KR20090113340A - 안정한 항체 제제 - Google Patents
안정한 항체 제제 Download PDFInfo
- Publication number
- KR20090113340A KR20090113340A KR1020097019642A KR20097019642A KR20090113340A KR 20090113340 A KR20090113340 A KR 20090113340A KR 1020097019642 A KR1020097019642 A KR 1020097019642A KR 20097019642 A KR20097019642 A KR 20097019642A KR 20090113340 A KR20090113340 A KR 20090113340A
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- KR
- South Korea
- Prior art keywords
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- Prior art date
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Cited By (4)
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| KR20140015208A (ko) * | 2012-07-25 | 2014-02-06 | 한미약품 주식회사 | 지속형 인슐린 및 인슐린분비 펩타이드의 복합체 액상 제제 |
| KR20140015207A (ko) * | 2012-07-25 | 2014-02-06 | 한미약품 주식회사 | 지속형 인슐린 결합체의 액상 제제 |
| KR20140018798A (ko) * | 2012-07-25 | 2014-02-13 | 한미약품 주식회사 | 지속형 인슐린분비 펩타이드 결합체 액상 제제 |
| KR20170115090A (ko) * | 2015-02-09 | 2017-10-16 | 유씨비 바이오파마 에스피알엘 | 약학 제제 |
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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 |
| US20160355591A1 (en) | 2011-05-02 | 2016-12-08 | Immunomedics, Inc. | Subcutaneous anti-hla-dr monoclonal antibody for treatment of hematologic malignancies |
| TW200838559A (en) * | 2006-11-29 | 2008-10-01 | Imclone Systems Inc | Insulin-like growth factor-1 receptor antagonists for modulation of weight and liposity |
| PE20090368A1 (es) | 2007-06-19 | 2009-04-28 | Boehringer Ingelheim Int | Anticuerpos anti-igf |
| EP3011953A1 (en) | 2008-10-29 | 2016-04-27 | Ablynx N.V. | Stabilised formulations of single domain antigen binding molecules |
| EP2346900A1 (en) | 2008-10-29 | 2011-07-27 | Wyeth LLC | Methods for purification of single domain antigen binding molecules |
| EP2358392B1 (en) * | 2008-11-12 | 2019-01-09 | MedImmune, LLC | Antibody formulation |
| EP2196476A1 (en) * | 2008-12-10 | 2010-06-16 | Novartis Ag | Antibody formulation |
| CN103396487A (zh) | 2008-12-12 | 2013-11-20 | 贝林格尔.英格海姆国际有限公司 | 抗igf抗体 |
| TWI505838B (zh) | 2010-01-20 | 2015-11-01 | Chugai Pharmaceutical Co Ltd | Stabilized antibody solution containing |
| WO2012028683A1 (en) | 2010-09-02 | 2012-03-08 | Novartis Ag | Antibody gel system for sustained drug delivery |
| JP6055412B2 (ja) * | 2010-09-17 | 2016-12-27 | バクスアルタ ゲーエムベーハー | 弱酸性〜中性のｐＨにおける、ヒスチジンを有する水性製剤を介した免疫グロブリンの安定化 |
| HRP20251174T1 (hr) | 2010-11-05 | 2025-11-21 | Novartis Ag | Postupci za liječenje psorijatičnog artritisa uporabom il-17 antagonista |
| JP6024025B2 (ja) | 2011-05-02 | 2016-11-09 | イミューノメディクス、インコーポレイテッドＩｍｍｕｎｏｍｅｄｉｃｓ， Ｉｎｃ． | 少容量投与用のアロタイプ選択抗体の限外濾過濃縮 |
| JP6526414B2 (ja) * | 2011-10-26 | 2019-06-05 | アムジエン・インコーポレーテツド | Ｕｖ光曝露から生じるタンパク質の改変と分解を減ずるまたは排除する方法 |
| LT2771031T (lt) | 2011-10-28 | 2018-08-27 | Prothena Biosciences Limited | Humanizuoti antikūnai, kurie atpažįsta alfa sinukleiną |
| UA115439C2 (uk) | 2012-01-27 | 2017-11-10 | Протена Біосаєнсиз Лімітед | Гуманізоване антитіло, яке розпізнає альфа-синуклеїн |
| UA118441C2 (uk) | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Антитіло, що розпізнає альфа-синуклеїн |
| CN104870469A (zh) | 2012-12-26 | 2015-08-26 | 沃克哈特有限公司 | 药物组合物 |
