                         SEQUENCE LISTING

<110>  Ablynx NV
 
<120>  Immunoglobulin single variable domain directed against human 
       CXCR4 and other cell associated proteins and methods to generate 
       them

<130>  P09-003-PCT-1

<160>  30    

<170>  PatentIn version 3.4

<210>  1
<211>  360
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Glu Gly Ile Ser Ser Ile Pro Leu Pro Leu Leu Gln Ile Tyr Thr 
1               5                   10                  15      


Ser Asp Asn Tyr Thr Glu Glu Met Gly Ser Gly Asp Tyr Asp Ser Met 
            20                  25                  30          


Lys Glu Pro Cys Phe Arg Glu Glu Asn Ala Asn Phe Asn Lys Ile Phe 
        35                  40                  45              


Leu Pro Thr Ile Tyr Ser Ile Ile Phe Leu Thr Gly Ile Val Gly Asn 
    50                  55                  60                  


Gly Leu Val Ile Leu Val Met Gly Tyr Gln Lys Lys Leu Arg Ser Met 
65                  70                  75                  80  


Thr Asp Lys Tyr Arg Leu His Leu Ser Val Ala Asp Leu Leu Phe Val 
                85                  90                  95      


Ile Thr Leu Pro Phe Trp Ala Val Asp Ala Val Ala Asn Trp Tyr Phe 
            100                 105                 110         


Gly Asn Phe Leu Cys Lys Ala Val His Val Ile Tyr Thr Val Asn Leu 
        115                 120                 125             


Tyr Ser Ser Val Leu Ile Leu Ala Phe Ile Ser Leu Asp Arg Tyr Leu 
    130                 135                 140                 


Ala Ile Val His Ala Thr Asn Ser Gln Arg Pro Arg Lys Leu Leu Ala 
145                 150                 155                 160 


Glu Lys Val Val Tyr Val Gly Val Trp Ile Pro Ala Leu Leu Leu Thr 
                165                 170                 175     


Ile Pro Asp Phe Ile Phe Ala Asn Val Ser Glu Ala Asp Asp Arg Tyr 
            180                 185                 190         


Ile Cys Asp Arg Phe Tyr Pro Asn Asp Leu Trp Val Val Val Phe Gln 
        195                 200                 205             


Phe Gln His Ile Met Val Gly Leu Ile Leu Pro Gly Ile Val Ile Leu 
    210                 215                 220                 


Ser Cys Tyr Cys Ile Ile Ile Ser Lys Leu Ser His Ser Lys Gly His 
225                 230                 235                 240 


Gln Lys Arg Lys Ala Leu Lys Thr Thr Val Ile Leu Ile Leu Ala Phe 
                245                 250                 255     


Phe Ala Cys Trp Leu Pro Tyr Tyr Ile Gly Ile Ser Ile Asp Ser Phe 
            260                 265                 270         


Ile Leu Leu Glu Ile Ile Lys Gln Gly Cys Glu Phe Glu Asn Thr Val 
        275                 280                 285             


His Lys Trp Ile Ser Ile Thr Glu Ala Leu Ala Phe Phe His Cys Cys 
    290                 295                 300                 


Leu Asn Pro Ile Leu Tyr Ala Phe Leu Gly Ala Lys Phe Lys Thr Ser 
305                 310                 315                 320 


Ala Gln His Ala Leu Thr Ser Val Ser Arg Gly Ser Ser Leu Lys Ile 
                325                 330                 335     


Leu Ser Lys Gly Lys Arg Gly Gly His Ser Ser Val Ser Thr Glu Ser 
            340                 345                 350         


Glu Ser Ser Ser Phe His Ser Ser 
        355                 360 


<210>  2
<211>  122
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody

<400>  2

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Thr 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 Gly Ile Lys Ser Ser Gly Asp Ser Thr Arg Tyr Ala Gly Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Met Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Tyr Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Ser Arg Val Ser Arg Thr Gly Leu Tyr Thr Tyr Asp Asn Arg 
            100                 105                 110         


Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120         


<210>  3
<211>  128
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody

<400>  3

Glu Val Gln Leu Met Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Asn Asn Tyr 
            20                  25                  30          


Ala Met Gly Trp Phe Arg Arg Ala Pro Gly Lys Glu Arg Glu Phe Val 
        35                  40                  45              


Ala Ala Ile Thr Arg Ser Gly Val Arg Ser Gly Val Ser Ala Ile Tyr 
    50                  55                  60                  


Gly Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
65                  70                  75                  80  


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 
                85                  90                  95      


Val Tyr Thr Cys Ala Ala Ser Ala Ile Gly Ser Gly Ala Leu Arg Arg 
            100                 105                 110         


Phe Glu Tyr Asp Tyr Ser Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125             


<210>  4
<211>  265
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody construct

<400>  4

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Thr 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 Gly Ile Lys Ser Ser Gly Asp Ser Thr Arg Tyr Ala Gly Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Met Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Tyr Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Ser Arg Val Ser Arg Thr Gly Leu Tyr Thr Tyr Asp Asn Arg 
            100                 105                 110         


Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 
        115                 120                 125             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Met Glu Ser 
    130                 135                 140                 


Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Ala 
145                 150                 155                 160 


Ala Ser Gly Arg Thr Phe Asn Asn Tyr Ala Met Gly Trp Phe Arg Arg 
                165                 170                 175     


Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Ala Ile Thr Arg Ser Gly 
            180                 185                 190         


Val Arg Ser Gly Val Ser Ala Ile Tyr Gly Asp Ser Val Lys Asp Arg 
        195                 200                 205             


Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln Met 
    210                 215                 220                 


Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Thr Cys Ala Ala Ser 
225                 230                 235                 240 


Ala Ile Gly Ser Gly Ala Leu Arg Arg Phe Glu Tyr Asp Tyr Ser Gly 
                245                 250                 255     


Gln Gly Thr Gln Val Thr Val Ser Ser 
            260                 265 


<210>  5
<211>  270
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody construct

<400>  5

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Thr 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 Gly Ile Lys Ser Ser Gly Asp Ser Thr Arg Tyr Ala Gly Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Met Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Tyr Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Ser Arg Val Ser Arg Thr Gly Leu Tyr Thr Tyr Asp Asn Arg 
            100                 105                 110         


Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 
        115                 120                 125             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val 
    130                 135                 140                 


Gln Leu Met Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu 
145                 150                 155                 160 


Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Asn Asn Tyr Ala Met 
                165                 170                 175     


Gly Trp Phe Arg Arg Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Ala 
            180                 185                 190         


Ile Thr Arg Ser Gly Val Arg Ser Gly Val Ser Ala Ile Tyr Gly Asp 
        195                 200                 205             


Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr 
    210                 215                 220                 


Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Thr Cys Ala Ala Ser Ala Ile Gly Ser Gly Ala Leu Arg Arg Phe Glu 
                245                 250                 255     


Tyr Asp Tyr Ser Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
            260                 265                 270 


<210>  6
<211>  352
<212>  PRT
<213>  Homo sapiens

<400>  6

Met Glu Gly Ile Ser Ile Tyr Thr Ser Asp Asn Tyr Thr Glu Glu Met 
1               5                   10                  15      


Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu 
            20                  25                  30          


Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile Tyr Ser Ile Ile 
        35                  40                  45              


Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile Leu Val Met Gly 
    50                  55                  60                  


Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr Arg Leu His Leu 
65                  70                  75                  80  


Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro Phe Trp Ala Val 
                85                  90                  95      


Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu Cys Lys Ala Val 
            100                 105                 110         


His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val Leu Ile Leu Ala 
        115                 120                 125             


Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His Ala Thr Asn Ser 
    130                 135                 140                 


Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys Val Val Tyr Val Gly Val 
145                 150                 155                 160 


Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe Ile Phe Ala Asn 
                165                 170                 175     


Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Asp Arg Phe Tyr Pro Asn 
            180                 185                 190         


Asp Leu Trp Val Val Val Phe Gln Phe Gln His Ile Met Val Gly Leu 
        195                 200                 205             


Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys Ile Ile Ile Ser 
    210                 215                 220                 


Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys Ala Leu Lys Thr 
225                 230                 235                 240 


Thr Val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp Leu Pro Tyr Tyr 
                245                 250                 255     


Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu Ile Ile Lys Gln 
            260                 265                 270         


Gly Cys Glu Phe Glu Asn Thr Val His Lys Trp Ile Ser Ile Thr Glu 
        275                 280                 285             


Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile Leu Tyr Ala Phe 
    290                 295                 300                 


Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala Leu Thr Ser Val 
305                 310                 315                 320 


Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly Lys Arg Gly Gly 
                325                 330                 335     


His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser Phe His Ser Ser 
            340                 345                 350         


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

<220>
<223>  Linker

<400>  7

Gly Gly Gly Gly Ser 
1               5   


<210>  8
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  Linker

<400>  8

Ser Gly Gly Ser Gly Gly Ser 
1               5           


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

<220>
<223>  Linker

<400>  9

Gly Gly Gly Gly Ser Gly Gly Gly Ser 
1               5                   


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

<220>
<223>  Linker

<400>  10

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10  


<210>  11
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Linker

<400>  11

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


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

<220>
<223>  Linker

<400>  12

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Gly 
1               5                   10                  15      


Gly Ser 
        


<210>  13
<211>  20
<212>  PRT
<213>  Artificial

<220>
<223>  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 
            20  


<210>  14
<211>  25
<212>  PRT
<213>  Artificial

<220>
<223>  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 
            20                  25  


<210>  15
<211>  30
<212>  PRT
<213>  Artificial

<220>
<223>  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 
            20                  25                  30  


<210>  16
<211>  35
<212>  PRT
<213>  Artificial

<220>
<223>  Linker

<400>  16

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>  17
<211>  115
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody

<400>  17

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Phe 
            20                  25                  30          


Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ser Ile Ser Gly Ser Gly Ser Asp Thr Leu Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr 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      


Thr Ile Gly Gly Ser Leu Ser Arg Ser Ser Gln Gly Thr Leu Val Thr 
            100                 105                 110         


Val Ser Ser 
        115 


<210>  18
<211>  23
<212>  PRT
<213>  Artificial

<220>
<223>  Tag

<400>  18

Ala Ala Ala Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asn Gly Ala 
1               5                   10                  15      


Ala His His His His His His 
            20              


<210>  19
<211>  352
<212>  PRT
<213>  Artificial

<220>
<223>  Mutant

<400>  19

Met Glu Gly Ile Ser Ile Tyr Thr Ser Asp Asn Tyr Thr Glu Glu Met 
1               5                   10                  15      


Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu 
            20                  25                  30          


Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile Tyr Ser Ile Ile 
        35                  40                  45              


Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile Leu Val Met Gly 
    50                  55                  60                  


Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr Arg Leu His Leu 
65                  70                  75                  80  


Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro Phe Trp Ala Val 
                85                  90                  95      


Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu Cys Lys Ala Val 
            100                 105                 110         


His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val Leu Ile Leu Ala 
        115                 120                 125             


Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His Ala Thr Asn Ser 
    130                 135                 140                 


Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys Val Val Tyr Val Gly Val 
145                 150                 155                 160 


Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe Ile Phe Ala Asn 
                165                 170                 175     


Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Asp Arg Val Tyr Pro Asn 
            180                 185                 190         


Asp Leu Trp Val Val Val Phe Gln Phe Gln His Ile Met Val Gly Leu 
        195                 200                 205             


Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys Ile Ile Ile Ser 
    210                 215                 220                 


Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys Ala Leu Lys Thr 
225                 230                 235                 240 


Thr Val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp Leu Pro Tyr Tyr 
                245                 250                 255     


Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu Ile Ile Lys Gln 
            260                 265                 270         


Gly Cys Glu Phe Glu Asn Thr Val His Lys Trp Ile Ser Ile Thr Glu 
        275                 280                 285             


Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile Leu Tyr Ala Phe 
    290                 295                 300                 


Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala Leu Thr Ser Val 
305                 310                 315                 320 


Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly Lys Arg Gly Gly 
                325                 330                 335     


His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser Phe His Ser Ser 
            340                 345                 350         


<210>  20
<211>  352
<212>  PRT
<213>  Artificial

<220>
<223>  Mutant

<400>  20

Met Glu Gly Ile Ser Ile Tyr Thr Ser Asp Asn Tyr Thr Glu Glu Met 
1               5                   10                  15      


Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu 
            20                  25                  30          


Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile Tyr Ser Ile Ile 
        35                  40                  45              


Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile Leu Val Met Gly 
    50                  55                  60                  


Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr Arg Leu His Leu 
65                  70                  75                  80  


Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro Phe Trp Ala Val 
                85                  90                  95      


Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu Cys Lys Ala Val 
            100                 105                 110         


His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val Leu Ile Leu Ala 
        115                 120                 125             


Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His Ala Thr Asn Ser 
    130                 135                 140                 


Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys Val Val Tyr Val Gly Val 
145                 150                 155                 160 


Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe Ile Phe Ala Asn 
                165                 170                 175     


Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Asp Arg Phe Tyr Pro Asn 
            180                 185                 190         


Asp Leu Trp Glu Val Val Phe Gln Phe Gln His Ile Met Val Gly Leu 
        195                 200                 205             


Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys Ile Ile Ile Ser 
    210                 215                 220                 


Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys Ala Leu Lys Thr 
225                 230                 235                 240 


Thr Val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp Leu Pro Tyr Tyr 
                245                 250                 255     


Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu Ile Ile Lys Gln 
            260                 265                 270         


Gly Cys Glu Phe Glu Asn Thr Val His Lys Trp Ile Ser Ile Thr Glu 
        275                 280                 285             


Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile Leu Tyr Ala Phe 
    290                 295                 300                 


Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala Leu Thr Ser Val 
305                 310                 315                 320 


Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly Lys Arg Gly Gly 
                325                 330                 335     


His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser Phe His Ser Ser 
            340                 345                 350         


<210>  21
<211>  352
<212>  PRT
<213>  Artificial

<220>
<223>  Mutant

<400>  21

Met Glu Gly Ile Ser Ile Tyr Thr Ser Asp Asn Tyr Thr Glu Glu Met 
1               5                   10                  15      


Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu 
            20                  25                  30          


Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile Tyr Ser Ile Ile 
        35                  40                  45              


Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile Leu Val Met Gly 
    50                  55                  60                  


Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr Arg Leu His Leu 
65                  70                  75                  80  


Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro Phe Trp Ala Val 
                85                  90                  95      


Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu Cys Lys Ala Val 
            100                 105                 110         


His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val Leu Ile Leu Ala 
        115                 120                 125             


Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His Ala Thr Asn Ser 
    130                 135                 140                 


Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys Val Val Tyr Val Gly Val 
145                 150                 155                 160 


Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe Ile Phe Ala Asn 
                165                 170                 175     


Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Val Arg Phe Tyr Pro Asn 
            180                 185                 190         


Asp Leu Trp Val Val Val Phe Gln Phe Gln His Ile Met Val Gly Leu 
        195                 200                 205             


Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys Ile Ile Ile Ser 
    210                 215                 220                 


Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys Ala Leu Lys Thr 
225                 230                 235                 240 


Thr Val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp Leu Pro Tyr Tyr 
                245                 250                 255     


Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu Ile Ile Lys Gln 
            260                 265                 270         


Gly Cys Glu Phe Glu Asn Thr Val His Lys Trp Ile Ser Ile Thr Glu 
        275                 280                 285             


Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile Leu Tyr Ala Phe 
    290                 295                 300                 


Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala Leu Thr Ser Val 
305                 310                 315                 320 


Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly Lys Arg Gly Gly 
                325                 330                 335     


His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser Phe His Ser Ser 
            340                 345                 350         


<210>  22
<211>  356
<212>  PRT
<213>  Homo sapiens

<400>  22

Met Ser Ile Pro Leu Pro Leu Leu Gln Ile Tyr Thr Ser Asp Asn Tyr 
1               5                   10                  15      


