Trivalent Phosphorus Compound Utilized Patents (Class 536/25.34)
  • Patent number: 11414452
    Abstract: The present invention is a process for the preparation of certain 5?-phosphoramidate nucleotide diastereoisomers. The phosphoramidates include those useful in the treatment of cancer such as NUC-3373 (5-fluoro-2?-deoxyuridine-5?-O-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate).
    Type: Grant
    Filed: June 14, 2018
    Date of Patent: August 16, 2022
    Assignee: NuCana plc
    Inventors: Hugh Griffith, Gordon Kennovin, Venkata Lakshmi Narasimha Rao Dammalapati, Mani Bushan Kotala
  • Patent number: 11142545
    Abstract: The invention herein describes a solid-phase synthetic method for preparing thiolated oligonucleotides without needing a capping step. The methods of the invention comprises repetition of a three-reaction per cycle, namely detritylation, coupling and sulfurization, without a capping step. In some embodiments, the synthetic methods of the present invention can be used for preparing an anti-sense oligonucleotide.
    Type: Grant
    Filed: June 22, 2017
    Date of Patent: October 12, 2021
    Assignee: BIOGEN MA INC.
    Inventors: Xianglin Shi, Jimin Yang, William F. Kiesman, Yannick Fillon
  • Patent number: 10876082
    Abstract: A surface treatment composition according to the present invention is a surface treatment composition having a pH of lower than 7 and used for treating the surface of a polished object to be polished having a layer containing tungsten, and the surface treatment composition contains a tungsten etching inhibitor and water, wherein the tungsten etching inhibitor is a compound containing a monocyclic or fused polycyclic aromatic hydrocarbon ring having two or more substituents, and the substituents contain at least a nitrogen-containing group and an anionic group.
    Type: Grant
    Filed: September 11, 2018
    Date of Patent: December 29, 2020
    Assignee: FUJIMI INCORPORATED
    Inventors: Satoru Yarita, Tsutomu Yoshino, Shogo Onishi, Yukinobu Yoshizaki, Yasuto Ishida
  • Patent number: 10844087
    Abstract: Provided is a means for preventing the inactivation of a photoresponsive nucleic acid probe by suppressing the formation of a photocrosslink between a modified nucleotide having a structure corresponding to the monomer of Formula (II) or an amino acid analogue of a nucleotide having a structure corresponding to the monomer of Formula (III) and a modified nucleotide having a structure corresponding to the monomer of Formula (I), wherein the modified nucleotide replaces at least one constituent nucleotide which is the photocrosslinkable 1-thyminyl or 1-uracilyl, by substituting at least one constituent nucleotide which is the photocrosslinkable 1-thyminyl or 1-uracilyl with a modified nucleotide having a structure corresponding to the monomer of Formula (I).
    Type: Grant
    Filed: October 30, 2014
    Date of Patent: November 24, 2020
    Assignee: JAPAN SCIENCE AND TECHNOLOGY AGENCY
    Inventors: Kenzo Fujimoto, Shigetaka Nakamura
  • Patent number: 10781484
    Abstract: Described herein, among other things, is a method of estimating efficiency of an oligonucleotide synthesis reaction. In some embodiments, the method comprises subjecting the products of one or more oligonucleotide synthesis reactions to LC-MS to produce a series of mass spectra, analyzing the mass spectra, and estimating the overall efficiency of an oligonucleotide synthesis reaction and/or the efficiency of addition of one or more of G, A, T or C individually in an oligonucleotide synthesis reaction.
    Type: Grant
    Filed: February 6, 2017
    Date of Patent: September 22, 2020
    Assignee: Agilent Technologies, Inc.
    Inventor: Joel Myerson
  • Patent number: 10385412
    Abstract: Disclosed are methods and kits for identifying and characterizing polynucleotide sequences in a sample which may include a heterogeneous sample. Some of the methods and kits are directed to the identification and characterization of a virus in a sample, which may include HIV capable of cause AIDS or AIDS-like symptoms. The virus may be HIV-1, and may also include drug resistant mutations. The methods may include reacting a mixture that includes, in addition to nucleic acid isolated from the sample, at least one oligonucleotide capable of specifically hybridizing to HIV nucleic acid where the oligonucleotide includes at least one non-natural base.” fu addition, the methods may include detection of one or more mutations in HIV nucleic acid that are associated with drug resistance.
