CN104490767A - 人抗TNF-α抗体的稳定高蛋白质浓度制剂 - Google Patents
人抗TNF-α抗体的稳定高蛋白质浓度制剂 Download PDFInfo
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| US20160279239A1 (en) | 2011-05-02 | 2016-09-29 | Immunomedics, Inc. | Subcutaneous administration of anti-cd74 antibody for systemic lupus erythematosus and autoimmune disease |
| US20090280065A1 (en) * | 2006-04-10 | 2009-11-12 | Willian Mary K | Uses and Compositions for Treatment of Psoriasis |
| MY151032A (en) * | 2002-07-19 | 2014-03-31 | Abbott Lab S A | Treatment of tnf? related disorders |
| US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
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| US9415102B2 (en) * | 2002-09-06 | 2016-08-16 | Alexion Pharmaceuticals, Inc. | High concentration formulations of anti-C5 antibodies |
| TW201705980A (zh) | 2004-04-09 | 2017-02-16 | 艾伯維生物技術有限責任公司 | 用於治療ＴＮＦα相關失調症之多重可變劑量療法 |
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| WO2006041970A2 (en) * | 2004-10-08 | 2006-04-20 | Abbott Biotechnology Ltd. | Treatment of respiratory syncytial virus (rsv) infection |
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| KR20150055116A (ko) | 2005-05-16 | 2015-05-20 | 애브비 바이오테크놀로지 리미티드 | 미란성 다발관절염의 치료를 위한 ｔｎｆ 억제제의 용도 |
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| US9605064B2 (en) * | 2006-04-10 | 2017-03-28 | Abbvie Biotechnology Ltd | Methods and compositions for treatment of skin disorders |
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| US20090317399A1 (en) * | 2006-04-10 | 2009-12-24 | Pollack Paul F | Uses and compositions for treatment of CROHN'S disease |
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| US20100021451A1 (en) | 2006-06-08 | 2010-01-28 | Wong Robert L | Uses and compositions for treatment of ankylosing spondylitis |
| JP5535623B2 (ja) | 2006-06-30 | 2014-07-02 | アッヴィ バイオテクノロジー リミテッド | 自動注射装置 |
| EP2684895A1 (en) * | 2006-10-27 | 2014-01-15 | AbbVie Biotechnology Ltd | Crystalline anti-hTNFalpha antibodies |
| AU2008233173B2 (en) | 2007-03-29 | 2013-09-19 | Abbvie Inc. | Crystalline anti-human IL-12 antibodies |
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| CA2693771A1 (en) * | 2007-07-13 | 2009-01-22 | Abbott Biotechnology Ltd. | Methods and compositions for pulmonary administration of a tnf.alpha. inhibitor |
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| US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
| TWI543768B (zh) * | 2007-11-30 | 2016-08-01 | 艾伯維生物技術有限責任公司 | 蛋白質調配物及製造其之方法 |
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| JP5677411B2 (ja) | 2009-04-29 | 2015-02-25 | アッヴィ バイオテクノロジー リミテッド | 自動注入機器 |
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| US20120014956A1 (en) | 2010-02-02 | 2012-01-19 | Hartmut Kupper | Methods and compositions for predicting responsiveness to treatment with tnf-alpha inhibitor |
| RS57543B1 (sr) | 2010-06-03 | 2018-10-31 | Abbvie Biotechnology Ltd | Primene i kompozicije za lečenje hidradenitis suppurativa (hs) |
| JP5919606B2 (ja) * | 2010-11-11 | 2016-05-18 | アッヴィ バイオテクノロジー リミテッド | 改良型高濃度抗ｔｎｆアルファ抗体液体製剤 |
