                         SEQUENCE LISTING

<110>  Pollack, Aryeh L.
 
<120>  ANTI-VEGF ANTAGONIST AND PEDF AGONIST CONSTRUCTS AND USES THEREOF

<130>  ARPO.001WO

<150>  US 62/652472
<151>  2018-04-04

<160>  22    

<170>  PatentIn version 3.5

<210>  1
<211>  418
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Gln Ala Leu Val Leu Leu Leu Cys Ile Gly Ala Leu Leu Gly His 
1               5                   10                  15      


Ser Ser Cys Gln Asn Pro Ala Ser Pro Pro Glu Glu Gly Ser Pro Asp 
            20                  25                  30          


Pro Asp Ser Thr Gly Ala Leu Val Glu Glu Glu Asp Pro Phe Phe Lys 
        35                  40                  45              


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


Leu Tyr Arg Val Arg Ser Ser Thr Ser Pro Thr Thr Asn Val Leu Leu 
65                  70                  75                  80  


Ser Pro Leu Ser Val Ala Thr Ala Leu Ser Ala Leu Ser Leu Gly Ala 
                85                  90                  95      


Glu Gln Arg Thr Glu Ser Ile Ile His Arg Ala Leu Tyr Tyr Asp Leu 
            100                 105                 110         


Ile Ser Ser Pro Asp Ile His Gly Thr Tyr Lys Glu Leu Leu Asp Thr 
        115                 120                 125             


Val Thr Ala Pro Gln Lys Asn Leu Lys Ser Ala Ser Arg Ile Val Phe 
    130                 135                 140                 


Glu Lys Lys Leu Arg Ile Lys Ser Ser Phe Val Ala Pro Leu Glu Lys 
145                 150                 155                 160 


Ser Tyr Gly Thr Arg Pro Arg Val Leu Thr Gly Asn Pro Arg Leu Asp 
                165                 170                 175     


Leu Gln Glu Ile Asn Asn Trp Val Gln Ala Gln Met Lys Gly Lys Leu 
            180                 185                 190         


Ala Arg Ser Thr Lys Glu Ile Pro Asp Glu Ile Ser Ile Leu Leu Leu 
        195                 200                 205             


Gly Val Ala His Phe Lys Gly Gln Trp Val Thr Lys Phe Asp Ser Arg 
    210                 215                 220                 


Lys Thr Ser Leu Glu Asp Phe Tyr Leu Asp Glu Glu Arg Thr Val Arg 
225                 230                 235                 240 


Val Pro Met Met Ser Asp Pro Lys Ala Val Leu Arg Tyr Gly Leu Asp 
                245                 250                 255     


Ser Asp Leu Ser Cys Lys Ile Ala Gln Leu Pro Leu Thr Gly Ser Met 
            260                 265                 270         


Ser Ile Ile Phe Phe Leu Pro Leu Lys Val Thr Gln Asn Leu Thr Leu 
        275                 280                 285             


Ile Glu Glu Ser Leu Thr Ser Glu Phe Ile His Asp Ile Asp Arg Glu 
    290                 295                 300                 


Leu Lys Thr Val Gln Ala Val Leu Thr Val Pro Lys Leu Lys Leu Ser 
305                 310                 315                 320 


Tyr Glu Gly Glu Val Thr Lys Ser Leu Gln Glu Met Lys Leu Gln Ser 
                325                 330                 335     


Leu Phe Asp Ser Pro Asp Phe Ser Lys Ile Thr Gly Lys Pro Ile Lys 
            340                 345                 350         


Leu Thr Gln Val Glu His Arg Ala Gly Phe Glu Trp Asn Glu Asp Gly 
        355                 360                 365             


Ala Gly Thr Thr Pro Ser Pro Gly Leu Gln Pro Ala His Leu Thr Phe 
    370                 375                 380                 


Pro Leu Asp Tyr His Leu Asn Gln Pro Phe Ile Phe Val Leu Arg Asp 
385                 390                 395                 400 


Thr Asp Thr Gly Ala Leu Leu Phe Ile Gly Lys Ile Leu Asp Pro Arg 
                405                 410                 415     


