                         SEQUENCE LISTING

<110>  Asia Biotech
 
<120>  PD-1 ANTIBODIES AND USES THEREOF

<130>  31623SG1

<160>  28    

<170>  PatentIn version 3.5

<210>  1
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy chain CDR1

<400>  1

Thr Tyr Gly Met Ser 
1               5   


<210>  2
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy chain CDR2

<400>  2

Thr Ile Ser Gly Gly Gly Arg Asp Thr Tyr Tyr Pro Asp Thr Val Lys 
1               5                   10                  15      


Gly 
    


<210>  3
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy chain CDR3

<400>  3

Gln Asp Tyr Gly Asn Tyr Val Trp Phe Ala Tyr 
1               5                   10      


<210>  4
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain CDR1

<400>  4

Arg Ala Ser Glu Ser Val Asp Ser Tyr Gly Ile Ser Phe Met His 
1               5                   10                  15  


<210>  5
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain CDR2

<400>  5

Ser Thr Ser Asn Arg Gly Ser 
1               5           


<210>  6
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain CDR3

<400>  6

Gln Gln Ser Gln Glu Val Pro Trp Thr 
1               5                   


<210>  7
<211>  360
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of hu67D9 heavy chain variable region

<400>  7
gaggtgcagc tcgtggaatc tgggggcgga ctggtgcagc ccggtggaag tctccggctg       60

agctgcgccg ctagtgggtt cactttttct acttacggga tgtcttgggt ccgacaggca      120

ccaggcaagg ggctggagtg ggtggctact atttctggag gaggccgaga cacctactac      180

cccgacaccg tcaagggacg ttttactatc agccgtgaca acagcaagaa taccctctac      240

cttcagatgt cttcactgcg agctgaagac accgctgtgt actattgtgc ccgtcaggac      300

tacggtaact acgtgtggtt cgcttactgg ggacagggaa ccctggtcac cgtctcctcg      360


<210>  8
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of hu67D9 heavy chain variable region

<400>  8

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


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


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


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


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


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


Ala Arg Gln Asp Tyr Gly Asn Tyr Val Trp Phe Ala Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  9
<211>  336
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of hu67D9 light chain variable region

<400>  9
gatattgttc tgacccagtc ccccgcttca ctggctgtga gtcctgggca gcgagctacc       60

atcagctgcc gggcttcaga gtccgtggat agctacggaa tttcatttat gcactggttc      120

cagcagaagc caggccaacc acctcagttg ctgatatatt cgacatctaa tcggggaagc      180

ggtgtgccag cccggtttag tggtagcggc tctggtacag atttctctct tacaattaac      240

ccagtggagg cggatgacac tgccaattac ttttgtcagc agagccagga agtgccttgg      300

acttttggtc agggcacgaa ggtagagatt aaacgg                                336


<210>  10
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of hu67D9 light chain variable region

<400>  10

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


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


Gly Ile Ser Phe Met His Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


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


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


<210>  11
<211>  1173
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of the DNA containing cDNA encoding the 
       extracellular region of human PD-1 fused to human Fc

<400>  11
aagcttcttg ccgccaccat gcagatccca caggcgccct ggccagtcgt ctgggcggtg       60

ctacaactgg gctggcggcc aggatggttc ttagactccc cagacaggcc ctggaacccc      120

cccaccttct ccccagccct gctcgtggtg accgaagggg acaacgccac cttcacctgc      180

agcttctcca acacatcgga gagcttcgtg ctaaactggt accgcatgag ccccagcaac      240

cagacggaca agctggccgc cttccccgag gaccgcagcc agcccggcca ggactgccgc      300

ttccgtgtca cacaactgcc caacgggcgt gacttccaca tgagcgtggt cagggcccgg      360

cgcaatgaca gcggcaccta cctctgtggg gccatctccc tggcccccaa ggcgcagatc      420

aaagagagcc tgcgggcaga gctcagggtg acagagagaa gggctagcga gcccaaatct      480

tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca      540

gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc      600

acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg      660

gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg      720

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac      780

aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc      840

aaagggcagc cccgagaacc acaggtgtac accctgcccc catctcggga ggagatgacc      900

aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg      960

gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac     1020

tccgacggct ccttcttcct ctatagcaag ctcaccgtgg acaagagcag gtggcagcag     1080

gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag     1140

agcctctccc tgtccccggg taaatgagaa ttc                                  1173


<210>  12
<211>  1443
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of the DNA containing cDNA encoding the 
       extracellular region of human PD-L1 fused to human Fc

