JP4809977B2 - 貧血の予防および治療用の方法および組成物 - Google Patents
貧血の予防および治療用の方法および組成物 Download PDFInfo
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| US7217689B1 (en) | 1989-10-13 | 2007-05-15 | Amgen Inc. | Glycosylation analogs of erythropoietin |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| EP0888385B1 (en) | 1996-03-14 | 2003-08-20 | Genentech, Inc. | Gdnf receptor and uses thereof |
| ES2221717T3 (es) | 1997-12-08 | 2005-01-01 | Emd Lexigen Research Center Corp. | Proteinas de fusion heterodimeras utiles para inmunoterapia dirigida e inmunoestimulacion general. |
| US7304150B1 (en) | 1998-10-23 | 2007-12-04 | Amgen Inc. | Methods and compositions for the prevention and treatment of anemia |
| US6555343B1 (en) | 1999-05-07 | 2003-04-29 | Genentech Inc. | Chimpanzee erythropoietin (CHEPO) polypeptides and nucleic acids encoding the same |
| US6831060B2 (en) | 1999-05-07 | 2004-12-14 | Genentech, Inc. | Chimpanzee erythropoietin (CHEPO) polypeptides and nucleic acids encoding the same |
| EP1177285A1 (en) * | 1999-05-07 | 2002-02-06 | Genentech, Inc. | Chimpanzee erythropoietin (chepo) polypeptides and nucleic acids encoding the same |
| US7067110B1 (en) | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| WO2001010912A1 (en) | 1999-08-09 | 2001-02-15 | Lexigen Pharmaceuticals Corp. | Multiple cytokine-antibody complexes |
| CA2391080A1 (en) | 1999-11-12 | 2001-05-25 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Erythropoietin forms with improved properties |
| JP5179689B2 (ja) | 2000-02-11 | 2013-04-10 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 抗体ベース融合タンパク質の循環系内半減期の増強 |
| US6926898B2 (en) | 2000-04-12 | 2005-08-09 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU5551601A (en) * | 2000-04-21 | 2001-11-07 | Amgen Inc | Methods and compositions for the prevention and treatment of anemia |
| MEP90708A (hr) | 2000-05-15 | 2011-12-20 | Nova farmaceutska smješa | |
| CZ2003214A3 (cs) | 2000-06-29 | 2003-08-13 | Merck Patent Gmbh | Zesílení odpovědi mediovaných fúzním proteinem protilátka-cytokin kombinovanou léčbou pomocí činidel zvyšujících uptake imunocytokinu |
| US7078376B1 (en) * | 2000-08-11 | 2006-07-18 | Baxter Healthcare S.A. | Therapeutic methods for treating subjects with a recombinant erythropoietin having high activity and reduced side effects |
| US7087224B2 (en) | 2000-10-31 | 2006-08-08 | Amgen Inc. | Method of treating anemia by administering IL-1ra |
| DK1366067T3 (da) | 2001-03-07 | 2012-10-22 | Merck Patent Gmbh | Ekspressionsteknologi for proteiner indeholdende en hybrid isotype-antistof-enhed |
| US6992174B2 (en) | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
| BR0209177A (pt) | 2001-05-03 | 2004-10-05 | Merck Patent Gmbh | Anticorpo especìfico a tumor recombinante e uso do mesmo |
| EP1454138B1 (en) | 2001-12-04 | 2012-01-18 | Merck Patent GmbH | Immunocytokines with modulated selectivity |
| CA2841097A1 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin and g-csf fusion proteins |
| WO2005003296A2 (en) | 2003-01-22 | 2005-01-13 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| MXPA05000063A (es) * | 2002-07-01 | 2005-04-08 | Kenneth S Warren Inst Inc | Citocinas recombinantes protectoras de tejido y acidos nucleicos que las codifican para la proteccion, restauracion y mejora de celulas, tejidos y organos respondedores. |
| WO2004009627A1 (en) * | 2002-07-19 | 2004-01-29 | Cangene Corporation | Pegylated erythropoietic compounds |
| ATE471946T1 (de) | 2002-12-17 | 2010-07-15 | Merck Patent Gmbh | Humanisierter antikörper (h14.18) des maus antikörpers 14.18, der gd2 bindet und seine fusion mit il-2 |
