ES2974895T3 - Formulación líquida que comprende un compuesto neutralizante de GM-CSF - Google Patents
Formulación líquida que comprende un compuesto neutralizante de GM-CSF Download PDFInfo
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- ES2974895T3 ES2974895T3 ES15720968T ES15720968T ES2974895T3 ES 2974895 T3 ES2974895 T3 ES 2974895T3 ES 15720968 T ES15720968 T ES 15720968T ES 15720968 T ES15720968 T ES 15720968T ES 2974895 T3 ES2974895 T3 ES 2974895T3
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Landscapes
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| US201461994319P | 2014-05-16 | 2014-05-16 | |
| US201462043636P | 2014-08-29 | 2014-08-29 | |
| PCT/EP2015/059709 WO2015169742A1 (en) | 2014-05-07 | 2015-05-04 | Liquid formulation comprising gm-csf neutralizing compound |
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| JOP20190255A1 (ar) | 2017-04-28 | 2019-10-27 | Amgen Inc | صيغ أجسام مضادة لـ rankl بشري، وطرق لاستخدامها |
| CN107167613B (zh) * | 2017-06-22 | 2018-10-02 | 深圳清华大学研究院 | 用于等离子体金芯片的蛋白点样缓冲液 |
| EA202190955A1 (ru) * | 2018-10-01 | 2021-08-17 | Эмджен Инк. | Способы снижения агрегации биспецифических антител |
| US11267858B2 (en) | 2019-05-31 | 2022-03-08 | Spectrum Pharmaceuticals, Inc. | Methods of treatment using G-CSF protein complex |
| US11684655B2 (en) | 2019-05-31 | 2023-06-27 | Spectrum Pharmaceuticals, Inc. | Methods of treating neutorpenia using G-CSF protein complex |
| BR112022007776A2 (pt) * | 2019-10-25 | 2022-07-05 | Amgen Inc | Composições e métodos para minimizar a perda de proteína em baixas concentrações de proteína |
| JP2023528305A (ja) * | 2020-05-29 | 2023-07-04 | アムジエン・インコーポレーテツド | 抗体製剤及びその使用 |
| EP4255483A4 (en) * | 2020-12-04 | 2025-07-09 | CSL Innovation Pty Ltd | METHODS OF TREATMENT OF INFLAMMATORY SKIN CONDITIONS |
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| KR102375269B1 (ko) * | 2021-01-27 | 2022-03-17 | 한미약품 주식회사 | 단백질 액상 제제 및 이의 제조방법 |
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| US4783441A (en) | 1979-04-30 | 1988-11-08 | Hoechst Aktiengesellschaft | Aqueous protein solutions stable to denaturation |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| DE3583880D1 (de) | 1984-04-09 | 1991-10-02 | Takeda Chemical Industries Ltd | Stabile interleukin-2-zusammensetzung. |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| GB8903593D0 (en) | 1989-02-16 | 1989-04-05 | Pafra Ltd | Storage of materials |
| US5747032A (en) | 1990-08-10 | 1998-05-05 | Amrad Corporation Limited | Monoclonal antibody to human granulocyte macrophage colony stimulating factor |
| US5580856A (en) | 1994-07-15 | 1996-12-03 | Prestrelski; Steven J. | Formulation of a reconstituted protein, and method and kit for the production thereof |
| PT2275119E (pt) * | 1995-07-27 | 2013-11-21 | Genentech Inc | Formulação de proteína liofilizada isotónica estável |
| US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
| WO1999054440A1 (en) | 1998-04-21 | 1999-10-28 | Micromet Gesellschaft Für Biomedizinische Forschung Mbh | CD19xCD3 SPECIFIC POLYPEPTIDES AND USES THEREOF |
| IL161677A0 (en) * | 2001-11-08 | 2004-09-27 | Protein Design Labs | Stable liquid pharmaceutical formulation of igg antibodies |
| MXPA04008215A (es) | 2002-02-27 | 2004-11-26 | Immunex Corp | Formulacion polipeptidica. |
| US7511476B2 (en) * | 2005-01-04 | 2009-03-31 | Digisensors, Inc. | Electromagnetic sensor systems and methods of use thereof |