    Type: Grant
    Filed: December 21, 2016
    Date of Patent: August 20, 2019
    Assignee: LUMINEX CORPORATION
    Inventor: Michael James Moser
  • Patent number: 10385090
    Abstract: Disclosed is a nucleoside derivative of formulae (I-1) or a salt thereof: in which R1, R2, R3, R5, A1 to A3, B, X, Y, and k are described herein. Also provided are a 5?-phosphate ester and a 3?-phosphoramidite derivative of the nucleoside derivative and substrate solutions thereof. A polynucleotide is produced using the 5?-phosphate ester or 3?-phosphoramidite derivative of the nucleoside derivative. A library of the produced polynucleotide is used in a method of selecting a nucleic acid aptamer. Further provided is a vesicular endothelial growth factor binding agent of formula (i).
    Type: Grant
    Filed: September 10, 2014
    Date of Patent: August 20, 2019
    Assignee: NATIONAL UNIVERSITY CORPORATION GUNMA UNIVERSITY
    Inventor: Masayasu Kuwahara
  • Patent number: 10377789
    Abstract: A compound represented by formula I or II below or a salt thereof: wherein B1 represents a purin-9-yl group or a 2-oxo-1,2-dihydropyrimidin-1-yl group that has any one or more substituents selected from the group consisting of a hydroxyl group, a hydroxyl group protected by a protecting group in nucleic acid synthesis, a C1 to C6 linear alkyl group, a C1 to C6 linear alkoxy group, a mercapto group, a mercapto group protected by a protecting group in nucleic acid synthesis, a C1 to C6 linear alkylthio group, an amino group, a C1 to C6 linear alkylamino group, an amino group protected by a protecting group in nucleic acid synthesis, and a halogen atom.
    Type: Grant
    Filed: September 19, 2013
    Date of Patent: August 13, 2019
    Assignee: Osaka University
    Inventors: Satoshi Obika, Yutaro Kotobuki, Reiko Waki
  • Patent number: 10189023
    Abstract: The invention relates to methods for conducting solid-phase binding assays. One example is an assay method having improved analyte specificity where specificity is limited by the presence of non-specific binding interactions.
    Type: Grant
    Filed: March 11, 2014
    Date of Patent: January 29, 2019
    Assignee: MESO SCALE TECHOLOGIES, LLC.
    Inventors: Eli N. Glezer, Sudeep Kumar, Pankaj Oberoi, George Sigal, Michael Tsionsky
  • Patent number: 10059947
    Abstract: The invention relates to nucleic acids and methods for restoring acid alpha-glucosidase (GAA) activity in patients with Pompe disease using splice-switching technology.
    Type: Grant
    Filed: September 10, 2014
    Date of Patent: August 28, 2018
    Assignee: SYNTHENA AG
    Inventors: Luis Garcia, Aurelie Avril
  • Patent number: 9701708
    Abstract: Provided herein are methods for the synthesis of oligomeric compounds wherein the standard coupling protocols are modified when coupling bicyclic nucleosides of Formula I. More particularly, the modified coupling protocols provide for a decrease in the ratio of phosphoramidite solution to activator solution in the coupling reagent with an increased contact time. The modified coupling protocols provide for oligomeric compounds having comparable yields to similar oligomeric compounds having modified nucleosides other than bicyclic nucleosides of Formula I.
    Type: Grant
    Filed: January 30, 2014
    Date of Patent: July 11, 2017
    Assignee: Ionis Pharmaceuticals, Inc.
    Inventors: Isaiah E. Cedillo, Michael T. Migawa, W. Brad Wan
  • Patent number: 9605261
    Abstract: The present invention relates to novel phosphoramidites, A-n-bz, C-n-bz, C-n-ac, G-n-ac and U are produced with an HPLC purity of greater than 98% and 31P NMR purity greater than 99%. A novel process of reverse 5??3? directed synthesis of RNA oligomers has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.
