CA2577423C - Therapeutic uses of inhibitors of rtp801 - Google Patents
Therapeutic uses of inhibitors of rtp801 Download PDFInfo
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- CA2577423C CA2577423C CA2577423A CA2577423A CA2577423C CA 2577423 C CA2577423 C CA 2577423C CA 2577423 A CA2577423 A CA 2577423A CA 2577423 A CA2577423 A CA 2577423A CA 2577423 C CA2577423 C CA 2577423C
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- rtp801
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| DE202004021954U1 (de) | 2003-09-12 | 2013-06-19 | Vessix Vascular, Inc. | Auswählbare exzentrische Remodellierung und/oder Ablation von atherosklerotischem Material |
| NZ553162A (en) | 2004-08-16 | 2010-03-26 | Quark Biotech Inc | Double stranded siRNA compounds that inhibit RRTP801 |
| US9713730B2 (en) | 2004-09-10 | 2017-07-25 | Boston Scientific Scimed, Inc. | Apparatus and method for treatment of in-stent restenosis |
| US8920414B2 (en) | 2004-09-10 | 2014-12-30 | Vessix Vascular, Inc. | Tuned RF energy and electrical tissue characterization for selective treatment of target tissues |
| US8396548B2 (en) | 2008-11-14 | 2013-03-12 | Vessix Vascular, Inc. | Selective drug delivery in a lumen |
| JP4991547B2 (ja) * | 2004-09-28 | 2012-08-01 | クアーク・ファーマスーティカルス、インコーポレイテッド | 脱毛症、急性腎不全および他の疾患の治療のためのオリゴリボヌクレオチドおよびその使用の方法 |
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| US8019435B2 (en) | 2006-05-02 | 2011-09-13 | Boston Scientific Scimed, Inc. | Control of arterial smooth muscle tone |
| WO2007141796A2 (en) | 2006-06-09 | 2007-12-13 | Quark Pharmaceuticals, Inc. | Therapeutic uses of inhibitors of rtp801l |
| JP2008167739A (ja) * | 2006-06-14 | 2008-07-24 | National Institute Of Advanced Industrial & Technology | Ｒｎａ干渉効果が高い修飾型二本鎖ｒｎａ |
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| WO2008104978A2 (en) * | 2007-02-28 | 2008-09-04 | Quark Pharmaceuticals, Inc. | Novel sirna structures |
| US7812002B2 (en) * | 2007-03-21 | 2010-10-12 | Quark Pharmaceuticals, Inc. | Oligoribonucleotide inhibitors of NRF2 and methods of use thereof for treatment of cancer |
| JP2010527914A (ja) * | 2007-04-26 | 2010-08-19 | クォーク ファーマシューティカルズ インコーポレーティッド | 呼吸器系への抑制性核酸分子の治療的送達 |
| SI2170403T1 (sl) * | 2007-06-27 | 2014-07-31 | Quark Pharmaceuticals, Inc. | Sestavki in postopki za inhibicijo ekspresije pro-apoptotskih genov |
| US20090062309A1 (en) * | 2007-08-28 | 2009-03-05 | Antonio Delgado-Almeida | Therapeutic compositions for the treatment of cardiovascular diseases and methods for use therefor |
| CA2701845A1 (en) * | 2007-10-03 | 2009-04-09 | Quark Pharmaceuticals, Inc. | Novel sirna structures |
| US8614311B2 (en) | 2007-12-12 | 2013-12-24 | Quark Pharmaceuticals, Inc. | RTP801L siRNA compounds and methods of use thereof |
| US20110105584A1 (en) * | 2007-12-12 | 2011-05-05 | Elena Feinstein | Rtp80il sirna compounds and methods of use thereof |
| RU2010138558A (ru) * | 2008-03-20 | 2012-03-27 | Кварк Фармасьютикалс. Инк, (Us) | Новые соединения миphk для ингибирования rtp801 |
| US9095569B2 (en) * | 2008-04-18 | 2015-08-04 | Collplant Ltd. | Methods of generating and using procollagen |
