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IP Update: Recent Patents, Patent Applications Awarded to Dicerna, Merck, Somagenics, and More

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Title: iRNA Agents with Biocleavable Tethers

Patent Number: 8,426,377

Filed: March 15, 2010

Lead Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals

“The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety … [that] includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group,” the patent’s abstract states. “The cleavable linking group … is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent … to target cells, but … upon entry into a target cell is cleaved to release the iRNA agent from [a] targeting agent.”


Title: Inhibition of Viral Gene Expression Using Small Interfering RNA

Patent Number: 8,426,380

Filed: March 2, 2011

Lead Inventor: Roger Kaspar, Somagenics

“The invention provides methods, compositions, and kits comprising small interfering RNA that are useful for inhibition of viral-mediated gene expression,” the patent’s abstract states. “Small interfering RNAs as described herein can be used in methods of treatment of [hepatitis C virus] infection … [and include] shRNA and siRNA constructs targeting the internal ribosome entry site sequence of HCV.”


Title: In Vivo Polynucleotide Delivery Conjugates Having Enzyme-sensitive Linkages

Patent Number: 8,426,554

Filed: Dec. 23, 2011

Lead Inventor: David Rozema, Arrowhead Research

The invention, the patent’s abstract states, is “directed to compositions for delivery of RNA interference polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.”


Title: siRNA Targeting Myeloid Differentiation Primary Response Gene

Patent Number: 8,426,579

Filed: Aug. 11, 2011

Lead Inventor: Anastasia Khvorova, Dharmacon (Thermo Fisher Scientific)

“Efficient sequence-specific gene silencing is possible through the use of siRNA technology,” the patent’s abstract states. “By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene-silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for MYD88.”


Title: RNA Interference-mediated Inhibition of FC-Epsilon-R1-Alpha Gene

Patent Number: 8,426,581

Filed: Sept.12, 2011

Lead Inventor: Vasant Jadhav, Merck

The invention, the patent’s abstract states, relates to “compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases, and conditions that respond to the modulation of FC-epsilon-R1-alpha gene expression and/or activity, and/or modulate an FC-epsilon-R1-alpha gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules … that are capable of mediating or that mediate RNA interference against FC-epsilon-R1-alpha gene expression.”


Title: Methods for Producing microRNAs

Patent Number: 8,426,675

Filed: June 7, 2011

Lead Inventor: Ross Dickins, Cold Spring Harbor Laboratory

“The invention relates to recombinant vectors for inducible and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene,” according to the patent’s abstract. “In certain embodiments, the invention relates to the use of … tetracycline-responsive RNA polymerase II promoters to direct inducible knockdown in certain cells of an integrated or an endogenous gene, such as p53. The invention also relates to a method for producing transgenic animals expressing inducible, reversible, and/or tissue-specific double-stranded RNA molecules that interfere with the expression of a target gene.”


Title: Therapeutic Uses of Inhibitors of RTP801

Application Number: 20130095117

Filed: Aug. 31, 2012

Lead Inventor: Elena Feinstein, Quark Pharmaceuticals

The invention comprises “novel molecules, compositions, methods, and uses for treating microvascular disorders, eye diseases, and respiratory conditions based upon inhibition of the RTP801 gene and/or protein,” according to the patent application’s abstract.


Title: Composition for Nucleic Acid Delivery Using Metal Nanoparticles and Preparing Method Thereof

Application Number: 20130095187

Filed: March 27, 2012

Lead Inventor: Sei Kwang Hahn, Postech

The invention, the patent application’s abstract states, “relates to a composition for nucleic acid delivery and a method for preparing the same.”


Title: miRNA-regulated Differentiation-dependent Self-deleting Cassette

Application Number: 20130095565

Filed: Dec. 3, 2012

Lead Inventor: David Frendewey, Regeneron Pharmaceuticals

The patent application, its abstract states, claims “targeting constructs and methods of using them … for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs [comprise] a promoter operably linked to a recombinase [that] … drives transcription of the recombinase in a differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3.

“Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3'-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells,” the abstract adds.
“The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.”


Title: Polymers for Delivering Molecules of Interest

Application Number: 20130096177

Filed: March 29, 2011

Lead Inventor: Guy Zuber, National Center for Scientific Research

The invention, the patent application’s abstract states, “relates to a new class of cationic polymers that self-assemble with a pH-sensitive dissolution switch, and their uses to deliver molecules of interest to a cell. The … invention also relates to compositions comprising said cationic polymers non-covalently associated with a molecule of interest, in particular with a siRNA.”


Title: siRNA Conjugates and Preparation Method Thereof

Application Number: 20130096288

Filed: Sept. 13, 2012

Lead Inventor: Bo Ram Han, Bioneer

The patent application, its abstract states, claims a “hybrid conjugate formed by covalently bonding siRNA and a polymeric compound for improving the in vivo stability of siRNA, and to a preparation method of the hybrid conjugate. The conjugate … can improve the in vivo stability of siRNA, thereby achieving an efficient delivery of therapeutic siRNA into cells and exhibiting the activity of siRNA even with a small dose of a relative low concentration. Therefore, the conjugate can advantageously be used as not only an siRNA treatment tool for cancers and other infectious disease, but also a novel type siRNA delivery system.”


Title: Single-stranded Extended Dicer-substrate Agents and Methods of the Specific Inhibition of Gene Expression

Application Number: 20130096290

Filed: Dec. 7, 2012

Inventor: Bob Brown, Dicerna Pharmaceuticals

The invention, the patent application’s abstract states, “provides compositions and methods for reducing expression of a target gene in a cell [by] contacting a cell with an isolated double-stranded nucleic acid in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a single-stranded extension. Such single-stranded extended Dicer-substrate siRNAs were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.”


Title: Compositions and Systems for the Regulation of Genes

Application Number: 20130096370

Filed: April 17, 2012

Lead Inventor: Didier Trono, Swiss Federal Institute of Technology

The invention comprises “compositions and methods of modulating or regulating eukaryotic gene expression through the controlled or regulated expression of polynucleotide constructs that encode siRNA or other desired exogenous nucleic acids or proteins,” the patent application’s abstract states. “Such constructs, and additional elements of the system may be transfected into the cells of interest and the expression of the siRNA, and hence the expression of the target gene of the siRNA, may be controlled through the administration of a compound to the cell, such as a small molecule or drug. Lentivirus vectors are employed in some embodiments of the invention including the generation of conditional knockdown animals.”


Title: Composition and Method for Prolonging the Shelf Life of Banana by Using RNA Interference

Application Number: 20130097732

Filed: July 6, 2012

Lead Inventor: Pung-Ling Huang, National Taiwan University

“The invention relates to a composition and method for prolonging the shelf life of banana by using interfering RNA,” the patent application’s abstract states. The method involves transferring a control cassette for ACC oxidase into a banana by a novel gene transfer method. The cassette comprises an interfering RNA, a gene transfer expression vector, and pharmaceutically acceptable carrier, and can block ACC oxidase expression to inhibit the biosynthesis of ethylene in a banana to delay ripening.

The Scan

Interfering With Invasive Mussels

The Chicago Tribune reports that researchers are studying whether RNA interference- or CRISPR-based approaches can combat invasive freshwater mussels.

Participation Analysis

A new study finds that women tend to participate less at scientific meetings but that some changes can lead to increased involvement, the Guardian reports.

Right Whales' Decline

A research study plans to use genetic analysis to gain insight into population decline among North American right whales, according to CBC.

Science Papers Tie Rare Mutations to Short Stature, Immunodeficiency; Present Single-Cell Transcriptomics Map

In Science this week: pair of mutations in one gene uncovered in brothers with short stature and immunodeficiency, and more.