                         SEQUENCE LISTING

<110>  ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)
 
<120>  IL10/FC FUSION PROTEINS USEFUL AS ENHANCERS OF IMMUNOTHERAPIES

<130>  P2401PC00

<150>  EP19198358.4
<151>  2019-09-19

<160>  17    

<170>  PatentIn version 3.5

<210>  1
<211>  160
<212>  PRT
<213>  Homo sapiens

<400>  1

Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His Phe Pro 
1               5                   10                  15      


Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe Ser Arg 
            20                  25                  30          


Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu Leu Leu 
        35                  40                  45              


Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys Gln Ala 
    50                  55                  60                  


Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro Gln Ala 
65                  70                  75                  80  


Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu Gly Glu 
                85                  90                  95      


Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg Phe Leu 
            100                 105                 110         


Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn Ala Phe 
        115                 120                 125             


Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu Phe Asp 
    130                 135                 140                 


Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile Arg Asn 
145                 150                 155                 160 


<210>  2
<211>  217
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Non-cytolytic IgG1 Fc

<400>  2

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


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            20                  25                  30          


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
        35                  40                  45              


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    50                  55                  60                  


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
65                  70                  75                  80  


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


Ala Leu Pro Ala Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
            100                 105                 110         


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
        115                 120                 125             


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
    130                 135                 140                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
145                 150                 155                 160 


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                165                 170                 175     


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
            180                 185                 190         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        195                 200                 205             


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215         


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

<220>
<223>  Flexible hinge 1

<400>  3

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


<210>  4
<211>  392
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IL-10/Fc fusion protein 1

<400>  4

Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His Phe Pro 
1               5                   10                  15      


Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe Ser Arg 
            20                  25                  30          


Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu Leu Leu 
        35                  40                  45              


Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys Gln Ala 
    50                  55                  60                  


Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro Gln Ala 
65                  70                  75                  80  


Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu Gly Glu 
                85                  90                  95      


Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg Phe Leu 
            100                 105                 110         


Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn Ala Phe 
        115                 120                 125             


Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu Phe Asp 
    130                 135                 140                 


Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile Arg Asn 
145                 150                 155                 160 


Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
                165                 170                 175     


Pro Glu Val Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
            180                 185                 190         


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
        195                 200                 205             


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
    210                 215                 220                 


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
225                 230                 235                 240 


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                245                 250                 255     


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
            260                 265                 270         


Leu Pro Ala Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
        275                 280                 285             


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
    290                 295                 300                 


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
305                 310                 315                 320 


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                325                 330                 335     


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
            340                 345                 350         


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
        355                 360                 365             


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
    370                 375                 380                 


Ser Leu Ser Leu Ser Pro Gly Lys 
385                 390         


<210>  5
<211>  216
<212>  PRT
<213>  Artificial sequence

<220>
<223>  IgG2 Fc

<400>  5

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


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
            20                  25                  30          


Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
        35                  40                  45              


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
    50                  55                  60                  


Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln 
65                  70                  75                  80  


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


Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro 
            100                 105                 110         


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
        115                 120                 125             


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
    130                 135                 140                 


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
145                 150                 155                 160 


Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
                165                 170                 175     


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
            180                 185                 190         


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
        195                 200                 205             


Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215     


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

<220>
<223>  Flexible hinge 2

<400>  6

Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro 
1               5                   10          


<210>  7
<211>  388
<212>  PRT
<213>  Artificial sequence

<220>
<223>  IL-10/Fc fusion protein 2

<400>  7

Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His Phe Pro 
1               5                   10                  15      


Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe Ser Arg 
            20                  25                  30          


Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu Leu Leu 
        35                  40                  45              


Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys Gln Ala 
    50                  55                  60                  


Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro Gln Ala 
65                  70                  75                  80  


Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu Gly Glu 
                85                  90                  95      


Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg Phe Leu 
            100                 105                 110         


Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn Ala Phe 
        115                 120                 125             


Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu Phe Asp 
    130                 135                 140                 


Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile Arg Asn 
145                 150                 155                 160 


Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
                165                 170                 175     


Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            180                 185                 190         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        195                 200                 205             


His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 
    210                 215                 220                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 
225                 230                 235                 240 


Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn 
                245                 250                 255     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 
            260                 265                 270         


Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln 
        275                 280                 285             


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
    290                 295                 300                 


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
305                 310                 315                 320 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                325                 330                 335     


Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            340                 345                 350         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        355                 360                 365             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Lys 
385             


<210>  8
<211>  217
<212>  PRT
<213>  Artificial sequence

<220>
<223>  IgG3 Fc

<400>  8

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


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            20                  25                  30          


Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Lys Trp Tyr 
        35                  40                  45              


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    50                  55                  60                  


Gln Tyr Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Leu His 
65                  70                  75                  80  


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


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln 
            100                 105                 110         


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
        115                 120                 125             


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
    130                 135                 140                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Ser Gly Gln Pro Glu Asn Asn 
145                 150                 155                 160 


Tyr Asn Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                165                 170                 175     


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Ile 
            180                 185                 190         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln 
        195                 200                 205             


