Granted Patent
B2
US 12,297,243 · App. 17/716,630 · Granted May 13, 2025
Methods and compositions for reducing the immunogenicity of chimeric notch receptors
Inventors:
Peter Emtage (Lafayette, CA); Amy E. Gilbert (San Francisco, CA); Anselm Levskaya (Oakland, CA); Spencer Scott (San Francisco, CA); Vladimir Anatolievich Slepushkin (Vallejo, CA)
Assignee:
Cell Design Labs, Inc.
C07K14/4702A61K48/00C07K14/4705C07K14/705C07K14/70517C07K14/71C07K16/28C07K16/2803C07K19/00C12N5/0645C12N5/10C12N15/63C12N15/85A61K2039/5156A61P35/04C07K16/462C07K2317/569C07K2317/622C07K2317/626C07K2317/70C07K2319/00C07K2319/02C07K2319/03C07K2319/09C07K2319/33C07K2319/41C07K2319/50C07K2319/70C07K2319/71C07K2319/80C07K2319/95C12N2740/16043C12N2830/15C12N2830/85
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Abstract
The present invention relates to methods and compositions for reducing the immunogenicity of chimeric Notch receptors, and specifically to transcription factors useful for controlling gene expression delivered to tissues by such chimeric Notch receptors.
Claims (10)
1. A chimeric Notch polypeptide comprising, from N-terminal to C-terminal and in covalent linkage: a) an extracellular domain comprising a binding agent that specifically binds to an antigen; b) a Notch 2 or Notch 3 core region; c) one or more proteolytic cleavage sites; and d) an intracellular domain comprising a transcriptional regulator; and
wherein said transcriptional regulator is from the Hepatocyte Nuclear Factor (HNF) transcriptional regulator family.
2. The chimeric Notch polypeptide of claim 1 , wherein said transcriptional regulator is HNF1 alpha or HNF1 beta.
3. The chimeric Notch polypeptide of claim 1 , wherein binding of the binding agent to the antigen induces cleavage of the Notch polypeptide at the one or more proteolytic cleavage sites, thereby releasing the intracellular domain and the transcriptional regulator.
4. The chimeric Notch polypeptide of claim 1 , wherein the transcriptional regulator comprises a DNA binding domain of human origin and a transactivation domain of human origin.
5. The chimeric Notch polypeptide of claim 4 , wherein the transactivation domain is selected from the group consisting of RelA (p65), YAP, WWTR1(TAZ), and CREB3(LZIP).
6. The chimeric Notch polypeptide of claim 1 , wherein said binding agent comprises an antibody.
7. The chimeric Notch polypeptide of claim 6 , wherein said antibody is selected from the group consisting of scFv, bispecific antibody, nanobody, and bite.
8. The chimeric Notch polypeptide of claim 7 , wherein said transcriptional regulator is a transcriptional activator.
9. The chimeric Notch polypeptide of claim 1 , wherein the Notch 2 or Notch 3 core region comprises human Lin12 LNR.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 9, 2022
From: GILBERT, AMY; SLEPUSHKIN, VLADIMIR; EMTAGE, PETER; LEVSKAYA, ANSELM; SCOTT, SPENCER
To: CELL DESIGN LABS, INC.
Reel/Frame 059866/0662 →
Continuity (4)
Provisional Application
62603993
· Jun 19, 2017
Provisional Application
62556765
· Sep 11, 2017
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