CA2322592A1 - Use of a peptide or antibody in the manufacture of a medicament for treating an erbb protein mediated tumor in combination with irradiation - Google Patents
Use of a peptide or antibody in the manufacture of a medicament for treating an erbb protein mediated tumor in combination with irradiation Download PDFInfo
- Publication number
- CA2322592A1 CA2322592A1 CA002322592A CA2322592A CA2322592A1 CA 2322592 A1 CA2322592 A1 CA 2322592A1 CA 002322592 A CA002322592 A CA 002322592A CA 2322592 A CA2322592 A CA 2322592A CA 2322592 A1 CA2322592 A1 CA 2322592A1
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- egfr
- cells
- protein
- erbb
- tumor
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- A61K2039/572—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Marine Sciences & Fisheries (AREA)
- Cell Biology (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7678898P | 1998-03-04 | 1998-03-04 | |
| US09/111,681 | 1998-07-08 | ||
| US09/111,681 US6417168B1 (en) | 1998-03-04 | 1998-07-08 | Compositions and methods of treating tumors |
| US60/076,788 | 1998-07-08 | ||
| PCT/US1999/004777 WO1999044645A1 (en) | 1998-03-04 | 1999-03-04 | Compositions and methods of treating tumors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2322592A1 true CA2322592A1 (en) | 1999-09-10 |
Family
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Family Applications (1)
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| CA002322592A Expired - Lifetime CA2322592A1 (en) | 1998-03-04 | 1999-03-04 | Use of a peptide or antibody in the manufacture of a medicament for treating an erbb protein mediated tumor in combination with irradiation |
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| EP (2) | EP3034093B1 (enExample) |
| JP (2) | JP2002505309A (enExample) |
| AT (1) | ATE334702T1 (enExample) |
| AU (1) | AU757237C (enExample) |
| CA (1) | CA2322592A1 (enExample) |
| CY (1) | CY1105475T1 (enExample) |
| DE (1) | DE69932600T2 (enExample) |
| DK (1) | DK1058562T3 (enExample) |
| ES (2) | ES2551932T3 (enExample) |
| HK (1) | HK1225997A1 (enExample) |
| PT (1) | PT1058562E (enExample) |
| WO (1) | WO1999044645A1 (enExample) |
Families Citing this family (101)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030108545A1 (en) * | 1994-02-10 | 2003-06-12 | Patricia Rockwell | Combination methods of inhibiting tumor growth with a vascular endothelial growth factor receptor antagonist |
| US7060808B1 (en) * | 1995-06-07 | 2006-06-13 | Imclone Systems Incorporated | Humanized anti-EGF receptor monoclonal antibody |
| EP1445322B2 (en) | 1995-06-15 | 2012-06-06 | Crucell Holland B.V. | Packaging systems for human recombinant adenovirus to be used in gene therapy |
| US6417168B1 (en) | 1998-03-04 | 2002-07-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods of treating tumors |
| EP1745799B1 (en) | 1998-03-04 | 2015-09-02 | The Trustees of The University of Pennsylvania | Compositions and methods of treating tumors |
| US20030224001A1 (en) * | 1998-03-19 | 2003-12-04 | Goldstein Neil I. | Antibody and antibody fragments for inhibiting the growth of tumors |
| ZA200007412B (en) * | 1998-05-15 | 2002-03-12 | Imclone Systems Inc | Treatment of human tumors with radiation and inhibitors of growth factor receptor tyrosine kinases. |
| US6929946B1 (en) * | 1998-11-20 | 2005-08-16 | Crucell Holland B.V. | Gene delivery vectors provided with a tissue tropism for smooth muscle cells, and/or endothelial cells |
| US7625859B1 (en) * | 2000-02-16 | 2009-12-01 | Oregon Health & Science University | HER-2 binding antagonists |
