ES2319305T3 - Quimeras del receptor del vegf para el tratamiento de trastornos oculares caracterizados por la permeabilidad vascular. - Google Patents
Quimeras del receptor del vegf para el tratamiento de trastornos oculares caracterizados por la permeabilidad vascular. Download PDFInfo
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- ES2319305T3 ES2319305T3 ES05001328T ES05001328T ES2319305T3 ES 2319305 T3 ES2319305 T3 ES 2319305T3 ES 05001328 T ES05001328 T ES 05001328T ES 05001328 T ES05001328 T ES 05001328T ES 2319305 T3 ES2319305 T3 ES 2319305T3
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| EP1353952B1 (en) | 1994-11-14 | 2007-04-11 | Ludwig Institute For Cancer Research | Flt4(vegfr-3) as a target for tumor imaging and anti-tumor therapy |
| 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 |
| US7070959B1 (en) | 1999-06-08 | 2006-07-04 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
| US7396664B2 (en) | 1999-06-08 | 2008-07-08 | Regeneron Pharmaceuticals, Inc. | VEGF-binding fusion proteins and nucleic acids encoding the same |
| US6833349B2 (en) * | 1999-06-08 | 2004-12-21 | Regeneron Pharmaceuticals, Inc. | Methods of treating inflammatory skin diseases |
| US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| US6734017B2 (en) | 2001-09-28 | 2004-05-11 | Isis Pharmaceuticals, Inc. | Antisense modulation of vascular endothelial growth factor receptor-2 expression |
| WO2004108069A2 (en) | 2002-05-04 | 2004-12-16 | Acorda Therapeutics, Inc. | Compositions and methods for promoting neuronal outgrowth |
| JP4730909B2 (ja) * | 2003-03-28 | 2011-07-20 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Ｖｅｇｆ媒介性活性を遮断することにより糖尿病を処置する方法 |
| EP2460881B1 (en) | 2003-05-16 | 2017-05-03 | Acorda Therapeutics, Inc. | Proteoglycan degrading mutants for treatment of CNS |
| US7959914B2 (en) | 2003-05-16 | 2011-06-14 | Acorda Therapeutics, Inc. | Methods of reducing extravasation of inflammatory cells |
| ES2831031T3 (es) * | 2003-05-16 | 2021-06-07 | Acorda Therapeutics Inc | Proteínas de fusión para el tratamiento del CNS |
| MXPA05008973A (es) * | 2003-05-28 | 2006-02-22 | Regeneron Pharma | Metodo de tratamiento de rechazo de trasplante de cornea. |
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| US7399612B2 (en) | 2003-06-30 | 2008-07-15 | Regeneron Pharmaceuticals, Inc. | VEGF-binding fusion proteins and nucleic acids encoding the same |
| AR046510A1 (es) | 2003-07-25 | 2005-12-14 | Regeneron Pharma | Composicion de un antagonista de vegf y un agente anti-proliferativo |
| US20050112061A1 (en) * | 2003-08-06 | 2005-05-26 | Jocelyn Holash | Use of a VEGF antagonist in combination with radiation therapy |
| MXPA06013345A (es) | 2004-05-18 | 2008-10-31 | Acorda Therapeutics Inc | Metodos para purificar condrointinasa y sus formulaciones estables. |
