DK2632472T3 - Rna-interferensmedieret hæmning af genekspression ved anvendelse af korte interfererende nukleinsyrer (sina) - Google Patents

Rna-interferensmedieret hæmning af genekspression ved anvendelse af korte interfererende nukleinsyrer (sina) Download PDF

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DK2632472T3
DK2632472T3 DK11836946.1T DK11836946T DK2632472T3 DK 2632472 T3 DK2632472 T3 DK 2632472T3 DK 11836946 T DK11836946 T DK 11836946T DK 2632472 T3 DK2632472 T3 DK 2632472T3
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nucleotides
nucleotide
sina
deoxy
nucleic acid
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Mark Cancilla
James J Cunningham
W Michael Flanagan
Henry J Haringsma
Denise Kenski
Matthew G Stanton
Steven M Stirdivant
Aarron Willingham
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Sirna Therapeutics Inc
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Claims (24)

1. Sammensætning, der omfatter: I) et dobbeltstrenget kort interfererende nukleinsyre (siNA) molekyle, der hæmmer ekspressionen af et målgen ved hjælp af RNA-interferens, som har en sense-streng og en antisense-streng og omfatter formel (A):
(A) hvor den øverste streng er sense-strengen, og den nederste streng er antisense-strengen af det dobbeltstrengede nukleinsyremolekyle; hvor antisense-strengen omfatter en sekvens, der har mindst 15 nukleotider, der er komplementære til en mål-RNA-sekvens, der kodes af målgenet, og sense-strengen omfatter en sekvens, der er komplementær til antisense-strengen; hver N uafhængigt er et nukleotid, der er umodificeret eller kemisk modificeret eller eventuelt er et ikke-nukleotid; hver B uafhængigt er en terminal cap, der er til stede eller fraværende; (N) er udhængende nukleotider, der hver uafhængigt er umodificeret eller kemisk modificeret; [N] er nukleotider i 5'-terminalen af antisense-strengen; XI og X2 uafhængigt er heltal fra 0 til 4; X3 er et heltal fra 15 til 30; X4 er et heltal fra 12 til 27; og X5 er et heltal fra 1 til 6, forudsat at summen af X4 og X5 er et heltal fra 15 til 30; og hvor (a) alle pyrimidinnukleotider i NX4-positioner er 2' -0- methylnukleotider ; (b) alle pyrinnukleotider i NX4-positioner er 2'- fluornukleotider; (c) alle pyrimidinnukleotider i NX3-positioner er 2' -0- methylnukleotider ; (d) alle pyrinnukleotider i NX3-positioner er 2'- fluornukleotider; (e) [N]-position-nukleotid(er) er en hvilken som helst kombination af ribonukleotider, deoxyribonukleotider, 2'-0- methylnukleotider eller 2'-fluornukleotider; og (f) nukleotidet i position 14 fra 5'-enden af antisense- strengen af det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle er et 2'-deoxy-2'-fluornukleotid; og II) et kationisk lipid, der omfatter (13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-l-amin.
2. Sammensætning ifølge krav 1, hvor: (a) alle pyrimidinnukleotider i Nx4-positioner er 2' -0- methylnukleotider; (b) alle pyrinnukleotider i Nx4-positioner er 2'-deoxy-2'- fluornukleotider; (c) alle pyrimidinnukleotider i Nx3~positioner er 2'-0- methylnukleotider; og (d) alle pyrinnukleotider i NX3-positioner er 2'-deoxy-2'- fluornukleotider.
3. Sammensætning ifølge krav 1, hvor X5 er 3.
4. Sammensætning ifølge krav 3, hvor de tre [N]-nukleotider i formel (A) er som vist ved 5'-[NI, N2, N3]-3', hvor: a. hver NI, N2 og N3 er et ribonukleotid; eller b. hver NI, N2 og N3 er et 2'-deoxy-2'-fluornukleotid; eller c. hver NI, N2 og N3 er et 2'-deoxynukleotid; eller d. hver NI, N2 og N3 er et 2'-O-methylnukleotid; og e. en hvilken som helst af NI, N2 eller N3 eventuelt omfatter en phosphorthioat-internukleotidbinding.
5. Sammensætning ifølge krav 3, hvor de tre [N]-nukleotider i formel (A) er som vist ved 5'-[NI, N2, N3]— 3', hvor: a. NI er et 2 '-deoxy-2 '-fluornukleotid, N2 er et 2 ' -deoxy-2 ' -fluornukleotid, og N3 er et 2'-deoxynukleotid; og b. en hvilken som helst af NI, N2 eller N3 eventuelt omfatter en phosphorthioat-internukleotidbinding.
6. Sammensætning ifølge krav 3, hvor de tre [N]-nukleotider i formel (A) er som vist ved 5'-[NI, N2, N3]-3', hvor: a. NI er et 2'-deoxynukleotid, N2 er et 2' -deoxy-2' -fluornukleotid, og N3 er et 2'-O-methylnukleotid; og b. en hvilken som helst af NI, N2 eller N3 eventuelt omfatter en phosphorthioat-internukleotidbinding.
7. Sammensætning ifølge krav 3, hvor de tre [N]-nukleotider i formel (A) er som vist ved 5'-[NI, N2, N3]-3', hvor: a. NI er et 2'-deoxynukleotid, N2 er et 2'-deoxy-2'-fluornukleotid, og N3 er et 2'-deoxynukleotid; og b. en hvilken som helst af NI, N2 eller N3 eventuelt omfatter en phosphorthioat-internukleotidbinding.
8. Sammensætning ifølge krav 3, hvor de tre [N]-nukleotider i formel (A) er som vist ved 5'-[NI, N2, N3]-3', hvor: a. NI er et 2 '-deoxy-2 '-fluornukleotid, N2 er et 2 ' -deoxy-2 ' -fluornukleotid, og N3 er et 2'-deoxy-2'-fluornukleotid; og b. en hvilken som helst af NI, N2 eller N3 eventuelt omfatter en phosphorthioat-internukleotidbinding.
9. Sammensætning ifølge krav 1, hvor XI er 2, og X2 er 2.
10. Sammensætning ifølge krav 1, hvor X5 er 3, XI er 2, og X2 er 2 .
11. Sammensætning ifølge krav 1, hvor det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle indbefatter en eller flere universelle basesubstitutioner.
12. Sammensætning ifølge krav 1, hvor det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle indbefatter en eller flere LNA-substitutioner.
13. Sammensætning ifølge krav 1, hvor en eller flere udhængende nukleotider af det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle er et 2 '-0- methylnukleotid.
14. Sammensætning ifølge krav 1, hvor det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle indbefatter mindst én phosphorthioat-internukleotidbinding.
15. Sammensætning ifølge krav 1, hvor X5 = 3; hver XI og X2 = 1 eller 2; X3 = 18, 19, 20, 21, 22 eller 24 og X4 = 17, 18, 19, 20, 21, 22 eller 23.
16. Sammensætning ifølge krav 1, hvor X5 = 3; hver XI og X2 = 2; X3 = 19 og X4 = 16.
17. Dobbeltstrenget kort interfererende nukleinsyre (siNA)-molekyle, der hæmmer ekspressionen af et målgen ved hjælp af RNA-interferens, som har en sense-streng og en antisense-streng og omfatter formul (A):
(A) hvor den øverste streng er sense-strengen, og den nederste streng er antisense-strengen af det dobbeltstrengede nukleinsyremolekyle; hvor antisense-strengen omfatter en sekvens, der har mindst 15 nukleotider, der er komplementære til en mål-RNA-sekvens, der kodes af målgenet, og sense-strengen omfatter en sekvens, der er komplementær til antisense-strengen; hver N uafhængigt er et nukleotid, der er umodificeret eller kemisk modificeret eller eventuelt er et ikke-nukleotid; hver B uafhængigt er en terminal cap, der er til stede eller fraværende; (N) er udhængende nukleotider, der hver uafhængigt er umodificeret eller kemisk modificeret; [N] er nukleotider i 5'-terminalen af antisense-strengen; XI og X2 uafhængigt er heltal fra 0 til 4; X3 er et heltal fra 15 til 30; X4 er et heltal fra 12 til 27; og X5 er et heltal fra 1 til 6, forudsat at summen af X4 og X5 er et heltal fra 15 til 30; og hvor (a) alle pyrimidinnukleotider i Nx4-positioner er 2'-to rnet hyl nukleotider ; (b) alle pyrinnukleotider i Nx4-positioner er 2'- fluornukleotider; (c) alle pyrimidinnukleotider i NX3-positioner er 2' -0- methylnukleotider; (d) alle pyrinnukleotider i Nx3-positioner er 2'- fluornukleotider; (e) [N]-position-nukleotid(er) er en hvilken som helst kombination af ribonukleotider, deoxyribonukleotider, 2'-0-methylnukleotider eller 2'-fluornukleotider; (f) nukleotidet i position 14 fra 5'-enden af antisense- strengen er et 2'-deoxy-2'-fluornukleotid, uanset om det er en purin eller pyrimidin; og (g) [N]-nukleotider i formel (A) er som vist ved 5'-[NI, N2, N3]-3', hvor i) NI er et 2'-deoxynukleotid, N2 er et 2' -deoxy-2' -fluornukleotid, og N3 er et 2'-deoxynukleotid; eller ii) NI er et 2'-deoxy-2'-fluornukleotid, N2 er et 2'-deoxy-2'-fluornukleotid, og N3 er et 2'-deoxy-2'-fluornukleotid; eller iii) NI er et 2'-deoxy-2 '-fluornukleotid, N2 er et 2'-deoxy-2'-fluornukleotid, og N3 er et 2'-deoxynukleotid; eller iv) NI er et 2'-deoxy nukleotid, N2 er et 2'-deoxy-2'-fluornukleotid, og N3 er et 2'-O-methylnukleotid; eller v) NI, N2 og N3 alle er ribonukleotider, der har phosphorthioat-internukleotidbindinger.
18. Polymer, der omfatter det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle ifølge krav 17.
19. Forbindelse, der omfatter det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle ifølge krav 17, der er kovalent bundet til en ligand.
20. Lipidnanopartikelsammensætning, der omfatter det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle ifølge krav 17.
21. Lipidnanopartikelsammensætning ifølge krav 20, der yderligere omfatter: (a) (13Z,16Z)-N,N-dimethyl-3,16-dien-l-amin; (b) kolesterol; (c) DSPC; og (d) PEG-DMG.
22. Lipidnanopartikelsammensætning ifølge krav 21, hvor molforholdet mellem (13Z, 16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-l-amin, kolesterol, DSPC og PEG-DMG er 50:30:10:2
23. Sammensætning, der omfatter det dobbeltstrengede korte interfererende nukleinsyre (siNA)-molekyle ifølge krav 17 og et farmaceutisk acceptabelt bæremiddel eller fortyndingsmiddel.
24. Sammensætning ifølge et hvilket som helst af kravene 1 til 16 og 23 til anvendelse til terapi.
DK11836946.1T 2010-10-29 2011-10-25 Rna-interferensmedieret hæmning af genekspression ved anvendelse af korte interfererende nukleinsyrer (sina) DK2632472T3 (da)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9181551B2 (en) 2002-02-20 2015-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US9657294B2 (en) 2002-02-20 2017-05-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
KR101881596B1 (ko) 2008-12-02 2018-07-24 웨이브 라이프 사이언시스 재팬 인코포레이티드 인 원자 변형된 핵산의 합성 방법
SG177564A1 (en) 2009-07-06 2012-02-28 Ontorii Inc Novel nucleic acid prodrugs and methods of use thereof
EP2609106A4 (en) 2010-08-26 2014-03-19 Merck Sharp & Dohme RNA INTERFERENCE-MEDIATED INHIBITION OF EXPRESSION OF PHD2 GENE (PROLYL HYDROXYLASE DOMAIN 2) USING SMALL INTERFERING NUCLEIC ACID (PANI)
EP2618847A4 (en) * 2010-09-20 2014-04-02 Merck Sharp & Dohme NOVEL CATIONIC LIPIDS WITH LOW MOLECULAR WEIGHT FOR OLIGONUCLEOTIDE DELIVERY
WO2012039448A1 (ja) 2010-09-24 2012-03-29 株式会社キラルジェン 不斉補助基
WO2012058210A1 (en) 2010-10-29 2012-05-03 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA)
SG194751A1 (en) 2011-06-30 2013-12-30 Arrowhead Res Corp Compositions and methods for inhibiting gene expression of hepatitis b virus
EP2734208B1 (en) 2011-07-19 2017-03-01 Wave Life Sciences Ltd. Methods for the synthesis of functionalized nucleic acids
KR102263352B1 (ko) 2011-11-18 2021-06-11 알닐람 파마슈티칼스 인코포레이티드 트랜스티레틴（ＴＴＲ） 관련 질병을 치료하기 위한 ＲＮＡｉ 제제, 조성 및 그의 사용방법
US20150299696A1 (en) 2012-05-02 2015-10-22 Sirna Therapeutics, Inc. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
EP2872485B1 (en) 2012-07-13 2020-12-16 Wave Life Sciences Ltd. Asymmetric auxiliary group
KR102213609B1 (ko) 2012-07-13 2021-02-08 웨이브 라이프 사이언시스 리미티드 키랄 제어
US20160317444A1 (en) * 2013-12-17 2016-11-03 Merck Sharp & Dohme Corp. Liposomal Formulations for Allosteric AKT Inhibitors
JPWO2015108048A1 (ja) 2014-01-15 2017-03-23 株式会社新日本科学 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤
WO2015108047A1 (ja) 2014-01-15 2015-07-23 株式会社新日本科学 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤
AU2015207773B2 (en) 2014-01-16 2021-06-17 Wave Life Sciences Ltd. Chiral design
DK3166615T3 (da) * 2014-07-10 2023-11-13 Replicor Inc Chelaterede phosphortioterede nukleinsyrepolymerer til anvendelse i kombination med en hbv-polymeraseinhibitor til behandlingen af hepatitis b- og hepatitis d-virusinfektioner
LT3329002T (lt) 2015-07-31 2021-01-11 Alnylam Pharmaceuticals, Inc. Transtiretino (ttr) irnr kompozicijos ir jų naudojimo būdai, skirti naudoti su ttr susijusių ligų gydymui arba prevencijai
AU2016306275A1 (en) 2015-08-07 2018-02-08 Arrowhead Pharmaceuticals, Inc. RNAi therapy for Hepatitis B virus infection
CR20180233A (es) 2015-10-09 2018-05-25 Wave Life Sciences Ltd Composiciones oligonucleotídicas y sus métodos
MA45340A (fr) * 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques du récepteur des androgènes et leurs utilisations
MA45471A (fr) * 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques de phosphatidylinositol-3-kinase et leurs utilisations
MA45328A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Compositions acide nucléique-polypeptide et utilisations de celles-ci
WO2017192544A1 (en) 2016-05-02 2017-11-09 Massachusetts Institute Of Technology AMPHIPHILIC NANOPARTICLES FOR CODELIVERY OF WATER-INSOLUBLE SMALL MOLECULES AND RNAi
JOP20170161A1 (ar) 2016-08-04 2019-01-30 Arrowhead Pharmaceuticals Inc عوامل RNAi للعدوى بفيروس التهاب الكبد ب
CA3043768A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents
MX2019008199A (es) 2017-01-06 2019-11-25 Avidity Biosciences Llc Composiciones de acido nucleico polipeptido y metodos de induccion de la omision de exon.
