Source: http://www.google.com/patents/US7829693?ie=ISO-8859-1
Timestamp: 2014-03-15 09:05:55
Document Index: 793191701

Matched Legal Cases: ['Application No. 02710786', 'Application No. 02710786', 'Application No. 02710786', 'application No. 02710786', 'application No. 02710786', 'application No. 02710786']

Patent US7829693 - Compositions and methods for inhibiting expression of a target gene - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsThe present invention relates to a double-stranded ribonucleic acid (dsRNA) having a nucleotide sequence which is substantially identical to at least a part of a target gene and which is no more than 49, preferably less than 25, nucleotides in length, and which comprises a complementary (antisense) RNA...http://www.google.com/patents/US7829693?utm_source=gb-gplus-sharePatent US7829693 - Compositions and methods for inhibiting expression of a target geneAdvanced Patent SearchPublication numberUS7829693 B2Publication typeGrantApplication numberUS 10/384,339Publication dateNov 9, 2010Filing dateMar 7, 2003Priority dateNov 24, 1999Also published asCA2432350A1, CN1630724A, DE10160151A1, DE50206993D1, EP1352061A2, EP1352061B1, EP1352061B9, EP1438405A1, EP2264173A2, US8546143, US20040175703, US20110111493, WO2002055693A2, WO2002055693A3Publication number10384339, 384339, US 7829693 B2, US 7829693B2, US-B2-7829693, US7829693 B2, US7829693B2InventorsRoland Kreutzer, Stefan Limmer, Sylvia Limmer, Philipp HadwigerOriginal AssigneeAlnylam Pharmaceuticals, Inc.Export CitationBiBTeX, EndNote, RefManPatent Citations (99), Non-Patent Citations (160), Referenced by (2), Classifications (43), Legal Events (3) External Links: USPTO, USPTO Assignment, EspacenetCompositions and methods for inhibiting expression of a target geneUS 7829693 B2Abstract The present invention relates to a double-stranded ribonucleic acid (dsRNA) having a nucleotide sequence which is substantially identical to at least a part of a target gene and which is no more than 49, preferably less than 25, nucleotides in length, and which comprises a complementary (antisense) RNA strand having a 1 to 4 nucleotide overhang at the 3′-end and a blunt 5′-end. The invention further relates to a pharmaceutical composition comprising the dsRNA and a pharmaceutically acceptable carrier. The pharmaceutical compositions are useful for inhibiting the expression of a target gene, as well as for treating diseases caused by expression of the target gene, at low dosages (i.e., less than 5 milligrams, preferably less than 25 micrograms, per kg body weight per day). The invention also relates to methods for inhibiting the expression of a target gene, as well as methods for treating diseases caused by the expression of the gene.
Patent CitationsCited PatentFiling datePublication dateApplicantTitleUS4309492Oct 7, 1980Jan 5, 1982Saft-Societe Des Accumulateurs Fixes Et De TractionElectric storage cell with a vibration-proof comb-type connectionUS5112734May 26, 1989May 12, 1992Gene-Trak SystemsTarget-dependent synthesis of an artificial gene for the synthesis of a replicatable rnaUS5225347Mar 19, 1990Jul 6, 1993Innovir Laboratories, Inc.Therapeutic ribozyme compositions and expression vectorsUS5246921Aug 5, 1992Sep 21, 1993The Wistar Institute Of Anatomy And BiologyMethod for treating leukemiasUS5340318Dec 9, 1992Aug 23, 1994Elastomeric Technologies, Inc.Conductive elastomeric element electronic connector assemblyUS5472802Oct 25, 1993Dec 5, 1995Ovonic Battery Company, Inc.Sealed hydride batteries, including a new lid-terminal seal and electrode tab collecting combUS5496698Dec 7, 1992Mar 5, 1996Ribozyme Pharmaceuticals, Inc.Method of isolating ribozyme targetsUS5525468Aug 1, 1994Jun 11, 1996Ribozyme Pharmaceuticals, Inc.Assay for Ribozyme target siteUS5574142Dec 15, 1992Nov 12, 1996Microprobe CorporationPeptide linkers for improved oligonucleotide deliveryUS5616459Aug 18, 1992Apr 1, 1997The Public Health Research Institute Of The City Of New York, Inc.Selection of ribozymes that efficiently cleave target RNAUS5635385Sep 15, 1993Jun 3, 1997Temple University-Of The Commonwealth System Of Higher EducationMulti-unit ribozyme inhibition of oncogene gene expressionUS5639655Apr 25, 1994Jun 17, 1997Ribozyme Pharmaceuticals, Inc.PML-RARA targeted ribozymesUS5712257May 23, 1995Jan 27, 1998Hem Research, Inc.Topically active compositions of mismatched dsRNAsUS5811275Jun 5, 1995Sep 22, 1998The Regents Of The University Of CaliforniaHIV-specific ribozymesUS5811300Sep 23, 1994Sep 22, 1998Ribozyme Pharmaceuticals, Inc.TNF-α ribozymesUS5814500Oct 31, 1996Sep 29, 1998The Johns Hopkins University School Of MedicineDelivery construct for antisense nucleic acids and methods of useUS5824519Nov 8, 1995Oct 20, 1998Medical University Of South CarolinaTissue-specific and target RNA-specific ribozymesUS5837510Jun 6, 