| CN106075664B (zh) | 2011-01-24 | 2019-07-02 | 艾伯维生物技术有限公司 | 具有模制抓握面的自动注射装置 |
| US9125893B2 (en) * | 2011-02-17 | 2015-09-08 | Kyowa Hakko Kirin Co., Ltd. | Highly concentrated anti-CD40 antibody pharmaceutical preparation |
| EP2702077A2 (en) | 2011-04-27 | 2014-03-05 | AbbVie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
| CA2831572C (en) | 2011-05-02 | 2019-11-26 | Immunomedics, Inc. | Ultrafiltration concentration of allotype selected antibodies for small-volume administration |
| GB201112429D0 (en) | 2011-07-19 | 2011-08-31 | Glaxo Group Ltd | Antigen-binding proteins with increased FcRn binding |
| WO2013096835A1 (en) * | 2011-12-23 | 2013-06-27 | Abbvie Inc. | Stable protein formulations |
| MX363700B (es) | 2012-03-07 | 2019-03-29 | Cadila Healthcare Ltd | Formulaciones farmaceuticas de anticuerpos tnf-alfa. |
| WO2013158273A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Methods to modulate c-terminal lysine variant distribution |
| US9150645B2 (en) | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
| US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
| US9249182B2 (en) | 2012-05-24 | 2016-02-02 | Abbvie, Inc. | Purification of antibodies using hydrophobic interaction chromatography |
| EP2863951A1 (en) * | 2012-06-12 | 2015-04-29 | Boehringer Ingelheim International GmbH | Pharmaceutical formulation for a therapeutic antibody |
| US8883979B2 (en) * | 2012-08-31 | 2014-11-11 | Bayer Healthcare Llc | Anti-prolactin receptor antibody formulations |
| AU2013309506A1 (en) | 2012-09-02 | 2015-03-12 | Abbvie Inc. | Methods to control protein heterogeneity |
| US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
| SG11201501715QA (en) | 2012-09-07 | 2015-05-28 | Coherus Biosciences Inc | Stable aqueous formulations of adalimumab |
| ES2806946T3 (es) * | 2012-10-26 | 2021-02-19 | Lupin Atlantis Holdings Sa | Composición farmacéutica estable de la proteína de fusión TNFR:Fc etanercept |
| US9649383B2 (en) * | 2012-11-19 | 2017-05-16 | Merck Sharp & Dohme Corp. | Liquid formulations for TNFR:Fc fusion proteins |
| US9844594B2 (en) | 2012-12-18 | 2017-12-19 | Merck Sharp & Dohme Corp. | Liquid formulations for an anti-TNF α antibody |
| CN102988984B (zh) * | 2012-12-21 | 2015-05-20 | 嘉和生物药业有限公司 | 增强稳定性的抗TNF-α人单克隆抗体的含水药物制剂 |
| JP2016505633A (ja) * | 2013-01-24 | 2016-02-25 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | ＴＮＦα抗原結合性タンパク質 |
| EP2830651A4 (en) | 2013-03-12 | 2015-09-02 | Abbvie Inc | HUMAN ANTIBODIES THAT BIND TNF-ALPHA AND PREPARATION METHODS |
| US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
| US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
| WO2014159579A1 (en) | 2013-03-14 | 2014-10-02 | Abbvie Inc. | MUTATED ANTI-TNFα ANTIBODIES AND METHODS OF THEIR USE |
| CN105025925A (zh) * | 2013-03-15 | 2015-11-04 | 拜尔健康护理有限责任公司 | 抗-催乳素受体抗体制剂 |
| CN103446583B (zh) * | 2013-03-21 | 2015-11-18 | 百奥泰生物科技(广州)有限公司 | 一种治疗TNF-α相关疾病的人抗体制剂 |
| JP2014202667A (ja) * | 2013-04-08 | 2014-10-27 | 株式会社島津製作所 | 抗体医薬用粒子径分布測定装置及び抗体医薬の粒子径分布測定方法 |
| WO2014193821A1 (en) * | 2013-05-28 | 2014-12-04 | Momenta Pharmaceuticals, Inc. | Pharmaceutical compositions comprising pyrophosphate |
