Nucleic Acid Expression Inhibitors Patents (Class 536/24.5)
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Patent number: 10329568Abstract: The present invention is related to a ribonucleic acid 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 whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.Type: GrantFiled: September 5, 2018Date of Patent: June 25, 2019Assignee: Silence Therapeutics GMBHInventors: Klaus Giese, Jörg Kaufmann, Anke Klippel-Giese
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Patent number: 10323246Abstract: The present invention is related to a ribonucleic acid 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 whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.Type: GrantFiled: August 15, 2017Date of Patent: June 18, 2019Assignee: Silence Therapeutics GMBHInventors: Klaus Giese, Jörg Kaufmann, Anke Klippel-Giese
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Patent number: 10302644Abstract: The invention provides, inter alia, methods of prognosing the survival of a multiple myeloma patient based levels of TP53RK in multiple myeloma cells of the patient. Also provided are methods of screening for therapeutic agents for treating multiple myeloma based on their ability to decrease TP53RK levels or activity in a patient with multiple myeloma.Type: GrantFiled: October 20, 2015Date of Patent: May 28, 2019Assignee: Dana-Farber Cancer Institute, Inc.Inventors: Teru Hideshima, Kenneth C. Anderson, Francesca Cottini
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Patent number: 10232055Abstract: This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules.Type: GrantFiled: October 31, 2016Date of Patent: March 19, 2019Assignee: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIAInventors: Katalin Kariko, Drew Weissman
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Patent number: 10219492Abstract: Provided herein are methods for altering respiratory syncytial virus (RSV) replication in a cell using oligonucleotides derived from tRNAs, also referred to as tRFs (tRNA-derived RNA Fragments). The oligonucleotides may be used to decrease or increase replication of RSV. Also provided herein are methods for treating a subject having or at risk of having an RSV infection, and animal models for evaluating viral and host factors in RSV pathogenesis.Type: GrantFiled: November 21, 2014Date of Patent: March 5, 2019Assignee: The Board of Regents of the University of Texas SystemInventors: Xiaoyong Bao, Yong Sun Lee
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Patent number: 10208309Abstract: The present invention relates to a novel siRNA, and a high-efficiency double-stranded oligo RNA structure containing the same, and a nanoparticle containing the high-efficiency double-stranded oligo RNA structure. The double-stranded oligo RNA structure has a structure in which a hydrophilic material and a hydrophobic material are conjugated to both ends of a double-stranded oligo RNA (siRNA) via a simple covalent bond or linker-mediated covalent bond in order to be efficiently delivered into cells, and may be converted into a nanoparticle form in an aqueous solution by hydrophobic interactions of double-stranded oligo RNA structures. It is preferable that the siRNA contained in the double-stranded oligo RNA structure is an siRNA specific for fibrosis or respiratory disease-related gene, particularly, amphiregulin or stratifin.Type: GrantFiled: April 6, 2015Date of Patent: February 19, 2019Assignee: BIONEER CORPORATIONInventors: Jeiwook Chae, Pyoung Oh Yoon, Boram Han, Mi Na Kim, Youngho Ko, Han Oh Park
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Patent number: 10202599Abstract: The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.Type: GrantFiled: August 8, 2012Date of Patent: February 12, 2019Assignee: Ionis Pharmaceuticals, Inc.Inventors: Punit P. Seth, Michael Oestergaard, Eric E. Swayze
