                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>   ANTI-alpha-SYNUCLEIN ANTIBODIES AND METHODS OF USE

<130>  Case P31869

<150>  EP13193892.0
<151>  2013-11-21

<160>  58    

<170>  PatentIn version 3.5

<210>  1
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human alpha-synuclein fragment

<400>  1

Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly 
1               5                   10      


<210>  2
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH1

<400>  2

Tyr Ala Met Ile 
1               


<210>  3
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH2

<400>  3

Pro Ser Gly Asn Thr Tyr Tyr Ala Asn 
1               5                   


<210>  4
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH3

<400>  4

Arg Asp Gly Thr Asp Lys Thr Phe Asn Ile 
1               5                   10  


<210>  5
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL1

<400>  5

Asn Val Tyr Gly Asp Asn 
1               5       


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

<220>
<223>  CDRL2

<400>  6

Glu Ala Ser Lys Leu Ala 
1               5       


<210>  7
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL3

<400>  7

Gly Glu Phe Leu Cys Thr Thr Ser Asp Cys 
1               5                   10  


<210>  8
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH1

<400>  8

Ser Tyr Ala Met Ile 
1               5   


<210>  9
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH2

<400>  9

Val Ile Tyr Pro Ser Gly Asn Thr Tyr Tyr Ala Asn Trp Ala Lys Gly 
1               5                   10                  15      


<210>  10
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL1

<400>  10

Gln Ala Ser Gln Asn Val Tyr Gly Asp Asn Tyr Leu Ala 
1               5                   10              


<210>  11
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL2

<400>  11

Glu Ala Ser Lys Leu Ala Ser 
1               5           


<210>  12
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL3

<400>  12

Gln Gly Glu Phe Leu Cys Thr Thr Ser Asp Cys Phe Thr 
1               5                   10              


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

<220>
<223>  heavy chain variable domain

<400>  13

Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro 
1               5                   10                  15      


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


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


Val Ile Tyr Pro Ser Gly Asn Thr Tyr Tyr Ala Asn Trp Ala Lys Gly 
    50                  55                  60                  


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


Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Arg Asp 
                85                  90                  95      


Gly Thr Asp Lys Thr Phe Asn Ile Trp Gly Pro Gly Thr Leu Val Thr 
            100                 105                 110         


Val Ser Leu 
        115 


<210>  14
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain

<400>  14

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


Thr Val Thr Ile Asn Cys Gln Ala Ser Gln Asn Val Tyr Gly Asp Asn 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu 
        35                  40                  45              


Ile Tyr Glu Ala Ser Lys Leu Ala Ser Gly Val Pro Pro Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Asp Val Gln 
65                  70                  75                  80  


Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Gln Gly Glu Phe Leu Cys Thr 
                85                  90                  95      


Thr Ser Asp Cys Phe Thr Phe Gly Gly Gly Thr Gly Val Val Val Arg 
            100                 105                 110         


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

<220>
<223>  CDRH1

<400>  15

Arg Tyr Ala 
1           


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

<220>
<223>  CDRH2

<400>  16

Asn Ser Ser Gly Ala 
1               5   


<210>  17
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH3

<400>  17

Trp Thr Tyr Asp Asp Tyr Gly Asp Phe Gln Gly Phe Asn Ile 
1               5                   10                  


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

<220>
<223>  CDRL1

<400>  18

Ser Val Tyr Asn Asn Asn Asp Leu Ala 
1               5                   


<210>  19
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL2

<400>  19

Arg Ala Ser Lys Leu Ala 
1               5       


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

<220>
<223>  CDRL3

<400>  20

Gly Gly Tyr Asp Asp Asp Ala Asp Met Gly Ala 
1               5                   10      


<210>  21
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH1

<400>  21

Arg Tyr Ala Met Ser 
1               5   


<210>  22
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH2

<400>  22

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


<210>  23
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL1

<400>  23

Gln Ser Ser Gln Ser Val Tyr Asn Asn Asn Asp Leu Ala 
1               5                   10              


<210>  24
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL2

<400>  24

Arg Ala Ser Lys Leu Ala Ser 
1               5           


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

<220>
<223>  CDRL3

<400>  25

Leu Gly Gly Tyr Asp Asp Asp Ala Asp Met Gly Ala 
1               5                   10          


<210>  26
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain

<400>  26

Gln Ser Val Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro 
1               5                   10                  15      


Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Asp Leu Ser Arg Tyr Ala 
            20                  25                  30          


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


Val Ile Asn Ser Ser Gly Ala Thr Tyr Tyr Ala Ser Trp Ala Lys Gly 
    50                  55                  60                  


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


Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg Trp Thr 
                85                  90                  95      


Tyr Asp Asp Tyr Gly Asp Phe Gln Gly Phe Asn Ile Trp Gly Pro Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Leu 
        115                 


