CA2767253A1 - Novel nucleic acid prodrugs and methods of use thereof - Google Patents
Novel nucleic acid prodrugs and methods of use thereof Download PDFInfo
- Publication number
- CA2767253A1 CA2767253A1 CA2767253A CA2767253A CA2767253A1 CA 2767253 A1 CA2767253 A1 CA 2767253A1 CA 2767253 A CA2767253 A CA 2767253A CA 2767253 A CA2767253 A CA 2767253A CA 2767253 A1 CA2767253 A1 CA 2767253A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- aryl
- nucleic acid
- hydrogen
- och2ch2s
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 292
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 292
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 288
- 229940002612 prodrug Drugs 0.000 title claims abstract description 223
- 239000000651 prodrug Substances 0.000 title claims abstract description 223
- 238000000034 method Methods 0.000 title claims abstract description 145
- 125000000217 alkyl group Chemical group 0.000 claims description 337
- 150000001875 compounds Chemical class 0.000 claims description 195
- 229910052739 hydrogen Inorganic materials 0.000 claims description 183
- 239000001257 hydrogen Substances 0.000 claims description 182
- 125000003118 aryl group Chemical group 0.000 claims description 154
- 125000004432 carbon atom Chemical group C* 0.000 claims description 131
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 122
- 230000000903 blocking effect Effects 0.000 claims description 118
- 125000001072 heteroaryl group Chemical group 0.000 claims description 105
- 125000000623 heterocyclic group Chemical group 0.000 claims description 104
- 206010028980 Neoplasm Diseases 0.000 claims description 94
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 93
- 125000003342 alkenyl group Chemical group 0.000 claims description 88
- 125000000304 alkynyl group Chemical group 0.000 claims description 88
- 201000011510 cancer Diseases 0.000 claims description 67
- 125000005647 linker group Chemical group 0.000 claims description 61
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 60
- 239000007787 solid Substances 0.000 claims description 60
- 229910052717 sulfur Inorganic materials 0.000 claims description 57
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 56
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 52
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 52
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 50
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- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22336909P | 2009-07-06 | 2009-07-06 | |
| US61/223,369 | 2009-07-06 | ||
| US24272209P | 2009-09-15 | 2009-09-15 | |
| US61/242,722 | 2009-09-15 | ||
| PCT/US2010/041068 WO2011005761A1 (en) | 2009-07-06 | 2010-07-06 | Novel nucleic acid prodrugs and methods use thereof |
Publications (1)
| Publication Number | Publication Date |
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| CA2767253A1 true CA2767253A1 (en) | 2011-01-13 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CA2767253A Abandoned CA2767253A1 (en) | 2009-07-06 | 2010-07-06 | Novel nucleic acid prodrugs and methods of use thereof |
Country Status (15)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11390642B2 (en) | 2016-08-23 | 2022-07-19 | Dicerna Pharmaceuticals, Inc. | Compositions comprising reversibly modified oligonucleotides and uses thereof |
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|---|---|---|---|---|
| KR101927905B1 (ko) * | 2008-04-03 | 2018-12-11 | 스프링 뱅크 파마슈티칼스, 인크. | 바이러스 감염증을 치료하기 위한 조성물 및 방법 |
| BRPI0923225A2 (pt) | 2008-12-02 | 2016-10-04 | Chiralgen Ltd | metodo para sintese de acidos nucleicos modificados no atomo de fosforo |
| KR101885383B1 (ko) | 2009-07-06 | 2018-08-03 | 웨이브 라이프 사이언시스 리미티드 | 신규한 핵산 프로드러그 및 그의 사용 방법 |
| JP5868324B2 (ja) | 2010-09-24 | 2016-02-24 | 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ | 不斉補助基 |
| CN103796657B (zh) | 2011-07-19 | 2017-07-11 | 波涛生命科学有限公司 | 合成官能化核酸的方法 |
| EP2873674B1 (en) | 2012-07-13 | 2020-05-06 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| SG11201500239VA (en) | 2012-07-13 | 2015-03-30 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| EP4219516A3 (en) | 2012-07-13 | 2024-01-10 | Wave Life Sciences Ltd. | Chiral control |
| CN104781271B (zh) * | 2012-08-20 | 2018-07-06 | 加利福尼亚大学董事会 | 具有生物可逆的基团的多核苷酸 |
| SG10201707135RA (en) * | 2013-03-01 | 2017-10-30 | Astex Pharmaceuticals Inc | Drug combinations |
| 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 |
| US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| 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 |
| KR102423317B1 (ko) | 2014-01-16 | 2022-07-22 | 웨이브 라이프 사이언시스 리미티드 | 키랄 디자인 |
| RU2708237C2 (ru) | 2014-08-22 | 2019-12-05 | Общество с ограниченной ответственностью "НооГен" | Модифицированные олигонуклеотиды и способ их получения |
| WO2016096938A1 (en) | 2014-12-16 | 2016-06-23 | Roche Innovation Center Copenhagen A/S | Chiral toxicity screening method |
| EP3712269A1 (en) | 2014-12-17 | 2020-09-23 | ProQR Therapeutics II B.V. | Targeted rna editing |
| JPWO2016208773A1 (ja) * | 2015-06-26 | 2018-04-12 | 協和発酵キリン株式会社 | オリゴヌクレオチド誘導体 |
| MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| EP3359523A4 (en) | 2015-10-09 | 2019-07-24 | Wave Life Sciences Ltd. | OLIGONUCLEOTIDE COMPOSITIONS AND RELATED METHODS |
| US20190070212A1 (en) * | 2016-03-11 | 2019-03-07 | Spring Bank Pharmaceuticals, Inc. | Compounds and compositions for the treatment of infections |
| MA43822A (fr) | 2016-03-13 | 2018-11-28 | Wave Life Sciences Ltd | Compositions et procédés de synthèse de phosphoramidite et d'oligonucléotides |
| WO2017184529A1 (en) | 2016-04-18 | 2017-10-26 | Sarepta Therapeutics, Inc. | Antisense oligomers and methods of using the same for treating diseases associated with the acid alpha-glucosidase gene |
| NZ747685A (en) | 2016-04-29 | 2023-05-26 | Sarepta Therapeutics Inc | Oligonucleotide analogues targeting human lmna |
| MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| MA45188A (fr) | 2016-06-03 | 2019-04-10 | Wave Life Sciences Ltd | Oligonucléotides, compositions et méthodes associées |
| JP7074345B2 (ja) | 2016-06-22 | 2022-05-24 | プロキューアール セラピューティクス ツー ベスローテン フェンノートシャップ | 一本鎖ｒｎａ編集オリゴヌクレオチド |
| WO2018005805A1 (en) | 2016-06-30 | 2018-01-04 | Sarepta Therapeutics, Inc. | Exon skipping oligomers for muscular dystrophy |
| CN109715202A (zh) * | 2016-07-15 | 2019-05-03 | 斯必乐维生物科学公司 | 用于治疗疾病的化合物、组合物和方法 |
| EP3500581A4 (en) | 2016-08-17 | 2021-10-06 | Solstice Biologics, Ltd. | POLYNUCLEOTIDE CONSTRUCTS |
| EP3507366B1 (en) | 2016-09-01 | 2020-10-07 | ProQR Therapeutics II B.V. | Chemically modified single-stranded rna-editing oligonucleotides |
| JP7296882B2 (ja) | 2016-11-23 | 2023-06-23 | ウェイブ ライフ サイエンシズ リミテッド | ホスホラミダイト及びオリゴヌクレオチド合成のための組成物及び方法 |
| JOP20170192A1 (ar) | 2016-12-01 | 2019-01-30 | Takeda Pharmaceuticals Co | داي نوكليوتيد حلقي |
| CA3047010A1 (en) | 2016-12-19 | 2018-06-28 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| LT3554554T (lt) | 2016-12-19 | 2022-11-25 | Sarepta Therapeutics, Inc. | Egzoną praleidžiantys oligomero konjugatai nuo raumenų distrofijos |
| WO2018118599A1 (en) | 2016-12-19 | 2018-06-28 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| JP7190794B2 (ja) | 2017-03-29 | 2022-12-16 | 塩野義製薬株式会社 | 核酸医薬及び多分岐脂質の複合体 |
| EP3601309A1 (en) | 2017-03-29 | 2020-02-05 | Roche Innovation Center Copenhagen A/S | Orthogonal protecting groups for the preparation of stereodefined phosphorothioate oligonucleotides |
| US11603532B2 (en) | 2017-06-02 | 2023-03-14 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
| JP2020524485A (ja) | 2017-06-02 | 2020-08-20 | ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． | オリゴヌクレオチド組成物及びその使用方法 |
| CN111051281A (zh) * | 2017-06-21 | 2020-04-21 | 波涛生命科学有限公司 | 用于合成的化合物、组合物和方法 |
| WO2019006455A1 (en) | 2017-06-30 | 2019-01-03 | Solstice Biologics, Ltd. | AUXILIARIES OF CHIRAL PHOSPHORAMIDITIS AND METHODS OF USE THEREOF |
| WO2019032612A1 (en) * | 2017-08-08 | 2019-02-14 | Wave Life Sciences Ltd. | OLIGONUCLEOTIDE COMPOSITIONS AND ASSOCIATED METHODS |
| JP7472018B2 (ja) | 2017-09-18 | 2024-04-22 | ウェーブ ライフ サイエンシーズ リミテッド | オリゴヌクレオチド調製のための技術 |
| EA201991450A1 (ru) | 2017-09-22 | 2019-12-30 | Сарепта Терапьютикс, Инк. | Конъюгаты олигомеров для пропуска экзона при мышечной дистрофии |
| US20210145852A1 (en) | 2017-09-28 | 2021-05-20 | Sarepta Therapeutics, Inc. | Combination Therapies for Treating Muscular Dystrophy |
| WO2019067979A1 (en) | 2017-09-28 | 2019-04-04 | Sarepta Therapeutics, Inc. | POLYTHERAPIES FOR TREATING MUSCLE DYSTROPHY |
| JP2020536060A (ja) | 2017-09-28 | 2020-12-10 | サレプタ セラピューティクス， インコーポレイテッド | 筋ジストロフィーを処置するための併用療法 |
| CN107892710B (zh) * | 2017-10-10 | 2021-04-13 | 河北大学 | 一种易于回收循环使用的负载型铂配合物氧化剂及其制备方法和应用 |
| US11596646B2 (en) | 2017-10-12 | 2023-03-07 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods thereof |
| WO2019079637A2 (en) | 2017-10-18 | 2019-04-25 | Sarepta Therapeutics, Inc. | ANTISENSE OLIGOMERIC COMPOUNDS |
| US10758629B2 (en) | 2018-05-29 | 2020-09-01 | Sarepta Therapeutics, Inc. | Exon skipping oligomer conjugates for muscular dystrophy |
| EP3806868A4 (en) | 2018-06-13 | 2022-06-22 | Sarepta Therapeutics, Inc. | EXON-SKIPPING OLIGOMERS FOR MUSCULAR DYSTROPHY |
| TW202020153A (zh) | 2018-07-27 | 2020-06-01 | 美商薩羅塔治療公司 | 用於肌肉萎縮症之外顯子跳躍寡聚物 |
| EP3831811A4 (en) | 2018-07-31 | 2022-04-20 | Fimecs, Inc. | HETEROCYCLIC COMPOUND |
| BR112021011018A2 (pt) | 2018-12-13 | 2021-08-31 | Sarepta Therapeutics, Inc. | Conjugados de oligômero para exon skipping para distrofia muscular |
| JP7224688B2 (ja) * | 2019-01-10 | 2023-02-20 | 南▲開▼大学 | 環状ジヌクレオチドプロドラッグ分子、その製造方法及び使用 |
| EP3955966A1 (en) | 2019-04-18 | 2022-02-23 | Sarepta Therapeutics, Inc. | Compositions for treating muscular dystrophy |
| JPWO2021020585A1 (US06656730-20031202-C00002.png) | 2019-07-31 | 2021-02-04 | ||
| WO2021216572A1 (en) | 2020-04-20 | 2021-10-28 | Massachusetts Institute Of Technology | Lipid compositions for delivery of sting agonist compounds and uses thereof |
| CN115885042A (zh) | 2020-05-22 | 2023-03-31 | 波涛生命科学有限公司 | 双链寡核苷酸组合物及其相关方法 |
| TW202241454A (zh) * | 2021-02-01 | 2022-11-01 | 日商第一三共股份有限公司 | 抗體－免疫賦活化劑共軛物之新穎製造方法 |
| WO2023055774A1 (en) | 2021-09-30 | 2023-04-06 | Sarepta Therapeutics, Inc. | Antisense oligonucleotides having one or more abasic units |
| WO2023152371A1 (en) | 2022-02-14 | 2023-08-17 | Proqr Therapeutics Ii B.V. | Guide oligonucleotides for nucleic acid editing in the treatment of hypercholesterolemia |
| WO2024013361A1 (en) | 2022-07-15 | 2024-01-18 | Proqr Therapeutics Ii B.V. | Oligonucleotides for adar-mediated rna editing and use thereof |
| WO2024013360A1 (en) | 2022-07-15 | 2024-01-18 | Proqr Therapeutics Ii B.V. | Chemically modified oligonucleotides for adar-mediated rna editing |
| WO2024064237A2 (en) | 2022-09-21 | 2024-03-28 | Sarepta Therapeutics, Inc. | Dmd antisense oligonucleotide-mediated exon skipping efficiency |
| GB202215614D0 (en) | 2022-10-21 | 2022-12-07 | Proqr Therapeutics Ii Bv | Heteroduplex rna editing oligonucleotide complexes |
| WO2024093947A1 (zh) * | 2022-10-31 | 2024-05-10 | 大睿生物医药科技(上海)有限公司 | 向细胞内递送siRNA的前药 |
Family Cites Families (687)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2878264A (en) | 1959-03-17 | Substituted amino alcohols | ||
| DE1144279B (de) | 1957-09-26 | 1963-02-28 | Robins Co Inc A H | Verfahren zur Herstellung von 3-Aryl-3-hydroxypyrrolidinen und deren Salzen |
| US3135766A (en) | 1961-10-03 | 1964-06-02 | Mead Johnson & Co | 3-substituted-3-pyrrolidinols |
| US3484473A (en) | 1967-05-12 | 1969-12-16 | Buckman Labor Inc | Methylene bisesters of thiolsulfonic acids |
| DE1934150A1 (de) | 1968-07-10 | 1970-01-15 | Pennwalt Corp | Neue 1-Alkanoyloxy-1,2,4,5-tetrahydro-3H,3-benzazepine |
