SI2929031T1 - Sestavki PCSK9 IRNA in postopki njihove uporabe - Google Patents
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Claims (15)
1. Sredstvo dvovijačne RNAi zmožno inhibicije izražanja proprotein konvertaze substilin/keksin 9 (PCSK9) v celici, kjer omenjeno sredstvo dvovijačne RNAi vsebuje: (a) smiselno vijačnico komplementarno s protismiselno vijačnico, kjer omenjena protismiselna vijačnica vsebuje področje, kije komplementarno z delom mRNA, ki kodira PCSK9, kjer ima vsaja vijačnica dolžino od približno 17 do približno 30 nukleotidov, kjer omenjena protismiselna vijačnica vsebuje vsaj 17 nukleotidov iz nukleobaznega zaporedja ACAAAAGCAAAACAGGUCUAG (SEQ ID NO: 412) in je sredstvo dvovijačne RNAi predstavljeno s formulo (III): smiselna: 5 νΗΚΧΧΧ^-^-ΥΥΥ-^-ίΖΖΖνΝ.-η^’ protismiselna: 3’np’-Na’-(X,X’X’)k-Nb-Y’Y,Y,-Nb,-(Z’Z’Z,)i-Na’-nq,5’ (III) kjer: je vsak i, j, k in 1 neodvisno 0 ali 1; p, p', q in q' neodvisno od 0 do 6; vsak Na in Na' neodvisno predstavlja oligonukleotidno zaporedje, ki vsebuje od 0 do 25 nukleotidov, ki so ali modificirani ali nemodificirani ali njihove kombinacije, kjer vsako zaporedje vsebuje vsaj dva različno modificirana nukleotida; vsaj Nb in Nb' neodvisno predstavlja oligonukleotidno zaporedje, ki vsebuje od 0 do 10 nukleotidov, ki so ali modificirani ali nemodificirani ali njihove kombinacije; vsak np, np', nq in nq', od katerih je vsak lahko prisoten ali ne, neodvisno predstavlja štrleči nukleotid; vsak XXX, ΥΥΥ, ZZZ, Χ'Χ'Χ', ΥΎΎ' in Ζ'Ζ’Ζ' neodvisno predstavlja ‘en *··*··* motiv izmed treh identičnih modifikacij na treh zaporednih nukleotidih; modifikacije na Nb se razlikujejo od modifikacij na Y in modifikacije na Nb' se razlikujejo od modifikacij na Y; kjer so modifikacije na nukleotidih 2'-0-metil ali 2'-fluoro modifikacije; in kjer je ligand eden ali več derivatov GalNAc, pripetih preko bivalentnega ali trivalentnega razvejanega linkeija; ali (b) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja asCfsaAfAfAfgCfaAfaAfcAfgGfuCfuagsasa in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja csusagacCfuGfudTuugcuuuugu, kjer so a, g, c in u 2'-0-metil (2'-OMe) modificirani nukleotidi A, G, C in U; Af, Gf, Cf in Uf so 2'-fluoro modificirani nukleotidi A, G, C in U; dT je deoksi-timin nukleotid in je fosforotioatna povezava; in, kjer je smiselna vijačnica konjugirana na vsaj en ligand.
2. Sredstvo dvovijačne RNAi po zahtevku 1, kjer (a) protismiselna vijačnica vsebuje nukleobazno zaporedje ACAAAAGCAAAACAGGUCUAGAA (SEQ ID NO: 418); (b) smiselna vijačnica vsebuje nukleobazno zaporedje AGACCUGUUUUGCUUUUGU (SEQ ID NO: 191); (c) smiselna vijačnica vsebuje nukleobazno zaporedje CUAGACCUGUUUUGCUUUUGU (SEQ ID NO: 197); (d) protismiselna vijačnica vsebuje nukleobazno zaporedje ACAAAAGCAAAACAGGUCUAGAA (SEQ ID NO: 418) in smiselna vijačnica vsebuje nukleobazno zaporedje CU AGACCUGUUUUGCUUUUGU (SEQ ID NO: 197); (e) protismiselna vijačnica vsebuje nukleobazno zaporedje ACAAAAGCAAAACAGGUCUAG (SEQ ID NO: 412) in smiselna vijačnica vsebuje nukleobazno zaporedje AGACCUGUUUUGCUUUUGU (SEQ ID NO: 191); ali (f) protismiselna vijačnica vsebuje nukleobazno zaporedje ACAAAAGCAAAACAGGUCUAGAA (SEQ ID NO: 418) in smiselna vijačnica vsebuje nukleobazno zaporedje CUAGACCUGUTUUGCUUUUGU (SEQ ID NO: 1665).
