Title:
OLIGONUCLEOTIDES FOR MODULATING PIAS4 EXPRESSION
Document Type and Number:
WIPO Patent Application WO/2019/137883
Kind Code:
A1
Abstract:
The present invention relates to antisense oligonucleotides that are capable of modulating expression of PIAS4 in a target cell. The antisense oligonucleotides hybridize to PIAS4 pre- mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of cancers such as pancreatic cancer, breast cancer and liver fibrosis using the antisense oligonucleotide.
Inventors:
PEDERSEN LYKKE (DK)
HAGEDORN PETER (DK)
HAGEDORN PETER (DK)
Application Number:
PCT/EP2019/050279
Publication Date:
July 18, 2019
Filing Date:
January 08, 2019
Export Citation:
Assignee:
ROCHE INNOVATION CT COPENHAGEN AS (DK)
International Classes:
C12N15/113; C12N9/10
Domestic Patent References:
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| WO2013120003A1 | 2013-08-15 | |||
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| WO2013154798A1 | 2013-10-17 | |||
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| EP2742135A1 | 2014-06-18 | |||
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BERGSTROM, CURRENT PROTOCOLS IN NUCLEIC ACID CHEMISTRY, 2009, pages 1.4.1
MERGNY; LACROIX, OLIGONUCLEOTIDES, vol. 13, 2003, pages 515 - 537
HANSEN ET AL., CHEM. COMM., 1965, pages 36 - 38
HOLDGATE ET AL., DRUG DISCOV TODAY, 2005
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SUGIMOTO ET AL., BIOCHEMISTRY, vol. 34, 1995, pages 11211 - 11216
MCTIGUE ET AL., BIOCHEMISTRY, vol. 43, 2004, pages 5388 - 5405
FREIER; ALTMANN, NUCL. ACID RES., vol. 25, 1997, pages 4429 - 4443
UHLMANN, CURR. OPINION IN DRUG DEVELOPMENT, vol. 3, no. 2, 2000, pages 293 - 213
DELEAVEY; DAMHA, CHEMISTRY AND BIOLOGY, vol. 19, 2012, pages 937
MORITA ET AL., BIOORGANIC & MED.CHEM. LETT., vol. 12, pages 73 - 76
SETH ET AL., J. ORG. CHEM., vol. 75, no. 5, 2010, pages 1569 - 81
MITSUOKA ET AL., NUCLEIC ACIDS RESEARCH, vol. 37, no. 4, 2009, pages 1225 - 1238
SETH, J. ORG. CHEM., vol. 75, no. 5, 2010, pages 1569 - 81
SETH ET AL., J. ORG. CHEM, 2010
T. W. GREENE; P. G. M. WUTS: "Protective Groups in Organic Chemistry", 1999, WILEY
VESTER ET AL., BIOORG. MED. CHEM. LETT., vol. 18, 2008, pages 2296 - 2300
MANGOS ET AL., J. AM. CHEM. SOC., vol. 125, 2003, pages 654 - 661
FLUITER ET AL., MOL. BIOSYST., vol. 10, 2009, pages 1039
RUKOV ET AL., NUCL. ACIDS RES., vol. 43, 2015, pages 8476 - 8487
MANOHARAN: "Antisense Drug Technology, Principles, Strategies, and Applications", 2001, MARCEL DEKKER, INC.