Gly Pro 
        


<210>  2
<211>  34
<212>  PRT
<213>  Homo sapiens

<400>  2

Ser Pro Pro Glu Glu Gly Ser Pro Asp Pro Asp Ser Thr Gly Ala Leu 
1               5                   10                  15      


Val Glu Glu Glu Asp Pro Phe Phe Lys Val Pro Val Asn Lys Leu Ala 
            20                  25                  30          


Ala Ala 
        


<210>  3
<211>  34
<212>  PRT
<213>  Homo sapiens

<400>  3

Asp Pro Phe Phe Lys Val Pro Val Asn Lys Leu Ala Ala Ala Val Ser 
1               5                   10                  15      


Asn Phe Gly Tyr Asp Leu Tyr Arg Val Arg Ser Ser Thr Ser Pro Thr 
            20                  25                  30          


Thr Asn 
        


<210>  4
<211>  105
<212>  DNA
<213>  Homo sapiens

<400>  4
agtcccccgg aggagggcag ccccgacccc gacagcaccg gggcactggt ggaggaagaa       60

gaccccttct tcaaggtgcc cgtgaacaag ctggcagccg catga                      105


<210>  5
<211>  105
<212>  DNA
<213>  Homo sapiens

<400>  5
gacccctttt tcaaagtccc cgtaaacaaa ctggctgccg ctgtcagcaa cttcggctac       60

gacctgtata gggtgagatc tagcacgagc cccaccacca actga                      105


<210>  6
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Bevacizumab HCVR

<400>  6

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


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


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


Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  


Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Lys Tyr Pro His Tyr Tyr Gly Ser Ser His Trp Tyr Phe Asp Val 
            100                 105                 110         


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             


<210>  7
<211>  369
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Bevacizumab HCVR

<400>  7
gaggtgcagc tggtggagag cgggggtggc ctggtgcaac ccggtggcag ccttaggctg       60

agctgcgccg caagcggcta cactttcacc aactatggca tgaactgggt gaggcaggcc      120

cctggcaagg gcctggagtg ggtcggctgg atcaacacct acaccggcga gcccacctac      180

gcagcagact tcaagaggag gttcaccttt agcctggaca ccagcaagag caccgcctac      240

ctgcagatga acagcctcag ggccgaggac accgccgtgt actactgcgc caagtacccc      300

cactactacg gcagcagcca ctggtacttc gacgtgtggg gccagggcac ccttgtgacc      360

gtgagctct                                                              369


<210>  8
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Bevacizumab LCVR

<400>  8

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


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


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


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


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


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


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


<210>  9
<211>  321
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Bevacizumab LCVR

<400>  9
gacatccaga tgacccagag ccccagctcc ctgagcgcca gcgtgggcga cagggtgacc       60

atcacctgca gcgcctcaca ggatattagc aactacctga attggtatca gcagaagccc      120

ggcaaggccc ccaaggtgct gatctacttc accagcagct tgcacagcgg cgtgcccagc      180

aggttcagcg gcagtggcag cggcaccgac ttcacactga ccattagcag cctgcaaccc      240

gaggacttcg ccacctacta ctgccagcag tacagcaccg tcccctggac cttcggccag      300

ggcaccaagg ttgagatcaa g                                                321


<210>  10
<211>  231
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Ranibizumab Heavy Chain

<400>  10

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Asp Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  


Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 
        115                 120                 125             


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


Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
145                 150                 155                 160 


Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                165                 170                 175     


Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
            180                 185                 190         


Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
        195                 200                 205             


Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 
    210                 215                 220                 


Ser Cys Asp Lys Thr His Leu 
225                 230     


<210>  11
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Ranibizumab HCVR

<400>  11

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Asp Phe Thr His Tyr 
            20                  25                  30          


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


Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Ala Asp Phe 
    50                  55                  60                  


Lys Arg Arg Phe Thr Phe Ser Leu Asp Thr Ser Lys Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             


<210>  12
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Ranibizumab Light Chain

<400>  12

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


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


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


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


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


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


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


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


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  13
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Ranibizumab LCVR