| US8431692B2 (en) * | 2008-06-06 | 2013-04-30 | Quark Pharmaceuticals, Inc. | Compositions and methods for treatment of ear disorders |
| US9433684B2 (en) | 2008-08-19 | 2016-09-06 | Nektar Therapeutics | Conjugates of small-interfering nucleic acids |
| ES2563984T3 (es) * | 2008-10-22 | 2016-03-17 | Quark Pharmaceuticals, Inc. | Métodos para el tratamiento de trastornos oculares |
| KR20110104504A (ko) | 2008-11-17 | 2011-09-22 | 미노우 메디컬, 인코포레이티드 | 조직 토폴로지의 지식 여하에 따른 에너지의 선택적 축적 |
| EP2410910A4 (en) * | 2009-03-27 | 2014-10-15 | Dexcom Inc | METHOD AND SYSTEMS FOR PROMOTING A BLOOD SUGAR MANAGEMENT |
| WO2011035065A1 (en) | 2009-09-17 | 2011-03-24 | Nektar Therapeutics | Monoconjugated chitosans as delivery agents for small interfering nucleic acids |
| TW201124160A (en) | 2009-11-26 | 2011-07-16 | Quark Pharmaceuticals Inc | SiRNA compounds comprising terminal substitutions |
| WO2011072091A1 (en) | 2009-12-09 | 2011-06-16 | Quark Pharmaceuticals, Inc. | Methods and compositions for treating diseases, disorders or injury of the cns |
| WO2011084193A1 (en) | 2010-01-07 | 2011-07-14 | Quark Pharmaceuticals, Inc. | Oligonucleotide compounds comprising non-nucleotide overhangs |
| AU2011238925B2 (en) | 2010-04-09 | 2016-06-16 | Vessix Vascular, Inc. | Power generating and control apparatus for the treatment of tissue |
| US9192790B2 (en) | 2010-04-14 | 2015-11-24 | Boston Scientific Scimed, Inc. | Focused ultrasonic renal denervation |
| US8473067B2 (en) | 2010-06-11 | 2013-06-25 | Boston Scientific Scimed, Inc. | Renal denervation and stimulation employing wireless vascular energy transfer arrangement |
| US9155589B2 (en) | 2010-07-30 | 2015-10-13 | Boston Scientific Scimed, Inc. | Sequential activation RF electrode set for renal nerve ablation |
| US9358365B2 (en) | 2010-07-30 | 2016-06-07 | Boston Scientific Scimed, Inc. | Precision electrode movement control for renal nerve ablation |
| US9463062B2 (en) | 2010-07-30 | 2016-10-11 | Boston Scientific Scimed, Inc. | Cooled conductive balloon RF catheter for renal nerve ablation |
| US9084609B2 (en) | 2010-07-30 | 2015-07-21 | Boston Scientific Scime, Inc. | Spiral balloon catheter for renal nerve ablation |
| US9408661B2 (en) | 2010-07-30 | 2016-08-09 | Patrick A. Haverkost | RF electrodes on multiple flexible wires for renal nerve ablation |
| US8974451B2 (en) | 2010-10-25 | 2015-03-10 | Boston Scientific Scimed, Inc. | Renal nerve ablation using conductive fluid jet and RF energy |
| US9220558B2 (en) | 2010-10-27 | 2015-12-29 | Boston Scientific Scimed, Inc. | RF renal denervation catheter with multiple independent electrodes |
| US9028485B2 (en) | 2010-11-15 | 2015-05-12 | Boston Scientific Scimed, Inc. | Self-expanding cooling electrode for renal nerve ablation |
| US9668811B2 (en) | 2010-11-16 | 2017-06-06 | Boston Scientific Scimed, Inc. | Minimally invasive access for renal nerve ablation |
| US9089350B2 (en) | 2010-11-16 | 2015-07-28 | Boston Scientific Scimed, Inc. | Renal denervation catheter with RF electrode and integral contrast dye injection arrangement |
| US9326751B2 (en) | 2010-11-17 | 2016-05-03 | Boston Scientific Scimed, Inc. | Catheter guidance of external energy for renal denervation |
