Recombinant monoclonal antibodies and corresponding antigens for colon and pancreatic cancers

Abstract

The present invention provides for recombinant monoclonal antibodies that bind to human colorectal and pancreatic carcinoma-associated antigens, along with nucleic acid sequences encoding the antibody chains, and the amino acid sequences corresponding to the nucleic acids, and uses for these antibodies, nucleic acids and amino acids.

1 - 24 . (canceled) 
     
     
         25 . An isolated monoclonal antibody, antigen-binding fragment, or derivative thereof, that binds to a human colorectal and pancreatic carcinoma-associated antigen (CPAA), wherein said CPAA is a 16C3 antigen. 
     
     
         26 . The antibody of  claim 25 , wherein the antibody has anti-tumor activity. 
     
     
         27 . The antibody of  claim 25 , wherein said fragment comprises a Fab, Fab′, F(ab′)2, Fv, CDR, paratope, or portion of an antibody that is capable of binding said antigen. 
     
     
         28 . The antibody of  claim 25 , wherein said antibody is a chimeric, humanized, anti-idiotypic, or bifunctional antibody. 
     
     
         29 . The antibody of  claim 28 , wherein the light chain of said humanized antibody
 (a) comprises the amino acid sequence of SEQ ID NO: 12, 14, 16, 17, 18, 19, 20, 21, and/or 29;   (b) is encoded by a nucleic acid that encodes the amino acid sequence of SEQ ID NOs: 12, 14, 16, 17, 18, 19, 20, 21, and/or 29;   (c) comprises a light chain component comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 4, a CDR2 comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 5, or a CDR3 comprising the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 6; or   (d) comprises a humanized variant of any one of (a)-(c);
 and wherein the heavy chain of said humanized antibody 
   (e) comprises the amino acid sequence of SEQ ID NO: 13, 15, 22, 23, 24, 25, 26, 27, and/or 28;   (f) is encoded by a nucleic acid that encodes the amino acid sequence of SEQ ID NOs: 13, 15, 22, 23, 24, 25, 26, 27, and/or 28;   (g) comprises a heavy chain component comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 7, a CDR2 comprising the amino acid sequence of SEQ ID NO: 8 or SEQ ID NO: 10, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 9 or SEQ ID NO: 11; or   (h) comprises a humanized variant of (e)-(g).   
     
     
         30 . The antibody of  claim 25 , wherein said antibody is conjugated to or is comprised in association with a cytotoxic agent, optionally which may be a moiety that inhibits DNA synthesis, a moiety that inhibits RNA synthesis, a moiety that inhibits protein synthesis, a radionuclide, chemotherapeutic drug, cytotoxic protein, and a ribosomal inhibiting protein,  212 Bi,  131 I,  188 Re,  90 Y, vindesine, methotrexate, adriamycin, cisplatin, pokeweed antiviral protein,  Pseudomonas  exotoxin A, ricin, diphtheria toxin, ricin A chain, a phospholipase enzyme, daunorubicin, doxorubicin, methotrexate, or Mitomycin C. 
     
     
         31 . The antibody of  claim 25 , wherein said antibody is conjugated to a label, optionally which may be a chemiluminescent agent, fluorescence-emitting metal, enzyme, enzyme cofactor, enzyme inhibitor, fluorescent agent, bioluminescent agent, and a radioactive label. 
     
     
         32 . A diagnostic kit comprising the antibody of  claim 25 . 
     
     
         33 . The kit of  claim 32 , wherein antibody is fixed to a solid phase support, optionally which may be a bead, test tube, sheet, culture dish, or test strip. 
     
     
         34 . A composition comprising the antibody of  claim 25  and a carrier. 
     
     
         35 . A method for diagnosing or treating colorectal or pancreatic carcinoma or associated pathologies and/or promoting tumor regression in a subject, comprising administering to a subject an effective amount of a monoclonal antibody, or an antigen-binding fragment or derivative thereof, that binds a colorectal and pancreatic carcinoma-associated antigen (CPAA), wherein said CPAA is a 16C3 antigen. 
     
     
         36 . The method of  claim 35 , wherein said CPAA is bound by a 16C3 monoclonal antibody. 
     
     
         37 . The method of  claim 35 , wherein the antibody has anti-tumor activity. 
     
     
         38 . The method of  claim 35 , wherein said fragment is a Fab, Fab′, F(ab′)2, Fv, CDR, paratope, or a portion of an antibody that is capable of binding the antigen. 
     
     
         39 . The method of  claim 35 , wherein said antibody is chimeric, humanized, anti-idiotypic, or bifunctional antibody. 
     
     
         40 . The method of  claim 35 , wherein said antibody is conjugated to or is comprised in association with a cytotoxic agent, optionally which may be a moiety that inhibits DNA synthesis, a moiety that inhibits RNA synthesis, a moiety that inhibits protein synthesis, a radionuclide, chemotherapeutic drug, cytotoxic protein, a ribosomal inhibiting protein,  212 Bi,  131 I,  188 Re,  90 Y, vindesine, methotrexate, adriamycin, cisplatin, pokeweed antiviral protein,  Pseudomonas  exotoxin A, ricin, diphtheria toxin, ricin A chain, a phospholipase enzyme, daunorubicin, doxorubicin, methotrexate, or Mitomycin C, or said antibody is conjugated to a label, optionally which may be a chemiluminescent agent, fluorescence-emitting metal, enzyme, enzyme cofactor, enzyme inhibitor, fluorescent agent, bioluminescent agent, or a radioactive label. 
     
     
         41 . The method of  claim 35 , wherein the subject has or is suspected of having pancreatic or colon cancer or is subject is a disease-free individual. 
     
     
         42 . The method of  claim 35 , wherein said antibody is administered in combination with another therapeutic agent, optionally which may be a chemotherapeutic or an immunosuppressive agent. 
     
     
         43 . An isolated nucleic acid encoding the heavy chain and/or light chain of the antibody of  claim 25 , which optionally is comprised in a vector or cell. 
     
     
         44 . A method of producing an antibody or an antigen-binding fragment thereof that binds the 16C3 CPAA or a heavy or light chain thereof, comprising expressing the isolated nucleic acid of  claim 43 .