Anti-pd-l1 antibody

Abstract

The present invention provides an anti-PD-L1 antibody capable of repeated administration even to animals other than rat. An anti-PD-L1 antibody comprising (a) a light chain comprising a light chain variable region containing CDR1 having the amino acid sequence of QSLLYSENQKDY (SEQ ID NO: 37), CDR2 having the amino acid sequence of WAT and CDR3 having the amino acid sequence of GQYLVYPFT (SEQ ID NO: 38) and the light chain constant region of an antibody of an animal other than rat; and (b) a heavy chain comprising a heavy chain variable region containing CDR1 having the amino acid sequence of GYTFTSNF (SEQ ID NO: 39), CDR2 having the amino acid sequence of IYPEYGNT (SEQ ID NO: 40) and CDR3 having the amino acid sequence of ASEEAVISLVY (SEQ ID NO: 41) and the heavy chain constant region of an antibody of an animal other than rat. A pharmaceutical composition comprising the above anti-PD-L1 antibody as an active ingredient. A method for preparing the above anti-PD-L1 antibody is also provided.

1 . An anti-PD-L1 antibody comprising (a) a light chain comprising a light chain variable region containing CDR1 having the amino acid sequence of QSLLYSENQKDY (SEQ ID NO: 37), CDR2 having the amino acid sequence of WAT and CDR3 having the amino acid sequence of GQYLVYPFT (SEQ ID NO: 38) and the light chain constant region of a canine antibody; and (b) a heavy chain comprising a heavy chain variable region containing CDR1 having the amino acid sequence of GYTFTSNF (SEQ ID NO: 39), CDR2 having the amino acid sequence of IYPEYGNT (SEQ ID NO: 40) and CDR3 having the amino acid sequence of ASEEAVISLVY (SEQ ID NO: 41) and the heavy chain constant region of a canine antibody. 
     
     
         2 . The antibody of  claim 1 , wherein the light chain variable region and the heavy chain variable region are derived from rat. 
     
     
         3 . The antibody of  claim 2 , wherein the light chain variable region is the light chain variable region of a rat anti-bovine PD-L1 antibody and the heavy chain variable region is the heavy chain variable region of a rat anti-bovine PD-L1 antibody. 
     
     
         4 . The antibody of  claim 3 , wherein the light chain variable region has the amino acid sequence as shown in SEQ ID NO. 1 and the heavy chain variable region has the amino acid sequence as shown in SEQ ID NO: 2. 
     
     
         5 . The antibody of  claim 1 , wherein the light chain constant region of a canine antibody has the amino acid sequence of the constant region of lambda chain or kappa chain. 
     
     
         6 . The antibody of  claim 1 , wherein the heavy chain constant region of a canine antibody has the amino acid sequence of the constant region of an immunoglobulin equivalent to human IgG4. 
     
     
         7 . The antibody of  claim 6 , wherein the animal other than rat is canine; the light chain constant region of the canine antibody has the amino acid sequence of the constant region of lambda chain; and the heavy chain constant region of the canine antibody has the amino acid sequence of the constant region of an immunoglobulin equivalent to human IgG4. 
     
     
         8 . The antibody of  claim 7 , wherein the light chain constant region of the canine antibody has the amino acid sequence as shown in SEQ ID NO: 3 and the heavy chain constant region of the canine antibody has the amino acid sequence as shown in SEQ ID NO: 4. 
     
     
         9 . The antibody of  claim 1  which has a four-chain structure comprising two light chains and two heavy chains. 
     
     
         10 . A pharmaceutical composition comprising the antibody of  claim 1  as an active ingredient. 
     
     
         11 . The pharmaceutical composition of  claim 10  for treatment of cancers and/or infections. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the cancers and/or infections are selected from the group consisting of neoplastic diseases, leukemia, Johne's disease, anaplasmosis, bacterial mastitis, mycotic mastitis, mycoplasma infections, tuberculosis,  Theileria orientalis  infection, cryptosporidiosis, coccidiosis, trypanosomiasis and leishmaniasis. 
     
     
         13 . An artificial genetic DNA comprising (a′) a DNA encoding a light chain comprising a light chain variable region containing CDR1 having the amino acid sequence of QSLLYSENQKDY (SEQ ID NO: 37), CDR2 having the amino acid sequence of WAT and CDR3 having the amino acid sequence of GQYLVYPFT (SEQ ID NO: 38) and the light chain constant region of a canine antibody and (b′) a DNA encoding a heavy chain comprising a heavy chain variable region containing CDR1 having the amino acid sequence of GYTFTSNF (SEQ ID NO: 39), CDR2 having the amino acid sequence of IYPEYGNT (SEQ ID NO: 40) and CDR3 having the amino acid sequence of ASEEAVISLVY (SEQ ID NO: 41) and the heavy chain constant region of a canine antibody. 
     
     
         14 . A vector comprising the artificial genetic DNA of  claim 13 . 
     
     
         15 . A host cell transformed with the vector of  claim 14 . 
     
     
         16 . A method of preparing an antibody, comprising culturing the host cell of  claim 15  and collecting an anti-PD-L1 antibody from the resultant culture. 
     
     
         17 . A DNA encoding a light chain comprising a light chain variable region containing CDR1 having the amino acid sequence of QSLLYSENQKDY (SEQ ID NO: 37), CDR2 having the amino acid sequence of WAT and CDR3 having the amino acid sequence of GQYLVYPFT (SEQ ID NO: 38) and the light chain constant region of a canine antibody. 
     
     
         18 . A DNA encoding a heavy chain comprising a heavy chain variable region containing CDR1 having the amino acid sequence of GYTFTSNF (SEQ ID NO: 39), CDR2 having the amino acid sequence of IYPEYGNT (SEQ ID NO: 40) and CDR3 having the amino acid sequence of ASEEAVISLVY (SEQ ID NO: 41) and the heavy chain constant region of a canine antibody. 
     
     
         19 . A method of treating cancers and/or infections in a subject, comprising administering to a subject in need thereof a pharmaceutically effective amount the antibody of  claim 1 .