DK2744831T3 - TRANSFERRIN-TUMSTATIN-FUSION PROTEIN AND PROCEDURES FOR PREPARING AND USING THE SAME - Google Patents
TRANSFERRIN-TUMSTATIN-FUSION PROTEIN AND PROCEDURES FOR PREPARING AND USING THE SAME Download PDFInfo
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- DK2744831T3 DK2744831T3 DK12824616.2T DK12824616T DK2744831T3 DK 2744831 T3 DK2744831 T3 DK 2744831T3 DK 12824616 T DK12824616 T DK 12824616T DK 2744831 T3 DK2744831 T3 DK 2744831T3
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- tumstatin
- transferrin
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| JP2016522249A (ja) * | 2013-06-20 | 2016-07-28 | ノバルティス アーゲー | 脈絡膜血管新生の治療におけるｖｅｇｆアンタゴニストの使用 |
| US11058750B2 (en) | 2015-12-03 | 2021-07-13 | Mor Research Applications Ltd. | Compositions and methods for treatment of ocular diseases |
| KR101818151B1 (ko) | 2016-03-25 | 2018-01-16 | 한국과학기술원 | 트렌스페린을 포함하는 허혈성망막병증 예방 및 치료용 조성물 |
| CN109053899B (zh) * | 2017-12-22 | 2021-11-16 | 湖南远泰生物技术有限公司 | 一种含人转铁蛋白抗原表位序列的嵌合体抗原受体 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5672683A (en) | 1989-09-07 | 1997-09-30 | Alkermes, Inc. | Transferrin neuropharmaceutical agent fusion protein |
| US20050192242A1 (en) | 1995-10-11 | 2005-09-01 | Neal Zane C. | Therapeutic fusion protein transgenes |
| IL140239A0 (en) * | 1998-06-17 | 2002-02-10 | Beth Israel Hospital | Anti-angiogenic proteins and methods of use thereof |
| JP2003517847A (ja) | 1999-12-23 | 2003-06-03 | 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 | トランスフェリンポリヌクレオチド、ポリペプチド、および抗体 |
| CN1628126A (zh) | 2001-08-30 | 2005-06-15 | 比奥雷克西斯药物公司 | 经修饰的运铁蛋白融合蛋白 |
| US8129504B2 (en) * | 2001-08-30 | 2012-03-06 | Biorexis Technology, Inc. | Oral delivery of modified transferrin fusion proteins |
| CA2841097A1 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin and g-csf fusion proteins |
| US20060122374A1 (en) * | 2002-02-07 | 2006-06-08 | Peter Mertins | Albumin-fused anti-angiogenesis peptides |
| WO2005034877A2 (en) | 2003-10-10 | 2005-04-21 | University Of Southern California | G-csf transferrin fusion proteins |
| JP2007526322A (ja) * | 2004-03-02 | 2007-09-13 | マサチューセッツ インスティテュート オブ テクノロジー | ナノセル薬物送達系 |
| US20080207502A1 (en) | 2004-10-14 | 2008-08-28 | Sopherion Therapeutics, Inc. | Anti-Angiogenic Peptides and Methods of Use Thereof |
| WO2006049983A2 (en) | 2004-10-27 | 2006-05-11 | Biorexis Pharmaceutical Corporation | Peptide yy modified transferrin fusion proteins |
| CA2606989A1 (en) * | 2005-04-29 | 2006-11-09 | Research Development Foundation | Vascular targeting of ocular neovascularization |
| WO2007087689A1 (en) | 2006-02-03 | 2007-08-09 | Crc For Asthma And Airways Ltd | A method of modulating cellular activity and agents for use therein |
| CN101070349B (zh) * | 2007-05-22 | 2010-10-13 | 山西康宝生物制品股份有限公司 | 具有选择性杀伤肿瘤新生血管内皮细胞作用的融合蛋白与应用 |
| CN101092452A (zh) * | 2007-05-23 | 2007-12-26 | 哈尔滨医科大学 | 肿瘤抑素抗血管生成小分子多肽、融合蛋白及两者制备方法 |
| WO2009086132A2 (en) * | 2007-12-20 | 2009-07-09 | University Of Southern California | Design of spacers to increase the expression of recombinant fusion proteins |
| AU2012222833B2 (en) | 2011-03-03 | 2017-03-16 | Zymeworks Inc. | Multivalent heteromultimer scaffold design and constructs |
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| PL2744831T3 (pl) | 2018-05-30 |
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| US9290562B2 (en) | 2016-03-22 |
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| CN103998470A (zh) | 2014-08-20 |
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| AU2012296588A1 (en) | 2014-04-03 |
| BR112014008680A2 (pt) | 2017-06-13 |
| CA2849015A1 (en) | 2013-02-21 |
| US20140179612A1 (en) | 2014-06-26 |
| AU2012296588B2 (en) | 2017-07-27 |
| JP6073888B2 (ja) | 2017-02-01 |
| CA2849015C (en) | 2017-08-08 |
| EP2744831A2 (en) | 2014-06-25 |
| WO2013025846A3 (en) | 2013-05-02 |
| EP2744831B1 (en) | 2017-12-06 |
| SI2744831T1 (en) | 2018-04-30 |
| CN110105453A (zh) | 2019-08-09 |
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