                         SEQUENCE LISTING

<110>  Aptitude Medical Systems, Inc
 
<120>  APTAMERS AND USE THEREOF

<130>  0014-PA-010

<160>  157   

<170>  PatentIn version 3.5

<210>  1
<211>  39
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  1
gcucuucagc cccgcgccgg gucccacucu gcgccgcuc                             39


<210>  2
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  2
gugcuucaua uccguccccc ccuugcugcg                                       30


<210>  3
<211>  44
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  3
auucugucuu uuuaaauaau guccccuugu ugcacauuac agaa                       44


<210>  4
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  4
uucugucuuu uuagauaaug uccccuuguu gcacauuaca                            40


<210>  5
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  5
gcucuucaau guuaacuacc aaucguugau cguuuugcag aaaauucc                   48


<210>  6
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  6
gcucuucggu guuaacuacc aaucguugau cguuuugcaa aaaauucc                   48


<210>  7
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  7
uccgcuugcg gagcagcuuc uguauucugc                                       30


<210>  8
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  8
uccgcuugcg gagcaucuuc uguauucugc                                       30


<210>  9
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  9
uccgcuugcg gagcaccuuc uguauucugc                                       30


<210>  10
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  10
ggaaaacagu auaaugucuu guuucuucuc                                       30


<210>  11
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  11
gguuuaucuu aacuuucugc uacgauacag uuuuuguuga                            40


<210>  12
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  12
ccaaccgugu aucugucuug cuugcggcgg uuuuguugug                            40


<210>  13
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  13
aguuauuugg uggagaggau ccauuuagcu uauacaauuc                            40


<210>  14
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  14
ccggccauug guggagauua uccuuugagu acgguuauuc                            40


<210>  15
<211>  45
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  15
uuucgcuaga uggcuaacac guauauuugu ggagaugcac uagcg                      45


<210>  16
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  16
cguggagaug cauucugucg aggauuggcu aacacgcgaa                            40


<210>  17
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  17
uccuuagaug gcuaacacgu auauuugugg agaugcacua                            40


<210>  18
<211>  38
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  18
cgcuagaugg cuaacacuau uguggagaug cacuagcg                              38


<210>  19
<211>  38
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  19
gcguagaugg cuaacacuau uguggagaug cacuacgc                              38


<210>  20
<211>  41
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  20
cgcuaguggc gaacacguau auuuguggcg augcacuagc g                          41


<210>  21
<211>  44
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  21
cgcuagaugg ccuaacacgu auauuugugg agauggcacu agcg                       44


<210>  22
<211>  36
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  22
cguggagaug cauucugucg aggauuggcu aacacg                                36


<210>  23
<211>  36
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  23
cguggagaug cauucugucg aagauuggcu aacacg                                36


<210>  24
<211>  34
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  24
cguggagaug cauucuucga gauuggcuaa cacg                                  34


<210>  25
<211>  36
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  25
cguggagaug cguuccgucg aggaucggcu aacacg                                36


<210>  26
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  26
cagguggaga ugcauucugu cgaagauugg cuaacaccug                            40


<210>  27
<211>  39
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  27
gccguggaga ugcguuccgu cgggaucggc uaacacggc                             39


<210>  28
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  28
gccguggaga ugcguuccgu cgaggaucgg cuaacacggc                            40


<210>  29
<211>  36
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  29
cguggcgaug cguuccgucg aggaucggcg aacacg                                36


<210>  30
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer

<400>  30
gcggauuggc uaacacgguc gacguggaga ugcauuccgc                            40


<210>  31
<211>  39
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(39)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  31
gcucuucagc cccgcgccgg gucccacucu gcgccgcuc                             39


<210>  32
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(30)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  32
gugcuucaua uccguccccc ccuugcugcg                                       30


<210>  33
<211>  44
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(44)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  33
auucugucuu uuuaaauaau guccccuugu ugcacauuac agaa                       44


<210>  34
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  34
uucugucuuu uuagauaaug uccccuuguu gcacauuaca                            40


<210>  35
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(48)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  35
gcucuucaau guuaacuacc aaucguugau cguuuugcag aaaauucc                   48


<210>  36
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(48)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  36
gcucuucggu guuaacuacc aaucguugau cguuuugcaa aaaauucc                   48


<210>  37
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(30)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  37
uccgcuugcg gagcagcuuc uguauucugc                                       30


