Novel anti-human muc1 antibody fab fragment

Abstract

The problem to be solved is to provide an anti-human MUC1 antibody Fab fragment that is expected to be useful in the diagnosis and/or treatment of a cancer, particularly, the diagnosis and/or treatment of breast cancer or bladder cancer, and a diagnosis approach and/or a treatment approach using a conjugate comprising the Fab fragment. The solution is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 8 or 10, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12, and a conjugate comprising the Fab fragment.

1 : A conjugate comprising one or more labeling moiety, wherein the labeling moiety is (i) a fluorescent dye and a linker or (ii) a fluorescent dye, and an anti-human MUC1 antibody Fab fragment selected from the group consisting of the following (a) and (b):
 (a) an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 8 or SEQ ID NO: 10 and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12; and   (b) an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region derived from a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 8 or SEQ ID NO: 10 by the modification of glutamine at amino acid position 1 of SEQ ID NO: 8 or SEQ ID NO: 10 into pyroglutamic acid, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12.   
     
     
         2 : The conjugate according to  claim 1  wherein the anti-human MUC1 antibody Fab fragment is selected from the group consisting of the following (a) and (b):
 (a) an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 2 or SEQ ID NO: 4 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6; and 
 (b) an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment derived from a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 2 or SEQ ID NO: 4 by the modification of glutamine at amino acid position 1 of SEQ ID NO: 2 or SEQ ID NO: 4 into pyroglutamic acid, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6. 
 
     
     
         3 : The conjugate according to  claim 1  wherein the anti-human MUC1 antibody Fab fragment is selected from the group consisting of the following (a) and (b):
 (a) an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 10 and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12; and 
 (b) an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment comprising a heavy chain variable region derived from a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 10 by the modification of glutamine at amino acid position 1 of SEQ ID NO: 10 into pyroglutamic acid, and a light chain comprising a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12. 
 
     
     
         4 : The conjugate according to  claim 3  wherein the anti-human MUC1 antibody Fab fragment is selected from the group consisting of the following (a) and (b):
 (a) an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 4 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6; and 
 (b) an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment derived from a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 4 by the modification of glutamine at amino acid position 1 of SEQ ID NO: 4 into pyroglutamic acid, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6. 
 
     
     
         5 : The conjugate according to  claim 4  wherein the anti-human MUC1 antibody Fab fragment is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 4 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6. 
     
     
         6 : The conjugate according to  claim 4  wherein the anti-human MUC1 antibody Fab fragment is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment derived from a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 4 by the modification of glutamine at amino acid position 1 of SEQ ID NO: 4 into pyroglutamic acid, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6. 
     
     
         7 : The conjugate according to  claim 1 , wherein the fluorescent dye is a fluorescent dye selected from the group consisting of the following formula (B) and the following formula (C): 
       
         
           
           
               
               
           
         
         wherein the wavy line represents binding to the anti-human MUC1 antibody Fab fragment or the linker. 
       
     
     
         8 : The conjugate according to  claim 7 , wherein the wavy line represents binding to the anti-human MUC1 antibody Fab fragment, and the anti-human MUC1 antibody Fab fragment is bound via an amino group thereof to the carbon atom of a labeling moiety terminal C(═O) group. 
     
     
         9 : The conjugate according to  claim 8 , wherein the labeling moiety is a fluorescent dye represented by formula (B). 
     
     
         10 : A conjugate selected from the group consisting of the following (a) to (c):
 (a) the conjugate according to  claim 9  wherein the anti-human MUC1 antibody Fab fragment is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 4 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6;   (b) the conjugate according to  claim 9  wherein the anti-human MUC1 antibody Fab fragment is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment derived from a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 4 by the modification of glutamine at amino acid position 1 of SEQ ID NO: 4 into pyroglutamic acid, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6; and   (c) a conjugate which is a mixture of (a) and (b).   
     
     
         11 : The conjugate according to  claim 8 , wherein the labeling moiety is a fluorescent dye represented by formula (C). 
     
     
         12 : A conjugate selected from the group consisting of the following (a) to (c):
 (a) the conjugate according to  claim 11  wherein the anti-human MUC1 antibody Fab fragment is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 4 and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6;   (b) the conjugate according to  claim 11  wherein the anti-human MUC1 antibody Fab fragment is an anti-human MUC1 antibody Fab fragment comprising a heavy chain fragment derived from a heavy chain fragment consisting of the amino acid sequence represented by SEQ ID NO: 4 by the modification of glutamine at amino acid position 1 of SEQ ID NO: 4 into pyroglutamic acid, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6; and   (c) a conjugate which is a mixture of (a) and (b).   
     
     
         13 : A composition comprising the conjugate according to  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         14 . (canceled) 
     
     
         15 : A composition comprising the conjugate according to  claim 10  and pharmaceutically acceptable carrier. 
     
     
         16 : A composition comprising the conjugate according to  claim 12  and a pharmaceutically acceptable carrier. 
     
     
         17 - 25 . (canceled) 
     
     
         26 : A method for diagnosing breast cancer or bladder cancer, comprising preoperatively or intraoperatively administering the conjugate according to  claim 1  to a subject in need thereof. 
     
     
         27 : A method for treating breast cancer or bladder cancer, comprising administering a therapeutically effective amount of the conjugate according to  claim 1  to a subject in need thereof.