Title:
CELL-BINDING MOLECULE-TUBULYSIN DERIVATIVE CONJUGATE AND PREPARATION METHOD THEREFOR
Document Type and Number:
WIPO Patent Application WO/2021/000067
Kind Code:
A1
Abstract:
Involved is the conjugation of a Tubulysin derivative (homolog) to a cell-binding molecule by using branched (side-chain) linkers, wherein the resulting conjugate has better pharmacokinetic properties, and thus can more accurately target and kill abnormal cells. Also involved are the conjugation of the Tubulysin homolog to a cell-binding agent, a method for synthesizing molecules contained therein, and a method for treating cancers, infections and autoimmune diseases in a targeted manner by using the conjugate. The Tubulysin conjugate with long branched linkers has an increased half-life during targeted delivery and has minimal exposure to non-target cells, tissues or organs during blood circulation, resulting in a reduced off-target toxicity.
Inventors:
ZHAO ROBERT (US)
YANG QINGLIANG (CN)
ZHAO LINYAO (CN)
HUANG YUANYUAN (CN)
YE HANGBO (CN)
GAI SHUN (CN)
LAI JUAN (CN)
LI WENJUN (CN)
BAI LU (CN)
CAO MINJUN (CN)
YANG QINGLIANG (CN)
ZHAO LINYAO (CN)
HUANG YUANYUAN (CN)
YE HANGBO (CN)
GAI SHUN (CN)
LAI JUAN (CN)
LI WENJUN (CN)
BAI LU (CN)
CAO MINJUN (CN)
Application Number:
PCT/CN2019/093946
Publication Date:
January 07, 2021
Filing Date:
June 29, 2019
Export Citation:
Assignee:
HANGZHOU DAC BIOTECH CO LTD (CN)
International Classes:
A61K47/00; A61P35/00; A61P37/02
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ELLIS, P. A. ET AL., J. CLIN. ONCOL., vol. 33, 2015
ASCO ANNUAL MEETING, 2015
SHEN, K. ET AL., SCI REP., vol. 6, 2016, pages 23262
GOEIJ, B. E.LAMBERT, J. M., CURR. OPIN. IMMUNOL., vol. 40, 2016, pages 14 - 23
BARRIOS, C. H. ET AL., J. CLIN. ONCOL., vol. 34, 2016
ASCO ANNUAL MEETING, 2016
LAMBERT, J. M., THER. DELIV., vol. 7, 2016, pages 279 - 82
ZHAO, R. Y. ET AL., J. MED. CHEM., vol. 54, 2011, pages 3606 - 23
HAMBLETT, K. J. ET AL., CLIN. CANCER RES., vol. 10, 2004, pages 7063 - 70
ZIMMERMAN, E.S. ET AL., BIOCONJ. CHEM., vol. 25, 2014, pages 1331 - 4 1
BOYLAN, N. J., BIOCONJ. CHEM.,, vol. 24, 2013, pages 1008 - 1016
STROP, P. ET AL., CHEM. BIOL., vol. 20, 2013, pages 161 - 67
WAKANKAR, A, MABS, vol. 3, 2011, pages 161 - 172
JUNUTULA, J. R. ET AL., NAT. BIOTECHNOL., vol. 26, 2008, pages 925 - 32
JUNUTULAJ. R. ET AL., CLIN. CANCER RES., vol. 16, 2010, pages 4769
HOFER, T. ET AL., BIOCHEMISTRY, vol. 48, 2009, pages 12047 - 57
LI, X. ET AL., METHODS, vol. 65, 2014, pages 133 - 8
ZHANG, C ET AL., NAT. CHEM., vol. 8, 2015, pages 1 - 9
OKELEY, N. M. ET AL., BIOCONJ. CHEM., vol. 24, 2013, pages 1650
AXUP, J. Y ET AL., PROC. NAT. ACAD. SCI. USA., vol. 109, 2012, pages 16101 - 6
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JONES, M. W., SOC., vol. 134, 2012, pages 1847 - 52
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SIEGMUND, V. ET AL., ANGEW. CHEMIE - INT. ED., vol. 54, 2015, pages 13420 - 4
KANG, H. J. ET AL., SCIENCE, vol. 318, 2007, pages 1625 - 8
ZAKERI, B. ET AL., PROC. NATL. ACAD. SCI. USA, vol. 109, 2012, pages E690 - 7
ZAKERI, B.HOWARTH, M., J. AM. CHEM. SOC., vol. 132, 2010, pages 4526 - 7
BALASUBRAMANIAN, R. ET AL., J. MED. CHEM., vol. 52, 2009, pages 238 - 40
