                         SEQUENCE LISTING

<110>  GeneSail(Shanghai) Co.,Ltd.
       GeneSailNova(Shanghai)Co.,Ltd.
 
<120>  A modified oncolytic virus, composition and use thereof

<130>  068615-8002WO02

<160>  40    

<170>  PatentIn version 3.5

<210>  1
<211>  149
<212>  PRT
<213>  Homo sapiens


<220>
<221>  PD-1 ECD G22-170
<222>  (1)..(149)

<400>  1

Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr Phe 
1               5                   10                  15      


Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp Asn Ala Thr Phe Thr 
            20                  25                  30          


Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr Arg 
        35                  40                  45              


Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu Asp 
    50                  55                  60                  


Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg Val Thr Gln Leu Pro 
65                  70                  75                  80  


Asn Gly Arg Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn Asp 
                85                  90                  95      


Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala Gln 
            100                 105                 110         


Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg Ala 
        115                 120                 125             


Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly Gln 
    130                 135                 140                 


Phe Gln Thr Leu Val 
145                 


<210>  2
<211>  144
<212>  PRT
<213>  Homo sapiens


<220>
<221>  TGF-beta receptor II ECD23-166
<222>  (1)..(144)

<400>  2

Thr Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val 
1               5                   10                  15      


Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys 
            20                  25                  30          


Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn 
        35                  40                  45              


Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala 
    50                  55                  60                  


Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His 
65                  70                  75                  80  


Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser 
                85                  90                  95      


Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe 
            100                 105                 110         


Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser 
        115                 120                 125             


Glu Glu Tyr Asn Thr Ser Asn Pro Asp Leu Leu Leu Val Ile Phe Gln 
    130                 135                 140                 


<210>  3
<211>  232
<212>  PRT
<213>  Homo sapiens


<220>
<221>  human IgG1-Fc region
<222>  (1)..(232)

<400>  3

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
1               5                   10                  15      


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
            20                  25                  30          


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
        35                  40                  45              


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
    50                  55                  60                  


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
65                  70                  75                  80  


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                85                  90                  95      


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
            100                 105                 110         


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
        115                 120                 125             


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
    130                 135                 140                 


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                165                 170                 175     


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
            180                 185                 190         


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
        195                 200                 205             


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
    210                 215                 220                 


Ser Leu Ser Leu Ser Pro Gly Lys 
225                 230         


<210>  4
<211>  17
<212>  PRT
<213>  Homo sapiens


<220>
<221>  CD33 Signal peptide
<222>  (1)..(17)

<400>  4

Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala 
1               5                   10                  15      


Met 
    


<210>  5
<211>  398
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD33 sp-PD-1-Fc

<400>  5

Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala 
1               5                   10                  15      


Met Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr 
            20                  25                  30          


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


Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr 
    50                  55                  60                  


Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu 
65                  70                  75                  80  


Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg Val Thr Gln Leu 
                85                  90                  95      


Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn 
            100                 105                 110         


Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala 
        115                 120                 125             


Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg 
    130                 135                 140                 


Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly 
145                 150                 155                 160 


Gln Phe Gln Thr Leu Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
                165                 170                 175     


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
            180                 185                 190         


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
        195                 200                 205             


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
    210                 215                 220                 


Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
225                 230                 235                 240 


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


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
            260                 265                 270         


Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
        275                 280                 285             


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
    290                 295                 300                 


Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
305                 310                 315                 320 


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
                325                 330                 335     


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


Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
        355                 360                 365             


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
    370                 375                 380                 


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
385                 390                 395             


<210>  6
<211>  393
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD33 sp-TGF-beta receptor II-Fc

<400>  6

Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala 
1               5                   10                  15      


Met Thr Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile 
            20                  25                  30          


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


Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser 
    50                  55                  60                  


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


Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys 
                85                  90                  95      


His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala 
            100                 105                 110         


Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe 
        115                 120                 125             


Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe 
    130                 135                 140                 


Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp Leu Leu Leu Val Ile Phe 
145                 150                 155                 160 


Gln Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
                165                 170                 175     


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
            180                 185                 190         


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
        195                 200                 205             


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
    210                 215                 220                 


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
225                 230                 235                 240 


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
                245                 250                 255     


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
            260                 265                 270         


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
        275                 280                 285             


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
    290                 295                 300                 


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
305                 310                 315                 320 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
                325                 330                 335     


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
            340                 345                 350         


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
        355                 360                 365             


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
    370                 375                 380                 


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
385                 390             


<210>  7
<211>  447
<212>  DNA
<213>  Homo sapiens


<220>
<221>  PD-1 ECD G22-170
<222>  (1)..(447)

<400>  7
ggctggttcc tcgactctcc cgacagacct tggaacccac ctacattcag ccccgccctc       60

ctcgtggtga ccgagggcga caacgccacc ttcacatgca gcttcagcaa cacatccgag      120

tctttcgtgc tgaactggta tcggatgtct ccatctaacc agaccgacaa gctcgccgcc      180

ttccccgagg accgctcgca gcctggccag gattgcagat tcagagtgac ccagctccca      240

aacggcaggg acttccacat gagcgtggtg cgcgcccgga gaaacgactc tggcacatac      300

ctgtgcggcg ccattagcct cgcccctaag gcccagatta aggagtccct gcgggccgag      360

ctgagagtga cagagcggag agccgaggtg cctaccgccc acccatctcc atctcctaga      420

cccgccggcc agttccagac actcgtg                                          447


<210>  8
<211>  432
<212>  DNA
<213>  Homo sapiens


<220>
<221>  TGF-beta receptor II ECD23-166
<222>  (1)..(432)

<400>  8
acaattcctc ctcacgtgca gaagagcgtg aataatgata tgattgtgac cgataataac       60

ggcgccgtga aatttcccca gctgtgtaag ttttgtgatg tgagattcag cacctgtgat      120

aatcagaagt cttgcatgtc taactgttcc atcacatcca tctgtgagaa gccacaggag      180

gtgtgcgtgg ccgtgtggag aaagaatgat gagaatatca cacttgagac cgtgtgccac      240

gacccaaaac tgccatacca cgattttatt ctggaggatg ccgcctctcc taagtgcatt      300

atgaaggaga agaagaagcc aggcgagacc ttctttatgt gtagctgttc ctctgatgag      360

tgtaatgata atattatctt cagcgaagag tataacacca gtaatcctga cctgctgctt      420

gtgattttcc ag                                                          432


<210>  9
<211>  696
<212>  DNA
<213>  Homo sapiens


<220>
<221>  human IgG1-Fc region for PD-1
<222>  (1)..(696)

