ES3001561T3 - Pharmaceutical compositions containing clostridium difficile toxoids a and b - Google Patents
Pharmaceutical compositions containing clostridium difficile toxoids a and b Download PDFInfo
- Publication number
- ES3001561T3 ES3001561T3 ES16174817T ES16174817T ES3001561T3 ES 3001561 T3 ES3001561 T3 ES 3001561T3 ES 16174817 T ES16174817 T ES 16174817T ES 16174817 T ES16174817 T ES 16174817T ES 3001561 T3 ES3001561 T3 ES 3001561T3
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- Prior art keywords
- toxoid
- toxoids
- aggregation
- excipients
- tween
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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| HRP20180054T1 (hr) | 2007-09-14 | 2018-02-09 | Sanofi Pasteur Biologics, Llc | Farmaceutski pripravci koji sadrže toksoide clostridium difficile a i b |
| DK2753352T4 (da) | 2010-09-03 | 2022-09-12 | Valneva Austria Gmbh | Isoleret polypeptid af toxin a og toxin b proteinerne fra c. difficile og anvendelser deraf |
| GB201105981D0 (en) * | 2011-04-08 | 2011-05-18 | Glaxosmithkline Biolog Sa | Novel process |
| ES2968629T3 (es) * | 2011-04-22 | 2024-05-13 | Wyeth Llc | Composiciones relacionadas con una toxina mutante de Clostridium difficile y sus procedimientos |
| KR101135486B1 (ko) * | 2011-05-25 | 2012-04-13 | 함종욱 | 보툴리눔 에이형 독소의 액상제품 |
| BR122016023101B1 (pt) | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| KR102149206B1 (ko) | 2012-11-08 | 2020-08-31 | 세센 바이오, 아이엔씨. | 인터루킨-6의 길항제 및 이의 용도 |
| HRP20190711T1 (hr) | 2012-12-05 | 2019-05-31 | Glaxosmithkline Biologicals S.A. | Imunogeni pripravak |
| CN111729077A (zh) | 2013-03-14 | 2020-10-02 | 武田疫苗股份有限公司 | 减毒活甲病毒制剂的组合物和方法 |
| CA2907156A1 (en) * | 2013-03-15 | 2014-09-18 | Sanofi Pasteur, Inc. | Toxins, compositions and related methods |
| BR112015023332A2 (pt) * | 2013-03-15 | 2017-08-22 | Sanofi Pasteur Inc | Toxóide, composições e método relacionados |
| EP3007724B1 (en) * | 2013-06-14 | 2023-07-05 | Sanofi Pasteur Inc. | Compositions and methods of immunizing against c. difficile |
| BR112015031541A2 (pt) * | 2013-06-17 | 2017-07-25 | De Staat Der Nederlanden Vert Door De Mini Van Vws Miniie Van Volksgezondheid Welzijn En Sport | métodos para o impedimento da agregação de componentes virais |
| US9930893B2 (en) * | 2014-02-10 | 2018-04-03 | The Johns Hopkins University | Inhibitors of DXP synthase and methods of use thereof |
| UA122673C2 (uk) | 2014-11-07 | 2020-12-28 | Елевен Байотерапьютікс, Інк. | Антитіло, що специфічно зв'язується з людським il-6 |
| US20180110849A1 (en) | 2015-05-15 | 2018-04-26 | Sanofi Pasteur, Inc. | Methods for immunizing against clostridium difficile |
| BE1023343B1 (nl) * | 2015-05-20 | 2017-02-09 | Mycartis Nv | Opslagbuffer |
| KR20180116359A (ko) | 2016-02-23 | 2018-10-24 | 세센 바이오, 아이엔씨. | 인터루킨-6의 길항제 제제 및 이의 용도 |
| PL3432916T3 (pl) | 2016-09-13 | 2020-04-30 | Allergan, Inc. | Niebiałkowo stabilzowane kompozycje toksyny clostridium |
| ES2986389T3 (es) * | 2018-05-21 | 2024-11-11 | Chugai Pharmaceutical Co Ltd | Formulación liofilizada sellada en un vial de vidrio |
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| US4879218A (en) * | 1982-09-13 | 1989-11-07 | Virginia Tech Intellectual Properties, Inc. | Antibody for C.difficile |
| US5736139A (en) * | 1989-10-31 | 1998-04-07 | Ochidian Pharmaceuticals, Inc. | Treatment of Clostridium difficile induced disease |
| JPH03193735A (ja) | 1989-12-22 | 1991-08-23 | Shionogi & Co Ltd | グリコペプチド系抗生物質の安定化組成物 |
| ES2104845T3 (es) * | 1991-10-16 | 1997-10-16 | Schering Corp | Composiciones lipofilas de sales de antibioticos oligosacaridos. |
| AU4646393A (en) | 1992-06-23 | 1994-01-24 | Interactive Biologics Associates | Pharmaceutical composition containing botulinum b complex |
| US5562909A (en) | 1993-07-12 | 1996-10-08 | Massachusetts Institute Of Technology | Phosphazene polyelectrolytes as immunoadjuvants |
