CN101386651A - 表达以及分泌制管张素和内皮抑制素的免疫融合物 - Google Patents
表达以及分泌制管张素和内皮抑制素的免疫融合物 Download PDFInfo
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- C07K14/475—Growth factors; Growth regulators
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- C—CHEMISTRY; METALLURGY
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
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- C—CHEMISTRY; METALLURGY
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- C12Y—ENZYMES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
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| CNB998124567A Expired - Fee Related CN100422332C (zh) | 1998-08-25 | 1999-08-25 | 表达以及分泌制管张素和endostatin的免疫融合物 |
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| AU (1) | AU761027B2 (https=) |
| BR (1) | BR9913331A (https=) |
| CA (1) | CA2339331C (https=) |
| CZ (1) | CZ302303B6 (https=) |
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| WO (1) | WO2000011033A2 (https=) |
| ZA (1) | ZA200101290B (https=) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2303401A1 (en) * | 1997-10-01 | 1999-04-08 | G.D. Searle & Co. | Fusion proteins comprising an angiostatin moiety and their use in anti-tumor treatment |
| ES2590912T3 (es) | 1997-12-08 | 2016-11-24 | Merck Patent Gmbh | Proteínas de fusión heterodiméricas útiles para inmunoterapia dirigida y estimulación general del sistema inmunitario |
| US20030105294A1 (en) * | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
| ES2267263T3 (es) * | 1998-04-15 | 2007-03-01 | Emd Lexigen Research Center Corp. | Coadministracion de un inhibidor de la angiogenesis para reforzar la respuesta inmunologica por medio de la mediacion de una proteina de fusion de una citoquina con un anticuerpo. |
| AU761027B2 (en) * | 1998-08-25 | 2003-05-29 | Merck Patent Gmbh | Expression and export of angiostatin and endostatin as immunofusis |
| US7067110B1 (en) | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| SK782002A3 (en) * | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| MXPA02001417A (es) | 1999-08-09 | 2002-08-12 | Lexigen Pharm Corp | Complejos multiples de citosina-anticuerpo. |
| IL131803A0 (en) * | 1999-09-08 | 2001-03-19 | Genena Ltd | Method for improving the efficiency of cancer gene therapy |
| CA2391080A1 (en) | 1999-11-12 | 2001-05-25 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Erythropoietin forms with improved properties |
| US20050202538A1 (en) * | 1999-11-12 | 2005-09-15 | Merck Patent Gmbh | Fc-erythropoietin fusion protein with improved pharmacokinetics |
| HUP0204475A2 (en) | 2000-02-11 | 2003-04-28 | Merck Patent Gmbh | Enhancing the circulating half-life of antibody-based fusion proteins |
| KR20030064275A (ko) | 2000-06-29 | 2003-07-31 | 메르크 파텐트 게엠베하 | 면역싸이토카인 흡수 증강제와의 조합 치료에 의한항체-싸이토카인 융합 단백질 매개 면역 반응 증강 |
| EP1197550A3 (en) * | 2000-08-25 | 2002-11-20 | Pfizer Products Inc. | Methods and compositions for diagnosing and treating disorders involving angiogenesis |
| US6803211B2 (en) | 2000-08-25 | 2004-10-12 | Pfizer Inc. | Methods and compositions for diagnosing and treating disorders involving angiogenesis |
| US7160858B2 (en) | 2000-09-01 | 2007-01-09 | Philadelphia, Health And Education Corporation | Methods and compositions for inhibiting angiogenesis |
| ES2272537T3 (es) * | 2000-09-01 | 2007-05-01 | Philadelphia, Health And Education Corporation | Metodos y composiciones para inhibir la angiogenesis. |
| RU2003129528A (ru) | 2001-03-07 | 2005-04-10 | Мерк Патент ГмбХ (DE) | Способ экспрессии белков, содержащих в качестве компонента гибридный изотип антитела |
| WO2002079415A2 (en) | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