<400>  9
gagcctaagt cttgcgacaa gacccacaca tgcccacctt gccccgcccc tgagctgctg       60

ggcggcccat ccgtgttcct gttcccacca aagccaaagg acacactcat gattagcagg      120

acacctgagg tgacatgcgt ggtggtggac gtgtctcacg aggaccccga ggtgaagttc      180

aactggtacg tggacggcgt ggaggtgcac aacgccaaga caaagcctag agaggagcag      240

tacaactcta cataccgcgt ggtgtccgtg ctcacagtgc tgcaccagga ctggctgaac      300

ggcaaggagt acaagtgcaa ggtgtccaac aaggccctcc ccgcccctat tgaaaaaacc      360

attagcaagg ccaagggcca gccacgcgag cctcaggtgt acacactgcc tccttctagg      420

gacgagctga ccaagaacca ggtgtccctc acatgcctcg tgaagggctt ctaccctagc      480

gacattgccg tggagtggga gtctaacggc cagcctgaga acaactacaa gacaacacca      540

cctgtgctcg actctgacgg ctctttcttc ctgtactcta agctcacagt ggacaagagt      600

agatggcagc agggcaacgt gttctcttgc tctgtgatgc acgaggccct gcacaaccac      660

tacacccaga agtctctgtc tctgtctcca ggcaag                                696


<210>  10
<211>  696
<212>  DNA
<213>  Homo sapiens


<220>
<221>  human IgG1-Fc region for TGF-beta receptor II
<222>  (1)..(696)

<400>  10
gagcctaagt cttgtgacaa gacacacaca tgccctccct gtccagcccc tgagctgctg       60

ggcggcccta gcgtgtttct gttcccccct aagcctaaag atacactgat gattagcaga      120

acaccagagg tgacctgtgt ggtggtggat gtgagccacg aggaccctga ggtgaagttt      180

aactggtatg tggatggagt ggaagtgcac aatgctaaga ccaagcctag agaggagcag      240

tataatagca catatagagt ggtgtctgtg ctgaccgtgc tgcaccagga ctggctgaat      300

ggcaaagagt ataaatgtaa ggtgagcaac aaggccctgc ccgcccccat tgagaaaacc      360

atctctaagg ctaagggaca gccaagagag cctcaggtgt atacactgcc tccttctaga      420

gatgagctga ccaaaaacca ggttagcctg acatgcctgg tgaaaggctt ctatccaagc      480

gatatcgctg tggaatggga gagcaatggc cagcctgaga ataattataa aaccacccca      540

ccagtgctgg atagcgatgg cagctttttc ctgtattcta agctgacagt ggataaatct      600

aggtggcagc agggcaatgt gtttagctgc tctgtgatgc acgaggccct gcacaatcac      660

tatacacaga agagcctgag cctgagccct ggcaag                                696


<210>  11
<211>  51
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CD33 Signal peptide for PD-1
<222>  (1)..(51)

<400>  11
atgccactgc tcctcctgct gccactgctc tgggccggcg ccctcgctat g                51


<210>  12
<211>  51
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CD33 Signal peptide for TGF-beta receptor II
<222>  (1)..(51)

<400>  12
atgcctctgc tgctgctgct gcctctgctg tgggccggcg ccctggccat g                51


<210>  13
<211>  1197
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CD33 sp-PD-1-Fc

<400>  13
atgccactgc tcctcctgct gccactgctc tgggccggcg ccctcgctat gggctggttc       60

ctcgactctc ccgacagacc ttggaaccca cctacattca gccccgccct cctcgtggtg      120

accgagggcg acaacgccac cttcacatgc agcttcagca acacatccga gtctttcgtg      180

ctgaactggt atcggatgtc tccatctaac cagaccgaca agctcgccgc cttccccgag      240

gaccgctcgc agcctggcca ggattgcaga ttcagagtga cccagctccc aaacggcagg      300

gacttccaca tgagcgtggt gcgcgcccgg agaaacgact ctggcacata cctgtgcggc      360

gccattagcc tcgcccctaa ggcccagatt aaggagtccc tgcgggccga gctgagagtg      420

acagagcgga gagccgaggt gcctaccgcc cacccatctc catctcctag acccgccggc      480

cagttccaga cactcgtgga gcctaagtct tgcgacaaga cccacacatg cccaccttgc      540

cccgcccctg agctgctggg cggcccatcc gtgttcctgt tcccaccaaa gccaaaggac      600

acactcatga ttagcaggac acctgaggtg acatgcgtgg tggtggacgt gtctcacgag      660

gaccccgagg tgaagttcaa ctggtacgtg gacggcgtgg aggtgcacaa cgccaagaca      720

aagcctagag aggagcagta caactctaca taccgcgtgg tgtccgtgct cacagtgctg      780

caccaggact ggctgaacgg caaggagtac aagtgcaagg tgtccaacaa ggccctcccc      840

gcccctattg aaaaaaccat tagcaaggcc aagggccagc cacgcgagcc tcaggtgtac      900

acactgcctc cttctaggga cgagctgacc aagaaccagg tgtccctcac atgcctcgtg      960

aagggcttct accctagcga cattgccgtg gagtgggagt ctaacggcca gcctgagaac     1020

aactacaaga caacaccacc tgtgctcgac tctgacggct ctttcttcct gtactctaag     1080

ctcacagtgg acaagagtag atggcagcag ggcaacgtgt tctcttgctc tgtgatgcac     1140

gaggccctgc acaaccacta cacccagaag tctctgtctc tgtctccagg caagtga        1197


<210>  14
<211>  1182
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CD33 sp-TGF-beta receptor II-Fc

<400>  14
atgcctctgc tgctgctgct gcctctgctg tgggccggcg ccctggccat gacaattcct       60

