ES2245833T5 - Antagonistas del factor de crecimiento celular del endotelio vascular y usos de los mismos - Google Patents
Antagonistas del factor de crecimiento celular del endotelio vascular y usos de los mismos Download PDFInfo
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- ES2245833T5 ES2245833T5 ES99968115T ES99968115T ES2245833T5 ES 2245833 T5 ES2245833 T5 ES 2245833T5 ES 99968115 T ES99968115 T ES 99968115T ES 99968115 T ES99968115 T ES 99968115T ES 2245833 T5 ES2245833 T5 ES 2245833T5
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US218481 | 1994-03-25 | ||
| US21848198A | 1998-12-22 | 1998-12-22 | |
| PCT/US1999/029475 WO2000037502A2 (en) | 1998-12-22 | 1999-12-09 | Vascular endothelial cell growth factor antagonists and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2245833T3 ES2245833T3 (es) | 2006-01-16 |
| ES2245833T5 true ES2245833T5 (es) | 2013-07-19 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99968115T Expired - Lifetime ES2245833T5 (es) | 1998-12-22 | 1999-12-09 | Antagonistas del factor de crecimiento celular del endotelio vascular y usos de los mismos |
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| Country | Link |
|---|---|
| US (7) | US20050244405A1 (enExample) |
| EP (3) | EP1579871A1 (enExample) |
| JP (2) | JP4731016B2 (enExample) |
| AT (1) | ATE300957T1 (enExample) |
| AU (2) | AU775806B2 (enExample) |
| CA (1) | CA2355976C (enExample) |
| DE (1) | DE69926536T3 (enExample) |
| DK (1) | DK1140173T4 (enExample) |
| ES (1) | ES2245833T5 (enExample) |
| IL (2) | IL143596A0 (enExample) |
| WO (1) | WO2000037502A2 (enExample) |
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| DE69926536T3 (de) | 1998-12-22 | 2013-09-12 | Genentech, Inc. | Antagonisten von vaskular-endothelialen zellwachstumsfaktoren und ihre anwendung |
| WO2000064946A2 (en) | 1999-04-28 | 2000-11-02 | Board Of Regents, The University Of Texas System | Compositions and methods for cancer treatment by selectively inhibiting vegf |
| US6703020B1 (en) | 1999-04-28 | 2004-03-09 | Board Of Regents, The University Of Texas System | Antibody conjugate methods for selectively inhibiting VEGF |
| LT3351246T (lt) | 2001-02-19 | 2019-07-10 | Novartis Pharma Ag | Rapamicino darinys, skirtas kieto naviko, susijusio su nereguliuojama angiogeneze, gydymui |
| PL392652A1 (pl) | 2001-05-16 | 2010-12-06 | Novartis Ag | Kombinacja zawierająca N-{5-[4-(4-metylo-piperazyno-metylo)-benzoiloamido]-2-metylofenylo}-4-(3-pirydylo)-2-pirymidyno-aminę oraz środek chemoterapeutyczny, jej zastosowanie, kompozycja farmaceutyczna ją zawierająca oraz zestaw zawierający taką kombinację |
| HRP20030840A2 (en) * | 2001-05-17 | 2005-08-31 | Applied Research Systems Ars Holding N.V. | Use of osteopontin for the treatment and/or prevention of neurologic diseases |
| WO2003002609A2 (en) * | 2001-06-28 | 2003-01-09 | Domantis Limited | Dual-specific ligand and its use |
| US20050271663A1 (en) * | 2001-06-28 | 2005-12-08 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| TWI315982B (en) | 2001-07-19 | 2009-10-21 | Novartis Ag | Combinations comprising epothilones and pharmaceutical uses thereof |
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| 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 |
