HUE035887T2 - PCSK9 iRNS készítmények és eljárások azok alkalmazására - Google Patents

PCSK9 iRNS készítmények és eljárások azok alkalmazására Download PDF

Info

Publication number
HUE035887T2
HUE035887T2 HUE13811327A HUE13811327A HUE035887T2 HU E035887 T2 HUE035887 T2 HU E035887T2 HU E13811327 A HUE13811327 A HU E13811327A HU E13811327 A HUE13811327 A HU E13811327A HU E035887 T2 HUE035887 T2 HU E035887T2
Authority
HU
Hungary
Prior art keywords
nucleotides
strand
rnai agent
pcsk9
nucleotide
Prior art date
Application number
HUE13811327A
Other languages
English (en)
Inventor
Anna Borodovsky
Rajeev G Kallanthottathil
Kevin Fitzgerald
Maria Frank-Kamenetsky
William Querbes
Martin Maier
Klaus Charisse
Satyanarayana Kuchimanchi
Muthiah Manoharan
Stuart Milstein
Original Assignee
Alnylam Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=49841845&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HUE035887(T2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Alnylam Pharmaceuticals Inc filed Critical Alnylam Pharmaceuticals Inc
Publication of HUE035887T2 publication Critical patent/HUE035887T2/hu

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/312—Phosphonates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • C12N2310/3533—Halogen
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/35—Special therapeutic applications based on a specific dosage / administration regimen

Claims (9)

  1. PCSX9 iRNS ké$%Kmények és eljárások »xokalkalmazásárst Szabadalmi igénypnotok
    1. Kctszálü RNSi szer, amely képes gátolni a Prs>profein konvertáz szubfiítzit) kevit; 9 (PCSK9) sejtbe!) expresszióját, -ahol a kétszáíú R.NSÍ szór tattal«)»»: (a) szensz szálak amely komplementet egy antíszensz szálfák ahol az antíszensz szál a PCSK9-t kódoló tnRNS egy részével kotnplenionísr régiót tartalmaz, ahol tnindegyik szál körülbelül 17 körülbelül 30 mikieotid hossztiságú, ahol az. antíszensz szál legalább 17 nokleotídot tartalmaz az. ACAAAAGCAAAACAGGG'CUAG (SEQ 11) NO: 412) nnklenbázis szekvenciából és a kétszáíú RNS) szert a következő (ül) képiéi reprezentálja: szensz: 5’ «„ -N3 -{X X X) rNb -Y Y Y -% -{Z Z 2), -W3 » ηή 3‘ «otíszensz: 3> npkN^(XTXVNb'’YW-NfcH2TZ>N8‘- rÇ 5’ {Ili} ahol: í, j, k, és l mindegyike függetlenül 0 vagy í : p, p\ q, és q! mindegyike függetlenül ü-ó; nhtdeg.yik N, és N3’ jelentése taggal lenül 0-25 nukleothlot tartalmazó oligonukleottd-szekvencia, amelyek vagy módosítottak vagy módosítatlanok vagy ezek kombinációja, mindegyik szekvencia Icgaíább két különböző módosított rmkleotidot tartalmaz; mindegyik N-és NY jelentése függetlenül 0-10 mikk-otidőt tartalmazó oligonukleottd-szekvenoa, amelyek vagy módosítottak vagy módosítatlanok vagy ezek kombinációja; mindegyik np, op\ t\, és n,,\ amelyek mindegyike jelen leltet van sent, jelentése függetlenít! táflógó íttíkieoficl; XXX, YYY, ZZZ, X’X'Xk Y’Y'Y’, és Z’Z'Z' mindegyike függetlenül bárom azonos módon módosított három egymást kővető mikieotid motívumát jelenti, az Nb-n lévő módosítások elférnek az Y-oo lévő módosítástól és az. N{,’-o lévő módosítások eltérnek az. Y n levő rnodositasíoi: ahol a ítukieofidökoí) lévő mödoättäsok ZM>:rneíir vagy 2’ -fluor módosítások ; és ahol a. ligandnrn egy vagy több GaiNAo származék btvalens· vagy trivalens elágazó kapesolómolekufán k.'iesz'dí kanesnis.t, vagy (h) anfiszemsz szálat, amely az asCfsaAfAtAfgCYaAfaAfcAfgGíuCíuagsasa nakleottd-szekvenctából és szensz szákit:, amely a csasagacCiuGfudlougouunugu nukleodd-szekveneiábói áll, ahol a, g, c, és u jelentése rendre 2’-ö-ntetil (2’-OMe) módosított A, G, G, and U nukieoiidok; Af, Gf, Gf és Gf jelentése rendre Z’-ílttor A, G, G és U módosított nttkleotidok; dT jelentése dezoxi-timtn nakleotíd és s jelentése foszfora inát kötés; és ahol a szensz szál konjugálva van legalább egy Ugandámhoz.
  2. 2. Az t. igénypont szerinti kétszáíú RW.SÍ szer, ahol (a) az. nntiszensz. szál az ACAAAAGCAAAACAGGUCUAGAA (SKQ 113 NO: 418} nukleobázís •szekvenciát tartalmazza: (it) a szensz szál az AöAGCí.SGUl.Pí.lt.ítít'.'i.íÍ.jl.ll.lGlJ (SEQ ID NO; 191) nukleobázís szekvenciái tartalmazza: <c) a szensz szál a COAGACCUGOUSIOGCOIIOUGU (SEQ ID NO; 197} nukleobázts szekvenciát tartalmazza; (d) az antiszensz szál az ACAAA AGCAAAACAGGllCUAGAA (SEQ ID NO: 418} nukleobázts szekvenciát tartalmazza és a szensz szál a CDAGACCUGUUUOGCUOOGGU (SEQ ÍD NO: 197) mtkleobázls szekvenciái tartalmazza; (e) az aaüszeosz szál az ACAAAAGCAAAACAGGUCUAG (SEQ ID NO: 412) nukíeoházis szekvenciát tartalmazza és a szensz szál a AGACCUGOUDQGCUU.UOGU (SEQ ID NO: 191) nttkleobűzís szekvenciát tartalmazza; vagy (0 az antiszensz szál az ACAAA.AGCAAAACAGGUCUAGAÁ (SEQ ID NO: 418} mtkleobázis szekvenciát mttalmazza és a szensz szál a CUAGACCUGDTUIJöCUDUUGU (SEQ 10 NO; 1665) nukleobázla szekvenciát tartalmazza;
