Novel compounds

Abstract

An antibody, or a derivate or a fragment thereof, having a binding structure for a target structure is described. The antibody is displayed in, and on the cell surface of, human gastrointestinal epithelial tumour cells and in a subpopulation of normal human gastrointestinal epithelial cells. Said binding structure comprises the complementarity determining region (CDR) sequences in the light chain comprising essentially the amino acids number 23-33 (CDR1), 49-55 (CDR2), 88-98 (CDR3) of the amino acid sequence shown in SEQ ID NO:2, and the CDR sequences in the heavy chain comprising essentially the amino acids number 158-162 (CDR1), 177-193 (CDR2, 226-238 (CDR3) of the amino acid sequence shown in SEQ ID NO:2, or other binding structures with similar unique binding properties. There is also described a target structure displayed in, or on the surface of tumour cells, vaccine compositions, pharmaceutical compositions as well as methods related to human malignant diseases.

1 - 16 . (canceled)  
     
     
         17 . A target structure displayed in, or on the surface of, tumour cells, said target structure 
 a) having the ability of being specifically blocked by and to specifically block a binding structure, wherein the binding structure is an antibody or antigen binding fragment of an antibody or a fragment thereof, and other binding structures with similar binding properties,    b) being displayed in, and on the surface of, human gastrointestinal epithelial cells,    c) having substantial homology with α6 and/or β4 integrin chains or variants thereof, representing a shared or unique epitope,    d) being highly expressed on the surface of tumour cells, and e) being a target for cytotoxic effector mechanism; wherein the antibody is an antibody, or a fragment thereof, having a binding structure for a target structure displayed in, and on the cell surface of, human gastrointestinal epithelial tumour cells, said binding structure comprising the complementarity determining region (CDR) sequences in the light chain comprising essentially the amino acids number 23-33 (CDR1), 49-55 (CDR2), 88-98 (CDR3) of the amino acid sequence shown in SEQ ID NO:2, and the CDR sequences in the heavy chain comprising essentially the amino acids number 158-162 (CDR1), 177-193 (CDR2), 226-238 (CDR3) of the amino acid sequence shown in SEQ ID NO:2.    
     
     
         18 . A target structure according to  claim 17 , wherein the antibody or antigen binding fragment is labeled and the binding thereof is inhibited by an unlabeled form of said binding structure and not by other binding structures, and not inhibiting the binding of other binding structures having other binding specificities.  
     
     
         19 . A target structure according to  claim 17 , wherein the antibody or antigen binding fragment comprises one or more of the complementarity determining region (CDR) sequences comprising essentially the amino acids number 23-33, 49-55,88-98,158-162,177-193,226-238 of the amino acid sequence shown in SEQ ID NO : 2, or other binding structures with similar unique binding properties.  
     
     
         20 . A target structure according to  claim 17 , wherein the antibody or antigen binding fragment is an antibody.  
     
     
         21 . (canceled)  
     
     
         22 . A target structure according to  claim 17 , which is expressed homogenously in human colonic epithelial cells and less in pancreatic duct and bile duct cells.  
     
     
         23 . A target structure according to  claim 17 , the expression of which is correlated to gastrointestinal epithelial differentiation.  
     
     
         24 . A target structure according to  claim 17 , which comprises essentially the amino acid sequence of a6 integrin shown in SEQ ID NO: 3 and/or of β4 integrin shown in SEQ ID NO: 4, and/or one or more fragments, and/or variants or splice variants, and or subunits, thereof.  
     
     
         25 . A target structure according to  claim 24 , which comprises homo- or hetero-monomers or homo- or hetero-multimers of said α6p4 integrin and/or of said one or more fragments and/or variants and/or subunits thereof.  
     
     
         26 . A target structure according to  claim 24 , which has an apparent molecular weight in its non-reduced form of from 90 to 140 kDa, most preferred from 80 to 160 kDa.  
     
     
         27 . A target structure according to  claim 24 , which comprises a peptide or polypeptide(s) comprising essentially any one of the amino acid sequences shown in SEQ ID NOs: 5-51, or comprises a molecule complexed to said polypeptide(s).  
     
     
         28 . A target structure according to  claim 24  recognised, exclusively or not, in its non-reduced form by the antibody or antigen binding fragment comprised by an antibody or a fragment thereof, having a binding structure for a target structure displayed in, and on the cell surface of, human gastrointestinal epithelial tumour cells, said binding structure comprising the complementarity determining region (CDR) sequences in the light chain comprising essentially the amino acids number 23-33 (CDR1), 49-55 (CDR2), 88-98 (CDR3) of the amino acid sequence shown in SEQ ID NO:2, and the CDR sequences in the heavy chain comprising essentially the amino acids number 158-162 (CDR1), 177-193 (CDR2), 226-238 (CDR3) of the amino acid sequence shown in SEQ ID NO:2.  
     
     
         29 - 34 . (canceled)  
     
     
         35 . A pharmaceutical composition comprising as an active principle a target structure as defined in  claim 17 .  
     
     
         36 - 52 . (canceled)  
     
     
         53 . A method for therapy of human malignant disease, whereby an antibody or a fragment thereof is administered to a human subject, whereby said antibody or fragment thereof has been changed by being genetically linked to molecules giving the combined molecule changed pharmaco-kinetic properties; 
 wherein the antibody is an antibody or a fragment thereof, having a binding structure for a target structure displayed in and on the cell surface of, human gastrointestinal epithelial tumor cells, said binding structure comprising the complementary determining region (CDR) sequences in the light chain comprising essentially the amino acids number 23-33 (CDR1), 49-55 (CDR2), 88-98 (CDR3) of the amino acid sequence shown in SEQ ID NO: 2, and the CDR sequence in the heavy chain comprising essentially the amino acids number 158-162 (CDR1), 177-193 (CDR2), 226-238 (CDR3) of the amino acid sequence shown in SEQ ID NO: 2.    
     
     
         54 . (canceled)