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Patent number: 10174327Abstract: The present disclosure provides an RNA oligonucleotide having a helical bend structure and a use thereof. Specifically, double strands formed by a complementary binding of two sequences have a helical bend structure in the RNA oligonucleotide. The RNA oligonucleotide can increase the expression of interferon-? or ISG56 and thus can be used as an immune system enhancer.Type: GrantFiled: May 26, 2016Date of Patent: January 8, 2019Assignee: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGYInventors: Byong-Seok Choi, Mi Kyung Lee, Janghyun Lee, Suk-Jo Kang, Eun Byeol Park
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Patent number: 10138485Abstract: Neutral lipid formulations for nucleic acid delivery are provided according to the invention. The neutral lipid formulations include hydrophobically modified polynucleotides and fat mixtures. Methods of using the neutral lipid formulations are also provided.Type: GrantFiled: September 22, 2009Date of Patent: November 27, 2018Assignee: RXi Pharmaceuticals CorporationInventors: Anastasia Khvorova, William Salomon, Joanne Kamens, Dmitry Samarsky, Tod M. Woolf, Michelle Miller, Karen G. Bulock
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Patent number: 10131910Abstract: The invention relates to the fields of medicine and immunology. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Usher syndrome type 2A and/or USH2A-associated non syndromic retina degeneration.Type: GrantFiled: July 9, 2015Date of Patent: November 20, 2018Assignee: STICHTING KATHOLIEKE UNIVERSITEITInventor: Hendrikus Antonius Rudolfus Van Wyk
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Patent number: 10119136Abstract: One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene in vivo. The dsRNA duplex comprises one or more 4?-modifications in one or both strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for in vivo therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.Type: GrantFiled: January 9, 2015Date of Patent: November 6, 2018Assignee: ALNYLAM PHARMACEUTICALS, INC.Inventors: Muthiah Manoharan, Shigeo Matsuda, Kallanthottathil G. Rajeev, Ivan Zlatev
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Patent number: 10106852Abstract: This invention is directed to mutated Activin A type I receptor proteins (ACVR1) and isolated nucleic acids encoding same. The invention also relates to the use of mutated ACVR1 in the diagnosis and treatment of Fibrodysplasia Ossificans Progressiva (FOP).Type: GrantFiled: October 22, 2014Date of Patent: October 23, 2018Assignee: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIAInventors: Frederick S. Kaplan, Eileen M. Shore
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Patent number: 10106792Abstract: The invention is directed to compositions and methods for selectively reducing the expression of a gene product from a desired target gene in a cell, as well as for treating diseases caused by the expression of the gene. More particularly, the invention is directed to compositions that contain double stranded RNA (“dsRNA”), and methods for preparing them, that are capable of reducing the expression of target genes in eukaryotic cells. The dsRNA has a first oligonucleotide sequence that is between 25 and about 30 nucleotides in length and a second oligonucleotide sequence that anneals to the first sequence under biological conditions. In addition, a region of one of the sequences of the dsRNA having a sequence length of at least 19 nucleotides is sufficiently complementary to a nucleotide sequence of the RNA produced from the target gene to trigger the destruction of the target RNA by the RNAi machinery.Type: GrantFiled: December 12, 2016Date of Patent: October 23, 2018Assignees: CITY OF HOPE, INTEGRATED DNA TECHNOLOGIES, INC.Inventors: John J. Rossi, Mark A. Behlke, Dongho Kim
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Patent number: 10100310Abstract: Disclosed herein are antisense compounds and methods for decreasing PKK mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate PKK-associated diseases, disorders, and conditions.Type: GrantFiled: April 11, 2017Date of Patent: October 16, 2018Assignee: Ionis Pharmaceuticals, Inc.Inventors: Susan M. Freier, Huynh-Hoa Bui