<400>  12
aagcttgccg ccaccatgag gatatttgct gtctttatat tcatgaccta ctggcatttg       60

ctgaacgcat ttactgtcac ggttcccaag gacctatatg tggtagagta tggtagcaat      120

atgacaattg aatgcaaatt cccagtagaa aaacaattag acctggctgc actaattgtc      180

tattgggaaa tggaggataa gaacattatt caatttgtgc atggagagga agacctgaag      240

gttcagcata gtagctacag acagagggcc cggctgttga aggaccagct ctccctggga      300

aatgctgcac ttcagatcac agatgtgaaa ttgcaggatg caggggtgta ccgctgcatg      360

atcagctatg gtggtgccga ctacaagcga attactgtga aagtcaatgc cccatacaac      420

aaaatcaacc aaagaatttt ggttgtggat ccagtcacct ctgaacatga actgacatgt      480

caggctgagg gctaccccaa ggccgaagtc atctggacaa gcagtgacca tcaagtcctg      540

agtggtaaga ccaccaccac caattccaag agagaggaga aacttttcaa tgtgaccagc      600

acactgagaa tcaacacaac aactaatgag attttctact gcacttttag gagattagat      660

cctgaggaaa accatacagc tgaattggtc atcccagaac tacctctggc acatcctcca      720

aatgaaagga ctgctagcga gcccaaatct tgtgacaaaa ctcacacatg cccaccgtgc      780

ccagcacctg aactcctggg gggaccgtca gtcttcctct tccccccaaa acccaaggac      840

accctcatga tctcccggac ccctgaggtc acatgcgtgg tggtggacgt gagccacgaa      900

gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca      960

aagccgcggg aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg     1020

caccaggact ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca     1080

gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac     1140

accctgcccc catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc     1200

aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac     1260

aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag     1320

ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat     1380

gaggctctgc acaaccacta cacgcagaag agcctctccc tgtccccggg taaatgagaa     1440

ttc                                                                   1443


<210>  13
<211>  888
<212>  DNA
<213>  Homo sapiens

<400>  13
aagcttgccg ccaccatgca gatcccacag gcgccctggc cagtcgtctg ggcggtgcta       60

caactgggct ggcggccagg atggttctta gactccccag acaggccctg gaaccccccc      120

accttctccc cagccctgct cgtggtgacc gaaggggaca acgccacctt cacctgcagc      180

ttctccaaca catcggagag cttcgtgcta aactggtacc gcatgagccc cagcaaccag      240

acggacaagc tggccgcctt ccccgaggac cgcagccagc ccggccagga ctgccgcttc      300

cgtgtcacac aactgcccaa cgggcgtgac ttccacatga gcgtggtcag ggcccggcgc      360

aatgacagcg gcacctacct ctgtggggcc atctccctgg cccccaaggc gcagatcaaa      420

gagagcctgc gggcagagct cagggtgaca gagagaaggg cagaagtgcc cacagcccac      480

cccagcccct cacccaggcc agccggccag ttccaaaccc tggtggttgg tgtcgtgggc      540

ggcctgctgg gcagcctggt gctgctagtc tgggtcctgg ccgtcatctg ctcccgggcc      600

gcacgaggga caataggagc caggcgcacc ggccagcccc tgaaggagga cccctcagcc      660

gtgcctgtgt tctctgtgga ctatggggag ctggatttcc agtggcgaga gaagaccccg      720

gagccccccg tgccctgtgt ccctgagcag acggagtatg ccaccattgt ctttcctagc      780

ggaatgggca cctcatcccc cgcccgcagg ggctcagctg acggccctcg gagtgcccag      840

ccactgaggc ctgaggatgg acactgctct tggcccctct gagaattc                   888


<210>  14
<211>  268
<212>  PRT
<213>  Homo sapiens

<400>  14

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


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


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


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


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


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


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


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


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


Gln Phe Gln Thr Leu Val Val Gly Val Val Gly Gly Leu Leu Gly Ser 
145                 150                 155                 160 


Leu Val Leu Leu Val Trp Val Leu Ala Val Ile Cys Ser Arg Ala Ala 
                165                 170                 175     


Arg Gly Thr Ile Gly Ala Arg Arg Thr Gly Gln Pro Leu Lys Glu Asp 
            180                 185                 190         


Pro Ser Ala Val Pro Val Phe Ser Val Asp Tyr Gly Glu Leu Asp Phe 
        195                 200                 205             