GB201711809D0 (en) 2017-07-21 2017-09-06 Governors Of The Univ Of Alberta Antisense oligonucleotide
JP7281452B2 (ja) 2017-09-14 2023-05-25 アローヘッド ファーマシューティカルズ インコーポレイテッド アンジオポエチン様３（ＡＮＧＰＴＬ３）の発現を阻害するためのＲＮＡｉ剤および組成物、ならびに使用方法
MA50267A (fr) 2017-09-19 2020-07-29 Alnylam Pharmaceuticals Inc Compositions et méthodes de traitement de l'amylose médiée par la transthyrétine (ttr)
WO2019089922A1 (en) 2017-11-01 2019-05-09 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof
MX2020005860A (es) 2017-12-06 2020-09-09 Avidity Biosciences Inc Composiciones y metodos de tratamiento de atrofia muscular y distrofia miotonica.
IL297818A (en) 2018-12-21 2023-01-01 Avidity Biosciences Inc Anti-transferrin receptor antibodies and uses thereof
JP2022545118A (ja) * 2019-08-23 2022-10-25 ユニバーシティー オブ マサチューセッツ Ｏ－メチルリッチ完全安定化オリゴヌクレオチド
JP2023537798A (ja) 2020-03-19 2023-09-06 アビディティー バイオサイエンシーズ，インク． 顔面肩甲上腕型筋ジストロフィーを処置するための組成物および方法
WO2021195469A1 (en) 2020-03-27 2021-09-30 Avidity Biosciences, Inc. Compositions and methods of treating muscle dystrophy
KR102379204B1 (ko) * 2020-12-18 2022-03-24 이화여자대학교 산학협력단 유전자 침묵 활성이 증가된 핵산 분자 및 이의 이용
EP4281085A1 (en) * 2021-01-22 2023-11-29 Alnylam Pharmaceuticals, Inc. Modified double stranded oligonucleotides
WO2022251322A1 (en) * 2021-05-28 2022-12-01 The Regents Of The University Of California Methods of using mir-3075-5p to improve insulin sensitivity and compositions therefor
WO2023014677A1 (en) 2021-08-03 2023-02-09 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof
AU2022345098A1 (en) 2021-09-16 2024-04-04 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy
TW202333749A (zh) 2021-10-29 2023-09-01 美商艾拉倫製藥股份有限公司 補體因子ｂ（ｃｆｂ）ｉｒｎａ組成物及其使用方法
TW202400787A (zh) 2022-03-16 2024-01-01 美商安彼瑞可股份有限公司 改良siRNA生物可利用性之GalNAc組合物
CN114557971B (zh) * 2022-04-25 2023-05-23 康希诺生物股份公司 一种核酸-脂质纳米颗粒的冷冻干燥保护剂及其制备方法和应用

Family Cites Families (711)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3126375A (en) 1964-03-24 Chioacyl
US2789118A (en) 1956-03-30 1957-04-16 American Cyanamid Co 16-alpha oxy-belta1, 4-pregnadienes
US2990401A (en) 1958-06-18 1961-06-27 American Cyanamid Co 11-substituted 16alpha, 17alpha-substituted methylenedioxy steroids
US3048581A (en) 1960-04-25 1962-08-07 Olin Mathieson Acetals and ketals of 16, 17-dihydroxy steroids
US3749712A (en) 1970-09-25 1973-07-31 Sigma Tau Ind Farmaceuti Triamcinolone acetonide esters and process for their preparation
SE378109B (da) 1972-05-19 1975-08-18 Bofors Ab
US3996359A (en) 1972-05-19 1976-12-07 Ab Bofors Novel stereoisomeric component A of stereoisomeric mixtures of 2'-unsymmetrical 16,17-methylenedioxy steroid 21-acylates, compositions thereof, and method of treating therewith
SE378110B (da) 1972-05-19 1975-08-18 Bofors Ab
US4319039A (en) 1979-06-15 1982-03-09 Merck & Co., Inc. Preparation of ammonium salt of hypocholesteremic fermentation product
US4294926A (en) 1979-06-15 1981-10-13 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4231938A (en) 1979-06-15 1980-11-04 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4444784A (en) 1980-08-05 1984-04-24 Merck & Co., Inc. Antihypercholesterolemic compounds
MX7065E (es) 1980-06-06 1987-04-10 Sankyo Co Un procedimiento microbiologico para preparar derivados de ml-236b
JPS5889191A (ja) 1981-11-20 1983-05-27 Sankyo Co Ltd ３−ヒドロキシ−ｍｌ−２３６ｂ誘導体の製造法
US5354772A (en) 1982-11-22 1994-10-11 Sandoz Pharm. Corp. Indole analogs of mevalonolactone and derivatives thereof
US4501729A (en) 1982-12-13 1985-02-26 Research Corporation Aerosolized amiloride treatment of retained pulmonary secretions
US4911165A (en) 1983-01-12 1990-03-27 Ethicon, Inc. Pliabilized polypropylene surgical filaments
IS1355B6 (is) 1984-11-12 1989-04-19 Lister Institute Of Preventive Medicine Fjölkjarna kannar
US4681893A (en) 1986-05-30 1987-07-21 Warner-Lambert Company Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
US4987071A (en) 1986-12-03 1991-01-22 University Patents, Inc. RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
US4885314A (en) 1987-06-29 1989-12-05 Merck & Co., Inc. Novel HMG-CoA reductase inhibitors
US4782084A (en) 1987-06-29 1988-11-01 Merck & Co., Inc. HMG-COA reductase inhibitors
US4820850A (en) 1987-07-10 1989-04-11 Merck & Co., Inc. Process for α-C-alkylation of the 8-acyl group on mevinolin and analogs thereof
PT88550A (pt) 1987-09-21 1989-07-31 Ml Tecnology Ventures Lp Processo para a preparacao de reagentes de ligacao nao nucleotidicos para sondas nucleotidicas
US5030447A (en) 1988-03-31 1991-07-09 E. R. Squibb & Sons, Inc. Pharmaceutical compositions having good stability
US5180589A (en) 1988-03-31 1993-01-19 E. R. Squibb & Sons, Inc. Pravastatin pharmaceuatical compositions having good stability
US4916239A (en) 1988-07-19 1990-04-10 Merck & Co., Inc. Process for the lactonization of mevinic acids and analogs thereof
EP0360390A1 (en) 1988-07-25 1990-03-28 Glaxo Group Limited Spirolactam derivatives
US5118853A (en) 1988-10-13 1992-06-02 Sandoz Ltd. Processes for the synthesis of 3-disubstituted aminoacroleins
US5290946A (en) 1988-10-13 1994-03-01 Sandoz Ltd. Processes for the synthesis of 3-(substituted indolyl-2-yl)propenaldehydes
MX18467A (es) 1988-11-23 1993-07-01 Pfizer Agentes terapeuticos de quinuclidinas
US5831066A (en) 1988-12-22 1998-11-03 The Trustees Of The University Of Pennsylvania Regulation of bcl-2 gene expression
US4929437A (en) 1989-02-02 1990-05-29 Merck & Co., Inc. Coenzyme Q10 with HMG-CoA reductase inhibitors
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5164372A (en) 1989-04-28 1992-11-17 Fujisawa Pharmaceutical Company, Ltd. Peptide compounds having substance p antagonism, processes for preparation thereof and pharmaceutical composition comprising the same
WO1990014090A1 (en) 1989-05-19 1990-11-29 Hem Research, Inc. SHORT THERAPEUTIC dsRNA OF DEFINED STRUCTURE
US5189164A (en) 1989-05-22 1993-02-23 Sandoz Ltd. Processes for the synthesis of syn-(E)-3,5-dihydroxy-7-substituted hept-6-enoic and heptanoic acids and derivatives and intermediates thereof
FI94339C (fi) 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
JP3058686B2 (ja) 1989-08-31 2000-07-04 シティ・オブ・ホープ キメラｄｎａ―ｒｎａ触媒活性配列
PH27357A (en) 1989-09-22 1993-06-21 Fujisawa Pharmaceutical Co Pyrazole derivatives and pharmaceutical compositions comprising the same
US5286634A (en) 1989-09-28 1994-02-15 Stadler Joan K Synergistic method for host cell transformation
EP0942000B1 (en) 1989-10-24 2004-06-23 Isis Pharmaceuticals, Inc. 2'-Modified oligonucleotides
IE903957A1 (en) 1989-11-06 1991-05-08 Sanofi Sa Aromatic amine compounds, their method of preparation and¹pharmaceutical compositions in which they are present
FR2654725B1 (fr) 1989-11-23 1992-02-14 Rhone Poulenc Sante Nouveaux derives de l'isoindolone, leur preparation et les compositions pharmaceutiques qui les contiennent.
FR2654726B1 (fr) 1989-11-23 1992-02-14 Rhone Poulenc Sante Nouveaux derives de l'isoindolone et leur preparation.
GB8929070D0 (en) 1989-12-22 1990-02-28 Fujisawa Pharmaceutical Co Peptide compounds,processes for preparation thereof and pharmaceutical composition comprising the same
US5232929A (en) 1990-11-28 1993-08-03 Pfizer Inc. 3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use
UA41251C2 (uk) 1990-01-04 2001-09-17 Пфайзер, Інк. Гідровані азотвмісні гетероциклічні сполуки, похідні піперидину, фармацевтична композиція та спосіб пригнічення активності речовини р в організмі
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US6153737A (en) 1990-01-11 2000-11-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US6395492B1 (en) 1990-01-11 2002-05-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
WO1991012266A1 (en) 1990-02-15 1991-08-22 Fujisawa Pharmaceutical Co., Ltd. Peptide compound
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
IE20010427A1 (en) 1990-04-10 2003-03-05 Canji Inc Gene therapy for cell proliferative diseases
US5420245A (en) 1990-04-18 1995-05-30 Board Of Regents, The University Of Texas Tetrapeptide-based inhibitors of farnesyl transferase
ATE113947T1 (de) 1990-06-01 1994-11-15 Pfizer 3-amino-2-arylchinuclidine, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zubereitungen.
US6168778B1 (en) 1990-06-11 2001-01-02 Nexstar Pharmaceuticals, Inc. Vascular endothelial growth factor (VEGF) Nucleic Acid Ligand Complexes
US5962219A (en) 1990-06-11 1999-10-05 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chemi-selex
EP0540526B1 (en) 1990-07-23 1994-12-28 Pfizer Inc. Quinuclidine derivatives
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
EP0550635B1 (en) 1990-09-28 1995-04-19 Pfizer Inc. Fused ring analogs of nitrogen containing nonaromatic heterocycles
DE552178T1 (de) 1990-10-12 1994-02-03 Max Planck Gesellschaft Abgeänderte ribozyme.
GB9023116D0 (en) 1990-10-24 1990-12-05 Fujisawa Pharmaceutical Co Peptide compounds,processes for preparation thereof and pharmaceutical composition comprising the same
ATE129409T1 (de) 1990-12-21 1995-11-15 Fujisawa Pharmaceutical Co Neue verwendung von peptidderivat.
HUT65612A (en) 1991-01-10 1994-07-28 Pfizer Process n-alcyl-quinuclidinium salts of p-antagonistic activity
DE69220258T2 (de) 1991-02-11 1997-12-18 Merck Sharp & Dohme Azabicyclische Verbindungen, diese enthaltende pharmazeutische Zubereitungen und ihre therapeutische Verwendung
ES2065175T3 (es) 1991-03-01 1995-02-01 Pfizer Derivados de 1-azabiciclo(3.2.2)nonan-3-amina.
US5747469A (en) 1991-03-06 1998-05-05 Board Of Regents, The University Of Texas System Methods and compositions comprising DNA damaging agents and p53
BR9205807A (pt) 1991-03-26 1994-06-28 Pfizer Preparação estéreo-seletiva de piperidinas substituidas
FR2677361A1 (fr) 1991-06-04 1992-12-11 Adir Nouveaux peptides et pseudopeptides, derives de tachykinines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
FR2676055B1 (fr) 1991-05-03 1993-09-03 Sanofi Elf Composes polycycliques amines et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant.
FR2676053B1 (fr) 1991-05-03 1993-08-27 Sanofi Elf Nouveaux composes dialkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant.
FR2676442B1 (fr) 1991-05-17 1993-08-06 Rhone Poulenc Rorer Sa Nouveau derives de perhydroisoindole, leur preparation et les compositions pharmaceutiques qui les contiennent.
FR2676447B1 (fr) 1991-05-17 1993-08-06 Rhone Poulenc Rorer Sa Nouveaux derives du thiopyranopyrrole et leur preparation.
FR2676446B1 (fr) 1991-05-17 1993-08-06 Rhone Poulenc Rorer Sa Nouveaux derives du thiopyranopyrrole, leur preparation et les compositions pharmaceutiques qui les contiennent.
FR2676443B1 (fr) 1991-05-17 1993-08-06 Rhone Poulenc Rorer Sa Nouveaux derives de perhydroisoindole et leur preparation.
WO1992020661A1 (en) 1991-05-22 1992-11-26 Merck & Co., Inc. N, n-diacylpiperazines
HUT65771A (en) 1991-05-22 1994-07-28 Pfizer Process for producing substituted 3-amino-quinuclidine derivatives and pharmaceutical compositions containing them
UA27776C2 (uk) 1991-05-31 2000-10-16 Пфайзер Інк. Похідні хінуклідину та їх фармацевтично прийнятні солі, що є антагоністами речовини р у ссавців, фармацевтична композиція, що має антагоністичну дію на речовину р у ссавців
GB9113219D0 (en) 1991-06-19 1991-08-07 Fujisawa Pharmaceutical Co Peptide compound,processes for preparation thereof and pharmaceutical composition comprising the same
DE4216134A1 (de) 1991-06-20 1992-12-24 Europ Lab Molekularbiolog Synthetische katalytische oligonukleotidstrukturen
KR0154882B1 (ko) 1991-06-20 1998-11-16 알렌 제이. 스피겔 질소 함유 헤테로사이클릭 화합물의 플루오로알콕시벤질아미노 유도체
TW202432B (da) 1991-06-21 1993-03-21 Pfizer
US5288730A (en) 1991-06-24 1994-02-22 Merck Sharp & Dohme Limited Azabicyclic compounds, pharmaceutical compositions containing them and their use in therapy
CA2110513A1 (en) 1991-07-05 1993-01-21 Christopher J. Swain Aromatic compounds, pharmaceutical compositions containing them and their use in therapy
WO1993001169A2 (en) 1991-07-05 1993-01-21 Merck Sharp & Dohme Limited Aromatic compounds, pharmaceutical compositions containing them and their use in therapy
EP0536817A1 (en) 1991-07-05 1993-04-14 MERCK SHARP & DOHME LTD. Azabicyclic compounds as tachykinin antagonists
ATE133658T1 (de) 1991-07-10 1996-02-15 Merck Sharp & Dohme Aromatische verbindungen diese enthaltende pharmazeutische zusammensetzungen und ihre therapeutische verwendung
WO1993001159A1 (en) 1991-07-10 1993-01-21 Merck Sharp & Dohme Limited Fused tricyclic compounds, pharmaceutical compositions containing them and their use in therapy
MY110227A (en) 1991-08-12 1998-03-31 Ciba Geigy Ag 1-acylpiperindine compounds.