| US7396810B1 (en) * | 2000-08-14 | 2008-07-08 | Oregon Health Sciences University | Compositions and methods for treating cancer by modulating HER-2 and EGF receptors |
| US7393823B1 (en) | 1999-01-20 | 2008-07-01 | Oregon Health And Science University | HER-2 binding antagonists |
| KR20020000223A (ko) * | 1999-05-14 | 2002-01-05 | 존 비. 랜디스 | 표피성장인자 수용체 길항제를 사용한 인간 난치성 종양의치료 방법 |
| US6913922B1 (en) * | 1999-05-18 | 2005-07-05 | Crucell Holland B.V. | Serotype of adenovirus and uses thereof |
| US20050232900A1 (en) * | 1999-05-18 | 2005-10-20 | Crucell Holland B.V. | Serotype of adenovirus and uses thereof |
| US20040013667A1 (en) * | 1999-06-25 | 2004-01-22 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
| US7041292B1 (en) | 1999-06-25 | 2006-05-09 | Genentech, Inc. | Treating prostate cancer with anti-ErbB2 antibodies |
| US20030086924A1 (en) * | 1999-06-25 | 2003-05-08 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
| CA2383493C (en) * | 1999-06-25 | 2010-08-10 | Genentech, Inc. | Treating prostate cancer with anti-erbb2 antibodies |
| US6949245B1 (en) * | 1999-06-25 | 2005-09-27 | Genentech, Inc. | Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies |
| EP1280923A2 (en) * | 2000-04-28 | 2003-02-05 | Millennium Pharmaceuticals, Inc. | 14094, a human trypsin family member and uses thereof |
| WO2002011677A2 (en) * | 2000-08-09 | 2002-02-14 | Imclone Systems Incorporated | Treatment of hyperproliferative diseases with epidermal growth factor receptor antagonists |
| US8071740B2 (en) * | 2000-11-17 | 2011-12-06 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis |
| US8039261B2 (en) * | 2000-11-17 | 2011-10-18 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis |
| US20050239738A1 (en) * | 2000-11-17 | 2005-10-27 | Rupert Schmidt-Ullrich | Genetic inhibition of epidermal growth factor receptor function and carcinoma cell radiosensitization |
| AU2003222427B8 (en) | 2000-11-17 | 2010-04-29 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same |
| US20100282634A1 (en) * | 2000-11-17 | 2010-11-11 | Dror Harats | Promoters Exhibiting Endothelial Cell Specificity and Methods of Using Same for Regulation of Angiogenesis |
| US20070286845A1 (en) * | 2000-11-17 | 2007-12-13 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis |
| US20080008704A1 (en) * | 2001-03-16 | 2008-01-10 | Mark Rubin | Methods of treating colorectal cancer with anti-epidermal growth factor antibodies |
| AU2002257132A1 (en) | 2001-04-06 | 2002-10-21 | The Trustees Of The University Of Pennsylvania | Erbb interface peptidomimetics and methods of use thereof |
| US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
| PT1392359E (pt) | 2001-05-11 | 2010-01-27 | Ludwig Inst For Cancer Res Ltd | Proteínas de ligação específica e suas utilizações |
| US7595378B2 (en) | 2001-06-13 | 2009-09-29 | Genmab A/S | Human monoclonal antibodies to epidermal growth factor receptor (EGFR) |
| WO2003012072A2 (en) * | 2001-08-03 | 2003-02-13 | The Trustees Of The University Of Pennsylvania | Monoclonal antibodies to activated erbb family members and methods of use thereof |
| AU2002365258A1 (en) * | 2001-10-12 | 2003-09-02 | University Of Vermont And State Agricultural College | Binding peptides specific for the extracellular domain of erbb2 and uses therefor |
| CA2463816C (en) * | 2001-10-19 | 2014-07-08 | Vascular Biogenics Ltd. | Polynucleotide constructs, pharmaceutical compositions and methods for targeted downregulation of angiogenesis and anticancer therapy |
| AU2002365396A1 (en) * | 2001-11-21 | 2003-06-10 | The Trustees Of The University Of Pennsylvania | Peptides, peptide compositions,and methods of use in binding p 185 |