MANOHARAN, ANTISENSE AND NUCLEIC ACID DRUG DEVELOPMENT, vol. 12, 2002, pages 103
CARUTHERS ET AL., METHODS IN ENZYMOLOGY, vol. 154, 1987, pages 287 - 313
"Remington's Pharmaceutical Sciences", 1985, MACK PUBLISHING COMPANY
LANGER, SCIENCE, vol. 249, 1990, pages 1527 - 1533
W CHIEN ET AL: "PIAS4 is an activator of hypoxia signalling via VHL suppression during growth of pancreatic cancer cells", BRITISH JOURNAL OF CANCER, vol. 109, no. 7, 3 September 2013 (2013-09-03), GB, pages 1795 - 1804, XP055556897, ISSN: 0007-0920, DOI: 10.1038/bjc.2013.531
LINA SUN ET AL: "Transcriptional repression of SIRT1 by protein inhibitor of activated STAT 4 (PIAS4) in hepatic stellate cells contributes to liver fibrosis", SCIENTIFIC REPORTS, vol. 6, no. 1, 21 June 2016 (2016-06-21), XP055556907, DOI: 10.1038/srep28432
TIMOTHY A. VICKERS ET AL: "Targeting of Repeated Sequences Unique to a Gene Results in Significant Increases in Antisense Oligonucleotide Potency", PLOS ONE, vol. 9, no. 10, 15 October 2014 (2014-10-15), pages e110615, XP055210012, DOI: 10.1371/journal.pone.0110615
YAMAMOTO H. ET AL., EMBO J., vol. 22, 2003, pages 2047 - 2059
DAHLE O. ET AL., EUR. J. BIOCHEM., vol. 270, 2003, pages 1338 - 1348
SUBRAMANIAN L., J ET AL., BIOL. CHEM., vol. 278, 2003, pages 9134 - 9141
SHINBO Y. ET AL., CELL DEATH DIFFER., vol. 13, 2006, pages 96 - 108
CONG L., J. BIOL. CHEM., vol. 286, 2011, pages 43793 - 43808
DANIELSEN J.R., J ET AL., CELL BIOL., vol. 197, 2012, pages 179 - 187
LINA SUN, ONCOTARGET, vol. 7, no. 28, 2016, pages 42892 - 42903
XU ET AL., THE JOURNAL OF BIOMEDICAL RESEARCH, vol. 30, no. 6, 2016, pages 496 - 501
YAN ET AL., NATURE COMMUNICATIONS, vol. 6, 2015, pages 8979
VICKERS, PLOS ONE, vol. 9, no. 10, October 2014 (2014-10-01)
HIRAO ET AL., ACCOUNTS OF CHEMICAL RESEARCH, vol. 45, 2012, pages 2055
BERGSTROM, CURRENT PROTOCOLS IN NUCLEIC ACID CHEMISTRY, 2009, pages 1.4.1
MERGNY; LACROIX, OLIGONUCLEOTIDES, vol. 13, 2003, pages 515 - 537
HANSEN ET AL., CHEM. COMM., 1965, pages 36 - 38
HOLDGATE ET AL., DRUG DISCOV TODAY, 2005
SANTALUCIA, PROC NATL ACAD SCI USA, vol. 95, 1998, pages 1460 - 1465
SUGIMOTO ET AL., BIOCHEMISTRY, vol. 34, 1995, pages 11211 - 11216
MCTIGUE ET AL., BIOCHEMISTRY, vol. 43, 2004, pages 5388 - 5405
FREIER; ALTMANN, NUCL. ACID RES., vol. 25, 1997, pages 4429 - 4443
UHLMANN, CURR. OPINION IN DRUG DEVELOPMENT, vol. 3, no. 2, 2000, pages 293 - 213
DELEAVEY; DAMHA, CHEMISTRY AND BIOLOGY, vol. 19, 2012, pages 937
MORITA ET AL., BIOORGANIC & MED.CHEM. LETT., vol. 12, pages 73 - 76
SETH ET AL., J. ORG. CHEM., vol. 75, no. 5, 2010, pages 1569 - 81
MITSUOKA ET AL., NUCLEIC ACIDS RESEARCH, vol. 37, no. 4, 2009, pages 1225 - 1238
SETH, J. ORG. CHEM., vol. 75, no. 5, 2010, pages 1569 - 81
SETH ET AL., J. ORG. CHEM, 2010
T. W. GREENE; P. G. M. WUTS: "Protective Groups in Organic Chemistry", 1999, WILEY
VESTER ET AL., BIOORG. MED. CHEM. LETT., vol. 18, 2008, pages 2296 - 2300
MANGOS ET AL., J. AM. CHEM. SOC., vol. 125, 2003, pages 654 - 661
FLUITER ET AL., MOL. BIOSYST., vol. 10, 2009, pages 1039
RUKOV ET AL., NUCL. ACIDS RES., vol. 43, 2015, pages 8476 - 8487
MANOHARAN: "Antisense Drug Technology, Principles, Strategies, and Applications", 2001, MARCEL DEKKER, INC.
MANOHARAN, ANTISENSE AND NUCLEIC ACID DRUG DEVELOPMENT, vol. 12, 2002, pages 103
CARUTHERS ET AL., METHODS IN ENZYMOLOGY, vol. 154, 1987, pages 287 - 313
"Remington's Pharmaceutical Sciences", 1985, MACK PUBLISHING COMPANY
LANGER, SCIENCE, vol. 249, 1990, pages 1527 - 1533
Attorney, Agent or Firm:
RUDOLPH HANSEN, Marianne (CH)
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