| US5902565A (en) * | 1993-12-24 | 1999-05-11 | Csl Limited | Spray dried vaccine preparation comprising aluminium adsorbed immunogens |
| US5512547A (en) * | 1994-10-13 | 1996-04-30 | Wisconsin Alumni Research Foundation | Pharmaceutical composition of botulinum neurotoxin and method of preparation |
| JPH08333277A (ja) | 1995-06-05 | 1996-12-17 | Hoechst Japan Ltd | ヒト血液凝固第ｘｉｉｉ因子の安定化された水性液製剤 |
| CN1195993A (zh) * | 1995-07-07 | 1998-10-14 | 奥拉瓦克斯有限公司 | 抗胃肠疾病的鼻内接种 |
| US5932223A (en) | 1996-09-26 | 1999-08-03 | Merck & Co., Inc. | Rotavirus vaccine formulations |
| EP0892054B1 (en) * | 1997-06-20 | 2006-11-29 | Intervet International BV | Clostridium perfringens vaccine |
| DE69829400T2 (de) * | 1997-10-20 | 2006-04-13 | Acambis, Inc., Cambridge | Passive immunisierung gegen durch clostridium difficile verursachte krankheit |
| US6969520B2 (en) * | 1997-10-20 | 2005-11-29 | Acambis Inc. | Active immunization against clostridium difficile disease |
| EP1568378B1 (en) * | 1997-10-20 | 2016-03-16 | Sanofi Pasteur Biologics, LLC | Immunization against Clostridium difficile disease |
| US6013635A (en) * | 1998-05-28 | 2000-01-11 | Synsorb Biotech, Inc. | Treatment of C. difficile toxin B associated conditions |
| JP2000117967A (ja) * | 1998-10-16 | 2000-04-25 | Fuji Photo Film Co Ltd | インクジェット記録方法 |
| FR2791895B1 (fr) | 1999-03-23 | 2001-06-15 | Pasteur Merieux Serums Vacc | Utilisation de trehalose pour stabiliser un vaccin liquide |
| DK1187629T3 (da) * | 1999-04-19 | 2005-01-17 | Glaxosmithkline Biolog Sa | Adjuvanssammensætning omfattende saponin og et immunostimulerende oligonucleotid |
| US6599715B1 (en) * | 1999-05-12 | 2003-07-29 | The Regents Of The University Of California | Real time viability detection of bacterial spores |
| US7780967B2 (en) * | 2000-02-08 | 2010-08-24 | Allergan, Inc. | Reduced toxicity Clostridial toxin pharmaceutical compositions |
| EP3192528A1 (en) | 2002-02-14 | 2017-07-19 | Chugai Seiyaku Kabushiki Kaisha | Formulation of anti-il6r antibody-containing solutions comprising a sugar as a stabilizer |
| WO2003088946A1 (en) * | 2002-04-19 | 2003-10-30 | The Regents Of The University Of Michigan | Polymer compositions that stabilize and control the release of formaldehyde-treated vaccine antigens |
| US20040235139A1 (en) * | 2002-12-23 | 2004-11-25 | Demain Arnold L. | Clostridium difficile culture and toxin production methods |
| DE10333317A1 (de) * | 2003-07-22 | 2005-02-17 | Biotecon Therapeutics Gmbh | Formulierung für Proteinarzneimittel ohne Zusatz von humanem Serumalbumin (HSA) |
| WO2005035573A1 (ja) | 2003-10-09 | 2005-04-21 | Chugai Seiyaku Kabushiki Kaisha | タンパク質溶液の安定化方法 |
| CN102139099A (zh) * | 2004-07-26 | 2011-08-03 | 莫茨药物股份两合公司 | 包含肉毒杆菌神经毒素的治疗组合物 |
| JP2008515996A (ja) * | 2004-10-13 | 2008-05-15 | イリプサ， インコーポレイテッド | 毒素結合性オリゴ糖および重合体粒子を含有する医薬組成物 |
| FR2881139A1 (fr) * | 2005-01-26 | 2006-07-28 | Agronomique Inst Nat Rech | Composition pour la lyophilisation de proteines |
| US8137677B2 (en) | 2005-10-06 | 2012-03-20 | Allergan, Inc. | Non-protein stabilized clostridial toxin pharmaceutical compositions |
| BRPI0613001B8 (pt) | 2005-10-06 | 2021-05-25 | Allergan Inc | composições farmacêuticas de toxina clostrídica estabilizada por uma não-proteína |
| WO2007044809A2 (en) * | 2005-10-11 | 2007-04-19 | Botulinum Toxin Research Associates, Inc. | Albumin-free botulinum toxin based pharmaceutical compositions containing a hyaluronidase and methods of use |
| EP2086581B1 (en) | 2006-11-07 | 2014-08-13 | Sanofi Pasteur Biologics, LLC | Stabilization of vaccines by lyophilization |
| HRP20180054T1 (hr) | 2007-09-14 | 2018-02-09 | Sanofi Pasteur Biologics, Llc | Farmaceutski pripravci koji sadrže toksoide clostridium difficile a i b |
| JP2012510497A (ja) * | 2008-12-03 | 2012-05-10 | ベーリンガー インゲルハイム フェトメディカ ゲゼルシャフト ミット ベシュレンクテル ハフツング | ワクチンの生産方法 |
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