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US3745162A (en) | 1970-08-31 | 1973-07-10 | Robins Co Inc A H | 1,2,3,4-tetrahydroisoquinoline-2-(thio)-carboxamides |
| GB1448437A (en) | 1973-02-24 | 1976-09-08 | Beecham Group Ltd | Diphenylpropylamines |
| US4022791A (en) | 1975-06-03 | 1977-05-10 | Pfizer Inc. | 2-Aminomethyl-3,4-dihydronaphthalenes |
| GB1504424A (en) | 1975-08-09 | 1978-03-22 | Beecham Group Ltd | Isoquinoline-derived aminoethers |
| BR7807288A (pt) | 1977-11-08 | 1979-06-12 | Genentech Inc | Processo para sintese de polinucleotidos |
| DD133885B1 (de) | 1978-01-04 | 1981-02-25 | Hans Lehmann | Mittel zur bekaempfung von phytopathogenen bakterien und pilzen |
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US5132418A (en) | 1980-02-29 | 1992-07-21 | University Patents, Inc. | Process for preparing polynucleotides |
| US4500707A (en) | 1980-02-29 | 1985-02-19 | University Patents, Inc. | Nucleosides useful in the preparation of polynucleotides |
| US4668777A (en) | 1981-03-27 | 1987-05-26 | University Patents, Inc. | Phosphoramidite nucleoside compounds |
| US4415732A (en) | 1981-03-27 | 1983-11-15 | University Patents, Inc. | Phosphoramidite compounds and processes |
| US4973679A (en) | 1981-03-27 | 1990-11-27 | University Patents, Inc. | Process for oligonucleo tide synthesis using phosphormidite intermediates |
| US4542142A (en) | 1982-11-22 | 1985-09-17 | Roussel Uclaf | Insecticidal cyclopropane carboxylic acid derivatives with 3-unsaturated-side chain |
| DE3329892A1 (de) | 1983-08-18 | 1985-03-07 | Köster, Hubert, Prof. Dr., 2000 Hamburg | Verfahren zur herstellung von oligonucleotiden |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| US5643889A (en) | 1984-07-11 | 1997-07-01 | Temple University-Of The Commonwealth System Of Pennsylvania | Cholesterol conjugates of 2'5'-oligoadenylate derivatives and antiviral uses thereof |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
| FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
| FR2576898B1 (fr) | 1985-02-01 | 1988-01-08 | Lafon Labor | Derives de 3-phenyl-tetrahydropyridine, procede de preparation et utilisation en therapeutique |
| JPH0658512B2 (ja) | 1985-04-12 | 1994-08-03 | 富士写真フイルム株式会社 | ハロゲン化銀写真感光材料 |
| US4659774A (en) | 1985-11-01 | 1987-04-21 | American Hoechst Corporation | Support for solid-phase oligonucleotide synthesis |
| US4840956A (en) | 1986-02-18 | 1989-06-20 | Warner-Lambert Company | Novel disubstituted-7-pyrrolidinoquinoline antibacterial agents |
| US4735949A (en) | 1986-02-18 | 1988-04-05 | Warner-Lambert Company | Disubstituted-7-pyrrolidinonaphthyridine antibacterial agents |
| IL83663A0 (en) | 1986-10-27 | 1988-01-31 | Robins Co Inc A H | Preparation of 3-pyrrolidinols |
| EP0366685B1 (en) | 1987-06-24 | 1994-10-19 | Howard Florey Institute Of Experimental Physiology And Medicine | Nucleoside derivatives |
| EP0302349B1 (en) | 1987-07-30 | 1993-09-29 | Bar Ilan University | Biologically active carboxylic acid esters |
| US4923901A (en) | 1987-09-04 | 1990-05-08 | Millipore Corporation | Membranes with bound oligonucleotides and peptides |
| US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US4945158A (en) | 1988-08-12 | 1990-07-31 | American Cyanamid Company | Antidiabetic phosphonates |
| US4943629A (en) | 1988-08-12 | 1990-07-24 | American Cyanamid Company | Antidiabetic alpha-substituted phosphonates |
| US5047524A (en) | 1988-12-21 | 1991-09-10 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
| US5262530A (en) | 1988-12-21 | 1993-11-16 | Applied Biosystems, Inc. | Automated system for polynucleotide synthesis and purification |
| JP2794461B2 (ja) | 1989-08-17 | 1998-09-03 | 有機合成薬品工業株式会社 | ホスホアミダイト化合物及びそれを用いたオリゴリボヌクレオチドの固相合成法 |
| US5141813A (en) | 1989-08-28 | 1992-08-25 | Clontech Laboratories, Inc. | Multifunctional controlled pore glass reagent for solid phase oligonucleotide synthesis |
| US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
| CA2029273A1 (en) | 1989-12-04 | 1991-06-05 | Christine L. Brakel | Modified nucleotide compounds |
| WO1991009594A1 (en) | 1989-12-28 | 1991-07-11 | Virginia Commonwealth University | Sigma receptor ligands and the use thereof |
| US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5620963A (en) | 1991-10-15 | 1997-04-15 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating protein kinase C having phosphorothioate linkages of high chiral purity |
| US5635488A (en) | 1991-10-15 | 1997-06-03 | Isis Pharmaceuticals, Inc. | Compounds having phosphorodithioate linkages of high chiral purity |
| US5914396A (en) | 1990-01-11 | 1999-06-22 | Isis Pharmaceuticals, Inc. | 2'-O-modified nucleosides and phosphoramidites |
| US5212295A (en) | 1990-01-11 | 1993-05-18 | Isis Pharmaceuticals | Monomers for preparation of oligonucleotides having chiral phosphorus linkages |
| US6339066B1 (en) | 1990-01-11 | 2002-01-15 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides which have phosphorothioate linkages of high chiral purity and which modulate βI, βII, γ, δ, Ε, ζ and η isoforms of human protein kinase C |
| AU651569B2 (en) | 1990-01-11 | 1994-07-28 | Isis Pharmaceuticals, Inc. | Compositions and methods for detecting and modulating RNA activity and gene expression |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US7101993B1 (en) | 1990-01-11 | 2006-09-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides containing 2′-O-modified purines |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5852188A (en) | 1990-01-11 | 1998-12-22 | Isis Pharmaceuticals, Inc. | Oligonucleotides having chiral phosphorus linkages |
| US5506212A (en) | 1990-01-11 | 1996-04-09 | Isis Pharmaceuticals, Inc. | Oligonucleotides with substantially chirally pure phosphorothioate linkages |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5457191A (en) | 1990-01-11 | 1995-10-10 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5151510A (en) | 1990-04-20 | 1992-09-29 | Applied Biosystems, Inc. | Method of synethesizing sulfurized oligonucleotide analogs |
| US5292875A (en) | 1990-04-20 | 1994-03-08 | Lynx Therapeutics, Inc. | Method of synthesizing sulfurized oligonucleotide analogs |
| JPH06500075A (ja) | 1990-05-23 | 1994-01-06 | アイシス・ファーマシューティカルス・インコーポレーテッド | Ｒｎａの５´キャップ構造の修飾によりｒｎａ活性を変調させるための組成物および方法 |
| US5783682A (en) | 1990-07-27 | 1998-07-21 | Isis Pharmaceuticals, Inc. | Oligonucleotide mimics having nitrogen-containing linkages |
| US5998603A (en) | 1994-09-29 | 1999-12-07 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analogs, and oligomers thereof |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5378825A (en) | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
| US6121433A (en) | 1990-07-27 | 2000-09-19 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having nitrogen-containing linkages |
| US5834607A (en) | 1990-07-27 | 1998-11-10 | Isis Pharmaceuticals, Inc. | Amines and methods of making and using the same |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5386023A (en) | 1990-07-27 | 1995-01-31 | Isis Pharmaceuticals | Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling |
| WO1994022886A1 (en) | 1993-03-30 | 1994-10-13 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5792844A (en) | 1990-07-27 | 1998-08-11 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent nitrogen atoms |
| US6087482A (en) | 1990-07-27 | 2000-07-11 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5223618A (en) | 1990-08-13 | 1993-06-29 | Isis Pharmaceuticals, Inc. | 4'-desmethyl nucleoside analog compounds |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
| ATE154246T1 (de) | 1990-07-27 | 1997-06-15 | Isis Pharmaceuticals Inc | Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren |
| US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| JPH04348044A (ja) | 1991-02-21 | 1992-12-03 | Matsushita Electron Corp | 半導体用樹脂封止装置 |
| US5512668A (en) | 1991-03-06 | 1996-04-30 | Polish Academy Of Sciences | Solid phase oligonucleotide synthesis using phospholane intermediates |
| US20020183502A1 (en) | 1991-05-21 | 2002-12-05 | Mesmaeker Alain De | Backbone-modified oligonucleotide analogs and methods for using same |
| US7015315B1 (en) | 1991-12-24 | 2006-03-21 | Isis Pharmaceuticals, Inc. | Gapped oligonucleotides |
| JPH04348077A (ja) | 1991-05-24 | 1992-12-03 | Nec Corp | 薄膜トランジスタ |
| US6414112B1 (en) | 1991-05-24 | 2002-07-02 | Ole Buchardt | Peptide nucleic acids having 2,6-diaminopurine nucleobases |
| US6538126B1 (en) | 1991-06-10 | 2003-03-25 | Lucky Limited | Hepatitis C diagnostics and vaccines |
| US5646267A (en) | 1991-08-05 | 1997-07-08 | Polish Academy Of Sciences | Method of making oligonucleotides and oligonucleotide analogs using phospholanes and enantiomerically resolved phospholane analogues |
| US5359052A (en) | 1991-08-05 | 1994-10-25 | Polish Academy Of Sciences | Chalcophospholanes useful in the synthesis of oligonucleoside phosphorothioates, phosphorodithioates and related selenates |
| US7119184B2 (en) | 1991-08-12 | 2006-10-10 | Isis Pharmaceuticals, Inc. | Oligonucleotides having A-DNA form and B-DNA form conformational geometry |
| US6369209B1 (en) | 1999-05-03 | 2002-04-09 | Isis Pharmaceuticals, Inc. | Oligonucleotides having A-DNA form and B-DNA form conformational geometry |
| US5607923A (en) | 1991-10-15 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating cytomegalovirus having phosphorothioate linkages of high chiral purity |
| US5661134A (en) | 1991-10-15 | 1997-08-26 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity |
| US5576302A (en) | 1991-10-15 | 1996-11-19 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity |
| US5599797A (en) | 1991-10-15 | 1997-02-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| CA2121144C (en) | 1991-10-15 | 2001-07-31 | Phillip Dan Cook | Oligonucleotides having chiral phosphorus linkages |
| US5654284A (en) | 1991-10-15 | 1997-08-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating RAF kinase having phosphorothioate linkages of high chiral purity |
| EP0538194B1 (de) | 1991-10-17 | 1997-06-04 | Novartis AG | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
| US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| US6235887B1 (en) | 1991-11-26 | 2001-05-22 | Isis Pharmaceuticals, Inc. | Enhanced triple-helix and double-helix formation directed by oligonucleotides containing modified pyrimidines |
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| DK1695979T3 (da) | 1991-12-24 | 2011-10-10 | Isis Pharmaceuticals Inc | Gappede modificerede oligonukleotider |
| GB9213601D0 (en) | 1992-06-26 | 1992-08-12 | Mastico Robert A | Protein based delivery system |
| US7067497B2 (en) | 1992-09-29 | 2006-06-27 | Isis Pharmaceuticals, Inc. | Modulation of telomere length by oligonucleotides having a G-core sequence |
| US6005107A (en) | 1992-12-23 | 1999-12-21 | Biochem Pharma, Inc. | Antiviral compounds |
| US6444656B1 (en) | 1992-12-23 | 2002-09-03 | Biochem Pharma, Inc. | Antiviral phosphonate nucleotides |
| DK0677056T3 (da) | 1993-01-25 | 1996-08-05 | Hybridon Inc | Oligonukleotid-alkylphosphonater og -alkylphosphonothioater |
| HU9501994D0 (en) | 1993-03-31 | 1995-09-28 | Sterling Winthrop Inc | Novel 5'-substituted nucleosides and oligomers produced therefrom |
| AU6551094A (en) | 1993-03-31 | 1994-10-24 | Sterling Winthrop Inc. | Bifunctional nucleosides, oligomers thereof, and methods of making and using the same |
| US5955591A (en) | 1993-05-12 | 1999-09-21 | Imbach; Jean-Louis | Phosphotriester oligonucleotides, amidites and method of preparation |
| US6015886A (en) | 1993-05-24 | 2000-01-18 | Chemgenes Corporation | Oligonucleotide phosphate esters |
| DE69412704T2 (de) | 1993-06-10 | 1999-02-04 | Idemitsu Petrochemical Co | Spritzgiessform |
| US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
| US5643989A (en) * | 1993-10-29 | 1997-07-01 | Azdel, Inc. | Fiber reinforced functionalized polyolefin composites |
