               SEQUENCE LISTING

<110> Merck Patent GmbH

<120> COMBINATION THERAPY UTILIZING DNA ALKYLATING AGENTS AND ATR INHIBITORS

<130> P18-215

<140> EPPCT/EP2019/077784
<141> 2019-10-14

<150> EP18200527.2
<151> 2018-10-15

<160> 29

<170> BiSSAP 1.3.6

<210> 1
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 1
gcaacaguau uucgguaua                                                 19


<210> 2
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 2
ggacuucucu ccaguaaac                                                 19


<210> 3
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 3
aaagauagau gguacaaca                                                 19


<210> 4
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 4
agauaugaag cgugccgua                                                 19


<210> 5
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 5
gagaaaggau uguagacua                                                 19


<210> 6
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 6
gcaacucgcc uaacagaua                                                 19


<210> 7
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 7
ccacgaaugu uaacucuau                                                 19


<210> 8
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 8
ccgcuaaucu ucuaacauu                                                 19


<210> 9
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 9
gcacauaccg ccugagucu                                                 19


<210> 10
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 10
ccaccaaggu uuucgauug                                                 19


<210> 11
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 11
gcucuucaau gacucaaca                                                 19


<210> 12
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 12
ucucaaggcc uccuaauag                                                 19


<210> 13
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 13
uagcgacuaa acacaucaa                                                 19


<210> 14
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 14
uagcgacuaa acacaucaa                                                 19


<210> 15
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 15
uagcgacuaa acacaucaa                                                 19


<210> 16
<211> 19
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA

<400> 16
augaacguga auugcucaa                                                 19


<210> 17
<211> 451
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAB

<400> 17
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr 
            20                  25                  30          
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Pro Lys Ser Cys 
    210                 215                 220                 
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
225                 230                 235                 240 
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                245                 250                 255     
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
            260                 265                 270         
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
        275                 280                 285             
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
    290                 295                 300                 
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
305                 310                 315                 320 
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                325                 330                 335     
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
            340                 345                 350         
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
        355                 360                 365             
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
    370                 375                 380                 
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
385                 390                 395                 400 
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                405                 410                 415     
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
            420                 425                 430         
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
        435                 440                 445             
Pro Gly Lys 
    450     

<210> 18
<211> 254
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 18
Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala 
1               5                   10                  15      
Ser Leu Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 
            20                  25                  30          
Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val 
        35                  40                  45              
Asn Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys 
    50                  55                  60                  
Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg 
65                  70                  75                  80  
Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser 
                85                  90                  95      
Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr 
            100                 105                 110         
Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr 
        115                 120                 125             
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 
    130                 135                 140                 
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 
145                 150                 155                 160 
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 
                165                 170                 175     
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 
            180                 185                 190         
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 
        195                 200                 205             
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 
    210                 215                 220                 
Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser Gly Gly Gly Gly Ser Leu Pro Glu Thr Gly Ser 
                245                 250                 

<210> 19
<211> 449
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 19
Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln 
1               5                   10                  15      
Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr 
            20                  25                  30          
Gly Val His Trp Val Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu 
        35                  40                  45              
Gly Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Pro Phe Thr 
    50                  55                  60                  
Ser Arg Leu Ser Ile Asn Lys Asp Asn Ser Lys Ser Gln Val Phe Phe 
65                  70                  75                  80  
Lys Met Asn Ser Leu Gln Ser Asn Asp Thr Ala Ile Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Leu Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
145                 150                 155                 160 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             
Lys 
    

<210> 20
<211> 455
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 20
Gln Val Gln Leu Lys Gln Ser Gly Pro Gly Leu Val Gln Pro Ser Gln 
1               5                   10                  15      
Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Asn Tyr 
            20                  25                  30          
Gly Val His Trp Val Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu 
        35                  40                  45              
Gly Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Pro Phe Thr 
    50                  55                  60                  
Ser Arg Leu Ser Ile Asn Lys Asp Asn Ser Lys Ser Gln Val Phe Phe 
65                  70                  75                  80  
Lys Met Asn Ser Leu Gln Ser Asn Asp Thr Ala Ile Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Leu Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
145                 150                 155                 160 
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys 
    210                 215                 220                 
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             
Lys Leu Pro Glu Thr Gly Ser 
    450                 455 