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Patent number: 10100004Abstract: Here described are compounds consisting of the structure (targeting molecule)m-linker-(targeting molecule)n, wherein the targeting molecule is a retinoid or a fat soluble vitamin having a specific receptor on the target cell; wherein m and n are independently 0, 1, 2 or 3; and wherein the linker comprises a polyethylene glycol (PEG) or PEG-like molecule, as well as compositions and pharmaceutical formulations including these compounds which are useful for the targeting and delivery of therapeutic agents; and methods of using these compositions and pharmaceutical formulations.Type: GrantFiled: June 8, 2016Date of Patent: October 16, 2018Assignee: Nitto Denko CorporationInventors: Yoshiro Niitsu, Joseph E. Payne, John A. Gaudette, Zheng Hou, Victor Knopov, Richard P. Witte, Mohammad Ahmadian, Loren A. Perelman, Yasunobu Tanaka, Violetta Akopian
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Patent number: 10036022Abstract: The invention relates to antisense oligonucleotidic sequences (ODN) against Smad7 suitably modified, and their uses in medical field as therapeutic biological agents, in particular in the treatment of chronic inflammatory bowel disease, such as Crohn's disease and ulcerative colitis.Type: GrantFiled: November 18, 2016Date of Patent: July 31, 2018Assignee: Nogra Pharma LimitedInventor: Giovanni Monteleone
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Patent number: 10004814Abstract: The present invention provides methods comprising the in vivo delivery of small nucleic acid molecules capable of mediating RNA interference and reducing the expression of myostatin, wherein the small nucleic acid molecules are introduced to a subject by systemic administration. Specifically, the invention relates to methods comprising the in vivo delivery of short interfering nucleic acid (siNA) molecules that target a myostatin gene expressed by a subject, wherein the siNA molecule is conjugated to a lipophilic moiety, such as cholesterol. The myostatin siNA conjugates that are delivered as per the methods disclosed are useful to modulate the in vivo expression of myostatin, increase muscle mass and/or enhance muscle performance. Use of the disclosed methods is further indicated for treating musculoskeletal diseases or disorders and/or diseases or disorders that result in conditions in which muscle is adversely affected.Type: GrantFiled: November 10, 2014Date of Patent: June 26, 2018Assignee: SIRNA THERAPEUTICS, INC.Inventors: Marija Tadin-Strapps, Tayeba Khan, Walter Richard Strapps, Laura Sepp-Lorenzino, Vasant Jadhav, Duncan Brown
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Patent number: 9999772Abstract: A system and method for performing deep brain stimulation (DBS) therapy are provided. The method and system include pre-operatively acquiring at least one pre-operative image of the brain with at least one imaging sub-system and determining a location of a Nucleus Basalis of Meynert (NBM) for therapy in the at least one pre-operative image, and intra-operatively acquiring at least one intra-operative image of the brain after obtaining an access opening through the skull. The method and system further provide performing surgical planning based on the pre-operative image in the intra-operative image, advancing a lead having DBS electrodes on the lead to a target position proximate to or within the NBM area, and coupling the lead to an implantable pulse generator (IPG) configured to deliver DBS pulses through the DBS electrodes to the NBM. Further, the IPG is configured to deliver DBS pulses for treating symptoms associated with Alzheimer's disease.Type: GrantFiled: April 3, 2014Date of Patent: June 19, 2018Assignee: PACESETTER, INC.Inventor: Lalit Venkatesan
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Patent number: 10000766Abstract: Provided is a strategy for generating transgenic plants with concurrent resistance to DNA and RNA viruses at one construction, so as to develop an RNA-directed DNA methylation (RdDM) transgenic system using a hairpin construct of Ageratum yellow vein virus (AYVV) promoter region residing in an intron to resist DNA virus infection by RdDM. Furthermore, the hairpin construct of the AYVV promoter region coupled with an untranslatable nucleocapsid protein (NP) fragment of Melon yellow sport virus (MYSV) is created to induce post-transcriptional gene silencing (PTGS) against MYSV. A method for providing transgenic plants conferring concurrent resistance to both AYVV and MYSV for control of DNA and RNA virus at the same time, and underlying RdDM and PTGS mechanisms, respectively, is also provided.Type: GrantFiled: July 17, 2015Date of Patent: June 19, 2018Assignee: NATIONAL CHUNG HSING UNIVERSITYInventors: Shyi-Dong Yeh, Ching-Fu Yang, Kuan-Chun Chen, Ya-Ling Huang