| PT1767546E (pt) | 2004-06-08 | 2012-03-20 | Chengdu Kanghong Biotechnologies Co Ltd | Proteína quimérica inibidora da angiogénese e utilização |
| WO2005123104A2 (en) | 2004-06-10 | 2005-12-29 | Regeneron Pharmaceuticals, Inc. | Use of vegf inhibitors for the treatment of human cancer |
| AU2005265071A1 (en) * | 2004-06-18 | 2006-01-26 | Memorial Sloan-Kettering Cancer Center | VEGF inhibitors for the treatment of malignant pleural effusion |
| MX2007001241A (es) | 2004-07-30 | 2007-07-11 | Regeneron Pharma | Metodos para tratar diabetes tipo i mediante el bloqueo de la actividad mediada de vegf. |
| ATE470454T1 (de) | 2004-09-13 | 2010-06-15 | Genzyme Corp | Multimere konstrukte |
| FR2878749B1 (fr) * | 2004-12-03 | 2007-12-21 | Aventis Pharma Sa | Combinaisons antitumorales contenant en agent inhibiteur de vegt et du 5fu ou un de ses derives |
| CA2621047A1 (en) * | 2005-02-02 | 2006-08-24 | Regeneron Pharmaceuticals, Inc. | Method of treating eye injury with local administration of a vegf inhibitor |
| KR101327270B1 (ko) | 2005-03-25 | 2013-11-08 | 리제네론 파라마큐티칼스 인코포레이티드 | 혈관내피성장인자 길항제 조제물 |
| US7485295B2 (en) | 2005-09-26 | 2009-02-03 | Acorda Therapeutics, Inc. | Compositions and methods of using chondroitinase ABCI mutants |
| PT1962895E (pt) † | 2005-12-16 | 2013-03-28 | Regeneron Pharma | Utilização terapêutica de um antagonista dll4 e de um inibidor fcev para inibição de crescimento de tumores |
| FR2895258B1 (fr) | 2005-12-22 | 2008-03-21 | Aventis Pharma Sa | Combinaison comprenant de la combretastatine et des agents anticancereux |
| US8216575B2 (en) | 2006-03-31 | 2012-07-10 | Chengdu Kanghong Biotechnologies Co., Ltd. | Inhibition of neovascularization with a soluble chimeric protein comprising VEGF FLT-1 and KDR domains |
| CN100502945C (zh) * | 2006-03-31 | 2009-06-24 | 成都康弘生物科技有限公司 | Vegf受体融合蛋白在治疗眼睛疾病中的应用 |
| MX2008016124A (es) | 2006-06-16 | 2009-01-20 | Regeneron Pharma | Formulaciones antagonistas de vegf adecuadas para la administracion intravitreal. |
| PT2066694E (pt) | 2006-09-29 | 2016-01-27 | Oncomed Pharm Inc | Composições e métodos de diagnóstico e tratamento do cancro |
| ES2473610T3 (es) | 2006-10-10 | 2014-07-07 | Acorda Therapeutics, Inc. | Composiciones y métodos de uso de mutantes de condroitinasa ABCI |
| FR2918279B1 (fr) * | 2007-07-05 | 2010-10-22 | Aventis Pharma Sa | Combinaisons antitumorales contenant un agent inhibiteur de vegf et de l'irinotecan |
| CN101575379B (zh) * | 2008-05-09 | 2012-05-30 | 上海抗体药物国家工程研究中心有限公司 | 可溶性vegfr双功能融合受体、其制备方法及用途 |
| US8901076B2 (en) | 2008-11-03 | 2014-12-02 | Molecular Partner AG | Binding proteins inhibiting the VEGF-A receptor interaction |
| CN101838329A (zh) * | 2009-03-18 | 2010-09-22 | 嘉和生物药业有限公司 | 抗血管新生融合蛋白 |
| DK2488204T3 (en) | 2009-10-16 | 2016-06-06 | Oncomed Pharm Inc | Therapeutic combination and use of DLL4 antagonist antibodies and blood pressure lowering agents |