<210> 21
<211> 235
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 21
Asp Ile Leu Leu Thr Gln Ser Pro Val Ile Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn 
            20                  25                  30          
Ile His Trp Tyr Gln Gln Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile 
        35                  40                  45              
Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Ser 
65                  70                  75                  80  
Glu Asp Ile Ala Asp Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr 
                85                  90                  95      
Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 
Gly Gly Gly Gly Ser Leu Pro Glu Thr Gly Ser 
225                 230                 235 

<210> 22
<211> 220
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAB

<400> 22
Asp Ile Leu Leu Thr Gln Ser Pro Val Ile Leu Ser Val Ser Pro Gly 
1               5                   10                  15      
Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn 
            20                  25                  30          
Ile His Trp Tyr Gln Gln Arg Thr Asn Gly Ser Pro Arg Leu Leu Ile 
        35                  40                  45              
Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn Ser Val Glu Ser 
65                  70                  75                  80  
Glu Asp Ile Ala Asp Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr 
                85                  90                  95      
Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys Leu Pro Glu Thr Gly Ser 
    210                 215                 220 

<210> 23
<211> 235
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 23
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gly Asn Ile His Asn Tyr 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Tyr Thr Thr Thr Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln His Phe Trp Ser Thr Pro Arg 
                85                  90                  95      
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    210                 215                 220                 
Gly Gly Gly Gly Ser Leu Pro Glu Thr Gly Ser 
225                 230                 235 

<210> 24
<211> 446
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 24
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Gly Tyr 
            20                  25                  30          
Gly Val Asn Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile 
        35                  40                  45              
Gly Met Ile Trp Gly Asp Gly Asn Thr Asp Tyr Asn Ser Ala Leu Lys 
    50                  55                  60                  
Ser Arg Val Thr Met Leu Lys Asp Thr Ser Lys Asn Gln Phe Ser Leu 
65                  70                  75                  80  
Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Glu Arg Asp Tyr Arg Leu Asp Tyr Trp Gly Gln Gly Ser Leu Val 
            100                 105                 110         
Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
        115                 120                 125             
Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 
Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
                165                 170                 175     
Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
            180                 185                 190         
Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
        195                 200                 205             
Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
    210                 215                 220                 
Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
225                 230                 235                 240 
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
                245                 250                 255     
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
            260                 265                 270         
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
        275                 280                 285             
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
    290                 295                 300                 
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
305                 310                 315                 320 
Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
                325                 330                 335     
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
            340                 345                 350         
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
        355                 360                 365             
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
    370                 375                 380                 
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
385                 390                 395                 400 
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
                405                 410                 415     
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
            420                 425                 430         
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445     

<210> 25
<211> 246
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 25
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn 
            20                  25                  30          
Ile His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Lys Tyr Ala Ser Glu Ser Ile Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Tyr Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Asn Tyr Asn Trp Pro Thr 
                85                  90                  95      
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser 
            100                 105                 110         
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 
        115                 120                 125             
Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser 
    130                 135                 140                 
Val Lys Val Ser Cys Lys Ala Ser Gly Phe Ser Leu Thr Asn Tyr Gly 
145                 150                 155                 160 
Val His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly 
                165                 170                 175     
Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Pro Phe Thr Ser 
            180                 185                 190         
Arg Val Thr Ile Thr Ser Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu 
        195                 200                 205             
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 
Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 
Leu Val Thr Val Ser Ser 
                245     

