NZ511408A - Flt4 (VEGFR-3) as a target for tumor imaging and anti-tumor therapy - Google Patents
Flt4 (VEGFR-3) as a target for tumor imaging and anti-tumor therapyInfo
- Publication number
- NZ511408A NZ511408A NZ511408A NZ51140899A NZ511408A NZ 511408 A NZ511408 A NZ 511408A NZ 511408 A NZ511408 A NZ 511408A NZ 51140899 A NZ51140899 A NZ 51140899A NZ 511408 A NZ511408 A NZ 511408A
- Authority
- NZ
- New Zealand
- Prior art keywords
- flt4
- compound
- fragment
- polypeptide
- cells
- Prior art date
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Classifications
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/179—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1858—Platelet-derived growth factor [PDGF]
- A61K38/1866—Vascular endothelial growth factor [VEGF]
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
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Landscapes
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
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| PCT/US1999/023525 WO2000021560A1 (en) | 1998-10-09 | 1999-10-08 | Flt4 (VEGFR-3) AS A TARGET FOR TUMOR IMAGING AND ANTI-TUMOR THERAPY |
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| NZ529063A NZ529063A (en) | 1998-10-09 | 1999-10-08 | Flt4 (VEGFR-3) as a target for tumor imaging and anti-tumor therapy |
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| US6818220B1 (en) | 1994-11-14 | 2004-11-16 | Licentia Ltd. | Vascular endothelial growth factor C (VEGF-C) protein and gene mutants thereof, and uses thereof |
| US7727761B2 (en) | 1995-08-01 | 2010-06-01 | Vegenics Limited | Vascular endothelial growth factor C (VEGF-C) protein and gene, mutants thereof, and uses thereof |
| US6361946B1 (en) | 1997-02-05 | 2002-03-26 | Licentia Ltd | Vascular endothelial growth factor C (VEGF-C) protein and gene, mutants thereof, and uses thereof |
| JPH11514976A (ja) | 1995-09-08 | 1999-12-21 | ジェネンテク・インコーポレイテッド | Ｖｅｇｆ−関連タンパク質 |
| US7125714B2 (en) | 1997-02-05 | 2006-10-24 | Licentia Ltd. | Progenitor cell materials and methods |
| EP1119371B1 (en) * | 1998-10-09 | 2010-11-24 | Vegenics Limited | Flt4 (VEGFR-3) AS A TARGET FOR TUMOR IMAGING AND ANTI-TUMOR THERAPY |
| US7223724B1 (en) | 1999-02-08 | 2007-05-29 | Human Genome Sciences, Inc. | Use of vascular endothelial growth factor to treat photoreceptor cells |
| EP1553414A1 (en) * | 1999-04-13 | 2005-07-13 | Medarex, Inc. | Methods for the diagnosis and treatment of metastatic prostate tumors |
| DE60131146T2 (de) | 2000-02-25 | 2008-03-06 | Ludwig Institute For Cancer Research | Material und verfahren die hybridvaskularendothelwachstumfaktoren dns und proteine enthalten und screeningverfahren für modulatoren |
| WO2002011769A1 (en) | 2000-08-04 | 2002-02-14 | Human Genome Sciences, Inc. | Vascular endothelial growth factor 2 |
| US7611711B2 (en) | 2001-01-17 | 2009-11-03 | Vegenics Limited | VEGFR-3 inhibitor materials and methods |
| JP4669984B2 (ja) * | 2001-01-19 | 2011-04-13 | ベジェニクス リミテッド | 腫瘍画像化のターゲットとしてのＦ１ｔ４（ＶＥＧＦＲ−３）および抗腫瘍療法 |
| EP1385864B1 (en) | 2001-04-13 | 2010-06-09 | Human Genome Sciences, Inc. | Anti-VEGF-2 antibodies |
| US7109165B2 (en) | 2001-05-18 | 2006-09-19 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
| US9994853B2 (en) | 2001-05-18 | 2018-06-12 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
| EP1411983A4 (en) * | 2001-06-26 | 2006-06-21 | Imclone Systems Inc | BISPECIFIC ANTIBODIES BINDING TO VEGF RECEPTORS |
| US20030113324A1 (en) * | 2001-10-01 | 2003-06-19 | Kari Alitalo | Neuropilin/VEGF-C/VEGFR-3 materials and methods |
| US9657294B2 (en) | 2002-02-20 | 2017-05-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| EP1432724A4 (en) * | 2002-02-20 | 2006-02-01 | Sirna Therapeutics Inc | INTERFERENCE MEDIATION INHIBITION OF GENE RNA FROM MAP KINASE |
