GB2553252B - Aptamers that block the catalytic cleft of complement Factor D - Google Patents
Aptamers that block the catalytic cleft of complement Factor D Download PDFInfo
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- GB2553252B GB2553252B GB1718801.2A GB201718801A GB2553252B GB 2553252 B GB2553252 B GB 2553252B GB 201718801 A GB201718801 A GB 201718801A GB 2553252 B GB2553252 B GB 2553252B
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| WO2017035405A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Amino compounds for treatment of immune and inflammatory disorders |
| WO2017035409A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Aryl, heteroaryl, and heterocyclic 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 |
| AR106018A1 (es) | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
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| 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 |
| 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. | THERAPY PLANS FOR TREATMENT OF PAROXYSMALER NIGHTLY HEMOGLOBINURIA |
| WO2019210194A1 (en) * | 2018-04-26 | 2019-10-31 | Vitrisa Therapeutics, Inc. | Pegylated compositions for ocular use, and methods thereof |
| WO2020051538A1 (en) | 2018-09-06 | 2020-03-12 | Achillion Pharmaceuticals, Inc. | Morphic forms of complement factor d inhibitors |
| JP7443375B2 (ja) | 2018-09-06 | 2024-03-05 | 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 | 医学的障害の治療のための大環状化合物 |
| KR20210093855A (ko) | 2018-09-25 | 2021-07-28 | 아칠리온 파르마세우티칼스 인코포레이티드 | 보체 인자 d 억제제의 형태체 형태 |
| WO2020131974A1 (en) | 2018-12-17 | 2020-06-25 | 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 |
| BR112021018456A2 (pt) | 2019-03-22 | 2021-11-23 | Achillion Pharmaceuticals Inc | Compostos farmacêuticos para o tratamento de distúrbios mediados por complemento |
| WO2021081395A1 (en) * | 2019-10-23 | 2021-04-29 | Gemini Therapeutics 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 |
| WO2025080823A1 (en) * | 2023-10-11 | 2025-04-17 | Regeneron Pharmaceuticals, Inc. | Treatment of macular degeneration with complement factor d (cfd) inhibitors |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015168468A1 (en) * | 2014-05-01 | 2015-11-05 | Genentech, Inc. | Anti-factor d antibody variants and uses thereof |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| ES2259800T3 (es) | 1990-06-11 | 2006-10-16 | Gilead Sciences, Inc. | Procedimientos de uso de ligandos de acido nucleico. |
| AU7808198A (en) | 1997-06-03 | 1998-12-21 | Biocryst Pharmaceuticals, Inc. | Novel compounds useful in the complement, coagulat and kallikrein pathways and method for their preparation |
| NZ503033A (en) | 1997-08-26 | 2003-01-31 | Gliatech Inc | Inhibition of complement activation using anti-properdin agents |
| 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 |
| US6998468B2 (en) | 2000-03-23 | 2006-02-14 | Tanox, Inc. | Anti-C2/C2a inhibitors of complement activation |
| WO2004075838A2 (en) | 2003-02-21 | 2004-09-10 | Rikshospitalet-Radiumhospitalet Hf | Method and compositions for the treatment of meconium aspiration syndrome |
| BRPI0506629A (pt) | 2004-02-10 | 2007-05-02 | Univ Colorado | inibição do fator b, a via alternativa do sistema complemento e métodos relacionados |
| US7803931B2 (en) | 2004-02-12 | 2010-09-28 | Archemix Corp. | Aptamer therapeutics useful in the treatment of complement-related disorders |
| EP1861114B1 (en) | 2005-03-11 | 2011-02-02 | Potentia Pharmaceuticals, Inc. | Compositions comprising modulators of g-protein-coupled receptor for treatment of macular degeneration |
| WO2006128006A1 (en) | 2005-05-26 | 2006-11-30 | The Regents Of The University Of Colorado | Inhibition of the alternative complement pathway for treatment of traumatic brain injury, spinal cord injury and related conditions |
| US8168584B2 (en) * | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
| JP5219819B2 (ja) | 2005-10-21 | 2013-06-26 | カタリスト・バイオサイエンシーズ・インコーポレイテッド | 補体活性化を阻害する修飾プロテアーゼ |
| SG10201804008UA (en) | 2005-11-04 | 2018-06-28 | Genentech Inc | Use of complement pathway inhibitors to treat ocular diseases |
| AU2006337093B2 (en) | 2005-12-22 | 2013-03-14 | Opko Pharmaceuticals, Llc. | Compositions and methods for regulating complement system |
| KR20080087814A (ko) | 2005-12-22 | 2008-10-01 | 알콘 리서치, 리미티드 | 보체 인자 ｈ의 위험 변이체가 있는 환자에서 연령 관련황반변성의 예방 및 치료를 위한 ｃ3-전환효소 저해제 |
| 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 |
