Hyperglycosylatedhuman coagulation factor VIII fusion protein and preparation method and application thereof

A technology of human blood coagulation factor and fusion protein, which is applied in the treatment of various blood coagulation related diseases, fusion protein of human blood coagulation factor VIII and its preparation field, can solve problems such as difficulty in expressing homodimeric FVIII fusion protein, and achieve stable expression , high output, good stability

Active Publication Date: 2017-01-04
AMPSOURCE BIOPHARMA (SHANGHAI) INC +3
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Problems solved by technology

According to reports, HEK-293 cells were transfected with the double expression vector of rFVIIIFc and Fc constructed by Biogen, and the fusion in the form of rFVIIIFc homodimer was not expected to be detected in the expressed product, and only the monomer-dimer was expressed. Polymeric hybrid rFVIIIFc fusion protein and Fc dimer, the company's researchers speculate that the possible reason is that the expression s...

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  • Hyperglycosylatedhuman coagulation factor VIII fusion protein and preparation method and application thereof
  • Hyperglycosylatedhuman coagulation factor VIII fusion protein and preparation method and application thereof
  • Hyperglycosylatedhuman coagulation factor VIII fusion protein and preparation method and application thereof

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Embodiment Construction

[0067] hCG-β carboxy-terminal peptide (CTP)

[0068] CTP is a short peptide derived from the carboxy-terminus of the β-subunit of human chorionic gonadotropin (hCG). The four reproductive-related polypeptide hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyrotropin (TSH) and chorionic gonadotropin (hCG) contain the same α-subunit and each specific β -subunit. Compared with the other three hormones, the half-life of hCG in vivo is significantly prolonged, which is mainly derived from the unique carboxy-terminal peptide (CTP) on its β-subunit (Fares FA et al., Proc NatlAcad Sci USA, 1992,89 (10): 4304 -4308). Natural CTP contains 37 amino acid residues, it has 4 O-glycosylation sites, and the terminal is a sialic acid residue. Negatively charged, highly sialylated CTP can resist its clearance by the kidney, thereby prolonging the half-life of the protein in vivo (Fares FA et al., Proc Natl Acad Sci USA, 1992, 89(10): 4304-4308). However, the present ...

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Abstract

The invention discloses a hyperglycosylated human coagulation factor VIII (FVIII) fusion protein and a preparation method and application thereof. The fusion protein successively contains human FVIII, a soft peptide connector, at least one human chorionic gonadotropin betasubunitcarboxyl terminal peptide rigid unit and prolonged half-life period portion (preferably ahumanIgG Fc variant) from an end N to an end C. The fusion protein has biological activity similar to that of recombinant FVIII and prolonged in-vivo activity half-life period, thereby improving the pharmacokinetics and drug efficacy.

Description

technical field [0001] The present invention relates to the field of fusion proteins, more specifically, to a fusion protein of human blood coagulation factor VIII (FVIII) and its preparation method and application, especially the application for treating various blood coagulation-related diseases. Background technique [0002] Coagulation factor VIII (FVIII), also known as antihemophilic factor, plays a very important role in the endogenous coagulation system. According to a large number of research results of FVIII molecular genetics, it is shown that the lack of FVIII in the sex chromosome X-linked gene will cause hemophilia A. According to statistics, the prevalence of hemophilia A in the male population is 1 / 5000, accounting for more than 80% of the total number of hemophilias. The current commonly used treatment for hemophilia A is replacement therapy, which is to supplement the lack of coagulation factor VIII in hemophilia patients. [0003] FVIII is a multistructur...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62C12N15/85C12N5/10A61K38/37A61K47/48A61P7/04
CPCC07K14/59C07K14/755C12N15/85A61K38/00C07K2319/31C07K2319/30C12N2800/107A61P7/04C07K14/745C07K2319/00A01K2217/075A01K2267/0381A01K2227/105A61K38/37C07K19/00C12N5/10C12N15/62A61K47/6811A61K47/65C07K7/06C07K7/08C07K2317/52
Inventor 李强朱文臣李媛丽朱成功高永娟任子甲朱鹿燕孙乃超王晓山刘宾李智王文文姜明王齐磊王莉蕊王淑亚朱松林高洁苏鸿声
Owner AMPSOURCE BIOPHARMA (SHANGHAI) INC
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