| US9060761B2 (en) | 2010-11-18 | 2015-06-23 | Boston Scientific Scime, Inc. | Catheter-focused magnetic field induced renal nerve ablation |
| US9192435B2 (en) | 2010-11-22 | 2015-11-24 | Boston Scientific Scimed, Inc. | Renal denervation catheter with cooled RF electrode |
| US9023034B2 (en) | 2010-11-22 | 2015-05-05 | Boston Scientific Scimed, Inc. | Renal ablation electrode with force-activatable conduction apparatus |
| CA2818024C (en) | 2010-12-06 | 2019-09-24 | Quark Pharmaceuticals, Inc. | Double stranded oligonucleotide compounds comprising positional modifications |
| US20120157993A1 (en) | 2010-12-15 | 2012-06-21 | Jenson Mark L | Bipolar Off-Wall Electrode Device for Renal Nerve Ablation |
| WO2012100095A1 (en) | 2011-01-19 | 2012-07-26 | Boston Scientific Scimed, Inc. | Guide-compatible large-electrode catheter for renal nerve ablation with reduced arterial injury |
| AU2012283908B2 (en) | 2011-07-20 | 2017-02-16 | Boston Scientific Scimed, Inc. | Percutaneous devices and methods to visualize, target and ablate nerves |
| WO2013016203A1 (en) | 2011-07-22 | 2013-01-31 | Boston Scientific Scimed, Inc. | Nerve modulation system with a nerve modulation element positionable in a helical guide |
| EP2765942B1 (en) | 2011-10-10 | 2016-02-24 | Boston Scientific Scimed, Inc. | Medical devices including ablation electrodes |
| EP2765940B1 (en) | 2011-10-11 | 2015-08-26 | Boston Scientific Scimed, Inc. | Off-wall electrode device for nerve modulation |
| US9420955B2 (en) | 2011-10-11 | 2016-08-23 | Boston Scientific Scimed, Inc. | Intravascular temperature monitoring system and method |
| US9364284B2 (en) | 2011-10-12 | 2016-06-14 | Boston Scientific Scimed, Inc. | Method of making an off-wall spacer cage |
| US9162046B2 (en) | 2011-10-18 | 2015-10-20 | Boston Scientific Scimed, Inc. | Deflectable medical devices |
| WO2013059202A1 (en) | 2011-10-18 | 2013-04-25 | Boston Scientific Scimed, Inc. | Integrated crossing balloon catheter |
| EP2773758B1 (en) | 2011-11-03 | 2017-06-07 | Quark Pharmaceuticals, Inc. | Compositions for use in neuroprotection |
| US20140323549A1 (en) * | 2011-11-08 | 2014-10-30 | Quark Pharmaceuticals, Inc. | Methods and compositions for treating diseases, disorders or injury of the nervous system |
| CN108095821B (zh) | 2011-11-08 | 2021-05-25 | 波士顿科学西美德公司 | 孔部肾神经消融 |
| US9119600B2 (en) | 2011-11-15 | 2015-09-01 | Boston Scientific Scimed, Inc. | Device and methods for renal nerve modulation monitoring |
| US9119632B2 (en) | 2011-11-21 | 2015-09-01 | Boston Scientific Scimed, Inc. | Deflectable renal nerve ablation catheter |
| US9265969B2 (en) | 2011-12-21 | 2016-02-23 | Cardiac Pacemakers, Inc. | Methods for modulating cell function |
| JP6158830B2 (ja) | 2011-12-23 | 2017-07-05 | べシックス・バスキュラー・インコーポレイテッド | 身体通路の組織又は身体通路に隣接する組織をリモデリングするためのシステム、方法及び装置 |
| US9433760B2 (en) | 2011-12-28 | 2016-09-06 | Boston Scientific Scimed, Inc. | Device and methods for nerve modulation using a novel ablation catheter with polymeric ablative elements |
| US9050106B2 (en) | 2011-12-29 | 2015-06-09 | Boston Scientific Scimed, Inc. | Off-wall electrode device and methods for nerve modulation |
