ES2342239T3 - Expresion y exportacion de angiostatina y de endostatina como inmunofusinas. - Google Patents
Expresion y exportacion de angiostatina y de endostatina como inmunofusinas. Download PDFInfo
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- ES2342239T3 ES2342239T3 ES99942468T ES99942468T ES2342239T3 ES 2342239 T3 ES2342239 T3 ES 2342239T3 ES 99942468 T ES99942468 T ES 99942468T ES 99942468 T ES99942468 T ES 99942468T ES 2342239 T3 ES2342239 T3 ES 2342239T3
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/515—Angiogenesic factors; Angiogenin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- 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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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6435—Plasmin (3.4.21.7), i.e. fibrinolysin
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
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- C12Y304/21007—Plasmin (3.4.21.7), i.e. fibrinolysin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- 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
-
- 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
- C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/81—Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
Landscapes
- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Animal Behavior & Ethology (AREA)
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- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Immunology (AREA)
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- Diabetes (AREA)
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9788398P | 1998-08-25 | 1998-08-25 | |
| US97883P | 1998-08-25 |
Publications (1)
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|---|---|
| ES2342239T3 true ES2342239T3 (es) | 2010-07-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99942468T Expired - Lifetime ES2342239T3 (es) | 1998-08-25 | 1999-08-25 | Expresion y exportacion de angiostatina y de endostatina como inmunofusinas. |
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|---|---|
| US (3) | US20030139365A1 (enExample) |
| EP (1) | EP1107989B1 (enExample) |
| JP (3) | JP2002523036A (enExample) |
| CN (2) | CN100422332C (enExample) |
| AT (1) | ATE462725T1 (enExample) |
| AU (1) | AU761027B2 (enExample) |
| BR (1) | BR9913331A (enExample) |
| CA (1) | CA2339331C (enExample) |
| CZ (1) | CZ302303B6 (enExample) |
| DE (1) | DE69942207D1 (enExample) |
| DK (1) | DK1107989T3 (enExample) |
| ES (1) | ES2342239T3 (enExample) |
| HK (1) | HK1042503A1 (enExample) |
| HU (1) | HUP0103329A3 (enExample) |
| NO (1) | NO20010918L (enExample) |
| PL (1) | PL202057B1 (enExample) |
| PT (1) | PT1107989E (enExample) |
| RU (1) | RU2240328C2 (enExample) |
| WO (1) | WO2000011033A2 (enExample) |
| ZA (1) | ZA200101290B (enExample) |
Families Citing this family (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1705248A1 (en) * | 1997-10-01 | 2006-09-27 | G.D. Searle LLC. | Fusion proteins comprising an angiostatin moiety and their use in anti-tumour 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 |
| EP1071468B1 (en) * | 1998-04-15 | 2006-06-14 | Lexigen Pharmaceuticals Corp. | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with angiogenesis inhibitor |
| ES2342239T3 (es) * | 1998-08-25 | 2010-07-02 | Merck Patent Gmbh | Expresion y exportacion de angiostatina y de endostatina como inmunofusinas. |
| 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 |
