                         SEQUENCE LISTING

<110>  AMGEN INC.
 
<120>  AFLIBERCEPT ATTRIBUTES AND METHODS OF CHARACTERIZING AND 
       MODIFYING THEREOF

<130>  A-2287-WO-PCT

<150>  62/798,903
<151>  2019-01-30

<160>  8     

<170>  PatentIn version 3.5

<210>  1
<211>  431
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein

<400>  1

Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu 
1               5                   10                  15      


Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val 
            20                  25                  30          


Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr 
        35                  40                  45              


Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe 
    50                  55                  60                  


Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu 
65                  70                  75                  80  


Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg 
                85                  90                  95      


Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile 
            100                 105                 110         


Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr 
        115                 120                 125             


Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys 
    130                 135                 140                 


His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly 
145                 150                 155                 160 


Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr 
                165                 170                 175     


Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met 
            180                 185                 190         


Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Asp Lys Thr 
        195                 200                 205             


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
    210                 215                 220                 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
225                 230                 235                 240 


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
                245                 250                 255     


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
            260                 265                 270         


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
        275                 280                 285             


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


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
305                 310                 315                 320 


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


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 
            340                 345                 350         


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
        355                 360                 365             


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
    370                 375                 380                 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
385                 390                 395                 400 


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                405                 410                 415     


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            420                 425                 430     


<210>  2
<211>  432
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein

<400>  2

Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu 
1               5                   10                  15      


Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val 
            20                  25                  30          


Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr 
        35                  40                  45              


Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe 
    50                  55                  60                  


Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu 
65                  70                  75                  80  


Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg 
                85                  90                  95      


Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile 
            100                 105                 110         


Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr 
        115                 120                 125             


Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys 
    130                 135                 140                 


His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly 
145                 150                 155                 160 


Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr 
                165                 170                 175     


Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met 
            180                 185                 190         


Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Asp Lys Thr 
        195                 200                 205             


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
    210                 215                 220                 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
225                 230                 235                 240 


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
                245                 250                 255     


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
            260                 265                 270         


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
        275                 280                 285             


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


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
305                 310                 315                 320 


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


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 
            340                 345                 350         


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
        355                 360                 365             


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
    370                 375                 380                 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
385                 390                 395                 400 


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                405                 410                 415     


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
            420                 425                 430         


<210>  3
<211>  339
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein

<400>  3

Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro 
1               5                   10                  15      


Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys 
            20                  25                  30          


Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr 
        35                  40                  45              


Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys 
    50                  55                  60                  


Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile 
65                  70                  75                  80  


Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser 
                85                  90                  95      


Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu 
            100                 105                 110         


Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
        115                 120                 125             


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
    130                 135                 140                 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
145                 150                 155                 160 


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
                165                 170                 175     


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
            180                 185                 190         


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
        195                 200                 205             


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
    210                 215                 220                 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
225                 230                 235                 240 


Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
                245                 250                 255     


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
            260                 265                 270         


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
        275                 280                 285             


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
    290                 295                 300                 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
305                 310                 315                 320 


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
                325                 330                 335     


Ser Pro Gly 
            


<210>  4
<211>  340
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein

<400>  4

Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro 
1               5                   10                  15      


Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys 
            20                  25                  30          


Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr 
        35                  40                  45              


Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys 
    50                  55                  60                  


Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile 
65                  70                  75                  80  


Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser 
                85                  90                  95      


Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu 
            100                 105                 110         


Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
        115                 120                 125             


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
    130                 135                 140                 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
145                 150                 155                 160 


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
                165                 170                 175     


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
            180                 185                 190         


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
        195                 200                 205             


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
    210                 215                 220                 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
225                 230                 235                 240 


Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
                245                 250                 255     


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
            260                 265                 270         


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
        275                 280                 285             


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
    290                 295                 300                 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
305                 310                 315                 320 


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
                325                 330                 335     


Ser Pro Gly Lys 
            340 


<210>  5
<211>  92
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein

<400>  5

Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu 
1               5                   10                  15      


Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val 
            20                  25                  30          


Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr 
        35                  40                  45              


Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe 
    50                  55                  60                  


Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu 
65                  70                  75                  80  


Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr 
                85                  90          


<210>  6
<211>  278
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein

<400>  6

Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr 
1               5                   10                  15      


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


Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg 
        35                  40                  45              


Val His Glu Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
    50                  55                  60                  


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
65                  70                  75                  80  


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                85                  90                  95      


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
            100                 105                 110         


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
        115                 120                 125             


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
    130                 135                 140                 


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
145                 150                 155                 160 


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                165                 170                 175     


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
            180                 185                 190         


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
        195                 200                 205             


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
    210                 215                 220                 


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
225                 230                 235                 240 


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


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
            260                 265                 270         


Leu Ser Leu Ser Pro Gly 
        275             


<210>  7
<211>  279
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein

<400>  7

Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr 
1               5                   10                  15      


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


Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg 
        35                  40                  45              


Val His Glu Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
    50                  55                  60                  


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
65                  70                  75                  80  


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                85                  90                  95      


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
            100                 105                 110         


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
        115                 120                 125             


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
    130                 135                 140                 


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
145                 150                 155                 160 


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                165                 170                 175     


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
            180                 185                 190         


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
        195                 200                 205             


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
    210                 215                 220                 


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
225                 230                 235                 240 


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


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
            260                 265                 270         


Leu Ser Leu Ser Pro Gly Lys 
        275                 


<210>  8
<211>  153
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Protein

<400>  8

Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu 
1               5                   10                  15      


Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val 
            20                  25                  30          


Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr 
        35                  40                  45              


Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe 
    50                  55                  60                  


Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu 
65                  70                  75                  80  


Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg 
                85                  90                  95      


Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile 
            100                 105                 110         


Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr 
        115                 120                 125             


Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys 
    130                 135                 140                 


His Gln His Lys Lys Leu Val Asn Arg 
145                 150             