EP0600952B1 (en) 1991-08-20 1996-04-17 MERCK SHARP & DOHME LTD. Azacyclic compounds, processes for their preparation and pharmaceutical compositions containing them
EP1082959A1 (en) 1991-09-20 2001-03-14 Glaxo Group Limited NK1 Antagonists for the treatment of depression
US5527808A (en) 1991-09-26 1996-06-18 Pfizer Inc. Fused tricyclic nitrogen containing heterocycles
US6335434B1 (en) 1998-06-16 2002-01-01 Isis Pharmaceuticals, Inc., Nucleosidic and non-nucleosidic folate conjugates
WO1993009116A1 (en) 1991-11-07 1993-05-13 Yoshitomi Pharmaceutical Industries, Ltd. Quinuclidine compound and medicinal use thereof
DK0613458T3 (da) 1991-11-12 1998-02-09 Pfizer Acykliske ethylendiaminderivater som substans P receptorantagonister
EP0545478A1 (en) 1991-12-03 1993-06-09 MERCK SHARP & DOHME LTD. Heterocyclic compounds as tachykinin antagonists
HU9203780D0 (en) 1991-12-12 1993-03-29 Sandoz Ag Stabilized pharmaceutical products of hmg-coa reductase inhibitor and method for producing them
GB9200535D0 (en) 1992-01-10 1992-02-26 Fujisawa Pharmaceutical Co New compound
GB9201179D0 (en) 1992-01-21 1992-03-11 Glaxo Group Ltd Chemical compounds
US5652094A (en) 1992-01-31 1997-07-29 University Of Montreal Nucleozymes
US5328927A (en) 1992-03-03 1994-07-12 Merck Sharpe & Dohme, Ltd. Hetercyclic compounds, processes for their preparation and pharmaceutical compositions containing them
JP2656702B2 (ja) 1992-03-23 1997-09-24 ファイザー製薬株式会社 ペプチド性キヌクリジン
FR2689888B1 (fr) 1992-04-10 1994-06-10 Rhone Poulenc Rorer Sa Nouveaux derives de perhydroisoindole, leur preparation et les compositions pharmaceutiques qui les contiennent.
WO1993021181A1 (en) 1992-04-15 1993-10-28 Merck Sharp & Dohme Limited Azacyclic compounds
GB2266529A (en) 1992-05-01 1993-11-03 Merck Sharp & Dohme Tetrahydroisoquinoline derivatives
WO1993023569A1 (en) 1992-05-11 1993-11-25 Ribozyme Pharmaceuticals, Inc. Method and reagent for inhibiting viral replication
US6469158B1 (en) 1992-05-14 2002-10-22 Ribozyme Pharmaceuticals, Incorporated Synthesis, deprotection, analysis and purification of RNA and ribozymes
US20030206887A1 (en) 1992-05-14 2003-11-06 David Morrissey RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA)
US5804683A (en) 1992-05-14 1998-09-08 Ribozyme Pharmaceuticals, Inc. Deprotection of RNA with alkylamine
US5977343A (en) 1992-05-14 1999-11-02 Ribozyme Pharmaceuticals, Inc. Synthesis, deprotection, analysis and purification of RNA and ribozymes
CA2134964C (en) 1992-05-18 1997-12-30 Manoj C. Desai Bridged aza-bicyclic derivatives as substance p antagonists
GB9211193D0 (en) 1992-05-27 1992-07-08 Merck Sharp & Dohme Therapeutic agents
US5719147A (en) 1992-06-29 1998-02-17 Merck & Co., Inc. Morpholine and thiomorpholine tachykinin receptor antagonists
CA2099233A1 (en) 1992-06-29 1993-12-30 Conrad P. Dorn Morpholine and thiomorpholine tachykinin receptor antagonists
US5637699A (en) 1992-06-29 1997-06-10 Merck & Co., Inc. Process for preparing morpholine tachykinin receptor antagonists
ATE171210T1 (de) 1992-07-02 1998-10-15 Hybridon Inc Selbststabilisierte oligonukleotide als therapeutika
US6582728B1 (en) 1992-07-08 2003-06-24 Inhale Therapeutic Systems, Inc. Spray drying of macromolecules to produce inhaleable dry powders
US5612336A (en) 1992-07-13 1997-03-18 Merck, Sharp & Dohme Ltd. Heterocyclic amide derivatives as tachykinin antagonists
EP0786522A2 (en) 1992-07-17 1997-07-30 Ribozyme Pharmaceuticals, Inc. Enzymatic RNA molecules for treatment of stenotic conditions
GB2268931A (en) 1992-07-22 1994-01-26 Merck Sharp & Dohme Azabicyclic tachykinin-receptor antagonists
ATE173725T1 (de) 1992-07-28 1998-12-15 Merck Sharp & Dohme Azazyklische verbindungen
GB2269170A (en) 1992-07-29 1994-02-02 Merck Sharp & Dohme Azatricyclic tachykinin antagonists
US6107062A (en) 1992-07-30 2000-08-22 Inpax, Inc. Antisense viruses and antisense-ribozyme viruses
WO1994003429A1 (en) 1992-07-31 1994-02-17 Merck Sharp & Dohme Limited Substituted amines as tachykinin receptor antagonists
JPH07506379A (ja) 1992-08-04 1995-07-13 ファイザー・インコーポレーテッド 物質ｐ受容体アンタゴニストとしての３−ベンジルアミノ−２−フェニル−ピペリジン
GB9216911D0 (en) 1992-08-10 1992-09-23 Merck Sharp & Dohme Therapeutic agents
NL9201440A (nl) 1992-08-11 1994-03-01 Univ Leiden Triantennaire clusterglycosiden, hun bereiding en toepassing.
PT655055E (pt) 1992-08-13 2001-03-30 Warner Lambert Co Antagonistas de taquiquinina
US5721255A (en) 1992-08-19 1998-02-24 Pfizer Inc. Substituted benzylamino nitrogen containing non-aromatic heterocycles
US5387595A (en) 1992-08-26 1995-02-07 Merck & Co., Inc. Alicyclic compounds as tachykinin receptor antagonists
US5482967A (en) 1992-09-04 1996-01-09 Takeda Chemical Industries, Ltd. Condensed heterocyclic compounds, their production and use
AU4973693A (en) 1992-09-10 1994-03-29 Merck Sharp & Dohme Limited Alcohols and ethers with aromatic substituents as tachykinin-antagonists
US6174868B1 (en) 1992-09-10 2001-01-16 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of hepatitis C virus-associated diseases
US6235886B1 (en) 1993-09-03 2001-05-22 Isis Pharmaceuticals, Inc. Methods of synthesis and use
GB9220286D0 (en) 1992-09-25 1992-11-11 Merck Sharp & Dohme Therapeutic agents
US5985558A (en) 1997-04-14 1999-11-16 Isis Pharmaceuticals Inc. Antisense oligonucleotide compositions and methods for the inibition of c-Jun and c-Fos
JP2656699B2 (ja) 1992-10-21 1997-09-24 ファイザー製薬株式会社 置換ベンジルアミノキヌクリジン
GB9222262D0 (en) 1992-10-23 1992-12-09 Merck Sharp & Dohme Therapeutic agents
GB9222486D0 (en) 1992-10-26 1992-12-09 Merck Sharp & Dohme Therapeutic agents
EP0666856B1 (en) 1992-10-28 2000-01-05 MERCK SHARP & DOHME LTD. 4-arylmethyloxymethyl piperidines as tachykinin antagonists
JP2656700B2 (ja) 1992-10-28 1997-09-24 ファイザー製薬株式会社 置換キヌクリジン誘導体
WO1994010167A1 (en) 1992-10-30 1994-05-11 Merck Sharp & Dohme Limited Tachykinin antagonists
ES2096312T3 (es) 1992-11-12 1997-03-01 Pfizer Derivado de quinuclidina como antagonista de la sustancia p.
US5261188A (en) 1992-11-23 1993-11-16 The Standard Products Company Belt weatherstrip with bulb
EP0681613B1 (en) 1992-12-04 2002-05-08 Yale University Ribozyme amplified diagnostics
EP0707638A4 (en) 1992-12-04 1998-05-20 Innovir Lab Inc REGULABLE NUCLEIC ACID FOR THERAPEUTIC USE AND METHODS OF USE THEREOF
WO1994013663A1 (en) 1992-12-10 1994-06-23 Pfizer Inc. Aminomethylene substituted non-aromatic heterocycles and use as substance p antagonists
US5604260A (en) 1992-12-11 1997-02-18 Merck Frosst Canada Inc. 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2
EP0673367A1 (en) 1992-12-14 1995-09-27 MERCK SHARP & DOHME LTD. 4-aminomethyl/thiomethyl/sulfonylmethyl-4-phenylpiperidines as tachykinin receptor antagonists
GB9226581D0 (en) 1992-12-21 1993-02-17 Merck Sharp & Dohme Therapeutic agents
EP0604181A1 (en) 1992-12-21 1994-06-29 Eli Lilly And Company Antitumor compositions and method of treatment
GB9300051D0 (en) 1993-01-04 1993-03-03 Merck Sharp & Dohme Therapeutic agents
WO1994015932A1 (en) 1993-01-15 1994-07-21 G.D. Searle & Co. Novel 3,4-diaryl thiophenes and analogs thereof having use as antiinflammatory agents
CA2154363A1 (en) 1993-01-22 1994-08-04 Bruce A. Sullenger Localization of therapeutic agents
EP0610793A1 (en) 1993-02-08 1994-08-17 Takeda Chemical Industries, Ltd. Tetracyclic morpholine derivatives and their use or analgesics
US5633266A (en) 1993-02-18 1997-05-27 Merck Sharp & Dohme Ltd. Azacyclic compounds compositions containing them and their use as tachykinin antagonists
AU6140694A (en) 1993-02-22 1994-09-14 Merck Sharp & Dohme Limited Aromatic compounds, compositions containing them and their use in therapy
WO1994019357A1 (en) 1993-02-23 1994-09-01 Merrell Dow Pharmaceuticals Inc. Farnesyl:protein transferase inhibitors as anticancer agents
US5298627A (en) 1993-03-03 1994-03-29 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
ATE166650T1 (de) 1993-03-04 1998-06-15 Pfizer Spiroazacyclischderivate als substanz p antagonisten
US5409944A (en) 1993-03-12 1995-04-25 Merck Frosst Canada, Inc. Alkanesulfonamido-1-indanone derivatives as inhibitors of cyclooxygenase
ES2122261T3 (es) 1993-03-17 1998-12-16 Minnesota Mining & Mfg Formulacion de aerosol que contiene un adyuvante de dispersion derivado de un ester, una amida o un mercaptoester.
CA2118985A1 (en) 1993-04-02 1994-10-03 Dinesh V. Patel Heterocyclic inhibitors of farnesyl protein transferase
US5496833A (en) 1993-04-13 1996-03-05 Merck Sharp & Dohme Limited Piperidine tachykinin receptor antagonists
DK0696280T3 (da) 1993-05-06 1998-01-12 Merrell Pharma Inc Substituerede pyrrolidin-3-yl-alkyl-piperidiner anvendelige som tachykinin-antagonister
EP0698015A1 (en) 1993-05-14 1996-02-28 Genentech, Inc. Preparation of n-cyanodithioimino-carbonates and 3-mercapto-5-amino-1h-1,2,4-triazole
US5602098A (en) 1993-05-18 1997-02-11 University Of Pittsburgh Inhibition of farnesyltransferase
IL109646A0 (en) 1993-05-19 1994-08-26 Pfizer Heteroatom substituted alkyl benzylamino-quinuclidines
ATE273700T1 (de) 1993-05-21 2004-09-15 Us Gov Health & Human Serv Neues verfahen zur hemmung der replication der virus - abhängigen reverse transciptase durch verwendung von dideoxydenucleotide-synthese inhibitoren
US5380738A (en) 1993-05-21 1995-01-10 Monsanto Company 2-substituted oxazoles further substituted by 4-fluorophenyl and 4-methylsulfonylphenyl as antiinflammatory agents
US5871914A (en) 1993-06-03 1999-02-16 Intelligene Ltd. Method for detecting a nucleic acid involving the production of a triggering RNA and transcription amplification
EP0702681A1 (en) 1993-06-07 1996-03-27 Merck & Co. Inc. Spiro-substituted azacycles as neurokinin antagonists
GB9602877D0 (en) 1996-02-13 1996-04-10 Merck Frosst Canada Inc 3,4-Diaryl-2-hydroxy-2,5- dihydrofurans as prodrugs to cox-2 inhibitors
US5436265A (en) 1993-11-12 1995-07-25 Merck Frosst Canada, Inc. 1-aroyl-3-indolyl alkanoic acids and derivatives thereof useful as anti-inflammatory agents
US5474995A (en) 1993-06-24 1995-12-12 Merck Frosst Canada, Inc. Phenyl heterocycles as cox-2 inhibitors
WO1995002051A2 (en) 1993-07-10 1995-01-19 Biognostik Gesellschaft für Biomolekulare Diagnostik mbH A pharmaceutical composition comprising antisense-nucleic acid for prevention and/or treatment of neuronal injury, degeneration and cell death and for the treatment of neoplasms
EP0634402A1 (en) 1993-07-14 1995-01-18 Takeda Chemical Industries, Ltd. Isochinolinone derivatives, their production and use
ES2121213T3 (es) 1993-07-15 1998-11-16 Pfizer Benciloxiquinuclidinas como antagonistas de la sustancia p.