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Patent number: 9982266Abstract: The present invention relates to a method and compositions for the treatment of cystic fibrosis.Type: GrantFiled: May 17, 2017Date of Patent: May 29, 2018Assignees: INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE), UNIVERSITE DE MONTPELLIERInventor: Magali Taulan-Cadars
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Patent number: 9944931Abstract: The present disclosure provides, in part, methods of discovering immunotherapy targets in vivo, therapeutic compositions (e.g., shRNA, immunoresponsive cells expressing shRNA and/or a chimeric antigen receptors (CAR)), and methods of use thereof.Type: GrantFiled: June 10, 2014Date of Patent: April 17, 2018Assignees: Dana-Farber Cancer Institute, Inc., The General Hospital CorporationInventors: Kai W. Wucherpfennig, Glenn Dranoff, Penghui Zhou, Donald Shaffer, Nir Hacohen, Harvey I. Cantor, Diana Alvarez Arias
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Patent number: 9944942Abstract: The present invention provides transgenic plants having increased tolerance to abiotic stress comprising a recombinant nucleic acid molecule, said recombinant nucleic acid molecule comprising a nucleotide sequence encoding miR319 operatively associated with a promoter, a nucleotide sequence that is antisense to a portion of consecutive nucleotides of a nucleotide sequence encoding PCF5, and/or a nucleotide sequence that encodes a portion of consecutive nucleotides of a nucleotide sequence encoding PCF5, which when expressed produces an antisense nucleotide sequence, wherein expression of the nucleotide sequence confers increased tolerance to abiotic stress. Also provided are methods and compositions for making said transgenic plants.Type: GrantFiled: November 8, 2012Date of Patent: April 17, 2018Assignee: CLEMSON UNIVERSITYInventors: Hong Luo, Dayong Li, Man Zhou, Qian Hu
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Patent number: 9914922Abstract: The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.Type: GrantFiled: April 22, 2013Date of Patent: March 13, 2018Assignee: Ionis Pharmaceuticals, Inc.Inventors: Susan M. Freier, Eric E. Swayze
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Patent number: 9868782Abstract: This invention features methods and compositions useful for treating and diagnosing diseases of the nervous system, retina, skin, muscle, joint, and cartilage using a Dragon family protein. Protein and nucleic acid sequences of human, murine, zebrafish, and C. elegans Dragon family members are also disclosed.Type: GrantFiled: October 26, 2011Date of Patent: January 16, 2018Assignee: The General Hospital CorporationInventors: Clifford J. Woolf, Tarek A. Samad
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Patent number: 9868949Abstract: The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preemclampsia, inflammation, chronic inflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1.Type: GrantFiled: February 27, 2014Date of Patent: January 16, 2018Assignee: Arrowhead Pharmaceuticals, Inc.Inventors: Brian Bettencourt, Shanthi Ganesh, Elizabeth George, Dieter Heusken, Stuart Milstein, Jonathan Solomon, Emily Thomas, Ivanka Toudjarska, Jennifer Tullai, Jan Weiler
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Patent number: 9856480Abstract: The invention provides DNAzymes which are capable to silence the expression of EGFR at allele-specific level. These allele-specific DNAzymes against EGFR T790M mutation will knockdown the expression of EGFR T790M mRNA while keeping EGFR wild-type mRNA intact. Hence, these allele-specific DNAzymes against EGFR T790M mutation may overcome T790M-derived TKI resistance accompanied with lower unwanted side effects on normal cells in lung cancer patients.Type: GrantFiled: January 14, 2014Date of Patent: January 2, 2018Assignees: National Taiwan University, ACADEMIA SINICAInventors: Pan-Chyr Yang, Wei-Yun Lai, Konan Peck, Cheng-Ju Chang, Chi-Yuan Chen, Shuenn-Chen Yang