| WO2013169927A1 (en) | 2012-05-08 | 2013-11-14 | Boston Scientific Scimed, Inc. | Renal nerve modulation devices |
| US9890215B2 (en) * | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
| WO2014032016A1 (en) | 2012-08-24 | 2014-02-27 | Boston Scientific Scimed, Inc. | Intravascular catheter with a balloon comprising separate microporous regions |
| WO2014043289A2 (en) | 2012-09-12 | 2014-03-20 | Quark Pharmaceuticals, Inc. | Double-stranded oligonucleotide molecules to ddit4 and methods of use thereof |
| WO2014043687A2 (en) | 2012-09-17 | 2014-03-20 | Boston Scientific Scimed, Inc. | Self-positioning electrode system and method for renal nerve modulation |
| WO2014047454A2 (en) | 2012-09-21 | 2014-03-27 | Boston Scientific Scimed, Inc. | Self-cooling ultrasound ablation catheter |
| US10398464B2 (en) | 2012-09-21 | 2019-09-03 | Boston Scientific Scimed, Inc. | System for nerve modulation and innocuous thermal gradient nerve block |
| WO2014059165A2 (en) | 2012-10-10 | 2014-04-17 | Boston Scientific Scimed, Inc. | Renal nerve modulation devices and methods |
| WO2014163987A1 (en) | 2013-03-11 | 2014-10-09 | Boston Scientific Scimed, Inc. | Medical devices for modulating nerves |
| WO2014143571A1 (en) | 2013-03-11 | 2014-09-18 | Boston Scientific Scimed, Inc. | Medical devices for modulating nerves |
| US9808311B2 (en) | 2013-03-13 | 2017-11-07 | Boston Scientific Scimed, Inc. | Deflectable medical devices |
| EP2967734B1 (en) | 2013-03-15 | 2019-05-15 | Boston Scientific Scimed, Inc. | Methods and apparatuses for remodeling tissue of or adjacent to a body passage |
| US10265122B2 (en) | 2013-03-15 | 2019-04-23 | Boston Scientific Scimed, Inc. | Nerve ablation devices and related methods of use |
| EP2967725B1 (en) | 2013-03-15 | 2019-12-11 | Boston Scientific Scimed, Inc. | Control unit for detecting electrical leakage between electrode pads and system comprising such a control unit |
| CN105143203A (zh) | 2013-04-17 | 2015-12-09 | 辉瑞大药厂 | 用于治疗心血管疾病的n-哌啶-3-基苯甲酰胺衍生物 |
| US10022182B2 (en) | 2013-06-21 | 2018-07-17 | Boston Scientific Scimed, Inc. | Medical devices for renal nerve ablation having rotatable shafts |
| US9943365B2 (en) | 2013-06-21 | 2018-04-17 | Boston Scientific Scimed, Inc. | Renal denervation balloon catheter with ride along electrode support |
| US9707036B2 (en) | 2013-06-25 | 2017-07-18 | Boston Scientific Scimed, Inc. | Devices and methods for nerve modulation using localized indifferent electrodes |
| WO2015002787A1 (en) | 2013-07-01 | 2015-01-08 | Boston Scientific Scimed, Inc. | Medical devices for renal nerve ablation |
| US10413357B2 (en) | 2013-07-11 | 2019-09-17 | Boston Scientific Scimed, Inc. | Medical device with stretchable electrode assemblies |
| WO2015006480A1 (en) | 2013-07-11 | 2015-01-15 | Boston Scientific Scimed, Inc. | Devices and methods for nerve modulation |
| CN105682594B (zh) | 2013-07-19 | 2018-06-22 | 波士顿科学国际有限公司 | 螺旋双极电极肾脏去神经支配气囊 |
| CN105555220B (zh) | 2013-07-22 | 2019-05-17 | 波士顿科学国际有限公司 | 用于肾神经消融的医疗器械 |
| JP6122217B2 (ja) | 2013-07-22 | 2017-04-26 | ボストン サイエンティフィック サイムド，インコーポレイテッドＢｏｓｔｏｎ Ｓｃｉｅｎｔｉｆｉｃ Ｓｃｉｍｅｄ，Ｉｎｃ． | 腎神経アブレーション用医療器具 |
| EP4049605A1 (en) | 2013-08-22 | 2022-08-31 | Boston Scientific Scimed Inc. | Flexible circuit having improved adhesion to a renal nerve modulation balloon |