1995Nov 17, 1998Goldsmith; Mark A.Methods and polynucleotide constructs for treating host cells for infection or hyperproliferative disordersUS5854067Jan 19, 1996Dec 29, 1998Betagene, Inc.Hexokinase inhibitorsUS5864028Jun 5, 1995Jan 26, 1999Gene Shears Pty. LimitedDegradation resistant mRNA derivatives linked to TNF-α ribozymesUS5866701Jun 17, 1993Feb 2, 1999Biotechnology Research And Development CorporationHIV targeted hairpin ribozymesUS5891717Jan 19, 1996Apr 6, 1999Betagene, Inc.Methods and compositions for inhibiting hexokinaseUS5898031Jun 6, 1996Apr 27, 1999Isis Pharmaceuticals, Inc.Oligoribonucleotides for cleaving RNAUS5908779Dec 1, 1993Jun 1, 1999University Of ConnecticutTargeted RNA degradation using nuclear antisense RNAUS5939262Jun 24, 1997Aug 17, 1999Ambion, Inc.Ribonuclease resistant RNA preparation and utilizationUS5968737Nov 12, 1996Oct 19, 1999The Board Of Regents, The University Of Texas SystemMethod of identifying inhibitors of glutathione S-transferase (GST) gene expressionUS5985620Nov 3, 1993Nov 16, 1999Gene Shears Pty. LimitedTNF-α RibozymesUS6057156Dec 4, 1997May 2, 2000Robozyme Pharmaceuticals, Inc.Enzymatic nucleic acid treatment of diseases or conditions related to levels of epidermal growth factor receptorsUS6071890Oct 19, 1995Jun 6, 2000Genzyme CorporationOrgan-specific targeting of cationic amphiphile/DNA complexes for gene therapyUS6077705May 14, 1997Jun 20, 2000Thomas Jefferson UniversityRibozyme-mediated gene replacementUS6080851Nov 16, 1993Jun 27, 2000American Home Products CorporationRibozymes with linked anchor sequencesUS6087164Oct 1, 1998Jul 11, 2000Yissum Research Development Company Of The Hebrew University Of JerusalemMethods and compositions for inducing tumor-specific cytotoxicityUS6087172Oct 31, 1997Jul 11, 2000Hisamitsu Pharmaceutical Co., Inc.Ribozymes targeted to human IL-15 mRNAUS6099823Jul 30, 1998Aug 8, 2000Millennium Pharmaceuticals, Inc.Compositions and methods for the treatment and diagnosis of cardiovascular diseaseUS6100087Mar 11, 1998Aug 8, 2000City Of HopeRibozymes targeted to human CCR5 mRNAUS6100444Feb 11, 1997Aug 8, 2000University Of Rochester Medical CenterProstate specific regulatory nucleic acid sequences and transgenic non-human animals expressing prostate specific antigenUS6107094Jun 6, 1997Aug 22, 2000Isis Pharmaceuticals, Inc.Oligoribonucleotides and ribonucleases for cleaving RNAUS6183959Jul 8, 1998Feb 6, 2001Ribozyme Pharmaceuticals, Inc.Method for target site selection and discoveryUS6187585 *May 7, 1999Feb 13, 2001Isis Pharmaceuticals, Inc.Oligonucleotide inhibition of epidermal growth factor receptor expressionUS6224868 *May 21, 1997May 1, 2001Thomas Jefferson UniversityReagent and processes for targeting mutant epidermal growth factor receptorsUS6225291Apr 21, 1998May 1, 2001University Of FloridaRod opsin mRNA-specific ribozyme compositions and methods for the treatment of retinal diseasesUS6245560May 18, 1994Jun 12, 2001The United States Of America As Represented By The Department Of Health And Human ServicesVector with multiple target response elements affecting gene expressionUS6245748Sep 25, 1998Jun 12, 2001Georgetown UniversityInhibition of an FGF-binding protein using ribozymesUS6255071Mar 19, 1997Jul 3, 2001Cold Spring Harbor LaboratoryMammalian viral vectors and their usesUS6346398Jan 11, 1996Feb 12, 2002Ribozyme Pharmaceuticals, Inc.Method and reagent for the treatment of diseases or conditions related to levels of vascular endothelial growth factor receptorUS6355415Sep 29, 1997Mar 12, 2002Ohio UniversityCompositions and methods for the use of ribozymes to determine gene functionUS6410176Jul 31, 2000Jun 25, 2002Plug Power, Inc.Voltage monitoring system for a fuel cell stackUS6423489May 30, 1995Jul 23, 2002Isis Pharmaceuticals, Inc.Compositions and methods for treatment of Hepatitis C virus-associated diseasesUS6482803Sep 1, 1995Nov 19, 2002Board Of Regents, The University Of Texas SystemModification of mutated P53 gene in tumors by retroviral delivery of ribozyme AUS6486299Sep 28, 1998Nov 26, 2002Curagen CorporationGenes and proteins predictive and therapeutic for stroke, hypertension, diabetes and obesityUS6506559Dec 18, 1998Jan 14, 2003Carnegie Institute Of WashingtonGenetic inhibition by double-stranded RNAUS6573046Oct 28, 1999Jun 3, 2003Valigen (Us), IncEukaryotic use of improved chimeric mutational vectorsUS20020086356Mar 30, 2001Jul 4, 2002Whitehead Institute For Biomedical ResearchRNA sequence-specific mediators of RNA interferenceUS20020114784Jan 4, 2002Aug 22, 2002Medical College Of Georgia Research Institute, Inc.Composition and method for in vivo and in vitro attenuation of gene expression using double stranded RNAUS20020123034Oct 12, 2001Sep 5, 2002Dan CanaaniGenetic screening methodsUS20020132346Mar 8, 2002Sep 19, 2002Jose CibelliUse of RNA interference for the creation