CA3011819A1 - Compositions and methods for inhibiting factor d - Google Patents
Compositions and methods for inhibiting factor d Download PDFInfo
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- CA3011819A1 CA3011819A1 CA3011819A CA3011819A CA3011819A1 CA 3011819 A1 CA3011819 A1 CA 3011819A1 CA 3011819 A CA3011819 A CA 3011819A CA 3011819 A CA3011819 A CA 3011819A CA 3011819 A1 CA3011819 A1 CA 3011819A1
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Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AP2016009438A0 (en) | 2014-02-25 | 2016-09-30 | Achillion Pharmaceuticals Inc | Aryl, heteroaryl, and heterocyclic compounds for treatment of complement mediated disorders |
| AR106018A1 (es) | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
| EP3340983B1 (en) | 2015-08-26 | 2023-10-04 | Achillion Pharmaceuticals, Inc. | Aryl, heteroaryl, and heterocyclic compounds for treatment of immune and inflammatory disorders |
| WO2017035405A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Amino compounds for treatment of immune and inflammatory disorders |
| WO2017035401A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Amide compounds for treatment of immune and inflammatory disorders |
| CN108934169A (zh) | 2016-01-20 | 2018-12-04 | 维特里萨医疗公司 | 用于抑制因子d的组合物和方法 |
| WO2018136827A1 (en) | 2017-01-20 | 2018-07-26 | Vitrisa Therapeutics, Inc. | Stem-loop compositions and methods for inhibiting factor d |
| WO2018136831A1 (en) * | 2017-01-20 | 2018-07-26 | Vitrisa Therapeutics, Inc. | Pseudoknot compositions and methods for inhibiting factor d |
| CN110603252A (zh) | 2017-03-01 | 2019-12-20 | 艾其林医药公司 | 用于治疗医学障碍的芳基、杂芳基和杂环药物化合物 |
| WO2018160891A1 (en) | 2017-03-01 | 2018-09-07 | Achillion Pharmaceutical, Inc. | Pharmaceutical compounds for treatment of medical disorders |
| WO2019022986A1 (en) * | 2017-07-24 | 2019-01-31 | Vitrisa Therapeutics, Inc. | NUCLEIC ACID COMPOSITIONS AND METHODS OF INHIBITING D-FACTOR |
| EP3661493A4 (en) | 2017-08-02 | 2021-04-14 | Achillion Pharmaceuticals, Inc. | TREATMENT DIET FOR THE TREATMENT OF PAROXYSTIC NOCTURAL HEMOGLOBINURIA |
| WO2019210194A1 (en) * | 2018-04-26 | 2019-10-31 | Vitrisa Therapeutics, Inc. | Pegylated compositions for ocular use, and methods thereof |
| MX2021002640A (es) | 2018-09-06 | 2021-07-16 | Achillion Pharmaceuticals Inc | Formas morficas de los inhibidores del factor d del complemento. |
| US11814391B2 (en) | 2018-09-06 | 2023-11-14 | Achillion Pharmaceuticals, Inc. | Macrocyclic compounds for the treatment of medical disorders |
| EP3856164B1 (en) | 2018-09-25 | 2024-08-07 | Achillion Pharmaceuticals, Inc. | Morphic forms of complement factor d inhibitors |
| US12239645B2 (en) | 2018-12-17 | 2025-03-04 | Achillion Pharmaceuticals, Inc. | Targeted dosing for the treatment of complement mediated disorders |
| WO2020146731A1 (en) * | 2019-01-11 | 2020-07-16 | Drive Therapeutics Llc | Compositions and methods for inhibiting vascular endothelial growth factor |
| JP7635138B2 (ja) | 2019-03-22 | 2025-02-25 | アキリオン ファーマシューティカルズ， インコーポレーテッド | 補体媒介性障害の治療のための医薬化合物 |