| AR081361A1 (es) | 2010-04-30 | 2012-08-29 | Molecular Partners Ag | Proteinas de union modificadas que inhiben la interaccion de receptor del factor de crecimiento endotelial vascular de glicoproteina a vegf-a |
| EP3327032A1 (en) | 2010-08-06 | 2018-05-30 | Genzyme Corporation | Vegf antagonist compositions and uses thereof |
| US20140080153A1 (en) * | 2011-01-07 | 2014-03-20 | Chugai Seiyaku Kabushiki Kaisha | Method for improving physical properties of antibody |
| KR20210030510A (ko) | 2011-01-13 | 2021-03-17 | 리제너론 파아마슈티컬스, 인크. | 혈관신생 눈 장애를 치료하기 위한 vegf 길항제의 용도 |
| JO3283B1 (ar) | 2011-04-26 | 2018-09-16 | Sanofi Sa | تركيب يتضمن أفليبيرسيبت, حمض فولينيك, 5- فلورويوراسيل (5- Fu) وإرينوسيتان (FOLFIRI) |
| KR101397088B1 (ko) | 2011-06-10 | 2014-05-19 | 강원대학교산학협력단 | 암세포 증식 억제와 혈관신생 억제를 위한 융합 단백질 및 이를 포함한 항암 조성물 |
| JO3370B1 (ar) * | 2011-11-10 | 2019-03-13 | Regeneron Pharma | طريقة لتثبيط نمو الورم عن طريق تثبيط مستقبل انترلوكين 6 |
| JP6138815B2 (ja) | 2011-12-01 | 2017-05-31 | エーピー バイオサイエンシーズ， インコーポレイテッド | 補体経路およびｖｅｇｆ経路に対するタンパク質インヒビターおよびそれらの使用方法 |
| CN103304668B (zh) * | 2012-03-12 | 2015-10-28 | 江苏健德生物药业有限公司 | Ultra-VEGF-trap免疫融合蛋白、其制备方法及其应用 |
| US10568934B2 (en) | 2012-05-07 | 2020-02-25 | Allergan, Inc. | Method of treating AMD in patients refractory to anti-VEGF therapy |
| WO2014006113A1 (en) | 2012-07-03 | 2014-01-09 | Sanofi | Method of treating cancer by effective amounts of aflibercept |
| AR093445A1 (es) | 2012-11-14 | 2015-06-10 | Regeneron Pharma | Metodos para tratar el cancer de ovario con antagonistas de dll4 |
| MY170528A (en) | 2013-02-18 | 2019-08-09 | Vegenics Pty Ltd | Vegfr-3 ligand binding molecules and uses thereof |
| AR095196A1 (es) | 2013-03-15 | 2015-09-30 | Regeneron Pharma | Medio de cultivo celular libre de suero |
| CN104193828B (zh) * | 2013-09-12 | 2017-04-05 | 北京韩美药品有限公司 | 同时阻断her2和vegfr信号通路的重组融合蛋白 |
| EP3628324A1 (en) | 2013-11-05 | 2020-04-01 | Allergan, Inc. | Method of treating conditions of the eye with an anti-vegf darpin |
| EP3828202A1 (en) | 2014-05-12 | 2021-06-02 | Formycon AG | Pre-filled plastic syringe containing a vegf antagonist |
| RS58957B1 (sr) | 2014-07-18 | 2019-08-30 | Sanofi Sa | Postupak za predviđanje ishoda tretmana sa afliberceptom kod pacijenta za kog se sumnja da boluje od raka |
| JP2016036322A (ja) * | 2014-08-11 | 2016-03-22 | 日本化薬株式会社 | 血管新生因子と結合するキメラタンパク質 |
| AU2015360496B2 (en) | 2014-12-11 | 2021-09-30 | Bayer Healthcare Llc | Treatment of age related macular degeneration with a small active choroidal neovascularization lesion |
| GB201503453D0 (en) | 2015-03-01 | 2015-04-15 | Jain Arjun | Endothelin-1"sponge" |
| TWI870789B (zh) | 2015-08-04 | 2025-01-21 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
| WO2017046140A1 (en) | 2015-09-18 | 2017-03-23 | Bayer Pharma Aktiengesellschaft | Treatment regimens for dr and rvo in dependence of the extent of retinal ischemia |