<210>  27
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain

<400>  27

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


Thr Val Thr Ile Ser Cys Gln Ser Ser Gln Ser Val Tyr Asn Asn Asn 
            20                  25                  30          


Asp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu 
        35                  40                  45              


Ile Tyr Arg Ala Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Lys 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Gly Val Gln 
65                  70                  75                  80  


Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Gly Tyr Asp Asp Asp 
                85                  90                  95      


Ala Asp Met Gly Ala Phe Gly Gly Gly Thr Glu Val Val Val Lys 
            100                 105                 110     


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

<220>
<223>  CDRH1

<400>  28

Arg Asp Thr Met Ile 
1               5   


<210>  29
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH2

<400>  29

Ser Ile Tyr Thr Asp Ser Gly Asn Thr Trp 
1               5                   10  


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

<220>
<223>  CDRH3

<400>  30

Asn Phe Ser Val 
1               


<210>  31
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL1

<400>  31

Val Tyr Asn Ser Asp Arg 
1               5       


<210>  32
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL2

<400>  32

Val Ser Lys Leu Ala 
1               5   


<210>  33
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL3

<400>  33

Leu Gly Gly Tyr Asp Cys Ser Ser Ala Glu Cys 
1               5                   10      


<210>  34
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRH2

<400>  34

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


Gly 
    


<210>  35
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL1

<400>  35

Gln Ala Ser Gln Ser Val Tyr Asn Ser Asp Arg Leu Ala 
1               5                   10              


<210>  36
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL2

<400>  36

Asp Val Ser Lys Leu Ala Ser 
1               5           


<210>  37
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDRL3

<400>  37

Leu Gly Gly Tyr Asp Cys Ser Ser Ala Glu Cys Asn Val 
1               5                   10              


<210>  38
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable domain

<400>  38

Gln Ser Leu Glu Glu Ser Gly Gly Arg Leu Val Thr Pro Gly Thr Pro 
1               5                   10                  15      


Leu Thr Leu Thr Cys Thr Val Ser Gly Ile Asp Leu Ser Arg Asp Thr 
            20                  25                  30          


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


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


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


Ile Thr Ser Pro Thr Thr Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg 
                85                  90                  95      


Asn Phe Ser Val Trp Gly Pro Gly Thr Leu Val Thr Val Ser Leu 
            100                 105                 110     


<210>  39
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable domain

<400>  39

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


Thr Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Val Tyr Asn Ser Asp 
            20                  25                  30          


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


Ile Tyr Asp Val Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Asp Val Gln 
65                  70                  75                  80  


Cys Asp Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Gly Tyr Asp Cys Ser 
                85                  90                  95      


Ser Ala Glu Cys Asn Val Phe Gly Gly Gly Thr Glu Val Val Val Lys 
            100                 105                 110         


<210>  40
<211>  140
<212>  PRT
<213>  Homo sapiens

<400>  40

Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu Gly Val Val 
1               5                   10                  15      


Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala Ala Gly Lys 
            20                  25                  30          


Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys Glu Gly Val 
        35                  40                  45              


Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys Glu Gln Val Thr 
    50                  55                  60                  


Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val Ala Gln Lys 
65                  70                  75                  80  


Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly Phe Val Lys 
                85                  90                  95      


Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly Ile 
            100                 105                 110         


Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr Glu Met Pro 
        115                 120                 125             


Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala 
    130                 135                 140 


<210>  41
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide

<400>  41

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


Gly Ser 
        


<210>  42
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rbHCfinal.up

<400>  42
aagcttgcca ccatggagac tgggctgcgc tggcttc                                37


<210>  43
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rbHCfinal.do

<400>  43
ccattggtga gggtgcccga g                                                 21


<210>  44
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rbLCfinal.up

<400>  44
aagcttgcca ccatggacay gagggccccc actc                                   34


<210>  45
<211>  26
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  rbLCfinal.do

<400>  45
cagagtrctg ctgaggttgt aggtac                                            26


<210>  46
<211>  324
<212>  PRT
<213>  Mus musculus

<400>  46

Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala 
1               5                   10                  15      


Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr 
            20                  25                  30          


Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser 
        35                  40                  45              


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu 
    50                  55                  60                  


Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val 
65                  70                  75                  80  


Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys 
                85                  90                  95      


Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro 
            100                 105                 110         


Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu 
        115                 120                 125             


Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser 
    130                 135                 140                 


Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu 
145                 150                 155                 160 


Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr 
                165                 170                 175     


Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn 
            180                 185                 190         


Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro 
        195                 200                 205             


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln 
    210                 215                 220                 


Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val 
225                 230                 235                 240 


Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val 
                245                 250                 255     


Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln 
            260                 265                 270         


Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn 
        275                 280                 285             


Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val 
    290                 295                 300                 


Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His 
305                 310                 315                 320 