  3. 3. Az Î. igénypont szerinti kétszínű RNSÍ szer, ahol ít kétszáló régió 17-23 nukíeotid pár bosszuságá, 17-25 nukíeotid pár hosszúságú, 23-2,7 nukíeotid pár hosszúságé, 19-21 nukíeotid pár hosszúságú, vagy 21-23 niskieotiií pár hosszúságú. 4» Az 1. igénypont szerinti kétszáiú R.NSí szer, ahol a tisRNS a következőket tartalmazza: ;;() antiszensz szál, amely az aCtaAlsAfgCfaAfaaeArgGmChtAfgsAfsa (SEQ 10 NO- 1151} nitkleotid-szekvencíából ált és szensz szál. amely a Cl'nAÍ'gAíéCl'nGfiJi'Olúi.ilgCíúlJluUfgl.lf'tSEQ ID NO: 60(1) íuíkieíitid-szökveneiábö! áll; tb) antiszensz szál, amely az aCfaAfAIAlgCIaAilmcAígGItfCíúAlgsAfsa (SEQ 10 NO: 1246} mtkleotid-szckvenciábóí till és szensz. szál, amely « CtúArgAícCiúGfOiGfuOígGfuuuOfgQf (SEQ ID NO: 695) nn kieoti díszek véne iából ál E (c} antiszensz szál, amely az tiCfaaaAigClaAfaacAfaCsiuCfnAfgsAisa (SEQ ID NO: 1253) nakleotid-szekvcnclábóí ál! és szensz szál, amely a CfijAlgAfcCluGftJftiíbtJIgCfaUftlRjfgllf (SEQ ID NO; 702} tmkleoíid^szekveneiából ált: (d) antiszensz szál,, ameiy az aCiaAfAfAtgCfaAfaaeAlgGfúCfusAfsg (.SEQ 10 NO: 1263) nukleotid-szekvenciúbél áll és szensz szál, amely az AfgAfeCfuGftjtUfuUfgCfounUfgUf (SEQ 1.1.) NO: 712.) nulíleotid-szekvenciából óit; (é) antiszensz szál, amely az aCtttaaA.fgCfaAfaacA:fgGtaCfa.s.A:fsg (SEQ 10 NO: 12.69} nukíeotid-szekvenciából áll és szensz szál. ameiy a A!'gAfcCiii(.>l'kitI.;ínl.JÍgCfuijn.;ílJi'gOf (SEQ H> NO: 718} nuk loot ni-szekvenciából áll; (f) antiszensz szál., amely az a.s.CÚmAláAfgClaAfaacAlgGfu.CfuA.fgsasa (SEQ 10 NO: 1369) nakíeotkl-szekveneiábói (dl és szensz szál, atneiy a CfsusAfgAtcCfuGtIlftJJuUlgCfúUfúOfgUf (SEQ ID NO: 6 18) nukíeot id-szék véne iából áll; (g) antiszensz szál, timely az asCisaAfáagCfaAlaaeAfgGittcuAfgsasa nukleotid-szekvenciábö! ál; és szensz. szál, amely a ClsusAígAlcCfuGfl) Ib'tuGfgcuuuugu nuklcolid^szekveneiából áll; vagy (b) antiszensz szót, amely az asCfsaAfaAfegCTaAfaaeÄlgGfuCisuAigsasa (SEQ ID NO: 1400} nukíeotid-szekvenciából ólt és szensz. szói, amely a crsusAfgAicCi'uGftJjlirubrgCrsuOfsuljtsgsUfs (SEQ 10 NO: 349) nnkSeotid-szekvenciábói áií;
    aboi a, g, e, és « jelentése rendre 2'-O-metil (2!-0Me) médositotl Λ, G, C, and U nukleotldok; Ai. Gf, Cf es Uf jelentése rendre z’-iktor A, G, C és 1.1 módosított nuklœtidok; dl jelentése dezjoxi-timin nnkleotld es s jelentése ioszforotioat kötés.
  4. 5. Az I -4. igénypontok bárnteiyike szerinti kéíszáló RNSi szer, ahoi a ligandont
  5. 6, Az 1-5. igénypontok bármelyike szét inti kétszáló RNSi szer, ahoi a Iigandutn a szensz szál 3' végéhez van kapcsolva.
  6. 7. A ö. igénypont szerinti kétszáló RNSi szer, ahol az RNSi szer a következő sén-án hentuiatoit ntódon van konjugálva a ligandutrthoz:
    -ahol X jelentése ö vagy S.
  7. 8. Az 1-7. igénypontok hártneíyike szerinti kétszáló RNSi szer, aíto! a szeitsz szál összesen 21 nukleotid és az antíszensz szál -összesen 23 nukleotid, 9, in vitro sejt. amely az 1-8. igénypontok báj-melyike szerinti kétszáló RNSi szert tartalmazza.
  8. 10, Gyógyászati készítmény, amely az 1-8. igénypontok bármely ike szerinti kéfszálú RNS; szert tartalmazza I L A íö. igénypont szerinti gyógyászati készítményben, ahol (ti) az RNSi szer poifereletien oldatban adandó be, ahoi előnyösen a pafiereíeilen oldat sóotdaí vagy víz; vagy (b) az RNSi szer puffere Iduttal adandó be, ahol előnyösen a pufleroídaí sőokíat acetálot. eitrátot, pralatnint, karbonátot, vagy foszfátot vagy ezek kombinációját tartalmazza, és ahol. legelőnyösebben a pufferoklat Sószt'át-pntrereit sóotdai (RBS). 12. kijárás PCSK9 expresszié gátlására sejt ben, amely eljárás magában foglalja; (a) a sejt eríntkezívtés.^· az l~fi. igénypontok bármelyike szerinti kétszálú RNSt szenei vagy a 10, vagy í 5. igénypont szerinti gyógyászait késztttnératyel; és. (b> az ta) tépésben eiőálkloit sejt fenntartásét a PCSK9 gebt mRNS transzkrtptnmttnak degradálásáhítz elegendő ideig, ezáltal gátolva a PCSK9 gén expresszsöját a sejtben. ahol s humán vagy állati szervezet terápiás kezelésére szolgáló ellátások ki vannak zárva.
  9. 13-Az 1-8, igénypontok bármelyike szerinti dsRNS vagy a 1(1. vagy 11, igénypont szerinti gyógyászati késziOnény, PCSK9 expresszié által közvetített rendellenességben szenvedd alany kezelési eljárásban történő alkalmazásra, 14, Λ 13. igénypont szerinti dsRNS vagy gyógyászati készítmény alkalmazásra, ahol (at az alany ember, fb> a rendellenesség .hiperkoiesztermémia; (et a kétszálú RNSi szer körülbelül 0,01 mg/kg - körülbelül 10 mg/kg, körülbelül 0,5 mg/kg körülbelül 50 mg/kg, vagy körülbelül !Ct tng/kg ·> körülbelül 30 mg/kg dózisban adandó be; és/vagy (d) a kétszálú RNSi szer szobkotán vagy intravénásán adandó be. I S, A 13, vagy 1.4. igénypont szerinti dsRNS vagy gyógyászati készítmény aikaltnazásra, ahol az. RNSi szer olyan adagolási rendben adandó be, amely íéiíölfési fázist ntajd az? követő fenntartási fázist foglal magában, ahol a fehölfési fázis 2 mg/kg, 1 mg/kg vagy 0,5 mg/kg dózis heti 5-szőri ixatdását foglalj magában, és ahol a fenntartási fázis 2 mg/kg, 1 mg/kg vagy 0,5 mg/kg dózis heti egyszeri, heti kétszeri, heti háromszori, kéthetente egyszeri, háromhetente egyszeri, havonta egyszeri, kéthavonta egyszeri, háromhavonta egyszeri, négyhavonta egyszeri, öthavonta egyszeri, vagy hafhavonta egyszeri beadását foglalja magában.
HUE13811327A 2012-12-05 2013-12-05 PCSK9 iRNS készítmények és eljárások azok alkalmazására HUE035887T2 (hu)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201261733518P 2012-12-05 2012-12-05
US201361793530P 2013-03-15 2013-03-15
US201361886916P 2013-10-04 2013-10-04
US201361892188P 2013-10-17 2013-10-17

