ZA200307682B - Combination methods of inhibiting tumor growth with a vascular endothelial growth factor receptor antagonist. - Google Patents
Combination methods of inhibiting tumor growth with a vascular endothelial growth factor receptor antagonist. Download PDFInfo
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- ZA200307682B ZA200307682B ZA200307682A ZA200307682A ZA200307682B ZA 200307682 B ZA200307682 B ZA 200307682B ZA 200307682 A ZA200307682 A ZA 200307682A ZA 200307682 A ZA200307682 A ZA 200307682A ZA 200307682 B ZA200307682 B ZA 200307682B
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Families Citing this family (111)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6582959B2 (en) * | 1991-03-29 | 2003-06-24 | Genentech, Inc. | Antibodies to vascular endothelial cell growth factor |
US20030206899A1 (en) * | 1991-03-29 | 2003-11-06 | Genentech, Inc. | Vascular endothelial cell growth factor antagonists |
US6448077B1 (en) * | 1994-02-10 | 2002-09-10 | Imclone Systems, Inc. | Chimeric and humanized monoclonal antibodies specific to VEGF receptors |
US20030108545A1 (en) * | 1994-02-10 | 2003-06-12 | Patricia Rockwell | Combination methods of inhibiting tumor growth with a vascular endothelial growth factor receptor antagonist |
IL117645A (en) * | 1995-03-30 | 2005-08-31 | Genentech Inc | Vascular endothelial cell growth factor antagonists for use as medicaments in the treatment of age-related macular degeneration |
ZA9811162B (en) | 1997-12-12 | 2000-06-07 | Genentech Inc | Treatment with anti-ERBB2 antibodies. |
EP1060242A4 (en) * | 1998-01-23 | 2003-09-17 | Imclone Systems Inc | Purified populations of stem cells |
US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
JP2002534468A (ja) | 1999-01-13 | 2002-10-15 | バイエル コーポレイション | p38キナーゼ阻害剤としてのω−カルボキシアリール置換ジフェニル尿素 |
IT1306704B1 (it) * | 1999-05-26 | 2001-10-02 | Sirs Societa Italiana Per La R | Anticorpi monoclonali e suoi derivati sintetici o biotecnologici ingrado di agire come molecole antagoniste per il ngf. |
US20040013667A1 (en) * | 1999-06-25 | 2004-01-22 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
US20030086924A1 (en) * | 1999-06-25 | 2003-05-08 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
US6949245B1 (en) | 1999-06-25 | 2005-09-27 | Genentech, Inc. | Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies |
AU2001259271A1 (en) * | 2000-04-28 | 2001-11-12 | Millennium Pharmaceuticals, Inc. | 14094, a novel human trypsin family member and uses thereof |
PL400669A1 (pl) | 2000-05-19 | 2012-11-05 | Genentech, Inc. | Genowa próba wykrywania odpowiedzi na antagoniste ErbB dla poprawienia prawdopodobienstwa i skutecznosci leczenia raka |
RU2264389C3 (ru) * | 2000-10-20 | 2018-06-01 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Азотсодержащие ароматические производные, их применение, лекарственное средство на их основе и способ лечения |
US7018371B2 (en) * | 2001-05-07 | 2006-03-28 | Xoft, Inc. | Combination ionizing radiation and radiosensitizer delivery devices and methods for inhibiting hyperplasia |