| BR112016000563A2 (pt) * | 2013-07-19 | 2017-09-05 | Hexal Ag | Método de preparar uma formulação farmacêutica, método de usar ácido hexanóico e/ou ácido cítrico ou pelo menos um sal dos mesmos, formulação farmacêutica e método de modular ou determinar respostas imunes relacionadas à administração de uma formulação farmacêutica |
| IL312865B2 (en) | 2013-09-11 | 2025-06-01 | Eagle Biologics Inc | Liquid protein formulations containing viscosity-lowering agents |
| EP3052640A2 (en) | 2013-10-04 | 2016-08-10 | AbbVie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
| WO2015057910A1 (en) | 2013-10-16 | 2015-04-23 | Oncobiologics, Inc. | Buffer formulations for enhanced antibody stability |
| US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
| US8946395B1 (en) | 2013-10-18 | 2015-02-03 | Abbvie Inc. | Purification of proteins using hydrophobic interaction chromatography |
| US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
| WO2015061584A1 (en) * | 2013-10-24 | 2015-04-30 | Medimmune, Llc | Stable, aqueous antibody formulations |
| US20150139988A1 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
| CN104666242B (zh) * | 2013-11-26 | 2018-01-02 | 信达生物制药(苏州)有限公司 | 一种稳定的抗TNF‑α抗体制剂及其用途 |
| CN106061468B (zh) * | 2013-11-29 | 2020-10-02 | 阿雷斯贸易股份有限公司 | 包含TNFR和Fc区的融合蛋白的液体制剂 |
| CN104707146B (zh) * | 2013-12-16 | 2019-04-16 | 浙江海正药业股份有限公司 | 一种含有阿达木单抗的药物组合物 |
| EP3125923B1 (en) * | 2014-03-29 | 2024-10-16 | Intas Pharmaceuticals Limited | Lyophilized pharmaceutical composition of fc-peptide fusion protein |
| EP2946766B1 (en) | 2014-05-23 | 2016-03-02 | Ares Trading S.A. | Liquid pharmaceutical composition |
| LT2946765T (lt) * | 2014-05-23 | 2016-11-25 | Ares Trading S.A. | Skysta farmacinė kompozicija |
| EP2946767B1 (en) * | 2014-05-23 | 2016-10-05 | Ares Trading S.A. | Liquid pharmaceutical composition |
| AU2015267051B2 (en) * | 2014-05-27 | 2022-03-17 | Academia Sinica | Fucosidase from bacteroides and methods using the same |
| EP3156071A4 (en) * | 2014-06-10 | 2018-01-10 | Meiji Seika Pharma Co., Ltd. | Stable aqueous adalimumab preparation |
| TW201628649A (zh) * | 2014-10-09 | 2016-08-16 | 再生元醫藥公司 | 減少醫藥調配物中微可見顆粒之方法 |
| EP3247718B1 (en) | 2015-01-21 | 2021-09-01 | Outlook Therapeutics, Inc. | Modulation of charge variants in a monoclonal antibody composition |
| UY36542A (es) * | 2015-01-28 | 2016-08-31 | Mabxience S A | Formulaciones farmacéuticas para anticuerpos anti-tnf-alfa |
| EP3053572A1 (en) * | 2015-02-06 | 2016-08-10 | Ares Trading S.A. | Liquid pharmaceutical composition |
| EP3078675A1 (en) | 2015-04-10 | 2016-10-12 | Ares Trading S.A. | Induction dosing regimen for the treatment of tnf alpha mediated disorders |
| US11229702B1 (en) | 2015-10-28 | 2022-01-25 | Coherus Biosciences, Inc. | High concentration formulations of adalimumab |
| HK1257295A1 (zh) | 2015-12-04 | 2019-10-18 | Novartis Ag | 用於免疫肿瘤学的组合物和方法 |
| WO2017136433A1 (en) * | 2016-02-03 | 2017-08-10 | Oncobiologics, Inc. | Buffer formulations for enhanced antibody stability |
