Grant
    Filed: October 21, 2014
    Date of Patent: September 12, 2017
    Assignee: Ionis Pharmaceuticals, Inc.
    Inventor: Dana Chreng
  • Patent number: 9657296
    Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.
    Type: Grant
    Filed: May 18, 2015
    Date of Patent: May 23, 2017
    Assignee: Geron Corporation
    Inventors: Sergei Gryaznov, Krisztina Pongracz
  • Patent number: 9085797
    Abstract: 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: Grant
    Filed: August 9, 2013
    Date of Patent: July 21, 2015
    Assignee: Life Technologies Corporation
    Inventors: Gulilat Gebeyehu, Richard Pires
  • Publication number: 20150119564
    Abstract: Methods for removing 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from a N-methylimidazole and methods for making oligonucleotides using N-methylimidazole are provided. In one embodiment, a method for removing 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from a feedstock containing N-methylimidazole includes contacting the feedstock with small or medium pore molecular sieves. The small or medium pore molecular sieves adsorb 1,3,5-trimethylhexahydro-1,3,5-triazine and N-methylenemethanamine from the feedstock. The method further includes separating the small or medium pore molecular sieves from the feedstock.
    Type: Application
    Filed: August 28, 2014
    Publication date: April 30, 2015
    Inventors: Venkatraman Mohan, Sandra M. Lorenz, Gregory Gajda
  • Publication number: 20150080565
    Abstract: The present invention provides a protected nucleotide for elongation, which can be purified efficiently and in a high yield by a liquid-liquid extraction operation, and can achieve an oligonucleotide production method by a phosphoramidite method. It has been found that the above-mentioned problem can be solved by a particular oligonucleotide comprising a protected base and/or particular oligonucleotide protected by a branched chain-containing aromatic group at 3?-position.
    Type: Application
    Filed: September 19, 2014
    Publication date: March 19, 2015
    Applicant: Ajinomoto Co., Inc.
    Inventors: Kunihiro HIRAI, Satoshi Katayama, Takayoshi Torii, Ryotaro Nakaya, Daisuke Takahashi
  • Patent number: 8981076
    Abstract: This invention relates to synthesis of novel -N-FMOC protected nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-FMOC as nucleoside base protecting group, which is highly base labile protecting group is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of FMOC protecting groups of the natural deoxy and ribonucleosides occurs under very mild deprotection conditions such as mild bases, secondary and tertiary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application.
    Type: Grant
    Filed: November 30, 2009
    Date of Patent: March 17, 2015
    Assignee: ChemGenes Corporation
    Inventors: Suresh C. Srivastava, Naveen P. Srivastava
  • Publication number: 20150072345
    Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(—O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.
    Type: Application
    Filed: September 11, 2014
    Publication date: March 12, 2015
    Inventors: Sergei M. Gryaznov, Ronald G. Schultz
  • Publication number: 20150045547
    Abstract: Methods for preparation of 2?,3?-dideoxynucleotides support structures, such as 2?,3?-dideoxyguanosine, 2?,3?-dideoxyadenosine, and 3?-deoxythymidine support structures are disclosed. Various methods of using such structures are also provided, such as their use for automated DNA synthesis and pyrophosphorolysis activated polymerization.
    Type: Application
    Filed: February 5, 2014
    Publication date: February 12, 2015
    Applicant: LIFE TECHNOLOGIES CORPORATION
    Inventors: Zhaochun MA, Khairuzzaman Bashar Mullah, Robert Eason
  • Publication number: 20140349292
    Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one internucleoside 3?-NHP(O)(S?)O-5? linkage, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive thiophosphoramidate oligonucleotides were found to retain the high RNA binding affinity of the parent oligonucleotide N3??P5? phosphoramidates and to exhibit a much higher acid stability.
    Type: Application
    Filed: July 9, 2014
    Publication date: November 27, 2014
    Inventors: Sergei Gryaznov, Krisztina Pongracz, Tracy Matray
  • Patent number: 8846885
    Abstract: The present invention provides a protected nucleotide for elongation, which can be purified efficiently and in a high yield by a liquid-liquid extraction operation, and can achieve an oligonucleotide production method by a phosphoramidite method. It has been found that the above-mentioned problem can be solved by a particular oligonucleotide comprising a protected base and/or particular oligonucleotide protected by a branched chain-containing aromatic group at 3?-position.
