US 11,897,932 B2
Receptors for ligand-dependent transcriptional regulation
Kole T. Roybal, San Francisco, CA (US); Raymond Liu, San Francisco, CA (US); and Iowis Zhu, San Francisco, CA (US)
Assigned to The Regents of the University of California, Oakland, CA (US)
Filed by The Regents of the University of California, Oakland, CA (US)
Filed on Mar. 30, 2021, as Appl. No. 17/217,635.
Application 17/217,635 is a continuation of application No. PCT/US2020/052324, filed on Sep. 23, 2020.
Claims priority of provisional application 62/935,024, filed on Nov. 13, 2019.
Claims priority of provisional application 62/905,248, filed on Sep. 24, 2019.
Prior Publication US 2021/0246186 A1, Aug. 12, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/705 (2006.01); A61K 35/17 (2015.01); C12N 5/0783 (2010.01)
CPC C07K 14/705 (2013.01) [A61K 35/17 (2013.01); C12N 5/0636 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/09 (2013.01); C07K 2319/74 (2013.01)] 17 Claims
 
1. A chimeric polypeptide comprising, from N-terminus to C-terminus:
a) an extracellular ligand-binding domain comprising a single chain variable fragment (scFv) having a binding affinity for a selected ligand;
b) a linking polypeptide comprising the sequence of SEQ ID NO: 19;
c) a transmembrane domain from a human Notch receptor comprising one or more ligand-inducible proteolytic cleavage sites; and
d) an intracellular domain comprising a transcriptional regulator, wherein binding of the selected ligand to the extracellular ligand-binding domain induces cleavage at the ligand-inducible proteolytic cleavage site disposed between the transcriptional regulator and the linking polypeptide,
and wherein the chimeric polypeptide does not comprise a LIN-12-Notch repeat (LNR) nor a heterodimerization domain (HD) of a Notch receptor.