| ES2382377T3 (es) | 2003-05-30 | 2012-06-07 | Gemin X Pharmaceuticals Canada Inc. | Compuestos triheterocíclicos, composiciones, y métodos para tratar cáncer |
| EP1699821B1 (en) | 2003-12-31 | 2012-06-20 | Merck Patent GmbH | Fc-ERYTHROPOIETIN FUSION PROTEIN WITH IMPROVED PHARMACOKINETICS |
| TWI376234B (en) | 2005-02-01 | 2012-11-11 | Msd Oss Bv | Conjugates of a polypeptide and an oligosaccharide |
| BRPI0611405A2 (pt) * | 2005-05-24 | 2010-09-08 | Avestha Gengraine Tech Pvt Ltd | método recombinante para a produção de uma proteìna estimuladora da eritropoese |
| EP3026109B1 (en) | 2005-12-08 | 2022-03-09 | Amgen Inc. | Improved production of glycoproteins using manganese |
| ES2434494T3 (es) | 2005-12-08 | 2013-12-16 | Amgen, Inc. | Células huésped mejoradas y métodos de cultivo |
| EP2498096A1 (en) | 2006-07-21 | 2012-09-12 | Amgen Inc. | Method of detecting and/or measuring hepcidin in a sample |
| AU2008304111B2 (en) | 2007-09-27 | 2014-04-24 | Amgen Inc. | Pharmaceutical formulations |
| US8796206B2 (en) | 2007-11-15 | 2014-08-05 | Amgen Inc. | Aqueous formulation of erythropoiesis stimulating protein stabilised by antioxidants for parenteral administration |
| EP2803675A3 (en) | 2008-01-25 | 2014-12-24 | Amgen, Inc | Ferroportin antibodies and methods of use |
| WO2009139822A1 (en) | 2008-05-01 | 2009-11-19 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
| CN101323630B (zh) * | 2008-07-25 | 2013-06-05 | 中国科学院上海有机化学研究所 | 一种过渡金属络合物、合成方法及其用途 |
| CA2742871C (en) | 2008-11-13 | 2018-10-23 | Herb Lin | Methods and compositions for regulating iron homeostasis by modulation of bmp-6 |
| EP3009447B1 (en) | 2009-07-24 | 2018-06-06 | Dr. Reddy's Laboratories, Ltd. | Production of erythropoiesis stimulating protein using metal ions |
| US8435516B2 (en) | 2009-10-12 | 2013-05-07 | Pfizer Inc. | Cancer treatment |
| US9662271B2 (en) | 2009-10-23 | 2017-05-30 | Amgen Inc. | Vial adapter and system |
| ES2545411T5 (es) | 2010-06-07 | 2024-04-05 | Amgen Inc | Dispositivo de administración de fármaco |
| WO2012135315A1 (en) | 2011-03-31 | 2012-10-04 | Amgen Inc. | Vial adapter and system |
| US20140178368A1 (en) | 2011-04-19 | 2014-06-26 | Leslie Lynne SHARP | Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer |
| LT2699293T (lt) | 2011-04-20 | 2019-04-25 | Amgen Inc. | Automatinio purškimo prietaisas |
| EP3045187B1 (en) | 2011-10-14 | 2019-04-10 | Amgen Inc. | Injector and method of assembly |
| JP2015535464A (ja) | 2012-11-21 | 2015-12-14 | アムジエン・インコーポレーテツド | 薬剤送達装置 |
| US10092703B2 (en) | 2013-03-15 | 2018-10-09 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
| TWI592183B (zh) | 2013-03-15 | 2017-07-21 | 安美基公司 | 本體輪廓可調適之自動注射器裝置 |
| CA2904357C (en) | 2013-03-15 | 2020-09-22 | Intrinsic Lifesciences Llc | Anti-hepcidin antibodies and uses thereof |
| US10492990B2 (en) | 2013-03-15 | 2019-12-03 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
| ES2853748T3 (es) | 2013-03-22 | 2021-09-17 | Amgen Inc | Inyector y método de montaje |
| MX2016005315A (es) | 2013-10-24 | 2016-08-11 | Amgen Inc | Sistema de administracion de farmacos con control sensible a la temperatura. |
| EP3060275B1 (en) | 2013-10-24 | 2019-07-03 | Amgen Inc. | Injector and method of assembly |
| WO2015119906A1 (en) | 2014-02-05 | 2015-08-13 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
| SG11201609219QA (en) | 2014-05-07 | 2016-12-29 | Amgen Inc | Autoinjector with shock reducing elements |
| US20170103186A1 (en) | 2014-06-03 | 2017-04-13 | Amgen Inc. | Systems and methods for supporting patient use of a drug delivery device |
