Title:
サイトカインをベースとした生理活性化薬剤およびその使用方法
Document Type and Number:
Japanese Patent JP7477885
Kind Code:
B2
Abstract:
The present disclosure provides a cytokine-based bioactivatable drug construct (“VitoKine”) platform that aims to reduce systemic mechanism-based toxicities and lead to broader therapeutic utility for proteins and cytokines such as IL-15 and IL-2 for the treatment of cancer, autoimmune diseases, inflammatory diseases, viral infection, transplantation and various other disorders. The novel VitoKine constructs of the present invention comprise: 1) a tissue or disease site targeting moiety D1 domain (“D1”), 2) a bioactivatable moiety D2 domain (“D2”), and a concealing moiety D3 domain (“D3”). Importantly, because the “active moiety” of the VitoKine construct will remain inert until activated locally by proteases that are upregulated in diseased tissues, this will limit binding of the active moiety to the receptors or to the targets in the peripheral or on the cell-surface of non-diseased cells and tissue to prevent over-activation of the pathway and reduce undesirable “on-target” “off tissue” toxicities. Additionally, the inertness of the VitoKine active moiety prior to protease activation will significantly decrease the potential antigen or target sink, and thus, prolong the in vivo half-life and result in improved biodistribution, bioavailability and therapeutic efficacy.
Inventors:
Li, Yueshen
Louis, Linyun
Su, Jin
Louis, Linyun
Su, Jin
Application Number:
JP2021520277A
Publication Date:
May 02, 2024
Filing Date:
June 20, 2019
Export Citation:
Assignee:
CUGENE INC.
International Classes:
A61K47/64; A61K38/02; A61K38/20; A61K45/00; A61K47/65; A61P35/00; A61P35/02; A61P35/04; A61P43/00; C07K14/495; C07K14/54; C07K19/00; C12N15/12; C12N15/19; C12N15/62; C12N15/63
Foreign References:
| WO2017156178A1 | ||||
| WO2017158436A1 |
Other References:
Development of an attenuated interleukin-2 fusion protein that can be activated by tumour-expressed proteases,Immunology,2011年,Vol.133, No.2,206-220
Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy,Expert Review of Clinical Immunology,2014年,Vol. 10, No.2,207-217
Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters,BioDrugs,2015年,Vol.29, No.4,215-239
Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy,Expert Review of Clinical Immunology,2014年,Vol. 10, No.2,207-217
Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters,BioDrugs,2015年,Vol.29, No.4,215-239
Attorney, Agent or Firm:
Kita Aoyama International Patent Attorney Corporation