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IP Update: Jul 8, 2010

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Title: Therapeutic Modulation of the Fas Pathway

Patent Number: 7,749,977

Filed: Oct. 24, 2006

Lead Inventor: Fruma Yehiely, Quark Pharmaceuticals

The invention, the patent's abstract states, comprises "a method for the identification of genes that are essential for the maintenance of specific cell phenotypes. …The method includes the initial step of identifying a cell type with a phenotype of interest.

"Gene inactivation is performed on an aliquot of cells of the cell type of interest," the abstract states. "Selection is then performed to an aliquot of the cell culture to which gene inactivation has been applied. Cells [that] continue to maintain the phenotype following gene inactivation have not had the gene of interest inactivated, whereas cells in which genes necessary for maintaining the phenotype have been inactivated have been lost. Utilizing subtraction analysis between treated and untreated aliquots, the gene in the cells [that] has been inactivated [and] affects the phenotype of interest is identified. Genes that are identified by the method are also disclosed, as well as antibodies directed against the gene product of the identified genes [and] a customized kit for the practice of the gene identification method."


Title: Compositions and Methods for Inhibiting Expression of Huntingtin Gene

Patent Number: 7,749,978

Filed: Nov. 26, 2007

Lead Inventor: Dinah Sah, Alnylam Pharmaceuticals

"The invention relates to a double-stranded ribonucleic acid for inhibiting the expression of the huntingtin gene comprising an antisense strand having a nucleotide sequence which is less than 25 nucleotides in length and which is substantially complementary to at least a part of the … gene," the patent's abstract states. "The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of the [huntingtin] gene, or a mutant form thereof, using the pharmaceutical composition; and methods for inhibiting the expression of the huntingtin gene in a cell."


Title: Compositions and Methods for siRNA Inhibition of Angiogenesis

Patent Number: 7,750,143

Filed: June 8, 2006

Lead Inventor: Michael Tolentino, University of Pennsylvania (Opko Health)

The patent, its abstract states, claims "RNA interference using small interfering RNAs … specific for the vascular endothelial growth factor gene and the VEGF receptor genes Flt-1 and Flk-1/KDR [that] inhibit expression of these genes. Diseases which involve angiogenesis stimulated by over-expression of VEGF, such as diabetic retinopathy, age-related macular degeneration, and many types of cancer can be treated by administering the small interfering RNAs."


Title: Methods and Compositions for Enhancing the Efficacy and Specificity of RNA Silencing

Patent Number: 7,750,144

Filed: Aug. 4, 2004

Lead Inventor: Phillip Zamore, University of Massachusetts

The invention, the patent's abstract states, "provides methods of enhancing the efficacy and specificity of RNA silencing. The invention also provides compositions for mediating RNA silencing. In particular, the invention provides siRNAs, siRNA-like molecules, shRNAs, vectors, and transgenes having improved specificity and efficacy in mediating silencing of a target gene. Therapeutic methods are also featured."


Title: Predicting Post-Treatment Survival in Cancer Patients with microRNAs

Patent Number: 7,745,134

Filed: April 9, 2008

Lead Inventor: Jian-Wei Chen, National Taiwan University

"This invention provides a method for predicting the post-treatment survival prospect of a cancer patient based on the expression levels of microRNAs hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221, and hsa-let-7a in that cancer patient," the patent's abstract states.


Title: Pharmaceutical Composition for Treating Cancer

Patent Number: 7,745,419

Filed: Sept. 19, 2008

Lead Inventor: Yu-Kyoung Oh, Korea University

The invention, the patent's abstract states, provides "a small interfering RNA that is capable of inhibiting intracellular expression of Wnt1 through complementary binding to a Wnt1 transcript base sequence, and a pharmaceutical composition for treating cancer comprising the same."

The siRNA of the invention, it adds, "is complementary to a base sequence of a Wnt1 transcript [and] provides apoptotic cancer cell death due to inhibition of expression of Wnt1 commonly expressed in cancer cells by RNA-mediated interference. Therefore, the composition of the … invention comprising the same can be used as an excellent anticancer drug."


Title: Modified iRNA Agents

Patent Number: 7,745,608

Filed: Aug. 10, 2004

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 other than ribose," the patent's abstract states. "The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents."