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Patent number: 9816092Abstract: Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.Type: GrantFiled: June 23, 2016Date of Patent: November 14, 2017Assignee: Ionis Phamaceuticals, Inc.Inventors: Brett P. Monia, Susan M. Freier, Andrew M. Siwkowski, Shuling Guo
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Patent number: 9796974Abstract: One aspect of the present invention relates to double-stranded RNAi (dsRNA) duplex agent capable of inhibiting the expression of a target gene. The dsRNA duplex comprises one or more motifs of three identical modifications on three consecutive nucleotides in one or both strand, particularly at or near the cleavage site of the strand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.Type: GrantFiled: November 16, 2012Date of Patent: October 24, 2017Assignee: ALNYLAM PHARMACEUTICALS, INC.Inventors: Kallanthottathil G. Rajeev, Tracy Zimmermann, Muthiah Manoharan, Martin Maier, Satyanarayana Kuchimanchi, Klaus Charisse
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Patent number: 9790494Abstract: The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.Type: GrantFiled: April 28, 2015Date of Patent: October 17, 2017Assignee: Translate Bio MA, Inc.Inventors: Eugen Uhlmann, Romesh Subramanian, Arthur M. Krieg
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Patent number: 9777272Abstract: The present invention relates to a method for treating a Leber congenital amaurosis in a patient harboring the mutation c.2991+1655 A>G in the CEP290 gene, comprising the step of administering to said patient at least one antisense oligonucleotide complementary to nucleic acid sequence that is necessary for preventing splicing of the cryptic exon inserted into the mutant c.2291+1655 A>G CEP290 mRNA.Type: GrantFiled: September 16, 2016Date of Patent: October 3, 2017Assignees: INSERM (Institut National de la Sante et de la Recherche Medicale), CNRS (Centre National de la Recherche Scientifique), GENETHON, UNIVERSITE PARIS DESCARTES, ENSCP—Chimie ParisTech—Ecole Nationale Superieure de Chimie de Paris, Universite d'Evry-Val-d'Essonne, ASSISTANCE PUBLIQUE HOPITAUX DE PARISInventors: Jean-Michel Rozet, Antoine Kichler, Isabelle Perrault, Josseline Kaplan, Xavier Gerard, Daniel Scherman, M. Arnold Munnich
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Patent number: 9771585Abstract: The present invention provides oligonucleotide inhibitors of miR-155 and compositions thereof. The invention further provides methods for treating cancer such as a T cell lymphoma in a subject by administering to the subject an oligonucleotide inhibitor of miR-155. The invention also provides methods for reducing or inhibiting the proliferation of malignant T cells by administering an oligonucleotide inhibitor of miR-155.Type: GrantFiled: June 3, 2016Date of Patent: September 26, 2017Assignee: MIRAGEN THERAPEUTICS, INC.Inventors: David Rodman, Anita Seto, Christina Dalby, Aimee Jackson, Xuan Beatty
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Patent number: 9745369Abstract: The present invention relates to compounds for use in modulating the toll-like receptor 4 (TLR4) signaling pathway, as well as to a pharmaceutical composition comprising said compounds.Type: GrantFiled: May 22, 2013Date of Patent: August 29, 2017Assignee: Rheinisch-Westfalische TechnischeInventors: Antje Ostareck-Lederer, Dirk Ostareck, Gernot Marx, Anke Liepelt, Jana Kloos
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Patent number: 9732340Abstract: The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.Type: GrantFiled: April 28, 2015Date of Patent: August 15, 2017Assignee: Translate Bio MA, Inc.Inventors: Eugen Uhlmann, Markus Weber, Romesh Subramanian, Thomas Dino Rockel, Arthur M. Krieg