FRIESTAD, G. K., ORG. LETT., vol. 6, 2004, pages 3249 - 52
PANDO, O. ET AL., J. AM. CHEM. SOC., vol. 133, 2011, pages 7692 - 5
REDDY, J. A. ET AL., MOL. PHARMACEUTICS, vol. 6, 2009, pages 1518 - 25
RAGHAVAN, B. ET AL., J. MED. CHEM., vol. 51, 2008, pages 1530 - 33
PATTERSON, A. W. ET AL., J. ORG. CHEM., vol. 73, 2008, pages 4362 - 9
FRIESTAD, G. K. ET AL., ORG. LETT., vol. 11, no. 24, 2009, pages 1095 - 8
WIPF, P. ET AL., ORG. LETT., vol. 9, no. 8, 2007, pages 1605 - 7
PELTIER, H. M. ET AL., J. AM. CHEM. SOC., vol. 128, 2006
CHANDRASEKHAR, S. ET AL., J. ORG. CHEM., vol. 74, 2009, pages 9531 - 4
LIU, Y. ET AL., MOL. PHARMACEUTICS, vol. 9, 2012, pages 168 - 75
KUBICEK, K. ET AL., ANGEW. CHEM. INT. ED. ENGL., vol. 49, 2010, pages 4809 - 12
CHAI, Y. ET AL., CHEM BIOL, vol. 17, 2010, pages 296 - 309
ULLRICH, A. ET AL., ANGEW. CHEM. INT. ED. ENGL., vol. 48, 2009, pages 4422 - 5
SANI, M. ET AL., ANGEW. CHEM. INT. ED. ENGL., vol. 46, 2007, pages 3526 - 9
DOMLING, A. ET AL., ANGEW. CHEM. INT. ED. ENGL., vol. 45, 2006, pages 7235 - 9
"The Handbook of Chemistry and Physics", 1997, CRC PRESS, INC., pages: 225 - 226
MATAYOSHI ET AL., SCIENCE, vol. 247, 1990, pages 954
SEIDAH ET AL., METH. ENZYMOL., vol. 244, 1994, pages 412
DENTE ET AL., GENE, vol. 148, no. 1, 1994, pages 595 - 13
BOUVIER ET AL., METH. ENZYMOL., vol. 248, 1995, pages 614
GEYSEN ET AL., PROC. NATL. ACAD. SCI. USA, vol. 82, 1985, pages 1418 - 82
KOHLER, G.MILSTEIN, C., NATURE, vol. 256, 1975, pages 495 - 7
"Antibodies--A Laboratory Manual", 1988, COLD SPRING HARBOR LABORATORY PRESS
DULBECCO ET AL.: "Virol", vol. 8, 1959, pages: 396
NIMAN ET AL., PROC. NATL. ACAD. SCI. USA, vol. 80, 1983, pages 4949 - 53
LEI ET AL., BIOCHEMISTRY, vol. 34, no. 20, 1995, pages 6675 - 88
LITTLE ET AL., BIOTECHNOLADV, vol. 12, no. 3, 1994, pages 539 - 55
CLACKSON ET AL., NATURE, vol. 352, 1991, pages 264 - 8
HUSE ET AL., SCIENCE, vol. 246, 1989, pages 1275 - 81
LIU ET AL., IMMUNOL REV., vol. 222, 2008, pages 9 - 27
ALMAGRO ET AL., FRONT BIOSCI, vol. 13, 2008, pages 1619 - 33
LAZAR ET AL., MOL IMMUNOL, vol. 44, no. 8, 2007, pages 1986 - 98
LI ET AL., PROC. NATL. ACAD. SCI. USA., vol. 103, no. 10, 2006, pages 3557 - 62
KIPRIYANOV ET AL., MOL BIOTECHNOL, vol. 26, 2004, pages 39 - 60
HOUDEBINE, CURR OPIN BIOTECHNOL, vol. 13, 2002, pages 625 - 9
BRANNIGAN ET AL., NAT REV MOL CELL BIOL., vol. 3, 2002, pages 964 - 70
ADAMS ET AL., J IMMUNOL METHODS., vol. 231, 1999, pages 249 - 60
SZARDENINGS, J RECEIVE SIGNAL TRANSFER RES, vol. 23, no. 4, 2003, pages 307 - 49
GERBE ET AL., MABS, vol. 1, no. 3, 2009, pages 247 - 53
NOVELLINO ET AL., CANCER IMMUNOL IMMUNOTHER, vol. 54, no. 3, 2005, pages 187 - 207
FRANKE ET AL., CANCER BIOTHER RADIOPHARM, vol. 15, 2000, pages 459 - 76
RICHARD C. LAROCK: "Remington: The Science and Practice of Pharmacy", 1999, LIPPINCOTT WILLIAMS & WILKINS
P. G. WUTST.W GREENE: "Greene's Protective Groups in Organic Synthesis", 2006, WILEY-INTERSCIENCE
R ZHAO ET AL., 14TH PEGS BOSTON, 3 May 2018 (2018-05-03)
JUE, R. ET AL., BIOCHEM, vol. 17, no. 25, 1978, pages 5399 - 5405
DUNCAN, R ET AL., ANAL. BIOCHEM., vol. 132, 1983, pages 68 - 73
FUJI, N ET AL., CHEM. PHARM. BULL., vol. 33, 1985, pages 362 - 367
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