| AU2003244817B2 (en) * | 2002-06-28 | 2010-08-26 | Domantis Limited | Antigen-binding immunoglobulin single variable domains and dual-specific constructs |
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| AU2004205684A1 (en) | 2003-01-23 | 2004-08-05 | Genentech, Inc. | Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture |
| MY150088A (en) | 2003-05-19 | 2013-11-29 | Irm Llc | Immunosuppressant compounds and compositions |
| PE20050158A1 (es) | 2003-05-19 | 2005-05-12 | Irm Llc | Compuestos inmunosupresores y composiciones |
| RS20050885A (sr) * | 2003-05-30 | 2008-04-04 | Genentech | Lečenje sa anti-vegf antitelima |
| US7582726B2 (en) | 2003-11-10 | 2009-09-01 | Ghc Research Development Corporation | VEGF receptor antagonists |
| US7803931B2 (en) | 2004-02-12 | 2010-09-28 | Archemix Corp. | Aptamer therapeutics useful in the treatment of complement-related disorders |
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| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| KR20080054417A (ko) | 2005-09-27 | 2008-06-17 | 노파르티스 아게 | 카르복시아민 화합물 및 hdac 의존성 질환의 치료에있어서의 그의 용도 |
| US9006224B2 (en) | 2005-11-21 | 2015-04-14 | Novartis Ag | Neuroendocrine tumor treatment |
| JP2009519011A (ja) * | 2005-12-01 | 2009-05-14 | ドマンティス リミテッド | インターロイキン1受容体1型に結合する非競合ドメイン抗体フォーマット |
| DK1991275T3 (en) * | 2006-03-08 | 2014-12-08 | Archemix Llc | Complement aptamers AND ANTI-C5 AGENTS FOR USE IN THE TREATMENT OF EYE DISEASES |
| TW200812615A (en) * | 2006-03-22 | 2008-03-16 | Hoffmann La Roche | Tumor therapy with an antibody for vascular endothelial growth factor and an antibody for human epithelial growth factor receptor type 2 |
| UA95797C2 (ru) * | 2006-03-22 | 2011-09-12 | Ф. Хоффманн-Ля Рош Аг | Терапия опухолей с использованием сосудистого эндотелиального фактора роста и антитела к рецептору типа 2 человеческого эпителиального фактора роста |
| EP2591775A1 (en) | 2006-04-05 | 2013-05-15 | Novartis AG | Combinations comprising mtor inhibitors for treating cancer |
| WO2007128820A1 (en) | 2006-05-09 | 2007-11-15 | Novartis Ag | Combination comprising an iron chelator and an anti-neoplastic agent and use thereof |
| GB0612721D0 (en) | 2006-06-27 | 2006-08-09 | Novartis Ag | Organic compounds |
| WO2008022349A2 (en) | 2006-08-18 | 2008-02-21 | Armagen Technologies, Inc. | Agents for blood-brain barrier delivery |
| KR20090073121A (ko) | 2006-09-29 | 2009-07-02 | 노파르티스 아게 | Pi3k 지질 키나제 억제제로서의 피라졸로피리미딘 |
| EP2491923A3 (en) | 2007-02-15 | 2012-12-26 | Novartis AG | Combinations of therapeutic agents for treating cancer |
| WO2008103301A2 (en) * | 2007-02-16 | 2008-08-28 | President And Fellows Of Harvard College | Treatment of the eye using macrophages and/or agents able to affect blood vessel morphology |
| EA200901301A1 (ru) | 2007-06-06 | 2010-06-30 | Домантис Лимитед | Полипептиды, вариабельные домены антител и антагонисты |
| EP2997976A1 (en) | 2007-07-27 | 2016-03-23 | Armagen Technologies, Inc. | Methods and compositions for increasing alpha-l-iduronidase activity in the cns |
| CN102036955B (zh) | 2008-03-26 | 2013-03-27 | 诺瓦提斯公司 | 脱乙酰酶b的异羟肟酸盐为基础的抑制剂 |
| EP2344161B1 (en) | 2008-10-16 | 2018-12-19 | Celator Pharmaceuticals, Inc. | Combinations of a liposomal water-soluble camptothecin with cetuximab or bevacizumab |
