                         SEQUENCE LISTING

<110>  F. HOFFMANN-LA ROCHE
       INSTITUT PASTEUR
       COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES 
       ALTERNATIVES
       CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
 
<120>  CAMELID SINGLE-DOMAIN ANTIBODY DIRECTED AGAINST PHOSPHORYLATED 
       TAU PROTEIN AND METHODS FOR PRODUCING CONJUGATES THEREOF

<130>  XRN/cc/F226-202

<150>  EP 14152928.9
<151>  2014-01-28

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of VHH Tau-A2

<400>  1

Ala Ala Ser Gly Arg Ser Phe Ser Gly Ser Thr Met Glu 
1               5                   10              


<210>  2
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of VHH Tau-A2

<400>  2

Ala Ile Arg Thr Ile Ser Ser Arg Thr Tyr Tyr Val Asp 
1               5                   10              


<210>  3
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of VHH Tau-A2

<400>  3

Arg Phe Ser Gly Thr Ile Gly Thr Thr Ser Ser Val Asp Tyr 
1               5                   10                  


<210>  4
<211>  128
<212>  PRT
<213>  Lama pacos


<220>
<221>  DOMAIN
<222>  (25)..(37)
<223>  CDR1 of VHH Tau-A2

<220>
<221>  DOMAIN
<222>  (52)..(64)
<223>  CDR2 of VHH Tau-A2

<220>
<221>  DOMAIN
<222>  (101)..(114)
<223>  CDR3 of VHH Tau-A2

<400>  4

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


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


Gly Ser Thr Met Glu Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Lys 
        35                  40                  45              


Phe Val Ala Ala Ile Arg Thr Ile Ser Ser Arg Thr Tyr Tyr Val Asp 
    50                  55                  60                  


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


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


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


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


<210>  5
<211>  119
<212>  PRT
<213>  Lama pacos

<400>  5

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


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


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


Ile Arg Thr Ile Ser Ser Arg Thr Tyr Tyr Val Asp Ser Val Lys Gly 
    50                  55                  60                  


Arg Phe Thr Ile Ser Arg Asp Ser Thr Lys Asn Thr Val Tyr Leu Gln 
65                  70                  75                  80  


Leu Asn Ser Leu Lys Val Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 
                85                  90                  95      


Arg Phe Ser Gly Thr Ile Gly Thr Thr Ser Ser Val Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Gln Val Thr Val 
        115                 


<210>  6
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  single phospho-peptide derived from the C-terminus of the tau 
       protein


<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Phosphorylation of the serine

<400>  6

Cys Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp 
1               5                   10                  15      


<210>  7
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer

<400>  7
cgccatcaag gtaccagttg a                                                 21


<210>  8
<211>  29
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer

<400>  8
gatgtgcagc tgcaggcgtc tggrggagg                                         29


<210>  9
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer

<400>  9
catgccatga ctcgcggccc agccggccat ggccgakgts cagct                       45


<210>  10
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer

<400>  10
ggactagttg cggccgctga ggagacggtg acctg                                  35


<210>  11
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Spacer

<400>  11

Gly Gly Gly Ser 
1               


<210>  12
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  His tag

<400>  12

His His His His His His 
1               5       


<210>  13
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Thrombin cleavage site

<400>  13

Leu Val Pro Arg Gly Ser 
1               5       


<210>  14
<211>  148
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VHH Tau-A2-SH


<220>
<221>  DOMAIN
<222>  (5)..(10)
<223>  6xHis tag

<220>
<221>  DOMAIN
<222>  (14)..(19)
<223>  Thrombin cleavage site

<220>
<221>  DOMAIN
<222>  (23)..(141)
<223>  VHH Tau-A2

<220>
<221>  DOMAIN
<222>  (142)..(145)
<223>  Spacer

<220>
<221>  DOMAIN
<222>  (146)..(148)
<223>  Spacer

<400>  14

Met Gly Ser Ser His His His His His His Ser Ser Gly Leu Val Pro 
1               5                   10                  15      


Arg Gly Ser Ala Ala Ala Gln Leu Gln Ala Ser Gly Gly Gly Leu Val 
            20                  25                  30          


Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Ser 
        35                  40                  45              


Phe Ser Gly Ser Thr Met Glu Trp Tyr Arg Gln Ala Pro Gly Lys Glu 
    50                  55                  60                  


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


Val Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Ser Thr Lys 
                85                  90                  95      


Asn Thr Val Tyr Leu Gln Leu Asn Ser Leu Lys Val Glu Asp Thr Ala 
            100                 105                 110         


Val Tyr Tyr Cys Ala Ala Arg Phe Ser Gly Thr Ile Gly Thr Thr Ser 
        115                 120                 125             


Ser Val Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Gly Gly Gly 
    130                 135                 140                 


Ser Cys Ser Ala 
145             


<210>  15
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VHH Tau-A2 variant

<400>  15

Asp Val Gln Leu Glu Ala 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 Ser Phe Ser Gly Ser 
            20                  25                  30          


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


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


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


Leu Gln Leu Asn Ser Leu Lys Gly Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Ala Arg Phe Ser Gly Thr Ile Gly Thr Thr Ser Ser Val Asp Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Gln Val Thr Val 
        115                 120     


<210>  16
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VHH Tau-A2 variant

<400>  16

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


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


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


Ile Arg Thr Gly Ser Ser Arg Thr Tyr Tyr Val Asp Ser Val Lys Gly 
    50                  55                  60                  


Arg Phe Thr Ile Ser Arg Asp Ser Thr Lys Asn Thr Val Tyr Leu Gln 
65                  70                  75                  80  


Leu Asn Ser Leu Lys Gly Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala 
                85                  90                  95      


Arg Phe Ser Gly Thr Ile Gly Thr Thr Ser Ser Val Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Gln Val Thr Val 
        115                 


<210>  17
<211>  150
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TauA2var-SH

<400>  17

Met Gly Ser Ser His His His His His His Ser Ser Gly Leu Val Pro 
1               5                   10                  15      


Arg Gly Ser Ala Ala Ala Asp Val Gln Leu Glu Ala Ser Gly Gly Gly 
            20                  25                  30          


Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 
        35                  40                  45              


Arg Ser Phe Ser Gly Ser Thr Met Glu Trp Tyr Arg Gln Ala Pro Gly 
    50                  55                  60                  


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


Tyr Tyr Val Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Ser 
                85                  90                  95      


Thr Lys Asn Thr Val Tyr Leu Gln Leu Asn Ser Leu Lys Gly Glu Asp 
            100                 105                 110         


Thr Ala Val Tyr Tyr Cys Ala Ala Arg Phe Ser Gly Thr Ile Gly Thr 
        115                 120                 125             


Thr Ser Ser Val Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Gly 
    130                 135                 140                 


Gly Gly Ser Cys Ser Ala 
145                 150 