<400>  13

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


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


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


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


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


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


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


<210>  14
<211>  431
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Aflibercept

<400>  14

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>  15
<211>  102
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Aflibercept VEGFR1 domain

<400>  15

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 
            100         


<210>  16
<211>  519
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Bevacizumab/Human IgG1/Human PEDF(24-57) Heavy chain

<400>  16

Met Asp Pro Lys Gly Ser Leu Ser Trp Arg Ile Leu Leu Phe Leu Ser 
1               5                   10                  15      


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


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


Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Arg Gln Ala 
    50                  55                  60                  


Pro Gly Lys Gly Leu Glu Trp Val Gly Trp Ile Asn Thr Tyr Thr Gly 
65                  70                  75                  80  


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


Asp Thr Ser Lys Ser Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala 
            100                 105                 110         


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Tyr Pro His Tyr Tyr Gly 
        115                 120                 125             


Ser Ser His Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr 
    130                 135                 140                 


Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 
145                 150                 155                 160 


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
                165                 170                 175     


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
            180                 185                 190         


Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 
        195                 200                 205             


Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 
    210                 215                 220                 


Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 
225                 230                 235                 240 


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


Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 
            260                 265                 270         


Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 
        275                 280                 285             


Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 
    290                 295                 300                 


Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 
305                 310                 315                 320 


Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 
                325                 330                 335     


Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 
            340                 345                 350         


Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 
        355                 360                 365             


Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
    370                 375                 380                 


Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 
385                 390                 395                 400 


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
                405                 410                 415     


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
            420                 425                 430         


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
        435                 440                 445             


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
    450                 455                 460                 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly 
465                 470                 475                 480 


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


Ser Thr Gly Ala Leu Val Glu Glu Glu Asp Pro Phe Phe Lys Val Pro 
            500                 505                 510         


Val Asn Lys Leu Ala Ala Ala 
        515                 


<210>  17
<211>  1567
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Bevacizumab/Human IgG1/Human PEDF (24-57) Heavy chain

<400>  17
cgccaccatg gaccccaagg gcagcctgag ctggagaatc ctgctgttcc tgagcctggc       60

