               SEQUENCE LISTING

<110> Affimed GmbH

<120> BISPECIFIC EGFR/CD16 ANTIGEN-BINDING PROTEIN

<130> A 3317PCT

<150> EP18161871.1
<151> 2018-03-14

<160> 45

<170> BiSSAP 1.3.6

<210> 1
<211> 120
<212> PRT
<213> artificial sequence


<220> 
<223> vh domain

<400> 1
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly 
            20                  25                  30          
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu 
        35                  40                  45              
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser 
    50                  55                  60                  
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      
Cys Ala Arg Asn Pro Ile Ser Ile Pro Ala Phe Asp Ile Trp Gly Gln 
            100                 105                 110         
Gly Thr Met Val Thr Val Ser Ser 
        115                 120 

<210> 2
<211> 108
<212> PRT
<213> artificial sequence


<220> 
<223> vl domain

<400> 2
Gln Pro Val Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Lys 
1               5                   10                  15      
Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val 
            20                  25                  30          
His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr 
        35                  40                  45              
Tyr Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly 
65                  70                  75                  80  
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Thr Ser Ser Asp His 
                85                  90                  95      
Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105             

<210> 3
<211> 8
<212> PRT
<213> homo sapiens


<400> 3
Ser Phe Phe Pro Pro Gly Tyr Gln 
1               5               

<210> 4
<211> 192
<212> PRT
<213> homo sapiens


<400> 4
Gly Met Arg Thr Glu Asp Leu Pro Lys Ala Val Val Phe Leu Glu Pro 
1               5                   10                  15      
Gln Trp Tyr Arg Val Leu Glu Lys Asp Ser Val Thr Leu Lys Cys Gln 
            20                  25                  30          
Gly Ala Tyr Ser Pro Glu Asp Asn Ser Thr Gln Trp Phe His Asn Glu 
        35                  40                  45              
Ser Leu Ile Ser Ser Gln Ala Ser Ser Tyr Phe Ile Asp Ala Ala Thr 
    50                  55                  60                  
Val Asp Asp Ser Gly Glu Tyr Arg Cys Gln Thr Asn Leu Ser Thr Leu 
65                  70                  75                  80  
Ser Asp Pro Val Gln Leu Glu Val His Ile Gly Trp Leu Leu Leu Gln 
                85                  90                  95      
Ala Pro Arg Trp Val Phe Lys Glu Glu Asp Pro Ile His Leu Arg Cys 
            100                 105                 110         
His Ser Trp Lys Asn Thr Ala Leu His Lys Val Thr Tyr Leu Gln Asn 
        115                 120                 125             
Gly Lys Gly Arg Lys Tyr Phe His His Asn Ser Asp Phe Tyr Ile Pro 
    130                 135                 140                 
Lys Ala Thr Leu Lys Asp Ser Gly Ser Tyr Phe Cys Arg Gly Leu Phe 
145                 150                 155                 160 
Gly Ser Lys Asn Val Ser Ser Glu Thr Val Asn Ile Thr Ile Thr Gln 
                165                 170                 175     
Gly Leu Ala Val Ser Thr Ile Ser Ser Phe Phe Pro Pro Gly Tyr Gln 
            180                 185                 190         



<210> 5
<211> 8
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 5
Gly Tyr Thr Phe Thr Ser Tyr Tyr 
1               5               

<210> 6
<211> 8
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 6
Ile Asn Pro Ser Gly Gly Ser Thr 
1               5               

<210> 7
<211> 13
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 7
Ala Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala Asp Tyr 
1               5                   10              

<210> 8
<211> 6
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 8
Asn Ile Gly Ser Lys Asn 
1               5       

<210> 9
<211> 5
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 9
Gln Asp Asn Lys Arg 
1               5   

<210> 10
<211> 9
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 10
Gln Val Trp Asp Asn Tyr Ser Val Leu 
1               5                   

<210> 11
<211> 8
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 11
Ile Glu Pro Met Tyr Gly Ser Thr 
1               5               

<210> 12
<211> 120
<212> PRT
<213> artificial sequence


<220> 
<223> vh

<400> 12
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      
Ser Leu Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
            20                  25                  30          
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              
Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 
    50                  55                  60                  
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala Asp Tyr Trp Gly Gln 
            100                 105                 110         
Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 