of lineage specific ES and other undifferentiated cells and production of differentiated cells in vitro by co-cultureUS20020162126May 24, 2001Oct 31, 2002David BeachMethods and compositions for RNA interferenceUS20020173478Nov 14, 2001Nov 21, 2002The Trustees Of The University Of PennsylvaniaPost-transcriptional gene silencing by RNAi in mammalian cellsUS20030027783May 17, 2002Feb 6, 2003Magdalena Zernicka-GoetzInhibiting gene expression with dsRNAUS20030108923Sep 26, 2002Jun 12, 2003Whitehead Institute For Biomedical ResearchRNA sequence-specific mediators of RNA interferenceUS20030125281May 28, 2002Jul 3, 2003David LewisCompositions and processes using siRNA, amphipathic compounds and polycationsUS20030143732Aug 20, 2002Jul 31, 2003Kathy FosnaughRNA interference mediated inhibition of adenosine A1 receptor (ADORA1) gene expression using short interfering RNAUS20030148341Nov 5, 2002Aug 7, 2003Sin Wun CheyGene amplification and overexpression in cancerUS20030157030Nov 4, 2002Aug 21, 2003Insert Therapeutics, Inc.methods and compositions for therapeutic use of rna interferenceUS20030176671Feb 7, 2002Sep 18, 2003The Burnham InstituteApoptosis modulator BCL-B and methods for making and using sameUS20030180756Nov 21, 2002Sep 25, 2003Yang ShiCompositions and methods for suppressing eukaryotic gene expressionUS20030190635Jul 25, 2002Oct 9, 2003Mcswiggen James A.RNA interference mediated treatment of Alzheimer's disease using short interfering RNAUS20030198627Aug 23, 2002Oct 23, 2003Gert-Jan ArtssiRNA knockout assay method and constructsCA2334951A1May 21, 1999Dec 23, 1999Xcellsis GmbhVoltage measuring deviceDE10100586C1Jan 9, 2001Apr 11, 2002Ribopharma AgInhibiting gene expression in cells, useful for e.g. treating tumors, by introducing double-stranded complementary oligoRNA having unpaired terminal basesDE10100587C1Jan 9, 2001Nov 21, 2002Ribopharma AgInhibiting expression of target genes, e.g. oncogenes, in cells, by introduction of complementary double-stranded oligoribonucleotide, after treating the cell with interferonDE10100588A1Jan 9, 2001Jul 18, 2002Ribopharma AgInhibiting expression of target genes, useful e.g. for treating tumors, by introducing into cells two double-stranded RNAs that are complementary to the targetDE10155280A1 Title not availableDE10158411A1 Title not availableDE10163098A1Dec 20, 2001Apr 30, 2003Ribopharma AgMethod for inhibiting viral replication, useful particularly for treating hepatitis C infection, by altering the 3'-untranslated region of the virusDE10230966A1Jul 10, 2002Jan 22, 2004Ina-Schaeffler KgElektromagnetisches Hydraulikventil, insbesondere Proportionalventil zur Steuerung einer Vorrichtung zur Drehwinkelverstellung einer Nockenwelle gegen�ber einer Kurbelwelle einer BrennkraftmaschineDE10230997A1Jul 9, 2002Jul 17, 2003Ribopharma AgMedikament zur Erh�hung der Wirksamkeit eines Rezeptor-vermittelt Apoptose in Tumorzellen ausl�senden ArzneimittelsDE19618797A1May 10, 1996Nov 13, 1997Bertling Wolf Prof DrVehikel zum Transport molekularer SubstanzDE19631919A1Aug 7, 1996Feb 12, 1998Deutsches KrebsforschAnti-Sinn-RNA mit Sekund�rstrukturDE19956568A1Nov 24, 1999Aug 17, 2000Roland KreutzerVerfahren und Medikament zur Hemmung der Expression eines vorgegebenen GensDE20023125U1Jan 29, 2000May 15, 2003Ribopharma AgMedikament zur Hemmung der Expression eines vorgegebenen GensEP1001666A2Nov 9, 1999May 17, 2000Ballard Power Systems Inc.Electrical contacting device for an electrochemical fuel cellEP1107340A2Oct 18, 2000Jun 13, 2001General Motors CorporationCorrosion resistant contact element for a PEM fuel cellEP1214945A2Jan 29, 2000Jun 19, 2002Ribopharma AGMethod and medicament for inhibiting the expression of a defined geneEP1263250A1Jun 1, 2001Dec 4, 2002Mobilkom Austria Aktiengesellschaft &amp; Co KGMethod to determine the location of a mobile station in a mobile radio systemWO1992019732A1Apr 24, 1992Oct 26, 1992Genset SaClosed sense and antisense oligonucleotides and uses thereofWO1994001550A1Jul 2, 1993Jan 20, 1994Sudhir AgrawalSelf-stabilized oligonucleotides as therapeutic agentsWO1998005770A2Aug 5, 1997Feb 12, 1998Deutches KrebsforschungszentruAntisense rna with a secondary structureWO1998053083A1May 20, 1998Nov 26, 1998Donald GriersonGene silencingWO1999015682A2Sep 22, 1998Apr 1, 1999David Charles BaulcombeGene silencing materials and methodsWO1999032619A1Dec 21, 1998Jul 1, 1999Carnegie Inst Of WashingtonGenetic inhibition by double-stranded rnaWO1999049029A1Mar 19, 1999Sep 30, 1999Gene Australia Limited AgControl of gene expressionWO1999053050A1Apr 7, 1999Oct 21, 1999Commw Scient Ind Res OrgMethods and means for obtaining modified phenotypesWO1999061631A1May 25, 1999Dec 2, 1999Jeng Shong ChenDsrna-mediated regulation of gene expression in plantsWO2000001846A2Jul 2, 1999Jan 13, 2000Thierry BogaertCharacterisation of gene function