US6410322B1 (en) 1993-07-27 2002-06-25 Hybridon Inc Antisense oligonucleotide inhibition of vascular endothelial growth factor expression
US5731294A (en) 1993-07-27 1998-03-24 Hybridon, Inc. Inhibition of neovasularization using VEGF-specific oligonucleotides
TW365603B (en) 1993-07-30 1999-08-01 Rhone Poulenc Rorer Sa Novel perhydroisoindole derivatives, their preparation and pharmaceutical compositions which contain them
GB9315808D0 (en) 1993-07-30 1993-09-15 Merck Sharp & Dohme Therapeutic agents
GB9317987D0 (en) 1993-08-26 1993-10-13 Glaxo Group Ltd Chemical compounds
JPH09502092A (ja) 1993-09-02 1997-03-04 リボザイム・ファーマシューティカルズ・インコーポレイテッド 非ヌクレオチドを含有する酵素性核酸
AU679566B2 (en) 1993-09-03 1997-07-03 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
WO1995007908A1 (en) 1993-09-17 1995-03-23 Pfizer Inc. Heteroarylamino and heteroarylsulfonamido substituted 3-benzylaminomethyl piperidines and related compounds
PT719253E (pt) 1993-09-17 2004-07-30 Pfizer Piperidinas 3-amino-5-carboxi-substituidas e pirrolidinas 3-amino-4-carboxi-substituidas como antagonistas de taquicinina
US5990090A (en) 1993-09-20 1999-11-23 The University Of Michigan Methods and compositions for treatment of diseases
IS4208A (is) 1993-09-22 1995-03-23 Glaxo Group Limited 3-(tetrazólýl-benzyl)amínó-piperadidín afleiður
US5728830A (en) 1993-09-22 1998-03-17 Kyowa Hakko Kogyo Co., Ltd. Farnesyltransferase inhibitor
AU7845194A (en) 1993-09-28 1995-04-18 General Hospital Corporation, The Using antisense oligonucleotides to modulate nerve growth and to reverse beta/A4 amyloid-induced morphology
US5624803A (en) 1993-10-14 1997-04-29 The Regents Of The University Of California In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides derived therefrom
US6323184B1 (en) 1993-10-15 2001-11-27 Thomas Jefferson University Arteriovenous and venous graft treatments: methods and compositions
EP0723538B1 (en) 1993-10-15 2001-12-12 Schering Corporation Tricyclic carbamate compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
IL111235A (en) 1993-10-15 2001-03-19 Schering Plough Corp Medicinal preparations for inhibiting protein G activity and for the treatment of malignant diseases, containing tricyclic compounds, some such new compounds and a process for the preparation of some of them
US5661152A (en) 1993-10-15 1997-08-26 Schering Corporation Tricyclic sulfonamide compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5719148A (en) 1993-10-15 1998-02-17 Schering Corporation Tricyclic amide and urea compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US6133242A (en) 1993-10-15 2000-10-17 Thomas Jefferson Univerisity Inhibition of extracellular matrix synthesis by antisense compounds directed to nuclear proto-oncogenes
US5721236A (en) 1993-10-15 1998-02-24 Schering Corporation Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
WO1995010514A1 (en) 1993-10-15 1995-04-20 Schering Corporation Tricyclic sulfonamide compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US5421818A (en) 1993-10-18 1995-06-06 Inner Ear Medical Delivery Systems, Inc. Multi-functional inner ear treatment and diagnostic system
US5861288A (en) 1993-10-18 1999-01-19 Ribozyme Pharmaceuticals, Inc. Catalytic DNA
ATE200677T1 (de) 1993-10-25 2001-05-15 Parke Davis & Co Substituierte tetra- und pentapeptid hemmstoffe der farnesyl protein transferase
CA2174339A1 (en) 1993-10-27 1995-05-04 Lech W. Dudycz 2'-amido and 2'-peptido modified oligonucleotides
WO1995011880A1 (en) 1993-10-27 1995-05-04 Merck Sharp & Dohme Limited Substituted amides as tachykinin antagonists
US5344991A (en) 1993-10-29 1994-09-06 G.D. Searle & Co. 1,2 diarylcyclopentenyl compounds for the treatment of inflammation
EP0677039B1 (en) 1993-11-04 1999-03-10 Abbott Laboratories Cyclobutane derivatives as inhibitors of squalene synthetase and protein farnesyltransferase
US5783593A (en) 1993-11-04 1998-07-21 Abbott Laboratories Inhibitors of squalene synthetase and protein farnesyltransferase
JP3597863B2 (ja) 1993-11-05 2004-12-08 ワーナー−ランバート・コンパニー タンパク質：ファルネシルトランスフェラーゼの置換されたジ‐およびトリペプチド阻害剤
DE4338704A1 (de) 1993-11-12 1995-05-18 Hoechst Ag Stabilisierte Oligonucleotide und deren Verwendung
US6060456A (en) 1993-11-16 2000-05-09 Genta Incorporated Chimeric oligonucleoside compounds
US6403577B1 (en) 1993-11-17 2002-06-11 Eli Lilly And Company Hexamethyleneiminyl tachykinin receptor antagonists
US5466823A (en) 1993-11-30 1995-11-14 G.D. Searle & Co. Substituted pyrazolyl benzenesulfonamides
IT1271462B (it) 1993-12-03 1997-05-28 Menarini Farma Ind Antagonisti delle tachichinine,procedimento per la loro preparazione e loro impiego in formulazioni farmaceutiche.
US5484799A (en) 1993-12-09 1996-01-16 Abbott Laboratories Antifungal dorrigocin derivatives
IL111960A (en) 1993-12-17 1999-12-22 Merck & Co Inc Morpholines and thiomorpholines their preparation and pharmaceutical compositions containing them
US6093702A (en) 1993-12-20 2000-07-25 The United States Of America As Represented By The Department Of Health And Human Services Mixtures of dideoxy-nucleosides and hydroxycarbamide for inhibiting retroviral spread
AU1339795A (en) 1993-12-21 1995-07-10 Eli Lilly And Company Non-peptide tachykinin receptor antagonists
US5854239A (en) 1993-12-29 1998-12-29 Pfizer Inc. Diazabicyclic neuokinin antagonists
PL181214B1 (pl) 1993-12-29 2001-06-29 Merck Sharp & Dohme Podstawione związki morfolinowe, sposób ich wytwarzania oraz zawierające je kompozycje farmaceutyczne
US5587471A (en) 1994-01-11 1996-12-24 Isis Pharmaceuticals, Inc. Method of making oligonucleotide libraries
WO1995019344A1 (en) 1994-01-13 1995-07-20 Merck Sharp & Dohme Limited Gem-disubstituted azacyclic tachykinin antagonists
US5444650A (en) 1994-01-25 1995-08-22 Nippondenso Co., Ltd. Semiconductor programmable read only memory device
US5728716A (en) 1994-01-28 1998-03-17 Merck Sharp & Dohme Limited Aralkylamino substituted azacyclic therapeutic agents
US5393790A (en) 1994-02-10 1995-02-28 G.D. Searle & Co. Substituted spiro compounds for the treatment of inflammation
GB9402688D0 (en) 1994-02-11 1994-04-06 Merck Sharp & Dohme Therapeutic agents
US5610165A (en) 1994-02-17 1997-03-11 Merck & Co., Inc. N-acylpiperidine tachykinin antagonists
US5631359A (en) 1994-10-11 1997-05-20 Ribozyme Pharmaceuticals, Inc. Hairpin ribozymes
US5902880A (en) 1994-08-19 1999-05-11 Ribozyme Pharmaceuticals, Inc. RNA polymerase III-based expression of therapeutic RNAs
IL112778A0 (en) 1994-03-04 1995-05-26 Merck & Co Inc Substituted heterocycles, their preparation and pharmaceutical compositions containing them
WO1995024612A1 (de) 1994-03-07 1995-09-14 International Business Machines Corporation Verfahren und vorrichtung zur schnellen interpolation von zwischenwerten aus periodischen phasenverschobenen signalen und zur erkennung von defekten in einem drehkörper
MX9603936A (es) 1994-03-07 1997-05-31 Inhale Therapeutic Syst Metodos y composiciones para el suministro pulmonar de insulina.
US6051256A (en) 1994-03-07 2000-04-18 Inhale Therapeutic Systems Dispersible macromolecule compositions and methods for their preparation and use
AU2122795A (en) 1994-03-15 1995-10-03 Eisai Co. Ltd. Isoprenyl transferase inhibitors
FR2718136B1 (fr) 1994-03-29 1996-06-21 Sanofi Sa Composés aromatiques aminés, procédé pour leur obtention et compositions pharmaceutiques les contenant.
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
IL113196A0 (en) 1994-03-31 1995-06-29 Bristol Myers Squibb Co Imidazole derivatives and pharmaceutical compositions containing the same
CA2187626C (en) 1994-04-13 2009-11-03 Michael G. Kaplitt Aav-mediated delivery of dna to cells of the nervous system
US5523430A (en) 1994-04-14 1996-06-04 Bristol-Myers Squibb Company Protein farnesyl transferase inhibitors
US5610145A (en) 1994-04-15 1997-03-11 Warner-Lambert Company Tachykinin antagonists
ZA953311B (en) 1994-04-29 1996-10-24 Lilly Co Eli Non-peptidyl tachykinin receptor antagonists
EP0758329A1 (en) 1994-05-05 1997-02-19 MERCK SHARP & DOHME LTD. Morpholine derivatives and their use as antagonists of tachikinins
SK142696A3 (en) 1994-05-07 1997-06-04 Boehringer Ingelheim Kg Amino acids derivative, method for preparation thereof, pharmaceutical compositions containing said compounds (ii) and their use
US5510510A (en) 1994-05-10 1996-04-23 Bristol-Meyers Squibb Company Inhibitors of farnesyl protein transferase
US6447796B1 (en) 1994-05-16 2002-09-10 The United States Of America As Represented By The Secretary Of The Army Sustained release hydrophobic bioactive PLGA microspheres
US5563255A (en) 1994-05-31 1996-10-08 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of raf gene expression
AU2604995A (en) 1994-06-01 1995-12-21 Hybridon, Inc. Branched oligonucleotides as pathogen-inhibitory agents
JPH10501228A (ja) 1994-06-06 1998-02-03 ワーナー−ランバート・コンパニー タキキニン（ｎｋ▲下１▼）受容体アンタゴニスト
DE69507476D1 (de) 1994-06-10 1999-03-04 Rhone Poulenc Rorer Sa Farnesyl-transferase-inhibitoren, ihre herstellung und sie enthaltende pharmazeutische zusammensetzungen
EP0686629A3 (en) 1994-06-10 1999-02-10 Eli Lilly And Company Cyclohexyl tachykinine receptor antagonists
US5571792A (en) 1994-06-30 1996-11-05 Warner-Lambert Company Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase
MX9700271A (es) 1994-07-12 1997-05-31 Lilly Co Eli Antagonistas heterociclicos del receptor de taquinicina.
CA2154116A1 (en) 1994-07-22 1996-01-23 Philip Arthur Hipskind 1-aryl-2-acetamidopentanone derivatives for use as tachykinin receptor antagonists
US5646262A (en) 1994-07-28 1997-07-08 Georgetown University Antisense oligonucleotides against hepatitis B viral replication
GB9415997D0 (en) 1994-08-08 1994-09-28 Merck Sharp & Dohme Therapeutic agents
GB9415996D0 (en) 1994-08-08 1994-09-28 Merck Sharp & Dohme Therapeutic agents
TW432061B (en) 1994-08-09 2001-05-01 Pfizer Res & Dev Lactams
WO1996005529A1 (en) 1994-08-09 1996-02-22 Micron Optics, Inc. Temperature compensated fiber fabry-perot filters
DE69514367T2 (de) 1994-08-11 2000-07-27 Banyu Pharma Co Ltd Substituierte amidderivate
CA2155448A1 (en) 1994-08-11 1996-02-12 Katerina Leftheris Inhibitors of farnesyl protein transferase
WO1996005169A1 (fr) 1994-08-12 1996-02-22 Banyu Pharmaceutical Co., Ltd. Derive d'acide amique n,n-bisubstitue
DK0777659T3 (da) 1994-08-15 2001-09-03 Merck Sharp & Dohme Morpholinderivater og deres anvendelse som terapeutiske midler
DE4429506B4 (de) 1994-08-19 2007-09-13 Degussa Gmbh Verfahren zur Extraktion natürlicher Carotinoid-Farbstoffe
US6146886A (en) 1994-08-19 2000-11-14 Ribozyme Pharmaceuticals, Inc. RNA polymerase III-based expression of therapeutic RNAs
DE4429653C2 (de) 1994-08-20 1997-04-03 Anton Dr More Konverter und Verfahren zum Frischen von Metallschmelzen insbesondere von Roheisen zu Stahl
KR100362620B1 (ko) 1994-08-25 2003-02-14 메렐 파마슈티칼스 인크. 알레르기성질환치료에유용한치환된피페리딘,이를포함하는약제학적조성물및이의제조방법
DE69405864T2 (de) 1994-08-29 1998-03-26 Akzo Nobel Nv Verfahren zur Herstellung von quaternären Diestern
GB9417956D0 (en) 1994-09-02 1994-10-26 Merck Sharp & Dohme Therapeutic agents
US6350934B1 (en) 1994-09-02 2002-02-26 Ribozyme Pharmaceuticals, Inc. Nucleic acid encoding delta-9 desaturase
GB9418545D0 (en) 1994-09-15 1994-11-02 Merck Sharp & Dohme Therapeutic agents
US5457107A (en) 1994-09-16 1995-10-10 Merck & Co., Inc. Polymorphic form of a tachykinin receptor antagonist
US5572594A (en) 1994-09-27 1996-11-05 Devoe; Lambert Ear canal device holder
US5820873A (en) 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
JPH10506399A (ja) 1994-09-30 1998-06-23 ノバルティス アクチェンゲゼルシャフト １−アシル−４−マリファチルアミノピペリジン化合物
US5753613A (en) 1994-09-30 1998-05-19 Inex Pharmaceuticals Corporation Compositions for the introduction of polyanionic materials into cells
US5885613A (en) 1994-09-30 1999-03-23 The University Of British Columbia Bilayer stabilizing components and their use in forming programmable fusogenic liposomes
TW397825B (en) 1994-10-14 2000-07-11 Novartis Ag Aroyl-piperidine derivatives
FR2725986B1 (fr) 1994-10-21 1996-11-29 Adir Nouveaux derives de piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP0709375B1 (en) 1994-10-25 2005-05-18 AstraZeneca AB Therapeutic heterocycles
GB9421709D0 (en) 1994-10-27 1994-12-14 Zeneca Ltd Therapeutic compounds
CA2162786A1 (en) 1994-11-22 1996-05-23 Philip Arthur Hipskind Heterocyclic tachykinin receptor antagonists
WO1996016443A1 (en) 1994-11-22 1996-05-30 Philips Electronics N.V. Semiconductor device with a carrier body on which a substrate with a semiconductor element is fastened by means of a glue layer and on which a pattern of conductor tracks is fastened
JPH08208687A (ja) 1994-11-25 1996-08-13 Sankyo Co Ltd グリセリルオリゴヌクレオチド
FR2727411B1 (fr) 1994-11-30 1997-01-03 Rhone Poulenc Rorer Sa Nouveaux derives de perhydroisoindole, leur preparation et les compositions pharmaceutiques qui les contiennent
JPH10510261A (ja) 1994-12-09 1998-10-06 ワーナー−ランバート・カンパニー タンパク質：ファルネシルトランスフェラーゼの置換テトラーおよびペンタペプチド阻害剤
US5716824A (en) 1995-04-20 1998-02-10 Ribozyme Pharmaceuticals, Inc. 2'-O-alkylthioalkyl and 2-C-alkylthioalkyl-containing enzymatic nucleic acids (ribozymes)
IL116323A0 (en) 1994-12-13 1996-03-31 Sandoz Ag Tachykinin antagonists their preparation and pharmaceutical compositions containing them
CA2207593A1 (en) 1994-12-13 1996-06-20 John Gustofson Method and reagent for treatment of arthritic conditions, induction of graft tolerance and reversal of immune responses
GB9426103D0 (en) 1994-12-23 1995-02-22 Merck Sharp & Dohme Therapeutic agents
CN1176652A (zh) 1995-01-09 1998-03-18 马格拉国际有限公司 胶乳表面的耐磨图象印刷
JP3929069B2 (ja) 1995-01-12 2007-06-13 ユニバーシティ オブ ピッツバーグ プレニルトランスフェラーゼの阻害剤
JP3925662B2 (ja) 1995-01-12 2007-06-06 グラクソ，グループ，リミテッド タキキニンアンタゴニスト活性を有するピペリジン誘導体
FR2729390A1 (fr) 1995-01-18 1996-07-19 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
US5872241A (en) 1995-01-25 1999-02-16 The Trustees Of Columbia University In The City Of New York Multiple component RNA catalysts and uses thereof
FR2729951B1 (fr) 1995-01-30 1997-04-18 Sanofi Sa Nouveaux composes heterocycliques, procede pour leur preparation et compositions pharmaceutiques en contenant
FR2730491B1 (fr) 1995-02-09 1997-03-14 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
FR2730492B1 (fr) 1995-02-09 1997-03-14 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
US5633272A (en) 1995-02-13 1997-05-27 Talley; John J. Substituted isoxazoles for the treatment of inflammation
GB9505492D0 (en) 1995-03-18 1995-05-03 Merck Sharp & Dohme Therapeutic agents
GB9505491D0 (en) 1995-03-18 1995-05-03 Merck Sharp & Dohme Therapeutic agents
US5554641A (en) 1995-03-20 1996-09-10 Horwell; David C. Nonpeptides as tachykinin antagonists
GB9505692D0 (en) 1995-03-21 1995-05-10 Glaxo Group Ltd Chemical compounds
US5684013A (en) 1995-03-24 1997-11-04 Schering Corporation Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US5700806A (en) 1995-03-24 1997-12-23 Schering Corporation Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
TW394773B (en) 1995-03-24 2000-06-21 Takeda Chemical Industries Ltd Cyclic compounds for antagonizing tachykinin receptor, substance p receptor and neurokinin a receptor, their production and pharmaceutical composition
IL117580A0 (en) 1995-03-29 1996-07-23 Merck & Co Inc Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them
US5565568A (en) 1995-04-06 1996-10-15 Eli Lilly And Company 2-acylaminopropanamides as tachykinin receptor antagonists
IL117798A (en) 1995-04-07 2001-11-25 Schering Plough Corp Tricyclic compounds useful for inhibiting the function of protein - G and for the treatment of malignant diseases, and pharmaceutical preparations containing them
US5712280A (en) 1995-04-07 1998-01-27 Schering Corporation Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
EP0820452B1 (en) 1995-04-07 2003-06-04 Schering Corporation Carbonyl-piperazinyl and piperidinil compounds which inhibit farnesyl protein transferase
US5891872A (en) 1995-04-07 1999-04-06 Schering Corporation Tricyclic compounds
US6372427B1 (en) 1995-04-12 2002-04-16 Hybridon, Inc. Cooperative oligonucleotides
ES2224164T3 (es) 1995-04-13 2005-03-01 Aventis Pharmaceuticals Inc. Nuevos derivados de piperazina sustituida que tienen actividad como antagonistas de los receptores de taququinina.