JP2005508298A (ja) * | 2001-06-20 | 2005-03-31 | イムクローン システムズ インコーポレイティド | アテローム性動脈硬化症及び他の炎症性疾患を処置する方法 |
JP2005515967A (ja) * | 2001-07-13 | 2005-06-02 | イムクローン システムズ インコーポレイティド | 乳癌を治療するためのvegfr−1抗体 |
CA2454251A1 (en) * | 2001-08-10 | 2003-02-20 | Imclone Systems Incorporated | Isolation and mobilization of stem cells expressing vegfr-1 |
EP2324825A1 (en) | 2002-02-11 | 2011-05-25 | Bayer Healthcare LLC | Aryl ureas with angiogenesis inhibiting activity |
US20030181377A1 (en) * | 2002-02-12 | 2003-09-25 | Vanderbilt University | Inhibition of VEGF receptor signaling reverses tumor resistance to radiotherapy |
EP1916001B1 (en) * | 2002-03-04 | 2011-05-25 | Imclone LLC | Human antibodies specific to KDR and uses thereof |
CN101474404A (zh) * | 2002-03-04 | 2009-07-08 | 伊姆克罗尼系统公司 | 用血管内皮生长因子受体拮抗剂抑制肿瘤生长的联合疗法 |
US7696320B2 (en) | 2004-08-24 | 2010-04-13 | Domantis Limited | Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor |
US20050186204A1 (en) * | 2002-06-28 | 2005-08-25 | Peter Carmeliet | Use of antibodies against FLT-1 for the treatment of osteoporosis |
KR20050065587A (ko) * | 2002-10-08 | 2005-06-29 | 이뮤노메딕스, 인코오포레이티드 | 항체 치료법 |
EP1572972A4 (en) * | 2002-11-21 | 2007-11-21 | Genentech Inc | THERAPY OF NON-MALIGNER DISEASES OR DISORDER WITH ANTI-ERBB2 ANTIBODIES |
EP1604665B1 (en) * | 2003-03-10 | 2011-05-11 | Eisai R&D Management Co., Ltd. | C-kit kinase inhibitor |
US20050043233A1 (en) | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
EP1473043A1 (en) * | 2003-04-29 | 2004-11-03 | Boehringer Ingelheim Pharma GmbH & Co.KG | Pharmaceutical combination for the treatment of diseases involving cell proliferation, migration or apotosis of myeloma cells, or angiogenesis |
JP4860474B2 (ja) | 2003-05-20 | 2012-01-25 | バイエル、ファーマシューテイカルズ、コーポレイション | Pdgfrによって仲介される病気のためのジアリール尿素 |
WO2005001087A2 (en) | 2003-06-11 | 2005-01-06 | Regeneron Pharmaceuticals, Inc. | Methods of modifying genes in eukaryotic cells |
AU2013200394B2 (en) * | 2003-07-23 | 2015-07-09 | Bayer Healthcare Llc | Fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions |
JP4777887B2 (ja) * | 2003-07-23 | 2011-09-21 | バイエル、ファーマシューテイカルズ、コーポレイション | 病気および状態の処置および防止のためのフロロ置換オメガカルボキシアリールジフェニル尿素 |
AR046510A1 (es) * | 2003-07-25 | 2005-12-14 | Regeneron Pharma | Composicion de un antagonista de vegf y un agente anti-proliferativo |
US20050027196A1 (en) * | 2003-07-30 | 2005-02-03 | Fitzgerald Loretta A. | System for processing patient radiation treatment data |
EP1653992A1 (en) * | 2003-08-06 | 2006-05-10 | Regeneron Pharmaceuticals, Inc. | Use of a vegf antagonist in combination with radiation therapy |
US20050196340A1 (en) * | 2003-08-06 | 2005-09-08 | Jocelyn Holash | Use of a VEGF antagonist in combination with radiation therapy |
CN100450998C (zh) * | 2003-11-11 | 2009-01-14 | 卫材R&D管理有限公司 | 脲衍生物的制备方法 |
WO2005069906A2 (en) * | 2004-01-16 | 2005-08-04 | Yale University | Methods and compositions relating to vascular endothelial growth factor and th2 mediated inflammatory diseases |
PT1735348E (pt) * | 2004-03-19 | 2012-07-24 | Imclone Llc | Anticorpo anti-receptor do factor de crescimento humano |
