US 11,666,581 B2
PROTAC antibody conjugates and methods of use
Thomas Pillow, San Francisco, CA (US); Jack Sadowsky, Dublin, CA (US); Leanna Staben, San Francisco, CA (US); Steven Staben, San Francisco, CA (US); Binqing Wei, Belmont, CA (US); Ingrid Wertz, South San Francisco, CA (US); Pragya Adhikari, Fremont, CA (US); Nicole Blaquiere, San Francisco, CA (US); Peter Dragovich, San Diego, CA (US); and Wayne Fairbrother, Burlingame, CA (US)
Assigned to Genentech, Inc., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on Nov. 19, 2018, as Appl. No. 16/194,897.
Application 16/194,897 is a continuation of application No. PCT/US2017/033611, filed on May 19, 2017.
Claims priority of provisional application 62/339,257, filed on May 20, 2016.
Prior Publication US 2019/0175612 A1, Jun. 13, 2019
Int. Cl. A61K 31/551 (2006.01); A61K 47/54 (2017.01); A61K 47/68 (2017.01); A61K 47/65 (2017.01); A61P 37/06 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01); C07K 16/32 (2006.01); C12N 9/00 (2006.01)
CPC A61K 31/551 (2013.01) [A61K 47/545 (2017.08); A61K 47/65 (2017.08); A61K 47/68 (2017.08); A61P 35/00 (2018.01); A61P 37/06 (2018.01); C07K 16/2827 (2013.01); C07K 16/32 (2013.01); C12N 9/93 (2013.01); C12Y 203/02007 (2013.01)] 22 Claims
 
1. A conjugate having the chemical structure
Ab-(L1-D)p,
wherein
D is a PROTAC having the structure E3LB-L2-PB, wherein
E3LB is an E3 ligase binding group covalently bound to L2, wherein the E3 ligase is a tetrahydro-benzodiazepinone or a pharmaceutically acceptable salt thereof, and
wherein E3LB is

OG Complex Work Unit Chemistry
L2 is a linker covalently bound to E3LB and PB, and
PB is a protein binding group covalently bound to L2;
Ab is an antibody covalently bound to L1;
L1 is a linker covalently bound to Ab and D; and
p has a value from about 1 to about 8.