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IP Update: Recent RNAi- and microRNA-Related Patents and Patent Applications: Sep 8, 2011

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Title: Methods and Compositions for Treating Gain-of-Function Disorders Using RNA Interference

Patent Number: 8,008,271

Filed: July 17, 2009

Lead Inventor: Zuoshang Xu, University of Massachusetts

The invention, the patent's abstract states, “relates to novel methods for treating dominant gain-of-function diseases. The invention provides methods for targeting regions of the copper zinc superoxide dismutase, which causes inherited amyotrophic lateral sclerosis, with RNAi agent. The invention further provides RNAi-resistant replacement genes containing mismatches with their respective RNAi agents. The invention also provides for vectors that express RNAi agent and RNAi resistant replacement gene of the ... invention.”


Title: RNAi Expression Constructs with Liver-Specific Enhancer/Promoter

Patent Number: 8,008,468

Filed: Feb. 16, 2006

Lead Inventor: Petrus Roelvink, Benitec

The invention, the patent's abstract states, “provides compositions and methods suitable for RNAi specifically in the liver so as to treat diseases or disorders.”


Title: RNA Interference-Mediated Inhibition of Human Immunodeficiency Virus Gene Expression Using Short Interfering Nucleic Acid

Patent Number: 8,008,472

Filed: May 11, 2010

Lead Inventor: James McSwiggen, Merck

“This invention relates to compounds, compositions, and methods useful for modulating human immunodeficiency virus gene expression using short interfering nucleic acid molecules,” the patent's abstract states. “This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of human immunodeficiency virus gene expression and/or activity by RNA interference using small nucleic acid molecules. ...The small nucleic acid molecules are useful in the treatment of HIV infection, AIDS, and/or disease and conditions related to HIV infection and/or AIDS in a subject or organism.”


Title: RNA Interference-Mediated Inhibition of TNF and TNF Receptor Gene Expression Using Short Interfering Nucleic Acid

Patent Number: 8,008,473

Filed: May 11, 2010

Lead Inventor: James McSwiggen, Merck

“This invention relates to compounds, compositions, and methods useful for modulating tumor necrosis factor and/or tumor necrosis factor receptor gene expression using short interfering nucleic acid molecules,” the patent's abstract states. “This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of tumor necrosis factor and/or tumor necrosis factor receptor gene expression and/or activity by RNA interference using small nucleic acid molecules.”


Title: siRNA Targeting KRAS

Patent Number: 8,008,474

Filed: May 3, 2010

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 directed to silencing KRAS, one can maximize the generation of an effective gene-silencing reagent, as well as methods for silencing genes.”


Title: Expression System

Patent Number: 8,012,747

Filed: Dec. 15, 2005

Inventor: Jacques Perrault, San Diego State University

The invention, the patent's abstract states, “relates generally to methods and compositions for expression of polypeptides or delivery of interfering RNAs in various cell types.”


Title: Oligonucleotides Comprising a Non-Phosphate Backbone Linkage

Patent Number: 8,013,136

Filed: July 1, 2009

Lead Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals

The invention, according to the patent's abstract, relates to a “ribonucleoside substituted with a phosphonamidite group at the 3' position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite.

“Another aspect of the ... invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety.

“Another aspect of the … invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage,” the abstract states. “Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.”


Title: RNA Interference-Mediated Inhibition of CXCR4 Gene Expression Using Short Interfering Nucleic Acid

Patent Number: 8,013,143

Filed: Dec. 12, 2008

Lead Inventor: James McSwiggen, Merck

“This invention relates to compounds, compositions, and methods useful for modulating chemokine receptor gene expression using short interfering nucleic acid molecules,” according to the patent's abstract. “This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of CXCR gene expression and/or activity by RNA interference using small nucleic acid molecules.”


Title: siRNA Targeting Cyclin-Dependent Kinase Inhibitor 1B

Patent Number: 8,013,145

Filed: Sept. 14, 2009

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 CDKN1B.”


Title: RNA Interference-Mediated Inhibition of Matrix Metalloproteinase 13 Gene Expression Using Short Interfering Nucleic Acid

Patent Number: 8,013,146

Filed: Dec. 17, 2009

Lead Inventor: James McSwiggen, Merck

“This invention relates to compounds, compositions, and methods useful for modulating matrix metalloproteinase gene expression using short interfering nucleic acid molecules,” the patent's abstract states. “This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of MMP13 gene expression and/or activity by RNA interference using small nucleic acid molecules.”


Title: microRNA Precursors

Patent Number: 8,014,956

Filed: Dec. 28, 2006

Lead Inventor: Yu-Ching Chang, Industrial Technology Research Institute

The invention, the patent's abstract states, comprises “methods of identifying microRNA motifs or microRNA precursors for a target gene or a set of target genes. Also disclosed are related computer-readable media.”