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Patent number: 9732348Abstract: The invention relates to a DNA aptamer that can inhibit the enzymatic activity of tyrosinase for the conversion of tyrosine into L-DOPA and dopaquinone, and to the dermatological and cosmetic uses thereof.Type: GrantFiled: December 20, 2013Date of Patent: August 15, 2017Assignees: L V M H Recherché, Institut National de la Sante et de la Recherche Medicale (INSERM)Inventors: Jean Hubert Cauchard, Robin Kurfurst, Sylvianne Schnebert, Eric Dausse, Jean-Jacques Toulme
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Patent number: 9670492Abstract: Disclosed herein are antisense compounds and methods for decreasing PKK mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate PKK-associated diseases, disorders, and conditions.Type: GrantFiled: August 28, 2014Date of Patent: June 6, 2017Assignee: Ionis Pharmaceuticals, Inc.Inventors: Susan M. Freier, Huynh-Hoa Bui
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Patent number: 9650638Abstract: This disclosure relates to DNA aptamer specifically binding to periostin, which is cancer-related protein, a composition for inhibiting cancer and/or cancer metastasis and/or a composition for diagnosis of cancer and/or cancer metastasis, comprising the same as an active ingredient, wherein the aptamer has different binding mechanism from the existing antibodies, and thus, may inhibit and diagnose cancer/cancer metastasis more effectively.Type: GrantFiled: November 12, 2012Date of Patent: May 16, 2017Assignees: UNIST (ULSAN NATIONAL INSTITUTE OF SCIENCE AND TECHNOLOGY), POSTECH ACADEMY-INDUSTRY FOUNDATIONInventors: Pann-Ghill Suh, Ii Shin Kim, Yu Jin Lee, Youn Dong Kim, Young Chan Chae, Jong Hun Im, Sung Ho Ryu
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Patent number: 9642873Abstract: The present invention provides compositions and methods for using combinations of TGF?1 and Cox-2 inhibitors and TGF?1 and Hoxb13 inhibitors for the treatment of various medical conditions, including skin scaring due to trauma wounds and surgery, corneal and retina scaring due to injury and surgery, internal organ scaring due to injury and surgery, heart tissue scaring due to heart attack and surgery, and lung, liver, and kidney fibrosis due to inflammation and injury. One example is to use siRNA inhibitors to silence TGF?1 and Cox-2 at the same time, resulting in significant less scar formation.Type: GrantFiled: May 4, 2011Date of Patent: May 9, 2017Assignee: Sirnaomics, Inc.Inventors: Patrick Y. Lu, Vera Simonenko, David Evans, John J. Xu
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Patent number: 9629867Abstract: Chemically modified small interfering RNAs (siRNAs) that include both phosphorodithioate modifications (PS2-RNA) and 2?-O-methyl modifications (MePS2) provide improved RNA silencing. Specific chemically modified siRNA that show enhanced silencing of RNAs involved in resistance to chemotherapeutic agents are provided.Type: GrantFiled: March 11, 2015Date of Patent: April 25, 2017Assignee: AM Biotechnologies, Inc.Inventor: Xianbin Yang
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Patent number: 9624508Abstract: The present invention discloses gene targets, constructs and methods for the genetic control of plant disease caused by nematodes of the genus Meloidogyne (root knot nematodes). The present invention relates to achieving a plant protective effect through the identification of target coding sequences and the use of recombinant DNA technologies for post-transcriptionally repressing or inhibiting expression of the target coding sequences in the cells of plant-parasitic nematodes. The disclosed gene targets show significant conservation at the nucleotide level between orthologs from different Meloidogyne species, facilitating genus-wide targeting by RNA interference.Type: GrantFiled: October 1, 2014Date of Patent: April 18, 2017Assignee: Monsanto Technology LLCInventors: John D. Bradley, Brandi J. Chiapelli, Bingli Gao, James P. McCarter, Michelle L. Gasper, Deryck Jeremy Williams