| RU2011129230A (ru) | 2008-12-18 | 2013-01-27 | Новартис Аг | Новая полиморфная форма 1-[4-[1-(4-циклогексил-3-трифторметилбензилоксиимино)этил]-2-этилбензил]азетидин-3-карбоновой кислоты |
| CN103204794A (zh) | 2008-12-18 | 2013-07-17 | 诺瓦提斯公司 | 新的盐 |
| KR20170062554A (ko) | 2008-12-18 | 2017-06-07 | 노파르티스 아게 | 1-[4-[1-(4-시클로헥실-3-트리플루오로메틸-벤질옥시이미노)-에틸]-2-에틸-벤질]-아제티딘-3-카르복실산의 헤미푸마레이트 염 |
| TW201031406A (en) | 2009-01-29 | 2010-09-01 | Novartis Ag | Substituted benzimidazoles for the treatment of astrocytomas |
| JP5873003B2 (ja) * | 2009-03-18 | 2016-03-01 | アーメイゲン・テクノロジーズ・インコーポレイテッドArmagen Technologies, Inc. | IgGデコイ受容体融合タンパク質の血液脳関門送達のための組成物および方法 |
| WO2010108503A1 (en) * | 2009-03-24 | 2010-09-30 | Life & Brain Gmbh | Promotion of neuronal integration in neural stem cell grafts |
| BRPI1012321A8 (pt) * | 2009-06-17 | 2016-09-27 | Abbott Biotherapeutics Corp | Anticorpos anti-vegf e seus usos |
| WO2010149755A1 (en) | 2009-06-26 | 2010-12-29 | Novartis Ag | 1, 3-disubstituted imidazolidin-2-one derivatives as inhibitors of cyp 17 |
| JP5823671B2 (ja) * | 2009-07-27 | 2015-11-25 | 国立大学法人 新潟大学 | 免疫製剤を含む脳梗塞治療用医薬品組成物 |
| WO2011013668A1 (ja) * | 2009-07-27 | 2011-02-03 | 国立大学法人新潟大学 | 虚血性イベントの治療用医薬品組成物 |
| US8652476B2 (en) | 2009-07-27 | 2014-02-18 | Niigata University | Pharmaceutical composition for treating ischemic events |
| JP5823672B2 (ja) * | 2009-07-27 | 2015-11-25 | 国立大学法人 新潟大学 | 受容体シグナル伝達阻害剤を含む脳梗塞治療用医薬品組成物 |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| EA201200260A1 (ru) | 2009-08-12 | 2012-09-28 | Новартис Аг | Гетероциклические гидразоны и их применение для лечения рака и воспаления |
| CN102573846B (zh) | 2009-08-17 | 2015-10-07 | 因特利凯公司 | 杂环化合物及其用途 |
| MX2012002179A (es) | 2009-08-20 | 2012-03-16 | Novartis Ag | Compuestos heterociclicos de oxima. |
| CA2771936A1 (en) | 2009-08-26 | 2011-03-03 | Novartis Ag | Tetra-substituted heteroaryl compounds and their use as mdm2 and/or mdm4 modulators |
| WO2011029915A1 (en) | 2009-09-10 | 2011-03-17 | Novartis Ag | Ether derivatives of bicyclic heteroaryls |
| EP2485761B1 (en) | 2009-10-09 | 2019-02-27 | Armagen, Inc. | Methods and compositions for increasing iduronate 2-sulfatase activity in the cns |
| PE20121471A1 (es) | 2009-11-04 | 2012-11-01 | Novartis Ag | Derivados de sulfonamida heterociclicos utiles como inhibidores de mek |
| EP2504339A1 (en) | 2009-11-25 | 2012-10-03 | Novartis AG | Benzene-fused 6-membered oxygen-containing heterocyclic derivatives of bicyclic heteroaryls |
| GEP20135998B (en) | 2009-12-08 | 2013-12-25 | Novartis Ag | Heterocyclic sulfonamide derivatives |
| AU2012265844A1 (en) | 2009-12-08 | 2013-05-02 | Novartis Ag | Heterocyclic sulfonamide derivatives |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| CU24130B1 (es) | 2009-12-22 | 2015-09-29 | Novartis Ag | Isoquinolinonas y quinazolinonas sustituidas |
| WO2011157787A1 (en) | 2010-06-17 | 2011-12-22 | Novartis Ag | Biphenyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives |
| EP2582681A1 (en) | 2010-06-17 | 2013-04-24 | Novartis AG | Piperidinyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives |
| WO2012035078A1 (en) | 2010-09-16 | 2012-03-22 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| US9127000B2 (en) | 2011-02-23 | 2015-09-08 | Intellikine, LLC. | Heterocyclic compounds and uses thereof |