Title: Method to Inhibit Ribonucleoase Dicer, Ribonuclease Dicer Inhibitor, and Use of RNA Aptamers as Ribonuclease Dicer Inhibitors

Application Number: 20110207197

Filed: Feb. 9, 2009

Lead Inventor: Marek Figlerowicz, Polish Academy of Sciences

The invention comprises a “method to inhibit ribonuclease Dicer, ribonuclease Dicer inhibitor, and use of RNA aptamers to inhibit ribonuclease Dicer,” according to the patent application's abstract. “More specifically, this solution relates to using RNA aptamers as ribonuclease Dicer inhibitors that act upon the competition basis, use of RNA aptamers as allosteric ribonuclease Dicer inhibitors, and use of RNA aptamers as selective inhibitors of emergence of the selected miRNAs.”


Title: Modulation of Gene Expression by Oligomers Targeted to Chromosomal DNA

Application Number: 20110207217

Filed: March 30, 2010

Lead Inventor: David Corey, University of Texas

“Synthesis of a target transcript of a gene is selectively increased in a mammalian cell by contacting the cell with a polynucleotide oligomer of 12 [to] 28 bases complementary to a region within a target promoter of the gene under conditions whereby the oligomer selectively increases synthesis of the target transcript,” according to the patent application's abstract.


Title: In Vivo Production of Small Interfering RNAs That Mediate Gene Silencing

Application Number: 20110207224

Filed: Feb. 21, 2011

Lead Inventor: Phillip Zamore, University of Massachusetts

“The invention provides engineered RNA precursors that when expressed in a cell are processed by the cell to produce targeted small interfering RNAs that selectively silence targeted genes by cleaving specific mRNAs using the cell's own RNA interference pathway,” the patent application's abstract states. “By introducing nucleic acid molecules that encode these engineered RNA precursors into cells in vitro with appropriate regulatory sequences, expression of the engineered RNA precursors can be selectively controlled both temporally and spatially.”


Title: piRNA and Uses Related Thereto

Application Number: 20110207625

Filed: March 16, 2011

Lead Inventor: Gregory Hannon, Cold Spring Harbor Laboratory

“The invention relates to small single stranded RNAs and analogs thereof, compositions comprising such piRNAs, and their uses in regulating target gene expression or as markers for certain disease states,” the patent application's abstract states.


Title: Smad7 Inhibitor Compositions and Uses Thereof

Application Number: 20110207795

Filed: Sept. 23, 2009

Lead Inventor: Andreas Steinbrecher, Alnylam Pharmaceuticals

The invention relates to “the use of a specific inhibitor of Smad7 expression or function for the preparation of a pharmaceutical composition for the prevention, amelioration, or treatment of a disease of the central nervous system and/or diseases related and/or caused by said disease of the central nervous system,” the patent application's abstract states. “Furthermore, methods for preventing, ameliorating and/or treating such diseases are disclosed.”


Title: Method for Treating Breast Cancer Using Adenine Nucleotide Translocator 2 siRNA or ANT2 shRNA

Application Number: 20110207798

Filed: Feb. 18, 2011

Lead Inventor: Chul Woo Kim, Bioinfra

The invention, the patent application's abstract states, “relates to adenine nucleotide translocator 2 siRNA or ANT2 shRNA suppressing the expression of ANT2 gene expression and anticancer agent containing the same. Furthermore, the … invention relates to methods for treating breast cancers or stem cells of a breast cancer by treating the same with ANT2 siRNA or ANT2 shRNA. In addition, the invention provides a method for inhibiting metastasis of breast cancer cells with ANT2 siRNA or ANT2 shRNA.”


Title: Compositions for Targeted Delivery of siRNA

Application Number: 20110207799

Filed: Feb. 22, 2011

Lead Inventor: David Rozema, Roche

The invention, the patent application's abstract states, “is directed compositions for targeted delivery of RNA interference polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.”


Title: Treatment and Prevention of Influenza

Application Number: 20110209231

Filed: May 16, 2008

Lead Inventor: Timothy Doran, Commonwealth Scientific and Industrial Research Organization

The invention relates to “nucleic acid molecules comprising a double-stranded region, and nucleic acid constructs encoding therefor, that are useful for the treatment and/or prevention of influenza. In particular, the ... invention relates to nucleic acid constructs encoding a double-stranded RNA molecule that can be used to produce transgenic poultry, for example chickens, such that they are at least less susceptible to an avian influenza infection. Also provided are nucleic acid molecules comprising a double-stranded region that can be used as a therapeutic to treat and/or prevent, for example, avian influenza in poultry.”


