Pharmaceutical combinations
The present disclosure relates generally to the fields of immunology and molecular biology. More specifically, provided herein are pharmaceutical combinations comprising (A) antibodies, or antigen-binding portions thereof, directed against LY75, and (B) a second anti-cancer entity; nucleic acids encoding antibody combinations; methods for preparing antibody combinations; and methods for the treatment of diseases, such as cancers mediated by LY75 expression or activity.
1 . A method of treating cancer in a subject comprising simultaneously, sequentially or separately administering to the subject in need thereof therapeutically-effective amounts of components (A) and (B) of a pharmaceutical combination comprising: (A) an anti-LY75 antibody, or an antigen-binding portion thereof, said antibody or portion thereof comprising: a) a heavy chain variable region comprising: i) a first vhCDR comprising SEQ ID NO:5; ii) a second vhCDR comprising SEQ ID NO: 6; and iii) a third vhCDR comprising SEQ ID NO: 7; and b) a light chain variable region comprising: i) a first vICDR comprising SEQ ID NO:8; ii) a second vICDR comprising SEQ ID NO: 9; and iii) a third vICDR comprising SEQ ID NO: 10; wherein the anti-LY75 antibody or antigen-binding portion thereof further comprises a covalently-attached drug, and wherein said drug is a maytansinoid or a derivative thereof and (B) ibrutinib or a pharmaceutically-acceptable salt thereof.
2 . The method of claim 1 , wherein the anti-LY75 antibody or antigen-binding portion thereof is internalized by a cell expressing LY75.
3 . The method of claim 1 , wherein the maytansinoid is DM4 or DM1.
4 . The method of claim 1 , wherein the cancer is diffuse large B-cell lymphoma (DLBCL) or Non-Hodgkin's lymphoma.
5 . The method of claim 1 , wherein the anti-LY75 antibody or an antigen-binding portion thereof comprises a heavy chain variable region comprising SEQ ID NO: 1 and a light chain variable region comprising SEQ ID NO: 2.
6 . The method of claim 1 , wherein the anti-LY75 antibody is a human IgG1 monoclonal antibody.
7 . The method of claim 1 , wherein (A) and/or (B) additionally comprise one or more pharmaceutically-acceptable diluents, excipients or carriers.