DK0820279T3 (da) 1995-04-14 2002-10-07 Smithkline Beecham Corp Dosisudmålende inhalator til Albuterol
US5831115A (en) 1995-04-21 1998-11-03 Abbott Laboratories Inhibitors of squalene synthase and protein farnesyltransferase
IL118101A0 (en) 1995-05-03 1996-09-12 Abbott Lab Inhibitors of farnesyltransferase
WO1996037489A1 (en) 1995-05-25 1996-11-28 Fujisawa Pharmaceutical Co., Ltd. 1-benzoyl-2-(indolyl-3-alkyl)-piperazine derivatives as neurokinin receptor antagonists
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
US5705385A (en) 1995-06-07 1998-01-06 Inex Pharmaceuticals Corporation 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
JP4335310B2 (ja) 1995-06-07 2009-09-30 ザ ユニバーシティ オブ ブリティッシュ コロンビア 疎水性脂質−核酸複合中間体を通して調製される脂質−核酸粒子、及び遺伝子移送のための使用
US5889136A (en) 1995-06-09 1999-03-30 The Regents Of The University Of Colorado Orthoester protecting groups in RNA synthesis
AU6034296A (en) 1995-06-16 1997-01-15 Warner-Lambert Company Tricyclic inhibitors of protein farnesyltransferase
GB9513121D0 (en) 1995-06-28 1995-08-30 Merck Sharp & Dohme Therapeutic agents
GB9513117D0 (en) 1995-06-28 1995-08-30 Merck Sharp & Dohme Therapeutic agents
GB9513118D0 (en) 1995-06-28 1995-08-30 Merck Sharp & Dohme Therapeutic agents
JP3042894B2 (ja) 1995-07-07 2000-05-22 ファイザー製薬株式会社 サブスタンスｐアンタゴニストとしての置換ベンゾラクタム化合物
FR2736641B1 (fr) 1995-07-10 1997-08-22 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
AT402617B (de) 1995-07-11 1997-07-25 Datacon Schweitzer & Zeindl Gm Anlage zum automatisierten, hermetischen anlage zum automatisierten, hermetischen verschliessen von gehäusen verschliessen von gehäusen
FR2736638B1 (fr) 1995-07-12 1997-08-22 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
CH690163A5 (fr) 1995-07-28 2000-05-31 Symphar Sa Dérivés gem-diphosphonates substitués utiles en tant qu'agents anti-cancers.
US5968909A (en) 1995-08-04 1999-10-19 Hybridon, Inc. Method of modulating gene expression with reduced immunostimulatory response
TW340842B (en) 1995-08-24 1998-09-21 Pfizer Substituted benzylaminopiperidine compounds
US6020343A (en) 1995-10-13 2000-02-01 Merck Frosst Canada, Inc. (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors
EP0858444A4 (en) 1995-10-18 1999-12-01 Merck & Co Inc CYCLOPENTYL-TACHYKININ RECEPTOR ANTAGONISTS
US6346398B1 (en) 1995-10-26 2002-02-12 Ribozyme Pharmaceuticals, Inc. Method and reagent for the treatment of diseases or conditions related to levels of vascular endothelial growth factor receptor
DE19541283A1 (de) 1995-11-06 1997-05-07 Boehringer Ingelheim Kg Neue Aminosäurederivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen
WO1997017070A1 (en) 1995-11-06 1997-05-15 University Of Pittsburgh Inhibitors of protein isoprenyl transferases
GB9523244D0 (en) 1995-11-14 1996-01-17 Merck Sharp & Dohme Therapeutic agents
EP0866865B1 (en) 1995-11-14 2002-02-06 Vimrx Holdings, Ltd. Chimeric oligomers having an rna-cleavage activity
ES2206607T3 (es) 1995-11-17 2004-05-16 Gesellschaft Fur Biotechnologische Forschung Mbh (Gbf) Derivados de epotilones, preparacion y utilizacion.
WO1997018813A1 (en) 1995-11-22 1997-05-29 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
WO1997020563A1 (en) 1995-11-22 1997-06-12 The Johns-Hopkins University Ligands to enhance cellular uptake of biomolecules
EP1019410A1 (en) 1995-11-23 2000-07-19 MERCK SHARP & DOHME LTD. Spiro-piperidine derivatives and their use as tachykinin antagonists
GB9524157D0 (en) 1995-11-25 1996-01-24 Pfizer Ltd Therapeutic agents
HU224225B1 (hu) 1995-12-01 2005-06-28 Sankyo Co. Ltd. Tachikinin receptor antagonista hatású heterociklusos vegyületek, ezek előállítási eljárása és alkalmazásuk gyógyszerkészítmények előállítására
CA2231105C (en) 1995-12-08 2005-09-13 Janssen Pharmaceutica N.V. Farnesyl protein transferase inhibiting (imidazol-5-yl)methyl-2-quinolinone derivatives
EP0865489A1 (en) 1995-12-08 1998-09-23 HYBRIDON, Inc. Modified vegf antisense oligonucleotides
GB9525296D0 (en) 1995-12-11 1996-02-07 Merck Sharp & Dohme Therapeutic agents
EP1019392B1 (en) 1995-12-22 2005-11-09 Schering Corporation Tricyclic amides useful for inhibition of g-protein function and for treatment of proliferative diseases
EP1108724B1 (en) 1996-01-16 2007-09-19 Sirna Therpeutics, Inc. Synthesis of methoxy nucleosides and enzymatic nucleic acid molecules
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
US6008372A (en) 1996-01-16 1999-12-28 Warner-Lambert Company Substituted dinaphthylmethyl and diheteroarylmethylacetyl histidine inhibitors of protein farnesyltransferase
US6495526B2 (en) 1996-01-23 2002-12-17 Gpc Biotech, Inc. Inhibitors of cell-cycle progression and uses related thereto
US6214805B1 (en) 1996-02-15 2001-04-10 The United States Of America As Represented By The Department Of Health And Human Services RNase L activators and antisense oligonucleotides effective to treat RSV infections
US6673927B2 (en) 1996-02-16 2004-01-06 Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. Farnesyl transferase inhibitors
AU715202B2 (en) 1996-04-03 2000-01-20 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
ES2311571T3 (es) 1996-04-12 2009-02-16 G.D. Searle Llc Derivados de bencenosulfonamida sustituidos como profarmacos de inhibidores de cox-2.