| US20220395557A1 (en) * | 2019-10-23 | 2022-12-15 | Gemini Therapeutics Sub, Inc. | Methods for treating patients having cfh mutations with recombinant cfh proteins |
| CN114686481B (zh) * | 2020-12-31 | 2023-08-15 | 北京键凯科技股份有限公司 | 一种抑制cfd表达的干扰rna及其制备方法和应用 |
| US20250129371A1 (en) * | 2023-10-11 | 2025-04-24 | Regeneron Pharmaceuticals, Inc. | Treatment Of Macular Degeneration With Complement Factor D (CFD) Inhibitors |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR970002255B1 (ko) | 1990-06-11 | 1997-02-26 | 넥스스타 파아마슈티컬드, 인크. | 핵산 리간드 |
| US5270163A (en) | 1990-06-11 | 1993-12-14 | University Research Corporation | Methods for identifying nucleic acid ligands |
| US6140490A (en) | 1996-02-01 | 2000-10-31 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands of complement system proteins |
| US6653340B1 (en) | 1997-06-03 | 2003-11-25 | Biocryst Pharmaceuticals, Inc. | Compounds useful in the complement, coagulat and kallikrein pathways and method for their preparation |
| US6333034B1 (en) | 1997-08-26 | 2001-12-25 | Gliatech, Inc. | Process for inhibiting complement activation via the alternative pathway |
| AU1252099A (en) | 1997-11-26 | 1999-06-15 | Medical Research Council | Improved selex procedure and an anti-cd4 aptamer |
| US6956107B2 (en) | 1998-02-20 | 2005-10-18 | Tanox, Inc. | Inhibitors of complement activation |
| US7112327B2 (en) | 1998-02-20 | 2006-09-26 | Tanox, Inc. | Inhibition of complement activation |
| GB9930659D0 (en) | 1999-12-24 | 2000-02-16 | Bio Discovery Ltd | Inhibitors of complement activation |
| ATE435873T1 (de) | 2000-03-23 | 2009-07-15 | Genentech Inc | Anti-c2/c2a inhibitoren zur komplement aktivierung |
| JP2006518750A (ja) | 2003-02-21 | 2006-08-17 | リクスホスピタレット−ラジウムホスピタレット・ホーエフ | 胎便吸引症候群の治療のための方法および組成物 |
| DK1713503T3 (da) | 2004-02-10 | 2013-11-04 | Univ Colorado Regents | Hæmning af faktor b, den alternative komplemenpathway og dertil relaterede fremgangsmåde |
| US7803931B2 (en) | 2004-02-12 | 2010-09-28 | Archemix Corp. | Aptamer therapeutics useful in the treatment of complement-related disorders |
| US20090117171A1 (en) | 2005-03-11 | 2009-05-07 | Cedric Francois | Compositions and methods for treatment of macular degeneration and related conditions |
| ES2548700T3 (es) | 2005-05-26 | 2015-10-20 | The Regents Of The University Of Colorado, A Body Corporate | Inhibición de la vía alternativa del complemento para el tratamiento de lesión cerebral traumática, lesión de médula espinal y afecciones relacionadas |
| US8168584B2 (en) * | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
| WO2007047995A2 (en) | 2005-10-21 | 2007-04-26 | Catalyst Biosciences, Inc. | Modified proteases that inhibit complement activation |
| ES2551202T5 (es) | 2005-11-04 | 2018-11-30 | Genentech, Inc. | Uso de inhibidores de la vía del complemento para tratar enfermedades oculares |
| US20070149616A1 (en) | 2005-12-22 | 2007-06-28 | Alcon Manufacturing, Ltd. | C3-Convertase Inhibitors for the Prevention and Treatment of Age-Related Macular Degeneration in Patients With At Risk Variants Of Complement Factor H |