| CN103492390A (zh) | 2011-03-08 | 2014-01-01 | 诺瓦提斯公司 | 氟苯基双环杂芳基化合物 |
| AU2012249421B9 (en) | 2011-04-28 | 2015-10-22 | Novartis Ag | 17alpha-hydroxylase/C17,20-lyase inhibitors |
| WO2012175487A1 (en) | 2011-06-20 | 2012-12-27 | Novartis Ag | Cyclohexyl isoquinolinone compounds |
| WO2012175520A1 (en) | 2011-06-20 | 2012-12-27 | Novartis Ag | Hydroxy substituted isoquinolinone derivatives |
| EP2755976B1 (en) | 2011-09-15 | 2018-07-18 | Novartis AG | 6-substituted 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyridines as c-met tyrosine kinase inhibitors |
| CN104080787B (zh) | 2011-11-29 | 2016-09-14 | 诺华股份有限公司 | 吡唑并吡咯烷化合物 |
| EP2785378B1 (en) | 2011-12-02 | 2020-05-13 | Armagen, Inc. | Methods and compositions for increasing arylsulfatase a activity in the cns |
| CN104125953A (zh) | 2011-12-23 | 2014-10-29 | 诺华股份有限公司 | 用于抑制bcl2与结合配偶体相互作用的化合物 |
| US9126980B2 (en) | 2011-12-23 | 2015-09-08 | Novartis Ag | Compounds for inhibiting the interaction of BCL2 with binding partners |
| AU2012355623A1 (en) | 2011-12-23 | 2014-07-17 | Novartis Ag | Compounds for inhibiting the interaction of BCL2 with binding partners |
| AU2012355619A1 (en) | 2011-12-23 | 2014-07-17 | Novartis Ag | Compounds for inhibiting the interaction of BCL2 with binding partners |
| KR20140107578A (ko) | 2011-12-23 | 2014-09-04 | 노파르티스 아게 | Bcl2와 결합 파트너의 상호작용을 억제하기 위한 화합물 |
| JO3357B1 (ar) | 2012-01-26 | 2019-03-13 | Novartis Ag | مركبات إيميدازوبيروليدينون |
| MX365139B (es) | 2012-03-13 | 2019-05-24 | Hoffmann La Roche | Uso de una terapia combinada de bevacizumab y paclitaxel en el tratamiento de cáncer de ovario epitelial resistente al platino, carcinoma de las trompas de falopio resistente al platino, o carcinoma peritoneal primario resistente al platino. |
| ES2894830T3 (es) | 2012-04-03 | 2022-02-16 | Novartis Ag | Productos combinados con inhibidores de tirosina·cinasa y su uso |
| CN104321325B (zh) | 2012-05-24 | 2016-11-16 | 诺华股份有限公司 | 吡咯并吡咯烷酮化合物 |
| US20140154255A1 (en) | 2012-11-30 | 2014-06-05 | Abbvie Biotherapeutics Inc. | Anti-vegf antibodies and their uses |
| US9403827B2 (en) | 2013-01-22 | 2016-08-02 | Novartis Ag | Substituted purinone compounds |
| US9556180B2 (en) | 2013-01-22 | 2017-01-31 | Novartis Ag | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the P53/MDM2 interaction |
| CN105246482A (zh) | 2013-03-15 | 2016-01-13 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
| WO2014155268A2 (en) | 2013-03-25 | 2014-10-02 | Novartis Ag | Fgf-r tyrosine kinase activity inhibitors - use in diseases associated with lack of or reduced snf5 activity |
| KR102049990B1 (ko) | 2013-03-28 | 2019-12-03 | 삼성전자주식회사 | c-Met 항체 및 VEGF 결합 단편이 연결된 융합 단백질 |
| WO2015022664A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
| US9227969B2 (en) | 2013-08-14 | 2016-01-05 | Novartis Ag | Compounds and compositions as inhibitors of MEK |
| WO2015022663A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Mdm2抑制劑與BRAF抑制劑之組合及其用途 |
| WO2015200905A2 (en) * | 2014-06-28 | 2015-12-30 | Oligasis, Llc | Dual pdgf/vegf antagonists |
| US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
| KR20170036037A (ko) | 2014-07-31 | 2017-03-31 | 노파르티스 아게 | 조합 요법 |