Gln Trp Arg Glu Lys Thr Pro Glu Pro Pro Val Pro Cys Val Pro Glu 
    210                 215                 220                 


Gln Thr Glu Tyr Ala Thr Ile Val Phe Pro Ser Gly Met Gly Thr Ser 
225                 230                 235                 240 


Ser Pro Ala Arg Arg Gly Ser Ala Asp Gly Pro Arg Ser Ala Gln Pro 
                245                 250                 255     


Leu Arg Pro Glu Asp Gly His Cys Ser Trp Pro Leu 
            260                 265             


<210>  15
<211>  360
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of the heavy chain variable region of 67D9

<400>  15
gaagtgattc tggtggagtc tgggggaggc ttagtgaagc ctggagggtc cctgaaagtc       60

tcctgtgcgg cctctggatt cactttcagt acctatggca tgtcttgggt tcgccagact      120

ccggagaaga ggctggagtg ggtcgcaacc attagtggtg gtggtcgtga cacctactat      180

ccagacactg tgaaggggcg attcaccatc tccagagaca atgccaaaaa taccctgtat      240

ctacaaatga gcagtctgag gtctgaggac acggccttgt attattgtgc aagacaggac      300

tatggtaact acgtatggtt tgcttactgg ggccaaggga ctctggtcac tgtctctgca      360


<210>  16
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of the heavy chain variable region of 67D9

<400>  16

Glu Val Ile Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 
1               5                   10                  15      


Ser Leu Lys Val Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gln Asp Tyr Gly Asn Tyr Val Trp Phe Ala Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ala 
        115                 120 


<210>  17
<211>  336
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of the light chain variable region of 67D9

<400>  17
gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc       60

atctcctgca gagccagcga aagtgttgat agttatggca ttagttttat gcactggttc      120

caacagaaac caggacagcc accccaactc ctcatctatt ctacatccaa ccgaggatcc      180

ggggtccctg ccaggtttag tggcagtggg tctgggacag acttcagcct caccatccat      240

cctatggagg aggatgatac tgcaatgtat ttctgtcagc aaagtcagga ggttccgtgg      300

acgttcggtg gaggcaccaa gctggaaatc aaacgg                                336


<210>  18
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of the light chain variable region of 67D9

<400>  18

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


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


Gly Ile Ser Phe Met His Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


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


Glu Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
            100                 105                 110         


<210>  19
<211>  1422
<212>  DNA
<213>  Homo sapiens

<400>  19
aagcttgccg ccaccatgaa cttcggactc agcttgattt tccttgtcct aattttaaaa       60

ggtgtccagt gtgaagtgat tctggtggag tctgggggag gcttagtgaa gcctggaggg      120

tccctgaaag tctcctgtgc ggcctctgga ttcactttca gtacctatgg catgtcttgg      180

gttcgccaga ctccggagaa gaggctggag tgggtcgcaa ccattagtgg tggtggtcgt      240

gacacctact atccagacac tgtgaagggg cgattcacca tctccagaga caatgccaaa      300

aataccctgt atctacaaat gagcagtctg aggtctgagg acacggcctt gtattattgt      360

gcaagacagg actatggtaa ctacgtatgg tttgcttact ggggccaagg gactctggtc      420

actgtctctg cagctagcac caagggccca tccgtcttcc ccctggcgcc ctgctccagg      480

agcacctccg agagcacagc cgccctgggc tgcctggtca aggactactt ccccgaaccg      540

gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc      600

ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg      660

ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacaag      720

agagttgagt ccaaatatgg tcccccatgc ccaccctgcc cagcacctga gttcctgggg      780

ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc      840

cctgaggtca cgtgcgtggt ggtggacgtg agccaggaag accccgaggt ccagttcaac      900

tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagttc      960

aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaacggc     1020

aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc     1080

tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag     1140

gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac     1200

atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc     1260

gtgctggact ccgacggctc cttcttcctc tacagcaggc taaccgtgga caagagcagg     1320

tggcaggagg ggaatgtctt ctcatgctcc gtgatgcacg aggctctgca caaccactac     1380

acacagaaga gcctctccct gtctctgggt aaatgagaat tc                        1422


<210>  20
<211>  738
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of the DNA containing the cDNA encoding the 
       c67D9 light chain

