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IP Update: Aug 12, 2010

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Title: iRNA Agents Targeted to the Rho-A Gene

Patent Number: 7,772,200

Filed: July 21, 2006

Lead Inventor: Juergen Soutschek, Alnylam Pharmaceuticals

"The invention relates to compositions and methods for modulating the expression of the RhoA gene, and more particularly to the down-regulation of RhoA, by chemically modified oligonucleotides," the patent's abstract states.


Title: Highly Branched HK Peptides as Effective Carriers of siRNA

Patent Number: 7,772,201

Filed: Nov. 17, 2005 PCT Filed: Nov. 17, 2005

Lead Inventor: Archibald Mixson, University of Maryland

The invention, the patent's abstract states, "is directed to methods of transfecting cells with siRNA by contacting a transfection complex with one or more cells [and] where the transfection complex includes a transport polymer and siRNA. … The invention is also directed to such transfection complexes, and to compositions that include such transfection complexes. The invention is further directed to methods of treating patients using the transfection complexes."


Title: Methods and Compositions for Controlling Efficacy of RNA Silencing

Patent Number: 7,772,203

Filed: July 14, 2008

Lead Inventor: Phillip Zamore, University of Massachusetts

"Based at least in part on an understanding of the mechanisms by which small RNAs mediate RNA silencing in plants, rules have been established for determining, for example, the degree of complementarity required between an RNAi-mediating agent and its target, i.e., whether mismatches are tolerated, the number of mismatches tolerated, the effect of the position of the mismatches, etc.," the patent's abstract states. "Such rules are useful, in particular, in the design of improved RNAi-mediating agents which allow for more exact control of the efficacy of RNA silencing."


Title: Oligonucleotides Comprising a Modified or Non-Natural Nucleobase

Application Number: 7,772,387

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'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. 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 that 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. 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: Anti-microRNA Oligonucleotide Molecules

Application Number: 7,772,389

Filed: Feb. 11, 2005 PCT Filed: Feb. 11, 2005

Lead Inventor: Thomas Tuschl, Rockefeller University

"The invention relates to isolated anti-microRNA molecules," the patent's abstract states. "In another embodiment, the invention relates to an isolated microRNA molecule. In yet another embodiment, the invention provides a method for inhibiting microRNA activity in a cell."


Title: Application of RNA Interference Targeting dhfr Gene to Cell for Producing Secretory Protein

Application Number: 20100197012

Filed: April 15, 2010

Lead Inventor: Shu-Chin Wu, National Tsing Hua University

"Biological materials are applied to a [Chinese hamster ovary] cell or the like for enhancing production of a species of protein," the patent application's abstract states. "The biological materials include an expression vector and a silencing vector.

The expression vector contains a dhfr gene "of a species of mammal and a gene encoding the species of protein," while the silencing vector includes "a DNA fragment for inducing RNA interference in the CHO cell to reduce expressions of both exogenous dhfr gene and endogenous dhfr gene after the biological material is applied to the CHO cell," the abstract notes. "The CHO cell is thus not limited to dhfr gene deficient type. The DNA fragment consists of nucleotides characterizing a segment of a dhfr gene of the CHO cell and a segment of a dhfr gene of the species of mammal."


Title: Modified Polynucleotides for Use in RNA Interference

Application Number: 20100197023

Filed: Nov. 25, 2009

Lead Inventor: Devin Leake, Dharmacon (Thermo Fisher Scientific)

The invention, the patent application's abstract states, comprises "methods and compositions for performing RNA interference comprising a wide variety of stabilized siRNAs suitable for use in serum-containing media and for in vivo applications, such as therapeutic applications.

"These siRNAs permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of one or more modifications including orthoesters, terminal conjugates, modified linkages, and 2' modified nucleotides," it adds. "Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications include phosphorylation of the first 5' terminal antisense nucleotide; 2' carbon modifications of the first and second or first, second, and third 5' terminal antisense nucleotides; and optionally 2' carbon modifications of the first and second or first, second, and third 5' terminal sense nucleotide. Control and ex aequo molecules are also provided … [while] siRNA molecules and related control, trackability, and ex aequo agents with specific stability modifications were developed."


Title: RNA Interference-Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase Gene Expression Using Short Interfering Nucleic Acid

Application Number: 20100197763

Filed: May 2, 2008 PCT Filed: May 2, 2008

Lead Inventor: Vasant Jadhav, Sirna Therapeutics (Merck)

The invention, the patent application's abstract states, "relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases, and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity."

It is also "directed to compounds, compositions, and methods relating to traits, diseases, and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases, and conditions, including but not limited to IL-6, IL-7, IL-8, IL-15, TNF-alpha, and matrix metalloproteinases, such as MMP-I, MMP-2, MMP-3, MMP-9, and MMP-12," it states. "Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules … capable of mediating RNA interference against cyclic nucleotide type 4 phosphodiesterase gene expression … [as well as] small nucleic acid molecules … that can inhibit the function of endogenous RNA molecules or RNAi pathway components … or that can inhibit the function of RISC to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism."


Title: Tissue-Specific microRNAs and Compositions and Uses Thereof

Application Number: 20100197772

Filed: Jan. 15, 2010

Lead Inventor: Andrea Califano, Columbia University

"The invention provides for isolated nucleic acid sequences of newly discovered microRNAs that have been identified to exist in normal human B cells and/or in tumor-related human B cells, using an integrated bioinformatics method and pipeline," the patent application's abstract states.


Title: Compositions and Methods for Inhibiting Expression of PTP1B Genes

Application Number: 20100197773

Filed: Jan. 29, 2010

Lead Inventor: Birgit Bramlage, Roche

"This invention relates to a double-stranded ribonucleic acid for inhibiting the expression of a PTP1B gene," the patent application's abstract states. "The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a PTP1B gene using said pharmaceutical composition; and methods for inhibiting the expression of PTP1B in a cell."


Title: microRNA Expression Abnormalities in Pancreatic, Endocrine, and Acinar Tumors

Application Number: 20100197774

Filed: Feb. 4, 2010

Lead Inventor: Carlo Croce, Ohio State University

The invention "provides novel methods and compositions for the diagnosis, prognosis, and treatment of pancreatic cancer," according to the patent application's abstract. "The invention also provides methods of identifying anti-pancreatic cancer agent."


Title: Single-Stranded and Double-Stranded Oligonucleotides Comprising a 2-Arylpropyl Moiety

Application Number: 20100197899

Filed: Oct. 23, 2009

Lead Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals

The invention "provides single-stranded and double-stranded oligonucleotides comprising at least one aralkyl ligand that improvise the pharmacokinetic properties of the oligonucleotide," the patent application's abstract states. "The aralkyl ligands of the present invention include naproxen, ibuprofen, and derivatives thereof. The … invention also provides method for modulating gene expression using the modified oligonucleotide compounds and compositions comprising those modified oligonucleotides."

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