| US20140255413A1 (en) | 2013-03-07 | 2014-09-11 | Boehringer Ingelheim International Gmbh | Combination therapy for neoplasia treatment |
| US9700485B2 (en) | 2013-04-24 | 2017-07-11 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
| NL1040254C2 (en) * | 2013-05-17 | 2014-11-24 | Ablynx Nv | Stable formulations of immunoglobulin single variable domains and uses thereof. |
| US10513555B2 (en) * | 2013-07-04 | 2019-12-24 | Prothena Biosciences Limited | Antibody formulations and methods |
| US9603927B2 (en) | 2014-02-28 | 2017-03-28 | Janssen Biotech, Inc. | Combination therapies with anti-CD38 antibodies |
| US9732154B2 (en) | 2014-02-28 | 2017-08-15 | Janssen Biotech, Inc. | Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia |
| WO2015155694A1 (en) | 2014-04-08 | 2015-10-15 | Prothena Biosciences Limited | Blood-brain barrier shuttles containing antibodies recognizing alpha-synuclein |
| EP3227338A4 (en) | 2014-12-04 | 2018-05-16 | Janssen Biotech, Inc. | Anti-cd38 antibodies for treatment of acute myeloid leukemia |
| CR20170526A (es) | 2015-05-20 | 2018-04-03 | Janssen Biotech Inc | ANTICUERPOS ANTI-CD38 PARA EL TRATAMIENTO DE AMILOIDOSIS DE CADENA LIGERA y OTRAS ENFERMEDADES MALIGNAS HEMATOLÓGICAS POSITIVAS PARA CD38 |
| AR104847A1 (es) * | 2015-06-17 | 2017-08-16 | Lilly Co Eli | Formulación de anticuerpo anti-cgrp |
| US20170044265A1 (en) | 2015-06-24 | 2017-02-16 | Janssen Biotech, Inc. | Immune Modulation and Treatment of Solid Tumors with Antibodies that Specifically Bind CD38 |
| PL3827845T3 (pl) | 2015-11-03 | 2022-07-11 | Janssen Biotech, Inc. | Formulacje podskórne przeciwciał anty-cd38 i ich zastosowania |
| JP6992262B2 (ja) * | 2016-03-31 | 2022-02-15 | 東ソー株式会社 | 変性抗体測定試薬の製造方法 |
| WO2018187074A1 (en) | 2017-04-03 | 2018-10-11 | Immunomedics, Inc. | Subcutaneous administration of antibody-drug conjugates for cancer therapy |
| CA3079242A1 (en) | 2017-10-31 | 2019-05-09 | Janssen Biotech, Inc. | Methods of treating high risk multiple myeloma |
| MX2021009851A (es) | 2019-02-18 | 2021-09-10 | Lilly Co Eli | Formulacion de anticuerpos terapeuticos. |
| CN112206320B (zh) * | 2019-07-12 | 2025-02-25 | 鲁南制药集团股份有限公司 | 一种cd47单克隆抗体冻干粉制剂及其制备工艺 |
| CN113967195A (zh) * | 2020-07-22 | 2022-01-25 | 三生国健药业（上海）股份有限公司 | 抗her2/pd1双特异性抗体冻干制剂及其制备方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0565233A (ja) * | 1991-03-08 | 1993-03-19 | Mitsui Toatsu Chem Inc | モノクローナル抗体含有凍結乾燥製剤 |
| EP0590058B1 (en) * | 1991-06-14 | 2003-11-26 | Genentech, Inc. | HUMANIZED Heregulin ANTIBODy |
| US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| IL155002A0 (en) * | 2000-10-12 | 2003-10-31 | Genentech Inc | Reduced-viscosity concentrated protein formulations |
| ES2706902T3 (es) * | 2001-06-26 | 2019-04-01 | Amgen Inc | Anticuerpos para OPGL |
| ATE454137T1 (de) * | 2001-07-25 | 2010-01-15 | Facet Biotech Corp | Stabile lyophilisierte pharmazeutische formulierung des igg-antikörpers daclizumab |
| WO2003068259A1 (fr) * | 2002-02-14 | 2003-08-21 | Chugai Seiyaku Kabushiki Kaisha | Produits pharmaceutiques en solution contenant des anticorps |
| AU2004212344B2 (en) * | 2003-02-13 | 2009-05-07 | Pfizer Products Inc. | Uses of anti-insulin-like growth factor I receptor antibodies |