<210> 13
<211> 106
<212> PRT
<213> artificial sequence


<220> 
<223> vl

<400> 13
Ser Tyr Val Leu Thr Gln Pro Ser Ser Val Ser Val Ala Pro Gly Gln 
1               5                   10                  15      
Thr Ala Thr Ile Ser Cys Gly Gly His Asn Ile Gly Ser Lys Asn Val 
            20                  25                  30          
His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Val Leu Val Ile Tyr 
        35                  40                  45              
Gln Asp Asn Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met 
65                  70                  75                  80  
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Asn Tyr Ser Val Leu 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105     

<210> 14
<211> 120
<212> PRT
<213> artificial sequence


<220> 
<223> vh

<400> 14
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      
Ser Leu Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
            20                  25                  30          
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              
Gly Ala Ile Glu Pro Met Tyr Gly Ser Thr Ser Tyr Ala Gln Lys Phe 
    50                  55                  60                  
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala Asp Tyr Trp Gly Gln 
            100                 105                 110         
Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 

<210> 15
<211> 328
<212> PRT
<213> artificial sequence


<220> 
<223> silenced Fc

<400> 15
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
1               5                   10                  15      
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
            20                  25                  30          
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
    50                  55                  60                  
Leu Ser Ser Val Val Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 
65                  70                  75                  80  
Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys 
                85                  90                  95      
Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
            100                 105                 110         
Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
        115                 120                 125             
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
    130                 135                 140                 
Val Val Ala Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
145                 150                 155                 160 
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
                165                 170                 175     
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
            180                 185                 190         
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
        195                 200                 205             
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
    210                 215                 220                 
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
225                 230                 235                 240 
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
                245                 250                 255     
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
            260                 265                 270         
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
        275                 280                 285             
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
    290                 295                 300                 
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
305                 310                 315                 320 
Lys Ser Leu Ser Leu Ser Pro Gly 
                325             

<210> 16
<211> 106
<212> PRT
<213> homo sapiens


<400> 16
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 
1               5                   10                  15      
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp 
            20                  25                  30          
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro 
        35                  40                  45              
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn 
    50                  55                  60                  
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys 
65                  70                  75                  80  
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val 
                85                  90                  95      
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser 
            100                 105     

<210> 17
<211> 10
<212> PRT
<213> artificial sequence


<220> 
<223> linker

<400> 17
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10  

<210> 18
<211> 18
<212> PRT
<213> artificial sequence


<220> 
<223> linker

<400> 18
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
1               5                   10                  15      
Gly Ser 
        

<210> 19
<211> 15
<212> PRT
<213> homo sapiens


<400> 19
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
1               5                   10                  15  

<210> 20
<211> 216
<212> PRT
<213> artificial sequence


<220> 
<223> silenced Fc

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

<210> 21
<211> 10
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 21
Gly Gly Ser Val Ser Ser Gly Ser Tyr Tyr 
1               5                   10  

<210> 22
<211> 7
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 22
Ile Tyr Tyr Ser Gly Ser Thr 
1               5           

<210> 23
<211> 12
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 23
Ala Arg Asn Pro Ile Ser Ile Pro Ala Phe Asp Ile 
1               5                   10          

<210> 24
<211> 6
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 24
Asn Ile Gly Ser Lys Ser 
1               5       

<210> 25
<211> 4
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 25
Tyr Asp Ser Asp 
1               

<210> 26
<211> 11
<212> PRT
<213> artificial sequence


<220> 
<223> cdr

<400> 26
Gln Val Trp Asp Thr Ser Ser Asp His Val Leu 
1               5                   10      

<210> 27
<211> 489
<212> PRT
<213> artificial sequence


<220> 
<223> tandem diabody

<400> 27
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly 
            20                  25                  30          
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu 
        35                  40                  45              
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser 
    50                  55                  60                  
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      
Cys Ala Arg Asn Pro Ile Ser Ile Pro Ala Phe Asp Ile Trp Gly Gln 
            100                 105                 110         
Gly Thr Met Val Thr Val Ser Ser Gly Gly Ser Gly Gly Ser Gly Gly 
        115                 120                 125             
Ser Ser Tyr Val Leu Thr Gln Pro Ser Ser Val Ser Val Ala Pro Gly 
    130                 135                 140                 
Gln Thr Ala Thr Ile Ser Cys Gly Gly His Asn Ile Gly Ser Lys Asn 
145                 150                 155                 160 
Val His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Val Leu Val Ile 
                165                 170                 175     
Tyr Gln Asp Asn Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly 
            180                 185                 190         
Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala 
        195                 200                 205             
Met Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Asn Tyr Ser Val 
    210                 215                 220                 
Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly 
                245                 250                 255     
Glu Ser Leu Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser 
            260                 265                 270         
Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp 
        275                 280                 285             
Met Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys 
    290                 295                 300                 
Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 
305                 310                 315                 320 
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr 
                325                 330                 335     
Cys Ala Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala Asp Tyr Trp Gly 
            340                 345                 350         
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Ser Gly Gly Ser Gly 
        355                 360                 365             
Gly Ser Gln Pro Val Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro 
    370                 375                 380                 
Gly Lys Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys 
385                 390                 395                 400 
Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val 
                405                 410                 415     
Ile Tyr Tyr Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser 
            420                 425                 430         
Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu 
        435                 440                 445             
Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Thr Ser Ser 
    450                 455                 460                 
Asp His Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ala Ala 
465                 470                 475                 480 
Ala Gly Ser His His His His His His 
                485                 