Thr Glu Glu Met Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys 
            20                  25                  30          


Phe Arg Glu Glu Asn Ala Asn Phe Asn Lys Ile Phe Leu Pro Thr Ile 
        35                  40                  45              


Tyr Ser Ile Ile Phe Leu Thr Gly Ile Val Gly Asn Gly Leu Val Ile 
    50                  55                  60                  


Leu Val Met Gly Tyr Gln Lys Lys Leu Arg Ser Met Thr Asp Lys Tyr 
65                  70                  75                  80  


Arg Leu His Leu Ser Val Ala Asp Leu Leu Phe Val Ile Thr Leu Pro 
                85                  90                  95      


Phe Trp Ala Val Asp Ala Val Ala Asn Trp Tyr Phe Gly Asn Phe Leu 
            100                 105                 110         


Cys Lys Ala Val His Val Ile Tyr Thr Val Asn Leu Tyr Ser Ser Val 
        115                 120                 125             


Leu Ile Leu Ala Phe Ile Ser Leu Asp Arg Tyr Leu Ala Ile Val His 
    130                 135                 140                 


Ala Thr Asn Ser Gln Arg Pro Arg Lys Leu Leu Ala Glu Lys Val Val 
145                 150                 155                 160 


Tyr Val Gly Val Trp Ile Pro Ala Leu Leu Leu Thr Ile Pro Asp Phe 
                165                 170                 175     


Ile Phe Ala Asn Val Ser Glu Ala Asp Asp Arg Tyr Ile Cys Asp Arg 
            180                 185                 190         


Phe Tyr Pro Asn Asp Leu Trp Val Val Val Phe Gln Phe Gln His Ile 
        195                 200                 205             


Met Val Gly Leu Ile Leu Pro Gly Ile Val Ile Leu Ser Cys Tyr Cys 
    210                 215                 220                 


Ile Ile Ile Ser Lys Leu Ser His Ser Lys Gly His Gln Lys Arg Lys 
225                 230                 235                 240 


Ala Leu Lys Thr Thr Val Ile Leu Ile Leu Ala Phe Phe Ala Cys Trp 
                245                 250                 255     


Leu Pro Tyr Tyr Ile Gly Ile Ser Ile Asp Ser Phe Ile Leu Leu Glu 
            260                 265                 270         


Ile Ile Lys Gln Gly Cys Glu Phe Glu Asn Thr Val His Lys Trp Ile 
        275                 280                 285             


Ser Ile Thr Glu Ala Leu Ala Phe Phe His Cys Cys Leu Asn Pro Ile 
    290                 295                 300                 


Leu Tyr Ala Phe Leu Gly Ala Lys Phe Lys Thr Ser Ala Gln His Ala 
305                 310                 315                 320 


Leu Thr Ser Val Ser Arg Gly Ser Ser Leu Lys Ile Leu Ser Lys Gly 
                325                 330                 335     


Lys Arg Gly Gly His Ser Ser Val Ser Thr Glu Ser Glu Ser Ser Ser 
            340                 345                 350         


Phe His Ser Ser 
        355     


<210>  23
<211>  122
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody

<400>  23

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 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 Gly Ile Lys Ser Ser Gly Asp Ser Thr Arg Tyr Ala Gly 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 Lys Ser Arg Val Ser Arg Thr Gly Leu Tyr Thr Tyr Asp Asn Arg 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  24
<211>  128
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody

<400>  24

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 Arg Thr Phe Asn Asn Tyr 
            20                  25                  30          


Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val 
        35                  40                  45              


Ala Ala Ile Thr Arg Ser Gly Val Arg Ser Gly Val Ser Ala Ile Tyr 
    50                  55                  60                  


Gly Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
65                  70                  75                  80  


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala 
                85                  90                  95      


Val Tyr Tyr Cys Ala Ala Ser Ala Ile Gly Ser Gly Ala Leu Arg Arg 
            100                 105                 110         


Phe Glu Tyr Asp Tyr Ser Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125             


<210>  25
<211>  128
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody

<400>  25

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Asn Asn Tyr 
            20                  25                  30          