    Type: Grant
    Filed: December 11, 2014
    Date of Patent: March 28, 2017
    Assignee: ChemGenes Corporation
    Inventors: Suresh C Srivastava, Divya Pandey, Satya P Bajpai, Naveen P Srivastava
  • Patent number: 9562261
    Abstract: Disclosed are methods and kits for identifying and characterizing polynucleotide sequences in a sample which may include a heterogeneous sample. Some of the methods and kits are directed to the identification and characterization of a virus in a sample, which may include HIV capable of cause AIDS or AIDS-like symptoms. The virus may be HIV-1, and may also include drug resistant mutations. The methods may include reacting a mixture that includes, in addition to nucleic acid isolated from the sample, at least one oligonucleotide capable of specifically hybridizing to HIV nucleic acid where the oligonucleotide includes at least one non-natural base. In addition, the methods may include detection of one or more mutations in HIV nucleic acid that are associated with drug resistance.
    Type: Grant
    Filed: December 10, 2014
    Date of Patent: February 7, 2017
    Assignee: LUMINEX CORPORATION
    Inventor: Michael James Moser
  • Patent number: 9535066
    Abstract: The present invention discloses specific human metapneumovirus monoclonal antibodies. The antibody is at least two-fold less reactive with non-human metapneumoviruses including, but not limited to, respiratory viruses or avian metapneumoviruses. Further, the antibody is at least two-fold more reactive with a human metapneumovirus (i.e., for example, Type A or Type B) than with non-human metapneumoviruses including, but not limited to, respiratory viruses or avian metapneumoviruses. Consequently, these novel antibodies are useful as a clinical diagnostic agent, especially when using fresh nasopharengeal aspirates. The invention also contemplates numerous diagnostic platforms that together with the novel antibodies can support economical, fast, and highly selective detection and identification of clinical inoculum samples.
    Type: Grant
    Filed: August 31, 2015
    Date of Patent: January 3, 2017
    Assignee: Diagnostic Hybrids, Inc.
    Inventors: Giuseppe Gerna, Antonella Sarasini, Maria Grazia Revello
  • Patent number: 9403865
    Abstract: Provided herein are methods for the solid phase synthesis of oligomeric compounds wherein at least one of the capping steps has been modified. More particularly, methods are provided wherein one or more of the capping steps is omitted or performed using reduced equivalents of acetic anhydride. In certain embodiments, the methods provide an enhanced purity profile. In certain embodiments, the methods provide an increased yield. The methods provided herein also provide at least an economic advantage over currently used methods in that reduced amounts of the mixture of capping reagents are required.
    Type: Grant
    Filed: August 15, 2013
    Date of Patent: August 2, 2016
    Assignees: Ionis Pharmaceuticals, Inc., Genzyme Corporation
    Inventors: Isaiah E. Cedillo, Darren Janczak, Phillip Michael Weaver
  • Patent number: 9157915
    Abstract: The present invention discloses specific human metapneumovirus monoclonal antibodies. The antibody is at least two-fold less reactive with non-human metapneumoviruses including, but not limited to, respiratory viruses or avian metapneumoviruses. Further, the antibody is at least two-fold more reactive with a human metapneumovirus (i.e., for example, Type A or Type B) than with non-human metapneumoviruses including, but not limited to, respiratory viruses or avian metapneumoviruses. Consequently, these novel antibodies are useful as a clinical diagnostic agent, especially when using fresh nasopharengeal aspirates. The invention also contemplates numerous diagnostic platforms that together with the novel antibodies can support economical, fast, and highly selective detection and identification of clinical inoculum samples.
    Type: Grant
    Filed: July 18, 2013
    Date of Patent: October 13, 2015
    Assignee: DIAGNOSTIC HYBRIDS, INC.
    Inventors: Giuseppe Gerna, Antonella Sarasini, Maria Grazia Revello
  • Publication number: 20150141637
    Abstract: The present invention provides novel tricyclic nucleosides and oligomeric compounds prepared therefrom. Incorporation of one or more of the tricyclic nucleosides into an oligomeric compound is expected to enhance one or more properties of the oligomeric compound. Such oligomeric compounds can also be included in double stranded compositions. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.
    Type: Application
    Filed: March 15, 2013
    Publication date: May 21, 2015
    Applicant: UNIVERSITÄT BERN
    Inventors: Christian Leumann, Branislav Dugovic, Jory Liétard
  • Patent number: 9035041
    Abstract: This invention relates to a process for preparing an oligonucleotide 5?-triphosphate.
    Type: Grant
    Filed: December 22, 2009
    Date of Patent: May 19, 2015
    Assignee: Alnylam Pharmaceuticals, Inc.