| US7638605B2 (en) * | 2003-05-01 | 2009-12-29 | ImClone, LLC | Fully human antibodies directed against the human insulin-like growth factor-1 receptor |
| AR046071A1 (es) * | 2003-07-10 | 2005-11-23 | Hoffmann La Roche | Anticuerpos contra el receptor i del factor de crecimiento de tipo insulinico y los usos de los mismos |
| CN1835975B (zh) * | 2003-08-13 | 2012-11-21 | 辉瑞产品公司 | 经修饰的人类igf-1r抗体 |
| CA2607663C (en) * | 2005-05-19 | 2014-08-12 | Amgen Inc. | Compositions and methods for increasing the stability of antibodies |
| MX2007016306A (es) * | 2005-06-15 | 2008-03-07 | Schering Corp | Formulaciones de anticuerpo anti-igf1r. |
| RU2008142359A (ru) * | 2006-03-28 | 2010-05-10 | Ф.Хоффманн-Ля Рош Аг (Ch) | Композиция человеческого моноклонального антитела к igf-1r |
-
2008
- 2008-03-20 UA UAA200909552A patent/UA96473C2/ru unknown
- 2008-03-20 CA CA002681743A patent/CA2681743A1/en not_active Abandoned
- 2008-03-20 EP EP08744136A patent/EP2136839A4/en not_active Withdrawn
- 2008-03-20 US US12/528,882 patent/US20100260766A1/en not_active Abandoned
- 2008-03-20 AU AU2008228823A patent/AU2008228823A1/en not_active Abandoned
- 2008-03-20 MX MX2009010179A patent/MX2009010179A/es not_active Application Discontinuation
- 2008-03-20 WO PCT/US2008/057718 patent/WO2008116103A2/en not_active Ceased
- 2008-03-20 EA EA200970880A patent/EA200970880A1/ru unknown
- 2008-03-20 CN CN200880009446A patent/CN101668540A/zh active Pending
- 2008-03-20 KR KR1020097019642A patent/KR20090113340A/ko not_active Abandoned
- 2008-03-20 BR BRPI0809112-9A patent/BRPI0809112A2/pt not_active IP Right Cessation
- 2008-03-20 JP JP2009554753A patent/JP2010522208A/ja active Pending
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2009
- 2009-08-10 IL IL200321A patent/IL200321A0/en unknown
- 2009-08-13 ZA ZA200905636A patent/ZA200905636B/xx unknown
- 2009-08-28 CR CR11005A patent/CR11005A/es not_active Application Discontinuation
- 2009-09-18 DO DO2009000222A patent/DOP2009000222A/es unknown
- 2009-09-18 TN TNP2009000382A patent/TN2009000382A1/fr unknown
- 2009-09-21 EC EC2009009642A patent/ECSP099642A/es unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140015208A (ko) * | 2012-07-25 | 2014-02-06 | 한미약품 주식회사 | 지속형 인슐린 및 인슐린분비 펩타이드의 복합체 액상 제제 |
| KR20140015207A (ko) * | 2012-07-25 | 2014-02-06 | 한미약품 주식회사 | 지속형 인슐린 결합체의 액상 제제 |
| KR20140018798A (ko) * | 2012-07-25 | 2014-02-13 | 한미약품 주식회사 | 지속형 인슐린분비 펩타이드 결합체 액상 제제 |
| KR20170115090A (ko) * | 2015-02-09 | 2017-10-16 | 유씨비 바이오파마 에스피알엘 | 약학 제제 |
Also Published As
| Publication number | Publication date |
|---|---|
| ECSP099642A (es) | 2009-11-30 |
| CN101668540A (zh) | 2010-03-10 |
| CA2681743A1 (en) | 2008-09-25 |
| UA96473C2 (ru) | 2011-11-10 |
| CR11005A (es) | 2010-08-05 |
| ZA200905636B (en) | 2010-10-27 |
| BRPI0809112A2 (pt) | 2014-08-26 |
| JP2010522208A (ja) | 2010-07-01 |
| EA200970880A1 (ru) | 2010-02-26 |
| DOP2009000222A (es) | 2009-12-15 |
| EP2136839A2 (en) | 2009-12-30 |
| EP2136839A4 (en) | 2010-04-07 |
| US20100260766A1 (en) | 2010-10-14 |
| WO2008116103A3 (en) | 2009-01-08 |
| MX2009010179A (es) | 2010-03-15 |
| WO2008116103A2 (en) | 2008-09-25 |
| TN2009000382A1 (en) | 2010-12-31 |
| IL200321A0 (en) | 2010-04-29 |
| AU2008228823A1 (en) | 2008-09-25 |
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