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IP Update: Dec 17, 2009

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Title: siRNA Targeting Superoxide Dismutase 1

Patent Number: 7,632,938

Filed: Oct. 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 nucleotide sequences for SOD1."


Title: siRNA Targeting Proto-Oncogene MET

Patent Number: 7,632,939

Filed: Oct. 30, 2007

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 proto-oncogene MET."


Title: Oligonucleotides Comprising a Ligand Tethered to a Modified or Non-Natural Nucleobase

Patent Number: 7,632,932

Filed: Aug. 4, 2005

Lead Inventor: Muthiah Manoharan, Alnylam Pharmaceuticals

The invention, the patent's abstract states, "relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl."

In certain embodiments, the ligand is a steroid or aromatic compound; only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a ligand tethered to an altered or non-natural nucleobase; both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a ligand tethered to an altered or non-natural nucleobase; or 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 ligand tethered to an altered or non-natural nucleobase," the abstract adds. "In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl." In other embodiments, the ligand is a steroid or aromatic compound; the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group; or at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.


Title: Means for Inhibiting the Expression of Protein Kinase 3

Application Number: 20090304678

Filed: July 20, 2007 PCT Filed: July 20, 2007

Lead Inventor: Jorg Kaufmann, Silence Therapeutics

The invention, the patent application's abstract states, "is related to a nucleic acid molecule comprising a double-stranded structure, whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and said first stretch is at least partially complementary to a target nucleic acid." According to the invention, the second strand also "comprises a second stretch of contiguous nucleotides [that is] at least partially complementary to the first stretch, whereby the first stretch comprises a nucleic acid sequence [that] is at least partially complementary to a nucleotide core sequence of the nucleic acid sequence."

The application specifically claims the use of the dsRNA to treat angiogenesis-related disorders of adipose tissue, the skin, heart, eye, lung, intestines, reproductive organs, bone, and joints.


Title: Methods and Compositions for Therapeutic Use of RNA Interference

Application Number: 20090304798

Filed: Jan. 9, 2009

Lead Inventor: Mark Davis, Insert Therapeutics (Calando Pharmaceuticals)

The invention "provides methods and compositions for attenuating expression of a target gene in vivo," according to the patent application's abstract. "In general, the method includes administering RNAi constructs that are targeted to particular mRNA sequences, or nucleic acid material that can produce siRNAs in a cell, in an amount sufficient to attenuate expression of a target gene by an RNA interference mechanism. … In particular, the subject method can be used to alter the growth, survival, or differentiation of cells for therapeutic and cosmetic purposes."


Title: Compounds and Methods for Modulating the Silencing of a Polynucleotide of Interest

Application Number: 20090306035

Filed: Aug. 25, 2006 PCT Filed: Aug. 25, 2006

Lead Inventor: Jin Peng, Emory University

The patent application, its abstract states, claims "methods and compositions comprising chemical compounds that modulate the silencing of a polynucleotide of interest in a cell. … Such chemical compounds when used in combination with an appropriate silencing element can be used to modulate the level of the polynucleotide targeted by the silencing element."

Included in the application are "methods of using such compositions both in therapies involving RNAi-mediated suppression of gene expression, as well as in vitro methods that allow for the targeted modulation of expression of a polynucleotide of interest," the abstract notes. "Pharmaceutical or cosmetic formulations comprising such compounds and silencing elements also are disclosed. Methods for screening a compound of interest for the ability to modulate the activity of a heterologous silencing element also are provided."


Title: Modulation of Immunostimulatory Properties of Short Interfering Ribonucleic Acid by Nucleotide Modification

Application Number: 20090306177

Filed: Sept. 15, 2006 PCT Filed: Sept. 15, 2006

Lead Inventor: Eugen Uhlmann, Coley Pharmaceutical (Pfizer)

"Double-stranded short interfering ribonucleic acid are modified to reduce or eliminate their immunostimulatory effect without significantly affecting their gene-silencing effect," the patent application's abstract states. "Modified siRNA include one or more 2' sugar modifications and, optionally, internucleotide linkages on the sense strand. Compositions containing the modified siRNA and methods of making and using the modified siRNA are disclosed. New and previously characterized siRNA can be synthesized to incorporate modifications according to the invention."


Title: Conjugated Double-Strand Compositions for Use in Gene Modulation

Application Number: 20090306178

Filed: March 27, 2007 PCT Filed: March 27, 2007

Lead Inventor: Balkrishen Bhat, Isis Pharmaceuticals

The invention, the patent application's abstract states, "provides conjugated double-stranded compositions wherein each strand is modified to have a motif defined by positioning of beta-D-ribonucleosides and/or sugar modified nucleosides. More particularly, the … compositions comprise a linked conjugate group on one strand and a non hybridizing region of 2'-modified nucleosides on the other strand. Each strand further comprises one or more phosphorothioate internucleoside linkage.

"The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes," the abstract notes. "In preferred embodiments, the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The … invention also provides methods for modulating gene expression."


Title: RNA Interference-Mediated Inhibition of MAP Kinase Gene Expression Using Short Interfering Nucleic Acid

Application Number: 20090306182

Filed: Dec. 12, 2008

Lead Inventor: James McSwiggen, Sirna Therapeutics (Merck)

"This invention relates to compounds, compositions, and methods useful for modulating mitogen activated protein kinase 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 MAP kinase gene expression and/or activity by RNA interference using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules … and methods used to modulate the expression of MAP kinase genes, such as Jun amino-terminal kinase, p38, ERK, and/or c-Jun."


Title: RNA Interference-Mediated Inhibition of Hepatitis C Virus Expression Using Short Interfering Nucleic Acid

Application Number: 20090306184

Filed: April 3, 2009

Lead Inventor: James McSwiggen, 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 gene expression and/or activity. The … invention 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 gene-expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases, and conditions.

"Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules … capable of mediating RNA interference against gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle formulations of such small nucleic acid molecules," the abstract notes. The invention "also relates to small nucleic acid molecules … that can inhibit the function of endogenous RNA molecules … to modulate gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs, including cocktails of such small nucleic acid molecules and lipid nanoparticle formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce diseases, traits, and conditions that are associated with gene expression or activity in a subject or organism."


Title: Nanogenomics for Medicine: siRNA Engineering

Application Number: 20090306185

Filed: May 12, 2009

Lead Inventor: Ancha Baranova, George Mason University

The patent application, its abstract states, claims "materials and methods for the delivery of siRNA and the production of nanoparticles useful for the delivery of siRNA. Methods of treating a disease or disorder using the nanoparticles described herein also are disclosed."


Title: Methods for Controlling Pests Using RNAi

Application Number: 20090306189

Filed: Sept. 18, 2006 PCT Filed: Sept. 18, 2006

Lead Inventor: Romaan Raemaekers, Devgen

The invention "relates to methods for controlling pest infestation using double-stranded RNA molecules," the patent application's abstract states. "The invention provides methods for producing transgenic cells expressing the double-stranded RNA molecules, as well as compositions and commodity products containing or treated with such molecules."


Title: Novel Compositions for the In Vivo Delivery of RNAi Agents

Application Number: 20090306194

Filed: June 5, 2009

Lead Inventor: Lance Ford, Asuragen (Bioo Scientific)

"This application describes emulsion formulations containing neutral phospholipids for delivering RNAi, anti-miRNA, or aptamer agents in vivo," the patent application's abstract states. "The application also relates to methods of making the formulations, and uses of the formulations as delivery agents."


Title: siRNA Targeting TNA-Alpha

Application Number: 20090306356

Filed: Sept. 12, 2008

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 TNF-alpha."

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