Title:
USE OF PROTEIN SEQUENCE CAPABLE OF BINDING TO SUBSTRATE IN PREPARATION OF PRODUCT FOR INHIBITING FIBRIN ASSEMBLY
Document Type and Number:
WIPO Patent Application WO/2023/077413
Kind Code:
A1
Abstract:
Provided are a protein containing an amino acid sequence capable of binding to a peptide fragment of a substrate GPRP, a fibrinogen-like protein 1 (FGL1) containing the amino acid sequence, and a fibrinogen domain (FD) of the FGL1, wherein a single FD protein also has a function the same as or similar to that of the FGL1. The FGL1 and FD, which have different action mechanisms from existing drugs, can inhibit fibrin assembly in the process of thrombogenesis by means of competing for fibrin substrate binding pockets. The FGL1 and FD can have a stronger affinity to the substrate by means of mutation, thereby effectively enhancing a usage effect of drugs for treating thrombus.
Inventors:
DONG XIANCHI (CN)
LIU WEN (CN)
DING JIANPING (CN)
SHI YU (CN)
XU SHUTONG (CN)
XU JIANBO (CN)
LIU WEN (CN)
DING JIANPING (CN)
SHI YU (CN)
XU SHUTONG (CN)
XU JIANBO (CN)
Application Number:
PCT/CN2021/128944
Publication Date:
May 11, 2023
Filing Date:
November 05, 2021
Export Citation:
Assignee:
UNIV NANJING (CN)
CENTER FOR EXCELLENCE IN MOLECULAR CELL SCIENCE (CN)
UNIV HUAZHONG AGRICULTURAL (CN)
CENTER FOR EXCELLENCE IN MOLECULAR CELL SCIENCE (CN)
UNIV HUAZHONG AGRICULTURAL (CN)
International Classes:
C07K14/475; A61K38/18; A61K39/00; A61K45/06; A61K47/64; A61K48/00; A61P7/02; C07K1/16; C07K1/22; C12N15/12; C12N15/85
Foreign References:
| CN108404119A | 2018-08-17 | |||
| CN1800382A | 2006-07-12 |
Other References:
"Doctoral Dissertation", 1 May 2016, SHANGHAI JIAOTONG UNIVERSITY, CN, article ZHOU, JINGYI: "Clinical and Molecular Pathological Study of Congenital Dysfibrinogenemia", pages: 1 - 135, XP009545892, DOI: 10.27307/d.cnki.gsjtu.2016.003213
XU, XIUCAI ET AL.: "Fibrinogen β Chain Gene Mutation Contributes to one Congenital Afibrinogenemia", CHINESE JOURNAL OF HEMATOLOGY, vol. 26, no. 3, 31 December 2005 (2005-12-31), pages 137 - 139, XP009545339
DATABASE Nucleotide NCBI; 17 October 2021 (2021-10-17), ANONYMOUS : "Homo sapiens fibrinogen like 1 (FGL1), transcript variant 1, mRNA ", XP093063177, Database accession no. NM_004467.4
HUANG, DANDAN ET AL.: "Identification and Molecular Pathogenesis Study of a Case of Inherited Dysfibrinogenemia", CHINESE JOURNAL OF CLINICAL LABORATORY SCIENCE, vol. 37, no. 9, 30 September 2019 (2019-09-30), pages 675 - 679, XP009545341
"Master's thesis", 21 April 2016, NORTH CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY, CN, article XIE, YANYAN: "Genetic Defect Analysis of a Chinese Family with Congenital Afibrinogenemia", pages: 1 - 55, XP009545949
"Master's thesis", 1 March 2019, HEBEI MEDICAL UNIVERSITY, CN, article LI, DANDAN: "Study of Clinical and Molecular Pathogenesis in Two Patients with Congenital Dysfibrinogenemia", pages: 1 - 38, XP009545948
