                         SEQUENCE LISTING

<110>  Molecular Partners AG
       Binz, Hans Kaspar
       Forrer, Patrik
       Stumpp, Michael Tobias
 
<120>  Modified binding proteins inhibiting the VEGF-A receptor 
       interaction

<130>  P384A

<150>  EP10161685.2
<151>  2010-04-30

<160>  9     

<170>  PatentIn version 3.5

<210>  1
<211>  1025
<212>  PRT
<213>  Artificial

<220>
<223>  Ankyrin repeat protein

<400>  1

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


Asp Asp Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Ala 
            20                  25                  30          


Phe Asp Trp Met Gly Trp Thr Pro Leu His Leu Ala Ala His Glu Gly 
        35                  40                  45              


His Leu Glu Ile Val Glu Val Leu Leu Lys Asn Gly Ala Asp Val Asn 
    50                  55                  60                  


Ala Thr Asp Val Ser Gly Tyr Thr Pro Leu His Leu Ala Ala Ala Asp 
65                  70                  75                  80  


Gly His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val 
                85                  90                  95      


Asn Thr Lys Asp Asn Thr Gly Trp Thr Pro Leu His Leu Ser Ala Asp 
            100                 105                 110         


Leu Gly Arg Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp 
        115                 120                 125             


Val Asn Ala Gln Asp Lys Phe Gly Lys Thr Ala Phe Asp Ile Ser Ile 
    130                 135                 140                 


Asp Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Ala Ala Ser 
145                 150                 155                 160 


Gly Ser Pro Ala Gly Ser Pro Thr Ser Thr Glu Glu Gly Thr Ser Glu 
                165                 170                 175     


Ser Ala Thr Pro Glu Ser Gly Pro Gly Thr Ser Thr Glu Pro Ser Glu 
            180                 185                 190         


Gly Ser Ala Pro Gly Ser Pro Ala Gly Ser Pro Thr Ser Thr Glu Glu 
        195                 200                 205             


Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Thr 
    210                 215                 220                 


Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Glu Ser Ala Thr Pro 
225                 230                 235                 240 


Glu Ser Gly Pro Gly Ser Glu Pro Ala Thr Ser Gly Ser Glu Thr Pro 
                245                 250                 255     


Gly Ser Glu Pro Ala Thr Ser Gly Ser Glu Thr Pro Gly Ser Pro Ala 
            260                 265                 270         


Gly Ser Pro Thr Ser Thr Glu Glu Gly Thr Ser Glu Ser Ala Thr Pro 
        275                 280                 285             


Glu Ser Gly Pro Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro 
    290                 295                 300                 


Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro Gly Ser Pro Ala 
305                 310                 315                 320 


Gly Ser Pro Thr Ser Thr Glu Glu Gly Thr Ser Thr Glu Pro Ser Glu 
                325                 330                 335     


Gly Ser Ala Pro Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro 
            340                 345                 350         


Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro Gly Thr Ser Thr 
        355                 360                 365             


Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Glu Ser Ala Thr Pro 
    370                 375                 380                 


Glu Ser Gly Pro Gly Ser Glu Pro Ala Thr Ser Gly Ser Glu Thr Pro 
385                 390                 395                 400 


Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Thr 
                405                 410                 415     


Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Glu Ser Ala Thr Pro 
            420                 425                 430         


Glu Ser Gly Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro 
        435                 440                 445             


Gly Ser Pro Ala Gly Ser Pro Thr Ser Thr Glu Glu Gly Thr Ser Glu 
    450                 455                 460                 


Ser Ala Thr Pro Glu Ser Gly Pro Gly Ser Glu Pro Ala Thr Ser Gly 
465                 470                 475                 480 


Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro 
                485                 490                 495     


Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Thr 
            500                 505                 510         


Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Thr Glu Pro Ser Glu 
        515                 520                 525             


Gly Ser Ala Pro Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro 
    530                 535                 540                 


Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Thr 
545                 550                 555                 560 


Glu Pro Ser Glu Gly Ser Ala Pro Gly Ser Pro Ala Gly Ser Pro Thr 
                565                 570                 575     


Ser Thr Glu Glu Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro 
            580                 585                 590         


Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro Gly Ser Glu Pro 
        595                 600                 605             


Ala Thr Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro 
    610                 615                 620                 


Glu Ser Gly Pro Gly Ser Glu Pro Ala Thr Ser Gly Ser Glu Thr Pro 
625                 630                 635                 640 


Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro Gly Thr Ser Thr 
                645                 650                 655     


Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Glu Ser Ala Thr Pro 
            660                 665                 670         


Glu Ser Gly Pro Gly Ser Pro Ala Gly Ser Pro Thr Ser Thr Glu Glu 
        675                 680                 685             


Gly Ser Pro Ala Gly Ser Pro Thr Ser Thr Glu Glu Gly Ser Pro Ala 
    690                 695                 700                 


Gly Ser Pro Thr Ser Thr Glu Glu Gly Thr Ser Glu Ser Ala Thr Pro 
705                 710                 715                 720 


Glu Ser Gly Pro Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro 
                725                 730                 735     


Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro Gly Ser Glu Pro 
            740                 745                 750         


Ala Thr Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu Ser Ala Thr Pro 
        755                 760                 765             


Glu Ser Gly Pro Gly Ser Glu Pro Ala Thr Ser Gly Ser Glu Thr Pro 
    770                 775                 780                 


Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro Gly Thr Ser Thr 
785                 790                 795                 800 


Glu Pro Ser Glu Gly Ser Ala Pro Gly Ser Pro Ala Gly Ser Pro Thr 
                805                 810                 815     


Ser Thr Glu Glu Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro 
            820                 825                 830         


Gly Ser Glu Pro Ala Thr Ser Gly Ser Glu Thr Pro Gly Thr Ser Glu 
        835                 840                 845             


Ser Ala Thr Pro Glu Ser Gly Pro Gly Ser Pro Ala Gly Ser Pro Thr 
    850                 855                 860                 


Ser Thr Glu Glu Gly Ser Pro Ala Gly Ser Pro Thr Ser Thr Glu Glu 
865                 870                 875                 880 


Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro Gly Thr Ser Glu 
                885                 890                 895     


Ser Ala Thr Pro Glu Ser Gly Pro Gly Thr Ser Glu Ser Ala Thr Pro 
            900                 905                 910         


Glu Ser Gly Pro Gly Thr Ser Glu Ser Ala Thr Pro Glu Ser Gly Pro 
        915                 920                 925             


Gly Ser Glu Pro Ala Thr Ser Gly Ser Glu Thr Pro Gly Ser Glu Pro 
    930                 935                 940                 


Ala Thr Ser Gly Ser Glu Thr Pro Gly Ser Pro Ala Gly Ser Pro Thr 
945                 950                 955                 960 


Ser Thr Glu Glu Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro 
                965                 970                 975     


Gly Thr Ser Thr Glu Pro Ser Glu Gly Ser Ala Pro Gly Ser Glu Pro 
            980                 985                 990         


Ala Thr Ser Gly Ser Glu Thr Pro  Gly Thr Ser Glu Ser  Ala Thr Pro 
        995                 1000                 1005             


Glu Ser  Gly Pro Gly Thr Ser  Thr Glu Pro Ser Glu  Gly Ser Ala 
    1010                 1015                 1020             


Pro Gly  
    1025 


<210>  2
<211>  168
<212>  PRT
<213>  Artificial

<220>
<223>  Ankyrin repeat protein

<400>  2

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


Asp Asp Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Ala 
            20                  25                  30          


Phe Asp Trp Met Gly Trp Thr Pro Leu His Leu Ala Ala His Glu Gly 
        35                  40                  45              


