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IP Update: Recent Patents, Patent Applications Awarded to Gradalis, Qiagen, Medtronic, and More

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Title: shRNA Molecules and Methods of Use

Patent Number: 8,252,526

Filed: Nov. 9, 2007

Lead Inventor: Donald Rao, Gradalis

The invention, the patent's abstract states, “relates to certain novel shRNA molecules and ... methods for reducing the expression level of a target gene. ... Such methods generally comprise providing a cell with one or more precursor nucleic acid sequences that encode two or more RNA molecules. A first RNA molecule comprises a double-stranded sequence, which includes a guide strand sequence that is complementary to a portion of an mRNA transcript encoded by the target gene. In addition, a second RNA molecule comprises a second double-stranded sequence, which includes a second guide strand sequence that is partially complementary to a portion of the mRNA transcript encoded by the target gene. Preferably, the second guide strand sequence comprises one or more bases that are mismatched with a nucleic acid sequence of the mRNA transcript encoded by the target gene.”


Title: Method for Identification of Polynucleotides Capable of Cleaving Target mRNA Sequences

Patent Number: 8,252,527

Filed: Feb. 19, 2008

Lead Inventor: John Sullivan, State University of New York

The invention, the patent's abstract states, comprises “methods for identifying a polynucleotide that can reduce the level of a target mRNA. The method can be performed by providing cells that express an RNA polynucleotide that contains a target mRNA sequence, an internal ribosome entry sequence, and a sequence encoding a secreted reporter protein; introducing to the cells a test polynucleotide; and measuring activity of the secreted reporter protein. A reduction in secreted reporter protein activity relative to a control cell into which the test polynucleotide has not been introduced is indicative that the test polynucleotide is capable of reducing the level of the target mRNA in the cells. The method is adaptable for high-throughput screening methods and is suited for identifying polynucleotides that can catalyze cleavage of target mRNA and/or act on target mRNA through and antisense or RNAi mechanism.”


Title: microRNAs and Their Methods of Use for the Treatment and Diagnosis of Schizophrenia and Schizophrenia Spectrum Disorders

Patent Number: 8,252,534

Filed: June 12, 2009

Lead Inventor: Steve Sommer, City of Hope

The invention comprises “a method of diagnosing, assessing susceptibility, and/or treating schizophrenia involving the identification and/or observation of microRNAs and variant miRNA,” according to the patent's abstract. “microRNA alleles associated with schizophrenia and schizophrenia spectrum disorders were identified and ultra-rare variants in the precursor or mature miRNA were identified. Functional analyses of ectopically expressed copies of the variant miRNA precursors demonstrate loss of function, gain of function, and altered expression levels. The ... invention also provides methods for selecting a preferred therapy for a particular subject or group of subjects or individuals at risk for or suffering from schizophrenia or psychosis by use of miRNAs.”


Title: RNA Interference Tags

Patent Number: 8,252,535

Filed: April 10, 2007

Lead Inventor: Wolfgang Biekle, Qiagen

“The invention relates to a method for inhibiting the expression of a target gene in a eukaryotic cell,” the patent's abstract states. “The method includes … transfecting [a] eukaryotic cell with a composition that includes a genetic construct that includes an siRNA tag, and a target gene that forms a transcription unit together with the siRNA tag; and introducing at least one siRNA that is complementary to the siRNA tag of the transfected genetic construct to inhibit the expression of the target gene.”


Title: microRNA Expression Signature for Predicting Survival and Metastases in Hepatocellular Carcinoma

Patent Number: 8,252,538

Filed: Nov. 1, 2007

Lead Inventor: Carlo Croce, Ohio State University

The invention comprises “methods and compositions for the diagnosis, prognosis, and treatment of hepatocellular carcinoma … [as well as] methods of identifying [anti-cancer] agents,” the patent's abstract states.


Title: Duplex Oligonucleotide Complexes and Methods for Gene Silencing by RNA Interference

Patent Number: 8,252,755

Filed: Sept. 20, 2007

Lead Inventor: Christina Yamada, Dharmacon (Thermo Fisher Scientific)

The patent, its abstract states, relates to ”duplex oligonucleotide complexes [that] can be administered to a cell, tissue or organism to silence a target gene without the aid of a transfection reagent. The duplex oligonucleotide complexes of the disclosure include a conjugate moiety that facilitates delivery to a cell, tissue, or organism.”


Title: Nucleic Acid-Functionalized Nanoparticles for Therapeutic Applications

Patent Number: 8,252,756

Filed: June 8, 2006

Lead Inventor: Chad Mirkin, Northwestern University

The invention, the patent's abstract states, comprises “materials and methods for regulating gene expression using nanoparticles functionalized with antisense oligonucleotides.”