Publications (1)

Publication Number Publication Date
HUE035887T2 true HUE035887T2 (hu) 2018-05-28

Family

ID=49841845

Family Applications (2)

Application Number Title Priority Date Filing Date
HUE13811327A HUE035887T2 (hu) 2012-12-05 2013-12-05 PCSK9 iRNS készítmények és eljárások azok alkalmazására
HUS2100021C HUS2100021I1 (hu) 2012-12-05 2021-06-04 PCSK9 iRNS készítmények és eljárások azok alkalmazására

Family Applications After (1)

Application Number Title Priority Date Filing Date
HUS2100021C HUS2100021I1 (hu) 2012-12-05 2021-06-04 PCSK9 iRNS készítmények és eljárások azok alkalmazására

Country Status (29)

Country Link
US (2) US10125369B2 (hu)
EP (3) EP4083209A1 (hu)
JP (4) JP6574383B2 (hu)
KR (2) KR20200035490A (hu)
CN (2) CN104854242B (hu)
AR (1) AR093835A1 (hu)
AU (3) AU2013355237C1 (hu)
BR (1) BR112015013105B1 (hu)
CA (1) CA2892160C (hu)
CY (1) CY1120195T1 (hu)
DK (1) DK2929031T5 (hu)
ES (1) ES2657608T3 (hu)
FR (1) FR21C1021I2 (hu)
HK (2) HK1213598A1 (hu)
HR (1) HRP20180126T2 (hu)
HU (2) HUE035887T2 (hu)
IL (2) IL238917B (hu)
LT (2) LT2929031T (hu)
LU (1) LUC00209I2 (hu)
MX (2) MX367076B (hu)
NL (1) NL301107I2 (hu)
NO (1) NO2021024I1 (hu)
NZ (1) NZ709013A (hu)
PL (1) PL2929031T4 (hu)
PT (1) PT2929031T (hu)
RS (1) RS56783B9 (hu)
SI (1) SI2929031T1 (hu)
WO (1) WO2014089313A1 (hu)
ZA (1) ZA201503829B (hu)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104105790A (zh) * 2011-11-18 2014-10-15 阿尔尼拉姆医药品有限公司 修饰的RNAi试剂
ES2657608T3 (es) * 2012-12-05 2018-03-06 Alnylam Pharmaceuticals, Inc. Composiciones de arni de pcsk9 y métodos de uso de las mismas
EP3019200B1 (en) * 2013-07-11 2022-03-23 Alnylam Pharmaceuticals, Inc. Oligonucleotide-ligand conjugates and process for their preparation
EP3186377A1 (en) 2014-08-20 2017-07-05 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents
WO2016057693A1 (en) * 2014-10-10 2016-04-14 Alnylam Pharmaceuticals, Inc. Methods and compositions for inhalation delivery of conjugated oligonucleotide
JOP20200115A1 (ar) * 2014-10-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات))
US20160319278A1 (en) * 2015-04-03 2016-11-03 University Of Massachusetts Fully stabilized asymmetric sirna
EP3340994A1 (en) * 2015-08-25 2018-07-04 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder
JP2019503394A (ja) 2016-01-31 2019-02-07 ユニバーシティ・オブ・マサチューセッツＵｎｉｖｅｒｓｉｔｙ Ｏｆ Ｍａｓｓａｃｈｕｓｅｔｔｓ 分岐オリゴヌクレオチド
EP3445385A4 (en) 2016-04-18 2019-11-20 The Trustees of Columbia University in the City of New York THERAPEUTIC GOALS INVOLVED IN THE PROGRESSION OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)
US11753638B2 (en) 2016-08-12 2023-09-12 University Of Massachusetts Conjugated oligonucleotides
US20180104360A1 (en) * 2016-10-18 2018-04-19 The Medicines Company Methods for Preventing Cardiovascular Events Through Proprotein Convertase Subtilisin Kexin 9 (PCSK9) Protein Reduction
FR3058061A1 (fr) * 2016-10-27 2018-05-04 Selexel Nouvelle utilisation d'oligonucleotides double brin
CN108265052B (zh) * 2016-12-30 2021-05-28 苏州瑞博生物技术股份有限公司 一种小干扰核酸和药物组合物及其用途
JP7458785B2 (ja) 2017-01-23 2024-04-01 リジェネロン・ファーマシューティカルズ・インコーポレイテッド ヒドロキシステロイド１７－βデヒドロゲナーゼ１３（ＨＳＤ１７Ｂ１３）バリアント及びその使用
JOP20190215A1 (ar) * 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
US11015198B2 (en) 2017-04-05 2021-05-25 Silence Therapeutics Gmbh Products and compositions
CN110325649A (zh) 2017-04-11 2019-10-11 雷杰纳荣制药公司 用于筛选羟基类固醇(17-β)脱氢酶(HSD17B)家族成员的调节剂的活性的测定法
KR102401796B1 (ko) 2017-04-13 2022-05-25 카딜라 핼쓰캐어 리미티드 신규의 펩타이드 기재 pcsk9 백신
JP7434151B2 (ja) 2017-10-11 2024-02-20 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Ｐｎｐｌａ３ ｉ１４８ｍの変異を発現している患者の肝疾患の治療におけるｈｓｄ１７ｂ１３の阻害
CN110945130B (zh) 2017-12-01 2024-04-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
EP3719128A4 (en) 2017-12-01 2021-10-27 Suzhou Ribo Life Science Co., Ltd. DOUBLE STRANDED OLIGONUCLEOTIDE, COMPOSITION AND CONJUGATE WITH DOUBLE STRANDED OLIGONUCLEOTIDE, METHOD OF MANUFACTURING THEREOF AND USE THEREOF
US11414665B2 (en) 2017-12-01 2022-08-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof
CN110997917B (zh) 2017-12-01 2024-04-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
JP7191101B2 (ja) * 2017-12-26 2022-12-16 アーゴーナ ファーマシューティカルズ リミテッド ＰＣＳＫ９遺伝子の発現を抑制するｓｉＲＮＡ分子及びその応用
CN109957565B (zh) * 2017-12-26 2023-04-07 广州市锐博生物科技有限公司 一种修饰的siRNA分子及其应用
CN110959011B (zh) 2017-12-29 2023-03-28 苏州瑞博生物技术股份有限公司 缀合物及其制备方法和用途
KR20210018267A (ko) * 2018-05-07 2021-02-17 알닐람 파마슈티칼스 인코포레이티드 간외 전달
US11918600B2 (en) 2018-08-21 2024-03-05 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof
US11896674B2 (en) 2018-09-30 2024-02-13 Suzhou Ribo Life Science Co., Ltd. SiRNA conjugate, preparation method therefor and use thereof
EP3898979A4 (en) 2018-12-19 2022-10-12 Alnylam Pharmaceuticals, Inc. AMYLOID PROTEIN PRECURSOR (APP) RNAI AGENT COMPOSITIONS AND METHODS OF USE THEREOF
CN113286888B (zh) * 2019-05-22 2023-12-22 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
CN110540992B (zh) * 2019-08-21 2021-02-09 武汉泽智生物医药有限公司 增强靶基因沉默效率的siRNA分子及其应用
EP4017504A4 (en) * 2019-08-23 2024-01-24 Univ Massachusetts O-METHYL-RICH FULLY STABILIZED OLIGONUCLEOTIDES
CN110638788A (zh) * 2019-10-25 2020-01-03 广州医科大学 一种能够沉默Pcsk9蛋白的siRNA、其纳米递送系统及应用
WO2022089486A1 (zh) * 2020-10-28 2022-05-05 江苏柯菲平医药股份有限公司 抑制PCSK9基因表达的siRNA及其修饰物与应用
CN113234725B (zh) * 2021-05-28 2022-02-18 厦门甘宝利生物医药有限公司 一种抑制pcsk9基因表达的rna抑制剂及其应用
US20230089502A1 (en) * 2021-06-17 2023-03-23 Sirnaomics, Inc. Products and compositions
CN115572241A (zh) * 2021-06-21 2023-01-06 润佳（苏州）医药科技有限公司 双价化合物、偶联物及其用途
WO2022271786A1 (en) 2021-06-23 2022-12-29 University Of Massachusetts Optimized anti-flt1 oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
CN117858883A (zh) 2021-08-09 2024-04-09 莱尔纳生物制药私人有限公司 GalNAc单体和GalNAc寡核苷酸缀合物
WO2023017004A1 (en) 2021-08-09 2023-02-16 Cargene Therapeutics Pte. Ltd. Inhibitory nucleic acids for pcsk9
CA3229020A1 (en) * 2021-09-14 2023-03-23 Stella PELENGARIS Treatment of cardiovascular disease
TW202333751A (zh) * 2021-12-16 2023-09-01 大陸商上海拓界生物醫藥科技有限公司 一種ｄｓｒｎａ、其製備方法及應用
WO2023134609A1 (zh) * 2022-01-13 2023-07-20 石药集团中奇制药技术（石家庄）有限公司 一种抑制PCSK9基因表达的RNAi剂及其应用
WO2023241591A1 (zh) * 2022-06-14 2023-12-21 大睿生物医药科技(上海)有限公司 调控PCSK9基因活性的siRNA分子
CN117563009A (zh) * 2023-09-01 2024-02-20 北京悦康科创医药科技股份有限公司 一种含有核糖环或其衍生结构的GalNAc化合物及其寡核苷酸缀合物
CN117384907B (zh) * 2023-12-11 2024-03-29 上海鼎新基因科技有限公司 抑制PCSK9表达的siRNA分子及其应用

