US 11,939,379 B2
Antibody chemically induced dimerizer (AbCID) as molecular switches for regulating cellular therapies
James A Wells, San Francisco, CA (US); Zachary B. Hill, San Francisco, CA (US); and Alexander J. Martinko, San Francisco, CA (US)
Assigned to The Regents of the University of California, Oakland, CA (US)
Appl. No. 16/614,786
Filed by The Regents of the University of California, Oakland, CA (US)
PCT Filed May 21, 2018, PCT No. PCT/US2018/033750
§ 371(c)(1), (2) Date Nov. 18, 2019,
PCT Pub. No. WO2018/213848, PCT Pub. Date Nov. 22, 2018.
Claims priority of provisional application 62/508,809, filed on May 19, 2017.
Prior Publication US 2020/0255519 A1, Aug. 13, 2020
Int. Cl. C07K 16/28 (2006.01); A61K 35/17 (2015.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01)
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)] 11 Claims
 
1. A system comprising:
(a) a first chemically-induced dimer (CID) component comprising (i) a first binding moiety that is a protein capable of interacting with a small molecule to form a complex; and (ii) a first adapter moiety linked to the first binding moiety; and
(b) a second CID component comprising (i) a second binding moiety that is a protein that binds to the complex between the small molecule and the first binding moiety at a site of the complex comprising at least a portion of the small molecule and a portion of the first binding moiety; and (ii) a second adapter moiety linked to the second binding moiety;
wherein the binding of the second binding moiety to the complex between the small molecule and the first binding moiety creates a dimer between the second CID component and the first CID component,
wherein the first adapter moiety comprises a T cell antigen-binding moiety and the second adapter moiety comprises a target cell antigen-binding moiety; or the second adapter moiety comprises a T cell antigen-binding moiety and the first adapter moiety comprises a target cell antigen-binding moiety,
wherein the target cell antigen-binding moiety is an extracellular antigen-binding moiety,
wherein the first CID component comprises an ABT-199 binding domain comprising the amino acid sequence of SEQ ID NO:315; and
wherein the second CID component comprises an antibody moiety comprising three heavy chain complementarity determining regions (CDRs) and three light chain CDRs of an antibody clone selected from antibody clone FAB-AZ11, FAB-AZ12, FAB-AZ13, FAB-AZ14, FAB-AZ15, FAB-AZ16, FAB-AZ17, FAB-AZ18, FAB-AZ19, FAB-AZ20, FAB-AZ21, FAB-AZ22, FAB-AZ23, FAB-AZ24, FAB-AZ25, FAB-AZ26, FAB-AZ27, FAB-AZ28, FAB-AZ29, FAB-AZ30, FAB-AZ31, FAB-AZ32, FAB-AZ33, FAB-AZ34, FAB-AZ35, FAB-AZ36, FAB-AZ37, FAB-AZ38, FAB-AZ39, FAB-AZ40, FAB-AZ41, FAB-AZ42, and FAB-AZ43.