AU2010204547B2 - 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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- AU2010204547B2 AU2010204547B2 AU2010204547A AU2010204547A AU2010204547B2 AU 2010204547 B2 AU2010204547 B2 AU 2010204547B2 AU 2010204547 A AU2010204547 A AU 2010204547A AU 2010204547 A AU2010204547 A AU 2010204547A AU 2010204547 B2 AU2010204547 B2 AU 2010204547B2
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2014202190A AU2014202190B2 (en) | 2009-01-16 | 2014-04-22 | New Stable Formulations of Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor Fusion Protein |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14544009P | 2009-01-16 | 2009-01-16 | |
| US14543609P | 2009-01-16 | 2009-01-16 | |
| US61/145,436 | 2009-01-16 | ||
| US61/145,440 | 2009-01-16 | ||
| PCT/US2010/021235 WO2010083434A2 (en) | 2009-01-16 | 2010-01-15 | New stable formulations of recombinant human albumin-human granulocyte colony stimulating factor |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2014202190A Division AU2014202190B2 (en) | 2009-01-16 | 2014-04-22 | New Stable Formulations of Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor Fusion Protein |
Publications (2)
| Publication Number | Publication Date |
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| AU2010204547A1 AU2010204547A1 (en) | 2011-07-28 |
| AU2010204547B2 true AU2010204547B2 (en) | 2014-01-23 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
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| AU2010204547A Ceased AU2010204547B2 (en) | 2009-01-16 | 2010-01-15 | New stable formulations of recombinant human albumin-human granulocyte colony stimulating factor fusion protein |
| AU2010204552A Ceased AU2010204552B2 (en) | 2009-01-16 | 2010-01-15 | New stable formulations of recombinant human albumin-human granulocyte colony stimulating factor fusion protein |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| AU2010204552A Ceased AU2010204552B2 (en) | 2009-01-16 | 2010-01-15 | New stable formulations of recombinant human albumin-human granulocyte colony stimulating factor fusion protein |
Country Status (16)
| Country | Link |
|---|---|
| US (4) | US20100227818A1 (enExample) |
| EP (2) | EP2387420A2 (enExample) |
| JP (2) | JP2012515222A (enExample) |
| KR (2) | KR20110132326A (enExample) |
| CN (2) | CN102378635A (enExample) |
| AU (2) | AU2010204547B2 (enExample) |
| BR (2) | BRPI1005159A2 (enExample) |
| CA (2) | CA2749786A1 (enExample) |
| EA (2) | EA201190079A1 (enExample) |
| IL (2) | IL214052A0 (enExample) |
| MX (2) | MX2011007582A (enExample) |
| NZ (2) | NZ594056A (enExample) |
| SG (3) | SG172940A1 (enExample) |
| UA (2) | UA103221C2 (enExample) |
| WO (2) | WO2010083434A2 (enExample) |
| ZA (1) | ZA201105171B (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA103221C2 (uk) * | 2009-01-16 | 2013-09-25 | Тева Фармасьютікал Індастріз Лтд. | Стабільний склад рекомбінантного альбуміну людини-гранулоцитарного колонієстимулюючого фактора людини |
| 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 |
| KR102513760B1 (ko) * | 2010-06-07 | 2023-03-27 | 암젠 인크 | 약물 전달 장치 |
| 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 |
| WO2014113359A1 (en) * | 2013-01-15 | 2014-07-24 | Teva Pharmaceutical Industries Ltd. | Formulations of albu-bche, preparation and uses thereof |
| US20140271538A1 (en) | 2013-03-15 | 2014-09-18 | 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 |
| SG10202008673WA (en) | 2015-03-06 | 2020-10-29 | Beyondspring Pharmaceuticals Inc | Method of treating cancer associated with a ras mutation |
