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Title:
PROTEASE-MEDIATED TARGET SPECIFIC CYTOKINE DELIVERY USING FUSION POLYPEPTIDE
Document Type and Number:
WIPO Patent Application WO/2023/002952
Kind Code:
A1
Abstract:
The present invention relates to fusion proteins comprising a ligand binding domain, a protease cleavage site, and a ligand moiety. The fusion proteins of the invention comprise a ligand binding domain, a ligand moiety, and a protease cleavage site that, when activated by cleavage by a protease, restores biological activity of the ligand. The invention also relates to methods of producing the fusion proteins, their uses and pharmaceutical compositions comprising said fusion proteins. The present invention also relates to a method of reducing the association between heavy chain variable domain (VH) and light chain variable domain (VL) within the ligand binding domain that promotes dissociation of one from the other. The present disclosure provides fusion proteins in which the ligand is fused to the C-terminus of the constant region, or the N-terminus of the ligand binding domain.

Inventors:
CHICHILI VISHNU PRIYANKA REDDY (SG)
NAMBU TAKERU (SG)
IGAWA TOMOYUKI (JP)
YAMAMOTO YOHEI (JP)
SATO MOTOHIKO (JP)
HIRONIWA NAOKA (SG)
Application Number:
PCT/JP2022/027893
Publication Date:
January 26, 2023
Filing Date:
July 15, 2022
Export Citation:
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Assignee:
CHUGAI PHARMACEUTICAL CO LTD (JP)
International Classes:
C07K19/00; C07K14/54; C07K16/24; C12P21/02; C40B40/10; C12N15/13; C12N15/62
Domestic Patent References:
WO2007076933A12007-07-12
WO2020246567A12020-12-10
WO2017205014A12017-11-30
Foreign References:
US20200207846A12020-07-02
US20210206845A12021-07-08
US20100015133A12010-01-21
Other References:
JOHN PUSKAS, DENISE SKROMBOLAS, ABIGAIL SEDLACEK, EDITH LORD, MARK SULLIVAN, JOHN FRELINGER: "Development of an attenuated interleukin-2 fusion protein that can be activated by tumour-expressed proteases", IMMUNOLOGY, BLACKWELL SCIENTIFIC PUBLICATIONS., vol. 133, no. 2, 23 June 2011 (2011-06-23), pages 206 - 220, XP055073392, ISSN: 00192805, DOI: 10.1111/j.1365-2567.2011.03428.x
Attorney, Agent or Firm:
HARUNA, Masao et al. (JP)
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