Title:
MODIFIED HUMAN SERUM ALBUMIN-THIOREDOXIN FUSION BODY
Document Type and Number:
WIPO Patent Application WO/2022/196683
Kind Code:
A1
Abstract:
Disclosed is a serum albumin-thioredoxin fusion body which is improved in the activity thereof and is stable with respect to the activity. A serum albumin-thioredoxin fusion body is provided, which is characterized in that the thioredoxin is a modified form in which at least a cysteine residue located at position-73 from the N-terminal of an amino acid sequence for the thioredoxin or located at a position equivalent to the position-73 is substituted by another amino acid residue. The serum albumin-thioredoxin fusion body is superior in the activity and stability thereof, is reduced in immunogenicity and has superior safety compared with a fusion body in which the thioredoxin is a non-modified form.
Inventors:
MATSUDA JUNICHI (JP)
NISHIDA KENTO (JP)
HIRASHIMA MASAKI (JP)
MARUYAMA TORU (JP)
WATANABE HIROSHI (JP)
MAEDA HITOSHI (JP)
NISHIDA KENTO (JP)
HIRASHIMA MASAKI (JP)
MARUYAMA TORU (JP)
WATANABE HIROSHI (JP)
MAEDA HITOSHI (JP)
Application Number:
PCT/JP2022/011580
Publication Date:
September 22, 2022
Filing Date:
March 15, 2022
Export Citation:
Assignee:
KM BIOLOGICS CO LTD (JP)
UNIV KUMAMOTO NAT UNIV CORP (JP)
UNIV KUMAMOTO NAT UNIV CORP (JP)
International Classes:
C12N15/62; A61K38/16; A61K47/64; A61P1/16; A61P9/00; A61P9/10; A61P11/00; A61P11/06; A61P13/12; A61P21/00; A61P25/00; A61P25/02; A61P25/16; A61P25/28; A61P29/00; A61P37/02; A61P39/06; C07K14/435; C07K14/765; C07K19/00; C12N5/10; C12N15/12; C12N15/14; C12N15/63; C12P21/02
Foreign References:
| JP2009055838A | 2009-03-19 | |||
| JPH10191977A | 1998-07-28 |
Other References:
ZHAO, H.L. ; XUE, C. ; WANG, Y. ; SUN, B. ; YAO, X.Q. ; LIU, Z.M.: "Elimination of the free sulfhydryl group in the human serum albumin (HSA) moiety of human interferon-@a2b and HSA fusion protein increases its stability against mechanical and thermal stresses", EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, ELSEVIER SCIENCE PUBLISHERS B.V., AMSTERDAM., NL, vol. 72, no. 2, 1 June 2009 (2009-06-01), NL , pages 405 - 411, XP026119125, ISSN: 0939-6411, DOI: 10.1016/j.ejpb.2009.01.008
CHA, M.K. ; KIM, I.H.: "Disulfide between Cys392 and Cys438 of human serum albumin is redox-active, which is responsible for the thioredoxin-supported lipid peroxidase activity", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, ACADEMIC PRESS, US, vol. 445, no. 1, 1 January 2006 (2006-01-01), US , pages 19 - 25, XP024942948, ISSN: 0003-9861, DOI: 10.1016/j.abb.2005.09.022
HOLMGREN A, THIOREDOXIN. ANN REV BIOCHEM, vol. 54, 1985, pages 237 - 271
TAGAYA Y ET AL.: "ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction", EMBO J, vol. 8, 1989, pages 757 - 764, XP000973574
NAKAMURA H ET AL., REDOX REGULATION OF CELLULAR ACTIVATION. ANNU REV IMMUNOL, vol. 15, 1997, pages 351 - 369
CHEN B ET AL.: "Thioredoxin 1 downregulates MCP-1 secretion and expression in human endothelial cells by suppressing nuclear translocation of activator protein 1 and redox factor-1", AM J PHYSIOL CELL PHYSIOL, vol. 298, 2010, pages C1170 - C1179
OHASHI S ET AL.: "Overexpression of redox-active protein thioredoxin-1 prevents development of chronic pancreatitis in mice", ANTIOXID REDOX SIGNAL, vol. 8, 2006, pages 1835 - 1845
YOSHIOKA J ET AL.: "Role of thioredoxin in cell growth from interactions with signaling molecules", ANTIOXID REDOX SIGNAL, vol. 8, 2006, pages 2143 - 2151
SON A ET AL.: "Direct association of thioredoxin-1 (TRX) with macrophage migration inhibitory factor (MIF) : regulatory role of TRX on MIF internalization and signaling", ANTIOXID REDOX SIGNAL, vol. 11, 2009, pages 2595 - 2605
IKUTA S ET AL.: "Albumin fusion of thioredoxin — The production and evaluation of its biological activity for potential therapeutic applications", J CONTROL RELEASE, vol. 147, 2010, pages 17 - 23, XP027272139
KODAMA A: "Albumin fusion renders thioredoxin an effective anti-oxidative and anti-inflammatory agent for preventing cisplatin-induced nephrotoxicity.", BIOCHEM BIOPHYS ACTA, vol. 1840, 2014, pages 1152 - 1162, XP028817260, DOI: 10.1016/j.bbagen.2013.12.007
TANAKA R ET AL.: "Albumin fusion prolongs the antioxidant and anti-inflammatory activities of thioredoxin in mice with acetaminophen-induced hepatitis", MOL PHARM, vol. 11, 2014, pages 1228 - 1238