    Type: Grant
    Filed: February 15, 2013
    Date of Patent: September 30, 2014
    Assignee: Ajinomoto Co., Inc.
    Inventors: Kunihiro Hirai, Satoshi Katayama, Takayoshi Torii, Ryotaro Nakaya, Daisuke Takahashi
  • Publication number: 20140256928
    Abstract: A protecting group for 1-nitrogen atom of an indole group including a sulfonylethyl carbamate group, wherein the protecting group is represented by the following General Formula (I) and capable of being removed from the 1-nitrogen atom of the indole group in an aprotic solvent: where R represents an alkyl group, a derivative of the alkyl group, a phenyl group or a derivative of the phenyl group.
    Type: Application
    Filed: May 9, 2014
    Publication date: September 11, 2014
    Applicant: APTA BIOSCIENCES LTD.
    Inventor: Tsuyoshi FUJIHARA
  • Patent number: 8822671
    Abstract: A 2?-modified ribonucleoside having an alkoxymethyl protective group can be imparted with a high duplex-forming ability by introducing, as a substituent, a halogen atom into the protective group moiety. A modified form of RNA having a halogen-substituted alkoxymethyl protective group exhibits a high duplex-forming ability that is comparable to the duplex-forming ability of a 2?-O-methyl modified nucleic acid.
    Type: Grant
    Filed: November 28, 2011
    Date of Patent: September 2, 2014
    Assignees: The University of Tokyo, Chiralgen, Ltd.
    Inventors: Mamoru Shimizu, Takeshi Wada, Kouichiro Arai
  • Patent number: 8816062
    Abstract: The compounds of formula (I) substantially in exo form or salts thereof, wherein: X is a biradical selected from —(CH2)n—*, —(CH2CH2O)nCH2CH2—*, methylcyclohexyl and methylphenyl; n is an integer ranging between 1 and 30; Y is a radical selected from —COOH, a substituted phosphoramidite radical and N-hydroxysuccinimide ester (or other active ester) of carboxylic acid; and * represents the place through which X binds to Y, are useful in a general process for solid-phase preparation of maleimide-oligonucleotide derivatives.
    Type: Grant
    Filed: May 2, 2011
    Date of Patent: August 26, 2014
    Assignee: Universitat de Barcelona
    Inventors: Ana María Grandas Sagarra, Albert Sánchez González, Enrique Pedroso Muller
  • Publication number: 20140200338
    Abstract: This invention pertains to methods for oligonucleotide synthesis, specifically the synthesis of oligonucleotides that contain a high content of guanine monomers. In more detail, the invention relates to a method for coupling a nucleoside phosphoramidite during the synthesis of an oligonucleotide to a universal support, to a first nucleoside, or to an extending oligonucleotide. The invention further relates to oligonucleotides obtainable by the methods of the invention.
    Type: Application
    Filed: October 15, 2013
    Publication date: July 17, 2014
    Applicant: CYTOS BIOTECHNOLOGY AG
    Inventor: BRIAN STEPHEN SPROAT
  • Patent number: 8765933
    Abstract: A process of stereoselectively synthesizing ?-nucleoside, e.g., 2?-deoxy-2,2?-difluorocytidine, is described. The process includes reacting a tetrahydrofuran compound of the following formula: in which wherein R1, R2, R3, R4, and L as defined in the specification, with a nucleobase derivative in the presence of an oxidizing agent.
    Type: Grant
    Filed: March 30, 2012
    Date of Patent: July 1, 2014
    Assignee: PharmaEssentia Corp.
    Inventors: Chungsun Chien, Pin-Shu Chien, Chan-Kou Hwang
  • Publication number: 20140179875
    Abstract: Described herein are novel solid-supported sulfurization reagents having the general structure: (I) wherein (P) is a polymer; X is a linker; R1 is an alkyl group, a cycloalkyl group, an aryl group, or a heterocycle; and R2 is an alkyl group, an aryl group, a methyleneacyloxy group having the formula —CH2—O—C(O)—R7, a methylene carbonate group having the formula —CH2—O—C(O)—OR8, or a methylene carbamate group having the formula —CH2—O—C(O)—NR9R10, wherein R7 is a C1 to C20 hydrocarbon residue, R8 is any alkyl, cycloalkyl, aryl, or heteroaryl, and R9 and R10 are independently hydrogen, alkyl, cycloalkyl, aryl, or heteroaryl. Other embodiments include solid-supported sulfurization reagents having the structure of Formula I, wherein (P) is a polystyrene-based solid support and X is an aromatic linker. Also described herein are methods for synthesizing the solid-supported sulfurization reagents and their use during the synthesis of oligonucleotides.
