US 12,324,841 B2
Methods of treating cancer with a combination of an anti-PD-1 antibody and an anti-tissue factor antibody-drug conjugate
Reshma Abdulla Rangwala, Philadelphia, PA (US); Esther C. W. Breij, Driebergen (NL); Sandra Verploegen, Nieuwegein (NL); Oyewale O. Abidoye, Bellevue, WA (US); Leonardo Viana Nicacio, Redmond, WA (US); Anthony Cao, Sammamish, WA (US); and Shyra Gardai, Bothell, WA (US)
Assigned to GENMAB A/S, Valby (DK); and MSD INTERNATIONAL GMBH, Luzerne (CH)
Appl. No. 17/053,753
Filed by GENMAB A/S, Valby (DK); and MSD International GmbH, Lucerne (CH)
PCT Filed May 7, 2019, PCT No. PCT/US2019/031166
§ 371(c)(1), (2) Date Nov. 6, 2020,
PCT Pub. No. WO2019/217455, PCT Pub. Date Nov. 14, 2019.
Claims priority of provisional application 62/753,725, filed on Oct. 31, 2018.
Claims priority of provisional application 62/668,088, filed on May 7, 2018.
Prior Publication US 2022/0088191 A1, Mar. 24, 2022
Int. Cl. A61K 47/68 (2017.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); A61P 35/00 (2006.01)
CPC A61K 47/6849 (2017.08) [A61K 39/3955 (2013.01); A61K 47/68031 (2023.08); A61K 47/6817 (2017.08); A61K 47/6845 (2017.08); A61K 47/6889 (2017.08); A61P 35/00 (2018.01); A61K 2039/545 (2013.01)] 28 Claims
 
1. A method of treating breast or cervical cancer that expresses tissue factor (TF) and programmed death-ligand 1 (PD-L1) in a subject, the method comprising administering to the subject an antibody or an antigen-binding fragment thereof, wherein the antibody binds to Programmed Death-1 (PD-1) and inhibits PD-1 activity, and an antibody-drug conjugate that binds to tissue factor TF, wherein the antibody-drug conjugate comprises an anti-TF antibody or an antigen-binding fragment thereof conjugated to monomethyl auristatin E, wherein the antibody-drug conjugate further comprises a linker between the anti-TF antibody or antigen-binding fragment thereof and the monomethyl auristatin E, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises:
(i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:17;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:18; and
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:19; and
wherein the light chain variable region comprises:
(i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:20;
(ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:21; and
(iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:22,
and wherein the anti-TF antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises:
(i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO:1;
(ii) a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2; and
(iii) a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3; and
wherein the light chain variable region comprises:
(i) a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4;
(ii) a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5; and
(iii) a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6.