Ser Pro Gly Lys 
                


<210>  47
<211>  107
<212>  PRT
<213>  Mus musculus

<400>  47

Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu 
1               5                   10                  15      


Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe 
            20                  25                  30          


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
        35                  40                  45              


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu 
65                  70                  75                  80  


Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
                85                  90                  95      


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
            100                 105         


<210>  48
<211>  106
<212>  PRT
<213>  Mus musculus

<400>  48

Gly Gln Pro Lys Ser Ser Pro Ser Val Thr Leu Phe Pro Pro Ser Ser 
1               5                   10                  15      


Glu Glu Leu Glu Thr Asn Lys Ala Thr Leu Val Cys Thr Ile Thr Asp 
            20                  25                  30          


Phe Tyr Pro Gly Val Val Thr Val Asp Trp Lys Val Asp Gly Thr Pro 
        35                  40                  45              


Val Thr Gln Gly Met Glu Thr Thr Gln Pro Ser Lys Gln Ser Asn Asn 
    50                  55                  60                  


Lys Tyr Met Ala Ser Ser Tyr Leu Thr Leu Thr Ala Arg Ala Trp Glu 
65                  70                  75                  80  


Arg His Ser Ser Tyr Ser Cys Gln Val Thr His Glu Gly His Thr Val 
                85                  90                  95      


Glu Lys Ser Leu Ser Arg Ala Asp Cys Ser 
            100                 105     


<210>  49
<211>  330
<212>  PRT
<213>  Homo sapiens

<400>  49

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
1               5                   10                  15      


Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
            20                  25                  30          


Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
    50                  55                  60                  


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
65                  70                  75                  80  


Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
        115                 120                 125             


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
    130                 135                 140                 


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
        195                 200                 205             


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 


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


Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
                245                 250                 255     


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
            260                 265                 270         


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
        275                 280                 285             


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
    290                 295                 300                 


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
305                 310                 315                 320 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 


<210>  50
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human Ig1 hole constant region

<400>  50

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
1               5                   10                  15      


Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
            20                  25                  30          


Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
    50                  55                  60                  


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
65                  70                  75                  80  


Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
        115                 120                 125             


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
    130                 135                 140                 


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
        195                 200                 205             


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 


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


Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr 
                245                 250                 255     


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
            260                 265                 270         


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
        275                 280                 285             


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
    290                 295                 300                 


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
305                 310                 315                 320 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 


<210>  51
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human Ig1 knob constant region

<400>  51

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
1               5                   10                  15      


Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
            20                  25                  30          


Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
    50                  55                  60                  


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
65                  70                  75                  80  


Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
        115                 120                 125             


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
    130                 135                 140                 


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
        195                 200                 205             


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 


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


Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
                245                 250                 255     


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
            260                 265                 270         


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
        275                 280                 285             


Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
    290                 295                 300                 


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
305                 310                 315                 320 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 


<210>  52
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human transferrin receptor fragment

<400>  52

Ile Gly Gln Asn Met Val Thr Ile Val Gln Ser Asn Gly Asn Leu 
1               5                   10                  15  


<210>  53
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human transferrin receptor fragment

<400>  53

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


<210>  54
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human transferrin receptor fragment

<400>  54

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


<210>  55
<211>  32
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptidic linker

<400>  55

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          


<210>  56
<211>  118
<212>  PRT
<213>  Mus musculus

<400>  56

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


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


Gly Met His Trp Ile Arg Gln Ala Pro Lys Lys Gly Leu Glu Trp Ile 
        35                  40                  45              


Ala Met Ile Tyr Tyr Asp Ser Ser Lys Met Asn Tyr Ala Asp Thr Val 
    50                  55                  60                  


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


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


Ala Val Pro Thr Ser His Tyr Val Val Asp Val Trp Gly Gln Gly Val 
            100                 105                 110         


Ser Val Thr Val Ser Ser 
        115             


<210>  57
<211>  107
<212>  PRT
<213>  Mus musculus

<400>  57

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


Glu Ile Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Gly Asn Trp 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Gln Leu Leu Ile 
        35                  40                  45              


Tyr Gly Ala Thr Ser Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Ser Arg Val Gln Val 
65                  70                  75                  80  


Glu Asp Ile Gly Ile Tyr Tyr Cys Leu Gln Ala Tyr Asn Thr Pro Trp 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys 
            100                 105         


<210>  58
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  L104V and L106I variant of SEQ ID NO: 57

<400>  58

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


Glu Ile Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Gly Asn Trp 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Gln Leu Leu Ile 
        35                  40                  45              


Tyr Gly Ala Thr Ser Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Gln Phe Ser Leu Lys Ile Ser Arg Val Gln Val 
65                  70                  75                  80  


Glu Asp Ile Gly Ile Tyr Tyr Cys Leu Gln Ala Tyr Asn Thr Pro Trp 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         