His Leu Glu Ile Val Glu Val Leu Leu Lys Asn Gly Ala Asp Val Asn 
    50                  55                  60                  


Ala Thr Asp Val Ser Gly Tyr Thr Pro Leu His Leu Ala Ala Ala Asp 
65                  70                  75                  80  


Gly His Leu Glu Ile Val Glu Val Leu Leu Lys His Gly Ala Asp Val 
                85                  90                  95      


Asn Thr Lys Asp Asn Thr Gly Trp Thr Pro Leu His Leu Ser Ala Asp 
            100                 105                 110         


Leu Gly His Leu Glu Ile Val Glu Val Leu Leu Lys Asn Gly Ala Asp 
        115                 120                 125             


Val Asn Ala Gln Asp Lys Phe Gly Lys Thr Ala Phe Asp Ile Ser Ile 
    130                 135                 140                 


Asp Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Ala Ala Gly 
145                 150                 155                 160 


Gly Gly Ser Gly Gly Gly Ser Cys 
                165             


<210>  3
<211>  135
<212>  PRT
<213>  Artificial

<220>
<223>  Ankyrin repeat protein

<400>  3

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


Asp Asp Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Ala 
            20                  25                  30          


Arg Asp Ser Thr Gly Trp Thr Pro Leu His Leu Ala Ala Pro Trp Gly 
        35                  40                  45              


His Pro Glu Ile Val Glu Val Leu Leu Lys Asn Gly Ala Asp Val Asn 
    50                  55                  60                  


Ala Ala Asp Phe Gln Gly Trp Thr Pro Leu His Leu Ala Ala Ala Val 
65                  70                  75                  80  


Gly His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val 
                85                  90                  95      


Asn Ala Gln Asp Lys Phe Gly Lys Thr Ala Phe Asp Ile Ser Ile Asp 
            100                 105                 110         


Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Ala Ala Gly Gly 
        115                 120                 125             


Gly Ser Gly Gly Gly Ser Cys 
    130                 135 


<210>  4
<211>  540
<212>  PRT
<213>  Artificial

<220>
<223>  Ankyrin repeat protein

<400>  4

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


Asp Asp Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Thr 
            20                  25                  30          


Ala Asp Ser Thr Gly Trp Thr Pro Leu His Leu Ala Val Pro Trp Gly 
        35                  40                  45              


His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val Asn 
    50                  55                  60                  


Ala Lys Asp Phe Gln Gly Trp Thr Pro Leu His Leu Ala Ala Ala Ile 
65                  70                  75                  80  


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


Asn Ala Gln Asp Lys Phe Gly Lys Thr Ala Phe Asp Ile Ser Ile Asp 
            100                 105                 110         


Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Ala Ala Gly Ser 
        115                 120                 125             


Gly Ser Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro 
    130                 135                 140                 


Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser 
145                 150                 155                 160 


Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro 
                165                 170                 175     


Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser 
            180                 185                 190         


Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala 
        195                 200                 205             


Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro 
    210                 215                 220                 


Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser 
225                 230                 235                 240 


Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro 
                245                 250                 255     


Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser 
            260                 265                 270         


Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala 
        275                 280                 285             


Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro 
    290                 295                 300                 


Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser 
305                 310                 315                 320 


Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro 
                325                 330                 335     


Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser 
            340                 345                 350         


Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala 
        355                 360                 365             


Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro 
    370                 375                 380                 


Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser 
385                 390                 395                 400 


Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro 
                405                 410                 415     


Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser 
            420                 425                 430         


Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala 
        435                 440                 445             


Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro 
    450                 455                 460                 


Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser 
465                 470                 475                 480 


Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser Pro Ala Ala Pro 
                485                 490                 495     


Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala Pro Ala Ala Ser 
            500                 505                 510         


Pro Ala Ala Pro Ala Pro Ala Ser Pro Ala Ala Pro Ala Pro Ser Ala 
        515                 520                 525             


