Search Patents
  • Patent number: 8519110
    Abstract: Dinucleotide cap analogs are disclosed, modified at different phosphate positions with a boranophosphate group or a phosphoroselenoate group. The analogs are useful as reagents in the preparation of capped mRNAs and have increased stability both in vitro and in vivo. They may be used as inhibitors of cap-dependent translation. Optionally, the boranophosphate or phosphoroselenoate group has a 2?-O or 3?-O-alkyl group, preferably a methyl group, producing analogs called BH3-ARCAs or Se-ARCAs. ARCAs may be modified with ?-, ?-, or ?-boranophosphate or phosphoroselenoate groups.
    Type: Grant
    Filed: June 4, 2009
    Date of Patent: August 27, 2013
    Assignee: Board of Supervisors of Louisiana State University And Agricultural and Mechanical College
    Inventors: Joanna Kowalska, Jacek Jemielity, Edward Darzynkiewicz, Robert E. Rhoads, Maciej Lukaszewicz, Joanna Zuberek
  • Patent number: 9295717
    Abstract: The present invention relates to modification of RNA with 5?-cap analogs of Formula (1): wherein R1-R6 and n are as described herein, in order to improve the stability and increase the expression of said RNA, in particular in immature antigen presenting cells. The present invention provides a vaccine composition comprising said stabilized RNA, immature antigen presenting cells comprising said stabilized RNA, and methods for stimulating and/or activating immune effector cells and for inducing an immune response in an individual using said stabilized RNA.
    Type: Grant
    Filed: August 3, 2010
    Date of Patent: March 29, 2016
    Assignees: BIONTECH AG, TRON-TRANSLATIONALE ONKOLOGIE AN DER UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ GEMEINNUTZIGE GMBH, UNIWERSYTET WARSZAWSKI
    Inventors: Ugur Sahin, Andreas Kuhn, Edward Darzynkiewicz, Jacek Jemielity, Joanna Kowalska
  • Publication number: 20100233757
    Abstract: New RNA cap analogs are disclosed containing one or more phosphorothioates groups. The analogs also contain modifications at the 2?-O position of 7-methylguanosine that prevent them from being incorporated in the reverse orientation during in vitro synthesis of mRNA and that hence are “anti-reverse cap analogs” (ARCAs). The ARCA modification ensures that the S atom is precisely positioned within the active sites of cap-binding proteins in both the translational and decapping machinery. The new S-ARCA analogs are resistant to in vivo decapping enzymes. Some S-ARCAs have a higher affinity for eIF4E than the corresponding analogs not containing a phosphorothioate group. When mRNAs containing the various S-ARCAs are introduced into cultured cells, some are translated as much as five-fold more efficiently than mRNAs synthesized with the conventional analog m7GpppG.
    Type: Application
    Filed: June 19, 2008
    Publication date: September 16, 2010
    Applicant: BOARD OF SUPERVISORS OF LOUSIANA STATE UNIVERSITY
    Inventors: Jacek Jemielity, Ewa M. Grudzien-Nogalska, Joanna Kowalska, Edward Darzynkiewicz, Robert E. Rhoads
  • Patent number: 8153773
    Abstract: New RNA cap analogs are disclosed containing one or more phosphorothioates groups. The analogs also contain modifications at the 2?-O position of 7-methylguanosine that prevent them from being incorporated in the reverse orientation during in vitro synthesis of mRNA and that hence are “anti-reverse cap analogs” (ARCAs). The ARCA modification ensures that the S atom is precisely positioned within the active sites of cap-binding proteins in both the translational and decapping machinery. The new S-ARCA analogs are resistant to in vivo decapping enzymes. Some S-ARCAs have a higher affinity for eIF4E than the corresponding analogs not containing a phosphorothioate group. When mRNAs containing the various S-ARCAs are introduced into cultured cells, some are translated as much as five-fold more efficiently than mRNAs synthesized with the conventional analog m7GpppG.
    Type: Grant
    Filed: June 19, 2008
    Date of Patent: April 10, 2012
    Assignees: Board of Supervisors of Louisiana State University and Agricultural and Mechanical College, University of Warsaw
    Inventors: Jacek Jemielity, Ewa M. Grudzien-Nogalska, Joanna Kowalska, Edward Darzynkiewicz, Robert E. Rhoads
  • Patent number: 7074596
    Abstract: The ability to synthesize capped RNA transcripts in vitro has been of considerable value in a variety of applications. However, one-third to one-half of the caps have, until now, been incorporated in the reverse orientation. Such reverse caps impair the translation of in vitro-synthesized mRNAs. Novel cap analogues, such as P1-3?-deoxy-7-methylguanosine-5?P3-guanosine-5?triphosphate and P1-3?-O,7-dimethylguanosine-5?P3-guanosine-5?triphosphate, have been designed that are incapable of being incorporated into RNA in the reverse orientation. Transcripts produced with SP6 polymerase using “anti-reverse” cap analogues were of the predicted length. Analysis of the transcripts indicated that reverse caps were not formed. The in vitro translational efficiency of transcripts with the novel “anti-reverse” cap analogues was significantly higher than that of transcripts formed with conventional caps.
    Type: Grant
    Filed: May 17, 2002
    Date of Patent: July 11, 2006
    Assignee: Board of Supervisors of Louisiana State University And Agricultural and Mechanical College
    Inventors: Edward Darzynkiewicz, Robert E. Rhoads, Janusz Stepinski