| EP1383785B1 (en) | 2001-05-03 | 2011-03-16 | Merck Patent GmbH | Recombinant tumor specific antibody and use thereof |
| DK1454138T3 (da) | 2001-12-04 | 2012-02-13 | Merck Patent Gmbh | Immunocytokiner med moduleret selektivitet |
| CN100543036C (zh) * | 2002-05-06 | 2009-09-23 | 得克萨斯州大学系统董事会 | 递送治疗或诊断试剂的导向蛋白质 |
| WO2004055056A1 (en) | 2002-12-17 | 2004-07-01 | Merck Patent Gmbh | Humanized antibody (h14.18) of the mouse 14.18 antibody binding to gd2 and its fusion with il-2 |
| US20050069521A1 (en) * | 2003-08-28 | 2005-03-31 | Emd Lexigen Research Center Corp. | Enhancing the circulating half-life of interleukin-2 proteins |
| US7524811B2 (en) | 2003-08-29 | 2009-04-28 | Children's Medical Center Corporation | Anti-angiogenic peptides from the N-terminus of endostatin |
| DE602004015142D1 (de) * | 2003-08-29 | 2008-08-28 | Childrens Medical Center | Antiangiogene peptide zur behandlung oder vorbeugung von endometriose |
| ES2305886T3 (es) | 2003-12-30 | 2008-11-01 | Merck Patent Gmbh | Proteinas de fusion de il-7 con porciones de anticuerpo, su preparacion y su empleo. |
| RU2370276C2 (ru) | 2003-12-31 | 2009-10-20 | Мерк Патент Гмбх | Fc-ЭРИТРОПОЭТИН СЛИТЫЙ БЕЛОК С УЛУЧШЕННОЙ ФАРМАКОКИНЕТИКОЙ |
| EP1702069A2 (en) | 2004-01-05 | 2006-09-20 | EMD Lexigen Research Center Corp. | Interleukin-12 targeted to oncofoetal fibronectin |
| AU2005206277B2 (en) | 2004-01-22 | 2011-06-23 | Merck Patent Gmbh | Anti-cancer antibodies with reduced complement fixation |
| JP2005301419A (ja) * | 2004-04-07 | 2005-10-27 | Hitachi Ltd | ディスクアレイ装置およびそのデータ処理方法 |
| US7670595B2 (en) * | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| ES2325344B1 (es) * | 2004-11-02 | 2010-06-09 | Univ Madrid Autonoma | Inhibidores de angiogenesis multifuncionales y multivalentes. |
| RU2437893C2 (ru) | 2004-12-09 | 2011-12-27 | Мерк Патент Гмбх | Варианты il-7 со сниженной иммуногенностью |
| RU2303997C2 (ru) * | 2005-09-27 | 2007-08-10 | Автономная некоммерческая организация Научно-технический центр "Фармбиопресс" | Конъюгат, обладающий избирательным действием по отношению к раковым опухолям |
| US20070104689A1 (en) * | 2005-09-27 | 2007-05-10 | Merck Patent Gmbh | Compositions and methods for treating tumors presenting survivin antigens |
| US7807409B2 (en) * | 2005-10-21 | 2010-10-05 | Roche Palo Alto Llc | Method for the recombinant expression of a polypeptide |
| PL1966238T3 (pl) | 2005-12-30 | 2012-09-28 | Merck Patent Gmbh | Warianty interleukiny-12p40 o polepszonej stabilności |
| ES2365046T3 (es) | 2005-12-30 | 2011-09-21 | Merck Patent Gmbh | Anticuerpos anti-cd19 con inmunogenicidad reducida. |
| EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| KR100888022B1 (ko) * | 2006-12-21 | 2009-03-09 | 재단법인 목암생명공학연구소 | 면역글로불린 Fc와 인간 아포리포단백질(a)크링글절편의 융합단백질 LK8Fc |
| US7981446B2 (en) * | 2007-11-26 | 2011-07-19 | Forhumantech. Co., Ltd. | Pharmaceutical compositions and methods for delivering nucleic acids into cells |
| AT506216B1 (de) | 2008-02-13 | 2009-07-15 | Peter Dr Hernuss | Zusammensetzung zur aufnahme über mukoses gewebe |
| RU2372354C1 (ru) * | 2008-02-28 | 2009-11-10 | Сергей Викторович Луценко | Слитый белок, имеющий активность ингибитора ангиогенеза |
| CA2754408A1 (en) * | 2009-03-30 | 2010-10-14 | Boehringer Ingelheim International Gmbh | Fusion proteins comprising canine fc portions |
| SG175233A1 (en) | 2009-04-22 | 2011-11-28 | Merck Patent Gmbh | Antibody fusion proteins with modified fcrn binding sites |
| KR101579318B1 (ko) * | 2010-04-29 | 2015-12-21 | 엘지전자 주식회사 | 태양 전지 및 그 제조 방법 |
| EP2723380B1 (en) | 2011-06-24 | 2019-08-21 | Stephen D. Gillies | Light chain immunoglobulin fusion proteins and methods of use thereof |