Title: siRNA Targeting Cyclin-Dependent Kinase 11

Patent Number: 7,745,610

Filed: May 29, 2007

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 CDK11."


Title: siRNA Targeting KRAS

Patent Number: 7,745,611

Filed: July 6, 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 directed to silencing KRAS, one can maximize the generation of an effective gene-silencing reagent, as well as methods for silencing genes."


Title: siRNA Targeting Interleukin-1 Receptor-Associated Kinase 4

Patent Number: 7,745,612

Filed: July 28, 2009

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

"Efficient sequence-specific gene silencing is possible through the use of siRNA technology," according to the patent's abstract. "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 IRAK4."


Title: Cationic Lipids and Methods of Use

Patent Number: 7,745,651

Filed: June 7, 2005

Lead Inventor: James Heyes, Protiva Biotherapeutics (Tekmira Pharmaceuticals)

The invention, the patent's abstract states, "provides compositions comprising cationic lipids, liposomes, and nucleic acid-lipid particles comprising the cationic lipids, and methods of using such compositions, liposomes, and nucleic acid-lipid particles."


Title: Methods and Compositions Concerning siRNAs as Mediators of RNA Interference

Application Number: 20100159591

Filed: June 15, 2009

Lead Inventor: Lance Ford, Life Technologies

The invention, the patent application's abstract states, "concerns an isolated siRNA of from about 5 to about 20 nucleotides that mediates RNA interference. Also disclosed are methods of reducing expression of a target gene in a cell comprising obtaining at least one siRNA of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 basepairs in length; and delivering the siRNA into the cell. The siRNAs can be chemically synthesized RNA or an analog of a naturally occurring RNA."


Title: Treating Picornavirus Infection by Targeting microRNA miR-141

Application Number: 20100160414

Filed: Dec. 15, 2009

Lead Inventor: Bing-Ching Ho, National Taiwan University College of Medicine

The invention, the patent application's abstract states, involves the "treatment of picornavirus infection by inhibiting miR-141 activity … [as well as] a method for [identifying] miR-141 inhibitory compounds and a method for identifying a target viral infection to be treated by anti-miR-141 therapy."


Title: siRNA Compositions and Methods for Potently Inhibiting Viral Infection

Application Number: 20100166661

Filed: Dec. 11, 2009

Lead Inventor: Bojian Zheng, University of Hong Kong

"No antiviral regimen has been consistently successful in treating H5N1 virus infection," the patent application's abstract states. "We demonstrate that a group of highly effective siRNAs targeting different H5N1 viral genes shares a unique motif, GGAGU/ACUCC. We further demonstrate that the effectiveness of siRNAs containing this motif is not sequence specific. The results suggested that the structure of the unique motif is critical in determining the potency of siRNA-mediated protective effects against viral infection and this potent in vivo protection is associated with early productions of beta-defensin and IL-6 induced by the motif. Provided are methods and prophylactic and therapeutic agents useful against other viral infections in addition to the H5N1 influenza virus."


Title: RNAi-Mediated Inhibition of Tumor Necrosis Factor Alpha-Related Conditions

Application Number: 20100166676

Filed: Feb. 4, 2010

Lead Inventor: Allan Shepard, Alcon

The patent application, its abstract states, claims "RNA interference … for inhibition of tumor necrosis factor alpha by silencing TNF alpha cell-surface receptor TNF receptor-1 mRNA expression, or by silencing TNF alpha-converting enzyme mRNA expression. Silencing such TNF alpha targets, in particular, is useful for treating patients having a TNF alpha-related condition or at risk of developing a TNF alpha-related condition such as the ocular conditions dry eye, allergic conjunctivitis, or ocular inflammation, or such as dermatitis, rhinitis, or asthma, for example."


Title: Individualized Cancer Therapy

Application Number: 20100166845

Filed: Oct. 30, 2009

Lead Inventor: David Shanahan, Gradalis

The invention, the patent application's abstract states, claims methods for treating cancer by "obtaining a specimen of cancer tissue and normal tissue from a patient; extracting total protein and RNA from the cancer tissue and normal tissue; obtaining a protein expression profile of the cancer tissue and normal tissue; identifying over-expressed proteins in the cancer tissue; comparing the protein expression profile to a gene expression profile; identifying at least one prioritized protein target by assessing connectivity of each said over-expressed protein to other cancer-related or stimulatory proteins; [and] designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding the prioritized target protein."