    Type: Application
    Filed: July 24, 2012
    Publication date: June 26, 2014
    Applicant: GIRINDUS AMERICA, INC.
    Inventors: Wieslaw Adam Mazur, Victor Sorokin, Steven Karl Laughlin
  • Patent number: 8759508
    Abstract: The compounds are of class of chromophoric 1,2,3-triazolyl equipped silyl linking groups that are useful in the chemical synthesis of RNA.
    Type: Grant
    Filed: May 16, 2008
    Date of Patent: June 24, 2014
    Assignee: GE Healthcare Dharmacon, Inc.
    Inventor: Michael Oren Delaney
  • Patent number: 8759509
    Abstract: A procedure for using thermolabile groups to protect a hydroxyl function, above all in nucleosides, nucleotides, oligomers, nucleic acids during the reactions of organic synthesis. Various new compounds that can be used to implement the procedure. The way of using thermolabile groups to protect hydroxyl functions consists in a primary, secondary and tertiary hydroxyl group converting into a groups during the reaction between a compound and a compound whose hydroxyl group is to be blocked. The blocking reaction is carried out by means of widely known methods appropriate for that purpose in the presence of a chemically basic catalyst. The obtained product has its hydroxyl group blocked. Then the compound with the group blocked can be used for the purposes of various chemical processes. After their completion, the hydroxyl group is unblocked by dissolving it in a solvent at a temperature of 50-95° C.
    Type: Grant
    Filed: June 1, 2011
    Date of Patent: June 24, 2014
    Assignee: Instytut Chemii Bioorganicznej Polskiej Akademii Nauk
    Inventor: Marcin Krzysztof Chmielewski
  • Publication number: 20140142253
    Abstract: The thiol modified oligonucleotides have vast number of applications in the field of nucleic acid chemistry. The conjugates generated by mono thiol groups are unstable at higher temperature, in high salt concentration buffers and in presence other thiols. There is strong need to develop a novel thiol modifier probes that can generate multiple thiol groups. Described herein are efficient processes and compounds, dithiolane phosphoramidites derivative and dithiolane succinyl supports. The advantage of our cyclic disulfide thiol modifier is multifold a) each incorporation introduces two thiol groups; b) it can be introduced at any desired site of oligonucleotides; c) The symmetrical branching nature of the spacer in the linker arm of dithiolane allows for clean oligo synthesis, where cleavage of the linker arm and thereby of loss of oligo chain is prevented.
    Type: Application
    Filed: October 28, 2013
    Publication date: May 22, 2014
    Applicant: ChemGenes Corporation
    Inventors: Suresh C. Srivastava, Santhosh Kumar Thatikonda, Sant K. Srivastav, Praveen K. Shukla, Alok Srivastava
  • Patent number: 8691970
    Abstract: An object of the present invention is to provide a useful and novel phosphoramidite compound for the synthesis of oligo-RNA. A phosphoramidite compound represented by general formula (1), wherein: BX represents a nucleobase optionally having a protecting group; and R1 is a substituent represented by general formula (2), wherein: R11, R12 and R13 are the same or different and each represents hydrogen or alkoxy; R2a and R2b are the same or different and each represents alkyl, or R2a and R2b taken together with the adjacent nitrogen atom may form a 5- to 6-membered saturated amino cyclic group, the amino cyclic group optionally having an oxygen or sulfur atom as a ring-composing member in addition to the adjacent nitrogen atom; and WG1 and WG2 are the same or different and each represents an electron-withdrawing group.
    Type: Grant
    Filed: August 25, 2005
    Date of Patent: April 8, 2014
    Assignee: Nippon Shinyaku Co., Ltd.
    Inventors: Tadaaki Ohgi, Kouichi Ishiyama, Yutaka Masutomi
  • Patent number: 8691968
    Abstract: The present invention provides compositions, methods, and kits relating to the protection and deprotection of molecules comprising nucleophilic groups, such as the protection and deprotection of thermostable polymerases. Also provided are methods of performing nucleic acid amplification using polymerases protected according to the invention.