| CN105555218B (zh) | 2013-09-04 | 2019-01-15 | 波士顿科学国际有限公司 | 具有冲洗和冷却能力的射频(rf)球囊导管 |
| CN105530885B (zh) | 2013-09-13 | 2020-09-22 | 波士顿科学国际有限公司 | 具有气相沉积覆盖层的消融球囊 |
| US9687166B2 (en) | 2013-10-14 | 2017-06-27 | Boston Scientific Scimed, Inc. | High resolution cardiac mapping electrode array catheter |
| US11246654B2 (en) | 2013-10-14 | 2022-02-15 | Boston Scientific Scimed, Inc. | Flexible renal nerve ablation devices and related methods of use and manufacture |
| EP3057520A1 (en) | 2013-10-15 | 2016-08-24 | Boston Scientific Scimed, Inc. | Medical device balloon |
| US9770606B2 (en) | 2013-10-15 | 2017-09-26 | Boston Scientific Scimed, Inc. | Ultrasound ablation catheter with cooling infusion and centering basket |
| JP6259099B2 (ja) | 2013-10-18 | 2018-01-10 | ボストン サイエンティフィック サイムド，インコーポレイテッドＢｏｓｔｏｎ Ｓｃｉｅｎｔｉｆｉｃ Ｓｃｉｍｅｄ，Ｉｎｃ． | 可撓性を備える導電性ワイヤを備えるバルーン・カテーテル、並びに関連する使用および製造方法 |
| WO2015061457A1 (en) | 2013-10-25 | 2015-04-30 | Boston Scientific Scimed, Inc. | Embedded thermocouple in denervation flex circuit |
| US11202671B2 (en) | 2014-01-06 | 2021-12-21 | Boston Scientific Scimed, Inc. | Tear resistant flex circuit assembly |
| JP6325121B2 (ja) | 2014-02-04 | 2018-05-16 | ボストン サイエンティフィック サイムド，インコーポレイテッドＢｏｓｔｏｎ Ｓｃｉｅｎｔｉｆｉｃ Ｓｃｉｍｅｄ，Ｉｎｃ． | 双極電極上の温度センサの代替配置 |
| US11000679B2 (en) | 2014-02-04 | 2021-05-11 | Boston Scientific Scimed, Inc. | Balloon protection and rewrapping devices and related methods of use |
| WO2015200905A2 (en) | 2014-06-28 | 2015-12-30 | Oligasis, Llc | Dual pdgf/vegf antagonists |
| IL290457B2 (en) | 2015-12-30 | 2025-02-01 | Kodiak Sciences Inc | Antibodies and their conjugates |
| US20180193270A1 (en) | 2016-11-29 | 2018-07-12 | PureTech Health LLC | Exosomes for delivery of therapeutic agents |
| KR101933217B1 (ko) * | 2017-12-28 | 2018-12-27 | (주) 에빅스젠 | 피부 염증 억제용 펩티드 및 이를 포함하는 피부 염증 예방 또는 치료용 조성물 |
| CA3092588A1 (en) | 2018-03-02 | 2019-09-06 | Kodiak Sciences Inc. | Il-6 antibodies and fusion constructs and conjugates thereof |
| CA3157509A1 (en) | 2019-10-10 | 2021-04-15 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
Family Cites Families (97)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| US4475196A (en) | 1981-03-06 | 1984-10-02 | Zor Clair G | Instrument for locating faults in aircraft passenger reading light and attendant call control system |
| US4447233A (en) | 1981-04-10 | 1984-05-08 | Parker-Hannifin Corporation | Medication infusion pump |
| US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| US4447224A (en) | 1982-09-20 | 1984-05-08 | Infusaid Corporation | Variable flow implantable infusion apparatus |
| US4487603A (en) | 1982-11-26 | 1984-12-11 | Cordis Corporation | Implantable microinfusion pump system |
| US4486194A (en) | 1983-06-08 | 1984-12-04 | James Ferrara | Therapeutic device for administering medicaments through the skin |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4959217A (en) | 1986-05-22 | 1990-09-25 | Syntex (U.S.A.) Inc. | Delayed/sustained release of macromolecules |
| US4925678A (en) | 1987-04-01 | 1990-05-15 | Ranney David F | Endothelial envelopment drug carriers |