Family Cites Families (264)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1861608A (en) 1929-12-21 1932-06-07 Emerson Electric Mfg Co Fan and means for directing the air current therethrough
US1861108A (en) 1930-01-24 1932-05-31 Eugene O Brace Integral clutch and transmission control
US3974808A (en) 1975-07-02 1976-08-17 Ford Motor Company Air intake duct assembly
US4708708A (en) 1982-12-06 1987-11-24 International Paper Company Method and apparatus for skiving and hemming
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US5139941A (en) 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
US4920016A (en) 1986-12-24 1990-04-24 Linear Technology, Inc. Liposomes with enhanced circulation time
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
FR2645866B1 (fr) 1989-04-17 1991-07-05 Centre Nat Rech Scient Nouvelles lipopolyamines, leur preparation et leur emploi
US5744101A (en) 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
NL8901881A (nl) 1989-07-20 1991-02-18 Rockwool Grodan Bv Drainagekoppelelement.
US5436146A (en) 1989-09-07 1995-07-25 The Trustees Of Princeton University Helper-free stocks of recombinant adeno-associated virus vectors
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
US5981276A (en) 1990-06-20 1999-11-09 Dana-Farber Cancer Institute Vectors containing HIV packaging sequences, packaging defective HIV vectors, and uses thereof
US5283185A (en) 1991-08-28 1994-02-01 University Of Tennessee Research Corporation Method for delivering nucleic acids into cells
US5252479A (en) 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
EP0624059A4 (en) 1991-11-22 1994-12-21 Affymax Technologies N.V. Combinatorial strategies for polymer synthesis.
US5587308A (en) 1992-06-02 1996-12-24 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
IL105914A0 (en) 1992-06-04 1993-10-20 Univ California Methods and compositions for in vivo gene therapy
CA2135313A1 (en) 1992-06-18 1994-01-06 Theodore Choi Methods for producing transgenic non-human animals harboring a yeast artificial chromosome
EP0786522A2 (en) 1992-07-17 1997-07-30 Ribozyme Pharmaceuticals, Inc. Enzymatic RNA molecules for treatment of stenotic conditions
US5783701A (en) 1992-09-08 1998-07-21 Vertex Pharmaceuticals, Incorporated Sulfonamide inhibitors of aspartyl protease
EP1024198A3 (en) 1992-12-03 2002-05-29 Genzyme Corporation Pseudo-adenoviral vectors for the gene therapy of haemophiliae
US5478745A (en) 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
DE69424406T2 (de) 1993-02-19 2000-10-26 Nippon Shinyaku Co Ltd Arzneistoffzusammensetzung, die ein nukleinsäurecopolymer enthält
US6191105B1 (en) 1993-05-10 2001-02-20 Protein Delivery, Inc. Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin
US6054299A (en) 1994-04-29 2000-04-25 Conrad; Charles A. Stem-loop cloning vector and method
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5556752A (en) 1994-10-24 1996-09-17 Affymetrix, Inc. Surface-bound, unimolecular, double-stranded DNA
US5665557A (en) 1994-11-14 1997-09-09 Systemix, Inc. Method of purifying a population of cells enriched for hematopoietic stem cells populations of cells obtained thereby and methods of use thereof
JP3269301B2 (ja) 1994-12-28 2002-03-25 豊田合成株式会社 ガラスラン用ゴム配合物
WO1996037194A1 (en) 1995-05-26 1996-11-28 Somatix Therapy Corporation Delivery vehicles comprising stable lipid/nucleic acid complexes
EP1489184A1 (en) 1995-06-07 2004-12-22 Inex Pharmaceutical Corp. Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
US5545531A (en) 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US7422902B1 (en) 1995-06-07 2008-09-09 The University Of British Columbia Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US5858397A (en) 1995-10-11 1999-01-12 University Of British Columbia Liposomal formulations of mitoxantrone
WO1997014809A2 (en) 1995-10-16 1997-04-24 Dana-Farber Cancer Institute Novel expression vectors and methods of use
US5854033A (en) 1995-11-21 1998-12-29 Yale University Rolling circle replication reporter systems
US5858401A (en) 1996-01-22 1999-01-12 Sidmak Laboratories, Inc. Pharmaceutical composition for cyclosporines
US5994316A (en) 1996-02-21 1999-11-30 The Immune Response Corporation Method of preparing polynucleotide-carrier complexes for delivery to cells
US6034135A (en) 1997-03-06 2000-03-07 Promega Biosciences, Inc. Dimeric cationic lipids
CA2294988C (en) 1997-07-01 2015-11-24 Isis Pharmaceuticals Inc. Compositions and methods for the delivery of oligonucleotides via the alimentary canal
US6436989B1 (en) 1997-12-24 2002-08-20 Vertex Pharmaceuticals, Incorporated Prodrugs of aspartyl protease inhibitors
ID25551A (id) 1997-12-24 2000-10-12 Vertex Pharma Bahan baku obat penghambat protease aspartil
CA2335393C (en) 1998-07-20 2008-09-23 Inex Pharmaceuticals Corporation Liposomal encapsulated nucleic acid-complexes
AU6430599A (en) 1998-10-09 2000-05-01 Cytogenix, Inc. Enzymatic synthesis of ssdna
BR9914773A (pt) 1998-10-09 2002-02-05 Ingene Inc Conjunto de elementos genéricos, método para a produção de dna de cordão único, transcrição de mrna, construção de ácido nucléico, transcrição de ssdna, vetor, sistema vetor, célula hospedeira, conjunto para a produção de uma sequência de ácido nucléico de cordão único, método para a produção in vivo ou in vitro de uma sequência de ácido nucléico de cordão único, transcrição de cdna de cordão único, ácido nucléico inibidor, molécula heteroduplex, e composição farmacêutica
TWI260322B (en) 1999-02-12 2006-08-21 Vertex Pharma Inhibitors of aspartyl protease
EP1156812A4 (en) 1999-02-23 2004-09-29 Isis Pharmaceuticals Inc MULTIPARTICULAR FORMULATION
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
US8273866B2 (en) 2002-02-20 2012-09-25 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SINA)
US20050032733A1 (en) 2001-05-18 2005-02-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA)
US20050182008A1 (en) 2000-02-11 2005-08-18 Sirna Therapeutics, Inc. RNA interference mediated inhibition of NOGO and NOGO receptor gene expression using short interfering nucleic acid (siNA)
US8202979B2 (en) 2002-02-20 2012-06-19 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
IT1318539B1 (it) 2000-05-26 2003-08-27 Italfarmaco Spa Composizioni farmaceutiche a rilascio prolungato per lasomministrazione parenterale di sostanze idrofile biologicamente
US20050209179A1 (en) 2000-08-30 2005-09-22 Sirna Therapeutics, Inc. RNA interference mediated treatment of Alzheimer's disease using short interfering nucleic acid (siNA)
US20060247194A1 (en) 2000-08-30 2006-11-02 Sirna Therapeutics , Inc. Rna interference mediated treatment of alzheimer's disease using short interfering nucleic acid (sina)
US20050277608A1 (en) 2001-05-18 2005-12-15 Sirna Therapeutics, Inc. RNA interference mediated inhibtion of vitamin D receptor gene expression using short interfering nucleic acid (siNA)
US20050267058A1 (en) 2001-05-18 2005-12-01 Sirna Therapeutics, Inc. RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (sINA)
US20050277133A1 (en) 2001-05-18 2005-12-15 Sirna Therapeutics, Inc. RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA)
US20050261219A1 (en) 2001-05-18 2005-11-24 Sirna Therapeutics, Inc. RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
US20050136436A1 (en) 2001-05-18 2005-06-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of G72 and D-amino acid oxidase (DAAO) gene expression using short interfering nucleic acid (siNA)
US20050176666A1 (en) 2001-05-18 2005-08-11 Sirna Therapeutics, Inc. RNA interference mediated inhibition of GPRA and AAA1 gene expression using short interfering nucleic acid (siNA)
US20070042983A1 (en) 2001-05-18 2007-02-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US20050233996A1 (en) 2002-02-20 2005-10-20 Sirna Therapeutics, Inc. RNA interference mediated inhibition of hairless (HR) gene expression using short interfering nucleic acid (siNA)
US20060148743A1 (en) 2001-05-18 2006-07-06 Vasant Jadhav RNA interference mediated inhibition of histone deacetylase (HDAC) gene expression using short interfering nucleic acid (siNA)
US20060241075A1 (en) 2001-05-18 2006-10-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of desmoglein gene expression using short interfering nucleic acid (siNA)
US20050159380A1 (en) 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of angiopoietin gene expression using short interfering nucleic acid (siNA)
US20050239731A1 (en) 2001-05-18 2005-10-27 Sirna Therapeutics, Inc. RNA interference mediated inhibition of MAP kinase gene expression using short interfering nucleic acid (siNA)
US20050130181A1 (en) 2001-05-18 2005-06-16 Sirna Therapeutics, Inc. RNA interference mediated inhibition of wingless gene expression using short interfering nucleic acid (siNA)
US20050233344A1 (en) 2001-05-18 2005-10-20 Sirna Therapeutics, Inc. RNA interference mediated inhibition of platelet derived growth factor (PDGF) and platelet derived growth factor receptor (PDGFR) gene expression using short interfering nucleic acid (siNA)