| RU2465283C1 (ru) * | 2011-06-27 | 2012-10-27 | Государственное бюджетное образовательное учреждение высшего профессионального образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения и социального развития Российской Федерации (ГБОУ ВПО Первый МГМУ им. И.М. Сеченова Минздравсоцразвити | Рекомбинантный гибридный полипептид, способный ингибировать пролиферацию эндотелиальных клеток человека in vitro, и способ его получения |
| EP2561888A1 (en) | 2011-08-23 | 2013-02-27 | Deutsches Krebsforschungszentrum | Protein comprising NC-1 for treating angiogenesis-related diseases |
| WO2014200312A1 (ko) * | 2013-06-14 | 2014-12-18 | 주식회사 엘지화학 | 유기태양전지 및 이의 제조방법 |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| US20160126391A1 (en) * | 2014-10-31 | 2016-05-05 | Byd Company Limited | Solar cell module and manufacturing method thereof |
| JP7033062B2 (ja) * | 2015-10-23 | 2022-03-09 | アポジェニックス アーゲー | 一本鎖cd137受容体アゴニストタンパク質 |
| EP3364995B1 (en) * | 2015-10-23 | 2021-08-04 | Apogenix AG | Single-chain cd27-receptor agonist proteins |
| CA3002741A1 (en) | 2015-10-23 | 2017-04-27 | Apogenix Ag | Single-chain gitr-receptor agonist proteins |
| JP7051697B2 (ja) | 2015-12-03 | 2022-04-11 | ハイデルベルク バイオテック ゲーエムベーハー | 線維症又は線維症関連疾患を治療及び診断するための手段及び方法 |
| RU2769282C2 (ru) | 2016-06-20 | 2022-03-30 | Кимаб Лимитед | Анти-PD-L1 и IL-2 цитокины |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| EP3534947A1 (en) | 2016-11-03 | 2019-09-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| CN109824779B (zh) * | 2017-11-23 | 2023-05-26 | 中山大学 | 一种包含IgG的Fc结构域和EB病毒包膜糖蛋白胞外域的融合蛋白 |
| CN112236448B (zh) | 2018-04-17 | 2025-02-11 | 海德堡生物技术有限公司 | 用包含NC-1-Fc的蛋白寡聚体治疗血管发生、纤维化和癌症相关疾病的手段和方法 |
| WO2020056152A1 (en) * | 2018-09-12 | 2020-03-19 | Chang Liu | Single chain constructs |
| US20240100134A1 (en) * | 2021-01-20 | 2024-03-28 | Monash University | Fusion proteins |
| US20250179209A1 (en) * | 2022-03-09 | 2025-06-05 | Immunofyx | Anti-cancer n-terminal fc conjugated immunotherapeutics |
Family Cites Families (12)
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| JPH05271294A (ja) * | 1992-01-24 | 1993-10-19 | Japan Found Cancer Res | ヒトプロヒビチンおよびそれをコードするdna |
| US5643783A (en) * | 1993-12-01 | 1997-07-01 | President And Fellows Of Harvard College | Collagen and uses therefor |
| US5541087A (en) * | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
| US5922852A (en) * | 1995-06-07 | 1999-07-13 | Oklahoma Medical Research Foundation | 3' untranslated region of the human prohibitin gene |
| US6346510B1 (en) * | 1995-10-23 | 2002-02-12 | The Children's Medical Center Corporation | Therapeutic antiangiogenic endostatin compositions |
| US5854205A (en) * | 1995-10-23 | 1998-12-29 | The Children's Medical Center Corporation | Therapeutic antiangiogenic compositions and methods |
| JP3840262B2 (ja) * | 1995-10-23 | 2006-11-01 | ザ チルドレンズ メディカル センター コーポレイション | 治療用の抗血管新生組成物および方法 |
| ES2267263T3 (es) * | 1998-04-15 | 2007-03-01 | Emd Lexigen Research Center Corp. | Coadministracion de un inhibidor de la angiogenesis para reforzar la respuesta inmunologica por medio de la mediacion de una proteina de fusion de una citoquina con un anticuerpo. |
| CN1305387A (zh) * | 1998-04-17 | 2001-07-25 | 利思进药品公司 | 通过共同给予前列腺素抑制剂增强抗体-细胞因子融合蛋白介导的免疫应答 |
| CA2331370A1 (en) * | 1998-06-03 | 1999-12-09 | The Children's Medical Center Corporation | Protein oligomer compositions comprising endostatin protein and methods of using the same |
| AU761027B2 (en) * | 1998-08-25 | 2003-05-29 | Merck Patent Gmbh | Expression and export of angiostatin and endostatin as immunofusis |
| US7524811B2 (en) * | 2003-08-29 | 2009-04-28 | Children's Medical Center Corporation | Anti-angiogenic peptides from the N-terminus of endostatin |
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