cctcacgtgc agaagagcgt gaataatgat atgattgtga ccgataataa cggcgccgtg      120

aaatttcccc agctgtgtaa gttttgtgat gtgagattca gcacctgtga taatcagaag      180

tcttgcatgt ctaactgttc catcacatcc atctgtgaga agccacagga ggtgtgcgtg      240

gccgtgtgga gaaagaatga tgagaatatc acacttgaga ccgtgtgcca cgacccaaaa      300

ctgccatacc acgattttat tctggaggat gccgcctctc ctaagtgcat tatgaaggag      360

aagaagaagc caggcgagac cttctttatg tgtagctgtt cctctgatga gtgtaatgat      420

aatattatct tcagcgaaga gtataacacc agtaatcctg acctgctgct tgtgattttc      480

caggagccta agtcttgtga caagacacac acatgccctc cctgtccagc ccctgagctg      540

ctgggcggcc ctagcgtgtt tctgttcccc cctaagccta aagatacact gatgattagc      600

agaacaccag aggtgacctg tgtggtggtg gatgtgagcc acgaggaccc tgaggtgaag      660

tttaactggt atgtggatgg agtggaagtg cacaatgcta agaccaagcc tagagaggag      720

cagtataata gcacatatag agtggtgtct gtgctgaccg tgctgcacca ggactggctg      780

aatggcaaag agtataaatg taaggtgagc aacaaggccc tgcccgcccc cattgagaaa      840

accatctcta aggctaaggg acagccaaga gagcctcagg tgtatacact gcctccttct      900

agagatgagc tgaccaaaaa ccaggttagc ctgacatgcc tggtgaaagg cttctatcca      960

agcgatatcg ctgtggaatg ggagagcaat ggccagcctg agaataatta taaaaccacc     1020

ccaccagtgc tggatagcga tggcagcttt ttcctgtatt ctaagctgac agtggataaa     1080

tctaggtggc agcagggcaa tgtgtttagc tgctctgtga tgcacgaggc cctgcacaat     1140

cactatacac agaagagcct gagcctgagc cctggcaagt ga                        1182


<210>  15
<211>  42
<212>  DNA
<213>  Vaccinia virus


<220>
<221>  pSE/L promoter
<222>  (1)..(42)

<400>  15
aaaaattgaa attttatttt ttttttttgg aatataaata ag                          42


<210>  16
<211>  10
<212>  DNA
<213>  Vaccinia virus


<220>
<221>  T5NT stop codon
<222>  (1)..(7)

<220>
<221>  misc_feature
<222>  (6)..(6)
<223>  n can be a, t, g or c.

<220>
<221>  misc_feature
<222>  (8)..(10)
<223>  n is absent.

<400>  16
tttttntnnn                                                              10


<210>  17
<211>  4392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  WR-GO-001

<400>  17
atggagaatg ttcctaatgt atactttaat cctgtgttta tagagcccac gtttaaacat       60