US20060211642A1 (en) 2001-05-18 2006-09-21 Sirna Therapeutics, Inc. RNA inteference mediated inhibition of hepatitis C virus (HVC) gene expression using short interfering nucleic acid (siNA)
US20050124566A1 (en) 2001-05-18 2005-06-09 Sirna Therapeutics, Inc. RNA interference mediated inhibition of myostatin gene expression using short interfering nucleic acid (siNA)
US20050159376A1 (en) 2002-02-20 2005-07-21 Slrna Therapeutics, Inc. RNA interference mediated inhibition 5-alpha reductase and androgen receptor gene expression using short interfering nucleic acid (siNA)
US9994853B2 (en) 2001-05-18 2018-06-12 Sirna Therapeutics, Inc. Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference
US20050070497A1 (en) 2001-05-18 2005-03-31 Sirna Therapeutics, Inc. RNA interference mediated inhibtion of tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
US20050124567A1 (en) 2001-05-18 2005-06-09 Sirna Therapeutics, Inc. RNA interference mediated inhibition of TRPM7 gene expression using short interfering nucleic acid (siNA)
US20050203040A1 (en) 2001-05-18 2005-09-15 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA)
US20050288242A1 (en) 2001-05-18 2005-12-29 Sirna Therapeutics, Inc. RNA interference mediated inhibition of RAS gene expression using short interfering nucleic acid (siNA)
US20050119212A1 (en) 2001-05-18 2005-06-02 Sirna Therapeutics, Inc. RNA interference mediated inhibition of FAS and FASL gene expression using short interfering nucleic acid (siNA)
US20050176665A1 (en) 2001-05-18 2005-08-11 Sirna Therapeutics, Inc. RNA interference mediated inhibition of hairless (HR) gene expression using short interfering nucleic acid (siNA)
US20050287128A1 (en) 2001-05-18 2005-12-29 Sirna Therapeutics, Inc. RNA interference mediated inhibition of TGF-beta and TGF-beta receptor gene expression using short interfering nucleic acid (siNA)
US20050233997A1 (en) 2001-05-18 2005-10-20 Sirna Therapeutics, Inc. RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA)
US20060019913A1 (en) 2001-05-18 2006-01-26 Sirna Therapeutics, Inc. RNA interference mediated inhibtion of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
US20050227935A1 (en) 2001-05-18 2005-10-13 Sirna Therapeutics, Inc. RNA interference mediated inhibition of TNF and TNF receptor gene expression using short interfering nucleic acid (siNA)
US20050119211A1 (en) 2001-05-18 2005-06-02 Sirna Therapeutics, Inc. RNA mediated inhibition connexin gene expression using short interfering nucleic acid (siNA)
US20050182006A1 (en) 2001-05-18 2005-08-18 Sirna Therapeutics, Inc RNA interference mediated inhibition of protein kinase C alpha (PKC-alpha) gene expression using short interfering nucleic acid (siNA)
US20050124569A1 (en) 2001-05-18 2005-06-09 Sirna Therapeutics, Inc. RNA interference mediated inhibition of CXCR4 gene expression using short interfering nucleic acid (siNA)
US20050158735A1 (en) 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proliferating cell nuclear antigen (PCNA) gene expression using short interfering nucleic acid (siNA)
US20050153914A1 (en) 2001-05-18 2005-07-14 Sirna Therapeutics, Inc. RNA interference mediated inhibition of MDR P-glycoprotein gene expression using short interfering nucleic acid (siNA)
US20050171040A1 (en) 2001-05-18 2005-08-04 Sirna Therapeutics, Inc. RNA interference mediated inhibition of cholesteryl ester transfer protein (CEPT) gene expression using short interfering nucleic acid (siNA)
US20050143333A1 (en) 2001-05-18 2005-06-30 Sirna Therapeutics, Inc. RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA)
US20050176024A1 (en) 2001-05-18 2005-08-11 Sirna Therapeutics, Inc. RNA interference mediated inhibition of epidermal growth factor receptor (EGFR) gene expression using short interfering nucleic acid (siNA)
US20050170371A1 (en) 2001-05-18 2005-08-04 Sirna Therapeutics, Inc. RNA interference mediated inhibition of 5-alpha reductase and androgen receptor gene expression using short interfering nucleic acid (siNA)
US20070032441A1 (en) 2001-05-18 2007-02-08 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (sina)
US20050124568A1 (en) 2001-05-18 2005-06-09 Sirna Therapeutics, Inc. RNA interference mediated inhibition of acetyl-CoA-carboxylase gene expression using short interfering nucleic acid (siNA)
US20060276422A1 (en) 2001-05-18 2006-12-07 Nassim Usman RNA interference mediated inhibition of B7-H1 gene expression using short interfering nucleic acid (siNA)
US20060142226A1 (en) 2001-05-18 2006-06-29 Sirna Therapeutics, Inc. RNA interference mediated inhibition of cholesteryl ester transfer protein (CETP) gene expression using short interfering nucleic acid (siNA)
US7517864B2 (en) 2001-05-18 2009-04-14 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US20050159379A1 (en) 2001-05-18 2005-07-21 Sirna Therapeutics, Inc RNA interference mediated inhibition of gastric inhibitory polypeptide (GIP) and gastric inhibitory polypeptide receptor (GIPR) gene expression using short interfering nucleic acid (siNA)
US20050222066A1 (en) 2001-05-18 2005-10-06 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US20070093437A1 (en) 2001-05-18 2007-04-26 Sirna Therapeutics, Inc. Rna interference mediated inhibition of xiap gene expression using short interfering nucleic acid (sina)
US20050196767A1 (en) 2001-05-18 2005-09-08 Sirna Therapeutics, Inc. RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acis (siNA)
US20050182007A1 (en) 2001-05-18 2005-08-18 Sirna Therapeutics, Inc. RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA)
US20050137155A1 (en) 2001-05-18 2005-06-23 Sirna Therapeutics, Inc. RNA interference mediated treatment of Parkinson disease using short interfering nucleic acid (siNA)
US20060019917A1 (en) 2001-05-18 2006-01-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of stromal cell-derived factor-1 (SDF-1) gene expression using short interfering nucleic acid (siNA)
US20060217331A1 (en) 2001-05-18 2006-09-28 Sirna Therapeutics, Inc. Chemically modified double stranded nucleic acid molecules that mediate RNA interference
US20050196781A1 (en) 2001-05-18 2005-09-08 Sirna Therapeutics, Inc. RNA interference mediated inhibition of STAT3 gene expression using short interfering nucleic acid (siNA)
US20070173473A1 (en) 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
US20070179104A1 (en) 2001-05-18 2007-08-02 Sirna Therapeutics, Inc. RNA interference mediated inhibition of winged helix nude (WHN) gene expression using short interfering nucleic acid (siNA)
US20050159382A1 (en) 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA)
WO2005014811A2 (en) 2003-08-08 2005-02-17 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF XIAP GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20080249040A1 (en) 2001-05-18 2008-10-09 Sirna Therapeutics, Inc. RNA interference mediated inhibition of sterol regulatory element binding protein 1 (SREBP1) gene expression using short interfering nucleic acid (siNA)
US20050176663A1 (en) 2001-05-18 2005-08-11 Sima Therapeutics, Inc. RNA interference mediated inhibition of protein tyrosine phosphatase type IVA (PRL3) gene expression using short interfering nucleic acid (siNA)
US20050191618A1 (en) 2001-05-18 2005-09-01 Sirna Therapeutics, Inc. RNA interference mediated inhibition of human immunodeficiency virus (HIV) gene expression using short interfering nucleic acid (siNA)
US20060287267A1 (en) 2001-05-18 2006-12-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of respiratory syncytial virus (RSV) expression using short interfering nucleic acid (siNA)
US20050164224A1 (en) 2001-05-18 2005-07-28 Sirna Therapeutics, Inc. RNA interference mediated inhibition of cyclin D1 gene expression using short interfering nucleic acid (siNA)
US20050209180A1 (en) 2001-05-18 2005-09-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA)
US20080188430A1 (en) 2001-05-18 2008-08-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA)
US20090299045A1 (en) 2001-05-18 2009-12-03 Sirna Therapeutics, Inc. RNA Interference Mediated Inhibition Of Interleukin and Interleukin Gene Expression Using Short Interfering Nucleic Acid (siNA)
US20070049543A1 (en) 2001-05-18 2007-03-01 Sirna Therapeutics, Inc. RNA interference mediated inhibition of 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-HSD-1) gene expression using short interfering nucleic acid siNA
US20050164967A1 (en) 2001-05-18 2005-07-28 Sirna Therapeutics, Inc. RNA interference mediated inhibition of platelet-derived endothelial cell growth factor (ECGF1) gene expression using short interfering nucleic acid (siNA)
US20050159378A1 (en) 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of Myc and/or Myb gene expression using short interfering nucleic acid (siNA)
US20050164968A1 (en) 2001-05-18 2005-07-28 Sirna Therapeutics, Inc. RNA interference mediated inhibition of ADAM33 gene expression using short interfering nucleic acid (siNA)
US20050176664A1 (en) 2001-05-18 2005-08-11 Sirna Therapeutics, Inc. RNA interference mediated inhibition of cholinergic muscarinic receptor (CHRM3) gene expression using short interfering nucleic acid (siNA)