<210>  38
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(30)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  38
uccgcuugcg gagcaucuuc uguauucugc                                       30


<210>  39
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(30)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  39
uccgcuugcg gagcaccuuc uguauucugc                                       30


<210>  40
<211>  30
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(30)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  40
ggaaaacagu auaaugucuu guuucuucuc                                       30


<210>  41
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  41
gguuuaucuu aacuuucugc uacgauacag uuuuuguuga                            40


<210>  42
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  42
ccaaccgugu aucugucuug cuugcggcgg uuuuguugug                            40


<210>  43
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  43
aguuauuugg uggagaggau ccauuuagcu uauacaauuc                            40


<210>  44
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  44
ccggccauug guggagauua uccuuugagu acgguuauuc                            40


<210>  45
<211>  45
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(45)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  45
uuucgcuaga uggcuaacac guauauuugu ggagaugcac uagcg                      45


<210>  46
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  46
cguggagaug cauucugucg aggauuggcu aacacgcgaa                            40


<210>  47
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  47
uccuuagaug gcuaacacgu auauuugugg agaugcacua                            40


<210>  48
<211>  38
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(38)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  48
cgcuagaugg cuaacacuau uguggagaug cacuagcg                              38


<210>  49
<211>  38
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  a represents 2'-O-methyl A, u represents 2'-O-methyl U, c 
       represents 2'-O-methyl C, g represents 2'-O-methyl G

<220>
<221>  misc_feature
<222>  (4)..(35)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (36)..(38)
<223>  a represents 2'-O-methyl A, u represents 2'-O-methyl U, c 
       represents 2'-O-methyl C, g represents 2'-O-methyl G

<400>  49
cgcuagaugg cuaacacuau uguggagaug cacuagcg                              38


<210>  50
<211>  38
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(3)
<223>  a represents locked nucleic acid (LNA) A, c represents locked 
       nucleic acid (LNA) C, g represents locked nucleic acid (LNA) G, u
       represents locked nucleic acid (LNA) U

<220>
<221>  misc_feature
<222>  (4)..(35)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (36)..(38)
<223>  a represents locked nucleic acid (LNA) A, c represents locked 
       nucleic acid (LNA) C, g represents locked nucleic acid (LNA) G, u
       represents locked nucleic acid (LNA) U

<400>  50
cgcuagaugg cuaacacuau uguggagaug cacuagcg                              38


<210>  51
<211>  38
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(38)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  51
gcguagaugg cuaacacuau uguggagaug cacuacgc                              38


<210>  52
<211>  41
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(41)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  52
cgcuaguggc gaacacguau auuuguggcg augcacuagc g                          41


<210>  53
<211>  44
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(44)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  53
cgcuagaugg ccuaacacgu auauuugugg agauggcacu agcg                       44


<210>  54
<211>  36
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(36)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  54
cguggagaug cauucugucg aggauuggcu aacacg                                36


<210>  55
<211>  36
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(36)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  55
cguggagaug cauucugucg aagauuggcu aacacg                                36


<210>  56
<211>  34
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(34)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  56
cguggagaug cauucuucga gauuggcuaa cacg                                  34


<210>  57
<211>  36
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(36)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  57
cguggagaug cguuccgucg aggaucggcu aacacg                                36


<210>  58
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  58
cagguggaga ugcauucugu cgaagauugg cuaacaccug                            40


<210>  59
<211>  39
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(39)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  59
gccguggaga ugcguuccgu cgggaucggc uaacacggc                             39


<210>  60
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  60
gccguggaga ugcguuccgu cgaggaucgg cuaacacggc                            40


<210>  61
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  61
gcggauuggc uaacacgguc gacguggaga ugcauuccgc                            40


<210>  62
<211>  36
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer


<220>
<221>  misc_feature
<222>  (1)..(36)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  62
cguggcgaug cguuccgucg aggaucggcg aacacg                                36


<210>  63
<211>  61
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer

<400>  63
gcauagauaa gccaacaaac guacauucuc uguuaguauu uucugcacac cgucgcuuag      60

u                                                                      61


<210>  64
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer

<400>  64
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcg                   48


<210>  65
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer

<400>  65
gccuuagaua agccaacaaa cguacauucu cuguuaguau uuucaggc                   48


<210>  66
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer

<400>  66
ccgauaagcc aacaaacgua cauucucugu uaguauucgg                            40