3. Sredstvo dvovijačne RNAi po zahtevku 1, kjer ima dvovijačno področje dolžino od 17 do 23 nukleotidnih parov, od 17 do 25 nukleotidnih parov, od 23 do 27 nukleotidnih parov, od 19 do 21 nukleotidnih parov ali od 21 do 23 nukleotidnih parov.
4. Sredstvo dvovijačne RNAi po zahtevku 1, kjer dsRNA vsebuje: (a) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja aCfaAfaAfgCfaAfaacAfgGfuCfuAfgsAfsa (SEQ ID NO: 1151) in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja CfuAfgAfcCfuGfUfUfuUfgCfuUfuUfgUf (SEQ ID NO: 600); (b) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja aCfaAfAfAfgCfaAfaacAfgGfuCfuAfgsAfsa (SEQ ID NO: 1246) in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja CfuAfgAfcCfuGfUfUfuUfgCfuuuUfgUf (SEQ ID NO: 695); (c) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja aCfaaaAfgCfaAfaacAfgGfuCfuAfgsAfsa (SEQ ID NO: 1253) in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja CiuAfgAfcCfuGfUfUfuUfgCfuUfUfUfgUf (SEQ ID NO: 702); (d) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja aCfaAfAfAfgCfaAfaacAfgGfuCfiisAfsg (SEQ ID NO: 1263) in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja AfgAfcCfuGfUfUfuUfgCfuuuUfgUf (SEQ ID NO: 712); (e) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja aCfaaaAfgCfaAfaacAfgGfuCfusAfsg (SEQ ID NO: 1269) in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja AfgAfcCfuGfUfUiuUfgCfuUfUfUfgUf (SEQ ID NO: 718); (f) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja asCfsaAfaAfgCfaAfaacAfgGfuCfuAfgsasa (SEQ ID NO: 1369) in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja ..... CfsusAfgAfcCfuGfUfUfuUfgCfuUfuUfgUf (SEQ ID NO: 818); (g) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja asCfsaAfaagCfaAfaacAfgGfucuAfgsasa in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja CfsusAfgAfcCfuGfUfUfuUfgcuuuugu; ali (h) protismiselno vijačnico, ki sestoji iz nukleotidnega zaporedja asCfsaAfaAfsgCfaAfaacAfgGfuCfsuAfgsasa (SEQ ID NO: 1400) in smiselno vijačnico, ki sestoji iz nukleotidnega zaporedja CfsusAfgAfcCfuGfUfUfuUfgCfsuUfsuUfsgsUfs (SEQ ID NO: 849); kjer so a, g, c in u 2'-0-metil (2'-OMe) modificirani nukleotidi A, G, C in U; Af, Gf, Cf in Uf so 2'-fluoro modificirani nukleotidi A, G, C in U; dT je deoksi-timin nukleotid in s je fosforotioatna povezava.
5. Sredstvo dvovijačne RNAi po kateremkoli zahtevku od 1 do 4, kjer je ligand
6. Sredstvo dvovijačne RNAi po kateremkoli zahtevku od 1 do 5, kjer je ligand pripet na konec 3' smiselne vijačnice.
7. Sredstvo dvovijačne RNAi po zahtevku 6, kjer je sredstvo RNAi konjugirano na ligand, prikazan na naslednji shemi
kjer X predstavlja O ali S.