US20050282188A1 (en) 2001-05-18 2005-12-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US20060142225A1 (en) 2001-05-18 2006-06-29 Sirna Therapeutics, Inc. RNA interference mediated inhibition of cyclin dependent kinase-2 (CDK2) gene expression using short interfering nucleic acid (siNA)
WO2005078097A2 (en) 2004-02-10 2005-08-25 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING MULTIFUNCTIONAL SHORT INTERFERING NUCLEIC ACID (Multifunctional siNA)
US20050182009A1 (en) 2001-05-18 2005-08-18 Sirna Therapeutics, Inc. RNA interference mediated inhibition of NF-Kappa B / REL-A gene expression using short interfering nucleic acid (siNA)
US20050079610A1 (en) 2001-05-18 2005-04-14 Sirna Therapeutics, Inc. RNA interference mediated inhibition of Fos gene expression using short interfering nucleic acid (siNA)
US20050153916A1 (en) 2001-05-18 2005-07-14 Sirna Therapeutics, Inc. RNA interference mediated inhibition of telomerase gene expression using short interfering nucleic acid (siNA)
US20050159381A1 (en) 2001-05-18 2005-07-21 Sirna Therapeutics, Inc. RNA interference mediated inhibition of chromosome translocation gene expression using short interfering nucleic acid (siNA)
US20050196765A1 (en) 2001-05-18 2005-09-08 Sirna Therapeutics, Inc. RNA interference mediated inhibition of checkpoint Kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA)
CA2526831C (en) 2001-05-18 2012-07-31 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (sina)
WO2005007855A2 (en) 2003-07-14 2005-01-27 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF B7-H1 GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20050176025A1 (en) 2001-05-18 2005-08-11 Sirna Therapeutics, Inc. RNA interference mediated inhibition of B-cell CLL/Lymphoma-2 (BCL-2) gene expression using short interfering nucleic acid (siNA)
US20050164966A1 (en) 2001-05-18 2005-07-28 Sirna Therapeutics, Inc. RNA interference mediated inhibition of type 1 insulin-like growth factor receptor gene expression using short interfering nucleic acid (siNA)
US20050148530A1 (en) 2002-02-20 2005-07-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US20050187174A1 (en) 2001-05-18 2005-08-25 Sirna Therapeutics, Inc. RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA)
US20080161256A1 (en) 2001-05-18 2008-07-03 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US20050256068A1 (en) 2001-05-18 2005-11-17 Sirna Therapeutics, Inc. RNA interference mediated inhibition of stearoyl-CoA desaturase (SCD) gene expression using short interfering nucleic acid (siNA)
US20050227936A1 (en) 2001-05-18 2005-10-13 Sirna Therapeutics, Inc. RNA interference mediated inhibition of TGF-beta and TGF-beta receptor gene expression using short interfering nucleic acid (siNA)
US20070270579A1 (en) 2001-05-18 2007-11-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
US20050260620A1 (en) 2001-05-18 2005-11-24 Sirna Therapeutics, Inc. RNA interference mediated inhibition of retinolblastoma (RBI) gene expression using short interfering nucleic acid (siNA)
US8008472B2 (en) 2001-05-29 2011-08-30 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of human immunodeficiency virus (HIV) gene expression using short interfering nucleic acid (siNA)
AU2002323151A1 (en) 2001-08-13 2003-03-03 University Of Pittsburgh Application of lipid vehicles and use for drug delivery
US7678897B2 (en) 2002-02-20 2010-03-16 Sirna Therapeutics, Inc. RNA interference mediated inhibition of platelet-derived endothelial cell growth factor (ECGF1) gene expression using short interfering nucleic acid (siNA)
US7910724B2 (en) 2002-02-20 2011-03-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of Fos gene expression using short interfering nucleic acid (siNA)
US7897752B2 (en) 2002-02-20 2011-03-01 Sirna Therapeutics, Inc. RNA interference mediated inhibition of telomerase gene expression using short interfering nucleic acid (siNA)
US8013143B2 (en) 2002-02-20 2011-09-06 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of CXCR4 gene expression using short interfering nucleic acid (siNA)
US20090093439A1 (en) 2002-02-20 2009-04-09 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF CHROMOSOME TRANSLOCATION GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US8258288B2 (en) 2002-02-20 2012-09-04 Sirna Therapeutics, Inc. RNA interference mediated inhibition of respiratory syncytial virus (RSV) expression using short interfering nucleic acid (siNA)
US7893248B2 (en) 2002-02-20 2011-02-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of Myc and/or Myb gene expression using short interfering nucleic acid (siNA)
US20090137510A1 (en) 2002-02-20 2009-05-28 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF NF-KAPPA B/ REL-A GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US7683166B2 (en) 2002-02-20 2010-03-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
US20090306182A1 (en) 2002-02-20 2009-12-10 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF MAP KINASE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20090192105A1 (en) 2002-02-20 2009-07-30 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF INTERCELLULAR ADHESION MOLECULE (ICAM) GENE EXPRESSION USING SHORT INTERFERING NUCELIC ACID (siNA)
US7667029B2 (en) 2002-02-20 2010-02-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of checkpoint kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA)
US7662952B2 (en) 2002-02-20 2010-02-16 Sirna Therapeutics, Inc. RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acid (siNA)
US7897753B2 (en) 2002-02-20 2011-03-01 Sirna Therapeutics, Inc. RNA interference mediated inhibition of XIAP gene expression using short interfering nucleic acid (siNA)
US20090137507A1 (en) 2002-02-20 2009-05-28 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF ANGIOPOIETIN GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20090099117A1 (en) 2002-02-20 2009-04-16 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF MYOSTATIN GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20100240730A1 (en) 2002-02-20 2010-09-23 Merck Sharp And Dohme Corp. RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA)
US8067575B2 (en) 2002-02-20 2011-11-29 Merck, Sharp & Dohme Corp. RNA interference mediated inhibition of cyclin D1 gene expression using short interfering nucleic acid (siNA)
US20050222064A1 (en) 2002-02-20 2005-10-06 Sirna Therapeutics, Inc. Polycationic compositions for cellular delivery of polynucleotides
US7683165B2 (en) 2002-02-20 2010-03-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
US7667030B2 (en) 2002-02-20 2010-02-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA)
US20090137509A1 (en) 2002-02-20 2009-05-28 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF PROLIFERATION CELL NUCLEAR ANTIGEN (PCNA) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20090253773A1 (en) 2002-02-20 2009-10-08 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF TNF AND TNF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US7928219B2 (en) 2002-02-20 2011-04-19 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (SINA)
US20050137153A1 (en) 2002-02-20 2005-06-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of alpha-1 antitrypsin (AAT) gene expression using short interfering nucleic acid (siNA)
US7700760B2 (en) 2002-02-20 2010-04-20 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA)
US7691999B2 (en) 2002-02-20 2010-04-06 Sirna Therapeutics, Inc. RNA interference mediated inhibition of NOGO and NOGO receptor gene expression using short interfering nucleic acid (siNA)
US7928218B2 (en) 2002-02-20 2011-04-19 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA)
US7928220B2 (en) 2002-02-20 2011-04-19 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of stromal cell-derived factor-1 (SDF-1) gene expression using short interfering nucleic acid (siNA)
US7935812B2 (en) 2002-02-20 2011-05-03 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA)
US20090137513A1 (en) 2002-02-20 2009-05-28 Sirna Therapeutics, Inc. RNA Interference Mediated Inhibition of Acetyl-CoA-Carboxylase Gene Expression Using Short Interfering Nucleic Acid (siNA)
US20090253774A1 (en) 2002-02-20 2009-10-08 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF PLATELET DERIVED GROWTH FACTOR (PDGF) AND PLATELET DERIVED GROWTH FACTOR RECEPTOR (PDGFR) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US7897757B2 (en) 2002-02-20 2011-03-01 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA)
CA2489174C (en) 2002-07-10 2013-02-05 Thomas Tuschl Rna-interference by single-stranded rna molecules
US6649638B1 (en) 2002-08-14 2003-11-18 Ppd Discovery, Inc. Prenylation inhibitors and methods of their synthesis and use
US20080161547A1 (en) 2002-11-14 2008-07-03 Dharmacon, Inc. siRNA targeting serine/threonine protein kinase AKT
US7612196B2 (en) 2002-11-14 2009-11-03 Dharmacon, Inc. siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B)