| US10538589B2 (en) | 2015-01-14 | 2020-01-21 | Armagen Inc. | Methods and compositions for increasing N-acetylglucosaminidase (NAGLU) activity in the CNS using a fusion antibody comprising an anti-human insulin receptor antibody and NAGLU |
| KR20250057128A (ko) | 2015-12-30 | 2025-04-28 | 코디악 사이언시스 인코포레이티드 | 항체 및 이의 접합체 |
| US10617756B2 (en) | 2017-01-05 | 2020-04-14 | Shimojani, LLC | Drug regimen for treatment of cerebral ischemia |
| AU2017444054B2 (en) | 2017-12-21 | 2021-10-07 | Hefei Institutes Of Physical Science, Chinese Academy Of Sciences | Class of pyrimidine derivative kinase inhibitors |
| MX2020009152A (es) | 2018-03-02 | 2020-11-09 | Kodiak Sciences Inc | Anticuerpos de il-6 y constructos de fusion y conjugados de los mismos. |
| CN114786731A (zh) | 2019-10-10 | 2022-07-22 | 科达制药股份有限公司 | 治疗眼部病症的方法 |
| EP4058465A1 (en) | 2019-11-14 | 2022-09-21 | Cohbar Inc. | Cxcr4 antagonist peptides |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
| US4485045A (en) | 1981-07-06 | 1984-11-27 | Research Corporation | Synthetic phosphatidyl cholines useful in forming liposomes |
| US4456550A (en) * | 1982-11-22 | 1984-06-26 | President And Fellows Of Harvard College | Vascular permeability factor |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4544545A (en) | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
| US5036003A (en) | 1987-08-21 | 1991-07-30 | Monsanto Company | Antibodies to VPF |
| WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
| US5240848A (en) | 1988-11-21 | 1993-08-31 | Monsanto Company | Dna sequences encoding human vascular permeability factor having 189 amino acids |
| US5147638A (en) | 1988-12-30 | 1992-09-15 | Oklahoma Medical Research Foundation | Inhibition of tumor growth by blockade of the protein C system |
| US5051257A (en) | 1989-05-09 | 1991-09-24 | Pietronigro Dennis D | Antineoplastic solution and method for treating neoplasms |
| US5332671A (en) | 1989-05-12 | 1994-07-26 | Genetech, Inc. | Production of vascular endothelial cell growth factor and DNA encoding same |
| US5137871A (en) * | 1989-07-28 | 1992-08-11 | Regents Of The University Of California | Treatment to reduce edema for brain and musculature injuries |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| EP0536350B1 (en) | 1991-02-22 | 2002-08-07 | American Cyanamid Company | Identification of a novel human receptor tyrosine kinase gene |
| 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 |
| WO1993012808A1 (en) * | 1991-12-20 | 1993-07-08 | Shuji Nakamura | A method for treating kaposi's sarcoma and blocking or inhibiting vascular permeability |
| ATE348110T1 (de) | 1992-10-28 | 2007-01-15 | Genentech Inc | Hvegf rezeptor als vegf antagonist |
| 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 |
| US6448077B1 (en) * | 1994-02-10 | 2002-09-10 | Imclone Systems, Inc. | Chimeric and humanized monoclonal antibodies specific to VEGF receptors |
| 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 |
| UA54427C2 (uk) * | 1996-05-01 | 2003-03-17 | Елі Ліллі Енд Компані | Спосіб лікування очних захворювань, які пов'язані з фактором васкулярного ендотеліального росту |
| 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 |
| SE9602463D0 (sv) * | 1996-06-24 | 1996-06-24 | Perstorp Ab | The use of growth factor modulating compounds |