| AU2006337093B2 (en) | 2005-12-22 | 2013-03-14 | Opko Pharmaceuticals, Llc. | Compositions and methods for regulating complement system |
| US20070196367A1 (en) | 2006-02-22 | 2007-08-23 | Valentin Dinu | Methods of preventing and treating Alzheimer's disease, age related macular degeneration and other diseases involving extra-cellular debris through the inhibition of the complement system |
| HUE026496T2 (en) | 2006-03-08 | 2016-06-28 | Archemix Llc | Complement-binding aptamers and anti-C5 agents for treating eye diseases |
| EP3028716B1 (en) | 2006-10-10 | 2020-09-16 | Regenesance B.V. | Complement inhibition for improved nerve regeneration |
| US8790924B2 (en) | 2006-10-19 | 2014-07-29 | Duke University | Reversible platelet inhibition |
| CN106084054A (zh) | 2006-11-02 | 2016-11-09 | 健泰科生物技术公司 | 人源化的抗‑d因子抗体 |
| EP2148691B1 (en) | 2007-02-05 | 2015-05-20 | Apellis Pharmaceuticals, Inc. | Compstatin analogues for use in the treatment of inflammatory conditions of the respiratory system |
| WO2008137236A2 (en) * | 2007-04-30 | 2008-11-13 | Alcon Research, Ltd. | Treatment of age-related macular degeneration using inhibitors of complement factor d |
| AR066660A1 (es) * | 2007-05-23 | 2009-09-02 | Genentech Inc | Prevencion y tratamiento de condiciones del ojo asociadas con su complemento |
| US20090092980A1 (en) | 2007-07-20 | 2009-04-09 | Christoph Arenz | miRNA PROCESSING INHIBITOR EFFICACY ASSAYS AND SUBSTANCES |
| AU2008293487A1 (en) | 2007-08-27 | 2009-03-05 | Novelmed Therapeutics, Inc. | Method of inhibiting complement activation with factor Bb specific antibodies |
| GB0718737D0 (en) | 2007-09-25 | 2007-11-07 | Glaxo Group Ltd | Antibodies |
| MX2010006422A (es) | 2007-12-11 | 2010-06-25 | Glaxo Group Ltd | Proteinas de union a antigenos. |
| CA2718588A1 (en) | 2008-02-19 | 2009-08-27 | The Trustees Of The University Of Pennsylvania | Complement inhibitors as therapeutic agents for treatment of cancer |
| WO2009108931A2 (en) | 2008-02-28 | 2009-09-03 | Case Western Reserve University | Method of treating cancer |
| ES2538114T3 (es) | 2008-03-03 | 2015-06-17 | Novelmed Therapeutics, Inc. | Anticuerpos anti-properdina |
| US8664362B2 (en) | 2008-03-03 | 2014-03-04 | NovelMed Therapeutics | Humanized and chimeric anti-properdin antibodies |
| US20110190221A1 (en) | 2008-03-28 | 2011-08-04 | Apellis Ag | Modulation and repletion/enhancement of the complement system for treatment of trauma |
| CR20170001A (es) | 2008-04-28 | 2017-08-10 | Genentech Inc | Anticuerpos anti factor d humanizados |
| EP2159286A1 (en) | 2008-09-01 | 2010-03-03 | Consiglio Nazionale Delle Ricerche | Method for obtaining oligonucleotide aptamers and uses thereof |
| US20110160636A1 (en) | 2008-09-10 | 2011-06-30 | Rekha Bansal | Device and method for inhibiting complement activation |
| GB0904427D0 (en) * | 2009-03-13 | 2009-04-29 | Lachmann Peter | Treatment of diseases related to hyperactivity of the complement system |
| WO2010131748A1 (ja) | 2009-05-15 | 2010-11-18 | 地方独立行政法人神奈川県立病院機構 | ペプチドを認識するアプタマー |
| AU2010266127B2 (en) | 2009-07-02 | 2015-11-05 | Musc Foundation For Research Development | Methods of stimulating liver regeneration |