| US5080646A (en) | 1988-10-03 | 1992-01-14 | Alza Corporation | Membrane for electrotransport transdermal drug delivery |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5270030A (en) | 1988-12-29 | 1993-12-14 | Bio-Technology General Corp. | Fibrin binding domain polypeptide and method of producing |
| US5225347A (en) | 1989-09-25 | 1993-07-06 | Innovir Laboratories, Inc. | Therapeutic ribozyme compositions and expression vectors |
| US5167616A (en) | 1989-12-14 | 1992-12-01 | Alza Corporation | Iontophoretic delivery method |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| EP1690935A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US5378825A (en) | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
| US5225182A (en) | 1991-10-31 | 1993-07-06 | Sharma Yash P | Vectored drug delivery system using a cephaloplastin linking agent and a methed of using the system |
| US6372249B1 (en) | 1991-12-16 | 2002-04-16 | Baylor College Of Medicine | Senscent cell-derived inhibitors of DNA synthesis |
| ATE515510T1 (de) | 1991-12-24 | 2011-07-15 | Isis Pharmaceuticals Inc | Durch dna-abschnitte unterbrochene modifizierte oligonukleotide |
| CA2135646A1 (en) | 1992-05-11 | 1993-11-25 | Kenneth G. Draper | Method and reagent for inhibiting viral replication |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| WO1994024704A1 (en) * | 1993-04-12 | 1994-10-27 | Bolger Justin C | Area bonding conductive adhesive preforms |
| GB9402161D0 (en) * | 1994-02-04 | 1994-03-30 | Wellcome Found | Chloropyrimidine intermediates |
| CA2219361C (en) | 1995-04-27 | 2012-02-28 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| WO1996034096A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| EP1972194A1 (en) | 1996-12-03 | 2008-09-24 | Amgen Fremont Inc. | Transgenic mammals having human ig loci including plural vh and vk regions and antibodies produced therefrom |
| JP3876002B2 (ja) | 1997-04-14 | 2007-01-31 | ミクロメート・アクチエンゲゼルシャフト | 抗ヒト抗原受容体を産生するための斬新な方法およびそれらの使用 |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| US20030104973A1 (en) | 1997-08-21 | 2003-06-05 | Quark Biotech, Inc. | Hypoxia-regulated genes |
| US7973156B2 (en) | 1997-08-21 | 2011-07-05 | Quark Pharmaceuticals Inc. | Hypoxia-regulated genes |
| ATE293633T1 (de) | 1997-08-21 | 2005-05-15 | Quark Biotech Inc | Hypoxie-regulierte gene |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| DE19816395A1 (de) | 1998-04-03 | 1999-10-07 | Metagen Gesellschaft Fuer Genomforschung Mbh | Menschliche Nukleinsäuresequenzen aus Ovar-Normalgewebe |
| US6399178B1 (en) * | 1998-07-20 | 2002-06-04 | Amerasia International Technology, Inc. | Rigid adhesive underfill preform, as for a flip-chip device |
| US6228585B1 (en) | 1998-09-04 | 2001-05-08 | Washington University | Gene markers for chronic mucosal injury |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| WO2000061620A1 (en) | 1999-04-09 | 2000-10-19 | Human Genome Sciences, Inc. | 49 human secreted proteins |
| CA2382748A1 (en) | 1999-06-11 | 2000-12-21 | Human Genome Sciences, Inc. | 50 human secreted proteins |
| WO2001005998A1 (en) | 1999-07-16 | 2001-01-25 | Human Genome Sciences, Inc. | Follistatin-3 |
