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Five RNAi-Related Patent Applications Published by the USPTO: Dec 9, 2005

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Title: Processes and Reagents for Oligonucleotide Synthesis and Purification

Number: 20050267300

Filed: April 5, 2005

Lead Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals

"The … invention relates to processes and reagents for oligonucleotide synthesis and purification," the patent application's abstract states. "One aspect of the … invention relates to compounds useful for activating phosphoramidites in oligonucleotide synthesis. Another aspect of the present invention relates to a method of preparing oligonucleotides via the phosphoramidite method using an activator of the invention. Another aspect of the present invention relates to sulfur-transfer agents," it adds.

"In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one," the abstract states. "Another aspect of the … invention relates to a method of preparing a phosphorothioate by treating a phosphite with a sulfur-transfer reagent of the invention. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the … invention relates to compounds that scavenge acrylonitrile produced during the deprotection of phosphate groups bearing ethylnitrile protecting groups. In a preferred embodiment, the acrylonitrile scavenger is a polymer-bound thiol," it states.

The abstract notes that "another aspect of the … invention relates to agents used to oxidize a phosphite to a phosphate. In a preferred embodiment, the oxidizing agent is sodium chlorite, chloroamine, or pyridine-N-oxide. Another aspect of the … invention relates to methods of purifying an oligonucleotide by annealing a first single-stranded oligonucleotide and second single-stranded oligonucleotide to form a double-stranded oligonucleotide; and subjecting the double-stranded oligonucleotide to chromatographic purification. In a preferred embodiment, the chromatographic purification is high-performance liquid chromatography."


Title: RNA Interference-Mediated Inhibition of Placental Growth Factor Gene Expression Using Short Interfering Nucleic Acid

Number: 20050267058

Filed: Aug. 10, 2004

Lead Inventor: James McSwiggen, Sirna Therapeutics

"This invention relates to compounds, compositions, and methods useful for modulating placental growth factor (e.g., PGF-1 or PlGF-1, PGF-2 or PlGF-2, and/or PGF-3 or PlGF-3) gene expression using short interfering nucleic acid molecules," the patent application'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 placental growth factor gene expression and/or activity by RNA interference using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid, short interfering RNA, double-stranded RNA, microRNA, and short hairpin RNA molecules and methods used to modulate the expression of placental growth factor genes."


Title: Use of Interfering RNA in the Production of Transgenic Animals

Number: 20050266561

Filed: Nov. 22, 2004

Inventor: Kevin Wells, Revivicor

"The invention provides cells and animals, as well as methods of producing cells and animals, that express at least one interfering RNA molecule to regulate the expression of a specific gene or family of genes," the patent application's abstract states. "The invention further provides novel iRNA molecules, as well as DNA templates for producing iRNA molecules."


Title: Reagents and Methods for Identification of RNAi Pathway Genes and Chemical Modulators of RNAi

Number: 20050266552

Filed: Dec. 5, 2004

Lead Inventor: John Doench, Massachusetts Institute of Technology

According to the patent application's abstract, the invention "provides reagents such as cells, cell lines, and vectors, that can be used to identify mammalian genes whose expression products play a role in RNA interference and/or to identify chemical modulators of RNAi, or for other purposes. The invention further provides a variety of methods for identifying such genes or modulators," the abstract states.

"In particular, the invention provides a mammalian cell comprising a nucleic acid that encodes a selectable marker and one or more nucleic acid templates for transcription of an RNAi-inducing agent integrated into the genome of the cell, wherein the RNAi-inducing agent reduces expression of the marker and is not naturally found in the cell," the abstract adds. "Additional cells and cell lines comprising nucleic acids that encode one or more additional markers are also provided. According to certain of the inventive methods cells such as these are mutagenized, transfected or infected with a library of genetic suppressor elements, or contacted with a test compound. Cells in which RNAi is inhibited or activated are identified using an appropriate selective condition or screening method. The identity of the mutated or inhibited gene or the identity of the compound is then determined."


Title: Intranasal Delivery of Nucleic Acid Molecules

Number: 20050265927

Filed: May 3, 2005

Lead Inventor: Patty Lee, Yale University

"Aerosol delivery of nucleic acids to the lungs using viral vectors, polymers, surfactants, or excipients has been described" by the patent application, its abstract states. "Compositions for intranasal administration are described that contain nucleic acids without viral or plasmid vectors and with little to no polymers, surfactants, or excipients.

"In one embodiment, the composition for intranasal delivery consists essentially of at least one nucleic acid and an aqueous solution," the abstract notes. "Suitable nucleic acids for intranasal delivery include, but are not limited to, dsDNA, dsRNA, ssDNA, ssRNA, short interfering RNA, micro-RNA, and antisense RNA. Methods for treatment, diagnosis, or prevention of at least one symptom or manifestation of a lung disease are also described consisting of administration by intranasal delivery an effective amount of a composition containing a nucleic acid. The composition may be formulated as a liquid or aerosol or other acceptable formulation for intranasal administration."

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