| ES2335657T3 (es) * | 2002-04-25 | 2010-03-31 | Crucell Holland B.V. | Medios y metodos para la produccion de vectores de adenovirus. |
| US20030202973A1 (en) * | 2002-04-29 | 2003-10-30 | Dr. George Pieczenik | Treatment of refractory human tumors with epidermal growth factor receptor and HER1 mitogenic ligand (EGFRML) antagonists |
| US20040229380A1 (en) * | 2002-05-21 | 2004-11-18 | Po-Ying Chan-Hui | ErbB heterodimers as biomarkers |
| US7402397B2 (en) | 2002-05-21 | 2008-07-22 | Monogram Biosciences, Inc. | Detecting and profiling molecular complexes |
| US20040229294A1 (en) | 2002-05-21 | 2004-11-18 | Po-Ying Chan-Hui | ErbB surface receptor complexes as biomarkers |
| EP1513543B1 (en) | 2002-05-23 | 2010-10-06 | The Trustees of The University of Pennsylvania | Fas peptide mimetics and uses thereof |
| AU2003249728A1 (en) | 2002-07-03 | 2004-01-23 | The Curators Of The University Of Missouri | ErbB-2 RECEPTOR TARGETING PEPTIDE |
| EP2263691B1 (en) * | 2002-07-15 | 2012-08-29 | F.Hoffmann-La Roche Ag | Treatment of cancer with the recombinant humanized monoclonal anti-erbb2 antibody 2C4 (rhuMAb 2C4) |
| CA2506320A1 (en) * | 2002-11-21 | 2004-06-10 | Genentech, Inc. | Therapy of non-malignant diseases or disorders with anti-erbb2 antibodies |
| EP1622941A2 (en) * | 2003-03-20 | 2006-02-08 | ImClone Systems Incorporated | Method of producing an antibody to epidermal growth factor receptor |
| WO2004087887A2 (en) * | 2003-04-01 | 2004-10-14 | Monogram Biosciences, Inc. | Intracellular complexes as biomarkers |
| EP1681983A4 (en) * | 2003-10-14 | 2008-12-10 | Monogram Biosciences Inc | RECEPTOR TYROSINE KINASE SIGNAL PATH ANALYSIS FOR DIAGNOSIS AND THERAPY |
| WO2005090407A1 (en) * | 2004-03-19 | 2005-09-29 | Imclone Systems Incorporated | Human anti-epidermal growth factor receptor antibody |
| US20110142822A1 (en) * | 2004-06-14 | 2011-06-16 | Kussie Paul H | Crystal of egfr extracellular domain and cetuximab fab fragment, and uses thereof |
| AU2005294347A1 (en) * | 2004-10-05 | 2006-04-20 | Oregon Health And Science University | Compositions and methods for treating disease |
| US20070009972A1 (en) * | 2005-02-16 | 2007-01-11 | Ginger Chao | Epidermal growth factor receptor polypeptides and antibodies |
| CN103251946A (zh) | 2005-02-23 | 2013-08-21 | 健泰科生物技术公司 | 使用her二聚化抑制剂在癌症患者中延长病情进展前时间或存活 |
| TW200642695A (en) * | 2005-03-08 | 2006-12-16 | Genentech Inc | Methods for identifying tumors responsive to treatment with her dimerization inhibitors (HDIs) |
| WO2008089448A2 (en) | 2007-01-19 | 2008-07-24 | Cornell Presearch Foundation, Inc. | Methods and compositions for promoting survival & proliferation of endothelial cells & stimulating angiogenesis |
| WO2008091701A2 (en) | 2007-01-25 | 2008-07-31 | Dana-Farber Cancer Institute | Use of anti-egfr antibodies in treatment of egfr mutant mediated disease |
| HRP20131113T1 (hr) | 2007-02-16 | 2014-01-17 | Merrimack Pharmaceuticals, Inc. | Protutijela protiv erbb3 i njihova uporaba |
| PE20090681A1 (es) * | 2007-03-02 | 2009-06-10 | Genentech Inc | Prediccion de respuesta a un inhibidor her |
| CA2680854C (en) | 2007-03-15 | 2017-02-14 | Ludwig Institute For Cancer Research | Treatment method using egfr antibodies and src inhibitors and related formulations |
| ES2417148T3 (es) | 2007-06-08 | 2013-08-06 | Genentech, Inc. | Marcadores de expresión génica de la resistencia tumoral al tratamiento con inhibidor de HER2 |
| MX2010001757A (es) | 2007-08-14 | 2010-09-14 | Ludwig Inst Cancer Res | Anticuerpo monoclonal 175 que activa el receptor egf y derivados y usos del mismo. |