| AU7680300A (en) | 1999-08-18 | 2001-03-13 | Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forschung E.V. | Human dna sequences |
| GB9927444D0 (en) | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
| DE10160151A1 (de) | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
| WO2003070918A2 (en) | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | Rna interference by modified short interfering nucleic acid |
| AU4592601A (en) | 2000-03-21 | 2001-10-03 | Millennium Predictive Medicine | Novel genes, compositions, kits, and method for identification, assessment, prevention, and therapy of ovarian cancer |
| KR20080023768A (ko) | 2000-03-30 | 2008-03-14 | 화이트헤드 인스티튜트 포 바이오메디칼 리서치 | Ｒｎａ 간섭의 ｒｎａ 서열 특이적인 매개체 |
| WO2001077289A2 (en) | 2000-04-06 | 2001-10-18 | Genetics Institute, Llc. | Polynucleotides encoding novel secreted proteins |
| US6727066B2 (en) | 2000-07-28 | 2004-04-27 | Incyte Corporation | Genes expressed in treated human C3A liver cell cultures |
| US6673545B2 (en) | 2000-07-28 | 2004-01-06 | Incyte Corporation | Prostate cancer markers |
| EP1325120A4 (en) | 2000-10-12 | 2005-05-25 | Nuvelo Inc | NUCLEIC ACIDS AND POLYPEPTIDES |
| US6673549B1 (en) | 2000-10-12 | 2004-01-06 | Incyte Corporation | Genes expressed in C3A liver cell cultures treated with steroids |
| US20020137077A1 (en) | 2000-10-25 | 2002-09-26 | Hopkins Christopher M. | Genes regulated in activated T cells |
| CN100523215C (zh) | 2000-12-01 | 2009-08-05 | 马普科技促进协会 | 介导rna干涉的小rna分子 |
| AU2002220920A1 (en) | 2000-12-08 | 2002-06-18 | Oxford Biomedica (Uk) Limited | Method for identification of genes involved in specific diseases |
| US20030165864A1 (en) | 2001-01-16 | 2003-09-04 | Lasek Amy W. | Genes regulated by DNA methylation in tumor cells |
| SG106054A1 (en) * | 2001-04-17 | 2004-09-30 | Micron Technology Inc | Method and apparatus for package reduction in stacked chip and board assemblies |
| US20040019001A1 (en) | 2002-02-20 | 2004-01-29 | Mcswiggen James A. | RNA interference mediated inhibition of protein typrosine phosphatase-1B (PTP-1B) gene expression using short interfering RNA |
| WO2003070910A2 (en) * | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US7125663B2 (en) | 2001-06-13 | 2006-10-24 | Millenium Pharmaceuticals, Inc. | Genes, compositions, kits and methods for identification, assessment, prevention, and therapy of cervical cancer |
| WO2003010128A2 (en) | 2001-07-25 | 2003-02-06 | Ciba Specialty Chemicals Holding Inc. | Perfluoroalkyl-substituted amines, acids, amino acids and thioether acids |
| WO2003010205A1 (en) | 2001-07-26 | 2003-02-06 | Duke University Medical Center | Genes induced by hypoxia |
| US20040063654A1 (en) | 2001-11-02 | 2004-04-01 | Davis Mark E. | Methods and compositions for therapeutic use of RNA interference |
| EP1432724A4 (en) | 2002-02-20 | 2006-02-01 | Sirna Therapeutics Inc | RNA inhibition mediated inhibition of MAP KINASE GENES |
| JP2003259877A (ja) | 2002-03-11 | 2003-09-16 | Sumitomo Pharmaceut Co Ltd | 肝線維症疾患マーカーおよびその利用 |
| AU2003240495A1 (en) | 2002-06-04 | 2003-12-19 | Incyte Corporation | Diagnostics markers for lung cancer |
| EP1857547B2 (en) | 2002-08-05 | 2020-12-02 | Silence Therapeutics GmbH | Further novel forms of interfering RNA molecules |