<210>  67
<211>  61
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer


<220>
<221>  misc_feature
<222>  (1)..(61)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  67
gcauagauaa gccaacaaac guacauucuc uguuaguauu uucugcacac cgucgcuuag      60

u                                                                      61


<210>  68
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer


<220>
<221>  misc_feature
<222>  (1)..(48)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  68
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcg                   48


<210>  69
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer


<220>
<221>  misc_feature
<222>  (1)..(48)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  69
gccuuagaua agccaacaaa cguacauucu cuguuaguau uuucaggc                   48


<210>  70
<211>  40
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer


<220>
<221>  misc_feature
<222>  (1)..(40)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  70
ccgauaagcc aacaaacgua cauucucugu uaguauucgg                            40


<210>  71
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer


<220>
<221>  misc_feature
<222>  (1)..(4)
<223>  a represents 2'-O-methyl A, u represents 2'-O-methyl U, c 
       represents 2'-O-methyl C, g represents 2'-O-methyl G

<220>
<221>  misc_feature
<222>  (5)..(44)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (45)..(48)
<223>  a represents 2'-O-methyl A, u represents 2'-O-methyl U, c 
       represents 2'-O-methyl C, g represents 2'-O-methyl G

<400>  71
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcg                   48


<210>  72
<211>  48
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer


<220>
<221>  misc_feature
<222>  (1)..(4)
<223>  a represents locked nucleic acid (LNA) A, u represents locked 
       nucleic acid (LNA) U, c represents locked nucleic acid (LNA) C, g
       represents locked nucleic acid (LNA) G

<220>
<221>  misc_feature
<222>  (5)..(44)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (45)..(48)
<223>  a represents locked nucleic acid (LNA) A, u represents locked 
       nucleic acid (LNA) U, c represents locked nucleic acid (LNA) C, g
       represents locked nucleic acid (LNA) G

<400>  72
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcg                   48


<210>  73
<211>  43
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer


<220>
<221>  misc_feature
<222>  (1)..(20)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (21)..(21)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (22)..(43)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  73
cgcauagaua agccaacaaa huucucuguu aguauuuucu gcg                        43


<210>  74
<211>  45
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer


<220>
<221>  misc_feature
<222>  (1)..(21)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (22)..(22)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (23)..(45)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  74
cgcauagaua agccaacaaa chauucucug uuaguauuuu cugcg                      45


<210>  75
<211>  86
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer

<400>  75
cgcuagaugg cuaacacuau uguggagaug cacuagcgcg cauagauaag ccaacaaacg      60

uacauucucu guuaguauuu ucugcg                                           86


<210>  76
<211>  86
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer

<400>  76
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcgcg cuagauggcu      60

aacacuauug uggagaugca cuagcg                                           86


<210>  77
<211>  86
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(86)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  77
cgcuagaugg cuaacacuau uguggagaug cacuagcgcg cauagauaag ccaacaaacg      60

uacauucucu guuaguauuu ucugcg                                           86


<210>  78
<211>  86
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(86)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  78
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcgcg cuagauggcu      60

aacacuauug uggagaugca cuagcg                                           86


<210>  79
<211>  10
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(10)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  79
uggcuaacac                                                             10


<210>  80
<211>  5
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(5)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  80
uggcu                                                                   5


<210>  81
<211>  6
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(6)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  81
uggcua                                                                  6


<210>  82
<211>  7
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(7)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  82
uggcuaa                                                                 7


<210>  83
<211>  8
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(8)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  83
uggcuaac                                                                8


<210>  84
<211>  9
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(9)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  84
uggcuaaca                                                               9


<210>  85
<211>  10
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer first concensus sequence

<400>  85
uggcuaacac                                                             10


<210>  86
<211>  5
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer first concensus sequence

<400>  86
uggcu                                                                   5


<210>  87
<211>  6
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer first concensus sequence

<400>  87
uggcua                                                                  6


<210>  88
<211>  7
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer first concensus sequence

<400>  88
uggcuaa                                                                 7


<210>  89
<211>  8
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer first concensus sequence

<400>  89
uggcuaac                                                                8


<210>  90
<211>  9
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer first concensus sequence

<400>  90
uggcuaaca                                                               9


<210>  91
<211>  11
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(11)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  91
guggagaugc a                                                           11


<210>  92
<211>  7
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(7)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  92
agaugca                                                                 7


<210>  93
<211>  8
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(8)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  93
gagaugca                                                                8


<210>  94
<211>  9
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(9)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  94
ggagaugca                                                              9