| MX2010003757A (es) * | 2007-10-16 | 2010-04-27 | Symphogen As | Composiciones que comprenden multimeros optimizados de her1 y her3 y sus metodos de uso. |
| US8557242B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | ERBB2 antibodies comprising modular recognition domains |
| GEP20156390B (en) | 2008-01-03 | 2015-11-10 | Scripps Research Inst | Antibody targeting through a modular recognition domain |
| US8574577B2 (en) | 2008-01-03 | 2013-11-05 | The Scripps Research Institute | VEGF antibodies comprising modular recognition domains |
| US8557243B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | EFGR antibodies comprising modular recognition domains |
| US8454960B2 (en) | 2008-01-03 | 2013-06-04 | The Scripps Research Institute | Multispecific antibody targeting and multivalency through modular recognition domains |
| BRPI0917871A2 (pt) * | 2008-08-15 | 2017-06-20 | Merrimack Pharmaceuticals Inc | agente terapêutico anti-erbb3 para uso em terapia de um tumor, métodos para predizer responsividade de um tumor de um agente terapêutco anti-erbb3, para selecionar terapia anti-erbb3 para um paciente, para predizer a resposta de células ao tratamento com um agente terapêutico, para identificar um biomarcador, e para evitar administração de uma droga para câncer anti-erbb3, e, kit para predizer a resposta das células ao tratamento com um agente terapêutico |
| AU2009308707A1 (en) * | 2008-10-31 | 2010-05-06 | Biogen Idec Ma Inc. | LIGHT targeting molecules and uses thereof |
| CN102356092B (zh) | 2009-03-20 | 2014-11-05 | 霍夫曼-拉罗奇有限公司 | 双特异性抗-her抗体 |
| JP2013522237A (ja) | 2010-03-11 | 2013-06-13 | メリマック ファーマシューティカルズ インコーポレーティッド | トリプルネガティブおよび基底様乳癌の治療におけるｅｒｂｂ３阻害剤の使用 |
| WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
| CA3051311A1 (en) | 2010-05-27 | 2011-12-01 | Genmab A/S | Monoclonal antibodies against her2 |
| EP2575880B1 (en) | 2010-05-27 | 2019-01-16 | Genmab A/S | Monoclonal antibodies against her2 epitope |
| WO2012009705A1 (en) | 2010-07-15 | 2012-01-19 | Zyngenia, Inc. | Ang-2 binding complexes and uses thereof |
| US9427458B2 (en) * | 2010-07-22 | 2016-08-30 | Consejo Nacional De Investigaciones Cientificas Y Tecnicas, Conicet | Methods for inhibiting cancer cell proliferation |
| TW201302793A (zh) | 2010-09-03 | 2013-01-16 | Glaxo Group Ltd | 新穎之抗原結合蛋白 |
| JP2014514314A (ja) | 2011-04-20 | 2014-06-19 | ゲンマブ エー／エス | Ｈｅｒ２およびｃｄ３に対する二重特異性抗体 |
| CN106432506A (zh) | 2011-05-24 | 2017-02-22 | 泽恩格尼亚股份有限公司 | 多价和单价多特异性复合物及其用途 |
| BR112014011886A2 (pt) | 2011-11-17 | 2017-05-16 | Bayer Medical Care Inc | métodos e técnicas para coleta, relatório e gestão de informações sobre procedimentos médicos diagnósticos |
| MX350957B (es) | 2011-11-23 | 2017-09-27 | Medimmune Llc | Moleculas de union especificas para her3 y usos de las mismas. |
| SG11201402510TA (en) | 2011-11-30 | 2014-06-27 | Genentech Inc | Erbb3 mutations in cancer |
| US10357566B2 (en) * | 2012-02-23 | 2019-07-23 | Daiichi Sankyo Europe Gmbh | HER3 inhibitor for modulating radiosensitivity |
| JP2015514710A (ja) | 2012-03-27 | 2015-05-21 | ジェネンテック， インコーポレイテッド | Ｈｅｒ３阻害剤に関する診断及び治療 |
| CN105163762B (zh) | 2013-03-14 | 2019-06-25 | 乔治敦大学 | 对神经毒剂的暴露的治疗 |
| EP3424530A1 (en) | 2013-03-15 | 2019-01-09 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
| EP4137519A1 (en) | 2013-08-09 | 2023-02-22 | The Trustees Of The University Of Pennsylvania | Fusion protein comprising ifn-gamma and anti-erbb antibody for the treatment of cancers |
| US11446516B2 (en) | 2013-08-09 | 2022-09-20 | The Trustees Of The University Of Pennsylvania | Methods of increasing response to cancer radiation therapy |
