US 12,331,121 B2
Efflux pump-cancer antigen multi-specific antibodies and compositions, reagents, kits and methods related thereto
William Robert Arathoon, Tiburon, CA (US); Evan Matthew Bishop, San Jose, CA (US); Raffaella Briante, Burlingame, CA (US); Alissa Loren Briggs, San Jose, CA (US); Suchismita Mohanty, Millbrae, CA (US); Paul David Ponath, San Francisco, CA (US); Cindy Tan, San Jose, CA (US); and Qianting Zhai, South San Francisco, CA (US)
Assigned to William Robert Arathoon Living Trust Dated August 29, 2016, Tiburon, CA (US)
Appl. No. 17/598,737
Filed by William Robert Arathoon Living Trust Dated August 29, 2016, Tiburon, CA (US)
PCT Filed Apr. 1, 2020, PCT No. PCT/US2020/026261
§ 371(c)(1), (2) Date Sep. 27, 2021,
PCT Pub. No. WO2020/206033, PCT Pub. Date Oct. 8, 2020.
Claims priority of provisional application 62/967,478, filed on Jan. 29, 2020.
Claims priority of provisional application 62/828,044, filed on Apr. 2, 2019.
Prior Publication US 2022/0204627 A1, Jun. 30, 2022
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 16/46 (2006.01)
CPC C07K 16/2827 (2013.01) [A61P 35/00 (2018.01); C07K 16/2863 (2013.01); C07K 16/2896 (2013.01); C07K 16/468 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/526 (2013.01); C07K 2317/55 (2013.01); C07K 2317/565 (2013.01); C07K 2317/71 (2013.01); C07K 2317/92 (2013.01)] 18 Claims
 
1. A bispecific antibody molecule that binds multidrug resistance protein 1 (MDR1) and CD47, the antibody molecule comprising two identical variable light (VL) chains, a first variable heavy (VH) chain, and a second VH chain,
wherein the VL chains each comprise an antigen-binding site for MDR1, the first VH chain comprises an antigen-binding site for MDR1, and the second VH chain comprises an antigen-binding site for CD47, and wherein the second VH chain binds CD47 when paired with one of the VL chains,
wherein the antigen binding site of the first VH chain comprises heavy chain CDRs 1-3 (HCDRs 1-3) of a VH chain having the sequence:
EVKVVESGGVLVRPGGSLKLSCAASGFTFSRYTMSWVRQTPEKRLEWVATISSGGGX2TYYPD SVKGRFTVSRDNAMSSLYLQMSSLRSEDTALYYCARYGAGDAWFAYWGQGTLVTVSS (SEQ ID NO: 9), wherein X2 is N, Q or S, and
wherein the antigen binding site of the second VH chain comprises HCDRs 1-3 of a VH chain having the sequence:
 
 (SEQ ID NO: 17)
 
 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYNMHWVRQAPGQRLE
 
 
 
 WMGTIYPGNDDTSYNQKFKDRVTITADTSASTAYMELSSLRSEDTA
 
 
 
 VYYCARGGYRAMDYWGQGTLVTVSS.
wherein the bispecific antibody binds to cancer cells expressing both MDR1 and CD47 while showing reduced binding to non-cancer cells expressing MDR1 and/or CD47,
wherein the antigen-binding site of the two VL chains comprises light chain CDRs 1-3 (LCDRs 1-3) of a VL chain having the sequence:
DVLMTQTPVSLSVSLGDQASISCRSSQSIVHSTGX1TYLEWYLQKPGQSPKLLIYKISNRFSGV PDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQASHFPRTFGGGTKLEIK (SEQ ID NO:1), wherein X1 is N, Q or S.