<210> 28
<211> 705
<212> PRT
<213> artificial sequence


<220> 
<223> heavy chain

<400> 28
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      
Ser Leu Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
            20                  25                  30          
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              
Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe 
    50                  55                  60                  
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala 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 Lys Ser Cys Asp 
    210                 215                 220                 
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly 
225                 230                 235                 240 
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Ala Val Ser His Glu 
            260                 265                 270         
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             
Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln 
    450                 455                 460                 
Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr 
465                 470                 475                 480 
Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly Ser Tyr Tyr Trp Ser 
                485                 490                 495     
Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile 
            500                 505                 510         
Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys Ser Arg Val 
        515                 520                 525             
Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser 
    530                 535                 540                 
Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asn Pro 
545                 550                 555                 560 
Ile Ser Ile Pro Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr 
                565                 570                 575     
Val Ser Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
            580                 585                 590         
Gly Ser Gly Gly Ser Gln Pro Val Leu Thr Gln Pro Pro Ser Val Ser 
        595                 600                 605             
Val Ala Pro Gly Lys Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile 
    610                 615                 620                 
Gly Ser Lys Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
625                 630                 635                 640 
Val Leu Val Ile Tyr Tyr Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu 
                645                 650                 655     
Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser 
            660                 665                 670         
Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp 
        675                 680                 685             
Thr Ser Ser Asp His Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val 
    690                 695                 700                 
Leu 
705 

<210> 29
<211> 212
<212> PRT
<213> artificial sequence


<220> 
<223> light chain

<400> 29
Ser Tyr Val Leu Thr Gln Pro Ser Ser Val Ser Val Ala Pro Gly Gln 
1               5                   10                  15      
Thr Ala Thr Ile Ser Cys Gly Gly His Asn Ile Gly Ser Lys Asn Val 
            20                  25                  30          
His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Val Leu Val Ile Tyr 
        35                  40                  45              
Gln Asp Asn Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met 
65                  70                  75                  80  
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Asn Tyr Ser Val Leu 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala 
            100                 105                 110         
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn 
        115                 120                 125             
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val 
    130                 135                 140                 
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu 
145                 150                 155                 160 
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser 
                165                 170                 175     
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr Ser 
            180                 185                 190         
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro 
        195                 200                 205             
Thr Glu Cys Ser 
    210         

<210> 30
<211> 734
<212> PRT
<213> artificial sequence


<220> 
<223> Bi-scFv-Fc

<400> 30
Ser Tyr Val Leu Thr Gln Pro Ser Ser Val Ser Val Ala Pro Gly Gln 
1               5                   10                  15      
Thr Ala Thr Ile Ser Cys Gly Gly His Asn Ile Gly Ser Lys Asn Val 
            20                  25                  30          
His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Val Leu Val Ile Tyr 
        35                  40                  45              
Gln Asp Asn Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met 
65                  70                  75                  80  
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Asn Tyr Ser Val Leu 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Gly Gly Ser 
            100                 105                 110         
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gln 
        115                 120                 125             
Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser 
    130                 135                 140                 
Leu Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Tyr 
145                 150                 155                 160 
Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly 
                165                 170                 175     
Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln 
            180                 185                 190         
Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met 
        195                 200                 205             
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
    210                 215                 220                 
Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala Asp Tyr Trp Gly Gln Gly 
225                 230                 235                 240 
Thr Leu Val Thr Val Ser Ser Glu Pro Lys Ser Cys Asp Lys Thr His 
                245                 250                 255     
Thr Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 
            260                 265                 270         
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
        275                 280                 285             
Pro Glu Val Thr Cys Val Val Val Ala Val Ser His Glu Asp Pro Glu 
    290                 295                 300                 
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
305                 310                 315                 320 
Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                325                 330                 335     
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
            340                 345                 350         
Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
        355                 360                 365             
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
    370                 375                 380                 
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
385                 390                 395                 400 
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                405                 410                 415     
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
            420                 425                 430         
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
        435                 440                 445             
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
    450                 455                 460                 
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly 
465                 470                 475                 480 
Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly 
                485                 490                 495     
Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val 
            500                 505                 510         
Ser Gly Gly Ser Val Ser Ser Gly Ser Tyr Tyr Trp Ser Trp Ile Arg 
        515                 520                 525             
Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser 
    530                 535                 540                 
Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser 
545                 550                 555                 560 
Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr 
                565                 570                 575     
Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asn Pro Ile Ser Ile 
            580                 585                 590         
Pro Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 
        595                 600                 605             
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
    610                 615                 620                 
Gly Ser Gln Pro Val Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro 
625                 630                 635                 640 
Gly Lys Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys 
                645                 650                 655     
Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val 
            660                 665                 670         
Ile Tyr Tyr Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser 
        675                 680                 685             
Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu 
    690                 695                 700                 
Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Thr Ser Ser 
705                 710                 715                 720 
Asp His Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                725                 730                 