| WO2015048008A2 (en) | 2013-09-24 | 2015-04-02 | Medimmune, Llc | Binding molecules specific for her3 and uses thereof |
| WO2015100459A2 (en) | 2013-12-27 | 2015-07-02 | Merrimack Pharmaceuticals, Inc. | Biomarker profiles for predicting outcomes of cancer therapy with erbb3 inhibitors and/or chemotherapies |
| WO2015157634A1 (en) | 2014-04-11 | 2015-10-15 | Kolltan Pharmaceuticals, Inc. | Anti-erbb antibodies and methods of use thereof |
| US10947500B2 (en) * | 2014-06-27 | 2021-03-16 | Angiocrine Bioscience, Inc. | Neural cells expressing adenovirus E4ORF1, and methods of making and using the same |
| US20180171027A1 (en) * | 2015-04-17 | 2018-06-21 | Celldex Therapeutics, Inc. | Biomarkers Related to Treatment of Cancer with HER3 and EGFR Inhibitors |
| US10184006B2 (en) | 2015-06-04 | 2019-01-22 | Merrimack Pharmaceuticals, Inc. | Biomarkers for predicting outcomes of cancer therapy with ErbB3 inhibitors |
| KR20190140952A (ko) | 2017-04-24 | 2019-12-20 | 제넨테크, 인크. | 막관통 및 인접막 도메인에서의 erbb2/her2 돌연변이 |
| US11430558B2 (en) | 2017-07-07 | 2022-08-30 | Bayer Healthcare Llc | System, method, and computer program product for peer exchange of data between injection systems |
| WO2019185164A1 (en) | 2018-03-29 | 2019-10-03 | Hummingbird Bioscience Holdings Pte. Ltd. | Her3 antigen-binding molecules |
| EP4284335A1 (en) | 2021-02-01 | 2023-12-06 | RegenxBio Inc. | Gene therapy for neuronal ceroid lipofuscinoses |
| TWI843989B (zh) | 2021-02-19 | 2024-06-01 | 美商美威高能離子醫療系統公司 | 用於粒子治療系統之支架 |
| CA3231706A1 (en) * | 2021-09-13 | 2023-03-16 | The Board Of Regents Of The University Of Texas System | Lilrb2-specific monoclonal antibodies and methods of their use |
| AU2023375470A1 (en) * | 2022-11-08 | 2025-06-19 | Purdue Research Foundation | Multivalent multispecific conjugates and related compositions and methods of use |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US600377A (en) * | 1898-03-08 | Spring saddle-post | ||
| US4394448A (en) | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4241046A (en) | 1978-11-30 | 1980-12-23 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| WO1985001871A1 (en) * | 1983-10-26 | 1985-05-09 | Greer Sheldon B | Method and materials for sensitizing neoplastic tissue to radiation |
| US5637677A (en) * | 1987-07-16 | 1997-06-10 | The Trustees Of The University Of Pennsylvania | Biologically active compounds and methods of constructing and using the same |
| US5824311A (en) | 1987-11-30 | 1998-10-20 | Trustees Of The University Of Pennsylvania | Treatment of tumors with monoclonal antibodies against oncogene antigens |
| JP3040121B2 (ja) | 1988-01-12 | 2000-05-08 | ジェネンテク，インコーポレイテッド | 増殖因子レセプターの機能を阻害することにより腫瘍細胞を処置する方法 |
| US5720937A (en) | 1988-01-12 | 1998-02-24 | Genentech, Inc. | In vivo tumor detection assay |
| US5470571A (en) | 1988-01-27 | 1995-11-28 | The Wistar Institute | Method of treating human EGF receptor-expressing gliomas using radiolabeled EGF receptor-specific MAB 425 |
| US5200178A (en) | 1988-02-26 | 1993-04-06 | The General Hospital Corporation | Method for tumor detection |
| AU4128089A (en) | 1988-09-15 | 1990-03-22 | Rorer International (Overseas) Inc. | Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5108921A (en) | 1989-04-03 | 1992-04-28 | Purdue Research Foundation | Method for enhanced transmembrane transport of exogenous molecules |
| US5705157A (en) | 1989-07-27 | 1998-01-06 | The Trustees Of The University Of Pennsylvania | Methods of treating cancerous cells with anti-receptor antibodies |