| US9181551B2 (en) | 2002-02-20 | 2015-11-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| WO2005049852A2 (en) * | 2003-11-17 | 2005-06-02 | University Of Florida | Methods and compositions for inducing apoptosis |
| ATE452188T1 (de) | 2004-02-10 | 2010-01-15 | Sirna Therapeutics Inc | Rna-interferenz-vermittelte hemmung der genexpression unter verwendung multifunktioneller sina (short interfering nucleic acid) |
| WO2005087177A2 (en) | 2004-03-05 | 2005-09-22 | Ludwig Institute For Cancer Research | Chimeric anti-vegf-d antibodies and humanized anti-vegf-d antibodies and methods of using same |
| US10508277B2 (en) | 2004-05-24 | 2019-12-17 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
| DE602006020881D1 (de) | 2005-08-15 | 2011-05-05 | Vegenics Pty Ltd | Enen eigenschaften |
| US9201063B2 (en) | 2006-11-16 | 2015-12-01 | General Electric Company | Sequential analysis of biological samples |
| US7629125B2 (en) | 2006-11-16 | 2009-12-08 | General Electric Company | Sequential analysis of biological samples |
| US8305579B2 (en) * | 2006-11-16 | 2012-11-06 | Thomas Pirrie Treynor | Sequential analysis of biological samples |
| US9677125B2 (en) | 2009-10-21 | 2017-06-13 | General Electric Company | Detection of plurality of targets in biological samples |
| US9328162B2 (en) | 2010-02-25 | 2016-05-03 | Schepens Eye Research Institute | Therapeutic compositions for the treatment of dry eye disease |
| DK2632472T3 (en) | 2010-10-29 | 2018-03-19 | Sirna Therapeutics Inc | RNA INTERFERENCE-MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERRING NUCLEIC ACIDS (SINA) |
| US20150246118A1 (en) | 2012-10-26 | 2015-09-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Lyve-1 antagonists for preventing or treating a pathological condition associated with lymphangiogenesis |
| HUE048687T2 (hu) | 2013-02-18 | 2020-08-28 | Vegenics Pty Ltd | Ligandum kötõ molekulák és alkalmazásaik |
| US10274503B2 (en) | 2013-05-08 | 2019-04-30 | Vegenics Pty Limited | Methods of using VEGF-C biomarkers for age-related macular degeneration (AMD) diagnosis |
| KR102131370B1 (ko) | 2013-10-18 | 2020-07-08 | 삼성전자주식회사 | Vegf-c에 특이적으로 결합하는 폴리펩타이드 및 그의 용도 |
| CN114262683B (zh) * | 2022-03-01 | 2022-06-17 | 中国科学院动物研究所 | 一种表达vegfr3 d2多肽的细菌制剂及其构建方法和应用 |
Family Cites Families (43)
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| US4543439A (en) | 1982-12-13 | 1985-09-24 | Massachusetts Institute Of Technology | Production and use of monoclonal antibodies to phosphotyrosine-containing proteins |
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| CA1329156C (en) | 1987-03-11 | 1994-05-03 | Ian Farquhar Campbell Mckenzie | Immunoglobulin conjugates |
| EP1762623A1 (en) | 1988-01-22 | 2007-03-14 | ZymoGenetics, Inc. | Methods for producing biologically active peptide dimers |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| CA2011450C (en) | 1989-03-07 | 2002-06-04 | Tadatsugu Taniguchi | Recombinant b-chain of the il-2 receptor |
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| AU1411092A (en) | 1991-01-31 | 1992-09-07 | Cor Therapeutics, Inc. | Domains of extracellular region of human platelet derived growth factor receptor polypeptides |
| US5256766A (en) | 1991-02-19 | 1993-10-26 | The Regents Of The University Of California | Recombinant thrombin receptor and related pharmaceuticals |
| SG49753A1 (en) | 1991-02-22 | 1998-06-15 | American Cyanamid Co | Identification of a novel human receptor tyrosine kinase gene |
| US5231001A (en) | 1991-03-14 | 1993-07-27 | The United States Of America As Represented By The Department Of Health And Human Services | Trk tyrosine kinase receptor is the physiological receptor for nerve growth factor |