| CA2961917A1 (en) | 2014-09-22 | 2016-03-31 | Intrinsic Lifesciences Llc | Humanized anti-hepcidin antibodies and uses thereof |
| ES3056224T3 (en) | 2014-10-14 | 2026-02-19 | Amgen Inc | Drug injection device with visual and audible indicators |
| US10799630B2 (en) | 2014-12-19 | 2020-10-13 | Amgen Inc. | Drug delivery device with proximity sensor |
| EP3689394A1 (en) | 2014-12-19 | 2020-08-05 | Amgen Inc. | Drug delivery device with live button or user interface field |
| HUE053145T2 (hu) | 2014-12-31 | 2021-06-28 | Checkmate Pharmaceuticals Inc | Kombinált tumor immunterápia |
| US10583245B2 (en) | 2015-02-17 | 2020-03-10 | Amgen Inc. | Drug delivery device with vacuum assisted securement and/or feedback |
| ES2905870T3 (es) | 2015-02-27 | 2022-04-12 | Amgen Inc | Dispositivo de suministro de fármacos que tiene un mecanismo de protección de aguja con un umbral de resistencia ajustable al movimiento de la protección de aguja |
| WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
| JP7082568B2 (ja) | 2015-12-09 | 2022-06-08 | アムジエン・インコーポレーテツド | 信号伝達キャップ付き自動注射器 |
| WO2017120178A1 (en) | 2016-01-06 | 2017-07-13 | Amgen Inc. | Auto-injector with signaling electronics |
| WO2017160799A1 (en) | 2016-03-15 | 2017-09-21 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
| WO2017189089A1 (en) | 2016-04-29 | 2017-11-02 | Amgen Inc. | Drug delivery device with messaging label |
| US11389588B2 (en) | 2016-05-02 | 2022-07-19 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
| MX2018013616A (es) | 2016-05-13 | 2019-02-21 | Amgen Inc | Montaje de cubierta protectora de vial. |
| WO2017200989A1 (en) | 2016-05-16 | 2017-11-23 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
| ES3066292T3 (en) | 2016-06-03 | 2026-05-12 | Amgen Inc | Impact testing apparatuses and methods for drug delivery devices |
| EP3478342B1 (en) | 2016-07-01 | 2025-03-12 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
| US20190328965A1 (en) | 2016-08-17 | 2019-10-31 | Amgen Inc. | Drug delivery device with placement detection |
| US11202818B2 (en) | 2016-09-14 | 2021-12-21 | President And Fellows Of Harvard College | Methods and compositions for modulating erythropoiesis |
| EP3532127B1 (en) | 2016-10-25 | 2026-04-08 | Amgen Inc. | On-body injector |
| WO2018136398A1 (en) | 2017-01-17 | 2018-07-26 | Amgen Inc. | Injection devices and related methods of use and assembly |
| AU2018220538B2 (en) | 2017-02-17 | 2023-12-14 | Amgen Inc. | Drug delivery device with sterile fluid flowpath and related method of assembly |
| MX2019009755A (es) | 2017-02-17 | 2019-10-07 | Amgen Inc | Mecanismo de insercion para dispositivo de suministro de farmacos. |
| WO2018165143A1 (en) | 2017-03-06 | 2018-09-13 | Amgen Inc. | Drug delivery device with activation prevention feature |
| KR102627069B1 (ko) | 2017-03-07 | 2024-01-18 | 암겐 인코포레이티드 | 과압에 의한 바늘 삽입 |
| SG11201908062QA (en) | 2017-03-09 | 2019-09-27 | Amgen Inc | Insertion mechanism for drug delivery device |
| WO2018172219A1 (en) | 2017-03-20 | 2018-09-27 | F. Hoffmann-La Roche Ag | Method for in vitro glycoengineering of an erythropoiesis stimulating protein |
| MX2019011416A (es) | 2017-03-28 | 2019-11-01 | Amgen Inc | Sistema y metodo para conjunto de jeringa y vastago de embolo. |
| AU2018280054B2 (en) | 2017-06-08 | 2023-07-13 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
| CA3066399A1 (en) | 2017-06-08 | 2018-12-13 | Amgen Inc. | Torque driven drug delivery device |
| MA49447A (fr) | 2017-06-22 | 2020-04-29 | Amgen Inc | Réduction des impacts/chocs d'activation d'un dispositif |