<210>  95
<211>  10
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-VEGF aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(10)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  95
uggagaugca                                                             10


<210>  96
<211>  11
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer second concensus sequence

<400>  96
guggagaugc a                                                           11


<210>  97
<211>  7
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer second concensus sequence

<400>  97
agaugca                                                                 7


<210>  98
<211>  8
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer second concensus sequence

<400>  98
gagaugca                                                                8


<210>  99
<211>  9
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer second concensus sequence

<400>  99
ggagaugca                                                              9


<210>  100
<211>  10
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-VEGF aptamer second concensus sequence

<400>  100
uggagaugca                                                             10


<210>  101
<211>  13
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  101
agauaagcca aca                                                         13


<210>  102
<211>  14
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(14)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  102
uagauaagcc aaca                                                        14


<210>  103
<211>  15
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer first concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(15)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  103
auagauaagc caaca                                                       15


<210>  104
<211>  15
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer first concensus sequence


<220>
<221>  misc_feature
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  104
cuagauaagc caaca                                                       15


<210>  105
<211>  13
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer first concensus sequence

<400>  105
agauaagcca aca                                                         13


<210>  106
<211>  14
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer first concensus sequence

<400>  106
uagauaagcc aaca                                                        14


<210>  107
<211>  15
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer first concensus sequence

<400>  107
auagauaagc caaca                                                       15


<210>  108
<211>  15
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer first concensus sequence

<400>  108
cuagauaagc caaca                                                       15


<210>  109
<211>  12
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(12)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  109
uguuaguauu uu                                                          12


<210>  110
<211>  13
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(13)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  110
uguuaguauu uuc                                                         13


<210>  111
<211>  14
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(14)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  111
uguuaguauu uucu                                                        14


<210>  112
<211>  14
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified anti-Ang2 aptamer second concensus sequence


<220>
<221>  misc_feature
<222>  (1)..(14)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  112
uguuaguauu uucg                                                        14


<210>  113
<211>  12
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer second concensus sequence

<400>  113
uguuaguauu uu                                                          12


<210>  114
<211>  13
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer second concensus sequence

<400>  114
uguuaguauu uuc                                                         13


<210>  115
<211>  14
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer second concensus sequence

<400>  115
uguuaguauu uucu                                                        14


<210>  116
<211>  14
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural anti-Ang2 aptamer second concensus sequence

<400>  116
uguuaguauu uucg                                                        14


<210>  117
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human VEGF121

<400>  117

Ala Pro Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys 
1               5                   10                  15      


Phe Met Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu 
            20                  25                  30          


Val Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys 
        35                  40                  45              


Pro Ser Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu 
    50                  55                  60                  


Gly Leu Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile 
65                  70                  75                  80  


Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe 
                85                  90                  95      


Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg 
            100                 105                 110         


Gln Glu Lys Cys Asp Lys Pro Arg Arg 
        115                 120     


<210>  118
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human VEGF121 receptor binding domain 1,human VEGF165 receptor 
       binding domain 1,monkey VEGF 165 receptor binding domain 1, Rat  
      VEGF 164 receptor binding domain 1,Rat VEGF 120 receptor binding 
       domain 1,Mouse VEGF 164 receptor binding  domain 1,Mouse VEGF 120
       

<400>  118

Phe Met Asp Val Tyr Gln Arg Ser Tyr 
1               5                   


<210>  119
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human VEGF121 receptor binding domain 2,human VEGF165 receptor 
       binding domain 2, Rabbit VEGF 189 receptor binding domain 2,monkey
       VEGF 165 receptor binding domain 2, Rat VEGF 164 receptor binding 
       domain 2,Rat VEGF 120 receptor binding domain 2,Mouse VEGF 164 
       

<400>  119

Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys 
1               5                   10                  15  


<210>  120
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human VEGF121 receptor binding domain 3,human VEGF165 receptor 
       binding domain 3,Monkey VEGF 165 receptor binding domain 3

<400>  120

Cys Asn Asp Glu Gly Leu 
1               5       


<210>  121
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human VEGF121 receptor binding domain 4,human VEGF165 receptor 
       binding domain 4, monkey VEGF 165 receptor binding domain 4,Rabbit
       VEGF 189 receptor binding domain 4,Rat VEGF 164 receptor binding 
       domain 4,Rat VEGF 120 receptor binding domain 4,Mouse VEGF 164 
       

