                         SEQUENCE LISTING

<110>  Ablynx nv
 
<120>  Prolonged inhibition of bone resorption

<130>  P11-013-PCT-1

<150>  US 61/491,066
<151>  2011-05-27

<160>  31    

<170>  PatentIn version 3.5

<210>  1
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR sequence

<400>  1

Ser Tyr Pro Met Gly 
1               5   


<210>  2
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR sequence

<400>  2

Ser Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  3
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR sequence

<400>  3

Tyr Ile Arg Pro Asp Thr Tyr Leu Ser Arg Asp Tyr Arg Lys Tyr 
1               5                   10                  15  


<210>  4
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  4

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 Arg Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Ala Tyr Ile Arg Pro Asp Thr Tyr Leu Ser Arg Asp Tyr Arg Lys 
            100                 105                 110         


Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120                 125     


<210>  5
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  5

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 Arg Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Ala Tyr Ile Arg Pro Asp Thr Tyr Leu Ser Arg Asp Tyr Arg Lys 
            100                 105                 110         


Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  6
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  6

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 Arg Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Ala Tyr Ile Arg Pro Asp Thr Tyr Leu Ser Arg Asp Tyr Arg Lys 
            100                 105                 110         


Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  7
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  7

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 Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Ala Tyr Ile Arg Pro Asp Thr Tyr Leu Ser Arg Asp Tyr Arg Lys 
            100                 105                 110         


Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  8
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  8

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 Arg Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Ala Tyr Ile Arg Pro Asp Thr Tyr Leu Ser Arg Asp Tyr Arg Lys 
            100                 105                 110         


Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  9
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  9

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 Arg Ser Tyr 
            20                  25                  30          


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


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


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


Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  10
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  10

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          


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


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


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


Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  11
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  11

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          


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


Ser Ser Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Glu 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 Ala Tyr Ile Arg Pro Asp Thr Tyr Leu Ser Arg Asp Tyr Arg Lys 
            100                 105                 110         


Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  12
<211>  385
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  12

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          


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


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


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


Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly 
        115                 120                 125             


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


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


Gly Phe Thr Phe Ser Ser Phe Gly Met Ser Trp Val Arg Gln Ala Pro 
                165                 170                 175     


Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Ser Asp 
            180                 185                 190         


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


Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu 
    210                 215                 220                 


Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Arg Ser 
225                 230                 235                 240 


Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 
                245                 250                 255     


Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 
            260                 265                 270         


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 
        275                 280                 285             


Ser Ser Tyr Pro Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg 
    290                 295                 300                 


Glu Phe Val Ser Ser Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala 
305                 310                 315                 320 


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn 
                325                 330                 335     


Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val 
            340                 345                 350         


Tyr Tyr Cys Ala Ala Tyr Ile Arg Pro Asp Thr Tyr Leu Ser Arg Asp 
        355                 360                 365             


Tyr Arg Lys Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
    370                 375                 380                 


Ser 
385 


<210>  13
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  13

Ala 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 Arg Ser Phe 
            20                  25                  30          


Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Glu Pro 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 Lys 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 Gln Val Thr 
            100                 105                 110         


Val Ser Ser 
        115 


<210>  14
<211>  115
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  14

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>  15
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nanobody sequence

<400>  15

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


Ser Leu Arg Leu Ala Cys Ala Ala Ser Glu Arg Ile Phe Asp Leu Asn 
            20                  25                  30          


Leu Met Gly Trp Tyr Arg Gln Gly Pro Gly Asn Glu Arg Glu Leu Val 
        35                  40                  45              


Ala Thr Cys Ile Thr Val Gly Asp Ser Thr Asn Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu His Met Asn Ser Leu Arg Pro Glu Asp Thr Gly Leu Tyr Tyr Cys 
                85                  90                  95      


Lys Ile Arg Arg Thr Trp His Ser Glu Leu Trp Gly Gln Gly Thr Gln 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  16
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  16

Gly Gly Gly Gly Ser 
1               5   


<210>  17
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  17

Ser Gly Gly Ser Gly Gly Ser 
1               5           


<210>  18
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  18

Gly Gly Gly Gly Ser Gly Gly Gly Ser 
1               5                   


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

<220>
<223>  Linker sequence

<400>  19

Gly Gly Gly Gly Ser Gly Gly Gly Ser 
1               5                   


<210>  20
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  20

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


<210>  21
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  21

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


<210>  22
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  22

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


Gly Ser 
        


<210>  23
<211>  20
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  23

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>  24
<211>  25
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  24

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>  25
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  25

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>  26
<211>  35
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  26

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>  27
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  27

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
1               5                   10                  15  


<210>  28
<211>  24
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  28

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>  29
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  29

Glu Pro Lys Thr Pro Lys Pro Gln Pro Ala Ala Ala 
1               5                   10          


<210>  30
<211>  62
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  30

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>  31
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker sequence

<400>  31

Ala Ala Ala 
1           


