Conjugated antiboides against ly75 for the treatment of cancer

Abstract

The invention provides antibodies which bind to LY75. Nucleic acid molecules encoding the antibodies, expression vectors, host cells and methods for expressing the antibodies are also provided. The antibodies may be used for the treatment of cancer, including pancreatic cancer, ovarian cancer, breast cancer, colorectal cancer, esophageal cancer, skin cancer, thyroid cancer, lung cancer, bladder cancer, multiple myeloma and lymphoma.

What we claim is: 
     
         1 .- 48 . (canceled) 
     
     
         49 . A composition for administering to a patient in need of a treatment for cancer expressing LY75, said composition comprising at least one member of the group consisting of:
 (1) an isolated antibody; (2) an antigen-binding portion thereof; and (3) combinations thereof;   wherein said isolated antibody, and said antigen-binding portion thereof, bind to LY75, and each comprises:   a) a heavy chain variable region comprising:   i) a first sequence comprising SEQ ID NO: 5;   ii) a second sequence comprising SEQ ID NO: 6; and   iii) a third sequence comprising SEQ ID NO: 7; and   b) a light chain variable region comprising:   i) a first sequence comprising SEQ ID NO: 8;   ii) a second sequence comprising SEQ ID NO: 9; and   iii) a third sequence comprising SEQ ID NO: 10;   wherein said first sequence of said heavy chain variable region, SEQ ID NO: 5, comprises a conservative sequence modification while maintaining at least 80% sequence identity.   
     
     
         50 . A composition for administering to a patient in need of a treatment for cancer expressing LY75, said composition comprising at least one member of the group consisting of:
 (1) an isolated antibody; (2) an antigen-binding portion thereof; and (3) combinations thereof;   wherein said isolated antibody, and said antigen-binding portion thereof, bind to LY75, and each comprises:   a) a heavy chain variable region comprising:   i) a first sequence comprising SEQ ID NO: 5;   ii) a second sequence comprising SEQ ID NO: 6; and   iii) a third sequence comprising SEQ ID NO: 7; and   b) a light chain variable region comprising:   i) a first sequence comprising SEQ ID NO: 8;   ii) a second sequence comprising SEQ ID NO: 9; and   iii) a third sequence comprising SEQ ID NO: 10; and   wherein at least one of said first, second, and third sequences of said heavy chain variable region and said first, second, and third sequences of said light chain variable region comprises a conservative sequence modification while maintaining at least 80% sequence identity.   
     
     
         51 . The composition of  claim 50  in which said heavy chain variable region further comprises:
 i) a fourth sequence comprising SEQ ID NO: 16; 
 ii) a fifth sequence comprising SEQ ID NO: 17; 
 iii) a sixth sequence comprising SEQ ID NO: 18; and 
 iv) a seventh sequence comprising SEQ ID NO: 19. 
 
     
     
         52 . The composition of  claim 50  in which said light chain variable region further comprises:
 i) a fourth sequence comprising SEQ ID NO: 20; 
 ii) a fifth sequence comprising SEQ ID NO: 21; 
 iii) a sixth sequence comprising SEQ ID NO: 22; and 
 iv) a seventh sequence comprising SEQ ID NO: 23. 
 
     
     
         53 . The composition of  claim 51  in which said light chain variable region further comprises:
 i) a fourth sequence comprising SEQ ID NO: 20; 
 ii) a fifth sequence comprising SEQ ID NO: 21; 
 iii) a sixth sequence comprising SEQ ID NO: 22; and 
 iv) a seventh sequence comprising SEQ ID NO: 23. 
 
     
     
         54 . The composition of  claim 50  wherein at least one of said first, second, and third sequences of said heavy chain variable region comprises a conservative sequence modification while maintaining at least 80% sequence identity. 
     
     
         55 . The composition of  claim 50  wherein at least one of said first, second, and third sequences of said light chain variable region comprises a conservative sequence modification while maintaining at least 80% sequence identity. 
     
     
         56 . The isolated antibody or an antigen-binding portion thereof according to  claim 50  further comprising a covalently attached moiety. 
     
     
         57 . The isolated antibody or an antigen-binding portion thereof according to  claim 56 , wherein said moiety is a drug. 
     
     
         58 . The isolated antibody or an antigen-binding portion thereof according to  claim 57 , wherein said drug is selected from the group consisting of a maytansinoid, a dolastatin, a hemiasterlin, an auristatin, a trichothecene, a calicheamicin, CC1065 and derivatives thereof. 
     
     
         59 . The isolated antibody or an antigen-binding portion thereof according to  claim 58 , wherein said drug is a maytansinoid selected from the group consisting of DM4 and DM1. 
     
     
         60 . The isolated antibody according to  claim 50 , wherein said antibody induces antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC). 
     
     
         61 . The isolated antibody according to  claim 60 , wherein the antibody is an engineered antibody having increased binding to Fc receptors and/or increased potency for ADCC, and/or a bispecific antibody. 
     
     
         62 . A pharmaceutical composition comprising an antibody, or antigen binding portion thereof, according to  claim 50 , together with one or more pharmaceutically acceptable diluents, excipients or carriers. 
     
     
         63 . A method of treating cancer expressing LY75 comprising administering to a patient in need thereof an antibody or an antigen-binding portion thereof of  claim 49  wherein the antibody or antigen-binding portion comprises a covalently attached drug conjugate. 
     
     
         64 . The method of  claim 63 , wherein the covalently attached drug conjugate is a maytansinoid. 
     
     
         65 . The method according to  claim 64  wherein the antibody induces antibody-dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC). 
     
     
         66 . The composition of  claim 50  wherein said second sequences of said heavy chain variable region comprises a conservative sequence modification while maintaining at least 90% sequence identity.