| US11071782B2 (en) | 2016-04-20 | 2021-07-27 | Coherus Biosciences, Inc. | Method of filling a container with no headspace |
| MD3479819T2 (ro) * | 2016-06-30 | 2024-07-31 | Celltrion Inc | Preparat farmaceutic lichid stabil |
| US11020686B2 (en) | 2016-08-16 | 2021-06-01 | Regeneron Pharmaceuticals, Inc. | Methods for quantitating individual antibodies from a mixture |
| BR112019006689A2 (pt) | 2016-10-25 | 2019-06-25 | Regeneron Pharma | métodos e sistemas para análise de dados de cromatografia |
| RU2665966C2 (ru) * | 2016-12-30 | 2018-09-05 | Закрытое Акционерное Общество "Биокад" | Водная фармацевтическая композиция рекомбинантного моноклонального антитела к ФНОα |
| US11608357B2 (en) | 2018-08-28 | 2023-03-21 | Arecor Limited | Stabilized antibody protein solutions |
| EP3372241A1 (en) * | 2017-03-06 | 2018-09-12 | Ares Trading S.A. | Liquid pharmaceutical composition |
| EP3372242A1 (en) * | 2017-03-06 | 2018-09-12 | Ares Trading S.A. | Liquid pharmaceutical composition |
| EP3601561A2 (en) | 2017-03-22 | 2020-02-05 | Novartis AG | Compositions and methods for immunooncology |
| EP3606964A4 (en) | 2017-04-03 | 2020-12-09 | Immunomedics, Inc. | SUBCUTANE ADMINISTRATION OF ANTIBODY DRUG CONJUGATES FOR CANCER THERAPY |
| US11845798B2 (en) | 2017-05-02 | 2023-12-19 | Merck Sharp & Dohme Llc | Formulations of anti-LAG3 antibodies and co-formulations of anti-LAG3 antibodies and anti-PD-1 antibodies |
| JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
| CN107485713B (zh) * | 2017-07-31 | 2018-08-28 | 百奥泰生物科技(广州)有限公司 | 针对TNF-α的抗体组合物及其应用 |
| KR20190024572A (ko) * | 2017-08-30 | 2019-03-08 | (주)셀트리온 | TNFα 관련 질환을 치료하기 위한 피하 투여 요법 |
| US12042538B2 (en) | 2017-09-19 | 2024-07-23 | Regeneron Pharmaceuticals, Inc. | Methods of reducing particle formation and compositions formed thereby |
| CN111491664A (zh) | 2017-09-20 | 2020-08-04 | 阿尔沃科技Hf公司 | 阿达木单抗的药物制剂 |
| JP7073486B2 (ja) | 2017-09-30 | 2022-05-23 | ▲拝▼西欧斯（北京）生物技▲術▼有限公司 | 興奮性神経毒性に関連した損傷の治療用ペプチド組成物 |
| EA201900360A1 (ru) * | 2017-12-29 | 2019-12-30 | Закрытое Акционерное Общество "Биокад" | ВОДНАЯ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ РЕКОМБИНАНТНОГО МОНОКЛОНАЛЬНОГО АНТИТЕЛА К ФНОα |
| TW202003036A (zh) * | 2018-03-23 | 2020-01-16 | 德商艾伯維德國有限及兩合公司 | 穩定水性抗-tau抗體調配物 |
| TWI853823B (zh) | 2018-07-02 | 2024-09-01 | 美商里珍納龍藥品有限公司 | 自混合物製備多肽之系統及方法 |
| KR20210089215A (ko) | 2018-11-07 | 2021-07-15 | 머크 샤프 앤드 돔 코포레이션 | 항-lag3 항체 및 항-pd-1 항체의 공동-제제 |
| AU2020244106A1 (en) * | 2019-03-18 | 2021-09-30 | Alvotech Hf | Aqueous formulations of TNF-alpha antibodies in high concentrations |
| EP4153234A1 (en) * | 2020-05-21 | 2023-03-29 | Shilpa Biologicals Private Limited | Pharmaceutical compositions comprising adalimumab |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6258562B1 (en) * | 1996-02-09 | 2001-07-10 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
| CN1326351A (zh) * | 1998-09-25 | 2001-12-12 | A+科学投资有限公司 | 应用某些药物治疗神经根损伤 |
| US20060153846A1 (en) * | 2002-08-16 | 2006-07-13 | Hans-Juergen Krause | Formulation of human antibodies for treating tnf-alpha associated disorders |