    Inventors: Ivan Zlatev, Francois Morvan, Jean-Jacques Vasseur, Francoise Debart, Muthiah Manoharan
  • Patent number: 9029528
    Abstract: 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.
    Type: Grant
    Filed: May 17, 2012
    Date of Patent: May 12, 2015
    Assignee: Ajinomoto Co., Inc.
    Inventors: Kunihiro Hirai, Satoshi Katayama
  • Publication number: 20150112053
    Abstract: A nucleic acid synthesis method enabling a reaction in a fluid (flow) with a highly dispersible liquid-phase support to improve coupling efficiency is provided. The method for synthesizing an oligonucleotide comprising: sequentially condensing and oxidizing a nucleoside phosphoramidite compound in the presence of an acid/azole complex compound using a starting raw material, i.e.
    Type: Application
    Filed: May 30, 2012
    Publication date: April 23, 2015
    Applicant: HOKKAIDO SYSTEM SCIENCE CO., LTD.
    Inventors: Shokaku Kim, Masanori Matsumoto
  • Patent number: 8933214
    Abstract: The present invention relates to novel phosphoramidites, A-n-bz, C-n-bz, C-n-ac, G-n-ac and U are produced with an HPLC purity of greater than 98% and 31P NMR purity greater than 99%. A novel process of reverse 5??3? directed synthesis of RNA oligomers has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.
    Type: Grant
    Filed: October 2, 2012
    Date of Patent: January 13, 2015
    Assignee: ChemGenes Corporation
    Inventors: Suresh C Srivastava, Divya Pandey, Satya P Bajpal, Naveen P Srivastava
  • 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
  • Publication number: 20140350235
    Abstract: A novel method for attaching oligonucleotides to a paramagnetic solid support is disclosed. Conventional methods of attachment require that oligonucleotides be pre-synthesized with specific end modifications, which is laborious and expensive. Instead, we attached oligonucleotides to paramagnetic beads by direct synthesis of the oligonucleotides on the surface of the beads. An external magnet was used to hold the paramagnetic beads in place during solid-phase synthesis. A magnetic force was applied directly to the beads to prevent their loss, in particular, during reagent purge-to-waste steps that involved high-pressure drain or vacuum. This method can be adapted for use in any laboratory working with conventional synthesis automation, and can be employed, for example, with single columns and multi-well titer plates.
    Type: Application
    Filed: May 18, 2014
    Publication date: November 27, 2014
    Applicant: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Michael S. Akhras, Michael A. Jensen
  • Publication number: 20140350234
    Abstract: The present invention is directed to n-alkylated synthetic nucleosides of high regiospecific purity and oligonucleotides that can be utilized for studies on reversal of cytotoxic and mutagenic DNA damage, and as diagnostic tools.
    Type: Application
    Filed: February 20, 2014
    Publication date: November 27, 2014
    Applicant: ChemGenes Corporation
    Inventors: Satya P. Bajpai, Sant K. Srivastav, Suresh C. Srivastava
  • Patent number: 8889851
    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: Grant
    Filed: November 6, 2012
    Date of Patent: November 18, 2014
    Assignee: Agilent Technologies, Inc.
    Inventors: Emily Marine Leproust, Jeremy Lackey
  • Patent number: 8889843
    Abstract: To provide an excellent dimer amidite which can be subjected to purification, preferably, whose protective groups can be removed under mild conditions, and a method for synthesizing a nucleic acid using the dimer amidite, a dimer amidite having a structure represented by the following General Formula (1) and a method for synthesizing a nucleic acid including performing condensation reaction of the dimer amidite are provided: wherein in General Formula (1), R1 and R2 each independently represent any one of groups selected from General formulas (2) to (4) and Structural Formulas (12) to (15) with a compound where R1 and R2 are each represent Structural Formulas (12) being excluded: ?and wherein in the General Formulas (2) to (4), R3 represents any one group represented by the following Structural Formulas (16) to (25):
    Type: Grant
    Filed: February 26, 2010
    Date of Patent: November 18, 2014
    Assignee: Apta Biosciences Ltd.