Title: Targeted Oligonucleotide Compositions for Modifying Gene Expression

Application Number: 20110212021

Filed: May 29, 2009

Lead Inventor: Frank Slack, Yale University

“The invention comprises compositions and methods for modifying gene expression,” the patent application's abstract states. “Modified oligos of the invention restore the lost function of let-7 wild type miRNA molecules that are prevented from silencing target genes by mutations occurring within their binding sites. Administration of a particular modified oligo leads to increased cell death in cancer cells carrying the LCS6 SNP.”


Title: Targeting PAX2 for the Treatment of Breast Cancer

Application Number: 20110212089

Filed: March 18, 2011

Inventor: Carlton Donald, Phigenix

The application “provides methods of prevention and/or treatment of breast cancer in a subject by inhibiting expression of PAX2,” according to the patent application's abstract. “In the cancer treatment methods disclosed, the method of inhibiting expression of PAX2 can be by administration of a nucleic acid encoding an siRNA for PAX2. A method of treating cancer in a subject by administering DEFB1 is also provided. Similarly, provided is a method of treating cancer in a subject by increasing expression of DEFB1 in the subject.”


Title: Method to Quantify siRNAs, miRNAs, and Polymorphic miRNAs

Application Number: 20110212494

Filed: Jan. 27, 2011

Lead Inventor: Ruoying Tan, Life Technologies

The invention, the patent application's abstract states, comprises “methods, compositions, and kits for quantifying target polynucleotides. In some embodiments, a reverse stem-loop ligation probe is ligated to the 3' end of a target polynucleotide, using a ligase that can ligate the 3' end of RNA to the 5' end of DNA using a DNA template, such as T4 DNA ligase. Following digestion to form an elongated target polynucleotide with a liberated end, a reverse transcription reaction can be performed, followed by a PCR. In some embodiments, the methods of the present teachings can discriminate between polymorphic polynucleotides that vary by as little as one nucleotide.”


Title: RNA Interference Suppression of Neurodegenerative Diseases and Methods of Use Thereof

Application Number: 20110212520

Filed: Dec. 9, 2010

Lead Inventor: Beverly Davidson, University of Iowa

The invention, the patent application's abstract states, “is directed to small interfering RNA molecules targeted against nucleic acid sequence that encodes huntingtin or ataxin-1, and methods of using these siRNA molecules.”


Title: microRNAs and Uses Thereof

Application Number: 20110213007

Filed: March 24, 2010

Lead Inventor: Isaac Bentwich, Rosetta Genomics

The patent application, its abstract states, claims “novel polynucleotides associated with prostate and lung cancer. The polynucleotides are miRNAs and miRNA precursors. Related methods and compositions that can be used for diagnosis, prognosis, and treatment of those medical conditions are disclosed. Also described herein are methods that can be used to identify modulators of prostate and lung cancer.”


Title: Complexes of Small Interfering Nucleic Acids

Application Number: 20110213013

Filed: Aug. 19, 2009

Lead Inventor: Samuel McManus, Nektar Therapeutics

The invention relates to “complexes of small-interfering nucleic acids,” according to the patent application's abstract. “Compositions of siNA suited for administration to a patient are described. Methods for delivering the compositions are also described.”


Title: Oligonucleotidic Sequences Able to Silence the Expression of the Cyclin D1-Trop2 Chimera and Uses Thereof in Medical Field

Application Number: 20110213015

Filed: Sept. 25, 2009

Lead Inventor: Saverio Alberti, University of Chieti

“The invention concerns RNA oligonucleotide sequences or sequences that are transcribed into RNA or analogous molecules able to silence the expression of the CYCLIN D1/TROP2 chimeric mRNA and their use in the treatment and the prevention of tumors,” according to the patent application's abstract.


Title: siRNA Capable of Inhibiting the Expression of an Oncogene Involved in Cervical Cancer

Application Number: 20110213128

Filed: Jan. 12, 2011

Lead Inventor: Akira Saito, NEC

The invention, the patent application's abstract states, “identifies the total nucleotide sequence of a novel oncogene from human, which is directly involved in such a cancerization mechanism as for cervical cancer induced by HPV infection of cervical epithelial cell and the amino acid sequence of an oncogenic protein encoded thereby, and to provide a full-length polynucleotide encoding a peptide chain of the oncogenic protein derived from the novel oncogene, which can be used for recombinant production of the oncogenic protein, and the peptide chain of the oncogenic protein produced recombinantly therewith. Specifically, the ... invention provides a novel oncogene polynucleotide from human involving development of cervical cancer.”

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