| US20080112953A1 (en) * | 2006-10-06 | 2008-05-15 | Amgen Inc. | Stable formulations |
Family Cites Families (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5237054A (en) * | 1987-02-20 | 1993-08-17 | Akzo Pharma | Stabilized aqueous composition containing antibodies |
| US5945098A (en) * | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
| US6277969B1 (en) * | 1991-03-18 | 2001-08-21 | New York University | Anti-TNF antibodies and peptides of human tumor necrosis factor |
| GB9122820D0 (en) * | 1991-10-28 | 1991-12-11 | Wellcome Found | Stabilised antibodies |
| ZA955642B (en) * | 1994-07-07 | 1997-05-06 | Ortho Pharma Corp | Lyophilized imaging agent formulation |
| US6090382A (en) * | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
| GB9610992D0 (en) * | 1996-05-24 | 1996-07-31 | Glaxo Group Ltd | Concentrated antibody preparation |
| US6171586B1 (en) * | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
| WO2000066160A1 (fr) * | 1999-04-28 | 2000-11-09 | Yamanouchi Pharmaceutical Co., Ltd. | Composition medicamenteuse parenterale a fragment d'anticorps monoclonal humanise et procede de stabilisation |
| DE10022092A1 (de) * | 2000-05-08 | 2001-11-15 | Aventis Behring Gmbh | Stabilisiertes Protein-Präparat und Verfahren zu seiner Herstellung |
| WO2002011753A1 (en) * | 2000-08-04 | 2002-02-14 | Chugai Seiyaku Kabushiki Kaisha | Protein injection preparations |
| UA81743C2 (uk) * | 2000-08-07 | 2008-02-11 | Центокор, Инк. | МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ |
| SE0003045D0 (sv) * | 2000-08-29 | 2000-08-29 | Probi Ab | New method |
| ES2332402T5 (es) * | 2000-10-12 | 2018-05-14 | Genentech, Inc. | Formulaciones de proteína concentradas de viscosidad reducida |
| US20030012786A1 (en) * | 2001-05-25 | 2003-01-16 | Teoh Leah S. | Use of anti-TNF antibodies as drugs in treating septic disorders of anemic patients |
| US20040156835A1 (en) * | 2001-05-30 | 2004-08-12 | Taiji Imoto | Protein preparation |
| CA2448218C (en) * | 2001-06-21 | 2012-05-29 | Genentech, Inc. | Sustained release formulation |
| JP4317010B2 (ja) * | 2001-07-25 | 2009-08-19 | ピーディーエル バイオファーマ，インコーポレイティド | ＩｇＧ抗体の安定な凍結乾燥医薬製剤 |
| ATE556591T1 (de) * | 2001-11-08 | 2012-05-15 | Abbott Biotherapeutics Corp | Stabile pharmazeutische flüssigformulierung von igg-antikörpern |
| AU2002359495A1 (en) * | 2001-11-30 | 2003-06-17 | Centocor, Inc. | Anti-tnf antibodies, compositions, methods and uses |
| GB0202633D0 (en) * | 2002-02-05 | 2002-03-20 | Delta Biotechnology Ltd | Stabilization of protein preparations |
| DE60334678D1 (de) * | 2002-02-14 | 2010-12-09 | Chugai Pharmaceutical Co Ltd | Antikörper enthaltende pharmazeutische lösungen |
| US20030161828A1 (en) * | 2002-02-19 | 2003-08-28 | Abbott Gmbh & Co. Kg | Use of TNF antagonists as drugs for the treatment of patients with an inflammatory reaction and without suffering from total organ failure |
| US20040009172A1 (en) * | 2002-04-26 | 2004-01-15 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
| EP1551875A4 (en) * | 2002-06-21 | 2006-06-28 | Biogen Idec Inc | TAMPON PREPARATIONS FOR CONCENTRATING ANTIBODIES AND METHODS FOR USE THEREOF |