<400>  121

Gln Ile Met Arg Ile Lys Pro His Gln Gly Gln His Ile 
1               5                   10              


<210>  122
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human VEGF121 receptor binding domain 5,human VEGF165 receptor 
       binding domain 5,monkey VEGF 165 receptor binding domain 5, Rabbit
       VEGF 189 receptor binding domain 5

<400>  122

Lys Cys Glu Cys Arg Pro Lys Lys 
1               5               


<210>  123
<211>  165
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human VEGF165,Monkey VEGF 165

<400>  123

Ala Pro Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys 
1               5                   10                  15      


Phe Met Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu 
            20                  25                  30          


Val Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys 
        35                  40                  45              


Pro Ser Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu 
    50                  55                  60                  


Gly Leu Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile 
65                  70                  75                  80  


Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe 
                85                  90                  95      


Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg 
            100                 105                 110         


Gln Glu Asn Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys His Leu Phe 
        115                 120                 125             


Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp Ser 
    130                 135                 140                 


Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys Arg Cys 
145                 150                 155                 160 


Asp Lys Pro Arg Arg 
                165 


<210>  124
<211>  189
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rabbit VEGF 189

<400>  124

Ala Pro Met Ala Glu Glu Gly Asp Asn Lys Pro His Glu Val Val Lys 
1               5                   10                  15      


Phe Met Glu Val Tyr Arg Arg Ser Tyr Cys Gln Pro Ile Glu Thr Leu 
            20                  25                  30          


Val Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys 
        35                  40                  45              


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


Ser Leu Glu Cys Val Pro Thr Glu Glu Phe Asn Val Thr Met Gln Ile 
65                  70                  75                  80  


Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe 
                85                  90                  95      


Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg 
            100                 105                 110         


Gln Glu Lys Lys Ser Val Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys 
        115                 120                 125             


Arg Lys Lys Ser Arg Tyr Lys Ser Trp Ser Val Pro Cys Gly Pro Cys 
    130                 135                 140                 


Ser Glu Arg Arg Lys His Leu Phe Val Gln Asp Pro Gln Thr Cys Lys 
145                 150                 155                 160 


Cys Ser Cys Lys Asn Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu 
                165                 170                 175     


Leu Asn Glu Arg Thr Cys Arg Cys Asp Lys Pro Arg Arg 
            180                 185                 


<210>  125
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rabbit VEGF 189 receptor binding domain 1

<400>  125

Phe Met Glu Val Tyr Arg Arg Ser Tyr 
1               5                   


<210>  126
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rabbit VEGF 189 receptor binding domain 3

<400>  126

Cys Asn Asp Glu Ser Leu 
1               5       


<210>  127
<211>  164
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rat VEGF 164

<400>  127

Ala Pro Thr Thr Glu Gly Glu Gln Lys Ala His Glu Val Val Lys Phe 
1               5                   10                  15      


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


Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro 
        35                  40                  45              


Ser Cys Val Pro Leu Met Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala 
    50                  55                  60                  


Leu Glu Cys Val Pro Thr Ser Glu Ser Asn Val Thr Met Gln Ile Met 
65                  70                  75                  80  


Arg Ile Lys Pro His Gln Ser Gln His Ile Gly Glu Met Ser Phe Leu 
                85                  90                  95      


Gln His Ser Arg Cys Glu Cys Arg Pro Lys Lys Asp Arg Thr Lys Pro 
            100                 105                 110         


Glu Asn His Cys Glu Pro Cys Ser Glu Arg Arg Lys His Leu Phe Val 
        115                 120                 125             


Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp Ser Arg 
    130                 135                 140                 


Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys Arg Cys Asp 
145                 150                 155                 160 


Lys Pro Arg Arg 
                


<210>  128
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rat VEGF 164 receptor binding domain 3,Rat VEGF 120 receptor 
       binding domain 3,Mouse VEGF 164 receptor binding  domain 3,Mouse 
       VEGF 120 receptor binding  domain 3

<400>  128

Cys Asn Asp Glu Ala Leu 
1               5       


<210>  129
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rat VEGF 164 receptor binding domain 5,Rat VEGF 120 receptor 
       binding domain 5,Mouse VEGF 164 receptor binding  domain 5,Mouse 
       VEGF 120 receptor binding  domain 5