    Inventor: Tsuyoshi Fujihara
  • 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: 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
  • Publication number: 20140100362
    Abstract: The present invention provides a process for preparing an isotope-containing phosphate compound easily. The process for preparing an isotope-containing phosphate compound according to the present invention includes the step of oxidizing a trivalent phosphorus compound with an oxidizing agent containing an isotope to synthesize a pentavalent phosphate compound to which the isotope has been introduced. The present invention preferably is applied to the synthesis of nucleic acids such as DNA and RNA, for example. The isotope preferably is a stable isotope. The oxidizing agent preferably is H218O, 3H-1,2-benzodithiol 3-one 1,1-dioxide having 34S, or a diisopropylethylamine-borane complex having 10B, for example.
    Type: Application
    Filed: May 7, 2012
    Publication date: April 10, 2014
    Applicant: BONAC CORPORATION
    Inventors: Tomohiro Hamasaki, Tadaaki Ohgi
  • 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
  • Publication number: 20130303745
    Abstract: A method for preparing an oligonucleotide comprising the steps of synthesizing a phosphoramidite by reacting a hydroxyl-containing compound of formula (A) with a phosphitylating agent in the presence of an activator compound of formula (I), to prepare a phosphitylated compound, then coupling the phosphitylated compound without isolation with a second compound having the formula (A), wherein R5, R3, R2, B are independently selected, but have the same definition as above in the presence of an activator II selected from the group of imidazole, imidazolium salts, and mixtures thereof, which are improved activators over activators disclosed in related art.
    Type: Application
    Filed: July 12, 2013
    Publication date: November 14, 2013
    Inventors: Meinolf LANGE, Andreas HOHLFELD, Andreas SCHONBERGER, Christina KIRCHHOFF, Olaf GROSSEL
  • Patent number: 8552175
    Abstract: The use of N-formamidino-5-amino-3H-1,2,4-dithiazole-3-thiones, 5-phenyl-3H-1,2,4-dithiazole-3-thiones, and derivatives thereof as novel, efficient sulfur-transfer reagents is disclosed. Sulfur transfer from these reagents to compounds containing a P(III) atom (e.g., triphenylphosphine, 5?-O-DMT-thymidine 2-cyanoethyl-(N,N-diisopropyl)phosphoramidite, and 5?-O-DMT-3?-O-levulinyl dithymidilyl 2-cyanoethyl phosphite), was studied in solution by 31P NMR and HPLC. The sulfur transfer from title compounds was also studied in the solid-phase synthesis of oligonucleotide phosphorothioates by phosphoramidite methods. In this application, the efficiency of the sulfur transfer reaction for 2?-deoxyoligonucleotides was better than 99.5%. The novel sulfurizing agents are synthesized, at low cost, using simple chemical methods.
    Type: Grant
    Filed: December 1, 2010
    Date of Patent: October 8, 2013
    Assignee: A.M. Chemicals, Inc.
    Inventor: Andrei P. Guzaev
  • 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
  • Publication number: 20130231473
    Abstract: A method for joining oligonucleotides. The method includes joining together one or more oligonucleotides by reacting an alkyne group lined to an oligonucleotide with an azide group linked to an oligonucleotide to form a triazole linkage. The alkyne group is a strained alkyne group. The method can include ligating together ends of one or more oligonucleotides or cross-linking strands of an oligonucleotide duplex. The methods described allow oligonucleotide strands to be ligated together without the need for a ligase enzyme.
    Type: Application
    Filed: March 1, 2012
    Publication date: September 5, 2013
    Inventors: Tom Brown, Afaf Helmy El-Sagheer
  • Patent number: 8461124
    Abstract: Conformationally locked 2?,4?-carbocylic nucleosides with improved thermal and nuclease stability are disclosed. Oligonucleotides incorporating the locked nucleosides, and methods of treating disease states, are also disclosed.
    Type: Grant
    Filed: March 11, 2008
    Date of Patent: June 11, 2013
    Inventor: Jyoti Chattopadhyaya
  • 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
  • Patent number: 8394948
    Abstract: Novel CE-phosphoramidites and CPG reagents have been synthesized from a serinol backbone. These reagents are useful to introduce functional groups or directly label oligonucleotides. The versatile serinol scaffold allows for labeling at any position (5? or 3? termini, or any internal position) during automated DNA synthesis. Multiple labels or functional groups can be achieved by repetitive coupling cycles. Optimal spacer arms and protected label moieties have been specially designed. Further, the natural 3-carbon atom internucleotide phosphate distance is retained when inserted internally.