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Patent number: 9617535Abstract: Compositions and methods of treatments of cells are provided for altering the phenotype of a cell by administering an oligonucleotide complex to the cell, the complex having two strands and chemical modifications.Type: GrantFiled: August 13, 2014Date of Patent: April 11, 2017Assignee: THE GENERAL HOSPITAL CORPORATIONInventors: David R. Tabatadze, Paul C. Zamecnik, Malay K. Raychowdhury, Horacio F. Cantiello
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Patent number: 9588119Abstract: Disclosed are increased expression of ERp57, ERp57-STAT3 complex, and ERp57-STAT3-Mcl-1 in laryngeal cancer, especially in radioresistant laryngeal cancer and their regulations on radioresistance of laryngeal cancer. As such, the efficacy of radiotherapy can be enhanced by diagnosing prognosis in laryngeal cancer and radioresistance of laryngeal cancer. Furthermore, provided are a method of screening a therapeutic agent for laryngeal cancer including selecting a candidate drug that inhibits the expression of ERp57 or inactivates ERp57, and a therapeutic method for inhibiting or treating laryngeal cancer or radioresistant laryngeal cancer, thereby being useful in the treatment of laryngeal cancer.Type: GrantFiled: June 23, 2015Date of Patent: March 7, 2017Assignee: KOREA INSTITUTE OF RADIOLOGICAL & MEDICAL SCIENCESInventors: Jae-Sung Kim, Sang-Gu Hwang, Young-Hoon Han
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Patent number: 9567589Abstract: The present invention provides an aptamer binding to NGF and capable of forming a potential secondary structure represented by the formula (I): wherein N is one nucleotide selected from the group consisting of A, G, C, U and T, N11-N13, N21-N23, N32-N38 and N42-N48 are the same or different and each is a bond or 1 or 2 nucleotides selected from the group consisting of A, G, C, U and T, N14, N24, N31, N41, N39 and N49 are the same or different and each is one nucleotide selected from the group consisting of A, G, C, U and T, N14 and N24, N31 and N41, and N39 and N49 each form a Watson-Crick base pair, N11-N12-N13-N14 and N21-N22-N23-N24 are nucleotide sequences capable of forming a stem structure in combination, and N31-N32-N33-N34-N35-N36-N37-N38-N39 and N41-N42-N43-N44-N45-N46-N47-N48-N49 are nucleotide sequences capable of forming a stem structure in combination.Type: GrantFiled: September 28, 2012Date of Patent: February 14, 2017Assignees: RIBOMIC INC., FUJIMOTO PHARMACEUTICAL CORPORATIONInventors: Ling Jin, Hisanao Hiramatsu
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Patent number: 9567580Abstract: Embodiments of the inventions relate to modulating NFAT activity, modulating store-operated Ca2+ entry into a cell and treating and/or preventing hyperactivity or inappropriate immune response by inhibiting the expression or activities of septin 4 (SEPT 4) and septin 5 (SEPT 5) proteins involved in the calcineurin/NFAT axis and T-cell activation.Type: GrantFiled: October 10, 2011Date of Patent: February 14, 2017Inventors: Anjana Rao, Patrick Hogan, Sonia Sharma
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Patent number: 9562235Abstract: A method of increasing tolerance of a plant to an abiotic stress or increasing biomass, vigor or yield of a plant is disclosed. The method comprising upregulating within the plant an exogenous polynucleotide of a microRNA or a precursor thereof, wherein the microRNA is selected from the group consisting of miR-156, miR-169, miR-164, miR-159, miR-167, miR-529, miR-168, ppt-miR395, sof-miR408a, ath-miR408, miR-1039, miR-1091, miR-1118, miR-1134 and miR-1129, thereby increasing the tolerance of the plant to the abiotic stress or increasing the biomass, vigor or yield of the plant.Type: GrantFiled: December 6, 2010Date of Patent: February 7, 2017Assignee: A.B. Seeds Ltd.Inventor: Rudy Maor
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Patent number: 9534220Abstract: A method and antisense compound for inhibiting the growth of pathogenic bacterial cells are disclosed. The compound contains no more than 12 nucleotide bases and has a targeting nucleic acid sequence of no fewer than 10 bases in length that is complementary to a target sequence containing or within 10 bases, in a downstream direction, of the translational start codon of a bacterial mRNA that encodes a bacterial protein essential for bacterial replication. The compound binds to a target mRNA with a Tm of between 50° to 60° C. The relatively short antisense compounds are substantially more active than conventional antisense compounds having a targeting base sequence of 15 or more bases.Type: GrantFiled: November 19, 2012Date of Patent: January 3, 2017Assignee: Sarepta Therapeutics, Inc.Inventors: Bruce L. Geller, Jesse D. Deere, Patrick L. Iversen