EA199801031A1 (ru) 1996-05-22 1999-06-24 Варнер-Ламберт Компани Ингибиторы протеинфарнезилтрансферазы
ATE267247T1 (de) 1996-05-24 2004-06-15 Aventis Pharma Gmbh Reagenz und verfahren zur inhibierung der n-ras expression
US20040161844A1 (en) 1996-06-06 2004-08-19 Baker Brenda F. Sugar and backbone-surrogate-containing oligomeric compounds and compositions for use in gene modulation
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
AU709409B2 (en) 1996-07-15 1999-08-26 Bristol-Myers Squibb Company Thiadioxobenzodiazepine inhibitors of farnesyl protein transferase
US5861419A (en) 1996-07-18 1999-01-19 Merck Frosst Canad, Inc. Substituted pyridines as selective cyclooxygenase-2 inhibitors
US6958239B2 (en) 1996-11-21 2005-10-25 Oligos Etc Inc. Three component chimeric antisense oligonucleotides
US5849902A (en) 1996-09-26 1998-12-15 Oligos Etc. Inc. Three component chimeric antisense oligonucleotides
TW520297B (en) 1996-10-11 2003-02-11 Sequus Pharm Inc Fusogenic liposome composition and method
AU756699B2 (en) 1996-12-03 2003-01-23 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
WO1998027104A1 (en) 1996-12-19 1998-06-25 Yale University Bioreactive allosteric polynucleotides
EP0948511B1 (en) 1996-12-24 2006-10-18 Sirna Therapeutics, Inc. Chemical synthesis of nucleosides analogs and their incorporation into polynucleotides
US6248878B1 (en) 1996-12-24 2001-06-19 Ribozyme Pharmaceuticals, Inc. Nucleoside analogs
JP2002511054A (ja) 1996-12-30 2002-04-09 メルク エンド カンパニー インコーポレーテッド ファルネシル蛋白トランスフェラーゼ阻害薬
WO1998029119A1 (en) 1996-12-30 1998-07-09 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US20030064945A1 (en) 1997-01-31 2003-04-03 Saghir Akhtar Enzymatic nucleic acid treatment of diseases or conditions related to levels of epidermal growth factor receptors
US6057156A (en) 1997-01-31 2000-05-02 Robozyme Pharmaceuticals, Inc. Enzymatic nucleic acid treatment of diseases or conditions related to levels of epidermal growth factor receptors
US6001311A (en) 1997-02-05 1999-12-14 Protogene Laboratories, Inc. Apparatus for diverse chemical synthesis using two-dimensional array
US6126919A (en) 1997-02-07 2000-10-03 3M Innovative Properties Company Biocompatible compounds for pharmaceutical drug delivery systems
AU6591798A (en) 1997-03-31 1998-10-22 Yale University Nucleic acid catalysts
US6235310B1 (en) 1997-04-04 2001-05-22 Valentis, Inc. Methods of delivery using cationic lipids and helper lipids
DE69841002D1 (de) 1997-05-14 2009-09-03 Univ British Columbia Hochwirksame verkapselung von nukleinsäuren in lipidvesikeln
US6835395B1 (en) 1997-05-14 2004-12-28 The University Of British Columbia Composition containing small multilamellar oligodeoxynucleotide-containing lipid vesicles
US6045528A (en) 1997-06-13 2000-04-04 Intraear, Inc. Inner ear fluid transfer and diagnostic system
CA2295207A1 (en) 1997-06-19 1998-12-23 Innovir Laboratories, Inc. Hammerhead ribozymes with extended cleavage rule
EP1017365B1 (en) 1997-06-23 2003-12-10 Sequus Pharmaceuticals, Inc. Liposome-entrapped polynucleotide composition and method
FR2766177B1 (fr) 1997-07-16 2000-04-14 Oreal Nouvelles bases d'oxydation cationiques, leur utilisation pour la teinture d'oxydation des fibres keratiniques, compositions tinctoriales et procedes de teinture
US6041181A (en) 1997-07-23 2000-03-21 International Business Machines Corporation Method of, system for, and computer program product for providing quick fusion in WHERE constructs
US6395713B1 (en) 1997-07-23 2002-05-28 Ribozyme Pharmaceuticals, Inc. Compositions for the delivery of negatively charged molecules
CA2301166A1 (en) 1997-07-24 1999-02-04 Yuan-Peng Zhang Liposomal compositions for the delivery of nucleic acid catalysts
AR013269A1 (es) 1997-08-04 2000-12-13 Scras Producto que contiene por lo menos un rna de doble filamento combinado con por lo menos un agente anti-viral, para la utilizacion terapeutica en eltratamiento de una enfermedad viral, en especial de la hepatitis viral
US5877309A (en) 1997-08-13 1999-03-02 Isis Pharmaceuticals, Inc. Antisense oligonucleotides against JNK
US6617156B1 (en) 1997-08-15 2003-09-09 Lynn A. Doucette-Stamm Nucleic acid and amino acid sequences relating to Enterococcus faecalis for diagnostics and therapeutics
IL135000A0 (en) 1997-09-12 2001-05-20 Exiqon As Bi- and tri-cyclic nucleoside, nucleotide and oligonucleotide analogues
KR20010030622A (ko) 1997-09-17 2001-04-16 리차드 알. 이킨 다중 표적 하이브리드형성 핵산과 그들의 제조, 구성,제제, 키트 및 응용
AU750947C (en) 1997-09-22 2003-05-22 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Nucleic acid catalysts with endonuclease activity
US6194151B1 (en) 1997-09-26 2001-02-27 Millenium Pharmaceuticals, Inc. Molecules of the TNF receptor superfamily and uses therefor
WO1999017120A1 (en) 1997-09-26 1999-04-08 Becton, Dickinson And Company Preparing conjugates using polyethylene glycol linkers
US6565885B1 (en) 1997-09-29 2003-05-20 Inhale Therapeutic Systems, Inc. Methods of spray drying pharmaceutical compositions
US6054576A (en) 1997-10-02 2000-04-25 Ribozyme Pharmaceuticals, Inc. Deprotection of RNA
US5932580A (en) 1997-12-01 1999-08-03 Yissum Research And Development Company Of The Hebrew University Of Jerusalem PDGF receptor kinase inhibitory compounds their preparation and compositions
US20030036517A1 (en) 1997-12-05 2003-02-20 Bruce A. Sullenger Nucleic acid mediated rna tagging and rna revision
AU1922999A (en) 1997-12-16 1999-07-05 Baylor College Of Medicine Needle-free injection of formulated nucleic acid molecules
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
EP2138191A1 (en) 1998-01-05 2009-12-30 University Of Washington Enhanced transport using membrane disruptive agents
US6410328B1 (en) 1998-02-03 2002-06-25 Protiva Biotherapeutics Inc. Sensitizing cells to compounds using lipid-mediated gene and compound delivery
US6111086A (en) 1998-02-27 2000-08-29 Scaringe; Stephen A. Orthoester protecting groups
AUPP249298A0 (en) 1998-03-20 1998-04-23 Ag-Gene Australia Limited Synthetic genes and genetic constructs comprising same I
SK287538B6 (sk) 1998-03-20 2011-01-04 Commonwealth Scientific And Industrial Research Organisation Syntetický gén obsahujúci dispergovanú alebo cudzorodú deoxyribonukleovú molekulu, génový konštrukt obsahujúci tento syntetický gén a prípravok obsahujúci tento syntetický gén
US6300131B1 (en) 1998-04-06 2001-10-09 Johns Hopkins University Telomerase-associated proteins
ATE507299T1 (de) 1998-04-08 2011-05-15 Commw Scient Ind Res Org Verfahren und mittel zum erhalt von veränderten phänotypen
JP2003525017A (ja) 1998-04-20 2003-08-26 リボザイム・ファーマシューティカルズ・インコーポレーテッド 遺伝子発現を調節しうる新規な化学組成を有する核酸分子
JP2002512794A (ja) 1998-04-29 2002-05-08 リボザイム・ファーマシューティカルズ・インコーポレーテッド ヌクレオチド三リン酸およびリボザイム内へのそれらの取り込み
AR020078A1 (es) 1998-05-26 2002-04-10 Syngenta Participations Ag Metodo para alterar la expresion de un gen objetivo en una celula de planta
GB9827152D0 (en) 1998-07-03 1999-02-03 Devgen Nv Characterisation of gene function using double stranded rna inhibition
JP2002520038A (ja) 1998-07-20 2002-07-09 アイネックス ファーマシューティカルズ コーポレイション リポソームカプセル化核酸複合体
US6440102B1 (en) 1998-07-23 2002-08-27 Durect Corporation Fluid transfer and diagnostic system for treating the inner ear
WO2000015524A1 (en) 1998-09-14 2000-03-23 Asc Machine Tools, Inc. Load former assembly
SG113454A1 (en) 1998-09-24 2005-08-29 Upjohn Co Alzheimer's disease secretase
WO2000021560A1 (en) 1998-10-09 2000-04-20 Ludwig Institute For Cancer Research Flt4 (VEGFR-3) AS A TARGET FOR TUMOR IMAGING AND ANTI-TUMOR THERAPY
US6995259B1 (en) 1998-10-23 2006-02-07 Sirna Therapeutics, Inc. Method for the chemical synthesis of oligonucleotides
IL126731A0 (en) 1998-10-23 1999-08-17 Intelligene Ltd A method of detection
CA2348779A1 (en) 1998-11-03 2000-05-11 Yale University Multidomain polynucleotide molecular sensors
US6069008A (en) 1998-11-25 2000-05-30 Isis Pharmaceuticals Inc. Antisense modulation of NF-kappa-B p65 subunit expression
AU776150B2 (en) 1999-01-28 2004-08-26 Medical College Of Georgia Research Institute, Inc. Composition and method for (in vivo) and (in vitro) attenuation of gene expression using double stranded RNA
JP2002536968A (ja) 1999-01-29 2002-11-05 イムクローン システムズ インコーポレイティド Ｋｄｒに特異的な抗体およびその使用
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
US6120484A (en) 1999-02-17 2000-09-19 Silverstein; Herbert Otological implant for delivery of medicament and method of using same
AU3369900A (en) 1999-02-19 2000-09-04 General Hospital Corporation, The Gene silencing
US5998206A (en) 1999-02-23 1999-12-07 Isis Pharmaceuticals Inc. Antisense inhibiton of human G-alpha-12 expression
GB9904387D0 (en) 1999-02-25 1999-04-21 Pharmacia & Upjohn Spa Antitumour synergistic composition
JP2002537828A (ja) 1999-03-10 2002-11-12 フォゲン リミティド 細胞への物質のデリバリー
US5998148A (en) 1999-04-08 1999-12-07 Isis Pharmaceuticals Inc. Antisense modulation of microtubule-associated protein 4 expression
EP1187633A4 (en) 1999-04-08 2005-05-11 Arch Dev Corp USE OF ANTI-VEGF ANTIBODY FOR INCREASING IRRADIATION IN CANCER THERAPY
EP2363478B1 (en) 1999-04-21 2019-07-24 Alnylam Pharmaceuticals, Inc. Methods and compositions for inhibiting the function of polynucleotide sequences
KR100782896B1 (ko) 1999-05-04 2007-12-06 엑시콘 에이/에스 Ｌ-리보-ｌｎａ 유사체
DE19925052B4 (de) 1999-06-01 2012-01-12 Alexander Cherkasky Proteinkomplexe für den zielgerichteten Transport von (Poly)Peptide und Nukleinsäuren und sequenzspezifische Integration von DNA-Vektoren
WO2000078431A1 (en) 1999-06-18 2000-12-28 N.V. Bekaert S.A. Hot gas filtration system
US6270625B1 (en) 1999-06-29 2001-08-07 The Mead Corporation Method for manufacturing colored stripped paper
JP2001072592A (ja) 1999-07-01 2001-03-21 Kyowa Hakko Kogyo Co Ltd テロメラーゼ阻害剤
CN1360631A (zh) 1999-07-09 2002-07-24 美国家用产品公司 在质粒序列转录过程中防止畸变rna形成的方法和组合物
WO2001005873A1 (en) 1999-07-14 2001-01-25 Alza Corporation Neutral lipopolymer and liposomal compositions containing same
AUPQ201499A0 (en) 1999-08-04 1999-08-26 Unisearch Limited Treatment of inflammatory and malignant diseases
JP2004512810A (ja) 1999-08-31 2004-04-30 サーナ・セラピューティクス・インコーポレイテッド 核酸に基づく遺伝子発現の調節剤
WO2001029058A1 (en) 1999-10-15 2001-04-26 University Of Massachusetts Rna interference pathway genes as tools for targeted genetic interference
US6545004B1 (en) 1999-10-27 2003-04-08 Cytokinetics, Inc. Methods and compositions utilizing quinazolinones
DE60028227T2 (de) 1999-10-27 2007-03-29 Cytokinetics, Inc., South San Francisco Chinazolinone benutzende verfahren und zusammenstellungen
GB9927444D0 (en) 1999-11-19 2000-01-19 Cancer Res Campaign Tech Inhibiting gene expression
DE10100586C1 (de) 2001-01-09 2002-04-11 Ribopharma Ag Verfahren zur Hemmung der Expression eines Ziegens
DE10160151A1 (de) 2001-01-09 2003-06-26 Ribopharma Ag Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens
WO2001038551A1 (en) 1999-11-29 2001-05-31 Cold Spring Harbor Laboratory Regulation of polycomb group gene expression for increasing seed size in plants
RU2164944C1 (ru) 1999-12-09 2001-04-10 Институт молекулярной биологии им. В.А. Энгельгардта РАН Способ изменения генетических свойств организма
WO2001049844A1 (en) 1999-12-30 2001-07-12 Rutgers, The State University Of New Jersey Compositions and methods for gene silencing
IT1316982B1 (it) 2000-01-17 2003-05-26 Univ Roma Isolamento e caratterizzazione di un gene per il silenziamento genicoda n.crassa e suoi usi.
US6602857B1 (en) 2000-01-18 2003-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US6261840B1 (en) 2000-01-18 2001-07-17 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US6831171B2 (en) 2000-02-08 2004-12-14 Yale University Nucleic acid catalysts with endonuclease activity
US20050233329A1 (en) 2002-02-20 2005-10-20 Sirna Therapeutics, Inc. Inhibition of gene expression using duplex forming oligonucleotides
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
WO2003070918A2 (en) 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated Rna interference by 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)
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)
US20080039414A1 (en) 2002-02-20 2008-02-14 Sima Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US20050020525A1 (en) 2002-02-20 2005-01-27 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified 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
US6401406B1 (en) 2000-02-11 2002-06-11 Domald K. Komara Retainment device for concrete block inspection plates
CA2400028A1 (en) 2000-02-14 2001-08-23 Arthur P. Bollon Libraries of optimum subsequence regions of mrna and genomic dna for control of gene expression
CA2403397A1 (en) 2000-03-16 2001-09-20 Genetica, Inc. Methods and compositions for rna interference
GB2377221B (en) 2000-03-17 2004-08-18 Benitec Australia Ltd Genetic silencing
JP2003528076A (ja) 2000-03-20 2003-09-24 メルク シャープ エンド ドーム リミテッド スルホンアミド置換架橋ビシクロアルキル誘導体
EP2319864A3 (de) 2000-03-22 2012-11-21 Sanofi-Aventis Deutschland GmbH Nematodes as model organisms for the investigation of neurodegenerative diseases, in particular parkinson's disease, use and method
GB0007268D0 (en) 2000-03-24 2000-05-17 Cyclacel Ltd Cell cycle progression proteins
WO2001075164A2 (en) 2000-03-30 2001-10-11 Whitehead Institute For Biomedical Research Rna sequence-specific mediators of rna interference
AU2001249723A1 (en) 2000-03-31 2001-10-15 Geron Corporation Telomerase inhibitor polynucleotides
KR20020097241A (ko) 2000-05-04 2002-12-31 에이브이아이 바이오파마 인코포레이티드 스플라이스-영역 안티센스 조성물 및 방법
US6824972B2 (en) 2000-05-22 2004-11-30 Baylor College Of Medicine Diagnosis and treatment of medical conditions associated with defective NFkappa B(NF-κB) activation
GB0012671D0 (en) 2000-05-24 2000-07-19 Merck Sharp & Dohme Therapeutic agents
US20100305186A1 (en) 2000-05-30 2010-12-02 Johnson & Johnson Research Pty Limited Methods for mediating gene suppression
WO2001096388A2 (en) 2000-06-09 2001-12-20 Corixa Corporation Compositions and methods for the therapy and diagnosis of colon cancer
WO2001096584A2 (en) 2000-06-12 2001-12-20 Akkadix Corporation Materials and methods for the control of nematodes
HUP0302779A3 (en) 2000-06-23 2005-12-28 Schering Ag Combinations and compositions which interfere with vegf/vegf and angiopoietin/tie receptor function and their use (ii)
EP1311277A4 (en) 2000-07-18 2004-08-25 Joslin Diabetes Center Inc FIBROSIS MODULATION METHOD
US7662791B2 (en) 2000-08-02 2010-02-16 University Of Southern California Gene silencing using mRNA-cDNA hybrids
CA2456008A1 (en) 2000-08-19 2002-02-28 Axordia Limited Stem cell differentiation
GB0020616D0 (en) 2000-08-21 2000-10-11 Quadrant Holdings Cambridge Particulates
US20030190635A1 (en) 2002-02-20 2003-10-09 Mcswiggen James A. RNA interference mediated treatment of Alzheimer's disease using short interfering RNA
AU8695901A (en) 2000-09-01 2002-03-13 Ribozyme Pharm Inc Methods for synthesizing nucleosides, nucleoside derivatives and non-nucleoside derivatives
US6613567B1 (en) 2000-09-15 2003-09-02 Isis Pharmaceuticals, Inc. Antisense inhibition of Her-2 expression
JP2002117576A (ja) 2000-10-03 2002-04-19 Tdk Corp 光記録媒体および光学的情報記録方法
US6998115B2 (en) 2000-10-10 2006-02-14 Massachusetts Institute Of Technology Biodegradable poly(β-amino esters) and uses thereof
US7427394B2 (en) 2000-10-10 2008-09-23 Massachusetts Institute Of Technology Biodegradable poly(β-amino esters) and uses thereof
GB0025173D0 (en) 2000-10-13 2000-11-29 Merck Sharp & Dohme Therapeutic agents
CA2427206C (en) 2000-11-02 2011-06-28 Merck Sharp & Dohme Limited Sulfamides as gamma-secretase inhibitors
ATE405585T1 (de) 2000-11-09 2008-09-15 Cenix Bioscience Gmbh Eukaryontische zellteilungsgene und deren verwendung in der diagnostik sowie in der behandlung von proliferativen erkrankungen
UA74849C2 (en) 2000-11-17 2006-02-15 Lilly Co Eli Lactam
AU2002217980A1 (en) 2000-12-01 2002-06-11 Cell Works Inc. Conjugates of glycosylated/galactosylated peptide
TR200401292T3 (tr) 2000-12-01 2004-07-21 Max@Planck@Gesellschaft�Zur�F�Rderung�Der�Wissenschaften RNAÁgirişimineÁyolÁaçanÁküçükÁRNAÁmolekülleri