| US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| DE4435728A1 (de) | 1994-01-19 | 1995-07-20 | Boehringer Mannheim Gmbh | Biotinsilan-Verbindungen und diese Verbindungen enthaltende Bindematrix |
| US6117679A (en) | 1994-02-17 | 2000-09-12 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
| ATE222604T1 (de) | 1994-02-22 | 2002-09-15 | Novozymes As | Methode zur herstellung einer variante eines lipolytischen enzymes |
| US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5871966A (en) | 1994-05-11 | 1999-02-16 | Novo Nordisk A/S | Enzyme with endo-1,3(4)-β- Glucanase activity |
| US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| DE69507197T2 (de) | 1994-05-31 | 1999-05-27 | Bayer Ag | Aminobenzofuryl- und -thienylderivate |
| HRP950288A2 (en) | 1994-05-31 | 1997-08-31 | Bayer Ag | Oxalylamino-benzofuran- and benzothienyl-derivatives |
| ES2267100T5 (es) | 1994-07-15 | 2011-04-08 | The University Of Iowa Research Foundation | Oligonucleótidos inmunomoduladores. |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| EP0779893B1 (en) | 1994-09-07 | 2001-06-27 | Hybridon, Inc. | Oligonucleotide prodrugs |
| US5681940A (en) | 1994-11-02 | 1997-10-28 | Icn Pharmaceuticals | Sugar modified nucleosides and oligonucleotides |
| WO1996019572A1 (en) | 1994-12-22 | 1996-06-27 | Hybridon, Inc. | Synthesis of stereospecific oligonucleotide phosphorothioates |
| GB9501465D0 (en) | 1995-01-25 | 1995-03-15 | King S College London | Nucleoside phosphorothioate derivatives,synthesis and use thereof |
| US6222025B1 (en) | 1995-03-06 | 2001-04-24 | Isis Pharmaceuticals, Inc. | Process for the synthesis of 2′-O-substituted pyrimidines and oligomeric compounds therefrom |
| US6166197A (en) | 1995-03-06 | 2000-12-26 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions |
| DE69638104D1 (de) | 1995-04-27 | 2010-02-11 | Takara Bio Inc | Für Lacto-N-biosidase kodierendes Gen |
| AU715125B2 (en) | 1995-05-11 | 2000-01-20 | Merck Serono Sa | IL-6 activity inhibitor |
| CA2221589A1 (en) | 1995-05-19 | 1996-11-21 | Glycomed Incorporated | Collection of activated glycoside compounds and their biological use |
| ES2151173T3 (es) | 1995-05-23 | 2000-12-16 | Hybridon Inc | Nuevos sintones para la sintesis estereoselectiva de oligonucleotidos. |
| AU5871196A (en) | 1995-05-23 | 1996-12-24 | Hybridon, Inc. | Methods and compounds for the synthesis of oligonucleotides and the oligonucleotides thereby produced |
| CA2223103A1 (en) | 1995-06-06 | 1996-12-12 | Isis Pharmaceuticals Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5932450A (en) | 1995-06-07 | 1999-08-03 | Gen-Probe Incorporated | Enzymatic synthesis of oligonucleotides using digestible templates |
| EP0751222B1 (en) | 1995-06-29 | 2006-03-01 | Takara Bio Inc. | Gene encoding endoglycoceramidase |
| EP0759470B1 (en) | 1995-06-29 | 2006-10-25 | Takara Bio Inc. | Gene encoding endoglycoceramidase activator |
| US6017700A (en) | 1995-08-04 | 2000-01-25 | Bayer Corporation | Cationic oligonucleotides, and related methods of synthesis and use |
| US5936080A (en) | 1996-05-24 | 1999-08-10 | Genta Incorporated | Compositions and methods for the synthesis of organophosphorus derivatives |
| WO1997009443A1 (en) | 1995-09-05 | 1997-03-13 | Michigan State University | PROCESS FOR THE ISOLATION AND PURIFICATION OF TAXOL AND TAXANES FROM TAXUS spp |
| US5734041A (en) | 1995-10-20 | 1998-03-31 | Mcgill University | Preparation of chiral phosphorothioate oligomers |
| US6160109A (en) | 1995-10-20 | 2000-12-12 | Isis Pharmaceuticals, Inc. | Preparation of phosphorothioate and boranophosphate oligomers |
| US6476216B1 (en) | 1995-10-20 | 2002-11-05 | Mcgill University | Preparation of phosphorothioate oligomers |
| US7018793B1 (en) | 1995-12-07 | 2006-03-28 | Diversa Corporation | Combinatorial screening of mixed populations of organisms |
| 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 |
| CN1215994A (zh) | 1996-02-15 | 1999-05-05 | 国家健康学会 | 对治疗rsv感染有效的rna酶l激活剂和反义寡核苷酸 |
| GB9604669D0 (en) | 1996-03-05 | 1996-05-01 | Ciba Geigy Ag | Chemical compounds |
| US5824669A (en) | 1996-03-22 | 1998-10-20 | Nitromed, Inc. | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
| DE69738254T2 (de) | 1996-05-10 | 2008-08-14 | Novozymes A/S | Methode zur bereitstellung von dna sequenzen |
| US5856465A (en) | 1996-05-24 | 1999-01-05 | Polska Akademia Nauk Centrum Badan Molekularnych I Makromolekularnych | Compositions and methods for the synthesis of chirally pure organophosphorus nucleoside derivatives |
| US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| DE19622783A1 (de) | 1996-06-07 | 1997-12-11 | Hoechst Ag | Isolierung der Biosynthesegene für Pseudo-Oligosaccharide aus Streptomyces glaucescens GLA.O und ihre Verwendung |
| US6130038A (en) | 1996-07-16 | 2000-10-10 | Gen-Probe Incorporated | Method for amplifying target nucleic acids using modified primers |
| AU717387B2 (en) | 1996-07-24 | 2000-03-23 | Rolf H. Berg | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| AU4156197A (en) * | 1996-08-21 | 1998-03-06 | Hybridon, Inc. | Oligonucleotide prodrugs |
| US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
| GB9621522D0 (en) | 1996-10-16 | 1996-12-04 | Biocompatibles Ltd | Synthesis of phosphorus compounds |
| US6639062B2 (en) | 1997-02-14 | 2003-10-28 | Isis Pharmaceuticals, Inc. | Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom |
| US6172209B1 (en) | 1997-02-14 | 2001-01-09 | Isis Pharmaceuticals Inc. | Aminooxy-modified oligonucleotides and methods for making same |
| US6369237B1 (en) | 1997-03-07 | 2002-04-09 | President And Fellows Of Harvard College | DNA glycosylase inhibitors, and uses related thereto |
| US6015887A (en) | 1997-04-11 | 2000-01-18 | Isis Pharmaceuticals, Inc. | Chiral peptide nucleic acids and methods for preparing same |
| US6468983B2 (en) | 1997-04-21 | 2002-10-22 | The Cleveland Clinic Foundation | RNase L activators and antisense oligonucleotides effective to treat telomerase-expressing malignancies |
| PL184612B1 (pl) | 1997-04-25 | 2002-11-29 | Pan | Sposób wytwarzania modyfikowanych P chiralnych analogów nukleotydów |
| CA2291839A1 (en) | 1997-05-28 | 1998-12-03 | Peter E. Nielsen | Conjugated peptide nucleic acids having enhanced cellular uptake |
| CN1268127A (zh) | 1997-06-27 | 2000-09-27 | 普罗格特-甘布尔公司 | 环状缩醛香料前体 |
| AU8512598A (en) | 1997-07-25 | 1999-02-16 | Hybridon, Inc. | Oligonuclotides having 3' terminal stereospecific phosphorothioates |
| US6767739B2 (en) | 2001-07-30 | 2004-07-27 | Isis Pharmaceuticals Inc. | Antisense modulation of microsomal triglyceride transfer protein expression |
| GB9717158D0 (en) | 1997-08-13 | 1997-10-22 | King S College London | Solution synthesis of oligonucleotides and their phosphorothioate analogues |
| US6383808B1 (en) | 2000-09-11 | 2002-05-07 | Isis Pharmaceuticals, Inc. | Antisense inhibition of clusterin expression |
| US6750344B1 (en) | 1997-09-05 | 2004-06-15 | Isis Pharmaceuticals, Inc. | Amine compounds and combinatorial libraries comprising same |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| DE19741715A1 (de) | 1997-09-22 | 1999-03-25 | Hoechst Ag | Pentopyranosyl-Nucleosid, seine Herstellung und Verwendung |
| US6232463B1 (en) | 1997-10-09 | 2001-05-15 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US6617438B1 (en) | 1997-11-05 | 2003-09-09 | Sirna Therapeutics, Inc. | Oligoribonucleotides with enzymatic activity |
| US6528640B1 (en) | 1997-11-05 | 2003-03-04 | Ribozyme Pharmaceuticals, Incorporated | Synthetic ribonucleic acids with RNAse activity |
| US6080543A (en) | 1997-12-08 | 2000-06-27 | E. & J. Gallo Winery | Detection of fungal pathogens |
| US6582936B1 (en) | 1997-12-12 | 2003-06-24 | The Regents Of The University Of California | Methods for making nucleic acids |
| US6248519B1 (en) | 1998-03-11 | 2001-06-19 | E & J Gallo Winery | Detection of fermentation-related microorganisms |
| US7045610B2 (en) | 1998-04-03 | 2006-05-16 | Epoch Biosciences, Inc. | Modified oligonucleotides for mismatch discrimination |
| WO1999056755A1 (en) | 1998-05-06 | 1999-11-11 | University Of Iowa Research Foundation | Methods for the prevention and treatment of parasitic infections and related diseases using cpg oligonucleotides |
| CA2328406A1 (en) | 1998-05-14 | 1999-11-18 | Hermann Wagner | Methods for regulating hematopoiesis using cpg-oligonucleotides |
| US6242589B1 (en) | 1998-07-14 | 2001-06-05 | Isis Pharmaceuticals, Inc. | Phosphorothioate oligonucleotides having modified internucleoside linkages |
| US6867294B1 (en) | 1998-07-14 | 2005-03-15 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
| WO2000006588A1 (en) | 1998-07-27 | 2000-02-10 | University Of Iowa Research Foundation | STEREOISOMERS OF CpG OLIGONUCLEOTIDES AND RELATED METHODS |
| ES2257068T3 (es) | 1998-08-10 | 2006-07-16 | Antigenics Inc. | Mezclas de adyuvantes de cpg y saponinas y metodos de empleo de las mismas. |
| WO2000023444A1 (en) | 1998-10-21 | 2000-04-27 | Abbott Laboratories | 5,7-disubstituted-4-aminopyrido[2,3-d]pyrimidine compounds |
| US6995259B1 (en) | 1998-10-23 | 2006-02-07 | Sirna Therapeutics, Inc. | Method for the chemical synthesis of oligonucleotides |
| US6451524B1 (en) | 1998-11-25 | 2002-09-17 | Isis Pharmaceuticals, Inc. | Identification of disease predictive nucleic acids |
| AU1742600A (en) | 1998-11-25 | 2000-06-13 | Isis Pharmaceuticals, Inc. | Identification of disease predictive nucleic acids |
| WO2000037658A2 (en) | 1998-12-21 | 2000-06-29 | Genencor International, Inc. | Chemically modified enzymes with multiple charged variants |
| WO2000040749A2 (en) | 1999-01-06 | 2000-07-13 | Genenews Inc. | Method for the detection of gene transcripts in blood and uses thereof |
| US6265172B1 (en) | 1999-02-08 | 2001-07-24 | University Of Kentucky | Diagnostic test and therapy for manganese superoxide dismutate (mNsod) associated diseases |
| US6121437A (en) | 1999-03-16 | 2000-09-19 | Isis Pharmaceuticals, Inc. | Phosphate and thiophosphate protecting groups |
| US6506594B1 (en) | 1999-03-19 | 2003-01-14 | Cornell Res Foundation Inc | Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays |
| GB9907245D0 (en) | 1999-03-29 | 1999-05-26 | Goldsborough Andrew | Cleavage of nucleic acids from solid supports |
| JP3072345B1 (ja) | 1999-03-31 | 2000-07-31 | 農林水産省家畜衛生試験場長 | 豚丹毒菌の組換えサブユニットワクチン |
| US5998148A (en) | 1999-04-08 | 1999-12-07 | Isis Pharmaceuticals Inc. | Antisense modulation of microtubule-associated protein 4 expression |
| US6977245B2 (en) | 1999-04-12 | 2005-12-20 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
| US6300069B1 (en) | 1999-05-03 | 2001-10-09 | Qiagen Gmbh | Generation and amplification of nucleic acids from ribonucleic acids |
| US6656730B1 (en) | 1999-06-15 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides conjugated to protein-binding drugs |
| US6066500A (en) | 1999-06-25 | 2000-05-23 | Isis Pharmaceuticals Inc. | Antisense modulation of Beta catenin expression |
| US6271004B1 (en) | 1999-06-25 | 2001-08-07 | Display Systems Biotech A/S | Method for improved reverse transcription at high temperatures |
| US6414135B1 (en) | 1999-07-07 | 2002-07-02 | Isis Pharmaceuticals, Inc. | C3′-methylene hydrogen phosphonate monomers and related compounds |
| US20030092647A1 (en) | 2001-08-08 | 2003-05-15 | Crooke Rosanne M. | Antisense modulation of cholesteryl ester transfer protein expression |
| US6147200A (en) | 1999-08-19 | 2000-11-14 | Isis Pharmaceuticals, Inc. | 2'-O-acetamido modified monomers and oligomers |
| US7264932B2 (en) | 1999-09-24 | 2007-09-04 | Applera Corporation | Nuclease inhibitor cocktail |
| RU2245149C2 (ru) | 1999-09-25 | 2005-01-27 | Юниверсити Оф Айова Рисерч Фаундейшн | Иммуностимулирующие нуклеиновые кислоты |
