Title:
ANTIBODY-DRUG CONJUGATE PRECURSOR AND INTERMEDIATE FOR SYNTHESIS THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/163234
Kind Code:
A1
Abstract:
The present invention provides: a method for improving the stability of an antibody-drug conjugate in vivo; and a conjugate precursor for producing a stabilized antibody-drug conjugate. More specifically, the present invention provides: an antibody-drug conjugate precursor represented by general formula (I): [wherein Z represents a reactive group capable of reacting with a functional group present in an antibody or a modified antibody; D represents an antitumor drug residue having such a structure that one hydrogen atom or one hydroxyl group is removed from an arbitrary position in an antitumor drug molecule, an analogue of the antitumor drug molecule or a derivative of the antitumor drug molecule or the analogue; and L represents a linker that links Z to D; wherein at least one of D and L has at least one lactonyl group as a substituent or a protecting group at an arbitrary position] or a salt thereof; an intermediate for the synthesis of the antibody-drug conjugate precursor or the salt thereof, or a salt of the intermediate; and others.
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Inventors:
TSUZAKI YASUNORI (JP)
MIZUNO GEN (JP)
KASHIWAGI TAKAMASA (JP)
TANAKA MASAYUKI (JP)
SHIMIZU HAYATO (JP)
NONOUCHI SHINPEI (JP)
MATSUSHITA TAKASHI (JP)
KIMURA TOMIO (JP)
MIZUNO GEN (JP)
KASHIWAGI TAKAMASA (JP)
TANAKA MASAYUKI (JP)
SHIMIZU HAYATO (JP)
NONOUCHI SHINPEI (JP)
MATSUSHITA TAKASHI (JP)
KIMURA TOMIO (JP)
Application Number:
PCT/JP2023/007434
Publication Date:
August 31, 2023
Filing Date:
February 28, 2023
Export Citation:
Assignee:
UBE CORP (JP)
International Classes:
A61K47/68; A61K31/337; A61K31/357; A61K31/407; A61K31/4375; A61K31/4745; A61K31/475; A61K31/513; A61K31/537; A61K31/5513; A61K31/5517; A61K31/675; A61K31/7034; A61K31/7036; A61K31/706; A61K38/07; A61K38/14; A61K39/395; A61K45/00; A61P35/00; C07K2/00; C07K14/435; C07K16/30; C07K19/00
Domestic Patent References:
| WO2014061277A1 | 2014-04-24 |
Foreign References:
| US20200115326A1 | 2020-04-16 |
Other References:
XIAO, DIAN ET AL.: "A bifunctional molecule-based strategy for the development of theranostic antibody-drug conjugate", THERANOSTICS, vol. 11, no. 6, 2021, pages 2550 - 2563, XP093087170, DOI: 10.7150/thno.51232
SU, ZHENG ET AL.: "Antibody-drug conjugates: Recent advances in linker chemistry", ACTA PHARMACEUTICA SINICA B, vol. 11, no. 12, 2021, pages 3889 - 3907, XP093087740, DOI: 10.1016/j.apsb.2021.03.042
LIU, LIANQ I ET AL.: "Synthesis and evaluation of highly releasable and structurally stable antibody-SN-38-conjugates", DRUG DELIVERY, vol. 28, no. 1, 2021, pages 2603 - 2617, XP093087176, DOI: 10.1080/10717544.2021.2008053
LAU, ULAND Y. ET AL.: "Lactone Stabilization is Not a Necessary Feature for Antibody Conjugates of Camptothecins", MOL. PHARMACEUTICS., vol. 15, 2018, pages 4063 - 4072, XP055618626, DOI: 10.1021/acs.molpharmaceut.8b00477
MONDAL, DEBOPROSAD ET AL.: "Improved Methodology for the Synthesis of a Cathepsin B Cleavable Dipeptide Linker, Widely Used in Antibody-Drug Conjugate Research", TETRAHEDRON LETTERS, vol. 59, 2018, pages 3594 - 3599, XP055732113, DOI: 10.1016/j.tetlet.2018.08.021
ANAMI YASUAKI, YAMAZAKI CHISATO M., XIONG WEI, GUI XUN, ZHANG NINGYAN, AN ZHIQIANG, TSUCHIKAMA KYOJI: "Glutamic acid–valine–citrulline linkers ensure stability and efficacy of antibody–drug conjugates in mice", NATURE COMMUNICATIONS, vol. 9, no. 1, XP093084676, DOI: 10.1038/s41467-018-04982-3
DI, LI ET AL.: "Development and application of high throughput plasma stability assay for drug discovery", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 297, 2005, pages 110 - 119, XP027624001
SU, ZHENG ET AL.: "Antibody-drug conjugates: Recent advances in linker chemistry", ACTA PHARMACEUTICA SINICA B, vol. 11, no. 12, 2021, pages 3889 - 3907, XP093087740, DOI: 10.1016/j.apsb.2021.03.042
LIU, LIANQ I ET AL.: "Synthesis and evaluation of highly releasable and structurally stable antibody-SN-38-conjugates", DRUG DELIVERY, vol. 28, no. 1, 2021, pages 2603 - 2617, XP093087176, DOI: 10.1080/10717544.2021.2008053
LAU, ULAND Y. ET AL.: "Lactone Stabilization is Not a Necessary Feature for Antibody Conjugates of Camptothecins", MOL. PHARMACEUTICS., vol. 15, 2018, pages 4063 - 4072, XP055618626, DOI: 10.1021/acs.molpharmaceut.8b00477
MONDAL, DEBOPROSAD ET AL.: "Improved Methodology for the Synthesis of a Cathepsin B Cleavable Dipeptide Linker, Widely Used in Antibody-Drug Conjugate Research", TETRAHEDRON LETTERS, vol. 59, 2018, pages 3594 - 3599, XP055732113, DOI: 10.1016/j.tetlet.2018.08.021
ANAMI YASUAKI, YAMAZAKI CHISATO M., XIONG WEI, GUI XUN, ZHANG NINGYAN, AN ZHIQIANG, TSUCHIKAMA KYOJI: "Glutamic acid–valine–citrulline linkers ensure stability and efficacy of antibody–drug conjugates in mice", NATURE COMMUNICATIONS, vol. 9, no. 1, XP093084676, DOI: 10.1038/s41467-018-04982-3
DI, LI ET AL.: "Development and application of high throughput plasma stability assay for drug discovery", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 297, 2005, pages 110 - 119, XP027624001
Attorney, Agent or Firm:
YAMAO, Norihito et al. (JP)
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