    Type: Grant
    Filed: September 28, 2010
    Date of Patent: March 12, 2013
    Assignees: Glen Research Corporation, Nelson Biotechnologies, Inc.
    Inventors: Paul S. Nelson, Hugh Mackie, Andrew Murphy
  • Patent number: 8389703
    Abstract: This invention relates to nucleoside, nucleotide, and oligonucleotide analogs that incorporate non-standard nucleobase analogs, defined to be those that present a pattern of hydrogen bonds to a paired nucleobase analog in a complementary strand that is different from the pattern presented by adenine, guanine, cytosine, and thymine. The invention is specifically concerned with nucleotide analogs that present the donor-donor-acceptor, hydrogen bonding patterns on pyrimidine analogs, and especially those that are analogs of ribonucleotides, including protected ribonucleotides suitable for phosphoramidite-based synthesis of RNA. The heterocycles on these nucleoside analogs are aminopyridones that have electron withdrawing groups attached to the position analogous to the 5-position of the ring in standard pyrimidines, including nitro, cyano, and carboxylic acid derivatives.
    Type: Grant
    Filed: November 2, 2011
    Date of Patent: March 5, 2013
    Inventors: Steven A. Benner, Hyo-Joong Kim
  • 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: 20120322994
    Abstract: A method for preparing an oligonucleotide comprising the steps of a) providing a hydroxyl containing compound having the formula (A), b) reacting said compound with a phosphitylating agent in the presence of an activator (activator I) having the formula (I) to prepare a phosphitylated compound; and c) reacting said phosphitylated compound without isolation with a second compound having the formula (A) wherein R5, R3, R2, B are independently selected, but have the same definition as above in the presence of an activator II different from activator I.
    Type: Application
    Filed: March 15, 2012
    Publication date: December 20, 2012
    Applicant: Girindus AG
    Inventors: Meinolf Lange, Andreas Schönberger, Andreas Hohlfeld, Olaf Grössel, Christina Kirchhoff, Fritz Link
  • 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
  • Patent number: 8309706
    Abstract: The invention provides methods for synthesizing oligonucleotides using nucleoside monomers having carbonate protected hydroxyl groups that are deprotected with ?-effect nucleophiles. The ?-effect nucleophile irreversibly cleave the carbonate protecting groups while simultaneously oxidizing the internucleotide phosphite triester linkage to a phosphodiester linkage. The procedure may be carried out in aqueous solution at neutral to mildly basic pH. The method eliminates the need for separate deprotection and oxidation steps, and, since the use of acid to remove protecting groups is unnecessary, acid-induced depurination is avoided. Fluorescent or other readily detectable carbonate protecting groups can be used, enabling monitoring of individual reaction steps during oligonucleotide synthesis. The invention is particularly useful in the highly parallel, microscale synthesis of oligonucleotides.
    Type: Grant
    Filed: September 6, 2007
    Date of Patent: November 13, 2012
    Assignee: Agilent Technologies, Inc.
    Inventors: Douglas J. Dellinger, Marvin H. Caruthers, Jason R. Betley
  • Patent number: 8309707
    Abstract: Novel technology for RNA synthesis in the reverse direction, involving a new class of products, 3?-DMT-5’-CE ribonucleoside phosphoramidites and 3?-DMT-5’-succinyl ribonucleoside solid supports, with per step coupling efficiency surpassing 99% in the RNA synthesis. This leads to high purity RNA. Examples of a large number of 20-21 mers and a few examples of long chain oligonucleotides are demonstrated. The data indicates dramatic improvement in coupling efficiency per step during oligonucleotide synthesis using the reverse RNA monomers (5??? direction) as compared to 3?-CE ribonucleoside phosphoramidites used in the conventional method of RNA synthesis (3??5? direction). The new process requires shorter coupling cycle time, approx. 4 minutes as compared to approx. 10 minutes using conventional RNA synthesis method (3??5? direction). Furthermore, almost complete absence of M+1 impurities in the reverse RNA synthesis methodology were observed, even when the last phosphoramidite was a macromolecule.