| DE60025832T2 (de) | 1999-08-09 | 2006-08-31 | Emd Lexigen Research Center Corp., Billerica | Mehrere zytokin-antikörper komplexen |
| 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 |
| CN1406249B (zh) | 2000-02-11 | 2010-06-16 | 默克专利股份有限公司 | 增加基于抗体的融合蛋白的循环半衰期 |
| PT1294401E (pt) | 2000-06-29 | 2007-11-09 | Merck Patent Gmbh | Aumento das respostas imunológicas mediadas por proteínas de fusão anticorpo-citoquina por tratamento combinado com agentes que aumentam a captação de imunocitoquinas |
| JP2003000268A (ja) * | 2000-08-25 | 2003-01-07 | Pfizer Prod Inc | 血管新生にかかわる疾患を診断および治療するための方法および組成物 |
| EP1197550A3 (en) * | 2000-08-25 | 2002-11-20 | Pfizer Products 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 |
| AU2001288648A1 (en) * | 2000-09-01 | 2002-03-13 | Philadelphia, Health And Education Corporation | Methods and compositions for inhibiting angiogenesis |
| RU2003129528A (ru) * | 2001-03-07 | 2005-04-10 | Мерк Патент ГмбХ (DE) | Способ экспрессии белков, содержащих в качестве компонента гибридный изотип антитела |
| US6992174B2 (en) | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
| CN100503639C (zh) | 2001-05-03 | 2009-06-24 | 默克专利有限公司 | 重组肿瘤特异性抗体及其应用 |
| EP2354791A1 (en) | 2001-12-04 | 2011-08-10 | Merck Patent GmbH | Immunocytokines with modulated selectivity |
| US7893033B2 (en) | 2002-05-06 | 2011-02-22 | Board Of Regents, The University Of Texas System | Targeting proteins to deliver therapeutic or diagnostic reagents |
| PT1572748E (pt) * | 2002-12-17 | 2010-09-28 | Merck Patent Gmbh | Anticorpo humanizado (h14.18) do anticorpo 14.18 de rato que se liga ao gd2 e a sua fusão com a 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 |
| JP2007529410A (ja) * | 2003-08-29 | 2007-10-25 | チルドレンズ メディカル センター コーポレーション | 子宮内膜症を治療又は防止するためのペプチド |
| BRPI0418286A (pt) | 2003-12-30 | 2007-05-02 | Merck Patent Gmbh | proteìnas de fusão de il-7 |
| KR20060124656A (ko) | 2003-12-31 | 2006-12-05 | 메르크 파텐트 게엠베하 | 개선된 약물동태를 가지는 Ｆｃ-에리스로포이에틴 융합단백질 |
| JP2007517506A (ja) | 2004-01-05 | 2007-07-05 | イーエムディー・レキシゲン・リサーチ・センター・コーポレーション | 標的化用化合物 |
| WO2005070967A2 (en) * | 2004-01-22 | 2005-08-04 | 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. |
| CN101072793B (zh) | 2004-12-09 | 2012-06-20 | 默克专利有限公司 | 具有降低的免疫原性的il-7变体 |
| 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 |
| CN101292036B (zh) * | 2005-10-21 | 2016-04-13 | 弗·哈夫曼-拉罗切有限公司 | 用于重组表达多肽的方法 |
| CN101351475B (zh) * | 2005-12-30 | 2013-05-15 | 默克专利有限公司 | 具有提高的稳定性的白细胞介素12p40变体 |
| DK2270050T3 (da) | 2005-12-30 | 2013-08-12 | Merck Patent Gmbh | Anti-CD19-antistoffer med nedsat immunogenicitet |
| 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 |
| JP2012521784A (ja) * | 2009-03-30 | 2012-09-20 | ベーリンガー・インゲルハイム・インテルナツィオナール・ゲーエムバーハー | イヌＦｃ部分を含む融合タンパク質 |
| AU2010238858A1 (en) | 2009-04-22 | 2011-12-08 | 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 |
| EP3626739A1 (en) | 2011-06-24 | 2020-03-25 | 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 |
| AU2016341402B2 (en) * | 2015-10-23 | 2020-08-27 | Apogenix Ag | Single-chain GITR-receptor agonist proteins |
| EP3364995B1 (en) * | 2015-10-23 | 2021-08-04 | Apogenix AG | Single-chain cd27-receptor agonist proteins |
| CN108368511B (zh) * | 2015-10-23 | 2022-12-06 | 阿珀吉科吉尼科斯股份公司 | 单链cd137受体激动剂蛋白 |
| EP3383424A1 (en) | 2015-12-03 | 2018-10-10 | Deutsches Krebsforschungszentrum | Means and methods for treating and diagnosing fibrosis or fibrosis-associated diseases |