| MY151032A (en) * | 2002-07-19 | 2014-03-31 | Abbott Lab S A | Treatment of tnf? related disorders |
| MY150740A (en) * | 2002-10-24 | 2014-02-28 | Abbvie Biotechnology Ltd | Low dose methods for treating disorders in which tnf? activity is detrimental |
| EP1592440A4 (en) * | 2003-02-10 | 2007-07-11 | Elan Pharm Inc | IMMUNOGLOBULIN PREPARATION AND METHOD OF PRODUCING THE SAME |
| RS51041B (sr) * | 2003-02-28 | 2010-10-31 | Ares Trading S.A. | Tečne formulacije tbp-1 proteina koji vezuju faktor tumorske nekroze |
| JP4607010B2 (ja) * | 2003-02-28 | 2011-01-05 | 中外製薬株式会社 | タンパク質含有安定化製剤 |
| HRP20050934B1 (hr) * | 2003-04-04 | 2014-09-26 | Genentech, Inc. | Formulacije s visokom koncentracijom antitijela i proteina |
| FR2853551B1 (fr) * | 2003-04-09 | 2006-08-04 | Lab Francais Du Fractionnement | Formulation stabilisante pour compositions d'immunoglobulines g sous forme liquide et sous forme lyophilisee |
| WO2005033143A1 (ja) * | 2003-10-01 | 2005-04-14 | Kyowa Hakko Kogyo Co., Ltd. | 抗体の安定化方法及び安定化された溶液状抗体製剤 |
| DE10355251A1 (de) * | 2003-11-26 | 2005-06-23 | Merck Patent Gmbh | Pharmazeutische Zubereitung enthaltend einen Antikörper gegen den EGF-Rezeptor |
| WO2005063291A1 (ja) * | 2003-12-25 | 2005-07-14 | Kirin Beer Kabushiki Kaisha | 抗体を含有する安定な水性医薬製剤 |
| DE602005004014T2 (de) * | 2004-03-12 | 2008-12-11 | Intercell Ag | Verfahren zur solubilisierung von peptid-mischungen |
| US7279448B2 (en) * | 2004-07-08 | 2007-10-09 | The United States Of America, As Represented By The Secretary Of Agriculture | Poly(hydroxy thioether) vegetable oil derivatives useful as lubricant additives |
| TW200621282A (en) * | 2004-08-13 | 2006-07-01 | Wyeth Corp | Stabilizing formulations |
| US7119876B2 (en) * | 2004-10-18 | 2006-10-10 | Asml Netherlands B.V. | Lithographic apparatus and device manufacturing method |
| JO3000B1 (ar) * | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
| TWI398272B (zh) * | 2005-03-08 | 2013-06-11 | Intervet Int Bv | 化學定義的安定劑 |
| KR101280273B1 (ko) * | 2005-04-18 | 2013-07-15 | 예다 리서치 앤드 디벨럽먼트 캄파니 리미티드 | 안정화된 항-ｂ형 간염 바이러스 (ｈｂｖ) 항체 제형 |
| KR20150055116A (ko) * | 2005-05-16 | 2015-05-20 | 애브비 바이오테크놀로지 리미티드 | 미란성 다발관절염의 치료를 위한 ｔｎｆ 억제제의 용도 |
| US20090148406A1 (en) * | 2005-07-02 | 2009-06-11 | Arecor Limited | Stable Aqueous Systems Comprising Proteins |
| MX2008001068A (es) * | 2005-07-29 | 2008-03-19 | Amgen Inc | Formulacion que inhibe la agregacion de proteina. |
| EA014513B1 (ru) * | 2005-08-03 | 2010-12-30 | Иммьюноджен, Инк. | Композиция иммуноконъюгата |
| US7790679B2 (en) * | 2005-08-05 | 2010-09-07 | Amgen Inc. | Pharmaceutical formulations |
| US20070041905A1 (en) * | 2005-08-19 | 2007-02-22 | Hoffman Rebecca S | Method of treating depression using a TNF-alpha antibody |
| NZ567286A (en) * | 2005-11-01 | 2012-03-30 | Abbott Biotechnolgy Ltd | Methods and compositions for diagnosing ankylosing spondylitis using biomarkers |
| WO2007076062A2 (en) * | 2005-12-21 | 2007-07-05 | Wyeth | Protein formulations with reduced viscosity and uses thereof |