| NZ571791A (en) | 2006-03-08 | 2012-03-30 | Archemix Llc | Complement binding aptamers and anti-C5 agents useful in the treatment of ocular disorders |
| EP2073898A1 (en) | 2006-10-10 | 2009-07-01 | Academisch Ziekenhuis Bij De Universiteit Van Amsterdam | Complement inhibition for improved nerve regeneration |
| US8790924B2 (en) | 2006-10-19 | 2014-07-29 | Duke University | Reversible platelet inhibition |
| TW201716437A (zh) | 2006-11-02 | 2017-05-16 | 建南德克公司 | 人類化之抗-因子ｄ抗體及其用途 |
| HUE026001T2 (en) | 2007-02-05 | 2016-04-28 | Apellis Pharmaceuticals Inc | Compstatin analogues for use in the treatment of the inflammatory condition of the respiratory system |
| CA2680833A1 (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 |
| CN101970002B (zh) | 2007-08-27 | 2016-05-18 | 诺福麦德治疗学股份有限公司 | 用因子Bb特异性抗体抑制补体活化的方法 |
| GB0718737D0 (en) | 2007-09-25 | 2007-11-07 | Glaxo Group Ltd | Antibodies |
| US8921523B2 (en) | 2007-12-11 | 2014-12-30 | Glaxo Group Limited | Humanized anti-beta-amyloid antibodies |
| AU2009215846B2 (en) | 2008-02-19 | 2014-08-14 | The Trustees Of The University Of Pennsylvania | Complement inhibitors as therapeutic agents for treatment of cancer |
| US8940299B2 (en) | 2008-02-28 | 2015-01-27 | Case Western Reserve University | Method of treating cancer |
| US8664362B2 (en) | 2008-03-03 | 2014-03-04 | NovelMed Therapeutics | Humanized and chimeric anti-properdin antibodies |
| DK2262831T3 (en) | 2008-03-03 | 2015-04-27 | Novelmed Therapeutics Inc | 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 |
| AU2010248380B2 (en) | 2009-05-15 | 2013-12-19 | Nec Solution Innovators, Ltd. | Aptamer that recognizes peptide |
| WO2011003098A1 (en) | 2009-07-02 | 2011-01-06 | Musc Foundation For Research Development | Methods of stimulating liver regeneration |
| EP2455469A4 (en) | 2009-07-16 | 2013-03-13 | Nec Software Ltd | FOR BINDING TO HMGB1 ABLE NUCLEIC ACID MOLECULE AND USE THEREOF |
| US20120190578A1 (en) | 2009-08-06 | 2012-07-26 | Washington University | 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 |
| BR112013010769A2 (pt) | 2010-11-01 | 2019-09-24 | Genentech Inc | predição de progressão para degeneração macular relacionada à idade avançada usando um escore poligênico |
| PT2661433T (pt) | 2011-01-04 | 2017-10-24 | Novartis Ag | Compostos de indole ou seus análogos úteis para o tratamento da degeneração macular relacionada com a idade (amd) |
| EP3524258B1 (en) | 2011-06-22 | 2025-10-01 | Apellis Pharmaceuticals, Inc. | Methods of treating chronic disorders with complement inhibitors |
| 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 |
| US9316647B2 (en) | 2011-12-30 | 2016-04-19 | Somalogic, Inc. | Aptamers and diagnostic methods for detecting the EGF receptor |
| RU2662932C2 (ru) | 2013-03-14 | 2018-07-31 | Карибо Биосайенсиз, Инк. | Композиции и способы с участием нуклеиновых кислот, нацеленных на нуклеиновые кислоты |
| SG11201601044XA (en) | 2013-08-12 | 2016-03-30 | Genentech Inc | Compositions and method for treating complement-associated conditions |
| US20150104445A1 (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 |
| US9732103B2 (en) | 2014-02-25 | 2017-08-15 | Achillion Pharmaceuticals, Inc. | Carbamate, ester, and ketone compounds for treatment of complement mediated disorders |
| 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 |
| US20180356408A1 (en) | 2015-11-19 | 2018-12-13 | Base Pair Biotechnologies, Inc. | Methods and materials for sensitive detection of target molecules |
| WO2017127761A1 (en) | 2016-01-20 | 2017-07-27 | Vitrisa Therapeutics, Inc. | Compositions and methods for inhibiting factor d |
| WO2017127762A1 (en) | 2016-01-20 | 2017-07-27 | Vitrisa Therapeutics, Inc. | Methods for improved aptamer selection |
| AU2017217677A1 (en) | 2016-02-08 | 2018-07-26 | 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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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015168468A1 (en) * | 2014-05-01 | 2015-11-05 | Genentech, Inc. | Anti-factor d antibody variants and uses thereof |
Non-Patent Citations (2)
| Title |
|---|
| Biotechnology and Bioengineering, 2015, vol. 112, no. 8, , OUELLET, E. et al., "Hi-Fi SELEX: A High-Fidelity Digital-PCR Based Therapeutic Aptamer Discovery Platform", pages 1506 - 1522 * |
| Chemical Communications, 2014, vol. 50, no. 63, LAO, Y.H. et al., "Selection of Aptamers Targeting the Sialic Acid Receptor of Hemagglutinin by Epitope-Specific SELEX", pages 8719 - 8722, * |
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