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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- C07K—PEPTIDES
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| WO2014180288A1 (zh) * | 2013-05-06 | 2014-11-13 | 中国药科大学 | 具有抑制肿瘤微环境血管再生和激活适应性免疫应答双功能的融合蛋白及其基因和应用 |
| 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 |
| WO1999065940A1 (en) * | 1998-06-17 | 1999-12-23 | Beth Israel Deaconess Medical Center | 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 |
| US8129504B2 (en) * | 2001-08-30 | 2012-03-06 | Biorexis Technology, Inc. | Oral delivery of modified transferrin fusion proteins |
| RU2004109222A (ru) | 2001-08-30 | 2005-10-20 | Байорексис Фармасьютикал Корпорейшн (Us) | Слитые белки модифицированного трансферрина |
| EP2261250B1 (en) | 2001-12-21 | 2015-07-01 | Human Genome Sciences, Inc. | GCSF-Albumin fusion proteins |
| AU2003244515A1 (en) * | 2002-02-07 | 2003-09-02 | Novozymes Delta Limited | Albumin-fused anti-angiogenesis peptides |
| EP1670428A4 (en) | 2003-10-10 | 2008-03-12 | Univ Southern California | HYBRID PROTEINS G-CSF-TRANSFERRIN |
| 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 |
| CA2583399A1 (en) * | 2004-10-14 | 2006-04-27 | 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 |
| WO2006119128A2 (en) * | 2005-04-29 | 2006-11-09 | Research Development Foundation | Vascular targeting of ocular neovascularization |
| US8227419B2 (en) | 2006-02-03 | 2012-07-24 | Crc For Asthma And Airways Ltd. | Method of treating conditions associated with airway tissue remodeling |
| 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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| EP2744831A4 (en) | 2015-03-11 |
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| WO2013025846A2 (en) | 2013-02-21 |
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| CN103998470A (zh) | 2014-08-20 |
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| US9290562B2 (en) | 2016-03-22 |
| BR112014008680A2 (pt) | 2017-06-13 |
| AU2012296588B2 (en) | 2017-07-27 |
| TR201802686T4 (tr) | 2018-03-21 |
| SI2744831T1 (en) | 2018-04-30 |
| EP2744831B1 (en) | 2017-12-06 |
| PT2744831T (pt) | 2018-03-05 |
| CA2849015A1 (en) | 2013-02-21 |
| AU2012296588A1 (en) | 2014-04-03 |
| JP6073888B2 (ja) | 2017-02-01 |
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