JP2009531036A - Ｖｅｇｆ受容体融合タンパク質およびそれらの使用 - Google Patents
Ｖｅｇｆ受容体融合タンパク質およびそれらの使用 Download PDFInfo
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Wood Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Ophthalmology & Optometry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100662572A CN100502945C (zh) | 2006-03-31 | 2006-03-31 | Vegf受体融合蛋白在治疗眼睛疾病中的应用 |
| PCT/CN2007/001021 WO2007112675A1 (fr) | 2006-03-31 | 2007-03-29 | Protéine de fusion du récepteur du vegf et son utilisation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009531036A true JP2009531036A (ja) | 2009-09-03 |
| JP2009531036A5 JP2009531036A5 (https=) | 2009-12-17 |
Family
ID=37736587
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009501824A Pending JP2009531036A (ja) | 2006-03-31 | 2007-03-29 | Ｖｅｇｆ受容体融合タンパク質およびそれらの使用 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20090264358A1 (https=) |
| EP (1) | EP2000483A4 (https=) |
| JP (1) | JP2009531036A (https=) |
| KR (1) | KR20090010030A (https=) |
| CN (1) | CN100502945C (https=) |
| AU (1) | AU2007234272A1 (https=) |
| BR (1) | BRPI0710223A2 (https=) |
| CA (1) | CA2647142A1 (https=) |
| RU (1) | RU2008136655A (https=) |
| WO (1) | WO2007112675A1 (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013516169A (ja) * | 2009-12-31 | 2013-05-13 | インダストリー−ユニバーシティー コーポレーション ファウンデーション ハンヤン ユニバーシティー | 抗血管新生活性を有する組換えアデノウイルス |
| JP2016037488A (ja) * | 2014-08-11 | 2016-03-22 | 日本化薬株式会社 | ＴＧＦβ阻害機能を持つキメラタンパク質 |
| JP2021534825A (ja) * | 2018-12-07 | 2021-12-16 | 榮昌生物制薬(烟台)股▲フン▼有限公司Remegen Co., Ltd. | 二機能血管新生阻害剤及びその用途 |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2633574T3 (es) | 2005-03-25 | 2017-09-22 | Regeneron Pharmaceuticals, Inc. | Formulaciones de antagonistas de VEGF |
| CA2654510C (en) | 2006-06-16 | 2015-03-17 | Regeneron Pharmaceuticals, Inc. | Vegf antagonist formulations suitable for intravitreal administration |
| CN101279092B (zh) * | 2007-04-02 | 2010-10-27 | 成都康弘生物科技有限公司 | Vegf受体融合蛋白在制备治疗与血管生成有关的疾病中的应用 |
| CN101721699B (zh) * | 2008-10-13 | 2012-11-07 | 成都康弘生物科技有限公司 | Vegf受体融合蛋白在制备治疗伴随vegf升高的炎症反应的药物中的应用 |
| CN102233132B (zh) * | 2010-04-28 | 2013-10-23 | 成都康弘生物科技有限公司 | Vegf受体融合蛋白在制备抑制眼表新生血管生长的药物中的应用 |
| CN103816115B (zh) * | 2010-08-31 | 2017-06-27 | 成都康弘生物科技有限公司 | 一种含有抑制血管增生的融合蛋白的药物组合物及用途 |
| CN102380096B (zh) * | 2010-08-31 | 2014-04-30 | 成都康弘生物科技有限公司 | 一种含有抑制血管增生的融合蛋白的药物组合物及用途 |
| KR20190049934A (ko) | 2011-01-13 | 2019-05-09 | 리제너론 파아마슈티컬스, 인크. | 혈관신생 눈 장애를 치료하기 위한 vegf 길항제의 용도 |
| KR102049990B1 (ko) | 2013-03-28 | 2019-12-03 | 삼성전자주식회사 | c-Met 항체 및 VEGF 결합 단편이 연결된 융합 단백질 |
| US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
| CN114306575A (zh) | 2014-12-11 | 2022-04-12 | 拜耳医药保健有限责任公司 | 具有小的活动性脉络膜新生血管病变的年龄相关性黄斑变性的治疗 |
| 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 |
| HUE059827T2 (hu) | 2017-11-30 | 2023-01-28 | Regeneron Pharma | VEGF-antagonista alkalmazása angiogén szembetegségek kezelésére |
| EP3758737A4 (en) | 2018-03-02 | 2022-10-12 | Kodiak Sciences Inc. | IL-6 ANTIBODIES AND FUSION CONSTRUCTS AND CONJUGATES THEREOF |
| DK4364724T3 (da) | 2018-05-10 | 2025-12-22 | Regeneron Pharma | Formuleringer med høj koncentration af VEGF-receptorfusionsprotein |
| EP3886946A1 (en) | 2019-06-05 | 2021-10-06 | Regeneron Pharmaceuticals, Inc. | Devices and methods for precision dose delivery |
| WO2021108530A1 (en) * | 2019-11-26 | 2021-06-03 | University Of Massachusetts | Recombinant adeno-associated virus for delivery of kh902 (conbercept) and uses thereof |
| SG11202110968VA (en) | 2019-12-06 | 2021-10-28 | Regeneron Pharma | Anti-vegf protein compositions and methods for producing the same |
| AU2021268026A1 (en) | 2020-05-08 | 2023-01-19 | Regeneron Pharmaceuticals, Inc. | VEGF traps and mini-traps and methods for treating ocular disorders and cancer |
| KR20240008821A (ko) | 2021-05-17 | 2024-01-19 | 리제너론 파아마슈티컬스, 인크. | 혈관신생성 눈 장애 치료를 위한 연장된 고용량 vegf 길항제 요법 |
