ANTI-EpCAM ANTIBODIES, COMPOSITIONS COMPRISING ANTI-EpCAM ANTIBODIES AND METHODS OF MAKING AND USING ANTI-EpCAM ANTIBODIES

Abstract

Provided herein are antibodies that selectively bind to EpCAM and its isoforms and homologs, and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.

1 . A method of treating cancer that expresses EpCAM in a subject in need thereof, comprising administering to the subject an effective amount of an antibody comprising:
 three heavy chain CDRs of a V H  region selected from the group consisting of SEQ ID NOS: 248, 252, and 253, and three light chain CDRs of a V L  region selected from the group consisting of SEQ ID NOS: 273, 277, and 278.   
     
     
         2 . The method of  claim 1 , wherein the antibody comprises:
 (a) three heavy chain CDRs and three light chain CDRs of an antibody comprising the V H  region SEQ ID NO: 248, and the V L  region SEQ ID NO: 273;   (b) three heavy chain CDRs and three light chain CDRs of an antibody comprising the V H  region SEQ ID NO: 252, and the V L  region SEQ ID NO: 277; or   (c) three heavy chain CDRs and three light chain CDRs of an antibody comprising the V H  region SEQ ID NO: 253, and the V L  region SEQ ID NO: 278.   
     
     
         3 . The method of  claim 1 , wherein the antibody comprises:
 (a) a V H  comprising: a CDR-H1 comprising SEQ ID NO: 23; a CDR-H2 comprising SEQ ID NO: 73; and a CDR-H3 comprising SEQ ID NO: 123, and a V L  region comprising a CDR L1 comprising SEQ ID NO: 148; a CDR L2 comprising SEQ ID NO: 173, and a CDR L3 comprising SEQ ID NO: 198, according to the Chothia numbering scheme;   (b) a V H  comprising: a CDR-H1 comprising SEQ ID NO: 48; a CDR-H2 comprising SEQ ID NO: 98; and a CDR-H3 comprising SEQ ID NO: 123, and a V L  region comprising a CDR L1 comprising SEQ ID NO: 148; a CDR L2 comprising SEQ ID NO: 173, and a CDR L3 comprising SEQ ID NO: 198, according to the Kabat numbering scheme;   (c) a V H  comprising: a CDR-H1 comprising SEQ ID NO: 27; a CDR-H2 comprising SEQ ID NO: 77; and a CDR-H3 comprising SEQ ID NO: 127, and a V L  region comprising a CDR L1 comprising SEQ ID NO: 152; a CDR L2 comprising SEQ ID NO: 177, and a CDR L3 comprising SEQ ID NO: 202, according to the Kabat numbering scheme;   (d) a V H  comprising: a CDR-H1 comprising SEQ ID NO: 52; a CDR-H2 comprising SEQ ID NO: 102; and a CDR-H3 comprising SEQ ID NO: 127, and a V L  region comprising a CDR L1 comprising SEQ ID NO: 152; a CDR L2 comprising SEQ ID NO: 177, and a CDR L3 comprising SEQ ID NO: 202, according to the Kabat numbering scheme; or   (e) a V H  comprising: a CDR-H1 comprising SEQ ID NO: 28; a CDR-H2 comprising SEQ ID NO: 78; and a CDR-H3 comprising SEQ ID NO: 128, and a V L  region comprising a CDR L1 comprising SEQ ID NO: 153; a CDR L2 comprising SEQ ID NO: 178, and a CDR L3 comprising SEQ ID NO: 203, according to the Chothia numbering scheme; or   (f) a V H  comprising: a CDR-H1 comprising SEQ ID NO: 53; a CDR-H2 comprising SEQ ID NO: 103; and a CDR-H3 comprising SEQ ID NO: 128, and a V L  region comprising a CDR L1 comprising SEQ ID NO: 153; a CDR L2 comprising SEQ ID NO: 178, and a CDR L3 comprising SEQ ID NO: 203, according to the Kabat numbering scheme.   
     
     
         4 . The method of  claim 1 , wherein the antibody comprises:
 (a) the V H  region SEQ ID NO: 248, and the V L  region SEQ ID NO: 273;   (b) the V H  region SEQ ID NO: 252, and the V L  region SEQ ID NO: 277; or   (c) the V H  region SEQ ID NO: 253, and the V L  region SEQ ID NO: 278.   
     
     
         5 .- 33 . (canceled) 
     
     
         34 . The method of  claim 1 , wherein the antibody further comprises at least one constant region domain. 
     
     
         35 . The method of  claim 34 , wherein the constant region comprises a sequence selected from the group consisting of SEQ ID NOs: 279, 281, and 282. 
     
     
         36 . The method of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         37 . The method of  claim 1 , wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM. 
     
     
         38 . The method of  claim 1 , wherein the antibody is humanized or human. 
     
     
         39 . The method of  claim 1 , wherein the antibody is aglycosylated. 
     
     
         40 . The method of  claim 1 , wherein the antibody is an antibody fragment. 
     
     
         41 . The method of  claim 40 , wherein the antibody fragment is selected from an Fv fragment, a Fab fragment, a F(ab′) 2  fragment, a Fab′ fragment, an scFv (sFv) fragment, and an scFv-Fc fragment. 
     
     
         42 . The method of  claim 41 , wherein the antibody is an scFv fragment. 
     
     
         43 . The method of  claim 42 , wherein the scFv fragment comprises a sequence selected from SEQ ID NOs: 337-361, with or without the N-terminal M residue. 
     
     
         44 . The method of  claim 41 , wherein the antibody is an scFv-Fc fragment. 
     
     
         45 . The method of  claim 44 , wherein the scFv-Fc fragment comprises a sequence selected from SEQ ID NOs: 204-228, with or without the N-terminal M residue. 
     
     
         46 . The method of  claim 1 , wherein the antibody has a k a  of about 6.52×10 4  M −1 ×sec −1  to about 3.51×10 5  M −1 ×sec −1  when associating with human EpCAM at a temperature of 25° C. 
     
     
         47 . The method of  claim 1 , wherein the antibody has a k d  of about 1.75×10 −3  sec −1  to about 1.74×10 −5  sec −1  when dissociating from human EpCAM at a temperature of 25° C. 
     
     
         48 . The method of  claim 1 , wherein the antibody has a K D  of about 7.21×10 −9  M to about 1.93×10 −1 ° M when bound to human EpCAM at a temperature of 25° C. 
     
     
         49 . The method of  claim 1 , wherein the antibody specifically binds cynomolgus EpCAM. 
     
     
         50 . The method of  claim 49 , wherein the antibody has a K D  of about 1.62×10 −7  M to about 1.17×10 −9  M when bound to cynomolgus EpCAM at a temperature of 25° C. 
     
     
         51 . The method of  claim 50 , wherein the ratio of K D  for human EpCAM to K D  for cynomolgus EpCAM is about 0.029 to about 6.162. 
     
     
         52 .- 64 . (canceled) 
     
     
         65 . The method of  claim 1 , wherein the cancer is a carcinoma. 
     
     
         66 . The method of  claim 1 , wherein the antibody is administered more than once and wherein the antibody is administered at least 15 days apart from each administration. 
     
     
         67 . The method of  claim 1 , wherein the antibody is administered subcutaneously, intravenously, intramuscularly, and intraarterially. 
     
     
         68 . The method of  claim 1 , wherein the antibody is administered intravenously.