公开(公告)号：US20220281936A1

公开(公告)日：2022-09-08

申请号：US17597793

申请日：2020-07-24

申请人： The University of Chicago

发明人： Jeffrey HUBBELL ,  Jun ISHIHARA ,  Juan MENDOZA ,  Aslan MANSUROV

IPC分类号： C07K14/54 ,  C07K14/715 ,  A61K47/68 ,  A61K39/395 ,  A61P35/00

摘要： he disclosure relates to the engineering of collagen-binding modification of masked therapeutic agents comprising one or more tumor-associated protease cleavage sites. Upon exposure to tumor-associated proteases in the tumor microenvironment, the polypeptide is cleaved, which unmasks the therapeutic agent, reducing off-target side effects and toxicity associated with systemic administration. Accordingly, aspects of the disclosure relate to a polypeptide comprising a therapeutic agent linked to a masking agent through a linker, wherein the linker comprises one or more tumor-associated protease cleavage sites, and wherein the masking agent blocks the association of the therapeutic agent to its therapeutic target, and further wherein the polypeptide is operatively linked to a collagen binding domain or a tumor-targeting agent.

公开(公告)号：US20240228586A1

公开(公告)日：2024-07-11

申请号：US18559180

申请日：2022-05-05

申请人： THE UNIVERSITY OF CHICAGO

发明人： Jeffrey HUBBELL ,  Jun ISHIHARA ,  Juan MENDOZA ,  Aslan MANSUROV

IPC分类号： C07K14/715 ,  A61K38/17 ,  A61K38/20 ,  A61K38/21 ,  A61K39/395 ,  A61K47/64 ,  A61K47/68 ,  A61P35/00 ,  C07K14/47 ,  C07K14/54 ,  C07K14/55 ,  C07K14/57

CPC分类号： C07K14/7155 ,  A61K38/1709 ,  A61K38/1793 ,  A61K38/2013 ,  A61K38/208 ,  A61K38/217 ,  A61K39/395 ,  A61K47/643 ,  A61K47/6843 ,  A61P35/00 ,  C07K14/47 ,  C07K14/5434 ,  C07K14/55 ,  C07K14/57 ,  C07K14/7156 ,  C07K2319/50

摘要： The disclosure relates to the engineering of collagen-binding modification of masked therapeutic agents comprising one or more tumor-associated protease cleavage sites. Upon exposure to tumor-associated proteases in the tumor microenvironment, the polypeptide is cleaved, which unmasks the therapeutic agent, reducing off-target side effects and toxicity associated with systemic administration. Accordingly, aspects of the disclosure relate to a polypeptide comprising a therapeutic agent linked to a masking agent through a linker, wherein the linker comprises one or more tumor-associated protease cleavage sites, and wherein the masking agent blocks the association of the therapeutic agent to its therapeutic target, and further wherein the polypeptide is operatively linked to a collagen binding domain or a tumor-targeting agent.