               SEQUENCE LISTING

<110> Ablynx NV

<120> METHOD FOR THE PRODUCTION AND PURIFICATION OF MULTIVALENT IMMUNGLOBULIN SINGLE VARIABLE DOMAINS

<130> 219277

<160> 71

<170> BiSSAP 1.3.6

<210> 1
<211> 630
<212> PRT
<213> Artificial Sequence


<220> 
<223> Compound A

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

<210> 2
<211> 517
<212> PRT
<213> Artificial Sequence


<220> 
<223> Compound B

<400> 2
Asp Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Ser Thr Ala 
            20                  25                  30          
Asp Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Phe Val 
        35                  40                  45              
Ala Arg Ile Ser Gly Ile Asp Gly Thr Thr Tyr Tyr Asp Glu Pro Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Val Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys 
                85                  90                  95      
Arg Ser Pro Arg Tyr Ala Asp Gln Trp Ser Ala Tyr Asp Tyr Trp Gly 
            100                 105                 110         
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly 
        115                 120                 125             
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro 
    130                 135                 140                 
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Ile Phe Ser 
145                 150                 155                 160 
Leu Pro Ala Ser Gly Asn Ile Phe Asn Leu Leu Thr Ile Ala Trp Tyr 
                165                 170                 175     
Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val Ala Thr Ile Glu Ser 
            180                 185                 190         
Gly Ser Arg Thr Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile 
        195                 200                 205             
Ser Arg Asp Asn Ser Lys Lys Thr Val Tyr Leu Gln Met Asn Ser Leu 
    210                 215                 220                 
Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Gln Thr Ser Gly Ser Gly 
225                 230                 235                 240 
Ser Pro Asn Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly 
                245                 250                 255     
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly 
            260                 265                 270         
Gly Gly Val Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
        275                 280                 285             
Ser Gly Phe Thr Phe Arg Ser Phe Gly Met Ser Trp Val Arg Gln Ala 
    290                 295                 300                 
Pro Gly Lys Gly Pro Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Ser 
305                 310                 315                 320 
Asp Thr Leu Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
                325                 330                 335     
Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro 
            340                 345                 350         
Glu Asp Thr Ala Leu Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Arg 
        355                 360                 365             
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
    370                 375                 380                 
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val 
385                 390                 395                 400 
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr 
                405                 410                 415     
Leu Ser Ser Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu 
            420                 425                 430         
Arg Glu Phe Val Ala Arg Ile Ser Gln Gly Gly Thr Ala Ile Tyr Tyr 
        435                 440                 445             
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
    450                 455                 460                 
Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 
465                 470                 475                 480 
Leu Tyr Tyr Cys Ala Lys Asp Pro Ser Pro Tyr Tyr Arg Gly Ser Ala 
                485                 490                 495     
Tyr Leu Leu Ser Gly Ser Tyr Asp Ser Trp Gly Gln Gly Thr Leu Val 
            500                 505                 510         
Lys Val Ser Ser Ala 
        515         

<210> 3
<211> 3
<212> PRT
<213> Artificial Sequence


<220> 
<223> 3A linker

<400> 3
Ala Ala Ala 
1           

<210> 4
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> 5GS linker

<400> 4
Gly Gly Gly Gly Ser 
1               5   

<210> 5
<211> 7
<212> PRT
<213> Artificial Sequence


<220> 
<223> 7GS linker

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

<210> 6
<211> 8
<212> PRT
<213> Artificial Sequence


<220> 
<223> 8GS linker

<400> 6
Gly Gly Gly Gly Ser Gly Gly Ser 
1               5               

<210> 7
<211> 9
<212> PRT
<213> Artificial Sequence


<220> 
<223> 9GS linker

<400> 7
Gly Gly Gly Gly Ser Gly Gly Gly Ser 
1               5                   

<210> 8
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> 10GS linker

<400> 8
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10  

<210> 9
<211> 15
<212> PRT
<213> Artificial Sequence


<220> 
<223> 15GS linker

<400> 9
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  

<210> 10
<211> 18
<212> PRT
<213> Artificial Sequence


<220> 
<223> 18GS linker

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

<210> 11
<211> 20
<212> PRT
<213> Artificial Sequence


<220> 
<223> 20GS linker

<400> 11
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      
Gly Gly Gly Ser 
            20  