cttcgagctg agctacggcg aggtgcagct ggtggagagc gggggtggcc tggtgcaacc      120

cggtggcagc cttaggctga gctgcgccgc aagcggctac actttcacca actatggcat      180

gaactgggtg aggcaggccc ctggcaaggg cctggagtgg gtcggctgga tcaacaccta      240

caccggcgag cccacctacg cagcagactt caagaggagg ttcaccttta gcctggacac      300

cagcaagagc accgcctacc tgcagatgaa cagcctcagg gccgaggaca ccgccgtgta      360

ctactgcgcc aagtaccccc actactacgg cagcagccac tggtacttcg acgtgtgggg      420

ccagggcacc cttgtgaccg tgagctctgc tagcaccaag ggccccagcg tgttccctct      480

ggcccccagc agcaagagca ccagcggcgg aaccgccgcc ctgggctgcc tggtgaagga      540

ctacttcccc gagcccgtga ccgtgtcctg gaacagcggc gctctgacca gcggagtgca      600

caccttccct gccgtgctgc agagcagcgg cctgtactcc ctgagcagcg tggtgaccgt      660

gcccagcagc agcctgggca cccagaccta catctgcaac gtgaaccaca agccctccaa      720

caccaaggtg gacaagaagg tggagcctaa gagctgcgac aagacccaca cctgccctcc      780

ctgccccgcc cccgagctgc tgggcggacc cagcgtgttc ctgttccctc ccaagcccaa      840

ggacaccctg atgatcagcc gcacccccga ggtgacctgc gtggtggtgg acgtgagcca      900

cgaggacccc gaggtgaagt tcaactggta cgtggacggc gtggaggtgc acaacgccaa      960

gaccaagcct cgggaggagc agtacaactc cacctaccgc gtggtgagcg tgctgaccgt     1020

gctgcaccag gactggctga acggcaagga gtacaagtgc aaggtgagca acaaggccct     1080

gcccgctccc atcgagaaga ccatcagcaa ggccaagggc cagccccggg agcctcaggt     1140

gtacaccctg ccccccagcc gcgaagagat gaccaagaac caggtgagcc tgacctgcct     1200

ggtgaagggc ttctacccct ccgacatcgc cgtggagtgg gagagcaacg gccagcctga     1260

gaacaactac aagaccaccc ctcccgtgct ggacagcgac ggcagcttct tcctgtacag     1320

caagctgacc gtggacaagt cccggtggca gcagggcaac gtgttcagct gcagcgtgat     1380

gcacgaggcc ctgcacaacc actacaccca gaagagcctg agcctgagcc ccggaggcgg     1440

aggtggtgca ggaggcggtg gaagtccccc ggaggagggc agccccgacc ccgacagcac     1500

cggggcactg gtggaggaag aagacccctt cttcaaggtg cccgtgaaca agctggcagc     1560

cgcatga                                                               1567


<210>  18
<211>  519
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Bevacizumab/Human IgG1/Human PEDF(44-77) Heavy chain

<400>  18

Met Asp Pro Lys Gly Ser Leu Ser Trp Arg Ile Leu Leu Phe Leu Ser 
1               5                   10                  15      


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


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


Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Arg Gln Ala 
    50                  55                  60                  


Pro Gly Lys Gly Leu Glu Trp Val Gly Trp Ile Asn Thr Tyr Thr Gly 
65                  70                  75                  80  


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


Asp Thr Ser Lys Ser Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala 
            100                 105                 110         


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Tyr Pro His Tyr Tyr Gly 
        115                 120                 125             


Ser Ser His Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr 
    130                 135                 140                 


Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 
145                 150                 155                 160 


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
                165                 170                 175     


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
            180                 185                 190         


Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly 
        195                 200                 205             


Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly 
    210                 215                 220                 


Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys 
225                 230                 235                 240 


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


Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu 
            260                 265                 270         


Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 
        275                 280                 285             


Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys 
    290                 295                 300                 


Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 
305                 310                 315                 320 


Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu 
                325                 330                 335     


Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 
            340                 345                 350         


Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 
        355                 360                 365             


Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
    370                 375                 380                 


Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 
385                 390                 395                 400 


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
                405                 410                 415     


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly 
            420                 425                 430         


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
        435                 440                 445             


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
    450                 455                 460                 


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly 
465                 470                 475                 480 


Ala Gly Gly Gly Gly Asp Pro Phe Phe Lys Val Pro Val Asn Lys Leu 
                485                 490                 495     


Ala Ala Ala Val Ser Asn Phe Gly Tyr Asp Leu Tyr Arg Val Arg Ser 
            500                 505                 510         


Ser Thr Ser Pro Thr Thr Asn 
        515                 


<210>  19
<211>  1567
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Bevacizumab/Human IgG1/Human PEDF(44-77) Heavy chain

<400>  19
cgccaccatg gaccccaagg gcagcctgag ctggagaatc ctgctgttcc tgagcctggc       60