using double stranded rna inhibitionWO2000044895A1Jan 29, 2000Aug 3, 2000Roland KreutzerMethod and medicament for inhibiting the expression of a defined geneWO2000044914A1Jan 28, 2000Aug 3, 2000Med College Georgia Res InstComposition and method for in vivo and in vitro attenuation of gene expression using double stranded rnaWO2000063364A2Apr 19, 2000Oct 26, 2000American Home ProdMethods and compositions for inhibiting the function of polynucleotide sequencesWO2002044321A2 *Nov 29, 2001Jun 6, 2002Max Planck GesellschaftRna interference mediating small rna molecules* Cited by examinerNon-Patent CitationsReference1"Introduction of DNA into Mammalian Cells," Current Protocols in Molecular Biology, Supplement 48, Edited by Frederick M. Ausubel et al., John Wiley & Sons, Inc., pp. 9.4.7-9.4.8 (1999).2Agrawal et al., "Self-Stabilized Oligonucleotides as Novel Antisense Agents," Delivery Strategies for Antisense Oligonucleotide Therapeutics, Edited by Saghir Akhtar, CRC Press, pp. 105-121 (1995).3 *Agrawal, S. et al., Molecular Med. Today, vol. 6, pp. 72-81 (2002).4Alfonzo et al., "The mechanism of U insertion/deletion RNA editing in kinetoplastid mitochondria" Nucleic Acids Res. 25:3751-3759 (1997).5Ambros, V., (2001), "Dicing Up RNAs", Science, 293:811-813.6Anderson et al., "Human gene therapy" Nature 392:25-30 (1998).7Annex to Decision on Reject of the Opposition, Opposition Application No. 02710786.1 for European Patent No. EP1352061, Aug. 25, 2009, 20 Pages (English translation of claims included within document).8Asanuma et al., "Photoregulation of the Formation and Dissociation of a DNA Duplex by Using the cis-trans Isomerization of Azobenzene" Angew. Chem. Int. Ed. 38:2393-2395 (1999).9Azhayeva et al., "Inhibitory properties of double helix forming circular oligonucleotides" Nucleic Acids Res. 25:4954-4961 (1997).10Bahramian et al., "Transcriptional and Posttranscriptional Silencing of Rodent alpha1(I) Collagen by a Homologous Transcriptionally Self-Silenced Transgene" Mol. Cell. Biol. 19:274-283 (1999).11Bahramian et al., "Transcriptional and Posttranscriptional Silencing of Rodent α1(I) Collagen by a Homologous Transcriptionally Self-Silenced Transgene" Mol. Cell. Biol. 19:274-283 (1999).12Barawkar et al., "Synthesis, biophysical properties, and nuclease resistance properties of mixed backbone oligodeoxynucleotides containing cationic internucleoside guanidinium linkages: Deoxynucleic guanidine/DNA chimeras" Proc. Natl. Acad. Sci. USA 95:11047-11052 (1998).13Bass, B.L., (2000), "Double-Stranded RNA as a Template for Gene Silencing", Cell, 101:235-238.14Bhan et al., "2',5'-Linked oligo-3'-deoxyribonucleoside phosphorothioate chimeras: thermal stability and antisense inhibition of gene expression" Nucleic Acids Res. 25:3310-3317 (1997).15Bhan et al., "2′,5′-Linked oligo-3′-deoxyribonucleoside phosphorothioate chimeras: thermal stability and antisense inhibition of gene expression" Nucleic Acids Res. 25:3310-3317 (1997).16Billy et al., "Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines" Proc. Natl. Acad. Sci. USA 98:14428-14433 (2001).17Borecky et al., "Therapeutic use of double-stranded RNAs in man" Tex. Rep. Biol. Med. 41:575-581 (1981-1982) (Abstract only).18Boutla et al., "Short 5′-Phosphorylated double-stranded RNAs induce RNA interference in Drosophila" Current Biol. 11:1776-80, 2001.19Braich et al., "Regiospecific Solid-Phase Synthesis of Branched Oligonucleotides. Effect of Vicinal 2',5'- (or 2',3'-) and 3',5'-Phosphodiester Linkages on the Formation of Hairpin DNA" Bioconjug. Chem. 8:370-377 (1997).20Braich et al., "Regiospecific Solid-Phase Synthesis of Branched Oligonucleotides. Effect of Vicinal 2′,5′- (or 2′,3′-) and 3′,5′-Phosphodiester Linkages on the Formation of Hairpin DNA" Bioconjug. Chem. 8:370-377 (1997).21 *Branch, A.D., Trends in Biochem. Sci., vol. 23, pp. 45-50 (1998).22Bumcrot et al., "RNAi Therapeutics: a potential new class of pharmaceutical drugs" Nature Chem. Biol. 2:711-719, 2006.23Caplen, N.J. et al., (2001), "Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems", Proc. Natl. Acad. Sci. USA, 98(17):9742-9747.24Caplen, N.J., (2002), "A new approach to the inhibition of gene expression", TRENDS in Biotechnology, 20(2):49-51.25Castelli et al., "The 2-5A system in viral infection and apoptosis" Biomed. Pharmacother. 