公开(公告)号：US20190062394A1

公开(公告)日：2019-02-28

申请号：US15767298

申请日：2016-10-10

Applicant: Intrexon Corporation

Inventor： Ramya YARLAGADDA ,  Charles REED ,  Charles Andrew (Marshall) STEWART ,  Peter EMTAGE ,  Rutul SHAH ,  Timothy CHAN

IPC: C07K14/54 ,  A61P35/00

Abstract: The present invention relates to modified forms of IL-12. These modified forms of IL-12 may be engineered to have a shortened in vivo half-life compared and/or enhanced localization of biological effects compared to that of corresponding non-modified form of IL-12. Short half-life and membrane bound forms of IL-12 may provide greater therapeutic control for in vivo therapeutic delivery, in particular when used in combination with ligand inducible delivery of IL-12. Modified forms of IL-12 engineered to have shortened in vivo half-life and/or enhanced localization of biological effects include heterodimeric p35/p40, single chain and membrane bound forms of IL-12 wherein a naturally occurring IL-12 amino acid sequence is genetically modified to destabilize IL-12 tertiary structure/polypeptide folding and enhance susceptibility of the IL-12 molecule to in vivo proteolytic degradation.