    Type: Grant
    Filed: July 2, 2009
    Date of Patent: April 8, 2014
    Assignee: Allelogic Biosciences Corporation
    Inventors: Fei Mao, Xing Xin, Wai-Yee Leung
  • Publication number: 20140066612
    Abstract: 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: Application
    Filed: August 9, 2013
    Publication date: March 6, 2014
    Applicant: LIFE TECHNOLOGIES CORPORATION
    Inventors: Gulilat GEBEYEHU, Richard Pires
  • Patent number: 8664357
    Abstract: According to the present invention, there is provided a process for the preparation of a first compound selected from peptides, oligonucleotides and peptide nucleic acids. The process comprises synthesizing the first compound and then separating the first compound formed in step (i) from a second compound, which is a reaction by-product of the synthesis of the first compound and/or an excess of a reagent used for the synthesis of a first compound by a process of diafiltration. The membrane used for the diafiltration process is stable in organic solvents and provides a rejection for the first compound which is greater than the rejection for the second compound.
    Type: Grant
    Filed: August 7, 2009
    Date of Patent: March 4, 2014
    Assignee: Imperial Innovations Limited
    Inventors: Andrew Guy Livingston, Ludmila Georgieva Peeva, Sheyung Wang Jerry So, Renato Campos Vasconceles, Robin John Leatherbarrow, Edward William Tate, Piers Robert James Gaffney
  • Publication number: 20140051846
    Abstract: Disclosed are O-protected compounds of the formula (I): wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, a method of preparing such compounds, and a method of preparing oligonucleotides such as RNA starting from such compounds. The O-protected compounds have one or more advantages, for example, the 2?-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and/or the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2?-O-(2-cyanoethyl)oxymethyl or 2?-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions.
    Type: Application
    Filed: March 29, 2012
    Publication date: February 20, 2014
    Applicant: TheUnited ofAmerica,asrepresentedbythe Secre -tary,Department ofHealthand Human Service
    Inventors: Serge L. Beaucage, Jacek Cieslak
  • Patent number: 8653254
    Abstract: There is a demand for a convenient production method of an NC type purine nucleoside. The present invention relates to a method of producing a purine nucleoside represented the formula (I?) or a salt thereof, which comprising reacting a pyrimidine nucleoside represented by the formula (I) or a salt thereof with a purine nucleobase represented by the formula B?H in the presence of a Lewis acid.
    Type: Grant
    Filed: March 30, 2010
    Date of Patent: February 18, 2014
    Assignee: Takeda Pharmaceutical Company Limited
    Inventors: Tadashi Umemoto, Yoji Hayase, Shumpei Murata, Kenichi Miyata
  • Patent number: 8647821
    Abstract: Described are devices and methods for detecting binding on an electrode surface. In addition, devices and methods for electrochemically synthesizing polymers and devices and methods for synthesizing and detecting binding to the polymer on a common integrated device surface are described.
    Type: Grant
    Filed: December 22, 2012
    Date of Patent: February 11, 2014
    Assignee: Intel Corporation
    Inventors: Hernan A. Castro, Gordon D. Holt, Brandon C. Barnett, Handong Li, Narayanan Sundararajan, Wei Wang
  • 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: 8614086
    Abstract: Described are quality control methods and devices for the reproducible manufacturing and integrity monitoring of polymers on electrochemical synthesis and detection chips. The devices and methods allow for simultaneous manufacturing and synthesis of polymers.
    Type: Grant
    Filed: December 28, 2006
    Date of Patent: December 24, 2013
    Assignee: Intel Corporation
    Inventors: Gordon Holt, Ghadeer Antanius, Brandon Barnett
  • Publication number: 20130317206
    Abstract: The present invention provides a solid-phase support for oligonucleotide synthesis for synthesizing long chain oligonucleotide, RNA oligonucleotide and modified oligonucleotide at high synthetic quantity and high purity with a low loading amount of a linker. Provided is a solid-phase support for oligonucleotide synthesis comprising a porous resin bead having a monovinyl monomer unit, a crosslinkable vinyl monomer unit and a polyethylene glycol unit and a cleavable linker loaded on its surface, the porous resin bead having a group capable of binding to a carboxy group by a dehydration condensation reaction on its surface, the cleavable linker having a carboxy group, wherein the carboxy group of the cleavable linker is bound to the group capable of binding to a carboxy group, by a dehydration condensation reaction, and a loading amount of the cleavable linker is 1 to 80 ?mol/g relative to the weight of the porous resin bead.