52:386-390 (1998).26 *Chirila, T.V. et al., Biomaterials, vol. 23, pp. 321-342 (2002).27Cobaleda, C. et al., (2000), "In vivo inhibition by a site-specific catalytic RNA subunit of Rnase P designed against the BCR-ABL oncogenic products: a novel approach for cancer treatment", Blood, 95(3):731-737.28Communication from the European Patent Office including Response to Patentee's Submission of May 21, 2010, filed by SIRNA Therapeutics on Sep. 7, 2010, in opposition to European Patent No. 1352061, 15 Pages.29 *Crooke, S.T., Antisense Research & Application, Chapter 1, pp. 1-50, Ed. by S. Crooke, Publ. by Springer-Verlag (1998).30Czauderna et al., "Structural variations and stabilizing modifications of synthetic siRNAs in mammalian cells," Nucleic Acids Res., 31(1):1-12 (2003).31Decision on Rejection of the Opposition, Opposition Application No. 02710786.1 for European Patent No. EP1352061, Aug. 25, 2009, 40 Pages.32Doench, J.G. et al., (2003), "siRNAs can function as miRNAs", Genes & Development, 17:438-442.33Dolinnaya et al., "Oligonucleotide circularization by template-directed chemical ligation" Nucleic Acids Res., 21:5403-5407 (1993).34Donz�, O. et al., (2002), "RNA interference in mammalian cells using siRNAs synthesized with T7 RNA Polymerase", Nucleic Acids Research, 30(10):e46(4pages).35Downward, J. et al., (1990), "Identification of a nucleotide exchange-promoting activity for p21ras", Proc. Natl. Acad. Sci. USA, 87:5998-6002.36 *Elbashir et al (Nature, vol. 411, pp. 494-498 (2001).37Elbashir, S.M. et al., (2001), "Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells", Nature, 411:494-498.38Elbashir, S.M. et al., (2001), "Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate", The EMBO Journal, 20(23):6877-6888.39Elbashir, S.M. et al., (2001), "RNA interference is mediated by 21- and 22-nucleotide RNAs", Genes & Development, 15:188-200.40English Abstract of DE 101 00 587 C1.41Expert-Bezan�on et al., "Precise localization of several covalent RNA-RNA cross-link in Escherichia coli 16S RNA" Eur. J. Biochem. 136:267-274 (1983).42Fire et al., "Production of antisense RNA leads to effective and specific inhibition of gene expression in C. elegans muscle" Development 113:503-514 (1991).43Fire, A. et al., (1998), "Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans", Nature, 391:806-811.44Fire, A., (1999), "RNA-triggered gene silencing", TIG, 15(9):358-363.45Gao et al., "Circularization of oligonucleotides by disulfide bridge formation" Nucleic Acids Res., 23:2025-2029 (1995).46Gautschi, O. et al., (2001), "Activity of a Novel bcl-2/bcl-xL-Bispecific Antisense Oligonucleotide Against Tumors of Diverse Histologic Origins", Journal of the National Cancer Institute, 93(6):463-471.47Gewirtz et al., "Nucleic Acid Therapeutics: State of the Art and future prospects" Blood 92:712-736, 1998.48Gibbs, J.B. et al., (1988), "Purification of ras GTPase activating protein from bovine brain", Proc. Natl. Acad. Sci. USA, 85:5026-5030.49Grasby et al., "Purine Functional Groups in Essential Residues of the Hairpin Ribozyme Required for Catalytic Cleavage of RNA" Biochemistry 34:4068-4076 (1995).50Griffey et al., "2'-O-Aminopropyl Ribonucleotides: A Zwitterionic Modification That Enhances the Exonuclease Resistance and Biological Activity of Antisense Oligonucleotides" J. Med. Chem. 39:5100-5109 (1996).51Griffey et al., "2′-O-Aminopropyl Ribonucleotides: A Zwitterionic Modification That Enhances the Exonuclease Resistance and Biological Activity of Antisense Oligonucleotides" J. Med. Chem. 39:5100-5109 (1996).52Grounds for Appeal in opposition to European Patent No. EP1352061, filed by SIRNA Therapeutics, filed on Jan. 4, 2010, 39 Pages.53Gryaznov et al., "Template controlled coupling and recombination of oligonucleotide blocks containing thiophosphoryl groups" Nucleic Acids Res. 21:1403-1408 (1993).54Ha et al., "A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation" Genes & Development 10:3041-3050 (1996).55Hamilton et al., "A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants" Science 286:950-952 (1999).56Hammond, S.M. et al., (2000), "An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells", Nature, 404:293-296.57Hanazawa et al., "Use of cDNA subtraction and RNA interference screens in combination reveals genes required for germ-line development in Caenorhabditis elegans" Proc. Natl. Acad. Sci. 97:8686-91, 2001.58Harborth, J. et al., (2001), "Identification of essential genes in cultured mammalian cells using small interfering RNAs", Journal of Cell Science, 114(24):4557-4565.59Harfe et al., "Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning" Genes Dev. 12:2623-2635 (1998).60Hoke et al., "Effects of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex infection" Nucleic Acids Res. 19:5743-5748 (1991).61Holen, T. et al., (2002), "Positional effects of short interfering RNAs targeting the human coagulation trigger Tissue Factor", Nucleic Acids Research, 30(8):1757-1766.62Horn et al., "Chemical synthesis and characterization of branched oligodeoxyribonucleotides (bDNA) for use as signal amplifiers in nucleic acid quantification assays" Nucleic Acids Res. 25:4842-4849 (1997).63Hornung et al., "Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7" Nature medicine 11:263-70, 2005.64Huang et al., "Epidermal growth factor receptor inhibition in cancer