| CA2386019C (en) | 1999-09-27 | 2011-06-21 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| US6949520B1 (en) | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| US20020082227A1 (en) | 1999-09-30 | 2002-06-27 | Scott Henry | Use of oligonucleotides for inhibition of complement activation |
| WO2001025488A2 (en) | 1999-10-06 | 2001-04-12 | Quark Biotech, Inc. | Method for enrichment of natural antisense messenger rna |
| GB9924285D0 (en) | 1999-10-14 | 1999-12-15 | Avecia Ltd | Process |
| US20010055761A1 (en) | 1999-10-29 | 2001-12-27 | Agilent Technologies | Small scale dna synthesis using polymeric solid support with functionalized regions |
| FR2800750B1 (fr) | 1999-11-05 | 2003-01-31 | Centre Nat Rech Scient | Proteines membranaires ctl (choline transporter like) impliquees dans le transport de la choline |
| AU1656601A (en) | 1999-11-12 | 2001-06-12 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
| US6322985B1 (en) | 1999-12-27 | 2001-11-27 | Technion Research And Development Foundation Ltd. | Abundant, well distributed and hyperpolymorphic simple sequence repeats in prokaryote genomes and use of same for prokaryote classification and typing |
| WO2001050349A1 (en) | 1999-12-30 | 2001-07-12 | Rutgers, The State University Of New Jersey | Electronic document customization and transformation utilizing user feedback |
| AU2743801A (en) | 1999-12-30 | 2001-07-16 | Cabot Corporation | Sensors with improved properties |
| US6649750B1 (en) | 2000-01-05 | 2003-11-18 | Isis Pharmaceuticals, Inc. | Process for the preparation of oligonucleotide compounds |
| US6159697A (en) | 2000-01-19 | 2000-12-12 | Isis Pharmaceuticals, Inc. | Antisense modulation of Smad7 expression |
| US7585847B2 (en) | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
| US6495677B1 (en) | 2000-02-15 | 2002-12-17 | Kanda S. Ramasamy | Nucleoside compounds |
| GB0004889D0 (en) | 2000-03-01 | 2000-04-19 | Avecia Ltd | Synthesis of oligonucleotides |
| US6936432B2 (en) | 2000-03-01 | 2005-08-30 | Message Pharmaceuticals | Bacterial RNase P proteins and their use in identifying antibacterial compounds |
| AU2001245823A1 (en) | 2000-03-17 | 2001-10-03 | Corixa Corporation | Novel amphipathic aldehydes and their use as adjuvants and immunoeffectors |
| DE10019756A1 (de) | 2000-04-20 | 2001-10-25 | Bayer Ag | Verfahren zur Herstellung von superabsorbierenden Polymeren aus Polyacrylnitrilen |
| ES2225553T3 (es) | 2000-04-20 | 2005-03-16 | F. Hoffmann-La Roche Ag | Derivados de pirrolidina y piperidina y su empleo para el tratamiento de trastornos neurodegenerativos. |
| US20020013287A1 (en) | 2000-05-09 | 2002-01-31 | Reliable Biopharmaceuticals, Inc. St Louis Missouri | Polymeric compounds useful as prodrugs |
| US6492171B2 (en) | 2000-05-16 | 2002-12-10 | Isis Pharmaceuticals, Inc. | Antisense modulation of TERT expression |
| US6815542B2 (en) | 2000-06-16 | 2004-11-09 | Ribapharm, Inc. | Nucleoside compounds and uses thereof |
| CA2416631C (en) | 2000-08-03 | 2011-11-22 | F. Hoffmann-La Roche Ag | Nucleic acid binding compounds containing pyrazolo[3,4-d]pyrimidine analogues of purin-2,6-diamine and their uses |
| US6725412B1 (en) | 2000-08-15 | 2004-04-20 | Dolby Laboratories Licensing Corporation | Low latency data encoder |
| US6809195B1 (en) | 2000-08-16 | 2004-10-26 | Isis Pharmaceuticals, Inc. | Process for the preparation of oligonucleotides |
| US6559279B1 (en) | 2000-09-08 | 2003-05-06 | Isis Pharmaceuticals, Inc. | Process for preparing peptide derivatized oligomeric compounds |
| CA2419894A1 (en) | 2000-09-15 | 2002-03-21 | Coley Pharmaceutical Gmbh | Process for high throughput screening of cpg-based immuno-agonist/antagonist |
| EP1191097A1 (en) | 2000-09-21 | 2002-03-27 | Leids Universitair Medisch Centrum | Induction of exon skipping in eukaryotic cells |
| GB0024752D0 (en) | 2000-10-10 | 2000-11-22 | Univ Belfast | Oxidative halogenation of aromatic compounds |
| EP1889630B1 (en) | 2000-10-18 | 2011-11-23 | GlaxoSmithKline Biologicals S.A. | Vaccines comprising MAGE antigen linked to protein D fragment |
| US6372492B1 (en) | 2000-10-30 | 2002-04-16 | Isis Pharmaceuticals, Inc. | Antisense modulation of talin expression |
| US6682889B1 (en) | 2000-11-08 | 2004-01-27 | Becton, Dickinson And Company | Amplification and detection of organisms of the Chlamydiaceae family |
| NL1016978C2 (nl) | 2000-12-22 | 2002-06-25 | Robert Jan Colenbrander | Inrichting en werkwijze voor het verpakken en bereiden van voedsel en werkwijze voor het vervaardigen van een dergelijke inrichting. |
| MY134070A (en) | 2001-01-22 | 2007-11-30 | Isis Pharmaceuticals Inc | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
| US8008459B2 (en) | 2001-01-25 | 2011-08-30 | Evolva Sa | Concatemers of differentially expressed multiple genes |
| WO2002059297A2 (en) | 2001-01-25 | 2002-08-01 | Evolva Biotech A/S | A library of a collection of cells |
| JP4454934B2 (ja) | 2001-01-26 | 2010-04-21 | コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼイション | 組換えクローニングを用いて効率のよいサイレンシング構築物を作製する方法および手段 |
| US20050277133A1 (en) | 2001-05-18 | 2005-12-15 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA) |
| WO2002097134A2 (en) | 2001-05-25 | 2002-12-05 | Isis Pharmaceuticals, Inc. | Modified peptide nucleic acid |
| GB0113523D0 (en) | 2001-06-04 | 2001-07-25 | Torotrak Dev Ltd | An Hydraulic control circuit for a continuosly variable transmission |
| US20030069410A1 (en) | 2001-06-14 | 2003-04-10 | Isis Pharmaceuticals, Inc. | Methods for preparing oligonucleotides having chiral phosphorothioate linkages |
| US20050019915A1 (en) | 2001-06-21 | 2005-01-27 | Bennett C. Frank | Antisense modulation of superoxide dismutase 1, soluble expression |
| JP4370161B2 (ja) | 2001-06-29 | 2009-11-25 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | Ｈｃｖｅ１ｅ２ワクチン組成物 |
| CA2452458A1 (en) | 2001-07-03 | 2003-01-16 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
| US7205399B1 (en) | 2001-07-06 | 2007-04-17 | Sirna Therapeutics, Inc. | Methods and reagents for oligonucleotide synthesis |
| US6440739B1 (en) | 2001-07-17 | 2002-08-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of glioma-associated oncogene-2 expression |
| US7425545B2 (en) | 2001-07-25 | 2008-09-16 | Isis Pharmaceuticals, Inc. | Modulation of C-reactive protein expression |
| US7888324B2 (en) | 2001-08-01 | 2011-02-15 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
| US6455308B1 (en) | 2001-08-01 | 2002-09-24 | Isis Pharmaceuticals, Inc. | Antisense modulation of serum amyloid A4 expression |
| US7227014B2 (en) | 2001-08-07 | 2007-06-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein (a) expression |
| US7259150B2 (en) | 2001-08-07 | 2007-08-21 | Isis Pharmaceuticals, Inc. | Modulation of apolipoprotein (a) expression |
| US7354909B2 (en) | 2001-08-14 | 2008-04-08 | The United States Of America As Represented By Secretary Of The Department Of Health And Human Services | Method for rapid generation of mature dendritic cells |
| EP1418877A2 (en) | 2001-08-24 | 2004-05-19 | Massachusetts Institute Of Technology | Reagents that facilitate the purification of compounds synthesized on a solid support |
| US7049122B2 (en) | 2001-09-21 | 2006-05-23 | Academia Sinica | Mutant-type lipases and applications thereof |
| US6933288B2 (en) | 2002-02-04 | 2005-08-23 | Isis Pharmaceuticals, Inc. | Pyranosyl cytosines: pharmaceutical formulations and methods |
| JP4348044B2 (ja) | 2002-02-12 | 2009-10-21 | 株式会社キラルジェン | 立体規則性の高いジヌクレオシドホスホロチオエートの製造法 |
| US20030159938A1 (en) | 2002-02-15 | 2003-08-28 | George Hradil | Electroplating solution containing organic acid complexing agent |
| US20040149587A1 (en) | 2002-02-15 | 2004-08-05 | George Hradil | Electroplating solution containing organic acid complexing agent |
| US20050096284A1 (en) | 2002-02-20 | 2005-05-05 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases 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) |
| WO2003073989A2 (en) | 2002-02-28 | 2003-09-12 | Biota, Inc. | Nucleoside 5'-monophosphate mimics and their prodrugs |
| WO2003072757A2 (en) | 2002-02-28 | 2003-09-04 | Biota, Inc. | Nucleotide mimics and their prodrugs |
| US7288376B2 (en) | 2002-03-22 | 2007-10-30 | Council Of Scientific And Industrial Research | Method of detection of SP-A2 gene variants useful for prediction of predisposition to aspergillosis |
| US20040102394A1 (en) | 2002-11-23 | 2004-05-27 | Isis Pharmaceuticals Inc. | Modulation of huntingtin interacting protein 2 expression |
| US7247621B2 (en) | 2002-04-30 | 2007-07-24 | Valeant Research & Development | Antiviral phosphonate compounds and methods therefor |
| WO2003097662A1 (en) | 2002-05-15 | 2003-11-27 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein b expression |
| WO2003100017A2 (en) | 2002-05-24 | 2003-12-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having modified nucleoside units |
| US20040014957A1 (en) | 2002-05-24 | 2004-01-22 | Anne Eldrup | Oligonucleotides having modified nucleoside units |
| US7507808B2 (en) | 2002-12-12 | 2009-03-24 | Isis Pharmaceuticals, Inc. | Modulation of endothelial lipase expression |
| AU2003248708A1 (en) | 2002-06-17 | 2003-12-31 | Isis Pharmaceuticals, Inc. | Oligomeric compounds that include carbocyclic nucleosides and their use in gene modulation |
| JP4598519B2 (ja) | 2002-06-20 | 2010-12-15 | サイトス バイオテクノロジー アーゲー | アジュバントとして使用するためのパッケージ化されたウィルス様粒子：調製法及び使用法 |
| WO2004003228A1 (en) | 2002-07-01 | 2004-01-08 | Unisearch Limited | Genotyping method |
| EP2333062A1 (en) | 2002-07-10 | 2011-06-15 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | RNA-interference by single-stranded RNA molecules |
| US20040023905A1 (en) | 2002-07-31 | 2004-02-05 | Isis Pharmaceuticals Inc. | Antisense modulation of LAR expression |
| US20050255086A1 (en) | 2002-08-05 | 2005-11-17 | Davidson Beverly L | Nucleic acid silencing of Huntington's Disease gene |
| US20050042646A1 (en) | 2002-08-05 | 2005-02-24 | Davidson Beverly L. | RNA interference suppresion of neurodegenerative diseases and methods of use thereof |
| US20080274989A1 (en) | 2002-08-05 | 2008-11-06 | University Of Iowa Research Foundation | Rna Interference Suppression of Neurodegenerative Diseases and Methods of Use Thereof |
| US8729036B2 (en) | 2002-08-07 | 2014-05-20 | University Of Massachusetts | Compositions for RNA interference and methods of use thereof |
| AU2003259735A1 (en) | 2002-08-08 | 2004-02-25 | Sirna Therapeutics, Inc. | Small-mer compositions and methods of use |
| AR040996A1 (es) | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
| US7414116B2 (en) | 2002-08-23 | 2008-08-19 | Illumina Cambridge Limited | Labelled nucleotides |
| KR101360955B1 (ko) | 2002-09-13 | 2014-02-10 | 레플리코르 인코포레이티드 | 비서열 상보적 항바이러스 올리고뉴클레오티드 |
| US7030230B2 (en) | 2002-10-25 | 2006-04-18 | Isis Pharmaceuticals, Inc. | Process of purifying phosphoramidites |
| BR0315810A (pt) | 2002-10-29 | 2005-09-13 | Coley Pharmaceutical Group Ltd | Uso de oligonucleotìdeos cpg no tratamento de infecção por vìrus da hepatite c |
| US20040147020A1 (en) | 2002-11-01 | 2004-07-29 | The Regents Of The University Of Colorado, A Body Corporate | Dopamine neurons from human embryonic stem cells |
| WO2004044134A2 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Phosphorous-linked oligomeric compounds and their use in gene modulation |
| CA2504694C (en) | 2002-11-05 | 2013-10-01 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| EP1560840B1 (en) | 2002-11-05 | 2015-05-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2'-modified nucleosides for use in gene modulation |
| CA2505090A1 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Conjugated oligomeric compounds and their use in gene modulation |
| US7381527B2 (en) | 2002-11-06 | 2008-06-03 | Council Of Scientific And Industrial Research | Method of detection of SP-A2 gene variants |