| WO2007092772A2 (en) * | 2006-02-03 | 2007-08-16 | Medimmune, Inc. | Protein formulations |
| SI1986612T1 (sl) * | 2006-02-07 | 2013-01-31 | Shire Human Genetic Therapies, Inc. | Stabilizirana spojina glukocerebrosidaze |
| NZ611859A (en) * | 2006-04-05 | 2014-12-24 | Abbvie Biotechnology Ltd | Antibody purification |
| WO2007120656A2 (en) * | 2006-04-10 | 2007-10-25 | Abbott Biotechnology Ltd. | Uses and compositions for treatment of rheumatoid arthritis |
| WO2007120626A2 (en) * | 2006-04-10 | 2007-10-25 | Abbott Biotechnology Ltd. | Uses and compositions for treatment of ankylosing spondylitis |
| US20080118496A1 (en) * | 2006-04-10 | 2008-05-22 | Medich John R | Uses and compositions for treatment of juvenile rheumatoid arthritis |
| US9605064B2 (en) * | 2006-04-10 | 2017-03-28 | Abbvie Biotechnology Ltd | Methods and compositions for treatment of skin disorders |
| US20080131374A1 (en) * | 2006-04-19 | 2008-06-05 | Medich John R | Uses and compositions for treatment of rheumatoid arthritis |
| US20080003220A1 (en) * | 2006-04-21 | 2008-01-03 | Amgen, Inc. | Buffering agents for biopharmaceutical formulations |
| US20100021451A1 (en) * | 2006-06-08 | 2010-01-28 | Wong Robert L | Uses and compositions for treatment of ankylosing spondylitis |
| JP5535623B2 (ja) * | 2006-06-30 | 2014-07-02 | アッヴィ バイオテクノロジー リミテッド | 自動注射装置 |
| KR20090060453A (ko) * | 2006-09-25 | 2009-06-12 | 메디뮨 엘엘씨 | 안정화된 항체 제제 및 그것의 용도 |
| TW200833357A (en) * | 2006-10-20 | 2008-08-16 | Amgen Inc | Stable polypeptide formulations |
| EP2684895A1 (en) * | 2006-10-27 | 2014-01-15 | AbbVie Biotechnology Ltd | Crystalline anti-hTNFalpha antibodies |
| CA2671571A1 (en) * | 2006-12-06 | 2008-06-12 | Wyeth | High protein concentration formulations containing mannitol |
| GB0700523D0 (en) * | 2007-01-11 | 2007-02-21 | Insense Ltd | The Stabilisation Of Proteins |
| CN103990116A (zh) * | 2007-04-26 | 2014-08-20 | 拜尔健康护理有限责任公司 | 稳定用于冷冻储藏的重组蛋白液体溶液的方法 |
| EP2165194A4 (en) * | 2007-05-31 | 2010-09-08 | Abbott Lab | BIOMARKERS FOR PREDICTING RESPONSABILITY TO TNF ALPHA INHIBITORS IN AUTOIMMUNE DISEASES |
| EP2150537A4 (en) * | 2007-06-01 | 2010-09-22 | Acologix Inc | STABLE PEPTIDE FORMULATION AT HIGH TEMPERATURE |
| WO2008150490A2 (en) * | 2007-06-01 | 2008-12-11 | Abbott Biotechnology Ltd. | Uses and compositions for treatment of psoriasis and crohn's disease |
| US20110014676A1 (en) * | 2007-06-29 | 2011-01-20 | Battelle Memorial Institute | Protein stabilization |
| CA2693771A1 (en) * | 2007-07-13 | 2009-01-22 | Abbott Biotechnology Ltd. | Methods and compositions for pulmonary administration of a tnf.alpha. inhibitor |
| US20090029794A1 (en) * | 2007-07-23 | 2009-01-29 | Yung-Hsiung Chen | Golf Club Head that Reduces a Contact Resistance with the Ground |
| WO2009020654A1 (en) * | 2007-08-08 | 2009-02-12 | Abbott Laboratories | Compositions and methods for crystallizing antibodies |
| EP2271671A2 (en) * | 2008-03-24 | 2011-01-12 | Abbott Biotechnology Ltd. | Tnf-alpha inhibitors for treating bone loss |
| JP5677411B2 (ja) * | 2009-04-29 | 2015-02-25 | アッヴィ バイオテクノロジー リミテッド | 自動注入機器 |