| JP7475860B2 (ja) | 2017-06-23 | 2024-04-30 | アムジエン・インコーポレーテツド | スイッチアセンブリにより起動されるキャップを含む電子薬物送達デバイス |
| JP7408398B2 (ja) | 2017-07-14 | 2024-01-05 | アムジエン・インコーポレーテツド | 二重ねじりばねシステムを有する針挿入後退システム |
| JP7649105B2 (ja) | 2017-07-21 | 2025-03-19 | アムジエン・インコーポレーテツド | 薬物容器のためのガス透過性シーリング部材及び組立方法 |
| EP3658206A1 (en) | 2017-07-25 | 2020-06-03 | Amgen Inc. | Drug delivery device with container access system and related method of assembly |
| WO2019022951A1 (en) | 2017-07-25 | 2019-01-31 | Amgen Inc. | DRUG DELIVERY DEVICE WITH GEAR MODULE AND ASSEMBLY METHOD THEREOF |
| US12318593B2 (en) | 2017-08-09 | 2025-06-03 | Amgen Inc. | Hydraulic-pneumatic pressurized chamber drug delivery system |
| EP3668567B1 (en) | 2017-08-18 | 2026-02-18 | Amgen Inc. | Wearable injector with sterile adhesive patch |
| US11103636B2 (en) | 2017-08-22 | 2021-08-31 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
| EP3691717B1 (en) | 2017-10-04 | 2023-02-08 | Amgen Inc. | Flow adapter for drug delivery device |
| EP4257164A3 (en) | 2017-10-06 | 2024-01-17 | Amgen Inc. | Drug delivery device with interlock assembly and related method of assembly |
| MA50348A (fr) | 2017-10-09 | 2020-08-19 | Amgen Inc | Dispositif d'administration de médicament comprenant un ensemble d'entraînement et procédé d'assemblage associé |
| ES3069718T3 (en) | 2017-11-03 | 2026-06-10 | Amgen Inc | System and approaches for sterilizing a drug delivery device |
| CA3079197A1 (en) | 2017-11-06 | 2019-05-09 | Amgen Inc. | Drug delivery device with placement and flow sensing |
| MA50569A (fr) | 2017-11-06 | 2020-09-16 | Amgen Inc | Ensembles de remplissage-finition et procédés associés |
| IL319987A (en) | 2017-11-10 | 2025-06-01 | Amgen Inc | Plungers for drug delivery devices |
| JP7747438B2 (ja) | 2017-11-16 | 2025-10-01 | アムジエン・インコーポレーテツド | 失速及び終点検出を有するオートインジェクタ |
| AU2018368340B2 (en) | 2017-11-16 | 2024-03-07 | Amgen Inc. | Door latch mechanism for drug delivery device |
| WO2019160866A2 (en) | 2018-02-13 | 2019-08-22 | Checkmate Pharmaceuticals, Inc. | Compositions and methods for tumor immunotherapy |
| BR112020020479A2 (pt) | 2018-04-09 | 2021-01-12 | Checkmate Pharmaceuticals | Empacotamento de oligonucleotídeos em partículas similares a vírus |
| US10835685B2 (en) | 2018-05-30 | 2020-11-17 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
| US11083840B2 (en) | 2018-06-01 | 2021-08-10 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
| US12303677B2 (en) | 2018-07-24 | 2025-05-20 | Amgen Inc. | Hybrid drug delivery devices with optional grip portion and related method of preparation |
| WO2020023336A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
| CA3103682A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Delivery devices for administering drugs |
| CN112469454B (zh) | 2018-07-24 | 2024-01-26 | 安进公司 | 用于施用药物的输送装置 |
| MA53320A (fr) | 2018-07-31 | 2021-11-03 | Amgen Inc | Ensemble de trajet de fluide pour dispositif d'administration de médicament |
| CA3106452A1 (en) | 2018-09-24 | 2020-04-02 | Amgen Inc. | Interventional dosing systems and methods |
| US12042642B2 (en) | 2018-09-28 | 2024-07-23 | Amgen Inc. | Muscle wire escapement activation assembly for a drug delivery device |
| WO2020072577A1 (en) | 2018-10-02 | 2020-04-09 | Amgen Inc. | Injection systems for drug delivery with internal force transmission |
| JP7547325B2 (ja) | 2018-10-05 | 2024-09-09 | アムジエン・インコーポレーテツド | 投薬量インジケータを有する薬物送達デバイス |
| MA53913A (fr) | 2018-10-15 | 2022-01-19 | Amgen Inc | Procédé d'assemblage de plate-forme pour dispositif d'administration de médicament |