cttcgagctg agctacggcg aggtgcagct ggtggagagc gggggtggcc tggtgcaacc      120

cggtggcagc cttaggctga gctgcgccgc aagcggctac actttcacca actatggcat      180

gaactgggtg aggcaggccc ctggcaaggg cctggagtgg gtcggctgga tcaacaccta      240

caccggcgag cccacctacg cagcagactt caagaggagg ttcaccttta gcctggacac      300

cagcaagagc accgcctacc tgcagatgaa cagcctcagg gccgaggaca ccgccgtgta      360

ctactgcgcc aagtaccccc actactacgg cagcagccac tggtacttcg acgtgtgggg      420

ccagggcacc cttgtgaccg tgagctctgc tagcaccaag ggccccagcg tgttccctct      480

ggcccccagc agcaagagca ccagcggcgg aaccgccgcc ctgggctgcc tggtgaagga      540

ctacttcccc gagcccgtga ccgtgtcctg gaacagcggc gctctgacca gcggagtgca      600

caccttccct gccgtgctgc agagcagcgg cctgtactcc ctgagcagcg tggtgaccgt      660

gcccagcagc agcctgggca cccagaccta catctgcaac gtgaaccaca agccctccaa      720

caccaaggtg gacaagaagg tggagcctaa gagctgcgac aagacccaca cctgccctcc      780

ctgccccgcc cccgagctgc tgggcggacc cagcgtgttc ctgttccctc ccaagcccaa      840

ggacaccctg atgatcagcc gcacccccga ggtgacctgc gtggtggtgg acgtgagcca      900

cgaggacccc gaggtgaagt tcaactggta cgtggacggc gtggaggtgc acaacgccaa      960

gaccaagcct cgggaggagc agtacaactc cacctaccgc gtggtgagcg tgctgaccgt     1020

gctgcaccag gactggctga acggcaagga gtacaagtgc aaggtgagca acaaggccct     1080

gcccgctccc atcgagaaga ccatcagcaa ggccaagggc cagccccggg agcctcaggt     1140

gtacaccctg ccccccagcc gcgaagagat gaccaagaac caggtgagcc tgacctgcct     1200

ggtgaagggc ttctacccct ccgacatcgc cgtggagtgg gagagcaacg gccagcctga     1260

gaacaactac aagaccaccc ctcccgtgct ggacagcgac ggcagcttct tcctgtacag     1320

caagctgacc gtggacaagt cccggtggca gcagggcaac gtgttcagct gcagcgtgat     1380

gcacgaggcc ctgcacaacc actacaccca gaagagcctg agcctgagcc ccggaggcgg     1440

aggtggtgca ggaggcggtg gagatccctt tttcaaagtc cccgtaaaca aactggctgc     1500

cgctgtcagc aacttcggct acgacctgta tagggtgaga tctagcacga gccccaccac     1560

caactga                                                               1567


<210>  20
<211>  234
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Bevacizumab/Human Ig/Human PEDF Light chain

<400>  20

Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


Gly Ser Thr Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser 
            20                  25                  30          


Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Gln Asp 
        35                  40                  45              


Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
    50                  55                  60                  


Lys Val Leu Ile Tyr Phe Thr Ser Ser Leu His Ser Gly Val Pro Ser 
65                  70                  75                  80  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
                85                  90                  95      


Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser 
            100                 105                 110         


Thr Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
        115                 120                 125             


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
    130                 135                 140                 


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
145                 150                 155                 160 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
                165                 170                 175     


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
            180                 185                 190         


Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
        195                 200                 205             


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
    210                 215                 220                 


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 


<210>  21
<211>  712
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Bevacizumab/Human Ig/Human PEDF Light chain

<400>  21
cgccaccatg gagaccgaca ccctgctgct ctgggtgctg ctgctctggg tgcccggctc       60

caccggagac atccagatga cccagagccc cagctccctg agcgccagcg tgggcgacag      120

ggtgaccatc acctgcagcg cctcacagga tattagcaac tacctgaatt ggtatcagca      180

gaagcccggc aaggccccca aggtgctgat ctacttcacc agcagcttgc acagcggcgt      240

gcccagcagg ttcagcggca gtggcagcgg caccgacttc acactgacca ttagcagcct      300

gcaacccgag gacttcgcca cctactactg ccagcagtac agcaccgtcc cctggacctt      360

cggccagggc accaaggttg agatcaagcg gaccgtggcc gcccccagcg tgttcatctt      420

ccctcccagc gacgagcagc tgaagtctgg caccgccagc gtggtgtgcc tgctgaacaa      480

cttctacccc cgcgaggcca aggtgcagtg gaaggtggac aacgccctgc agagcggcaa      540

cagccaggag agcgtgaccg agcaggactc caaggacagc acctacagcc tgagcagcac      600

cctgaccctg agcaaggccg actacgagaa gcacaaggtg tacgcctgcg aggtgaccca      660

ccagggactg tctagccccg tgaccaagag cttcaaccgg ggcgagtgct aa              712


<210>  22
<211>  504
<212>  PRT
<213>  Homo sapiens

<400>  22

Met Phe Pro Arg Glu Lys Thr Trp Asn Ile Ser Phe Ala Gly Cys Gly 
1               5                   10                  15      