tctttattaa gtgtttataa acacagatta atagttttat ttgaagtatt cgttgtattc      120

attctaatat atgtattttt tagatctgaa ttaaatatgt tcttcatgcc taaacgaaaa      180

atacccgatc ctattgatag attacgacgt gctaatctag cgtgtgaaga cgataaatta      240

atgatctatg gattaccatg gatgacaact caaacatctg cgttatcaat aaatagtaaa      300

ccgatagtgt ataaagattg tgcaaagctt ttgcgatcaa taaatggatc acaaccagta      360

tctcttaacg atgttcttcg cagatgatga ttcatttttt aagtatttgg ctagtcaaga      420

tgatgaatct tcattatctg atatattgca aatcactcaa tatctagact ttctgttatt      480

attattgatc caatcaaaaa ataaattaga agccgtgggt cattgttatg aatctctttc      540

agaggaatac agacaattga caaaattcac agactttcaa gattttaaaa aactgtttaa      600

caaggtccct attgttacag atggaagggt caaacttaat aaaggatatt tgttcgactt      660

tgtgattagt ttgatgcgat tcaaaaaaga atcctctcta gctaccaccg caatagatcc      720

tgttagatac atagatcctc gtcgcaatat cgcattttct aacgtgatgg atatattaaa      780

gtcgaataaa gtgaacaata attaattctt tattgtcaag gcctagaaaa acctcacttg      840

cctggagaca gagacagaga cttctgggtg tagtggttgt gcagggcctc gtgcatcaca      900

gagcaagaga acacgttgcc ctgctgccat ctactcttgt ccactgtgag cttagagtac      960

aggaagaaag agccgtcaga gtcgagcaca ggtggtgttg tcttgtagtt gttctcaggc     1020

tggccgttag actcccactc cacggcaatg tcgctagggt agaagccctt cacgaggcat     1080

gtgagggaca cctggttctt ggtcagctcg tccctagaag gaggcagtgt gtacacctga     1140

ggctcgcgtg gctggccctt ggccttgcta atggtttttt caataggggc ggggagggcc     1200

ttgttggaca ccttgcactt gtactccttg ccgttcagcc agtcctggtg cagcactgtg     1260

agcacggaca ccacgcggta tgtagagttg tactgctcct ctctaggctt tgtcttggcg     1320

ttgtgcacct ccacgccgtc cacgtaccag ttgaacttca cctcggggtc ctcgtgagac     1380

acgtccacca ccacgcatgt cacctcaggt gtcctgctaa tcatgagtgt gtcctttggc     1440

tttggtggga acaggaacac ggatgggccg cccagcagct caggggcggg gcaaggtggg     1500

catgtgtggg tcttgtcgca agacttaggc tccacgagtg tctggaactg gccggcgggt     1560

ctaggagatg gagatgggtg ggcggtaggc acctcggctc tccgctctgt cactctcagc     1620

tcggcccgca gggactcctt aatctgggcc ttaggggcga ggctaatggc gccgcacagg     1680

tatgtgccag agtcgtttct ccgggcgcgc accacgctca tgtggaagtc cctgccgttt     1740

gggagctggg tcactctgaa tctgcaatcc tggccaggct gcgagcggtc ctcggggaag     1800

gcggcgagct tgtcggtctg gttagatgga gacatccgat accagttcag cacgaaagac     1860

tcggatgtgt tgctgaagct gcatgtgaag gtggcgttgt cgccctcggt caccacgagg     1920

agggcggggc tgaatgtagg tgggttccaa ggtctgtcgg gagagtcgag gaaccagccc     1980

atagcgaggg cgccggccca gagcagtggc agcaggagga gcagtggcat ggcttattta     2040

tattccaaaa aaaaaaaata aaatttcaat ttttactagt aaaaattgaa attttatttt     2100

ttttttttgg aatataaata aggatgcctc tgctgctgct gctgcctctg ctgtgggccg     2160

gcgccctggc catgacaatt cctcctcacg tgcagaagag cgtgaataat gatatgattg     2220

tgaccgataa taacggcgcc gtgaaatttc cccagctgtg taagttttgt gatgtgagat     2280

tcagcacctg tgataatcag aagtcttgca tgtctaactg ttccatcaca tccatctgtg     2340

agaagccaca ggaggtgtgc gtggccgtgt ggagaaagaa tgatgagaat atcacacttg     2400

agaccgtgtg ccacgaccca aaactgccat accacgattt tattctggag gatgccgcct     2460

ctcctaagtg cattatgaag gagaagaaga agccaggcga gaccttcttt atgtgtagct     2520

gttcctctga tgagtgtaat gataatatta tcttcagcga agagtataac accagtaatc     2580

ctgacctgct gcttgtgatt ttccaggagc ctaagtcttg tgacaagaca cacacatgcc     2640

ctccctgtcc agcccctgag ctgctgggcg gccctagcgt gtttctgttc ccccctaagc     2700

ctaaagatac actgatgatt agcagaacac cagaggtgac ctgtgtggtg gtggatgtga     2760

gccacgagga ccctgaggtg aagtttaact ggtatgtgga tggagtggaa gtgcacaatg     2820

ctaagaccaa gcctagagag gagcagtata atagcacata tagagtggtg tctgtgctga     2880

ccgtgctgca ccaggactgg ctgaatggca aagagtataa atgtaaggtg agcaacaagg     2940

ccctgcccgc ccccattgag aaaaccatct ctaaggctaa gggacagcca agagagcctc     3000

aggtgtatac actgcctcct tctagagatg agctgaccaa aaaccaggtt agcctgacat     3060

gcctggtgaa aggcttctat ccaagcgata tcgctgtgga atgggagagc aatggccagc     3120

ctgagaataa ttataaaacc accccaccag tgctggatag cgatggcagc tttttcctgt     3180

attctaagct gacagtggat aaatctaggt ggcagcaggg caatgtgttt agctgctctg     3240

tgatgcacga ggccctgcac aatcactata cacagaagag cctgagcctg agccctggca     3300

agtgactttt tatgagctcg aattctatta tattttttat ctaaaaaact aaaaataaac     3360

attgattaaa ttttaatata atacttaaaa atggatgttg tgtcgttaga taaaccgttt     3420

atgtattttg aggaaattga taatgagtta gattacgaac cagaaagtgc aaatgaggtc     3480

gcaaaaaaac tgccgtatca aggacagtta aaactattac taggagaatt attttttctt     3540

agtaagttac agcgacacgg tatattagat ggtgccaccg tagtgtatat aggatctgct     3600

cccggtacac atatacgtta tttgagagat catttctata atttaggagt gatcatcaaa     3660

tggatgctaa ttgacggccg ccatcatgat cctattttaa atggattgcg tgatgtgact     3720

ctagtgactc ggttcgttga tgaggaatat ctacgatcca tcaaaaaaca actgcatcct     3780

tctaagatta ttttaatttc tgatgtgaga tccaaacgag gaggaaatga acctagtacg     3840

gcggatttac taagtaatta cgctctacaa aatgtcatga ttagtatttt aaaccccgtg     3900

gcgtctagtc ttaaatggag atgcccgttt ccagatcaat ggatcaagga cttttatatc     3960

ccacacggta ataaaatgtt acaacctttt gctccttcat attcagctga aatgagatta     4020

ttaagtattt ataccggtga gaacatgaga ctgactcgag ttaccaaatc agacgctgta     4080

aattatgaaa aaaagatgta ctaccttaat aagatcgtcc gtaacaaagt agttgttaac     4140

tttgattatc ctaatcagga atatgactat tttcacatgt actttatgct gaggaccgtg     4200

tactgcaata aaacatttcc tactactaaa gcaaaggtac tatttctaca acaatctata     4260

tttcgtttct taaatattcc aacaacatca actgaaaaag ttagtcatga accaatacaa     4320

cgtaaaatat ctagcaaaaa ttctatgtct aaaaacagaa atagcaagag atccgtacgc     4380

agtaataaat ag                                                         4392


<210>  18
<211>  3199
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  WR-GO-002

<400>  18
atggagaatg ttcctaatgt atactttaat cctgtgttta tagagcccac gtttaaacat       60