8. Sredstvo dvovijačne RNAi po kateremkoli zahtevku od 1 do 7, kjer ima ..... smiselna vijačnica skupno 21 nukleotidov in ima protismiselna vijačnica skupno 23 nukleotidov.
9. In vitro celica, ki vsebuje sredstvo dvovijačne RNAi po kateremkoli zahtevku od 1 do 8.
10. Farmacevtski sestavek, ki vsebuje sredstvo dvovijačne RNAi po kateremkoli zahtevku od 1 do 8.
11. Farmacevtski sestavek po zahtevku 10, kjer (a) je omenjeno sredstvo RNAi namenjeno administraciji v nepufirani raztopini, kjer je omenjena nepufirana raztopina prednostno slanica ali voda; ali (b) je omenjeno sredstvo RNAi namenjeno administraciji z raztopino pufra, kjer je omenjena raztopina pufra prednostno vsebuje acetat, citrat, prolamin, karbonat ali fosfat ali katerokoli njihovo kombinacijo in, kjer je omenjena raztopina pufra najbolj prednostno fiziološka raztopina s fosfatnim pufrom (PBS).
12. Postopek inhibiranja izražanja PCSK9 v celici, kjer postopek obsega: (a) kontaktiranje celice s sredstvom dvovijačne RNAi, po kateremkoli zahtevku od 1 do 8 ali s farmacevtskim sestavkom po kateremkoli zahtevku 10 ali 11; in (b) vzdrževanje celice pridobljene v koraku (a) dovolj časa, da dosežemo degradacijo transkripta mRNA k gena PCSK9, s čimer inhibiramo izražanje gena PCSK9 v celici, kjer so postopki zdravljenja človeškega ali živalskega živega telesa s terapijo izključeni.
13. dsRNA po kateremkoli zahtevku od 1 do 8 ali farmacevtski sestavek po zahtevku 10 ali 11 za uporabo v postopku zdravljenja subjekta, ki ima motnjo, pri kateri posreduje izražanje PCSK9.
»·· · · 14. dsRNA ali farmacevtski sestavek za uporabo po zahtevku 13, kjer (a) je subjekt človek; (b) motnja je hiperholesterolemija; (c) sredstvo dvovijačne RNAi bo administrirano v odmerku od približno 0.01 mg/kg do približno 10 mg/kg, približno 0.5 mg/kg do približno 50 mg/kg ali od približno 10 mg/kg do približno 30 mg/kg; in/ali (d) sredstvo dvovijačne RNAi bo administrirano subkutano ali intravenozno.
15. dsRNA ali farmacevtski sestavek za uporabo po zahtevku 13 ali 14, kjer bo omenjeno sredstvo RNAi administrirano v dozirnem režimu, ki obsega fazo nalaganja, kiji sledi faza vzdrževanja, kjer faza nalaganja vsebuje administracijo odmerka 2 mg/kg, 1 mg/kg ali 0.5 mg/kg, petkrat na teden, in kjer faza vzdrževanja vsebuje administracijo odmerka 2 mg/kg, 1 mg/kg ali 0.5 mg/kg enkrat na teden, dvakrat na teden, trikrat na teden, enkrat na vsaka dva tedna, enkrat na vsake tri tedne, enkrat na mesec, enkrat na vsaka dva meseca, enkrat na vsake tri mesece, enkrat na vsake štiri mesece, enkrat na vsakih pet mesecev ali enkrat na vsakih šest mesecev.