US7781575B2 (en) 2002-11-14 2010-08-24 Dharmacon, Inc. siRNA targeting tumor protein 53 (p53)
US7582747B2 (en) 2002-11-14 2009-09-01 Dharmacon, Inc. siRNA targeting inner centromere protein antigens (INCENP)
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US20090023908A1 (en) 2002-11-14 2009-01-22 Dharmacon, Inc. siRNA targeting ribosomal protein S2 (RPS2)
US7951935B2 (en) 2002-11-14 2011-05-31 Dharmacon, Inc. siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC)
US7592442B2 (en) 2002-11-14 2009-09-22 Dharmacon, Inc. siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2)
US20090005548A1 (en) 2002-11-14 2009-01-01 Dharmacon, Inc. siRNA targeting nuclear receptor interacting protein 1 (NRIP1)
US20090030190A1 (en) 2002-11-14 2009-01-29 Dharmacon, Inc. siRNA targeting 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2)
US9879266B2 (en) 2002-11-14 2018-01-30 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US20080207884A1 (en) 2002-11-14 2008-08-28 Dharmacon, Inc. siRNA targeting 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC)
US20080268457A1 (en) 2002-11-14 2008-10-30 Dharmacon, Inc. siRNA targeting forkhead box P3 (FOXP3)
US8937172B2 (en) 2002-11-14 2015-01-20 Thermo Fisher Scientific Inc. siRNA targeting catenin, beta-1 (CTNNB1)
US20090043084A1 (en) 2002-11-14 2009-02-12 Dharmacon, Inc. siRNA targeting minichromosome maintenance deficient 3 (MCM3)
US7619081B2 (en) 2002-11-14 2009-11-17 Dharmacon, Inc. siRNA targeting coatomer protein complex, subunit beta 2 (COPB2)
US9771586B2 (en) 2002-11-14 2017-09-26 Thermo Fisher Scientific Inc. RNAi targeting ZNF205
US8198427B1 (en) 2002-11-14 2012-06-12 Dharmacon, Inc. SiRNA targeting catenin, beta-1 (CTNNB1)
US7635770B2 (en) 2002-11-14 2009-12-22 Dharmacon, Inc. siRNA targeting protein kinase N-3 (PKN-3)
US20100113307A1 (en) 2002-11-14 2010-05-06 Dharmacon, Inc. siRNA targeting vascular endothelial growth factor (VEGF)
US20090182134A1 (en) 2002-11-14 2009-07-16 Dharmacon, Inc. siRNA targeting phosphatases
US20090227780A1 (en) 2002-11-14 2009-09-10 Dharmacon, Inc. siRNA targeting connexin 43
US7977471B2 (en) 2002-11-14 2011-07-12 Dharmacon, Inc. siRNA targeting TNFα
US9839649B2 (en) 2002-11-14 2017-12-12 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US20090005547A1 (en) 2002-11-14 2009-01-01 Dharmacon, Inc. siRNa targeting neuropilin 1 (NRP1)
US20090023907A1 (en) 2002-11-14 2009-01-22 Dharmacon, Inc. siRNA targeting kinesin spindle protein (KSP)
US9719094B2 (en) 2002-11-14 2017-08-01 Thermo Fisher Scientific Inc. RNAi targeting SEC61G
US9719092B2 (en) 2002-11-14 2017-08-01 Thermo Fisher Scientific Inc. RNAi targeting CNTD2
US7691998B2 (en) 2002-11-14 2010-04-06 Dharmacon, Inc. siRNA targeting nucleoporin 62kDa (Nup62)
WO2006006948A2 (en) 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
US10011836B2 (en) 2002-11-14 2018-07-03 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US20080221316A1 (en) 2002-11-14 2008-09-11 Dharmacon, Inc. siRNA targeting ethanolamine Kinase I1 (EKI1)
EP2213738B1 (en) 2002-11-14 2012-10-10 Dharmacon, Inc. siRNA molecules targeting Bcl-2
CA2528963A1 (en) 2003-06-27 2005-01-13 Sirna Therapeutics, Inc. Rna interference mediated treatment of alzheimer's disease using short interfering nucleic acid (sina)
WO2005007854A2 (en) 2003-07-09 2005-01-27 Sirna Therapeutics, Inc. Polycationic compositions for cellular delivery of polynucleotides
WO2005007859A2 (en) 2003-07-11 2005-01-27 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF ACETYL-COA CARBOXYLASE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
WO2005035759A2 (en) 2003-08-20 2005-04-21 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF HYPOXIA INDUCIBLE FACTOR 1 (HIF1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
EP1670915A2 (en) 2003-09-16 2006-06-21 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF HEPATITIS C VIRUS (HCV) EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
WO2005045032A2 (en) 2003-10-20 2005-05-19 Sima Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF EARLY GROWTH RESPONSE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
WO2005045039A2 (en) 2003-10-23 2005-05-19 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF INTERCELLULAR ADHESION MOLECULE (ICAM) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20070185043A1 (en) 2003-10-23 2007-08-09 Sima Therapeutics, Inc. Rna interference mediated inhibition of nogo and nogo receptor gene expression using short interfering nucleic acid (sina)
WO2005045034A2 (en) 2003-10-23 2005-05-19 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED TREATMENT OF PARKINSON DISEASE USING SHORT INTERERING NUCLEIC ACID (siNA)
WO2005045037A2 (en) 2003-10-23 2005-05-19 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF 5-ALPHA REDUCTASE AND ANDROGEN RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
WO2005045038A2 (en) 2003-10-23 2005-05-19 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF GPRA AND AAA1 GENE EXPRESSION USING SHORT NUCLEIC ACID (siNA)
EP1682661A2 (en) 2003-10-23 2006-07-26 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using short interfering nucleic acid (sina)
US20100145038A1 (en) 2003-11-24 2010-06-10 Merck & Co., Inc. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
WO2005105995A2 (en) 2004-04-14 2005-11-10 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED TREATMENT OF POLYGLUTAMINE (POLYQ) REPEAT EXPANSION DISEASES USING SHORT INTERFERING NUCLEIC ACID (siNA)
WO2006017447A1 (en) 2004-08-02 2006-02-16 University Of Iowa Research Foundation Methods of inhibiting vegf-c
US20110313024A1 (en) 2004-08-20 2011-12-22 Leonid Beigelman RNA INTERFERENCE MEDIATED INHIBITION OF PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9 (PCSK9) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US7427605B2 (en) 2005-03-31 2008-09-23 Calando Pharmaceuticals, Inc. Inhibitors of ribonucleotide reductase subunit 2 and uses thereof
WO2007091269A2 (en) 2006-02-08 2007-08-16 Quark Pharmaceuticals, Inc. NOVEL TANDEM siRNAS
ES2564303T3 (es) 2006-04-07 2016-03-21 Idera Pharmaceuticals, Inc. Compuestos de ARN inmunomodulador estabilizado (SIMRA) para TLR7 y TLR8
NZ572666A (en) * 2006-05-11 2010-11-26 Alnylam Pharmaceuticals Inc Compositions comprising double stranded rna and methods for inhibiting expression of the pcsk9 gene
EP2052079A2 (en) * 2006-07-17 2009-04-29 Sirna Therapeutics Inc. Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina)
CA2927045A1 (en) 2006-10-03 2008-04-10 Muthiah Manoharan Lipid containing formulations
DK2410053T4 (da) * 2006-10-18 2020-08-31 Ionis Pharmaceuticals Inc Antisense-forbindelser
MX2009005527A (es) 2006-11-27 2009-06-08 Isis Pharmaceuticals Inc Metodos para el tratamiento de hipercolesterolemia.
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
CN101795715A (zh) 2007-07-09 2010-08-04 艾德拉药物股份有限公司 稳定化免疫调控性rna(simra)化合物
CA2708173C (en) 2007-12-04 2016-02-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
CN101493631B (zh) 2008-01-24 2012-01-25 鸿富锦精密工业（深圳）有限公司 机械快门及使用该机械快门的相机模组
WO2009134487A2 (en) * 2008-01-31 2009-11-05 Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of dsrna targeting the pcsk9 gene
NZ588583A (en) 2008-04-15 2012-08-31 Protiva Biotherapeutics Inc Novel lipid formulations for nucleic acid delivery
CA2764158A1 (en) 2009-06-01 2010-12-09 Halo-Bio Rnai Therapeutics, Inc. Polynucleotides for multivalent rna interference, compositions and methods of use thereof
TR201811076T4 (tr) 2009-06-10 2018-08-27 Arbutus Biopharma Corp Geliştirilmiş lipit formulasyonu.
EA201270019A1 (ru) 2009-06-15 2012-06-29 Элнилэм Фармасьютикалз, Инк. Двуцепочечная рнк, включенная в липидный состав и мишенью которой является ген pcsk9
ES2538347T3 (es) 2009-08-27 2015-06-19 Idera Pharmaceuticals, Inc. Composiciones para inhibir expresión genética y usos de las mismas
US8562589B2 (en) 2009-12-24 2013-10-22 Rani Therapeutics, Llc Swallowable drug delivery device and method of delivery
US20130289094A1 (en) 2010-10-29 2013-10-31 Alnylam Pharmaceuticals, Inc. Compositions and Methods for Inhibition of PCSK9 Genes
CN104105790A (zh) 2011-11-18 2014-10-15 阿尔尼拉姆医药品有限公司 修饰的RNAi试剂
ES2800065T3 (es) 2011-11-18 2020-12-23 Alnylam Pharmaceuticals Inc Agentes de iARN, composiciones y métodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (TTR)
ES2657608T3 (es) * 2012-12-05 2018-03-06 Alnylam Pharmaceuticals, Inc. Composiciones de arni de pcsk9 y métodos de uso de las mismas
US9513606B1 (en) 2013-04-05 2016-12-06 The Boeing Company Safety systems and methods for production environments
US10833934B2 (en) 2015-06-30 2020-11-10 British Telecommunications Public Limited Company Energy management in a network
EP3340994A1 (en) 2015-08-25 2018-07-04 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder
US10799808B2 (en) 2018-09-13 2020-10-13 Nina Davis Interactive storytelling kit
CN111845757A (zh) 2019-04-30 2020-10-30 通用汽车环球科技运作有限责任公司 分心驾驶消除系统
CN110649043B (zh) 2019-09-30 2021-11-19 厦门天马微电子有限公司 阵列基板、显示面板、显示装置及阵列基板的制备方法
KR102318555B1 (ko) 2020-03-19 2021-10-29 한국과학기술연구원 광소자용 역나노콘과 그 제조방법