therapy: biology, rationale and preliminary clinical results" Investig. New Drugs 17:259-69, 1999.65Hunter, "Genetics: A touch of elegance with RNAi" Curr. Biol. 9:R440-R442 (1999).66Iwase et al., "Gene regulation by decoy approach (I): synthesis and properties of photo-crosslinked oligonucleotides" Nucleic Acids Symp. Ser. 37:203-204 (1997).67Jacobs et al., "When Two Strands Are Better Than One: The Mediators and Modulators of the Cellular Responses to Double-Stranded RNA" Virology 219:339-349 (1996).68J�schke et al., "Synthesis and Analytical Characterization of RNA-Polyethylene Glycol Conjugates" Nucleosides & Nucleotides 15:1519-1529 (1996).69Jiang and Milner, "Selective silencing of viral gene expression in HPV-positive human cervical carcinoma cells treated with siRNA, a primer of RNA interference" Oncogene 21:6041-6048 (2002).70Judge et al., "Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA" Nature Biotech 23:457-62, 2005.71Kaufman, "Double-stranded RNA-activated protein kinase mediates virus-induced apoptosis: A new role for an old actor" Proc. Natl. Acad. Sci. USA 96:11693-11695 (1999).72Kennerdell et al., "Use of dsRNA-Mediated Genetic Interference to Demonstrate that frizzled and frizzled 2 Act in the Wingless Pathway" Cell 95:1017-1026 (1998).73Kreutzer et al., "Specific inhibition of viral gene expression by double-stranded RNA in vitro" Annual Fall Meeting of the GBH, Abstract for Poster Paper No. 328, p. S169 (1999).74Kumar et al., "Antisense RNA: function and fate of duplex RNA in cells of higher eukaryotes" Microbiol. Mol. Biol. Rev. 62:1415-1434 (1998).75Lee et al., "The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs with Antisense Complementarity to lin-14" Cell 75:843-854 (1993).76Lewis, D.L. et al., (2002), "Efficient delivery of siRNA for inhibition of gene expression in postnatal mice", Nature Genetics, 32:107-108.77Li et al., "Double-stranded RNA injection produces null phenotypes in zebrafish" Dev. Biol. 210:238, Abstract No. 346 (1999).78Lima, W., et al., "Cleavage of Single Strand RNA Adjacent to RNA-DNA Duplex Regions by Escherichia coli RNase H1," The Journal of Biological Chemistry, Oct. 31, 1997, pp. 27513-27516, vol. 272, No. 44.79Lin et al., "Policing rogue genes" Nature 402:128-129 (1999).80Lipardi, C. et al., (2001), "RNAi as Random Degradative PCR: siRNA Primers Convert mRNA into dsRNAs that Are Degraded to Generate New siRNAs", Cell, 107:297-307.81Lipinski et al., "Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings" Adv. Drug Deliv. Rev. 23:3-25 (1997).82Lipson et al., "Psoralen Cross-Linking of Ribosomal RNA" Methods Enzymol. 164:330-341 (1988).83Liu et al., "Detection of a Novel ATP-Dependent Cross-Linking Protein at the 5' Splice-Site UI Small Nuclear RNA Duplex by Methylene Blue-Mediated Photo-Cross-Linking" Mol. Cell. Biol. 18:6910-6920 (1998).84Liu et al., "Detection of a Novel ATP-Dependent Cross-Linking Protein at the 5′ Splice-Site UI Small Nuclear RNA Duplex by Methylene Blue-Mediated Photo-Cross-Linking" Mol. Cell. Biol. 18:6910-6920 (1998).85Lowy, D.R. et al., (1993), "Function and Regulation of RAS", Annu. Rev. Biochem., 62:851-891.86Ma et al., "Design and Synthesis of RNA Miniduplexes via a Synthetic Linker Approach", Biochemistry 32:1751-1758 (1993).87Majumdar et al., "Targeted gene knockout mediated by triple helix forming oligonucleotides" Nat. Genet. 20:212-214 (1998).88Manche, L. et al., (1992), "Interactions between Double-Stranded DNA Regulators and the Protein Kinase DAI", Molecular and Cellular Biology, 12(11):5238-5248.89Marques et al., "Activation of the mammalian immune system by siRNAs" Nature Biotech 11:139-1405, 2005.90Martinez et al., "Synthetic small inhibiting RNAs: Efficient tools to inactivate oncogenic mutations and restore p53 pathways" Proc. Nat. Acad. Sc. 99:14849-14854 (2002).91McCaffrey, A.P. et al., (2002), "RNA interference in adult mice", Nature, 418:38-39.92Micura et al., "Cyclic Oligoribonucleotides (RNA) by Solid-Phase Synthesis" Chem. Eur. J. 5:2077-2082 (1999).93Milhaud et al., "Free and Liposome-Encapsulated Double-Stranded RNAs as Inducers of Interferon, Interleukin-6, and Cellular Toxicity" J. Interferon Res., 11:261-265 (1991).94Minks et al., "Structural Requirements of Double-stranded RNA for the Activation of 2',5'Oligo(A) Polymerase and Protein Kinase of Interferon-treated HeLa Cells" J. Biol. Chem. 254(20):10180-10183 (1979).95Minks et al., "Structural Requirements of Double-stranded RNA for the Activation of 2′,5′Oligo(A) Polymerase and Protein Kinase of Interferon-treated HeLa Cells" J. Biol. Chem. 254(20):10180-10183 (1979).96Minutes of the oral proceedings of the Opposition Division, Opposition Application No. 02710786.1 for European Patent No. EP1352061, Aug. 25, 2009, 11 Pages.97Misquitta et al., "Targeted disruption of gene function in Drosophila