The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Mar. 26, 2024

Filed:

May. 21, 2018
Applicant:

The Regents of the University of California, Oakland, CA (US);

Inventors:

James A Wells, San Francisco, CA (US);

Zachary B. Hill, San Francisco, CA (US);

Alexander J. Martinko, San Francisco, CA (US);

Assignee:
Attorney:
Primary Examiner:
Assistant Examiner:
Int. Cl.
CPC ...
C07K 16/28 (2006.01); A61K 35/17 (2015.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01);
U.S. Cl.
CPC ...
C07K 16/2809 (2013.01); A61K 35/17 (2013.01); A61K 39/3955 (2013.01); A61K 2039/5156 (2013.01); C07K 2317/24 (2013.01); C07K 2317/92 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/033 (2013.01); C07K 2319/30 (2013.01);
Abstract

Chemically induced dimerizers (AbCIDs) have emerged as one of the most powerful tools to artificially regulate signaling pathways in cells; however, no facile method to identify or design these systems currently exists. The present invention provides a methodology to rapidly generate antibody-based chemically induced dimerizers (AbCIDs) from known small-molecule-protein complexes by selecting for synthetic antibodies that recognize the chemical epitope created by the bound small molecule. Success of this strategy is demonstrated by generating ten chemically-inducible antibodies against the BCL-xL/ABT-737 complex. Three of the antibodies are highly selective for the BCL-xL/ABT-737 complex over BCL-xL alone. Two exemplary important cellular applications of AbCIDs are demonstrated by applying them intracellularly to induce CRISPRa-mediated gene expression and extracellularly to regulate CAR T-cell activation with the small molecule, ABT-737. ABT-737 is not toxic at the concentrations used to activate AbCIDs in cells. AbCIDs provided by this invention are new and orthogonal AbCIDs, expanding the limited toolbox of available CIDs.


Find Patent Forward Citations

Loading…