Pro Ala Ala Ser Pro Ala Ala Pro Ala Pro Ala Ser 
    530                 535                 540 


<210>  5
<211>  135
<212>  PRT
<213>  Artificial

<220>
<223>  Ankyrin repeat protein

<400>  5

Gly Ser Asp Leu Gly Lys Lys Leu Leu Glu Ala Ala Arg Val Gly Gln 
1               5                   10                  15      


Asp Asp Glu Val Arg Ile Leu Met Ala Asp Gly Ala Asp Val Asn Ala 
            20                  25                  30          


Ser Asp Phe Lys Gly Asp Thr Pro Leu His Leu Ala Ala Ser Gln Gly 
        35                  40                  45              


His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val Asn 
    50                  55                  60                  


Ala Tyr Asp Met Leu Gly Trp Thr Pro Leu His Leu Ala Ala Asp Leu 
65                  70                  75                  80  


Gly His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val 
                85                  90                  95      


Asn Ala Gln Asp Arg Phe Gly Lys Thr Ala Phe Asp Ile Ser Ile Asp 
            100                 105                 110         


Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Ala Ala Gly Ser 
        115                 120                 125             


Pro Ser Thr Ala Asp Gly Cys 
    130                 135 


<210>  6
<211>  130
<212>  PRT
<213>  Artificial

<220>
<223>  Ankyrin repeat protein

<400>  6

Gly Ser Asp Leu Gly Lys Lys Leu Leu Glu Ala Val Arg Ala Gly Gln 
1               5                   10                  15      


Asp Asp Glu Val Arg Ile Leu Met Thr Asn Gly Ala Asp Val Asn Ala 
            20                  25                  30          


Lys Asp Gln Phe Gly Phe Thr Pro Leu Gln Leu Ala Ala Tyr Asn Gly 
        35                  40                  45              


His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val Asn 
    50                  55                  60                  


Ala Phe Asp Ile Phe Gly Trp Thr Pro Leu His Leu Ala Ala Asp Leu 
65                  70                  75                  80  


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


Asn Ala Gln Asp Lys Phe Gly Arg Thr Ala Phe Asp Ile Ser Ile Asp 
            100                 105                 110         


Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Ala Ala Ser Gly 
        115                 120                 125             


Ser Cys 
    130 


<210>  7
<211>  168
<212>  PRT
<213>  Artificial

<220>
<223>  Ankyrin repeat protein

<400>  7

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


Asp Asp Glu Val Arg Ile Leu Met Ala Asn Gly Ala Asp Val Asn Ala 
            20                  25                  30          


Val Asp Tyr Ile Gly Trp Thr Pro Leu His Leu Ala Ala Ala Tyr Gly 
        35                  40                  45              


His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Ser Ala Asp Val Asn 
    50                  55                  60                  


Ala Glu Asp Phe Ala Gly Tyr Thr Pro Leu His Leu Ala Ala Ser Asn 
65                  70                  75                  80  


Gly His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp Val 
                85                  90                  95      


Asn Thr Lys Asp Asn Thr Gly Trp Thr Pro Leu His Leu Ser Ala Asp 
            100                 105                 110         


Leu Gly His Leu Glu Ile Val Glu Val Leu Leu Lys Tyr Gly Ala Asp 
        115                 120                 125             


Val Asn Thr Gln Asp Lys Phe Gly Lys Thr Ala Phe Asp Ile Ser Ile 
    130                 135                 140                 


Asp Asn Gly Asn Glu Asp Leu Ala Glu Ile Leu Gln Lys Ala Ala Gly 
145                 150                 155                 160 


Ser Pro Ser Thr Ala Asp Gly Cys 
                165             


<210>  8
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  Polypeptide linker

<400>  8

Gly Gly Gly Ser Gly Gly Gly Ser Cys 
1               5                   


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

<220>
<223>  Polypeptide linker

<400>  9

Gly Ser Pro Ser Thr Ala Asp Gly Cys 
1               5                   