by RNA interference (RNA-i): A role for nautilus in embryonic somatic muscle formation" Proc. Natl. Acad. Sci. USA 96:1451-1456 (1999).98Montgomery et al., "RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans" Proc. Natl. Acad. Sci. USA 95:15502-15507 (1998).99Montgomery, M.K. et al., (1998), "Double-stranded RNA as a mediator in sequence-specific genetic silencing and co-suppression", TIG, 14(7):255-258.100Moss et al., "The Cold Shock Domain Protein LIN-28 Controls Developmental Timing in C. elegans and Is Regulated by the lin-4 RNA" Cell 88:637-646 (1997).101Ng�, H. et al., (1998), "Double-stranded RNA induces mRNA degradation in Trypanosoma brucei", Proc. Natl. Acad. Sci., 95:14687-14692.102Nielsen et al., "A novel class of conformationally restricted oligonucleotide analogues: synthesis of 2',3'-bridged monomers and RNA-selective hybridization" Chem. Commun. pp. 825-826 (1997).103Nielsen et al., "A novel class of conformationally restricted oligonucleotide analogues: synthesis of 2′,3′-bridged monomers and RNA-selective hybridization" Chem. Commun. pp. 825-826 (1997).104Nikiforov et al., "Oligodeoxynucleotides containing 4-thiothymidine and 6-thiodeoxyguanosine as affinity labels for the Eco RV restriction endonuclease and modification methylase" Nucleic Acids Res. 20:1209-1214 (1992).105Notice of Appeal in opposition to European Patent No. EP1352061, filed by SIRNA Therapeutics, filed on Oct. 23, 2009, 39 Pages.106Notice of Opposition by SIRNA Therapeutics, Inc. against EP application No. 02710786.1 (Feb. 28, 2007).107Nykanen, "ATP Requirements and small interfering RNA structure in the RNA interference pathway" Cell 107:309-21, 2001.108 *Opalinska, J.B. et al., Nature Reviews, vol. 1, pp. 503-514 (2002).109Paddison, P.J. et al., (2002), "Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells", Genes & Development, 16:948-958.110Park et al., "Specific inhibition of HIV-1 gene expression by double-stranded RNA" Nucleic Acids Res. Suppl. No. 1:219-20, 2001.111Parrish S. et al. Nov. 2000, Functional Anatomy of a dsRNA Trigger: Differential Requirement for the Two Trigger Strands in RNA Interference, Molecular Cell, vol. 6, 1077-87.112Patentees Observations filed in opposition proceedings for EP application No. 02710786.1 (Oct. 15, 2007).113Pegram et al., "Phase II Study of Receptor-Enhanced Chemosensitivity Using Recombinant Humanized Anti-p185HER2/neu Monoclonal Antibody Plus Cisplatin in Patients With HER2/neu-Overexpressing Metastatic Breast Cancer Refractory to Chemotherapy Treatment" J. Clin. Oncol. 16:2659-2671 (1998).114 *Peracchi, A., Rev. Med. Virol., vol. 14, pp. 47-64 (2003).115Petition by Sirna Therapeutics in opposition proceedings for European Patent No. 1352061 (May 14, 2009).116Randall, G. et al., (2003), "Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs", PNAS, 100(1):235-240.117Response to Grounds of Appeal Filed by Opponent in opposition to European Patent No. EP1352061, filed by Alnylam Europe AG on May 21, 2010, 15 Pages.118Reynolds et al., "Rational siRNA Design for RNA Interference" Nature Biotechnology 22:326-330 (2004).119Schlingensiepen et al., Blackwell Science Ltd., vol. 6, 1997, "Antisense�From Technology to Therapy".120Seydoux et al., "Repression of gene expression in the embryonic germ lineage of C. elegans" Nature 382:713-716 (1996).121Sharp et al., "RNAi and double-strand RNA" Genes Dev. 13:139-141 (1999).122Sharp et al., "RNA Interference" Science 287:2432-33, 2000.123Sharp, P.A., (2001), "RNA interference-2001", Genes & Development, 15:485-490.124Sharp, P.A., (2001), "RNA interference�2001", Genes & Development, 15:485-490.125Shi et al., "A CBP/p300 homolog specifies multiple differentiation pathways in Caenorhabditis elegans" Genes Dev. 12:943-955 (1998).126Sijen, T. et al., (2001), "On the Role of RNA Amplification in dsRNA-Triggered Gene Silencing", Cell, 107:465-476.127Skripkin et al., "Psoralen crosslinking between human immunodeficiency virus type 1 RNA and primer tRNA3Lys" Nucleic Acids Res. 24:509-514 (1996).128Sledz et al., "Activation of interferon system by short-interfering RNAs" Nature Cell Biol. 5:834-839, 2003.129Sp�nkuch-Schmitt et al., "Effect of RNA Silencing of Polo-Like Kinase-1 (PLK1) on Apoptosis and Spindle Formation in Human Cancer Cells" J. Nat. Cancer Inst. 94:1863-1877 (2002).130Strauss, "Candidate �Gene Silencers� Found" Science 286:886 (1999).131Submission and Auxiliary Request by Sirna Therapeutics in opposition proceedings for European Patent No. 1352061 (May 13, 2009).132Summons to Attend oral proceedings in the opposition proceedings for EP application No. 02710786.1 (Mar. 17, 2009).133Thompson, "Shortcuts from gene sequence to function" Nature 17:1158-1159 (1999).134Tijsterman, M. et al., (2002), "The Genetics of RNA Silencing", Annu. Rev. Genet., 36:489-519.135Timmons et