| WO2017065559A1 (ko) | 2015-10-15 | 2017-04-20 | (주)알테오젠 | Igg fc 도메인을 가지는 융합 단백질의 생산방법 |
| KR101936049B1 (ko) | 2015-10-15 | 2019-01-08 | (주)알테오젠 | IgG Fc 도메인을 가지는 융합 단백질의 생산방법 |
| WO2018218013A2 (en) | 2017-05-24 | 2018-11-29 | Sio2 Medical Products, Inc. | Sterilizable pharmaceutical package for ophthalmic formulations |
| JP7430485B2 (ja) | 2015-11-18 | 2024-02-13 | エスアイオーツー・メディカル・プロダクツ・インコーポレイテッド | 眼科用製剤のための薬剤パッケージ |
| WO2017085253A1 (en) | 2015-11-18 | 2017-05-26 | Formycon Ag | Pre-filled plastic syringe containing a vegf antagonist |
| US10925927B2 (en) | 2015-11-18 | 2021-02-23 | Formycon Ag | Pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist |
| WO2017084616A1 (en) * | 2015-11-19 | 2017-05-26 | Zhuhai Tairuishang Biopharm Ltd. | Methods and compositions for binding vegf |
| WO2017096031A1 (en) | 2015-12-03 | 2017-06-08 | Regeneron Pharmaceuticals, Inc. | Methods of associating genetic variants with a clinical outcome in patients suffering from age-related macular degeneration treated with anti-vegf |
| EP3407868A1 (en) | 2016-01-26 | 2018-12-05 | Formycon AG | Liquid formulation of a vegf antagonist |
| WO2018070390A1 (ja) | 2016-10-12 | 2018-04-19 | 第一三共株式会社 | 抗ｒｏｂｏ４抗体と他剤を含む組成物 |
| WO2018094316A1 (en) | 2016-11-21 | 2018-05-24 | Just Biotherapeutics, Inc. | Aflibercept formulations and uses thereof |
| US20200237997A1 (en) | 2017-05-24 | 2020-07-30 | Formycon Ag | Sterilizable pre-filled pharmaceutical packages comprising a liquid formulation of a vegf-antagonist |
| WO2018215580A1 (en) | 2017-05-24 | 2018-11-29 | Formycon Ag | Method for sterilizing prefilled plastic syringes containing a vegf antagonist |
| TW201904610A (zh) | 2017-06-14 | 2019-02-01 | 德商拜耳製藥公司 | 用於治療新生血管型青光眼之非抗體vegf拮抗劑 |
| WO2019020777A1 (en) | 2017-07-26 | 2019-01-31 | Formycon Ag | LIQUID FORMULATION OF A VEGF ANTAGONIST |
| KR102578087B1 (ko) | 2017-08-17 | 2023-09-18 | 저스트-에보텍 바이오로직스, 아이엔씨. | 숙주세포 갈렉틴(galectins) 및 다른 오염물(contaminant)로부터 글리코실화 단백질을 정제하는 방법 |
| KR102732284B1 (ko) | 2017-11-20 | 2024-11-19 | 저스트-에보텍 바이오로직스, 아이엔씨. | 등장화제로서 라이신 염을 함유하는 아플리베르셉트 제제 및 그것의 용도 |
| KR20250052478A (ko) | 2017-11-27 | 2025-04-18 | 4디 몰레큘러 테라퓨틱스 아이엔씨. | 아데노-관련 바이러스 변이체 캡시드 및 혈관 신생을 억제하기 위한 용도 |
| EP4279135A3 (en) * | 2017-11-30 | 2024-02-21 | Regeneron Pharmaceuticals, Inc. | Use of a vegf antagonist to treat diabetic retinopathy |
| MX2020005699A (es) * | 2017-12-13 | 2020-10-16 | Regeneron Pharma | Dispositivos y sistemas para manipulacion de soportes de lecho de columna para cromatografia y metodos relacionados. |
| WO2019147944A1 (en) | 2018-01-26 | 2019-08-01 | The Regents Of The University Of California | Methods and compositions for treatment of angiogenic disordres using anti-vegf agents |
| CA3092588A1 (en) | 2018-03-02 | 2019-09-06 | Kodiak Sciences Inc. | Il-6 antibodies and fusion constructs and conjugates thereof |