| ATE153858T1 (de) | 1990-04-06 | 1997-06-15 | Univ Pennsylvania | Ligand für das neu-gen-produkt |
| US5367060A (en) | 1991-05-24 | 1994-11-22 | Genentech, Inc. | Structure, production and use of heregulin |
| WO1993014781A1 (en) | 1992-01-24 | 1993-08-05 | The Regents Of The University Of California | Novel peptides and method for altering the activity of allosteric proteins |
| ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
| EP0616812B1 (en) | 1993-03-24 | 1999-11-03 | Berlex Biosciences | Combination with anti-hormonal compounds and binding molecules for the treatment of cancer |
| US6733752B1 (en) * | 1994-03-30 | 2004-05-11 | The Trustees Of The University Of Pennsylvania | Prevention of tumors with monoclonal antibodies against neu |
| WO1994022478A1 (en) * | 1993-03-30 | 1994-10-13 | The Trustees Of The University Of Pennsylvania | PREVENTION OF TUMORS WITH MONOCLONAL ANTIBODIES AGAINST $i(NEU) |
| GB9401182D0 (en) | 1994-01-21 | 1994-03-16 | Inst Of Cancer The Research | Antibodies to EGF receptor and their antitumour effect |
| WO1995024190A2 (en) * | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
| WO1995030331A1 (en) | 1994-05-05 | 1995-11-16 | The Trustees Of The University Of Pennsylvania | Compositions and methods of treating tumors |
| US6100377A (en) | 1994-06-10 | 2000-08-08 | The Trustees Of The University Of Pennsylvania | Constrained peptides |
| US5707618A (en) | 1995-03-24 | 1998-01-13 | Genzyme Corporation | Adenovirus vectors for gene therapy |
| DE69533187T2 (de) | 1995-04-28 | 2005-07-07 | Hewlett-Packard Development Co., L.P., Houston | Elektrooptische Anzeigevorrichtung |
| US5663144A (en) * | 1995-05-03 | 1997-09-02 | The Trustees Of The University Of Pennsylvania | Compounds that bind to p185 and methods of using the same |
| US6281010B1 (en) | 1995-06-05 | 2001-08-28 | The Trustees Of The University Of Pennsylvania | Adenovirus gene therapy vehicle and cell line |
| US5756283A (en) | 1995-06-05 | 1998-05-26 | The Trustees Of The University Of Pennsylvania | Method for improved production of recombinant adeno-associated viruses for gene therapy |
| AU6267896A (en) | 1995-06-07 | 1996-12-30 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth oftumors |
| PT896586E (pt) * | 1996-03-27 | 2007-01-31 | Genentech Inc | Anticorpos de erbb3 |
| DE69740038D1 (enExample) | 1996-07-12 | 2010-12-16 | Genentech Inc | |
| JP2001504326A (ja) | 1996-10-18 | 2001-04-03 | ジェネンテック インコーポレーテッド | 抗ＥｒｂＢ２抗体 |
| AU5243198A (en) | 1996-10-30 | 1998-05-22 | Uab Research Foundation, The | Enhancement of tumor cell chemosensitivity and radiosensitivity using single chain intracellular antibodies |
| US6074640A (en) * | 1997-10-30 | 2000-06-13 | Uab Research Foundation | Enhancement of tumor cell radiosensitivity using single chain intracellular antibodies |
| US6027892A (en) * | 1996-12-30 | 2000-02-22 | Chang Esther H | Compositions and methods for reducing radiation and drug resistance in cells |
| US6235883B1 (en) * | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| ZA9811162B (en) | 1997-12-12 | 2000-06-07 | Genentech Inc | Treatment with anti-ERBB2 antibodies. |
| EP1745799B1 (en) | 1998-03-04 | 2015-09-02 | The Trustees of The University of Pennsylvania | Compositions and methods of treating tumors |
| US6417168B1 (en) | 1998-03-04 | 2002-07-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods of treating tumors |
| BR9910511A (pt) | 1998-05-15 | 2001-11-20 | Imclone Systems Inc | Tratamento de tumores humanos com radiação einibidores de tirosina cinases receptoras de fatorde crescimento |