DIB N., QUELIN F., TERNISIEN C., HANSS M., MICHALAK S., DE MAZANCOURT P., ROUSSELET M.C., CALÈS P.: "Fibrinogen angers with a new deletion (γ GVYYQ 346‐350) causes hypofibrinogenemia with hepatic storage", JOURNAL OF THROMBOSIS AND HAEMOSTASIS, JOHN WILEY & SONS, vol. 5, no. 10, 1 October 2007 (2007-10-01), pages 1999 - 2005, XP093063186, ISSN: 1538-7836, DOI: 10.1111/j.1538-7836.2007.02713.x
VU D., NEERMAN-ARBEZ M.: "Molecular mechanisms accounting for fibrinogen deficiency: from large deletions to intracellular retention of misfolded proteins", JOURNAL OF THROMBOSIS AND HAEMOSTASIS, JOHN WILEY & SONS, vol. 5, 1 July 2007 (2007-07-01), pages 125 - 131, XP093063189, ISSN: 1538-7836, DOI: 10.1111/j.1538-7836.2007.02465.x
OKUMURA, N. ET AL.: "A novel variant fibrinogen, deletion of Bh111Ser in coiled-coil region, affecting fibrin lateral aggregation.", CLINICA CHIMICA ACTA., vol. 365, 17 October 2005 (2005-10-17), pages 160 - 167, XP025058785, DOI: 10.1016/j.cca.2005.08.014
XU, XIUCAI ET AL.: "Fibrinogen β Chain Gene Mutation Contributes to one Congenital Afibrinogenemia", CHINESE JOURNAL OF HEMATOLOGY, vol. 26, no. 3, 31 December 2005 (2005-12-31), pages 137 - 139, XP009545339
DATABASE Nucleotide NCBI; 17 October 2021 (2021-10-17), ANONYMOUS : "Homo sapiens fibrinogen like 1 (FGL1), transcript variant 1, mRNA ", XP093063177, Database accession no. NM_004467.4
HUANG, DANDAN ET AL.: "Identification and Molecular Pathogenesis Study of a Case of Inherited Dysfibrinogenemia", CHINESE JOURNAL OF CLINICAL LABORATORY SCIENCE, vol. 37, no. 9, 30 September 2019 (2019-09-30), pages 675 - 679, XP009545341
"Master's thesis", 21 April 2016, NORTH CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY, CN, article XIE, YANYAN: "Genetic Defect Analysis of a Chinese Family with Congenital Afibrinogenemia", pages: 1 - 55, XP009545949
"Master's thesis", 1 March 2019, HEBEI MEDICAL UNIVERSITY, CN, article LI, DANDAN: "Study of Clinical and Molecular Pathogenesis in Two Patients with Congenital Dysfibrinogenemia", pages: 1 - 38, XP009545948
DIB N., QUELIN F., TERNISIEN C., HANSS M., MICHALAK S., DE MAZANCOURT P., ROUSSELET M.C., CALÈS P.: "Fibrinogen angers with a new deletion (γ GVYYQ 346‐350) causes hypofibrinogenemia with hepatic storage", JOURNAL OF THROMBOSIS AND HAEMOSTASIS, JOHN WILEY & SONS, vol. 5, no. 10, 1 October 2007 (2007-10-01), pages 1999 - 2005, XP093063186, ISSN: 1538-7836, DOI: 10.1111/j.1538-7836.2007.02713.x
VU D., NEERMAN-ARBEZ M.: "Molecular mechanisms accounting for fibrinogen deficiency: from large deletions to intracellular retention of misfolded proteins", JOURNAL OF THROMBOSIS AND HAEMOSTASIS, JOHN WILEY & SONS, vol. 5, 1 July 2007 (2007-07-01), pages 125 - 131, XP093063189, ISSN: 1538-7836, DOI: 10.1111/j.1538-7836.2007.02465.x
OKUMURA, N. ET AL.: "A novel variant fibrinogen, deletion of Bh111Ser in coiled-coil region, affecting fibrin lateral aggregation.", CLINICA CHIMICA ACTA., vol. 365, 17 October 2005 (2005-10-17), pages 160 - 167, XP025058785, DOI: 10.1016/j.cca.2005.08.014
Attorney, Agent or Firm:
BEIJING ZHI CHENG HAN FANG IP AGENCY CO., LTD. (CN)
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