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Patent number: 9534012Abstract: An affinity substrate for the selective binding of a protein of blood plasma includes a solid substrate material on which are immobilized deoxyribonucleic aptamers specifically binding with the plasma protein.Type: GrantFiled: February 19, 2010Date of Patent: January 3, 2017Assignee: LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIESInventors: Gerald Perret, Michel Nogre
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Patent number: 9518257Abstract: A method for efficiently producing homozygous organisms from a heterozygous non-human starting organism, comprising providing of a heterozygous starting organism; allowing the starting organism to produce haploid cells; creating homozygous organisms from the haploid cells thus obtained; and selecting the organisms having the desired set of chromosomes; wherein during production of the haploid cells no recombination occurs in order to obtain a limited number of genetically different haploid cells. Recombination can also be prevented or suppressed.Type: GrantFiled: February 11, 2014Date of Patent: December 13, 2016Assignee: RIJK ZWAAN ZAADTEELT EN ZAADHANDEL B.V.Inventors: Robert Helene Ghislain Dirks, Cornelis Maria Petrus Van Dun, Kornelius Reinink, Jacobus Petrus Cornelis De Wit
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Patent number: 9518263Abstract: The invention provides compositions and methods for signal activated RNA interference (saRNAi), preferably in vivo. The invention provides polynucleotides that switches between an inactive form and an active form upon covalent or non-covalent interaction with one or more specific chemical signals, such as disease-specific mRNA, miRNA, or other cellular RNA products with sequences that characterize diseased states of the cell. The interaction between the subject polynucleotides and the signals is preferably mediated by hybridization, which exposes, facilitates the formation, and/or allows the formation of a substrate that can be processed by proteins of the RNAi pathway (such as Dicer). The input and output of multiple different polynucleotides of the invention can form an in vivo signaling network. In addition, the multiple input signals can be integrated to modulate the activity of the subject polynucleotides.Type: GrantFiled: April 20, 2015Date of Patent: December 13, 2016Assignee: California Institute of TechnologyInventors: Si-ping Han, Robert D. Barish, William A. Goddard, III
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Patent number: 9493771Abstract: Short interfering ribonucleic acid (siRNA) for oral administration, said siRNA comprising two separate RNA strands that are complementary to each other over at least 15 nucleotides, wherein each strand is 49 nucleotides or less, and wherein at least one of which strands contains at least one chemical modification.Type: GrantFiled: February 11, 2014Date of Patent: November 15, 2016Assignee: NOVARTIS AGInventors: Francois Jean-Charles Natt, Eric Billy, Juerg Hunziker, Christian Rene Schnell
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Patent number: RE46873Abstract: The present invention provides small interfering RNA (siRNA) molecules, compositions containing them, and methods of using them for improvement of skin scarless wound healing and other skin conditions, such as psoriasis and lupus-caused cutaneous lesions. The invention includes siRNA molecules and compositions containing them that inhibit the expression of one or more genes that promote pathological or undesired processes in wound healing and methods of using them.Type: GrantFiled: May 26, 2016Date of Patent: May 29, 2018Assignee: Sirnaomics, Inc.Inventors: Patrick Y. Lu, Ling Li, Vera Simonenko