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IP Update: Nov 19, 2009

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Title: siRNA Targeting Coatomer Protein Complex, Subunit Beta 2

Number: 7,619,081

Filed: May 30, 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 COPB2.”


Title: Devices, Systems, and Methods for Improving [Memory] and/or Cognitive Function Through Brain Delivery of siRNA

Number: 7,618,948

Filed: Oct. 19, 2005

Inventor: William Kaemmerer, Medtronic

The invention, the patent’s abstract states, “relates to devices, systems, and methods for improving memory and/or cognitive function by brain delivery of compositions of small interfering RNA or vectors containing the DNA encoding for small interfering RNA. Such compositions can be administered using devices, systems, and methods for direct delivery of the compositions to the brain, or using devices, systems, methods of delivery, and compositions that deliver small interfering RNA or vectors containing the DNA encoding the small interfering RNA across the blood-brain barrier.

“The … invention also provides valuable small interfering RNA vectors, and methods for reduction of BACE1 levels in the hippocampus, cerebral cortex, or other regions of the brain that have beneficial effects on improving memory and/or cognitive function in a subject,” the abstract adds.


Title: Delivery of Double-Stranded RNA into the Central Nervous System

Number: 20090280058

Filed: March 4, 2009

Lead Inventor: Carol Troy, Columbia University

The invention, the patent application’s abstract states, “provides for compositions and methods for in vivo delivery of a cell-permeable complex to cells of the central nervous system, wherein the cell-permeable complex decreases the level of a functional target protein encoded by a target mRNA molecule. In preferred embodiments of the invention, the cell-permeable complex comprises an siRNA nucleic acid molecule operably linked to a cell-penetrating peptide, wherein the cell-penetrating peptide facilitates transport of the cell-permeable complex across both the blood brain barrier and cell membrane of a target cell,” the abstract notes. “The methods of the invention further encompass the utilization of convection-enhanced delivery methods such as intracerebral clysis to deliver the cell-permeable complex to the target cells of the central nervous system.”


Title: Targets for Regulating Multiple Sclerosis

Number: 20090280113

Filed: May 11, 2009

Lead Inventor: Kareem Graham, Stanford University

The invention, the patent application’s abstract states, comprises “methods … for decreasing demyelinating inflammatory disease in a subject by inhibiting the activity of chemokine-like receptor 1. Methods are also provided for screening for agents that find use in treating demyelinating inflammatory disease in a subject.”

The application specifically claims the use of an siRNA to inhibit CMKLR1.


Title: Ferritin as a Therapeutic Target in Abnormal Cells

Number: 20090280166

Filed: April 13, 2009

Lead Inventor: James Connor, Pennsylvania State University

The patent application, its abstract states, claims “compositions for treatment of iron-related diseases [using] an inhibitor of ferritin. An inhibitor of ferritin is active to reduce the level of H ferritin protein in a cell and/or to reduce the activity of H ferritin in a cell. Compositions providing cytoprotection, regulation of iron, increasing longevity and viability of cells are described.”

The application specifically claims “a method of inhibiting cancerous tumor growth in a mammal [using] … a composition comprising liposomes associated with an effective amount of siRNA directed against H-ferritin.”


Title: Enhancement of Drug Therapy by miRNA

Number: 20090280167

Filed: May 7, 2009

Lead Inventor: Vuong Trieu, Abraxis BioScience

“This invention provides methods and compositions for screening of microRNA capable of modulating gene expression in the apoptotic pathway in the presence of HSP90 inhibitor,” the patent application’s abstract states. “The use of miRNA for enhancing the activity of therapeutic agents not limited to HSP90 inhibitor is also disclosed. The diagnostic use of miRNA for predicting response to therapy not limited to therapeutic agents is also disclosed. A method for the identification and therapeutic application of small molecules which are modulators of these nucleic acids are also included in this application.”


Title: Asymmetric Functionalized Nanoparticles and Methods of Use

Number: 20090280188

Filed: June 25, 2007 PCT Filed: June 25, 2007

Lead Inventor: Chad Mirkin, Northwestern University

The invention, the patent application’s abstract states, comprises “asymmetrically functionalized nanoparticles … [and] methods of preparing asymmetrically functionalized nanoparticles. Asymmetrically functionalized nanoparticles can be used in various therapeutic methods,” including siRNA delivery.


Title: Stabilized siRNAs as Transfection Controls and Silencing Reagents

Number: 20090280567

Filed: June 17, 2009

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

The invention, the patent application’s abstract states, comprises “RNA molecules, including siRNA molecules and related control, trackability and ex aequo agents, with specific stability modifications. … These molecules are particularly advantageous as transfection control reagents.

The molecules include first and second 5' terminal sense nucleotides with 2'-O-alkyl groups and a label on the first 5' terminal sense nucleotide, in conjunction with at least one additional 2'-O-alkyl pyrimidine modified sense nucleotide, and … at least one 2' fluoro modified pyrimidine antisense nucleotide and a phosphorylated first 5' terminal antisense nucleotide; or a first and second 5' terminal antisense nucleotide with 2'-O-alkyl modifications and at least one additional 2'-O-alkyl pyrimidine modified antisense nucleotide,” the abstract adds.


Title: RNA Interference-Mediated Inhibition of Respiratory Syncytial Virus Expression Using Short Interfering Nucleic Acid

Number: 20090281164

Filed: Oct. 8, 2008

Lead Inventor: James McSwiggen, Sirna Therapeutics (Merck)

“This invention relates to compounds, compositions, and methods useful for modulating respiratory syncytial virus gene expression using short interfering nucleic acid molecules,” according to the patent application’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 RSV gene expression and/or activity by RNA interference using small nucleic acid molecules … The application also relates to methods of treating diseases and conditions associated with RSV gene expression, such as RSV infection, respiratory failure, bronchiolitis, and pneumonia, as well as providing dosing regimens and treatment protocols.”


Title: siRNA Targeting V-myc Myelocytomatosis Viral Oncogene Homolog

Number: 20090281297

Filed: June 16, 2009

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

“Efficient sequence-specific gene silencing is possible through the use of siRNA technology,” the patent application’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 MYC.”


Title: Oligonucleotides Comprising a Modified or Non-Natural Nucleobase

Number: 20090281298

Filed: July 1, 2009

Lead Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals

“One aspect of the … invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase,” the patent application’s abstract states. “In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl.

“In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase,” it notes. While in other embodiments, “both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety,” the abstract adds.

“Another aspect of the … invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl,” the abstract states. “In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.”


Title: Oligonucleotides Comprising a Non-Phosphate Backbone Linkage

Number: 20090281299

Filed: July 1, 2009

Lead Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals

“One aspect of the … invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3'-position,” according to the patent application’s abstract. “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,” it notes. “Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage … [and] 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,” it adds. “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.”

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