| JP4986109B2 (ja) | 2002-11-13 | 2012-07-25 | ジェンザイム・コーポレーション | アポリポタンパク質ｂ発現のアンチセンス調節 |
| US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| AU2003295600A1 (en) | 2002-11-14 | 2004-06-15 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
| CA2518475C (en) | 2003-03-07 | 2014-12-23 | Alnylam Pharmaceuticals, Inc. | Irna agents comprising asymmetrical modifications |
| AU2003225705A1 (en) | 2003-03-07 | 2004-09-30 | Ribapharm Inc. | Cytidine analogs and methods of use |
| WO2004083432A1 (en) | 2003-03-21 | 2004-09-30 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure |
| GB0306657D0 (en) | 2003-03-24 | 2003-04-30 | Avecia Ltd | Process and compounds |
| US7537767B2 (en) | 2003-03-26 | 2009-05-26 | Cytis Biotechnology Ag | Melan-A- carrier conjugates |
| WO2004084940A1 (en) | 2003-03-26 | 2004-10-07 | Cytos Biotechnology Ag | Packaging of immunostimulatory oligonucleotides into virus-like particles: method of preparation and use |
| ITRM20030149A1 (it) | 2003-04-02 | 2004-10-03 | Giuliani Spa | Oligonucleotidi (odn) antisenso per smad7 e loro usi in campo medico |
| US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
| US7452901B2 (en) | 2003-04-25 | 2008-11-18 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
| US20090247488A1 (en) | 2003-04-25 | 2009-10-01 | Carina Cannizzaro | Anti-inflammatory phosphonate compounds |
| WO2004096233A2 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Nucleoside phosphonate conjugates |
| US7470724B2 (en) | 2003-04-25 | 2008-12-30 | Gilead Sciences, Inc. | Phosphonate compounds having immuno-modulatory activity |
| CN101410120A (zh) | 2003-04-25 | 2009-04-15 | 吉里德科学公司 | 抗炎的膦酸酯化合物 |
| US7407965B2 (en) | 2003-04-25 | 2008-08-05 | Gilead Sciences, Inc. | Phosphonate analogs for treating metabolic diseases |
| US7432261B2 (en) | 2003-04-25 | 2008-10-07 | Gilead Sciences, Inc. | Anti-inflammatory phosphonate compounds |
| WO2005002626A2 (en) | 2003-04-25 | 2005-01-13 | Gilead Sciences, Inc. | Therapeutic phosphonate compounds |
| US20050261237A1 (en) | 2003-04-25 | 2005-11-24 | Boojamra Constantine G | Nucleoside phosphonate analogs |
| ATE490788T1 (de) | 2003-04-25 | 2010-12-15 | Gilead Sciences Inc | Antivirale phosphonate analoge |
| AU2004233989A1 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Anti-cancer phosphonate analogs |
| US7045306B2 (en) | 2003-04-28 | 2006-05-16 | The General Hospital Corporation | Method for identifying compounds in vitro that modulate the dysregulation of transcription of transcription mediated by mutant huntingtin protein |
| US7214491B2 (en) | 2003-05-07 | 2007-05-08 | E. I. Du Pont De Nemours And Company | Δ-12 desaturase gene suitable for altering levels of polyunsaturated fatty acids in oleaginous yeasts |
| AU2004239114B2 (en) | 2003-05-14 | 2008-03-13 | Japan Science And Technology Agency | Inhibition of the expression of huntingtin gene |
| CN1984921B (zh) * | 2003-06-03 | 2010-06-16 | Isis药物公司 | 存活蛋白表达的调节 |
| EA200600069A1 (ru) | 2003-06-20 | 2006-08-25 | Коли Фармасьютикал Гмбх | Низкомолекулярные антагонисты toll-подобных рецепторов (tlr) |
| WO2005013901A2 (en) | 2003-07-31 | 2005-02-17 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding rnas |
| JP2011088935A (ja) | 2003-08-08 | 2011-05-06 | Chiralgen Ltd | リン原子修飾ヌクレオチド類縁体の製造のための光学活性ヌクレオシド３’−ホスホロアミダイト |
| JP2005089441A (ja) | 2003-08-08 | 2005-04-07 | Toudai Tlo Ltd | 立体規則性の高いリン原子修飾ヌクレオチド類縁体の製造法 |
| US7825235B2 (en) | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
| EP1664071A1 (en) | 2003-08-21 | 2006-06-07 | Griffith University | Novel sulfenamide oxides |
| BRPI0413684A (pt) | 2003-08-21 | 2006-10-24 | Univ Griffith | compostos, composição farmacêutica e respectivos métodos de preparação, de tratamento de infecção microbiana e de extermìnio de microrganismo e usos |
| KR20060123707A (ko) | 2003-08-27 | 2006-12-04 | 바이오타, 인코포레이티드 | 치료제로서의 신규 트리시클릭 뉴클레오시드 또는뉴클레오티드 |
| ATE555118T1 (de) | 2003-08-28 | 2012-05-15 | Takeshi Imanishi | Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung |
| WO2005028494A1 (ja) | 2003-09-02 | 2005-03-31 | Takeshi Wada | ５'-ホスフィチル化モノマーおよびh-ホスホネートオリゴヌクレオチド誘導体の製造方法 |
| WO2005023828A1 (ja) | 2003-09-02 | 2005-03-17 | Takeshi Wada | リボヌクレオチド又はリボヌクレオチド誘導体の製造方法 |
| US20050053981A1 (en) | 2003-09-09 | 2005-03-10 | Swayze Eric E. | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
| BRPI0414222B8 (pt) | 2003-09-09 | 2021-05-25 | Geron Corp | compostos oligonucleotídeos modificados para inibição da telomerase, métodos, composição farmacêutica e usos relacionados |
| US20050074801A1 (en) | 2003-09-09 | 2005-04-07 | Monia Brett P. | Chimeric oligomeric compounds comprising alternating regions of northern and southern conformational geometry |
| US8680063B2 (en) | 2003-09-12 | 2014-03-25 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
| WO2005027980A1 (en) | 2003-09-12 | 2005-03-31 | University Of Massachusetts | Rna interference for the treatment of gain-of-function disorders |
| GB0323968D0 (en) | 2003-10-13 | 2003-11-19 | Glaxosmithkline Biolog Sa | Immunogenic compositions |
| SG123799A1 (en) | 2003-10-30 | 2006-07-26 | Coley Pharm Gmbh | C-class oligonucleotide analogs with enchanced immunostimulatory potency |
| WO2005042716A2 (en) | 2003-10-31 | 2005-05-12 | President And Fellows Of Harvard College | Nucleic acid binding oligonucleotides |
| US7846436B2 (en) | 2003-11-28 | 2010-12-07 | Chemgenes Corporation | Oligonucleotides and related compounds |
| AU2003300239A1 (en) | 2003-12-29 | 2005-07-21 | Galapagos Genomics N.V. | Modulators of bone homeostasis identified in a high-throughput screen |
| WO2005070859A1 (ja) | 2004-01-27 | 2005-08-04 | Takeshi Wada | フルオラス担体およびそれを用いたオリゴヌクレオチド誘導体の製造方法 |
| US20050176045A1 (en) | 2004-02-06 | 2005-08-11 | Dharmacon, Inc. | SNP discriminatory siRNA |
| WO2005076744A2 (en) | 2004-02-18 | 2005-08-25 | Frutarom Ltd. | Method for the preparation of peptide-oligonucleotide conjugates |
| JP3976742B2 (ja) | 2004-02-27 | 2007-09-19 | 江守商事株式会社 | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド |
| WO2005085272A1 (ja) | 2004-03-05 | 2005-09-15 | Takeshi Wada | ボラノホスフェートモノマーおよびそれを用いたオリゴヌクレオチド誘導体の製造方法 |
| WO2005092909A1 (ja) | 2004-03-25 | 2005-10-06 | Toudai Tlo, Ltd. | 立体規則性の高いリボヌクレオチド類縁体及びデオキシリボヌクレオチド類縁体の製造法 |
| US20050244869A1 (en) | 2004-04-05 | 2005-11-03 | Brown-Driver Vickie L | Modulation of transthyretin expression |
| US20050267300A1 (en) | 2004-04-05 | 2005-12-01 | Muthiah Manoharan | Processes and reagents for oligonucleotide synthesis and purification |
| TWI350168B (en) | 2004-05-07 | 2011-10-11 | Incyte Corp | Amido compounds and their use as pharmaceuticals |
| WO2005116268A2 (en) | 2004-05-27 | 2005-12-08 | The Government Of The United States Of America As Represented By The Secretary, Department Of Health | Differential expression of molecules associated with acute stroke |
| US7759318B1 (en) | 2004-05-28 | 2010-07-20 | Isis Pharmaceuticals, Inc. | Identification of novel pathways, genes and promoter motifs regulating adipogenesis |
| JP2008501694A (ja) | 2004-06-03 | 2008-01-24 | アイシス ファーマシューティカルズ、インク． | 遺伝子調節の使用のために個別に修飾された鎖を有する二本鎖組成物 |
| EP4047096A1 (en) | 2004-06-28 | 2022-08-24 | The University Of Western Australia | Antisense oligonucleotides for inducing exon skipping and methods of use thereof |
| PT2409713E (pt) | 2004-08-10 | 2015-10-09 | Genzyme Corp | Oligonucleótidos para utilização em modulação dos níveis de lipoproteínas e colesterol em humanos |
| WO2006022323A1 (ja) | 2004-08-26 | 2006-03-02 | Nippon Shinyaku Co., Ltd. | ホスホロアミダイト化合物及びオリゴｒｎａの製法 |
| CA2578046A1 (en) | 2004-09-07 | 2006-03-16 | Archemix Corp. | Aptamer medicinal chemistry |
| US7884086B2 (en) | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
| WO2006031461A2 (en) | 2004-09-09 | 2006-03-23 | Isis Pharmaceuticals, Inc. | Pyrrolidinyl groups for attaching conjugates to oligomeric compounds |
| JP2008513507A (ja) | 2004-09-17 | 2008-05-01 | アイシス ファーマシューティカルズ インコーポレイティッド | 増強されたアンチセンスオリゴヌクレオチド |
| US20090036355A1 (en) | 2004-10-13 | 2009-02-05 | Sanjay Bhanot | Antisense Modulation of PTP1B Expression |
| US7622451B2 (en) | 2004-11-03 | 2009-11-24 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
| US8212011B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues |
| US8212012B2 (en) | 2004-11-03 | 2012-07-03 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| US9120774B2 (en) | 2004-11-03 | 2015-09-01 | University Of Kansas | Novobiocin analogues having modified sugar moieties |
| CA2585091C (en) | 2004-11-03 | 2016-07-19 | University Of Kansas | Novobiocin analogues as anticancer agents |
| KR100721928B1 (ko) | 2004-11-05 | 2007-05-28 | 주식회사 바이오씨에스 | ＣｐＧ 올리고데옥시뉴클레오티드를 함유하는 피부질환의치료 또는 예방용 약학적 조성물 |
| EP1657307A1 (en) | 2004-11-16 | 2006-05-17 | Immunotech S.A. | Oligonucleotides that induce the secretion of GM-CSF |
| CA2589406A1 (en) | 2004-12-09 | 2006-06-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inducing an immune response in a mammal and methods of avoiding an immune response to oligonucleotide agents such as short interfering rnas |
| US9809824B2 (en) | 2004-12-13 | 2017-11-07 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | CpG oligonucleotide prodrugs, compositions thereof and associated therapeutic methods |
| WO2006066260A2 (en) | 2004-12-17 | 2006-06-22 | Thiosense, Inc. | Compositions of and methods for producing phosphorus-chiral monomers and oligomers |
| US20070099851A1 (en) | 2004-12-30 | 2007-05-03 | Linn Gregory S | Stable analogues of ribose-1-phosphate and methods for treating diabetes and other metabolic disorders |
| US20060183763A1 (en) | 2004-12-31 | 2006-08-17 | Pfizer Inc | Novel pyrrolidyl derivatives of heteroaromatic compounds |
| KR100980898B1 (ko) | 2005-01-28 | 2010-09-07 | 권형주 | 마이코박테리아 유래 면역기능 증진, 면역질환 치료, 아토피성 피부질환 및/또는 면역세포 생존용 올리고뉴크레오타이드 |
| JP2008531018A (ja) | 2005-02-24 | 2008-08-14 | コーリー ファーマシューティカル グループ，インコーポレイテッド | 免疫刺激性オリゴヌクレオチド |
| US8222257B2 (en) | 2005-04-01 | 2012-07-17 | The Regents Of The University Of California | Phosphono-pent-2-en-1-yl nucleosides and analogs |
| PL1877070T3 (pl) | 2005-05-05 | 2009-06-30 | Antisense Pharma Gmbh | Zastosowanie terapeutyczne TGF-beta2 antysensownych oligonukleotydów |
| US7902352B2 (en) | 2005-05-06 | 2011-03-08 | Medtronic, Inc. | Isolated nucleic acid duplex for reducing huntington gene expression |
| EP1885854B1 (en) | 2005-05-06 | 2012-10-17 | Medtronic, Inc. | Methods and sequences to suppress primate huntington gene expression |
| PL2548560T3 (pl) | 2005-06-23 | 2015-11-30 | Biogen Ma Inc | Kompozycje i sposoby modulowania splicingu SMN2 |
| US9133517B2 (en) | 2005-06-28 | 2015-09-15 | Medtronics, Inc. | Methods and sequences to preferentially suppress expression of mutated huntingtin |
| EP2062980B1 (en) | 2005-06-28 | 2011-08-31 | Medtronic, Inc. | Methods and sequences to preferentially suppress expression of mutated huntingtin gene. |
| US20090162316A1 (en) | 2005-07-05 | 2009-06-25 | Harvard University | Liver targeted conjugates |
| JP4984634B2 (ja) | 2005-07-21 | 2012-07-25 | ソニー株式会社 | 物理情報取得方法および物理情報取得装置 |
| ES2372538T3 (es) | 2005-07-28 | 2012-01-23 | Id-Fish Technology, Inc. | Procedimiento para mejorar la permeabilidad celular a partículas foráneas. |
| EP1931782B2 (en) | 2005-08-29 | 2016-04-20 | Regulus Therapeutics Inc | Methods for use in modulating mir-122a |
| EP1937312B1 (en) | 2005-08-30 | 2016-06-29 | Ionis Pharmaceuticals, Inc. | Chimeric oligomeric compounds for modulation of splicing |
| US7700567B2 (en) | 2005-09-29 | 2010-04-20 | Supergen, Inc. | Oligonucleotide analogues incorporating 5-aza-cytosine therein |
| US20070077993A1 (en) | 2005-09-30 | 2007-04-05 | Midgley Timothy M | Method and apparatus for collecting user game play data and crediting users in a gaming environment |