<400>  129

Arg Cys Glu Cys Arg Pro Lys Lys 
1               5               


<210>  130
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rat VEGF 120

<400>  130

Ala Pro Thr Thr Glu Gly Glu Gln Lys Ala His Glu Val Val Lys Phe 
1               5                   10                  15      


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


Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro 
        35                  40                  45              


Ser Cys Val Pro Leu Met Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala 
    50                  55                  60                  


Leu Glu Cys Val Pro Thr Ser Glu Ser Asn Val Thr Met Gln Ile Met 
65                  70                  75                  80  


Arg Ile Lys Pro His Gln Ser Gln His Ile Gly Glu Met Ser Phe Leu 
                85                  90                  95      


Gln His Ser Arg Cys Glu Cys Arg Pro Lys Lys Asp Arg Thr Lys Pro 
            100                 105                 110         


Glu Lys Cys Asp Lys Pro Arg Arg 
        115                 120 


<210>  131
<211>  164
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mouse VEGF 164

<400>  131

Ala Pro Thr Thr Glu Gly Glu Gln Lys Ser His Glu Val Ile Lys Phe 
1               5                   10                  15      


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


Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro 
        35                  40                  45              


Ser Cys Val Pro Leu Met Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala 
    50                  55                  60                  


Leu Glu Cys Val Pro Thr Ser Glu Ser Asn Ile Thr Met Gln Ile Met 
65                  70                  75                  80  


Arg Ile Lys Pro His Gln Ser Gln His Ile Gly Glu Met Ser Phe Leu 
                85                  90                  95      


Gln His Ser Arg Cys Glu Cys Arg Pro Lys Lys Asp Arg Thr Lys Pro 
            100                 105                 110         


Glu Asn His Cys Glu Pro Cys Ser Glu Arg Arg Lys His Leu Phe Val 
        115                 120                 125             


Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp Ser Arg 
    130                 135                 140                 


Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys Arg Cys Asp 
145                 150                 155                 160 


Lys Pro Arg Arg 
                


<210>  132
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mouse VEGF 120

<400>  132

Ala Pro Thr Thr Glu Gly Glu Gln Lys Ser His Glu Val Ile Lys Phe 
1               5                   10                  15      


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


Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro 
        35                  40                  45              


Ser Cys Val Pro Leu Met Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala 
    50                  55                  60                  


Leu Glu Cys Val Pro Thr Ser Glu Ser Asn Ile Thr Met Gln Ile Met 
65                  70                  75                  80  


Arg Ile Lys Pro His Gln Ser Gln His Ile Gly Glu Met Ser Phe Leu 
                85                  90                  95      


Gln His Ser Arg Cys Glu Cys Arg Pro Lys Lys Asp Arg Thr Lys Pro 
            100                 105                 110         


Glu Lys Cys Asp Lys Pro Arg Arg 
        115                 120 


<210>  133
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mouse VEGF 120 receptor binding  domain 4

<400>  133

Gln Ile Met Arg Ile Lys Pro His Gln Ser Gln His Ile 
1               5                   10              

<210>  134
<211>  17
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VEGF forward primer

<400>  134
cgccctcgtc ccatctc                                                     17


<210>  135
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VEGF reverse primer

<400>  135
cgttctcggt tggtgttc                                                    18


<210>  136
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Ang2 forward primer

<400>  136
atccagagtg acgctcttca gca                                              23


<210>  137
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Ang2 reverse primer

<400>  137
tgaagagcgt cactctggat                                                  20


<210>  138
<211>  93
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer

<400>  138
uuucgcuaga uggcuaacac guauauuugu ggagaugcac uagcgcgcau agauaagcca      60

acaaacguac auucucuguu aguauuuucu gcg                                   93


<210>  139
<211>  84
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer

<400>  139
cguggagaug cauucugucg aagauuggcu aacacgcgca uagauaagcc aacaaacgua      60

cauucucugu uaguauuuuc ugcg                                             84


<210>  140
<211>  93
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer

<400>  140
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcguu ucgcuagaug      60

gcuaacacgu auauuugugg agaugcacua gcg                                   93


<210>  141
<211>  84
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer

<400>  141
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcgcg uggagaugca      60

uucugucgaa gauuggcuaa cacg                                             84


<210>  142
<211>  87
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer


<220>
<221>  misc_feature
<222>  (39)..(39)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<400>  142
cgcuagaugg cuaacacuau uguggagaug cacuagcghc gcauagauaa gccaacaaac      60

