US 12,465,637 B2
Compositions and methods for modulation of antibody activity
John Karanicolas, Philadelphia, PA (US); Jittasak Khowsathit, Philadelphia, PA (US); and Daniel Pushparaju Yeggoni, Philadelphia, PA (US)
Assigned to Institute for Cancer Research, Philadelphia, PA (US); and University of Kansas, Lawrence, KS (US)
Appl. No. 17/600,831
Filed by Institute for Cancer Research, Philadelphia, PA (US); and University of Kansas, Lawrence, KS (US)
PCT Filed Apr. 29, 2020, PCT No. PCT/US2020/030354
§ 371(c)(1), (2) Date Oct. 1, 2021,
PCT Pub. No. WO2020/223273, PCT Pub. Date Nov. 5, 2020.
Claims priority of provisional application 62/840,465, filed on Apr. 30, 2019.
Prior Publication US 2022/0175918 A1, Jun. 9, 2022
Int. Cl. A61K 39/395 (2006.01); A61K 31/137 (2006.01); A61K 31/404 (2006.01); A61K 31/416 (2006.01); A61K 31/517 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01)
CPC A61K 39/3955 (2013.01) [A61K 31/137 (2013.01); A61K 31/404 (2013.01); A61K 31/416 (2013.01); A61K 31/517 (2013.01); A61P 35/00 (2018.01); C07K 16/2818 (2013.01); C07K 2317/55 (2013.01); C07K 2317/622 (2013.01)] 26 Claims
OG exemplary drawing
 
1. An allosteric antibody comprising at least three amino acid substitutions at positions corresponding to Trp110 and Val37 in the heavy chain and a substitution corresponding to Phe98 in its light chain within an antigen-binding antibody, wherein the numbering is based on the positioning in the 4D5Flu antibody, wherein said amino acid substitutions form a contiguous cavity within the allosteric antibody which can be bound by an effector molecule, wherein the effector molecule comprises the amino acid side chains, or analog thereof, that were removed from the antibody by the at least three substitutions, wherein the allosteric antibody has reduced binding affinity for antigen, and wherein the binding affinity of the allosteric antibody for antigen is increased or restored upon binding with an effector molecule.