| US8357665B2 (en) | 2005-10-12 | 2013-01-22 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| US9308252B2 (en) | 2005-10-27 | 2016-04-12 | Cook Biotech, Inc. | Extracellular matrix materials as vaccine adjuvants for diseases associated with infectious pathogens or toxins |
| CA2627134A1 (en) | 2005-10-28 | 2007-05-03 | Tosoh Corporation | Method of preparing carotenoid synthesizing microorganism and method of producing carotenoids |
| JP5111385B2 (ja) | 2005-10-28 | 2013-01-09 | アルナイラム ファーマシューティカルズ， インコーポレイテッド | ハンチンチン遺伝子の発現を抑制するための組成物および方法 |
| BRPI0618473A2 (pt) * | 2005-11-11 | 2011-08-30 | Pfizer | combinações e métodos de uso de um oligodeoxinucleotìdeo imunomodulador |
| WO2007064291A1 (en) | 2005-11-30 | 2007-06-07 | Jyoti Chattopadhyaya | Method and compounds for rna synthesis |
| EP1957507B1 (en) | 2005-12-02 | 2018-10-24 | Ionis Pharmaceuticals, Inc. | Antibacterial 4,5-substituted aminoglycoside analogs having multiple substituents |
| US8076303B2 (en) | 2005-12-13 | 2011-12-13 | Spring Bank Pharmaceuticals, Inc. | Nucleotide and oligonucleotide prodrugs |
| RS53029B (en) | 2005-12-21 | 2014-04-30 | Pfizer Products Inc. | CARBONYLAMINE PIROLOPYRAZOLES, POWERFUL KINASE INHIBITORS |
| US7951934B2 (en) | 2006-01-26 | 2011-05-31 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to huntingtin |
| CA2640171C (en) | 2006-01-27 | 2014-10-28 | Isis Pharmaceuticals, Inc. | 6-modified bicyclic nucleic acid analogs |
| PT2405002E (pt) | 2006-02-15 | 2015-01-05 | Adiutide Pharmaceuticals Gmbh | Composições e métodos para formulações de oligonucleotídeos |
| JP4713514B2 (ja) | 2006-02-20 | 2011-06-29 | エフ．ホフマン−ラ ロシュ アーゲー | 改善された標識試薬 |
| US8383660B2 (en) | 2006-03-10 | 2013-02-26 | Pfizer Inc. | Dibenzyl amine compounds and derivatives |
| AU2007234451A1 (en) | 2006-03-31 | 2007-10-11 | Atom Acquisition, Llc | Reagents useful for synthesizing rhodamine-labeled oligonucleotides |
| WO2007118222A2 (en) | 2006-04-06 | 2007-10-18 | Ibis Biosciences, INC | Compositions for the use in identification of fungi |
| KR101176697B1 (ko) | 2006-04-20 | 2012-08-23 | 에프. 호프만-라 로슈 아게 | 케모카인 수용체의 다이아제판 유도체 조절자 |
| BRPI0710889A2 (pt) | 2006-04-24 | 2011-08-16 | Sigma Alimentos Sa De Cv | método para a detecção e quantificação múltipla e simultánea de patogênicos mediante a reação em cadeia da polimerasa em tempo real |
| WO2007127219A2 (en) | 2006-04-25 | 2007-11-08 | Immune Disease Institute, Inc. | Targeted delivery to leukocytes using protein carriers |
| GB0608838D0 (en) | 2006-05-04 | 2006-06-14 | Novartis Ag | Organic compounds |
| ES2471978T3 (es) | 2006-05-05 | 2014-06-27 | Isis Pharmaceuticals, Inc. | Compuestos y procedimientos para modular la expresión de ApoB |
| EP2023936A4 (en) | 2006-05-05 | 2010-11-24 | Isis Pharmaceuticals Inc | COMPOSITIONS AND THEIR USES ASSOCIATED WITH THE ALPHA PTPR RECEPTOR |
| US20090012120A1 (en) | 2006-05-10 | 2009-01-08 | Board Of Trustees Of Michigan State University | Synthesis of N-heterocycles, beta-amino acids, and allyl amines via aza-payne mediated reaction of ylides and hydroxy aziridines |
| WO2007134181A2 (en) | 2006-05-11 | 2007-11-22 | Isis Pharmaceuticals, Inc. | 5'-modified bicyclic nucleic acid analogs |
| US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
| WO2007139190A1 (ja) | 2006-05-31 | 2007-12-06 | Toray Industries, Inc. | 免疫刺激オリゴヌクレオチド及びその医薬用途 |
| US8097596B2 (en) | 2006-06-30 | 2012-01-17 | Lakewood-Amedex, Inc. | Compositions and methods for the treatment of muscle wasting |
| CA2662704A1 (en) | 2006-07-07 | 2008-01-10 | University Of Massachusetts | Rna silencing compositions and methods for the treatment of huntington's disease |
| AU2007272906B2 (en) | 2006-07-12 | 2013-01-31 | The Regents Of The University Of California | Transducible delivery of nucleic acids by reversible phosphotriester charge neutralization protecting groups |
| CA2659155A1 (en) | 2006-07-20 | 2008-01-24 | Amgen Inc. | Substituted azole aromatic heterocycles as inhibitors of 11.beta.-hsd-1 |
| GB0614947D0 (en) | 2006-07-27 | 2006-09-06 | Isis Innovation | Epitope reduction therapy |
| CA2660052A1 (en) | 2006-08-04 | 2008-02-07 | Isis Pharmaceuticals, Inc. | Compositions and methods for the modulation of jnk proteins |
| AT504194B1 (de) | 2006-09-07 | 2008-07-15 | Oesterr Rotes Kreuz | Bakteriennachweis |
| US8138330B2 (en) | 2006-09-11 | 2012-03-20 | Sigma-Aldrich Co. Llc | Process for the synthesis of oligonucleotides |
| NZ575437A (en) | 2006-09-27 | 2012-02-24 | Coley Pharm Gmbh | Cpg oligonucleotide analogs containing hydrophobic t analogs with enhanced immunostimulatory activity |
| EP2092065B2 (en) | 2006-10-18 | 2019-07-24 | Ionis Pharmaceuticals, Inc. | Antisense compounds |
| WO2008051763A1 (en) | 2006-10-23 | 2008-05-02 | Irm Llc | Cathepsin proteases inhibitors |
| EP2104738A2 (en) * | 2006-10-26 | 2009-09-30 | Coley Pharmaceuticals GmbH | Oligoribonucleotides and uses thereof |
| FR2908414B1 (fr) | 2006-11-13 | 2012-01-20 | Centre Nat Rech Scient | Immobilisation de proteines membranaires sur un support par l'intermediaire d'une molecule amphiphile |
| EP2099454A4 (en) | 2006-11-17 | 2010-11-10 | Abbott Lab | AMINOPYRROLIDINES AS CHEMOKINE RECEPTOR ANTAGONISTS |
| TW200838551A (en) | 2006-11-27 | 2008-10-01 | Isis Pharmaceuticals Inc | Methods for treating hypercholesterolemia |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| CN101610671A (zh) | 2006-12-12 | 2009-12-23 | 艾德拉药物股份有限公司 | 合成的tlr9激动剂 |
| UY30892A1 (es) | 2007-02-07 | 2008-09-02 | Smithkline Beckman Corp | Inhibidores de la actividad akt |
| EP2125852B1 (en) | 2007-02-15 | 2016-04-06 | Ionis Pharmaceuticals, Inc. | 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom |
| BRPI0809320A2 (pt) | 2007-03-24 | 2014-09-23 | Genzyme Corp | Método |
| US7960353B2 (en) | 2007-05-10 | 2011-06-14 | University Of Kansas | Novobiocin analogues as neuroprotective agents and in the treatment of autoimmune disorders |
| WO2008141308A2 (en) | 2007-05-11 | 2008-11-20 | Adynxx, Inc. | Gene expression and pain |
| WO2008143343A1 (ja) | 2007-05-24 | 2008-11-27 | Kyorin Pharmaceutical Co., Ltd. | １４位置換基に複素芳香環カルボン酸構造を有するムチリン誘導体 |
| GB0710186D0 (en) | 2007-05-29 | 2007-07-04 | Texas Instr Denmark | PWM loop with minimum allasing error property |
| US8278425B2 (en) | 2007-05-30 | 2012-10-02 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
| US8188301B2 (en) | 2007-06-05 | 2012-05-29 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Disubstituted phenylpyrrolidines as modulators of cortical catecholaminergic neurotransmission |
| EP2173760B2 (en) | 2007-06-08 | 2015-11-04 | Isis Pharmaceuticals, Inc. | Carbocyclic bicyclic nucleic acid analogs |
| EP2164865A2 (en) | 2007-06-13 | 2010-03-24 | Hochschule Mannheim | Compounds for the modulation of huntingtin aggregation, methods and means for identifying such compounds |
| ATE462787T1 (de) | 2007-06-18 | 2010-04-15 | Commissariat Energie Atomique | Reversibles sirna-silencing eines mutierten und endogenen huntington-wildtypgens und dessen anwendung zur behandlung von morbus huntington |
| GB0712494D0 (en) | 2007-06-27 | 2007-08-08 | Isis Innovation | Substrate reduction therapy |
| CA2692579C (en) | 2007-07-05 | 2016-05-03 | Isis Pharmaceuticals, Inc. | 6-disubstituted bicyclic nucleic acid analogs |
| AU2008279509B2 (en) | 2007-07-09 | 2011-07-21 | Idera Pharmaceuticals, Inc. | Stabilized immune modulatory RNA (SIMRA) compounds |
| TWI413530B (zh) | 2007-07-20 | 2013-11-01 | Kao Corp | 有機聚矽氧 |
| CA2694718A1 (en) | 2007-07-31 | 2009-02-05 | University Of Saskatchewan | Genetic variation in pro-melanin-concentrating hormone gene affects carcass traits in cattle |
| WO2009017803A2 (en) | 2007-08-02 | 2009-02-05 | The Texas A & M University System | Antisense microrna and uses therefor |
| AU2008286735A1 (en) | 2007-08-15 | 2009-02-19 | Idera Pharmaceuticals, Inc. | Toll like receptor modulators |
| MX2010003606A (es) | 2007-10-01 | 2010-07-02 | Isis Pharmaceuticals Inc | Modulacion antisentido de la expresion del receptor del factor de crecimiento fibroblastico 4. |
| KR100886139B1 (ko) | 2007-11-13 | 2009-02-27 | 주식회사 삼천리제약 | 올리고뉴클레오타이드의 제조방법 |
| AR069869A1 (es) | 2007-12-21 | 2010-02-24 | Exelixis Inc | Derivados de benzofuro[3,2-d]pirimidinas inhibidores de proteinquinasas,composiciones farmaceuticas que los comprenden y usos de los mismos en el tratamiento del cancer. |
| TWI340765B (en) | 2007-12-26 | 2011-04-21 | Ind Tech Res Inst | Oligonucleotide sequences and dna chip for identifying filamentous microorganisms and the identification method thereof |
| WO2009089659A1 (en) | 2008-01-18 | 2009-07-23 | Shanghai Targetdrug Co., Ltd. | Pyrollidine-based compounds |
| WO2009098197A1 (en) | 2008-02-04 | 2009-08-13 | Biofocus Dpi B.V. | Target sequences and methods to identify the same, useful in treatment of neurodegenerative diseases |
| JP2009190983A (ja) | 2008-02-12 | 2009-08-27 | Tokyo Institute Of Technology | オリゴヌクレオチド誘導体 |
| WO2009117589A1 (en) | 2008-03-21 | 2009-09-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising tricyclic nucleosides and methods for their use |
| US20110269814A1 (en) | 2008-03-26 | 2011-11-03 | Alnylam Pharamaceuticals, Inc. | 2'-f modified rna interference agents |
| KR101927905B1 (ko) | 2008-04-03 | 2018-12-11 | 스프링 뱅크 파마슈티칼스, 인크. | 바이러스 감염증을 치료하기 위한 조성물 및 방법 |
| DK2285819T3 (da) | 2008-04-04 | 2013-12-02 | Isis Pharmaceuticals Inc | Oligomere forbindelser omfattende neutralt bundne, terminale bicykliske nukleosider |
| US8350022B2 (en) | 2008-04-04 | 2013-01-08 | Universitaet Hamburg | Method for the stereoselective synthesis of phosphorus compounds |
| CA2726866A1 (en) | 2008-05-09 | 2009-11-12 | The University Of British Columbia | Methods and compositions for the treatment of huntington's disease |
| US8679750B2 (en) | 2008-05-09 | 2014-03-25 | The University Of British Columbia | Methods and compositions for the treatment of Huntington'S disease |
| JP5727367B2 (ja) | 2008-05-15 | 2015-06-03 | ダイナバックス テクノロジーズ コーポレイション | 免疫賦活オリゴヌクレオチドを使用する長期疾患改良 |
| WO2009143387A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc. | Modulation of smrt expression |
| WO2009143390A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc. | Methods for modulating expression of rbp4 |
| WO2009143391A2 (en) | 2008-05-22 | 2009-11-26 | Isis Pharmaceuticals, Inc | Methods for modulation expression of creb |
| WO2009148605A2 (en) | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| EP2320895A2 (en) | 2008-07-03 | 2011-05-18 | Exelixis, Inc. | Cdk modulators |
| US8410070B2 (en) | 2008-09-12 | 2013-04-02 | University Of Louisville Research Foundation, Inc. | Compositions and methods for treating cancer, inhibiting proliferation, and inducing cell death |
| WO2010030858A1 (en) | 2008-09-15 | 2010-03-18 | Enanta Pharmaceuticals, Inc. | 4'-allene-substituted nucleoside derivatives |
| EP2346883B1 (en) | 2008-09-23 | 2016-03-23 | Scott G. Petersen | Self delivering bio-labile phosphate protected pro-oligos for oligonucleotide based therapeutics and mediating rna interference |
| US8604192B2 (en) | 2008-09-24 | 2013-12-10 | Isis Pharmaceuticals, Inc. | Cyclohexenyl nucleic acids analogs |
| DK2356129T3 (da) | 2008-09-24 | 2013-05-13 | Isis Pharmaceuticals Inc | Substituerede alpha-L-bicykliske nukleosider |
| US20110257251A1 (en) | 2008-10-07 | 2011-10-20 | Presidents And Fellows Of Harvard College | Telomerase inhibitors and methods of use thereof |
| CN102449151A (zh) | 2008-10-22 | 2012-05-09 | 夸克医药公司 | 治疗眼部疾病的方法 |
| CN102264374B (zh) | 2008-10-24 | 2015-01-07 | Isis制药公司 | 5′和2′双取代的核苷和由其制备的低聚化合物 |
| EP2358398A2 (en) | 2008-10-24 | 2011-08-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| BRPI0923225A2 (pt) | 2008-12-02 | 2016-10-04 | Chiralgen Ltd | metodo para sintese de acidos nucleicos modificados no atomo de fosforo |
| CN102307889A (zh) | 2008-12-23 | 2012-01-04 | 集润德斯股份公司 | 硫化剂及其用于寡核苷酸合成的用途 |