guacauucuc uguuaguauu uucugcg                                          87


<210>  143
<211>  88
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer


<220>
<221>  misc_feature
<222>  (39)..(40)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<400>  143
cgcuagaugg cuaacacuau uguggagaug cacuagcghh cgcauagaua agccaacaaa      60

cguacauucu cuguuaguau uuucugcg                                         88


<210>  144
<211>  89
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer


<220>
<221>  misc_feature
<222>  (39)..(41)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<400>  144
cgcuagaugg cuaacacuau uguggagaug cacuagcghh hcgcauagau aagccaacaa      60

acguacauuc ucuguuagua uuuucugcg                                        89


<210>  145
<211>  90
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer


<220>
<221>  misc_feature
<222>  (39)..(42)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<400>  145
cgcuagaugg cuaacacuau uguggagaug cacuagcghh hhcgcauaga uaagccaaca      60

aacguacauu cucuguuagu auuuucugcg                                       90


<210>  146
<211>  91
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer


<220>
<221>  misc_feature
<222>  (39)..(43)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<400>  146
cgcuagaugg cuaacacuau uguggagaug cacuagcghh hhhcgcauag auaagccaac      60

aaacguacau ucucuguuag uauuuucugc g                                     91


<210>  147
<211>  92
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  natural bispecifc aptamer


<220>
<221>  misc_feature
<222>  (39)..(44)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<400>  147
cgcuagaugg cuaacacuau uguggagaug cacuagcghh hhhhcgcaua gauaagccaa      60

caaacguaca uucucuguua guauuuucug cg                                    92


<210>  148
<211>  93
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(93)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  148
uuucgcuaga uggcuaacac guauauuugu ggagaugcac uagcgcgcau agauaagcca      60

acaaacguac auucucuguu aguauuuucu gcg                                   93


<210>  149
<211>  84
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(84)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  149
cguggagaug cauucugucg aagauuggcu aacacgcgca uagauaagcc aacaaacgua      60

cauucucugu uaguauuuuc ugcg                                             84


<210>  150
<211>  93
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(93)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  150
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcguu ucgcuagaug      60

gcuaacacgu auauuugugg agaugcacua gcg                                   93


<210>  151
<211>  84
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (1)..(84)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  151
cgcauagaua agccaacaaa cguacauucu cuguuaguau uuucugcgcg uggagaugca      60

uucugucgaa gauuggcuaa cacg                                             84


<210>  152
<211>  87
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(38)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (39)..(39)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (40)..(87)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  152
cgcuagaugg cuaacacuau uguggagaug cacuagcghc gcauagauaa gccaacaaac      60

guacauucuc uguuaguauu uucugcg                                          87


<210>  153
<211>  88
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(38)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (39)..(40)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (41)..(88)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  153
cgcuagaugg cuaacacuau uguggagaug cacuagcghh cgcauagaua agccaacaaa      60

cguacauucu cuguuaguau uuucugcg                                         88


<210>  154
<211>  89
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(38)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (39)..(41)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (42)..(89)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  154
cgcuagaugg cuaacacuau uguggagaug cacuagcghh hcgcauagau aagccaacaa      60

acguacauuc ucuguuagua uuuucugcg                                        89


<210>  155
<211>  90
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(38)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (39)..(42)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (43)..(90)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  155
cgcuagaugg cuaacacuau uguggagaug cacuagcghh hhcgcauaga uaagccaaca      60

aacguacauu cucuguuagu auuuucugcg                                       90


<210>  156
<211>  91
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(38)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (39)..(43)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (44)..(91)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<400>  156
cgcuagaugg cuaacacuau uguggagaug cacuagcghh hhhcgcauag auaagccaac      60

aaacguacau ucucuguuag uauuuucugc g                                     91


<210>  157
<211>  92
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  modified bispecific aptamer


<220>
<221>  misc_feature
<222>  (1)..(38)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<220>
<221>  misc_feature
<222>  (39)..(44)
<223>  h denotes hexa-ethyleneglycol (Heg)  linker

<220>
<221>  misc_feature
<222>  (45)..(92)
<223>  a represents 2'-fluoroadenylic acid, u represents 
       2'-fluorouridylic acid, c represents 2'-fluorocytidylic acid, g 
       represents 2'-fluoroguanylic acid

<400>  157
cgcuagaugg cuaacacuau uguggagaug cacuagcghh hhhhcgcaua gauaagccaa      60

caaacguaca uucucuguua guauuuucug cg                                    92