<210> 31
<211> 121
<212> PRT
<213> artificial sequence


<220> 
<223> vh

<400> 31
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Ile Asp Leu Ser Asn Tyr 
            20                  25                  30          
Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile 
        35                  40                  45              
Gly Ile Ile Trp Ala Ser Gly Thr Thr Phe Tyr Ala Thr Trp Ala Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Val Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Thr Val Pro Gly Tyr Ser Thr Ala Pro Tyr Phe Asp Leu Trp Gly 
            100                 105                 110         
Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     

<210> 32
<211> 110
<212> PRT
<213> artificial sequence


<220> 
<223> vl

<400> 32
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Gln Ser Ser Pro Ser Val Trp Ser Asn 
            20                  25                  30          
Phe Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 
        35                  40                  45              
Ile Tyr Glu Ala Ser Lys Leu Thr Ser Gly Val Pro Ser Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gly Gly Gly Tyr Ser Ser Ile 
                85                  90                  95      
Ser Asp Thr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110 

<210> 33
<211> 20
<212> DNA
<213> artificial sequence


<220> 
<223> primer

<400> 33
taatacgact cactataggg                                                20


<210> 34
<211> 18
<212> DNA
<213> artificial sequence


<220> 
<223> primer

<400> 34
tagaaggcac agtcgagg                                                  18


<210> 35
<211> 6
<212> PRT
<213> artificial sequence


<220> 
<223> linker

<400> 35
Gly Gly Ser Gly Gly Ser 
1               5       

<210> 36
<211> 9
<212> PRT
<213> artificial sequence


<220> 
<223> linker

<400> 36
Gly Gly Ser Gly Gly Ser Gly Gly Ser 
1               5                   

<210> 37
<211> 21
<212> PRT
<213> Artificial Sequence


<220> 
<223> linker

<400> 37
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
1               5                   10                  15      
Gly Ser Gly Gly Ser 
            20      

<210> 38
<211> 8
<212> PRT
<213> Artificial Sequence


<220> 
<223> HCDR1

<400> 38
Gly Tyr Thr Phe Thr Ser Tyr Tyr 
1               5               

<210> 39
<211> 13
<212> PRT
<213> Artificial Sequence


<220> 
<223> HCDR3

<400> 39
Ala Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala Asp Tyr 
1               5                   10              

