                         SEQUENCE LISTING

<110>  Regeneron Pharmaceuticals, Inc.
       Lobov, Ivan B
 
<120>  METHODS OF TREATING EYE DISORDERS WITH APLNR ANTAGONISTS AND VEGF INHIBITORS

<130>  125984-239667

<150>  62/502,621
<151>  2017-05-06

<160>  23    

<170>  PatentIn version 3.5

<210>  1
<211>  384
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  1
gaggtacaac tggtggagtc tgggggaggc ttggcccagc cgggggggtc cctgagactc       60

tcctgtgcag cctctggttt cactttcagt aactattgga tgagctgggt ccgccaggct      120

ccagggaagg ggctggagtg ggtggccaat ataaaacaag atgggagtga gaaatactat      180

ttggagtctg tgaagggccg attcaccatc tccagagaca acgccaagaa tttattgtat      240

ctgcaaatga acagcctgag agccgaggac acggctgttt tttactgtgc gagacctgga      300

ctattacgct ttttggagcc tgggaggcgc tactactccg gtatgaacgt ctggggccaa      360

gggaccacgg tcaccgtctc ctca                                             384


<210>  2
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  2

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


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


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


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


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


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


Ala Arg Pro Gly Leu Leu Arg Phe Leu Glu Pro Gly Arg Arg Tyr Tyr 
            100                 105                 110         


Ser Gly Met Asn Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 125             


<210>  3
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  3

Gly Phe Thr Phe Ser Asn Tyr Trp 
1               5               


<210>  4
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  4

Ile Lys Gln Asp Gly Ser Glu Lys 
1               5               


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

<220>
<223>  synthetic

<400>  5

Ala Arg Pro Gly Leu Leu Arg Phe Leu Glu Pro Gly Arg Arg Tyr Tyr 
1               5                   10                  15      


Ser Gly Met Asn Val 
            20      


<210>  6
<211>  321
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  6
gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc       60

atcacttgct gggccagtca gggcattcgc agttatttag cctggtatca gcaaaaacca      120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca      180

aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct      240

gaagattttg caacttatta ctgtcaacag tttaatagtt acccgtggac gttcggccaa      300

gggaccaagg tggaaatcaa a                                                321


<210>  7
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic

<400>  7

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


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


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


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


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


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


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


<210>  8
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  8

Gln Gly Ile Arg Ser Tyr 
1               5       


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

<220>
<223>  synthetic

<400>  9

Ala Ala Ser 
1           


<210>  10
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  10

Gln Gln Phe Asn Ser Tyr Pro Trp Thr 
1               5                   


<210>  11
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  11
ctacagcata agagttaccc tcggacg                                           27


<210>  12
<211>  378
<212>  DNA
<213>  Artificial sequence

<220>
<223>  synthetic

<400>  12
caggtgaagt tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc       60

tcctgtgcag cgtctggatt caccttcagt aactatgtca tacactgggt ccgccaggct      120

ccaggcaagg ggctggagtg ggtggcggtt atatggtatg atggaagtaa taaatactat      180

gcagactccg tgaagggccg attcaccatc tccagagaca actccaagaa tacgctgtat      240

ttgcaaatga acagcctgag agccgaggac acggctgtgt attactgtgc gagagatcgg      300

gtggttcggg gagtcgatta ctactactac tacggtttgg acgtctgggg ccaagggacc      360

tcggtcaccg tctcctca                                                    378


<210>  13
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  13

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


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


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


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


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


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


Ala Arg Asp Arg Val Val Arg Gly Val Asp Tyr Tyr Tyr Tyr Tyr Gly 
            100                 105                 110         


Leu Asp Val Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser 
        115                 120                 125     


<210>  14
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  14

Gly Phe Thr Phe Ser Asn Tyr Val 
1               5               


<210>  15
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  15

Ile Trp Tyr Asp Gly Ser Asn Lys 
1               5               


<210>  16
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  16

Ala Arg Asp Arg Val Val Arg Gly Val Asp Tyr Tyr Tyr Tyr Tyr Gly 
1               5                   10                  15      


Leu Asp Val 
            


<210>  17
<211>  321
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  17
gaaatagtga tgacgcagtc tccagccacc ctgtctgtgt ctccagggga aagagccacc       60

ctctcctgca gggccagtca gagtgttaga agcaacttag cctggtacca acagaaacct      120

ggccaggctc ccaggctcct catctatggt gcatcctcca gggccactgg tatcccagcc      180

aggttcagtg gcactgggtc tgggacagag ttcactctca ccatcagcag cctgcagtct      240

gacgattttg cagtttatta ctgtcagcaa tataataagt ggcctcggac gttcggccaa      300

gggaccaagg tggaaatcaa g                                                321


<210>  18
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  18

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Ser Asn 
            20                  25                  30          


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


Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  


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


Asp Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asn Lys Trp Pro Arg 
                85                  90                  95      


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


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

<220>
<223>  synthetic

<400>  19

Gln Ser Val Arg Ser Asn 
1               5       


<210>  20
<211>  3
<212>  PRT
<213>  Artificial sequence

<220>
<223>  synthetic

<400>  20

Gly Ala Ser 
1           


<210>  21
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  21

Gln Gln Tyr Asn Lys Trp Pro Arg Thr 
1               5                   


<210>  22
<211>  380
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  synthetic

