PT1734987E - Interfero-beta para teraputica antivrica de doenãas respiratërias - Google Patents
Interfero-beta para teraputica antivrica de doenãas respiratërias Download PDFInfo
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- PT1734987E PT1734987E PT05708482T PT05708482T PT1734987E PT 1734987 E PT1734987 E PT 1734987E PT 05708482 T PT05708482 T PT 05708482T PT 05708482 T PT05708482 T PT 05708482T PT 1734987 E PT1734987 E PT 1734987E
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| US8318423B2 (en) * | 2004-07-06 | 2012-11-27 | Focus Diagnostics, Inc. | Methods and compositions for detecting rhinoviruses |
| EP1922081B1 (en) * | 2005-09-09 | 2012-08-15 | Imperial Innovations Limited | Interferon lambda therapy for treatment of respiratory diseases |
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| US7871603B2 (en) | 2007-05-18 | 2011-01-18 | Synairgen Research Limited | Interferon-beta and/or lambda for use in treating rhinovirus infection in the elderly |
| GB0713402D0 (en) * | 2007-07-11 | 2007-08-22 | Cardiff & Vale Nhs Trust | A method of diagnosing a condition using a neural network |
| BRPI0819932A2 (pt) * | 2007-12-13 | 2019-07-30 | Glaxo Group Ltd | composição, uso de uma composição, dispositivo nebulizador, inalador ou intranasal, processos para produzir uma composição farmacêutica e uma composição polipeptídica, e, uso de um tampão fisiologicamente aceitável. |
| AU2009344851A1 (en) * | 2008-12-19 | 2011-06-23 | The Regents Of The University Of California | Use of epidermal growth factor inhibitors in the treatment of viral infection |
| EP2506759A4 (en) | 2009-12-02 | 2015-05-20 | Neetour Medical Ltd | SURVEILLANCE BASED ON HEMODYNAMIA AND ASSESSMENT OF RESPIRATORY DISEASES |
| DK2544705T3 (en) * | 2010-03-12 | 2016-09-19 | Synairgen Res Ltd | INTERFERON BETA TO USE IN THE LOWER AIR TRANSMISSION CAUSED BY INFLUENZA |
| PL3669892T3 (pl) | 2010-09-22 | 2024-10-07 | Ena Respiratory Pty Ltd | Kompozycja do zastosowania w metodzie immunostymulacyjnej |
| JP6730926B2 (ja) | 2014-01-08 | 2020-07-29 | プロージット ソウル バイオテクノロジー （ベイジン） カンパニー リミテッド | 融合ポリペプチドおよび使用方法 |
| JP7317796B2 (ja) * | 2017-07-24 | 2023-07-31 | ノババックス，インコーポレイテッド | 呼吸器疾患を治療するための方法および組成物 |
| FI3728289T3 (fi) | 2017-12-21 | 2025-11-11 | Axelia Oncology Pty Ltd | Optimoidut yhdisteet |
| WO2020168033A2 (en) * | 2019-02-13 | 2020-08-20 | University Of Florida Research Foundation, Inc. | Targeting lung-resident tnfr2+ cdc2 (r2d2) subpopulation to treat asthma |
| KR20220050873A (ko) | 2019-06-26 | 2022-04-25 | 악셀리아 온콜로지 피티와이 리미티드 | 신규한 분자 |
| US20230338475A1 (en) | 2020-07-20 | 2023-10-26 | Synairgen Research Limited | USE OF INHALED INTERFERON-BETA TO IMPROVE OUTCOME IN SARS-CoV-2 INFECTED PATIENTS |
| GB202014114D0 (en) * | 2020-09-08 | 2020-10-21 | Synairgen Res Ltd | Use of inhaled interferon-beta to treat virus-induced exacerbations in copd patients undergoing treatment with a systemic corticosteroid |
| DK4240396T5 (da) * | 2020-11-04 | 2025-04-07 | Ethris Gmbh | Ifn-lambda-mrna til behandling af virusinfektioner |
| US20250281576A1 (en) * | 2021-01-13 | 2025-09-11 | Abion Inc. | Prophylactic administration method against respiratory virus, comprising administering interferon-beta to potential respiratory virus-infected subject |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6596260B1 (en) * | 1993-08-27 | 2003-07-22 | Novartis Corporation | Aerosol container and a method for storage and administration of a predetermined amount of a pharmaceutically active aerosol |
| ES2245780T3 (es) * | 1994-05-18 | 2006-01-16 | Nektar Therapeutics | Metodos y composiciones para la formulacion de interferones como un polvo seco. |
| US6030609A (en) * | 1995-05-19 | 2000-02-29 | Case Western Reserve University | Method and composition for treating paramyxovirus |
| US20010031253A1 (en) * | 1996-07-24 | 2001-10-18 | Gruenberg Micheal L. | Autologous immune cell therapy: cell compositions, methods and applications to treatment of human disease |
| AU780270B2 (en) * | 2000-02-23 | 2005-03-10 | Association Francaise Contre Les Myopathies | Treatment of immune diseases |
| GB2362884A (en) | 2000-05-30 | 2001-12-05 | Isis Innovation | Extended duration of airway gene therapy |
| EP1334128A2 (en) | 2000-11-02 | 2003-08-13 | Maxygen Aps | New multimeric interferon beta polypeptides |
| WO2002072019A2 (en) * | 2001-03-13 | 2002-09-19 | Vical Incorporated | Interferon-beta polynucleotide therapy for autoimmune and inflammatory diseases |
| AU2003215136A1 (en) | 2002-02-08 | 2003-09-02 | University Of Medicine And Dentistry Of New Jersey | Ifn-a/b-independent mechanism of antiviral protection |
| US20040037809A1 (en) * | 2002-06-28 | 2004-02-26 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of interferon beta |
| WO2004037995A2 (en) | 2002-10-23 | 2004-05-06 | Zymogenetics, Inc. | Methods for treating viral infection using il-28 and il-29 |
| US7157559B2 (en) | 2003-08-07 | 2007-01-02 | Zymogenetics, Inc. | Homogeneous preparations of IL-28 and IL-29 |
| GB0405634D0 (en) | 2004-03-12 | 2004-04-21 | Univ Southampton | Anti-virus therapy for respiratory diseases |
| WO2005097165A2 (en) | 2004-04-02 | 2005-10-20 | Zymogenetics, Inc. | Il-28 and il-29 cysteine mutants for treating viral infection |
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2004
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- 2005-03-07 PL PL05708482T patent/PL1734987T3/pl unknown
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| HK1097181A1 (en) | 2007-06-22 |
| CA2558212C (en) | 2012-11-27 |
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| JP4807526B2 (ja) | 2011-11-02 |
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| EP2206512A2 (en) | 2010-07-14 |
| WO2005087253A2 (en) | 2005-09-22 |
| EP1734987A2 (en) | 2006-12-27 |
| ES2343732T3 (es) | 2010-08-09 |
| EP1734987B1 (en) | 2010-05-05 |
| CA2558212A1 (en) | 2005-09-22 |
| US20130209399A1 (en) | 2013-08-15 |
| US20070134763A1 (en) | 2007-06-14 |
| PL1734987T3 (pl) | 2010-10-29 |
| US7569216B2 (en) | 2009-08-04 |
| ATE466591T1 (de) | 2010-05-15 |
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