<210> 40
<211> 6
<212> PRT
<213> Artificial Sequence


<220> 
<223> LCDR1

<400> 40
Asn Ile Gly Ser Lys Asn 
1               5       

<210> 41
<400> 41
000

<210> 42
<211> 9
<212> PRT
<213> Artificial Sequence


<220> 
<223> LCDR3

<400> 42
Gln Val Trp Asp Asn Tyr Ser Val Leu 
1               5                   

<210> 43
<211> 705
<212> PRT
<213> Artificial Sequence


<220> 
<223> heavy chain

<400> 43
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      
Ser Leu Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 
            20                  25                  30          
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              
Gly Ala Ile Glu Pro Met Tyr Gly Ser Thr Ser Tyr Ala Gln Lys Phe 
    50                  55                  60                  
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala 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 Lys Ser Cys Asp 
    210                 215                 220                 
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly 
225                 230                 235                 240 
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Ala Val Ser His Glu 
            260                 265                 270         
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             
Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln 
    450                 455                 460                 
Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr 
465                 470                 475                 480 
Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly Ser Tyr Tyr Trp Ser 
                485                 490                 495     
Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile 
            500                 505                 510         
Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys Ser Arg Val 
        515                 520                 525             
Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser 
    530                 535                 540                 
Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asn Pro 
545                 550                 555                 560 
Ile Ser Ile Pro Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr 
                565                 570                 575     
Val Ser Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
            580                 585                 590         
Gly Ser Gly Gly Ser Gln Pro Val Leu Thr Gln Pro Pro Ser Val Ser 
        595                 600                 605             
Val Ala Pro Gly Lys Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile 
    610                 615                 620                 
Gly Ser Lys Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
625                 630                 635                 640 
Val Leu Val Ile Tyr Tyr Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu 
                645                 650                 655     
Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser 
            660                 665                 670         
Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp 
        675                 680                 685             
Thr Ser Ser Asp His Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val 
    690                 695                 700                 
Leu 
705 

<210> 44
<211> 212
<212> PRT
<213> Artificial Sequence


<220> 
<223> light chain

<400> 44
Ser Tyr Val Leu Thr Gln Pro Ser Ser Val Ser Val Ala Pro Gly Gln 
1               5                   10                  15      
Thr Ala Thr Ile Ser Cys Gly Gly His Asn Ile Gly Ser Lys Asn Val 
            20                  25                  30          
His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Val Leu Val Ile Tyr 
        35                  40                  45              
Gln Asp Asn Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met 
65                  70                  75                  80  
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Asn Tyr Ser Val Leu 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala 
            100                 105                 110         
Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn 
        115                 120                 125             
Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val 
    130                 135                 140                 
Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val Glu 
145                 150                 155                 160 
Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser 
                165                 170                 175     
Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr Ser 
            180                 185                 190         
Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala Pro 
        195                 200                 205             
Thr Glu Cys Ser 
    210         

<210> 45
<211> 734
<212> PRT
<213> Artificial Sequence


<220> 
<223> heavy chain

<400> 45
Ser Tyr Val Leu Thr Gln Pro Ser Ser Val Ser Val Ala Pro Gly Gln 
1               5                   10                  15      
Thr Ala Thr Ile Ser Cys Gly Gly His Asn Ile Gly Ser Lys Asn Val 
            20                  25                  30          
His Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Val Leu Val Ile Tyr 
        35                  40                  45              
Gln Asp Asn Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met 
65                  70                  75                  80  
Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Asn Tyr Ser Val Leu 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Ser Gly Gly Ser 
            100                 105                 110         
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gln 
        115                 120                 125             
Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser 
    130                 135                 140                 
Leu Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Tyr 
145                 150                 155                 160 
Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly 
                165                 170                 175     
Ala Ile Glu Pro Met Tyr Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln 
            180                 185                 190         
Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met 
        195                 200                 205             
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
    210                 215                 220                 
Arg Gly Ser Ala Tyr Tyr Tyr Asp Phe Ala Asp Tyr Trp Gly Gln Gly 
225                 230                 235                 240 
Thr Leu Val Thr Val Ser Ser Glu Pro Lys Ser Cys Asp Lys Thr His 
                245                 250                 255     
Thr Cys Pro Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val 
            260                 265                 270         
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
        275                 280                 285             
Pro Glu Val Thr Cys Val Val Val Ala Val Ser His Glu Asp Pro Glu 
    290                 295                 300                 
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
305                 310                 315                 320 
Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                325                 330                 335     
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
            340                 345                 350         
Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
        355                 360                 365             
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
    370                 375                 380                 
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
385                 390                 395                 400 
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                405                 410                 415     
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
            420                 425                 430         
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
        435                 440                 445             
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
    450                 455                 460                 
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly 
465                 470                 475                 480 
Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly 
                485                 490                 495     
Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val 
            500                 505                 510         
Ser Gly Gly Ser Val Ser Ser Gly Ser Tyr Tyr Trp Ser Trp Ile Arg 
        515                 520                 525             
Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser 
    530                 535                 540                 
Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser 
545                 550                 555                 560 
Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr 
                565                 570                 575     
Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asn Pro Ile Ser Ile 
            580                 585                 590         
Pro Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 
        595                 600                 605             
Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
    610                 615                 620                 
Gly Ser Gln Pro Val Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro 
625                 630                 635                 640 
Gly Lys Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys 
                645                 650                 655     
Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val 
            660                 665                 670         
Ile Tyr Tyr Asp Ser Asp Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser 
        675                 680                 685             
Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Val Glu 
    690                 695                 700                 
Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Thr Ser Ser 
705                 710                 715                 720 
Asp His Val Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
                725                 730                 