    Type: Application
    Filed: May 23, 2013
    Publication date: November 28, 2013
    Inventors: Eri MAETA, Kenjiro MORI, Kazuya MIWA
  • 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
  • Publication number: 20130267697
    Abstract: The present invention provides a protected nucleotide for elongation, which can be purified efficiently and in a high yield by a liquid-liquid extraction operation, and can achieve an oligonucleotide production method by a phosphoramidite method. It has been found that the above-mentioned problem can be solved by a particular oligonucleotide comprising a protected base and/or particular oligonucleotide protected by a branched chain-containing aromatic group at 3?-position.
    Type: Application
    Filed: February 15, 2013
    Publication date: October 10, 2013
    Inventors: Kunihiro Hirai, Satoshi Katayama, Takayoshi Torii, Ryotaro Nakaya, Daisuke Takahashi
  • Patent number: 8552174
    Abstract: Methods of deprotecting polynucleotides are disclosed. One aspect of the method of deprotecting polynucleotides, among others, includes: providing a polynucleotide, wherein the polynucleotide includes at least one nucleotide monomer that has at least one protecting group selected from the following: a base having a protecting group, a 2?-hydroxyl protecting group, and a combination thereof, and deprotecting at least one of the protecting groups of the polynucleotide by introducing the polynucleotide to a solution including an ?-effect nucleophile.
    Type: Grant
    Filed: March 23, 2006
    Date of Patent: October 8, 2013
    Assignees: Agilent Technologies, Inc., The Regents of the University of Colorado
    Inventors: Douglas J. Dellinger, Zoltan Timar, Agnieszka Sierzchala, Geraldine Dellinger, Marvin H. Caruthers, Joel Myerson
  • Patent number: 8541569
    Abstract: The present invention provides building blocks and methods for synthesizing very pure RNA in a form that can efficiently be modified at the 3? end. Reverse RNA monomer phosphoramidites have been developed for RNA synthesis in 5??3? direction, leading to very clean oligo synthesis that allows for the introduction of various modifications at the 3?-end cleanly and efficiently. Higher coupling efficiency per step have been observed during automated oligo synthesis with the reverse RNA amidites disclosed herein, resulting in a greater ability to achieve higher purity and produce very long oligonucleotides. The use of the reverse RNA phosphoramidites in the synthetic process of this invention leads to oligonucleotides free of N+1 species.
    Type: Grant
    Filed: February 19, 2010
    Date of Patent: September 24, 2013
    Assignee: ChemGenes Corporation
    Inventors: Suresh C. Srivastava, Naveen P. Srivastava
  • Patent number: 8524882
    Abstract: 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: Grant
    Filed: June 3, 2011
    Date of Patent: September 3, 2013
    Assignee: Life Technologies Corporation
    Inventors: Gulilat Gebeyehu, Richard Pires
  • Publication number: 20130197209
    Abstract: The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3?-OH blocking group covalently attached thereto, such that the 3? carbon atom has attached a group of the structure —O—Z wherein Z is any of —C(R?)2-O—R?, —C(R?)2-N(R?)2, —C(R?)2-N(H)R?, —C(R?)2-S—R? and —C(R?)2-F, wherein each R? is or is part of a removable protecting group; each R? is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R?)2 represents an alkylidene group of formula ?C(R??)2 wherein each R?? may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R? is exchanged for H or, where Z is —C(R?) 2-F, the F is e
    Type: Application
    Filed: March 8, 2013
    Publication date: August 1, 2013
    Applicant: ILLUMINA CAMBRIDGE LIMITED
    Inventors: John MILTON, Xiaolin Wu, Mark Smith, Joseph Brennan, Colin Bames, Xiaohai Liu, Silke Ruediger
  • Publication number: 20130197208
    Abstract: The present invention provides massively parallel oligonucleotide synthesis and purification for applications that utilize large collections of defined high-fidelity oligonucleotides (e.g., from about 101 to about 105 different sequences, generally between 25-160 bases in length).
    Type: Application
    Filed: November 20, 2012
    Publication date: August 1, 2013
    Applicant: Affymetrix, Inc.
    Inventor: Affymetrix, Inc.