| US20120014956A1 (en) * | 2010-02-02 | 2012-01-19 | Hartmut Kupper | Methods and compositions for predicting responsiveness to treatment with tnf-alpha inhibitor |
-
2010
- 2010-05-03 WO PCT/US2010/033387 patent/WO2010129469A1/en not_active Ceased
- 2010-05-03 EP EP10772644.0A patent/EP2427211A4/en not_active Withdrawn
- 2010-05-03 CN CN201080030083.9A patent/CN102458469B/zh not_active Expired - Fee Related
- 2010-05-03 NZ NZ595694A patent/NZ595694A/xx not_active IP Right Cessation
- 2010-05-03 SG SG10201401995UA patent/SG10201401995UA/en unknown
- 2010-05-03 AU AU2010246168A patent/AU2010246168A1/en not_active Abandoned
- 2010-05-03 RU RU2011149327/15A patent/RU2560701C2/ru not_active IP Right Cessation
- 2010-05-03 CA CA2760185A patent/CA2760185A1/en not_active Abandoned
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- 2010-05-03 SG SG2011074341A patent/SG175188A1/en unknown
- 2010-05-03 US US12/772,595 patent/US20100278822A1/en not_active Abandoned
- 2010-05-03 KR KR1020117029006A patent/KR20120038406A/ko not_active Withdrawn
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- 2010-05-03 CN CN201410669393.5A patent/CN104490767A/zh active Pending
- 2010-05-04 TW TW104107818A patent/TW201526923A/zh unknown
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2011
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2014
- 2014-01-31 US US14/170,026 patent/US20140141007A1/en not_active Abandoned
- 2014-01-31 US US14/170,061 patent/US20140141008A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6258562B1 (en) * | 1996-02-09 | 2001-07-10 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
| CN1326351A (zh) * | 1998-09-25 | 2001-12-12 | A+科学投资有限公司 | 应用某些药物治疗神经根损伤 |
| US20060153846A1 (en) * | 2002-08-16 | 2006-07-13 | Hans-Juergen Krause | Formulation of human antibodies for treating tnf-alpha associated disorders |
| US20080112953A1 (en) * | 2006-10-06 | 2008-05-15 | Amgen Inc. | Stable formulations |
Non-Patent Citations (1)
| Title |
|---|
| HANNS-CHRISTIAN MAHLER ET AL: "Induction and analysis of aggregates in a liquid IgG1-antibody formulation", 《EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| SG175188A1 (en) | 2011-11-28 |
| CA2760185A1 (en) | 2010-11-11 |
| AU2010246168A1 (en) | 2011-11-10 |
| NZ595694A (en) | 2013-09-27 |
| WO2010129469A8 (en) | 2012-02-23 |
| JP2012526121A (ja) | 2012-10-25 |
| TWI480064B (zh) | 2015-04-11 |
| US20140141008A1 (en) | 2014-05-22 |
| WO2010129469A1 (en) | 2010-11-11 |
| NZ613809A (en) | 2015-02-27 |
| KR20120038406A (ko) | 2012-04-23 |
| TW201043263A (en) | 2010-12-16 |
| UY32609A (es) | 2010-12-31 |
| US20100278822A1 (en) | 2010-11-04 |
| RU2011149327A (ru) | 2013-06-10 |
| TW201526923A (zh) | 2015-07-16 |
| IL215643A0 (en) | 2012-01-31 |
| AR076748A1 (es) | 2011-07-06 |
| EP2427211A4 (en) | 2013-05-01 |
| EP2427211A1 (en) | 2012-03-14 |
| MX2011011772A (es) | 2012-02-08 |
| US20140141007A1 (en) | 2014-05-22 |
| CN102458469A (zh) | 2012-05-16 |
| CN102458469B (zh) | 2014-12-24 |
| RU2560701C2 (ru) | 2015-08-20 |
| SG10201401995UA (en) | 2014-08-28 |
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