| SG161292A1 (en) * | 2005-04-18 | 2010-05-27 | Micromet Ag | Antibody neutralizers of human granulocyte macrophage colony stimulating factor |
| EP2468773A3 (en) | 2005-05-18 | 2012-09-19 | MorphoSys AG | Anti-GM-CSF Antibodies and uses therefor |
| JP4736037B2 (ja) * | 2005-10-26 | 2011-07-27 | 株式会社イーベック | ヒトｇｍ−ｃｓｆに結合するヒトのモノクローナル抗体並びにその抗原結合部分 |
| US7741450B2 (en) | 2006-02-08 | 2010-06-22 | Morphotek Inc. | Antibodies to GM-CSF |
| KR101451546B1 (ko) | 2006-03-27 | 2014-10-16 | 메디뮨 리미티드 | Ｇｍ-ｃｓｆ 수용체에 대한 결합 성분 |
| EP1970384A1 (en) | 2007-03-14 | 2008-09-17 | Ganymed Pharmaceuticals AG | Monoclonal antibodies for treatment of cancer |
| JP5513380B2 (ja) | 2007-06-25 | 2014-06-04 | アムジエン・インコーポレーテツド | 肝細胞増殖因子に対する特異的結合剤の組成物 |
| TW200918553A (en) * | 2007-09-18 | 2009-05-01 | Amgen Inc | Human GM-CSF antigen binding proteins |
| KR20100102108A (ko) | 2007-11-13 | 2010-09-20 | 에베크 인코포레이티드 | ｈＧＭ-ＣＳＦ에 결합하는 모노클로날 항체 및 이를 포함하는 의약 조성물 |
| KR101824512B1 (ko) | 2008-04-28 | 2018-02-02 | 휴머니건, 아이엔씨. | 과립구-대식세포 콜로니 자극 인자에 대한 항체 |
| WO2010077422A2 (en) * | 2008-10-29 | 2010-07-08 | Wyeth Llc | Formulations of single domain antigen binding molecules |
| US20110158987A1 (en) * | 2009-12-29 | 2011-06-30 | F. Hoffmann-Laroche Ag | Novel antibody formulation |
| KR20220028177A (ko) * | 2012-09-20 | 2022-03-08 | 모르포시스 아게 | 류마티스 관절염에 대한 치료 |
| AR093297A1 (es) * | 2012-10-31 | 2015-05-27 | Amgen Res Munich Gmbh | Formulacion liquida que comprende un compuesto neutralizante de gm-csf |
-
2015
- 2015-05-04 KR KR1020167031014A patent/KR102385802B1/ko active Active
- 2015-05-04 AU AU2015257798A patent/AU2015257798C1/en active Active
- 2015-05-04 EA EA201691883A patent/EA201691883A1/ru unknown
- 2015-05-04 CN CN201580037108.0A patent/CN106659785B/zh active Active
- 2015-05-04 JP JP2016566811A patent/JP6769879B2/ja active Active
- 2015-05-04 ES ES15720968T patent/ES2974895T3/es active Active
- 2015-05-04 EP EP15720968.5A patent/EP3139960B1/en active Active
- 2015-05-04 US US15/307,214 patent/US11173208B2/en active Active
- 2015-05-04 WO PCT/EP2015/059709 patent/WO2015169742A1/en not_active Ceased
- 2015-05-04 AR ARP150101336A patent/AR100268A1/es not_active Application Discontinuation
- 2015-05-04 BR BR112016025126-1A patent/BR112016025126B1/pt active IP Right Grant
- 2015-05-04 MX MX2016014411A patent/MX387451B/es unknown
- 2015-05-07 TW TW104114614A patent/TWI682788B/zh active
-
2016
- 2016-10-14 ZA ZA2016/07097A patent/ZA201607097B/en unknown
- 2016-10-20 PH PH12016502100A patent/PH12016502100A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW201622702A (zh) | 2016-07-01 |
| KR20160149210A (ko) | 2016-12-27 |
| CA2946230A1 (en) | 2015-11-12 |
| BR112016025126A2 (pt) | 2018-02-20 |
| BR112016025126A8 (pt) | 2022-08-09 |
| MX387451B (es) | 2025-03-18 |
| AU2015257798C1 (en) | 2020-10-22 |
| WO2015169742A1 (en) | 2015-11-12 |
| CN106659785B (zh) | 2021-04-30 |
| PH12016502100A1 (en) | 2017-02-06 |
| ZA201607097B (en) | 2024-11-27 |
| BR112016025126B1 (pt) | 2024-02-15 |
| CN106659785A (zh) | 2017-05-10 |
| US20170252436A1 (en) | 2017-09-07 |
| MX2016014411A (es) | 2017-04-06 |
| AR100268A1 (es) | 2016-09-21 |
| AU2015257798A1 (en) | 2016-11-17 |
| US11173208B2 (en) | 2021-11-16 |
| EA201691883A1 (ru) | 2017-05-31 |
| EP3139960A1 (en) | 2017-03-15 |
| KR102385802B1 (ko) | 2022-04-13 |
| AU2015257798B2 (en) | 2020-04-23 |
| JP6769879B2 (ja) | 2020-10-14 |
| TWI682788B (zh) | 2020-01-21 |
| EP3139960B1 (en) | 2024-01-17 |
| JP2017514868A (ja) | 2017-06-08 |
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