tctttattaa gtgtttataa acacagatta atagttttat ttgaagtatt cgttgtattc      120

attctaatat atgtattttt tagatctgaa ttaaatatgt tcttcatgcc taaacgaaaa      180

atacccgatc ctattgatag attacgacgt gctaatctag cgtgtgaaga cgataaatta      240

atgatctatg gattaccatg gatgacaact caaacatctg cgttatcaat aaatagtaaa      300

ccgatagtgt ataaagattg tgcaaagctt ttgcgatcaa taaatggatc acaaccagta      360

tctcttaacg atgttcttcg cagatgatga ttcatttttt aagtatttgg ctagtcaaga      420

tgatgaatct tcattatctg atatattgca aatcactcaa tatctagact ttctgttatt      480

attattgatc caatcaaaaa ataaattaga agccgtgggt cattgttatg aatctctttc      540

agaggaatac agacaattga caaaattcac agactttcaa gattttaaaa aactgtttaa      600

caaggtccct attgttacag atggaagggt caaacttaat aaaggatatt tgttcgactt      660

tgtgattagt ttgatgcgat tcaaaaaaga atcctctcta gctaccaccg caatagatcc      720

tgttagatac atagatcctc gtcgcaatat cgcattttct aacgtgatgg atatattaaa      780

gtcgaataaa gtgaacaata attaattctt tattgtcaag gcctagaaaa acctcgaggc      840

ttatttatat tccaaaaaaa aaaaataaaa tttcaatttt tactagtaaa aattgaaatt      900

ttattttttt tttttggaat ataaataagg atgcctctgc tgctgctgct gcctctgctg      960

tgggccggcg ccctggccat gacaattcct cctcacgtgc agaagagcgt gaataatgat     1020

atgattgtga ccgataataa cggcgccgtg aaatttcccc agctgtgtaa gttttgtgat     1080

gtgagattca gcacctgtga taatcagaag tcttgcatgt ctaactgttc catcacatcc     1140

atctgtgaga agccacagga ggtgtgcgtg gccgtgtgga gaaagaatga tgagaatatc     1200

acacttgaga ccgtgtgcca cgacccaaaa ctgccatacc acgattttat tctggaggat     1260

gccgcctctc ctaagtgcat tatgaaggag aagaagaagc caggcgagac cttctttatg     1320

tgtagctgtt cctctgatga gtgtaatgat aatattatct tcagcgaaga gtataacacc     1380

agtaatcctg acctgctgct tgtgattttc caggagccta agtcttgtga caagacacac     1440

acatgccctc cctgtccagc ccctgagctg ctgggcggcc ctagcgtgtt tctgttcccc     1500

cctaagccta aagatacact gatgattagc agaacaccag aggtgacctg tgtggtggtg     1560

gatgtgagcc acgaggaccc tgaggtgaag tttaactggt atgtggatgg agtggaagtg     1620

cacaatgcta agaccaagcc tagagaggag cagtataata gcacatatag agtggtgtct     1680

gtgctgaccg tgctgcacca ggactggctg aatggcaaag agtataaatg taaggtgagc     1740

aacaaggccc tgcccgcccc cattgagaaa accatctcta aggctaaggg acagccaaga     1800

gagcctcagg tgtatacact gcctccttct agagatgagc tgaccaaaaa ccaggttagc     1860

ctgacatgcc tggtgaaagg cttctatcca agcgatatcg ctgtggaatg ggagagcaat     1920

ggccagcctg agaataatta taaaaccacc ccaccagtgc tggatagcga tggcagcttt     1980

ttcctgtatt ctaagctgac agtggataaa tctaggtggc agcagggcaa tgtgtttagc     2040

tgctctgtga tgcacgaggc cctgcacaat cactatacac agaagagcct gagcctgagc     2100

cctggcaagt gactttttat gagctcgaat tctattatat tttttatcta aaaaactaaa     2160

aataaacatt gattaaattt taatataata cttaaaaatg gatgttgtgt cgttagataa     2220

accgtttatg tattttgagg aaattgataa tgagttagat tacgaaccag aaagtgcaaa     2280

tgaggtcgca aaaaaactgc cgtatcaagg acagttaaaa ctattactag gagaattatt     2340

ttttcttagt aagttacagc gacacggtat attagatggt gccaccgtag tgtatatagg     2400

atctgctccc ggtacacata tacgttattt gagagatcat ttctataatt taggagtgat     2460

catcaaatgg atgctaattg acggccgcca tcatgatcct attttaaatg gattgcgtga     2520

tgtgactcta gtgactcggt tcgttgatga ggaatatcta cgatccatca aaaaacaact     2580

gcatccttct aagattattt taatttctga tgtgagatcc aaacgaggag gaaatgaacc     2640

tagtacggcg gatttactaa gtaattacgc tctacaaaat gtcatgatta gtattttaaa     2700

ccccgtggcg tctagtctta aatggagatg cccgtttcca gatcaatgga tcaaggactt     2760

ttatatccca cacggtaata aaatgttaca accttttgct ccttcatatt cagctgaaat     2820

gagattatta agtatttata ccggtgagaa catgagactg actcgagtta ccaaatcaga     2880

cgctgtaaat tatgaaaaaa agatgtacta ccttaataag atcgtccgta acaaagtagt     2940

tgttaacttt gattatccta atcaggaata tgactatttt cacatgtact ttatgctgag     3000

gaccgtgtac tgcaataaaa catttcctac tactaaagca aaggtactat ttctacaaca     3060

atctatattt cgtttcttaa atattccaac aacatcaact gaaaaagtta gtcatgaacc     3120

aatacaacgt aaaatatcta gcaaaaattc tatgtctaaa aacagaaata gcaagagatc     3180

cgtacgcagt aataaatag                                                  3199


<210>  19
<211>  3214
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  WR-GO-003

<400>  19
atggagaatg ttcctaatgt atactttaat cctgtgttta tagagcccac gtttaaacat       60