<400>  22

Met Glu Glu Gly Gly Asp Phe Asp Asn Tyr Tyr Gly Ala Asp Asn Gln 
1               5                   10                  15      


Ser Glu Cys Glu Tyr Thr Asp Trp Lys Ser Ser Gly Ala Leu Ile Pro 
            20                  25                  30          


Ala Ile Tyr Met Leu Val Phe Leu Leu Gly Thr Thr Gly Asn Gly Leu 
        35                  40                  45              


Val Leu Trp Thr Val Phe Arg Ser Ser Arg Glu Lys Arg Arg Ser Ala 
    50                  55                  60                  


Asp Ile Phe Ile Ala Ser Leu Ala Val Ala Asp Leu Thr Phe Val Val 
65                  70                  75                  80  


Thr Leu Pro Leu Trp Ala Thr Tyr Thr Tyr Arg Asp Tyr Asp Trp Pro 
                85                  90                  95      


Phe Gly Thr Phe Phe Cys Lys Leu Ser Ser Tyr Leu Ile Phe Val Asn 
            100                 105                 110         


Met Tyr Ala Ser Val Phe Cys Leu Thr Gly Leu Ser Phe Asp Arg Tyr 
        115                 120                 125             


Leu Ala Ile Val Arg Pro Val Ala Asn Ala Arg Leu Arg Leu Arg Val 
    130                 135                 140                 


Ser Gly Ala Val Ala Thr Ala Val Leu Trp Val Leu Ala Ala Leu Leu 
145                 150                 155                 160 


Ala Met Pro Val Met Val Leu Arg Thr Thr Gly Asp Leu Glu Asn Thr 
                165                 170                 175     


Thr Lys Val Gln Cys Tyr Met Asp Tyr Ser Met Val Ala Thr Val Ser 
            180                 185                 190         


Ser Glu Trp Ala Trp Glu Val Gly Leu Gly Val Ser Ser Thr Thr Val 
        195                 200                 205             


Gly Phe Val Val Pro Phe Thr Ile Met Leu Thr Cys Tyr Phe Phe Ile 
    210                 215                 220                 


Ala Gln Thr Ile Ala Gly His Phe Arg Lys Glu Arg Ile Glu Gly Leu 
225                 230                 235                 240 


Arg Lys Arg Arg Arg Leu Leu Ser Ile Ile Val Val Leu Val Val Thr 
                245                 250                 255     


Phe Ala Leu Cys Trp Met Pro Tyr His Leu Val Lys Thr Leu Tyr Met 
            260                 265                 270         


Leu Gly Ser Leu Leu His Trp Pro Cys Asp Phe Asp Leu Phe Leu Met 
        275                 280                 285             


Asn Ile Phe Pro Tyr Cys Thr Cys Ile Ser Tyr Val Asn Ser Cys Leu 
    290                 295                 300                 


Asn Pro Phe Leu Tyr Ala Phe Phe Asp Pro Arg Phe Arg Gln Ala Cys 
305                 310                 315                 320 


Thr Ser Met Leu Cys Cys Gly Gln Ser Arg Cys Ala Gly Thr Ser His 
                325                 330                 335     


Ser Ser Ser Gly Glu Lys Ser Ala Ser Tyr Ser Ser Gly His Ser Gln 
            340                 345                 350         


Gly Pro Gly Pro Asn Met Gly Lys Gly Gly Glu Gln Met His Glu Lys 
        355                 360                 365             


Ser Ile Pro Tyr Ser Gln Glu Thr Leu Val Val Asp 
    370                 375                 380 


<210>  23
<211>  458
<212>  PRT
<213>  Homo sapiens

<400>  23

Met Val Ser Tyr Trp Asp Thr Gly Val Leu Leu Cys Ala Leu Leu Ser 
1               5                   10                  15      


Cys Leu Leu Leu Thr Gly Ser Ser Ser Gly Ser Asp Thr Gly Arg Pro 
            20                  25                  30          


Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu 
        35                  40                  45              


Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr 
    50                  55                  60                  


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


Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr 
                85                  90                  95      


Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His 
            100                 105                 110         


Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile 
        115                 120                 125             


Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu 
    130                 135                 140                 


Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile 
145                 150                 155                 160 


Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu 
                165                 170                 175     


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


Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gln Gly Leu 
        195                 200                 205             


Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr 
    210                 215                 220                 


Phe Val Arg Val His Glu Lys Asp Lys Thr His Thr Cys Pro Pro Cys 
225                 230                 235                 240 


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
                245                 250                 255     


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
            260                 265                 270         


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
        275                 280                 285             


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
    290                 295                 300                 


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
305                 310                 315                 320 


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
                325                 330                 335     


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
            340                 345                 350         


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
        355                 360                 365             


Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
    370                 375                 380                 


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
385                 390                 395                 400 


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
                405                 410                 415     


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
            420                 425                 430         


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
        435                 440                 445             


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    450                 455             