Ala Met Gly Trp Phe Arg Arg Ala Pro Gly Lys Glu Arg Glu Phe Val 
        35                  40                  45              


Ala Ala Ile Thr Arg Ser Gly Val Arg Ser Gly Val Ser Ala Ile Tyr 
    50                  55                  60                  


Gly Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys 
65                  70                  75                  80  


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 
                85                  90                  95      


Val Tyr Thr Cys Ala Ala Ser Ala Ile Gly Ser Gly Ala Leu Arg Arg 
            100                 105                 110         


Phe Glu Tyr Asp Tyr Ser Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125             


<210>  26
<211>  122
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody

<400>  26

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Thr 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 Gly Ile Lys Ser Ser Gly Asp Ser Thr Arg Tyr Ala Gly 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 Tyr Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Ser Arg Val Ser Arg Thr Gly Leu Tyr Thr Tyr Asp Asn Arg 
            100                 105                 110         


Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120         


<210>  27
<211>  270
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody construct

<400>  27

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Thr 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 Gly Ile Lys Ser Ser Gly Asp Ser Thr Arg Tyr Ala Gly Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Met Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Tyr Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Ser Arg Val Ser Arg Thr Gly Leu Tyr Thr Tyr Asp Asn Arg 
            100                 105                 110         


Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 
        115                 120                 125             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val 
    130                 135                 140                 


Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu 
145                 150                 155                 160 


Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Asn Asn Tyr Ala Met 
                165                 170                 175     


Gly Trp Phe Arg Arg Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Ala 
            180                 185                 190         


Ile Thr Arg Ser Gly Val Arg Ser Gly Val Ser Ala Ile Tyr Gly Asp 
        195                 200                 205             


Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr 
    210                 215                 220                 


Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Thr Cys Ala Ala Ser Ala Ile Gly Ser Gly Ala Leu Arg Arg Phe Glu 
                245                 250                 255     


Tyr Asp Tyr Ser Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
            260                 265                 270 


<210>  28
<211>  270
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody construct

<400>  28

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Thr 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 Gly Ile Lys Ser Ser Gly Asp Ser Thr Arg Tyr Ala Gly 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 Tyr Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Lys Ser Arg Val Ser Arg Thr Gly Leu Tyr Thr Tyr Asp Asn Arg 
            100                 105                 110         


Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 
        115                 120                 125             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val 
    130                 135                 140                 


Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly Ser Leu 
145                 150                 155                 160 


Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Asn Asn Tyr Ala Met 
                165                 170                 175     


Gly Trp Phe Arg Arg Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Ala 
            180                 185                 190         


Ile Thr Arg Ser Gly Val Arg Ser Gly Val Ser Ala Ile Tyr Gly Asp 
        195                 200                 205             


Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr 
    210                 215                 220                 


Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Thr Cys Ala Ala Ser Ala Ile Gly Ser Gly Ala Leu Arg Arg Phe Glu 
                245                 250                 255     


Tyr Asp Tyr Ser Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
            260                 265                 270 


<210>  29
<211>  0
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody construct

<400>  29
000
<210>  30
<211>  270
<212>  PRT
<213>  Artificial

<220>
<223>  Nanobody construct

<400>  30

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 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 Gly Ile Lys Ser Ser Gly Asp Ser Thr Arg Tyr Ala Gly 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 Lys Ser Arg Val Ser Arg Thr Gly Leu Tyr Thr Tyr Asp Asn Arg 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 
        115                 120                 125             


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val 
    130                 135                 140                 


Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
145                 150                 155                 160 


Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Asn Asn Tyr Ala Met 
                165                 170                 175     


Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Ala 
            180                 185                 190         


Ile Thr Arg Ser Gly Val Arg Ser Gly Val Ser Ala Ile Tyr Gly Asp 
        195                 200                 205             


Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr 
    210                 215                 220                 


Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr 
225                 230                 235                 240 


Tyr Cys Ala Ala Ser Ala Ile Gly Ser Gly Ala Leu Arg Arg Phe Glu 
                245                 250                 255     


Tyr Asp Tyr Ser Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
            260                 265                 270 


