Title:
FUSION PROTEIN OF MUTATED SINGLE-CHAIN HUMAN COAGULATION FACTOR VIII, PREPARATION METHOD THEREFOR, AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/063562
Kind Code:
A1
Abstract:
Disclosed is a fusion protein of a mutated recombinant single-chain human coagulation factor VIII (FVIII), a preparation method therefor, and a use thereof. The fusion protein sequentially comprises, from an N-terminus to a C-terminus, a mutated single-chain human FVIII having a partially deleted B-domain, a flexible peptide linker, at least one rigid unit of a carboxyl-terminal peptide of a human chorionic gonadotropin beta subunit, and a half-life prolonging moiety (preferably an IgG Fc variant). The fusion protein has a similar biological activity to a recombinant FVIII, a prolonged active half life in vivo, and better stability in vitro and in vivo, and thus improves the pharmacokinetics and efficacy of the fusion protein.
Inventors:
GAO YONGJUAN (CN)
JIA SHIXIANG (CN)
ZHENG YUNCHENG (CN)
JIN YINGYING (CN)
WANG ZHU (CN)
DONG ZHAO (CN)
CHEN SI (CN)
SUN BILL (CN)
LI QIANG (CN)
JIA SHIXIANG (CN)
ZHENG YUNCHENG (CN)
JIN YINGYING (CN)
WANG ZHU (CN)
DONG ZHAO (CN)
CHEN SI (CN)
SUN BILL (CN)
LI QIANG (CN)
Application Number:
PCT/CN2019/107432
Publication Date:
April 02, 2020
Filing Date:
September 24, 2019
Export Citation:
Assignee:
AMPSOURCE BIOPHARMA SHANGHAI INC (CN)
PHARMAB INC (CN)
PHARMAB INC (CN)
International Classes:
C07K19/00; A61K38/00; A61P7/00; C12N9/00; C12N15/00
Domestic Patent References:
| WO2013106789A1 | 2013-07-18 |
Foreign References:
| CN106279436A | 2017-01-04 | |||
| CN107787328A | 2018-03-09 | |||
| CN201280031137A | 2012-06-25 | |||
| KR101027427B1 | 2011-04-11 | |||
| KR20100099179A | 2010-09-10 | |||
| CN201280066663A | 2012-12-28 | |||
| US4399216A | 1983-08-16 | |||
| US4818679A | 1989-04-04 |
Other References:
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PETERS R T ET AL., J THROMB HAEMOST, vol. 11, no. 1, 2013, pages 670 - 678
SANDBERG H ET AL., SEMIN HEMATOL, vol. 38, 2001, pages 4 - 12
TURECEK PL ET AL., HAMOSTASEOLOGIE, vol. 1, 2012, pages 29 - 38
PAUL R ET AL., J BIOL CHEM, vol. 279, 2004, pages 6213 - 6216
SHIELDS RL ET AL., J BIOL CHEM, vol. 276, no. 9, 2001, pages 6591 - 604
FARES F A ET AL., PROC NATL ACAD SCI USA, vol. 89, no. 10, 1992, pages 4304 - 4308
EFFERIS R ET AL., IMMUNOL REV, vol. 163, 1998, pages 59 - 76
ROOPENIAN ET AL., NAT. RVIEW IMMUNOLOGY, vol. 7, 2007, pages 715 - 725
PAUL RHINTON ET AL., J IMMUNOL, vol. 176, 2006, pages 346 - 356
DATTA-MANNAN A ET AL., MABS. TAYLOR&FRANCIS, vol. 4, 2012, pages 267 - 273
OLANDER RM ET AL., DEV BIOL STAND, vol. 86, 1996, pages 338
See also references of EP 3858865A4
PETERS R T ET AL., J THROMB HAEMOST, vol. 11, no. 1, 2013, pages 670 - 678
SANDBERG H ET AL., SEMIN HEMATOL, vol. 38, 2001, pages 4 - 12
TURECEK PL ET AL., HAMOSTASEOLOGIE, vol. 1, 2012, pages 29 - 38
PAUL R ET AL., J BIOL CHEM, vol. 279, 2004, pages 6213 - 6216
SHIELDS RL ET AL., J BIOL CHEM, vol. 276, no. 9, 2001, pages 6591 - 604
FARES F A ET AL., PROC NATL ACAD SCI USA, vol. 89, no. 10, 1992, pages 4304 - 4308
EFFERIS R ET AL., IMMUNOL REV, vol. 163, 1998, pages 59 - 76
ROOPENIAN ET AL., NAT. RVIEW IMMUNOLOGY, vol. 7, 2007, pages 715 - 725
PAUL RHINTON ET AL., J IMMUNOL, vol. 176, 2006, pages 346 - 356
DATTA-MANNAN A ET AL., MABS. TAYLOR&FRANCIS, vol. 4, 2012, pages 267 - 273
OLANDER RM ET AL., DEV BIOL STAND, vol. 86, 1996, pages 338
See also references of EP 3858865A4
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