| DE10124566A1 (de) | 2001-05-15 | 2002-11-21 | Zeiss Carl | Optisches Abbildungssystem mit Polarisationsmitteln und Quarzkristallplatte hierfür |
| US6828474B2 (en) | 2002-03-06 | 2004-12-07 | National Starch & Chemical Investment Holding Corporation | Method of grain production for heterozygous waxy sugary-2 maize |
| US8561398B2 (en) | 2009-05-05 | 2013-10-22 | Florida Renewable Energy Corporation | Fluid-based power generation system |
| ES2736256T3 (es) | 2011-03-14 | 2019-12-27 | Drug Delivery Solutions Ltd | Composición oftálmica |
| US9507157B2 (en) | 2014-12-17 | 2016-11-29 | Zhen Tang | Size-adjustable elliptical laser marker |
| TWI713998B (zh) | 2019-02-22 | 2020-12-21 | 南亞塑膠工業股份有限公司 | 一種含二氧化鈦漿料的製作及應用於回收聚酯纖維 |
-
1998
- 1998-07-08 US US09/111,681 patent/US6417168B1/en not_active Expired - Lifetime
-
1999
- 1999-03-04 ES ES06076149.1T patent/ES2551932T3/es not_active Expired - Lifetime
- 1999-03-04 AU AU28021/99A patent/AU757237C/en not_active Expired
- 1999-03-04 PT PT99908641T patent/PT1058562E/pt unknown
- 1999-03-04 EP EP15183218.5A patent/EP3034093B1/en not_active Revoked
- 1999-03-04 JP JP2000534245A patent/JP2002505309A/ja active Pending
- 1999-03-04 EP EP99908641A patent/EP1058562B1/en not_active Revoked
- 1999-03-04 WO PCT/US1999/004777 patent/WO1999044645A1/en not_active Ceased
- 1999-03-04 DE DE69932600T patent/DE69932600T2/de not_active Expired - Lifetime
- 1999-03-04 CA CA002322592A patent/CA2322592A1/en not_active Expired - Lifetime
- 1999-03-04 ES ES99908641T patent/ES2270586T3/es not_active Expired - Lifetime
- 1999-03-04 DK DK99908641T patent/DK1058562T3/da active
- 1999-03-04 AT AT99908641T patent/ATE334702T1/de active
-
2002
- 2002-03-19 US US10/100,952 patent/US7625558B2/en not_active Expired - Lifetime
-
2006
- 2006-09-14 CY CY20061101312T patent/CY1105475T1/el unknown
-
2008
- 2008-05-02 US US12/114,475 patent/US20090010935A1/en not_active Abandoned
-
2011
- 2011-04-05 US US13/080,313 patent/US20120014965A1/en not_active Abandoned
- 2011-10-11 JP JP2011224347A patent/JP5719270B2/ja not_active Expired - Lifetime
-
2013
- 2013-03-12 US US13/796,468 patent/US20130204069A1/en not_active Abandoned
-
2014
- 2014-09-12 US US14/485,525 patent/US20150010551A1/en not_active Abandoned
-
2015
- 2015-06-03 US US14/729,798 patent/US20160289334A2/en not_active Abandoned
-
2016
- 2016-12-21 HK HK16114528.4A patent/HK1225997A1/en unknown
-
2017
- 2017-02-01 US US15/422,046 patent/US20170355778A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2802199A (en) | 1999-09-20 |
| US20160289334A2 (en) | 2016-10-06 |
| US20170355778A1 (en) | 2017-12-14 |
| DK1058562T3 (da) | 2006-11-13 |
| EP1058562A4 (en) | 2003-02-05 |
| JP5719270B2 (ja) | 2015-05-13 |
| ES2270586T3 (es) | 2007-04-01 |
| JP2012017341A (ja) | 2012-01-26 |
| PT1058562E (pt) | 2006-11-30 |
| AU757237B2 (en) | 2003-02-06 |
| EP1058562B1 (en) | 2006-08-02 |
| EP3034093A1 (en) | 2016-06-22 |
| US6417168B1 (en) | 2002-07-09 |
| US20020165193A1 (en) | 2002-11-07 |
| DE69932600T2 (de) | 2007-08-09 |
| US20150010551A1 (en) | 2015-01-08 |
| DE69932600D1 (de) | 2006-09-14 |
| ATE334702T1 (de) | 2006-08-15 |
| WO1999044645A1 (en) | 1999-09-10 |
| EP3034093B1 (en) | 2019-03-13 |
| JP2002505309A (ja) | 2002-02-19 |
| AU757237C (en) | 2004-03-18 |
| ES2551932T3 (es) | 2015-11-24 |
| US20130204069A1 (en) | 2013-08-08 |
| US20090010935A1 (en) | 2009-01-08 |
| EP1058562A1 (en) | 2000-12-13 |
| US7625558B2 (en) | 2009-12-01 |
| US20160083478A1 (en) | 2016-03-24 |
| CY1105475T1 (el) | 2010-04-28 |
| US20120014965A1 (en) | 2012-01-19 |
| HK1225997A1 (en) | 2017-09-22 |
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