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Application Number | Priority Date | Filing Date | Title |
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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 | |
PCT/US2013/073349 WO2014089313A1 (en) | 2012-12-05 | 2013-12-05 | PCSK9 iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
EP13811327.9A EP2929031B9 (en) | 2012-12-05 | 2013-12-05 | Pcsk9 irna compositions and methods of use thereof |
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Families Citing this family (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK3366775T3 (da) * | 2011-11-18 | 2022-08-01 | Alnylam Pharmaceuticals Inc | Modificerede rnai-midler |
BR112015013105B1 (pt) * | 2012-12-05 | 2022-02-08 | Alnylam Pharmaceuticals, Inc | Agente de rnai de fita dupla capaz de inibir a expressão de pcsk9, seus usos, composição farmacêutica e método de inibição da expressão de pcsk9 em uma célula in vitro |
EP3019200B1 (en) * | 2013-07-11 | 2022-03-23 | Alnylam Pharmaceuticals, Inc. | Oligonucleotide-ligand conjugates and process for their preparation |
EP3812462A1 (en) | 2014-08-20 | 2021-04-28 | Alnylam Pharmaceuticals, Inc. | Modified double-stranded rna agents |
US20170304459A1 (en) * | 2014-10-10 | 2017-10-26 | 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 |
US10633653B2 (en) | 2015-08-14 | 2020-04-28 | University Of Massachusetts | Bioactive conjugates for oligonucleotide delivery |
IL293355B2 (en) * | 2015-08-25 | 2024-07-01 | Alnylam Pharmaceuticals Inc | Methods and preparations for the treatment of a disorder related to the PCSK9 gene |
EP3408391A4 (en) | 2016-01-31 | 2019-08-28 | University of Massachusetts | BRANCHED OLIGONUCLEOTIDES |
US20190255143A1 (en) | 2016-04-18 | 2019-08-22 | The Trustees Of Columbia University In The City Of New York | Therapeutic targets involved in the progression of nonalcoholic steatohepatitis (nash) |
CA3033368A1 (en) | 2016-08-12 | 2018-02-15 | 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 |
CN118325899A (zh) | 2017-01-23 | 2024-07-12 | 瑞泽恩制药公司 | Hsd17b13变体及其应用 |
JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
DK3607069T3 (da) | 2017-04-05 | 2022-11-21 | Silence Therapeutics Gmbh | Produkter og sammensætninger |
MX2019012169A (es) | 2017-04-11 | 2019-12-11 | Regeneron Pharma | Ensayos para evaluar la actividad de moduladores de miembros de la familia de hidroxiesteroide (17-beta) deshidrogenasa (hsd17b). |
BR112019020148A2 (pt) | 2017-04-13 | 2020-05-05 | Cadila Healthcare Ltd | peptídeo |
JP7406793B2 (ja) | 2017-06-23 | 2023-12-28 | ユニバーシティー オブ マサチューセッツ | 2テイル自己デリバリー型siRNAおよび関連方法 |
MX2020003561A (es) | 2017-10-11 | 2020-08-03 | Regeneron Pharma | Inhibicion de la hsd17b13 en el tratamiento de la enfermedad hepatica en pacientes que expresan la variacion pnpla3 i148m. |
CN118291456A (zh) | 2017-12-01 | 2024-07-05 | 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 |
WO2019105418A1 (zh) | 2017-12-01 | 2019-06-06 | 苏州瑞博生物技术有限公司 | 双链寡核苷酸、含双链寡核苷酸的组合物与缀合物及制备方法和用途 |
EP3719126A4 (en) | 2017-12-01 | 2021-10-20 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, COMPOSITION AND CONJUGATE CONTAINING NUCLEIC ACID, ASSOCIATED PREPARATION PROCESS AND USE |
JP7360716B2 (ja) | 2017-12-01 | 2023-10-13 | スーチョウ リボ ライフ サイエンス カンパニー、リミテッド | 核酸、当該核酸を含む組成物および複合体ならびに調製方法と使用 |
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 |
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 |
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 |
AU2018394875B2 (en) | 2017-12-29 | 2023-08-03 | Suzhou Ribo Life Science Co., Ltd. | Conjugates and preparation and use thereof |
KR20210018267A (ko) * | 2018-05-07 | 2021-02-17 | 알닐람 파마슈티칼스 인코포레이티드 | 간외 전달 |
EP3842534A4 (en) | 2018-08-21 | 2022-07-06 | Suzhou Ribo Life Science Co., Ltd. | NUCLEIC ACID, COMPOSITION AND CONJUGATE CONTAINING NUCLEIC ACID AND METHOD OF USE THEREOF |