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215         


<210>  9
<211>  62
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Flexible hinge 3

<400>  9

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>  10
<211>  439
<212>  PRT
<213>  Artificial sequence

<220>
<223>  IL-10/Fc fusion protein 3

<400>  10

Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His Phe Pro 
1               5                   10                  15      


Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe Ser Arg 
            20                  25                  30          


Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu Leu Leu 
        35                  40                  45              


Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys Gln Ala 
    50                  55                  60                  


Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro Gln Ala 
65                  70                  75                  80  


Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu Gly Glu 
                85                  90                  95      


Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg Phe Leu 
            100                 105                 110         


Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn Ala Phe 
        115                 120                 125             


Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu Phe Asp 
    130                 135                 140                 


Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile Arg Asn 
145                 150                 155                 160 


Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro Arg Cys 
                165                 170                 175     


Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro 
            180                 185                 190         


Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Glu 
        195                 200                 205             


Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro Ala Pro 
    210                 215                 220                 


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 


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


Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Lys Trp Tyr Val Asp 
            260                 265                 270         


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
        275                 280                 285             


Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
    290                 295                 300                 


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
305                 310                 315                 320 


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg 
                325                 330                 335     


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
            340                 345                 350         


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
        355                 360                 365             


Ile Ala Val Glu Trp Glu Ser Ser Gly Gln Pro Glu Asn Asn Tyr Asn 
    370                 375                 380                 


Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
385                 390                 395                 400 


Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Ile Phe Ser 
                405                 410                 415     


Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln Lys Ser 
            420                 425                 430         


Leu Ser Leu Ser Pro Gly Lys 
        435                 


<210>  11
<211>  217
<212>  PRT
<213>  Artificial sequence

<220>
<223>  IgG4 Fc


<220>
<221>  misc_feature
<222>  (85)..(85)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (95)..(95)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (108)..(108)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (110)..(110)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (186)..(186)
<223>  Xaa can be any naturally occurring amino acid

<400>  11

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


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            20                  25                  30          


Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr 
        35                  40                  45              


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    50                  55                  60                  


Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
65                  70                  75                  80  


Gln Asp Trp Leu Xaa Gly Lys Glu Tyr Lys Cys Lys Val Ser Xaa Lys 
                85                  90                  95      


Gly Leu Gly Ser Ser Ile Glu Lys Thr Ile Ser Xaa Ala Xaa Gly Gln 
            100                 105                 110         


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met 
        115                 120                 125             


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
    130                 135                 140                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
145                 150                 155                 160 


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                165                 170                 175     


Tyr Ser Arg Leu Thr Val Asp Lys Ser Xaa Trp Gln Glu Gly Asn Val 
            180                 185                 190         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        195                 200                 205             


Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    210                 215         


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

<220>
<223>  Flexible hinge 4

<400>  12

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 
1               5                   10          


<210>  13
<211>  389
<212>  PRT
<213>  Artificial sequence

<220>
<223>  IL-10/Fc fusion protein 4


<220>
<221>  misc_feature
<222>  (257)..(257)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (267)..(267)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (280)..(280)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (282)..(282)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (358)..(358)
<223>  Xaa can be any naturally occurring amino acid

<400>  13

Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His Phe Pro 
1               5                   10                  15      


Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe Ser Arg 
            20                  25                  30          


Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu Leu Leu 
        35                  40                  45              


Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys Gln Ala 
    50                  55                  60                  


Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro Gln Ala 
65                  70                  75                  80  


Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu Gly Glu 
                85                  90                  95      


Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg Phe Leu 
            100                 105                 110         


Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn Ala Phe 
        115                 120                 125             


Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu Phe Asp 
    130                 135                 140                 


Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile Arg Asn 
145                 150                 155                 160 


Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe 
                165                 170                 175     


Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            180                 185                 190         


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        195                 200                 205             


Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    210                 215                 220                 


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
225                 230                 235                 240 


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                245                 250                 255     


Xaa Gly Lys Glu Tyr Lys Cys Lys Val Ser Xaa Lys Gly Leu Gly Ser 
            260                 265                 270         


Ser Ile Glu Lys Thr Ile Ser Xaa Ala Xaa Gly Gln Pro Arg Glu Pro 
        275                 280                 285             


Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    290                 295                 300                 


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
305                 310                 315                 320 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                325                 330                 335     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 
            340                 345                 350         


Thr Val Asp Lys Ser Xaa Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        355                 360                 365             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    370                 375                 380                 


Leu Ser Leu Gly Lys 
385                 


<210>  14
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Flexible hinge 5

<400>  14

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Pro Pro Cys Pro 
1               5                   10                  15  


<210>  15
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  CPPCP domain

<400>  15

Cys Pro Pro Cys Pro 
1               5   


<210>  16
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  Flexible hinge 6

<400>  16

Gly Gly Ser Cys Pro Pro Cys Pro 
1               5               


<210>  17
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  Flexible hinge 7

<400>  17

Gly Gly Gly Gly Ser Cys Pro Pro Cys Pro 
1               5                   10  