Also Published As

Publication number Publication date
DK2929031T5 (da) 2021-08-23
CN108220295A (zh) 2018-06-29
KR20150091097A (ko) 2015-08-07
CA2892160C (en) 2021-03-23
NO2021024I1 (no) 2021-06-04
LTPA2021510I1 (hu) 2021-06-25
AR093835A1 (es) 2015-06-24
EP2929031A1 (en) 2015-10-14
HK1256621A1 (zh) 2019-09-27
BR112015013105B1 (pt) 2022-02-08
US10125369B2 (en) 2018-11-13
FR21C1021I1 (hu) 2021-07-16
NZ749002A (en) 2020-10-30
AU2020201441A1 (en) 2020-03-19
MX2015007035A (es) 2015-09-25
CY1120195T1 (el) 2018-12-12
AU2013355237B2 (en) 2019-11-28
AU2013355237A1 (en) 2015-07-02
BR112015013105A2 (pt) 2017-09-12
JP6574383B2 (ja) 2019-09-11
EP2929031B1 (en) 2017-10-25
AU2022224712A1 (en) 2022-11-10
US20230002772A1 (en) 2023-01-05
KR102096014B9 (ko) 2020-04-03
LUC00209I2 (hu) 2022-10-07
JP2016506240A (ja) 2016-03-03
MX2019009283A (es) 2019-12-11
ES2657608T3 (es) 2018-03-06
IL292159A (en) 2022-06-01
LTC2929031I2 (hu) 2022-10-10
WO2014089313A1 (en) 2014-06-12
CA2892160A1 (en) 2014-06-12
CN104854242A (zh) 2015-08-19
NL301107I1 (nl) 2021-06-09
EP2929031B9 (en) 2020-08-12
JP2021097680A (ja) 2021-07-01
IL238917A0 (en) 2015-07-30
RS56783B9 (sr) 2021-12-31
KR20200035490A (ko) 2020-04-03
FR21C1021I2 (fr) 2022-04-22
PL2929031T3 (pl) 2018-04-30
EP4083209A1 (en) 2022-11-02
PT2929031T (pt) 2018-01-19
JP7239335B2 (ja) 2023-03-14
JP2023103244A (ja) 2023-07-26
EP3336187A1 (en) 2018-06-20
ZA201503829B (en) 2020-05-27
HK1213598A1 (zh) 2016-07-08
PL2929031T4 (pl) 2022-06-27
HRP20180126T2 (hr) 2021-08-20
NZ709013A (en) 2020-01-31
LT2929031T (lt) 2018-02-12
CN104854242B (zh) 2018-03-16
HRP20180126T1 (hr) 2018-02-23
CN108220295B (zh) 2022-09-02
RS56783B1 (sr) 2018-04-30
JP2019103501A (ja) 2019-06-27
MX367076B (es) 2019-08-05
AU2013355237C1 (en) 2022-09-22
US20160017335A1 (en) 2016-01-21
DK2929031T3 (da) 2018-01-29
SI2929031T1 (en) 2018-02-28
IL238917B (en) 2022-05-01
HUS2100021I1 (hu) 2021-06-28
NL301107I2 (nl) 2021-06-24
KR102096014B1 (ko) 2020-04-03

Similar Documents

Publication Publication Date Title
US20230002772A1 (en) PCSK9 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
US11130953B2 (en) Angiopoietin-like 3 (ANGPTL3) iRNA compositions and methods of use thereof
US20160354404A1 (en) Compositions and Methods for Inhibition of PCSK9 Genes
WO2011038031A1 (en) Dual targeting sirna agents
RU2774821C2 (ru) КОМПОЗИЦИИ иРНК ДЛЯ СХОДНОГО С АНГИОПОЭТИНОМ 3 (ANGPTL3) БЕЛКА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
EA037110B1 (ru) КОМПОЗИЦИИ С иРНК К PCSK9 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
EA042137B1 (ru) КОМПОЗИЦИИ НА ОСНОВЕ iRNA TMPRSS6 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