US20020130430A1 (en) 2000-12-29 2002-09-19 Castor Trevor Percival Methods for making polymer microspheres/nanospheres and encapsulating therapeutic proteins and other products
US6401408B1 (en) 2001-01-29 2002-06-11 Plastics Research Corporation Molded plastic stake with multiple shoulders
US20030087855A1 (en) 2001-09-13 2003-05-08 Isis Pharmaceuticals Inc. Antisense modulation of protein kinase R expression
WO2004028341A2 (en) 2001-03-19 2004-04-08 Decode Genetics Ehf. Susceptibility gene for human stroke; methods of treatment
US20050164220A1 (en) 2001-03-19 2005-07-28 Decode Genetics Ehf. Susceptibility gene for human stroke: method of treatment
JP2004532022A (ja) 2001-03-26 2004-10-21 サーナ・セラピューティクス・インコーポレイテッド Ｂ型肝炎ウイルスおよびｃ型肝炎ウイルスの複製のオリゴヌクレオチド媒介性阻害
EP1386004A4 (en) 2001-04-05 2005-02-16 Ribozyme Pharm Inc MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID
GB0108592D0 (en) 2001-04-05 2001-05-23 Merck Sharp & Dohme Therapeutic agents
GB0108591D0 (en) 2001-04-05 2001-05-23 Merck Sharp & Dohme Therapeutic agents
JP2004527531A (ja) 2001-04-10 2004-09-09 メルク　エンド　カムパニー　インコーポレーテッド 癌を治療する方法
WO2002083675A2 (en) 2001-04-10 2002-10-24 Merck Sharp & Dohme Limited Inhibitors of akt activity
WO2002083139A1 (en) 2001-04-10 2002-10-24 Merck & Co., Inc. Inhibitors of akt activity
WO2002083140A1 (en) 2001-04-10 2002-10-24 Merck & Co., Inc. Inhibitors of akt activity
WO2002083138A1 (en) 2001-04-10 2002-10-24 Merck & Co., Inc. Inhibitors of akt activity
US20030077829A1 (en) 2001-04-30 2003-04-24 Protiva Biotherapeutics Inc.. Lipid-based formulations
US20060217331A1 (en) 2001-05-18 2006-09-28 Sirna Therapeutics, Inc. Chemically modified double stranded nucleic acid molecules that mediate RNA interference
US20070042983A1 (en) 2001-05-18 2007-02-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
WO2003070912A2 (en) 2001-06-06 2003-08-28 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF EPIDERMAL GROWTH FACTOR 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)
WO2003070972A2 (en) 2002-02-20 2003-08-28 Sirna Therapeutics Inc. RNA INTERFERENCE MEDIATED INHIBITION OF CHROMOSOME TRANSLOCATION 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)
US20050137155A1 (en) 2001-05-18 2005-06-23 Sirna Therapeutics, Inc. RNA interference mediated treatment of Parkinson disease using short interfering nucleic acid (siNA)
WO2003072590A1 (en) 2002-02-20 2003-09-04 Sirna Therapeutics, Inc. Rna interference mediated inhibition of map kinase genes
US20050282188A1 (en) 2001-05-18 2005-12-22 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
WO2004097020A2 (en) 2003-04-25 2004-11-11 Sirna Therapeutics, Inc. Rna interference mediated inhibition of map kinase gene expression
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)
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)
US20040219671A1 (en) 2002-02-20 2004-11-04 Sirna Therapeutics, Inc. RNA interference mediated treatment of parkinson disease using short interfering nucleic acid (siNA)
WO2003070884A2 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF MDR P-GLYCOPROTEIN GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
WO2003070969A2 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF BCL2 GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20030130186A1 (en) 2001-07-20 2003-07-10 Chandra Vargeese Conjugates and compositions for cellular delivery
US20040019001A1 (en) 2002-02-20 2004-01-29 Mcswiggen James A. RNA interference mediated inhibition of protein typrosine phosphatase-1B (PTP-1B) gene expression using short interfering RNA
US20030124513A1 (en) 2001-05-29 2003-07-03 Mcswiggen James Enzymatic nucleic acid treatment of diseases or conditions related to levels of HIV
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)
US20030175950A1 (en) 2001-05-29 2003-09-18 Mcswiggen James A. RNA interference mediated inhibition of HIV gene expression using short interfering RNA
EP2415486B1 (en) 2001-05-18 2017-02-22 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
EP1627061B1 (en) 2001-05-18 2009-08-12 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED 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)
US20050048529A1 (en) 2002-02-20 2005-03-03 Sirna Therapeutics, Inc. RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) 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)
WO2003070750A2 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc Rna interference mediated inhibition of hepatitis c virus
WO2003070910A2 (en) 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGF 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)
WO2003072705A2 (en) 2002-02-20 2003-09-04 Sirna Therapeutics, Inc. Rna interference mediated inhibition of cyclin d1 gene expression using short interfering nucleic acid (sina)
WO2003070983A1 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc RNA INTERFERENCE MEDIATED INHIBITION OF PROTEIN KINASE C ALPHA (PKC-ALPHA) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US7109165B2 (en) 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
WO2003070917A2 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc. Rna interference mediated inhibition of myc and myb genes or genes of their respective pathways
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)
AU2002312059B2 (en) 2001-05-25 2009-01-15 Duke University Modulators of pharmacological agents
EP1390385A4 (en) 2001-05-29 2004-11-24 Sirna Therapeutics Inc MODULATION OF DISEASES AND DISEASES OF THE FEMALE REPRODUCTION SYSTEM BASED ON NUCLEIC ACID
FR2826666B1 (fr) 2001-07-02 2004-07-02 Novaleads Procede de selection d'agents bio-actifs par couplage de luminescence et systeme cellulaire vivant pour la mise en oeuvre de ce procede
US20050055208A1 (en) 2001-07-03 2005-03-10 Kibkalo Alexandr A. Method and apparatus for fast calculation of observation probabilities in speech recognition
US6586524B2 (en) 2001-07-19 2003-07-01 Expression Genetics, Inc. Cellular targeting poly(ethylene glycol)-grafted polymeric gene carrier
EP1430140B1 (en) 2001-08-01 2010-09-15 University of Utah N-terminally truncated isoforms of pde3a cyclic phosphodiesterases
GB0119152D0 (en) 2001-08-06 2001-09-26 Merck Sharp & Dohme Therapeutic agents
WO2003013526A1 (en) 2001-08-08 2003-02-20 Merck & Co. Inc. Anticoagulant compounds
WO2003016572A1 (en) 2001-08-17 2003-02-27 Eli Lilly And Company Oligonucleotide therapeutics for treating hepatitis c virus infections
EA006225B1 (ru) 2001-08-21 2005-10-27 Мерк Шарп Энд Домэ Лимитед Новые циклогексилсульфоны
JP4344858B2 (ja) 2001-09-13 2009-10-14 カリフォルニア インスティチュート オブ テクノロジー 細胞内で抗ウイルス性小ｒｎａ分子を発現させる方法
GB0122318D0 (en) 2001-09-14 2001-11-07 Novartis Ag Organic compounds
US7514415B2 (en) 2002-08-01 2009-04-07 The United States Of America As Represented By The Department Of Health And Human Services Method of treating inflammatory arthropathies with suppressors of CpG oligonucleotides
US20050191627A1 (en) 2001-09-28 2005-09-01 Incyte Corporation Enzymes
FR2830767B1 (fr) 2001-10-12 2004-03-12 Optis France Sa Dispositif de delivrance de medicaments par iontophorese ou electroporation introculaire
FR2830766B1 (fr) 2001-10-12 2004-03-12 Optis France Sa Dispositif de delivrance de medicaments par iontophorese transpalpebrale
CA2478681A1 (en) 2001-10-22 2003-05-01 University Of Rochester Telomerase interference
AUPR894201A0 (en) 2001-11-19 2001-12-13 Women's And Children's Hospital Respiratory delivery for gene therapy and lentiviral delivery particle
ES2401326T3 (es) 2001-11-21 2013-04-18 Astellas Pharma Inc. Procedimiento para inhibir la expresión génica
US7060498B1 (en) 2001-11-28 2006-06-13 Genta Salus Llc Polycationic water soluble copolymer and method for transferring polyanionic macromolecules across biological barriers
US7141540B2 (en) 2001-11-30 2006-11-28 Genta Salus Llc Cyclodextrin grafted biocompatible amphilphilic polymer and methods of preparation and use thereof
EP1465896A4 (en) 2001-12-06 2006-01-11 Merck & Co Inc MITOTIC INHIBITORS OF KINESIN
AU2002351183B2 (en) 2001-12-06 2008-05-08 Merck Sharp & Dohme Corp. Mitotic kinesin inhibitors
DE60231439D1 (de) 2001-12-06 2009-04-16 Merck & Co Inc Mitotische kinesinhemmer
CA2467722A1 (en) 2001-12-06 2003-06-19 Merck & Co., Inc. Thienopyrimidinone derivatives as mitotic kinesin inhibitors
DE60232994D1 (de) 2001-12-06 2009-08-27 Merck & Co Inc Inhibitoren von mitotischem kinesin
US20050118594A1 (en) 2001-12-14 2005-06-02 Chawla Narinder K. Enzymes
EP1572902B1 (en) 2002-02-01 2014-06-11 Life Technologies Corporation HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES
ATE508188T1 (de) 2002-02-01 2011-05-15 Life Technologies Corp Oligonukleotid-zusammensetzungen mit verbesserter wirksamkeit
CA2476530A1 (en) 2002-02-14 2003-08-21 City Of Hope Methods for producing interfering rna molecules in mammalian cells and therapeutic uses for such molecules
EP1472265A4 (en) 2002-02-20 2005-06-15 Sirna Therapeutics Inc INHIBITION OF POLYCOMB GROUP PROTEIN EZH2 GENERATED BY RNA INTERFERENCE USING SHORT INTERFERING NUCLEIC ACID (siNA)
US8232383B2 (en) 2002-02-20 2012-07-31 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
AU2003216265A1 (en) 2002-02-20 2003-09-09 Ribozyme Pharmaceuticals, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF G72 AND D-AMINO ACID OXIDASE (DAAO) 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)
AU2003219781A1 (en) 2002-02-20 2003-09-09 Sirna Therapeutics, Inc RNA INTERFERENCE MEDIATED INHIBITION OF PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) 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)
EP1432725A4 (en) 2002-02-20 2005-03-30 Sirna Therapeutics Inc RNA INTERFERENCE-MEDIATED INHIBITION OF TELOMERASEGENEXPRESSION WITH SHORT INTERFERING NUCLEIC ACID (SINA)
CA2477014A1 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc. Rna interference mediated inhibition of tnf and tnf receptor superfamily gene expression using short interfering nucleic acid (sina)
EP1465910A4 (en) 2002-02-20 2005-03-16 Sirna Therapeutics Inc INHIBITION OF EXPRESSION OF RNA I-MEDIATED GENE CHECKPOINT KINASE-1 (CHK-1) USING NEAR-INTERFERENCE NUCLEIC ACID
US20050266422A1 (en) 2002-02-20 2005-12-01 Sirna Therapeutics, Inc. Fluoroalkoxy, nucleosides, nucleotides, and polynucleotides
WO2003106476A1 (en) 2002-02-20 2003-12-24 Sirna Therapeutics, Inc Nucleic acid mediated inhibition of enterococcus infection and cytolysin toxin activity
JP2005517450A (ja) 2002-02-20 2005-06-16 サーナ・セラピューティクス・インコーポレイテッド 短干渉核酸（ｓｉＮＡ）を用いるＲＮＡ干渉媒介性標的発見および標的評価
JP2005517423A (ja) 2002-02-20 2005-06-16 サーナ・セラピューティクス・インコーポレイテッド 短干渉核酸（ｓｉＮＡ）を用いるＴＧＦ−ベータおよびＴＧＦ−ベータレセプター遺伝子の発現のＲＮＡ干渉媒介性阻害
EP1710307A3 (en) 2002-02-20 2007-06-06 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA)
EP1432724A4 (en) 2002-02-20 2006-02-01 Sirna Therapeutics Inc RNA inhibition mediated inhibition of MAP KINASE GENES
AU2003249597B2 (en) 2002-03-08 2007-06-28 Merck Sharp & Dohme Corp. Mitotic kinesin inhibitors
DE60327618D1 (de) 2002-03-27 2009-06-25 Aegera Therapeutics Inc Gegen iap gerichtete antisense-nukleobasen und deren verwendungen
JP4394960B2 (ja) 2002-04-08 2010-01-06 メルク エンド カムパニー インコーポレーテッド Ａｋｔ活性阻害薬
US20050130977A1 (en) 2002-04-08 2005-06-16 Lindsley Craig W. Inhibitors of akt activity
WO2003086404A1 (en) 2002-04-08 2003-10-23 Merck & Co., Inc. Fused quinoxaline derivatives as inhibitors of akt activity
AU2003226250B2 (en) 2002-04-08 2007-08-16 Merck Sharp & Dohme Corp. Inhibitors of Akt activity
WO2003084473A2 (en) 2002-04-08 2003-10-16 Merck & Co., Inc. Method of treating cancer
GB0209997D0 (en) 2002-05-01 2002-06-12 Merck Sharp & Dohme Therapeutic agents
WO2003093252A1 (en) 2002-05-01 2003-11-13 Merck Sharp & Dohme Limited Heteroaryl substituted spirocyclic sulfamides for inhibition of gamma secretase
GB0209991D0 (en) 2002-05-01 2002-06-12 Merck Sharp & Dohme Therapeutic agents
GB0209995D0 (en) 2002-05-01 2002-06-12 Merck Sharp & Dohme Therapeutic agents
AU2003231799A1 (en) 2002-05-23 2003-12-12 Merck & Co., Inc. Mitotic kinesin inhibitors
AU2003299517A1 (en) 2002-05-23 2004-05-25 Merck & Co., Inc. Mitotic kinesin inhibitors
AU2003237686A1 (en) 2002-05-24 2003-12-12 Max-Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. Rna interference mediating small rna molecules
CA2388441A1 (en) 2002-06-10 2003-12-10 Wei-Ping Min Immunomodulation using rna interference
BR0311784A (pt) 2002-06-14 2005-03-08 Merck & Co Inc Composto, composição farmacêutica, métodos de tratar ou prevenir o câncer, de modular a formação do fuso mitótico e de inibir a cinesina mitótica e processo para fabricar uma composição farmacêutica
DE60312516T2 (de) 2002-06-14 2007-11-22 Merck & Co., Inc. Inhibitoren von mitotischem kinesin
US20040077540A1 (en) 2002-06-28 2004-04-22 Nastech Pharmaceutical Company Inc. Compositions and methods for modulating physiology of epithelial junctional adhesion molecules for enhanced mucosal delivery of therapeutic compounds
US6989442B2 (en) 2002-07-12 2006-01-24 Sirna Therapeutics, Inc. Deprotection and purification of oligonucleotides and their derivatives
US20040146858A1 (en) 2002-07-24 2004-07-29 Immusol, Inc. Novel siRNA gene libraries and methods for their production and use
US7148342B2 (en) 2002-07-24 2006-12-12 The Trustees Of The University Of Pennyslvania Compositions and methods for sirna inhibition of angiogenesis
US20050106731A1 (en) 2002-08-05 2005-05-19 Davidson Beverly L. siRNA-mediated gene silencing with viral vectors
US8216609B2 (en) 2002-08-05 2012-07-10 Torrent Pharmaceuticals Limited Modified release composition of highly soluble drugs
EP1389637B1 (en) 2002-08-05 2012-05-30 Silence Therapeutics Aktiengesellschaft Blunt-ended interfering RNA molecules
AU2003260370B2 (en) 2002-08-05 2008-05-22 Silence Therapeutics Gmbh Further novel forms of interfering RNA molecules
US7923547B2 (en) 2002-09-05 2011-04-12 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US20050020521A1 (en) 2002-09-25 2005-01-27 University Of Massachusetts In vivo gene silencing by chemically modified and stable siRNA
GB0223040D0 (en) 2002-10-04 2002-11-13 Merck Sharp & Dohme Therapeutic compounds
GB0223039D0 (en) 2002-10-04 2002-11-13 Merck Sharp & Dohme Therapeutic compounds
GB0223038D0 (en) 2002-10-04 2002-11-13 Merck Sharp & Dohme Therapeutic compounds
US7235580B2 (en) 2002-10-18 2007-06-26 Merck & Co., Inc. Mitotic kinesin inhibitors
US8133903B2 (en) 2003-10-21 2012-03-13 Los Angeles Biomedical Research Institute at Harbor—UCLA Medical Center Methods of use of inhibitors of phosphodiesterases and modulators of nitric oxide, reactive oxygen species, and metalloproteinases in the treatment of peyronie's disease, arteriosclerosis and other fibrotic diseases
US7399764B2 (en) 2002-10-30 2008-07-15 Merck & Co., Inc. Inhibitors of Akt activity
US20040102360A1 (en) 2002-10-30 2004-05-27 Barnett Stanley F. Combination therapy
GB0225474D0 (en) 2002-11-01 2002-12-11 Merck Sharp & Dohme Therapeutic agents
GB0225475D0 (en) 2002-11-01 2002-12-11 Merck Sharp & Dohme Therapeutic agents
US9150605B2 (en) 2002-11-05 2015-10-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
WO2004043977A2 (en) 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. 2’-fluoro substituted oligomeric compounds and compositions for use in gene modulations
JP3839453B2 (ja) 2002-11-22 2006-11-01 株式会社バイオシンクタンク Ｒｎａ干渉の標的塩基配列検索方法、ｒｎａ干渉を生じさせるポリヌクレオチドの塩基配列設計方法、２本鎖ポリヌクレオチドの作製方法、遺伝子の発現抑制方法、塩基配列処理装置、塩基配列処理方法をコンピュータに実行させるプログラム、記録媒体、および、塩基配列処理システム
JP4590270B2 (ja) 2002-12-20 2010-12-01 メルク・シャープ・エンド・ドーム・コーポレイション 有糸分裂キネシン阻害剤
AU2003297230B2 (en) 2002-12-20 2009-11-26 Merck Sharp & Dohme Corp. Mitotic kinesin inhibitors
AU2004210972A1 (en) 2003-02-11 2004-08-26 Immusol Incorporated siRNA libraries optimized for predetermined protein families
US7816337B2 (en) 2003-02-18 2010-10-19 Roche Madison Inc. Reversible attachment of a membrane active polymer to a polynucleotide
NZ542059A (en) * 2003-02-28 2009-11-27 Florey Howard Inst Therapeutic compositions comprising an aryl sulphonate such as suramin, for the treatment of a pathological condition or event of the systemic vasculature resulting form the producation of reactive oxygen species.