CN111655297A (zh) | 2018-09-30 | 2020-09-11 | 苏州瑞博生物技术有限公司 | 一种siRNA缀合物及其制备方法和用途 |
CA3124090A1 (en) | 2018-12-19 | 2020-06-25 | Alnylam Pharmaceuticals, Inc. | Amyloid precursor protein (app) rnai agent compositions and methods of use thereof |
US20230313195A1 (en) * | 2019-05-22 | 2023-10-05 | Suzhou Ribo Life Science Co., Ltd. | Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use |
JP2022547790A (ja) | 2019-08-09 | 2022-11-16 | ユニバーシティー オブ マサチューセッツ | Snpを標的とする化学修飾オリゴヌクレオチド |
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 |
WO2021041247A1 (en) * | 2019-08-23 | 2021-03-04 | University Of 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 |
CN117795072A (zh) * | 2021-06-17 | 2024-03-29 | 圣诺制药公司 | 产品和组合物 |
CN115572241B (zh) * | 2021-06-21 | 2024-08-30 | 润佳(苏州)医药科技有限公司 | 双价化合物、偶联物及其用途 |
BR112023026862A2 (pt) | 2021-06-23 | 2024-03-05 | Beth Israel Deaconess Medical Ct Inc | Compostos de oligonucleotídeos anti-flt1 otimizados para tratamento de pré-eclâmpsia e outros distúrbios angiogênicos |
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 Khan | Treatment of cardiovascular disease |
WO2023109945A1 (zh) * | 2021-12-16 | 2023-06-22 | 上海拓界生物医药科技有限公司 | 一种dsRNA、其制备方法及应用 |
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 |
WO2024083220A1 (zh) * | 2022-10-21 | 2024-04-25 | 上海京新生物医药有限公司 | 配体-寡核苷酸共轭物及用于该共轭物的接头 |
CN118086311B (zh) * | 2023-05-25 | 2024-08-09 | 苏州时安生物技术有限公司 | 抑制PCSK9基因表达的siRNA、其缀合物和药物组合物及用途 |
CN116854754B (zh) * | 2023-09-01 | 2023-12-12 | 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)
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 |
US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear 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 |
US5677195A (en) | 1991-11-22 | 1997-10-14 | 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 |
AU4528493A (en) | 1992-06-04 | 1994-01-04 | Regents Of The University Of California, The | In vivo gene therapy with intron-free sequence of interest |
JPH07508410A (ja) | 1992-06-18 | 1995-09-21 | ジェンファーム インターナショナル インコーポレイテッド | 酵母人工染色体を有するトランスジェニック非ヒト動物の製造方法 |
EP0654077A4 (en) | 1992-07-17 | 1996-03-13 | Ribozyme Pharm Inc | PROCESS AND REAGENT FOR THE TREATMENT OF DISEASES IN ANIMALS. |
US5783701A (en) | 1992-09-08 | 1998-07-21 | Vertex Pharmaceuticals, Incorporated | Sulfonamide inhibitors of aspartyl protease |
EP0905253A3 (en) | 1992-12-03 | 2000-11-02 | Genzyme Corporation | Adenoviral vector deleted of all E4-ORF except ORF6 |
US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
DE69422163T2 (de) | 1993-02-19 | 2000-06-15 | Nippon Shinyaku Co., Ltd. | Glycerolderivat, vorrichtung und pharmazeutische zusammensetzung |
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 |
EP0833613A1 (en) | 1995-05-26 | 1998-04-08 | Somatix Therapy Corporation | Delivery vehicles comprising stable lipid/nucleic acid complexes |
US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
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 |
US5545531A (en) | 1995-06-07 | 1996-08-13 | Affymax Technologies N.V. | Methods for making a device for concurrently processing multiple biological chip assays |
IL122290A0 (en) | 1995-06-07 | 1998-04-05 | Inex Pharmaceuticals Corp | Lipid-nucleic acid complex its preparation and use |
US5858397A (en) | 1995-10-11 | 1999-01-12 | University Of British Columbia | Liposomal formulations of mitoxantrone |
CA2234931C (en) | 1995-10-16 | 2010-01-19 | 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 |
AU731909B2 (en) | 1997-07-01 | 2001-04-05 | 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 |
TR200002402T2 (tr) | 1997-12-24 | 2001-01-22 | Vertex Pharmaceuticals Incorporated | Aspartil proteaz inhibitörü ön-ilaçlar. |