TANAKA R ET AL.: "Long-Acting Human Serum Albumin-Thioredoxin Fusion Protein Suppresses Bleomycin-Induced Pulmonary Fibrosis Progression", J PHARMACOL EXP THER, vol. 345, 2013, pages 271 - 283
TANAKA R ET AL., THERAPEUTIC IMPACT OF HUMAN SERUM ALBUMIN-THIOREDOXIN FUSION PROTEIN ON INFLUENZA VIRUS-INDUCED LUNG INJURY MICE FRONT IMMUNOL, vol. 5, 2014, pages 561
JONES DP: "Radical-free biology of oxidative stress", AM J PHYSIOL CELL PHYSIOL, vol. 295, 2008, pages C849 - C868
GO Y-M ET AL.: "Reactive aldehyde modification of thioredoxin-1 activates early steps of inflammation and cell adhesion", AM J PATHOL, vol. 171, 2007, pages 1670 - 1681
ZHAO HL ET AL.: "Elimination of the free sulfhydryl group in the human serum albumin (HSA) moiety of human interferon-alpha2b and HSA fusion protein increases its stability against mechanical and thermal stresses", EUR J PHARM BIOPHARM, vol. 72, 2009, pages 405 - 411, XP026119125, DOI: 10.1016/j.ejpb.2009.01.008
CHA, M.K. ; KIM, I.H.: "Disulfide between Cys392 and Cys438 of human serum albumin is redox-active, which is responsible for the thioredoxin-supported lipid peroxidase activity", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, ACADEMIC PRESS, US, vol. 445, no. 1, 1 January 2006 (2006-01-01), US , pages 19 - 25, XP024942948, ISSN: 0003-9861, DOI: 10.1016/j.abb.2005.09.022
HOLMGREN A, THIOREDOXIN. ANN REV BIOCHEM, vol. 54, 1985, pages 237 - 271
TAGAYA Y ET AL.: "ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction", EMBO J, vol. 8, 1989, pages 757 - 764, XP000973574
NAKAMURA H ET AL., REDOX REGULATION OF CELLULAR ACTIVATION. ANNU REV IMMUNOL, vol. 15, 1997, pages 351 - 369
CHEN B ET AL.: "Thioredoxin 1 downregulates MCP-1 secretion and expression in human endothelial cells by suppressing nuclear translocation of activator protein 1 and redox factor-1", AM J PHYSIOL CELL PHYSIOL, vol. 298, 2010, pages C1170 - C1179
OHASHI S ET AL.: "Overexpression of redox-active protein thioredoxin-1 prevents development of chronic pancreatitis in mice", ANTIOXID REDOX SIGNAL, vol. 8, 2006, pages 1835 - 1845
YOSHIOKA J ET AL.: "Role of thioredoxin in cell growth from interactions with signaling molecules", ANTIOXID REDOX SIGNAL, vol. 8, 2006, pages 2143 - 2151
SON A ET AL.: "Direct association of thioredoxin-1 (TRX) with macrophage migration inhibitory factor (MIF) : regulatory role of TRX on MIF internalization and signaling", ANTIOXID REDOX SIGNAL, vol. 11, 2009, pages 2595 - 2605
IKUTA S ET AL.: "Albumin fusion of thioredoxin — The production and evaluation of its biological activity for potential therapeutic applications", J CONTROL RELEASE, vol. 147, 2010, pages 17 - 23, XP027272139
KODAMA A: "Albumin fusion renders thioredoxin an effective anti-oxidative and anti-inflammatory agent for preventing cisplatin-induced nephrotoxicity.", BIOCHEM BIOPHYS ACTA, vol. 1840, 2014, pages 1152 - 1162, XP028817260, DOI: 10.1016/j.bbagen.2013.12.007
TANAKA R ET AL.: "Albumin fusion prolongs the antioxidant and anti-inflammatory activities of thioredoxin in mice with acetaminophen-induced hepatitis", MOL PHARM, vol. 11, 2014, pages 1228 - 1238
TANAKA R ET AL.: "Long-Acting Human Serum Albumin-Thioredoxin Fusion Protein Suppresses Bleomycin-Induced Pulmonary Fibrosis Progression", J PHARMACOL EXP THER, vol. 345, 2013, pages 271 - 283
TANAKA R ET AL., THERAPEUTIC IMPACT OF HUMAN SERUM ALBUMIN-THIOREDOXIN FUSION PROTEIN ON INFLUENZA VIRUS-INDUCED LUNG INJURY MICE FRONT IMMUNOL, vol. 5, 2014, pages 561
JONES DP: "Radical-free biology of oxidative stress", AM J PHYSIOL CELL PHYSIOL, vol. 295, 2008, pages C849 - C868
GO Y-M ET AL.: "Reactive aldehyde modification of thioredoxin-1 activates early steps of inflammation and cell adhesion", AM J PATHOL, vol. 171, 2007, pages 1670 - 1681
ZHAO HL ET AL.: "Elimination of the free sulfhydryl group in the human serum albumin (HSA) moiety of human interferon-alpha2b and HSA fusion protein increases its stability against mechanical and thermal stresses", EUR J PHARM BIOPHARM, vol. 72, 2009, pages 405 - 411, XP026119125, DOI: 10.1016/j.ejpb.2009.01.008
Attorney, Agent or Firm:
KONNO, Akio et al. (JP)
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