GB0406446D0 (en) * | 2004-03-23 | 2004-04-28 | Astrazeneca Ab | Combination therapy |
AU2005231436A1 (en) * | 2004-04-02 | 2005-10-20 | Adventrx Pharmaceuticals, Inc. | Use of 5,10-methylene tetrahydrofolate for the treatment of cancer |
EP1761264A1 (en) * | 2004-06-03 | 2007-03-14 | F.Hoffmann-La Roche Ag | Treatment with irinotecan (cpt-11) and an egfr-inhibitor |
EP1797877A4 (en) | 2004-09-13 | 2010-12-15 | Eisai Co Ltd | JOINT USE OF A SULFONAMIDE-BASED COMPOUND AND AN ANGIOGENESIS INHIBITOR |
US8772269B2 (en) * | 2004-09-13 | 2014-07-08 | Eisai R&D Management Co., Ltd. | Use of sulfonamide-including compounds in combination with angiogenesis inhibitors |
WO2006030826A1 (ja) | 2004-09-17 | 2006-03-23 | Eisai R & D Management Co., Ltd. | 医薬組成物 |
CN102397542B (zh) * | 2004-11-18 | 2014-05-07 | 英克隆有限责任公司 | 抗血管内皮生长因子受体-1的抗体 |
US7598043B2 (en) * | 2004-11-19 | 2009-10-06 | Cornell Research Foundation, Inc. | Use of vascular endothelial growth factor receptor 1+ cells in treating and monitoring cancer and in screening for chemotherapeutics |
JP5202956B2 (ja) * | 2004-11-19 | 2013-06-05 | コーネル リサーチ ファンデーション インコーポレーティッド | 癌の治療およびモニタリングならびに化学療法薬に関するスクリーニングにおける血管内皮増殖因子受容体1+細胞の使用法 |
US20060160157A1 (en) * | 2005-01-19 | 2006-07-20 | Zuckerman Mathew M | Method, compositions and classification for tumor diagnostics and treatment |
JP2008528486A (ja) | 2005-01-21 | 2008-07-31 | ジェネンテック・インコーポレーテッド | Her抗体の一定投薬 |
RU2404806C2 (ru) | 2005-02-23 | 2010-11-27 | Дженентек, Инк. | Продление времени до прогрессирования заболевания или продолжительности жизни у онкологических больных с применением ингибиторов димеризации her |
WO2006096861A2 (en) * | 2005-03-08 | 2006-09-14 | Genentech, Inc. | METHODS FOR IDENTIFYING TUMORS RESPONSIVE TO TREATMENT WITH HER DIMERIZATION INHIBITORS (HDIs) |
JP2006316040A (ja) | 2005-05-13 | 2006-11-24 | Genentech Inc | Herceptin(登録商標)補助療法 |
WO2007014335A2 (en) * | 2005-07-27 | 2007-02-01 | The University Of Texas System | Combinations comprising gemcitabine and tyrosine kinase inhibitors for the treatment of pancreatic cancer |
JP5066446B2 (ja) * | 2005-08-01 | 2012-11-07 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 血管新生阻害物質の効果を予測する方法 |
EP2281901B1 (en) | 2005-08-02 | 2013-11-27 | Eisai R&D Management Co., Ltd. | Anti-tumour pharmaceutical composition with angiogenesis inhibitors |
CA2627598C (en) * | 2005-11-07 | 2013-06-25 | Eisai R & D Management Co., Ltd. | Use of combination of anti-angiogenic substance and c-kit kinase inhibitor |
CA2629648A1 (en) * | 2005-11-15 | 2007-05-24 | Neovista Inc. | Methods and apparatus for intraocular brachytherapy |
EP1964837A4 (en) * | 2005-11-22 | 2010-12-22 | Eisai R&D Man Co Ltd | Antitumor agent against multiple myeloma |
CA2652442C (en) * | 2006-05-18 | 2014-12-09 | Eisai R & D Management Co., Ltd. | Antitumor agent for thyroid cancer |
EP2044939A1 (en) * | 2006-06-29 | 2009-04-08 | Eisai R&D Management Co., Ltd. | Therapeutic agent for liver fibrosis |