WO2000003683A2 (en) | 1998-07-20 | 2000-01-27 | Inex Pharmaceuticals Corporation | Liposomal encapsulated nucleic acid-complexes |
MXPA01003643A (es) | 1998-10-09 | 2003-07-21 | Ingene Inc | Produccion de adnss in vivo. |
IL142490A0 (en) | 1998-10-09 | 2002-03-10 | Ingene Inc | ENZYMATIC SYNTHESIS OF ssDNA |
US6319946B1 (en) | 1999-02-12 | 2001-11-20 | Vertex Pharmaceuticals Incorporated | Inhibitors of aspartyl protease |
AU3243300A (en) | 1999-02-23 | 2000-09-14 | Isis Pharmaceuticals, Inc. | Multiparticulate formulation |
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 |
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) |
US7833992B2 (en) | 2001-05-18 | 2010-11-16 | Merck Sharpe & Dohme | Conjugates and compositions for cellular delivery |
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) |
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) |
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 |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
US20050282188A1 (en) | 2001-05-18 | 2005-12-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of 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) |
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) |
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) |
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) |
US20080161256A1 (en) | 2001-05-18 | 2008-07-03 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of 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) |
US9994853B2 (en) | 2001-05-18 | 2018-06-12 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
US20060217331A1 (en) | 2001-05-18 | 2006-09-28 | Sirna Therapeutics, Inc. | Chemically modified double stranded nucleic acid molecules that mediate RNA interference |
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) |
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) |
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) |
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) |
US20070042983A1 (en) | 2001-05-18 | 2007-02-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of 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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
US20050137155A1 (en) | 2001-05-18 | 2005-06-23 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of Parkinson disease 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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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 |
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) |
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) |
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) |
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) |
US20050119211A1 (en) | 2001-05-18 | 2005-06-02 | Sirna Therapeutics, Inc. | RNA mediated inhibition connexin 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) |
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) |
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) |
US20070270579A1 (en) | 2001-05-18 | 2007-11-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of 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) |
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) |
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) |
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) |
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) |
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) |
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) |
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 |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
US20050222064A1 (en) | 2002-02-20 | 2005-10-06 | Sirna Therapeutics, Inc. | Polycationic compositions for cellular delivery of polynucleotides |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