<210> 26
<211> 470
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 26
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      
Gly Ser Thr Gly Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val 
            20                  25                  30          
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 
        35                  40                  45              
Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly 
    50                  55                  60                  
Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr 
65                  70                  75                  80  
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
                85                  90                  95      
Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
            100                 105                 110         
Val Tyr Tyr Cys Ala Lys Asp Arg Arg Ile Thr His Thr Tyr Trp Gly 
        115                 120                 125             
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
    130                 135                 140                 
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
145                 150                 155                 160 
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
                165                 170                 175     
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
            180                 185                 190         
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
        195                 200                 205             
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
    210                 215                 220                 
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys 
225                 230                 235                 240 
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
                245                 250                 255     
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            260                 265                 270         
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        275                 280                 285             
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    290                 295                 300                 
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
305                 310                 315                 320 
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                325                 330                 335     
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            340                 345                 350         
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Phe Arg Pro Glu Val 
        355                 360                 365             
His Leu Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    370                 375                 380                 
Leu Thr Cys Leu Ala Arg Gly Phe Tyr Pro Lys Asp Ile Ala Val Glu 
385                 390                 395                 400 
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Ser 
                405                 410                 415     
Arg Gln Glu Pro Ser Gln Gly Thr Thr Thr Phe Ala Val Thr Ser Lys 
            420                 425                 430         
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
        435                 440                 445             
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Thr Ile 
    450                 455                 460                 
Ser Leu Ser Pro Gly Lys 
465                 470 

<210> 27
<211> 240
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 27
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      
Gly Ser Thr Gly Glu Pro Val Leu Thr Gln Pro Pro Ser Val Ser Val 
            20                  25                  30          
Ala Pro Gly Glu Thr Ala Thr Ile Pro Cys Gly Gly Asp Ser Leu Gly 
        35                  40                  45              
Ser Lys Ile Val His Trp Tyr Gln Gln Arg Pro Gly Gln Ala Pro Leu 
    50                  55                  60                  
Leu Val Val Tyr Asp Asp Ala Ala Arg Pro Ser Gly Ile Pro Glu Arg 
65                  70                  75                  80  
Phe Ser Gly Ser Lys Ser Gly Thr Thr Ala Thr Leu Thr Ile Ser Ser 
                85                  90                  95      
Val Glu Ala Gly Asp Glu Ala Asp Tyr Phe Cys Gln Val Tyr Asp Tyr 
            100                 105                 110         
His Ser Asp Val Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
        115                 120                 125             
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 
    130                 135                 140                 
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 
145                 150                 155                 160 
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 
                165                 170                 175     
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn 
            180                 185                 190         
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys 
        195                 200                 205             
Ser His Lys Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val 
    210                 215                 220                 
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser Leu Pro Glu Thr Gly Ser 
225                 230                 235                 240 



<210> 28
<211> 240
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 28
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      
Gly Ser Thr Gly Glu Pro Val Leu Thr Gln Pro Pro Ser Val Ser Val 
            20                  25                  30          
Ala Pro Gly Glu Thr Ala Thr Ile Pro Cys Gly Gly Asp Ser Leu Gly 
        35                  40                  45              
Ser Lys Ile Val His Trp Tyr Gln Gln Arg Pro Gly Gln Ala Pro Leu 
    50                  55                  60                  
Leu Val Val Tyr Asp Asp Ala Ala Arg Pro Ser Gly Ile Pro Glu Arg 
65                  70                  75                  80  
Phe Ser Gly Ser Lys Ser Gly Thr Thr Ala Thr Leu Thr Ile Ser Ser 
                85                  90                  95      
Val Glu Ala Gly Asp Glu Ala Asp Tyr Phe Cys Gln Val Tyr Asp Tyr 
            100                 105                 110         
His Ser Asp Val Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
        115                 120                 125             
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 
    130                 135                 140                 
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 
145                 150                 155                 160 
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 
                165                 170                 175     
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn 
            180                 185                 190         
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys 
        195                 200                 205             
Ser His Lys Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val 
    210                 215                 220                 
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser Leu Pro Glu Thr Gly Ser 
225                 230                 235                 240 



<210> 29
<211> 447
<212> PRT
<213> Artificial Sequence


<220> 
<223> mAb

<400> 29
Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Asp Arg Arg Ile Thr His Thr Tyr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         
Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
        115                 120                 125             
Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
    130                 135                 140                 
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
145                 150                 155                 160 
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                165                 170                 175     
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
            180                 185                 190         
Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
        195                 200                 205             
Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His 
    210                 215                 220                 
Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
225                 230                 235                 240 
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                245                 250                 255     
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
            260                 265                 270         
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        275                 280                 285             
Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
305                 310                 315                 320 
Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                325                 330                 335     
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            340                 345                 350         
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        355                 360                 365             
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    370                 375                 380                 
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
385                 390                 395                 400 
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                405                 410                 415     
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445         