| US5367057A (en) | 1991-04-02 | 1994-11-22 | The Trustees Of Princeton University | Tyrosine kinase receptor flk-2 and fragments thereof |
| US5185438A (en) | 1991-04-02 | 1993-02-09 | The Trustees Of Princeton University | Nucleic acids encoding hencatoporetic stem cell receptor flk-2 |
| US5270458A (en) | 1991-04-02 | 1993-12-14 | The Trustees Of Princeton University | Nucleic acids encoding fragments of hematopoietic stem cell receptor flk-2 |
| AU669124B2 (en) | 1991-09-18 | 1996-05-30 | Kyowa Hakko Kirin Co., Ltd. | Process for producing humanized chimera antibody |
| JPH07506242A (ja) | 1992-01-09 | 1995-07-13 | ヘルシンキ ユニバーシティ ホルディング リミテッド | Ｔｉｅ，新規内皮細胞受容体チロシンキナーゼ |
| AU3482493A (en) | 1992-01-22 | 1993-09-01 | New England Deaconess Hospital | Novel protein tyrosine kinases |
| US6331302B1 (en) | 1992-01-22 | 2001-12-18 | Genentech, Inc. | Protein tyrosine kinase agonist antibodies |
| US5635177A (en) | 1992-01-22 | 1997-06-03 | Genentech, Inc. | Protein tyrosine kinase agonist antibodies |
| US5660827A (en) | 1992-03-05 | 1997-08-26 | Board Of Regents, The University Of Texas System | Antibodies that bind to endoglin |
| US6824777B1 (en) | 1992-10-09 | 2004-11-30 | Licentia Ltd. | Flt4 (VEGFR-3) as a target for tumor imaging and anti-tumor therapy |
| US5776755A (en) | 1992-10-09 | 1998-07-07 | Helsinki University Licensing, Ltd. | FLT4, a receptor tyrosine kinase |
| CA2145985C (en) | 1992-10-28 | 2003-09-16 | Napoleone Ferrara | Vascular endothelial cell growth factor antagonists |
| US5712395A (en) | 1992-11-13 | 1998-01-27 | Yissum Research Development Corp. | Compounds for the treatment of disorders related to vasculogenesis and/or angiogenesis |
| US5763441A (en) | 1992-11-13 | 1998-06-09 | Sugen, Inc. | Compounds for the treatment of disorders related to vasculogenesis and/or angiogenesis |
| DE4337197C1 (de) | 1993-10-30 | 1994-08-25 | Biotest Pharma Gmbh | Verfahren zur selektiven Herstellung von Hybridomazellinien, die monoklonale Antikörper mit hoher Zytotoxizität gegen humanes CD16-Antigen produzieren, sowie Herstellung bispezifischer monoklonaler Antikörper unter Verwendung derartiger monoklonaler Antikörper und des CD30-HRS-3-Antikörpers zur Therapie menschlicher Tumore |
| US5700823A (en) | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| US6608182B1 (en) | 1994-03-08 | 2003-08-19 | Human Genome Sciences, Inc. | Human vascular endothelial growth factor 2 |
| CN1267550C (zh) | 1994-03-08 | 2006-08-02 | 人体基因组科学有限公司 | 血管内皮生长因子2 |
| GB9410534D0 (en) | 1994-05-26 | 1994-07-13 | Lynxvale Ltd | Improvements in or relating to growth factor inhibitors |
| ES2263152T3 (es) * | 1994-06-09 | 2006-12-01 | Licentia Oy | Anticuerpo monoclonal contra el receptor flt4 tirosina quinasa y su uso en diagnostico y terapia. |
| US5763733A (en) | 1994-10-13 | 1998-06-09 | Enzon, Inc. | Antigen-binding fusion proteins |
| US6645933B1 (en) * | 1995-08-01 | 2003-11-11 | Helsinki University Licensing Ltd. Oy | Receptor ligand VEGF-C |
| WO1998033917A1 (en) | 1994-11-14 | 1998-08-06 | The Ludwig Institute For Cancer Research | Vascular endothelial growth factor c (vegf-c) protein and gene, mutants thereof, and uses thereof |
| JPH11514976A (ja) | 1995-09-08 | 1999-12-21 | ジェネンテク・インコーポレイテッド | Ｖｅｇｆ−関連タンパク質 |
| US6100071A (en) | 1996-05-07 | 2000-08-08 | Genentech, Inc. | Receptors as novel inhibitors of vascular endothelial growth factor activity and processes for their production |
| AU3968597A (en) * | 1996-08-02 | 1998-02-25 | Children's Medical Center Corporation | Method of regulating the female reproductive system through angiogenesis inhibitors |