<210> 12
<211> 25
<212> PRT
<213> Artificial Sequence


<220> 
<223> 25GS linker

<400> 12
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      
Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            20                  25  

<210> 13
<211> 30
<212> PRT
<213> Artificial Sequence


<220> 
<223> 30GS linker

<400> 13
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            20                  25                  30  

<210> 14
<211> 35
<212> PRT
<213> Artificial Sequence


<220> 
<223> 35GS linker

<400> 14
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
            20                  25                  30          
Gly Gly Ser 
        35  

<210> 15
<211> 40
<212> PRT
<213> Artificial Sequence


<220> 
<223> 40GS linker

<400> 15
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
            20                  25                  30          
Gly Gly Ser Gly Gly Gly Gly Ser 
        35                  40  

<210> 16
<211> 15
<212> PRT
<213> Artificial Sequence


<220> 
<223> G1 hinge

<400> 16
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
1               5                   10                  15  

<210> 17
<211> 24
<212> PRT
<213> Artificial Sequence


<220> 
<223> 9GS-G1 hinge

<400> 17
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Pro Lys Ser Cys Asp Lys 
1               5                   10                  15      
Thr His Thr Cys Pro Pro Cys Pro 
            20                  

<210> 18
<211> 12
<212> PRT
<213> Artificial Sequence


<220> 
<223> Llama upper long hinge region

<400> 18
Glu Pro Lys Thr Pro Lys Pro Gln Pro Ala Ala Ala 
1               5                   10          

<210> 19
<211> 62
<212> PRT
<213> Artificial Sequence


<220> 
<223> G3 hinge

<400> 19
Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys 
1               5                   10                  15      
Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro 
            20                  25                  30          
Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu 
        35                  40                  45              
Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro 
    50                  55                  60          

<210> 20
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 20
Lys Glu Arg Glu 
1               

<210> 21
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 21
Lys Gln Arg Glu 
1               

<210> 22
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 22
Gly Leu Glu Trp 
1               

<210> 23
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 23
Lys Glu Arg Glu Leu 
1               5   

<210> 24
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 24
Lys Glu Arg Glu Phe 
1               5   

<210> 25
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 25
Lys Gln Arg Glu Leu 
1               5   

<210> 26
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 26
Lys Gln Arg Glu Phe 
1               5   

<210> 27
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 27
Lys Glu Arg Glu Gly 
1               5   

<210> 28
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 28
Lys Gln Arg Glu Trp 
1               5   

<210> 29
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 29
Lys Gln Arg Glu Gly 
1               5   

<210> 30
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 30
Thr Glu Arg Glu 
1               

<210> 31
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 31
Thr Glu Arg Glu Leu 
1               5   

<210> 32
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 32
Thr Gln Arg Glu 
1               

<210> 33
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 33
Thr Gln Arg Glu Leu 
1               5   

<210> 34
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 34
Lys Glu Cys Glu 
1               

<210> 35
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 35
Lys Glu Cys Glu Leu 
1               5   

<210> 36
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 36
Lys Glu Cys Glu Arg 
1               5   

<210> 37
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 37
Lys Gln Cys Glu 
1               

<210> 38
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 38
Lys Gln Cys Glu Leu 
1               5   

<210> 39
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 39
Arg Glu Arg Glu 
1               

<210> 40
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 40
Arg Glu Arg Glu Gly 
1               5   

<210> 41
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 41
Arg Gln Arg Glu 
1               

<210> 42
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 42
Arg Gln Arg Glu Leu 
1               5   

<210> 43
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 43
Arg Gln Arg Glu Phe 
1               5   

<210> 44
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 44
Arg Gln Arg Glu Trp 
1               5   