    Type: Grant
    Filed: September 8, 2009
    Date of Patent: November 13, 2012
    Assignee: ChemGenes Corporation
    Inventors: Suresh C. Srivastava, Divya Pandey, Satya P Bajpai, Naveen P Srivastava
  • Patent number: 8304532
    Abstract: A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large-scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3?-protected compound of formula: with a nucleotide derivative having a 5?-protection group, or reacting a 5?-protected compound of formula with a nucleotide derivative having a 3?-protection group.
    Type: Grant
    Filed: May 25, 2011
    Date of Patent: November 6, 2012
    Assignees: Girindus AG, Centre National de la Recherche Scientifique, University of Montpellier II
    Inventors: Ilaria Adamo, Cecile Dueymes, Andreas Schonberger, Jean-Louis Imbach, Albert Meyer, Francois Morvan, Francoise Debart, Jean-Jacques Vasseur, Meinolf Lange, Fritz Link
  • Patent number: 8299225
    Abstract: To provide an excellent amidite for synthesizing modified nucleic acid, which enables a protective group therein to be removed under a moderate condition, thereby stably producing a hydroxyl group-containing modified nucleic acid, and a method for synthesizing modified nucleic acid using the amidite. Specifically, an amidite for synthesizing modified nucleic acid, expressed by General Formula (I): where X represents a base, Y represents a substituent, Z represents a protective group for protecting a hydroxyl group in the substituent, and Q represents one of a hydrogen atom, a hydroxyl group and a hydroxyl group protected by a protective group, wherein the protective group can be removed in an aprotic solvent, and when the protective group is removed, the hydroxyl group emerges in the substituent, and a method for synthesizing modified nucleic acid using the amidite.
    Type: Grant
    Filed: October 12, 2010
    Date of Patent: October 30, 2012
    Assignee: Fujitsu Limited
    Inventor: Tsuyoshi Fujihara
  • Patent number: 8202985
    Abstract: Nucleotide monomers, polynucleotides, methods of making each, and methods of deprotecting each, are disclosed. An embodiment of the nucleotide monomer, among others, includes a nucleotide monomer having a heterobase protecting group selected from structures I through III as described herein. An embodiment of the polynucleotide, among others, includes a plurality of nucleotide moieties having a heterobase protecting group selected from one of structures I through III as described herein.
    Type: Grant
    Filed: March 23, 2006
    Date of Patent: June 19, 2012
    Assignees: Agilent Technologies, Inc., The Regents of the University of Colorado
    Inventors: Douglas J. Dellinger, Zoltan Timar, Agnieszka Sierzchala, Geraldino Dellinger, Marvin H. Caruthers
  • Patent number: 8202983
    Abstract: Aspects of the invention include 2? protected nucleoside monomers that are protected at the 2? site with thiocarbon protecting groups. Thiocarbon protecting groups of interest include thiocarbonate, thionocarbonate, dithiocarbonate groups, as well as thionocarbamate protecting groups. Aspects of the invention further include nucleic acids that include the protecting groups of the invention, as well as methods of synthesizing nucleic acids using the protecting groups of the invention.
    Type: Grant
    Filed: May 9, 2008
    Date of Patent: June 19, 2012
    Assignee: Agilent Technologies, Inc.
    Inventors: Douglas J. Dellinger, Agnieszka Sierzchala, John Turner, Joel Myerson, Zoltan Kupihar, Fernando Ferreira, Marvin H. Caruthers, Geraldine F. Dellinger
  • Publication number: 20120142763
    Abstract: This disclosure relates to nucleic acid constructs modified to have a reduced net anionic charge. The constructs comprise phosphotriester and/or phosphothioate protecting groups. The disclosure also provides methods of making and using such constructs.
    Type: Application
    Filed: June 1, 2010
    Publication date: June 7, 2012
    Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
    Inventors: Steven F. Dowdy, Bryan R. Meade, Khirud Gogoi
  • 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: 20120095201
    Abstract: Provided herein is a method for replacing the allyl group in a compound of formula R—O-allyl, R2N(allyl), RNH(allyl), RN(allyl)2 or R—S-allyl with a hydrogen, using a transition metal and one or more phosphine ligands.
    Type: Application
    Filed: October 25, 2011
    Publication date: April 19, 2012
    Applicant: ILLUMINA CAMBRIDGE LIMITED
    Inventors: John MILTON, Xiaolin Wu, Mark Smith, Joseph Brennan, Colin Barnes, Xiaohai Liu, Silke Ruediger