JP6953433B2 - Ｖｅｇｆアンタゴニストを含む液体医薬組成物および同医薬組成物を含有する充填済みシリンジ - Google Patents
Ｖｅｇｆアンタゴニストを含む液体医薬組成物および同医薬組成物を含有する充填済みシリンジ Download PDFInfo
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- C—CHEMISTRY; METALLURGY
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
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| EP16152767.6 | 2016-01-26 | ||
| EP16152767 | 2016-01-26 | ||
| EP16199497.5 | 2016-11-18 | ||
| EP16199497 | 2016-11-18 | ||
| PCT/EP2017/051662 WO2017129685A1 (en) | 2016-01-26 | 2017-01-26 | Liquid formulation of a vegf antagonist |
Publications (3)
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| JP2019504882A JP2019504882A (ja) | 2019-02-21 |
| JP2019504882A5 JP2019504882A5 (OSRAM) | 2019-12-12 |
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| EP (1) | EP3407868A1 (OSRAM) |
| JP (1) | JP6953433B2 (OSRAM) |
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| CA (1) | CA3011638C (OSRAM) |
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Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2432155C3 (ru) | 2006-06-16 | 2017-11-17 | Ридженерон Фармасьютикалз, Инк. | Составы антагониста vegf, подходящие для интравитреального введения |
| KR101808234B1 (ko) | 2015-06-23 | 2017-12-12 | (주)알테오젠 | IgG Fc 도메인을 가지는 융합 단백질의 안정한 액상 제제 |
| EP3518971A4 (en) * | 2016-09-28 | 2020-05-13 | Board Of Regents, The University Of Texas System | Antibody and protein therapeutic formulations and uses thereof |
| EP3541365A1 (en) * | 2016-11-21 | 2019-09-25 | Just Biotherapeutics, Inc. | Aflibercept formulations and uses thereof |
| US10918754B2 (en) | 2017-03-27 | 2021-02-16 | Regeneron Pharmaceuticals, Inc. | Sterilisation method |
| WO2019020777A1 (en) | 2017-07-26 | 2019-01-31 | Formycon Ag | LIQUID FORMULATION OF A VEGF ANTAGONIST |
| EP3684332A1 (en) | 2017-09-18 | 2020-07-29 | Amgen Inc. | Vegfr-fc fusion protein formulations |
| MA50908A (fr) * | 2017-11-17 | 2020-09-23 | Amgen Inc | Formulations de protéines de fusion vegfr-fc |
| CN111356471A (zh) | 2017-11-20 | 2020-06-30 | 济世发展生物药业有限公司 | 包含赖氨酸盐作为张力调节剂的阿柏西普制剂及其用途 |
| KR20210021299A (ko) | 2018-05-10 | 2021-02-25 | 리제너론 파아마슈티컬스, 인크. | 고농도 vegf 수용체 융합 단백질 함유 제제 |
| BR112020026348A2 (pt) * | 2018-08-30 | 2021-03-30 | Regeneron Pharmaceuticals, Inc. | Método para avaliar a estequiometria e distribuição de tamanho de complexos de proteínas, para selecionar um medicamento de proteína principal e para caracterizar complexos de proteínas, e, composição farmacêutica |
| KR20200029374A (ko) * | 2018-09-10 | 2020-03-18 | 삼성바이오에피스 주식회사 | 단백질을 포함하는 액상 조성물 |
| WO2020087003A1 (en) | 2018-10-26 | 2020-04-30 | Amgen Inc. | Formulations comprising a tris buffer and a protein |
| IL281717B2 (en) * | 2018-10-29 | 2025-07-01 | Hoffmann La Roche | Antibody formulation |
| CN120241997A (zh) | 2019-02-18 | 2025-07-04 | 伊莱利利公司 | 治疗性抗体制剂 |
| KR20230152810A (ko) | 2019-12-06 | 2023-11-03 | 리제너론 파아마슈티컬스, 인크. | 항-vegf 단백질 조성물 및 이를 생산하는 방법 |
| KR20220149690A (ko) * | 2020-03-04 | 2022-11-08 | 상하이 헨리우스 바이오테크, 인크. | 베바시주맙을 포함하는 약물 조제용 제제 |
| JP2023525034A (ja) | 2020-05-08 | 2023-06-14 | 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トラップおよびミニトラップならびに眼障害およびがんの治療方法 |
| US20230312683A1 (en) * | 2020-07-31 | 2023-10-05 | Celltrion Inc. | Stable pharmaceutical preparation |
| US11723955B1 (en) | 2022-05-13 | 2023-08-15 | Allgenesis Biotherapeutics Inc. | VEGFR fusion protein pharmaceutical composition |