  • Publication number: 20130178612
    Abstract: Chiral auxiliaries useful for efficiently producing a phosphorus atom-modified nucleic acid derivative with high stereoregularity, and compounds represented by the following the general formula (I) or the general formula (XI) for introducing the chiral auxiliaries.
    Type: Application
    Filed: September 22, 2011
    Publication date: July 11, 2013
    Applicant: CHIRALGEN, LTD.
    Inventors: Takeshi Wada, Mamoru Shimizu
  • Publication number: 20130158248
    Abstract: The compounds of formula (I) substantially in exo form or salts thereof, wherein: X is a biradical selected from —(CH2)n—*, —(CH2CH2O)nCH2CH2—*, methylcyclohexyl and methylphenyl; n is an integer ranging between 1 and 30; Y is a radical selected from —COOH, a substituted phosphoramidite radical and N-hydroxysuccinimide ester (or other active ester) of carboxylic acid; and * represents the place through which X binds to Y, are useful in a general process for solid-phase preparation of maleimide-oligonucleotide derivatives.
    Type: Application
    Filed: May 2, 2011
    Publication date: June 20, 2013
    Applicant: UNIVERSITAT DE BARCELONA
    Inventors: Ana María Grandas Sagarra, Albert Sánchez González, Enrique Pedroso Muller
  • Publication number: 20130137861
    Abstract: A reagent for oligonucleotide synthesis or purification, wherein the reagent has a structure of: X—C-L-H??(Formula A) wherein X is a phosphoramidite group, an H-phosphonate group, an acetal group, or an isocyanate; C is a direct bond or a cleavable adaptor represented by —Ca-Cb—; L is a hydrocarbyl chain; and H is a terminal alkyne or an activated cyclooctyne. The reagent of Formula (A) can be used in the synthesis and purification of oligonucleotides.
    Type: Application
    Filed: November 6, 2012
    Publication date: May 30, 2013
    Applicant: AGILENT TECHNOLOGIES, INC.
    Inventor: Agilent Technologies, Inc.
  • Patent number: 8445734
    Abstract: The present invention discloses novel and improved nucleosidic and nucleotidic compounds that are useful in the light-directed synthesis of oligonucleotides, as well as, methods and reagents for their preparation. These compounds are characterized by novel photolabile protective groups that are attached to either the 5?- or the 3?-hydroxyl group of a nucleoside moiety. The photolabile protective group is comprised of a 2-(2-nitrophenyl)-ethyoxycarbonyl skeleton with at least one substituent on the aromatic ring that is either an aryl, an aroyl, a heteroaryl or an alkoxycarbonyl group. The present invention includes the use of the aforementioned compounds in light-directed oligonucleotide synthesis, the respective assembly of nucleic acid microarrays and their application.
    Type: Grant
    Filed: June 2, 2010
    Date of Patent: May 21, 2013
    Assignee: NIGU Chemie GmbH
    Inventors: Sigrid Buehler, Markus Ott, Wolfgang Pfleiderer
  • Publication number: 20130123486
    Abstract: This invention describes reagent precursors and methods for chemical and biochemical reactions. These reagent precursors that can be activated in solution upon irradiation to generate reagents required for the subsequent chemical reactions. Specifically, photogenerated reagents (PGR) are useful for controlling parallel combinatorial synthesis and various chemical and biochemical reactions.
    Type: Application
    Filed: November 16, 2011
    Publication date: May 16, 2013
    Inventor: Xiaolian GAO
  • Publication number: 20130122507
    Abstract: The present invention provides a method for amplification of a target nucleic acid sequence or signal, wherein an amplification reaction mixture is used which contains at least one reversibly modified oligonucleotide having a non-hydroxyl group 3? end which can be converted into a hydroxyl 3? end upon exposure to a chemical and/or irradiation and/or a range of temperature. The present invention also provides a reversibly modified oligonucleotide as described above, and a nucleic acid amplification reaction mixture and kit comprising such an oligonucleotide.
    Type: Application
    Filed: November 20, 2012
    Publication date: May 16, 2013
    Inventor: Wanli Bi
  • Patent number: 8431693
    Abstract: The present invention relates to processes and reagents for oligonucleotide synthesis and purification. One aspect of the present invention relates to compounds useful for activating phosphoramidites in oligonucleotide synthesis. Another aspect of the present invention relates to a method of preparing oligonucleotides via the phosphoramidite method using an activator of the invention. Another aspect of the present invention relates to sulfur-transfer agents. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to a method of preparing a phosphorothioate by treating a phosphite with a sulfur-transfer reagent of the invention. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to compounds that scavenge acrylonitrile produced during the deprotection of phosphate groups bearing ethylnitrile protecting groups.