| JP7719714B2 (ja) | 2018-10-15 | 2025-08-06 | アムジエン・インコーポレーテツド | ダンピング機構を有する薬物送達装置 |
| WO2020091956A1 (en) | 2018-11-01 | 2020-05-07 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
| MA54057A (fr) | 2018-11-01 | 2022-02-09 | Amgen Inc | Dispositifs d'administration de médicament à rétraction partielle d'élément d'administration de médicament |
| TWI831847B (zh) | 2018-11-01 | 2024-02-11 | 美商安進公司 | 部分針頭縮回之藥物遞送裝置及其操作方法 |
| EP3958934B1 (en) | 2019-04-24 | 2025-04-09 | Amgen Inc. | Syringe sterilization verification assemblies and methods |
| US20220273887A1 (en) | 2019-08-23 | 2022-09-01 | Amgen Inc. | Drug delivery device with configurable needle shield engagement components and related methods |
| BR112023024278A2 (pt) | 2021-05-21 | 2024-01-30 | Amgen Inc | Método de otimizar uma receita de enchimento para um recipiente de fármacos |
| WO2023209074A1 (en) | 2022-04-28 | 2023-11-02 | Institut National de la Santé et de la Recherche Médicale | Methods of restoring erythropoiesis in patients suffering from a sf3b1 mutant myelodysplastic syndrome by correcting coasy mis-splicing |
| JP2025536587A (ja) | 2022-11-02 | 2025-11-07 | エフ． ホフマン－ラ ロシュ アーゲー | 糖タンパク質組成物を生産するための方法 |
| WO2026030152A1 (en) | 2024-07-29 | 2026-02-05 | Amgen Inc. | System and method for assessing transferability of a fill recipe |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08506023A (ja) * | 1993-08-17 | 1996-07-02 | アムジエン・インコーポレーテツド | エリトロポエチン類似体 |
| WO1997009996A1 (de) * | 1995-09-14 | 1997-03-20 | Boehringer Mannheim Gmbh | Pharmazeutische kombinationspräparate enthaltend erythropoietin und eisenpräparate |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4954437A (en) | 1986-09-15 | 1990-09-04 | Integrated Genetics, Inc. | Cell encoding recombinant human erythropoietin |
| AU646822B2 (en) * | 1989-10-13 | 1994-03-10 | Kirin-Amgen Inc. | Erythropoietin isoforms |
| US5716644A (en) * | 1992-06-11 | 1998-02-10 | Alkermes, Inc. | Composition for sustained release of non-aggregated erythropoietin |
| US5541458A (en) * | 1994-11-14 | 1996-07-30 | Hewlett-Packard Company | Power supply for timed residual power after turn off |
| ES2208798T3 (es) * | 1997-09-01 | 2004-06-16 | Aventis Pharma Deutschland Gmbh | Eritropoyetina humana recombinante con un perfil de glicosilacion ventajoso. |
-
1999
- 1999-10-18 DE DE69935345.9T patent/DE69935345T3/de not_active Expired - Lifetime
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- 1999-10-18 WO PCT/US1999/024435 patent/WO2000024893A2/en not_active Ceased
- 1999-10-18 DK DK99955046T patent/DK1123313T3/da active
- 1999-10-18 PT PT99955046T patent/PT1123313E/pt unknown
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- 1999-10-18 EP EP07004087A patent/EP1813624B1/en not_active Expired - Lifetime
- 1999-10-18 KR KR1020017005047A patent/KR20010075661A/ko not_active Ceased
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- 1999-10-22 TW TW088118320A patent/TWI234583B/zh not_active IP Right Cessation
-
2001
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-
2007
- 2007-03-07 CY CY20071100322T patent/CY1107584T1/el unknown
-
2009
- 2009-01-21 IL IL196645A patent/IL196645A/en not_active IP Right Cessation
-
2010
- 2010-06-07 JP JP2010130046A patent/JP5558213B2/ja not_active Expired - Fee Related
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08506023A (ja) * | 1993-08-17 | 1996-07-02 | アムジエン・インコーポレーテツド | エリトロポエチン類似体 |
| WO1997009996A1 (de) * | 1995-09-14 | 1997-03-20 | Boehringer Mannheim Gmbh | Pharmazeutische kombinationspräparate enthaltend erythropoietin und eisenpräparate |
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