US6977223B2 (en) 2003-03-07 2005-12-20 Massachusetts Institute Of Technology Three dimensional microfabrication
EP1608733B1 (en) 2003-04-02 2011-12-07 Dharmacon, Inc. Modified polynucleotides for use in rna interference
GB0308318D0 (en) 2003-04-10 2003-05-14 Merck Sharp & Dohme Therapeutic agents
DE602004026047D1 (de) 2003-04-24 2010-04-29 Merck Sharp & Dohme Hemmer der akt aktivität
EP1622616B1 (en) 2003-04-24 2011-06-15 Merck Sharp & Dohme Corp. Inhibitors of akt activity
AU2004233827B2 (en) 2003-04-24 2009-05-28 Merck Sharp & Dohme Corp. Inhibitors of Akt activity
AU2004233835B2 (en) 2003-04-24 2010-02-25 Merck Sharp & Dohme Corp. Inhibitors of Akt activity
EP3222294A1 (en) 2003-04-30 2017-09-27 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US7410964B2 (en) 2003-05-16 2008-08-12 Merck Sharp & Dohme Ltd. Cyclohexyl sulphones as gamma-secretase inhibitors
US7179619B2 (en) 2003-07-10 2007-02-20 Irm Llc Methods and compositions for inhibiting herpesviral replication
AU2004257373B2 (en) 2003-07-16 2011-03-24 Arbutus Biopharma Corporation Lipid encapsulated interfering RNA
GB0318447D0 (en) 2003-08-05 2003-09-10 Merck Sharp & Dohme Therapeutic agents
EP1656140A4 (en) 2003-08-13 2009-03-04 Merck & Co Inc INHIBITORS OF MITOTIC KINESINE
CA2534729A1 (en) 2003-08-15 2005-02-24 Merck & Co., Inc. Mitotic kinesin inhibitors
US7666862B2 (en) 2003-08-15 2010-02-23 Merck & Co., Inc. Mitotic Kinesin Inhibitors
PE20050730A1 (es) 2003-08-15 2005-09-20 Merck & Co Inc Derivados de 2,5-dihidropirrol 2,2-disustituidos como inhibidores de quinesinas mitoticas
US20060234984A1 (en) 2003-08-15 2006-10-19 Coleman Paul J Mitotic kinesin inhibitors
NZ592917A (en) 2003-09-15 2012-12-21 Protiva Biotherapeutics Inc Stable polyethyleneglycol (PEG) dialkyloxypropyl (DAA) lipid conjugates
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)
US7943179B2 (en) 2003-09-23 2011-05-17 Massachusetts Institute Of Technology pH triggerable polymeric particles
CA2539042A1 (en) 2003-09-24 2005-04-07 Merck Sharp & Dohme Limited Gamma-secretase inhibitors
CN101579529A (zh) 2003-09-29 2009-11-18 托皮根药品公司 治疗包括炎症状况的疾病的寡核苷酸组合物和方法
WO2005045034A2 (en) 2003-10-23 2005-05-19 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED TREATMENT OF PARKINSON DISEASE USING SHORT INTERERING NUCLEIC ACID (siNA)
CA2543013A1 (en) 2003-10-23 2005-05-19 Sirna Therapeutics, Inc. Rna interference mediated inhibition of nogo and nogo receptor gene expression using short interfering nucleic acid (sina)
WO2005044354A1 (en) 2003-11-03 2005-05-19 Glaxo Group Limited A fluid dispensing device
EP1693450A4 (en) 2003-11-21 2007-10-31 Bio Think Tank Co Ltd METHOD FOR DETECTING RNAi ACTIVITY AND miRNA ACTIVITY
US20100145038A1 (en) 2003-11-24 2010-06-10 Merck & Co., Inc. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
WO2005054494A2 (en) 2003-11-26 2005-06-16 University Of Massachusetts Sequence-specific inhibition of small rna function
US20060019912A1 (en) 2003-12-19 2006-01-26 Chiron Corporation Cell transfecting formulations of small interfering RNA related compositions and methods of making and use
US7294640B2 (en) 2004-02-06 2007-11-13 Merck & Co., Inc. Mitotic kinesin inhibitors
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)
US20050182005A1 (en) 2004-02-13 2005-08-18 Tuschl Thomas H. Anti-microRNA oligonucleotide molecules
ATE499364T1 (de) 2004-04-09 2011-03-15 Merck Sharp & Dohme Hemmer der akt aktivität
WO2005100356A1 (en) 2004-04-09 2005-10-27 Merck & Co., Inc. Inhibitors of akt activity
MXPA06012076A (es) 2004-04-20 2007-01-25 Nastech Pharm Co Metodos y composiciones para mejorar el suministro de arn bicatenario o un acido nucleico hibrido bicatenario para regular la expresion genetica en celulas de mamifero.
US7811602B2 (en) 2004-05-17 2010-10-12 Tekmira Pharmaceuticals Corporation Liposomal formulations comprising dihydrosphingomyelin and methods of use thereof
EP1781593B1 (en) 2004-06-07 2011-12-14 Protiva Biotherapeutics Inc. Cationic lipids and methods of use
US20060019258A1 (en) 2004-07-20 2006-01-26 Illumina, Inc. Methods and compositions for detection of small interfering RNA and micro-RNA
US20060062758A1 (en) 2004-09-21 2006-03-23 Nastech Pharmaceutical Comapny Inc. Tight junction modulator peptide PN159 for enhanced mucosal delivery of therapeutic compounds
WO2007086883A2 (en) * 2005-02-14 2007-08-02 Sirna Therapeutics, Inc. Cationic lipids and formulated molecular compositions containing them
US7404969B2 (en) * 2005-02-14 2008-07-29 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules
AU2006279454B2 (en) 2005-08-17 2011-12-15 Sirna Therapeutics, Inc. Chemically modified short interfering nucleic acid molecules that mediate rna interference
US20090176725A1 (en) 2005-08-17 2009-07-09 Sirna Therapeutics Inc. Chemically modified short interfering nucleic acid molecules that mediate rna interference
GB0605337D0 (en) 2006-03-17 2006-04-26 Genomica Sau Treatment of CNS conditions
US7915399B2 (en) 2006-06-09 2011-03-29 Protiva Biotherapeutics, Inc. Modified siRNA molecules and uses thereof
CN102614528B (zh) 2006-08-18 2014-02-26 箭头研究公司 用于体内递送多核苷酸的多缀合物
WO2008137751A2 (en) * 2007-05-02 2008-11-13 Sirna Therapeutics, Inc. Rna interference mediated inhibition of cyclic nucleotide type 4 phosphodiesterase (pde4b) gene expression using short interfering nucleic acid (sina)
MY153691A (en) 2007-05-22 2015-03-13 Arcturus Therapeutics Inc Hydroxymethyl substituted rna oligonucleotides and rna complexes
AU2008333811B2 (en) 2007-12-04 2014-05-01 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
CA2708171C (en) 2007-12-04 2018-02-27 Alnylam Pharmaceuticals, Inc. Folate conjugates
CA2713379A1 (en) 2008-01-31 2009-11-05 Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of dsrna targeting the pcsk9 gene
AU2009238175C1 (en) 2008-04-15 2023-11-30 Arbutus Biopharma Corporation Novel lipid formulations for nucleic acid delivery
US20090263407A1 (en) * 2008-04-16 2009-10-22 Abbott Laboratories Cationic Lipids and Uses Thereof
US8315366B2 (en) 2008-07-22 2012-11-20 Shoretel, Inc. Speaker identification and representation for a phone
AU2009303345B2 (en) 2008-10-09 2015-08-20 Arbutus Biopharma Corporation Improved amino lipids and methods for the delivery of nucleic acids
WO2010048536A2 (en) 2008-10-23 2010-04-29 Alnylam Pharmaceuticals, Inc. Processes for preparing lipids
US20100168205A1 (en) 2008-10-23 2010-07-01 Alnylam Pharmaceuticals, Inc. Methods and Compositions for Prevention or Treatment of RSV Infection Using Modified Duplex RNA Molecules
HUE037082T2 (hu) 2008-11-10 2018-08-28 Arbutus Biopharma Corp Új lipidek és készítmények terápiás hatóanyagok szállítására
KR20110110776A (ko) 2008-12-18 2011-10-07 다이서나 파마수이티컬, 인크. 유전자 발현의 특이적 억제를 위한 연장된 다이서 기질 제제 및 방법
US20120101148A1 (en) 2009-01-29 2012-04-26 Alnylam Pharmaceuticals, Inc. lipid formulation
WO2010093788A2 (en) 2009-02-11 2010-08-19 Dicerna Pharmaceuticals, Inc. Multiplex dicer substrate rna interference molecules having joining sequences
JP2010196550A (ja) 2009-02-24 2010-09-09 Mitsubishi Heavy Ind Ltd 回転軸とレバーの取付構造、回転軸とレバーの取付方法、及び、流体機械
AU2010226604A1 (en) * 2009-03-19 2011-10-13 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of BTB and CNC homology 1, basic leucine zipper transcription factor 1 (Bach 1) gene expression using short interfering nucleic acid (siNA) sequence listing
JP2012521763A (ja) * 2009-03-27 2012-09-20 メルク・シャープ・エンド・ドーム・コーポレイション 低分子干渉核酸（ｓｉＮＡ）を用いたシグナル伝達性転写因子１（ＳＴＡＴ１）遺伝子発現のＲＮＡ干渉媒介性阻害
CA2757613C (en) 2009-04-03 2023-10-17 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of kras by asymmetric double-stranded rna
DK2440183T3 (da) 2009-06-10 2018-10-01 Arbutus Biopharma Corp Forbedret lipidformulering
US20110027559A1 (en) 2009-07-31 2011-02-03 Glen Harold Kirby Water based environmental barrier coatings for high temperature ceramic components
WO2011028550A1 (en) 2009-08-24 2011-03-10 Merck Sharp & Dohme Corp. Segmented micro rna mimetics
WO2011088554A1 (en) 2010-01-20 2011-07-28 Magna International Inc. Bi-metallic component and method of making the same
EP3372684B1 (en) 2010-08-24 2020-10-07 Sirna Therapeutics, Inc. Single-stranded rnai agents containing an internal, non-nucleic acid spacer
WO2012058210A1 (en) 2010-10-29 2012-05-03 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA)
WO2012068187A1 (en) 2010-11-19 2012-05-24 Merck Sharp & Dohme Corp. Poly(amide) polymers for the delivery of oligonucleotides
WO2013074974A2 (en) 2011-11-18 2013-05-23 Alnylam Pharmaceuticals, Inc. Modified rnai agents
US20150299696A1 (en) 2012-05-02 2015-10-22 Sirna Therapeutics, Inc. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
ES2905257T3 (es) 2013-07-03 2022-04-07 Dicerna Pharmaceuticals Inc Métodos y composiciones para la inhibición específica de alfa-1 antitripsina mediante ARN bicatenario

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