KR101472600B1 (ko) * | 2006-08-28 | 2014-12-15 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미분화형 위암에 대한 항종양제 |
WO2008093855A1 (ja) * | 2007-01-29 | 2008-08-07 | Eisai R & D Management Co., Ltd. | 未分化型胃癌治療用組成物 |
JP2010520225A (ja) | 2007-03-02 | 2010-06-10 | ジェネンテック, インコーポレイテッド | 低her3発現に基づくher二量化インヒビターに対する応答を予測する方法 |
BRPI0810374A2 (pt) | 2007-04-17 | 2014-10-29 | Imclone Llc | Inibidores específicos do pdgfrbeta |
WO2008154249A2 (en) | 2007-06-08 | 2008-12-18 | Genentech, Inc. | Gene expression markers of tumor resistance to her2 inhibitor treatment |
US9551033B2 (en) | 2007-06-08 | 2017-01-24 | Genentech, Inc. | Gene expression markers of tumor resistance to HER2 inhibitor treatment |
KR100883430B1 (ko) * | 2007-06-13 | 2009-02-12 | 한국생명공학연구원 | 혈관내피성장인자 수용체를 중화하는 인간 단클론항체 및그 용도 |
EP2170956B1 (en) | 2007-06-15 | 2014-10-22 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Treatment of tumors using specific anti-l1 antibody |
CA2704000C (en) | 2007-11-09 | 2016-12-13 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
WO2009096377A1 (ja) * | 2008-01-29 | 2009-08-06 | Eisai R & D Management Co., Ltd. | 血管阻害物質とタキサンとの併用 |
AU2009213738B2 (en) | 2008-02-11 | 2015-01-22 | Curetech Ltd. | Monoclonal antibodies for tumor treatment |
BRPI0812682A2 (pt) | 2008-06-16 | 2010-06-22 | Genentech Inc | tratamento de cáncer de mama metastático |
CN102333544A (zh) | 2009-02-06 | 2012-01-25 | 通用医疗公司 | 治疗血管损伤的方法 |
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 |
US8663210B2 (en) | 2009-05-13 | 2014-03-04 | Novian Health, Inc. | Methods and apparatus for performing interstitial laser therapy and interstitial brachytherapy |
US20120121586A1 (en) | 2009-05-29 | 2012-05-17 | Astrid Kiermaier | Modulators for her2 signaling in her2 expressing patients with gastric cancer |
WO2011028642A1 (en) | 2009-09-04 | 2011-03-10 | University Of Louisville Research Foundation, Inc. | Genetic determinants of prostate cancer risk |
RU2587619C2 (ru) | 2010-02-18 | 2016-06-20 | Дженентек, Инк. | Антагонисты неурегулина и применение их в лечении злокачественного новообразования |
WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
CN102958523B (zh) | 2010-06-25 | 2014-11-19 | 卫材R&D管理有限公司 | 使用具有激酶抑制作用的组合的抗肿瘤剂 |
WO2012069466A1 (en) | 2010-11-24 | 2012-05-31 | Novartis Ag | Multispecific molecules |
SG191153A1 (en) | 2010-12-23 | 2013-07-31 | Hoffmann La Roche | Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery |
WO2012144463A1 (ja) | 2011-04-18 | 2012-10-26 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療剤 |
JO3283B1 (ar) | 2011-04-26 | 2018-09-16 | Sanofi Sa | تركيب يتضمن أفليبيرسيبت, حمض فولينيك, 5- فلورويوراسيل (5- Fu) وإرينوسيتان (FOLFIRI) |
ES2705950T3 (es) | 2011-06-03 | 2019-03-27 | Eisai R&D Man Co Ltd | Biomarcadores para predecir y valorar la capacidad de respuesta de sujetos con cáncer de tiroides y de riñón a compuestos de lenvatinib |
WO2013025853A1 (en) | 2011-08-17 | 2013-02-21 | Genentech, Inc. | Neuregulin antibodies and uses thereof |
US9327023B2 (en) | 2011-10-25 | 2016-05-03 | The Regents Of The University Of Michigan | HER2 targeting agent treatment in non-HER2-amplified cancers having HER2 expressing cancer stem cells |