| WO2010080953A1 (en) | 2009-01-08 | 2010-07-15 | Isis Pharmaceuticals, Inc. | Transgenic murine model of human lipoprotein metabolism, hypercholesterolemia and cardiovascular disease |
| KR20100087540A (ko) | 2009-01-28 | 2010-08-05 | 삼성전자주식회사 | 잉크젯 기록용 잉크 조성물 |
| US20120264806A1 (en) | 2009-02-06 | 2012-10-18 | Bennett C Frank | Oligomeric compounds and excipients |
| US8202974B2 (en) | 2009-02-10 | 2012-06-19 | Idera Pharmaceuticals, Inc. | Synthetic RNA-based agonists of TLR7 |
| JP5766617B2 (ja) | 2009-02-20 | 2015-08-19 | ユニバーシティ・オブ・カンザス | 修飾された糖部分を有するノボビオシン類似体 |
| AU2010221419B2 (en) | 2009-03-02 | 2015-10-01 | Alnylam Pharmaceuticals, Inc. | Nucleic acid chemical modifications |
| WO2010107838A1 (en) | 2009-03-16 | 2010-09-23 | Isis Pharmaceuticals, Inc. | Targeting apolipoprotein b for the reduction of apolipoprotein c-iii |
| EP2415777B1 (en) | 2009-03-31 | 2015-07-29 | Takeda Pharmaceutical Company Limited | Process for producing nucleoside |
| WO2010118263A1 (en) | 2009-04-08 | 2010-10-14 | University Of Massachusetts | Single-nucleotide polymorphism (snp) targeting therapies for the treatment of huntington's disease |
| CA2759098A1 (en) | 2009-04-14 | 2010-10-21 | Smith Holdings, Llc | Methods and compositions for the treatment of medical conditions involving cellular programming |
| US9260493B2 (en) | 2009-05-07 | 2016-02-16 | The Regents Of The University Of California | Transducible delivery of nucleic acids using modified dsRNA binding domains |
| KR20120052909A (ko) | 2009-06-01 | 2012-05-24 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 핵산 수송용 조성물 및 이의 사용 방법 |
| BRPI1011072B1 (pt) | 2009-06-05 | 2021-09-28 | Infectious Disease Research Institute | Composto de gla, composições de vacina e farmacêutica compreendendo dito composto, bem como uso dos mesmos para estimular, induzir ou acentuar uma resposta imune em um indivíduo |
| DK3305302T3 (en) | 2009-06-17 | 2018-11-19 | Biogen Ma Inc | COMPOSITIONS AND PROCEDURES FOR MODULATING SMN2 SPLITING BY AN INDIVIDUAL |
| JP5670097B2 (ja) | 2009-06-19 | 2015-02-18 | 花王株式会社 | 二層分離型毛髪化粧料 |
| JPWO2010150789A1 (ja) | 2009-06-23 | 2012-12-10 | 武田薬品工業株式会社 | 核酸の合成法 |
| WO2011005764A1 (en) | 2009-07-06 | 2011-01-13 | Ada Technologies, Inc. | Electrochemical device and method for long-term measurement of hypohalites |
| KR101885383B1 (ko) | 2009-07-06 | 2018-08-03 | 웨이브 라이프 사이언시스 리미티드 | 신규한 핵산 프로드러그 및 그의 사용 방법 |
| US8927513B2 (en) | 2009-07-07 | 2015-01-06 | Alnylam Pharmaceuticals, Inc. | 5′ phosphate mimics |
| EP2451974A2 (en) | 2009-07-08 | 2012-05-16 | Idera Pharmaceuticals, Inc. | Oligonucleotide-based compounds as inhibitors of toll-like receptors |
| EP2458005A1 (en) | 2009-07-23 | 2012-05-30 | Galaxy Pharma Inc. | Fgf21 cis-element binding substance |
| WO2011015572A1 (en) | 2009-08-03 | 2011-02-10 | Galapagos Nv | Molecular targets and compounds, and methods to identify the same, useful in the treatment of neurodegenerative diseases |
| WO2011015573A1 (en) | 2009-08-03 | 2011-02-10 | Galapagos Nv | Molecular targets and compounds, and methods to identify the same, useful in the treatment of neurodegenerative diseases |
| UA107360C2 (en) | 2009-08-05 | 2014-12-25 | Biogen Idec Inc | Bicyclic aryl sphingosine 1-phosphate analogs |
| WO2011017521A2 (en) | 2009-08-06 | 2011-02-10 | Isis Pharmaceuticals, Inc. | Bicyclic cyclohexose nucleic acid analogs |
| US8927553B2 (en) | 2009-08-10 | 2015-01-06 | Daljit Singh Dhanoa | Deuterium-enriched alkyl sulfonamides and uses thereof |
| SI2475675T1 (sl) | 2009-09-11 | 2017-03-31 | Ionis Pharmaceuticals, Inc. | Modulacija ekspresije huntingtina |
| WO2011034072A1 (ja) | 2009-09-16 | 2011-03-24 | 株式会社キラルジェン | Rna及びその誘導体合成のための新規保護基 |
| WO2011038288A1 (en) | 2009-09-25 | 2011-03-31 | Isis Pharmaceuticals, Inc. | Modulation of ttc39 expression to increase hdl |
| JP5629324B2 (ja) | 2009-10-15 | 2014-11-19 | ファイザー・インク | ピロロ［２，３−ｄ］ピリミジン化合物 |
| TWI475051B (zh) | 2009-11-18 | 2015-03-01 | Kao Corp | Organic polysiloxane |
| JP5809408B2 (ja) | 2009-11-25 | 2015-11-10 | 花王株式会社 | 毛髪化粧料 |
| US8735417B2 (en) | 2009-12-17 | 2014-05-27 | Merck Sharp & Dohme Corp. | Aminopyrimidines as Syk inhibitors |
| CA2782782A1 (en) | 2009-12-28 | 2011-07-07 | Achira Labs Pvt. Ltd. | Diagnostic gel composition, method for making a diagnostic gel composition |
| CN106146591B (zh) | 2010-01-08 | 2020-07-31 | Ionis制药公司 | 血管生成素样3表达的调节 |
| US8750507B2 (en) | 2010-01-25 | 2014-06-10 | Cisco Technology, Inc. | Dynamic group creation for managed key servers |
| AU2011213562B2 (en) | 2010-02-08 | 2016-07-07 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| EP3628750A1 (en) | 2010-02-08 | 2020-04-01 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| US8703754B2 (en) | 2010-02-10 | 2014-04-22 | Glaxosmithkline Llc | 6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)-7,9-dihydro-8H-purin-8-one maleate |
| JP5847700B2 (ja) | 2010-03-05 | 2016-01-27 | 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ | リボヌクレオシドホスホロチオエートの製造方法 |
| WO2011127175A1 (en) | 2010-04-06 | 2011-10-13 | Isis Pharmaceuticals, Inc. | Modulation of cd130 (gp130) expression |
| CA2795750A1 (en) | 2010-04-07 | 2011-10-13 | Isis Pharmaceuticals, Inc. | Modulation of cetp expression |
| US9725479B2 (en) | 2010-04-22 | 2017-08-08 | Ionis Pharmaceuticals, Inc. | 5′-end derivatives |
| JP6005628B2 (ja) | 2010-04-28 | 2016-10-12 | アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 修飾ヌクレオシド、その類似体、およびこれらから調製されるオリゴマー化合物 |
| EP3091027B1 (en) | 2010-04-28 | 2018-01-17 | Ionis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
| US20130156845A1 (en) | 2010-04-29 | 2013-06-20 | Alnylam Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
| WO2011135396A1 (en) | 2010-04-30 | 2011-11-03 | Cellectis | Method for modulating double-strand break-induced homologous recombination |
| GB201008902D0 (en) | 2010-05-27 | 2010-07-14 | Imp Innovations Ltd | Membrane enhanced polymer sythesis |
| WO2012030683A2 (en) | 2010-08-31 | 2012-03-08 | Merck Sharp & Dohme Corp. | Novel single chemical entities and methods for delivery of oligonucleotides |
| JP5868324B2 (ja) | 2010-09-24 | 2016-02-24 | 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ | 不斉補助基 |
| WO2012043633A1 (ja) | 2010-09-30 | 2012-04-05 | 独立行政法人国立精神・神経医療研究センター | 優性変異遺伝子発現抑制剤 |
| KR101381048B1 (ko) | 2010-10-20 | 2014-04-14 | 씨제이제일제당 (주) | Ｏ-포스포세린 생산 균주 및 이로부터 생산된 ｏ-포스포세린으로부터 ｌ-시스테인 또는 이의 유도체의 생산방법 |
| EP2632472B1 (en) | 2010-10-29 | 2017-12-13 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina) |
| AU2011325956B2 (en) | 2010-11-12 | 2016-07-14 | The General Hospital Corporation | Polycomb-associated non-coding RNAs |
| JP6093924B2 (ja) | 2010-11-30 | 2017-03-15 | 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ | ２’−ｏ−修飾ｒｎａ |
| US20140050778A1 (en) | 2010-12-28 | 2014-02-20 | University Of Rochester | Nucleic acid binding compounds, methods of making, and use thereof |
| US10017764B2 (en) | 2011-02-08 | 2018-07-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| WO2012109667A1 (en) | 2011-02-12 | 2012-08-16 | University Of Iowa Research Foundation | Therapeutic compounds |
| US9353371B2 (en) | 2011-05-02 | 2016-05-31 | Ionis Pharmaceuticals, Inc. | Antisense compounds targeting genes associated with usher syndrome |
| FR2975600B1 (fr) | 2011-05-24 | 2013-07-05 | Assist Publ Hopitaux De Paris | Agents pour le traitement de tumeurs |
| CN103796657B (zh) | 2011-07-19 | 2017-07-11 | 波涛生命科学有限公司 | 合成官能化核酸的方法 |
| MX2014000797A (es) | 2011-07-19 | 2014-07-09 | Univ Idaho | Sonda y metodo para direccionar acidos nucleicos. |
| EP2742135B2 (en) | 2011-08-11 | 2020-06-10 | Ionis Pharmaceuticals, Inc. | Linkage modified gapped oligomeric compounds and uses thereof |
| EP2751269B1 (en) | 2011-08-29 | 2016-03-23 | Ionis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
| US20140080896A1 (en) | 2011-08-30 | 2014-03-20 | The Regents Of The University Of California | Identification of small molecules that facilitate therapeutic exon skipping |
| CA2846307C (en) | 2011-08-31 | 2020-03-10 | Hospital District Of Helsinki And Uusimaa | Method for diagnosing a neurodegenerative disease |
| WO2013036833A1 (en) | 2011-09-09 | 2013-03-14 | Mayo Foundation For Medical Education And Research | Detecting frontotemporal dementia and amyotrophic lateral sclerosis |
| ES2832531T3 (es) | 2011-11-30 | 2021-06-10 | Sarepta Therapeutics Inc | Oligonucleótidos para el tratamiento de enfermedades por expansión de repeticiones |
| KR200460641Y1 (ko) | 2011-12-07 | 2012-06-04 | 이형호 | 휴대가 용이한 와인 잔 |
| DK2790736T3 (en) | 2011-12-12 | 2018-05-07 | Oncoimmunin Inc | In vivo delivery of oligonucleotides |
| AU2012353330B2 (en) | 2011-12-16 | 2018-04-19 | National University Corporation Tokyo Medical And Dental University | Chimeric double-stranded nucleic acid |
| CN102675386B (zh) | 2011-12-24 | 2014-07-02 | 河南科技大学 | 一种龙胆苦苷分离提纯方法 |
| US8957042B2 (en) | 2012-03-07 | 2015-02-17 | The Texas A&M University System | Cancer treatment targeting non-coding RNA overexpression |
| EP3932931A1 (en) | 2012-03-13 | 2022-01-05 | Gilead Sciences, Inc. | A nebulizer comprising a pharmaceutical composition comprising 2'- substituted carba-nucleoside analogs for antiviral treatment |
| KR20130114435A (ko) | 2012-04-09 | 2013-10-17 | 삼성전자주식회사 | 다수의 전극을 갖는 생분자 검출 장치 |
| CN110025628B (zh) | 2012-04-23 | 2023-03-31 | 维科医疗有限公司 | 治疗神经肌肉障碍的具有改善特性的rna调节寡核苷酸 |
| AU2013266393B2 (en) | 2012-05-22 | 2017-09-28 | Idenix Pharmaceuticals Llc | D-amino acid compounds for liver disease |
| SG11201407967TA (en) | 2012-05-30 | 2015-01-29 | Hokkaido System Science Co Ltd | Oligonucleotide synthesis method using highly dispersible liquid-phase support |
| EP2873674B1 (en) | 2012-07-13 | 2020-05-06 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| SG11201500239VA (en) | 2012-07-13 | 2015-03-30 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| EP4219516A3 (en) | 2012-07-13 | 2024-01-10 | Wave Life Sciences Ltd. | Chiral control |
| EP2879718B1 (en) | 2012-08-06 | 2023-06-07 | Alnylam Pharmaceuticals, Inc. | Processes for the preparation of carbohydrate conjugated rna agents |
| KR102237882B1 (ko) | 2012-08-15 | 2021-04-07 | 아이오니스 파마수티컬즈, 인코포레이티드 | 변형된 캡핑 프로토콜을 이용하는 올리고머 화합물 제조 방법 |
| CA2887884A1 (en) | 2012-10-12 | 2014-04-17 | Isis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| US10577604B2 (en) | 2012-10-15 | 2020-03-03 | Ionis Pharmaceuticals, Inc. | Methods for monitoring C9ORF72 expression |
| PT2906696T (pt) | 2012-10-15 | 2019-12-16 | Univ California | Métodos para modular a expressão de c9orf72 |
| BR112015008399A8 (pt) | 2012-10-15 | 2017-10-03 | Ionis Pharmaceuticals Inc | Composto para modular a expressão de c90rf72, seu uso, oligonucleotídeo modificado, composto de fita dupla e composição |
| RU2015119999A (ru) | 2012-10-29 | 2016-12-20 | Кокристал Фарма, Инк. | Пиримидиновые нуклеозиды и их монофосфатные пролекарства для лечения вырусных инфекций и рака |
| EP2725029A1 (en) | 2012-10-29 | 2014-04-30 | Laboratoire Biodim | New antibacterial compounds and biological applications thereof |
| JP6358955B2 (ja) | 2012-10-31 | 2018-07-18 | 武田薬品工業株式会社 | 新規修飾核酸 |
| PL2920304T3 (pl) | 2012-11-15 | 2019-07-31 | Roche Innovation Center Copenhagen A/S | Koniugaty oligonukleotydowe |
| KR20150088305A (ko) | 2012-11-26 | 2015-07-31 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | Fgfr3 발현의 조절을 위한 조성물 및 방법 |
| WO2014099941A1 (en) | 2012-12-19 | 2014-06-26 | Idenix Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
| EP2951305B1 (en) | 2013-01-30 | 2018-08-15 | F.Hoffmann-La Roche Ag | Lna oligonucleotide carbohydrate conjugates |
| WO2014118272A1 (en) | 2013-01-30 | 2014-08-07 | Santaris Pharma A/S | Antimir-122 oligonucleotide carbohydrate conjugates |
| ES2817050T3 (es) | 2013-02-04 | 2021-04-06 | Ionis Pharmaceuticals Inc | Compuestos antisentido selectivos y usos de los mismos |