| JP5582580B2 (ja) | 2009-07-16 | 2014-09-03 | Ｎｅｃソリューションイノベータ株式会社 | Ｈｍｇｂ１結合核酸分子およびその用途 |
| WO2011017229A2 (en) | 2009-08-06 | 2011-02-10 | Tufts - New England Medical Center | Plasma complement components as expression markers for age-related macular degeneration and related phenotypes |
| US20110165648A1 (en) | 2009-11-04 | 2011-07-07 | Menno Van Lookeren Campagne | Co-crystal structure of factor D and anti-factor D antibody |
| PL2635704T3 (pl) | 2010-11-01 | 2017-09-29 | F.Hoffmann-La Roche Ag | Przewidywanie progresji do zaawansowanego zwyrodnienia plamki żółtej związanego z wiekiem z zastosowaniem wskaźnika poligenicznego |
| WO2012093101A1 (en) | 2011-01-04 | 2012-07-12 | Novartis Ag | Indole compounds or analogues thereof useful for the treatment of age-related macular degeneration (amd) |
| CN103796667A (zh) | 2011-06-22 | 2014-05-14 | 艾普莱斯制药公司 | 用补体抑制剂治疗慢性障碍的方法 |
| US10966945B2 (en) | 2011-08-01 | 2021-04-06 | Aurin Biotech Inc. | Selective inhibition of the membrane attack complex of complement by low molecular weight components of the aurin tricarboxylic synthetic complex |
| RU2633510C2 (ru) | 2011-09-28 | 2017-10-12 | Рибомик Инк. | Аптамер против ngf и его применение |
| MX355567B (es) | 2011-12-30 | 2018-04-23 | Quest Diagnostics Invest Inc | Aptameros y metodos de diagnostico para detectar el receptor de egf. |
| AU2014235794A1 (en) | 2013-03-14 | 2015-10-22 | Caribou Biosciences, Inc. | Compositions and methods of nucleic acid-targeting nucleic acids |
| CR20160132A (es) | 2013-08-12 | 2016-08-25 | Genentech Inc | Composiciones y método para tratar condiciones asociadas con el complemento |
| WO2015054569A1 (en) | 2013-10-10 | 2015-04-16 | Viropharma Holdings Limited | Methods of inhibiting the alternative pathway of complement immune system activation and compositions used therein |
| AP2016009438A0 (en) | 2014-02-25 | 2016-09-30 | Achillion Pharmaceuticals Inc | Aryl, heteroaryl, and heterocyclic compounds for treatment of complement mediated disorders |
| SG11201608868PA (en) * | 2014-05-01 | 2016-11-29 | Genentech Inc | Anti-factor d antibody variants and uses thereof |
| TWI623617B (zh) | 2014-08-29 | 2018-05-11 | 國立清華大學 | 對卵巢癌具有專一性之適合體及其應用 |
| JP2018535679A (ja) | 2015-11-19 | 2018-12-06 | ベース ペア バイオテクノロジーズ，インク． | 標的分子の高感度検出のための方法及び材料 |
| EP3405575A4 (en) | 2016-01-20 | 2019-06-26 | Vitrisa Therapeutics, Inc. | PROCESS FOR IMPROVED APTAMER SELECTION |
| CN108934169A (zh) | 2016-01-20 | 2018-12-04 | 维特里萨医疗公司 | 用于抑制因子d的组合物和方法 |
| CA3012718A1 (en) | 2016-02-08 | 2017-08-17 | Vitrisa Therapeutics, Inc. | Compositions with improved intravitreal half-life and uses thereof |
| WO2018136831A1 (en) | 2017-01-20 | 2018-07-26 | Vitrisa Therapeutics, Inc. | Pseudoknot compositions and methods for inhibiting factor d |
| WO2018136827A1 (en) | 2017-01-20 | 2018-07-26 | Vitrisa Therapeutics, Inc. | Stem-loop compositions and methods for inhibiting factor d |
| WO2019022986A1 (en) | 2017-07-24 | 2019-01-31 | Vitrisa Therapeutics, Inc. | NUCLEIC ACID COMPOSITIONS AND METHODS OF INHIBITING D-FACTOR |
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