<210> 45
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 45
Gln Glu Arg Glu 
1               

<210> 46
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 46
Gln Glu Arg Glu Gly 
1               5   

<210> 47
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 47
Gln Gln Arg Glu 
1               

<210> 48
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 48
Gln Gln Arg Glu Trp 
1               5   

<210> 49
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 49
Gln Gln Arg Glu Leu 
1               5   

<210> 50
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 50
Gln Gln Arg Glu Phe 
1               5   

<210> 51
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 51
Lys Gly Arg Glu 
1               

<210> 52
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 52
Lys Gly Arg Glu Gly 
1               5   

<210> 53
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 53
Lys Asp Arg Glu 
1               

<210> 54
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 54
Lys Asp Arg Glu Val 
1               5   

<210> 55
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 55
Asp Glu Cys Lys Leu 
1               5   

<210> 56
<211> 5
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 56
Asn Val Cys Glu Leu 
1               5   

<210> 57
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 57
Gly Val Glu Trp 
1               

<210> 58
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 58
Glu Pro Glu Trp 
1               

<210> 59
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 59
Gly Leu Glu Arg 
1               

<210> 60
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 60
Asp Gln Glu Trp 
1               

<210> 61
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 61
Asp Leu Glu Trp 
1               

<210> 62
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 62
Gly Ile Glu Trp 
1               

<210> 63
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 63
Glu Leu Glu Trp 
1               

<210> 64
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 64
Gly Pro Glu Trp 
1               

<210> 65
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 65
Glu Trp Leu Pro 
1               

<210> 66
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 66
Gly Pro Glu Arg 
1               

<210> 67
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 67
Gly Leu Glu Arg 
1               

<210> 68
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Motif

<400> 68
Glu Leu Glu Trp 
1               

<210> 69
<211> 363
<212> PRT
<213> Artificial Sequence


<220> 
<223> Compound C

<400> 69
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 Thr Phe Ser Asp Tyr 
            20                  25                  30          
Trp Met Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Glu Ile Asn Thr Asn Gly Leu Ile Thr Lys Tyr Pro Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Ser Pro Ser Gly Phe Asn Arg Gly Gln Gly Thr Leu Val Thr 
            100                 105                 110         
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu 
        115                 120                 125             
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu 
    130                 135                 140                 
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe Gly Met Ser Trp 
145                 150                 155                 160 
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser 
                165                 170                 175     
Gly Ser Gly Ser Asp Thr Leu Tyr Ala Asp Ser Val Lys Gly Arg Phe 
            180                 185                 190         
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn 
        195                 200                 205             
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly 
    210                 215                 220                 
Ser Leu Ser Arg Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly 
225                 230                 235                 240 
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly 
                245                 250                 255     
Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
            260                 265                 270         
Ser Gly Phe Thr Phe Ser Asp Tyr Trp Met Tyr Trp Val Arg Gln Ala 
        275                 280                 285             
Pro Gly Lys Gly Leu Glu Trp Val Ser Glu Ile Asn Thr Asn Gly Leu 
    290                 295                 300                 
Ile Thr Lys Tyr Pro Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
305                 310                 315                 320 
Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro 
                325                 330                 335     
Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Pro Ser Gly Phe Asn 
            340                 345                 350         
Arg Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        355                 360             