al., "Specific interference by ingested dsRNA" Nature 395:854 (1998).136Tuschl, T. et al., (1999), "Targeted mRNA degradation by double-stranded RNA in vitro", Genes & Development, 13:3191-3197.137Uhlmann, E. et al. Jun. 1, 1990, "Antisense Nucleotides: A New Therapeutic Principal" Chemical Reviews, American Chemical Society, Easton, US vol. 90, No. 4, pp. 543-584, ISSN:0009-2665.138Veal et al., "Sequence-specific RNAse cleavage of gag mRNA from HIV-1 infected cells by an antisense oligonucleotide in vitro" Nucleic Acids Res. 26:5670-75, 1998.139Verma et al., "Gene therapy�promises, problems and prospects" Nature 389:239-242 (1997).140Voinnet et al., "Systemic signalling in gene silencing" Nature 389:553 (1997).141Wagner et al., "Double-stranded RNA poses puzzle" Nature 391:744-745 (1998).142Wang et al., "Circular RNA oligonucleotides. Synthesis, nucleic acid binding properties, and a comparison with circular DNAs" Nucleic Acids Res. 22:2326-2333 (1994).143Wang et al., "RNA Conformation in the Tat�TAR Complex Determined by Site-Specific Photo-Cross-Linking" Biochemistry 35:6491-6499 (1996).144Wargelius et al., "Double-Stranded RNA Induces Specific Developmental Defects in Zebrafish Embryos" Biochem. Biophys. Res. Commun. 263:156-161 (1999).145Waterhouse et al., "Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA" Proc. Natl. Acad. Sci. USA 95:13959-13964 (1998).146Watkins et al., "In vivo UV cross-linking of U snRNAs that participate in trypanosome trans-splicing" Genes Dev. 5:1859-1869 (1991).147Wengel, "Synthesis of 3′-C- and 4′-C-Branched Oligodeoxynucleotides and the Development of Locked Nucleic Acid (LNA)" Acc. Chem. Res. 32:301-310 (1999).148Wess et al., "Early days of RNAi" BioCentury vol. 11, No. 12, 2003.149Wianny, F. et al., (2000), "Specific interference with gene function by double-stranded RNA in early mouse development", Nature Cell Biology, 2:70-75.150Wild, K. et al., (1999), "The 2 � structure of helix 6 of the human signal recognition particle RNA", Structure, (11):1345-1352.151Wild, K. et al., (1999), "The 2 Å structure of helix 6 of the human signal recognition particle RNA", Structure, (11):1345-1352.152Wu, H., et al., "Properties of Clones and Expressed Human RNase H1," The Journal of Biological Chemistry, Oct. 1, 1999, pp. 28270-28278, vol. 274, No. 40.153Yang, D. et al., (2000), "Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos", Current Biology, 10:1191-1200.154Yu, J. et al., (2002), "RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells", PNAS, 99(9):6047-6052.155 *Zamore et al., Cell, vol. 101, pp. 25-33 (2000).156Zamore, "RNA interference: listening to the sound of silence" Nature Struc. Biol. 8:748-750, 2001.157Zamore, P.D. et al., (2000), "RNAi: Double-Stranded RNA Directs the ATP-Dependent Cleavage of mRNA at 21 to 23 Nucleotide Intervals", Cell, 101:25-33.158Z-Axis Connector Company, LCD Connectors, www.z-axiscc.com/prodlcd.htm, Accessed Jul. 19, 2001.159Z-Axis Connector Company, Silver STAX, www.z-axiscc.com/prodstax.htm, Accessed Jul. 19, 2001.160Zwieb et al., "Evidence for RNA-RNA cross-link formation in Escherichia coli ribosomes" Nucleic Acids Res. 5:2705-2720 (1978).* Cited by examinerReferenced byCiting PatentFiling datePublication dateApplicantTitleUS8546143 *Sep 29, 2010Oct 1, 2013Alnylam Pharmaceuticals, Inc.Compositions and methods for inhibiting expression of a target geneUS20110111493 *Sep 29, 2010May 12, 2011Roland KreutzerCompositions and Methods For Inhibiting Expression Of A Target Gene* Cited by examinerClassifications U.S. Classification536/24.5, 435/91.1, 435/455, 536/23.1, 435/458, 536/24.31, 435/91.31, 435/6.16International ClassificationC07H21/02, A61K9/127, C07H21/04, A61P33/06, A61K47/48, A61P35/00, A61K31/7115, A61P25/28, A61K38/00, C12N15/88, A61P35/04, C12N15/09, A61K47/34, A61P37/02, A61P9/00, A61K31/7105, A61K48/00, A61P43/00, A61P31/12, C12Q1/68, A61P5/00, C12N15/113, A61K31/7125, C12N15/11, A61K31/713Cooperative ClassificationC12N15/111, C12N15/1131, C12N15/1138, C12N2310/53, A61K38/00, C12N2320/50, C12N2310/14European ClassificationC12N15/113E, C12N15/113A, C12N15/11MLegal EventsDateCodeEventDescriptionApr 12, 2011CCCertificate of correctionAug 7, 2009ASAssignmentOwner name: ALNYLAM PHARMACEUTICALS, INC., MASSACHUSETTSFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ALNYLAM EUROPE AG;REEL/FRAME:023070/0300Effective date: 20090805Owner name: ALNYLAM PHARMACEUTICALS, INC.,MASSACHUSETTSFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ALNYLAM EUROPE AG;REEL/FRAME:23070/300Jul 28, 2003ASAssignmentOwner name: RIBOPHARMA AG, GERMANYFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:KREUTZER, ROLAND;LIMMER, STEFAN;LIMMER, SYLVIA;AND OTHERS;REEL/FRAME:014326/0757;SIGNING DATES FROM 20030520 TO 20030523RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services©2012 Google