Titles: Method and Compositions for the Treatment of Eye Disorders with Increased Intraocular Pressure

Patent Numbers: 8,252,758; 8,252,759; 8,258,110

Filed: July 9, 2008

Lead Inventor: Ana Jimenez, Sylentis

The patents, their abstracts state, claim “methods and compositions that decrease intraocular pressure of the eye. The compositions of the invention comprise short interfering nucleic acid molecules including, but not limited to, siRNA that decrease expression of genes associated with production or drainage of intraocular fluid. The compositions of the invention can be used in the preparation of a medicament for the treatment of an eye condition displaying increased [intraocular pressure] such as glaucoma, infection, inflammation, uveitis, and diabetic retinopathy. The methods of the invention comprise the administration to a patient in need thereof an effective amount of one or more siNAs of the invention.”


Title: Compositions and Methods for Diagnosing and Treatment Melanoma

Patent Number: 8,252,760

Filed: March 24, 2009

Lead Inventor: Eva Hernando, New York University

The patent, its abstract states, claims “compositions and methods for the diagnosis, prognosis, prevention, and treatment of melanoma or melanoma-associated symptoms. The compositions are microRNA molecules associated with melanoma, as well as various nucleic acid molecules relating thereto or derived therefrom.”


Title: RNAi Therapeutic for Treatment of Hepatitis C Infection

Patent Number: 8,252,763

Filed: Feb. 28, 2011

Inventor: Hengli Tang, Florida State University

The invention comprises “small interfering RNAs or small hairpin RNA and compositions comprising same … that specifically target human cyclophilin A to effectively inhibit hepatitis C infection in a cell,” according to the patent's abstract. “Such siRNA and shRNAs may have a length of from about 19 to about 29 contiguous nucleotides corresponding to a specific region of human cyclophilin A cDNA of from about nucleotide 155 to about nucleotide 183 having particular potency against CyPA and HCV. Such siRNA and shRNAs may be formulated as naked compositions or as pharmaceutical compositions. DNA polynucleotides, plasmids, and viral or non-viral vectors are also provided that encode siRNA or shRNA molecules, which may be delivered directly to cells or in combination with known delivery agents, such as lipids, polymers, [or] encapsulated lipid particles, such as liposomes. Methods for treating, managing inhibiting, preventing ... HCV infection using such siRNA and shRNAs and compositions comprising same are also provided.”


Title: RNAi Probes Targeting Cancer-Related Proteins

Patent Number: 8,252,918

Filed: Aug. 21, 2003

Lead Inventor: Martin Gleave, University of British Columbia

Certain “RNAi sequences ... are useful as therapeutics in the treatment of cancers of various types ... and Alzheimer's disease,” the patent's abstract states. “These sequences target clusterin, IGFBP-5, IGFBP-2, both IGFBP-2 and -5 simultaneously, Mitf, and B-raf. The invention ... provides for the use of these RNAi sequences in the treatment of cancers of various types ... and Alzheimer's disease, and a method of treating such conditions through the administration of the RNA molecules with RNAi activity.”


Title: Compositions and Methods Related to miRNA Modulation of Neovascularization or Angiogenesis

Patent Number: 8,258,111

Filed: May 8, 2009

Lead Inventor: Jikui Shen, Johns Hopkins University

The invention, the patent's abstract states, “concerns methods and compositions for diagnosing and/or treating vascular diseases including cancer, cardiac diseases, vascular diseases of the eye, and inflammatory diseases. The methods involve measuring the levels of one or multiple miRNAs in patient samples and using the test results to diagnose and/or predict an optimal treatment regimen for the patient. Compositions described in the invention include nucleic acids that function as miRNAs or miRNA inhibitors that can be introduced to a patient to reduce or increase vascularization as needed.”


Title: Methods and Sequences to Suppress Primate [Huntingtin] Gene Expression

Patent Number: 8,258,112

Filed: Sept. 10, 2009

Lead Inventor: William Kaemmerer, Medtronic

The invention, the patent's abstract states, comprises “sequences, molecules, and methods used to suppress the expression of [Huntington's disease] genes encoding for huntingtin protein in primates including Macaca mulatto and Homo sapiens. These sequences, molecules and methods aid in the study of the pathogenesis of [Huntington's disease] and can also provide a treatment for this disease.”


Title: Method for Promoting Angiogenesis, Vascularization, or Vessel Repair

Patent Number: 8,258,113

Filed: Oct. 30, 2008

Lead Inventor: Stefanie Dimmeler, T2Cure

“The invention relates to a method for influencing the miR-92 expression in a cell … [by] reducing the miR-92 expression in [a] cell in order to promote the vascularization or vessel repair by introducing an antisense molecule against miR-92 into the cell, or [by] increasing the miR-92 expression in the cell for an inhibition of the tumor angiogenesis by introducing a construct [that includes an expressible miR-92 sequence] into the cell,” according to the patent's abstract.

The invention also relates to “an agent for reducing the miR-92 activity or expression in a cell in the form of an antisense molecule against miR-92, or an agent for increasing the miR-92 expression in a cell in the form of a construct for expressing miR-92,” the abstract adds.


