Abstract: The current disclosure describes materials and methods for identifying subjects that would benefit from treatment with a DNA topoisomerase 1 inhibitor, based on the levels of cullin 4B gene, RNA and protein levels in the subject. The disclosure identifies CUL4B as a predictive biomarker for cancer diagnosis and the subsequent treatment with directed therapeutic agents. The current disclosure also identifies novel therapeutic agents that modulate the level of CUL4B expression, and sensitize a subject to treatment with a second therapeutic agent.
Abstract: Provided herein are novel synthetic short hairpin RNA (shRNA) molecules and compositions and kits comprising such molecules, as well as methods of making and using these molecules, compositions, and kits.
Abstract: The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.
Type:
Grant
Filed:
January 26, 2017
Date of Patent:
October 9, 2018
Assignee:
Translate Bio MA, Inc.
Inventors:
Eugen Uhlmann, Markus Weber, Romesh Subramanian, Thomas Dino Rockel, Arthur M. Krieg
Abstract: The invention relates to the field of oligonucleotide therapeutics, and in particular to the use of a cleavable, e.g. a phosphodiester region covalently attached to a conjugate, a targeting group or blocking group to enhance the properties of the oligonucleotides, for example to improve the therapeutic index.
Type:
Grant
Filed:
November 14, 2013
Date of Patent:
September 18, 2018
Assignee:
Roche Innovation Center Copenhagen A/S
Inventors:
Nanna Albaek, Henrik Frydenlund Hansen, Susanne Kammler, Jacob Ravn, Henrik Orum
Abstract: The invention provides for a method for selectively reducing the expression of a mutant mRNA and/or protein having an expanded nucleotide repeat relative to a wild-type mRNA, comprising contacting a cell with an antisense oligonucleotide of sufficient length and complementarity to the expanded nucleotide repeat. More particularly it relates to selectively reducing the expression of mutant Huntington protein associated with Huntington's disease. The antisense oligonucleotide comprising either a nucleotide or a repeated three nucleotide sequence as defined in the claims.
Type:
Grant
Filed:
November 30, 2012
Date of Patent:
September 4, 2018
Assignee:
SAREPTA THERAPEUTICS, INC.
Inventors:
Peter Linsley, Brian James Leppert, Gunnar J. Hanson
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.
Abstract: Disclosed herein are double-stranded RNA nucleic acid molecules, which include at least one pyrazolotriazine nucleotide analog and have been modified to exhibit one of the following, increased on-target activity, increased target specificity, enhanced nuclease stability, reduced off target activity and/or reduced immunogenicity when compared to an unmodified or similarly modified dsRNA; pharmaceutical compositions comprising such molecules and methods of use thereof in therapy.
Abstract: The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing. The RNAi constructs may be, for instance, miRNA constructs that are miRNA modulators.
Type:
Grant
Filed:
March 23, 2011
Date of Patent:
August 7, 2018
Assignee:
RXi Pharmaceuticals Corporation
Inventors:
Anastasia Khvorova, William Salomon, Joanne Kamens, Dmitry Samarsky, Tod M. Woolf, James Cardia
Abstract: This present invention provides methods for the detection of small molecules in samples comprising the steps a) coupling a nanoparticle (NP) or microparticle (MP) to an aptamer specific for the small molecule to be detected to form a NP-aptamer conjugate b) contacting the NP-aptamer conjugate with the sample; and c) detecting a change in the size, surface potential, or mobility of the NP-aptamer conjugate, wherein the change is indicative of the presence of the small molecule. The present invention also provides for and a biosensor comprising nanoparticles coupled to aptamers to provide nanoparticle aptamer-conjugates (NP-aptamer).
Type:
Grant
Filed:
February 5, 2014
Date of Patent:
July 17, 2018
Assignee:
AURAMER BIO LIMITED
Inventors:
Omar Ahmed Alsager, Justin Mark Hodgkiss, Shalen Kumar, Kenneth Patrick McNatty
Abstract: Methods and compositions relating to motor neurons derived from induced pluripotent stem cells of subjects having a neurodegenerative disease, where the motor neurons exhibit phenotypes characteristic of the neurodegenerative disease, are provided herein. In particular, the present invention provides methods for screening putative therapeutic agents and methods for diagnosing living subjects as having a neurodegenerative disease. In addition, the present invention provides therapeutic gene transfer methods for treating or preventing a neurodegenerative disease in a subject in need thereof.
Abstract: The invention relates to a RNA interference triggers for inhibiting the expression of an AAT gene through the mechanism of RNA interference. The invention also relates to a pharmaceutical composition comprising the AAT RNAi trigger together with an excipient capable of improving delivery of the RNAi trigger to a liver cell in vivo. Delivery of the AAT RNAi trigger to liver cells in vivo provides for inhibition of AAT gene expression and treatment of alpha 1-antitrypsin deficiency and associated diseases.