tctttattaa gtgtttataa acacagatta atagttttat ttgaagtatt cgttgtattc      120

attctaatat atgtattttt tagatctgaa ttaaatatgt tcttcatgcc taaacgaaaa      180

atacccgatc ctattgatag attacgacgt gctaatctag cgtgtgaaga cgataaatta      240

atgatctatg gattaccatg gatgacaact caaacatctg cgttatcaat aaatagtaaa      300

ccgatagtgt ataaagattg tgcaaagctt ttgcgatcaa taaatggatc acaaccagta      360

tctcttaacg atgttcttcg cagatgatga ttcatttttt aagtatttgg ctagtcaaga      420

tgatgaatct tcattatctg atatattgca aatcactcaa tatctagact ttctgttatt      480

attattgatc caatcaaaaa ataaattaga agccgtgggt cattgttatg aatctctttc      540

agaggaatac agacaattga caaaattcac agactttcaa gattttaaaa aactgtttaa      600

caaggtccct attgttacag atggaagggt caaacttaat aaaggatatt tgttcgactt      660

tgtgattagt ttgatgcgat tcaaaaaaga atcctctcta gctaccaccg caatagatcc      720

tgttagatac atagatcctc gtcgcaatat cgcattttct aacgtgatgg atatattaaa      780

gtcgaataaa gtgaacaata attaattctt tattgtcaag gcctagaaaa acctcacttg      840

cctggagaca gagacagaga cttctgggtg tagtggttgt gcagggcctc gtgcatcaca      900

gagcaagaga acacgttgcc ctgctgccat ctactcttgt ccactgtgag cttagagtac      960

aggaagaaag agccgtcaga gtcgagcaca ggtggtgttg tcttgtagtt gttctcaggc     1020

tggccgttag actcccactc cacggcaatg tcgctagggt agaagccctt cacgaggcat     1080

gtgagggaca cctggttctt ggtcagctcg tccctagaag gaggcagtgt gtacacctga     1140

ggctcgcgtg gctggccctt ggccttgcta atggtttttt caataggggc ggggagggcc     1200

ttgttggaca ccttgcactt gtactccttg ccgttcagcc agtcctggtg cagcactgtg     1260

agcacggaca ccacgcggta tgtagagttg tactgctcct ctctaggctt tgtcttggcg     1320

ttgtgcacct ccacgccgtc cacgtaccag ttgaacttca cctcggggtc ctcgtgagac     1380

acgtccacca ccacgcatgt cacctcaggt gtcctgctaa tcatgagtgt gtcctttggc     1440

tttggtggga acaggaacac ggatgggccg cccagcagct caggggcggg gcaaggtggg     1500

catgtgtggg tcttgtcgca agacttaggc tccacgagtg tctggaactg gccggcgggt     1560

ctaggagatg gagatgggtg ggcggtaggc acctcggctc tccgctctgt cactctcagc     1620

tcggcccgca gggactcctt aatctgggcc ttaggggcga ggctaatggc gccgcacagg     1680

tatgtgccag agtcgtttct ccgggcgcgc accacgctca tgtggaagtc cctgccgttt     1740

gggagctggg tcactctgaa tctgcaatcc tggccaggct gcgagcggtc ctcggggaag     1800

gcggcgagct tgtcggtctg gttagatgga gacatccgat accagttcag cacgaaagac     1860

tcggatgtgt tgctgaagct gcatgtgaag gtggcgttgt cgccctcggt caccacgagg     1920

agggcggggc tgaatgtagg tgggttccaa ggtctgtcgg gagagtcgag gaaccagccc     1980

atagcgaggg cgccggccca gagcagtggc agcaggagga gcagtggcat ggcttattta     2040

tattccaaaa aaaaaaaata aaatttcaat ttttactagt aaaaattgaa attttatttt     2100

ttttttttgg aatataaata aggtcgactt tttatgagct cgaattctat tatatttttt     2160

atctaaaaaa ctaaaaataa acattgatta aattttaata taatacttaa aaatggatgt     2220

tgtgtcgtta gataaaccgt ttatgtattt tgaggaaatt gataatgagt tagattacga     2280

accagaaagt gcaaatgagg tcgcaaaaaa actgccgtat caaggacagt taaaactatt     2340

actaggagaa ttattttttc ttagtaagtt acagcgacac ggtatattag atggtgccac     2400

cgtagtgtat ataggatctg ctcccggtac acatatacgt tatttgagag atcatttcta     2460

taatttagga gtgatcatca aatggatgct aattgacggc cgccatcatg atcctatttt     2520

aaatggattg cgtgatgtga ctctagtgac tcggttcgtt gatgaggaat atctacgatc     2580

catcaaaaaa caactgcatc cttctaagat tattttaatt tctgatgtga gatccaaacg     2640

aggaggaaat gaacctagta cggcggattt actaagtaat tacgctctac aaaatgtcat     2700

gattagtatt ttaaaccccg tggcgtctag tcttaaatgg agatgcccgt ttccagatca     2760

atggatcaag gacttttata tcccacacgg taataaaatg ttacaacctt ttgctccttc     2820

atattcagct gaaatgagat tattaagtat ttataccggt gagaacatga gactgactcg     2880

agttaccaaa tcagacgctg taaattatga aaaaaagatg tactacctta ataagatcgt     2940

ccgtaacaaa gtagttgtta actttgatta tcctaatcag gaatatgact attttcacat     3000

gtactttatg ctgaggaccg tgtactgcaa taaaacattt cctactacta aagcaaaggt     3060

actatttcta caacaatcta tatttcgttt cttaaatatt ccaacaacat caactgaaaa     3120

agttagtcat gaaccaatac aacgtaaaat atctagcaaa aattctatgt ctaaaaacag     3180

aaatagcaag agatccgtac gcagtaataa atag                                 3214


<210>  20
<211>  233
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-PD-1 antibody-LC

<400>  20

Met Ala Trp Ser Pro Leu Phe Leu Thr Leu Ile Thr His Cys Ala Gly 
1               5                   10                  15      


Ser Trp Ala Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230             


<210>  21
<211>  459
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-PD-1 antibody-HC

<400>  21

Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 
1               5                   10                  15      


Ala His Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln 
            20                  25                  30          


Pro Gly Arg Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe 
        35                  40                  45              


Ser Asn Ser Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Val Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala 
65                  70                  75                  80  


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


Thr Leu Phe Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val 
        115                 120                 125             


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


Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 
145                 150                 155                 160 


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


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
            180                 185                 190         


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
        195                 200                 205             


Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 
    210                 215                 220                 


Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 
225                 230                 235                 240 


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


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


Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 
        275                 280                 285             


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


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


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


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


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


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


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


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


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


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


Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    450                 455                 


<210>  22
<211>  5338
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  WR-GO-004

<400>  22
atggagaatg ttcctaatgt atactttaat cctgtgttta tagagcccac gtttaaacat       60