| WO2025217334A1 (en) * | 2024-04-09 | 2025-10-16 | Regeneron Pharmaceuticals, Inc. | Low concentration vegf receptor fusion protein containing formulations |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6124449A (en) | 1990-06-11 | 2000-09-26 | Nexstar Pharmaceuticals, Inc. | High affinity TGFβ nucleic acid ligands and inhibitors |
| US5731424A (en) | 1990-06-11 | 1998-03-24 | Nexstar Pharmaceuticals, Inc. | High affinity TGFβ nucleic acid ligands and inhibitors |
| US5731144A (en) | 1990-06-11 | 1998-03-24 | Nexstar Pharmaceuticals, Inc. | High affinity TGFβ nucleic acid ligands |
| US6582959B2 (en) | 1991-03-29 | 2003-06-24 | Genentech, Inc. | Antibodies to vascular endothelial cell growth factor |
| ATE348110T1 (de) | 1992-10-28 | 2007-01-15 | Genentech Inc | Hvegf rezeptor als vegf 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 |
| JP4531132B2 (ja) | 1995-06-02 | 2010-08-25 | ギリード・サイエンシズ・インコーポレーテッド | 増殖因子に対する高親和性オリゴヌクレオチドリガンド |
| SI1695985T1 (sl) | 1997-04-07 | 2011-06-30 | Genentech Inc | Postopki za tvorbo humaniziranih protiteles z naključno mutagenezo |
| WO1998045331A2 (en) | 1997-04-07 | 1998-10-15 | Genentech, Inc. | Anti-vegf antibodies |
| US20020032315A1 (en) | 1997-08-06 | 2002-03-14 | Manuel Baca | Anti-vegf antibodies |
| US6703020B1 (en) | 1999-04-28 | 2004-03-09 | Board Of Regents, The University Of Texas System | Antibody conjugate methods for selectively inhibiting VEGF |
| CA2376379C (en) | 1999-06-08 | 2007-08-07 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
| WO2005044853A2 (en) | 2003-11-01 | 2005-05-19 | Genentech, Inc. | Anti-vegf antibodies |
| CN102614134B (zh) * | 2005-03-25 | 2016-09-07 | 瑞泽恩制药公司 | Vegf拮抗剂制剂 |
| RU2432155C3 (ru) * | 2006-06-16 | 2017-11-17 | Ридженерон Фармасьютикалз, Инк. | Составы антагониста vegf, подходящие для интравитреального введения |
| EP3219294A1 (en) * | 2006-06-20 | 2017-09-20 | Ben-Gurion University of The Negev Research and Development Authority | Amphiphilic peptides and hydrogel matrices thereof for bone repair |
| KR102095257B1 (ko) | 2008-06-25 | 2020-04-01 | 노바르티스 아게 | Ｖｅｇｆ를 억제하는 안정하고 가용성인 항체 |
| WO2010060748A1 (en) | 2008-11-03 | 2010-06-03 | Molecular Partners Ag | Binding proteins inhibiting the vegf-a receptor interaction |
| 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 |
| US20130323242A1 (en) * | 2012-06-01 | 2013-12-05 | Ophthotech Corp. | Compositions comprising an anti-pdgf aptamer and a vegf antagonist |
| KR20150033620A (ko) * | 2012-06-01 | 2015-04-01 | 옵쏘테크 코포레이션 | 항-pdgf 압타머 및 vegf 길항제를 포함하는 조성물 |
| JP2015528454A (ja) * | 2012-08-28 | 2015-09-28 | ノバルティス アーゲー | 眼血管増殖性疾患の処置におけるｖｅｇｆアンタゴニストの使用 |
| EP3010525A1 (en) * | 2013-06-20 | 2016-04-27 | Novartis AG | Use of a vegf antagonist in treating choroidal neovascularisation |
| ES2875878T3 (es) | 2013-11-18 | 2021-11-11 | Formycon Ag | Composición farmacéutica de un anticuerpo anti-VEGF |
| WO2015173260A1 (en) | 2014-05-12 | 2015-11-19 | Formycon Ag | Pre-filled plastic syringe containing a vegf antagonist |
| KR101808234B1 (ko) * | 2015-06-23 | 2017-12-12 | (주)알테오젠 | IgG Fc 도메인을 가지는 융합 단백질의 안정한 액상 제제 |
| EP3377151A1 (en) | 2015-11-18 | 2018-09-26 | Formycon AG | Pre-filled plastic syringe containing a vegf antagonist |
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| US20200237862A1 (en) | 2020-07-30 |
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| EP3407868A1 (en) | 2018-12-05 |
| JP2019504882A (ja) | 2019-02-21 |
| US20190030123A1 (en) | 2019-01-31 |
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