    Type: Grant
    Filed: February 28, 2011
    Date of Patent: April 30, 2013
    Assignee: Alnylam Pharmaceuticals, Inc.
    Inventors: Muthiah Manoharan, Michael F. Jung, Kallanthottathil G. Rajeev, Rajendra K. Pandey, Gang Wang
  • Publication number: 20130085272
    Abstract: A procedure for using thermolabile groups to protect a hydroxyl function, above all in nucleosides, nucleotides, oligomers, nucleic acids during the reactions of organic synthesis. Various new compounds that can be used to implement the procedure. The way of using thermolabile groups to protect hydroxyl functions consists in a primary, secondary and tertiary hydroxyl group converting into a groups during the reaction between a compound and a compound whose hydroxyl group is to be blocked. The blocking reaction is carried out by means of widely known methods appropriate for that purpose in the presence of a chemically basic catalyst. The obtained product has its hydroxyl group blocked. Then the compound with the group blocked can be used for the purposes of various chemical processes. After their completion, the hydroxyl group is unblocked by dissolving it in a solvent at a temperature of 50-95° C.
    Type: Application
    Filed: June 1, 2011
    Publication date: April 4, 2013
    Applicant: INSTYTUT CHEMII BIOORGANICZNEJ POLSKIEJ AKADEMII NAUK
    Inventor: Marcin Krzysztof Chmielewski
  • Publication number: 20130030166
    Abstract: Minor groove binder phosphoramidites having unique structures have been synthesized according to particular methods. These minor groove binder phosphoramidites are useful in the preparation of oligonucleotide conjugates, particularly those for use as probes and primers.
    Type: Application
    Filed: July 24, 2012
    Publication date: January 31, 2013
    Inventors: Alexei Vorobiev, Eugeny A. Lukhtanov
  • 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
  • Patent number: 8318860
    Abstract: The invention relates to a method for the fluid-phase synthesis of a polymer formed from n monomers.
    Type: Grant
    Filed: September 17, 2008
    Date of Patent: November 27, 2012
    Inventors: Christian Wolfrum, Wolfgang Prinz
  • Publication number: 20120296074
    Abstract: The problem of the present invention is provision of a method of producing an n+p-mer oligonucleotide efficiently in a high yield, which includes use of, as a starting material, an n-mer oligonucleotide wherein the 3?-terminal hydroxyl group is protected, and the 5?-terminal hydroxyl group is protected by a temporary protecting group, and continuously performing, in a solution, (1) a deprotection step of the 5?-terminal hydroxyl group, (2) a 5?-terminal elongation step by the addition of a p-mer oligonucleotide wherein the 3?-position is phosphoramidited, and (3) an oxidation step or a sulfurization step of a phosphite triester moiety. It has been found that the above-mentioned problem can be solved by adding a particular cation scavenger during the deprotection step, applying a neutralization treatment after completion of the deprotection reaction, and using a particular oxidizing agent or sulfurizing agent in the oxidation step or sulfurization step.
    Type: Application
    Filed: May 17, 2012
    Publication date: November 22, 2012
    Applicant: AJINOMOTO CO., INC.
    Inventors: Kunihiro HIRAI, Satoshi KATAYAMA
  • Publication number: 20120289691
    Abstract: A method of deprotecting a solid support bound polynucleotide includes the step of contacting the polynucleotide with a composition comprising a diamine under conditions sufficient to deprotect the 2?-protected ribonucleotide residue. The solid support bound polynucleotide has at least one 2?-protected ribonucleotide residue, which has the following structure: wherein BP is a protected or unprotected heterocycle; R12 is a protecting group selected from a hydrocarbyl, a substituted hydrocarbyl, an aryl, and a substituted aryl; X is O or S; and PG is a thionocarbamate protecting group.
    Type: Application
    Filed: June 22, 2012
    Publication date: November 15, 2012
    Applicant: AGILENT TECHNOLOGIES, INC.
    Inventors: Douglas J. Dellinger, Joel Myerson, Agnieszka Sierzchala, Geraldine F. Dellinger, Zoltan Timar