Title: RNA Molecules and Vectors for Gene Silencing

Patent Number: 8,258,285

Filed: Dec. 17, 2004

Lead Inventor: David Baulcombe, Plant Bioscience

“The invention relates to short RNA molecules of about 25 nucleotides in length, which comprise antisense RNA complementary to a targeted mRNA and corresponding sense RNA molecules,” the patent's abstract states “These short RNA molecules are effective in post-transcriptional gene silencing.”


Title: Reduction of Off-Target RNA Interference Toxicity

Patent Number: 8,258,286

Filed: May 29, 2008

Lead Inventor: Beverly Davidson, University of Iowa

According to the patent's abstract, “the invention is directed to RNA interference molecules targeted against a nucleic acid sequence, and methods of using these RNAi molecules to reduce off-target toxicity.”


Title: Interfering RNAs Targeting the Morbillivirus Nucleoprotein Gene

Patent Number: 8,258,287

Filed: Dec. 12, 2006

Lead Inventor: Emmanuel Albina, Center for International Cooperation in Agronomic Research for Development

“The invention relates to interfering RNAs directed against conserved regions of the mRNA of the N gene encoding the morbillivirus nucleoprotein,” the patent's abstract states. “The invention also relates to the use of said interfering RNAs for the production of medicaments for use in the treatment or prevention of a morbillivirus infection.”


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

Patent Number: 8,258,288

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,” the patent'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 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: Methods for Diagnosing Breast and Lung Cancer Using miR-210 and miR-213

Application Number: 20120214689

Filed: Feb. 27, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Colon, Stomach, Prostate, and Pancreas Cancer Using miR-223

Application Number: 20120214690

Filed: Feb. 27, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Breast Cancer Using miR-21, miR-125-1, miR-125b-2, and miR-145

Application Number: 20120214691

Filed: Feb. 27, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Pancreatic Cancer Using miR-103-1, miR-103-2, miR-24-2, and miR-107

Application Number: 20120214692

Filed: Feb. 27, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Breast Cancer Using microRNAs

Application Number: 20120214693

Filed: Feb. 28, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Colon Cancer Using microRNAs

Application Number: 20120214694

Filed: Feb. 28, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Lung Cancer Using microRNAs

Application Number: 20120214695

Filed: Feb. 28, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Pancreatic Cancer Using microRNAs

Application Number: 20120214696

Filed: Feb. 28, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Prostate Cancer Using microRNAs

Application Number: 20120214697

Filed: Feb. 28, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Stomach Cancer Using microRNAs

Application Number: 20120214698

Filed: Feb. 28, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Breast Cancer Using microRNA Signatures

Application Number: 20120214699

Filed: Feb. 29, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Colon Cancer Using microRNA Signatures

Application Number: 20120214700

Filed: Feb. 29, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Lung Cancer Using microRNA Signatures

Application Number: 20120214701

Filed: Feb. 29, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Prostate Cancer Using microRNA Signatures

Application Number: 20120214702

Filed: Feb. 29, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods for Diagnosing Stomach Cancer Using microRNA Signatures

Application Number: 20120214703

Filed: Feb. 29, 2012

Lead Inventor: Carlo Croce, Ohio State University

The invention provides “novel methods and compositions for the diagnosis and treatment of solid cancers,” the patent application's abstract states. “The invention also provides methods of identifying inhibitors of tumorigenesis.”


Title: Methods and Compositions for Treating Neurological Disease

Application Number: 20120214861

Filed: Sept. 21, 2011

Lead Inventor: Neil Aronin, University of Massachusetts

“This invention relates to methods and compositions for treating neurological disease, and more particularly to methods of delivering iRNA agents to neural cells for the treatment of neurological diseases,” the patent application's abstract states.


Title: Anti-miR-1 Therapy for Wound Healing

Application Number: 20120214863

Filed: Aug. 4, 2010

Lead Inventor: Chandan Sen, Ohio State University

The patent application, its abstract states, claims “methods for modulating gene expression in a skin cell by administering to the cell an amount of a therapeutic composition in an amount sufficient to modulate the expression of miR-1, and therapeutic compositions and uses thereof.”


Title: Inhibition of Viral Gene Expression Using Small Interfering RNA

Application Number: 20120220033

Filed: Jan. 27, 2012

Lead Inventor: Roger Kaspar, Somagenics

“The invention provides methods, compositions, and kits comprising small interfering RNA that are useful for inhibition of viral-mediated gene expression,” the patent application's abstract states. “Small interfering RNAs as described herein can be used in methods of treatment of [hepatitis C virus] infection … [and] shRNA and siRNA constructs targeting the internal ribosome entry site sequence of [the virus] are described.”


Title: siRNA Targeting Catenin, Beta-1

Application Number: 20120220496

Filed: May 8, 2012

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 nucleotide sequences for CTNNB1.”

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