Title:
RECOMBINANT FUSION PROTEASE CAPABLE OF ELIMINATING IN VIVO IMMUNOGLOBULIN A, PREPARATION METHOD THEREFOR, AND APPLICATION IN TREATING IGA NEPHROPATHY
Document Type and Number:
WIPO Patent Application WO/2022/214108
Kind Code:
A1
Abstract:
An AK183 protease-based recombinant fusion protein, and an application thereof in preparing a drug for IgA nephropathy and other related diseases mediated by IgA complex deposition. The recombinant fusion protein structure includes a human symbiotic bacteria protease AK183 active area and a human immunoglobulin fragment, the human immunoglobulin fragment being located at the N end of the protease AK183 active area. Also provided is a method for preparing the recombinant fusion protein. The recombinant fusion protein recombines and fuses the natural AK183 protease with the human immunoglobulin fragment, and has comprehensive advantages such as extended plasma half-life, effective removal of circulating and renal IgA complexes, and significant reduction of protease immunogenic side effects on the human body. The present invention is suitable for specifically treating IgA nephropathy and other related diseases mediated by IgA complex deposition.
Inventors:
LV JICHENG (CN)
JIN JING (US)
XIE XINFANG (US)
ZHANG HONG (CN)
JIN JING (US)
XIE XINFANG (US)
ZHANG HONG (CN)
Application Number:
PCT/CN2022/095803
Publication Date:
October 13, 2022
Filing Date:
May 28, 2022
Export Citation:
Assignee:
UNIV PEKING FIRST HOSPITAL (CN)
UNIV NORTHWESTERN (US)
UNIV NORTHWESTERN (US)
International Classes:
C12N9/52; A61K38/48; A61P13/12; A61P31/00; C12N1/21; C12N15/57; C12N15/70
Domestic Patent References:
| WO2015127438A1 | 2015-08-27 |
Foreign References:
| US20120114629A1 | 2012-05-10 | |||
| US20140335087A1 | 2014-11-13 | |||
| US20050136062A1 | 2005-06-23 | |||
| CN108179142A | 2018-06-19 | |||
| US20100261252A1 | 2010-10-14 |
Other References:
XIE XINFANG, LI JINGYI, LIU PAN, WANG MANLIU, GAO LI, WAN FENG, LV JICHENG, ZHANG HONG, JIN JING: "Chimeric Fusion between Clostridium Ramosum IgA Protease and IgG Fc Provides Long-Lasting Clearance of IgA Deposits in Mouse Models of IgA Nephropathy", JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, WILLIAMS AND WILKINS, BALTIMORE, MD., US, vol. 33, no. 5, 16 February 2022 (2022-02-16), US , pages 918 - 935, XP009540210, ISSN: 1046-6673, DOI: 10.1681/ASN.2021030372
JI XINGLI, WANG LI : "Potential Value of IgA Protease in Treatment ff IgA Nephropathy", JOURNAL OF MILITARY SURGEON IN SOUTHWEST CHINA, vol. 18, no. 6, 30 November 2016 (2016-11-30), pages 552 - 554, XP055976359, ISSN: 1672-7193, DOI: 10.3969/j.issn.1672-7193.2016.06.019
KOSOWSKA KLAUDIA, REINHOLDT JESPER, RASMUSSEN LONE KJÆR, SABAT ARTUR, POTEMPA JAN, KILIAN MOGENS, POULSEN KNUD: "The Clostridium ramosum IgA Proteinase Represents a Novel Type of Metalloendopeptidase", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 277, no. 14, 1 April 2002 (2002-04-01), US , pages 11987 - 11994, XP055976363, ISSN: 0021-9258, DOI: 10.1074/jbc.M110883200
13 November 2014 (2014-11-13), ANONYMOUS: "Chain A, Ig Gamma-1 Chain C Region", XP009540400, Database accession no. 4CDH_A
WANG LI, LI XUEYING, SHEN HONGCHUN, MAO NAN, WANG HONGLIAN, CUI LUKE, CHENG YUAN, FAN JUNMING: "Bacterial IgA protease-mediated degradation of agIgA1 and agIgA1 immune complexes as a potential therapy for IgA Nephropathy", SCIENTIFIC REPORTS, vol. 6, no. 1, 1 November 2016 (2016-11-01), XP055902122, DOI: 10.1038/srep30964
JI XINGLI, WANG LI : "Potential Value of IgA Protease in Treatment ff IgA Nephropathy", JOURNAL OF MILITARY SURGEON IN SOUTHWEST CHINA, vol. 18, no. 6, 30 November 2016 (2016-11-30), pages 552 - 554, XP055976359, ISSN: 1672-7193, DOI: 10.3969/j.issn.1672-7193.2016.06.019
KOSOWSKA KLAUDIA, REINHOLDT JESPER, RASMUSSEN LONE KJÆR, SABAT ARTUR, POTEMPA JAN, KILIAN MOGENS, POULSEN KNUD: "The Clostridium ramosum IgA Proteinase Represents a Novel Type of Metalloendopeptidase", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 277, no. 14, 1 April 2002 (2002-04-01), US , pages 11987 - 11994, XP055976363, ISSN: 0021-9258, DOI: 10.1074/jbc.M110883200
13 November 2014 (2014-11-13), ANONYMOUS: "Chain A, Ig Gamma-1 Chain C Region", XP009540400, Database accession no. 4CDH_A
WANG LI, LI XUEYING, SHEN HONGCHUN, MAO NAN, WANG HONGLIAN, CUI LUKE, CHENG YUAN, FAN JUNMING: "Bacterial IgA protease-mediated degradation of agIgA1 and agIgA1 immune complexes as a potential therapy for IgA Nephropathy", SCIENTIFIC REPORTS, vol. 6, no. 1, 1 November 2016 (2016-11-01), XP055902122, DOI: 10.1038/srep30964
Attorney, Agent or Firm:
BEIJING ZHAOJUN UNION INTELLECTUAL PROPERTY LAW FIRM (CN)
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