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Eight RNAi-Related Patent Applications Published By US Patent Office

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Title: Treatment of Cancer by Inhibiting BRAF Expression. Number: 20050019918. Filed: April 29, 2004. Lead Inventor: Hidetoshi Sumimoto, Keio University School of Medicine.

“The … invention relates to a therapeutic method using RNAi directed at BRAF, of which the point mutation, especially V599E, occurs frequently in melanomas,” the patent application’s abstract states. “RNAi specific for the mutated BRAF will provide a specific therapeutic intervention for cancers such as malignant melanoma.

“Several target sequences for RNAi were selected in the protein coding region of the BRAF mRNA,” the abstract notes. “The short-hairpin RNA expression cassette was constructed on the lentiviral vector. One recombinant viral vector for the mutated BRAF V599E and two other vectors sites for wild type BRAF were constructed to infect various malignant melanoma cell lines, and the effects on the growth inhibition and the signaling of MAPK pathway were examined. The inhibitory effect on the invasion ability of malignant melanoma cell line and in vivo growth of a malignant melanoma cell line were examined,” it adds.


Title: Novel Lipids for Transfection of Nucleic Acids. Number: 20050014962. Filed: May 24, 2004. Lead Inventor: Gulilat Gebeyehu, Invitrogen.

The patent application, its abstract states, covers “cationic lipid compositions … that are useful for efficient delivery of macromolecules, such as nucleic acids, into a wide variety of eukaryotic cell types [as well as] methods for using the compositions.”


Title: RNA Interference-Mediated Inhibition of Muscarinic Cholinergic Receptor Gene Expression Using Short-Interfering Nucleic Acid. Number: 20050014172. Filed: March 11, 2004. Lead Inventor: Ivan Richards, Sirna Therapeutics.

“The … invention relates to compounds, compositions, and methods useful for modulating the expression of genes associated with respiratory and pulmonary disease, such as cholinergic muscarinic receptor genes, 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 cholinergic muscarinic receptor genes, or other genes involved in pathways of cholinergic muscarinic receptor 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 M3 muscarinic acetylcholine receptor or cholinergic receptor muscarinic,” the abstract adds.


Title: Compositions and Systems for the Regulation of Genes. Number: 20050014166. Filed: Nov. 24, 2003. Lead Inventor: Didier Trono, Institut Clayton de la Recherche.

According to the patent application’s abstract, 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. 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,” the abstract notes. “Lentivirus vectors are employed in some embodiments of the invention including the generation of conditional knockdown animals.”


Title: Inhibiting Gene Expression with dsRNA. Number: 20050026290. Filed: Aug. 1, 2003. Lead Inventor: Joseph Anthony Ciardi, University of Pennsylvania.

“The … invention relates to the altering or controlling inhibition of gene expression in a cell using a methodology involving a dsRNA,” the patent application’s abstract states.

“The use of the method in plants and plant cells has been found to be particularly beneficial,” the abstract notes. “For example the inhibition of a hormone signaling gene in a plant, such as the EIN2 gene, permits the modulating of flower longevity in the selected plant. This is accomplished by using our RNAi technology in inhibiting the expression of an ethylene-modulated gene or an ethylene signaling gene in plants and plant cells. This method provides for the use of RNAi technology in inhibiting the expression of a hormone signaling gene in a plant, particularly in the floral parts of a plant.”


Title: Methods and Compositions for Selective RNAi-Mediated Inhibition of Gene Expression in Mammal Cells. Number: 20050026286. Filed: March 4, 2004. Lead Inventor: Jen-Tsan Chi, Stanford University School of Medicine.

According to the patent application’s abstract, the invention comprises “RNAi arrays and methods for using the same.

“The subject arrays are characterized by having two or more distinct RNAi agents,” the abstract notes. “The arrays find use in methods where cells are contacted with the arrays and the activity of the RNAi agents is determined by evaluating the contacted cells. The subject arrays and methods find use in a variety of applications, such as high throughput loss of function genomic applications.”


Title: RNA Interference-Mediating Small RNA Molecules. Number: 20050026278. Filed: April 27, 2004. Lead Inventor: Thomas Tuschl, Rockefeller University (Max-Planck Institute).

“Double-stranded RNA induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference,” the abstract notes. “Using a Drosophila in vitro system, we demonstrate that 19-23 [nucleotide] short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs are generated by an RNase III-like processing reaction from long dsRNA.”

The abstract adds that “chemically synthesized siRNA duplexes with overhanging 3’ ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.”


Title: SiRNA Libraries Optimized for Predetermined Protein Families. Number: 20050026172. Filed: Feb. 10, 2004. Lead Inventor: Henry Li, Immusol.

The patent application, its abstract states, covers “libraries for generating small interfering RNA … where the members of the library are optimized to inhibit the expression of genes that encode a predetermined family of proteins. The members of the library target at least mRNA encoding all members of the family of proteins. Methods for generating siRNA libraries of the present invention are also provided,” the abstract adds.