EP2785864A2 (en) | 2011-11-30 | 2014-10-08 | F. Hoffmann-La Roche AG | Erbb3 mutations in cancer |
EP2788500A1 (en) | 2011-12-09 | 2014-10-15 | F.Hoffmann-La Roche Ag | Identification of non-responders to her2 inhibitors |
EP2831115A1 (en) | 2012-03-27 | 2015-02-04 | F. Hoffmann-La Roche AG | Diagnosis and treatments relating to her3 inhibitors |
CA2889298C (en) | 2012-11-30 | 2024-01-02 | Anton Belousov | Identification of patients in need of pd-l1 inhibitor cotherapy |
US9334239B2 (en) | 2012-12-21 | 2016-05-10 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
CA2930987A1 (en) | 2013-01-11 | 2014-07-17 | Massachusetts Eye And Ear Infirmary | Cyp450 lipid metabolites reduce inflammation and angiogenesis |
ES2687968T3 (es) | 2013-05-14 | 2018-10-30 | Eisai R&D Management Co., Ltd. | Biomarcadores para pronosticar y evaluar la reactividad de sujetos con cáncer de endometrio a compuestos con lenvatinib |
TW201622744A (zh) * | 2014-03-04 | 2016-07-01 | 美國禮來大藥廠 | 癌症之組合療法 |
MA40354A (fr) | 2014-07-18 | 2017-05-24 | Sanofi Sa | Procédé permettant de prédire le résultat d'un traitement avec de l'aflibercept d'un patient suspecté de souffrir d'un cancer |
KR102329681B1 (ko) | 2014-08-28 | 2021-11-23 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 고순도의 퀴놀린 유도체 및 이를 제조하는 방법 |
US20180028662A1 (en) | 2015-02-25 | 2018-02-01 | Eisai R&D Management Co., Ltd. | Method for Suppressing Bitterness of Quinoline Derivative |
WO2016140717A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer |
SG11201707949XA (en) * | 2015-04-14 | 2017-10-30 | Academia Sinica | Anti-vegfr2 human antibody for anti-angiogenic and targeted cancer therapy |
US11369623B2 (en) | 2015-06-16 | 2022-06-28 | Prism Pharma Co., Ltd. | Anticancer combination of a CBP/catenin inhibitor and an immune checkpoint inhibitor |
KR102587702B1 (ko) | 2015-08-20 | 2023-10-12 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 종양 치료제 |
US20190151346A1 (en) | 2016-05-10 | 2019-05-23 | INSERM (Institute National de la Santé et de la Recherche Médicale) | Combinations therapies for the treatment of cancer |
CN106892980B (zh) * | 2017-01-25 | 2020-08-04 | 长春金赛药业有限责任公司 | 抗vegfr2单克隆抗体及其应用 |
JP2020519576A (ja) | 2017-05-16 | 2020-07-02 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 肝細胞癌の治療 |
WO2019017401A1 (ja) * | 2017-07-18 | 2019-01-24 | 協和発酵キリン株式会社 | 抗ヒトccr1モノクローナル抗体 |
CN114174334A (zh) | 2019-03-22 | 2022-03-11 | 反射制药有限公司 | 针对vegf的d-肽化合物 |
Family Cites Families (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US301299A (en) | 1884-07-01 | Vehicle-spring | ||
US2132498A (en) | 1936-07-22 | 1938-10-11 | Smith | Roller bit |
KR870008714A (ko) | 1986-03-07 | 1987-10-20 | 사까이 유미 | 도광섬유 조명장치 |
US5194596A (en) | 1989-07-27 | 1993-03-16 | California Biotechnology Inc. | Production of vascular endothelial cell growth factor |
DE4003229A1 (de) | 1990-02-03 | 1991-08-08 | Bosch Gmbh Robert | Elektromagnetisch betaetigbares ventil |
