CA2749802C - New stable formulations of recombinant human albumin-human granulocyte colony stimulating factor fusion protein - Google Patents
New stable formulations of recombinant human albumin-human granulocyte colony stimulating factor fusion protein Download PDFInfo
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- CA2749802C CA2749802C CA2749802A CA2749802A CA2749802C CA 2749802 C CA2749802 C CA 2749802C CA 2749802 A CA2749802 A CA 2749802A CA 2749802 A CA2749802 A CA 2749802A CA 2749802 C CA2749802 C CA 2749802C
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| EA201190079A1 (ru) | 2009-01-16 | 2013-02-28 | Тева Фармасьютикал Индастриз, Лтд. | Новые стабильные составы рекомбинантного альбумина человека-гранулоцитарного колониестимулирующего фактора человека |
| EP2384759A1 (en) | 2010-05-06 | 2011-11-09 | Suomen Punainen Risti Veripalvelu | Sulphated hyaluronic acid in combination with G-CSF for use in mobilising blood stem cells |
| MX2012014180A (es) * | 2010-06-07 | 2013-05-06 | Amgen Inc | Dispositivo de administracion de farmacos. |
| CN102628869B (zh) * | 2012-04-19 | 2014-04-02 | 上海蓝怡科技有限公司 | 提高甲胎蛋白抗体冻干稳定性的制剂 |
| CA2896793A1 (en) | 2013-01-15 | 2014-07-24 | Teva Pharmaceutical Industries Ltd. | Formulations of albu-bche, preparation and uses thereof |
| WO2014147489A2 (en) | 2013-03-15 | 2014-09-25 | Teva Pharmaceutical Industries Ltd. | Recombinant human albumin-human granulocyte colony stimulating factor for the prevention of neutropenia in pediatric patients |
| MA40904A (fr) * | 2014-11-03 | 2017-09-12 | Hygeia Tech Inc | Compositions d'ester de phorbol et procédés pour traiter ou réduire la durée d'une cytopénie |
| KR102626155B1 (ko) | 2015-03-06 | 2024-01-17 | 비욘드스프링 파마수티컬스, 인코포레이티드. | Ras 돌연변이와 관련된 암의 치료 방법 |
| BE1023343B1 (nl) * | 2015-05-20 | 2017-02-09 | Mycartis Nv | Opslagbuffer |
| AU2016291708B2 (en) | 2015-07-13 | 2020-12-24 | Beyondspring Pharmaceuticals, Inc | Plinabulin compositions |
| EP3328415B1 (en) * | 2015-07-30 | 2020-11-25 | Endor Technologies, S.L. | Colony stimulating factor for use in pancreatic or colon cancer treatment |
| EP3413885A4 (en) | 2016-02-08 | 2019-09-18 | Beyondspring Pharmaceuticals, Inc. | COMPOSITIONS WITH TUCARESOL OR ITS ANALOG |
| SG11201810872UA (en) | 2016-06-06 | 2019-01-30 | Beyondspring Pharmaceuticals Inc | Composition and method for reducing neutropenia |
| CN106222221A (zh) * | 2016-08-05 | 2016-12-14 | 山东科兴生物制品有限公司 | 制备重组人粒细胞刺激因子原液的纯化方法 |
| US11278665B2 (en) | 2016-11-22 | 2022-03-22 | Eitan Medical Ltd. | Method for delivering a therapeutic substance |
| US11633393B2 (en) | 2017-01-06 | 2023-04-25 | Beyondspring Pharmaceuticals, Inc. | Tubulin binding compounds and therapeutic use thereof |
| US11400086B2 (en) | 2017-02-01 | 2022-08-02 | Beyondspring Pharmaceuticals, Inc. | Method of reducing chemotherapy-induced neutropenia |
| US20210088505A1 (en) * | 2017-04-07 | 2021-03-25 | La Jolla Institute For Allergy And Immunology | Unipotent Neutrophil Progenitor Cells, Methods of Preparation, and Uses Thereof |
| CN109420159A (zh) * | 2017-08-23 | 2019-03-05 | 江苏泰康生物医药有限公司 | 一种重组蛋白药物的新型稳定制剂 |
| JP7350015B2 (ja) | 2018-01-24 | 2023-09-25 | ビヨンドスプリング ファーマシューティカルズ，インコーポレイテッド | プリナブリンの投与による血小板減少症を軽減するための組成物および方法 |
| KR20200116477A (ko) * | 2018-02-01 | 2020-10-12 | 비욘드스프링 파마수티컬스, 인코포레이티드. | 플리나불린 및 g-csf 제제의 투여를 통해 화학요법-유도된 호중구감소증을 감소시키기 위한 조성물 및 방법 |
| US11583633B2 (en) | 2018-04-03 | 2023-02-21 | Amgen Inc. | Systems and methods for delayed drug delivery |
| US11357909B2 (en) | 2018-10-05 | 2022-06-14 | Eitan Medical Ltd. | Triggering sequence |
| CN111383745A (zh) * | 2018-12-29 | 2020-07-07 | 医渡云（北京）技术有限公司 | 计算机数据处理方法、装置、存储介质及设备 |