tctttattaa gtgtttataa acacagatta atagttttat ttgaagtatt cgttgtattc      120

attctaatat atgtattttt tagatctgaa ttaaatatgt tcttcatgcc taaacgaaaa      180

atacccgatc ctattgatag attacgacgt gctaatctag cgtgtgaaga cgataaatta      240

atgatctatg gattaccatg gatgacaact caaacatctg cgttatcaat aaatagtaaa      300

ccgatagtgt ataaagattg tgcaaagctt ttgcgatcaa taaatggatc acaaccagta      360

tctcttaacg atgttcttcg cagatgatga ttcatttttt aagtatttgg ctagtcaaga      420

tgatgaatct tcattatctg atatattgca aatcactcaa tatctagact ttctgttatt      480

attattgatc caatcaaaaa ataaattaga agccgtgggt cattgttatg aatctctttc      540

agaggaatac agacaattga caaaattcac agactttcaa gattttaaaa aactgtttaa      600

caaggtccct attgttacag atggaagggt caaacttaat aaaggatatt tgttcgactt      660

tgtgattagt ttgatgcgat tcaaaaaaga atcctctcta gctaccaccg caatagatcc      720

tgttagatac atagatcctc gtcgcaatat cgcattttct aacgtgatgg atatattaaa      780

gtcgaataaa gtgaacaata attaattctt tattgtcaag gcctagaaaa accttacttc      840

cctaggctga gactcagtga tttttgggtg taatggttgt gcaacgcttc gtgcatcacg      900

gagcaggaaa agacattacc ttcctgccaa cggcttttat caacggtcag gcgcgagtac      960

agaaagaagc tgccgtcgct gtcaagcacg ggtggagtag tcttatagtt attctctggt     1020

tggccattac tctcccactc cacggctata tcgctagggt aaaaaccctt aaccagacag     1080

gtcagactta cctggttttt agtcatttct tcctgtgagg gtggtagggt gtagacctga     1140

ggttcccgag gctgtccctt ggctttgcta attgtctttt cgatggaaga gggcaatcct     1200

ttgtttgaca ccttgcactt atattccttg ccattcagcc aatcctggtg caacactgtc     1260

agcacgctga cgacccgata ggttgaattg aattgttcct cgcggggttt cgtctttgcg     1320

ttatgcactt caacgccgtc tacgtaccag ttgaattgca cttcgggatc ctcttgagag     1380

acatcaacca cgacacaagt cacttccggg gtccggctaa tcattagggt gtccttaggt     1440

tttggtggga acagaaacac ggacggtcca cccaagaact cgggggcagg acacggaggg     1500

caggggggtc catacttgga ttcgacccgc ttatctactt tagtattaga gggcttgtgg     1560

tcaacgttac aggtataagt tttcgtgcct agactagatg aaggaacagt gaccacggaa     1620

gatagtgaat agaggcccga gctctgcagc acggcaggga atgtgtgcac tccagaggtc     1680

agggcgccgc tgttccagga cacagtcacc ggttctggaa agtagtcctt cacgagacat     1740

cctagcgcag ctgtgctttc gcttgtgctc ctactgcagg gggcgagcgg gaacactgag     1800

ggtcccttgg tgcttgccga acttacggtc accaatgtgc cctgtcccca gtaatcgtcg     1860

tttgtggcgc agtagtatac ggctgtgtcc tcagcccgca gtgaattcat ctgtaggaac     1920

aatgtatttt tagagttgtc cctactaatg gtgaaccgtc ccttcacaga gtcggcgtaa     1980

taacgcttgg agccgtcata ccagataact gccacccact ccaagccctt gcctggcgct     2040

tgccgtaccc agtgcatccc gctgttagaa aaggtgatgc cggaagcctt acagtccaat     2100

cttagtgatc tgcctggctg gacaactccg ccgcctgact caaccagctg tacttggctg     2160

tgggcgcctg ttgccgcggc aaccaagaac aggattctcc aggtccaatc catctcgagc     2220

ttatttatat tccaaaaaaa aaaaataaaa tttcaatttt taaaaaattg aaattttatt     2280

tttttttttt ggaatataaa taaggtcgac atggcatggt ccccattatt tctgaccttg     2340

attactcact gcgccggctc ttgggctgaa atcgtactca cgcagtcccc tgctactctg     2400

agtctctcac caggagaacg cgctaccctt tcttgccgtg cgtcacagtc agtatcgtcc     2460

tatctggctt ggtatcagca aaaaccaggt caggcccccc gattattgat ttatgatgca     2520

tctaaccggg ctacagggat tcctgccaga tttagcggta gcgggagtgg aactgacttc     2580

actctaacca ttagctccct tgagccagag gatttcgccg tctactactg tcagcagtct     2640

tccaactggc ctcgtacttt cggacaggga acaaaggtgg aaatcaaacg taccgtggct     2700

gcacccagcg tgttcatttt tccaccaagc gacgagcagc tcaagagcgg aaccgcatcc     2760

gtagtatgtc tcctcaataa cttctaccca cgagaagcca aagtgcagtg gaaggtggat     2820

aatgccttgc aatccggaaa cagccaagaa agcgtgaccg aacaggattc aaaagacagc     2880

acctattctc tgtccagcac attgacactg agtaaagctg attatgagaa gcacaaggtc     2940

tacgcgtgtg aggttacaca tcaaggattg tcttcaccag tcaccaagag tttcaataga     3000

ggagagtgct gagaattctt tttattaaaa attgaaattt tatttttttt ttttggaata     3060

taaataagga tgcctctgct gctgctgctg cctctgctgt gggccggcgc cctggccatg     3120

acaattcctc ctcacgtgca gaagagcgtg aataatgata tgattgtgac cgataataac     3180

ggcgccgtga aatttcccca gctgtgtaag ttttgtgatg tgagattcag cacctgtgat     3240

aatcagaagt cttgcatgtc taactgttcc atcacatcca tctgtgagaa gccacaggag     3300

gtgtgcgtgg ccgtgtggag aaagaatgat gagaatatca cacttgagac cgtgtgccac     3360

gacccaaaac tgccatacca cgattttatt ctggaggatg ccgcctctcc taagtgcatt     3420

atgaaggaga agaagaagcc aggcgagacc ttctttatgt gtagctgttc ctctgatgag     3480

tgtaatgata atattatctt cagcgaagag tataacacca gtaatcctga cctgctgctt     3540

gtgattttcc aggagcctaa gtcttgtgac aagacacaca catgccctcc ctgtccagcc     3600

cctgagctgc tgggcggccc tagcgtgttt ctgttccccc ctaagcctaa agatacactg     3660

atgattagca gaacaccaga ggtgacctgt gtggtggtgg atgtgagcca cgaggaccct     3720

gaggtgaagt ttaactggta tgtggatgga gtggaagtgc acaatgctaa gaccaagcct     3780

agagaggagc agtataatag cacatataga gtggtgtctg tgctgaccgt gctgcaccag     3840

gactggctga atggcaaaga gtataaatgt aaggtgagca acaaggccct gcccgccccc     3900

attgagaaaa ccatctctaa ggctaaggga cagccaagag agcctcaggt gtatacactg     3960

cctccttcta gagatgagct gaccaaaaac caggttagcc tgacatgcct ggtgaaaggc     4020

ttctatccaa gcgatatcgc tgtggaatgg gagagcaatg gccagcctga gaataattat     4080

aaaaccaccc caccagtgct ggatagcgat ggcagctttt tcctgtattc taagctgaca     4140

gtggataaat ctaggtggca gcagggcaat gtgtttagct gctctgtgat gcacgaggcc     4200

ctgcacaatc actatacaca gaagagcctg agcctgagcc ctggcaagtg actttttatg     4260

agctcgaatt ctattatatt ttttatctaa aaaactaaaa ataaacattg attaaatttt     4320

aatataatac ttaaaaatgg atgttgtgtc gttagataaa ccgtttatgt attttgagga     4380

aattgataat gagttagatt acgaaccaga aagtgcaaat gaggtcgcaa aaaaactgcc     4440

gtatcaagga cagttaaaac tattactagg agaattattt tttcttagta agttacagcg     4500

acacggtata ttagatggtg ccaccgtagt gtatatagga tctgctcccg gtacacatat     4560

acgttatttg agagatcatt tctataattt aggagtgatc atcaaatgga tgctaattga     4620

cggccgccat catgatccta ttttaaatgg attgcgtgat gtgactctag tgactcggtt     4680

cgttgatgag gaatatctac gatccatcaa aaaacaactg catccttcta agattatttt     4740

aatttctgat gtgagatcca aacgaggagg aaatgaacct agtacggcgg atttactaag     4800

taattacgct ctacaaaatg tcatgattag tattttaaac cccgtggcgt ctagtcttaa     4860

atggagatgc ccgtttccag atcaatggat caaggacttt tatatcccac acggtaataa     4920

aatgttacaa ccttttgctc cttcatattc agctgaaatg agattattaa gtatttatac     4980

cggtgagaac atgagactga ctcgagttac caaatcagac gctgtaaatt atgaaaaaaa     5040

gatgtactac cttaataaga tcgtccgtaa caaagtagtt gttaactttg attatcctaa     5100

tcaggaatat gactattttc acatgtactt tatgctgagg accgtgtact gcaataaaac     5160

atttcctact actaaagcaa aggtactatt tctacaacaa tctatatttc gtttcttaaa     5220

tattccaaca acatcaactg aaaaagttag tcatgaacca atacaacgta aaatatctag     5280

caaaaattct atgtctaaaa acagaaatag caagagatcc gtacgcagta ataaatag       5338


<210>  23
<211>  5
<212>  PRT
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-HCDR1
<222>  (1)..(5)

<400>  23

Asn Ser Gly Met His 
1               5   


<210>  24
<211>  17
<212>  PRT
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-HCDR2
<222>  (1)..(17)

<400>  24

Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  25
<211>  4
<212>  PRT
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-HCDR3
<222>  (1)..(4)

<400>  25

Asn Asp Asp Tyr 
1               


<210>  26
<211>  11
<212>  PRT
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-LCDR1
<222>  (1)..(11)

<400>  26

Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala 
1               5                   10      


<210>  27
<211>  7
<212>  PRT
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-LCDR2
<222>  (1)..(7)

<400>  27

Asp Ala Ser Asn Arg Ala Thr 
1               5           


<210>  28
<211>  9
<212>  PRT
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-LCDR3
<222>  (1)..(9)

<400>  28

Gln Gln Ser Ser Asn Trp Pro Arg Thr 
1               5                   


<210>  29
<211>  113
<212>  PRT
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-VH
<222>  (1)..(113)