WO1992014748A1 (en) | 1991-02-22 | 1992-09-03 | American Cyanamid Company | Identification of a novel human receptor tyrosine kinase gene |
US5367057A (en) | 1991-04-02 | 1994-11-22 | The Trustees Of Princeton University | Tyrosine kinase receptor flk-2 and fragments thereof |
US5270458A (en) | 1991-04-02 | 1993-12-14 | The Trustees Of Princeton University | Nucleic acids encoding fragments of hematopoietic stem cell receptor flk-2 |
US5185438A (en) | 1991-04-02 | 1993-02-09 | The Trustees Of Princeton University | Nucleic acids encoding hencatoporetic stem cell receptor flk-2 |
JPH05244982A (ja) | 1991-12-06 | 1993-09-24 | Sumitomo Chem Co Ltd | 擬人化b−b10 |
WO1993012220A1 (en) | 1991-12-12 | 1993-06-24 | Berlex Laboratories, Inc. | RECOMBINANT AND CHIMERIC ANTIBODIES TO c-erbB-2 |
US5861301A (en) | 1992-02-20 | 1999-01-19 | American Cayanamid Company | Recombinant kinase insert domain containing receptor and gene encoding same |
WO1993021319A1 (en) | 1992-04-08 | 1993-10-28 | Cetus Oncology Corporation | HUMANIZED C-erbB-2 SPECIFIC ANTIBODIES |
CA2085291A1 (en) | 1992-07-30 | 1994-01-31 | Martin L. Breitman | Novel receptor tyrosine kinase |
EP1167384B1 (en) | 1992-10-28 | 2006-12-13 | Genentech, Inc. | HVEGF Receptor as Vascular endothelial cell growth factor antagonists |
EP0669988B2 (en) | 1992-10-29 | 2009-07-08 | The Australian National University | Angiogenesis inhibitory antibodies |
US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
US5712395A (en) | 1992-11-13 | 1998-01-27 | Yissum Research Development Corp. | Compounds for the treatment of disorders related to vasculogenesis and/or angiogenesis |
US5981569A (en) | 1992-11-13 | 1999-11-09 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Substituted phenylacrylonitrile compounds and compositions thereof for the treatment of disease |
CN1701814A (zh) | 1992-11-13 | 2005-11-30 | 马克斯普朗克科学促进协会 | 作为血管内皮生长因子受体的f1k-1 |
JPH07131958A (ja) | 1993-11-04 | 1995-05-19 | Odawara Eng:Kk | ステータ巻線機 |
AUPM379394A0 (en) | 1994-02-10 | 1994-03-03 | Ludwig Institute For Cancer Research | Immunointeractive molecules - i |
US5861499A (en) * | 1994-02-10 | 1999-01-19 | Imclone Systems Incorporated | Nucleic acid molecules encoding the variable or hypervariable region of a monoclonal antibody that binds to an extracellular domain |
US5840301A (en) * | 1994-02-10 | 1998-11-24 | Imclone Systems Incorporated | Methods of use of chimerized, humanized, and single chain antibodies specific to VEGF receptors |
DE69536015D1 (de) | 1995-03-30 | 2009-12-10 | Pfizer Prod Inc | Chinazolinone Derivate |
GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
WO1996040210A1 (en) * | 1995-06-07 | 1996-12-19 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth of tumors |
PT888349E (pt) | 1996-01-23 | 2002-10-31 | Novartis Ag | Pirrolopirimidinas e processos para a sua preparacao |
GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
WO1997049688A1 (en) | 1996-06-24 | 1997-12-31 | Pfizer Inc. | Phenylamino-substituted tricyclic derivatives for treatment of hyperproliferative diseases |