| IL315347A (en) | 2022-03-15 | 2024-11-01 | Regeneron Pharma | Prolonged high-dose VEGF antagonist regimens for the treatment of angiogenic ocular disorders |
| IL315374A (en) | 2022-03-15 | 2024-11-01 | Regeneron Pharma | Prolonged high-dose VEGF antagonist regimens for the treatment of angiogenic ocular disorders |
| TW202412840A (zh) | 2022-09-16 | 2024-04-01 | 大陸商齊魯製藥有限公司 | 一種穩定的高濃度自緩衝藥物組合物 |
| USD1120314S1 (en) | 2022-11-30 | 2026-03-24 | Regeneron Pharmaceuticals, Inc. | Dose delivery device |
| CN121712520A (zh) | 2023-06-23 | 2026-03-20 | 瑞泽恩制药公司 | 用于治疗血管生成性眼病的延长的高剂量vegf拮抗剂方案 |
| CN120204358A (zh) * | 2023-12-27 | 2025-06-27 | 成都康弘生物科技有限公司 | 一种含有抗vegf的融合蛋白的药物组合物 |
| WO2025217334A1 (en) | 2024-04-09 | 2025-10-16 | Regeneron Pharmaceuticals, Inc. | Low concentration vegf receptor fusion protein containing formulations |
| CN118108862B (zh) * | 2024-04-29 | 2024-08-09 | 上海鼎新基因科技有限公司 | 抗血管新生的融合蛋白及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005000895A2 (en) * | 2003-06-30 | 2005-01-06 | Regeneron Pharmaceuticals, Inc. | Vegf traps and therapeutic uses thereof |
| CN1706867A (zh) * | 2004-06-08 | 2005-12-14 | 成都康弘科技实业（集团）有限公司 | 抑制血管新生的融合蛋白质及其用途 |
| WO2005121176A1 (en) * | 2004-06-08 | 2005-12-22 | Chengdu Kanghong Biotechnologies Co. Ltd | Angiogenesis-inhibiting chimeric protein and the use |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101433715B (zh) * | 1999-06-08 | 2013-04-17 | 里珍纳龙药品有限公司 | 具有改善的药物动力学特性的修饰嵌合多肽 |
| MXPA06003164A (es) * | 2003-09-23 | 2006-06-05 | Novartis Ag | Combinaciones de un inhibidor del receptor de vegf con otros agentes terapeuticos. |
-
2006
- 2006-03-31 CN CNB2006100662572A patent/CN100502945C/zh not_active Expired - Lifetime
-
2007
- 2007-03-29 KR KR1020087025464A patent/KR20090010030A/ko not_active Withdrawn
- 2007-03-29 WO PCT/CN2007/001021 patent/WO2007112675A1/zh not_active Ceased
- 2007-03-29 CA CA002647142A patent/CA2647142A1/en not_active Abandoned
- 2007-03-29 EP EP07720595A patent/EP2000483A4/en not_active Withdrawn
- 2007-03-29 RU RU2008136655/13A patent/RU2008136655A/ru not_active Application Discontinuation
- 2007-03-29 BR BRPI0710223-2A patent/BRPI0710223A2/pt not_active IP Right Cessation
- 2007-03-29 JP JP2009501824A patent/JP2009531036A/ja active Pending
- 2007-03-29 AU AU2007234272A patent/AU2007234272A1/en not_active Abandoned
-
2008
- 2008-09-29 US US12/241,017 patent/US20090264358A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005000895A2 (en) * | 2003-06-30 | 2005-01-06 | Regeneron Pharmaceuticals, Inc. | Vegf traps and therapeutic uses thereof |
| CN1706867A (zh) * | 2004-06-08 | 2005-12-14 | 成都康弘科技实业（集团）有限公司 | 抑制血管新生的融合蛋白质及其用途 |
| WO2005121176A1 (en) * | 2004-06-08 | 2005-12-22 | Chengdu Kanghong Biotechnologies Co. Ltd | Angiogenesis-inhibiting chimeric protein and the use |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013516169A (ja) * | 2009-12-31 | 2013-05-13 | インダストリー−ユニバーシティー コーポレーション ファウンデーション ハンヤン ユニバーシティー | 抗血管新生活性を有する組換えアデノウイルス |
| JP2016037488A (ja) * | 2014-08-11 | 2016-03-22 | 日本化薬株式会社 | ＴＧＦβ阻害機能を持つキメラタンパク質 |
| JP2021534825A (ja) * | 2018-12-07 | 2021-12-16 | 榮昌生物制薬(烟台)股▲フン▼有限公司Remegen Co., Ltd. | 二機能血管新生阻害剤及びその用途 |
| JP2023052623A (ja) * | 2018-12-07 | 2023-04-11 | 榮昌生物制薬（烟台）股▲フン▼有限公司 | 二機能血管新生阻害剤及びその用途 |
| JP7516381B2 (ja) | 2018-12-07 | 2024-07-16 | 榮昌生物制薬（烟台）股▲フン▼有限公司 | 二機能血管新生阻害剤及びその用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2000483A9 (en) | 2009-03-18 |
| CN1915427A (zh) | 2007-02-21 |
| KR20090010030A (ko) | 2009-01-28 |
| WO2007112675A8 (fr) | 2009-07-09 |
| EP2000483A2 (en) | 2008-12-10 |
| AU2007234272A1 (en) | 2007-10-11 |
| BRPI0710223A2 (pt) | 2011-08-02 |
| CN100502945C (zh) | 2009-06-24 |
| EP2000483A4 (en) | 2009-10-28 |
| CA2647142A1 (en) | 2007-10-11 |
| WO2007112675A1 (fr) | 2007-10-11 |
| RU2008136655A (ru) | 2010-05-10 |
| US20090264358A1 (en) | 2009-10-22 |
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