<400>  20
aagcttgccg ccaccatgga gaaagacaca ctcctgctat gggtcctgct tctctgggtt       60

ccaggttcca caggtgacat tgtgctgacc caatctccag cttctttggc tgtgtctcta      120

gggcagaggg ccaccatctc ctgcagagcc agcgaaagtg ttgatagtta tggcattagt      180

tttatgcact ggttccaaca gaaaccagga cagccacccc aactcctcat ctattctaca      240

tccaaccgag gatccggggt ccctgccagg tttagtggca gtgggtctgg gacagacttc      300

agcctcacca tccatcctat ggaggaggat gatactgcaa tgtatttctg tcagcaaagt      360

caggaggttc cgtggacgtt cggtggaggc accaagctgg aaatcaaacg gactgtggct      420

gcaccatctg tcttcatctt cccgccatct gatgagcagt tgaaatctgg aactgcctct      480

gttgtgtgcc tgctgaataa cttctatccc agagaggcca aagtacagtg gaaggtggat      540

aacgccctcc aatcgggtaa ctcccaggag agtgtcacag agcaggacag caaggacagc      600

acctacagcc tcagcagcac cctgacgctg agcaaagcag actacgagaa acacaaagtc      660

tacgcctgcg aagtcaccca tcagggcctg agctcgcccg tcacaaagag cttcaacagg      720

ggagagtgtt aggaattc                                                    738


<210>  21
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of c67D9 heavy chain

<400>  21

Glu Val Ile Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 
1               5                   10                  15      


Ser Leu Lys Val Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gln Asp Tyr Gly Asn Tyr Val Trp Phe Ala Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


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


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


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


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


Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro 
    210                 215                 220                 


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val 
225                 230                 235                 240 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                245                 250                 255     


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            260                 265                 270         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        275                 280                 285             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
305                 310                 315                 320 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                325                 330                 335     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            340                 345                 350         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        355                 360                 365             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    370                 375                 380                 


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
385                 390                 395                 400 


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


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440                 445         


<210>  22
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of c67D9 light chain

<400>  22

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


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


Gly Ile Ser Phe Met His Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


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


Glu Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
            100                 105                 110         


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
        115                 120                 125             


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
145                 150                 155                 160 


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                165                 170                 175     


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


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


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215             


<210>  23
<211>  362
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequences of PD-1-Fc fusion protein

<400>  23

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


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


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


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


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


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


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


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


Ala Ser Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
    130                 135                 140                 


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
145                 150                 155                 160 


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
                165                 170                 175     


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
            180                 185                 190         


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
        195                 200                 205             


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
    210                 215                 220                 


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
225                 230                 235                 240 


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
                245                 250                 255     


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 
            260                 265                 270         


Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
        275                 280                 285             


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
    290                 295                 300                 


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


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
                325                 330                 335     


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
            340                 345                 350         


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        355                 360         


<210>  24
<211>  455
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequences of PD-L1-Fc fusion protein

<400>  24

Phe Thr Val Thr Val Pro Lys Asp Leu Tyr Val Val Glu Tyr Gly Ser 
1               5                   10                  15      


Asn Met Thr Ile Glu Cys Lys Phe Pro Val Glu Lys Gln Leu Asp Leu 
            20                  25                  30          


Ala Ala Leu Ile Val Tyr Trp Glu Met Glu Asp Lys Asn Ile Ile Gln 
        35                  40                  45              


Phe Val His Gly Glu Glu Asp Leu Lys Val Gln His Ser Ser Tyr Arg 
    50                  55                  60                  


Gln Arg Ala Arg Leu Leu Lys Asp Gln Leu Ser Leu Gly Asn Ala Ala 
65                  70                  75                  80  


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


Met Ile Ser Tyr Gly Gly Ala Asp Tyr Lys Arg Ile Thr Val Lys Val 
            100                 105                 110         


Asn Ala Pro Tyr Asn Lys Ile Asn Gln Arg Ile Leu Val Val Asp Pro 
        115                 120                 125             


Val Thr Ser Glu His Glu Leu Thr Cys Gln Ala Glu Gly Tyr Pro Lys 
    130                 135                 140                 


Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser Gly Lys 
145                 150                 155                 160 


Thr Thr Thr Thr Asn Ser Lys Arg Glu Glu Lys Leu Phe Asn Val Thr 
                165                 170                 175     


Ser Thr Leu Arg Ile Asn Thr Thr Thr Asn Glu Ile Phe Tyr Cys Thr 
            180                 185                 190         


Phe Arg Arg Leu Asp Pro Glu Glu Asn His Thr Ala Glu Leu Val Ile 
        195                 200                 205             


Pro Glu Leu Pro Leu Ala His Pro Pro Asn Glu Arg Thr Ala Ser Glu 
    210                 215                 220                 


Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
225                 230                 235                 240 