| ES2327440T3 (es) | 1996-08-23 | 2009-10-29 | Vegenics Limited | Factor recombinante de crecimiento de las celulas endoteliales vasculares-d (vegf-d). |
| US7947472B2 (en) | 1997-12-24 | 2011-05-24 | Vegenics Limited | Expression vectors and cell lines expressing vascular endothelial growth factor D |
| EP1119371B1 (en) * | 1998-10-09 | 2010-11-24 | Vegenics Limited | Flt4 (VEGFR-3) AS A TARGET FOR TUMOR IMAGING AND ANTI-TUMOR THERAPY |
| KR101681886B1 (ko) | 2015-04-06 | 2016-12-12 | 서울대학교산학협력단 | 지르코니아 결합능을 가지는 펩타이드 |
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1999
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- 1999-10-08 CA CA2345276A patent/CA2345276C/en not_active Expired - Fee Related
- 1999-10-08 DK DK99956525.2T patent/DK1119371T3/da active
- 1999-10-08 AT AT99956525T patent/ATE489108T1/de active
- 1999-10-08 CN CNB998142859A patent/CN100340291C/zh not_active Expired - Fee Related
- 1999-10-08 DE DE69942981T patent/DE69942981D1/de not_active Expired - Lifetime
- 1999-10-08 NZ NZ511408A patent/NZ511408A/en unknown
- 1999-10-08 JP JP2000575533A patent/JP4841724B2/ja not_active Expired - Fee Related
- 1999-10-08 ES ES99956525T patent/ES2357406T3/es not_active Expired - Lifetime
- 1999-10-08 WO PCT/US1999/023525 patent/WO2000021560A1/en not_active Ceased
- 1999-10-08 AU AU13121/00A patent/AU774266B2/en not_active Ceased
- 1999-10-08 NZ NZ529063A patent/NZ529063A/en unknown
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2001
- 2001-04-06 NO NO20011759A patent/NO20011759L/no unknown
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2004
- 2004-09-03 AU AU2004208675A patent/AU2004208675B2/en not_active Ceased
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2011
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- 2011-08-17 JP JP2011178553A patent/JP5642637B2/ja not_active Expired - Fee Related
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2013
- 2013-04-18 US US13/865,711 patent/US20140072511A1/en not_active Abandoned
- 2013-05-07 JP JP2013097900A patent/JP2013209382A/ja active Pending
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2014
- 2014-10-01 US US14/504,028 patent/US20150158928A1/en not_active Abandoned
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2015
- 2015-04-06 JP JP2015077656A patent/JP2015157829A/ja active Pending
- 2015-12-29 US US14/982,422 patent/US20160184405A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP4841724B2 (ja) | 2011-12-21 |
| CN100340291C (zh) | 2007-10-03 |
| ES2357406T3 (es) | 2011-04-26 |
| JP2002527404A (ja) | 2002-08-27 |
| JP5642637B2 (ja) | 2014-12-17 |
| AU2004208675B2 (en) | 2006-03-02 |
| NZ529063A (en) | 2005-07-29 |
| JP5784310B2 (ja) | 2015-09-24 |
| DE69942981D1 (de) | 2011-01-05 |
| AU774266B2 (en) | 2004-06-24 |
| US20160184405A1 (en) | 2016-06-30 |
| CN1329504A (zh) | 2002-01-02 |
| CA2345276C (en) | 2011-03-29 |
| JP2012019790A (ja) | 2012-02-02 |
| AU2004208675A1 (en) | 2004-09-30 |
| US20100278736A1 (en) | 2010-11-04 |
| EP1119371B1 (en) | 2010-11-24 |
| US8444957B2 (en) | 2013-05-21 |
| DK1119371T3 (da) | 2011-03-07 |
| NO20011759D0 (no) | 2001-04-06 |
| US20150158928A1 (en) | 2015-06-11 |
| ATE489108T1 (de) | 2010-12-15 |
| WO2000021560A1 (en) | 2000-04-20 |
| AU1312100A (en) | 2000-05-01 |
| JP2011121957A (ja) | 2011-06-23 |
| CA2345276A1 (en) | 2000-04-20 |
| EP1119371A1 (en) | 2001-08-01 |
| WO2000021560A9 (en) | 2000-09-21 |
| NO20011759L (no) | 2001-06-11 |
| JP2015157829A (ja) | 2015-09-03 |
| US20140072511A1 (en) | 2014-03-13 |
| JP2013209382A (ja) | 2013-10-10 |
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| RENW | Renewal (renewal fees accepted) | ||
| PSEA | Patent sealed | ||
| CORR | Corrigendum |
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