EP1520022B1 (en) | 2002-07-10 | 2015-07-22 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | 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 |
US8937172B2 (en) | 2002-11-14 | 2015-01-20 | Thermo Fisher Scientific Inc. | siRNA targeting catenin, beta-1 (CTNNB1) |
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) |
US20090030190A1 (en) | 2002-11-14 | 2009-01-29 | Dharmacon, Inc. | siRNA targeting 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) |
US20090023908A1 (en) | 2002-11-14 | 2009-01-22 | Dharmacon, Inc. | siRNA targeting ribosomal protein S2 (RPS2) |
US20090023907A1 (en) | 2002-11-14 | 2009-01-22 | Dharmacon, Inc. | siRNA targeting kinesin spindle protein (KSP) |
US9879266B2 (en) | 2002-11-14 | 2018-01-30 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
US20080268457A1 (en) | 2002-11-14 | 2008-10-30 | Dharmacon, Inc. | siRNA targeting forkhead box P3 (FOXP3) |
US20080161547A1 (en) | 2002-11-14 | 2008-07-03 | Dharmacon, Inc. | siRNA targeting serine/threonine protein kinase AKT |
US7635770B2 (en) | 2002-11-14 | 2009-12-22 | Dharmacon, Inc. | siRNA targeting protein kinase N-3 (PKN-3) |
US20090182134A1 (en) | 2002-11-14 | 2009-07-16 | Dharmacon, Inc. | siRNA targeting phosphatases |
US7582747B2 (en) | 2002-11-14 | 2009-09-01 | Dharmacon, Inc. | siRNA targeting inner centromere protein antigens (INCENP) |
US20080207884A1 (en) | 2002-11-14 | 2008-08-28 | Dharmacon, Inc. | siRNA targeting 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) |
US20090005548A1 (en) | 2002-11-14 | 2009-01-01 | Dharmacon, Inc. | siRNA targeting nuclear receptor interacting protein 1 (NRIP1) |
US7977471B2 (en) | 2002-11-14 | 2011-07-12 | Dharmacon, Inc. | siRNA targeting TNFα |
US7612196B2 (en) | 2002-11-14 | 2009-11-03 | Dharmacon, Inc. | siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B) |
US20080221316A1 (en) | 2002-11-14 | 2008-09-11 | Dharmacon, Inc. | siRNA targeting ethanolamine Kinase I1 (EKI1) |
US20100113307A1 (en) | 2002-11-14 | 2010-05-06 | Dharmacon, Inc. | siRNA targeting vascular endothelial growth factor (VEGF) |
WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
US9719092B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting CNTD2 |
US20090005547A1 (en) | 2002-11-14 | 2009-01-01 | Dharmacon, Inc. | siRNa targeting neuropilin 1 (NRP1) |
US7781575B2 (en) | 2002-11-14 | 2010-08-24 | Dharmacon, Inc. | siRNA targeting tumor protein 53 (p53) |
US20090043084A1 (en) | 2002-11-14 | 2009-02-12 | Dharmacon, Inc. | siRNA targeting minichromosome maintenance deficient 3 (MCM3) |
US7691998B2 (en) | 2002-11-14 | 2010-04-06 | Dharmacon, Inc. | siRNA targeting nucleoporin 62kDa (Nup62) |
US9228186B2 (en) | 2002-11-14 | 2016-01-05 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
US9719094B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting SEC61G |
DK2284266T3 (da) | 2002-11-14 | 2014-01-13 | Thermo Fisher Scient Biosciences Inc | sIRNA-MOLEKYLE MOD TP53 |
US20090227780A1 (en) | 2002-11-14 | 2009-09-10 | Dharmacon, Inc. | siRNA targeting connexin 43 |
US8198427B1 (en) | 2002-11-14 | 2012-06-12 | Dharmacon, Inc. | SiRNA targeting catenin, beta-1 (CTNNB1) |
US9839649B2 (en) | 2002-11-14 | 2017-12-12 | Thermo Fisher Scientific 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 |
US9771586B2 (en) | 2002-11-14 | 2017-09-26 | Thermo Fisher Scientific Inc. | RNAi targeting ZNF205 |
US7619081B2 (en) | 2002-11-14 | 2009-11-17 | Dharmacon, Inc. | siRNA targeting coatomer protein complex, subunit beta 2 (COPB2) |
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) |
JP2007505606A (ja) | 2003-09-16 | 2007-03-15 | サーナ・セラピューティクス・インコーポレイテッド | 低分子干渉核酸(siNA)を使用したC型肝炎ウィルス(HCV)発現のRNA干渉媒介性抑制 |
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) |
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) |