| JP2004121218A (ja) | 2002-08-06 | 2004-04-22 | Jenokkusu Soyaku Kenkyusho:Kk | 気管支喘息または慢性閉塞性肺疾患の検査方法 |
| EP2311980A1 (en) | 2002-08-20 | 2011-04-20 | Millennium Pharmaceuticals, Inc. | Compositions, kits, and methods for identification, assessment, prevention, and therapy of cervical cancer |
| CA2500687A1 (en) | 2002-10-02 | 2004-04-15 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
| AU2003303144A1 (en) | 2002-10-18 | 2004-07-29 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
| ES2319891T3 (es) | 2002-10-18 | 2009-05-14 | Silence Therapeutics Ag | Factor implicado en la metastasis y usos del mismo. |
| AU2003298607B9 (en) | 2002-10-29 | 2011-08-04 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
| WO2004042024A2 (en) * | 2002-11-01 | 2004-05-21 | The Trustees Of The University Of Pennsylvania | COMPOSITIONS AND METHODS FOR siRNA INHIBITION OF HIF-1 ALPHA |
| US9150605B2 (en) | 2002-11-05 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2′-modified nucleosides for use in gene modulation |
| EP2305813A3 (en) | 2002-11-14 | 2012-03-28 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| WO2004045545A2 (en) | 2002-11-18 | 2004-06-03 | Fox Chase Cancer Center | Compositions and methods for the treatment of cancer, screening of putative anti-cancer compounds, and assessing cancer progression |
| WO2004076633A2 (en) | 2003-02-21 | 2004-09-10 | University Of Utah Research Foundation | Hypoxia inducible vegf plasmid for ischemic disease |
| EP1608255A4 (en) | 2003-04-01 | 2008-06-25 | Univ Johns Hopkins Med | ENDOTHELIAL CELL EXPRESSION PATTERN IN CHEST |
| WO2005016000A1 (en) | 2003-08-05 | 2005-02-24 | Avalon Pharmaceuticals | Derivatives of cyclic quinone and uses thereof |
| NZ553162A (en) | 2004-08-16 | 2010-03-26 | Quark Biotech Inc | Double stranded siRNA compounds that inhibit RRTP801 |
| JP4991547B2 (ja) | 2004-09-28 | 2012-08-01 | クアーク・ファーマスーティカルス、インコーポレイテッド | 脱毛症、急性腎不全および他の疾患の治療のためのオリゴリボヌクレオチドおよびその使用の方法 |
| US7825099B2 (en) | 2006-01-20 | 2010-11-02 | Quark Pharmaceuticals, Inc. | Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes |
| UY30097A1 (es) * | 2006-01-20 | 2007-08-31 | Atugen Ag | Usos terapeuticos de inhibidores de rtp801 |
| US7910566B2 (en) | 2006-03-09 | 2011-03-22 | Quark Pharmaceuticals Inc. | Prevention and treatment of acute renal failure and other kidney diseases by inhibition of p53 by siRNA |
| WO2008054534A2 (en) | 2006-05-11 | 2008-05-08 | Quark Pharmaceuticals, Inc. | Screening systems utilizing rtp801 |
| WO2007141796A2 (en) | 2006-06-09 | 2007-12-13 | Quark Pharmaceuticals, Inc. | Therapeutic uses of inhibitors of rtp801l |
| DE102006031683A1 (de) * | 2006-07-08 | 2008-01-17 | Zf Friedrichshafen Ag | Verfahren zum Betreiben eines Antriebsstrangs |
| WO2008106102A2 (en) | 2007-02-26 | 2008-09-04 | Quark Pharmaceuticals, Inc. | Inhibitors of rtp801 and their use in disease treatment |
| RU2010138558A (ru) | 2008-03-20 | 2012-03-27 | Кварк Фармасьютикалс. Инк, (Us) | Новые соединения миphk для ингибирования rtp801 |
| KR20100057710A (ko) | 2008-11-10 | 2010-06-01 | 삼성전자주식회사 | 발광 다이오드 및 이를 포함하는 백라이트 유니트 |
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