Type:
Grant
Filed:
June 16, 2015
Date of Patent:
June 26, 2018
Assignee:
Arrowhead Pharmaceuticals, Inc.
Inventors:
Christine I Wooddell, David L Lewis, Darren H Wakefield, Lauren Almeida, Steven B Kanner
Abstract: The present invention relates to synthetic oligonucleotide mimetics of miRNAs. In particular, the present invention provides double-stranded, chemically-modified oligonucleotide mimetics of miR-29. Pharmaceutical compositions comprising the mimetics and their use in treating or preventing conditions associated with dysregulation of extracellular matrix genes, such as tissue fibrotic conditions, are also described.
Type:
Grant
Filed:
June 7, 2016
Date of Patent:
June 12, 2018
Assignee:
MIRAGEN THERAPEUTICS, INC.
Inventors:
Rusty L. Montgomery, Christina M. Dalby, Eva Van Rooij, Corrie Gallant-Behm
Abstract: This invention provides UNA oligomers for selectively inhibiting V30M TTR expression, which can be used in treating amyloidosis. The UNA oligomers can have a first strand and a second strand, each of the strands being 19-29 monomers in length, the monomers being UNA monomers and nucleic acid monomers. Embodiments include pharmaceutical compositions and methods for treating or preventing TTR-related amyloidosis by administering a UNA oligomer to a subject.
Type:
Grant
Filed:
March 25, 2015
Date of Patent:
May 29, 2018
Assignee:
Arcturus Therapeutics, Inc.
Inventors:
Kiyoshi Tachikawa, Joseph E. Payne, Padmanabh Chivukula
Abstract: Disclosed herein are methods for reducing expression of C90RF72 mRNA and protein in an animal with C90RF72 specific inhibitors. Such methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Such C90RF72 specific inhibitors include antisense compounds. Examples of neurodegenerative diseases that can be treated, prevented, and ameliorated with the administration C90RF72 specific inhibitors include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticalbasal degeneration syndrome (CBD), atypical Parkinsonian syndrome, and olivopontocerellar degeneration (OPCD).
Type:
Grant
Filed:
October 15, 2013
Date of Patent:
May 8, 2018
Assignees:
Ionis Pharmaceuticals, Inc., Ludwig Institute for Cancer Research, The Regents of the University of California
Inventors:
C. Frank Bennett, Susan M. Freier, Frank Rigo, Don W. Cleveland, Clotilde Lagier-Tourenne, John M. Ravits, Michael W. Baughn
Abstract: Oligonucleotides with activity in preventing poly(A) adenylation at intron 9 of the KCNH2 gene, as well as pharmaceutical compositions comprising the oligonucleotides and methods of using the oligonucleotides to treat long QT syndrome in a subject are disclosed. The oligonucleotides include antisense sequences corresponding to sites termed DSE-1 and DSE-2 in intron 9.
Type:
Grant
Filed:
August 8, 2016
Date of Patent:
May 1, 2018
Assignee:
Oregon Health & Science University
Inventors:
Zhengfeng Zhou, Qiuming Gong, Matthew Stump
Abstract: The present invention generally relates to methods for selecting aptamers. More specifically, the invention provides methods for the selection of at least one aptamer for use in combination with another epitope binding agent such as another aptamer, an antibody, or a double stranded nucleic acid. The invention also encompasses methods for simultaneously selecting at least two aptamers that each recognize distinct epitopes on a target molecule.
Abstract: This invention provides UNA single-stranded oligomers for therapeutics. The UNA oligomers can be composed of one or more 2?-3?-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used for therapeutics that target oligonucleotides, nucleic acids, or RNAs to reduce their activity.
Abstract: The present disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5?-(Tx)GxGxcsasasgscsastscscsTxGxT-3? and 5?-(Gx)TxTxascstsgscscststscsTxTxA-3?, wherein capital letters designate a beta-D-oxy-LNA nucleotide analog, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analog or a 2-deoxynucleotide, subscript āsā designates a phosphorothioate link between neighboring nucleotides/LNA nucleotide analogs, and subscript āxā designates either a phosphorothioate link or a phosphorodiester link between neighboring nucleotides/LNA nucleotide analogs, and wherein the sequence is optionally extended by up to five 2-deoxynucleotide units. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-1a (HIF-1a), e.g. in the treatment of cancer diseases, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, or treating an angiogenic disease, e.g.
Type:
Grant
Filed:
August 22, 2016
Date of Patent:
April 10, 2018
Assignee:
Roche Innovation Center Copenhagen A/S
Inventors:
Majken Westergaard, Charlotte Albaek Thrue, Frank Rasmussen, Henrik Frydenlund Hansen