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) |
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) |
WO2005044981A2 (en) | 2003-10-23 | 2005-05-19 | 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) |
US7858769B2 (en) | 2004-02-10 | 2010-12-28 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using multifunctional short interfering nucleic acid (multifunctional siNA) |
EP1735443A2 (en) | 2004-04-14 | 2006-12-27 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED TREATMENT OF POLYGLUTAMINE (POLYQ) REPEAT EXPANSION DISEASES USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US7150970B2 (en) | 2004-08-02 | 2006-12-19 | 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) |
AU2006230436B2 (en) | 2005-03-31 | 2011-11-24 | 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 |
WO2007117686A2 (en) | 2006-04-07 | 2007-10-18 | Idera Pharmaceuticals, Inc. | Stabilized immune modulatory rna (simra) compounds for tlr7 and tlr8 |
AU2007249329C1 (en) | 2006-05-11 | 2011-03-24 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the PCSK9 gene |
CA2658183A1 (en) * | 2006-07-17 | 2008-01-24 | Sirna Therapeutics Inc. | Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina) |
WO2008042973A2 (en) | 2006-10-03 | 2008-04-10 | Alnylam Pharmaceuticals, Inc. | Lipid containing formulations |
DK2092065T4 (da) * | 2006-10-18 | 2019-10-21 | Ionis Pharmaceuticals Inc | Antisense-forbindelser |
US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
MX2009005527A (es) | 2006-11-27 | 2009-06-08 | Isis Pharmaceuticals Inc | Metodos para el tratamiento de hipercolesterolemia. |
EP2357231A2 (en) | 2007-07-09 | 2011-08-17 | Idera Pharmaceuticals, Inc. | Stabilized immune modulatory RNA (SIMRA) compounds |
EP4074344A1 (en) | 2007-12-04 | 2022-10-19 | Arbutus Biopharma Corporation | 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 |
BRPI0907008A2 (pt) * | 2008-01-31 | 2015-07-07 | Alnylam Pharmaceuticals Inc | Métodos otimizados para liberação de dsrna alvejando o gene pcsk9 |
CA2721333C (en) | 2008-04-15 | 2020-12-01 | Protiva Biotherapeutics, Inc. | Novel lipid formulations for nucleic acid delivery |
US9200276B2 (en) | 2009-06-01 | 2015-12-01 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent RNA interference, compositions and methods of use thereof |
PL3431076T3 (pl) | 2009-06-10 | 2022-01-31 | Arbutus Biopharma Corporation | Ulepszona formulacja lipidowa |
KR20120050429A (ko) | 2009-06-15 | 2012-05-18 | 알닐람 파마슈티칼스 인코포레이티드 | Pcsk9 유전자를 표적으로 하는 지질 제형된 dsrna |
HUE026020T2 (en) | 2009-08-27 | 2016-05-30 | Idera Pharmaceuticals Inc | Preparation for inhibiting gene expression and its uses |
US8759284B2 (en) | 2009-12-24 | 2014-06-24 | Rani Therapeutics, Llc | Therapeutic agent preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device |
WO2012058693A2 (en) * | 2010-10-29 | 2012-05-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibition of pcsk9 genes |
DK3366775T3 (da) | 2011-11-18 | 2022-08-01 | Alnylam Pharmaceuticals Inc | Modificerede rnai-midler |
DK3301177T3 (da) | 2011-11-18 | 2020-06-15 | Alnylam Pharmaceuticals Inc | Rnai-midler, sammensætninger og fremgangsmåder til anvendelse deraf til behandling af transthyretin (ttr)-forbundne sygdomme |
BR112015013105B1 (pt) | 2012-12-05 | 2022-02-08 | Alnylam Pharmaceuticals, Inc | Agente de rnai de fita dupla capaz de inibir a expressão de pcsk9, seus usos, composição farmacêutica e método de inibição da expressão de pcsk9 em uma célula in vitro |
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 |
IL293355B2 (en) | 2015-08-25 | 2024-07-01 | Alnylam Pharmaceuticals Inc | Methods and preparations for the treatment of a disorder related to the PCSK9 gene |
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 |
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