| 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 |
| CN112316120A (zh) * | 2019-08-05 | 2021-02-05 | 天津派格生物技术有限公司 | 使用低动员型g-csf有效且安全治疗粒细胞减少症的方法 |
| CA3160599A1 (en) * | 2019-12-05 | 2021-06-10 | Jae Hyuk Choi | Methods of treating chemotherapy or radiotherapy induced neutropenia |
| KR102485892B1 (ko) * | 2020-04-09 | 2023-01-09 | 주식회사 에이프릴바이오 | 고양이 과립구 집락 자극인자 및 혈청 알부민에 대한 항원 결합 단편을 포함하는 융합 단백질 및 이의 용도 |
| CN111751552B (zh) * | 2020-06-18 | 2022-09-16 | 广州市伊川生物科技有限公司 | 一种缺血修饰白蛋白测定试剂盒及其使用方法 |
| WO2022216908A1 (en) | 2021-04-09 | 2022-10-13 | Beyondspring Pharmaceuticals, Inc. | Therapeutic compositions and methods for treating tumors |
| US11723955B1 (en) | 2022-05-13 | 2023-08-15 | Allgenesis Biotherapeutics Inc. | VEGFR fusion protein pharmaceutical composition |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU213344B (en) | 1987-04-09 | 1997-05-28 | Delta Biotechnology Ltd | Process for producing of stable dezintegrating plasmid-vectors |
| JPH01215289A (ja) | 1988-02-22 | 1989-08-29 | Toa Nenryo Kogyo Kk | 遺伝子組換えによる正常ヒト血清アルブミンａの製造方法 |
| FR2649991B2 (fr) | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| FR2686900B1 (fr) | 1992-01-31 | 1995-07-21 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides ayant une activite de stimulation des colonies de granulocytes, leur preparation et compositions pharmaceutiques les contenant. |
| FR2686899B1 (fr) * | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| DE4242863A1 (de) * | 1992-12-18 | 1994-06-23 | Boehringer Mannheim Gmbh | Stabile lyophilisierte pharmazeutische Zubereitungen von G-CSF |
| DE19549232C2 (de) * | 1995-12-20 | 1998-05-20 | Boehringer Mannheim Gmbh | Verwendung von G-CSF in Kombination mit einem Chemotherapeutikum bei der Behandlung von Erkrankungen, die eine periphere Stammzelltransplantation erfordern |
| US7321023B2 (en) | 1997-11-07 | 2008-01-22 | Incyte Corporation | SP16 protein |
| EP1060746A4 (en) * | 1998-03-06 | 2002-06-19 | Chugai Pharmaceutical Co Ltd | PROTEIN-FREE PREPARATIONS |
| US6555660B2 (en) * | 2000-01-10 | 2003-04-29 | Maxygen Holdings Ltd. | G-CSF conjugates |
| US6831158B2 (en) | 2000-01-10 | 2004-12-14 | Maxygen Holdings Ltd. | G-CSF conjugates |
| AU2001266557A1 (en) | 2000-04-12 | 2001-10-23 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| CA2449593A1 (en) * | 2001-06-08 | 2002-12-19 | Powderject Vaccines, Inc. | Spray freeze-dried compositions |
| JP5424521B2 (ja) | 2001-12-21 | 2014-02-26 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | アルブミン融合タンパク質 |
| EP1572936A2 (en) * | 2002-03-05 | 2005-09-14 | Eli Lilly And Company | Heterologous g-csf fusion proteins |
| CN1241946C (zh) * | 2002-07-01 | 2006-02-15 | 美国福源集团 | 对多种细胞具刺激增生作用的人血清白蛋白重组融合蛋白 |
| CA2513213C (en) * | 2003-01-22 | 2013-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| WO2004082640A2 (en) | 2003-03-19 | 2004-09-30 | New Century Pharmaceuticals, Inc. | Human serum albumin conjugates with therapeutic compounds |
| US6972332B1 (en) * | 2004-05-20 | 2005-12-06 | Acura Pharmaceuticals, Inc. | Process for the production of opiates |
| EP1924596A4 (en) * | 2005-08-12 | 2009-07-29 | Human Genome Sciences Inc | ALBUM INFUSION PROTEINS |
| CA2584927C (en) * | 2006-04-13 | 2011-02-08 | Wix Filtration Corp. | A body for actuating a standpipe of a replaceable filter element |
| JP2008146587A (ja) * | 2006-12-13 | 2008-06-26 | Sony Corp | 表示装置、表示プログラム、表示方法、画像提供装置、画像提供プログラム、画像提供方法及び記録媒体 |
| EA201190079A1 (ru) | 2009-01-16 | 2013-02-28 | Тева Фармасьютикал Индастриз, Лтд. | Новые стабильные составы рекомбинантного альбумина человека-гранулоцитарного колониестимулирующего фактора человека |
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