| US6750044B1 (en) * | 1996-10-17 | 2004-06-15 | Genentech, Inc. | Variants of vascular endothelial cell growth factor having antagonistic properties, nucleic acids encoding the same and host cells comprising those nucleic acids |
| WO1998045331A2 (en) * | 1997-04-07 | 1998-10-15 | Genentech, Inc. | Anti-vegf antibodies |
| US6884879B1 (en) * | 1997-04-07 | 2005-04-26 | Genentech, Inc. | Anti-VEGF antibodies |
| US20020032315A1 (en) | 1997-08-06 | 2002-03-14 | Manuel Baca | Anti-vegf antibodies |
| US20070059302A1 (en) | 1997-04-07 | 2007-03-15 | Genentech, Inc. | Anti-vegf antibodies |
| US6093740A (en) * | 1997-04-30 | 2000-07-25 | Eli Lilly And Company | Therapeutic treatment for skin disorders |
| CA2290598A1 (en) * | 1997-05-22 | 1998-11-26 | Peter Mclaren Black | Ganglioside gm3 induced apoptosis of neural cells |
| AU7671298A (en) | 1997-05-27 | 1998-12-30 | National Research Council Of Canada | High level expression of glycosyltransferases |
| WO1998054332A1 (en) | 1997-05-27 | 1998-12-03 | Meiji Seika Kaisha, Ltd. | Cellulase preparation containing highly active cellulase sce3 |
| ID24587A (id) * | 1998-03-23 | 2000-07-27 | Koninkl Philips Electronics Nv | Pemberian kode dan penguraian kode aritmatika dari suatu sinyal informasi |
| AU1908000A (en) * | 1998-11-06 | 2000-05-29 | Basf Aktiengesellschaft | Inhibition of the formation of vascular hyperpermeability |
| AU1728800A (en) * | 1998-11-18 | 2000-06-05 | Genentech Inc. | Antibody variants with higher binding affinity compared to parent antibodies |
| DE69926536T3 (de) | 1998-12-22 | 2013-09-12 | Genentech, Inc. | Antagonisten von vaskular-endothelialen zellwachstumsfaktoren und ihre anwendung |
-
1999
- 1999-12-09 DE DE69926536T patent/DE69926536T3/de not_active Expired - Lifetime
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- 1999-12-09 EP EP05075989A patent/EP1579871A1/en not_active Withdrawn
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- 1999-12-09 AU AU24797/00A patent/AU775806B2/en not_active Expired
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- 1999-12-09 EP EP08012346A patent/EP2016953A3/en not_active Withdrawn
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- 2001-06-06 IL IL143596A patent/IL143596A/en not_active IP Right Cessation
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- 2003-08-26 US US10/648,816 patent/US20050244405A1/en not_active Abandoned
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-
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- 2004-11-16 AU AU2004231159A patent/AU2004231159B2/en not_active Expired
-
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- 2006-09-29 US US11/536,871 patent/US8007799B2/en not_active Expired - Fee Related
-
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- 2008-04-21 US US12/107,041 patent/US7998931B2/en not_active Expired - Fee Related
- 2008-04-25 US US12/110,223 patent/US8287873B2/en not_active Expired - Fee Related
-
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- 2011-01-21 JP JP2011011313A patent/JP2011137003A/ja active Pending
-
2012
- 2012-05-31 US US13/485,827 patent/US20120237514A1/en not_active Abandoned
-
2013
- 2013-12-20 US US14/137,022 patent/US20140363432A1/en not_active Abandoned
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