The method further comprises "designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding a protein of higher priority in the signaling pathway in which the first protein is a component; incorporating the first cassette into a first delivery vehicle; providing a patient with an effective amount of the first delivery vehicle; extracting total protein and RNA from the treated cancer tissue; identifying over-expressed proteins in the treated cancer tissue; designing a second RNA interference expression cassette to modulate the expression of a second prioritized protein in the treated tissue; incorporating the second cassette into a second delivery vehicle," it adds.

The method then calls for the previously treated patient to receive "an effective amount of the second delivery vehicle, [and then] identifying a novel protein signal following prior treatment with protein specific knockdown; identifying a gene mutation provided by gene sequencing/microarray on assessment of other protein signals; and identifying of a novel protein signal as a result of determination of the gene mutation and assessment of other protein signals to, directly or indirectly, modify the expression of such proteins."


Title: Therapeutic Uses of Inhibitors of RTP801L

Application Number: 20100168204

Filed: Oct. 29, 2009

Lead Inventor: Elena Feinstein, Quark Pharmaceuticals

The invention "provides novel molecules, compositions, methods, and uses for treating microvascular disorders, eye diseases, respiratory conditions, and hearing disorders based upon inhibition of the RTP801L gene and/or protein," the patent application's abstract states.


Title: Methods and Compositions for Prevention or Treatment of RSV Infection Using Modified Duplex RNA Molecules

Application Number: 20100168205

Filed: Oct. 23, 2009

Lead Inventor: Rachel Meyers, Alnylam Pharmaceuticals

"Methods and compositions are provided for the prevention or treatment of RSV infection in a human," the patent application's abstract states. "The methods include administering one or more doses of a composition comprising an siRNA. The dose can be formulated for topical or parenteral administration. Topical administration includes administration as a nasal spray, or by inhalation of respirable particles or droplets. The siRNA preferably comprises a sense strand and antisense strand with modified nucleotides."


Title: GNAQ-Targeted dsRNA Compositions and Methods for Inhibiting Expression

Application Number: 20100168206

Filed: Dec. 10, 2009

Lead Inventor: Jared Gollob, Alnylam Pharmaceuticals

"The invention relates to a double-stranded ribonucleic acid targeting a G-alpha q subunit of a heterotrimeric G gene, and methods of using the dsRNA to inhibit expression of GNAQ," the patent application's abstract states.


Title: Compositions and Methods for siRNA Inhibition of Angiogenesis

Application Number: 20100168207

Filed: Dec. 11, 2009

Lead Inventor: Michael Tolentino, University of Pennsylvania (Opko Health)

The invention, the patent application's abstract states, claims "RNA interference using small interfering RNAs which are specific for the vascular endothelial growth factor gene and the VEGF receptor genes Flt-1 and Flk-1/KDR inhibit expression of these genes. Diseases which involve angiogenesis stimulated by over-expression of VEGF, such as diabetic retinopathy, age-related macular degeneration, and many types of cancer, can be treated by administering the small interfering RNAs."


Title: RNA Interference-Mediated Treatment of Alzheimer's Disease Using Short Interfering Nucleic Acid

Application Number: 20100168208

Filed: Dec. 17, 2009

Lead Inventor: James McSwiggen, Sirna Therapeutics (Merck)

The invention "concerns methods and reagents useful in modulating BACE gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic-discovery applications," the patent application's abstract states. "Specifically, the invention relates to small nucleic acid molecules … capable of mediating RNA interference against beta-secretase, amyloid precursor protein, pin-1, presenillin 1, and/or presenillin 2 gene expression and/or activity. The small nucleic acid molecules are useful in the treatment of Alzheimer's disease and any other condition that responds to modulation of BACE, APP, pin-1, PS-1, and/or PS-2 expression or activity."


Title: Methods and Compositions for Modulating the siRNA and RNA-Directed DNA Methylation Pathways

Application Number: 20100169996

Filed: Jan. 18, 2008 PCT Filed: Jan. 18, 2008

Lead Inventor: Lionel Navarro, Centre National de la Recherche Scientifique

The patent application, its abstract states, claims "methods to identify nucleotide sequences whose expression will enhance resistance to pathogen infection … [as well as the] use of such nucleotide sequences to enhance resistance with minimal side effects on development."

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