| BE1023343B1 (nl) * | 2015-05-20 | 2017-02-09 | Mycartis Nv | Opslagbuffer |
| CN109516981B (zh) | 2015-07-13 | 2019-10-22 | 大连万春布林医药有限公司 | 普那布林组合物 |
| JP2018522030A (ja) * | 2015-07-30 | 2018-08-09 | エンドール テクノロジーズ, エス.エレ.Endor Technologies, S.L. | 膵癌又は大腸癌の治療用コロニー刺激因子 |
| US10912748B2 (en) | 2016-02-08 | 2021-02-09 | Beyondspring Pharmaceuticals, Inc. | Compositions containing tucaresol or its analogs |
| KR20240091084A (ko) | 2016-06-06 | 2024-06-21 | 비욘드스프링 파마수티컬스, 인코포레이티드. | 호중구감소증을 줄이는 조성물 및 방법 |
| 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 |
| EP3544658B1 (en) | 2016-11-22 | 2024-07-03 | LTS Device Technologies Ltd | Apparatus for delivering a therapeutic substance |
| JP2020503363A (ja) | 2017-01-06 | 2020-01-30 | 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 | チューブリン結合化合物およびその治療的使用 |
| IL268305B2 (en) | 2017-02-01 | 2024-08-01 | Beyondspring Pharmaceuticals Inc | Plinabulin in combination with one or more g-csf drug for use in the therapeutic treatment of docetaxel-induced |
| WO2018187786A1 (en) * | 2017-04-07 | 2018-10-11 | 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 |
| US11786523B2 (en) | 2018-01-24 | 2023-10-17 | Beyondspring Pharmaceuticals, Inc. | Composition and method for reducing thrombocytopenia |
| AU2019216305B2 (en) * | 2018-02-01 | 2024-11-21 | Beyondspring Pharmaceuticals, Inc. | Composition and method for reducing chemotherapy-induced neutropenia via the administration of plinabulin and a G-CSF agent |
| US11583633B2 (en) | 2018-04-03 | 2023-02-21 | Amgen Inc. | Systems and methods for delayed drug delivery |
| EP3632487B1 (en) | 2018-10-05 | 2024-06-12 | LTS Device Technologies 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 |
| KR20220110747A (ko) * | 2019-12-05 | 2022-08-09 | 한미약품 주식회사 | 화학 요법 또는 방사선 요법으로 유도된 호중구감소증을 치료하는 방법 |
| 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 |
| JP2024513505A (ja) | 2021-04-09 | 2024-03-25 | 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 | 腫瘍を治療するための組成物及び方法 |
| US11723955B1 (en) * | 2022-05-13 | 2023-08-15 | Allgenesis Biotherapeutics Inc. | VEGFR fusion protein pharmaceutical composition |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993015199A1 (fr) * | 1992-01-31 | 1993-08-05 | Rhone-Poulenc Rorer S.A. | Nouveaux polypeptides biologiquement actifs, leur preparation et composition pharmaceutique les contenant |
| US20070244047A1 (en) * | 2001-12-21 | 2007-10-18 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US20080143751A1 (en) * | 2006-12-13 | 2008-06-19 | Yoshihiro Chosokabe | Apparatus, method, and computer program for displaying image, and apparatus, method, and computer program for providing image, and recording medium |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR8806573A (pt) * | 1987-04-09 | 1989-10-31 | Delta Biotechnology Ltd | Vetor de levedo |
| 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. |
| 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 |
| US6831158B2 (en) * | 2000-01-10 | 2004-12-14 | Maxygen Holdings Ltd. | G-CSF conjugates |
| US6555660B2 (en) * | 2000-01-10 | 2003-04-29 | Maxygen Holdings Ltd. | G-CSF conjugates |
| CA2405550A1 (en) | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2002302814A1 (en) * | 2001-06-08 | 2002-12-23 | Powderject Vaccines, Inc. | Spray freeze-dried compositions |
| WO2003076567A2 (en) * | 2002-03-05 | 2003-09-18 | 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 |
| KR20080071119A (ko) | 2005-08-12 | 2008-08-01 | 휴먼 게놈 사이언시즈, 인코포레이티드 | 알부민 융합 단백질 |
| CA2584927C (en) * | 2006-04-13 | 2011-02-08 | Wix Filtration Corp. | A body for actuating a standpipe of a replaceable filter element |