ES2267136T3 (es) | 1996-11-21 | 2007-03-01 | Kyowa Hakko Kogyo Kabushiki Kaisha | Anticuerpo monocional antirreceptor fit-1 del vegf humano. |
DE69839338T2 (de) | 1997-02-05 | 2008-07-10 | Warner-Lambert Company Llc | Pyrido (2,3-d) pyrimidine und 4-amino-pyrimidine als inhibitoren der zellulären proliferation |
AU3850299A (en) | 1998-05-20 | 1999-12-06 | Kyowa Hakko Kogyo Co. Ltd. | Vegf activity inhibitors |
UA72749C2 (en) | 1998-09-29 | 2005-04-15 | White Holdings Corp | Substituted 3-cyanoquinolines, a method for the preparation thereof (variants), pharmaceutical composition based thereon, a method for the treatment, inhibiting the growth or elimination of neoplasms and a method for the treatment, inhibiting progressing or elimination of polycystic kidney disease using them |
GB9824579D0 (en) * | 1998-11-10 | 1999-01-06 | Novartis Ag | Organic compounds |
WO2000031048A1 (en) | 1998-11-19 | 2000-06-02 | Warner-Lambert Company | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases |
US6297238B1 (en) * | 1999-04-06 | 2001-10-02 | Basf Aktiengesellschaft | Therapeutic agents |
-
2001
- 2001-03-02 US US09/798,689 patent/US6811779B2/en not_active Expired - Fee Related
-
2002
- 2002-03-04 WO PCT/US2002/006762 patent/WO2002070008A1/en not_active Application Discontinuation
- 2002-03-04 IL IL15769302A patent/IL157693A0/xx unknown
- 2002-03-04 EE EEP200300428A patent/EE200300428A/xx unknown
- 2002-03-04 PL PL02364719A patent/PL364719A1/xx unknown
- 2002-03-04 RU RU2003129228/14A patent/RU2003129228A/ru not_active Application Discontinuation
- 2002-03-04 KR KR10-2003-7011532A patent/KR20040023590A/ko not_active Application Discontinuation
- 2002-03-04 CZ CZ20032586A patent/CZ20032586A3/cs unknown
- 2002-03-04 JP JP2002569180A patent/JP2005506288A/ja active Pending
- 2002-03-04 EP EP02717550A patent/EP1379276A4/en not_active Ceased
- 2002-03-04 MX MXPA03007909A patent/MXPA03007909A/es unknown
- 2002-03-04 BR BR0207977-1A patent/BR0207977A/pt not_active Application Discontinuation
- 2002-03-04 HU HU0303378A patent/HUP0303378A2/hu unknown
- 2002-03-04 CA CA002439933A patent/CA2439933A1/en not_active Abandoned
-
2003
- 2003-09-01 NO NO20033856A patent/NO20033856L/no not_active Application Discontinuation
- 2003-09-30 BG BG108214A patent/BG108214A/xx unknown
- 2003-10-01 ZA ZA200307682A patent/ZA200307682B/en unknown
Also Published As
Publication number | Publication date |
---|---|
RU2003129228A (ru) | 2005-03-10 |
HUP0303378A2 (hu) | 2003-12-29 |
CZ20032586A3 (cs) | 2004-08-18 |
CA2439933A1 (en) | 2002-09-12 |
JP2005506288A (ja) | 2005-03-03 |
EP1379276A4 (en) | 2004-06-30 |
EE200300428A (et) | 2004-10-15 |
BR0207977A (pt) | 2005-02-01 |
NO20033856D0 (no) | 2003-09-01 |
KR20040023590A (ko) | 2004-03-18 |
WO2002070008A1 (en) | 2002-09-12 |
EP1379276A1 (en) | 2004-01-14 |
MXPA03007909A (es) | 2005-06-03 |
US20030103973A1 (en) | 2003-06-05 |
NO20033856L (no) | 2003-11-03 |
PL364719A1 (en) | 2004-12-13 |
US6811779B2 (en) | 2004-11-02 |
IL157693A0 (en) | 2004-03-28 |
BG108214A (en) | 2004-09-30 |
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