<400>  29

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


Gly Met 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 Lys Arg Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser 
    


<210>  30
<211>  110
<212>  PRT
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-VL
<222>  (1)..(110)

<400>  30

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


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


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


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


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


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


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


<210>  31
<211>  15
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-HCDR1
<222>  (1)..(15)

<400>  31
aacagcggga tgcac                                                        15


<210>  32
<211>  51
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-HCDR2
<222>  (1)..(51)

<400>  32
gttatctggt atgacggctc caagcgttat tacgccgact ctgtgaaggg a                51


<210>  33
<211>  12
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-HCDR3
<222>  (1)..(12)

<400>  33
aacgacgatt ac                                                           12


<210>  34
<211>  33
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-LCDR1
<222>  (1)..(33)

<400>  34
cgtgcgtcac agtcagtatc gtcctatctg gct                                    33


<210>  35
<211>  21
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-LCDR2
<222>  (1)..(21)

<400>  35
gatgcatcta accgggctac a                                                 21


<210>  36
<211>  27
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-LCDR3
<222>  (1)..(27)

<400>  36
cagcagtctt ccaactggcc tcgtact                                           27


<210>  37
<211>  339
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-VH
<222>  (1)..(339)

<400>  37
caagtacagc tggttgagtc aggcggcgga gttgtccagc caggcagatc actaagattg       60

gactgtaagg cttccggcat caccttttct aacagcggga tgcactgggt acggcaagcg      120

ccaggcaagg gcttggagtg ggtggcagtt atctggtatg acggctccaa gcgttattac      180

gccgactctg tgaagggacg gttcaccatt agtagggaca actctaaaaa tacattgttc      240

ctacagatga attcactgcg ggctgaggac acagccgtat actactgcgc cacaaacgac      300

gattactggg gacagggcac attggtgacc gtaagttcg                             339


<210>  38
<211>  330
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-VL
<222>  (1)..(330)

<400>  38
gaaatcgtac tcacgcagtc ccctgctact ctgagtctct caccaggaga acgcgctacc       60

ctttcttgcc gtgcgtcaca gtcagtatcg tcctatctgg cttggtatca gcaaaaacca      120

ggtcaggccc cccgattatt gatttatgat gcatctaacc gggctacagg gattcctgcc      180

agatttagcg gtagcgggag tggaactgac ttcactctaa ccattagctc ccttgagcca      240

gaggatttcg ccgtctacta ctgtcagcag tcttccaact ggcctcgtac tttcggacag      300

ggaacaaagg tggaaatcaa acgtaccgtg                                       330


<210>  39
<211>  1379
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-HC
<222>  (1)..(983)

<400>  39
atggattgga cctggagaat cctgttcttg gttgccgcgg caacaggcgc ccacagccaa       60

gtacagctgg ttgagtcagg cggcggagtt gtccagccag gcagatcact aagattggac      120

tgtaaggctt ccggcatcac cttttctaac agcgggatgc actgggtacg gcaagcgcca      180

ggcaagggct tggagtgggt ggcagttatc tggtatgacg gctccaagcg ttattacgcc      240

gactctgtga agggacggtt caccattagt agggacaact ctaaaaatac attgttccta      300

cagatgaatt cactgcgggc tgaggacaca gccgtatact actgcgccac aaacgacgat      360

tactggggac agggcacatt ggtgaccgta agttcggcaa gcaccaaggg accctcagtg      420

ttcccgctcg ccccctgcag taggagcaca agcgaaagca cagctgcgct aggatgtctc      480

gtgaaggact actttccaga accggtgact gtgtcctgga acagcggcgc cctgacctct      540

ggagtgcaca cattccctgc cgtgctgcag agctcgggcc tctattcact atcttccgtg      600

gtcactgttc cttcatctag tctaggcacg aaaacttata cctgtaacgt tgaccacaag      660

ccctctaata ctaaagtaga taagcgggtc gaatccaagt atggaccccc ctgccctccg      720

tgtcctgccc ccgagttctt gggtggaccg tccgtgtttc tgttcccacc aaaacctaag      780

gacaccctaa tgattagccg gaccccggaa gtgacttgtg tcgtggttga tgtctctcaa      840

gaggatcccg aagtgcaatt caactggtac gtagacggcg ttgaagtgca taacgcaaag      900

acgaaacccc gcgaggaaca attcaattca acctatcggg tcgtcagcgt gctgacagtg      960

ttgcaccagg attggctgaa tggcaaggaa tataagtgca aggtgtcaaa caaaggattg     1020

ccctcttcca tcgaaaagac aattagcaaa gccaagggac agcctcggga acctcaggtc     1080

tacaccctac caccctcaca ggaagaaatg actaaaaacc aggtaagtct gacctgtctg     1140

gttaagggtt tttaccctag cgatatagcc gtggagtggg agagtaatgg ccaaccagag     1200

aataactata agactactcc acccgtgctt gacagcgacg gcagcttctt tctgtactcg     1260

cgcctgaccg ttgataaaag ccgttggcag gaaggtaatg tcttttcctg ctccgtgatg     1320

cacgaagcgt tgcacaacca ttacacccaa aaatcactga gtctcagcct agggaagta      1379


<210>  40
<211>  702
<212>  DNA
<213>  Homo sapiens


<220>
<221>  anti-PD-1 antibody-LC
<222>  (1)..(315)

<400>  40
atggcatggt ccccattatt tctgaccttg attactcact gcgccggctc ttgggctgaa       60

atcgtactca cgcagtcccc tgctactctg agtctctcac caggagaacg cgctaccctt      120

tcttgccgtg cgtcacagtc agtatcgtcc tatctggctt ggtatcagca aaaaccaggt      180

caggcccccc gattattgat ttatgatgca tctaaccggg ctacagggat tcctgccaga      240

tttagcggta gcgggagtgg aactgacttc actctaacca ttagctccct tgagccagag      300

gatttcgccg tctactactg tcagcagtct tccaactggc ctcgtacttt cggacaggga      360

acaaaggtgg aaatcaaacg taccgtggct gcacccagcg tgttcatttt tccaccaagc      420

gacgagcagc tcaagagcgg aaccgcatcc gtagtatgtc tcctcaataa cttctaccca      480

cgagaagcca aagtgcagtg gaaggtggat aatgccttgc aatccggaaa cagccaagaa      540

agcgtgaccg aacaggattc aaaagacagc acctattctc tgtccagcac attgacactg      600

agtaaagctg attatgagaa gcacaaggtc tacgcgtgtg aggttacaca tcaaggattg      660

tcttcaccag tcaccaagag tttcaataga ggagagtgct ga                         702