| UA103221C2 (uk) * | 2009-01-16 | 2013-09-25 | Тева Фармасьютікал Індастріз Лтд. | Стабільний склад рекомбінантного альбуміну людини-гранулоцитарного колонієстимулюючого фактора людини |
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2010
- 2010-01-15 UA UAA201109963A patent/UA103221C2/uk unknown
- 2010-01-15 SG SG2011050358A patent/SG172940A1/en unknown
- 2010-01-15 CA CA2749786A patent/CA2749786A1/en not_active Abandoned
- 2010-01-15 SG SG2011050366A patent/SG172941A1/en unknown
- 2010-01-15 US US12/688,754 patent/US20100227818A1/en not_active Abandoned
- 2010-01-15 CN CN2010800127233A patent/CN102378635A/zh active Pending
- 2010-01-15 WO PCT/US2010/021235 patent/WO2010083434A2/en not_active Ceased
- 2010-01-15 MX MX2011007582A patent/MX2011007582A/es active IP Right Grant
- 2010-01-15 AU AU2010204547A patent/AU2010204547B2/en not_active Ceased
- 2010-01-15 MX MX2011007583A patent/MX2011007583A/es active IP Right Grant
- 2010-01-15 US US12/688,655 patent/US8323634B2/en not_active Expired - Fee Related
- 2010-01-15 UA UAA201109961A patent/UA105201C2/uk unknown
- 2010-01-15 EA EA201190079A patent/EA201190079A1/ru unknown
- 2010-01-15 JP JP2011546399A patent/JP2012515222A/ja active Pending
- 2010-01-15 CN CN201080012749.8A patent/CN102395379B/zh not_active Expired - Fee Related
- 2010-01-15 SG SG2014003073A patent/SG196821A1/en unknown
- 2010-01-15 JP JP2011546396A patent/JP5753095B2/ja not_active Expired - Fee Related
- 2010-01-15 BR BRPI1005159A patent/BRPI1005159A2/pt not_active IP Right Cessation
- 2010-01-15 EP EP10701082A patent/EP2387420A2/en not_active Withdrawn
- 2010-01-15 KR KR1020117018153A patent/KR20110132326A/ko not_active Ceased
- 2010-01-15 NZ NZ594056A patent/NZ594056A/xx not_active IP Right Cessation
- 2010-01-15 NZ NZ594055A patent/NZ594055A/xx not_active IP Right Cessation
- 2010-01-15 AU AU2010204552A patent/AU2010204552B2/en not_active Ceased
- 2010-01-15 BR BRPI1004940A patent/BRPI1004940A2/pt not_active IP Right Cessation
- 2010-01-15 EP EP10700685A patent/EP2387419A2/en not_active Withdrawn
- 2010-01-15 KR KR1020117018162A patent/KR20110132327A/ko not_active Ceased
- 2010-01-15 EA EA201190080A patent/EA023344B1/ru not_active IP Right Cessation
- 2010-01-15 WO PCT/US2010/021241 patent/WO2010083439A2/en not_active Ceased
- 2010-01-15 CA CA2749802A patent/CA2749802C/en not_active Expired - Fee Related
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2011
- 2011-07-12 IL IL214052A patent/IL214052A0/en unknown
- 2011-07-12 IL IL214051A patent/IL214051A0/en unknown
- 2011-07-13 ZA ZA2011/05171A patent/ZA201105171B/en unknown
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2012
- 2012-10-25 US US13/660,915 patent/US8993519B2/en not_active Expired - Fee Related
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2014
- 2014-12-18 US US14/574,553 patent/US20150202268A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993015199A1 (fr) * | 1992-01-31 | 1993-08-05 | Rhone-Poulenc Rorer S.A. | Nouveaux polypeptides biologiquement actifs, leur preparation et composition pharmaceutique les contenant |
| US20030022308A1 (en) * | 1992-01-31 | 2003-01-30 | Aventis Behring L.L.C. | Fusion polypeptides of human serum albumin and a therapeutically active polypeptide |
| US20070244047A1 (en) * | 2001-12-21 | 2007-10-18 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US20080143751A1 (en) * | 2006-12-13 | 2008-06-19 | Yoshihiro Chosokabe | Apparatus, method, and computer program for displaying image, and apparatus, method, and computer program for providing image, and recording medium |
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