Phe Leu Gly Val Tyr Tyr Val Gly Val Ala Ser Cys Leu Arg Glu His 
            20                  25                  30          


Ala Pro Phe Leu Val Ala Asn Ala Thr His Ile Tyr Gly Ala Ser Ala 
        35                  40                  45              


Gly Ala Leu Thr Ala Thr Ala Leu Val Thr Gly Val Cys Leu Gly Glu 
    50                  55                  60                  


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


Leu Gly Pro Leu His Pro Ser Phe Asn Leu Val Lys Ile Ile Arg Ser 
                85                  90                  95      


Phe Leu Leu Lys Val Leu Pro Ala Asp Ser His Glu His Ala Ser Gly 
            100                 105                 110         


Arg Leu Gly Ile Ser Leu Thr Arg Val Ser Asp Gly Glu Asn Val Ile 
        115                 120                 125             


Ile Ser His Phe Asn Ser Lys Asp Glu Leu Ile Gln Ala Asn Val Cys 
    130                 135                 140                 


Ser Gly Phe Ile Pro Val Tyr Cys Gly Leu Ile Pro Pro Ser Leu Gln 
145                 150                 155                 160 


Gly Val Arg Tyr Val Asp Gly Gly Ile Ser Asp Asn Leu Pro Leu Tyr 
                165                 170                 175     


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


Ile Cys Pro Gln Asp Ser Ser Thr Asn Ile His Glu Leu Arg Val Thr 
        195                 200                 205             


Asn Thr Ser Ile Gln Phe Asn Leu Arg Asn Leu Tyr Arg Leu Ser Lys 
    210                 215                 220                 


Ala Leu Phe Pro Pro Glu Pro Leu Val Leu Arg Glu Met Cys Lys Gln 
225                 230                 235                 240 


Gly Tyr Arg Asp Gly Leu Arg Phe Leu Gln Arg Asn Gly Leu Leu Asn 
                245                 250                 255     


Arg Pro Asn Pro Leu Leu Ala Leu Pro Pro Ala Arg Pro His Gly Pro 
            260                 265                 270         


Glu Asp Lys Asp Gln Ala Val Glu Ser Ala Gln Ala Glu Asp Tyr Ser 
        275                 280                 285             


Gln Leu Pro Gly Glu Asp His Ile Leu Glu His Leu Pro Ala Arg Leu 
    290                 295                 300                 


Asn Glu Ala Leu Leu Glu Ala Cys Val Glu Pro Thr Asp Leu Leu Thr 
305                 310                 315                 320 


Thr Leu Ser Asn Met Leu Pro Val Arg Leu Ala Thr Ala Met Met Val 
                325                 330                 335     


Pro Tyr Thr Leu Pro Leu Glu Ser Ala Leu Ser Phe Thr Ile Arg Leu 
            340                 345                 350         


Leu Glu Trp Leu Pro Asp Val Pro Glu Asp Ile Arg Trp Met Lys Glu 
        355                 360                 365             


Gln Thr Gly Ser Ile Cys Gln Tyr Leu Val Met Arg Ala Lys Arg Lys 
    370                 375                 380                 


Leu Gly Arg His Leu Pro Ser Arg Leu Pro Glu Gln Val Glu Leu Arg 
385                 390                 395                 400 


Arg Val Gln Ser Leu Pro Ser Val Pro Leu Ser Cys Ala Ala Tyr Arg 
                405                 410                 415     


Glu Ala Leu Pro Gly Trp Met Arg Asn Asn Leu Ser Leu Gly Asp Ala 
            420                 425                 430         


Leu Ala Lys Trp Glu Glu Cys Gln Arg Gln Leu Leu Leu Gly Leu Phe 
        435                 440                 445             


Cys Thr Asn Val Ala Phe Pro Pro Glu Ala Leu Arg Met Arg Ala Pro 
    450                 455                 460                 


Ala Asp Pro Ala Pro Ala Pro Ala Asp Pro Ala Ser Pro Gln His Gln 
465                 470                 475                 480 


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


Pro Val Ile Gly Ala Leu Gly Leu 
            500                 


