CN112673026A - 突变型单链人凝血因子viii融合蛋白及其制备方法与用途 - Google Patents

突变型单链人凝血因子viii融合蛋白及其制备方法与用途 Download PDF

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CN112673026A
CN112673026A CN201980059489.0A CN201980059489A CN112673026A CN 112673026 A CN112673026 A CN 112673026A CN 201980059489 A CN201980059489 A CN 201980059489A CN 112673026 A CN112673026 A CN 112673026A
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fusion protein
human
fviii
amino acid
acid sequence
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高永娟
贾世香
郑云程
金莹莹
王著
董炤
陈思
孙乃超
李强
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Xuhua Shanghai Biological R & D Center Co ltd
Anyuan Pharmaceutical Technology Shanghai Co ltd
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Xuhua Shanghai Biological R & D Center Co ltd
Anyuan Pharmaceutical Technology Shanghai Co ltd
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745Blood coagulation or fibrinolysis factors
    • C07K14/755Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36Blood coagulation or fibrinolysis factors
    • A61K38/37Factors VIII
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • C07K14/59Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/30Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/31Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/90Fusion polypeptide containing a motif for post-translational modification
    • C07K2319/91Fusion polypeptide containing a motif for post-translational modification containing a motif for glycosylation

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Peptides Or Proteins (AREA)

Abstract

本发明公开了一种突变型重组单链人凝血因子VIII(FVIII)融合蛋白、其制备方法及用途。该融合蛋白从N端到C端依次包含缺失部分B‑结构域的突变型单链人FVIII、柔性肽接头、至少1个人绒毛膜促性腺激素β亚基羧基末端肽刚性单元和延长半衰期部分(优选人IgG Fc变体)。该融合蛋白具有与重组FVIII类似的生物学活性及延长的体内活性半衰期,以及更好的体外和体内稳定性,从而改善融合蛋白的药代动力学和药效。

Description

PCT国内申请,说明书已公开。

Claims (17)

  1. PCT国内申请,权利要求书已公开。
CN201980059489.0A 2018-09-26 2019-09-24 突变型单链人凝血因子viii融合蛋白及其制备方法与用途 Pending CN112673026A (zh)

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CN201811123918.XA CN110950964B (zh) 2018-09-26 2018-09-26 突变型单链人凝血因子viii融合蛋白及其制备方法与用途
CN201811123918X 2018-09-26
PCT/CN2019/107432 WO2020063562A1 (zh) 2018-09-26 2019-09-24 突变型单链人凝血因子viii融合蛋白及其制备方法与用途

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CN112673026A true CN112673026A (zh) 2021-04-16

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CN202110532012.9A Active CN113105562B (zh) 2018-09-26 2018-09-26 突变型单链人凝血因子viii在制备融合蛋白中的应用
CN201980059489.0A Pending CN112673026A (zh) 2018-09-26 2019-09-24 突变型单链人凝血因子viii融合蛋白及其制备方法与用途

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CN202110532012.9A Active CN113105562B (zh) 2018-09-26 2018-09-26 突变型单链人凝血因子viii在制备融合蛋白中的应用

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US (1) US20220033476A1 (zh)
EP (1) EP3858865A4 (zh)
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BR (1) BR112021005831A2 (zh)
WO (1) WO2020063562A1 (zh)

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CN113461827A (zh) * 2020-03-31 2021-10-01 安源医药科技(上海)有限公司 高效分离纯化重组人凝血因子VIII Fc融合蛋白的方法
CN111808170A (zh) * 2020-06-29 2020-10-23 江苏为真生物医药技术股份有限公司 多肽、hla-dr蛋白及其制备方法和应用
WO2023227015A1 (zh) * 2022-05-25 2023-11-30 江苏晟斯生物制药有限公司 具有延长的半衰期的fviii融合蛋白缀合物及其应用
CN116036244B (zh) * 2023-02-24 2023-09-19 北京基科晟斯医药科技有限公司 培重组人凝血因子VIII-Fc融合蛋白用于治疗含抑制物的血友病A的用途

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CN110950964A (zh) 2020-04-03
CN113105562B (zh) 2023-12-01
EP3858865A9 (en) 2024-02-14
EP3858865A4 (en) 2023-04-19
CN113105562A (zh) 2021-07-13
US20220033476A1 (en) 2022-02-03
EP3858865A1 (en) 2021-08-04
CN110950964B (zh) 2021-06-18
WO2020063562A1 (zh) 2020-04-02
BR112021005831A2 (pt) 2021-07-27

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