| WO2017220989A1 (en) | 2016-06-20 | 2017-12-28 | Kymab Limited | Anti-pd-l1 and il-2 cytokines |
| 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 |
| US11845784B2 (en) | 2018-04-17 | 2023-12-19 | Heidelberg Biotech Gmbh | Means and methods for the treatment of angiogenesis-, fibrosis- and cancer-related diseases with protein oligomers comprising NC-1-Fc |
| 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 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US5854205A (en) * | 1995-10-23 | 1998-12-29 | The Children's Medical Center Corporation | Therapeutic antiangiogenic compositions and methods |
| ES2206602T3 (es) * | 1995-10-23 | 2004-05-16 | The Children's Medical Center Corporation | Compuestos y metodos terapeuticos inhibidores de angiogenesis. |
| US6346510B1 (en) * | 1995-10-23 | 2002-02-12 | The Children's Medical Center Corporation | Therapeutic antiangiogenic endostatin compositions |
| EP1071468B1 (en) * | 1998-04-15 | 2006-06-14 | Lexigen Pharmaceuticals Corp. | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with angiogenesis inhibitor |
| MXPA00010151A (es) * | 1998-04-17 | 2002-08-06 | Lexigen Pharm Corp | Mejoramiento de las respuestas inmunes mediadas por proteina de fusion de anticuerpo-citocina mediante la soadministracion con inhibidores de prostaglandina. |
| KR20010052566A (ko) * | 1998-06-03 | 2001-06-25 | 윌리엄 뉴 | 엔도스타틴 단백질을 포함하는 단백질 올리고머 조성물 및이의 사용방법 |
| ES2342239T3 (es) * | 1998-08-25 | 2010-07-02 | Merck Patent Gmbh | Expresion y exportacion de angiostatina y de endostatina como inmunofusinas. |
| 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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1999
- 1999-08-25 ES ES99942468T patent/ES2342239T3/es not_active Expired - Lifetime
- 1999-08-25 EP EP99942468A patent/EP1107989B1/en not_active Expired - Lifetime
- 1999-08-25 HU HU0103329A patent/HUP0103329A3/hu unknown
- 1999-08-25 JP JP2000566305A patent/JP2002523036A/ja active Pending
- 1999-08-25 PL PL346703A patent/PL202057B1/pl unknown
- 1999-08-25 CZ CZ20010643A patent/CZ302303B6/cs not_active IP Right Cessation
- 1999-08-25 DE DE69942207T patent/DE69942207D1/de not_active Expired - Lifetime
- 1999-08-25 AU AU55836/99A patent/AU761027B2/en not_active Ceased
- 1999-08-25 WO PCT/US1999/019329 patent/WO2000011033A2/en not_active Ceased
- 1999-08-25 PT PT99942468T patent/PT1107989E/pt unknown
- 1999-08-25 CN CNB998124567A patent/CN100422332C/zh not_active Expired - Fee Related
- 1999-08-25 AT AT99942468T patent/ATE462725T1/de active
- 1999-08-25 CN CNA2008102106518A patent/CN101386651A/zh active Pending
- 1999-08-25 BR BR9913331-8A patent/BR9913331A/pt not_active IP Right Cessation
- 1999-08-25 HK HK02104318.5A patent/HK1042503A1/zh unknown
- 1999-08-25 RU RU2001105917/13A patent/RU2240328C2/ru not_active IP Right Cessation
- 1999-08-25 CA CA2339331A patent/CA2339331C/en not_active Expired - Fee Related
- 1999-08-25 DK DK99942468.2T patent/DK1107989T3/da active
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- 2001-02-23 NO NO20010918A patent/NO20010918L/no not_active Application Discontinuation
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2002
- 2002-11-12 US US10/292,418 patent/US20030139365A1/en not_active Abandoned
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2006
- 2006-06-27 US US11/475,627 patent/US8206718B2/en not_active Expired - Fee Related
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