| JP6613143B2 (ja) | 2013-02-22 | 2019-11-27 | サーナ・セラピューティクス・インコーポレイテッド | ２’ヌクレオシド間結合を含有する低分子干渉核酸（ｓｉＮＡ）分子 |
| AU2014222150A1 (en) | 2013-03-01 | 2015-09-10 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
| EA201500984A1 (ru) | 2013-03-28 | 2016-04-29 | Зингента Партисипейшнс Аг | Способы контроля устойчивых к неоникотиноидам вредителей |
| MX2015013628A (es) | 2013-03-28 | 2016-02-18 | Syngenta Ltd | Metodos para controlar las plagas resistentes a neonicotinoides. |
| AU2014259759B2 (en) | 2013-05-01 | 2020-06-18 | Ionis Pharmaceuticals, Inc. | Compositions and methods |
| CA2907694A1 (en) | 2013-05-24 | 2014-11-27 | Roche Innovation Center Copenhagen A/S | Oligonucleotide modulators of b-cell cll/lymphoma 11a (bcl11a) and uses thereof |
| EP3015467A4 (en) | 2013-05-24 | 2016-11-02 | Ajinomoto Kk | PROCESS FOR THE PRODUCTION OF MORPHOLINO-OLIGONUCLEOTIDE |
| EP3004347B1 (en) | 2013-05-30 | 2018-09-26 | National University Corporation Tokyo Medical and Dental University | Double-stranded agents for delivering therapeutic oligonucleotides |
| CN105324119A (zh) | 2013-06-16 | 2016-02-10 | 国立大学法人东京医科齿科大学 | 具有外显子跳跃效应的双链反义核酸 |
| AU2014284152B2 (en) | 2013-06-21 | 2020-01-23 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
| PT3013959T (pt) | 2013-06-27 | 2020-02-04 | Roche Innovation Ct Copenhagen As | Oligómeros antissentido e conjugados dirigidos para pcsk9 |
| TW202246503A (zh) | 2013-07-19 | 2022-12-01 | 美商百健Ｍａ公司 | 用於調節τ蛋白表現之組合物 |
| AU2014292926B2 (en) | 2013-07-25 | 2020-03-05 | Exicure Operating Company | Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use |
| EP3027617A4 (en) | 2013-07-31 | 2017-04-12 | Ionis Pharmaceuticals, Inc. | Methods and compounds useful in conditions related to repeat expansion |
| CN105579442A (zh) | 2013-09-06 | 2016-05-11 | 先正达参股股份有限公司 | 杀虫化合物 |
| WO2015051169A2 (en) | 2013-10-02 | 2015-04-09 | Moderna Therapeutics, Inc. | Polynucleotide molecules and uses thereof |
| CA2926218A1 (en) | 2013-10-03 | 2015-04-09 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
| EP3052627B1 (en) | 2013-10-04 | 2018-08-22 | Novartis AG | Novel formats for organic compounds for use in rna interference |
| BR112016007751A2 (pt) | 2013-10-11 | 2017-09-12 | Ionis Pharmaceuticals Inc | composições para modulação de expressão de c9orf72 |
| WO2015057738A1 (en) | 2013-10-14 | 2015-04-23 | Isis Pharmaceuticals, Inc. | Methods for modulating expression of c9orf72 antisense transcript |
| WO2015057727A1 (en) | 2013-10-14 | 2015-04-23 | Isis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
| NZ719477A (en) | 2013-11-11 | 2022-05-27 | Sangamo Therapeutics Inc | Methods and compositions for treating huntington’s disease |
| WO2015071388A1 (en) | 2013-11-14 | 2015-05-21 | Roche Innovation Center Copenhagen A/S | Apob antisense conjugate compounds |
| US20150167017A1 (en) | 2013-12-13 | 2015-06-18 | Moderna Therapeutics, Inc. | Alternative nucleic acid molecules and uses thereof |
| US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| 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 |
| KR102423317B1 (ko) | 2014-01-16 | 2022-07-22 | 웨이브 라이프 사이언시스 리미티드 | 키랄 디자인 |
| CA2942515A1 (en) | 2014-03-18 | 2015-09-24 | University Of Massachusetts | Raav-based compositions and methods for treating amyotrophic lateral sclerosis |
| EP3137476B1 (en) | 2014-04-28 | 2019-10-09 | Ionis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
| BR122020024443B1 (pt) | 2014-05-01 | 2022-02-22 | Ionis Pharmaceuticals, Inc | Composto e composição farmacêutica para modulação da expressão de angptl3 |
| CN106413760B (zh) | 2014-05-08 | 2020-01-14 | 桑格摩生物科学股份有限公司 | 用于治疗亨廷顿病的方法和组合物 |
| CN107075514A (zh) | 2014-05-20 | 2017-08-18 | 衣阿华大学研究基金会 | 亨廷顿氏病的治疗化合物 |
| US20160017327A1 (en) | 2014-07-11 | 2016-01-21 | The Johns Hopkins University | Phosphorodiamidate morpholino oligomers (pmos) and their use in suppression of mutant huntingtin expression and attenuation of neurotoxicity |
| CA2955250A1 (en) | 2014-07-16 | 2016-01-21 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
| EP2982758A1 (en) | 2014-08-04 | 2016-02-10 | Centre Hospitalier Universitaire Vaudois (CHUV) | Genome editing for the treatment of huntington's disease |
| ES2799409T3 (es) | 2014-08-07 | 2020-12-17 | Takeda Pharmaceuticals Co | Lípido catiónico |
| WO2016024205A1 (en) | 2014-08-15 | 2016-02-18 | Pfizer Inc. | Oligomers targeting hexanucleotide repeat expansion in human c9orf72 gene |
| WO2016037191A1 (en) | 2014-09-05 | 2016-03-10 | Health Research, Inc. | Use of huntingtin-derived plasmids and peptides for active immunization as a huntington's disease (hd) therapeutic |
| JP2017535552A (ja) | 2014-11-17 | 2017-11-30 | アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | アポリポタンパク質Ｃ３（ＡＰＯＣ３）ｉＲＮＡ組成物およびその使用方法 |
| EP3220921A1 (en) | 2014-11-19 | 2017-09-27 | Roche Innovation Center Copenhagen A/S | Lna chiral phosphorothioates |
| WO2016096938A1 (en) | 2014-12-16 | 2016-06-23 | Roche Innovation Center Copenhagen A/S | Chiral toxicity screening method |
| JP6839094B2 (ja) | 2014-12-24 | 2021-03-03 | ユニクア・アイピー・ベーフェー | ＲＮＡｉで誘発されるハンチンチン遺伝子抑制 |
| US9688707B2 (en) | 2014-12-30 | 2017-06-27 | Ionis Pharmaceuticals, Inc. | Bicyclic morpholino compounds and oligomeric compounds prepared therefrom |
| US10793855B2 (en) | 2015-01-06 | 2020-10-06 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of C9ORF72 antisense transcript |
| AU2016215155A1 (en) | 2015-02-04 | 2017-08-17 | F. Hoffmann-La Roche Ag | Tau antisense oligomers and uses thereof |
| EP3254104B1 (en) | 2015-02-04 | 2021-08-25 | Bristol-Myers Squibb Company | Methods of selecting therapeutic molecules |
| US20180023081A1 (en) | 2015-02-04 | 2018-01-25 | Bristol-Myers Squibb Company | Lna oligonucleotides with alternating flanks |
| MX2017010369A (es) | 2015-02-10 | 2017-12-14 | Genzyme Corp | Arni variante. |
| JP2018510621A (ja) | 2015-02-13 | 2018-04-19 | アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | パタチン様ホスホリパーゼドメイン含有３（ＰＮＰＬＡ３）ｉＲＮＡ組成物およびその使用方法 |
| US10370659B2 (en) | 2015-02-23 | 2019-08-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for increasing antisense activity |
| WO2016141236A1 (en) | 2015-03-03 | 2016-09-09 | Ionis Pharmaceuticals, Inc. | Compositions for modulating mecp2 expression |
| WO2016145142A1 (en) | 2015-03-10 | 2016-09-15 | Emory University | Nucleotide and nucleoside therapeutics compositions and uses related thereto |
| WO2016154096A1 (en) | 2015-03-20 | 2016-09-29 | Ionis Pharmaceuticals, Inc. | Modulation of smggds expression |
| US9809817B2 (en) | 2015-04-03 | 2017-11-07 | University Of Massachusetts | Oligonucleotide compounds for targeting huntingtin mRNA |
| US10851371B2 (en) | 2015-04-10 | 2020-12-01 | Ionis Pharmaceuticals, Inc. | Modulation of SMN expression |
| US10407678B2 (en) | 2015-04-16 | 2019-09-10 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of C9ORF72 antisense transcript |
| ES2791995T3 (es) | 2015-04-16 | 2020-11-06 | Ionis Pharmaceuticals Inc | Composiciones para modular la expresión de C90RF72 |
| WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
| AU2016285724A1 (en) | 2015-06-29 | 2017-11-16 | Ionis Pharmaceuticals, Inc. | Modified CRISPR RNA and modified single CRISPR RNA and uses thereof |
| CN109477106B (zh) | 2015-07-10 | 2022-10-04 | Ionis制药公司 | 二酰基甘油酰基转移酶2(dgat2)的调节剂 |
| US10494632B2 (en) | 2015-07-10 | 2019-12-03 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (IGFALS) compositions and methods of use thereof |
| EP3324980B1 (en) | 2015-07-17 | 2021-11-10 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
| MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| TW201718620A (zh) | 2015-07-27 | 2017-06-01 | 阿尼拉製藥公司 | 黃嘌呤脫氫酶（ＸＤＨ）ｉＲＮＡ組成物及其使用方法 |
| PL3329002T3 (pl) | 2015-07-31 | 2021-04-19 | Alnylam Pharmaceuticals, Inc. | Kompozycje irna transtyretyny (ttr) i sposoby ich zastosowania do leczenia lub zapobiegania chorobom związanym z ttr |
| US20190055550A1 (en) | 2015-08-24 | 2019-02-21 | Roche Innovation Center Copenhagen A/S | LNA-G Process |
| WO2017035340A1 (en) | 2015-08-25 | 2017-03-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder |
| PE20181131A1 (es) | 2015-09-02 | 2018-07-17 | Alnylam Pharmaceuticals Inc | COMPOSICIONES DE ARNi PARA LIGANDO 1 DE MUERTE CELULAR PROGRAMADA 1 (PD-L1) Y METODOS DE USO DE LAS MISMAS |
| WO2017048620A1 (en) | 2015-09-14 | 2017-03-23 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting patatin-like phospholipase domain containing 3 (pnpla3) and methods of use thereof |
| CA3000709A1 (en) | 2015-10-01 | 2017-04-06 | Memorial Sloan-Kettering Cancer Center | Inhibitors of menaquinone biosynthesis |
| US10874686B2 (en) | 2015-10-01 | 2020-12-29 | Memorial Sloan-Kettering Cancer Center | Anthranilyl-adenosinemonosulfamate analogs and uses thereof |
| KR20180073584A (ko) | 2015-10-02 | 2018-07-02 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | 올리고뉴클레오타이드 접합 방법 |
| EP3359523A4 (en) | 2015-10-09 | 2019-07-24 | Wave Life Sciences Ltd. | OLIGONUCLEOTIDE COMPOSITIONS AND RELATED METHODS |
| EP3183347A4 (en) | 2015-10-17 | 2018-04-18 | Lifesplice Pharma LLC | Splice modulating oligonucleotides and methods of use thereof |
| WO2017068087A1 (en) | 2015-10-22 | 2017-04-27 | Roche Innovation Center Copenhagen A/S | Oligonucleotide detection method |
| WO2017067970A1 (en) | 2015-10-22 | 2017-04-27 | Roche Innovation Center Copenhagen A/S | In vitro toxicity screening assay |
| US11260073B2 (en) | 2015-11-02 | 2022-03-01 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating C90RF72 |
| PE20210451A1 (es) | 2015-11-12 | 2021-03-08 | Hoffmann La Roche | Oligonucleotidos para inducir la expresion paterna de ube3a |
| MA43822A (fr) | 2016-03-13 | 2018-11-28 | Wave Life Sciences Ltd | Compositions et procédés de synthèse de phosphoramidite et d'oligonucléotides |
| US20170283496A1 (en) | 2016-03-14 | 2017-10-05 | Roche Innovation Center Copenhagen A/S | Oligonucleotides for reduction of pd-l1 expression |
| KR102372122B1 (ko) | 2016-03-18 | 2022-03-07 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | 아실-보호된 l-lna-구아노신 단량체 |
| WO2017165489A1 (en) | 2016-03-23 | 2017-09-28 | Emory University | Antiviral agents for treating zika and dengue virus infections |
| EP3443094B1 (en) | 2016-04-13 | 2022-10-19 | Ionis Pharmaceuticals, Inc. | Methods for reducing c9orf72 expression |
| JP6985288B2 (ja) | 2016-04-14 | 2021-12-22 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | トリチル−モノ−ＧａｌＮＡｃ化合物とその利用 |
| MA45290A (fr) | 2016-05-04 | 2019-03-13 | Wave Life Sciences Ltd | Procédés et compositions d'agents biologiquement actifs |
| MA45270A (fr) | 2016-05-04 | 2017-11-09 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| WO2017194498A1 (en) | 2016-05-12 | 2017-11-16 | Roche Innovation Center Copenhagen A/S | Enhanced coupling of stereodefined oxazaphospholidine phosphoramidite monomers to nucleoside or oligonucleotide |
| CA3023621C (en) | 2016-05-13 | 2021-07-27 | F. Hoffmann-La Roche Ag | Protein-based sample collection matrices and devices |
| WO2017198775A1 (en) | 2016-05-18 | 2017-11-23 | Eth Zurich | Stereoselective synthesis of phosphorothioate oligoribonucleotides |
| MA45188A (fr) | 2016-06-03 | 2019-04-10 | Wave Life Sciences Ltd | Oligonucléotides, compositions et méthodes associées |
| EP3473270B1 (en) | 2016-06-20 | 2022-11-30 | Genahead Bio, Inc. | Antibody-drug conjugate |
| US20190264267A1 (en) | 2016-07-25 | 2019-08-29 | Wave Life Sciences Ltd. | Phasing |
| JP7296882B2 (ja) | 2016-11-23 | 2023-06-23 | ウェイブ ライフ サイエンシズ リミテッド | ホスホラミダイト及びオリゴヌクレオチド合成のための組成物及び方法 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11390642B2 (en) | 2016-08-23 | 2022-07-19 | Dicerna Pharmaceuticals, Inc. | Compositions comprising reversibly modified oligonucleotides and uses thereof |
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