US 12,453,781 B2
Methods of treating cancer with a combination of an anti-VEGF antibody and an anti-tissue factor antibody-drug conjugate
Reshma Abdulla Rangwala, Philadelphia, PA (US); Sandra Verploegen, Nieuwegein (NL); Esther C. W. Breij, Driebergen (NL); Oyewale O. Abidoye, Bellevue, WA (US); and Leonardo Viana Nicacio, Redmond, WA (US)
Assigned to Genmab A/S, Valby (DK)
Appl. No. 17/289,616
Filed by Genmab A/S, Copenhagen V (DK)
PCT Filed Oct. 28, 2019, PCT No. PCT/US2019/058300
§ 371(c)(1), (2) Date Apr. 28, 2021,
PCT Pub. No. WO2020/092210, PCT Pub. Date May 7, 2020.
Claims priority of provisional application 62/752,904, filed on Oct. 30, 2018.
Prior Publication US 2021/0402003 A1, Dec. 30, 2021
Int. Cl. A61K 47/68 (2017.01); A61K 9/00 (2006.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07K 16/22 (2006.01); C07K 16/36 (2006.01)
CPC A61K 47/6869 (2017.08) [A61K 9/0019 (2013.01); A61K 39/3955 (2013.01); A61K 39/39558 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07K 16/22 (2013.01); C07K 16/36 (2013.01); A61K 2039/507 (2013.01); A61K 2039/54 (2013.01); A61K 2039/545 (2013.01); C07K 2317/24 (2013.01); C07K 2317/565 (2013.01)] 36 Claims
 
1. A method of treating cervical cancer in a subject, the method comprising administering to the subject an anti-VEGF antibody or antigen-binding fragment thereof 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 an auristatin or a functional analog thereof or a functional derivative thereof;
wherein the anti-TF antibody or antigen-binding fragment thereof of the antibody-drug conjugate 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,
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, and
wherein the CDRs of the anti-TF antibody or antigen-binding fragment thereof of the antibody-drug conjugate are defined by the IMGT numbering scheme.