<210> 70
<211> 515
<212> PRT
<213> Artificial Sequence


<220> 
<223> Compound D

<400> 70
Asp Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Ser Thr Ala 
            20                  25                  30          
Asp Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Phe Val 
        35                  40                  45              
Ala Arg Ile Ser Gly Ile Asp Gly Thr Thr Tyr Tyr Asp Glu Pro Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Val Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys 
                85                  90                  95      
Arg Ser Pro Arg Tyr Ala Asp Gln Trp Ser Ala Tyr Asp Tyr Trp Gly 
            100                 105                 110         
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly 
        115                 120                 125             
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro 
    130                 135                 140                 
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser 
145                 150                 155                 160 
Ser Tyr Val Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu 
                165                 170                 175     
Phe Val Ser Thr Ile Asn Trp Ala Gly Ser Arg Gly Tyr Tyr Ala Asp 
            180                 185                 190         
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr 
        195                 200                 205             
Val Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr 
    210                 215                 220                 
Tyr Cys Ala Ala Ser Ala Gly Gly Phe Leu Val Pro Arg Val Gly Gln 
225                 230                 235                 240 
Gly Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly 
                245                 250                 255     
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly 
            260                 265                 270         
Gly Gly Val Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala 
        275                 280                 285             
Ser Gly Phe Thr Phe Arg Ser Phe Gly Met Ser Trp Val Arg Gln Ala 
    290                 295                 300                 
Pro Gly Lys Gly Pro Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Ser 
305                 310                 315                 320 
Asp Thr Leu Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
                325                 330                 335     
Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro 
            340                 345                 350         
Glu Asp Thr Ala Leu Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Arg 
        355                 360                 365             
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
    370                 375                 380                 
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val 
385                 390                 395                 400 
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser 
                405                 410                 415     
Leu Asp Tyr Tyr Gly Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu 
            420                 425                 430         
Arg Glu Gly Val Ser Cys Ile Ser Ser Ser Glu Gly Asp Thr Tyr Tyr 
        435                 440                 445             
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
    450                 455                 460                 
Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 
465                 470                 475                 480 
Leu Tyr Tyr Cys Ala Thr Asp Leu Ser Asp Tyr Gly Val Cys Ser Arg 
                485                 490                 495     
Trp Pro Ser Pro Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Lys Val 
            500                 505                 510         
Ser Ser Ala 
        515 

<210> 71
<211> 505
<212> PRT
<213> Artificial Sequence


<220> 
<223> Compound E

<400> 71
Asp Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Ser Thr Ala 
            20                  25                  30          
Asp Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Phe Val 
        35                  40                  45              
Ala Arg Ile Ser Gly Ile Asp Gly Thr Thr Tyr Tyr Asp Glu Pro Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Val Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys 
                85                  90                  95      
Arg Ser Pro Arg Tyr Ala Asp Gln Trp Ser Ala Tyr Asp Tyr Trp Gly 
            100                 105                 110         
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly 
        115                 120                 125             
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro 
    130                 135                 140                 
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ile Ile Phe Ser 
145                 150                 155                 160 
Ile Asn Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu 
                165                 170                 175     
Leu Val Ala Asp Ile Phe Pro Phe Gly Ser Thr Glu Tyr Ala Asp Ser 
            180                 185                 190         
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val 
        195                 200                 205             
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr 
    210                 215                 220                 
Cys His Ser Tyr Asp Pro Arg Gly Asp Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 
Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu 
                245                 250                 255     
Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly Ser 
            260                 265                 270         
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Arg Ser Phe Gly 
        275                 280                 285             
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Pro Glu Trp Val Ser 
    290                 295                 300                 
Ser Ile Ser Gly Ser Gly Ser Asp Thr Leu Tyr Ala Asp Ser Val Lys 
305                 310                 315                 320 
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
                325                 330                 335     
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Thr 
            340                 345                 350         
Ile Gly Gly Ser Leu Ser Arg Ser Ser Gln Gly Thr Leu Val Thr Val 
        355                 360                 365             
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val 
    370                 375                 380                 
Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly Ser Leu Arg Leu Ser 
385                 390                 395                 400 
Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr Val Met Gly Trp Phe 
                405                 410                 415     
Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Thr Ile Asn Trp 
            420                 425                 430         
Ala Gly Ser Arg Gly Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 
        435                 440                 445             
Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser 
    450                 455                 460                 
Leu Arg Pro Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala Ser Ala Gly 
465                 470                 475                 480 
Gly Phe Leu Val Pro Arg Val Gly Gln Gly Tyr Asp Tyr Trp Gly Gln 
                485                 490                 495     
Gly Thr Leu Val Lys Val Ser Ser Ala 
            500                 505 