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


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


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


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


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


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                325                 330                 335     


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
            340                 345                 350         


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


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


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


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


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


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


Leu Ser Leu Ser Pro Gly Lys 
    450                 455 


<210>  25
<211>  1431
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of the DNA containing the cDNA encoding the 
       hu67D9 heavy chain

<400>  25
aagcttgccg ccaccatgga ttttcaggtg cagattttca gcttcctgct aatcagtgcc       60

tcagtcataa tatccagagg agaggtgcag ctcgtggaat ctgggggcgg actggtgcag      120

cccggtggaa gtctccggct gagctgcgcc gctagtgggt tcactttttc tacttacggg      180

atgtcttggg tccgacaggc accaggcaag gggctggagt gggtggctac tatttctgga      240

ggaggccgag acacctacta ccccgacacc gtcaagggac gttttactat cagccgtgac      300

aacagcaaga ataccctcta ccttcagatg tcttcactgc gagctgaaga caccgctgtg      360

tactattgtg cccgtcagga ctacggtaac tacgtgtggt tcgcttactg gggacaggga      420

accctggtca ccgtctcctc ggctagcacc aagggcccat ccgtcttccc cctggcgccc      480

tgctccagga gcacctccga gagcacagcc gccctgggct gcctggtcaa ggactacttc      540

cccgaaccgg tgacggtgtc gtggaactca ggcgccctga ccagcggcgt gcacaccttc      600

ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc      660

agcagcttgg gcacgaagac ctacacctgc aacgtagatc acaagcccag caacaccaag      720

gtggacaaga gagttgagtc caaatatggt cccccatgcc caccctgccc agcacctgag      780

ttcctggggg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcatgatc      840

tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga ccccgaggtc      900

cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa gccgcgggag      960

gagcagttca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg     1020

ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc ctccatcgag     1080

aaaaccatct ccaaagccaa agggcagccc cgagagccac aggtgtacac cctgccccca     1140

tcccaggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctac     1200

cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc     1260

acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaggct aaccgtggac     1320

aagagcaggt ggcaggaggg gaatgtcttc tcatgctccg tgatgcacga ggctctgcac     1380

aaccactaca cacagaagag cctctccctg tctctgggta aatgagaatt c              1431


<210>  26
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of hu67D9 heavy chain

<400>  26

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


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


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


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


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


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


Ala Arg Gln Asp Tyr Gly Asn Tyr Val Trp Phe Ala Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


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


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


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


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


Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro 
    210                 215                 220                 


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val 
225                 230                 235                 240 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                245                 250                 255     


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            260                 265                 270         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        275                 280                 285             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
305                 310                 315                 320 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                325                 330                 335     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            340                 345                 350         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        355                 360                 365             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    370                 375                 380                 


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
385                 390                 395                 400 


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


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440                 445         


<210>  27
<211>  742
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleotide sequence of the DNA containing the cDNA encoding the 
       hu67D9 light chain

<400>  27
aagcttgccg ccaccatgga ttttcaggtg cagattttca gcttcctgct aatcagtgcc       60

tcagtcataa tatccagagg agatattgtt ctgacccagt cccccgcttc actggctgtg      120

agtcctgggc agcgagctac catcagctgc cgggcttcag agtccgtgga tagctacgga      180

atttcattta tgcactggtt ccagcagaag ccaggccaac cacctcagtt gctgatatat      240

tcgacatcta atcggggaag cggtgtgcca gcccggttta gtggtagcgg ctctggtaca      300

gatttctctc ttacaattaa cccagtggag gcggatgaca ctgccaatta cttttgtcag      360

cagagccagg aagtgccttg gacttttggt cagggcacga aggtagagat taaacggact      420

gtggctgcac catctgtctt catcttcccg ccatctgatg agcagttgaa atctggaact      480

gcctctgttg tgtgcctgct gaataacttc tatcccagag aggccaaagt acagtggaag      540

gtggataacg ccctccaatc gggtaactcc caggagagtg tcacagagca ggacagcaag      600

gacagcacct acagcctcag cagcaccctg acgctgagca aagcagacta cgagaaacac      660

aaagtctacg cctgcgaagt cacccatcag ggcctgagct cgcccgtcac aaagagcttc      720

aacaggggag agtgttgaat tc                                               742


<210>  28
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of hu67D9 light chain

<400>  28

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


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


Gly Ile Ser Phe Met His Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


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


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


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
        115                 120                 125             


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
145                 150                 155                 160 


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                165                 170                 175     


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


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


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215             


