Patents by Inventor Robert E. Rhoads
Robert E. Rhoads has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20140342402Abstract: A method is disclosed for stabilizing histone stem-loop-containing mRNA by the addition of a chain-terminating nucleoside. The novel, synthetic mRNA contains a 3? histone stem-loop sequence. At the 3? end of the mRNA a chain-terminating nucleoside is incorporated, for example 3?-deoxyadenosine (cordycepin). The chain-terminating nucleoside blocks the addition of a 3?-terminal oligo(U) sequence to the mRNA containing the histone stem-loop. When the 3?-terminal oligo(U) sequence cannot be added, degradation of the mRNA is retarded. The mRNA then remains available to the translational machinery for a longer time, resulting in higher levels of protein synthesis.Type: ApplicationFiled: January 3, 2013Publication date: November 20, 2014Applicant: Board of Supervisors of Louisiana State University and Agricultural and Mechanical CollegeInventors: Robert E. Rhoads, Wei Su, William F. Marzluff
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Patent number: 8519110Abstract: 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: GrantFiled: June 4, 2009Date of Patent: August 27, 2013Assignee: Board of Supervisors of Louisiana State University And Agricultural and Mechanical CollegeInventors: Joanna Kowalska, Jacek Jemielity, Edward Darzynkiewicz, Robert E. Rhoads, Maciej Lukaszewicz, Joanna Zuberek
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Patent number: 8153773Abstract: 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: GrantFiled: June 19, 2008Date of Patent: April 10, 2012Assignees: Board of Supervisors of Louisiana State University and Agricultural and Mechanical College, University of WarsawInventors: Jacek Jemielity, Ewa M. Grudzien-Nogalska, Joanna Kowalska, Edward Darzynkiewicz, Robert E. Rhoads
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Publication number: 20110092574Abstract: 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: ApplicationFiled: June 4, 2009Publication date: April 21, 2011Inventors: Joanna Kowalska, Jacek Jemielity, Edward Derzynkiewicz, Robert E. Rhoads, Maciej Lukaszewicz, Joanna Zuberek
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Publication number: 20100233757Abstract: 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: ApplicationFiled: June 19, 2008Publication date: September 16, 2010Applicant: BOARD OF SUPERVISORS OF LOUSIANA STATE UNIVERSITYInventors: Jacek Jemielity, Ewa M. Grudzien-Nogalska, Joanna Kowalska, Edward Darzynkiewicz, Robert E. Rhoads
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Patent number: 7074596Abstract: 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: GrantFiled: May 17, 2002Date of Patent: July 11, 2006Assignee: Board of Supervisors of Louisiana State University And Agricultural and Mechanical CollegeInventors: Edward Darzynkiewicz, Robert E. Rhoads, Janusz Stepinski
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Publication number: 20030194759Abstract: 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: ApplicationFiled: May 17, 2002Publication date: October 16, 2003Inventors: Edward Darzynkiewiz, Robert E. Rhoads, Janusz Stepinski
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Patent number: 6180385Abstract: Methods of making and using Picornavirus L proteinase peptides (PLPPs) are provided, including, but not limited to, expression of DNA encoding all or a portion thereof, such as a Picornavirus L proteinase (PLP) and variants thereof, as well as methods for determining active sites and inhibitors of a PLP.Type: GrantFiled: October 25, 1996Date of Patent: January 30, 2001Assignee: Boehringer Ingelheim Vetmedica GmbHInventors: Timothy Skern, Regina Kirchweger, Elisabeth Ziegler, Dieter Blaas, Hans-Dieter Liebig, Barry J. Lamphear, Debra Waters, Robert E. Rhoads, Wolfgang Sommergruber, Horst Ahorn
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Patent number: 5646009Abstract: A hybrid vector carrying a first and second DNA segments operationally linked thereto, the first DNA segment encoding a protein capable of cross-linking to the cap structure of mRNA and mediating ribosome-binding, and the second DNA segment encoding a polypeptide or protein, the vector being capable of replication, transcription and translation to express the factor and the polypeptide or protein upon transformation of a eukaryotic host, and the polypeptide or protein being expressed at a level higher than the level of expression thereof in the absence of the first DNA segment. A eukaryotic host is transformed with this hybrid vector. Also disclosed is a method of increasing the synthesis of a polypeptide or protein in a eukaryotic host cell.Type: GrantFiled: January 19, 1994Date of Patent: July 8, 1997Assignee: The University of Kentucky Research FoundationInventors: Robert E. Rhoads, Arrico De Benedetti
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Patent number: 4710566Abstract: The synthesis of a new affinity medium, the p-aminophenyl-.gamma.-ester of 7-methylguanosine-5'-triphosphate coupled to Sepharose, for use in affinity chromatography is claimed. An improved method in terms of speed and purity for the isolation of messenger ribonucleic acid cap-binding protein is claimed. The synthesis of the p-aminophenyl-.gamma.-ester of 7-methylguanosine-5'-triphosphate is described.Type: GrantFiled: December 27, 1984Date of Patent: December 1, 1987Assignee: Yale UniversityInventors: John W. Kozarich, Robert E. Rhoads