| TW202016125A (zh) * | 2018-05-10 | 2020-05-01 | 美商再生元醫藥公司 | 用於定量及調節蛋白質黏度之系統與方法 |
| EP3790532A1 (en) | 2018-05-10 | 2021-03-17 | Regeneron Pharmaceuticals, Inc. | High concentration vegf receptor fusion protein containing formulations |
| US11519020B2 (en) | 2018-05-25 | 2022-12-06 | Regeneron Pharmaceuticals, Inc. | Methods of associating genetic variants with a clinical outcome in patients suffering from age-related macular degeneration treated with anti-VEGF |
| CN111378044B (zh) | 2018-12-28 | 2022-07-15 | 长春金赛药业有限责任公司 | 抗体融合蛋白、制备方法及其应用 |
| WO2020229584A1 (en) | 2019-05-16 | 2020-11-19 | Formycon Ag | Method for reducing methionine oxidation in recombinant proteins |
| JP2022546082A (ja) | 2019-09-03 | 2022-11-02 | アムジエン・インコーポレーテツド | 薬物送達のための注入デバイス及び注入デバイスのためのパッケージ |
| EP4031208A1 (en) | 2019-09-16 | 2022-07-27 | Amgen Inc. | Method for external sterilization of drug delivery device |
| WO2021072265A1 (en) | 2019-10-10 | 2021-04-15 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
| AU2020393842A1 (en) | 2019-11-25 | 2022-06-16 | The Regents Of The University Of California | Long-acting VEGF inhibitors for intraocular neovascularization |
| IL293286A (en) | 2019-12-06 | 2022-07-01 | Regeneron Pharma | vegf mini-traps and methods of using them |
| NZ781142A (en) | 2019-12-06 | 2023-05-26 | Regeneron Pharma | Anti-vegf protein compositions and methods for producing the same |
| MX2022010177A (es) | 2020-02-24 | 2022-09-12 | Amgen Inc | Envases y sistemas para su uso durante la esterilizacion externa de dispositivos de administracion de farmacos. |
| KR20230008830A (ko) | 2020-05-08 | 2023-01-16 | 리제너론 파마슈티칼스 인코포레이티드 | Vegf 트랩 및 미니-트랩 및 안구 장애 및 암의 치료 방법 |
| CA3216832A1 (en) | 2021-04-26 | 2022-11-03 | Celanese Eva Performance Polymers Llc | Implantable device for sustained release of a macromolecular drug compound |
| EP4145456A1 (en) | 2021-09-06 | 2023-03-08 | Bayer AG | Prediction of a change related to a macular fluid |
| JP2024543158A (ja) | 2021-11-24 | 2024-11-19 | スーチョウ ライト フェリー バイオメッド．カンパニー，リミティド | 多重特異性リガンド結合分子及びその用途 |
| EP4549455A1 (en) * | 2022-08-02 | 2025-05-07 | Panolos Bioscience, Inc. | Modified fusion protein and use thereof |
| EP4588469A1 (en) | 2022-09-16 | 2025-07-23 | Qilu Pharmaceutical Co., Ltd. | Stable high-concentration self-buffering pharmaceutical composition |
| WO2025033876A1 (ko) * | 2023-08-04 | 2025-02-13 | 주식회사 파노로스바이오사이언스 | 변형된 융합 단백질과 scFv의 결합체 및 이의 용도 |
| WO2025213011A1 (en) | 2024-04-05 | 2025-10-09 | Amgen Inc. | Method of assessing stopper movement in a drug delivery device |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9506466D0 (en) * | 1994-08-26 | 1995-05-17 | Prolifix Ltd | Cell cycle regulated repressor and dna element |
| 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 |
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